Isolation and characterization of porcine beta-casein. Porcine beta-casein was isolated by chromatography on DEAE-cellulose. The protein had a molecular weight of 24 900 as determined by gel filtration on Sephadex G-100 in guanidine-HCl. Its amino acid composition differed from bovine beta-casein especia-ly in respect to serine, alanine and leucine. In common with bovine beta-casein the N-terminal amino acid was arginine; the C-terminal was either alanine or valine, while the C-terminal of bovine beta-casein is valine. At any temperature porcine beta-casein was more sensitive to Ca2+ than bovine beta-casein, while at a fixed Ca2+ concentration porcine beta-casein aggregated at a lower temperature than bovine beta-casein. Porcine beta-casein was susceptible to hydrolysis by calf chymosin but the proteolytic specificity differed from that of calf chymosin on bovine beta-casein.


Quaternary structure of DNA-dependent RNA polymerase from Escherichia coli. Measurement of distances by fluorescence energy transfer. Distances between the subunits in Escherichia coli RNA polymerase (core and holo enzyme) and the rifamycin binding site have been determined using the nonradiative energy transfer technique. The appropriate donor and acceptor labels have been chosen in order to optimize the spectral overlap and maximize the energy transfer. Spacer linked derivatives of rifamycin SV possessing nitrobenzo-oxadiazole groups (energy acceptor) were synthesized for this purpose. The donor label, acetylaminoethylaminonaphthalene sulfonate, was introduced into the intact enzyme, and the subunits were separated. Enzyme molecules selectively labelled on one kind of subunit were produced by mixed reconstitution techniques employing labelled and non labelled subunits. The labelled beta'-subunit could not be prepared in sufficient amounts. Energy transfer distances between the enzyme-bound rifamycin derivative and the subunits were determined to be approximately 5.9 nm for sigma, 7.2 nm for alpha 2 and 6.1 nm for beta.


Shape of proteins S3 and S17 from the small subunit of Escherichia coli ribosome. The shapes of proteins S3 and S17 purified from the 30 S subunit of Escherichia coli A19 were studied by hydrodynamic methods. The proteins have s020,w values of 2.1 +/- 0.1 S and 1.2 +/- 0.1 S and D020,w values of 7.4 +/- 0.5 . 10(-7) cm2/s and 11.4 +/- 0.6 . 10(-7) cm2/s. The respective molecular weights determined by sedimentation equilibrium are 25 800 +/- 500 and 9900 +/- 300. The intrinsic viscosity values for the two proteins are 5.8 +/- 0.3 ml/g and 4.2 +/- 0.2 ml/g. From these hydrodynamic parameters a slightly elongated shape for S3 and a globular shape for S17 have been concluded.


Stimulation of dehydrogenase synthesis by cadmium in a cadmium-resistant strain of Saccharomyces cerevisiae. The activity of dehydrogenase in Saccharomyces cerevisiae was estimated by reduction of 2,3,5-triphenyltetrazolium chloride. By the adaptation of yeast to cadmium, the high activity of dehydrogenase was observed. Furthermore, the activity of dehydrogenase in Cd-resistant cells was increased by growing in medium containing CdSO4. However, the activity of dehydrogenase was inhibited by the addition of CdSO4 to the reaction mixture. The activity of dehydrogenase in Cd-sensitive cells was increased slightly by incubation with low concentrations of CdSO4. High activity of dehydrogenase in Cd-resistant cells was completely negated by the addition of cycloheximide to the incubation medium. The increase of dehydrogenase activity is due partly to de novo synthesis of protein.


The primary structure of ribosomal protein S7 from E. coli strains K and B. Ribosomal proteins S7 from 30S subunits of Escherichia coli strains K and B differ extensively in their aminoacid compositions. The experimental details which led to the determination of the complete primary structures of proteins S7K and S7B are presented. Protein S7K consists of a single polypeptide chain of 177 aminoacids giving a calculated molecular weight of 19, 732, whereas protein S7B has 153 residues which amount to a molecular weight of 17,131. Aminoacid sequences were determined by a combination of automated Edman degradation of the intact proteins in a modified Beckman sequenator and sequencing of peptides obtained by digestion with trypsin. Staphylococcus aureus protease, thermolysin and pepsin, either by solid-phase Edman degradation or by dansyl-Edman degradation. Additional information about the primary structure was derived from peptides resulting from chemical cleavages of the protein by 2-(2-nitrophenyl-sulphenyl)-3-methyl 3' bromoindolenine at its tryptophanyl bonds and by cyanogen bromide at its methionyl bonds leading to large fragments. The mutational event occurring between S7B and S7K was characterized. Protein S7K contains an additional sequence of 24 aminoacids at its C-terminal end. The aminoacid sequence of both proteins S7K and S7B was compared to the published sequences of the other ribosomal proteins of Escherichia coli and predictions for the secondary structure of these proteins were made.


[Dehydrogenases reducing NAD+ in the presence of D (-) 3- phosphoglycerate in mycobacteria (BCG, H37Ra, M. phlei)]. Referring to the elution volume on a Sephadex G-150 column only one specific peak is obtained, the same for the BCG, H37Ra and Mycobacterium phlei strains grown on Sauton synthetic medium. Some properties of these partially purified dehydrogenases are studied (conservation and dialysis in media of different salt concentrations, equilibrium constant, Km, heat stability). All enzyme preparations from tubercle bacilli (BCG, H37Ra) are readily inactivated by heat and are very unstable in solutions of low ionic strength. In contrast, under the same experimental conditions, all enzyme samples from M. phlei are, comparatively, much more stable towards these factors [heat, salt (potassium phosphate, NaCl) concentration].


The existence and neurobiological significance of neuronal and glial forms of the glycolytic enzyme enolase. The isoenzymes of the glycolytic enzyme enolase have been separated and purified. The structural and functional properties of two brain enolases are described. Immunocytochemical techniques have established that one brain enolase is restricted to neuronal cells (neuron-specific enolase, NSE) while the other is localized in glial cells (nonneuronal enolase, NNE). The brain enolases, therefore, represent the first example of functional markers for neuronal and glial cell types in brain. The two enzymes are structurally distinct with the evidence establishing that they are products of separate genes. Functionally, the neuronal enolase has been demonstrated to be uniquely stable to concentrations of chloride salts that rapidly inactivate the glial enzyme. NSE may therefore represent an adaptation of this enzyme that is specifically suited to the neuronal milieu. A specific radioimmunoassay is described for NNE and NSE with the studies reported indicating that neuronal enzyme levels vary considerably when different brain areas are compared, suggesting a relationship between functional activity and levels of NSE. In addition to being a marker for neuronal cells, NSE has also been found to be present in various glands. The cells of the APUD series (amine precursor uptake and decarboxylation cells) in the pituitary, adrenal medulla, pineal, thyroid, and pancreas have been shown to contain NSE. NSE is, therefore, also a marker for these neuronlike endocrine cells since they are the only cells other than neurons that contain this protein.


The early outgrowth of catecholaminergic fibers and the development of the nucleus of the locus coeruleus in tissue culture of newborn mice in Leighton tubes. A simple and reliable method of sampling explants from the nucleus of the Locus Coeruleus of newborn mice and their cultivation in Leighton tubes is described. This technique reliably provides cultures available for experiments lasting, at least, ten days. The cells of the nucleus of the Locus Coeruleus and newly formed norepinephrine-containing fibers are demonstrated by fluorescence histochemistry together with pharmacological tests. Their morphological characteristics before and after fixation and staining are described. Electron microscopy confirmed the healthy condition of these cultures.


Lecithin: cholesterol-acyl-transferase (LCAT) activity in renal allograft patients. Preliminary report. LCAT activity is impaired in chronic renal failure. Our data show that LCAT activity is restored in successful renal transplant patients. Hence, relationship between kidney and LCAT activity can be postulated, but the underlying mechanisms are not yet fully clarified.


Apparent identity of mechanisms of genetic resistance to marrow transplantation and natural killer cell activity. Because the phenomenon of in vitro lysis of lymphoma cells by spleen natural killer (NK) cells bears genetic and effector cell resemblances to genetic resistance to bone marrow transplantation, they were compared for additional known unique characteristics of the latter phenomenon. Like GR to BMT, NK cell activity first appeared abruptly at about 3 weeks of post-natal age; was radioresistant to 1 100 R whole body irradiation, but was quantitatively diminished by higher exposures or delay of test post-irradiation; was suppressed by pretreatment with either cyclophosphamide, carrageenan, silica particles, anti-bone marrow serum or anti-thymus serum. The many unique identical characteristics of these two effector mechanisms indicates that they represent two manifestations of the same basic phenomenon of natural immunity. This is in accord with other data indicating that GR to BMT is directed at Hh antigens which, like TL antigens, may in some mouse strains appear on both leukemic cells and normal hemopoietic cells.


Comparison of van 't Hoff and calorimetrically determined enthalpies of binding of N-phosphonacetyl-L-aspartate to E. coli aspartate transcarbamylase. A comparison has been made of the values obtained by direct calorimetric measurements and van 't Hoff analysis, under similar conditions, for the enthalpy of binding of the bisubstrate analog N-phosphonacetyl-L-aspartate (PALA) to E. coli aspartate transcarbamylase and its catalytic subunit. In the case of the catalytic subunit, data were obtained at both saturating and non-saturating concentrations of L-Asp, and at two ionic strengths. Despite a 1000-fold difference in protein concentrations, and the obligatory omission of carbamyl phosphate in the calorimetric experiments, the values obtained by the two methods are shown to agree to within 15% when appropriate corrections are made. These results suggest that subunit dissociation is not a significant factor at the low protein concentrations used in the van 't Hoff analysis, and, conversely, that aggregation of the protein is negligible at the high protein concentrations used in the calorimetric experiments. They also imply that, at pH 8.3, the enthalpic difference between the two conformational states of the enzyme which exist in the presence and absence of substrates is less than 2.5 kcal/mol. In addition, the trends in the three sets of data for the catalytic subunit indicate that ionic bonds are involved in binding PALA to the active site, and that non-productive binding by L-Asp is negligible under these experimental conditions.


Simultaneous determination of n-hexane, 2-hexanone and 2,5-hexanedione in biological tissues by gas chromatography mass spectrometry. A quantitative method is reported for the determination of n-hexane, 2-hexanone and 2,5-hexanedione in biological tissues by stable isotope dilution using gas chromatography mass spectrometry. n-[2H14]Hexane, 2-[2H5]hexanone and 2,5-[2H10]hexanedione are used as the isotopic diluents. After tissue homogenization and extraction of the three compounds in the presence of the deuterated internal standards, analysis is carried out in a single gas chromatographic injection by selected ion monitoring. Principal advantages of the technique are the ease of sample handling, rapidity of analysis and low limits of detection. The methodology is used to determine the organ distribution, pharmacokinetics and metabolism of n-hexane to 2-hexanone and 2,5-hexanedione in rats following inhalation exposure.


Immobilization of enzymes and microbial cells using carrageenan as matrix. Conditions for the gelation k-carrageenan, which is a new polymer for immobilization of enzymes and microbial cells, were investigated in detail. k-Carrageenan was easily induced to gel by contact with metal ions, amines, amino acid derivatives, and water-miscible organic solvents. By using this property of k-carrageenan, the immobilization of enzymes and microbial cells was investigated. Several kinds of enzymes and microbial cells were easily immobilized with high enzyme activities. Immobilized preparations were easily tailor-made to various shape such as cube, bead, and membrane. The obtained immobilized preparations were stable, and columns packed with them were used for continuous enzyme reaction for a long period. Their operational stabilities were enhanced by hardening with glutaraldehyde and hexamethylenediamine.


Alternate method of calculating the free-energy change accompanying the growth of saccharomyces cerevisiae (Hansen) on three substrates. A method is described for determining the free energy of formation of the cells of Saccharomyces cerevisiae (Hansen) that are formed as the result of anaerobic growth on glucose, and aerobic growth on glucose and ethanol. The method is based on the direct relationship that exists between the enthalpy changes and the free-energy changes that accompany the oxidation of 1 g cellular material formed during these growth reactions and the degree of reduction of the same material. When the results of these calculations are used together with the free energies of formation of the reactants and of other products of a given growth reaction, it becomes possible to calculate the free-energy change accompanying this reaction. These free-energy changes are in excellent agreement with those calculated by another method based on the hypothesis that the free-energy change accompanying the conversion of the substrate plus other reactants into cellular material plus other products is equal to zero.


The use of steroïd hormone receptors in the treatment of human breast cancer: a review. Basic research into the mechanisms of steroid hormone action in breast cancer has led to significant advances in our understanding and treatment of this disease. The hypothesis that measurement of estrogen receptor (ER) in breast cancer tissue might be useful in predicting the endocrine dependence of a tumor has been proven to be correct. The absence of ER connotes hormone independence and precludes a trial of endocrine therapy. Tumors selected for hormonal treatment on the basis of a positive ER respond to endocrine therapy at nearly twice the rate of those chosen by clinical criteria alone. However, a third of ER positive tumors fail to respond. Recently, research has been directed toward increasing the accuracy of the assay in the ER positive group. The concentration of ER in the tumor and the measurement of progesterone receptor (PgR) appear to improve the predictive accuracy of the test. The ER status of primary breast cancer is also a marker for the length of time to recurrence after mastectomy and for ultimate patient survival. Thus, in addition to its importance in the selection of treatment for advanced disease, the ER assay may also prove valuable in planning new adjuvant treatment strategies.


[Spontaneous transformation and long term culture of foetal mouse glial cells (author's transl)]. Six cell lines originated from foetal mouse brain were maintained in vitro for more than two years. The morphology of most of these cultures suggests their glial character. This is corroborated, for some lines, by the presence of specific glial protein (Glial fibrillary acidic protein, or GFAP). Five out of these lines remained not transplantable in animals during all the experiments. However one of them went through a spontaneous transformation at the eleventh population doubling. This culture, after transformation remained glial and when injected in animals, induced GFAP containing tumors.


[Malignant lymphomas in Burgundy, France (1976--1977): a new approach using computerized pathological diagnoses (author's transl)]. Pathology laboratories in the Burgundy region have recently been equipped with mini-computers using the same software and working method. This report brings together their histological records, stored on magnetic discs, and describes the first results of this regional data base. Malignant lymphomas were chosen as a pilot study and evaluated between January 1976 and December 1977. After a brief presentation of the method, 246 cases of malignant lymphoma are analysed: 95 of Hodgkins disease, 103 of non-Hodgkins malignant lymphoma of the nodes and 48 cases of extranodal non-Hodgkins malignant lymphoma. The distribution of patients in terms of sex and ten year age groups is analysed, together with the various incidence rates for a year in Burgundy and in its four administrative units (Cote-d'Or, Nievre, Saone-et-Loire and Yonne).


[Transitional tumours of urinary bladder (author's transl)]. An overall survey of the transitional epithelium of the bladder and its carcinomas. This study is based upon the recent literature, in particular the considerable contribution of scanner electron microscopy. a) The transitional epithelium has the reputation of having a simple structure and even behaviour. In fact, it is complex with highly specialised surface cells. It has marked powers of regeneration after aggressions of various types. b) Tumours of the transitional epithelium are defined in relation to rupture of the basal lamina. Invasive carcinomas are classified according to their histological stage of penetration, their pure or partially metaplasic type and their degree defined according to the criteria of Broders. There exists a correlation between these three types of evaluation. Non-invasive carcinomas are either papillary--putting into question the reality of benign bladder papilloma--or flat mucosal and then often associated closely or at a distance with an invasive carcinoma. c) Abnormal regeneration, dysplasia or hyperplasia as a result of aggressions of different types or developing in isolation represent a high risk histologically, implying the need for careful follow-up and surveillance. d) Histopathological study of urothelial or transitional tumours is simple in operative specimens but difficult in biopsies. It requires close cooperation between surgeons and pathologists to ensure correct orientation of the fragments.


Library school education for medical librarianship. This paper reviews the current situation in library school education for medical librarianship in the United States and Canada based on information from a questionnaire sent to teachers of courses in medical librarianship in accredited library schools. Since 1939, when the first course devoted entirely to medical librarianship was offered at Columbia University, courses have been introduced into the curricula of at least forty-seven of the ALA-accredited library schools. In 1978 there were seventy courses available through forty-seven library schools. Possibilities for specialization in medical librarianship are examined. Course content is reviewed. Implications of the MLA certification examination for library school courses are explored.


Residency selection process: description and annotated bibliography. Specialty and residency training choices of medical students will affect the quality, mode, and geographic location of their future practice; the importance of such choices should not be underestimated. Medical school librarians have largely ignored the opportunity to interact with both medical students and medical school officials in providing sources needed to assist these career decisions, and for the most part students and administrators have ignored the opportunity to utilize the medical library in this process. This article presents an overview of the processes and procedures in which third- and fourth-year medical students are involved in selecting specialty and residency training, and provides a detailed description of the resources which the medical student should consult in order to make thoughtful, informed career decisions. The article urges medical school advisers and medical librarians to work as partners in providing information on specialty and residency selection to medical students.


Assessment of patients for psychotherapy. Factors in the patient which have been commonly cited by therapists as relevant in assessment for psychotherapy are examined as well as the research done on them. These factors are discussed under four categories: (a) factors related to the illness, (b) personal factors related to the treatment, (c) personal factors not directly associated with the illness and (d) current life circumstances. Research on methods of assessing patient suitability is discussed together with an account of the reasons for the rather disappointing contribution of systematic research.


Premenstrual syndrome: a double-blind controlled trial of progesterone and placebo. Patients with premenstrual syndrome recorded their symptoms daily using menstrual distress questionnaires. These were analysed by a least mean square method of fitting sine waves. After recording an untreated cycle, patients were given progesterone 200 mg b.d. and placebo in a double-blind crossover manner; 75 per cent of patients were then given progesterone 400 mg b.d. and placebo in a similar manner. Treated cycles were rated by both daily menstrual distress questionnaires and retrospective self-assessment. Both rating methods showed there was no significant difference between progesterone and placebo in reducing symptoms of premenstrual syndrome, and in the majority of cases placebo was more effective, although never significantly so.


Controlled studies of the acute antidepressant effects of lithium. In two randomized double-blind controlled trials on 63 depressed female in-patients subject to recurrent affective disorder (bipolar and unipolar manic-depressive psychosis) lithium was shown to have major acute antidepressant effects. At the end of three weeks lithium produced more uniform improvement than did imipramine; lithium in combination with tryptophan (in the form of Optimax) was superior to tryptophan alone--the latter drug having no discernible antidepressant activity in this group of patients. Lithium did not produce an antidepressant effect until the second and third week of both trials.


Wound sepsis following gastrointestinal surgery: a comparison of topical and two-dose systemic cephradine. A prospective study of the effect of the route of administration of prophylactic antibiotic on the wound infection rate following gastrointestinal surgery was performed. Patients were randomly allocated to one of three groups: group 1 received no form of antibiotic prophylaxis; group 2 received 1 g of cephradine applied topically to the wound at closure; group 3 received 1 g of cephradine intravenously at induction of anaesthesia and a further intravenous dose of 500 mg 4 h later. Wound infections occurred in 12 of 83 patients in the control group (14.5 per cent), in 6 of the 83 patients in the group who received topical antibiotic (7.2 per cent) and in 3 of the 82 patients who received systemic antibiotics (3.6 per cent). Only the group who received systemic antibiotic showed a statistically significant reduction in the incidence of wound infections compared with the control group (P = 0.03).


Leucocyte ascorbate levels and postoperative deep venous thrombosis. Forty-four general surgical patients were included in a prospective, randomized double-blind controlled trial of ascorbic acid (500 mg b.d.) or placebo for 7 days before operation. This was to test the hypothesis that vitamin C may reduce the instance of deep venous thrombosis postoperatively. Venous blood samples were taken before entering the trial, just immediately before surgery, on the day of operation and on three further occasions at 3-day intervals postoperatively for leucocyte ascorbic acid concentration (LAC). Venous thrombosis was diagnosed using the 125I-fibrinogen test and the leg scans interpreted by Roberts' criteria. There was no significant difference in the incidence of DVT between the treatment and placebo groups. In those with DVT (n = 23) the mean LAC on the day of operation was not significantly different from that in those without DVT. However, on the sixth and ninth postoperative days LAC levels were significantly lower in the DVT group. These results suggest that the administration of ascorbic acid preoperatively does not reduce the incidence of DVT, but a striking decrease in the LAC levels in the DVT patients is in keeping with the hypothesis that the initial event in the pathogenesis of DVT is adherence of leucocytes to the venous endothelium.


Cimetidine in treatment of reflux oesophagitis with peptic stricture. Twenty patients with reflux oesophagitis causing a tight peptic oesophageal stricture entered a randomised double-blind crossover trial in which they received cimetidine, 1.6 g daily, and matching placebo each for six months. The gross endoscopic appearances of oesophagitis, though not the grades of histopathological changes, showed significant improvement during treatment with cimetidine. The need for dilatation of the strictures, however, was not reduced.


Copulatory behavior and the initiation of pregnancy in California voles (Microtus californicus). The copulatory behavior of Microtus californicus and its effect on pregnancy initiation were examined in two experiments. In experiment 1 18 males and 18 females which had received exogenous hormones participated in 54 tests of copulatory behavior, each continued to a satiety criterion of 30 min with no copulations. The basic pattern involved no lock, intravaginal thrusting, ejaculation possible on a single insertion and multiple ejaculation. Ejaculation frequency ranged from 1 to 5, with a mean of 2.2. In experiment 2, it was found that all females receiving satiety tests of copulatory behavior while in male-induced estrus ovulated and became pregnant. Whereas all 10 females receiving one ejaculation ovulated, only 60% became pregnant. Thus, it appears that copulation beyond one ejaculation functions in increasing the likelihood of pregnancy. By comparing different species of Microtus it is proposed that copulatory patterns in which males persist for many thrusts and ejaculations may have evolved in conjunction with ornate penile morphology, large litter sizes, and high stimulus requirements for the initiation of ovulation and a funtional luteal phase.


Descending pathways of the nucleus of the optic tract in the rat. The descending pathways of the nucleus of the optic tract (pars lateralis) (NOTL) in the rat were examined in Nauta-Gygax impregnated sections and further confirmed by the horseradish peroxidase labeling technique. Following stereotactic lesions in the NOTL, visual cortex, and superior colliculus, projections which orginate in the NOTL were identified by elimination of the tectofugal and tectopetal fibers of the superior colliculus. The descending fibers from the NOTL appeared to be organized into three bundles. (1) The NOTL-contralateral NOTL fibers, which connect bilateral NOTLs through a part of the posterior commissure. (2) The NOTL-nucleus tegmenti pontis and inferior olivary nucleus fibers, which project to the ventromedial part of the nucleus tegmenti pontis and the dorsal cap of the inferior olivary nucleus, ipsilaterally to the NOTL. (3) The NOTL-pontine nuclei fibers, which terminate within the medial one-third of the pars lateralis of the ipsilateral pontine nuclei with topical relations.


Topographical origin and ganglion cell type of the retino-pulvinar projection in the cat. In order to examine the pattern of the retino-pulvinar projection in the cat, the existence of which has been recently demonstrated using autoradiographic fiber tracing technique, a small amount of horseradish peroxidase (HRP) was injected into the lateral part of the pulvinar nucleus at various rostocaudal levels. The retrogradely labeled ganglion cells were analyzed in terms of their topographical location and cell size, as seen inretinal whole mounts. The results were compared with those obtained following injections into the lateral geniculate nucleus. Retrogradely labeled cells were found in the retina bilaterally after injections of HRP into the pulvinar nucleus. Pulvinar injections produced labeling of retinal cells in the nasal half of the retina contralaterally, and in the temporal half ipsilaterally. The labeled cells were diffusely distributed in a retinotopically organized fashion. The representation of the area centralis in the retino-pulvinar projection is displaced rostrally as compared with the retino-geniculate projection. All labeled cells after pulvinar injections were medium to small size and no large cells were encountered.


Basal forebrain facilitation of reflex swallowing in the cat. In adult cats anaesthetized with urethane, electrical and chemical stimulation of the basal forebrain facilitated reflex swallowing elicited by electrical stimulation of the superior laryngeal nerve. A systematic stereotaxic mapping study using electrical stimulation revealed that the facilitatory sites were distributed along the course of the ansa peduncularis, specifically its rostral forebrain and hypothalamic components associated with the anterior amygdalar area, substantia innominata, lateral preoptic area, anterior hypothalamus and nucleus accumbens. By means of acute discrete radiofrequency lesions, the descending pathways mediating facilitatory influences from the nucleus accumbens and the amygdala to the brain stem were found to traverse the lateral hypothalamus. Ventral tegmental facilitatory sites in the midbrain are likely to be associated with these descending pathways; however, there is evidence for independent participation of this region of the brain in the control of swallowing. Chemical stimulation by means of microinjections of dopamine and apomorphine into the amygdala and nucleus accumbens also enhanced reflex swallowing. It is concluded that the results of this investigation implicate the basal forebrain as a site of integration of viscero-olfacto-gustatory information needed for the enactment of ingestive behaviour.


Cell-type-specific markers for distinguishing and studying neurons and the major classes of glial cells in culture. We have used 4 cell-type-specific markers to identify individual glial and neuronal cells in dissociated cell cultures of neonatal rat sciatic nerve, dorsal root ganglia (DRG), optic nerve, cerebellum, corpus callosum, cerebral cortex and leptomeninges. Schwann cells were identified with antibodies against rat neural antigen-1 (Ran-1), neurons with tetanus toxin, astrocytes with antibody against the glial fibrillary acidic protein (GFAP) and oligodendrocytes with antibody against galactocerebroside. All of these ligands react with cell surface molecules except for anti-GFAP antibody which binds to intracellular glial filaments. Using two-fluorochrome immunofluorescence we have studied the distribution of various glycoproteins and glycolipids on these 4 major neural cell types in short-term cultures. We have found that (1) although Ran-1 is expressed on glial and neuronal tumours, it was not found on normal astrocytes, oligodendrocytes or neurons; (2) Thy-1 was present on fibroblasts and some neurons but not on the majority of leptomeningeal cells or on oligodendrocytes or astrocytes in short-term cultures (however, it was expressed on some astrocytes in longer term cultures); (3) the 'large external transformation sensitive' (LETS) protein could be detected on fibroblasts and leptomeningeal cells but not on neurons or glial cells; (4) GM1 was present on all neurons, most oligodendrocytes and approx. 50% of other cell types; sulfatide and GM3 were only detectable on oligodendrocytes, while globoside was only found on some neurons. In addition, we were able to identify putative microglial cells by the presence of cell surface receptors for IgG and by their phagocytic activity; they did not express and of the cell-type-specific defining markers.


Identification, characterization and stereotaxic mapping of intraneuronal alpha-melanocyte stimulating hormone-like immunoreactive peptides in discrete regions of the rat brain. A highly specific antibody to alpha-melanocyte stimulating hormone (alpha-MSH) was used to histochemically localize and biochemically identify and quantitate alpha-MSH immunoreactivity in nerve fibers and cell bodies of the rat brain. alpha-MSH-like immunoreactivity was contained in fibers throughout the brain. The distribution of alpha-MSH was determined by immunocytochemistry as well as by radioimmunoassay combined with microdissection techniques. High concentrations of alpha-MSH were contained in the nucleus interstitialis stria terminalis, the median eminence and the medial preoptic, anterior hypothalamic, periventricular, paraventricular, arcuate, dorsomedial, and posterior hypothalamic nuclei. Moderate alpha-MSH concentrations were noted in the amygdala, septum, central gray, dorsal raphe, and the nucleus tractus solitarius. Cell bodies containing alpha-MSH were observed only in the arcuate nucleus. The alpha-MSH-like compound in brain had similar immunochemical and electrophoretic properties of standard alpha-MSH but high pressure liquid chromatographic analysis demonstrated that the alpha-MSH-like immunoreactivity was comprised of one major and two minor components. The major immunoreactive peak had an identical retention time as alpha-MSH and therefore may be chemically identical to alpha-MSH. The similar retention times and immunoreactivity of the other two compounds suggest a similarity in size and structure to alpha-MSH. These observations demonstrate that fibers containing alpha-MSH emanate from the arcuate nucleus to innervate many other regions of the rat brain.


Theories of the dorsal bundle extinction effect. Selective destruction of the noradrenaline systems in the rat brain using the neurotoxin 6-hydroxydopamine has been found to cause resistance to extinction in a number of behavioural situations. Several theories concerning the behavioural mechanism altered by the lesion, and hence about the role of noradrenaline in normal brain functioning, are proposed and evaluated. Theories suggesting a role for noradrenaline in activity, perseveration, internal inhibition, frustrative non-reward, motivation, or secondary reinforcement, fail to explain all the available evidence and direct tests of each theory fails to support its predictions. A model which suggests that noreadrenaline is involved in attentional behaviour, specifically in filtering out or learning to ignore irrelevant environmental stimuli, is successful in explaining all available data and direct tests of the lesioned rats' attentional capacity serve to confirm many of the predictions of an attentional theory of the dorsal bundle extinction effect.


Sets of neurons in somatic cerebral cortex of the cat and their ontogeny. The process of set formation is briefly reviewed and five monothetic schemes for classification of neurons in the somatic cerebral cortex are described. Criteria for evaluation of neuronal sets are presented and applied to the five different monothetic classification schemes. Classification by size and distribution of peripheral receptive fields orders existing data on cortical neurons better than classification by possession of an axon in the pyramidal tract, by modality, by lability of receptive field, or by 'lemniscal properties'; however, no monothetic scheme orders all the data. A useful polythetic scheme, using s and m terminology is suggested. The ontogeny of the cerebral cortex is reviewed in detail. It is suggested that sa neurons are Golgi type II neurons while m neurons are Golgi type I neurons. The hypothesis is presented that wide-field or m neurons develop and are recognizable before small-field or sa neurons in ontogeny. Evidence regarding this hypothesis is indirect, often conflicting, but suggestive that the hypothesis may be correct. The idea that m neurons may also be phylogenetically older than sa neurons is presented and shown to be consistent with ontogenetic data and interpretations.


Awareness, muscle relaxants and balanced anaesthesia. The incidence of awareness during insufficient anaesthesia is reported to be one per cent. It is usually due to the use of muscle relaxants, a balanced technique and the lightest possible depth of anaesthesia. Increased incidences were noted in open-heart surgery, during intubation-endoscopy procedures and in caesarean delivery patients. Experiences of awareness are disturbing to patients, who are usually benefited by a sympathetic and forthright explanation of the event. Fourteen representative cases of the problem are reported. Since no adequate sign or test exists for detection of awareness during very light anaesthesia or with associated paralysis, more meticulous attention is required in using relaxants or the balanced technique. Greater anaesthetic supplementation and reduction in the use of relaxants are recommended to halt the recurrence of this most serious anaesthetic problem.


Bacterial filters - are they necessary on anaesthetic machines? At the Vancouver General Hospital the effectiveness of the system for decontamination of anaesthetic equipment was evaluated to determine the need for bacterial filters on anaesthetic machines. Two groups of patients were studied. Group I consisted of 33 patients, none of whom had clinical symptoms of respiratory tract disease. Group II consisted of 17 patients who had lower respiratory tract secretions. In the latter group 16 had chronic bronchitis and had cystic fibrosis. Of 550 bacterial cultures taken from the anaesthetic equipment immediately before and after anaesthesia in our 50 patients, only five yielded a growth of non-pathogenic bacteria. The results of this study indicate that bacterial colonization of anaesthetic equipment is of a low order and is adequately controlled by pasteurization even after use in patients with chronic lower respiratory tract disease. The use of bacterial filters does not appear justified if a strict regimen of cleaning and pasteurization is followed.


Simple apparatus for blocking small animal brains. A modification of previously described devices for blocking small animal brains is presented. The apparatus is easily constructed and allows for blocking at varous angles of both fixed and unfixed tissue of most small laboratory animals.


Prenatal immunization against experimental enteric colibacillosis in piglets. To establish a model for the study of prenatal immunization against enteric colibacillosis a proportion of the litters of seven sows were immunized in utero 18 to 22 days before term by intra-amniotic and intramuscular injection of Escherichia coli antigen and the litters challenged at birth with either homologous or heterologous strains. Protection against homologous challenge was demonstrated in some but not all vaccinated piglets. The study was severely compromised by the occurrence of intrauterine death in a significant proportion of vaccinated piglets.


Studies on experimental enteric salmonellosis in ponies. Clinical, bacteriological, serological and haematological observations were made on 13 adult ponies orally inoculated with Salmonella typhimurium. The results were compared to two control ponies and four others infected by accidental transmission. The clinical responses in inoculated ponies included pyrexia lasting four days and neutropaenia during the first five days after inoculation followed by a neutrophilia. Pyrexia and neutropaenia was associated with maximal shedding of organisms in the rectal faeces. Changes in the character of the faeces occurred between one and two days after inoculation and appeared to be associated with the serological response. Serological responses occurred in all the infected ponies except one. At necropsy, of the 14 ponies with positive cultures in the colon, seven had negative cultures in the rectal faeces. Serological studies performed on 43 clinically normal horses indicated a correlation between age and salmonella agglutination titre.


The effects of repeated administration of Escherichia coli lipopolysaccharides to ponies. Repeated exposure of ponies in Escherichia coli endotoxin resulted in attenuation of the packed cell volume, beta-glucuronidase, capillary refill time and neutrophil responses usually accompanying endotoxin administration. An overall decrease in severity of clinical response including reduced mortality was also apparent in ponies with repeated endotoxin exposure. Modification of the febrile response was not observed in any of the experimental groups.


Local lymphokine production in ocular inflammatory diseases. We took samples of the aqueous humour and subretinal fluid from 12 patients suffering from various types of ocular inflammation. The presence of leucocyte migration inhibition factor in these fluids was determined using the leucocyte migration inhibition test. Our results indicated that this test differentiated ocular inflammatory reactions due to cell mediated immunity from those due to other mechanisms.


Increase in the in vitro susceptibility of Staphylococcus aureus to antimicrobial agents in the presence of Candida albicans. In experiments with mixed cultures of Staphylococcus aureus and Candida albicans both in the absence and in the presence of 5-fluorocytosine (5-FC), we have observed that (1) there is an inhibition of S. aureus growth in mixed cultures with C. albicans in media supplemented with 1 microgram/mL of 5-fc and that 5-FC has no effect on staphylococci in pure cultures; (2) this inhibition occurred with clinically isolated and laboratory strains and could be reversed by specific metabolites; (3) Staphylococcus aureus was inhibited by filtrates of C. albicans cultures treated with 5-FC and this seemed to be favored by some C. albicans filterable product which can affect the cell wall and the permeability of the staphylococcal cells since they become sensitive to 5-FC; (4) nine other commonly used antimicrobials showed an increased inhibitory activity against S. aureus in mixed cultures with C. albicans; and (5) there is a decrease in the number of precipitating antigens of S. aureus and of the activity of alpha toxin when this species was grown with both C. albicans and 5-FC. Our results indicate that the susceptibility of some species to antimicrobials could be significantly modified in the presence of other species. One cannot exclude that a similar phenomenon could happen in hosts under treatment with antibiotics against infection.


Structural and biochemical examination of ghosts derived from a deep rough (heptose-deficient lipopolysaccharide) strain and a smooth strain of Escherichia coli. Outer membrane derived 'ghosts' can be readily generated from both smooth and deep rough (heptose-deficient LPS) strains of Escherichia coli 08. MORPHOlogical and biochemical studies confirmed that 'ghosts' of both strains are composed of protein (four major proteins), LPS, and phospholipid (cardiolipin and phosphatidylethanolamine) in the form of a single membrane of roughly the same shape as intact normal cells. The ghost membrane cleaves only slightly in freeze-etch preparations of ghosts derived from the smooth strain as compared to the extensive cleavage plane of ghosts derived from the rough strain. The asymmetrical distribution of ghost proteins was visualized, by critical point drying and shadowing with platinum, as a relatively smooth outer surface with some discernible particles (10-15 nm) and an extremely particulate inner surface (10-15-mm particles. Ghosts derived from the smooth strain retained their structure following chloroform-methanol extraction, while ghosts derived from the rough strain fragmented with chloroform-methanol extraction. Evidence is presented that LPS-protein interactions as well as protein-protein interactions are significant in maintaining the ghost structure.


The influence of cations on the permeability of the outer membrane of Salmonella typhimurium and other gram-negative bacteria. The high sensitivity of rough mutants of Salmonella typhimurium, S. minnesota, and Escherichia coli 08 (i.e. with defects in the carbohydrate core of the lipopolysaccharide) to several antibiotics and to the dye gentian violet could be substantially reduced by the addition of cations (Mg2+, Na+) into the growth medium. One heptoseless mutant of S. typhimurium (chemotype Re) and its isogenic smooth parent strain were studied in more detail. The uptake of gentian violet was about 20% in the smooth strain, about 60% in the Re strain grown without additional cations, but decreased to about 15% in the same strain, when cations had been present during growth. In all cases, almost 50% of the gentian violet taken up by the cells was membrane-bound. The total membranes of the Re strain grown in nutrient broth without additional Mg2+ ions were reduced in the 36K and 34K major outer membrane proteins compared with the smooth strain; when grown with added cations the Re total membranes (and even whole cells) did not revert to the protein pattern of the smooth strain.


Outgrowth and sporulation studies on Clostridium botulinum type E: influence of isoleucine. A defined medium (CDM) is described which supported growth and sporulation of type E strains of Clostridium botulinum, but not sporulation of other serotypes of C. botulinum or C. sporogenes. As compared to growth in complex medium, spore outgrowth was delayed and both the growth rate and the cell yield was reduced. However, efficiency of sporulation of the type E MSpt strain in a chemically defined medium (CDM) was the same as that in complex medium and, in fact, sporulation was nearly synchronous and completed within 3 h of the first appearance of phase-bright endospores, compared with completion in 9 h in TPGY. Growth studies with CDM, from which single amino acids were omitted, showed that isoleucine was essential for outgrowth of heat-activated spores of the MSp+ strain, whereas valine was required for that of the Ts-25 mutant. Radioactive isoleucine was incorporated by germinating MSp+ spores at an earlier stage and at a more rapid rate than labelled methionine or mixed amino acids. Uptake studies showed that isoleucine accumulated in a prominent acid-soluble pool during outgrowth, a period when its incorporation into protein was not evident. The results suggest that the isoleucine may be required for a purpose other than protein synthesis during outgrowth.


Treatment of Parkinson's disease with sodium valproate: clinical, pharmacological, and biochemical observations. Because there is biochemical evidence of decreased GABAergic function in Parkinson's disease, sodium valproate, an inhibitor of GABA catabolism, was administered to eight Parkinsonian patients. Valproate treatment did not significantly alter any Parkinsonian feature, but tended to increase the dyskinesia in the "on-off" patients. The increased dyskinesias were not a result of altered peripheral metabolism of L-dopa. Despite obtaining high plasma levels of valproate, no consistent alteration of CSF GABA levels could be demonstrated. Thus, in these patients, an effect of valproate on GABA metabolism is unproven, and in turn, the role of GABA in Parkinsonism and dyskinesia uncertain.


The use of baclofen in treatment of spasticity in multiple sclerosis. Baclofen was used in a double-blind crossover placebo-controlled trial to treat spasticity in patients with multiple sclerosis (MS). While on Baclofen, patients obtained a significant (p less than 0.001) reduction in spasticity compared to controls. The drug was particularly effective in alleviating flexor and extensors spasms, as well as their associated pain. Side effects were common in this study, but were usually well tolerated by the patients. The commonest side effects were sedation, nausea and vomiting. There were no changes in hepatic, renal, or hematological function in any patients. Increase weakness due to loss of spasticity for support was also a fairly common complaint. The drug seems best indicated in patients in whom spasticity is not required for support or other activities of daily living. Careful monitoring of the patient is essential for effective use of this drug.


Roles for insulin and glucagon in the development of ruminant ketosis -- a review. Ketonemia can be a physiological response to a reduction in dietary intake. It also may occur when energy demands exceed the energy intake. Normally, alimentary ketogenesis is the major source of ketone bodies in ruminants. During ketonemia there is increased hepatic ketone body production. During physiological ketosis, the mobilization of free fatty acids is inadequate to support a high rate of hepatic ketogenesis. However, during clinical ketosis, the hormonal status (low insulin, high glucagon/insulin ratio) in combination with hypoglycemia promotes excessive lipid mobilization and a greater hepatic removal of fatty acids and switches the liver to a higher rate of ketogenesis. The low insulin, furthermore, can impair maximal ketone body utilization, thus exacerbating the hyperketonemia.


Free flying sparrows as carriers of salmonellosis. Salmonella typhimurium was isolated from nine of 60 wild sparrows trapped in the Guelph area. While this organism was isolated from birds trapped at several different locations, the highest prevalence was in sparrows trapped in close proximity to an animal clinic. The significance of these findings in relation to human and animal salmonellosis is discussed.


Action of amyloglucosidase on oxidised amylose. The Michaelis constant and maximal velocity of alpha-amylase-free amyloglucosidase decrease with increasing periodate oxidation of amylose. These kinetic features have been explained on the basis of competitive inhibition by the oxidised non-reducing end of the (1 leads to 4)-alpha-D-glucan chain with the active centres of the enzyme. A kinetic model is proposed to demonstrate this special kind of inhibition where the concentration of inhibitor is directly proportional to the substrate concentration. The experimental data fitted this model, and the plots of 1/Km and 1/V against the ratio of oxidised/unoxidised non-reducing end-groups were straight lines.


A computerised dichromatic earpiece densitometer for the measurement of cardiac output. This study assesses a precalibrated dichromatic earpiece densitometer and microprocessor for the measurement of cardiac output by indocyanine green dye dilution. The measured cardiac output is compared with values of cardiac output simultaneously determined using a cuvette densitometer. The microprocessor computation of cardiac output agreed very closely with the cardiac output determined by manual calculation from the same dye dilution curves (standard deviation +/- 1.47%). The reproducibility of the earpiece densitometer (standard deviation +/- 5.2%) was virtually identical to that of the cuvette densitometer (+/- 5.3%). In a comparison of earpiece and cuvette densitometers for 60 measurements of cardiac output following pulmonary arterial injection of dye and for 50 measurements following femoral venous injection of dye, correlation coefficients were 0.83 and 0.78 and the standard deviations of the differences of simultaneous measurements were 7.2% and 8.3% respectively. The instrument offers an accurate reproducible and relatively noninvasive technique for measuring cardiac output.


Electron microscopical-immunocytochemical evidence of ecdysteroids in the prothoracic gland of Galleria mellonella. Fixation of prothoracic glands of Galleria mellonella with a solution containing saponin permits immunocytochemical staining of the entire gland. By this means ecdysteroids were demonstrated electron microscopically to be present in the hyaloplasm and microtubules.


Indicator dilution curves in the diagnosis of D-transposition of the great arteries in infancy. Paired right and left atrial indicator dilution curves performed in a series of 17 patients with D-transposition of the great arteries (D-TGA) were reviewed. Taken together, the patterns obtained from patients who had trivial mixing between the pulmonary and systemic circulations were distinctive and easily recognizable. In the presence of substantial degrees of intracardiac mixing, however, the paired curves recorded become virtually identical and cannot be distinguished from curves recorded from patients with other forms of cyanotic congenital heart disease characterized by obligatory admixture. Thus paired atrial dye curves demonstrate a high degree of diagnostic specificity for the infant with D-TGA at greatest risk, normally those with a small intracardiac shunt. Such a procedure should facilitate early balloon atrial septostomy and obviate deterioration in the infant's condition due to prolonged catheter manipulation and/or angiography.


Replication of each copy of the yeast 2 micron DNA plasmid occurs during the S phase. Saccharomyces cerevisiae contains 50-100 copies per cell of a circular plasmid called 2 micron DNA. Replication of this DNA was studied in two ways. The distribution of replication events among 2 micron DNA molecules was examined by density transfer experiments with asynchronous cultures. The data show that 2 micron DNA replication is similar to chromosomal DNA replication: essentially all 2 micron duplexes were of hybrid density at one cell doubling after the density transfer, with the majority having one fully dense strand and one fully light strand. The results show that replication of 2 micron DNA occurs by a semiconservative mechanism where each of the plasmid molecules replicates once each cell cycle. 2 micron DNA is the only known example of a multiple-copy, extrachromosomal DNA in which every molecule replicates in each cell cycle. Quantitative analysis of the data indicates that 2 micron DNA replication is limited to a fraction of the cell cycle. The period in the cell cycle when 2 micron DNA replicates was examined directly with synchronous cell cultures. Synchronization was accomplished by sequentially arresting cells in G1 phase using the yeast pheromone alpha-factor and incubating at the restrictive temperature for a cell cycle (cdc 7) mutant. Replication was monitored by adding 3H-uracil to cells previously labeled with 14C-uracil, and determining the 3H/14C ratio for purified DNA species. 2 micron DNA replication did not occur during the G1 arrest periods. However, the population of 2 micron DNA doubled during the synchronous S phase at the permissive temperature, with most of the replication occurring in the first third of S phase. Our results indicate that a mechanism exists which insures that the origin of replication of each 2 micron DNA molecule is activated each S phase. As with chromosomal DNA, further activation is prevented until the next cell cycle. We propose that the mechanism which controls the replication initiation of each 2 micron DNA molecule is identical to that which controls the initiation of chromosomal DNA.


Actomyosin organisation for adhesion, spreading, growth and movement in chick fibroblasts. Examination of the actomyosin structures and their relation to adhesion, movement and growth in the first fibroblasts migrating from chick heart explants shows striking differences with fibroblasts adapted to grow in culture. The latter have focal adhesions which seem to immobilize them for anchorage-dependent growth, rather than facilitate their movement. The fibroblasts specialized for movement from the explants, though equally well spread, make contact with substratum through extensive areas of relatively unspecialized membrane, have less well developed stress fibres and a low growth rate.


[Autochthonous malaria and malarian liver. Apropos of 1 case]. Report of the case of a patient, store-keeper at the Roissy airport, suffering from an autochtonous primo-invasion falciparum malaria. The clinical symptoms were hectic fever and painful hepatomegalia, followed 14 days after by  a typical tertian fever. All investigations being negative, a laparoscopy was carried out, which showed a black liver, and a biopsy demonstrated the malaria pigment in Küpffer cells. Malaria was confirmed by the study of a blood smear. This diagnostic hypothesis had not been raised, because of the absence of any epidemiologic argument. It seems necessary to think of autochthonous malaria among the etiologies of prolonged summer fevers in people living or working in the neighbourhood of airports, the more so that the frequency of this peculiar mode of contamination should logically increase.


[Comparative study of immunoenzyme technics, ELISA and on formed antigens, in the immunologic diagnosis of African trypanosomiasis]. The enzyme linked immunosorbent assay (ELISA) for the serodiagnosis of human african trypanosomiasis is described, comparatively with the immunoperoxidase technique using blood streamforms of Trypanosoma brucei as antigen. Practical aspects for measuring the amount of antibody in serum samples from infected rabbits and from patients with african sleeping sickness are discussed. ELISA does offer important advantages over the other method used namely: -- quantitative estimates are possible, -- it bends itself readily to large scale series, owing the fact that it can be fully automatic. These qualities will be turned to full account when the different classes of antibodies present in trypanosomiasis suffers can be examined by means of specific antigenic fractions.


Assessment of left ventricular function in secundum atrial septal defect by computer analysis of the M-mode echocardiogram. Left ventricular function in 53 patients with secundum atrial septal defect was assessed by computer-assisted analysis of the left ventricular echocardiogram and by cardiac catheterization. The patients were divided into two groups, those younger and those older than 60 years, to investigate the effect of aging on left ventricular function. Cavity size was significantly smaller than normal (p less than 0.01) and septal motion was abnormal in 86%, but values for cardiac index, left ventricular end-diastolic pressure, velocity of circumferential fiber shortening, left ventricular filling rate, and duration of rapid filling were normal in both groups. Regional dynamics assessed in terms of peak rates of systolic thickening and diastolic thinning of the septum and posterior wall were also normal in both groups. We concluded that, although left ventricular minor dimensions are small, and septal motion is reversed in the majority of patients with atrial septal defect, left ventricular function is normal, and it does not appear to deteriorate with increased age, pulmonary hypertension, or the presence of right ventricular failure. The abnormal septal motion appears to be compensated for by enhanced septal and posterior wall percentage thickening.


[Indirect immunofluorescence in the therapeutic surveillance of trypanosomiasis (preliminary note)]. The authors have studied the evolution of fluorescent antibodies in the serum and the C. S. F. of treated Sleeping Sickness patients regularly examined when coming to Brazzaville for their periodical controls. They have observed more than 200 patients who were followed during three years. The authors demonstrated that curing patients show the following particularities: -- serum becomes negative less rapidly than C. S. F., -- delay of negativation of the serum varies according to the stage of the disease, -- the C. S. F. positive in fluorescence becomes negative in less than twelve months. On the other hand, relapsing patients show some striking differences, such as: -- C. S. F. remains always strongly fluorescent positive, -- the serology remains positive too, but can present some fluctuations. Some very particular cases such as "nuclear fluorescence only" or discrepancy between IFAT and clinico-parasitological data are then analysed. From a practical point of view, it appears that, as often as not, the evolution of fluorescent antibodies in serum and in C. S. F. allows to prognose either the cure or the relapse less than one year after treatment.


[Comparative study of the value of Schistosoma mansoni and Schistosoma haematobium antigens in the indirect immunofluorescent reaction applied to the diagnosis of rectal S. intercalatum bilharziasis]. A comparative study of the value of antigenic sections of S. mansoni and S. haematobium in indirect immunofluorescence applied to the diagnosis of S. intercalatum rectal bilharziosis (in 66 cases) shows that far better results are obtained with S. haematobium antigen (83,3 0/0 positive reactions with higher titers dilution) than with S. mansoni (33,3 0/0 positive reactions).


[Filarian elephantiasis in French Polynesia (Wuchereria bancrofti var. pacifica). Health study on 274 subjects. I Epidemiological and Clinical aspects]. Twenty-five years after the fight started against Wuchereria bancrofti var. pacifica in French Polynesia and which was based upon mass chimiotherapy by diethylcarbamazine (Banocide), a survey realized in 1975 and 1976 among 274 patients with elephantiasis allows us to give precise details of the local clinical and epidemiological aspects. Since 1950 the number of clinical cases varies along with the parasitological incidence, but with a certain delay which is explained by the late and irreversible elephantiasis characteristics. The overall prevalence is actually low. However the occurrence of new cases, although very rare, is still possible. Among sick patients the lymphangitic crisis frequency whose aspect lead to evoke a bacterial participation, is low. Women are less frequently and less severely involved than men. Localisations are essentially restricted to the lower limbs. Several limbs are involved in approximately 50 0/0 of the cases. The scrotum involvement is rare, the one of the breast is found only once. Among men we can notice a 33 0/0 incidence of associated hydroceles. A past history of chyluria is not rare.


[Filarian elephantiasis in French Polynesia (Wuchereria bancrofti var. pacifica). II. Biological aspects]. Realized in French Polynesia among 274 patients with elephantiasis, this survey studied the microfilaremia, the eosinophily, the immunoglobulin titers and the antifilarian antibodies (done by passive hemagglutination) for Wuchereria bancrofti var. pacifica. Patients with elephantiasis seldom have circulating microfilariae in their blood. Hypereosinophily is frequent but rarely high. It is similar to the one patients with microfilaremia. There is a trend towards neutropenia during lymphangitic crisis that occur on an elephantiasis limb. The IgE titer is clearly increased, the IgG one is lesser elevated. The mean values are identical to those encoutered among microfilariae asymptomatic cariers. On the other hand the serodiagnosis is more frequently positive among elephantiasic patients.


Pitfalls to avoid when comparing CK-MB fractionation by antibody inhibition reaction and DEAE-Sephadex column chromatography. 1. We compare the Roche ion-exchange column chromatography and the Merck antibody inhibition reaction for CK-MB fractionation in 51 sera. Measurements of total CK and CK-MB activities must be done under the same conditions for each method in order to correlate the results. 2. A decisional value must be used for the interpretation of CK-MB results. We have used 10% for the inhibition assay and 3% for the chromatography procedure. The use of a percentage should be preferred to use of CK-MB activity alone. 3. When the % of CK-MB was established for the 51 patients only 4 results disagreed between the two methods. Three of these could be explained by a lack of sensitivity of the column chromatography procedure. 4. The antibody assay produces reliable results. Since CK-BB and CK-MB are simultaneously measured, the method is therefore prone to interference by CK-BB when present in serum. The assay is greatly affected by the presence of adenylate kinase in serum. It is not necessary to run a serum blank with this procedure when the serum in pre-incubated for 7 minutes with the reagents. 5. The Roche method also produces reliable results but offers less sensitivity when total CK remains in the normal range. The procedure is much less affected by the presence of adenylate kinase.


Oral orthopedics and movement of maxillary segments. A roentgen stereophotogrammetric study. An infant with a complete unilateral cleft of the lip and palate underwent maxillary expansion treatment using an oral orthopedic appliance. Movement of the maxillary bone segments was studied by means of metallic implants and roentgen stereophotogrammetry, and intra-oral changes were recorded by measuring transverse dimensions on casts. Expansion treatment had almost no influence on the positions of the maxillary segments, and movements of the segments showed little agreement with measures on casts. The findings suggest that the appropriate use of the term oral orthopedics and the evaluation of treatment effects would benefit from evaluating the movement of the segments by methods other than measurements of casts.


Fluorescence polarization immunoassay for cortisol. A fluorescence polarization immunoassay for serum cortisol was established using cortisol 21-amine which was readily coupled with fluorescein isothiocyanate. The proposed method is sufficiently sensitive, reliable, specific and simple for routine determination of serum cortisol. The assay is rapid, without separation of antibody-bound and free ligands. The minimal amount of cortisol detected was 1.5 ng/tube and the measurable range was from 1.5 to 100 micrograms/dl. There was a good correlation between values obtained from radioimmunoassay and the proposed method.


Duchenne muscular dystrophy: 45Ca exchange in cultured skin fibroblasts and the effect of calcium ionophore A23187. Calcium exchange was studied in skin fibroblasts cultured from eight subjects with Duchenne muscular dystrophy, four with Limb Girdle dystrophy and eight normal controls using 45Ca. No difference was found in the time course of calcium exchange between the groups, nor in the level of 45Ca when maximal exchange had occurred. Treatment of the cultures with the calcium ionophore A23187 resulted in higher levels of calcium exchange over a 2-H period. The increase was similar in the cultures from the 3 patient groups studied.


Hypotrypsinaemia in diabetes mellitus.

Hypotrypsinaemia in diabetes mellitus. Plasma trypsin concentrations were measured in 403 fasting diabetics and 106 healthy controls. Basal trypsin concentrations in the normal subjects were 88 +/- 6 ng/ml (mean +/- S.E.M.). Mean plasma trypsin concentrations in diabetics treated with diet alone (n = 74) were 45 +/- 2 ng/ml, while in a group of young (less than 35 years, n = 88) insulin-dependent diabetics, they were very low at 29 +/- 2 ng/ml and these levels were inversely related to insulin dosage. The findings may help in the understanding of the pathophysiological changes in the exocrine pancreas in the diabetic state and may also shed some light on the physiological interrelationship between the endocrine and exocrine pancreas.


Action of human pancreatic and salivary alpha-amylases on maltooligosaccharides: evaluation of kinetic parameters. The kinetic studies on the reactions of human pancreatic and salivary alpha-amylases with several maltooligosaccharides (maltotetraose, maltopentaose, maltohexaose, and maltoheptaose) were carried out. The susceptibility to hydrolysis with human pancreatic alpha-amylase decreased in the order of maltopentaose, maltohexaose, maltotetraose, and maltoheptaose, while with human salivary alpha-amylase maltopentaose was hydrolysed slightly slower than maltohexaose but fairly faster than maltotetraose or maltoheptaose from a viewpoint of the rates of reactions based on the amount of substrate changed. The relative rates of production of substrates, utilized in the coupled yeast alpha-glucosidase reaction, increased in the order of maltoheptaose, maltohexaose, maltotetraose, and maltopentaose with human pancreatic alpha-amylase, while with human salivary alpha-amylase in the order of maltoheptaose, maltotetraose, maltohexaose, and maltopentaose. Thus, maltopentaose was considered to be the best substrate over maltotetraose, maltohexaose or maltoheptaose for the alpha-glucosidase coupled method of alpha-amylase determination.


The acquisition of antigens in the intercellular substance of mouse skin by schistosomula of Schistosoma mansoni. Serum from patients suffering from the autoimmune skin disease pemphigus vulgaris has been used to demonstrate the presence of intercellular substance (ICS) on the surface of these chistosomula of Schistosoma mansoni which has penetrated mouse skin in vitro or during a percutaneous infection. ICS was absent from mechanically transformed schistosomula or those formed in the peritoneal cavity of mice. Schistosomula which penetrated mouse skin rapidly in vitro acquired very little of the ICS. It was found during a percutaneous infection that schistosomula recovered from the skin after 10 min had no detectable ICS, while those recovered after 2 hr and 24 hr gained increasing quantities of the material. It is concluded that schistosomula which are delayed in their exit from the skin acquire more ICS. However, this material must be shed during subsequent migration since schistosomula from lung and liver, and 7-week-old worms do not posses it. The implications of the findings are discussed.


Immunofluorescence studies on the occurrence and localization of the CEA-related biliary glycoprotein I (BGP I) in normal human gastrointestinal tissues. Biliary glycoprotein, I(BGP I) is a carcinoembryonic antigen (CEA) cross-reactive glycoprotein of normal human bile. Its occurrence and localization was studied in normal human gastrointestinal tissues by means of direct immunofluorescence using immunadsorbent purified BGP I antibodies with high selectivity for BGP I, as compared to CEA and 'non-specific cross-reacting antigen' (NCA). As controls fluorescein-labelled CEA and NCA were used. Specific BGP I fluorescence was only found in the biliary tract, i.e. in bile canaliculi, in the lumen of large bile ducts and on the surface of the gall bladder mucosa. No fluorescence was found in the hepatocytes or in the cells lining larger bile ducts or the gall bladder. Fluorescence probably due to cross-reaction with NCA was obtained in the cytoplasm of macrophages in different organs and on the surface of bowel epithelium.


Antibody production and DNA synthesis of human lymphocyte subpopulations induced by PPD tuberculin. Purified protein derivative (PPD) of tuberculin was found to induce antibody secretion and DNA synthesis in human lymphocytes from blood, spleen, tonsil and lymph node. Antibody secretion was measured as plaque-forming cells (PFC) against fluorescein isothiocyanate (FITC) coupled sheep red blood cells (SRBC) in a haemolysis-in-gel assay. Peak antibody secretion by 100 micrograms/ml of PPD was usually seen on day 6 for blood lymphocytes, and varied from day 3 to day 6 for spleen cells. Peak DNA synthesis for blood lymphocytes stimulated by various concentrations of PPD ranged from day 4 to day 7. The highest number of PFC in tonsil and spleen cells was induced by PPD compared to Staphylococcus aureus bacteria Cowan 1, lipopolysaccharide (LPS) and pokeweed mitogen (PWM). Antibody secretion by PPD was not affected when phagocytic cells were removed by iron treatment. PPD stimulated a higher DNA synthesis in unseparated lymphocytes or mixtures of T and B cells than in enriched T or B cell suspensions. PPD did not induce PFC in B cells enriched by the removal of sheep erythrocyte rosette-forming cells (E-RFC). However, more PFC were stimulated by PPD in enriched E-RFC compared to unseparated lymphocytes, which may indicate that most of the FITC-SRBC reactive B cells also form rosettes with SRBC.


Locating salmonella resistance gene on mouse chromosome 1. The inherited resistance of inbred mouse strains to Salmonella typhimurium injected subcutaneously has been reported to be controlled primarily by a single gene designated Ity. Resistant mice have the dominant allele Ityr and sensitive mice are homozygous for the recessive allele Itys. This paper describes studies undertaken to locate the gene using readily distinguishable phenotypes as chromosome markers. Appropriate F1 backcross and F2 generations of hybrids between resistant and susceptible inbred strains of mice, with or without the particular phenotypic markers, were tested both for susceptibility to salmonella sci and presence of the marker. Independent segregation of the characteristics eliminated all chromosomes except Chromosome 1. C57L mice resistant to S. typhimurium, Ityr Ityr and leaden, ln ln, located on Chromosome 1, were crossed with BALB/c mice sensitive to S. typhimurium and non-leaden. In the F2 generation mice, ln always segregated with Ityr. The presence of only one leaden mouse sensitive to S. typhimurium out of sixty leaden F2 mice tested linked Ityr closely with ln on Chromosome 1. This result will be of use in further experiments with hybrid populations by enabling us to predetermine resistance or sensitivity to S. typhimurium without infecting the mice, so permitting experiments on the nature of the inheritance in unsensitized mice.


Antigenic competition between horse and sheep red blood cells as a hormone-dependent phenomenon. Various mechanisms for understanding antigenic competition have been proposed, such as macrophage availability, suppressor cells and their soluble products. In view of the regulatory function of some hormones on the immune system, the role of immunosuppressive adrenal corticosteroids in antigenic competition was investigated. When horse red blood cells (HRBC) were injected into rats a five-fold increase in corticosterone blood levels was measured by day 6 and a strong decrease was noted on day 11. In animals injected with HRBC and on day 6 with a second antigen (sheep red blood cells, SRBC), the corticosteroid level was high on day 11. Such high levels are immunosuppressive. To impede such increases in adrenal hormone levels, rats were adrenalectomized. Adrenalectomized or sham-operated animals receiving SRBC only showed no difference in plaque-forming cell (PFC) numbers. All sham-operated rats injected first with HRBC and 5 days later with SRBC showed the expected antigenic competition. Adrenalectomized rats also injected with both antigens sequentially had a five fold increase in number of PFC when compared with the sham-operated controls which had received both antigens. A detailed analysis of these data revealed that a proportion of adrenalectomized animals had PFC numbers within the normal range. In vitro, hydrocortisone enhances the response of spleen cells when only one antigen (SRBC) is present. Prior addition of the unrelated antigen (HRBC) impedes this enhancement. Thus, in a hydrocortisone-enriched culture medium, the presence of the first antigen can interfere with the immune response to the second unrelated antigen, mimicking in vitro a condition of antigenic competition. These findings indicate that hormones may have a role in antigenic competition.


Hepatitis B core antigen immune complexes in the liver of hepatitis B patients. Single liver biopsies from 102 clinically diagnosed hepatitis patients were examined by immunofluorescence for the presence of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg), complement and immunoglobulin deposition, and for their capacity to fix human complement in vitro. Of the sixty-five HBsAg positive livers, fifty-three were histologically diagnosed as chronic hepatitis, three as acute hepatitis, five as acute hepatitis with signs of transition to chronicity, and four as 'near normal liver'. In the group with chronic hepatitis, HGcAg was observed in thirty-nine livers, all of which also had HBsAg. Thirty-five of these thirty-nine cases also had the ability to fix complement in vitro in the hepatocyte nuclei and/or cytoplasm. Of these thirty-five cases, twenty-nine were positive for immunoglobulin deposition on the nuclei. All of these cases had antibody to HBcAg in the blood, but only five had anti-HBs. The frequency of in vitro complement fixation and immunoglobulin deposition was higher in active forms of the disease, such as chronic aggressive hepatitis and active cirrhosis, than in non-active disease such as chronic persistent hepatitis and mild cirrhosis. By the application of double fluorescent staining techniques, complement fixation was observed in some HBcAg-positive nuclei. In the 'near normal liver' cases there was no intrahepatic accumulation of HBcAg, and despite the presence of anti-HBc in the blood, in vitro complement fixation and immunoglobulin deposition were both absent. The group of three HBsAg ositive 'acute hepatitis with signs of transition to chronicity' cases behaved similarly to those with chronic aggressive hepatitis and had circulating anti-HBc, in vitro complement fixation and immunoglobulin deposition in the hepatocytes. None had circulating anti-HBs. In the group sith HBs-positive acute hepatitis, anti-HGc in the blood was the only other evidence of hepatitis B virus infection.


Human transfer factor in vitro. II. Augmentation of the secretion of leucocyte migration inhibitory factor (LIF) by leucocyte dialysate and by its components L-serine and glycine. The effect of human transfer factor (TF) or its components L-serine and/or glycine in tuberculin (PPD), or leucoagglutinin (LA) induced leucocyte migration inhibitory factor (LIF) secretion was studied. Augmentation of LIF secretion was seen with low concentration ( = 0.078 g/l) of TF when lymphocytes were cultured in minimum essential medium for suspension cultures (MEM-S), a culture medium lacking L-serine and glycine. High concentrations (0.3125-5.0 g/l dry weight) of TF were inhibitory in MEM-S. In RPMI 1640, a culture medium containing L-serine and glycine, TF was either inhibitory or had no effect. The combination of L-serine and glycine, at concentrations equivalent or lower than the optimum of TF, had an augmenting effect on LIF secretion identical to that of TF, but no inhibition at higher concentrations was seen. The results indicate that human TF contains components which have suppressive or augmenting effects on LIF secretion in vitro. The augmenting effect may be mainly due to L-serine and glycine and thus not related to TF's activity in vivo.


Immunochemical characteristics of antibodies to DNA in patients with active systemic lupus erythematosus. To investigate the suggestion that qualitative immunochemical characteristics of antibodies to DNA (anti-DNA) may be of importance in the pathogenesis of nephritis in systemic lupus erythematosus (SLE), we used the Crithidia luciliae (CL) immunofluorescence test to determine the titre, immunoglobulin (Ig) class and complement-fixing activity of anti-DNA in thirty-five patients with active SLE. Eighteen of these patients had active lupus nephritis (Group I) and the remaining seventeen had no clinical evidence of renal involvement (Group II). Anti-DNA was detected in twenty-eight patients, and was present more frequently and in higher titre (P less than 0.01) in Group I than in Group II. Anti-DNA of all three Ig classes studied (IgG, IgM and IgA) was present in twenty-three out of twenty-eight cases. The ratio of IgG to IgM anti-DNA did not differ in the two groups of patients. Complement-fixing antibodies were detected in thirteen patients in Group I and five patients in Group II. The titre of complement-fixing activity was strongly correlated with titre of anti-DNA. DNA-binding capacity was also determined in these by a millipore filter (MF) assay. A highly significant correlation between DNA binding by MF and CL was found in Group I patients, while no correlation was found in Group II patients. These findings suggest that (1) anti-DNA with specificity for determinants found in CL, presumably native DNA, are more highly correlated with the presence of active renal lupus than are antibodies directed toward other DNA determinants, and (2) the major characteristic of anti-DNA found to be associated with nephritis was quantity of antibody. Most patients had anti-DNA of all Ig classes regardless of the presence of renal disease. Complement-fixing activity of anti-DNA could not be related to the occurrence of renal disease independently of anti-DNA titre.


Viral infections and IgM autoantibodies to cytoplasmic intermediate filaments. Seventy-four out of 113 sera from patients with infectious hepatitis, chickenpox, measles and mumps reacted with both smooth muscle and cytoplasmic filaments in cultured fibroblasts and neuroblastoma. Five out of eighty-five control sera also reacted in this way. That the cytoplasmic structures are intermediate filaments was suggested by their rearrangement into coils of perinuclear filaments in colchicine- or vinblastine-treated fibroblasts, but not in cytochalasin B-treated cells. The idenity of these structures was confirmed by the demonstration that the same structures reacted with the post-viral sera and a rabbit and human anti-intermediate filament antibody. Immunoabsorption studies showed that twenty-seven out of thirty-two positive sera were neutralised by skeletin, the intermediate filament protein from smooth muscle. In all but one of the sera, the antibody was IgM. Antibody titres fell in the second specimen in eleven out of fourteen pairs of acute and convalescent sera. The association between viral infections and autoantibodies suggest that production of antibodies suggests that production of antibody to intermediate filaments may be initiated by viruses.


Detection and analysis of human granulocyte--monocyte precursors using semi-solid cultures. The in vitro cloning of haemopoietic precursors is a rapidly growing field. The data reviewed above and the current practical applications of the techniques can be expected to increase quite rapidly in the next decade. Despite the technical problems of tissue culture and the special problems associated with culturing human cells, it is clear that these procedures can be effectively applied at the clinical level. The value of the data obtained will vary directly with the quality of the culture techniques. Any centre undertaking these techniques must be prepared to properly equip the culture laboratory, appoint a full-time staff member for the work and maintain a constant surveillance of the quality of the culture work.


Regional muscle transposition for rehabilitation of the paralyzed face. Masseter and temporalis muscle transpositions may be considered in cases of longstanding facial paralysis and in the congenital absence of the facial nerve or muscles. The basic advantage of this technique is the introduction of a large volume of living and dynamic muscle into the face. Additional advantages include simplicity, the support provided, enhancement of the possibility of myoneurotization, and no loss of other significant function. In many instances, facial movement improves for a period of approximately two years, and the long-range effect would suggest some degree of rehabilitation of the facial muscles. Our combined experience with over 100 muscle transpositions indicates the efficacy and success of this technique in selected patients.


Nerve suture and grafting to restore the extratemporal facial nerve. A concept for dealing with extratemporal lesions of the facial nerve is based on cadaver studies performed by Meissl. In spite of plexiform arrangement and fiber exchange, areas and fascicle groups can be differentiated within the cross section of the facial nerve which contain a great percentage of the fibers supplying a certain muscle group. An attempt should be made to unite the corresponding parts by direct coaptation, or, if nerve defect exists, by nerve grafts.


Pharmacokinetics of antibiotics in pregnancy and labour. Few of the articles published on antibiotics and pregnancy are concerned with pharmacokinetics. It is particularly difficult to evaluate possible alterations in pharmacokinetic parameters that may be due to pregnancy. Most data available have been obtained in connection with abortion or delivery. Such data may not be representative for pregnancy as such. Marked changes in most organ systems, particularly in renal function, but in composition and amounts of body fluids as well, make it likely that several pharmacokinetic parameters change, possibly gradually as pregnancy progresses. Accumulated data for several beta-lactam antibiotics, and also for aminoglycosides indicate that antibiotics eliminated mainly by renal excretion will produce lower levels in serum or plasma in pregnant women than in other individuals. Also, the half-life of certain antibiotics in serum is shorter during pregnancy. Transplacental passage occurs for all antibiotics according to the physicochemical properties of the drug. Bolus injections to a pregnant woman are more efficient than continuous infusion in producing high levels of antibiotic in fetal serum and amniotic fluid. Fetal tissue levels are higher following multiple doses than after a single dose. Lower serum levels of antibiotics in pregnant women than in other individuals following the same dosage will be unsatisfactory as micr-organisms are less likely to be affected.


Clinical pharmacokinetics of local anaesthetics. The introduction of the new long acting local anaesthetics, bupivacaine and etidocaine, has stimulated an expansion of interest in regional anaesthesia, particularly for obstetrical applications and pain therapy.  System toxicity following injection of local anesthetics occurs albeit infrequently, and tentative correlations have been made between the onset of CNS and cardiovascular effects and circulating drug concentrations in both adults and neonates. Amongst other factors, interpretation of these relationships depends upon blood distribution and plasma binding of the agents, sampling sites and acid-base balance. The disposition kinetics and placental transfer of the amide type agents have been well characterised. In adults their clearance is almost entirely hepatic but in neonates an increase in the renal component is, in part, a reflection of the immaturity of some of the enzymes responsible for their metabolism. Ester type agents are rapidly hydrolysed by plasma pseudocholinesterase and this has led to a preference for chloroprocaine in some obstetric procedures. Major determinants of the systemic absorption of the agents after perineural administration include their physicochemical and vasoactive properties, perfusion and tissue binding at the site of injection and whether or not adrenaline has been added. In respect of blood drug concentrations achieved after various regional anaesthetic procedures, the margin of systemic safety appears to favour bupivacaine and etidocaine compared to shorter acting analogues such as lignocaine and mepivacaine. The time course of local anaesthetic remaining at the site of injection has been calculated following intravenous regional anaesthesia and peridural block. This has allowed prediction of the local and systemic accumulation of the drugs following contined dosage. Blood concentrations of local anaesthetics after perineural injection are not closely related to age, weight or pregnancy but may be influenced by diseases associated with haemodynamic changes and by other drugs given at or around the time of regional blockade.


A computer program for the morphometric analysis of cell profiles. A computer program which yields values for the volumes, surface areas, and volume/surface area ratios of cell profiles is described for use on a desktop calculator (minicomputer). This program uses standard morphometric procedures, and incorporates data obtained from electron micrographs at two levels of sampling. The main program yields values for the 'average cell volume' at the tissue level of sampling. Two options at the cellular level of sampling are also included which yield values for the volumes, surface areas and volume/surface area ratios for the organelles. The first option allows an analysis of 'whole cells' containing equatorial profiles through the nucleus, while the second option permits a 'fractional' approach using segments of the cells. Finally, some of the advantages of the two options are discussed.


Software development of the EMI head scanner. A method has been developed to run the general purpose operating system RDOS on the same disc of the head scanner computer as is used for scanner software and data. This made it possible to develop additional software in high level programming language for image processing, based on original image data on the disc. All new images produced by the program are stored on the disc in the same format as the original images. This makes it possible to handle processed images exactly as the original ones and to do multiple operations. The following processing has been included in the program so far: subtraction, smoothing, density profiles, vertical reconstructions, magnification and labelling. A set of operator commands has been developed which are very similar to the ordinary commands for the scanner, which makes the program to appear being a direct extension of the standard scanner software.


A three-year clinical trial with levonorgestrel silastic implants. Silastic implants containing the progestin, levonorgestrel, were tested as long-term contraceptives in 101 women. After three full years of exposure and 2,998 woman-months of use, no pregnancies had occurred. The continuation rates were 87% at 12 months, 79% at 24 months and 66% at 36 months. The most important side effect was excessive or irregular bleeding during the first year. No treatment was offered for this side effect other than vitamins and iron or change of method, with the exception of 3 cases where ethinyl estradiol was used one time for 2 weeks each. Bleeding disturbances led 8 patients to ask for removal of implants. Other side effects were headache, acne and lower abdominal pain. Blood and urine analysis tested 17 different parameters and all but plasma cortisol remained within normal limits throughout the study. A general tendency toward lowered cortisol values was observed and two subjects had more than one value below the normal limit for the population during the study. Glucose tolerance tests during the second year were abnormal in two women with familial diabetes but they returned to normal values spontaneously at the next test. It is concluded that levonorgestrel implants offer effective protection against pregnancy during the first three years of continuous use. Their acceptability and few side effects justify larger trials, especially if treatment of bleeding irregularities is introduced.


Cirrhotic hyperglobulinemia: increased rates of immunoglobulin synthesis by circulating lymphoid cells. We have measured immunoglobulin (Ig) synthesis by circulating lymphoid cells of 20 patients with cirrhotic hyperglobulinemia (CH) and 20 age-matched controls. We used specific anti-Ig antisera to precipitate Ig synthesized from [14C] amino acid precursors in 13 controls and employed an electroimmunoassay of the "rocket" type to measure Ig elaborated by cultured cells in 4 patient-control pairs. In addition, we studied 3 patient-control pairs by absorption of elaborated Ig onto an anti-Ig-coated solid phase, bromoacetylcellulose. The synthetic index (SI; the ratio of Ig synthesis by a CH patient and a control) was elevated in every case. Mean SI by coprecipitation was 7.2 +/- 5.4 (mean +/- SD), by rocket" 7.3 +/- 3.0 for IgG and 2.2 +/- 0.8 for IgA, and by immunoabsorption 13.8 +/- 8.4 for IgG. Three cirrhotic nonhyperglobulinemic patient-control pairs showed a mean SI of 1.0 +/- 0.1. CH and control populations showed equal numbers of membrane Ig-positive B lymphocytes by immunofluorescence. We conclude that (1) peripheral blood lymphoid cells are appropriate for study of differences in Ig synthetic capacity among individuals; (2) CH is associated with increased in vitro Ig synthesis; and (3) CH lymphocytes may be an appropriate cell population for the study of control mechanisms in Ig synthesis.


Metoclopramide therapy in patients with delayed gastric emptying: a randomized, double-blind study. Twenty-eight patients with delayed gastric emptying as measured by an abnormal barium "burger" were treated with metoclopramide in a randomized, double-blind fashion. Five had diabetic gastroparesis, four had undergone vagotomy and pyloroplasty, and 19 were idiopathic. Patients received either metoclopramide or placebo for a three-week period and symptoms were scored prestudy, at weekly intervals, and at termination of the study. Ten of 17 patients on metoclopramide and four of 14 on placebo decreased their symptom score to a level below entry criteria, indicating a significant metoclopramide effect when compared to placebo. The mean total sumptom score for the metoclopramide group was 18.4 prestudy and 7.2 poststudy while for placebo was 19.1 prestudy and 12.9 poststudy. Although improvement on placebo was significant, these patients were still symptomatic. The improvement on metoclopramide was significantly greater than the improvement on placebo. Metoclopramide is an effective agent in treating the symptom complex of delayed gastric emptying.


Randomized double-masked trial of sodium oxyferriscorbone for the treatment of gastric ulcers. A double-blind 4-week trial of sodium oxyferriscorbone versus placebo (distilled water) was conducted in 46 outpatients with endoscopically confirmed gastric ulcer. Ulcer healing occurred in 15 of 20 patients receiving sodium oxyferriscorbone (75%) and in 7 of 20 patients receiving placebo (35%). Patients receiving sodium oxyferriscorbone experienced less pain and required less antacid than those receiving placebo (P less than 0.05). Side effects were reported in 12 patients, 7 while receiving sodium oxyferriscorbone and 5 while receiving placebo. Six patients did not complete the study due to ulcer complications. Routine laboratory tests revealed no persistent abnormalities that could be related to the treatment. Five placebo-treated patients that were therapeutic failures were switched to sodium oxyferriscorbone and healing was observed within 3 weeks. It is concluded that sodium oxyferriscorbone is effective in enhancing healing of gastric ulcers.


Contribution of environmental factors to variability in human drug metabolism. Drug metabolism in 96 London factory and office workers has been studied after simultaneous single doses of antipyrine (phenazone) and paracetamol (acetaminophen). Metabolic clearance of both drugs was significantly greater in subjects eating meat more than once a week than in those who ate meat less frequently. The precise contribution of diet could not be clearly defined since 90% of "meat-eaters" were European while all except one of the "vegetarians" were Asian. Clearance of both drugs increased with both alcohol and cigarette consumption. Regular intake of coffee and/or tea had a similar effect but, in the case of paracetamol, this did not attain statistical significance. Antipyrine clearance was lower among women who took the oral contraceptive pill than among those who did not, while paracetamol clearance was not significantly different. These findings may have implications for the use of drugs which are administered regularly in order to achieve steady-state plasma and tissue concentrations.


Influence of cigarette smoking on drug metabolism in man. The pervasiveness of tobacco use in our society and the frequency of altered disposition of many common therapeutic and recreational drugs in smokers makes it apparent that the smoking habit should be considered as one of the primary sources of drug interactions in man. Each scientific report dealing with drug disposition should list the smoking status of the subjects studied as smoking should be included as a basic characteristic of each subject along with age, race, body weight, and presence and type of disease. Most of the experimental work in human and animal systems indicates that the dominant effect of smoking is enhanced disposition caused by induction of hepatic microsomal enzymes. The primary causal agents are probably the polynuclear aromatic hydrocarbons which are potent and persistent in tissues. There are numerous examples of both an increased metabolism rate and absence of an effect of smoking on drug disposition in man. This selectivity is consistent with the known inductive effects of P-448 stimulators in animal systems. Studies with theophylline have demonstrated that both tobacco and marijuana markedly alter its clearance in man. However, smoking is only one of numerous factors which can perturb hepatic biotransformation as patient surveillance studies show that age and cardiac and liver disease may be of greater importance in actual patients undergoing therapy.


Penfluridol: a neuroleptic drug designed for long duration of action. 1. Penfluridol is a unique, long-acting, oral neuroleptic belonging to the diphenylbutylpiperidines. The synthesis of penfluridol represented the result of a well-planned scientific search for a highly lipophilic compound structurally related to haloperidol and pimozide. 2. Because of its unusual lipophilicity, penfluridol distributes extensively in fatty tissues following oral administration. This depot effect produces a very slow release of drug from the tissues, and results in a very long duration of activity. 3. Penfluridol is extensively metabolized by oxidative N-dealkylation to afford, as isolated metabolites, the beta-glucuronide conjugate of the diphenylbutyric acid derivative A1 and the unconjugated basic piperidine moiety B1. It is assumed, at this time, that the pharmacological activity is attributable to the parent compound. 4. When administered clinically at oral doses of 20 to 100 mg/week, penfluridol has been found to be an effective antipsychotic agent. This frequency of dosing is consistent with the pharmacokinetic behavior of the drug in man, and does not appear to result in any inappropriate accumulation of the drug in patients. Wide variations in steady-state levels and plasma elimination half-life have been observed in patient populations.