Combined light and electron-microscope morphometric studies of acute puromycin aminonucleoside nephropathy in rats. Morphometric observations were made on rats injected subcutaneously daily with puromycin aminonucleoside after two, four, six and eight daily injections. As a result it was possible to correlate the morphological alterations of the various glomerular components with the biochemical manifestations of the nephrotic syndrome particularly the onset of proteinuria. There was already significant loss of foot processes of the glomerular epithelial cells by the 2nd day, that is before the onset of proteinuria, suggesting that the loss of foot processes is a consequence of some metabolic impairment produced by the puromycin aminonucleoside which also subsequently causes the proteinuria. Swelling of the glomerular epithelial cells became significant by the 6th and 8th day of injection after the development of proteinuria, suggesting that it is a consequence of the increased amount of protein in the glomerular filtrate. Two independent morphometric methods suggest a decrease in the amount of glomerular basement membrane. Unfortunately because of difficulties in the determination of mean glomerular volumes it is not possible to be absolutely certain that this is a true finding, however it is what would be expected if the synthesis of basement membrane was depressed by the puromycin aminonucleoside.


The response of the newborn rat to injury. II. Histopathological aspects and mononuclear cell turnover. Histopathological investigations of skin lesions induced by subcutaneous implantation of glass coverslips were carried out in rats between birth and adulthood. Differences were found between the cellular reactions of newborn and adult rats to this irritant. An increased number of cells was found in the skin lesions of newborn rats, compared with adults. Uptake of a 30-min. pulse of tritiated thymidine by mononuclear cells was found to be higher in newborn skin lesions than in those of adult rats. The reverse was observed for the mononuclear cells adherent to implanted glass coverslips. Giant cells were less evident on coverslips removed from the skin of newborn rats.


Scanning electron micrographs of cancellous bone from the human sternum. Thick sections from the manubrium and the first and second sternabrae were polished and the marrow removed. Low magnification scanning electron micrographs show that the cancellous bone near the medial plane is lightly constructed, is not markedly anisotropic and does not vary greatly from place to place. In the lateral parts of the sternabrae the trabeculae are somewhat thicker and the spaces between them are larger. Measurements on the polished surface lead to numerical values of a number of parameters characteristic of the surface patterns, such as the relative surface occupied by bone, the mean widths of the trabecular sections, the mean path lengths through the bone or marrow, and a number representing the departure from isotropy of the pattern. Parameters characteristic of the three-dimensional trabecular structure can be deduced, viz., the relative volume of bone, the area of the interface between bone and marrow and the mean thickness of the trabeculae. The sternum is compared with other bones which have been investigated by the same methods. There is little resemblance to the rib or to the proximal femur. The cancellous bone in the sternum and in the lumbar vertebral body are similar in appearance but the former has slighter trabeculae and larger marrow spaces.


First reported successful management of Serratia marcescens bacteremia after open heart surgery in a child. A 7 and one-half yr-old girl developed bacteremia from S. marcescens following debanding of the pulmonary artery and closure of multiple ventricular septal defects with a Dacron patch and multiple Teflon pledgets. The site of entry was probably a radial arterial catheter left in place for 8 days. Infection was eradicated by a combination of gentamicin and carbenicillin over a 4-wk period. Of 12 cases of postoperative Serratia bacteremia in adults following valve replacement, only four survived. Antibiotics of proven effectiveness against the specific isolated Serratia strain, prompt therapy sustained for 6 wk offers the prospect for cure of this serious complication of cardiac surgery.


The validity of projective techniques and their research and clinical contribution. Numerous surveys have alternately demonstrated either a decline or continued vitality of diagnostic assessment and projective techniques in clinical psychology. This paper examines some of the factors which have contributed to the ambivalent attitudes about projective procedures. The first part of the paper considers questions about the limitations and potential contributions of projective techniques in research. The second portion of the paper examines some of the issues which limit the contributions of diagnostic assessment and projective techniques in clinical practice. A proposal is made for conceptualizing diagnostic assessment as a more integral part of the therapeutic process.


Professional training, psychodiagnostic skill, and kinetic family drawings. On the basis of Kinetic Family Drawings, doctoral level clinicians, predoctoral interns, and hospital secretaries judged 36 children to be normal or disturbed and indicated their degree of confidence in each rating. The groups were not found to differ in overall diagnostic accuracy or in degree of confidence, but professional training level did appear related to the ability to better a chance level of performance. The performance of a KFD expert was no better than the mean performance of judges in the three experimental groups.


Chloroquine resistance in malaria: variations of substrate-stimulated chloroquine accumulation. The response of [14C]chloroquine accumulation to the provision of substrate was evaluated using washed erythrocytes infected with Plasmodium berghei CS (chloroquine-susceptible), with P. berghei CR (chloroquine-resistant), with Plasmodium vinckei CS, with P. vinckei CR, or with a strain of P. berghei spontaneously resistant to chloroquine, Plasmodium berghei yoelii 17X. Erythrocytes infected with chloroquine-resistant parasites had a blunted response, particularly to low glucose concentrations. In the presence of 0.5 mM glucose in one set of experiments, for example, chloroquine accumulation increased by a factor of 8 in erythrocytes infected with P. berghei CS whereas there was no increase in erythrocytes infected with P. berghei CR or with P. berghei yoelii 17X; the difference between P. vinckei CS and P. vinckei CR was less dramatic. In every case except for P. berghei CR, the process of chloroquine accumulation in the presence of 5 mM glucose exhibited a component which became saturated at low concentrations of chloroquine in the medium. For P. berghei CR, plotting steady-state accumulation of chloroquine as a function of the concentration of chloroquine in the medium yielded a sigmoid curve, revealing that higher concentrations of chloroquine (above 100 mM) somehow relieve the blunted response to glucose and suggesting that the variation is in the process of accumulation rather than in substrate utilization.


A study of posterior palatal seals with varying palatal forms. A study was carried out to determine the depth and width of posterior palatal seals in different shapes of palates. Four different methods of developing the posterior palatal seal were utilized on each patient. The width of the posterior palatal seal area was compared with original models which were produced by plaster impressions.


Prosthetic implications of Eagle's syndrome. Eagle's syndrome can produce symptoms that may be easily confused with those resulting from wearing a prosthetic restoration. The symptoms resulting from elongated styloid processes and methods of diagnosis and treatment of these processes were described. A patient with Eagle's syndrome has been presented. The symptoms were initially suspected to be due to an ill-fitting mandibular removable partial denture. Further clinical and radiographic examination led to the diagnosis of Eagle's syndrome, and surgical correction was done. The prosthodontist should consider surgery as a possible treatment when the symptoms of the syndrome cannot be attributed to a prosthetic restoration. Various radiographic projections and panoramic radiography are valuable in confirming the presence of a calcified stylohyoid ligament or an elongated styloid process.


Phonetic considerations of chromium alloy palates for complete dentures. Two useful approaches for the construction of dentures with a chromium alloy palate have been described. The phonetic considerations were recognized, and allowances were made for their vital role when determining the palatal contours of both the metal and plastic portions of the denture base.


Variations in a removable maxillary partial denture design by dentists. Fifty-seven different removable partial denture designs for a patient were submitted by 57 dentists. Many designs were adequate to provide true health service for the patient. Others, however, could prove detrimental if worn by the patient. Dentists should be concerned with partial denture design if patients are to have prostheses that are functional and compatible with the oral environment.


Restoration of teeth with subgingival and subosseous fractures. Subgingival and subosseous fractured teeth may be repaired and should continue to function if treated by use of sound restorative techniques. Three recommendations are offered. The fractured tooth segment should be used to make a custom matrix. Minor gingival surgery will aid in gaining access to a subgingival margin. Amalgam is well tolerated and may be used subgingivally.


Children's schemata of man and woman: a comparison with the schemata of heterosexual and homosexual populations. The present study was designed to examine the man-woman schemata employed by children and compare them with those used by different sexually mature populations. A central hypothesis of the investigation was that the frequency with which children use various male-female schemata more closely resembles the frequency with which homosexuals use these schemata than either group resembles the pattern pervasive in mature heterosexual populations. The Ss were 70 white boys and 70 white girls in the fourth grade of large urban public schools. The task was the free placement of figures cut from felt on a flannel board. One group of figures contained a man, a woman, and two rectangles, while the other group consisted of two man figures and two woman figures. The schemata employed by the children in their figure arrangements were significantly different from those of adult heterosexuals and resembled those of adult homosexuals. The discussion includes the consideration of a "bracketing schema" that is employed far more often by adult heterosexuals than it is by children or homosexuals.


Serum proteins promoting [3H]thymidine uptake by Trypanosoma (Schizotrypanum) cruzi (Chagas) in vitro. Five proteins capable of stimulating [3H]thymidine uptake by Trypanosoma cruzi in vitro were isolated from fetal calf serum by (NH4)2SO4 precipitation and ion exchange column chromatography. The proteins were partially characterized by immunodiffusion, immunoelectrophoresis, polyacrylamide gel disc electrophoresis, and SDS electrophoresis. As estimated by SDS electrophoresis, using 4 standards, the molecular weight of protein 1 was 100,000, that of protein 2 was 76,000, and that of proteins 3-5 was 68,000 daltons.


Ethical problems in the management of myelomeningocele and hydrocephalus. The Milroy Lecture 1975. Within the last generation the application of major advances in drug therapy, intensive care, transfusion techniques, surgery, anaesthesia, and radiotherapy, together with a vast expansion of knowledge due to increased investigative facilities, have led to an unprecedented, dramatic and beneficial increase in the number of persons who would previously have died, or lived with severe handicaps, but can now be cured. Techniques have also been developed to prolong the lives of many people who are now able to enjoy several extra years of productive and meaningful existence, and to alleviate and improve the quality of life of many seriously handicapped persons, enabling them to become integrated as useful and contented members of the community. Choosing from numerous examples of paediatric experience, it is notable that many more extremely premature infants now survive without physical or intellectual damage; infection can almost always be cured, including neonatal and all other forms of pyogenic meningitis and the now rare cases of tuberculous meningitis and miliary tuberculosis. The few remaining new cases of Rh-haemolytic disease are also readily cured. There are outstanding successes in the treatment of childhood malignancy. Paediatric surgery has made great strides. The prognosis of congenital heart disease, of obstructions of the alimentary canal and many other conditions has improved beyond recognition. Unfortunately, the indiscriminate use of advanced techniques of all types has also kept alive those who would have died but now live with distressing physical or mental handicaps or both, often for many years, without hope of ever having an independent existence compatible with human dignity. There are many examples, including those who have sustained major brain or spinal cord injuries.


Unusal signs and symptoms associated with oral contraceptive medication. A review of medical literature concerning case history reports of adverse clinical manifestations of hormonal contraceptives is presented. While extremely rare, these side-effects often present with obscure etiology, and the physician is cautioned to be aware of their occurrence.


Screening obstetric out-patients for bacteriuria. Two hundred urine samples were obtained at the out-patient Obstetric-Gynecology Clinic, Loyola University Medical Center, from women in various stages of pregnancy. The specimens were screened for bacteriuria using a new dehydrated and miniaturized culture medium and the results compared with standard agar cultures. Of the urines examined, 6.5% proved to be bacteriuruic (greater than 10(5) organisms/ml) based on agar cultures; results from the new culture method correlated well, yielding 11 true positives versus 13 from the agar plate and only 2 false positives in 200.


Antimalarials. Synthesis and antimalarial activity of 1-(4-methoxycinnamoyl)-4-(5-phenyl-4-oxo-2-oxazolin-2-yl)piperazine and derivatives. The preparation and activity against Plasmodium berghei of derivatives of 1-(4-methoxycinnamoyl)-4-(5-phenyl-4-oxo-2-oxazolin-2-yl)piperazine are described. Replacement of the cinnamoyl group was accomplished by acylation or alkylation of 1-(5-phenyl-4-oxo-2-oxazolin-2-yl)piperazine. Modifications of the 5-phenyl group were prepared either by a sequence of reactions involving mandelic ester-pemoline-piperazine pemoline or by the reaction of 5-aryl-2-thio-2,4-oxazolidinedione with piperazine or N-substituted piperazines. In a similar manner, pemoline was allowed to react with N-arylpiperazine, hexahydro-1H-1,4-diazepine, and 2,6-dimethylpiperazine to provide N-arylpiperazine pemoline derivatives and variations in the piperazine moiety. Several compounds in which the 2-oxazolin-4-one ring was replaced with other heterocyclic rings were prepared as were several open-chain analogs. Five compounds (three of them substituted in the para position of the 5-phenyl group and two N-arylpiperazine pemoline derivatives) were found to be active against Plasmodium berghei. The remaining active compound possessed changes in the cinnamoyl group and substitution on the 5-phenyl group.


Antimalarials. 3. 3-Substituted 1-naphthalenemethanols. The synthesis and antimalarial activity of 22 3-substituted 1-naphthalenemethanols whose substitution was patterned after the antimalarial 2-substituted 4-quinolinemethanols are described. The compounds were active against Plasmodium berghei in mice, the most active being 6-chloro-alpha-(dibutylaminomethyl)-3-(3,4-dichlorophenyl)-1-naphthalenemethanol hydrochloride (3b). The naphthalenemethanols tested, 1b and 2b, were not photosensitizing to albino mice. Structure-activity relationships between the naphthalene and quinoline isosteres are discussed.


Antimalarials. 10. Substituted 3-halo- and 3-methoxy-2-aryl-4-quinoline(di-n-butylaminomethyl)methanols. Four 2-aryl-4-quinoline(di-n-butylaminomethyl)methanols with Br, Cl, F, or OMe in position 3 were synthesized by modifications of standard reactions. The antimalarial activity decreased with increased size of the 3-substituent. The 3-F-4',6,8-Cl3 compound was the most active (at 2.5 mg/kg) and was completely curative at 80 mg/kg against P. berghei in mice.


Antagonism of luteinizing hormone release and of ovulation by an analog of the luteinizing hormone-releasing hormone. Two varients of LH-RH, less than Glu-D-Phe-Trp-D-Ala-Leu-Arg-Pro-Gly-NH2 (I) and less than Glu-D-Phe-Trp-Ser-Tyr-D-Ala-Leu-Arg-Pro-NHCH2CH3 (II), have been synthesized by solid-phase methods. Both peptides strongly inhibit the LH-RH induced secretion of LH in an in vitro assay; however, only I proved effective in preventing ovulation in the 4-day cycling rat.


Luteinizing hormone-releasing hormone. Antiovulatory activity of analogs substituted in positions 2 and 6. Ten analogs of luteinizing hormone-releasing hormone (LH-RH) substituted in position 2 with D-amino acids and at 6 with either a D-amino acid or a nonasymmetric amino acid were synthesized by solid-phase methodology and assayed for antiovulatory activity. [D-Phe2]-LH-RH substituted in the 6 position with D-Ala, D-Leu, D-Arg, D-(Ph)Gly, D-Phe, or 2-Me-Ala possessed varying degrees of antiovulatory activity. [D-p-F-Phe2-D-Ala6]-LH-RH was one of the most active antiovulatory compounds, while the [D-p-Cl-Phe2-D-Ala6]-LH-RH analog was devoid of activity at a comparable dose.


Comparison of membrane organization in mitochondria from yeast and rat liver by nuclear magnetic resonance spectroscopy. Proton magnetic resonance (PMR) and carbon-13 magnetic resonance (CMR) spectra of intact, unsonicated yeast and rat liver motochondria show differences which may be correlated with the composition of the membranes. High resolution PMR and CMR signals in intact yeast mitochondria have been assigned to regions of fluid lipid-lipid interaction on the basis of spectra of extracted lipid and protein, and the temperature dependence of NMR signals from the intact membrane. PMR spectra suggest that about 20% of total yeast phospholipid is in regions where both intramolecular fatty acid chain mobility and lateral diffusion of entire phospholipid molecules are possible. No such regions apear to exist in rat liver mitochondria. For both yeast and rat liver mitochondria, comparison of PMR and CMR spectra suggests that about 50% of phospholipid appears to be in regions where intramolecular fatty acid chain motion is considerable, but lateral diffusion is restricted. The remaining phospholipid appears to have little inter- or intramolecular mobility. Since NMR observation of lipid extracts from membranes indicates that phospholipid-sterol interactions do not account for the spectra of intact mitochondria, these effects are interpreted in terms of extensive lipid-protein interactions.


Proton magnetic resonance spectroscopy of promitochondrial membranes from yeast grown under different regimes of lipid supplementation. Promitochondrial membranes, prepared from Saccharomyces cerevisiae grown anaerobically under different conditions of lipid supplementation, have been examined by PMR spectroscopy. Promitochondria from cells cultured anaerobically in media containing both unsaturated fatty acid and sterol supplements, or containing unsaturated fatty acid alone, yield high resolution spectra similar to those which are characteristic of aerobic mitochondria. By contrast, promitochondrial membranes from cells grown only with sterol supplementation in order to deplete unsaturated fatty acid and total phospholipid content of the organelles, yielded PMR spectra which were very substantially broadened. These spectra are similar to those obtained with rat liver mitochondria. PMR spectra of promitochondria from each cell type dispersed in trifluoroacetic acid, or of extracted lipids or residual proteins similarly dispersed, were different only in detail. It appears, therefore, that in the native state membranes of unsaturated fatty acid-depleted promitochondria are structurally different from promitochondria of the other two cell types. The difference may be a consequence of altered lipid-to-protein ratios, and thus of changes in the extent of lipid domain formation in the membranes of these organelles.


Topological formulation of finger-tip patterns: comparison of complete and incomplete 21 trisomics with normal subjects. Description of the topological formulation of finger-print patterns is given and illustrated by examples. In particular, the way of setting up a dictionary of total finger pattern types for the two hands separately and combined is explained. Samples of 302 normal individuals, 225 complete 21-trisomics and 173 incomplete 21-trisomics are analysed here using this method. The frequencies of the commonest total finger pattern types are compared in the three groups, using dictionaries, in which all the formulae have been listed. The mean values of radial and ulnar components for each pair of homologous fingers separately are also compared. The method is recommended for comparisons of populations, particularly if the use of a computer is expected; it can also be helpful in evaluating the total finger pattern type of any individual, in terms of the probability of belonging to one population or another, particularly if the total palmar and sole pattern types can be compared as well. Some limitations of the method from a statistical point of view are also discussed.


Electron microscopy of critical point dried whole cultured cells. To determine the overall fine structure of whole, unsectioned cells, cells from rat embryos were cultured on Formvar, glutaraldehyde/osmium-fixed, transferred to grids, dehypdrated, critical point dried, then examined by transmission electron microscopy at either 80 or 1000 kV. In contrast to air-dried material, critical point dried cells revealed each component clearly and with excellent contrast. All normal cytoplasmic structures (including coated vesicles, polyribosomes, microtubules and other fine components) were readily identifiable. Extensive structures such as microtubules and the endoplasmic reticulum (which appear fragmented in sections) were well displayed. At 1000 kV the beam readily penetrated even the thick nuclear and perinuclear cell regions and produced exceptionally crisp images. The methods described provide a simplified approach to the study of overall cell fine structure.


Immersion fixation of rapidly frozen, untreated tissues and suspensions of cells including spermatozoa. Small pieces of tissue, and cell suspensions in plastic artificial insemination (AI) 'straws', were frozen rapidly in Freon-12 at -155 degrees C, without pre-treatment. Peripheral fragments were thawed directly in 2% glutaraldehyde at 0 degrees C, and processed for transmission electron microscopy (TEM) studies. Preservation of ultrastructure was satisfactory, and freezing artifacts were minimal.


New techniques for the preparation of uniform layers of nuclear emulsions for use in micro-autoradiography. A procedure is described whereby liquid emulsion can be used to coat glass coverslips to produce films of emulsion suitable for quantitative evaluation of grain density in micro-autoradiographs. Any thickness of emulsion layer can be produced from 3 mum upwards, depending on the volume and dilution of the emulsion dispensed. The uniformity and reproducibility of the films have been tested by observing light transmission of undeveloped preparations using a microscope photometer.


Microscopic tracing of deuterium.

Microscopic tracing of deuterium. The development of the ion microprobe analyser has made it possible to follow stable isotopes with microscopic resolution in biological and other materials. An ion microprobe using an oxygen primary beam has been found to produce relatively few mass 2 ions (+ or -) on organic samples. This technique should permit the use of deuterium as a practical tracer with a resolution of about 1 mum in the plane of the section and 2 nm in the depth dimension with available instruments.


Removal of glass coverslips from cultures flat embedded in epoxy resins using hydrofluoric acid. A technique is described which the glass coverslip of a culture, flat embedded in epoxy resins can be removed easily using hydrofluoric acid. Removal by this method leaves the surface of the resin quite smooth and suitable for subsequent thin or ultrathin sectioning for electron microscopy.


The myofibrillar M-band in the cryo-section-analysis of section thickness. Information regarding the formation and the thickness of cryo-sections is of importance for an adequate interpretation of cryo-sectioned biological material. In this study we have taken advantage of the regular arrangement of filaments in myofibrils in an analysis of these matters. It is concluded that the sections are formed partly by fracturing in a way similar to that visualized in replicas made by the freeze-fracturing and -etching procedure.


A container for processing small volumes of cell suspensions for critical point drying. The attachment of lymphocytes to glass or filters, in order to facilitate handling for processing prior to scanning electron microscopy, may introduce artefacts in surface topography. A container has therefore been adapted, from an embedding capsule, for the preparation of small volumes of cell suspensions.


Mutagenic topography of the E. coli chromosome. The lactose fermenting genes in E. coli have been transposed to various chromosomal locations. The bacterial strains were mutagenized with different chemical mutagens and the frequency of Lac negative mutant colonies was measured as a function of lactose gene location in the chromosome. There appears to be a highly mutable location between 58-60 minutes on the E. coli map. This region does not appear to be correlated with the origin of DNA replication or with the terminus. The possible significance of this mutable region in the evolution of new bacterial genes is discussed.


Ipsilateral lower extremity flaps in children. A technique utilizing an ipsilateral thigh or buttock flap in children is described. Its advantages are the ease with which the patients ambulate and the extremely good tolerance of this position, as well as the placement of the donor scar sufficiently high to enable it to be hidden under most clothing.


Hemodynamic alterations with positive end-expiratory pressure: the contribution of the pulmonary vasculature. The hemodynamic responses to positive end-expiratory pressure (PEEP) ventilation have been evaluated. A rise in pulmonary capillary wedge pressure which follows the use of PEEP may not reflect changes in left atrial pressure and may be associated with a fall in cardiac output. This increase in pulmonary capillary wedge pressure suggests that there is a high resistance to flow in the pulmonary circulation and that a lower level of PEEP should be used.


F-Factor-mediated restriction of bacteriophage T7: synthesis of RNA and protein in T7-infected Escherichia coli F- and F+ cells. Bacteriophage T7 is unable to productively infect Escherichia coli strains carrying the sex factor F. T7 phage development, in terms of RNA and protein synthesis, was compared in T7-infected isogenic F- and F+ strains of E. coli. Slightly less T7 early mRNA and early protein were synthesized in F+ cells. In addition to the defect in T7 late protein production in F+ cells reported by others, significantly less T7 late mRNA was synthesized, about one-half of that produced in T7-infected F- cells. Moreover, host RNA synthesis was not completely inhibited. The protein-synthesizing ability of T7-infected F+ cells decayed much faster than that of F- cells both in vivo and in vitro. This faster decay appears to explain the failure of F+ cells to produce T7 late protein in vivo, even in the presence of a considerable amount of translatable T7 late mRNA. Therefore, it may not be necessary to postulate the involvement of specific translational discrimination against T7 late mRNA, although it appears that F-factor-mediated restriction of T7 involves changes in transcription as well as translation.


F-Factor-mediated restriction of bacteriophage T7: protein synthesis in cell-free systems from T7-infected Escherichia coli F- and F+ cells. A characteristic phenomenon in the F-factor-mediated inhibition of T7 phage is a virtual absence of T7 late protein synthesis in T7-infected Escherichia coli male cells, in spite of the presence of T7 late mRNA which is translatable in vitro when isolated from the cell. To determine whether the translational defect in T7-infected F+ cells is due to a T7 late mRNA-specific translational block, or to a general decrease of F+ cell translational activity, we compared the activities of cell-free, protein-synthesizing systems prepared from isogenic F- and F+ cells harvested at different times of T7 infection. The cell-free systems from uninfected F- and F+ cells translated T7late mRNA equally as well as MS2 RNA and T7early mRNA. The activity of cell-free systems from T7-infected F+ cells to translate MS2 RAN, T7 early mRNA, and T7 late mRNA decreased concomitantly at a much faster rate than that of T7-infected F- cells. Therefore, the abortive infection of F+ cells by T7 does not result from a T7 late mRNA-specific translational inhibition, although a general reduction of the translational activity appears to be a major factor for the inability of the F+ cells to produce a sufficient amount of T7 late proteins.


Bacteriophage P22 virion protein which performs an essential early function. I. Analysis of 16-ts mutants. The product of gene 16 of phage P22, P16, is a head protein. P16 does not play an essential role in phage assembly since particles formed without this protein appear normal by electron microscopy examination (Botstein et al., 1973). P16 is essential when the particle infects a cell in the following cycle of infection (Botstein et al., 1973; King et al., 1973). We have characterized a mutant of P22 carrying a temperature-sensitive allele of gene 16. This mutant has previously been referred to as P22 25-ts (Levine et al., 1970, 1972) and P22 X-ts (Bezdek and Soska, 1970, 1973). P22 16-ts behaves as an early mutant at the nonpermissive temperature. Temperature shift experiments show that P16 of the infecting virion acts within the first 10 min at 25 C and that gene 16 product is required late in the latent period for incorporation into infectious phage. Induction does not require P16 for the production of particles. Particles produced either in a P22 16-ts thermal shift-up infection or after induction of 16-ts lysogens at 41 C are missing P16 and are, therefore, defective. P16 in P22 16-ts virions formed at the permissive temperature appears to be heat labile; it is inactivated after infection at 41 C. A simple assay for defective particles based on a complementation test is described.


Bacteriophage P22 virion protein which performs an essential early function. II. Characterization of the gene 16 function. P16 is a virion protein and, as such, is incorporated into the phage head as a step in morphogenesis. The role of P16 in assembly is not essential since particles are formed without this protein which appear normal by electron microscopy. P16 is essential when the particle infects a cell in the following cycle of infection. In the absence of functional P16, the infection does not appear to proceed beyond release of phage DNA from the capsid. No known genes are expressed, no DNA is transcribed, and the host cell survives the infection, continuing to grow and divide normally. The P16 function is required only during infection for the expression of phage functions. Induction in the absence of P16 proceeds with the expression of early and late genes and results in particle formation. P16 must be incorporated during morphogenesis into progeny particles after both infection and induction for the progeny to be infectious. The P16 function is necessary for transduction as well as for infection. Its activity is independent of new protein synthesis and it is not under immunity control. P16 can act in trans, but appears to act preferentially on the phage or phage DNA with which it is packaged. The data from complementation studies are compatible with P16 release from the capsid with the phage DNA. In the absence of P16 the infection is blocked, but the phage genome is not degraded. The various roles which have been ruled out for P16 are: (i) an early regulatory function, (ii) an enzymatic activity necessary for phage production, (iii) protection of phage DNA from host degradation enzymes, (iv) any generalized alteration of the host cell, (v) binding parental DNA to the replication complex, and (vi) any direct involvement in the replication of P22 DNA. P16 can be responsible for: (i) complete release of the DNA and disengagement from the capsid, (ii) bringing the released DNA to some necessary cell site or compartment such as the cytoplasm, (iii) removal of other virion proteins from the injected DNA, and (iv) alterations of the structure of the injected DNA.


Nuclear polyhedrosis virus detection: relative capabilities of clones developed from Trichoplusia ni ovarian cell line TN-368 to serve as indicator cells in a plaque assay. Cloned cell lines from the established Trichoplusia ni line TN-368 appear to differ from one another in their relative capabilities to serve as plaque assay indicator cell lines for Autographa californica nuclear polyhedrosis virus. Although there seems to be little correlation between their relative generation times and their efficiency in supporting plaque formation as indicator cell lines, there does seem to be a relationship within a given line between its capability to serve as an indicator and its phase of growth as a population; i.e., lag, logarithmic, or stationary. Both the parent line and clone 10 were more efficient indicators when they were in the logarithmic phase of growth than when in either the lag or stationary phases. Also, there appears to be a rough correlation between the capability of a given clone to serve as an indicator and the rate at which polyhedra first appear in the nuclei of the infected cells, with the best indicators producing polyhedra first. Increased incubation time has no effect on equalizing the plaque assay results for the less efficient clones. It was observed, also, that those clones that are the least efficient as plaque assay indicators produce the most external PFU per cell.


Chemical stability of bacteriophage T7 early mRNA. T7 early mRNA produced by a gene 1 amber mutant phage, T7 am27, is chemically stable interms of acid insolubility and T7 DNA hybridizability. However, the messenger activity of individual T7 early mRNA species, transcripts of gene 1, gene 0.7, and gene 1.3, decay with a half-life of about 6.5 min at 30 C. An extensive secondary structure is present in all T7 early mRNA species and is probably responsible for the chemical stability of the RNAs after the loss of functional activity. It is unlikely that ribosomes protect T7 early mRNA from nucleolytic degradation.


Radiation nephritis: a review.

Radiation nephritis: a review. Radiation nephritis is a process of necrosis, atrophy and sclerosis that follows exposure of the kidney to ionizing radiation. Experimental studies with electron microscopy demonstrate that this process begins as degeneration of the glomerular endothelium and the tubular epithelium, and their basement membranes, leading to collapse of these structures and the development of interstitial fibrosis. Rather late and complicating events are necrosis and thrombosis of arteries and arterioles, contributing to the destruction of the renal parenchyma. The process is the same with large doses (5,000 to 10,000 rads) and with medium doses (1,000 to 3,000 rads), the only difference being the extent and the speed with which the lesions develop and the frequency of arterial necrosis.


Chemotherapy of advanced prostatic carcinoma with cyclophosphamide or 5-fluorouracil: results of first national randomized study. The National Prostatic Cancer Project has randomized this study for endocrine-resistant prostatic cancer patients for treatment with standard hormonal or other therapies compared to 5-fluorouracil and cyclophosphamide. Both agents were found at the probability level of 0.05 to have a significant advantage over standard treatment in terms of objective response, subjective improvement and minimal toxicity. Additional chemotherapy protocols are currently under way. This randomized trial is the first report of such a national study completed to date. We are much encouraged by this program and believe that additional agents now under consideration will provide additionally encouraging results.


[Studies on the disc method for the determination of bacterial sensitivity to sulfobenzylpenicillin (author's transl)]. The MIC''s of sulfobenzylpenicillin (SB-PC) were determined by the two-fold serial agar-dilution method for 108 bacterial strains of 21 species. The diameters of inhibition zones of these bacterial strains by the 30 mug and 200 mug SB-PC discs were also measured. The relation between the MIC and the diameter of the inhibition zone was found to be expressed as a primary regression line in all cases of the conventional method (cultured for about 16 hours), delayed assay method (cultured for about 24 hours) and rapid methods (5 to approximately 6 hours and 3 to approximately 4 hours culture m ethods). Thus, it was confirmed that the single-disc method can be employed for the susceptibility test of SB-PC. Subsequently, variations of MICs obtained by the disc-diffusion method were compared with those obtained by the serial agar-dilution method.


[In vitro examination on antibacterial activities of broad-spectrum antibiotics against gram-negative clinical isolates (author's transl)]. In vitro studies were undertaken on clinically isolated strains of various bacteria to examine the antibacterial activity of ampicillin (AB-PC), carbenicillin (CB-PC), sulbenicillin (SB-PC) cephalothin (CET), cefazolin (CEZ) and gentamicin (GM). Fifty three % of Escherichia coli strains 53.3% of Citrobacter sp., 80% of Proteus mirabilis, 42.9% of Morganella and 80% of Bacteroides sp. were susceptible (MIC being not higher than 12.5 mug/ml) to AB-PC. The eight other species were not so susceptible to this penicillin. CB-PC and SB-PC were almost as effective as AB-PC against Escherichia coli and Citrobacter sp. They were less active against Klebsiella sp., but more active against Enterobacter sp., Serratia sp., indole-positive Proteus group and Pseudomonas sp. than AB-PC, SB-PC was more effective than CB-PC against Pseudomonas sp. The strains of Pseudomonas sp. which were resistant to higher concentrations of CB-PC and SB-PC were pyocyanine-negative strains. All strains (100%) of Escherichia coli, Klebsiella sp. and Citrobacter sp. were susceptible to CET and CEZ, while none of Enterobacter sp. , Serratia sp., Proteus vulgaris. Morganella, Rettgerella, Providencia and Pseudomonas sp. were susceptible to these cephalosporins. The MICs of CET and CEZ against Bacteroides sp. were moderately low. Some strains of Providencia and Alkaligenes sp. were resistant of GM but the other 10 species were not resistant to this antibiotic, though it showed comparatively high MICs against Bacteroides sp. When seen from the MIC distribution of each antibiotic, there was a tendency that the strains isolated from the pus were more resistant than those isolated from the other sources (urine, sputum and bile).


[Sensitivity of bacteria inducing urinary infections to 3 drugs (amoxicillin, ampicillin and cephalexin) and clinical efficacy of amoxicillin (author's transl)]. MIC of amoxicillin (AMPC), ampicillin (ABPC) and cephalexin (CEX) against bacteria detected from the patients suffering from urinary infections was determined and the clinical efficacy of AMPC was examined. As the result of determining MIC of AMPC against the detected Escherichia coli, 85.4% showed the value of less than 6.25 mcg/ml. AMPC and ABPC seem to be well correlated with each other regarding MIC, and AMPC showed 1 approximately to 2 stage lower concentration than CEX. In connection to clinical efficacy of AMPC, the oral administration at a daily dose of 750 mg gave the effectiveness rate of 92.5%. Few side effects were caused by administering AMPC and this is an excellent drug for healing acute simple urinary infections.


Responses of Clostridium botulinum type B and E progenitor toxins to some clostridial sulfhydryl-dependent proteases. Sulfhydryl-dependent proteases produced by Clostridium botulinum types A, B, and F, Clostridium histolyticum, Clostridium sporogenes and Clostridium perfringens activate preferentially type E over type B progenitor toxin but less efficiently than trypsin. The results explain why activable toxin is demonstrable in culture of a strongly proteolytic type B strain.


Adjuvant action of capsular polysaccharide of Klebsiella pneumoniae on antibody response. IV. The roles of antigen and adjuvant for induction of primary and secondary antibody responses and for development of immunological memory to bovine serum albumin. A study was performed to clarify the roles of primary and secondary injections of antigen and adjuvant (capsular polysaccharide of Klebsiella pneumoniae, CPS-K) in induction of antibody responses and in the development of immunological memory in mice to bovine serum albumin (BSA). A primary injection of BSA alone neither induced significant primary antibody response nor increased immunological memory for a secondary antibody response but, if primary injections of BSA and CPS-K were performed simultaneously, high antibody responses were induced. Moreover, a prior injection of BSA alone or CPS-K alone decreased the level of primary antibody response and the degree of increase in memory following the subsequent injection of BSA mixed with CPS-K. In contrast, a secondary injection of BSA alone into mice once primed with a mixture of BSA and CPS-K elicited very high secondary type antibody response and increased secondarily the memory for a tertiary antibody response. Injection of CPS-K simultaneously with or shortly before or after the secondary injection of BSA did not increase the level of the secondary antibody response and the degree of the secondary increase in memory. Augmentation of the secondary antibody response was elicited by simultaneous injection of CPS-K only when the secondary response was induced inadequately by a suboptimum or supraoptimum dose of antigen.


In vitro reconstitution of anti-sheep erythrocyte antibody response of T cell-depleted spleen cells by allogeneic T cells or by factors derived from them. Restoration of the impaired antibody response to sheep erythrocytes (SRBC) in cultures of mouse spleen cells, which were deprived of thymus-derived lymphocytes (T cells) by treatment with anti-mouse brain-associated theta (BA theta) antiserum and complement, was studied by adding a small portion of syngeneic or allogeneic normal spleen cells in vitro. Allogeneic spleen cells had a far greater effect than syngeneic spleen cells on the restoration, as far as the normal spleen cells added were able to recognize the alloantigens on the anti-BA theta serum-treated spleen cells (bone marrow-derived lymphocytes). Treatment of the allogeneic spleen cells with mitomycin C did not affect their activity in the restoration of the impaired antibody response. The possibility that the role of T cells in the antibody response to SRBC may be replaced by a nonspecific mediator derived from T cells reacting with allogeneic cells was proven by the finding that supernatant of the mixed allogeneic spleen cell cultures restored the impaired anti-SRBC antibody response of the T cell-depleted spleen cells. The effect of such culture supernatant on the restoration of the antibody response was greatest when it was added to the T cell-depleted spleen cell cultures one day after cultivation with SRBC, suggesting that the effectiveness may result from triggering of the proliferation and differentiation of antibody-forming cell precursors, which have already reacted with the antigen, to antibody-forming cells.


Relation between enhanced antibody responses elicited by adjuvant injection and those elicited by secondary antigenic stimulation. An attempt was made to determine if there is any common mechanism in the enhanced antibody response caused either by injection of adjuvant, such as bacterial endotoxin (LPS) and complexed poly-nucleotides, or by secondary antigenic stimulation. LPS inoculated in mice 4 days before injection of sheep red cells (SRBC) and polyA:U invalidated the adjuvant effect of polyA:U injected together with SRBC, and the hemolysin plaque-forming cell (PFC) response of such mice was similar to that of the mice which received SRBC alone. When mice primed with SRBC 24 days in advance were injected with LPS and 4 days later re-stimulated with SRBC, their PFC response to the secondary stimulation was suppressed to less than one tenth of the normal secondary PFC response. The suppressive effect of LPS on the secondary antibody response was abolished if the serum collected from mice injected with LPS was given to the primed and LPS-injected mice at the time of the secondary antigenic stimulation. From these results we discussed the possibility that some common mediator might play a role in the enhanced antibody response elicited by either adjuvant injection or secondary injection of antigen.


Studies of Mycobacterium lepraemurium in cell culture. II. Pathogenicity of Mycobacterium lepraemurium maintained in mouse foot pad cell culture and interaction of the bacilli with the infected cells. A serially diluted bacterial suspension of the Kurume-42 strain of Mycobacterium lepraemurium maintained for 1255 days in a mouse foot pad (MFP) cell culture was inoculated in mice subcutaneously. The ID50 value was estimated at more than 10.7 and less than 85 organisms, indicating that pathogenicity of the organism had been maintained well in a long-term cell culture. The cells infected and maintained for a long period in the cell culture showed all the stages of cell mitosis. This suggests that the bacterial increase in cell cultures of M. lepraemurium is not only due to rephagocytosis of the bacilli released from the infected cells but also to a constant intracellular growth cycle of the bacilli accompanied by mitosis of the infected cells. In acid phosphatase activity, no appreciable differences were noted between the infected and uninfected cells as far as the present cell culture system was concerned. Most of the bacilli within the cells were ultrastructurally normal. Solid bacilli in phagosomes were surrounded by less electron-dense clear zones.


Editorial: The primary glomerular filtration barrier--basement membrane or epithelial slits? In 1961, based on results obtained with the particulate tracer ferritin, Farquhar, Wissig and Palade [15] proposed a functional model for the glomerulus and defined a role for each of its components in the filtration process: a) the basement membrane as the main filter; b) the endothelium as a valve, which by the number and size of its fenestrae, controls access to the filter; c) the epithelium as a monitor which partially recovers proteins that leak through the filter; and d) the mesangium which serves to recondition and unclog the filter by incorporating and disposing of filtration residues which accumulate against it. In 1966, based on results obtained with the histochemically demonstrable tracers, horseradish peroxidase and myeloperoxidase, Graham and Karnovsky [24] questioned the basement membrane as the site of the main filter and proposed instead that it functioned as a crude prefilter with the epithelial slits representing the final critical barrier. While the concept of the "two-barriers-in-series" has enjoyed wide acceptance, the validity of certain of the experimental data used to support the original hypothesis has been questioned [23, 29, 37]. In the meantime, additional experimental evidence obtained largely with the use of particulate tracers (especially dextrans [23, 43, 44]), has provided strong support for the concept that the basement membrane acts as the main barrier to the passage of molecules in the same size range as plasma proteins (32, 000 to 125,000 mol wt). With respect to the function of the other layers in filtration, additional new information that has come to light has supported the roles proposed above. Work with both particulate [16, 60] and enzymatic [24, 29] tracers, as well as studies by Michael et al [61, 62] with aggregated serum ablumin, supported the phagocytic (unclogging) function of the mesangium. There is evidence from work with particulate tracers (particularly that with dextrans in nephrotic animals [43, 44]) which supports the monitoring function proposed for the epithelium. Recognizing that their work with histochemically demonstrable tracers may have certain technical limitations, Karnovsky, Ainsworth and Schneeberger [29, 37, 38] have recently taken the position that there is no definitive answer to the question of which structure-basement membrane or epithelial slits-represents the principal filter, and have suggested that more information is needed in order to make such a decision. But, in fact, the bulk of the evidence available at present favors the basement membrane as the primary filtration barrier in the glomerulus. Substantial evidence based on work with electronopaque tracers (including recent studies with dextrans) indicates retention of a variety of tracers by the basement membrane. On the other hand, unequivocal demonstration of retention of any tracer by the slits is still lacking.


An ultrastructural study of the mechanisms of proteinuria in aminonucleoside nephrosis. Sprague-Dawley rats injected i.v. with a single dose of puromycin aminonucleoside (PAN) developed massive proteinuria five days later. Electron microscopic studies of perfusion-fixed glomeruli showed that loss of epithelial foot processes and their replacement by flattened expanses of epithelial cytoplasm began at two days and was extensive by four days after the injection of PAN. At and after five days (correlating with the onset and persistence of massive proteinuria), areas of focal loss of the epithelial covering on the outside of the glomerular basement membrane (GBM) were observed in 30% of glomeruli. Intravenously administered ferritin was distributed normally in most sections of the GBM of nephrotic animals, but abnormally deep penetration of particles was observed in GBM segments that lacked an external covering of epithelium. The same changes were found following in situ fixation of superficially placed glomeruli of Munich-Wistar rats with PAN nephrosis. We propose that the massive, early proteinuria in PAN nephrosis may be primarily due to a glomerular epithelial lesion, leading to scattered focal defects in the external covering of the GBM. Increased bulk flow of glomerular filtrate across the GBM in such areas may explain the highly selective proteinuria found in this form of the nephrotic syndrome.


Experimental Escherichia coli urinary infection in the rat. Twenty-six urinary strains of Escherichia coli belonging to O-sero-groups commonly associated with urinary infection but differeing in serum sensitivity and K antigen content were examined for their ability to survive in the kidneys following inoculation into the bladder of male Wistar rats. Reproducibility studies showed that some strains consistently caused kidney infection whereas others were consistently unable to do so. However, the ability to infect the kidneys was not correlated with serum resistance or K antigen content. Some evidence for the nature of the factors responsible for kidney infection came from a study of various mutants derived from E.coli LP729 (serotype 09), which produces negligible amounts of K antigen and is rapidly killed by serum after a delay of one hour. Both LP729 and a serum-resistant mutant derived from it caused kidney infections, but two rough variants derived from the serum-resistant mutant were unable to infect the rat kidneys. One variant was devoid of lipopolysaccharide O-side chains; the other showed the delayed serum-killing effect characteristic of LP729 and retained 09 specificity with a full complement of O-side chains, suggesting that loss of surface components unrelated to O or K specificity may be responsible for failure to invade the kidneys.


Immunogenicity of Escherichia coli O antigen in upper urinary tract infection. The role of immunogenicity of the infecting organism (Escherichia coli) in the antibody response to O antigen in upper urinary tract infection was investigated. Heat-killed vaccines were prepared from "immunogenic" organisms which had produced upper urinary tract infection associated with high titers of hemagglutinating antibody to O antigen and "nonimmunogenic" organisms which had produced upper urinary tract infection without a rise in antibody titer. "Immunogenic" 06 vaccine produced high titers of antibody in patients regarded as possibly "poor producers" of antibody, but "nonimmunogenic" 011 vaccine was not associated with a rise in titer in patients previously regarded as "good producers". These vaccines were significantly different in immunogenicity (P less than 0.05). Five vaccines were tested in 50 rats. The difference in hemagglutinating titers to O antigen between 06 and 011 was highly significant (P less than 0.001). Immunogenicity of the infecting organism appears to be a significant factor in determining antibody response to O antigen in upper tract infection.


[A railway accident a hundred years ago as reason for systematic testing of colour vision (author's transl)]. Holmgren's supposition that colour blindness was one of the causes for the train-disaster which happened on 15th November 1875 near Lagerlunda had been passed on as an established fact. The course of the accident is outlined on the basis of the court records. It shows that not colour blindness, but the fact that the engine-driver and the station-master were acting contrary to regulations resulted in the head-on collision with the opposite train. After this event systematic testing of colour vision in railway-men was instituted and the methods of examination were considerably improved.


[Pilocarpine-ocusert-p-40 in the handicapped glaucoma patient (author's transl)]. A group of 15 patients with chronic open angle glaucoma had been selected for this study. All of them were handicapped in the long-term self-medication of their antiglaucomatous eye drops either by visual function loss or by, physical or mental disorders. A preliminary test was made in each patient whether there was an essential difference in the therapeutic effect after self-medication and after optimal local application of the miotics by the doctor. Each of the selected patients had profile tonometry after self-medication, after medication by the observer and after Pilocarpine-Ocusert-P-40. There was evidence that the most pronounced therapeutic effect could be achieved by the correct placement of the antiglaucomatous drug in the individual eye. The results on the ocusert system indicate that pilocarpine ocuserts are advantageous over the incorrect placement of different miotics by the handicapped patient. The results had been statistically evaluated using the t-test. The possibilities of using the ocuserts in the elderly glaucoma patient are discussed.


[Use of muscle surgery sutures in retinal detachment operations (author's transl)]. In cases of surgery in retinal detachment, borrowing of techniques employed in strabismus surgery is recommended. The opening of the conjunctiva and Tenon's capsule and careful placement of the final suture as published by Cüppers avoids or at least diminishes postoperative cicatrization, retraction, and resulting disturbances of motility and double images. In case where one are several muscles have to be cut, the exact strabismic muscle surgery helps this treatment. In these cases, statistical results are mentioned. Furthermore in cases of high myopia and especially those combined with nystagmus, the so called Cüpper's "Fadenoperation" gives excellent results. Three cases operated on by this technique, in which no other method succeeded, are demonstrated.


[Lamellar corneal graft and transposition of a conjunctival flap for surgical treatment of pterygium (author's transl)]. In advanced primary and recurrent pterygium extensive excision and lamellar corneal grafting have been performed. Closure of the conjunctival wound is achieved by transposition of a temporal conjunctival flap to the excised area. In a follow-up period up to 15 months no recurrence have been observed. The functional and cosmetical results are satisfactory.


[The operative treatment of nystagmus-caused variable squint angles with Cüppers "Fadenoperation" (author's transl)]. THE "Fadenoperation" developed by Cüppers is described. With this, the arc of contact is changed with retension of the anatomical insertion. It is indicated when an innervational factor is to be influenced, especially by the treatment of an instable squint angle caused by nystagmus. A differentiation between a static and dynamic angle must be made. Only the static angle can be corrected by common recession and resection. The dynamic angle can be corrected by the "Fadenoperation" described by Cüppers. The difficulty in recognizing the nystagmus and determining the width of the static and dynamic angle is described in detail. Satisfying results were attained, following these criteria, shown by 19 (76%) of the operated convergent squinters with an instable angle.


[Hypo and hypercalcemia as an emergency]. 1. Hypo- and hypercalcemia can be explained as derangements of the calcium homeostasis. Hypocalcemic tetany usually alarming the patient tremendously is, at least in adults, rarely life-threatening. Hypercalcemia leads in 30% of the cases to clinical symptoms which may inadvertedly pass into a state of hypercalcemic crisis. This latter requires an often difficult emergency treatment. 2. Hypocalcemic tetany may be reversed by administering calcium i.v. or, in severe cases, by a calcium infusion. Only rarely are magnesium supplements necessary to let the tetany disappear. Vitamin D or dihydrotachysterol (DHT) do not correct hypocalcemia immediately, since their effects may be delayed up to 15-25 days. In order to normalize the serum calcium permanently, vitamin D or DHT treatment should be instituted as rarely as possible. 3. Initially, hypercalcemic crisis is best treated by forced intravenous fluid administration with normal saline (and furosemide) in combination with high doses of prednisone. Fluid-, sodium- and potassium balances ought to be checked during this type of treatment. A first evaluation of the effectiveness of these measures is recommended after 24 hours: treatment is continued in patients who respond favorably, while subjects who do not show a significant decrease of the serum calcium may either be given a phosphate infusion or mithramycine as a bolus. Calcitonin appears to be useful only to start treatment before institution of a phosphate infusion.


[Discelectrophoretic analysis of the tubular proteinuria (author's transl)]. The urinary protein pattern following tubular damage is different from other proteinurias. The tubular proteinuria consists of micromolecular proteins of MW 10-70000. The disturbed tubular function probably leads to a diminished reabsorption of these microproteins from the tubular fluids. By determining the molecular weight of the urinary proteins by SDS-PAA-electrophoresis tubular proteinurias may be distinguished from glomerular and extrarenal forms. Tubular proteinurias are found in inflammatory, degenerative and vascular tubulopathies. The course of acute tubular diseases reveals proteinurias of different micromolecular composition depending of the improving tubular function; this supports the concept of a selective tubular reabsorption of microproteins. Tubular proteinurias are associated with normal as well as with impaired glomerular filtration, which, in part, might influence the amount of microproteins excreted.


[Immunglobulin levels after kidney transplantation and during rejection crisis (author's transl)]. In the first three weeks after kidney transplantation the patients were examined for daily changes in immunoglobulin levels. Only very seldom was a decrease of IgM detected in our patients who had undergone splenectomy. During half of the rejection crisis there were indeed short periods of increase (spikes) in immunoglobulins. These were observed always before or concomitantly with the clinical diagnosis of a rejection reaction. In order to determine the connection between immunoglobulin-spikes and an approaching rejection episode the general one-sided binominal test was used. A significant relation was established between IgM peaks and an approaching rejection crisis. No such relation could be found for the IgA peaks observed. The IgG globulins showed no consistent pattern during a transplantation rejection. A persistent fall of the IgG globulins was noted in the first ten days after renal allograft with the immunosuppressive regimen of an initial gramme of methylprednisolon and high dosage of azothioprine. A good correlation was observed with the simultaneous depression of serum albumin concentrations. As losses of protein in urine are minimal (already confirmed by other authors), it must be assumed that in the first place a high rate of catabolism and a restriction in the protein synthesis is responsible for the decrease in the IgG globulins and the serum albumins.


Pathogenesis of cerebellar hypoplasia produced by lymphocytic choriomeningitis virus infection of neonatal rats. II. An ultrastructural study of the immune-mediated pathology. Lymphocytic choriomeningitis virus, following inoculation of 4-day-old rats, produces an acute destructive but nonfatal necrosis of the cerebellum which is immunologically mediated. An ultrastructural study of the developing lesion indicated the following sequence of events: first, lymphocytic choriomengitis virions appear in the intercellular spaces of apparently normal neural parenchyma, followed shortly thereafter (5 days after infection) by adherence of monocytes to vascular endothelium with migration into tissue and morphologic transformation into activated macrophages, concomitant with necrosis of neural cells which progresses from 1 to 3 weeks after infection. Removal of debris overlaps with and is followed by astrogliosis, collagen deposition, and vascular changes. Finally, several months after infection, an increasing infiltration of plasma cells occurs, accompanied by gradual disappearance of virus from the neural parenchyma. These morphologic observations suggest that the acut immunopathology is cell-mediated whereas local antibody production may play an important role in clearance of virus from persistently infected tissue.


Segmental flexibility in the myosin molecule: evidence from binding studies of myosin fragments with actin. From comparative studies of the association with polymeric actin of the bifunctional species heavy meromyosin and its monofunctional constituents, information about the relative freedom of these paired elements can be derived. An isotherm for the former binding process is presented which involves, as an experimentally determinable parameter, the local concentration of second segment after the first of a pair is attached to the lattice. From combined data for these two association reactions a value of 10(-4) M is obtained for this quantity. The large degree of segmental flexibility reported for the free heavy meromyosin is still manifested in the association with actin.


On the enthalpy of binding of ADP to heavy meromyosin. The binding of ADP to heavy meromyosin has been studied by microcalorimetry. Minute amounts of myokinase interfere with binding measurements, but by selection of appropriate conditions, we can estimate that the value of the apparent deltaHbinding lies between - 1.0 and - 3.0 kcal per mole of ADP bound (0.3 M KC1, 2 mM MgC12, 20mM Tris, pH 8.00, 20 degrees C). Values of deltaHbinding reported to date are an order of magnitude larger, and we suggest that these values are artifactual results due to myokinase contamination.


Bilateral chylothorax - complication in malignancy. Bilateral chylothorax is a rare condition caused by traumas and disorders with perforation or destruction of main lymphatics in the thorax leading to lymph leakage. Two patients with bilateral chylothorax are presented one of whom was successfully operated on. Etiology, diagnostics and therapy of this condition are discussed.


Hypertension.

Hypertension. Hypertension, a health problem of epidemic proportions, has not been controlled successfully. Screening efforts are increasing the detection of cases, and current emphasis on treatment rather than detailed evaluation is increasing the incidence of control of hypertension. Patient compliance is crucial, however, because all of the currently available treatments require daily taking of pills by patients who commonly do not understand their disease or the need for treatment. Efforts at increased public education and improved doctor-patient relationships are important if the epidemic is to be overcome. This paper reviews diagnosis, evaluation, treatment, public education, and patient compliance.


Health care in a changing society: the health services of Israel. In the pre-State era, Israeli society displayed an "ascetic" orientation with emphasis on austerity and egalitarianism. The medical profession was influenced by the basic philosophy of the country and coped successfully with the country's health problems, mainly by lowering morbidity and mortality rates. With the emergence of the State of Israel, mass immigration of people with different backgrounds, cultures, and values occurred, and health problems of the disability, dissatisfaction, and discomfort type arose. The existing medical organizations were unable to handle them. The story of three such organizations is detailed in brief: the first medical school in Jerusalem, the greatest supplier of curative services--the workers' sick fund (Kupa Holim), and the Ministry of Health. Their impact on the health services of the country is described. These services are splintered into numerous self-contained authorities and an understanding of the overall needs is lacking. This state of affairs reflects the antagonistic interests of the political powers behind the various health agencies. A concensus within the health field on the nature of the problems and their solution could be reached if the health organizations accepted a broader philosophy of health, comprising its somatic, mental, and social aspects, and if they commit themselves to applying this philosophy in their activities. This may lead to considerable changes in medical education, more attention being focused on the social functions of medicine than on medical technology; health care would become more comprehensive and would cover all aspects of health in its preventive, curative, and rehabilitative stages. Failure to meet the health needs of the changing society will constitute a false reading of the public pulse. Of late, the voices demanding the conquest of social diseases and the attainment of health in its broadest sense are becoming more and more audible.


An emergency room's patients: their characteristics and utilization of hospital services. Utilization of the emergency room at an urban community hospital is studied in a format designed to accomplish three complementary objectives: 1) to characterize a sample of individual patients, rather than an unweighted sample of visits, 2) to estimate the number of individuals served during a specified period and the magnitude of the relationship between these patients and the utilization of other hospital services, and 3) to introduce the patient's "frequency-of-visit" as an important variable in the analysis of emergency room utilization. Some specific findings are: 1) the vast majority of patients who used the emergency room did so very infrequently; 46,527 visits were made in one year by an estimated 34,286 different patients; 2) an estimated 2,586 patients made three or more visits during the year; a disproportionately large number of these "high-frequency" users were black, low-income, and from inner-city areas; a relatively small percentage of their visits were for accidental injury, 3) approximately 53 per cent of the hospital's inpatient admissions and 68 per cent of the inpatient days were generated by patients who also made at least one emergency room visit during the year studied.


A study of consumer attitudes about health care: the role of the emergency room. Contrary to the traditional role of the emergency room (ER) as a care source for the treatment of urgent medical needs, it is evident that substantial numbers of people now use the ER for the treatment of nonurgent problems. In this paper, we report on public opinion about the role of the ER, the accessibility of medical care, and factors that prompt the use of the ER rather than other sources of care. The data result from a community survey of households (N = 521) in the area of Rochester, New York, representative of a population of about 580,000 people. The findings, which relate ER utilization to source of payment, use of other sources of care, demographic variables, and consumer attitudes illustrate the rationality of the patient's use of ER facilities and reflect the patient's view of the ER as a place to obtain medical treatment when other sources are not available.


Characteristics of patients and care provided in health-related and skilled nursing facilities. This survey study of 433 admissions to four health-related facilities and 738 admissions to 40 skilled nursing facilities in the Rochester region describes the reasons for placement, the patients' physical, mental, and functional characteristics and their personal, nursing, and other care requirements in the institutional setting. The differences and similarities between the two levels of care and between the four HRF's are analyzed in the light of national data; the appropriateness of placement is evaluated and the implications for regulatory systems are discussed.


Adam Politzer, otology and the Centennial Exhibition of 1876. The Centennial Exhibition of 1876 was held in Philadelphia. Among the exhibits was a collection of temporal bone dissections produced by Adam Politzer of Vienna. This exhibit included both normal and pathological temporal bones, and emphasized the relationship of the tympanic membrane to the middle ear, external canal and bony labyrinth. At the close of the Centennial Exhibition the collection was purchased by the College of Physicians of Philadelphia. This collection and the congress associated with the Centennial had a tangible effect on the otology in this country.


Preoperative laminagraphic evaluation of the sphenoid sinus for transsphenoidal surgery. In recent years the transethmoidal and transnasal approaches to the pituitary gland have become increasingly popular. In each case, detailed preoperative analysis of the anatomy of the sphenoid sinus and its boundaries is crucial in facilitating entry to the pituitary fossa and in reducing intraoperative complications. Certain operative difficulties and complications are the result of the marked variability in the anatomy of the sphenoid bone and its sinus. These include: loss of orientation within a capacious sinus; perforation of the carotid artery or cavernous sinus; injury to the optic nerve or ophthalmic artery; and violation of the subarachnoid space with resultant pneumocephalus or cerebrospinal fluid rhinorrhea. Pneumatization develops originally within the presphenoid, beginning anteriorly and proceeding posteriorly. Around the time of puberty the pneumatization usually penetrates up to the spheno-occipital synchondrosis. Dense bony septa remain within the sinus along the plane of fusion of the various sphenoidal segments. Preoperative laminagraphy of these ridges and septa is extremely helpful in planning the safest and most direct route to the sella. Laminagraphy is preferable to routine skull films because the septal detail is unobscured by overlying facial structures. Pleuridirectional laminagraphic motion (circular or hypocycloidal) is preferred to linear motion because of the clarity and detail that they provide.


The investigation of Horace Green.

The investigation of Horace Green. Horace Green is often regarded as the "Father of American Laryngology." Original in his thinking, innovative in his methods, outspoken in support of his views, Green was often violently criticized by his contemporaries. One medical society attempted to force his resignation as a member. In 1855, the New York Academy of Medicine ordered an investigation of Green and his methods. Honest to the core of his being, Green welcomed the investigation and cooperated in every way possible. Although the investigators' findings were inconclusive, time did bring vindication to Green and to some of his views.


Arterial blood gas changes following nasal packing in dogs. Previous clinical studies pertaining to blood gas changes following nasal packing have agreed that the packing is frequently followed by hypoxia but have found differing responses in arterial PCO2 to nasal packing. This is of more than incidental importance, because the mechanisms by which hypoxia develops should determine the method by which the hypoxia is treated. The various causes of hypoxia are reviewed, and a method of instituting an indwelling systemic arterial catheter for the purpose of drawing sequential blood samples for gas determinations is described. Using the indwelling arterial catheters, arterial blood was sampled from a series of awake, unsedated dogs before, during, and after the dogs were subjected to anterior and posterior nasal packing. Blood gas determinations showed significant depressions of PO2 and elevations of PCO2 during the period when the packing was in place. The altered blood gas values quickly returned to essentially normal (control) values after the packing was removed. In order to help assess the degree of lower airway response to an upper airway stimulus as a cause of these blood gas changes, the protocol was repeated in previously laryngectomized dogs. In these animals no consistently significant change occurred in either the PO2 or PCO2 following either the packing or its removal. Our findings suggest that airway obstruction (and hypoventilation) rather than increased bronchomotor tone is the main cause of hypoxia in awake dogs with anterior and posterior packing. Because of the likelihood of hypoventilation and significant hypercarbia in patients in whom nasal packing is employed, we discourage the routine usage of oxygen, unless blood gas levels are checked prior to the institution of oxygen therapy.


Experimental congenital malformations.

Experimental congenital malformations. Traditional approaches to human and experimental teratology are briefly described, with roles of pathologists indicated. Some approaches to experimental teratology which pathologists might use are then described and illustrated. These include identification of subclasses of malformation types, study of the chronologic sequence of maldevelopment, study of embryo death, and examination of tumor-malformation relationships. The malformations used to illustrate these approaches are cleft palate, anencephaly, hydrocephalus, and intestinal atresia. The final section deals with general methodology in experimental teratology; a listing of books dealing with experimental teratology is included.


Experimental muscle diseases.

Experimental muscle diseases. The mode of pathological reaction of the skeletal muscle fibres to injury is now well understood as a result of the large number of experimental studies and the wide variety of techniques applied to the problem, as recounted above. The most notable aspect of the reaction of the injured muscle fibre is the remarkable stereotyped character of the resulting changes as demonstrated by many diverse agents producing surprisingly similar results. The initial lesion is essentially local coagulative necrosis of the muscle fibre. If the animal survies, such necrosis is inevitably followed by a series of biological reactions inherent in muscle and which lead to the removal of dbris and the proliferation of myoblasts...


The nude mouse: a model of deficient T-cell function. Congenitally athymic nude mice (nu/nu) are presented as a model for the study of cell-mediated immunologic deficiencies. These mice possess a vestigial thymus which is incapable of producing mature T-cells as shown by a decreased lymphocyte population carrying the theta antigen and depleted 'thymus-dependent' areas in their peripheral lymphoid organs. However, they have T-cell precursors in their bone marrow. Nude mice lack 'thymosin', a thymic factor secreted by the epithelial cells of the thymus. They also have impaired T-cell functions as demonstrated by an absence of delayed hypersensitivity reactions, an inability to reject skin allografts and a decreased antibody response to some T-dependent antigens. But their response to T-independent antigens is normal. The presence of circulating auto-antibodies and immune-complex type glomerulonephritis in nude mice reinforces the hypothesis that spontaneous autoimmunity and B-cell hyperactivity are associated with T-cell deficiency. On the other hand, they are not especially susceptible to spontaneous tumor development. Correlations are made between the pathologic findings in nude mice and some congenital cellular immunologic disorders in man.


Experimental pathology of aging.

Experimental pathology of aging. We have been concerned in the first section of this review with those diseases that are aging processes, or appear to be so. Some of these (e.g., cardiovascular, pulmonary, neoplasia) cause the death of a large proportion of animals, while others (e.g., osteoporosis, amyloidosis), though clearly progressive with age, are nonfatal. Many diverse factors influence the normal process of aging. Restriction of dietary caloric intake prolongs  lifespan and decreases the incidence and severity of diseases associated with aging, probably by depressing anterior pituitary gland function...


Experimental liver diseases.

Experimental liver diseases. The use of animal models in the experimental production of liver diseases similar to those of man is still in its infancy. There is a need to discover new models more closely related to counterpart syndromes in man in the fields of hepatorenal syndrome, neonatal jaundice, Wilson's disease, cholelithiasis, viral hepatitis, biliary atresia, and cirrhosis, to mention only a few. With the continued indiscriminate inbreeding of companion animals as well as the planned inbreeding of laboratory animals, there is little doubt that many more will soon be available. The current availability of mutant rats and sheep with bilirubin transport defects has allowed for a better understanding of how organic anions are transported by the liver. Many other currently available experimental animal models herein briefly reviewed have been only superficially studied. It is the intent of this chapter to provide for post-doctoral students an appreciation for the many animal model systems available for experimental hepatic research.


Experimental studies on osteoporosis.

Experimental studies on osteoporosis. Nutritional secondary hyperparathyroidism (NSH) defines a spontaneous and experimental disease in most domesticated and in some wild animals, caused by dietary calcium deficiency and/or phosphorus excess. Calcium deficiency results directly in hypocalcemia, and phosphorus excess induces hyperphosphatemia which causes hypocalcemia. Secondary hyperparathyroidism thus results and the plasma parameters return to normal and are maintained but only at the expense of progressive bone loss. The bone loss is generalized but the bones are not uniformly affected. The hierarchy of bone loss is, in decreasing order, the jaw bones, especially the alveolar bone, other skull bones, ribs, vertebrae and, finally, long bones. Osteocytic osteolysis is the main mechanism of resorption and application of this concept is a condition sine qua non in the interpretation of the histologic lesions. The early loss of alveolar bone constitutes the initial event in periodontal disease in animals. The osseous lesions in animal NSH are reversible by correction of dietary calcium and phosphorus levels, provided a hyperostotic osteodystrophia fibrosa has not yet developed. The applicability of animal NSH as a model for human osteopenic conditions, including periodontal disease and spinal osteoporosis, is supported by the very inadequate calcium and phosphorus nutrition in most Western countries. The diet is deficient in calcium and excessive in phosphorus; both conditions induce NSH in animals. The degree of dietary calcium deficiency, as influenced by geographic, economic, and social factors, is positively correlated to the degree of periodontal disease and osteoporosis in the population. Evidence is presented to show that the radiographic and histologic manifestations of human periodontal disease and osteoporosis are the same as those of animal NSH. Periodontal disease is therefore considered a fore-runner to the clinically more important spinal osteoporosis. Limited experiments in human periodontal disease indicate that added dietary calcium can positively influence the alveolar bone loss.


[The scientific work of W. J. Schmidt (author's transl)]. Ten examples from W. J. Schmidt's workshop illustrate the method of ultrastructural research before the advent of the electron microscope. The consistency is shown with which the research worker W. J. Schmidt pursued his goal, how he succeeded in making fundamental discoveries with his polarizing microscope, and interpreted the results of his indirect structural investigations in such a forward-looking and clearsighted manner that many of them were confirmed by direct reproduction in the electron microscope. This makes W. J. Schmidt one of the great pioneers of ultramicroscopic structural research. He was an extremely prolific writer. His list of publications numbers 404 scientific contributions, three classical books among them. The last of these three monographs was written in 1971; its title is "Polarizing Microscopy in Dental Tissues"; it deals with the ultrastructure of teeth, a subject which never ceased to attract his attention during the more than 50 years of his career as a scientist. It was his intention to write such a textbook on the ultrastructure of teeth during his retirement, a task which he accomplished in spite of the infirmities of old age, thanks to his unbroken will to work. Another characteristic feature of W. J. Schmidt was his extraordinary insistence on complete independence; there are only four among his 404 publications which he wrote, at an advanced age, jointly with Helmut Ruska, and the dental monograph he published in callaboration with A. Keil. Everything else was entirely his own effort. His capacity for work was almost inexhaustible. In 1937, for instance, he published 18 scientific papers, among them his richly illustrated protoplasm monograph of 388 pages. His inflexible will to observe everything personally and to interpret and edit his findings alone was part of his special intellectual constitution. In discussions he stubbornly defended his point view and considered suggestions and new ideas only after he had tested them with his own experiments. This had already become evident at the beginning of his career in a discussion with Ambronn of the nature of birefringence of organized substances. But once he had accepted something as proved he propounded it with persistence and enthusiasm.


A mechanical stage for the combined use of two microscopes with a comparison eyepiece. When comparing two histological sections with the aid of a comparison eyepiece, it appears very difficult to move the two specimens in conjunction. A single common mechanical stage meets this problem, providing identical movement of two specimens. Details of its construction are described.


A review of bacteria in L-phase and their possible clinical significance. L-phase bacteria are bacterial variants produced by adverse conditions in the environment. Although variant growth may be perpetuated for generations, the changes are not of genetic origin, but due solely to the environment which causes damage to the bacterial cell wall. Since the structure of Gram-positive and Gram-negative cell walls is fundamentally different, the degraded variant which will occur in each case will also be different. Such variants are seldom detected in routine diagnostic laboratories because they will not grow on normal media, as their optimal conditions of growth are changed. L-phase variants bear a strong resemblance to the mycoplasmas; both are resistant to penicillin, both lack characteristic bacterial cell wall constituents, and their colonial and cellular morphology are similar. Since the conditions for mycoplasma cultivation are, at this time, more clearly understood, they provide useful models for handling fragile L-phase organisms. L-phase bacteria may be readily produced in vitro by the action of penicillin, and it is theoretically possible for conversion to occur in vivo just as readily during phagocytosis, by the action of bacteriophage, antibiotic therapy, and other defence mechanisms of the host. In the clinical field, the most difficult problem is the assessment of the significance of the isolation of L-phase bacteria in the individual case because they have not been observed with certainty in the pathological process. It is probable that such organisms may be clinically significant in cases of chronic and recurrent infection, since these bacteria will survive the defence mechanisms of the host which are largely directed at the cell wall.


A method of bloodless circumcision.

A method of bloodless circumcision. A method of circumcision is described which allows accurate removal of the correct amount of tissue. The method is based on the  concept of removal of a flat strp of skin rather than a fold. The removal of the correct amount of tissue with the minimal amount of bleeding and minimal risk to the frenal vessels is effected. The treatment after operation is simple and the results are invariably satisfactory. Damage to the urethra and glans is virtually impossible. Delineation of the incisions with ink before beginning is an important step in the procedure.


Double-blind trial of mazindol in overweight patients. A 12-week double-blind trial involving 50 patients from a suburban general practice showed a highly significant loss of weight in the group taking 2 mg of mazindol (Sanorex) per day.


Plasma phenytoin levels produced by various phenytoin preparations. A cross-over study was conducted to compare the plasma phenytoin levels produced by different phenytoin preparations available in Australia. The preparations were found not to be equivalent, a liquid suspension product producing higher levels compared with capsule and tablet formulations. The clinical significance and possible explantation are discussed.


Prophylactic use of gentamicin in colonic and rectal surgery. A double-blind trial was performed to test whether a single intramuscular injection of 80 mg of gentamicin would significantly reduce the incidence of septic complications of elective colonic and rectal surgery. The gentamicin was given at the time of anaesthetic premedication, the operations were performed by either of two surgeons, and the patients were followed up by an independent investigator. Eighty patients satisfactorily completed the trial. There was no significant difference in the incidence of postoperative wound infection, intraperitoneal abscess formation and faecal fistula between the 41 patients who received the gentamicin and the 39 who received the placebo. However, the mortality was significantly lower in the gentamicin group, in which there was only one death.


[Acupuncture - has it a demonstrable bronchospasmolytic effect in bronchial asthma (author's transl)]. In 12 patients with bronchial asthma the effects of acupuncture (45 tests altogether) on airway resistance have been investigated. In 9 patients there was a significant decrease of airway resistance 10 minutes, 1 hour and 2 hours after the end of acupuncture. The lowest level for airway resistance (70,1% of control value) was reached during the first hour after acupuncture. The possibility of a merely suggestive effect could be excluded, because "placebo-acupunctures" did not change airway resistance significantly. The comparison with a parasympatholytic acting drug as a metered aerosol (Atrovent) demonstrated that acupuncture had a some-what weaker bronchospasmolytic effect. 3 patients showed after repeated acupunctures no reaction whatever.


Evaluation of a test kit for identification of anaerobic bacteria. A test kit for identification of anaerobic bacteria--API--has been compared for accuracy in individual tests and for identification on the genus or species level with pre-reduced anaerobically sterilized media methods on 241 anaerobic strains. The microsystem was found to be reliable and permits identification of the clinically most significance anaerobic bacteria if it is supplemented with other tests such as gaschromatographic analysis, morphology, lecithinase, lipase and antibiotic sensitivity pattern.


Transformation of lymphocytes in patients with certain bacterial infections. The state of cell-mediated immunity was measured by the morphological method of lymphocyte transformation with and without PHA, in a group of 56 patients with bacterial infections and in a group of healthy controls. The patients were divided into three subgroups according to the aetiology: 1. Patients with Gram-positive infections, 2. Patients with Gram-negative infections, and 3. mixed infections. The transformation values with PHA were significantly (t-test) higher in the Gram-positive subgroups than in the control group. Transformation in cultures stimulated by PHA was much higher in the subgroup of patients with Gram-positive aetiology; the difference between the values in the Gram-negative and in the Gram-positive subgroups was also significant. A decrease of transformation value below 50% was observed in 6 out of 18 patients with Gram-negative aetiology, whereas in the Gram-positive group it was noted in only 2 out of 21 patients.


Photon attenuation in computed tomography. The analysis and understanding of results of computed tomography (CT) require an understanding of photon attenuation in matter. The high sensitivity and resolution of these devices coupled with the use of a polychromatic photon source require a level and breadth of understanding about photon attenuation not usually required in any particular subspecialty of radiological physics. With this goal in mind, a discussion of narrow-beam photon attenuation in matter is given and related to those problems currently underway in the field of computed tomography. Measurements and calculations of tissue properties are presented. Calculations of descriptive quantities relevant to polychromatic source attenuation and CT scanning are described and presented.


Spectral effects on three-dimensional reconstruction from rays. Continuous bremsstrahlung spectra were calculated for 120 kVp for constant and sinusoidal potentials. Fluorescent radiation for the tungsten target was added to the bremsstrahlung, and the spectra were attenuated through various filter materials. A drawing of an object to be scanned was divided into an array of small squares in which the composition was assumed to be constant. Transmission data for 120 rays at each of 120 angles spanning a range of 180 degrees were calculated. Two algorithms for the reconstruction of attenuation coefficients from projection data, an algebraic reconstruction technique (ART) and the convolution method, were utilized to reconstruct effective coefficients. The effect of spectral filtration on the quality of the reconstruction was evaluated. Lightly filtered x-ray beams give rise to severe distortions in image quality, with values of the reconstructed coefficients rising toward the periphery of the object. Highly filtered beams give rise to images with less pronounced distortion.


[Dental implantations of ceramics-coated metals]. Recent studies and personal experience of the Authors in the field of dental implants have encountered the same fundamental problem which arises with orthopedic prosthesis procedures. The basic problem is that of adhesion between the bone tissue and the metal implant. Chrome-cobalt alloy, Tantalum and Titanium are the metals of most recent use. The Authors therefore proceeded to investigate the behaviour of alveolar bone tissue in the proximity of artificial teeth made of alloy (platinum-gold) covered with ceramic, as used in prosthetic dentistry. The experiment was carried out in a dog and a man. In the dog, two of its mandibular teeth were substituted with the same ceramic-gold implants: the first, a replica of natural tooth, was placed in the socket and held in place by metal splint and mandibular circumferential wirings. The other implant, without a replicated crown, was left free, within the alveolus, without contacting the near or opposing teeth. A solid smooth surfaced alumina device, shaped like a small cylinder, was implanted in the upper femoral epiphysis of the same animal.


[Bridge supports on horizontal selfthreading parapulpar pins and slices]. A new technique for the construction of small bridges consisting of the attachment of braces to live teeth by means of horizontal parapulpar pins and slices is described.


Transduction by phage P1CM clr-100 in Salmonella typhimurium. Phage P1 does not adsorb to S. typhinurium wild type cells. It does adsorb to rough derivatives including strains with mutations in the galE gene. Phage strain P1CM clr-100 can be efficiently propagated in S. typhimurium derivatives, either by induction of a lysogene, or by lytic infection. Phage P1 lysates are able to mobilize genetic markers in a generalized fashion. The transduction system is essentially identical to that in Escherichia coli, except that CaCl2 is not required for efficient adsorption. Two regions of the S. typhimurium chromosome were mapped by P1-mediated transduction. Several examples of genes linked by P1, and unlinked by P22, are presented. The relative efficiency of P1 over P22 in transduction was not determined, however. Data presented indicate unambigously that the gene order for the trp region is: his ... dad A-hem A-trp-pyrF ... pyrC but known markers in between were not used. The gene order for the cys A region was determined to be as follows: pheA ... purC-cys A-trz A-pts-dsd-aro D-purF ... his, and special mapping problems for this region are discussed.


The effect of gene concentration and relative gene dosage on gene output in Escherichia coli. The differential rate of synthesis of several Escherichia coli gene products was measured under conditions in which the average number of copies of the corresponding chromosomal gene had been changed by altering the replication velocity of the chromosome. The data show that in steady state exponential cultures the output of genes in a fully repressed, fully derepressed, or non-repressible state is proportional to the average number of copies of the gene per unit mass (gene: mass ratio) and does not depend on the number of copies of the gene relative to all other genes (gene: DNA ratio). In contrast, the output of a gene which was under regulation by endogenously generated effectors was independent of such changes in gene frequency. The relationship found between the number of copies of a gene per unit of cell mass and enzyme output provides a new method for determining the location of the chromosome origin and the direction of replication in bacteria.


Independence of F replication and chromosome replication in Escherichia coli. Data are presented which show that F replication is not coupled to any stage of the replication cycle of the host chromosome or to cell division, and is probably not related to surface area. It is also shown that the initiation mass of F increases progressively as the growth rate increases, the number of copies of F per unit of mass falling by half between doubling times of 0.8 and 2.7 generations per hour. It is further shown that the presence of an F particle does not influence the initiation mass of the chromosome.


Genetics of alcohol dehydrogenase in Saccharomyces cerevisiae. II. Two loci controlling synthesis of the glucose-repressible ADH II. Two unlinked loci controlling the glucose-repressible alcohol dehydrogenase (ADH II) in Saccharomyces cerevisiae were investigated. One locus (AD R2) was characterized by electrophoretically slow and fast alleles and by inactive adr2 mutant alleles. The ADH II pattern of heteroallelic slow X fast diploids indicates a tetrameric structure of the enzyme. AD R2 was considered as the structural gene, which codes for the ADH II subunits. Allelic adr2-f mutants could be classified by their response to the slow wild type allele (AD RS-S) in heterozygous diploids. In most cases, only the slow band appeared. In three adr2-f/ADR2-S crosses hybrid enzymes between inactive fast and active slow enzymes were formed. It was demonstrated, that allelic interactions at the protein level are not restricted to electrophoretical behaviour of hybrid enzymes. They also influence specific activities and substrate affinities. The other locus investigated, AD R1, was characterized by ADH II negative mutants (adr1) and by allelic mutants which generate only very low activity (ADR1-L). ADR1 does not influence the electrophoretic properties of slow and fast ADH II proteins. adr1 mutants have an intact structural gene, which is not expressed. The gene has probably a regulatory function with respect to ADH II synthesis.