Health aspects of chloroform--a review.

Health aspects of chloroform--a review. First prepared in 1831, chloroform was initially employed as an "ideal" anesthetic. Chloroform was later found to cause heart and liver damage and, with the discovery of safer agents, lost importance as a medical anesthetic. Today chloroform is used primarily as a solvent in industry, in the production of antibiotics, as a cleaning agent, and as an ingredient in pharmaceutical and veterinary formulations. A recent report issued by the National Cancer Institute implicates chloroform as a carcinogen in laboratory rodents. These findings, in conjunction with enforcement of the Delaney Clause have generated renewed interest in chemicals such as chloroform which are not only used in a variety of industrial applications, but which are also available to the general public in a number of food and cosmetic products.


Comparison of the relative mutagenic activity for eight antineoplastic drugs in the Ames Salmonella/microsome and TK+/- mouse lymphoma assays. Eight antineoplastic drugs were evaluated for their ability to induce mutation in the Ames Salmonella/microsome and the TK+/- mouse lymphoma assay. Dose response data were utilized to determine the relative potency of each of these drugs. They were then ranked based on this information. Vincristine, the most potent compound tested in the mouse lymphoma assay, was not active in the Salmonella assay, nor were DTIC and Methotrexate. Excluding these compounds from the comparison ranking, we found that the only difference in the order between the Ames and lymphoma assays was between Daunomycin and Adriamycin. Daunomycin was most potent in the Ames assay, compounds was reversed in the mouse lymphoma assay. This observation of relative activity is of interest because it underscores the ability to extrapolate between microbial and mammalian test systems, provided one keeps in mind the differences associated with chromosome structure and modes of segregation in these two cell types. Furthermore, it is suggested that relative potency ranking may provide prospective insight into expectations of risk for human populations exposed to these drugs.


Dextranomer: a review of its general properties and therapeutic efficacy. Dextranomer is a hydrophilic dextran polymer advocated as a 'cleansing agent' for various types of exudating wounds or ulcers, including stasis (venous) ulcers and decubitus ulcers. It appears to exert its effect by a capillary action which absorbs wound exudate, as well as wound debris and micro-organisms, into the dextranomer beads or into the spaces between the beads, thus removing such products from the wound surface. Dextranomer is an aid to wound or ulcer management, and does not directly affect tissue repair in such ulcers, but as with other 'cleansing' agents or techniques, removal of debris (and possibly micro-organisms) from the wound could be expected to promote natural healing. Reports of its effectiveness in open studies, often in patients with seemingly resistant lesions, have been encouraging. Similarly, in comparative trials results have usually favoured dextranomer, but a clear indication of the relative efficacy and benefits as compared with other treatments used for exudating lesions has not yet emerged. Further well designed comparative studies are needed to provide such information.


Immunological distinction between neurofilament and glial fibrillary acidic proteins by mouse antisera and their immunohistological characterization. Antisera were raised in mice to the presumed protein subunits of the two types of 100 A filaments in nervous tissue, glial fibrillary acidic (GFA) protein and neurofilament (NF) protein. These antisera detect a pronounced antigenic distinction between these two proteins. Antiserum to GFA protein reacts only with astroglial cells and is therefore similar to antisera prepared in rabbits. Mouse antiserum to NF protein reacts with neurons and their processes known to be rich in 100 A filaments. Postsynaptic densities do not detectably react with anti-NF antiserum when assayed by the indirect immunoperoxidase method and studied at the electron microscopic level. The two antisera do not react with actin, myosin oe nervous system, NF protein is immunohistologically detectable at embryonic day 13 (the earliest stage tested). GFA protein is not detectable with this method during embryonal development but becomes apparent only at early postnatal ages. In several species (rabbit, rat, chicken, fish, turtle, and frog) anti-NF protein antiserum only reacts with neurons, and anti-GFA protein antiserum stains glia exclusively. On the surface of trypsin-dissociated, single liver cerebellar cells from 7-day-old mice, each antiserum detects antigenic specificities which are cross-reactive with its corresponding antigen.


[The mandibular position and the masticatory surface complex in rehabilitations with total prostheses]. The construction principles for a complete denture were discussed in terms of the jaw relation and the masticatory surface complex with special reference to the conservation and preservation of the prosthetic support material. The habitual, neuromuscularly determined, position is recommended as a starting position of the mandible for the construction of this alignment; intraoral, central rod analysis of the support is helpful for the determination. When the lateral teeth are aligned, masticatory stability should be considered. The occluding surfaces therefore should be reduced, and the occlusal cusps determined according to the transversal interval of the crests for the maxilla and the mandible. In terms of the occlusion (articulation) concept, the biomechanical demands shold be determined on the basis of unobstructed sliding movements; a completely balanced occlusion seems to be the most advantageous in spite of certain disadvantages. The desired goal may be achieved with a unilaterally balanced occlusion. Based on previous experience, canine guidance as articulation concept has proved to be less suitable since symmetrical stress is unobtainable with at least one crest.


[Determination and position of the masticatory surface complex and clinically necessary corrections (with special regard to Fehr's calotte articulation)]. The individual calotte articulation recommended by C. U. Fehr in 1947 has been used at the Free University of W. Berlin for clinical teaching since this time. The following studies were described and/or recalled and contrasted with other methods for determining position: 1. Studies of Grabert mandibular posture compared with the Ivo-Tray model. 2. Stoebe's studies of calottes with various radii, 3. Eichner's and Schmitthelm's  roentgencinematographic studies, 4. Reese's study of biting force, 5. Husemann's comparison of different relational determinations, 6. Sauer's study of the success of reocclusion. Based on the clinical results and also the results of difficult comparative studies. we see no reason to depart from functional determination of relation using calotte-shaped, curved wax walls. Clinical example of the grinding surface complex, which is part of the method, guarantees construction of the complete denture within the range of tissue adaptation. No elaborate apparatuses are required. Even complicated tracing methods do not eliminate the possibility of additional work (e.g., removal of pressure areas, reocclusion).


[Masticatory surface complex and stress on the prosthesis bed]. The reproducibility of a calotte-shaped movement with the Dentatus articulator was reported. A calotte mounted in the upper part of the articulator was read by a electronic pointer mounted in the lower part of the articulator during lateral excursions. It was shown that calotte-shaped movements are reproducible with an accuracy of 60 mu and that the condyle path inclincation and incisal guidance are more important than the Bennett angle.


[Reproducibility of the jaw relation record]. The jaw relations in edentulous patients were determined with the use of the gotic arch and wax bite blocks. To compare the different methods interchangeable tracing devices and wax registrations were used. This apparatus was alternatingly used by various investigators, but with the same base plate. A quick and reliable survey of the results was possible with this experimental procedure. Our study confirmed the superior reproducibility of the graphic method with centrally supported needle.


[The so-called "Camper's" plane as a reference plane for the construction of artificial sets of teeth]. Various reference points given in the literature use Camper's plane as an analogous plane for the occlusal plane. The original assumption that both planes run parallel to each other could not be confirmed. The measured angular deviations between both planes do not differ appreciably, regardless of the reference point or the examination method. It therefore was suggested that the teeth be aligned according to the plane: arbitrary hinge axis point - subnasal (AG-SN plane). A re-evaluation of more than 100 subjects with complete dentition showed an average angular deviation of 3.87 degrees with the occlusal plane.


[Theoretical physical thoughts on the masticatory stability of complete dentures]. On the basis of physical-theoretical representations, the standard parameters and influencial dimensions for occlusally stable tooth alignment with complete dentures were explained, and suggestions were given for a statistically favorable construction of the grinding surfaces.


[The effect of the arrangement of the artificial sets of teeth on the physical stability of total protheses]. The effect of masticatory forces within and outside the stable stress-bearing areas of the complete upper denture on the pressure gradient and the flow of saliva into the space under the prosthesis were demonstrated with standardized tests. It was shown that masticatory stress within the stable area led to a continual increase in pressure in the space under the prosthesis. Masticatory force outside the stable area led to a decrease in pressure and an equalization of pressure in this space as well as dislocation and tilting of the complete denture. Due to masticatory force outside the stable area, the shape of the ridge influences the stability of the complete denture.


[Possibilities and limits of prosthetic rehabilitation of the reduced dentition]. The initial findings are crucial for determining the time and the extent of possible prosthetic treatment. The patients to be fitted with a prosthesis are divided into several groups, on the basis of the present state and the reaction of the masticatory organ to external irritation, into resistant and insufficient states. The topography (not the number) of abutment teeth, the relationship of the edentulous parts of the jaw to the number of remaining teeth, the extent and the course of future prosthetic surfaces, the possibility of the equilibrium and distribution of force, the antagonistic relationship of the teeth with each other and hygienic factors limit the prosthetic possibilities. The free-end saddle represents a particular problem in the fitting of a dental prosthesis; its variant forms are discussed and, on the basis of many years of successful controls, the possibility and the limitations for the fitting of prostheses were pointed out.


[The functional capability of removable partial dentures in various classifications of reduced dentitions]. Based on the functional capability of the prosthesis, 462 removable partial dentures worn by 351 patients were grouped into five classifications (according to the topographical distribution of the remaining teeth E. Körber, K. Eichner and V. L. Steffel, and according to the number of remaining teeth per jaw). A statistical evaluation of the data showed that the Steffel classification provided the most reliable prognostic indications for the expected functional state.


[The dimensions of cast bar dentures].

[The dimensions of cast bar dentures]. The influence of the moment of inertia on the periodontal alterations developing in abutment teeth was determined in 181 cast sublingual partial bar dentures after an average of 4 1/2 years. A significant influence could not be established. A considerable increase in the degree of loosening and/or pocket depth was observed when the dimensions were too small. It therefore is recommended that the minimal dimensions of the sublingual bars with segmental profile should not be less than 3.2 mm in height and 1.6 mm in width.


[Caries in supporting teeth with and without crowns]. On the basis of 1718 teeth in 212 patients fitted with removable partial dentures, it was established that the frequency of caries in uncontrolled noncrowned abutment teeth for partial dentures was twice as high and the number of extractions three times as high as in the control group. The special risk for abutment teeth was effectively reduced by using artificial crowns. The concept of crowning abutment teeth is discussed.


Agonist (ovulation induction) and post-coital contraceptive properties of [D-Ala6] and [D-Trp6]-LHRH series. Seven derivatives of LH-RH, representing the [D-Ala6] or [D-Trp6] series, with or without a Fujino modification, were evaluated for ovulation-inducing (agonist and post-coital contraceptive activity in rats. Six of these analogues had a high degree of agonist and pregnancy-terminating potency. In general, several modifications can result in a particular series of composite molecules that possess a biologic potency greater than each of its predecessors; this correlation of structure with activity was more consistent in the [D-Ala6]-series than in the [D-Trp6]-series. The relationship between structural modifications, resistance to enzyme degradation (based on literature reports) and increased biologic potency is discussed.


Evaluation of in vitro incubation systems for the study of gonadotropin release. A detailed study was undertaken in order to determine if a pituitary-half incubation system were a suitable model for the study of anterior pituitary response to estradiol and LHRH. Considerable variation in the gonadotropin content of randomized pituitary halves was observed. Much less variation was found in matched halves. During the initial thirty minutes incubation of pituitary halves, a large spontaneous release of gonadotropins was observed. Time course secretion studies indicated that by four hours incubation, in the presence of 50 ng/ml LHRH, cumulative secretion of LH and FSH had far exceeded that of controls. Elevations in both cumulative secretion and rate of secretion were evident within 15-30 minutes of incubation. Regardless of LHRH dose, only 2-4% of either gonadotropin was secreted. Estradiol in the range of 10, 100, 500, 1,000 and 50,000 pg/ml had no significant effect on pituitary response to LHRH or on basal release, tissue levels or total gonadotropin. Based on these results, it was concluded that while the pituitary-half incubation system may be suitable for studying LHRH induced gonadotropin secretion, it is apparently of insufficient sensitivity to allow the collection of meaningful data concerning the effects of estradiol alone on gonadotropin secretion or estradiol modulation of LHRH induced gonadotropin secretion.


Bombesin stimulates the release of insulin and glucagon, but not pancreatic somatostatin, from the isolated perfused dog pancreas. Synthetic bombesin, perfused in the isolated canine pancreas at a rate of 340-380 ng/min for 10 min, elicited a 4-fold rise in insulin to a peak at 2 min; a rapid decline followed discontinuation of bombesin. Glucagon rose by 50% to a peak at 6 min, but remained elevated after discontinuation of the bombesin. Somatostatin-like immunoreactivity was not significantly affected by perfusion with bombesin.


Mode of gonadotropin secretion in infantile female rats and the role of estrogen in feedback regulation. The temporal aspects of gonadotropin release were studied in infantile (14-day-old) female rats. Blood samples were collected using vena cava cannulae at 10-, 15-, 20-, or 30-min intervals and assayed for either LH alone or for both LH and FSH. Within individual animals, blood LH levels exhibited a degree of variability suggestive of a pulsatile release of the hormone. Wide fluctuations in circulating FSH were also observed, indicating that FSH might also be secreted in a pulsatile manner. Peak values for both gonadotropins were 2- to 5-fold higher than baseline levels. The majority of pups exhibited a nonrhythmic release of hormones. In some animals, LH and FSH appeared to be secreted in a temporally coincident manner. Administration of LHRH to cannulated pups evoked a simultaneous discharge of both gonadotropins. To determine whether endogenous 17 beta-estradiol (E2) plays a physiological role in the control of LH secretion in infantile rats, circulating LH levels were monitored in cannulated pups which had been treated twice daily with anti-E2 serum for 4 days. Passive immunization to E2 did not affect pulsatile LH  secretion. Therefore, the results of this study demonstrate that in infantile female rats, LH is secreted in a pulsatile manner which is independent of E2 feedback regulation.


Evidence for the involvement of an energy-dependent process in gonadotropin-releasing hormone-stimulated luteinizing hormone release by rat anterior pituitary. The involvement of an energy-dependent process in gonadotropin-releasing hormone-(GnRH) stimulated LH release in the anterior pituitary has been examined. Inhibitors of both glycolysis and oxidative phosphorylation inhibited stimulation by GnRH of LH release in a time- and dose-dependent manner. Iodoacetate and 2-deoxyglucose inhibited GnRH-stimulated LH release, and this inhibition was not overcome by the addition of pyruvate. Similarly carbonyl cyanide m-chlorophenylhydrazine, an uncoupler of oxidative phosphorylation, and sodium azide, an inhibitor of electron transport, decreased ATP levels, enhanced lactate accumulation, and inhibited GnRH-stimulated LH release. These studies demonstrate that inhibition of glycolysis and oxidative phosphorylation with metabolic inhibitors lead to inhibition of GnRH-stimulated LH release. Based on these results, it is postulated that GnRH-stimuoated LH release is dependent on an energy-dependent process.


Chronic effects of [D-Trp6,Pro9-NEt]luteinizing hormone-releasing factor on reproductive processes in the male rat. Chronic administration of a potent LRF agonist, [D-Trp6,Pro9-NEt]LFR (A), to intact adult male rats induced a dose-related decrease in testicular and accessory organ weights, diminished production of testosterone (T), and disrupted tubular morphology, indicative of suppression of spermatogenesis. Transient elevations of plasma progesterone levels and a marked reduction of PRL secretion were also observed in A-treated rats. The effects of A on testicular weights, T levels, and seminiferous tubule morphology were already apparent 3 days after the first injection. Administration of A was equally effective when administered daily or at 1- to 4-day intervals in lowering steroid levels and testicular weights. After a 1-week daily exposure to A, seminal vesicles and prostate weights as well as T levels returned to control values within 1--2 weeks. Testicular weights, however, were still depressed 4 weeks after cessation of treatment, and germinal epithelium was disrupted in 30--40% of the tubules. Measurement of T and LH plasma levels after each daily injection of A indicated a blunting of succeeding A-induced elevations of LH and T, which lasted up to 72 h after a single administration of A. The observation that cultured pituitary cells repeatedly exposed to A showed a similar blunting of LRF-induced LH elevation suggests that the decrease in pituitary responsiveness was not exclusively due to steroid feedback. Administration of T propionate to A-treated intact rats was unable to restore normal testicular weights and seminiferous tubule morphology, whereas in hypophysectomized rats, T propionate maintained qualitatively normal spermatogenesis even in the presence of A. These results coupled with the observation that high levels of hCG and PMS gonadotropin had effects similar to those of A on the tubular morphology of intact rats suggest the importance of pituitary secretion in mediating the deleterious effects of A on reproductive functions in the male rat.


Pentosephosphate shunt activity of rat pancreatic islets: its dependence on glucose concentration. Although several attempts have been made to establish a relationship between glucose concentration and pentosephosphate shunt (PPS) activity of pancreatic islets in vitro, no such relationship has been found. Recently it has been shown that exogenous insulin, when added in vitro, inhibited islet PPS activity. Since it was possible that the failure to detect such a relationship was due to insulin released into the incubation medium, we reinvestigated the subject, introducing GPAIS (guinea pig antiinsulin serum) to bind insulin in the medium. When five islets were incubated with 16.7 mM glucose for 90 min, the absolute rate as well as the percentage of islet PPS activity were found to be significantly higher (P less than 0.05) in the presence of GPAIS than in its absence. In the presence of GPAIS, the absolute rate and the percentage of islet PPS activity increased in a dose-related manner (18, 43, and 124 pmol/five islets.90 min and 2.3%, 3.2%, 9.4%, respectively) when the glucose concentration was raised from 5.6 to 11.1 and 16.7 mM. Our data, therefore, indicate that the activity of islet PPS activity in vitro depends on the concentration of glucose, provided that insulin does not accumulate in the incubation medium. This suggests that PPS activity might play a role in glucose-induced insulin secretion. However, whether the PPS contributes to the secretory mechanism by producing a signal for insulin secretion or by forming cofactors required by the secretory mechanism remains to be established.


Chronic obstructive pulmonary disease (COPD) in horses: aetiological studies: responses to intradermal and inhalation antigenic challenge. Micropolyspora faeni and Aspergillus fumigatus were identified as common causes of respiratory hypersensitivity in horses affected with chronic obstructive pulmonary disease (COPD). Rye grass pollen and an Actinomycete evoked respiratory allergy in a few horses. Not infrequently, individual horses were found to have respiratory hypersensitivity to two or more antigens. The methods used to examine for allergy were intradermal testing and inhalation challenge with environmental antigens. An intradermal test using an M faeni extract was demonstrated to be suitable for diagnostic use in horses previously accurately diagnosed as suffering from COPD. In contrast, the A fumigatus antigen used proved unsatisfactory for such a purpose. Skin reaction to M faeni and A fumigatus extracts by horses affected with COPD indicated that the hypersensitivity was a dual one--a weak response shortly after injection followed by an Arthus-like response 4 to 8 hours later. As a parameter for monitoring responses to inhalation challenge, maximum intrathoracic pressure change (max delta Ppl) proved satisfactory, whereas changes in partial pressure of arterial oxygen (PaO2) did not.


50-S subunit from Escherichia coli ribosomes. Isolation of active ribosomal proteins and protein complexes. A method is described for the isolation of highly purified proteins from the 50-S subunit of Escherichia coli ribosomes. All the proteins from the large subunit could be isolated with the exception of L14, L26, L31 and L34. The isolated proteins are functionally active in reconstituted particles. The method consists of successive NH4Cl/EtOH and LiCl washing steps, which split off distinct groups of proteins from the ribosome. The protein groups are further separated by a combination of gel filtration (Sephadex G-100) and ion-exchange chromatography (carboxymethylcellulose) in the presence of 6 M urea, at neutral pH and 4 degrees C. The purity of the proteins was analyzed by two-dimensional gel electrophoresis. In addition, ten protein complexes were isolated and identified.


The binding of non-cognate Tyr-tRNATyr to poly(uridylic acid)-programmed Escherichia coli ribosomes. The poly(U)-dependent binding of Tyr-tRNATyr to Escherichia coli ribosomes has been studied using a highly purified system. Binding is maximal at 10 mM magnesium acetate (up to 0.7 molecule Tyr-tRNATyr/ribosome), and requires the presence of elongation factor (EF) T (a mixture of EF-Ts and EF-Tu), GTP, NH4+ ions and an aminoglycoside antibiotic (streptomycin, neomycin B, kanamycin B or gentamicin C1a). Under limiting and up to saturating concentrations of EF-T, one molecule of GTP is hydrolyzed per molecule of Tyr-tRNATyr bound, suggesting that 'proof-reading' mechanisms involving the hydrolysis of GTP are inoperative in the presence of the antibiotics. Binding of Tyr-tRNATyr apparently takes place at the ribosomal acceptor site, since peptide bonds are readily formed with N-acetyl-Phe-tRNA prebound to the ribosomal donor site. In contrast to Phe-tRNAPhe binding, Tyr-tRNATyr binding is impaired by the omission of the 50-S subunit, the replacement of GTP by its non-hydrolyzable analogs guanyl-5'-yl methylene diphosphonate and guanyl-5'-yl iminodiphosphonate, and also by the presence of the antibiotic streptogramin A. This suggests that the correct interaction of Tyr-tRNATyr with the peptidyl transferase centre is essential for the stability of this ligand on the ribosome. Moreover, the aminoglycoside antibiotics are also necessary, even after the binding reaction is complete, to maintain Tyr-tRNATyr on the ribosome.


Lack of correlation between affinity of the tRNA for the aminoacyl-tRNA synthetase and aminoacylation capacity as studied with modified tRNAPhe. The interactions of several modified yeast tRNAPhe [tRNAPhe lacking 7-methylguanine; a fragment comprising about 3/4 of the whole molecule: tRNAPhe (18--76); tRNAPhe (18--76) lacking 7-methylguanine] with yeast phenylalanyl-tRNA synthetase were studied. Upon excision of the 5'-quarter of the tRNAPhe molecule, the residual fragment still tightly binds to the synthetase, but can no longer by aminoacylated. Surprisingly, upon removal of the 7-methylguanine base at position 46 in this fragment, althought the affinity drops by a factor 10, a significant aminoacylation is restored. These results are discussed in terms of molecular flexibility and a model is proposed for tRNA-enzyme interaction, involving multisite recognition.


Irreversible inactivation of pyruvate decarboxylase in the presence of substrate and an oxidant. An example of paracatalytic enzyme inactivation. Pyruvate decarboxylase from yeast is progressively inactivated in the presence of pyruvate and an extrinsic oxidant such as 2,6-dichloroindophenol or hexacyanoferrate(III). The inactivation is linked to the oxidation of the hydroxyethylthiamine diphosphate intermediate to acetate. Removal of low-molecular compounds by gel filtration does not reactivate the enzyme. The rate of inactivation obeys saturation kinetics with respect to substrate concentration and is independent of enzyme concentration. In analogy to the paracatalytic inactivation of other enzymes forming oxidizable carbanion intermediates [Christen, P. (1977) Methods Enzymol.46, 48--54], the oxidation of enzyme-bound hydroxyethylthiamine diphosphate is thought to generate a transiently reactive intermediate which, without being released from the enzyme, covalently modifies a group at or near the active site. Reconstitution experiments indicate that the protein rather than the coenzyme moiety is modified.


Studies on a proteinase B mutant of yeast. Yeast mutant lacking proteinase B activity have been isolated [Wolf, D. H. and Ehmann, C. (1978) FEBS Lett. 92, 121--124]. One of these mutants (HP232) is characterized in detail. Absence of the vacuolar localized enzyme is confirmed by checking for proteinase B activity in isolated mutant vacuoles. Defective proteinase B activity segregates 2:2 in meiotic tetrads. The mutation is shown to be recessive. Mutant proteinase B activity is not only absent against the synthetic substrate. Azocoll, but also against the physiological substrate pre-chitin synthetase, cytoplasmic malate dehydrogenase and fructose-1,6-bisphosphatase. The mutant shows normal vegetative growth, a phenomenon not consistent with the idea that proteinase B might be the activating principle of chitin synthetase zymogen in vivo. Fluorescence microscopy shows normal chitin insertion. Enzymes underlying carbon-catabolite inactivation in wild-type cells (a mechanism proposed to be possibly triggered by proteinase B) such as cytoplasmic malate dehydrogenase, fructose-1,6-bisphosphatase, phosphoenolpyruvate carboxykinase and isocitrate lyase, are inactivated also in the mutant. NADP-dependent glutamate dehydrogenase, which is found to be inactivated in glucose-starved wild-type cells, proceeds normally in the mutant. Mutant cells show more than 40% reduced protein degradation under starvation conditions. Sporulating diploids, homozygous for proteinase B absence, also exhibit an approximately 40% reduced protein degradation as compared to homozygous wild-type diploids or diploids heterozygous for the mutant gene. The time of the appearance of the first ascospores of diploid cells, homozygous for proteinase B deficiency, is delayed about 50% and sporulation frequency is reduced to about the same extent as compared to homozygous wild-type diploids or diploids heterozygous for the mutant gene.


Protein . nucleic-acid reaction kinetics. Theoretical analysis of the binding reaction between DNA and RNA polymerase. This paper presents methods developed in order to analyze experimental results concerning the binding of Escherichia coli DNA-dependent RNA polymerase to DNA at high and at low DNA concentrations, using the filter retention assay. The basis hypotheses, under which the mathematical expressions for describing the kinetics of binding are derived, are as follows. (a) At low DNA concentration: equivalence and independence of the specific binding sites; first-order dependence of the binding reaction on both DNA and protein concentration. (b) At high DNA concentration: equivalence and independence of the non-specific binding sites; no direct transfer or one-dimensional sliding of the protein along the DNA. Comparison between theoretical predictions and experimental results at high DNA concentration will allow one to determine the relative value of the rates of binding of RNA polymerase to different promoters (between 1 and 2 in T5 DNA). Binding experiments performed at low DNA concentration are reported in this paper: these results and the analysis which is reported allow one to determine the value of the rate constant of formation of non-filterable complexes for the system fd DNA (replicative form) . RNA-polymerase (kappa a = 3.3 X 10(8) M-1 s-1 in 0.1 M NaCl, 0.01 M MgCl2).


Reconstitution of active 30-S ribosomal subunits in vitro using heat-denatured 16-S rRNA. 30-S ribosomal subunits which have been reconstituted using heat-denatured 16-S rRNA can participate in the synthesis of lysosyme in vitro. Therefore all the information contributed by 16-S rRNA to the reconstitution process is carried in the primary sequence of this RNA. The specific protein-synthesizing activity of 30-S subunits reconstituted from 30-S subunit proteins and heat-denatured 16-S rRNA is about one third of that observed if unheated 16-S rRNA is used and is comparable to the activity of 30-S particles isolated after dissociation of 70-S ribosomes in the presence of 0.1 mM Mg2+.


Isolation of plasmid-protein complexes from Escherichia coli. A procedure is described for the isolation of complexes between pMB9 plasmids and protein from Escherichia coli which are stable during centrifugation on sucrose gradients and are not destroyed in the presence of competitor DNA. The proteins in these complexes have been analysed by dodecyl sulphate/polyacrylamide gel electrophoresis. Only 10 polypeptide species are found in significant quantities, many of which are bound to both the plasmid and host DNA. We have also detected the presence of one protein which binds to a specific DNA sequence inserted in the plasmid.


On the binding of tRNA to Escherichia coli RNA polymerase. The fixation of tRNA to Escherichia coli RNA polymerase has been investigated. Bound and free tRNA have been separated and quantified after filtration through cellulose nitrate filters, centrifugation or sucrose gradients or electrophoresis in polyacrylamide gels. We detect no differences between the fixation of E. coli fMet-tRNAfMet, Met-tRNAmMet or uncharged unfractionated tRNA to RNA polymerase. Tight complexes, with a long residence time, are formed between core enzyme and tRNA with a dissociation constant of less than 1 nM. Complexes exist between tRNA and both monomer and dimer forms of the core enzyme. In the monomer complex, one tRNA is bound per alpha 2 beta beta' unit, whereas in the dimer complex only 0.5 tRNA molecule is fixed per alpha 2 beta beta' unit. In contrast to the core enzyme, very little tRNA fixes tightly to the holoenzyme at salt concentrations greater than 80 mM. At lower salt concentrations tRNA fixation results in a loss of sigma subunit from the holo enzyme to the resulting core enzyme where it binds tightly. DNA fixation reduces the binding of tRNA to RNA polymerase and tRNA fixation reduces the binding of DNA. However, binding of DNA to polymerase is not competitive with binding of tRNA, and ternary complexes between RNA polymerase, DNA and tRNA are shown to exist. Our results are discussed in relation to other studies concerning the effects of tRNA upon RNA polymerase.


Iron supply of Escherichia coli with polymer-bound ferricrocin. Uptake of ferric iron from ferricrocin was studied in Escherichia coli using a polymer-coupled ferricrocin that was unable to penetrate into the cell. Ferricrocinyl polyethylene glycol succinate (Mr 7000 -- 8500) promoted growth of E. coli K-12 AB2847 aroB under iron-limiting conditions. In iron-starved cells, uptake of 55Fe could be demonstrated; the amount of iron accumulated amounted to 10% of that observed with free ferricrocin. The iron supply by ferricrocin bound to polyethylene glycol was strictly dependent upon the functions expressed by the tonA and the tonB genes, as was the iron uptake promoted by free ferricrocin. Polymer-bound ferricrocin protected cells against colicin M and phage T5 by competition for the common tonA-coded outer membrane receptor protein. In addition, the rate of iron transport via the negatively charged ferricrocinyl succinate was as fast as via the neutral ferricrocin molecule. No ligand was found associated with the cells. Penetration of chelator beyond receptor is not necessary for siderophore-mediated iron uptake. It is concluded that sufficient amounts of iron can be released from the polymer complex to satisfy growth requirements.


Intermediate-sized filaments present in Sertoli cells are of the vimentin type. The cytoplasmic structure of Sertoli cells of rat testes has been studied by electron microscopy of ultrathin sections. Sertoli cells contain numerous intermediate-sized (7-11 nm) filaments which form a meshwork extending throughout the whole cytoplasm. Often the frequency of such filaments appears especially high in juxtanuclear and cortical regions, including the apical recesses containing the spermatids. Examination of frozen sections of testes by indirect immunofluorescence microscopy using guinea pig antibodies to prekeratin and vimentin has shown the absence of intermediate-sized filaments of the cytokeratin type in all cells of the testes but the presence of filaments of the vimentin type in Sertoli cells as well as in cells of the interstitial space. These results show that the intermediate-sized filaments, abundant in Sertoli cells, are of the vimentin type. In addition we conclude that the "germ epithelium" differs from others true epithelia by the absence of cytokeratin filaments and typical desmosomes and, in Sertoli cells, the presence of vimentin filaments, suggestive of a mesenchymal character or derivation.


Jakob-Creutzfeldt disease: analysis of EEG and evoked potentials under basal conditions and neuroactive drugs. EEG and evoked potential (EP) recordings of a female (aged 70) affected with Jakob-Creutzfeldt disease (JCD) are reported. A comparison of neurophysiological tests under basal conditions and pharmacological stimulation with methylphenidate, diazepam and piracetam was performed. Diazepam and methylphenidate produced a flattening of triphasic complexes and changes in background activity; piracetam did not seem to influence the abnormal brain bioelectrical environment. The authors conclude that EEG and EP abnormalities in JCD can be ascribed to two separate and interacting sources: (1) exaggerated massive excitatory input coming from a deep thalamic pace-maker throughout the diffuse projecting system, and (2) lack of inhibitory intracortical mechanisms.


Cardiac output distribution after left colon anastomosis in the rat. Resection and anastomosis of the left colon result in an aysmmetric breakdown of preexisting collagen in the colonic wall during the first days of healing. Suture technique influences this reaction. To study the regional blood flow in the colon after resection and anastomosis a tracer microsphere technique was used for determination of the cardiac output distribution in four groups of rats: unoperated and sham-operated controls and rats with left colon anastomosis sutured either by continuous or interrupted sutures. There were no differences in the organ distribution of caridac output between unoperated and sham-operated controls. Left colon resection and anastomosis led to an increased regional blood flow in the colon, which was most marked proximal to the anastomosis and furthermore more pronounced in animals with anastomosis made of continuous suture than in those made of interrupted sutures. Further, resection and anastomosis resulted in an increased cardiac output distribution to the visceral organs. The visceral increase was most pronounced in animals with continuous suture. This increase was predominantly observed in the kidneys and in the colon. The latter is interpreted as being due to an increased metabolic demand induced by resection and anastomosis.


Controlled blocking of hepatic artery flow with enzymatically degradable microspheres combined with oncolytic drugs. A new method for intermittent hepatic arterial flow arrest has been used in combination with intraarterial 5-fluorouracil (5-Fu) for the treatment of secondary liver neoplasms in 12 patients. Polysaccharide microspheres with a half-life of 1 h were infused together with 5-Fu via a percutaneously introduced catheter into the hepatic artery. There were no significant side effects to the treatment. Clinical effects and overall survival were comparable to those of hepatic artery ligation.


Platelet-activating factor and macrophages. I. Evidence for the release from rat and mouse peritoneal macrophages and not from mastocytes. Platelet-activating factor (PAF) is a phospholipid mediator of anaphylaxis, released from basophils of several mammalian species, that aggregates platelets and releases their vasoactive amines. The ionophore A23 187 induced the release of PAF from rat and mouse peritoneal cells, a mixed cell population that was fractionated using 5--15% Ficoll gradients and adherence to plastic petri dishes. PAF was associated with large, acid phosphatase-containing, adherent mononuclear cells. Mastocytes did not release PAF but released histamine by the action of ionophore or 48/80; they could not be held responsible for inactivation of PAF or inhibition of the PAF-induced platelet aggregation. These data indicate that, besides blood basophils, peritoneal macrophages are a likely source for PAF, a result that adds a new important function to the macrophage:aggregation of platelets and liberation of their inflammatory and vasoactive substances.


Hypotensive and renovascular actions of 6-keto-prostaglandin E1, a metabolite of prostacyclin. Either intra-aortic or intravenous injections of a stable prostaglandin metabolite, 6-keto-prostaglandin E1 (6-keto-PGE1), caused similar dose-dependent falls in blood pressure and reductions in renovascular resistance in the anesthetized rat. The threshold dose was 0.3 microgram/kg. A maximum hypotensive effect occured at 10 micrograms/kg, but renal blood flow was further reduced by a dose of 30 microgram/kg. 6-keto-PGE1, like prostacyclin, could be a circulating hormone.


The effects of captopril (SQ 14,225) on bradykinin-induced bronchoconstriction in the anesthetized guinea pig. The effect of captopril (SQ 14,225) a potent inhibitor of angiotensin converting enzyme (ACE: kininase II) on the bronchoconstrictor response to bradykinin was studied in the anesthetized guinea pig. The i.v. administration of captopril caused a profound long lasting hypotension without affecting pulmonary resistance or dynamic compliance. Similarly, the i.v. administration of bradykinin caused small increases in pulmonary resistance and decreases in dynamic compliance which were not altered by the administration of captopril. However, after beta-receptor blockade with propranolol, bradykinin-induced changes in resistance and compliance were enhanced; additional captopril administration further potentiated the bradykinin effects. The prostaglandin synthetase inhibitor indomethacin antagonized the bradykinin-induced bronchoconstriction in beta-blocked animals and its potentiation by captopril. In the isolated perfused guinea pig lung, bradykinin caused a dose dependent release of a prostaglandin-like substance which was significantly increased by captopril and antagonized by indomethacin. These results suggest that bradykinin causes a prostaglandin-mediated bronchoconstriction. Captopril, a potent inhibitor of ACE, prevents the degradation of bradykinin thus potentiating the bradykinin-induced bronchoconstriction, an effect observed in intact animals only in the absence of pulmonary beta-receptor activation.


Electroanatomy of tectal efferent connections related to eye movements in the horizontal plane. 1. Excitatory and inhibitory oligosynaptic pathways from the superior colliculus (CS) to ocular motoneurons engaged in horizontal eye movements were investigated in cats using acute and chronic brain stem transections in combination with intracellular recordings. 2. Isolation of the medial ponto-bulbar tegmentum from vestibular nuclei and adjacent lateral tegmental structures did not impair short-latency EPSPs and IPSPs induced by collicular stimulation in lateral rectus motoneurons (LR-MNs). On the contrary, responses were enhanced after chronic de-efferentation of vestibular nuclei. This suggests compensatory synaptic rearrangement in the tecto-reticulo-abducens pathways. 3. Midsagittal mesencephalic transections eliminated not only crossed excitatory but also ipsilateral inhibitory CS action on LR-MNs indicating that underlying pathways undergo decussation within the midbrain. 4. Midsagittal transections at different pontine and bulbar levels were performed to locate the second decussation of the inhibitory pathway. Ipsilateral IPSPs were eliminated only by deep lesions extending for about 1.5 mm rostral and caudal to the 6th nuclei. 5. Investigation of medial rectus motoneurons (MR-MNs) revealed two types of excitatory responses to CS-stimulation: (a) di- or trisynaptic EPSPs characterized by a fast rising phase and pronounced frequency potentiation; (b) slowly rising EPSPs displaying little or no frequency potentiation. 'Fast' EPSPs were abolished by all types of pontine lesions interrupting transmission through the contralateral 'abducens region' and may thus be relayed by internuclear neurons within or adjacent to the 6th nucleus. 'Slow' EPSPs persisted after transverse sections at midpontine and rostral pontine levels. 6. The trajectory of tectofugal inhibitory pathway to MR-MNs could not be followed due to a marked suppression of IPSPs under pentobarbital anesthesia. Persistence of IPSPs in LR-MNs under same conditions indicated that reciprocal inhibition of LR- and MR-MNs is mediated by different populations of inhibitory interneurons.


Septo-hippocampal connections and the hippocampal theta rhythm. Recordings were made of spontaneous hippocampal theta activity in free-moving rats, before and after a variety of lesions. Three recording sites were used to monitor activity in the dorsal hippocampus, the ventral hippocampus, or close to the site of the hippocampal flexure. Electrolytic lesions were made in the medial septal area or the dorso-lateral septal area; surgical transections were made of the fimbria or dorso-medial area of the fornix. Following lesions restricted to the medial septal area, theta was abolished throughout the hippocampus; after lesions restricted to the dorso-lateral septal area theta was retained. Fimbria lesions abolished it in the dorsal, but not the ventral, hippocampus. In some subjects the hippocampal formation was subsequently stained for cholinesterase: cholinesterase staining loss was generally associated with theta loss, but this was not clear at the flexure recording site. It was confirmed that theta is dependent upon the integrity of the medial septal area. It was concluded that damage to hippocampal afferents from the septum does abolish theta, while damaging the feedback efferents does not.


Studies on experimental ancylostomiasis: transfer of acquired immunity to Ancylostoma caninum in mice through sensitized thymus and bone marrow cells. An attempt has been made to transfer acquired immunity to Ancylostoma caninum infective larvae from infected Swiss albino female mice to nonimmune, isologous recipients of same sex, through immunized thymus and bone marrow cells. Immunized cells from donors infected with a single high dose of 1000 larvae were found to be more immunocompetent than cells from donors infected with a single, but low dose of 500 larvae.


The home observation assessment method (HOAM): real-time naturalistic observation of families in their homes. The Home Observation Assessment Method (HOAM) is a new method developed to carry out objective coding of family interaction over extended time periods in a home setting. It is a computer-compatible coding system that permits on-line data reduction of interactional variables emphasizing contextual and structural dimensions of family behavior. To date, the HOAM has been applied to the study of 31 families observed for a total of over 250 sessions. Initial analysis of data from these sessions indicates that coder reliability is high and that the HOAM successfully measures dimensions of family behavior independent of architectural aspects of the home setting. Preliminary findings also indicate that although families differ dramatically along the interactional dimensions measured by the HOAM, all families studied spent remarkably little time in decision-making behavior, suggesting that behavior in the home is predominantly "maintenance-oriented."


Participation of brain stimulation reward substrates in memory: anatomical and biochemical evidence. On the basis of the pioneering leads provided by James Olds, brain stimulation reward has been shown to be a) derived from specific anatomical locations, b) influenced by psychotropic drugs, and c) functionally related to feeding behavior and sexual activity. These results recommend the view that it is worthwhile to understand, not necessarily the curious intracranial self-stimulation behavior itself, but the physiological function of the substrate revealed by the intracranial self-stimulation (ICSS) technique. I have suggested that certain components of the brain stimulation reward system may function as a memory consolidation system. In view of the biological specificity of brain reinforcement pathways, I suggest the hypothesis that activity in the mesocortical dopaminergic brain stimulation reward pathways participates in the memory consolidation process. Consequent to activity in such anatomical systems, phosphorylation of band F in the frontal cortex is altered. Thus, intracranial self-stimulation pathways are considered to play a role in memory formation by providing a biochemical residual following learning.


Hypothalamic self-stimulation and stimulation escape in relation to feeding and mating. This review begins with James Olds' discovery that self-stimulation at various brain sites can be influenced by food intake or androgen treatment. It then describes our research designed to reveal the functional significance of self-stimulation. The evidence suggests that lateral hypothalamic self-stimulation is controlled by many of the same factors that control feeding. We believe this control is exerted by at least two neural mechanisms. One is the classical, medial hypothalamic satiety system. Another is an adrenergic system ascending from the midbrain to the lateral hypothalamus. Damage to either one can disinhibit self-stimulation and feeding, thus contributing to obesity. Some of our studies use rats with two electrodes, one that induces feeding and one that induces mating. There are two response levers in the test cage, one for self-stimulation and one for escape from automatic stimulation. With the feeding electrode, rats self-stimulated less and escaped more after a meal than before. The same shift occurred after an anorectic dose of insulin or the commercial appetite suppressant phenylpropanolamine. With the sex electrode the shift from reward to aversion occurred after ejaculation. The review ends with credit to James Olds for pioneering this line of research into the neuropsychology of reinforcement.


The significance of clinical assessment of brain tissue oxygenation in different pathological conditions: an overview. The development of methods of measurement of brain oxygenation in man is reviewed and the possible clinical potential of some new and established laboratory techniques is evaluated. Advantages and problems associated with the various approaches are considered together with the difficulties that are encountered in interpretation of data obtained and the factors that may increase such difficulties. It is concluded that invasive techniques that can only be used intraoperatively are of limited value but may be helpful in confirming the edges of ischemic areas or the restoration of adequate local blood flow. Chronically implanted devices have been useful in detecting epileptic foci and in evaluation of anesthetic regimes in patients with brain lesions. Infrared spectroscopy may offer possibilities for noninvasive whole brain monitoring in patients, but the method lacks resolution.


Prolonged amenorrhea and oral contraceptives. Of 106 consecutive women referred for secondary amenorrhea of more than 1 year's duration, 65 were diagnosed as having functional amenorrhea. Of these 65, 29 had amenorrhea directly following discontinuation of oral contraceptives (OC group) and 36 had never used oral contraceptives (NOC group). There was no difference in the incidence of prior menstrual irregularity in either group. Similarly, there was no difference in the resting serum estrone, estradiol, luteinizing hormone, follicle-stimulating hormone, and prolactin levels between the OC and NOC groups. Nor was there a difference between the OC and NOC groups in response to medroxyprogesterone acetate, clomiphene citrate, or luteinizing hormone-releasing factor. Of 106 patients, 17 were proven to have prolactinomas. Eight patients had a prior history of OC use, whereas nine did not. With the exception of elevated serum prolactin levels, there were no significant differences in biochemical tests or history of oral contraceptive use between the prolactinoma group and patients with prolonged "functional" amenorrhea (OC plus NOC groups). The lack of historical or biochemical difference between the OC and NOC subjects indicates homogeneity between groups, and does not support the existence of a "postpill" syndrome.


Extrahypothalamic luteinizing hormone-releasing factor (LRF): release of immunoreactive LRF in vitro. The human placenta in vitro releases luteinizing hormone-releasing factor (LRF) which is immunologically indistinguishable from hypothalamic LRF. The release of LRF by placental tissue increased during the 4 days of culture and exceeded the original tissue content more than 5-fold. These data suggest that the human placenta may synthesize an LRF molecule immunologically identical with hypothalamic LRF.


Effect of D-leucine-6-luteinizing hormone-releasing hormone ethylamide in patients with hypogonadotropic hypogonadism with anosmia. Four men with hypogonadotropic hypogonadism and anosmia were tested with acute intravenous injections of luteinizing hormone-releasing hormone (LH-RH) and D-leucine-6-LH-RH-ethylamide (D-L eu-6-LH-RH-EA) with a 1-week interval. Each patient was then treated with this drug for 60 days and tested again after this period with an intravenous injection of D-L eu-6-LH-RH-EA. The administration of LH-RH resulted in a significant increase in the LH level in only one patient and in follicle-stimulating hormone (FSH) and testosterone increases in none. The analog D-Leu-6-LH-RH-EA resulted in significant increases in LH levels in two patients, in FSH levels in three, and in testosterone levels in one. Results obtained after treatment were closely similar to those observed before treatment. Clinical improvement in terms of increased libido, erection, pubic hair growth, and testicular size was observed. D-Leu-6-LH-RH-EA could be useful in the treatment of patients with hypogonadotropic hypogonadism, a possibility deserving further studies.


[Contribution of I. M. Sechenov to the development of respiratory physiology and biophysics]. Analysis of I. M. Sechenov's scientific heritage, of the data cited in his "Autobiographic Notes", and of his contemporaries' memoirs showed that problems of physiology and biophysics of respiration closely followed the problems of central nervous system and psychology in the scientist's creative work. The principle of resumed vacuum is shown to have major significance for extraction of the blood gases and invention of absorptiometer underlying further modifications of the model. I. M. Sechenov's studies in binding of CO2 by different blood components and saline solutions, in interrelationship of oxygen binding by erythrocytes and output of carbonic acid, in solubility of carbonic acid in water, as well as other problems studied by the eminent Russian physiologist, are reviewed.


Technical aspects of the macrophage electrophoretic mobility test in transplantation immunity. Transplantation immunity against a product of the D-region of mouse H-2 gene complex was examined by the macrophage electrophoretic mobility assay. The results obtained with the MEM assay depended upon selection of the guinea pig peritoneal exudate macrophages used for measurements. The macrophages 16--20 micrometers in diameter and containing liquid paraffin droplets were best suited for electrophoretic mobility measurements. The cells, containing liquid paraffin droplets but smaller than 16 micrometers in diameter, were affected by lymphocyte-antigen interaction product(s) much less. The increasing antigen concentration resulted in a sharp rise of macrophage percentage slowing from zero but reached a plateau value. The critical number of lymph node cells for a significant response was not less than 10(5) cells and there was a direct relationship between the number of lymphocytes and the magnitude of the response.


Decrease in the ability of bone marrow CFUs to produce macroscopic colonies of haematopoietic tissue in the spleens of partially irradiated young rats. Experiments were carried out on Wistar rats aged from 3--5 weeks, in order to determine the repopulation capacity of bone marrow CFUs after total body and partial body irradiation. CFUs were derived either from the own marrow, or from bone marrow of isologous donors. In totally irradiated hosts, macroscopic spleen colonies were formed after transplantation of both autologous and isologous marrow cells, whereas no visible colonies were detectable in partially irradiated rats, in spite of an increased haematopoietic activity of the spleen and higher concentration of circulating CFUs. Intravenous application of trypsin resulted in an increase in the number of CFUs in peripheral blood in both intact and partially irradiated rats. CFUs derived from bone marrow of PBR rats form MSC only when transplanted into isologous TBR recipients, but not at autorepopulation. The possibility is discussed that a repressor is released from unirradiated bone marrow of young rats which inhibits the colony-forming capacity of migrating CFUs.


[Levuroses appearing in cases of severe burns]. The preconditions for the development of systemic mycoses, mainly levuroses, caused by opportunistic organisms are particularly favorable in the severely burned patients: on the one hand as a consequence of suppression of immunity, on the other hand by the overgrowth of these fungi in the digestive tract as a side-effect of the antibacterial chemotherapy which is necessary for the treatment of the original disease. Since such mycoses are usually very severe, mostly life endangering, their prophylaxis and early diagnosis are highly important. The aspects and measurements, most important in this connection, are discussed on the basis of our experience.


[Actinomycetales in cutaneous pathology]. After discussing the classification of the Actinomycetales, the authors give a detailed description of the epidemiology and particularly of the clinical features of cutaneous diseases induced by genera such as Actinomyces, Norcardia and Streptomyces. Histopathological and immunological studies, together with laboratory and differential diagnostics, are also examined. In the last section, present therapeutic treatments are briefly outlined.


[Opportunistic fungi as producers of gray colonies and mycetomata]. Madurella grisea Mackinnon, Ferrada and Montemayor, 1949, is not the unique species that produces gray colonies and black-grained mycetomata. Perhaps, it is not one species, because its grains and colonies may be confounded with those of several species that can be distinguished through their fertile structures. I take this opportunity to compare some characters of Pyrenochaeta romeroi, Phoma-Phillosticta sp., Chaetosphaeronema larense, Pyrenochaeta mackinnonii, Plendomus avramii and of another aleurisopores Dematiacea with those assigned to Madurella grisea. The need is stressed for the search, the introduction and the divulgation of new methods fostering the formation of disseminating structures (pycnidospores in this case), in order to ensure the proper specification of the agent in every case of mycetoma.


[Fungal maxillary sinusitis].

[Fungal maxillary sinusitis]. Since 1969, 600 patients suffering from maxillary sinusitis have been systematically controlled clinically as well as mycologically. We discovered 81 cases of maxillary sinusitis (13,4%). Aspergillus fumigatus and Candida albicans  were the most frequently isolated fungi. Three clinical forms could be distinguished: (1) a muco-purulent form (35 cases); (2) a budding and/or caseous form (22 cases), and (3) a pseudotumoral form (24 cases). 42 patients treated with a 1% econazol (base) solution were healed.


[Experimental aspergillosis in mice].

[Experimental aspergillosis in mice]. The experimentally induced aspergillosis of mice is discussed as a useful parameter for the screening of new antimycotics. There are important differences between this test model and aspergillus infections in humans. Mice must be infected intravenously with more than 10(6) spores of Aspergillus fumigatus to provoke multiple abscess formation in the kidneys which induces an acute, lethal course of infection. Intratracheal administration of 2 x 10(6) spores did not evoke any symptoms. The therapeutic efficacy of several antimycotics was examined; amphotericin B, 5-fluorocytosine and BAY h 4364--as the only imidazole-derivative--proved to be effective.


[Recent progress in immunologic technics for the diagnosis of systemic mycoses]. The new immunological techniques used for the diagnosis of systemic mycoses are very specific. Purified antigens are now available and new methods allow the detection of various classes of specific antibodies. Precipitation tests, such as bidimensional electrophoresis and electroimmunodiffusion, are compared with passive agglutination tests; radioimmunoassay and enzyme immunoassays are analyzed. The value and utilization of cellular immunity and various other tests are discussed.


[Enzyme cytochemical and immunocytological differentiation of infiltrative cells in the skin in mycosis fungoides]. In 4 patients with mycosis fungoides in the praemycotic, infiltrative and tumour stage of the disease, a differentiation and functional characterization of the infiltrate cells, obtained from cell suspensions and cutaneous smears, was carried out by means of enzyme cytochemical and immunological methods. The lymphocyte-associated acid esterase is considered to be a marker for mature T-cell populations. Apart from monocytes and histiocytes, acid esterase-positive small lymphocytoid cells with T-cell properties are found in the praenycotic stage. In the tumour stage, large lymphocytoid cells become increasingly prevalent, they show no acid esterase activity, but an intracytoplasmatic-localized reaction in the acid phosphatase activity. On the basis of the cytochemical pattern, it is assumed that these cells represent proliferating lymphoblasts.


Clinical trial of Debrisan in superficial ulceration. A total of thirty cases of sacral ana leg uleration, burns, and infected sinuses were treated with Debrisan in glycerine (4/1 v/v), after removal of adherent necrotic tissue surgically. The preparation was effective in cleansing the wound, in most cases reducing the bacterial colonization, and lessening the local inflammation and oedema. Production of healthy granulation tissue resulted and the lesions healed faster than expected. One-third of the lesions failed to respond to treatment, and the reasons for this are discussed. With some patient selection, this preparation proved to be valuable in the treatment of superficial ulcers and surgical wounds, in those lesions with sufficient exudate to enable Debrisan to act.


A comparative clinical trial of diflunisal and ibuprofen in the control of pain in osteoarthritis. A randomized double-blind study in ambulatory patients with osteoarthritis of hip and/or knee was conducted, comparing the efficacy and safety of diflunisal 500 mg daily with ibuprofen 1200 mg daily, and a period of 8 weeks. Thirty-five patients participated in the study. The results revealed no significant differences between the treatment groups with regard to the efficacy parameters.


A controlled comparative trial of mianserin and diazepam in the treatment of anxiety states in psychiatric out-patients. Forty psychiatric out-patients with primary anxiety entered a double-blind trial comparing 2 weeks of treatment with mianserin 30--60 mg daily or diazepam 15--30 mg daily, followed by 2 weeks of single-blind placebo administration. Both drugs were effective anti-anxiety agents, but mianserin was significantly superior in efficacy as measured by the Physician's Global Rating of Severity of Illness. No differences between treatments were apparent using the Hamilton Rating Scale for Anxiety. There was no significant differences in terms of side-effects and both drugs increased anticholinergic effects such as dry mouth, blurred vision and constipation over baseline values. With one exception in the mianserin group, all patients who entered placebo treatment became worse.


A placebo controlled, double-blind evaluation of levamisole in the reduction of the frequency, duration and severity of attacks in children suffering from recurrent upper respiratory tract infections. In a double-blind placebo controlled study of levamisole in the treatment of children with recurrent upper respiratory tract infection (URI) eighty-six patients took part. Medication was given once a week, in a single body-weight adjusted dose. The children treated with levamisole had a statistically significantly reduced incidence of episodes of infection which were severe, less prolonged and required less antibiotics. No side-effects were reported.


The clinical effect of ketotifen in bronchial asthma. A therapeutical trial using ketotifen, a prophylactic agent for the long-term treatment of bronchial asthma, was undertaken. Twenty-nine patients with a mean age of 33 years and suffering from bronchial asthma for six months to 20 years (mean 8.6 years) were treated for three months. Ketotifen demonstrated good results in alleviating the impact of the disease on the asthmatic patient. The lowering of the frequency of asthmatic attacks, their duration and the degree of dyspnoea was accompanied by a normalization of lung function parameters. An analysis of further respiratory investigations showed that the best results are to be obtained in the uncomplicated asthmatic. The need for the prophylactic treatment of asthma with an agent such as ketotifen is stressed, as only in this way can irreversible changes be prevented.


Injectable depot corticosteroid therapy in hay fever. Forty-two patients with stable hay fever were treated with injections of long-acting corticosteroids. They were randomly assigned to either 2 ml of betamethasone dipropionate + betamethasone phosphate (Diprospan) or 2 ml of methylprednisolone acetate (Depomedrol). Eye and nose symptoms were evaluated according to a four-step scale of weekly intervals. Both steroids were highly efficacious in reducing the symptoms with maximal effect one week after injection and slow diminution during subsequent weeks. However, Diprospan showed a significantly better effect than Depomedrol on all symptoms. It is concluded that depot injectable formulations of corticosteroids are a useful therapeutical alternative in hay fever.


Appearance of gastrin and somatostatin in the human fetal stomach, duodenum and pancreas. The gestational time of appearance of gastrin and somatostatin in the human fetal stomach, duodenum and pancreas was examined. Immunoreactive gastrin (IRG) is detected in antral, duodenal and pancreatic extracts of a 7.0-cm (crown-heel length) fetus. More IRG is extracted from the duodenum than the antrum. Duodenal IRG concentration from fetuses of 16.0--26.0 cm are higher than younger fetal and adult concentrations. Antral IRG concentrations are one tenth of the adult contents. Very small IRG concentrations are present in the human fetal pancreas. Gastrin immunohistochemical staining is positive first in duodenal (6.5-cm fetus) and later in antral (12.5-cm fetus) mucosa; pancreatic tissue is negative for gastrin immunohistochemistry. Type IV cells are encountered in antral and duodenal mucosa of 4.0-cm fetuses; other endocrine cells appear with fetal growth. Not until much later in gestation (21.0 cm) do typical G cells appear. These results suggest that early in fetal life gastrin is produced by the type IV cell. Somatostatin immunohistochemical staining is positive in stomach, duodenum and pancreas in 6.5-cm fetuses. Immature D cells are found in antral and duodenal mucosa of 5.0-cm fetuses and mature D cells in 11.0-cm fetuses.


Effect of 2-deoxyglucose on [32P] phosphate and insulin release from perifused rat pancreatic islets. The effect of 2-deoxyglucose on glucose mediated insulin and [32P]phosphate release was studied by perifusion of isolated rat pancreatic islets. When islets were perifused with media containing 2.8 mmol/l glucose and 20 mmol/l 2-deoxyglucose for 60 minutes and then exposed to media containing 8.3 or 16.7 mmol/l glucose and 20 mmol/l 2-deoxyglucose for the next 15 minutes, insulin release at either glucose concentration was prompt but blunted. Similarly, islets preincubated (90 min) with [32P] orthophosphate, then perifused with 20 mmol/l 2-deoxyglucose for 75 min and stimulated by either 8.3 or 16.7 mmol/l glucose for the final 15 minutes or 2-deoxyglucose exposure demonstrated obtundation of [32P]phosphate release. Perifusion of islets with 20 mmol/l 2-deoxyglucose alone induced no heightened 32P efflux. These studies suggest that 2-deoxyglucose affects initial events in stimulus-secretion coupling of glucose mediated insulin release.


Interactions of alpha-ketoisocaproate, glucose and arginine in the secretion of glucagon and insulin from the perfused rat pancreas. The effects of alpha-ketoisocaproate (KIC, 10 mmol/l) on glucagon and insulin release were studied in the in vitro perfused rat pancreas. The experiments were performed at low glucose concentration (3.3 mmol/l) in the absence or presence of arginine (10 mmol/l). In all the experiments KIC induced a marked and not rapidly reversible inhibition of glucagon release. This inhibition was more pronounced in the absence (76 percent) than presence of arginine (61 percent). These inhibitory patterns closely duplicated those which were seen in parallel experiments which included a rise in the concentration of glucose (from 3.3 to 11.1 mmol/l). KIC was also a potent stimulator of insulin release. The results are compatible with the view that the intracellular metabolism of KIC and glucose plays an essential role in the regulation of glucagon release by exogenous substrates.


Early functional and morphologic vascular renal consequences of the diabetic state. Renal hyperfunction and hypertrophy are characteristic findings in the early diabetic state, both in diabetes mellitus and in experimental diabetes. A number of structure-function relationships and their likely mechanisms are discussed. The metabolically induced hypertrophy of glomerular capillaries possibly plays a central role. Its cause is not known, but recent results on its time-course emphasize the probable long-term consequences of the irreversibility of the accumulation of basement membrane material.


Immunogenicity of a killed E. coli 0111:K58 vaccine administered orally to children. A killed E. coli 0111:K58 vaccine was administered by the oral route to 16 children ranging from 3 months to 7 years of age. The antibody response was measured at different times after the vaccination through the titration of agglutinating antibodies in serum and in fecal extracts, and the detection of specific IgA immunoglobulins in the intestinal content. All vaccines developed antibody response detectable both inserum and in fecal samples. Coproantibodies tended to appear earlier and to attain higher titers than circulating antibodies; they were all least in part IgA immunoglobulins, since the content of specific IgA in the fecal extracts was proportional to the agglutinating titer.


[In vitro antibacterial activity of fosfomycin]. We have studied the "in vitro" antibacterial activity of phosphonomycin against 93 freshly isolated bacterial strains. Phosphonomycin posses a good activity mainly against Gram positive bacteria. A marked increase in the antibacterial activity "in vitro" is obtained when phosphonomycin is combined with other antibitoics having a similar mechanism of action (i.e. inhibition of cell-wall synthesis). We have also determined the frequency of phosphonomycin-resistant mutants in some of the strains tested for antibacterial activity. High frequency of resistant strains have found in Klebsiella spp.


Intramural hematoma of the small intestine presenting with major upper gastrointestinal hemorrhage. Case report and review of the literature. We report a case of an anticoagulated patient presenting with a massive upper gastrointestinal hemorrhage, abdominal pain, and a palpable abdominal mass, demonstrated to be an intramural hematoma of the jejunum. Approximately two-thirds of intramural hematomas of the small intestine are preceded by abdominal trauma with the remainder associated with pancreatic disease, alcoholism, unknown causes, or clotting defects. Spontaneous occurrence of intramural hemorrhage is uncommon. Of the varied clinical presentations, gastrointestinal bleeding, previously thought unusual, is seen in 30% of cases, although major hemorrhage is rare. Conversely, reports of intramural hematoma of the small intestine as a case of major gastrointestinal bleeding has not been recognized. A review of the literature follows, and the authors stress that abdominal trauma should raise the possibility of an intramural hematoma of the small bowel.


[Effect of the carbon/nitrogen ratio on the antibiotic activity of prodigiosin]. The antibacterical activity of prodigiosin varies according to the C/N ratio in the cultural media for S. marcescens. In organic media, as nutrient agar, peptone or soytone, the optimal ratio lies between 4 and 5, and higher values are required for "mineral media" where the nitrogen source is essentially an ammonium salt. The separate C source would be probably used as "acetate source" for the synthesis of the terminal alkylpyrrole.


Changes in mammalian sperm morphology after X-ray and chemical exposures. Sperm head morphology in mammals provides a unique approach to quantiating the effects of environmental agents on the germ cells. In unperturbed male mice, the sperm of each genotype can be reproducibly characterized by the shape of the head, the overall percent of sperm with head-shape abnormalities and the types of shape abnormalities seen. Genetic studies show that sperm shape is highly heritable, and that the fraction of abnormal sperm is controlled by a multitude of autosomal factors plus probably involvement of the sex chromosomes.--Exposure to ionizing radiation or certain chemical agents in vivo leads to dosage-dependent increase in the fraction of sperm with head-shape abnormalities. These results are documented in numerous mammalian species, including man. Evidence from mouse studies suggests that in general sperm shape is affected by those agents considered to be mutagenic. Since sperm samples are easily obtained and sperm morphology is rapidly quantitated, these observations suggest that sperm morphology in the mouse may be an applicable screen for environmental effects on germ cells. Changes in sperm are also seen in the offspring of male mice exposed to irradiation or a chemical alkylating agent. Preliminary evidence suggests that these changes represent heritable sperm shape abnormalities that can be further transmitted to subsequent generations.--The problems of determining the genetic implications of induced sperm abnormalities in exposed males are discussed. It is suggested that sperm morphology testing may have a direct application in man.


Isoelectric focusing and electrophoresis combined as a method for defining new point mutations in the mouse. Isoelectric focusing followed by electrophoresis is a method that allows the survey of the expression of an enormous number of genes in one organism when this method is used for separation of complex protein solutions from the tissue of the organism (protein-mapping method). This makes it possible to use this method for developing a test system aiming at the detection of newly induced or spontaneous point mutations in mammals. A large number of loci could be tested on a relatively small number of individuals. The protein-mapping method was used for the separation of mouse tissue extracts containing soluble proteins or total cell proteins. Several modifications of the method are described. The applicability of this method for defining genetic differences of proteins was demonstrated by an investigation of different strains of mice. Thereafter, a mutagenicity test was initiated with the protein-mapping method. Mice were treated with methyl-nitroso-urea as a potential mutagenic substance and the fetuses of the F1 generation were investigated. Preliminary results suggest that new point mutations were detected with this method.


In vivo somatic mutation systems in the mouse. In an effort to meet the need for a fast and cheap in vivo prescreen for inherited mammalian point mutations, a somatic forward-mutation method, originally developed in an X-ray experiment, has more recently been tested in work with chemical mutagens. The method makes use of coat-color mutations because (a) the gene product is usually locally expressed, (b) mosaics can be detected with minimal effort, and (c) opportunities for making comparison with induction of germinal point mutations are greatest.--Following treatment of embryos that are heterozygous at specific coat-color loci, various induced genetic changes can result in expression of the recessive (RS) in clones derived from "mutant" melanocyte precursor cells. However, other events, such as decrease in the number of precursor cells, or disturbed differentiation, can also result in spots, which with careful classification can usually be distinguished from RS's on the basis of their location and color. When this is done, the relative RS frequencies for a series of compounds at least roughly parallel the relative spermatogonial mutation rates. The fact that easily measurable (though low) RS rates are obtained with compounds that have yielded negative results in spermatogonial tests is not surprising in view of the fact that RS's can be caused by several mechanisms besides point mutation.--In spite of the parallelism observed in one laboratory, the usefulness of the in vivo somatic mutation method as a prescreen could come to be doubted because of major discrepancies between results of similar experiments at different laboratories. However, it appears probable that at least some of these discrepancies are due to failure to discriminate between spots that probably resulted from melanocyte insufficiency and spots that resulted from expression of the recessive.--Reverse somatic mutation systems can potentially avoid some of the pitfalls of forward mutation systems. Such system are still in developmental stages.


Quantitative characters of potential value in studying mutagenesis. The use of polygenic characters in testing for mutagenicity appears promising. Characters chosen should be easily measured and highly heritable, with a reasonable proportion of the genetic variance being of the additive type, as this implies that polygenic mutations affecting the character would be detectable in the heterozygous state. Changes in such characters may arise as a result of pleiotropic effects of major gene mutations that affect early steps in metabolic pathways.--No single character is likely to be entirely satisfactory; rather a diverse group of biochemical, anatomical and physiological characters, including growth and behavior, should be studied. Mandible shape appears to be particularly promising. The characters may be analysed simultaneously using multivariate techniques. Special attention should be paid to the detection of outliers, which may then be investigated by more classical methods for the presence of mutants. Thus, easily measured, highly heritable polygenic characters may be useful in screening animals for the presence of mutations.


Unscheduled DNA synthesis (DNA repair) in the germ cells of male mice--its role in the study of mammalian mutagenesis. Unscheduled DNA synthesis (UDS) has been found to occur in vivo in specific meiotic and postmeiotic germ cell stages of male mice after mutagen treatment. Techniques and problems involved in measuring UDS are discussed, including the administration of tritium-labeled thymidine ([3H]dT) and mutagens, and the detection of UDS using liquid scintillation counting (LSC) and autoradiography. The sensitivity of detection of UDS in the male germ cells is compared to that of other genetic end points, and the possible role of UDS in the actual repair of genetic damage is considered. Possible areas for future research on the role of UDS in repair of genetic damage in the mouse are suggested.


An assay for histocompatibility gene mutations in mice. A method used for detecting histocompatibility gene mutations by tailskin graft tests in mice is described. Advantages and disadvantages are found for this assay system. The results of published work point to some interesting features of the H-gene mutational event, but also leave many questions yet to be answered.


Cytological methods for the study of meiotic properties in mice. Cytological methods now available produce excellent preparations of many of the meiotic stages in both male and female mice. Large samples of these stages can be obtained from males, limited samples from females. Some of these stages are useful for the identification of structural heterozygosity. As yet, the potentially valuable stage of pachytene can be used only for looking at specific chromosome bivalents and cannot be used for extensive genome analysis. The later stages of diakinesis and first metaphase have proved most rewarding for study and have enabled us to identify the meiotic configurations resulting from several different kinds of translocations and from paracentric inversions. It is possible, however, that many smaller rearrangements between and within chromosomes escape detection.


Regulatory mutants at the his1 locus of yeast. The his1 gene in Saccharomyces cerevisiae codes for phosphoribosyl transferase, an allosteric enzyme that catalyzes the initial step in histidine biosynthesis. Mutants that specifically alter the feedback regulatory function were isolated by selecting his1 prototrophic revertants that overproduce and excrete histidine. The prototrophs were obtained from diploids homoallelic for his1--7 and heterozygous for the flanking markers thr3 and arg6. Among six independently derived mutant isolates, three distinct levels of histidine excretion were detected. The mutants were shown to be second-site alterations mapping at the his1 locus by recovery of the original auxotrophic parental alleles. The double mutants, HIS1--7e, are dominant with respect to catalytic function but recessive in regulatory function. When removed from this his1--7 background, the mutant regulatory site (HIS1-e) still confers prototrophy but not histidine excretion. To yield the excretion phenotype, the primary and altered secondary sites are required in cis array. Differences in histidine excretion levels correlate with resistance to the histidine analogue, triazoalanine.


A cluster of three genes responsible for allantoin degradation in Saccharomyces cerevisiae. Mutant strains of Saccharomyces cerevisiae unable to utilize allantoin as sole nitrogen source were isolated and divided into three groups on the basis of their biochemical and genetic characteristics. The three loci associated with these mutant classes were designated dal1 (allantoinase minus), dal2 (allantoicase minus) and dal4 (allantoin transport minus). All three loci are located in a cluster that is proximal to the lys1 locus on the right arm of chromosome IX. The gene order and intergenic distances were estimated to be: dal1--2.5 cM--dal4--1.9cM--dal2--4.6cM-lys1.


Ultraviolet-induced reversion of cyc1 alleles in radiation-sensitive strains of yeast. III. rev3 mutant strains. The role of the REV3 gene function in UV-induced mutagensis in the yeast Saccharomyces cerevisiae has been examined by determining the reversion of 12 well-defined cyc1 mutations in diploid strains homozygous for the rev3--1 or rev3--3 allele. The 12 cyc1 alleles include one ochre, one amber, four initiation, two proline missense, and four frameshift mutations. We find that the rev3 mutations reduce the frequency of UV-induced reversion of all of the cyc1 alleles, though different classes of alleles respond to a different extent. These results imply that the REV3 gene function is required for the production of a wide variety of mutational events, though probably not all, and show that each of the three REV loci have different mutational phenotypes. Such diverse phenotypes are not predicted by the unitary model for bacterial mutagenesis (CAILLET-FAUQUET, DEFAIS and RADMAN 1977; WITKIN 1976), suggesting that this is at best an incomplete description of eukaryotic mutagenesis.


[Protective action of colicinogenic factor Ib-P9 on Escherichia coli cells defective in known repair functions after ultraviolet irradiation]. The presence of the plasmid colicinogenic factor Ib-P9 in Escherichia coli wild type cells is shown to increase bacterial survival after UV irradiation and the action of N-methyl-N'-nitro-N-nitrosoguanidine. The ability of the plasmid to cause the UV protection is observed in uvrA, uvrB, uvrC, polA, recB, recF E. coli strains, but the plasmid does not restore the UV resistance of the mutant cells to the wild type level. The protective effect of the plasmid CoI Ib-P9 depends on the recA+lexA+ genotype of the cells. The inhibition of protein synthesis (amino acid starvation) before and after UV irradiation does not prevent the UV protection by ColIb-P9. The nature of the plasmid-associated repair functions is discussed.


Duodenal endocrine cells in adult coeliac disease. Using immunohistochemical techniques we studied duodenal biopsies from 18 patients with coeliac disease and 24 patients with normal duodenal morphology. We had access to antisera against the following gastrointestinal peptides: cholecystokinin (CCK), gastric inhibitory peptide (GIP), gastrin-17, glucagon-enteroglucagon, motilin, neurotensin, pancreatic peptide (PP), secretin, somatostatin, substance P and vasoactive intestinal peptide (VIP). The somatostatin, GIP, CCK, and glucagon cells were increased in number in coeliac disease. The number of motilin cells was slightly increased, while secretin cells were reduced. Cells storing gastrin-17, substance P, or neurotensin were rare in all patients regardless of diagnosis. No PP immunoreactive cells were found and VIP was localised to neurons only. In biopsies from patients having a mucosa with ridging of villi the number of the various endocrine cell types did not differ from that in the control group.


Randomised trial of steroid therapy in acute liver failure. Report from the European Association for the Study of the Liver (EASL). A randomised, un-blinded clinical trial of hydrocortisate treatment in acute liver failure was carried out by 17 European centres. During a four year period 40 patients entered the study, 26 in the steroid group and 14 in the control group. The groups were found to be comparable, and the survival was 12 and 14%, respectively. A number of clinical and laboratory data, particularly HBsAg-positivity, appeared to carry some prognostic information, irrespective of treatment, but statistical significance was not achieved. Pooling of the present results with those from relevant published reports indicates a significant negative effect of steroid treatment in acute liver failure (P less than 0.2).


Double-blind randomised clinical trial of a pepsin-inhibitory pentapeptide (pepstatin) in the treatment of duodenal ulcer. In a double-blind randomised clinical trial a specific inhibition of peptic activity with a pentapeptide, pepstatin, had no significant advantage over placebo in the ulcer healing and symptomatology of duodenal ulcer. Thus, the inhibition of pepsin in human gastric juice does not appear to have a major influence on the healing of duodenal ulcer.


Double-blind controlled trial of cimetidine in the healing of gastric ulcer. Sixty patients with gastric ulcers were treated for four weeks with either 1 g cimetidine per day or with identical tablets containing lactose. The healing rate, assessed by endoscopy, was 23 out of 35 (66%) in the patients given cimetidine and 13 out of 25 (52%) in those given placebo. The difference between the groups is not significant. During each of the four weeks of the study the cimetidine group experienced significantly fewer attacks of pain and consumed less antacids than the placebo treated patients.


Some clinical and theoretical aspects on prostaglandins in obstetrics and gynecology. The present article discusses two aspects on prostaglandins, both related to the control of uterine contractility. One concerns a clinical problem, induction of abortion, and argues in favor of systemic instead of intrauterine administration of prostaglandins and the choice of E instead of F analogues. The other relates to the stimulatory effect on the myometrium of some recently detected endogenous prostaglandins. The discussion regarding the endogenous control of myometrial contractility has so far exclusively been focused upon the classical prostaglandins. It is, however, felt that substances like PGH2, PGI2 and thromboxane A2 may play a significant role in the regulation of uterine activity.


Surgical correction of the hand in epidermolysis bullosa dystrophica. Epidermolysis bullosa dystrophica (polydysplastic type) is a rare congenital skin anomaly which, in the hands, because they are exposed to repeated trauma, results in a severe "mitten"-like deformity. Functional benefit was obtained in three patients by separation of the digits and application of split-thickness grafts. Wolfe grafts or "split-off" (epidermis) grafts. Arthrodesis of the interphalangeal joints and filleting of the little finger to provide a flap which could be turned in to the palm, resulted in an improvement in hand function.


Management of the viable soft tissue cover in degloving injuries. A new method of management of pure degloving injuries has been presented. Return of the distally based flap to its bed without longitudinal tension, use of a temporary biological dressing to protect exposed structures, and early, delayed repair of the residual defect are suggested. The improved survival of the flap and earlier rehabilitation of the patient have been gratifying.


Eikenella corrodents infection of the hand. The clinical presentation and course of two patients with Eikenella corrodens infection of the hand is recorded. This recently recognised organism must not be regarded as a harmless commensal and should be differentiated from the Bacteroides group because of its resistance to clindamycin. Radical surgical debridement is the most important aspect of therapy.


New omomyid primates (Haplorhini, Tarsiiformes) from middle Eocene rocks of west-central Hot Springs County, Wyoming. Three new genera and four new species of omomyid primates constitute the first record of the Primates from upland middle Eocene rocks of Wyoming. One of these, Strigorhysis, gen. nov., possesses broadly basined molars with highly crenulated enamel which probably indicates a good deal of tough vegetable matter in its diet. Each of the new genera could have descended from known Wasatchian or early middle Eocene anaptomorphines: Aycrossia, gen. nov., is a plausible derivative of Tetonius or Chlororhysis; Strigorhysis, gen. nov., is most similar to Absarokius noctivagus; and Gazinius, gen. nov., most closely resembles Absarokius and Anaptomorphus. The anaptomorphines were probably equally as diverse as the better documented omomyines in the middle Eocene, but may have preferred upland environments at the margins of the Tertiary basins of the Rocky Mountain Interior.


[Primary small-intestinal neoplasms. Discussion of own experiences and of the literature]. There is a relatively long delay in diagnosis of malignant tumors of the small bowel and operation is often carried out too late. These tumors cause symptoms in about 90% of the cases (according to our own experiences in 20 of 21 cases). In the discussion of the symptoms there is a description given that might be a help for "earlier thinking of it". Anamnesis and exploratory laparotomy are of paramount importance for the diagnosis in time. Operation carried  out in time leeds to a relatively favourable prognosis. Out of 5 patients who did not have metastases at the time of operation there are 3 alive for longer than 8 years post operationem. From the German literature of the past 10 years (288 cases) the following data were subsumized in a table: radical resection, operation mortality, 5-year-survival, delay of diagnosis, ileus/perforation, diagnosis by barium studies of the small bowel.


[The perforated gastroduodenal ulcer. Clinical aspects and diagnosis as well as treatment and results]. Reviewing our cases from 1960-1978 an increasing rate of perforation in gastroduodenal ulcers is registered. The perforation-rate of all treated ulcers is 17%. The most important data of anamnesis and clinical findings are analyzed. The diagnosis was correct preoperatively in 93,5%. The diagnosis has to be established as soon as possible, as the prognosis depends on surgical therapy in due time. General state, duration of anamnesis and the severity of peritonitis are criteria for deciding on suture of the perforated ulcer or resection therapy. Both--suture and resection--show identical late results, if indication was correct. The lethality in patients with a perforated ulcer is high and depends on duration of perforation, age and general state of the patient as well as severity of peritonitis. In our collective lethality was 26%. The good early results after resection therapy are depending on the selected collective and on the fact, that resection therapy is performed under better circumstances than suture.


[Historical reminiscences: the schizophrenic psychosis of the Empress of Mexico (author's transl)]. Quite a number of reports have been published on psychotic developments in the mental make-up of kings and rulers, especially during the past century. Particularly remarkable is the great interest which has been evinced to date on the fate of King Ludwig II of Bavaria. On the other hand, the tragedy of the Belgian Princess Charlotte, who was Empress of Mexico for a few years by the side of her husband, Maximilian of Austria, is hardly known. I could not find anything about her in psychiatric literature, but there are numerous biographical hints in books on history dealing with the dramatic episode of the short-lived Mexican empire. I found some of the most essential information on the personality and psychosis of Empress Charlotte in the book written by Countess H. de Reinach-Foussemagne. The following description is necessarily sketchy and should be considered as a preliminary report to a more comprehensive interpretation of Charlotte's personality.


The identification of 'casein' in human breast cancer. A retrospective study of ninety-six cases of breast cancer was carried out to determine the prognostic values of a casein immunolocalization technique. This was performed using an indirect immunofluorescence method with antisera raised in rabbits to pooled human casein. Fluorescence positivity was graded according to its intensity and distribution. The pathology of each tumour was studied and the tumour type, histological grade and tissue response assessed. The relationship between these observations and the casein content of the tumour was studied. In addition the correlation between casein content and age, menopausal state, clinical staging and survival was investigated. The incidence of casein positivity in our series was 50% with approximately half of the positive cases showing strong fluorescence. There was a relationship between casein content and the age of the patients, with casein being more frequently found in tumours from younger patients. Tumours with a high casein content, in general, show a poorer survival than the group as a whole. This difference in survival was most marked in the first eight years after operation and restricted to those tumours in clinical stage I and histological grade I. The presence of casein in the tumours did not appear to be related to the other factors examined.


Immunohistochemical identification of renal lysozyme during allograft rejection in man. An immunoperoxidase staining method was used to identify lysozyme in biopsy or transplantectomy specimens of human renal allografts during reversible and irreversible rejection of the grafts. Proximal tubules in apparently functioning nephrons showed lysozyme staining. In irreversibly rejected grafts, infiltrating mononuclear phagocytes in and near peritubular and glomerular capillaries also stained intensely for lysozyme. In acute necrotizing arteritis, lysozyme-positive cells (mononuclear phagocytes) infiltrated the blood vessel wall. The presence of infiltrating lysozyme-positive cells in the transplant was consistent with poor graft survival. The variation in lysozyme staining of proximal tubular cells apparently was a reflection of the differences in the reabsorption capacity of the tubular cells, attributable to the tubular dysfunction of renal allografts. The infiltrating lysozyme-positive cells probably contribute to the increased urinary excretion of lysozyme during acute rejection.


M.A. turned M.D. heads HEW's quality bureau. Helen Smits, M.D., one of the few women to head a federal health bureaucracy, looks for ways to improve the quality, while reducing the cost, of health care.


Corporate approach lends control over complex environment. Strategic corporate planning offers hospitals a tool for dealing with an uncertain future, an increasingly complex environment, and an accelerated rate of change. Through corporate planning, the institution can capture opportunities, maximize its potential, and control its destiny.


Planning ensures local and referral care for remote rural area. Remote, rural populations need at least some inpatient services to be provided within their communities. Replacement of an obsolete small, rural hospital in Alaska shows how planning can ensure provision of hospital services locally and through referral.


Concanavalin a: modification of kidney graft immunogenicity in a double transplant model. This study determines the effectiveness of flush graft pretreatment with concanavalin A (Con A) in minimally immunosuppressed recipients receiving double kidney transplantation. Significant prolongation of survival was seen when both kidneys from the same unrelated donor were treated with Con A, when both kidneys from different unrelated donors were treated with Con A, or when the allogeneic kidney was treated with Con A, and the syngeneic kidney was untreated. There was no significant prolongation in kidney allograft survival when one of the two allogeneic kidneys was treated with Con A, whether they came from the same, or different donors. If only the syngeneic kidney was treated with Con A and no treatment was given to the allogeneic kidney, also no prolongation of survival was observed. Thus, this study fully agrees with previous data indicating that Con A is not acting by systemic immunosuppression, but by local changes that modify the kidney immunogenicity. The theoretical implications associated with the prolongation of graft survival after flush pretreatment with Con A are activation of suppressor T cells, enhancement, physico-chemical modifications of the cell membrane and/or others.