Successful transplantation of the thymus in Nezelof's syndrome. A 6-month-old girl with congenital thymic dysplasia or Nezelof's syndrome (lack of T cell function and normal levels of immunoglobulins) was given a transplant of a human thymus gland from a 14-week-old fetus and is surviving 36 months after transplant. Her clinical condition is the principal index of the success of the transplant since most in vitro and in vivo data indicate a full immunologic restoration has not been achieved. However, the number of E-rosettes in the peripheral blood has increased, the number of surface immunoglobulin-bearing cells has decreased, but there is little improvement in mitogen responsitivity. Immunoglobulin levels have increased with age, but there is no demonstrable specific antibody activity. Nevertheless, she remains free of infection, living in an unprotected environment.


Existence of a sodium current in the tubular membrane of frog twitch muscle fibre; its possible role in the activation of contraction. 1. The membrane current of frog twitch muscle fibre has been recorded together with contraction in the test gap of a double sucrose gap apparatus. 2. In Ringer, the inward current sometimes shows 2 phases with the same threshold and the same reversal potential: a rapid one (early inward current) and a slower one (late inward current). The mechanical threshold is near the inward current threshold. The amplitude of the contraction increases progressively with depolarizations, without modification of its time to peak. Experiments with variation of the pulse duration and with conditioning depolarization show that a part of the contraction seems to be correlated with the late inward current. 3. Experiments in a sodium free solution, with low TTX concentration, and on glycerol treated fibres show that the late inward current corresponds to a tubular sodium current. 4. A method is described to separate the two phases of inward current. The smooth development of the current-voltage relation of the late inward current, its diminution without modification in time to peak under the action of TTX, and the exponential decay of its tail current all suggest that the tubular membrane potential is sufficiently well controlled. 5. In the experiments where the tubular membrane potential seems to be controlled, a part of the contraction depends on the tubular sodium current, perhaps involving a mechanism of sodium induced calcium release.


[Upper gastrointestinal bleeding: comparison between the diagnostic conclusions of emergency fibroscopy and those of surgery (author's transl)]. Amongst 1035 patients who underwent oesophago-gastro-duodenal fibroscopy as an emergency for an upper gastrointestinal haemorrhage between January 1973 and May 1977, 100 required surgery. The operative findings were compared with those of endoscopy. In 92 cases, surgical exploration found the same lesions that the endoscopist had reported as being responsible for the haemorrhage. In 14 of these patients, surgical exploration provided complementary data to the endoscopic findings. In the other 8 patients, there was disagreement between the surgical and endoscopic findings. In particular, there were 5 diagnostic errors: 2 false negatives, 1 error of localisation of the lesion and 2 errors of interpretation. The earlier endoscopy is performed, the better are the results: discovery of the bleeding lesion and elimination of other non-haemorrhagic lesions.


[Pan-lobular emphysema: relationship with serum alpha-1-antitrypsin levels, Pi phenotype and the HLA system (author's transl)]. Pi phenotypes have been studied in a group of 433 patients. Patients with panacinar emphysema and/or bullae were identified from careful analysis of their clinical, physiological, radiological and anatomical characteristics. Twenty-five p.cent of the emphysematous patients were MZ; there was no significant difference in the alpha-1-antitrypsin plasmatic levels between the groups. The HLA antigens were studied in order to try to identify the possible cofactors in the development of emphysema. The role of occupational pollutants and/or of tobacco is discussed. The frequency of the MZ phenotype in our series differs from previous publications. This discrepancy is discussed on the basis of the criterious used to identify the emphysematous patients.


[Pulmonary emphysema and hepatic involvement by alpha-1 antitrypsin deficiency in two adults with a PiZ phenotype (author's transl)]. Two unreleated adult males were found to be suffering from an association of pan-lobular severe emphysema and hepatomegally of unknown origin which led to the discovery of a marked deficit in alpha-1 antitrypsin (A1-AT) in relation to a PiZ phenotype. Liver biopsy revealed cirrhosis with portal fibrosis in one case and in both cases fatty infiltration with the accumulation of a glycoprotein antigenically identical to A1-AT. Electron microscopy showed this protein to be situated within the dilated lumina of the endoplasmic reticulum of the hepatocytes. A1-AT deficiency is usually associated with pulmonary involvement only in the adult and liver involvement only in the child. The association of the two remains rare--hence the interest of the two cases reported.


[The pathogenesis of psoriasis : realities and hypotheses (author's transl)]. Our pathogenic pattern, may be summarised in 7 propositions : - psoriasis is a proliferative disease of the epidermis. - the increased mitotic activity is related to imbalance of cyclic nucleotides and of prostaglandins. - this imbalance may be explained by abnormalities of the membranes of the keratinocytes. - this alteration in cell membranes results from immunological phenomena located in psoriatic epidermis. - the disturbance of immunity with production of auto-antibodies may be related to a deficiency in a sub-population of thymus-dependent lymphocytes. - this cyclic deficiency could be due to a viral agent whose penetration and persistence in the body would be dependent upon multiple genetic factors. - numerous external factors may act upon the various steps of this pathogenic chain, to worsen a pre-existent imbalance and precipitate the development of the lesions.


[Targets and mechanisms of levamisole-induced immunostimulation (author's transl)]. Levamisole modify the functions of neutrophils, of macrophages and of T-cells in normal, healthy men and animals. Hormone-like products are synthetized after levamisole administration, even in athymic mice, to recruit T cells from precommitted precursor cells and to activate mature T cells. Levamisole-induced immunostimulation is associated with activities of its sulphur moiety more than with cholinergic properties of the imidazole moiety. Levamisole activities are modulated by genetic and environmental factors and by the degree of antigenic stimulus. Immunostimulation by levamisole depends upon individual responsiveness. Practical usefulness of levamisole therapy will be optimal if acquired experimental findings are taken in account to determine the schedules of treatment.


Extracellular nucleases of pseudomonas BAL 31. III. Use of the double-strand deoxyriboexonuclease activity as the basis of a convenient method for the mapping of fragments of DNA produced by cleavage with restriction enzymes. We have previously characterized an extracellular nuclease from Pseudomonas BAL 31 which, in addition to other activities, displays a double-strand exonuclease activity which progressively shortens both strands of linear duplex DNA molecules from both termini. This degradation is accomplished without the introduction of detectable scissions away from the ends of the duplexes. When this nuclease is used to produce a series of progressively shortened samples from a linear duplex DNA, subsequent digestion of these samples with a site-specific restriction endonuclease and analysis of the resulting fragments by gel electrophoresis permits the rapid establishment of the order of the restriction enzyme fragments through the entire genome. This is accomplished by noting from the electropherograms the order in which the various restriction enzyme fragments become noticeably shortened or disappear. Using this method, the five cleavage sites for the endonuclease Hpa I and the single cleavage sites for the nucleases Hpa II and Pst I have been mapped in PM2 bacteriophage DNA. In a more stringent test of the method, 18 of the 24 fragments produced by cleavage of coliphage lambdab2b5c DNA with the Pst I nuclease have been mapped, and five of the six remaining fragments have been assigned to small regions of the genome.


Possible prevention and treatment of steroid-induced osteoporosis. Patients with steroid-induced, juvenile and senile osteoporosis were studied using balance techniques. The changes in calciun and phosphorus balance associated with glucocorticoid therapy were corrected with vitamin D and bendrofluazide given in combination. No hypercalcaemia occurred in osteoporotic patients who continued to receive glucocorticoids. Calcium and phosphorus balance was also improved in the osteoporotic subjects not receiving steroids, but these patients became hypercalcaemic during treatment. It is suggested that vitamin D, bendrofluazide and steroids antagonize the actions of one another on the renal tubule, gut and bone and in this way prevent the increased calciuria which occurs with glucocorticoid therapy. Since the increased calciuria and negative calcium balance induced by glucocorticoids is considered to be the result of excessive bone resorption, an adequate dose of bendrofluazide and vitamin D in combination might prevent the development of, or even reverse, steroid-induced osteoporosis.


Molecular mechanism of mitogen action: processing of receptor induced by epidermal growth factor. An affinity labeling technique used previously for identification of a membrane receptor for epidermal growth factor (EGF) was exploited to investigate the physiological fate of receptor after binding of EGF. Incubation of affinity-labeled cells at 37 degrees resulted in a time-dependent loss of radioactivity from the EGF-receptor covalent complex (M(r) 190,000). Ninety percent of the radioactivity lost from the band of M(r) 190,000 during a 1-hr incubation at 37 degrees appeared in three bands of M(r) 62,000, 47,000, and 37,000. The crosslinked EGF-receptor complex (M(r) 190,000) on intact cells was accessible to the action of trypsin at 4 degrees and cofractionated with the plasmalemmal fraction. The proteolytic processing products of receptor were inaccessible to trypsin and banded with the lysosomal fraction upon subcellular fractionation. The rate of internalization and proteolytic processing of radiolabeled receptor was the same as the rate of reduction of binding activity induced by EGF. A study of the relationship between EGF-induced receptor internalization and processing, and stimulation of DNA synthesis, showed that both these processes were half-maximally stimulated at approximately 0.1 nM EGF, a concentration at which only 10% of the receptor sites are occupied. These data indicate that at concentrations of EGF subsaturating for binding but optimal for biological activity, there is a slow, continuous process of receptor internalization and degradation which could be limiting for EGF-induced mitogenesis.


Direct visualization of binding, aggregation, and internalization of insulin and epidermal growth factor on living fibroblastic cells. We have studied in detail the binding of fluorescent derivatives of insulin and epidermal growth factor to 3T3 fibroblasts. We have used two types of fluorescent analogues of insulin and epidermal growth factor: highly fluorescent derivatives which have seven to eight rhodamine molecules or fluorescent derivatives which have a single rhodamine molecule per one molecule of insulin or epidermal growth factor. Both types of analogue retained substantial binding affinity as determined by radioreceptor assays and biological activity. The cells labeled with the fluorescent analogues were visualized with a sensitive video intensification microscopic system that enabled us to directly observe the location of the fluorescent hormone on the surface and within the living fibroblasts. We found that both insulin and epidermal growth factor initially bound diffusely to the cell surface and, at 4 degrees , remained dispersed. Within a few minutes at 23 degrees or 37 degrees the hormone-receptor complexes aggregated into patches that could be readily removed by trypsin but not by excess native hormone. The hormone-receptor complexes, which were initially mobile in the plane of the membrane, become immobilized later as the consequence of the receptor aggregation or internalization. Within approximately 30 min at 37 degrees , much of the labeled hormone was found within the cell in endocytic vesicles that moved about in the cytoplasm in a saltatory manner. The aggregation and immobilization of the hormone-receptor complexes could be due to either hormone-hormone interactions on the cell membrane or a hormone-induced conformational change in the hormone-receptor complex. Aggregation and internalization of hormone-receptor complexes could be associated with certain aspects of hormone action, hormone degradation, down regulation of receptors, or negative cooperativity of hormone binding.


Regulation of antibody heterogeneity by suppressor T cells: diminishing suppressor T cell activity increases the number of dinitrophenyl clones in mice immunized with dinitrophenyl-poly(Glu,Lys,Phe) or dinitrophenyl-poly(Glu,Lys,Ala). The anti-hapten responses to the dinitrophenyl (Dnp) conjugate of the random linear terpolymers poly(L-Glu,LLys,LPhe), GLphi, or poly(LGlu,LLys,LAla), GLA, are of highly restricted heterogeneity. Thus, individual mice of most responder strains express an average of two to four anti-Dnp clones to Dnp-GLphi or Dnp-GLA, as measured by isoelectric focusing techniques. To explore whether suppressor T cells regulate the heterogeneity of the anti-hapten response to Dnp conjugates of these polypeptides, various procedures aimed at reducing suppressor T-cell activity were tested for their ability to alter the restricted isoelectric focusing spectrotypes. These procedures, such as adult thymectomy, administration of low doses of cyclophosphamide, and in vivo treatment with anti-I-J antisera, significantly increased the magnitude and heterogeneity of the anti-Dnp antibody response to Dnp-GLphi and Dnp-GLA in strains of mice that possessed responder Ir genes. Such methods failed to alter the nonresponder status of mice that lacked the appropriate Ir genes. Thus, in systems under Ir gene control suppressor T-cell mechanisms appear to be involved in the regulation of the heterogeneity of hapten-specific B-cell responses.


Decamethonium both opens and blocks endplate channels. Miniature endplate currents, endplate current fluctuations ("membrane noise"), and voltage-jump current relaxations were studied in voltage-clamped frog muscle fibers during decamethonium action. All three types of experiments revealed two kinetic processes controlling the opening of endplate channels, one that reflects agonist action and another that reflects local anesthetic-like blocking activity. The kinetic constants for these two steps were evaluated from measurements of the fast and slow time constants as a function of decamethonium concentration. At -130 mV membrane potential and 13 degrees, the mean open time of decamethonium-activated channels is 2.8 msec. The forward and backward rate constants for channel blocking are 1.7 X 10(7) M-1 sec-1 and 10(3) sec-1. The voltage dependencies of the channel lifetime and of the blocking equilibrium are similar to those seen with pure agonists and local anesthetics, respectively.


Computed tomography in craniopharyngiomas. Computed tomographic examinations of 28 children and 12 adults with surgically proved craniopharyngiomas were retrospectively studied for characteristic findings that might be diagnostic of this tumor. It was found that 8 of 10 children and 2 of 4 adults examined pre-operatively had at least 2 of 3 findings: calcification, cyst, or contrast enhancement on CT. The remaining pre-operative patients did not receive contrast in their initial exams. Unusual presentation of the tumor in adults is also discussed.


Extravasation of contrast material from vascular ectasia of the cecum detected with 99mTc-pertechnetate. A case of vascular ectasia of the cecum is presented. The isotopic pattern did not differ from that of Meckel's diverticulum. The authors suggest that studies with 99mTc may be helpful in screening for areas of pathology in cases of lower gastrointestinal bleeding.


Transcatheter embolization for treatment of Mallory-Weiss tears of the esophagogastric junction. Five patients with Mallory-Weiss tears of the esophagus and massive uncontrolled upper gastrointestinal bleeding were treated by Gelfoam embolization of the left gastric artery. Four of the five required no further therapy. In one case permanent hemostasis was not achieved due to extension of the tear to branches of the inferior phrenic artery. Since Mallory-Weiss tears are usually self-healing, embolization is potentially the primary treatment modality. Surgery can be reserved for treatment of transmural perforation or recurrent bleeding.


The transjugular technique of hepatic venography and biopsy, cholangiography, and obliteration of esophageal varices. The transjugular technique facilitates various diagnostic and therapeutic procedures in the liver. Even in patients with defective hemostasis, severe ascites, or marked obesity, liver biopsy or cholangiography can be performed with relative safety. It also provides an alternative route for entry into the portal system.


An angiographic study of the temporal horn. The anatomy of the posterior cerebral artery (PCA) and its branches is described. On the vertebral angiogram, displacement of these vessels is a sign of corresponding displacement of the temporal horn, which in turn is an indication of a mass involving the temporal lobe, diencephalon, or midbrain. Specific angiographic criteria for localization of the temporal horn include (a) the position of the lateral choroid artery (LCA) as it runs within the choroidal fissure; (b) the temporal branches of the PCA as they cross the parahippocampal gyrus and pass into the collateral sulcus; and (c) the crural and ambient segments of the PCA as they pass around the midbrain.


Metrizamide ventriculography and computed tomography in lesions about the third ventricle. Metrizamide ventriculography was used in 24 patients with suspected lesions in and near the third ventricle. The diagnoses were aqueduct stenosis (6), upper brain stem expansions (5), third ventricular tumors (6), craniopharyngiomas (2), subarachnoid cyst (1) and normal (1). Computed tomography was used as the guide to predict the likely causes of obstruction and to determine if ventricular shunting was appropriate before or after ventriculography. Several cases required pneumoencephalography in combination with ventriculography in order to determine whether an upper brain stem lesion was intrinsic or extrinsic.


The effects of DL-5-hydroxytryptophan on ethanol consumption by rats. Rats were offered access to either distilled water or a 12% v/v solution of ethanol as their only fluid during a one hour period daily. After daily fluid consumption has achieved a stable baseline, either distilled water or DL-5-hydroxytryptophan (5HTP) in doses of 50, 100 or 200 mg/kg was injected intraperitoneally one hour prior to the drinking session. While each of the three doses of 5HTP caused a significant reduction in ethanol intake, distilled water had no effect. Water consumption was unaffected by 5HTP or distilled water injections. Varying the pretreatment interval from 0.5, 1, 4 to 8 hours for the 100 mg/kg 5HTP dose resulted in a significant decrease in ethanol consumption at 0.5 and 1 hour pretreatment intervals only. In approximately 25% of the rats tested, 5HTP resulted in a prolonged rejection of ethanol so severe that it resulted in death. Selected rats offered water during this ethanol rejection period readily drank it and survived.


The effect of temperature on cutaneous CO2, loss and conductance in the bullfrog. Cutaneous and pulmonary CO2 loss were measured simultaneously in bullfrogs, Rana catesbeiana, at either 10, 20 or 30 degrees C. Arterial blood samples were taken in each experiment and analysed for [H+] and total plasma [CO2]. These values were used to calculate Pa(CO2) by means of the Henderson-Hasselbalch equation. Both [H+] and Pa(CO2) increased with temperature as previously observed. Skin CO2 loss was measured using a titration method. (At 30 degrees C it was necessary to add calcium hypochlorite (5-9 ppm) to block bacterial growth and respiration). Skin CO2 loss rose with temperature but the mean fraction of the total CO2 lost by this route decreased from about 50% at 10 degrees C to less than a third at 30 degrees C. At each temperature, over 90% of an incremental increase in total CO2 loss was excreted via the lungs while skin loss was relatively constant over a wide range of total loss values. The increase in skin CO2 loss with temperature corresponded to a proportional increase in the estimated transcutaneous P(CO2) difference. (This difference was assumed to equal Pa(CO2) minus ambient P(CO2.) Consequently, the skin CO2 conductance (skin CO2 loss/transcutaneous P(CO2) was not significantly influenced by temperature. This apparent temperature independence of skin CO2 conductance may be important for acid-base regulation of skin breathers in response to temperature change.


Urinary excretion of porphyrins in two cases of porphyria cutanea tarda during a period of various treatments. The urinary excretion of porphyrins in two cases of porphyria cutanea tarda (PCT) has been followed during a period in which various treatments have been tried. In one patient pyridoxal-5-phosphate (P-5-P) injections lead to a dramatic increase in porphyrin excretion. In another P-5-P treatment was followed by a significant decrease in porphyrin excretion. p-Aminobenzoic acid (PABA) apparently had no effect on porphyrin excretion, while repeated phlebotomies had the expected effect. In both patients all variations in the total amount of porphyrins excreted were almost exclusively due to the variations in the amounts of heptacarboxylic porphyrin type III and uroporphyrin I. A secondary finding was an increase in hexa- and penta-carboxylic porphyrins type III without a concomitant increase in coproporphyrin III.


Coexistence of haemophilia A and von Willebrand's disease in the same kindred. A clinical and laboratory investigation of a kindred in which haemophilia A and autosomal recessive von Willebrand's disease (VWD) were concomitantly present is described. 3 male patients were shown to be hemizygotes for moderate haemophilia A, one female appeared to be haemophilia A carrier and 3 males showed laboratory findings consistent with heterozygosity for autosomal recessive VWD. In one woman, the pedigree and laboratory findings suggest the possibility of double heterozygosity.


Sequential changes in T and B lymphocyte responses to Herpes simplex virus in man. Lymphocytes of seven patients with primary herpetic infection, twenty-three patients with recurrent herpes labialis and of nineteen control subjects were separated into T and B enriched cells by the use of nylon wool columns. In the absence of a herpetic infection the thymidine incorporation and macrophage migration inhibition responses to herpes simplex virus (HSV), Candida albicans and PPD, and the thymidine incorporation induced by PHA were functions of T cells. When a herpetic infection was present, the unfractionated lymphocyte response to HSV was increased, as measured by thymidine incorporation, but the T cell response was unchanged. However, T cells did show an increased response to HSV when prepared by elimination of cells forming rosettes with zymosan-complement. T cells of some patients were stimulated by contact with zymosan, and this correlated with the response to C. albicans. It is suggested that lymphocyte responses to HSV in man are mediated by T cells, but that these cells are specifically retained by nylon wool columns at the time of a herpetic infection. This may be associated with acquisition of an Fc receptor by the sensitized T cells.


The recovery of mice from influenza virus infection: adoptive transfer of immunity with immune T lymphocytes. Transfer of primary or secondary influenza-immune spleen cells to mice infected intranasally with influenza virus resulted in a significant clearance of virus from the lungs and the protection of the recipients from death. The antiviral activity was associated only with intact, viable cells and was not due to carryover of virus. The effector cell population responsible for the antiviral effect was shown to be T cells. Thus, the removal of adherent, phagocytic and Ig+ cells did not affect the antiviral activity, whereas it was destroyed with antitheta serum and complement. Antiviral activity was specific and was best expressed if the virus used to infect the recipients and to generate immune cells was the same strain. Further work will be necessary to define rigorously the role of different viral antigens in cell-mediated immune response to influenza virus infection.


Immunological and functional characteristics of peripheral blood and synovial fluid lymphocytes from patients with rheumatoid arthritis. Spontaneous (SCMC) and antibody dependent cellular cytotoxicity (ADCC); mitogenic responsiveness (PHA, Con A, PPD, dextran and pokeweed) as well as lymphocyte subpopulations (E-, EA-, EAC-rosettes, S-Ig) were studied simultaneously in peripheral blood (PBL) and synovial fluid lymphocytes (SFL) of fifteen patients with rheumatoid arthritis. Marked differences were observed in the cytotoxic activity of SFL and PBL. Whereas SCMC activity of SFL was always significantly elevated above the cytotoxic levels of PBL, the reverse was true for the ADCC reaction; here, 50% of the patients showed a decreased cytotoxicity of SFL compared to PBL. Synovial fluid neutrophils (SFN) were found to be inactive in both cytotoxic assays. No differences were found in ADCC activity of PBL between normal controls and RA patients. In SCMC assays a significantly increased activity of control PBL was only observed at L/T ratios of 100:1. Overnight incubation of PBL from RA patients and normal controls resulted in a marked decrease in SCMC and, to a smaller extent, in ADCC activity. SFL from three out of four patients lost less SCMC activity after overnight incubation than the corresponding PBL. In one patient even an increased activity in both cytotoxic systems was obtained. Regarding lymphocyte populations, T-cells were significantly decreased in PBL of RA patients. With the exception of a significantly lowered percentage of C3 receptor positive cells in SFL, no significant differences were recorded in the lymphocyte distribution between the patients' PBL and SFL. In the RA patients, the response to T-cell mitogens was significantly depressed in SFL while PPD and pokeweed reactivity was equal to that of PBL.


Isolated retinas synthesize visual pigments from tetinol congeners delivered by liposomes. Isolated vertebrate retinas bathed in circulating Ringer solution cannot regenerate all of their bleached visual pigments. When dioleoyl-lecithin vesicles containing certain retinol congeners are added to the Ringer solution, such retinas begin to regenerate pigment immediately. The visual pigment of a bleached perfused retina can now be restored fully, making the isolated retina an independent unit for study. Loposomes can protect oxygen-sensitive, lipid-soluble substances and deliver them to living cells.


Analysis of adenosine-mediated pyrimidine starvation using cultured wild-type and mutant mouse T-lymphoma cells. Using the S49 T-cell lymphoma system for the study of immunodeficiency diseases, we characterized several variants in purine salvage and transport pathways and studied their responses to the cytotoxic action of adenosine (5-20 micron) in the presence of adenosine deaminase (ADA) inhibitors. Both an adenosine transport deficient mutant and a mutant lacking adenosine (ado) kinase activity are resistant to the cytotoxic effects of adenosine up to 15 micron. Variants lacking hypoxanthine-guanine phosphoribosyl transferase or adenine phosphoribosyltransferase are sensitive to the killing action of adenosine. We monitored the intracellular concentrations of purine and pyrimidine nucleotides, orotate, and PPriboseP in mutant and wild-type cells following the addition of adenosine and an ADA inhibitor. We conclude that at low concentrations, adenosine must be phosphorylated to deplete the cell of pyrimidine nucleotides and PPriboseP and to promote the accumulation of orotate. These alterations account for one mechanism of adenosine toxicity.


Humoral immunity in experimental hyposplenism. The immune response to an intravenous bolus of sheep erythrocytes, a large particulate antigen, was examined in weanling Sprague-Dawley rats after varying reduction in spleen size by splenic artery ligation (SAL) or partial amputation (pSx), and the results were compared with splenectomized (Sx) and sham-operated controls. Whereas SAL and pSx rats both produced higher 5 day (primary response) hemolysin antibody titers (P less than 0.001) than Sx rats, levels were lower (P less than 0.05) than in sham-operated rats with larger spleens (P less than 0.001). A similar heterophile pattern was seen in SAL rats at 22 days (secondary response). Within each group there was a positive correlation between splenic weight and serum hemolysin titer (r greater than 0.81) (P less than 0.001). Whereas spleen weight of sham-operated rats increased only 58%, splenic remnants in pSx rats enlarged 139% to 412%, with the greatest percentage of growth in the smallest remnants (25 mg) and the least in the largest remnants (200 mg). These data demonstrate a measurable immunologic advantage of splenic remnants (hyposplenism) over asplenism. This difference, although suboptimal as compared with that of a whole spleen (eusplenism), nonetheless may bolster body defenses to certain forms of bacterial sepsis.


Primary lymphoproliferative conditions of lung. The clinical, laboratory, and pathological features of six primary lymphoproliferative conditions of the lung are described. These comprise two patients with malignant lymphomas, one with pseudolymphoma, one with lymphoid interstitial pneumonia (LIP), one with lymphomatoid granulomatosis, and one with plasma cell granuloma. We recommend that the term 'premalignant lymphoma' be used for pseudolymphoma since the condition, although tending to remain localised, has a malignant potential. A combination of dyspnoea, cough, and pyrexia were the presenting features in our cases of premalignant and malignant lymphoma although they may often be discovered accidentally by chest radiography. The patient with LIP presented with the usual symptoms of dyspnoea and cough. The initial manifestations of the patient with lymphomatoid granulomatosis were skin radh and peripheral neuropathy nine months before the pulmonary symptoms, a not unusual occurrence. Plasma cell granuloma is often asymptomatic but our patient presented with cough, chest pain, haemoptysis. Premalignant lymphoma tends to pursue a benign course although exceptionally it may become disseminated. Malignant lymphoma may remain localised for many years but a significant proportion metastasise. Lymphomatoid granulomatosis and LIP have a varied course but both may terminate in malignant lymphoma. Plasma cell granuloma is always benign. The interrelationships of these conditions and their differential diagnosis are discussed.


A double-antibody radioimmunoassay for serum progesterone using progesterone-3-(O-carboxymethyl) oximino-[125I]-iodo-histamine as radioligand. A reliable, convenient and economical radioimmunoassay (RIA) for serum progesterone has been established and tested. This procedure employs diethyl ether extraction followed by RIA utilizing rabbit anti-11 alpha-hydroxyprogesterone 11-hemisuccinyl-bovine serum albumin (progesterone-11 alpha-BSA) serum, progresterone-3-(O-carboxymethyl) oximino-[125I]-iodohistamine (progesterone-3-[125I]) as radioligand and goat anti-rabbit gamma globulin as second antibody. In conjunction with antiprogesterone-11 alpha-BSA serum, the overall assay specificity of the progesterone-3-[125I] RIA is similar to that of the [3H]-progesterone method using dextran-coated charcoal. The results of serum progesterone measurements during the menstrual cycle obtained by the progesterone-3-[125I] RIA appear comparable to those of [3H]-progesterone assays which employ similar anti-progesterone-11 alpha-BSA sera. The progesterone-3-[125I] double-antibody RIA, however, is more convenient and less expensive than the [3H]-progesterone RIA method.


[Corticosteroid synthesis in chicken adrenals as affected by o,p'-DDD]. The corticosteroids biosynthesis in adrenals with administration of o,p'-DDD in doses of 40, 100, 200 mg/kg was studied for two weeks in experiments on chickens. The corticosteroids biosynthesis was judged by formation of corticosterone, hydrocortisone and desoxycorticosterone by 2% adrenal homogenates from the precursors (pregnelonone and 11-hydroxyprogesterone) introduced into the incubation medium. The formed corticosteriods were isolated chromatographically, then they were identified and quantitatively determined by spectrophotometry following the reaction with tetrazolium blue. The data of the studies performed by thin-layer chromatography show the inhibition of the 11-beta-hydroxylizing system with administration of o,p'-DDD in a dose of 50 mg/kg and stimulation of 21-hydroxylation of steroids. When introducing the inhibitor in a larger amount, most enzymatic systems participating in the process of the corticosteroids biosynthesis are inhibited.


Clinical diagnosis of psychogenic rheumatism. Rheumatic symptoms that are a somatic expression of emotional disturbance are common, and often are mistakenly attributed by physicians to organic disease. Psychogenic rheumatism is encountered most frequently among middle-aged women. The typical complaint is of widespread pain and stiffness, often with report of swelling and paresthesia, but symptoms characteristically are vague. Overt psychiatric disturbance may be apparent. Distinction from organic disease should not be difficult if physicians recognize the typical presentation, and find that symptoms fail to correspond to patterns of organic disorders. When organic disease coexists with psychogenic rheumatism, as often is the case, the objective abnormalities are insufficient to explain the symptoms.


[Biosynthesis of pyridoxal-5'-phosphate in lymphocytes stimulated by alloantigens in vitro]. Dynamics of alterations in pyridoxal kinase activity (key enzyme in biosynthesis of pyridoxal-5'-phosphate) was studied in lymphocytes of mice BALB/c, stimulated by irradiated cells from spleen of mice C3H in vitro. The cytolytic activity of lymphocytes was estimated by amount of Na251CrO4 realised from lysed cell-targets into medium. Maintenance of animals on a diet without pyridoxine within 1-3 weeks did not affect on the capacity of lymphocytes to proliferative in vitro and on their cytolytic activity. At the same time pyridoxal kinase activity was increased 2.5-3-fold in stimulated lymphocytes in presence of pyridoxal. Km value was 2.5-5.0.10(-5) M of pyridoxal for preparations of pyridoxal kinase from lymphocytes either with normal or with increased enzymatic activity. Lymphocytes of mice, kept on the diet without pyridoxine within 5-6 weeks, were characterized by distinctly decreased proliferative and cytolytic activities. Pyridoxal-5'-phosphate, added to incubation mixture in vitro, as distinct from pyridoxal, restored partially the impaired functions of T-lymphocytes.


[Water-tight closure of spinal dura with a new clot suture technique (author's transl)]. A new clot-suturing Technique (using high-concentration fibrinogen solutions) for water-tight closure of the dura is reported. Six dogs underwent laminectomy of the thoracic spine with medial longitudinal incision in the chordal dura. After the dural split had been sealed with natural tissue adhesive and closure of the wound in layers, the animals were sacrificed at intervals of 1 to 21 days postoperatively and the chordal segments involved were removed and histologically examined. Early fibrinolysis of the clot was prevented by adding a natural proteinase inhibitor and factor XIII concentrate to the clotting substances. Histological analysis showed that healing was almost complete after 2 weeks, with delicate connective tissue overgrowing the dural split. After complete reabsorption of fibrin, the originally abundant absorbent granulation tissue had largely disappeared. Among the satisfactory results of fibrin suturing are optimum healing tendency in the fibrin-sutured region, absence of tissue irritation and neurotoxicity, which are known attributes of the synthetic alkl-cyano-acrylate tissue adhesives.


[Antiviral immunity study in systemic diseases]. The investigation of antiviral antibody titers to 8 different antigens: measles, influenza A2 and B, parainfluenza types 1, 2, 3, adenovirus and smallpox, of interferon in the blood serum, the interferon-synthesizing activity of the peripheral blood leukocytes in patients with autoimmune diseases in the period of the disease exacerbation revealed a number of immunological features. Thus, in all groups of patients antibody titers were high to measles, influenza, parainfluenza type 3 viruses, and titers of leukocyte interferon and interferon in the blood serum were 3-4-fold lower than in the control group.


The effects of increased Waler salinity on the fine structure and acid phosphatase activity in frog pancreas (Rana temporaria L.). Morphological alterations and AcPase activity in frog pancreas under the influence of high salinity water were investigated by electron microscopy. The 1% increase in the sodium chloride concentration of the water in which the animals were kept induced severe degranulation of all islet cell types and the stimulation of the autophagocytosis process. The latter was particularly obvious in the acinar cells, in which the occurrence of various morphological types of lysosomes was recorded. Other involutional changes in both endocrine and exocrine pancreas included lipid accumulation, mitochondria shrinkage, nuclear pycnosis and plasmalemma lysis. The ultrastructural modifications, mainly ascribed to the disturbance of the ionic balance of the body fluid, were accompanied by a general increase of the histochemically demonstrable AcPase activity. The enzyme was exclusively detected in lysosomes, GOLGI complex, and in different types of islet secretory granules. Several hypotheses concerning the functional significance of the enzym distribution are discussed.


[Manifestations of influenza-virus variability during its cultivation in the system of passively immunized chick embryos]. A method of immunological actions on the influenza virus in the system of chick embryos passively immunized with isologous sera was elaborated. With the aid of the suggested method it was possible to induce in strains (with different hemagglutinin type and different degree of attenuation) the transformation of signs characterizing the virus variability in the epidemic process. Variants of the vaccine strains of the influenza virus with increased immunogenic activity and signs of antigenic "outrunning" were obtained. Experimental vaccines from these variants were nonreactogenic for humans and caused a more frequent seroconversion than the initial strain. The diagnostic agents from the variants revealed antibodies in human sera and gamma-globulin, similarly to the "new" viruses isolated from man. The theoretical significance and the aspects of practical utilization of the data obtained are discussed.


[Indicators of cellular and humoral immunity in chronic opisthorchiasis]. Quantitative content of T- and B-lymphocytes in the peripheral blood was studied after Mendes in 30 patients suffering from chronic opisthorcosis and in 30 practically healthy persons; immunoglobulins--M, G, and A were examined after Mancini, and the presence of autoantibodies in the blood serum was studied by indirect method of mast cells degranulation. There was revealed a reduction of the T-cell count to 28.8 +/- 2.28% (normal value--52.9 +/- 3.32%) and a fall of IgM level to 163.4 +/- 16.2 (207.2 +/- 10.5 in donors) in the patients; macrophages count was almost doubled. Autoantibodies to the antigens of the liver, gastric mucosa and the gall bladder wall were revealed in 1/3 of the patients.


[Inactivation of the colony forming cells in bone marrow by allogenic T-lymphocytes]. Bone marrow cells together with allogeneic cortisone-resistant thymocytes or the lymph node cells of intact mice treated with antilymphocytic T or O-antisera were transplanted to the lethally irradiated mice. The antisera eliminated the capacity of T lymphocytes to inactivate allogeneic stem cells. Cortisone-resistant thymocytes displayed a strong inactivating action. The principal role in the processes of inactivation of genetically foreign stem cells was played by T lymphocytes. B lymphocytes possessed no properties of killer cells. The presence of B lymphocytes in the population of killer cells apparently failed to serve as a determinant one for the development of inactivation processes.


[Immunological precursors of influenza epidemics]. The authors studied the immuno-epidemiological manifestations of ciculation and variability of the influenza virus during the periods preceding the officiallly recorded rise of the incidence of this disease. The following epidemic precursors were revealed: a) an increase of the number of persons who fell sick with subclinical form of the disease, accompanied by a rise in the population of the antibody level to the type of influenza virus whose latest variant later caused an epidemic morbidity elevation; b) a progressive predominance of the causative agent of the developing epidemic in the etiology of influenza; c) a growth of the collective immunity indices from the "minimal" to the "critical" levels; d) an increase of the sero-conversion multiplicity and of the antibody level in those who sustained the disease during the epidemic development. These precursors could be revealed at the period of from 1 1/2 to 6 months before the beginning of the morbidity growth caused by viruses of endogenous or of exogenous origin.


[Indications of arteriography and of emergency embolization in gastrointestinal tract and abdominal hemorrhages (author's transl)]. A propos 24 cases of gastro-intestinal tract's embolization of which eleven were performed in emergency for bleeding, the principle indications are described and illustrated. In some cases embolization gracefully replaces the ligation by a rapid and simple procedure at the time of diagnostic arteriography, preparing with safety the operative cure. In other cases embolization alone is curative: arteriovenous fistulas, telangiectases in 'Osler-'s disease, radiotherapic bleeding lesions, inoperable cancers. This implies the presence of trained radiologic teams and a tight collaboration with intensive care, endoscopy and surgery in large medical center. In this view the existence of radio-surgical rooms is useful.


Functional examination of the pancreatic secretion with 4-(n-acetyl-l-tyrosyl)aminobenzoic acid. The oral dose of 2g 4-(N-acetyl-L-tyrosyl) aminobenzoic acid was used to establish the secretion of pancreatic chymotrypsin after stimulation with Lundh's test-meal in 45 persons. By action of chymotrypsin 4-aminobenzoic acid is split in the small intestine. The extent of its excretion in the urine serves as an indicator of exocrine pancreatic secretion. The 4-aminobenzoic acid in the urine is estimated after acid hydrolysis by the diazotation reaction. The average value (x +/- SE) of 4-aminobenzoic acid excreted in an 8-hr urine sample amounts to 69.4 +/- 3.0% with the lower limit of the normal values (x - 2 SD) 49.6%. The corresponding values in patients with pancreatic maldigestion were significantly decreased (25.1 +/- 3.6%). Reduction of the collection period of urine to 6 hrs is sufficient for the demonstration of more advanced forms of pancreatic insufficiency. In cases of disturbances of absorption in the small intestine an extension of the urine collection period to 8 hrs is recommended. We consider this oral test to be a suitable screening method which can be conveniently used in out-patient practice.


Post-hypoxic intention myoclonus treated with 5-hydroxy-tryptophan and an extracerebral decarboxylase inhibitor. Post-hypoxic intention myoclonus successfully treated by long-term administration of the combination of 5-hydroxytryptophan and carbidopa is described. Persistent euphoria and diarrhoea were essential side effects. Methysergide (12 mg/day) blocked the therapeutic effect, indicating a specific serotoninergic function of precursor loading with 5-hydroxytryptophan. Tryptophan (8 g/day) had no effect on the myoclonus suggesting a reduced tryptophan hydroxylase activity. Plasma concentrations of 5-hydroxytryptophan in the range of 10--30 micromoles per liter were obtained during maintenance therapy with 900 mg 5-hydroxytryptophan per day in combination with 150 mg carbidopa per day.


[Proportion of B- and T-lymphocytes in lymph nodes removed from patients with Hodgkin's disease]. The proportions of T and B lymphocytes were determined in lymph nodes removed from 30 patients with Hodgkin's disease and in 18 control lymph nodes. In all lymph nodes obtained from patients with Hodgkin's disease histological examination demonstrated presence of typical granulation tissue of type Ns, Mc, Ld (changes of Lp type were not found). In the control lymph nodes no neoplastic changes or inflammatory reactions were observed. For identification of T cells the rosette test E was used and for identification of B cells --- the EAC rosette test and tests for presence of Ig on their surface by the immunofluorescent method (L Ig+). It was found that the proportions of T and B cells in the lymph nodes obtained from patients with Hodgkin's disease were not different from those in control lymph nodes. The percent values of T and B cells were similar in all three histological types of changes in Hodgkin's disease. Early radiotherapy was not connected with a change in T and B cell proportions in the irradiated lymph nodes.


[Proportions and absolute count of T- and B-lymphocytes in peripheral blood and their blastic transformation induced by mitogens in splenectomized and non-splenectomized patients with Hodgkin's disease]. Investigations were carried out on the effects of splenectomy on the immune state of patients with Hodgkin's disease during remission. In similarly treated non-splenectomized and splenectomized patients the proportions and absolute count of T and B lymphocytes were determined in peripheral blood. For identification of T cells the rosette test E was applied. B cells were identified by the method of EAC rosette test and by determination of immunoglobulins on their surface. For functional assessment of lymphocytes their blastic transformation was determined after stimulation with PHA, Con A and PWM. It was found that the proportions and counts of T and B lymphocytes in preripheral blood were not different in both groups. The values of blastic index in the cultures of lymphocytes stimulated with mitogens were higher, on the other hand, in non-splenectomized patients in relation to splenectomized ones. In the light of these investigations it is suggested that splenectomy in patients with Hodgkin's disease caused functional disturbances of lymphocytes. Further investigations are indispensable for establishing whether lymphocyte function impairment manifests itself with clinically detectable disorders of immune processes.


[Intracranial supratentorial "arachnoid/ cysts. A report of nine cases and review of literature (author's transl)]. The author describes nine cases who presented with supratentorial arachnoid cysts. The clinical pictures, diagnostic techniques, physiopathological hypotheses and therapeutic aspects are discussed. Additionally the value and use of computerized axial tomography in the diagnostic procedure are evaluated in the article.


The pre- and postoperative ENG findings in clinical otosclerosis and the late hearing results. 125 patients suffering from otosclerosis underwent oto-neurological investigations preoperatively and again daily from the second to sixth day postoperatively. An abnormal ENG in the form of a spontaneous or positional nystagmus, directional preponderance or a diminished caloric reaction could be found preoperatively in 30% of the patients. No statistically significant difference between patients with or without abnormal ENG findings could be shown in the late postoperative hearing results of 3 years in a series of different types of operations. Nearly half of the patients had postoperative nystagmus. On the second day nystagmus beat towards the operated ear in 22.3% of the patients. On the sixth day there was nystagmus only in one-third of the patients and it then beat towards towards the operated ear in only 12.1% of the patients and away from the operated ear in 12.6%. No statistically significant correlation could be found between the nystagmus findings and the late hearing results after 3 years' observation in this series of different types of operation.


[Discrimination curve of color hues].

[Discrimination curve of color hues]. The hue discrimination curve has been studied in 48 cases of acquired dyschromatopsias not as it is the rule in relation with the nosology but in relation with the classifications as they are given by the test of Farnsworth. The results show with evidence different characters according to the type of dyschromatopsia: protan deutan or tritan.


Quantification of vestibular compensation in unilateral Meniere's disease. The main parameters of the vestibulo-ocular reflex (i.e. the gain or reflectivity, the long-time constant of the semicircular canals, the time constant of the mechano-neural transduction, and that of the central leaky integrator) were computed from the post-rotational nystagmic responses of unilateral Meniere's patients. Comparison with normal subjects showed a decrease of the first two parameters both in CW and CCW responses. No significant changes were observed in the remaining parameters. Probably due to a process of central compensation, a high level of symmetry was observed mainly in longstanding patients.


Drug prescribing patterns in the elderly: a cross-sectional study of in-patients. A cross-sectional one-day survey of drug prescribing and use in elderly in-patients was carried out in Dundee hospitals. Altogether 873 patients were studied and analyses of prescribing patterns were carried out by patient categories--medical, surgical, geriatric, psychiatric and mentally subnormal--and by major drug groups. While the average number of drugs prescribed per patient on the study day was 3.3, which was not excessive, other results highlighted some possible problems of therapy, viz. the wide range of drugs used within drug groups, the common use of psychotropic drugs, dose regimes which although used in a geriatric population differed little from general adult dosages, and which sometimes involved many administrations per day. Examples were described relating to the use of nitrazepam, phenothiazines and tricyclic antidepressants.


Serum histamine levels following administration of ultrastructural tracers in three strains of rats. Intravenous administration of the electron-opaque tracer ferritin resulted in substantial elevation of serum histamine levels in both the Munich--Wistar and Wistar-Furth strains of albino rats. Lewis rats were unaffected. Similarly, infusion of the non-protein tracer dextran was followed by greatly elevated serum histamine concentrations in Munich-Wistar and Lewis, but not in Wistar-Furth, rats. In sharp contrast with these results were those obtained using the tracer polyvinylpyrrolidone (PVP). PVP infusion caused no elevation of serum histamine levels in any of the rat strains studied. Caution in the use of such tracers is thus advised, since serum histamine concentration affects vascular permeability. Careful matching of ultrastructural tracer and strain of experimental animal is prerequisite in permeability studies.


Fendosal (HP 129): a potent anti-inflammatory and analgesic compound. Fendosal (HP 129) is one of a series of potent non-steroidal anti-inflammatory agents. Fendosal was compared with aspirin in several anti-inflammatory and analgesic bioassay procedures. Results indicate that fendosal has an anti-inflammatory activity 1.4 times greater than does aspirin in carrageenan-induced rat paw edema. Fendosal is 6.9 to 9.5 times more active than aspirin in the prophylactic and therapeutic adjuvant-induced polyarthritis models of chronic inflammation. The analgesic activity of fendosal is considered to be superior to that of aspirin, with the advantage of a prolonged duration of action. The gastric-irritating properties of fendosal are very low in comparison with those of aspirin. Fendosal has a much wider separation of effective and gastric-irritating doses than does aspirin.


Radiosensitivity of different B and T subpopulations of lymphocytes in the mouse spleen. X-irradiation was used as a tool to investigate the radiosensitivity of different B and T precursor subpopulations as detected by three in vitro culture systems. The culture systems utilized in this study included antigen reactive cell assays (ARCA), polyclonal mitogen assays (PMA), and polyclonal effector cell assays (PECA). The order of radiosensitivity of these systems in both the B and T cell series was ARCA greater than PMA greater than PECA (D37 values for B cell responses: ARCA = 88.8 R, PMA = 125 R, PECA = 223 R; D37 values for T cell responses: ARCA = 160 R, PMA = 441 R and PECA = 1095 R). With all assay systems the B cell response was more radiosensitive than the T cell response. The extrapolation number (n) from the radiation survival curves was approximately 2.0 for T cell responses and approximately 1.0 for B cell responses. The value of 1.0 for B cell responses suggest that their extreme radiosensitivity may be due in part to a lack of repair mechanisms. These findings also suggest that the more primitive precursor cells are more apt to undergo cellular proliferation upon activation and that this event is more radiosensitive than is the final differentiation event of precursor cells into a progeny of functional end-stage cells.


Electrophysiologic characteristics of concealed bypass tracts: clinical and electrocardiographic correlates. Twelve of 60 consecutively studied patients undergoing electrophysiologic study for paroxysmal supraventricular tachycardia had atrioventricular (A-V) bypass tracts functioning as the retrograde limb of the reentrant circuit. None had evidence of preexcitation in the surface electrocardiogram, but in two patients anterograde preexcitation could be produced by pacing from the coronary sinus. In all 12 patients with concealed bypass tracts the retrograde atrial activation sequence or effect of left bundle branch block aberration during the tachycardia, or both, confirmed the left-sided bypass tract. A negative P wave in lead I during the tachycardia was also diagnostic of a left-sided bypass tract. Dual A-V nodal pathways were found in five patients with concealed bypass tracts but were unrelated to the development of the tachycardia. When compared with supraventricular tachycardia due to A-V nodal reentry, clinical findings suggestive of a concealed bypass tract included: (1) P wave following the QRS complex (12 of 12 versus 12 of 40), (2) negative P wave in lead I during the tachycardia, and (3) bundle branch block aberration during the tachycardia (8 of 12 versus 3 of 40). Other characteristics of patients with concealed bypass tracts that were of less value in individual cases were shorter cycle lengths of tachycardia, younger patient age and lesser incidence of organic heart disease.


Direct method for determining regional myocardial shortening after bypass surgery from radiopaque markers in man. A new method is described for determining localized epicardial shortening in regions newly perfused after saphenous vein bypass grafting. Four to six radiopaque markers are sutured to the ventricular epicardium in pairs, 2 cm apart and 0 to 3 cm distal to the coronary anastomosis. Shortening fraction and time to onset of shortening are reported in 56 patients examined noninvasively with use of cinefluorography 1 week to 6 months after operation. The right coronary bypass region showed the greatest improvement in shortening fraction in 6 months (from 10.1 to 16.7 percent); the left anterior descending region showed the least (but still significant) improvement (from 8.6 to 11.5 percent). Paradoxical systolic expansion occurred predominantly in the region of the left anterior descending coronary bypass (95 percent of all such occurrences). Measurement error, observer variability and beat to beat variability were less important than the physiologic changes in the postoperative period. This technique is a direct method providing heretofore unavailable follow-up information on localized shortening in newly perfused myocardium after coronary bypass grafting.


Diagnosis of pneumonia by counterimmunoelectrophoresis of respiratory secretions. Several recent studies in adults have indicated that counterimmunoelectrophoresis (CIE) of sputum can distinguish persons with pneumococcal pneumonia vs those in whom merely colonization of pneumococcus occurs--CIE being positive in the former and negative in the latter. Counterimmunoelectrophoretic determinations were done on nasopharyngeal (NP) secretions in 20 children with bacterial pneumonia as evidenced by physical and radiological findings, leukocytosis, response to a penicillin, and in some cases, evidence of bloodstream invasion. Thirty-five children with other types of respiratory illness served as controls. Ten of 16 children from the pneumonia group had pneumococcal antigen in their NP secretions. Four of the six patients without pneumonia had evidence of disease associated with type 14 pneumococcus, which is not generally detected by CIE. The four additional patients with pneumonia had Haemophilus influenzae type b, and H influenzae type b antigen was present in the NP secretions. In the control group, one patient had pneumococcal antigen, and one patient had H influenzae type b antigen in the NP secretions, although 17/35 were positive for pneumococcus by culture. Counterimmunoelectrophoretic determinations of NP secretins are reliable in distinguishing patients with pneumococcal pneumonia vs those who are merely carriers (P less than .001).


Endoscopic papillotomy and removal of gallstones. Summarizing our results we come to the following conclusions: 1. In high risk but operable patients, EPT is a useful treatment in cases with choledocholithiasis and with papillary stenosis. 2. The risk of the procedure is lower than by surgical intervention. 3. Complications can occur in 7.3%, most of them within 24 hours. 4. The mortality rate was 1.7% and depends on the precise selection of the patients; on the knowledge of the post-papillotomy treatment and on the experience of the examiner. 5. This procedure, at the present time, should be limited to centers with well trained and experienced endoscopists.


Surface morphology of mouse and rat thymic lymphocytes: an in situ scanning electron microscopic study. The present paper deals with a scanning electron microscopic investigation which was undertaken in order to make a direct study of geometrical conformations of thymocytes, to determine the effect of external mechanical forces and finally to analyse the relation of the cell surface morphology to the differentiation and release of thymocytes into circulation. Thymocytes in situ revealed a striking polyhedral configuration with distinct edges and angles that permit a close orientation of cells in a minimum space. This conformation is probably acquired under the influence of forces in the microenvironment of the cells. The immature thymocytes in the cortex were smooth surfaced and constituted a homogenous population with regards to surface morphology except for slight variations in the size and angles of varoius facets of the polyhedra. A minority of the cell population occupying the medulla, however, exhibited a departure in possessing surface undulations and stubby protuberances. Thymocytes isolated in suspension and those in postcapillary venules of thymus did not show the polyhedral shape characteristic of the cells in thymic tissue. They were always rounded, with their surfaces often exhibiting undulations or microvilli. The variations observed in situ are discussed in light of external mechanical forces, cell surface characteristics and the inherent properties of differentiating thymocytes.


Effect of the proteinase inhibitor aprotinin in the management of hemorrhagic shock in the dog. Aprotinin, a proteinase inhibitor, was evaluated as a pharmacologic aid in dogs subjected to lethal hemorrhagic shock. Survival time, hemodynamic changes, and plasma enzyme analysis were measured as criteria for drug effects. Mixed-breed dogs (n = 14) were divided into 2 groups of 7 each: nontreated dogs in shock (group 1) and aprotinin-treated dogs in shock (group 2). One of 7 dogs in group 1 and 2 of 7 dogs in group 2 survived. Survival time, for the remaining dogs in group 1 (190 min, n = 6) and group 2 (188 min, n = 5) were not significantly different. There was no significant difference in mean arterial pressure, mean pulmonary arterial pressure, cardiac output, or left ventricle systolic pressure associated with aprotinin treatment at any time after hemorrhagic shock. There was no significant difference in plasma lactic acid, aspartate aminotransferase, alanine aminotransferase, creatine phosphokinase, alpha-amylase, and beta-glucuronidase associated with treatment at any time; however, there were significant (P less than 0.05) increases with time. The gastrointestinal tract was the site of most obvious lesions found at necropsy. Lesions varied considerably in extent and severity without apparent correlation to the treatment regimen. These experiments did not show beneficial effects of aprotinin in dogs subjected to hemorrhagic shock, but neither did they completely rule out some valuable actions that may have been obscured by the type of model used.


Effects of atrial arrhythmias on aortocoronary bypass graft blood velocity in man. Utilizing a Doppler ultrasonic flowmeter catheter, phasic instantaneous aortocoronary saphenous vein bypass blood velocity was recorded during various atrial arrhythmias in 17 patients. Atrial premature beats, supraventricular tachycardia and atrial fibrillation reduced peak bypass graft blood velocity in relation to the heart rate and diastolic cycle length. Such changes were more evident during the systolic fraction of bypass blood flow. In a single subject, systolic blood velocity alternans was observed during the course of atrial tachycardia. It is concluded that such study provides insight into the dynamics of bypass graft blood flow velocity during atrial arrhythmias.


Hemophilus influenzae type F pneumonia in adults. A 69-year-old man was hospitalized with fatal bacteremic Hemophilus influenzae type F pneumonia. Three cases of type F pneumonia have been reported previously. When compared with 22 reported cases of bacteremic type B pneumonia, patients with type F infection were more likely to be elderly males who succumbed to their infection (p less than 0.05). Statistically significant differences in the incidence of underlying conditions or in the extent of pneumonia were not present.


Intermediate alpha1-antitrypsin deficiency and chronic obstructive pulmonary disease in Yugoslavia. As part of a larger investigation of factors associated with chronic obstructive pulmonary disease among Yugoslavian men, an attempt was made to measure the role played by alpha1-antitrypsin deficiency in the causation of those diseases. Almost 3,000 men from Tuzla, an industrial and mining center in central Bosnia, were screened for alpha1-antitrypsin deficiency. Twenty-six men heterozygous for the Pi MZ phenotype were found in this population. The men with the Pi MZ phenotype were compared with a random sample from the total population. The analysis of the data showed that there is an apparent physiologic impairment associated with Pi Z heterozygosity that produces a shift in the relationships between the different lung volumes without over-all hyperinflation, namely, an increase in residual volume at the expense of vital capacity. However, because of the low prevalence of the Pi Z gene, it does not appear to account for much of the high rate of chronic obstructive pulmonary disease found in this population.


Influenzal vaccine response in systemic lupus erythematosus. The response of patients with systemic lupus erythematosus and normal subjects to systemic immunization and boosting with influenza A vaccines was studied. Symptoms after vaccination were somewhat more frequent in the patients than in the normal subjects; however, all symptoms were minor and no major flare of illness occurred. No significant induction or increase of pre-existing autoantibodies among the patients was detected after vaccination. The immunogenecity of the vaccinations, as assessed by antibody titers, was similar in the patient and control groups. No correlation between serologic response to influenzal antigens and HLA was found. Thus, in this group of patients with systemic lupus erythematosus, who were either in remission or had mild-to-moderate disease activity, killed influenzal vaccination caused no apparent worsening of disease activity.


Activation of the kallikrein-kinin system in Rocky Mountain spotted fever. Activation of the kallikrein-kinin system, as indicated by increased plasma kallikrein and depleted plasma kininogen, prekallikrein, and kallikrein inhibitor, was observed in five patients with Rocky Mountain spotted fever. Four of the patients had petechial rashes characteristic of vasculitis. Three patients had alterations in coagulation consistent with disseminated intravascular coagulation, although no hemorrhagic syndrome was found. Our data, along with the known physiologic actions of kinins, suggest a possible role for the kallikrein-kinin system in the pathophysiology of vasculitis, disseminated intravascular coagulation, circulatory shock, and other complications of infection with Rickettsia rickettsii.


Intraerythrocytic parasitosis in humans with Entopolypoides species (family Babesiidae). Association with hepatic dysfunction and serum factors inhibiting lymphocyte response to phytohemagglutinin. We have observed two cases of human infection with intraerythrocytic protozoa. The organisms appeared to be in the Entopolypoides group, which had not previously been associated with human infection. One patient was asplenic. Both patients had hepatic dysfunction, and their serum samples contained blocking factors that interfered in vitro with the stimulation of normal lymphocytes by phytohemagglutinin. It appears that in humans, as well as in experimental animals, host factors are important in resistance to infection by intraerythrocytic parasites. These factors include the presence of a spleen and cell-mediated and humoral immunities. Possibly similar infections will be observed in patients with other impairments of T-cell function, such as those induced by malignancy, thymic dysfunction, or immunosuppressive drugs.


Clinical and antibody responses after influenza immunization in systemic lupus erythematosus. After immunization with A/New Jersey/76 and A/Victoria/75 influenza vaccines, 11 patients with systemic lupud erythematosus were serially evaluated for changes in disease activity, serologic abnormalities, and their capability to generate specific antibodies. One patient, with active disease, developed a diffuse, proliferative glomerulonephritis. None of the other patients or control subjects had significant local or systemic side effects. Significant levels of antibodies were generated to A/New Jersey/76 in eight of the 11 patients and in seven of eight control subjects and to A/Victoria/75 in seven of 11 patients and five of eight control subjects. The geometric mean responses of both total and IgG antibodies to each viral antigen were no different in patients with systemic lupus erythematosus than in control subjects. In patients with stable systemic lupus erythematosus, immunization with killed influenza viral vaccine appears to be safe and effective.


Ventricular arrhythmias in chronic stable angina pectoris with surgical or medical treatment. Since both propranolol therapy and saphenous-vein bypass surgery have become accepted treatments for patients with symptomatic coronary-artery disease, it is important to determine if either influences the prevalence of ventricular arrhythmias in these patients. Six-hour dynamic electrocardiography was done on 130 patients with chronic stable angina pectoris at least 1 year after being randomized to surgical or medical therapy. All surgical patients had saphenous-vein grafting; 90% of the medical patients received propranolol. Data analysis showed that even though the overall prevalence of premature ventricular contractions was no different in medical and surgical patients, the prevalence of complex premature ventricular contractions was significantly higher in surgically treated patients not receiving propranolol than in propranolol-treated medical patients (p less than 0.05). However, the survival rate was no different in either group, and the quality of life in the surgical patients remained superior.


Antimicrobial susceptibility of Haemophilus ducreyi. The susceptibility of 19 isolates of Haemophilus ducreyi from a recent chancroid outbreak and four reference strains was determined in vitro to 13 antimicrobial agents. The rabbit intradermal test for virulence was positive for all of the local isolates, but not for the reference strains. The "nonvirulent" reference strains were inhibited by lower minimum inhibitory concentrations (MICs) of most agents tested. For the virulent isolates, the range of MICs (in micrograms per milliliter) of the following were: of vancomycin, 8 to 128; of polymyxin, 32 to 128; of cloxacillin, 32 to 64; of tetracycline, 0.5 to 32; of cephalothin, 4 to 8; of doxycycline, 0.25 to 8; and of kanamycin, 1 to 8. Three strains were resistant to penicillin and ampicillin (MIC >/= 128 mug/ml), and these three strains produced beta-lactamase. The remainder were susceptible to 4 mug/ml. All strains were susceptible to rifampin (MIC </= 1 mug/ml), chloramphenicol (MIC </= 4 mug/ml), sulfisoxazole (MIC </= 8 mug/ml), and nalidixic acid (MIC </= 8 mug/ml). These susceptibilities of H. ducreyi indicate several antimicrobial agents that may be effective for chancroid treatment and support the use of vancomycin in a selective medium for the culture of chancroid genital ulcers.


Nitrate reduction: new method for testing the antibiotic susceptibility of Haemophilus influenzae. We have developed a new micro-broth-dilution assay for determining the antimicrobial susceptibility of Haemophilus influenzae. This assay is based on the ability of viable H. influenzae to reduce nitrates to nitrites. Bacterial viability is detected by a positive nitrite reaction rather than visible turbidity. The nitrate reduction assay was compared with a standard microassay using 51 isolates of H. influenzae and six beta-lactam antibiotics. Although there was good agreement between the two methods, the nitrate reduction assay was more sensitive in detecting viable bacteria, and so established a more accurate estimate of the minimal inhibitory concentration. The nitrate reduction assay offered the additional advantage that it could be used to determine the minimal bactericidal concentration without having to subculture the broth. Ampicillin, penicillin, and cefamandole were equally effective in vitro against susceptible strains (minimal inhibitory concentrations, 0.125 to 0.5 mug/ml), whereas all three antibiotics were ineffective against two beta-lactamase-producing strains. Using the nitrate reduction assay, resistance to cefamandole was detectable with inoculum sizes ranging from 10(4) to 10(6) colony-forming units per ml, while the turbidity assay detected resistance only with the largest inoculum.


Restriction enzyme analysis of plasmids from Haemophilus influenzae. Examination of Haemophilus influenzae strains isolated in New Orleans revealed ampicillin-resistant strains with plasmids of size classes not previously detected in North America. The molecular weight of plasmids in five ampicillin-resistant strains ranged from 0.8 x 10(6) daltons (0.8 Mdal) to 36 Mdal. The molecular weights of the plasmids were determined by sucrose gradient centrifugation, electron microscopy, and agarose gel electrophoresis. Plasmids of the previously detected 30-Mdal size class were found in three of the five ampicillin-resistant strains. Restriction enzyme analysis is consistent with a close relationship between these three 30-Mdal plasmids. Of the two remaining ampicillin-resistant strains, one contained a single plasmid of 36 Mdal and the other contained two plasmids of 0.8 and 2.3 Mdal.


In vitro susceptibility of Haemophilus influenzae to sulfamethoxazole-trimethoprim and cefaclor, cephalexin, and cephradine. Sulfamethoxazole-trimethoprim and three oral cephalosporins, cefaclor, cephalexin, and cephradine, were evaluated in vitro as possible alternatives to chloramphenicol in the treatment of non-central nervous system infections due to ampicillin-resistant Haemophilus influenzae. Sixty-four isolates of H. influenzae, including 31 beta-lactamase-positive strains, were tested by the agar dilution method. All strains were inhibited by 0.78/0.039 mug sulfamethoxazole-trimethoprim per ml and by 0.78 mug of chloramphenicol per ml. At 6.25 mug/ml, 100, 11, and 3% of all strains were inhibited by cefaclor, cephalexin, and cephradine, respectively. Thus, on the basis of drug concentrations presumably achievable in serum, 100% of strains were susceptible to sulfamethoxazole-trimethoprim, chloramphenicol, and cefaclor. However, a considerable inoculum effect was noted with both beta-lactamase-positive and -negative strains, when tested with sulfamethoxazole-trimethoprim; the minimal inhibitory concentrations of cefaclor were only slightly affected. Also, synergistic effects of sulfamethoxazole-trimethoprim, sulfamethoxazole-erythromycin, and sulfamethoxazole-cefaclor were seen when combinations were tested against both beta-lactamase-positive and -negative strains, as determined by minimal inhibitory concentrations measured by the broth dilution method and by killing curve analyses. These results support further evaluation of these combinations and of cefaclor alone for the treatment of non-central nervous system infections due to H. influenzae.


Haemophilus influenzae susceptibility testing within four hours by a modification of the Autobac I system. By adding an XV strip to the eugonic broth or substituting Levinthal broth, the standard Autobac I susceptibility testing system may be used to determine susceptibility of Haemophilus influenzae to antimicrobial agents. Complete concordance was attained in testing 30 strains (5 resistant) by Autobac I, disk diffusion, and broth dilution methods. Autobac I results were available within 4 h after isolation of the organism.


Blood loss and bank blood requirement in coronary bypass surgery. With the use of nonblood prime and refinement in perfusion and surgical techniques, blood requirement for coronary bypass operations has been reduced to a minimum. Of 240 patients (average number of bypasses, 3.07; average pump time, two hours and 22 minutes), no blood was used in pump prime or before perfusion. During perfusion, 29 patients (12%) received 34 units of blood in the pump-oxygenator, and after bypass 64 patients (27%) received 65 units of blood in the operating room (average intraoperative use, 203 ml per patient). For the total hospital stay, the blood requirement was 728 ml per patient. For the last 60 patients operated on, the figure was 328 ml. There were no surgical deaths, and only 1 reexploration for postoperative hemorrhage (0.4%). Discharge hemoglobin level averaged 11.8 gm, whereas the admission hemoglobin level had averaged 13.8 gm. Autotransfusion, avoidance of entry into the pleural space, shorter perfusion time, postoperative platelet count of more than 150,000, and normal partial thromboplastin time tend to reduce blood requirement, but not to a striking degree. Bank blood requirement for the coronary bypass program accounted for 3.7% of the hospital need and 2% of the community need.


Transfusion of 2,3 DPG-enriched red blood cells to improve cardiac function. Attempts were made to enhance oxygen availability in patients undergoing coronary artery bypass operations by transfusing red blood cells enriched in 2,3 diphosphoglycerate (2,3 DPG) to 150% of normal. In this study of 22 patients, 11 received red blood cells with high 2,3 DPG levels and 11 received red blood cells with 70% of normal 2,3 DPG levels (control). Immediately following cardiopulmonary bypass the 11 patients who received high 2,3 DPG red blood cells had a P50 value of 31.6 mm Hg; the value in control patients was 28.3 mm Hg (p less than 0.05). Oxygen consumption values were 135 and 106 ml/min/m2, respectively (p less than 0.05). Mixed venous oxygen tensions were similar in the two groups, but the arteriovenous content difference was higher in the high 2,3 DPG group (p less than 0.05). Cardiac indices increased significantly in response to a fluid load in the high 2,3 DPG group compared with controls at comparable filling pressures. We believe the improved myocardial performance in response to a fluid challenge is a result of increased oxygen availability.


Adult polycystic kidney disease and lattice corneal dystrophy: occurrence in a single family. Most ophthalmologic disorders reported with renal cystic disease have been associated with either medullary cystic disease or juvenile nephrophthisis. A family we investigated demonstrated two previously unreported autosomal dominant disorders: adult polycystic kidney disease and lattice corneal dystrophy.


The problem-oriented medical record applied to communicative disorders. A continuing interest in clarity of reporting generated a change in our reporting format from the traditional report to the problem-oriented structure. This article discusses the differences and the advantages and disadvantages of each.


[Neuronal structure of the frog vestibular ganglion]. Neuronal organization of the vestibular ganglion of the nerve VIII in the frog (Rana temporaria) has been studied by means of light and electron microscopy. It has been stated that bipolar ganglion-forming neurons are not quite identical in their structure. They differ in size, fine organization of their cytoplasm and in the manner they construct their glial sheaths. Among ganglial neurons, two types are distinguished: myelinizated and unmyelinizated neurons. A considerable part is composed by neurons coated with myelin sheath which can be constructed according to compact or loose type of myelin. Myelinizated neurons are mostly large cells, with their cytoplasm saturated with organells. Unmyelinizated neurons are coated with a simple sheath composed of one layer of lemmocytes processes. These neurons are much smaller in size, their cytoplasm is poor in organells and contains large amount of neurophilaments.


Retinitis pigmentosa. Visual loss.

Retinitis pigmentosa. Visual loss. A total of 174 patients (347 eyes) with retinitis pigmentosa were categorized by genetic type and assessed as to the degree of central visual loss. The degree of central visual loss was mildest in cases of autosomal-dominant inheritance and most extensive in cases of X-linked recessive inheritance. Slightly more than one third (34%) of all eyes had acuity of 20/200 or less, while only 55% had vision of 20/60 or better. The data in this study provide general guidelines for counseling individual patients with retinitis pigmentosa as to the potential and extent of future central visual loss.


Isolated trochlear nerve palsies in herpes zoster ophthalmicus. The clinical course of six patients with isolated trochlear nerve palsy as the only ocular motor manifestation of herpes zoster ophthalmicus has been analyzed. Spontaneous recovery occurred in only three. Review of the literature does not clarify the mechanism of such palsies, which potentially may result from the following conditions: local orbital muscle inflammation and ischemia; contiguous intracavernous spread of inflammation from the trigeminal nerve; and a concurrent but independent motor neuropathy or ganglionitis.


Diagnostic limulus lysate assay for endophthalmitis and keratitis. The limulus lysate assay is an inexpensive, reliable, and rapid means of detecting and presence of Gram-negative endotoxin. In all ten cases of experimentally induced Proteus endophthalmitis in rabbits, the assay was positive, and the assay was appropriately negative in all ten cases of Staphylococcal endophthalmitis, ten cases of Candida endophthalmitis, and ten cases of sterile endophthalmitis in rabbits. In a clinical assessment of keratitis, the assay of corneal scrapings was positive in 11 of 13 Gram-negative corneal ulcers. In a similar study of clinical endophthalmitis, both Gram-negative cases had a negative limulus assay, but two cases are insufficient to be conclusive. The assay may prove to be a useful adjunct both to standard diagnostic evaluations and in the rapid direction of appropriate therapy for these conditions.


The limulus lysate test. A rapid test for diagnosis of Pseudomonas keratitis or endophthalmitis. The limulus amebocyte lysate test has been shown to be a highly sensitive indicator of endotoxin. Our studies showed that as little as 5 ng of endotoxin could be detected in aqueous or vitreous humor in vitro, although 10 microgram endotoxin injected into the aqueous could not be detected. Subsequent studies showed that by diluting the aqueous equally with saline solution, this inhibitory effect could be overcome. Detection of endotoxin elaborated from Pseudomonas aeruginosa was made as early as 24 hours after induced Pseudomonas keratitis or endophthalmitis, whereas staphylococcal-induced keratitis or endophthalmitis gave negative results. Positive cultures using trypticase soy broth or agar slants were observed on all infected animals. Thus, this technique should have ready application for rapid detection of Pseudomonas keratitis or endophthalmitis.


The significance of urinary melanoma antigen excretion and the ability of thymosin to raise the level of depleted lymphocytes in vitro in malignant melanoma. One hundred and fifty-six patients were screened for the presence of urinary melanoma antigen and serum cytoplasmic antibody. It was found that 44% of symptomless Stage 1 patients tested five to 15 years after operation had detectable antigen (Ag) in their urine; the urines of 67% of Stage 2A (local recurrence) patients were positive for Ag; while in only 38% of those patients graded 2B (lymph-node involvement) were these tests positive. Urines of 83% of patients with generalized metastases (Stage 3) were positive. A sequential study was made of 23 patients seen and treated in 1976. Of this group, 14 reverted from a positive state to a negative one following excision of their tumour, while six were negative on first postoperative testing and subsequently became positive. Three out of the 23 remained persistently negative. T lymphocyte levels were assessed in 71 melanoma patients, and a stage-related fall was noticed. Thymosin (Hoffman LaRoche) on in vitro incubation significantly raised the levels of T lymphocytes.


Linear model for visual-vestibular interaction. The results of experiments are evaluated in terms of a simple model for the interaction of eye movement responses to simultaneous optokinetic and vestibular stimuli. The model predictions agree with the results of these experiments and explain many clinical observations concerning the effect of vision on nystagmus. The model accounts for the dominance of the visual system's response over the vestibular system's response at low frequencies. It also accounts for the inability of patients with decreased smooth pursuit system response to suppress the vestibulo-ocular reflex during simultaneous optokinetic and vestibular stimulations. The model provides useful information for the design of combined optokinetic and vestibular stimuli for test vestibulo-ocular reflexes.


Current status of space medicine and exobiology. An overview of the present state of aerospace medicine and planetary biology is given with emphasis on the ongoing search for extraterrestrial life and life science studies being made both by independent and cooperative investigations of the United States, the Soviet Union, the European Space Agency, and countries with an interest in gravitational physiology, radiation, planetary quarantine, exobiology, and general space biology. A suitable animal model for outer space medical research, in-orbit vestibular function investigations, biomedical problems in the Earth's normal 1-G gravitational intensity, and biological satellite experiments are discussed. The scope of exobiology, life detection programs, solar system organic chemistry, and attempted elucidation of the question of the origin and early evolution of life are also discussed. Evaluation of data acquired from a variety of sources indicates that all phases of exobiology lead to biopoesis and chemical evolution, with allied aviation, space, and environmental medicine being the major part of the search for extraterrestrial life.


Clues from genetic and epidemiologic studies. There are clear indications that genetic variables influence the pathogenesis of SLE. The frequency of the disease in first-degree relatives of SLE subjects appears to be in the range of 1-2%, but this is in great excess relative to the frequency of SLE in the general population. The frequency of concordance of the disease in monozygotic twin pairs is in excess of 50%. The frequency of concordance of dizygotic twins may be no higher than that in other first-degree relatives. Data in twins support the conclusion that familial aggregation is due to genetic rather than to other familial factors. The high female-to-male ratio of patients with SLE may reflect sex hormonal influence on immunoreactivity rather than the genetic aspects of sex per se. The approximately threefold higher incidence of SLE in black subjects relative to white, in some studies, may reflect a heightened activity of the humoral immune system in blacks.


HLA-D and Ia antigens in rheumatoid arthritis and systemic lupus erythematosus. The HLA-D region in the HLA chromosomal complex is concerned with cellular interactions and regulation of the immune response. Rheumatoid arthritis (RA) has been found to be associated with one of the HLA-D antigens. In two separate studies from this laboratory it was found that HLA-Dw4 was more frequent in RA patients than in normal controls. The patients were Caucasians suffering from erosive, rheumatoid factor positive RA. Combined results of the two studies showed HLA-Dw4 to be present in 52% of the 130 patients, compared to 13% in 119 controls (P less than 10(-6). Ia antigens were determined serologically in isolated B cells. The antigen Ia4, associated with HLA-Dw4, was increased in RA patients (70%), compared to normal controls (28%). In SLE, typing was difficult because of fragility of the B cells. Preliminary results in 14 SLE patients suggested that Ia4 was also increased in this disease. It seems likely that these associations are a reflection of genetic factors related to the immune response involved in the pathogenesis of RA and perhaps also of SLE.


B lymphocyte development, heterogeneity, and function. Thymus-independent (B) lymphocytes are a heterogeneous group of cells which, it is increasingly clear, undergo an ordered sequence of differentiation steps from stem cells to antibody producing cells. Through the study of the immunologic potential of B lymphocytes from neonatal mice and from mice with an X-linked immune defect, it has become possible to assign certain functions to cells of distinct differentiated states. Furthermore, a differentiation antigen, Lyb 5, has been identified which acts as a marker of a particular subset of B lymphocytes in normal mice. Initial studies of the functional properties of Lyb 5+ and Lyb 5- B lymphocytes are described.


Loss of suppressor T cells in the pathogenesis of the autoimmunity of NZB/W mice. Loss of suppressor T cells was demonstrated in NZB/W mice, an animal model of autoimmunity. As NZB/W mice matured they lost splenic T cells that could be activated by concanavalin A (Con A) to become suppressor cells and lost the ability to produce the regulator of humoral immune responses, soluble immune response suppressor (SIRS). However, NZB/W spleen cells retained the capacity to respond to suppressor signals from Con A pulsed normal spleen cells. Thrice weekly administration of SIRS containing supernatants of Con A pulsed normal spleen cells to young NZB/W mice lead to a striking reduction in the manifestations of autoimmunity.


Proliferative reactivity of T cells to autologous, cell-associated antigens. T cells capable of proliferating in response to signals from autologous cells can be demonstrated in normal peripheral blood. The stimulating cell is contained among populations enriched in B cells, "null" cells, and monocytes, but not among populations enriched in T cells. Density gradient fractionation indicated that the autologous reactive T cell may represent a subpopulation of cells responsive in allogeneic mixed lymphocyte cultures. This was confirmed by negative selection (BUDR and light) experiments which also indicated that the "autologous" stimulus can be mediated by at least some allogeneic cells. In a portion of patients with active systemic lupus erythematosus, autologous reactivity was reversibly blocked. Prior incubation of either responding T or stimulator cells at 37 degrees C restored this reactivity.


Etiology and pathogenesis of a spontaneous lupus-like syndrome in mice. Two recently described murine strains, MRL/1 and BXSB, develop a lupus-like syndrome resulting in a 50% mortality by the fifth month of age. Comparison of the immunopathological and virological characteristics of these mice with those of the NZB/NZW F1 mouse reveals several pathogenetic common denominators but no obvious common etiologic factors. In all three kinds of mice, the lupus-like syndrome consists of a fatal immune complex type glomerulonephritis and complete or near complete thymic cortical atrophy plus lymphoid hyperplasia that varies in degree among the three kinds of mice. The nephritic glomeruli contain a concentration of antinuclear antibodies plus varying amounts of stainable gp70. This syndrome is consistently correlated with abnormally elevated serum IgG levels, antinuclear antibodies, anti ds- and ssDNA antibodies, and circulating immune complexes, as well as depressed serum hemolytic complement. Features that differ among the three kinds of mice include: H2 type, anti-lymphocyte antibody, cryoglobulins, T-B cell ratios, sex incidence of disease, vasculitis, and oncornaviral flora. The serum gp70 levels in the three mice also differ considerably, but all are within the range of gp70 levels found in some immunologically normal strains.


The unity of genes in the major histocompatibility complex. The major histocompatibility complex (MHC) of the mouse can be genetically divided into several regions specialized to performing specific functions. Thus the class I regions (K and D) code for antigens that activate effector (killer) T cells, class II region (I) for antigens causing T-cell proliferation, and class III regions (s) for complement components. A strong case is made for the theory that the division of labor within the MHC is not absolute. Evidence is presented that class I antigens can sometimes cause as strong T-cell proliferation as class II antigens; that class II antigens can generate effector T cells; and that class I antigens may be involved in the immune response to some antigens. The fact that different regions can perform similar functions argues for the unity of the MHC genes.


Cellular immune response in virus infections. Two levels of specificity exist in the killing of virus infected target cells by immune effector T cells. One relates to the classic specificity for the virus, and the second involves the necessity for sharing expression of genes mapping in K and D but not I regions. Among the theories that could explain this is that of dual recognition with separate T-cell receptors detecting H-2 and viral antigen. Support for this possibility was provided by experimental influenza virus infection where evidence of specific recognition of viral products was obtained.


Prolymphocytic leukaemia of T-cell type: immunological, enzymatic and ultrastructural morphometric characteristics. A case of prolymphocytic leukaemia with immunological characteristics of T-cell type is reported. Three noteworthy findings can be emphasized: the presence of C3 receptors on the T-prolymphocytes, the study of the acid-phosphatase isoenzymatic pattern, which showed an increased band 3 with absence of band 3b, and the morphometric ultrastructural investigation. Cytochemistry and ultrastructural morphometry may be useful for a more precise characterization of prolymphocytic leukaemia and help to distinguish it from other lymphoproliferative disorders.


Disorder is characteristic of nerve myelin. An X-ray diffraction pattern from the myelin in frog sciatic nerve has been obtained using the intense synchrotron radiation from the storage ring, SPEAR. Data with good statistical accuracy are obtained in a few minutes by using a scintillation counter or position-sensitive detector. The same indications for stacking disorder are seen as in previous conventional exposures which required one to two days. Thus, the stacking disorder is characteristic of myelin in a freshly dissected nerve. The present data, obtained with a more nearly monochromatic X-ray beam than in the previous study, remove one of two ambiguities which bear on the possible phasing of the higher order Bragg reflections.


The effect of copper on frog skin: the role of sulphydryl groups. 1. Cu2+ at a concentration of 10-4 M, when applied to the external side of the frog skin produces an increase in the short-circuit current (Isc). 2. This effect was studied in skins of Rana temporaria adapted to cold,(5 degrees C) and room temperature (20 degrees C), skins of Rana pipiens adapted to cold, and the results compared with those obtained previously with Rana ribibunda. 3. The observed effect is less dependent upon the adaptation to cold than upon the functional state of the skin: skins with low short circuit currents have a bigger response to Cu2+ than skins with high Isc. 4. A species difference cannot be ruled out since skins of Rana ribibunda exhibiting high Isc give good responses to Cu2+. 5. 5,5' -dithiobis (2-nitrobenzoic acid), a sulphydryl-oxidizing reagent, produces an effect similar to that of Cu2+, and dithiothreitol an SH-reducing agent, reverses the effect of this ion. 6. Cu2+ also induces an increase in the unidirectional K+ fluxes and unmasks a net outward potassium flux. 7. The outward K+ flux induced by Cu2+ is sensitive to ouabain. 8. It is concluded that Cu2+ increases the permeability of the external barrier of the frog skin to Na+ and K+, probably by reacting with SH groups.


The use of the fluorescent probe alpha-parinaric acid to determine the physical state of the intracytoplasmic membranes of the photosynthetic bacterium, Rhodopseudomonas sphaeroides. alpha-Parinaric acid has been used to determine the degree of ordering of the hydrocarbon region of purified intracytoplasmic membranes of Rhodopseudomonas sphaeroides. The usefulness of alpha-parinaric acid as a probe of membrane fluidity was established by comparison of its fluorescent properties in phosphatidylcholine vesicles with those of the more commonly used fluorescent probe, 1,6-diphenyl-1,3,5-hexatriene. Both fluorescent probes were shown to monitor similar environments in the phosphatidylcholine vesicles when the phospholipids were maintained at temperatures above their phase transition temperature. The rotational mobility of alpha-parinaric acid in the intracytoplasmic membranes was determined from 0 to 50 degrees C, a region where no phase transitions were detectable. The rotational mobility of alpha-parinaric acid dissolved in vesicles formed from total extracted intracytoplasmic membrane phospholipids, was 2--3-fold greater than that measured in the intact intracytoplasmic membranes; demonstrating that the presence of protein greatly reduces the mobility of the phospholipid acyl chains of the intracytoplasmic membranes. Due to the high protein content of these membranes, the perturbing effect of protein on acyl chain mobility may extend to virtually all the intracytoplasmic membrane phospholipid.