Platelet membrane glycoproteins implicated in ristocetin-induced aggregation. Studies of the proteins on platelets from patients with Bernard-Soulier syndrome and von Willebrand's disease. The antibiotic ristocetin only aggregates platelets in the presence of plasma von Willebrand factor. Platelets from patients with Bernard-Soulier syndrome do not aggregate upon addition of ristocetin although, in contrast to von Willebrand's disease, plasma levels of factor VIII complex (factor VIII clotting activity, von Willebrand factor activity, and von Willebrand antigen) are normal. The membrane surface of normal platelets was modified and compared to the surface of platelets from a patient with Bernard-Soulier syndrome in an attempt to identify the receptor involved in von Willebrand factor-ristocetin-induced aggregation. After the incubation of washed normal platelets with a preparation of ristocetin previously shown to contain a proteolytic contaminant, the aggregation response is significantly decreased on addition or normal plasma. Analaysis by gel electrophoresis of such platelets when stained for carbohydrate revealed a decrease in the relative amounts of membrane glycopro-eins. Chymotrypsin-treated normal platelets had less membrane glycoproteins in addition to giving a reduced aggregation response in ristocetin-induced aggregation. Staining of gels for protein and carbohydrate indicated that there was an extensive change in the surface of Bernard-Soulier platelets, whereas those from patients with von Willebrand's disease appeared the same as normal. Platelets from patients were labeled by the lactoperoxidase iodination technique. Not only was the relative intensity of staining of platelet-specific proteins and glycoproteins changed in Bernard-Soulier platelets, but the iodination of the glycoproteins on the membrane surface relative to other membrane constituents was lower. In contrast, platelets from patients with von Willebrand's disease showed a normal exposure of membrane components. These data suggest therefore that membrane glycoproteins may play a functional role in ristocetin-induced aggregation.


Immunoglobulin-bearing and complement-receptor lymphocytes constitute the same population in human peripheral blood. Complement-receptor lymphocytes have generally been considered to be a subpopulation of bone-marrow derived (B) lymphocytes. However, the present studies show that essentially all cells with integral surface immunoglobulin from normal human peripheral blood bear receptors for the third component of complement. Moreover, after removal of phagocytes, all cells with complement receptors bear surface Ig. Thus, circulating B cells and complement-receptor lymphocytes are the same population.


Absolute macrophage dependency of T lymphocyte activation by mitogens. A T lymphocyte subpopulation that contains only 0.3% macrophages and less than 2% B lymphocytes has been prepared from guinea pig lymph node cells by the use of two different types of adherence columns. This subpopulation does not porliferate in response to the mitogens Con A or PHA unless additional macrophages are added. The means by which macrophages restore T cell responsiveness to PHA has been investigated. Marcophages appear to function via two different distinct mechanisms in this experimental situation. The first mechanism involves the binding of PHA to the macrophage followed by the "presentation" of the mitogen to the T lymphocyte in a manner that induces cell activation. This presentation function requires that the macrophage be viable and metabolically active. The second mechanism by which macrophages function is by the elaboration of a soluble factor or factors. The presence of these factors has been reliably and reproducibly demonstrated by using a double-chambered, Marbrook-type tissue culture vessel. This soluble factor can induce activation of T lympohcytes with surface bound PHA in the apparent absence of any form of macrophage presentation. In contrast, the function of this factor is clearly distinct from that of the reducing agent, 2-mercaptoethanol, (2-ME) since 2-ME does not enable this T cell subpopulation to be activated by mitogens. On the basis of these observations, we propose that two distinct signals are required to activate this T lymphocyte subpopulation. One signal is delivered by the interaction of the mitogen with the T cell surface, and the second signal is delivered by a soluble factor(s) produced by macrophages. Whether all types of T lymphocytes require two signals to be activated, remains to be established.


Studies on the mechanism of lymphocyte-mediated cytolysis. VI. A reappraisal of the requirement for protein synthesis during T cell-mediated lysis. The role of protein synthesis in the mechanism of T cell-mediated cytolysis has been re-investigated. Cytolytically active (C57BL/L anti-DBA/2) spleen cells treated with pactamycin (10-7 M to 10-6 M) exhibited suppressed protein synthesis (100 +/- 5%), but unimpeded lytic activity. Drug-treated effector cells, incubated for prolonged (up to 24 hr) periods of time in the presence and absence of antigen, showed no siginificant diminution of lytic activity although the incorporation of 3H-leucine into protein was totally ablated. Studies with emetine, another irreversible inhibitor of protein synthesis, gave identical results. These findings are difficult to reconcile with the hypothesis that effector T cells lysis via a soluble protein mediator.


Thymosin restores T cell function and reduces the incidence of amyloid disease in casein-treated mice. Evidence is presented that T cell impairment appears to be specifically related to the pathogenesis of experimental amyloidosis. This conclusion is based on the finding that thymosin administration improves T cell function as measured by mitogen stimulation of spleen cell suspension and at the same time reduces the incidence and severity of amyloid disease in casein-treated mice.


Experimental autoimmune orchitis: in vitro induction of an autoimmune disease. Experimental autoimmune orchitis (EAO) can be induced in vitro. Normal lymph node lymphocytes cultured with autologous dissociated testis cells form rosette-like aggregates and later undergo blast transformation and proliferation. These stimulated lymphocytes cause in vivo EAO lesions, when injectd into syngeneic recipients. Moreover, their autoimmune reactivity can be monitored by an in vitro cytostasis assay. Density gradient analysis of the early lymphocyte-testis cultures reveals that the autoimmune reactive lymphocytes are enriched in the rosette populations. It therefore appears that testicular self-antigens are recognized by clonally preformed autologous lymphocytes.


Cellular receptors for lymphotoxin: correlation of binding and cytotoxicity in sensitive and resistant target cells. The binding of radioactively labeled lymphotoxin (LT) to both lymphotoxin-sensitive and -resistant cell clones was examined. The sensitive clone had a low- capacity, high-affinity ("specific") binding component, the curve of which closely followed the cytotoxicity curve of the lymphocyte mediator. The capacity of this binding component was calculated to be about 600 molecules of LT/cell. In addition, there was a low-affinity, high-capacity ("nonspecific") binding component. In striking contrast, the high-affinity, low-capacity ("specific") component was absent or greatly diminished from the resistant clone, whereas the low-affinity, high-capacity ("nonspecific") component was present at a similar level as in the sensitive cells. These binding characteristics closely resemble those observed by us and other investigators working with a variety of steroid hormones in steroid-sensitive and- resistant cell lines.


A microculture method for the generation of primary immune responses in vitro. A microculture method for the generation and study of the primary immune response of murine spleen cells to defined antigens in vitro is described. Many of the variable parameters which occur in culture systems have been studied in an attempt to define the optimal culture conditions for this system. Cultures of 10(6) CBA spleen cells consistently produced an immune response of 300-600 hapten-specific plaque-forming cells after 3 days of incubation with the T cell-independent antigens DNP-POL and NIP-POL. Cultures were set up in Microtest II tissue culture plates in a volume of 0.2 ml of medium containing 10(-4) M 2-mercaptoethanol. The system described has the advantages of being highly efficient and reproducible and utilises small amounts of cells, medium and antigen. It provides a simple, economic and reliable approach for the systematic study of the immune response in vitro.


Influenza virus infection in nude mice.

Influenza virus infection in nude mice. The role of T-cell function in influenza virus infection was studied by aerosol infection of nude mice with an influenza A virus (PR-8 strain). Nude mice died somewhat later than normal mice, and the antibody response of nude mice to the virus was minimal. Furthermore, nude mice did not eliminate the virus, which persisted for relatively long periods (two to three weeks).


Electrophoretic heterogeneity of normal factor VIII/Von Willebrand protein, and abnormal electrophoretic mobility in patients with Von Willebrand's disease. Crossed antigen-antibody electrophoresis was used to determine the electrophoretic properties of factor VIII/Von Willebrand (F. VIII/VW) protein in normal plasma using a specific rabbit antiserum against purified human factor VIII. The electrohoretic patterns in seven patients with severe Von Willebrand's disease in two different families were studied. In these patients the prolonged bleeding time was related to a functionally abnormal F. VIII/VW protein which was unable to induce platelet aggregation in presence of ristocetin. F. VIII/VW protein had an increased electrophoretic mobility in all the patients. The electrophoretic pattern was similar in different members of the same family but differed from one family to the other. Plasma samples collected after transfusion of normal cryoprecipitate to one member of the first family showed an increasing amount of F. VIII/VW protein, but even one hour after transfusion only one peak migration in an abnormal position was found. However, when mixed in vitro with normal plasma, the plasmas of the same patient showed two peaks, one in position of normal F. VIII/VW protein and one with increased electrophoretic mobility. These results suggest that normal F. VIII/VW protein transfused to recipients with Von Willebrand's disease synthesizing a functionally deficient factor undergoes a rapid alteration.


Stimulus-secretion coupling in an insect salivary gland: cell activation by elevated potassium concentrations. 1. Fluid secretion by isolated salivary glands was stimulated by elevating the external potassium concentration. 2. The stimulatory effect of potassium was dependent on external calcium and was potentiated by a subthreshold dose of 5-hydroxytryptamine (5-HT). 3. During the action of 120 mM potassium there was a large calciumdependent decrease in transepithelial resistance similar to that produced with 5-HT at normal potassium concentrations. 4. These results on Calliphora salivary glands are compared with other cases where cells are activated by high potassium. In most cases, the effect of high potassium is dependent upon calcium, suggesting that the latter plays a primary role in cell activation.


Combining medical information with a business data system. The School of Primary Medical Care at the University of Alabama in Huntsville is presently developing and implementing a computerized clinical data system that incorporates data from the Family Practice Center and the community hospital. The system can be used for the problem-oriented medical record, business and billing, the teaching program, community medicine research, and the evaluation of medical students and family practice residents. This paper discusses plans for the total system and the present degree of implementation.


The nutritional requirements of methicillin-dependent and -resistant strains of Pediococcus cerevisiae. A new methicillin-dependent and -resistant substrain (called MRD) of Pediococcus cerevisiae was developed by serial passages followed by replica-plating. Other methicillin-resistant, but not -dependent, substrains were isolated after treatment of the same parent strain with a mutagen. A methicillin-independent partial revertant, still resistant to the drug, was isolated from the original methicillin-dependent and -resistant substrain (CRD) developed several years ago. The requirements of some of these strains for acetate, vitamins and amino acids were compared. All except the parent methicillin-sensitive strain required pantothenate for growth, but no other consistent differences were found. The parent, but not strain CRD, grew without lysine added to the medium, though 19 other amino acids were needed by each strain. Both of these strains fermented glucose to lactate (mainly the L-isomer) in the absence or presence of methicillin.


Diagnosis and treatment of abscess of the central ganglia. The authors present four cases of abscess of the thalamus and basal ganglia and review an additional 10 cases from the literature. These abscesses appear to be metastatic and are usually associated with a cardiac septal defect or a preceding intrathoracic infection. Fever, elevated white blood count, and/or meningismus, in combination with angiography demonstrating an avascular mass, help distinguish abscess from tumor in this location. The authors advocate aspiration rather than excision.


Fluoroscopy of foramen ovale as an aid to thermocoagulation of the Gasserian ganglion; technical note. The authors described a fluoroscopic method of guiding percutaneous needle penetration of the foramen ovale. The advantages are simplicity, speed, accuracy, and comfortable patient positioning. Radiation exposure is minimized.


Effects of luminance and stimulus distance on accommodation and visual resolution. Measurements of accommodation and visual resolution were obtained at a number of luminance levels and stimulus distances. With reductions in luminance the eye approached a "fixed-focus" condition of accommodation for intermediate distances, resulting in successively larger errors in accommodation for both near and far stimuli. The visual resolution values were initially affected by both the luminance and distance of the stimulus. Subsequent measurements of resolution, following the correction of accommodative errors, were found to be independent of the stimulus distance. The findings are discussed with regard to the problems of "night myopia" and variations in visual resolution with stimulus distance.


Blood loss and hypotensive anesthesia in oral-facial corrective surgery. To evaluate accurately changes in blood volume during oral-facial corrective surgery, double-tagged radioisotope blood volume studies were performed preoperatively and postoperatively. Unexpectedly large RCV deficits that were not consistent with EBL were observed in studies conducted at two separate facilities. Hypotensive general anesthesia was used for the intended purpose of reducing blood loss in oral-facial corrective surgery. Various physiological parameters were measured preoperatively, intraoperatively, and postoperatively to evaluate patient response to this anesthetic method. The MAP was reduced from 89.94 +/- 2.13 to 72.79 +/- 1.63 mm Hg under the influence of NaN infusion supplemented with halothane. No dose-response relationship existed between NaN and the intraoperative MAP. A 44% reduction in the measured red cell volume was observed in comparison to a previously studied group of patients who underwent similar surgical procedures under normotensive anesthesia. It is concluded from an extensive review of the literature that the most vulnerable period for serious complications is in the immediate postoperative period. No significant complications or adverse effects were observed in this study. It cannot be emphasized too strongly that the safety of this hypotensive technique lies in constant and careful monitoring of the patient and meticulous attention to all details of anesthetic management.


Liver disease associated with alpha1-antitrypsin deficiency in childhood. Liver disease in children with alpha1-antitrypsin deficiency and protease inhibitor type ZZ does not necessarily carry a bad prognosis. Fourteen of our 18 patients presented with the neonatal hepatitis syndrome and four had hepatomegaly without jaundice. Although four patients have died of cirrhosis and its complications, and three have severe liver disease, most of the 11 others, of whom four are over 13 years of age, have relatively little clinical, biochemical, or histologic evidence of liver disease. Persistent elevation of SGOT during the third year of life and renal or pulmonary problems were associated with a poor prognosis. Liver biopsy early in the course of the disease was not helpful prognostically but was useful in assessment of the severity of liver disease and demonstration of alpha1AT storage, alpha1AT deficiency was found in 29% of our patients who presented with the neonatal hepatitis syndrome. One of seven apparently healthy Pi type ZZ sibs of our patients had significant liver disease which had not been suspected previously.


An outbreak of Hemophilus influenzae type b meningitis in an enclosed hospital population. Five cases of HITB maningitis occurred within six months in an enclosed population of 28 to 32 chronically ill children. Studies of nasopharyngeal carriage and serum HITB anticapsular antibodies were started after the third case occurred. Two patients had low (less than 0.04 and 0.05mug/ml) antibodies and were not carriers when studied prior to onset of their disease. The carriage rate was approximately 20% among the children. Carriage was usually prolonged, and acquisition was not prevented by high antibody levels. Attempts to arrest this outbreak with type b polysaccharide immunization and ampicillin therapy are discussed in the context of HITB meningitis as a contagious disease.


Mechanical properties of frog skeletal muscles in iodoacetic acid rigor. 1. Methods have been developed for describing the length: tension characteristics of frog skeletal muscles which go into rigor at 4 degrees C following iodoacetic acid poisoning either in the presence of Ca2+ (Ca-rigor) or its absence (Ca-free-rigor). 2. Such rigor muscles showed less resistance to slow stretch (slow rigor resistance) that to fast stretch (fast rigor resistance). The slow and fast rigor resistances of Ca-free-rigor muscles were much lower than those of Ca-rigor muscles. 3. The slow rigor resistance of Ca-rigor muscles was proportional to the amount of overlap between the contractile filaments present when the muscles were put into rigor. 4. Withdrawing Ca2+ from Ca-rigor muscles (induced-Ca-free rigor) reduced their slow and fast rigor resistances. Readdition of Ca2+ (but not Mg2+, Mn2+ or Sr2+) reversed the effect. 5. The slow and fast rigor resistances of Ca-rigor muscles (but not of Ca-free-rigor muscles) decreased with time. 6. The sarcomere structure of Ca-rigor and induced-Ca-free rigor muscles stretched by 0.2lo was destroyed in proportion to the amount of stretch, but the lengths of the remaining intact sarcomeres were essentially unchanged. This suggests that there had been a successive yielding of the weakeast sarcomeres. 7. The difference between the slow and fast rigor resistance and the effect of calcium on these resistances are discussed in relation to possible variations in the strength of crossbridges between the thick and thin filaments.


Discrete and discontinuous action of brown widow spider venom on the presynaptic nerve terminals of frog muscle. 1. A study was made of the effects of the venom of the brown widow spider (Latrodectus geometricus) on end-plates of the frog sartorius muscle. 2. The increase in the frequency of the minature end-plate potentials  (m.e.p.p.s), elicited by the venom in normal-"Ca2+" Ringer solution, occurs in discrete volleys having a sharp onset and end. The frequency of the m.e.p.p.s is high (up to 300 sec-1) and relatively constant during the volley. 3. The volleys recur at intervals during a period from 5 to 10 min after addition of the venom until the onset of electrical silence, up to 4 hr later. The activity occurs in groups containing volleys of loing and short duration. 4. Simultaneous intracellular and extracellular recording from single end-plates indicates that the volleys originate at highly localized areas of the nerve terminals. The high-frequency release of m.e.p.p.s in hypertonic sol solutions, which was studied for comparison purposes, occurs randomly over the entire end-plate. Volleys originating simultaneously at different sites are often superimposed in the intracellular recordings. 5. In high-"Ca2+" Ringer solution, the initial frequency of the m.e.p.p.s in a volley is comparatively higher. However, the frequency drops to one half its value in a few seconds. The volley then terminates or else the frequency of m.e.p.p.s remains high for some time and the volley has no sharp end. Activity occurs in groups containing both long and short volleys. Many more short (less than 5 sec) and long (greater than 30 sec) volleys occur in high-"Ca2+" solution than in normal-"Ca2+" solutions. 6. In low-"Ca2+", high-"Mg2+" Ringer solution, the volleys of m.e.p.p.s are fewer in number and much longer in duration. Intra- and extra-cellular recording of uninterruped activity during long periods suggests that in this solution the m.e.p.p.s originate diffusely rather than at discrete areas of the nerve terminals. 7. Implications of the above data on possible modes of action of the venom are discussed.


Two mechanisms for the meperidine block of action potential production in frog's skeletal muscle; non-specific and opiate drug receptor mediated blockade. The effects of meperidine and naloxone, and their interaction effects on action potential production in frog's sartorius muscle fibres, were studied with intracellular micro-electrode techniques. 1. Meperidine, a narcotic analgesic drug, depressed the rate of rise, the rate of fall and the amplitude of the action potentials. 2. At a meperidine concentration of 0-35 mM, the depression in the action potential maximum rate of rise followed a diphasic time course. At first there was a rapid reduction in the maximum rate of rise which was levelling off at about 60% of control 60-90 min after drug application. This was followed by the second phase during which there was an initial rapid decrease in the maximum rate of rise and all surface fibres were inexcitable by 180 min. 3. The addition of naloxone, a narcotic antagonist, in low concentrations (3 X 10(-5) to 3 X 10(-4) mM) at 70-90 min blocked the second phase of the meperidine-induced depression. 4. With lower concentrations of meperidine (0-18 and 0-07 mM) the depression usually developed more slowly (up to 6 hr with the latter dose) and the addition of low naloxone concentrations partially antagonized the effects of meperidine. However, under no conditions was it possible to completely antagonize the effects of meperidine by the addition of naloxone. 5. A linear relation was found between action potential amplitude and the action potential maximum rate of fall. 6. Meperidine caused a shift in the relation of rate of fall against amplitude to higher action potential amplitudes, indicating that the drug inhibited the increase in potassium conductivity (gK) associated with the falling phase of the action potential. 7. When low naloxone concentrations antagonized the effects of meperidine on the rate of rise and restored action potential amplitudes to control levels, the effect of meperidine on the maximum rate of fall was not antagonized. 8. Larger naloxone concentrations (1-5 X 10(-2) mM or more) depressed the action potential rate of rise but did not alter the relation between action potential amplitude and the maximum rate of fall. 9. It is proposed that meperidine blocks action potential production by two mechanisms: (i) a non-specific mechanism in which the increases in both gNa and gK ar depressed and (ii) an opiate drug receptor mediated mechanism causing a specific depression of gNa. 10. The impression gained from the results is that there are opiate drug receptors located on the inner surface of the muscle membrane associated with the 'sodium channels' and that drug activation of these receptors by either meperidine or high naloxone concentrations interferes with the opening of the 'sodium channels' normally produced by membrane depolarization.


A study of hypothalmic neurosecretory cells of bullfrogs in vitro. Neurosecretory cells of preoptic nuclei of bullfrogs were studied in isolated hypothalamo-hypophysial preparations under constant perfusion with oxygenated Ringer solution at 15-17 degress C. Antidromic potentials were recorded following stimuli applied to the posterior lobe of the pituitary or the stalk. 2. Intracellularly and extracellularly recorded potentials resembled those obtained in vivo from neurosecretory cells of the mammalian hypothalamus. They were unique in that the antidromic potential had a long duration (10-20 msec) and a distinct notch on the rising phase (between A and B spikes). The conduction velocity of the stalk fibres in vitro at this temperature was 0-1--0-2 m/sec. 3. When two successive stimuli were given to the posterior lobe or to the stalk separated by intervals of between 30 and 65 msec, the test (second) response showed a longer delay of the B spike. This delay between the A and B components was as long as 10 msec. Further shortening of stimulus intervals produced block of B spikes in the test response. A complete separation of A and B spikes occur spontaneously in a few instances. 4. Evidence indicated that inhibitory recurrent axon collaterals play a role in the control of bullfrog neurosecretory cells. Antidromic potentials were inhibited by a 'conditioning' stimulus for as long as 300-400 msec, even when the stimulus did not evoke an antidromic potential. 5. It was found that in addition to the inhibitory interaction there is a facilitatory recurrent axon collateral system which operates within the nuclei. The evidence for this is: (1) stimulation of the posterior lobe, with single subthreshold pulses evoked an action potential if preceded by another stimulus of subthreshold or just threshold intensity. The durations of such facilitatory effects were found to be 20--400 msec; (2) a single pulse given to the posterior lobe did occasionally evoke two spikes from neurosecretory cells; the second spike which occurred 15-30 msec after the first had the characteristics of a trans-synaptically produced potential; (3) gradual changes in the intensity of stimuli applied to the neural lobe produced a sudden shift in latencies ranging between 15 and 30 msec. The potentials having long latency also showed characteristics of those transsynaptically excited. In addition, an increase in excitability of neurosecretory cells by antidromic stimulation was confirmed by using orthodromically induced action potentials in in vivo studies. Possible functional significance of inhibitory and excitatory recurrent collateral system in neurosecretory cells was discussed. 6. Two to threefold increase in NaCl concentration of a perfusate slightly increased the latency and refractory period of antidromic potential but not the shape of the potential. Norepinephrine added to a perfusate (1 mug/ml). augmented the separation of A and B spikes of the antidromic potential. Acetylcholine at a concentration of 1 mug/ml. did not have an appreciable effect on the antidromic potential.


Calcium content and exchange in frog skeletal muscle. Calcium content and exchange in frog ELD IV muscle were examined employing the efflux technique. 2. Muscle calcium was found to exchange with four time constants, 21-5 sec 2-7, 32 and 1244 min. 3. All calcium was found to be exchangeable with more than half the total amount residing in an extracellular compartment. 4. Results obtained from ELD IV muscles and single fibres were identical. 5. Muscle calcium content was found to remain constant up to 20 hr in vitro. 6. Extra exchange of calcium occurs upon contraction. This extra exchange appears to occur in the most slowly exchanging component. 7. The data are discussed in relation to morphological and autoradiographic findings and a model of calcium exchange in skeletal muscle is presented.


Lymphocyte subpopulations in normals and patients with rheumatoid arthritis and ankylosing spondylitis. Seventy-four normal persons, 48 patients with rheumatoid arthritis, and 25 patients with ankylosing spondylitis, were examined in respect to lymphocyte subpopulations in the peripheral blood. The simultaneous enumeration of T lymphocytes (E rosettes), B lymphocytes (surface immunoglobulin), as well as null cells and double marker cells was performed. No significant differences could be observed in the three examined groups in respect to the absolute or the relative lymphocyte counts, suggesting that possible immunological impairment assumed in rheumatoid arthritis and ankylosing spondylitis, is due not to reduced cell numbers, but to a possible functional disorder.


Cellular and humoral immune parameters of synovial fluid and blood in rheumatoid arthritis. Thymus derived (T) and bone marrow derived (B) cells from joint fluid and peripheral blood of 15 patients with rheumatoid arthritis and 10 controls with other inflammatory joint diseases were studied. High absolute numbers and high percentages of T cells in the synovial fluid, T plus B cell sums exceeding 100 per cent in synovial fluid or blood, and fewer complement receptors compared to surface Ig bearing cells in joint fluid or blood was found only in rheumatoid arthritis. T and B cell numbers did not correlate with disease activity. No differences in T and B cells were found between patients positive or negative for rheumatoid factor. (J Rheumatol 2: 363-372, 1975).


Acute mitral regurgitation from ruptured chordae tendineae in systemic lupus erythematosus. A patient with systemic lupus erythematosus developed acute mitral regurgitation due to ruptured chordae tendineae, requiring mitral valve replacement. Typical changes of Libman-Sacks endocarditis were observed in the excised mitral valve. Immunofluorescent studies revealed antinuclear antibody and deposits of immunoglobulins and complement within small vessels.


Development of two manifestations of T-lymphocyte reactivity during tumor growth: altered kinetics associated with elevated growth rates. Tumor-specific, cell-mediated immune responses (CMI) in mice were measured during the growth of transplantable tumors with the use of lymphocyte-mediated cytotoxicity and the recently developed leukocyte adherence inhibition (LAI) microtest. When both tests were used in parallel to assess CMI, no consistent correlation was found, which suggested that each test was a measure of the activity of a functionally different T-lymphocyte subpopulation. The results of blocking factor (BF) assays with both tests agreed in 78% of the instances; the LAI microtest was much more sensitive for BF determination than lymphocyte cytotoxicity, since blocking serum concentrations as low as 0.25% could demonstrate BF activity in the microstest. In other experiments, the kinetics of development of tumor-specific CMI was followed in normal mice and those under toxic stress; the stressed animals showed depressed humoral and cell-mediated immune responses and enhanced tumor growth rates after the inoculation of tumor cells. In normal mice, a cytotoxic response always appeared in the spleens and regional lymph nodes 3-5 days before an LAI response. Enhanced tumor growth rates in the animals under toxic stress were associated with a reversal in the order in which these two manifestations of T-lymphocyte responsiveness developed; LAI responses always developed before, and often in the complete absence of, cytotoxicity.


Neonatal meningitis and mastoiditis caused by Hemophilus influenzae. A newborn infant developed Hemophilus influenzae meningitis associated with acute coalescent mastoiditis and a cutaneous abscess in the mastoid region. Mastoidectomy was followed by prompt recovery from the meningitis, which had failed to clear previously despite antibiotic therapy. Mastoiditis may exist as an infective focus in neonatal meningitis more frequently than has been appreciated. Mastoid roentgenograms are usually the only clue to diagnosis of this infection and should be obtained in patients with neonatal meningitis responding poorly to antibiotic therapy.


"Normal-pressure" hydrocephalus. Relationship of clinical and radiographic findings to improvement following shunt surgery. Analysis of 25 patients who fulfilled clinical and radiographic criteria for the diagnosis of "normal pressure" hydrocephalus (NPH) demonstrated (1) a significant relationship between presence of motor signs with good outcome and absence of motor signs with poor outcome following ventricular shunting, (2) symptoms and signs of parkinsonism in 40% of patients in whom the diagnosis of NPH was made, and (3) no reliable relationship between radiographic measurements or cisternogram appearance and outcome following shunting. The clinical picture is the most important factor in selection of NPH patients for surgery.


Finding recent tuberculous infection in New Orleans. Results of tuberculin skin tests on New Orleans children from the inner city and Contact Investigation Program. We tested infants and preschool-age children from the New Orleans Health Department programs for tuberculosis contact investigation and for tuberculin skin testing. About 7.8% (34 of 438) of the contacts and about 0.78% (107 of 13,797) of those given skin tests were tuberculosis-infected. Both programs, we concluded, detected enough recent tuberculous infection to be worthwhile as screening procedures.


Difference in calcium content of atrial and ventricular muscle. The calcium content and inulin space of the atrial and ventricular muscle were determined in isolated perfused heart of the toad, bullfrog, guinea pig, rat, and cat. In all species studied, the total and "cellular" calcium content of the atrium were higher than those of the ventricle. A high calcium content of the atrial muscle was also observed in fresh unperfused hearts. The total calcium content of atrial and ventricular muscles increased when extracellular phosphate concentration was increased. When severe ventricular arrhythmia such as fibrillation occurred during perfusion, the total calcium content of the ventricle increased. The decay of tissue calcium content with calcium washout was examined in the toad, guinea pig, and rat heart. It was revealed that about 80 percent of total calcium existed as "exchangeable" calcium in both atrial and ventricular muscles. When the extracellular calcium concentration ([Ca]o) was altered in the toad, guinea pig, and rat heart preparation, the cellular calcium content of atrial muscle varied in proportion to [Ca]o, whereas that of ventricular muscle remained fairly constant at a higher [Ca]o value. The development of contractile tension in the atrial and ventricular muscles at various [Ca]o values corresponded well to these changes in the cellular calcium content except for the rat ventricle in which the contractile tension was almost proportional to [Ca]o. The relationship between the development of contractile tension and the level of cellular calcium content or [Ca]o was discussed.


[Surgical treatment of severe forms of ischemic heart disease]. Over 400 operations of an indirect revascularization of the myocardium have been performed at the A.I. Bakulev institute of Cardiovascular Surgery of the USSR Academy of Medical Sciences. Since 1970, the direct method have been developed, predominantly those of aorto-coronary bypass. Careful examination of 709 patients was carried out, 445 of them were subjected to selective coronary angiography, 108 were operated on. In 1974, 56 operations were undertaken, among them 36 aorto-coronary bypasses, in 6 of them with a preliminary endarterectomy from the coronary artery, 8 double bypasses, 6 procedures for acute myocardial infarction, 5 combined operations of aorto-coronary bypass and resections of cardiac aneurysms, and 15 resections of postinfarction aneurysms of the heart. Twelve patients died in the postoperative period, mainly due to acute cardiac insufficiency. The high figures of mortality are caused not only by the faults of the surgical procedures but also by the grave initial state of the patients (multiple coronary lesions large focal cardiosclerosis due to preceeding infarctions, high degree of initial cardiac insufficiency). The improvement of the results of surgery for the ischaemic heart disease will depend on the perfection of the surgical technique, on proper selection of the patients, and on the precise determination of the indications for such treatment.


[Tritanopia and dominantly inherited optic atrophy (author's transl)]. The clinical picture of hereditary dominant optic atrophy is described and the particular importance of the concomitant tritan dyschromatopsia is stressed. Most cases of tritanopia are acquired, congenital ones are rare. Wright has studied 17 tritanopes - the greatest series ever reported. A full analysis of colour vision is given, but no detailed information about other visual functions and the condition of the fundi. As single members of  families affected by cominantly inherited optic atrophy show typical tritanopia, a visual acuity of 6/8 and hardly any pallor of their disks, it is possible that such isolated cases are regarded wrongly as congenital tritanopes.


Effect of tryptophan on polyriboadenylic acid and polyadenylic acid-messenger ribonucleic acid in rat liver. The administration of tryptophan to fasted rats 1 hour before killing resulted in marked increases in the amounts of hepatic polyriboadenylic acid (poly(A)) and poly(a)-containing-mRNA in the cytoplasm and a shift in hepatic polyribosomes toward heavier aggregates. When animals were treated with cordycepin, or actinomycin D, to both, there was disaggregation of hepatic polyribosomes and inhibition of poly(A) synthesis. Administration of tryptophan to fasted animals pretreated with cordycepin, or actinomycin D, or both induced a shift in hepatic polyribosomes toward heavier aggregates and an increase in in vitro protein synthesis. Fasted rats that received [U-14C] adenosine to prelabel hepatic poly (A) and then were treated with cordycepin, or actinomycin D, or both before tubefeeding tryptophan revealed increased hepatic levels of labeled polyribosomal poly (A) in comparison with controls. Fasted rats that received 14C-orotic acid to prelabel poly (A)-mRNA and then were treated with actinomycin D after 1 hour and with tryptophan along with cycloheximide after 1 1/2 hours revealed marked increases in labeling of hepatic poly (A)-mRNA associated with polyribosomes in comparison with controls. These findings suggest that tryptophan may act to stimulate the transport of poly (A)-containing-mRNA into the cytoplasm of the liver.


[Effect of hypokinesia and varying microclimate on vestibular function]. The functional state of the vestibular system of the bed rested man is characterized by a decrease of the nystagmic parameters, increase of autonomic reactions and elongation of illusory sensations. This may reduce the static and kinetic stability of man to acceleration. The bed rest induced vestibular changes can be attributed to the functional changes in higher compartments of the central nervous system. The influence of an altered atmosphere on the vestibular function is insignificant.


[Eye movements occurring during head rotation on artificial gravity stands]. On the basis of previously advanced theories the direction and pattern of eye movements induced by stimulation of semicircular canals onboard artificial gravity stations are predicted. The resulting data are important to describe expected disorientation illusions of vestibular origin as well as vestibular effects on the visual functions of tracking and fixation onboard artificial gravity stations.


Bedside hemodynamic monitoring. Its value in the diagnosis of tamponade complicating cardiac surgery. Cardiac tamponade may be a difficult clinical diagnosis in the early postoperative period in patients undergoing open-hear surgery, particularly when the anterior or lateral pericardium is left open. Bedside monitoring of intracardiac pressures and determination of a "pressure plateau" between right atrial, right ventricular diastolic, pulmonary arterial diastolic, and pulmonary capillary wedge pressures are useful in the early diagnosis of cardiac tamponade. The value of such hemodynamic monitoring in the  diagnosis and treatment of cardiac tamponade in three patients with aorta-coronary artery bypass surgery in the early postoperative period is reported. Appropriate therapy, carried out on the basis of these studies, minimized the occurrence of further morbidity or possible death.


[Diffuse immunological lung damage due to heterologous anti-thymocyte serum]. Heterologous anti-rat-thymocyte-serum produces an acute hemorrhagic pulmonary lesion. Pneumotoxicity is dependant upon complement since preparatory C' - depletion protects the experimental animal from its letal properties. Absorption of serum with finely dispersed homologous tissue suspensions of lung and thymus is eliminative of toxicity while prophylactic administration of histamin antagonists seems to be non-influential in the genesis of the pulmonary lesions.


[Effect of active interferonization and anti-thymocyte globulin on the growth of virus-induced hamster melanoma A-Mel-S]. The present data show that biological and synthetic inducers of interferon are able to reduce the growth of a transplantable malignant melanoma in the Syrian hamster. The advantage of the biological inducer H-MP are that it is not toxic for humans and that a high titer of interferon can be maintained over a long period of time.


[Effect of strophanthin on intestinal blood flow. A contribution to the physiopathology of hemorrhagic enteropathy]. The purpose of the present study was to compare in canine experiments hemodynamic and angiographic effects on mesenteric circulation. I. v. administration of strophanthin is leading to an increase of arterial pressure and a decrease of mesenteric blood flow. Most consistent angiographic changes are attenuation and local vasoconstriction of peripheral vessels. The relationship between digitalis administration and mesenteric underperfusion leading to non-occlusive mesenteric ischemia is discussed.


[Local gastric fibrinolysis activation]. Hemorrhagic gastric juice contains a higher fibrinolytic activity than normal gastric juice. It is liberated from damaged muco and possibly from hemolytic erythrocytes.


[Effect of coronary bypass surgery on myocardial pressure and ventricular function in the dog]. In 7 dogs a severe stenosis of the left circumflex coronary artery (CCA) is produced in the course of 18 days. The influence of myocardial revascularization on left ventricular function and on intramyocardial pressures in the areas supplied by the CCA and by the left anterior descending coronary artery is studied. Neither under control conditions nor during acute left ventricular pressure load does opening a bypass graft between the carotid artery and CCA induce a significant change in total ventricular function (dp/dtmax, Vmax, left ventricular enddiastolic pressure). However, immediately after opening the graft intramyocardial pressure rises in the CCA area indicating a regional improvement of myocardial function.


[Animal experiments on influencing ischemic myocardial damage following temporary coronary artery ligation]. Ischemic myocardial damage produced by temporary coronary artery occlusion of 60 min duration is diminished by beta-sympathicolytic acting TrasicorR (3 mg per kg) and osmotically cell-dehydrating Manitol (1 g per kg). Trasylol, a proteinases inhibiting substance, caused a favourable effect at very high doses (100 000 DIE per kg) only. The extent and irreversibility of myocardial ischemic damage was determined by experiments of 180 min duration by intravital fluorochromatisation with acrine orange, determination of hydrogen ion concentration at frozen section of heart muscle with pH-indicatorpaper and enzymehistochemical and histochemical methods.


[Immunotherapy of cancer: reality or hope? (AUTHOR'S TRANSL)]. The reality of immunotherapy of cancer is still in the trial stages. Supportive immunotherapy combined with conventional cancer therapy can prolong the duration of remission and perhaps raise the cure rate for many neoplastic diseases such as acute leukemias, sarcomas and malignant melanomas. Our knowledge of the immunologic reactions is still incomplete. We expect further progress  but we have no evidence that the immune response will be able to prevent or reverse all malignant growth.


[Coronary heart disease: pathlogy (author's transl)]. The review deals first with the importance of the risk factors for coronary heart disease, the progression of coronary arteriosclerosis and the location of atherosclerotic lesions. The areas of blood supply to the coronary arteries and the effects of coronary insufficiency in the myocardium are discussed. Finally the aneurysm and the morphologic changes in aortocoronary venous bypass are described.


[Coronary heart disease and bypass surgery: a clinical cardiologist's view (author's transl)]. The main goal of bypass surgery (BPS) is improvement of angina pectoris (AP), of performance of LV function, and of the prognosis of AP. Recently reported statistics indicate a significant improvement of the prognosis after BPS, especially in double or triple vessel disease. The main indication remains severe AP with significantly impaired performance, but prognostic aspects can also affect the decision of BPS. The area of regional ischemia should be determined by means of angiography during stress, and regional flow should be measured (scintigraphy etc.) to allow a more accurate definition of critical narrowings.


Core cooling after hypoxia and ischaemia. Two patients sustained severe circulatory inadequacy before and during thoracotomy for coronary surgery. Both patients were promptly cote cooled to between 20 degrees and 25 degrees C. After coronary surgery, each patient was rewarmed and the operation was terminated uneventfully in each case, No important cerebral deficit was apparent despite periods of circulatory insufficiency and arrest which were well beyond the usually accepted limits. It is suggested that prompt core cooling may exert a protective effect in this context.


Pre- and postjunctional neuromuscular blockade by carbachol. Carbachol, when applied to the bathing Ringer solution of frog sartorius muscles, caused depolarization of the endplate and a blockade of endplate potentials (EPP's), miniature EPP's (mepp's) and the iontophoretic acetylcholine potential. In muscles treated with an analog of hemicholinium-3, alpha, alpha'bis(dimethylammonium acetaldehyde diethylacetal)-p-p'-diacetylbiphenyl dibromide (DMAE), depolarization of the endplate by carbachol was blocked and the blockade by carbachol of the iontophoretic acetylcholine potential was prevented. These responses to carbachol were attributed to a postjunctional action that was antagonized by DMAE. In contrast, the blockade by carbachol of EPP's and mepp's was enhanced in DMAE-treated muscles at a time when carbachol-induced depolarization was blocked. This response to carbachol was attributed to a pre-junctional action. Carbachol either blocked transmitter release by a mechanism that was insensitive to DMAE or enhanced the prejunctional blocking actions of DMAE. Succinylcholine had actions similar to carbachol. DMAE prevented depolarization by succinylcholine but enhanced neuromuscular blockade by succinylcholine. SKF 525-A (beta-diethylaminoethyl diphenylpropylacetate hydrochloride), like DMAE, prevented depolarization but not transmission blockade caused by carbachol.


[Corticalization of 2 regions of the visual system in the evolution of vertebrates]. Data on the evolution of the visual system in the phylogenetic scale of vertebrates are reported. Visual projections in the telencephalon of cyclostomes (lampreys) and retinothalamo-telencephalic channel in elasmobranches (skates) are shown. In amphibians (frogs) and reptiles (turtles) the existence of two visual subsystems (retino-thalamo-telencephalic and retino-tecto-thalamo-telencephalic) is determined, both being overlapped partially at the level of n. geniculatus lateralis and totally in the telencephalon. In turtles earlier visual and tectal impulses towards the telencephalon proved to be relayed in n. geniculatus lateralis and later ones--in n. rotundus. In mammals (rats) visual tecto-cortical connections are shown to have one synaptic relay in thalamic structures since cortical potentials evoked by stimulation of the colliculus superior in rats posses a rather short latency. Significant latency shortening of tectal visual responses in monkeys, as compared with the latency of the respective potentials in turtles (chronic identical experiments), supports the idea of the progressive development of the tectal division of the visual system in the vertebrate phylogony. It is concluded that both divisions of the visual system--retino-thalamic and retino-tectal underwent corticalization at earlier evolutionary stages.


[Changes in the receptive field of pigeon tectum neurons subjected to vestibular and acoustic stimulation]. The changes in the receptive fields of neurons in the deep layers of the tectum opticum were studied as induced by labyrinthine and sound stimulation. Variations in the size of the receptive field, the particular direction of sensitive cells movement, duration of the reaction and amount of impulses in it were found. The results obtained and data from the literature allow one to suggest an active role of tectum opticum in the transformation of signals from the retina depending on the kind of information from other sensory systems.


[A pharmacologic analysis of the slow potential arising in response to adequate stimulation of the frog olfactory bulb]. The nature of slow potential recorded in the frog olfactory bulb in response to natural stimulation was studied using application of different pharmacological substances. Three suppositions were checked up: 1) if the slow potential is of neuro-glial nature; 2) whether it reflects the primary afferent depolarization in the terminations of olfactory fibres which is responsible for the presynaptic inhibition in the olfactory bulb (as the dorsal root potential in the spinal cord); 3) if it reflects postsynaptic potentials. The slow potential was found to have many pharmacological properties similar to those of the dorsal root potential in the spinal cord. However, the slow potential appears to be more a complicated response and includes at least one more component--a depolarization of dendrites of unknown nature.


Persisting intrapituitary recessus infundibuli. X-ray examination of the intracranial ventricles with Dimer X made it possible to make the diagnosis of obstructive hydrocephalus due to a mass lesion of the midbrain and abnormal intrasellar recess of the third ventricle in a 34 year old female patient. Considering the location and ontogenetic and phylogenetic facts one can diagnose the second pathological finding as a persisting intrapituitary recessus infundibuli. A malformation due to inhibition during development is to be assumed.


[Diverticulosis of Meckel's diverticulum in childhodd. 1 year's experience]. 12 cases of Meckel's diverticulosis, submitted to operation, are examined. In the 41% of the patients, the ascertained seat of the disease was the diverticulum. The following complications were observed: phlogosis, enterorrhagia due to ulcer and occlusion for invagination. Mortality was of 8.3%.


Alpha-1-antitrypsin variants in New Zealand. Twelve percent of a sample of New Zealand Europeans were found to have variant forms of alpha-1-antitrypsin. The distribution of different variants was similar to that found in other Northern European populations. Four percent were heterozygotes for the deficiency state (Z allele) which predisposes to both emphysema and cirrhosis. An initial survey of New Zealand Maoris suggests that although they have a lower overall incidence of variants, there is an increased frequency of the deficiency Z allele. This may be a contributory factor to the susceptibility of the Maori to respiratory and liver disease.


Alpha-1-antitrypsin deficiency in a Southland family. After diagnosis of an alpha-1-antitrypsin deficiency in a patient with emphysema, three complete generations of his family were screened for the defect. Half of the 42 subjects had a defective phenotype (18 were MZ, two were ZZ, and one SZ). Of this group, five had other avoidable risk factors predisposing to emphysema, and a further 10 were children. The four oldest subjects had radiological evidence of emphysema. Patients at risk were advised to stop smoking and avoid occupational exposure to lung irritants.


Mitogenic stimulation of lymphocytes in cancer patients. Peripheral blood lymphocytes obtained from 16 controls, 16 untreated cancer patients and 15 cancer patients treated with irradiation were cultured with phytohemagglutinin (PHA) and pokeweed mitogen (PWM). The cultures were terminated on 3 and 7 days of incubation, and mitotic rates were obtained. The mitotic rates of untreated cancer patients for both mitogens did not differ significantly from those of controls. However, the mitotic rate obtained for 3-day PHA culture of the radiation-treated cancer patients was significantly different from controls, whereas the 7-day mitotic rate stimulated by PWM was significantly lower than the untreated cancer patients and controls.


Liver in alpha1-antitrypsin deficiency: morphologic observations and in vitro synthesis of alpha1-antitrypsin. In an effort to characterize the hepatic abnormality in patients with alpha1-antitrypsin deficiency, three unrelated children with the disorder (Pi types ZZ and SZ), two heterozygous parents (Pi type MZ), and three normal subjects (Pi type MM) were studied. As expected, the livers of the ZZ- and SZ-deficient subjects showed abnormal accumulation of alpha1-antitrypsin in the cisternae of the rough endoplasmic reticulum as judged by immunofluorescent and electron microscopic studies. Their parents (MZ phenotype) demonstrated identical although less extensive hepatic abnormalities. Short term cultures of liver tissue in the presence of radiolabeled amino acids showed both synthesis and release of alpha1-antitrypsin in normal control subjects and in the patients with the Z protein. Radiolabeled intracellular alpha1-antitrypsin could not be found. These studies demonstrate synthesis of alpha1-antitrypsin by the livers of normal and genetically deficient subjects in vitro, and suggest several possible mechanisms for alpha1-antitrypsin deficiency.


Morula forms of E rosettes: distribution, specific inhibition, and enhancement. Rosetts-forming cells (RFC) with more than 10 sheep red blood cells (SRBC's) per cell defined as morula-forming cells (MFC) were studied in human lymphoid organs and in the peripheral blood (PBL). MFC are most common in the thymus (more than 50%) and the frequency is much less in peripheral lymphoid tissues and in the blood (29.8% in those less than 5 years old; 14.9% in adults). There is very slight decrease in total RFC in PBL over age 5, but the changes in MFC are quite striking. Treatment with antihuman thymus antiserum (ATS) and with anti-human lymphoblastic antiserum (ATL) resulted in significant inhibition of total rosette and morula rosette formation. No inhibition was seen using normal brain antiserum, anti-IgM antiserum, or anti-L chain antiserum. In two patients with chronic lymphocytic leukemia and in some cases of thymic deficiency the ratio of MFC to total RFC was unusually high. After culture with phytohemagglutinin (PHA) and conversion to blast forms or after surface peturbation by papain or freeze-thaw treatment, MFC numbers were increased.


The significance of the Babinski sign in the newborn-a reappraisal. A study of the clinical significance and the stimulus methods used to elicit the Babinski sign in normal newborns has been carried out. Although the most frequent response to cutaneous nociceptive stimulation of the lateral sole in neonates was extension of the great toe, a small but significant number of flexor responses were obtained. Consequently, the Babinski sign has limited clinical usefulness as a reflex indicating the presence or absence of neurological disease in the newborn. In reviewing previous studies in the literature, it was apparent that the widely differing percentages of extensor plantars reported in newborns was related directly to differences in the technique of examination.


Feedback of isotonic muscle contraction on neuromuscular impulse transmission in the frog. The effect of isotonic contraction on neuromuscular impulse transmission was studied in the in vivo M. gastrocnemius preparation of the frog. The N. ischiadicus was stimulated regularly with single pulses at different frequencies in the range of 1/8 to 8 Hz. When steady state conditions were reached, each half-minute a second stimulus was added to one of these pulses. The interval between the pulses of the pair was varied within the contraction cycle of the first stimulus. Compound extracellular or single intracellular action potentials were recorded from the muscle. At frequencies of 1/2-2 Hz a depression of the amplitude of the second compound muscle action potential of up to 50% of the first response was found when the muscle contracted isotonically. However, the second response was facilitated during an isometric contraction. The time course of the depression was equal to that of muscle shortening during the twitch, while the time course of facilitation corresponded roughly to that of facilitation of transmitter release. At lower frequencies the "isotonic depression" or "isometric facilitation" was not or only slightly present. However, at 1/8 Hz the depression could be evoked or increased by curarization. At frequencies higher than 2 Hz facilitation dominated over depression under isotonic conditions. With flexible intracellular micro-electrodes it was shown that the depression of the amplitude of the compound muscle action potential observed during the isotonic twitch was due to a reduction in neuromuscular impulse transmission. It is concluded that the isotonic depression is a negative feedback effect of the change of length of the contracting muscle on synaptic impulse transmission, probably due to an effect of length on transmitter release.


Recovery of sensitivity to acetylcholine following desensitization in muscles of different vertebrate species. The recovery after desensitization (DS) of the frog sartorius muscle postsynaptic membrane has a constant rate with a half-time of about 6 sec at 22 degrees C. Several other avian and mammalian species were also examined to answer the question, whether this parameter differs in muscles of different function and acetylcholine receptor properties. The following muscles were studied using iontophoretic microapplication of ACh: frog m. cutaneus pectoris, chick anterior and posterior latissimus dorsi, innervated and denervated rat diaphragm, and diaphragm of awake and hibernating golden hamsters. In all cases, desensitization developed when series of 6-20 short ACh doses were applied to the end-plate region of the muscle fibre membrane without any DS potentiating drugs. Rate of DS onset was dependent on the dose and/or  frequency of ACh application. The rate of recovery, however, differs very little in all the muscles studied, the half-times being in the range of 5-6 sec at 22 degrees C. A similar rate of DS recovery was thus found in muscles with different pharmacological properties of cholinoreceptors (e.g. different sensitivity of frog and rat innervated and denervated muscles to d-tubocurarine), or different ionic pathways during activation (hibernating golden hamster). These results support the assumption that desensitization is not of receptor origin and indicate that the system operating during DS does not undergo substantial changes during the functional differentiation of vertebrate muscle membrane.


Effect of kinins on the central action of serotonin. Kinins, the biologically active peptides, potentiate the central stimulatory effects of NA and depressant action of acetylcholine as have been shown by the authors previously. The aim of the work has been to study the effects of these peptides on the central action of 5-HT. For experiments female Wistar rats were used. 5-HT given ivc to the animals and 5-HTP applied ip resulted in an increase of the pain threshold to the electrical stimuli and in a worse motor coordination. Bradykinin injected ivc or kallikrein ip to some extent abolished these effects. The biochemical tests revealed that bradykinin ivc lead to a significant decrease in 5-HT content in the midbrain. In experiments in vitro this peptide increased markedly the release of the platelets 5-HT and inhibited the uptake of this mediator to platelets. The results have shown that kinins can attenuate the central action of 5-HT. This effect can be ascribed, at least in part to a kinin-induced changes of 5-HT concentration in some structures of the central nervous system.


[Immunological status of patients with amebic hepatic abscess]. The authors studied 10 cases of amoebic hepatic abscess documented by clinical evidence and confirmed by laboratory tests, liver scan and a good response to treatment. The immunological state of the patients was determined by protein electrophoresis, immunoelectrophoresis, counter-immunoelectrophoresis, radial immunodiffusion and roset formation for T and B lymphocytes. It is concluded that the alterations of cellular and humoral immunity is evident in cases of amoebic hepatic abscess; this alterations are more clear in the acute form of the illness and the immunological deficiency is more significant in the celular immunity.


Different responses of lymphoid cells from tumor-bearing as compared to tumor-immunized mice when sensitized to tumor specific antigens in vitro. Lymphoid cells from spleen and lymph nodes of BALB/c mice were sensitized in vitro by cocultivation with cells from syngeneic methylcholanthrene-induced sarcomas. The donor mice were either immunized in vivo by tumor transplantation followed by excision ("tumor-excised mice") or were carrying a progressively growing tumor ("tumor-bearing mice"). The cell-mediated immune response of the sensitized cells was compared by a 36-hr microcytotoxicity assay. Lymphoid cells from tumor-excised mice were cytotoxic when tested after 3 days and also after 6 days of sensitization in vitro. Lymphoid cells from tumor-bearing mice were cytotoxic to cells of the tumor borne when tested after 3 days in culture. However, the cytotoxic effect was lost after 6 days of contact with the sensitizing tumor in vitro. Preliminary data suggest that the cultured lymphoid cells of tumor-bearing mice which have lost cytotoxicity, can suppress the reactivity of in vitro sensitized lymphoid cells from tumor-excised mice.


Separation of T cell subpopulations capable of DNA synthesis, lymphotoxin release, and regulation of antigen and phytohemagglutinin responses on the basis of density and adherence properties. T memory cells specifically responsive to ovalbumin and performing the diverse functions of DNA synthesis, lymphotoxin release, and regulation can be isolated in enriched numbers in the most buoyant fractions (A+B) of bovine serum albumin gradients on day 9 after sensitization. At least 20-30% of these cells are capable of mounting a blastogenic response to ovalbumin. A+B cells responding to ovalbumin with DNA synthesis have adherent properties and are further enriched on passage through glass wool. The subpopulations capable of entering into blastogenesis and DNA synthesis and of lymphotoxin release are unresponsive to T mitogens. A+B cells are capable of either potentiating or suppressing DNA synthetic responses to both phytohemagglutinin and antigen when added to 5 X 10(5) D cells in different proportions. Potentiation or suppression of phytohemagglutinin responses were observed with 1 X 10(5) A+B cells, and total suppression was observed with A+B in the range of 4 X 10(3) to 2 X 10(4). The response to antigen was sometimes inhibited in the same cell combinations that gave a potentiated response to phytohemagglutinin and vice versa. Regulatory cells in this system were not macrophages since their effect was not mimicked by addition of peritoneal macrophages, and ablation of macrophages by carrageenan affected neither the potentiation nor suppression.


H-2 gene complex restricts transfer of delayed-type hypersensitivity in mice. Sensitized lymphocytes can transfer a state of delayed-type hypersensitivity to soluble protein antigens to naive mice only if donor and recipient share the I-A region of the H-2 gene complex. Identity at the K or D region is not essential. The restriction is unlikely to result from ineffective homing of the injected cells or from their early destruction. It is thought to reflect a requirement for an Ir-gene controlled mechanism which governs effective interaction between sensitized T lymphocytes and antigen presented on the surface of macrophages.


Specific human B lymphocyte alloantigens linked to HL-A. Sera, previously found to react specifically with B lymphoid cultured cells, were tested on isolated T and B peripheral blood lymphocytes in a microcytotoxicity assay. Studies were performed on lymphocytes obtained from several large Amish families. The sera used in these studies were cytotoxic to peripheral blood, B lymphocytes, but not cytotoxic to T lymphocytes. The antigens detected followed the inheritance pattern of HL-A haplotypes. The strong linkage disequilibrium with HL-A antigens suggests that genes controlling the expression of B lymphocyte antigens are linked to genes controlling HL-A alloantigens.


Factor-VIII-related antigen: multiple molecular forms in human plasma. Analysis of Factor-VIII-related antigen (vWAg) in normal plasma by crossed immunoelectrophoresis reveals an asymmetric pattern indicative of molecular heterogeneity. This asymmetric pattern apparently results from the presence of multiple molecular forms of VWAg with distinct, though partially overlapping, mobilities on crossed immunoelectrophoresis. Evidence for this conclusion has been obtained by separating these forms, one from another, utilizing cryoprecipitation, agarose gel chromatography, and ion-exchange chromatography. Variation in the relative destribution of VWAg forms in liver disease and disseminated intravascular coagulation suggests that the processes which govern generation and/or breakdown of these forms can be altered by disease.


Inhibition of cell-mediated cytolysis of trinitrophenyl-derivatized target cells by alloantisera directed to the products of the K and D loci of the H-2 complex. The role of the products of the K and D loci of the H-2 complex as target antigens for cytotoxic T cells generated to modified syngeneic cells has been investigated. Spleen cells, when cocultured with trinitrophenyl-derivatized syngeneic cells, generate cytolytic T cells that lyse most effectively tumor or spleen targets that are trinitrophenyl-derivatized and H-2 identical to the sensitizing cell. Cytolysis is inhibited by alloantisera to the K and/or D specificities of the target cells and by anti-dinitrophenyl antisera. Cytolic cells generated in this manner are also able to lyse, though less efficiently, trinitrophenyl-derivatized tumor and spleen targets that do not share products of the K and D loci with the sensitizing cell, and this cytolysis is also blocked by alloantisera directed to the H-2 serological specificities of such targets.


Inhibition of in vitro immune responses by antisera to H-2 or Ir gene products. Heat aggregated IgG and antisera reacting with Ir-1 products (Ia antigens) inhibited the in vitro primary responses of mouse spleen cells to SRBC by 50-90% and depressed EA but not EAC rosette formation by 70-90%. These experiments suggest that alloantisera to the H-2 complex express at least part of their inhibitory properties by blocking the Fc receptor on B cells, and the data support the concept that certain Ia antigens and the Fc receptor are identical or closely associated. In addition, these studies showed that the immune response may be inhibited by antisera that react with H-2K and H-2D gene products.


Colony stimulating factor (CSF) from human leukemic urine: affinity chromatography and isoelectric focusing. Biological activities associated with colony-stimulating factor (CSF) from human leukemic urine were found to be selectively retained on an affinity adsorbent of Con A-Sepharose. Elution of activity was achieved using a linear gradient of eith alpha-methyl-D-mannopyranoside (alphaMM) or alpha-methyl-D-glucopyranoside (alphaMG), and resulted in significant increases in specific biological activity. Rechromatography of appropriate fractions indicated that retention of CSF activities was not artifactual. Pretreatment of the affinity matrix with alphaMM completely inhibited binding of CSF. Affinity chromatography of CSF on a Blue Dextran-Sepharose adsorbent was found to be an effective method for removing albumin, a major protein contaminant in urinary preparations. Treatment of CSF with neuraminidase had no effect on its in vitro activity; however, such treatment resulted in an increase in the isoelectric point of CSF from pH 3.5 to pH 4.7, as determined using both sucrose and polyacrylamide gel stabilized pH gradients. Relatively broad regions of biological activity were observed following isoelectric focusing of both neuraminidase-treated and untreated CSF, suggesting that activity was associated with a heterogeneous/polydisperse population of molecular species.


Activation of T-lymphocyte helper function by brief exposure to antigen-pulsed macrophages. In this report we investigated the ability of macrophage-associated OVA to stimulate purified OVA-immune T-lymphocytes to produce nonspecific helper activity for antibody production. T-cell activation required only a brief contact between the antigen-pulsed macrophages and T-lymphocytes and was maximal after a 4-hr contact. T-cell activation occurred at 37 but not at 4 degrees C, indicating that the macrophages and/or lymphocytes must be metabolically active for efficient activation. In addition, we compared the ability of antigen-pulsed syngeneic or allogeneic macrophages to activate T-cells for helper function.


Control of the rat's sniffing behavior by response-independent and dependent schedules of reinforcing brain stimulation. The rat's sniffing response occurs in continuous bursts, at approximately 5-11 Hz. In the present experiments, the analog signal from a thermo-couple probe in the nasal cavity was digitized to provide a discrete logic pulse, defining a sniff, and permitting on-line presentations of reinforcing brain stimulation contingent on momentary sniffing patterns. Schedules of reinforcer presentation included response-independent fixed interval (temporal conditioning), continuous reinforcement (CRF), and differential reinforcement of low rates (DRL 10 sec). Under temporal conditioning, bursts of sniffing were observed immediately after stimulation, and an acceleration in sniffing developed preceding stimulation. Under CFR, operant rate-intensity functions were found to be similar to traditional bar-press data. Under DRL, sniffs were effectively paced by the criterion interval, and interresponse time analyses revealed evidence of temporal discrimination. The behavioral patterns were interpreted in terms of the interplay of operant and respondent functions.


Behavioral supersensitivity to 5-hydroxytryptophan induced by chronic methysergide pretreatment. The administration of 5-hydroxytryptophan to intact guinea pigs results in rhythmic myoclonic behavior. This behavior is blocked acutely by methysergide, but is intensified in animals chronically pretreated with methysergide. Brain serotonin concentrations of guinea pigs pretreated with methysergide did not differ from saline-treated animals. These results are compatible with the hypothesis that prolonged methysergide administration can result in pharmacologically-induced denervation hypersensitivity at central serotonin receptors.


Effects of phenylalanine and 5-hydroxytryptophan on seizure severity in mice. The degree of audiogenic seizure was measured in DBA/2J (phenylalanine hydroxylase deficient) mice as a function of dietary phenylalanine (Phe) and injected 5-hydroxytryptophan (5-HTP), the precursor of serotonin (5-HT). Phe was shown to exacerbate seizures significantly, and seizure severity was found to be directly related to dietary concentration when animals were not treated with exogenous 5-HTP. 5-htp was observed to significantly ameliorate seizures. The seizure-intensifying effect of Phe was reversible by 5-HTP injection and protection against seizures was directly related to 5-HTP concentration for animals on a high Phe diet. The results of this study indicate that Phe and 5-HTP are mutually antagonistic in modulating audiogenic seizure suceptibility.


Demonstration of bleeding from Meckel's diverticulum by means of selective arteriography of the superior mesenteric artery. The diagnosis of a bleeding Meckel's diverticulum was made in a young man who presented several episodes of rectal bleeding over a period of 3 years. Attempted diagnosis by barium studies did not reveal the diverticulum. Angiography of the superior mesenteric artery revealed a wide and tortuous ileal branch -and at its distal end extravasation of contrast medium, within the walls of the diverticulum. It is suggested that in case of major bleeding from the lower GI tract, arteriography should be performed before other contrast medium studies.


Radiological diagnosis of intracranial processes in children. In children with suspected brain tumours, clinical features and simple radiological procedures such as cranial X-rays give little information on the localization of the process. Even at the slightest suspicion of a tumour, extensive neuroradiological studies are indicated. The diagnostic importance of ventriculography, pneumoencephalography and angiography is discussed with reference to 28 patients.


Atypical radiographic features in Pneumocystis carinii pneumonia. The chest films in 30 proved cases of Pneumocystis carinii pneumonia were reviewed to determine the incidence of atypical radiographic findings. Seventeen of 30 patients or 56% presented at least one atypical radiographic finding during the course of the disease. Unilateral distribution, lobar involvement, abscess formation, fulminant progression, and atelectatic changes were observed in more than half the patients. A classic radiographic presentation, justifying treatment without biopsy, was seen in only 13 of the 30 patients.


[Deficiency of alpha-1-antitrypsin and the allele Pi nul]. Alpha-1-antitrypsin is a glycoprotein in human serum that inhibits several proteases. It is a polymorphic protein. A single autosomal locus (Pi), with multiple codominant alleles is responsible of the synthesis of alpha-1-antitrypsin. Of particular interest are alleles that lead to lower than normal concentrations of alpha-1-antitrypsin in serum, namely, PiS, PiP and PiZ. Some of these subjects carry a high risk of developing chronic obstructive pulmonary disease, especially when they are homozygotes for PiZ. In children, cirrhosis of the liver are also found in association with homozygosity for PiZ. recently, TALAMO discovered a subject whose serum contained no alpha-1-antitrypsin; this was the first case of total deficiency, and the patient carried a double dose of the so-called Pi--allele (Pi nul). We were able to demonstrate that a single dose of this allele exists in three families which we have studied in this paper. In a fourth family, the propositus carries Pi-- in duplicate. We report here the second case of the strange homozygous phenotype, Pi--. Surprisingly, we have found that alpha-1-antitrypsin is not completely absent in this serum; its concentration is 200 times lower than normal (less than 10 microgrammes per ml). At the moment, the existence of the Pi-- allele is obvious, but the significance of this small quantity of alpha-1-antitrypsin in the serum of such a patient remains unknown.


[Adhesion and aggregation in the subendothelium: hereditary platelet function disorder]. Platelet adhesion to a thrombogenic surface and adhesion-induced aggregation were investigated using a perfusion system at a blood flow rate similar to that observed in arteries. Morphometric measurements revealed diminished adhesion of platelets but normal surface-induced aggregation with blood of patients with von Willebrand's disease and with Bernard-Soulier syndrome. In contrast, surface-induced aggregation was defective with blood of patients with storage pool disease, thrombasthenia and with blood of healthy volunteers after Aspirin ingestion. These findings may explain the defective hemostasis in these patients. They suggest that platelet adhesion and aggregation are governed by different mechanisms.


What retains water in living cells?

What retains water in living cells? Three types of evidence are presented showing that the retention of cell water does not necessarily depend on the possession of an intact cell membrane. The data agree with the concept that water retention in cells is due to multilayer adsorption on proteins and that the maintenance of the normal state of water relies on the presence of adenosine triphosphate as a cardinal adsorbent, controlling the protein conformations.


Activation of transplant immunity: effect of donor leukocytes on thyroid allograft rejection. The survival of thyroid allografts in mice was prolonged by either holding the grafts in vitro culture for 20 to 27 days or by cobalt-60 irradiation of the donor 2 days before transplantation  with or without the intravenous injection of colloidal carbon just before removing the thyroid from the donor. In both cases the rejection process was restored by an intravenous injection of recipients with living peritoneal exudate cells (50 to 80 percent macrophages) syngeneic to the thyroid donor.


Influence of cadmium and other trace metals on human alpha1-antitrypsin: an in vitro study. The effect of trace metals on plasma alpha1-antitrypsin was studied in vitro by adding known concentrations of trace metals, either alone or in combination, to plasma. Cadmium was the only trace metal that reduced the concentration of alpha1-antitrypsin and depressed the trypsin inhibitory capacity. No such effects were found with divalent lead, mercury, nickel, iron, and zinc ions. The present study appears to offer a plausible explanation for the emphysema that occurs in industrial workers exposed to cadmium.


Merocyanine 540 as an optical probe of transmembrane electrical activity in the heart. Frog hearts stained with merocyanine 540 shows a 1.5 to 2.0 percent increase in fluorescence intensity at 585 nanometers during the cardiac action potential when excited with a 540-nonometer light beam. Fluorometric action potentials similar to those recorded with intracellular microelectrodes in pacemaker, atrial, and ventricular tissues were recorded by focusing a 1-millimeter excitation beam on various regions of the heart. The signal-to-noise ratio for a single action potential ranged between 10/1 and 40/1. In spontaneously pacing hearts the slower rate of rise of the fluorescence action potential is due to the slow propagation of the electrical signal. In solutions containing normal calcium concentrations the fluorometric signal is altered by contractions. Merocyanine 540 is biologically inert as it stains the cardiac cell membrane and acts as a sensitive optical probe of the change in transmembrane potential.


Benign bone tumors.

Benign bone tumors. There is little information in the literature concerning the role of bone scanning in benign bone neoplasms except for sporadic reports. Since the advent of 99mTc-polyphosphate, bone imaging has proven feasible and useful in locating the cause of bone pain, such as in osteoid osteomas, which are not always radiologically apparent, and in evaluating whether or not a radiologic lesion is indeed benign and solitary. Blood-pool images are particularly important in neoplastic disease, since the absence of hyperemia in the immediate postinjection period favors the diagnosis of a benign neoplasm, as does low-grade uptake on the delayed study. The scan, including pinhole magnification images, is especially valuable in diagnosing lesions in the spine and pelvis, which are poorly seen radiologically. We have studied various types of benign bone tumors, including simple and aneurysmal bone cysts, fibrous cortical defects, and nonossifying fibromas, all of which had minimal or no increased uptake of the radiopharmaceutical, unless traumatized. Although osteochondromas and enchondromas showed varied accumulation of activity, the scan was useful in differentiating these from sarcomatous lesions. All osteoid osteomas demonstrated marked activity, and could be accurately located preoperatively, as could the extent of fibrous dysplasia. The bone scan in the reticuloses also showed abnormal accumulation of activity, and aided in arriving at the prognosis and treatment of histiocytic bone lesions.


Creation of a reliable gastric bleed in dogs for angiographic studies. A method of creating a brisk and reliable bleed from the left gastric artery of the dog has been developed. This has been quantitated and emonstrated by celiac and left gastric arteriography. Such a model lends itself to studies on the pharmacologic or embolic control of bleeding of the stomach.


Intestinal fistula complicating pancreatic abscess. Intestinal fistulization following acute pancreatitis is a complication of abscess formation and may occur after initial surgical drainage. It should be suspected in anyone with protracted pancreatitis in whom an abdominal mass suddenly disappears or in whom gastrointestinal bleeding develops. Although transient improvement may occur, decompression will often be incomplete and will usually be followed by recurrent sepsis or severe life threatening hemorrhage. For this reason, spontaneous fistulization into the intestine does not eliminate the need for adequate surgical drainage. With fistulas into the colon, drainage should be combined with proximal diverting colostomy. Some duodenal fistulas may respond to abscess drainage and intravenously administered hyperalimentation, while others may require drainage plus conversion from a side to an end fistula.


A simple test to determine the site of bleeding in the upper part of the gastrointestinal tract. A noninvasive test has been developed to distinguish variceal bleeding from bleeding due to gastritis or ulcer disease. The test is based on the ability of shed blood to lower the pO2 of the gastric saline solution irrigant. It correctly predicted the site of bleeding in four of five patients with variceal hemorrhage and nine of nine patients with bleeding from gastritis or ulcers.


The liver as a privileged site for parathyroid alloimplanation in the rat. It has been suggested that the liver suppresses the immune response to alloantigen. This hypothesis was tested utilizing parathyroid implantation into the liver and muscles of inbred rats. Recipients were parathyroidectomized and, after significant hypocalcemia, donor parathyroids from minor histoincompatible rats were implanted either in liver or in thigh hamstring. In one experimental group second-set grafting also was tested. Graft survivals were evaluated by (1) duration of functional response (DFR), the period of time during which the serum calcium level remained above the postparathyroidectomy baseline, (2) maximal response (MR), the proximity of the postimplantation calcium peak response to the normal preparathyroidectomy calcium level. Parathyroid implants survived significantly longer in the liver compared to the muscle, only when implanted across minor histocompatible barriers. It is suggested that the liver may contain an inhibitor, capable of suppressing the lymphocytes and thus suppressing immune response, which can be demonstrated when the histocompatibility barrier is weak.


Clinical observations and their relationship to laboratory findings in the haemophilias. Continuous observations in shcool terms have been made on the frequency of spontaneous bleeding episodes in a group of adolescent boys suffereing from haemophilia (39 cases), Christmas disease (9 cases), and von Willebrand's disease (2 cases). The observations suggest that in haemophilia other factors, besides the deficient factor VIII, affect the bleeding frequency. In the two boys with von Willebrand's disease, the lower level of factor VIII was associated with the milder symptoms; whereas in boys with Christmas disease clinical severity and laboratory results seemed to be correlated.


Analysis of 140 consecutive autopsy cases of cerebrovascular strokes in northern Japan. On the autopsy findings of the 140 consecutive stroke cases, some characteristics of cerebrovascular diseases in this district were discussed. Predominance of intracranial hemorrhage (cerebral hemorrhage and subarachnoid hemorrhage) over cerebral infarction was still evident. Ruptured intracranial aneurysms were demonstrated in 98% of fatal subarachnoid hemorrhage. Compared with the autopsy data of other institutions, the age of death was generally low, the median age for cerebral hemorrhage, subarachnoid hemorrhage and cerebral infarction falling in the fourth, fifth, and sixth decade, respectively. Cerebellar hemorrhage was relatively frequent, while blood dyscrasias and other symptomatic hemorrhage constituted only a small part in contrast with the report of American authors. A dominant role of hypertension in causing strokes was concluded from both the heart weight and the clinical records.


Enhancement of gustatory neural response to salts following adaptation of frog tongue to quinine-HCI. After a frog tongue was adapted to 0.001 M quinine-HCl(Q-HCl), a change in the gustatory neural responses to salts was investigated. The initial phasic response to a variety of salt solutions such as 0.1 M NaCl, KCl, LiCl, MgCl2 and CaCl2 was greatly potentiated as a result of the Q-HCl adaptation. A weaker enhancement of the response to salts was observed after the tongue was adapted to deionized water, compared with the control response to salts during Ringer adaptation. Therefore, the Q-HCl-induced enhancement of salt responses is due to the summated effect of Q-HCl solute and water solvent. Concerning the enhancing mechanism of Q-HCl, it is postulated that the membrane potential of some salt-sensitive taste cells will be displaced in the hyperpolarizing direction during the Q-HCl adaptation, and that large depolarization, which may be related to the enhanced nerve response, will be produced by applying salts after Q-HCl.


[Hemorrhages after stomatological-surgical interventions. Experiences with patients of the stomatological emergency service at the university stomatological clinic in Halle]. The author reports of experiences with 627 patients presenting with haermorrhage at the night emergency service of a university clinic of stomatology. Postoperative bleedings occurred mainly in the molar region. In 6 patients, an underlying disease until then unknown was recognized as a cause; a further 3 patients were under anticoagulant therapy which had not received the attention it deserved. Local surgical and medicamentous therapy is of special importance in the treatment of postoperative bleeding.


Multiple target cell killing by the cytolytic T lymphocyte and the mechanism of cytotoxicity. Previous reports have shown that one cytolytic T lymphocyte (CTL) can kill more than one allogeneic target cell, but have not established whether after its action on one or more target cells, each CTL can attack a second set of target cells at a later time. The experiments described here show that one CTL can kill more than six target cells, and they suggest that CTL can do this sequentially in time. Hence, the small number of specifically sensitized lymphocytes found in rejecting grafts could play an important role. Moreover, sequential killing would imply that CTL are not harmed during their interaction with specific target cells. If killing were effected by secretion of a nonspecific toxin, the killer cell would then have evolved some device for resisting its own toxin in order to survive. Whether or not this is the case has not yet been fully resolved.


Recurrent corneal granular dystrophy: a clinicopathologic study. Recurrence of granular corneal dystrophy occurred in two patients following two successive penetrating corneal grafts. In the first patient, the deposits involved the central stroma of the donor cornea, almost to the level of Descemet's membrane. The second patient had predominantly subepithelial deposits in bilateral recurrences. Electron microscopy revealed rod-shaped, electron dense material typical of granular dystrophy in both patients.


[Chemotherapy of gestational chorionepithelioma]. The department of Gynecology and Obstetrics of Florence University reports the following findings for the chemotherapy of gestational choriocarcinoma during the period 1962-74. Sixteen cases, 11 of which were rated high risk cases, were given chemotherapy with MTX alone or in association with other cytotoxic agents. In the 12 surviving cases that may be considered the incidence of complete remission (from 4 to 13 years) is 67%. Of the 8 cases rated as cured 3 were high risk cases at the beginning of treatment. Intermittent chemotherapy with MTX only was given by slow intravenous injection at doses of 3 to 4 mg/kg for 24-48 h followed from the 48th h by folinic acid treatment for 1-2 days. This schedule is recommended because of its negligible toxicity as a replacemen for intramuscular MTX in 5-day courses, which carries a fairly high risk of toxicity.


[Gastrointestinal hemorrhage as a complication of different diseases and conditions]. The author presents an analysis of the cause of bleeding in 37 patients and the genesis of development of erosions, acute ulcers of the mucous membrane of the stomach and duodenum (57 observations). Some recommendations on the diagnosis and prophylaxis of gastrointestinal hemorrhages are given.


[Profuse hemorrhage into the digestive tract in aortic diseases]. Four observations of the aortic aneurysm rupture with hemorrhage into the jejunum (2 cases), duodenum (1 case), esophagus (1 case) are reported. The causes of development of pathological changes in the aortic wall were as follows; atherosclerosis - in 3 patients, tuberculosis - in 1.


[Allergic gastric hemorrhage in a case of milk hypersensitivity]. In a 50-year-old patient who was repeatedly hospitalised on account of melaena and twice operated without finding an ulcer the cause of the haemorrhage was first unknown. In the sixth massive haemorrhage endoscopically was established a haemorrhagic erosive gastritis which underwent a spontaneous retrogression (gastroscopic control). Since the skin test on milk was positive, it was not thought of an allergic gastritis by milk and a provocation test was carried out twice which had a positive result (haemorrhagic erosive gastritis after instillation of milk into the stomach). With the publication of this case the attention shall be turned to the gastric haemorrhage caused by a nutritive allergy as well as to the diagnostic value of the simply producible provocation test.


[T- and B-lymphocytes in the so-called collagenoses]. Lymphocytes of peripheral blood of patients with systemic lupus erythematosus, scleroderma and dermatomyositis were investigated, and relatively, with regard to T- or B-cell characteristics. T-lymphocytes of most patients with SLE were decreased both absolutely. B-lymphocytes mostly showed only a relative increase. Successful immunosuppressive treatment usually accompanied by normalization of T-cell number and with decrease of B-cells. This differentiation of lymphocytes is an additional aid in the determination of activity of SLE and a useful index of immunosuppressive-cytostatic treatment.


[Dynamics of the antismallpox antibodies detectable in the passive hemagglutination reaction with various animal immunization schemes]. Dynamics of accumulation and preservation of antibodies detectable in the PHAT (PHAT-AT) was studied on rabbits and guinea pigs with the use of various doses of the living inactivated virus and their combination in comparison with the virus-neutralizing antibodies, antihemagglutinins and precipitins. Accumulation of the virus-neutralizing antibodies did not coincide in time with the curve of the PHAT-AT accumulation; the titres of the virus-neutralizing antibodies were higher than the PHAT-AT titres. At the same time the percentage of seroconversions determined by PHAT was equal to 100 and the PHAT-AT level directly depended on the immunizing dose, the time of administration and the type of the antigen. On the basis of the data obtained PHAT could be recommended as a test for the assessment of the immunological efficacy of the smallpox vaccinations.


Effects of thyroxine on T-cell counts and tumour cell rejection in mice. In an attempt to study the effect of thyroxine on peripheral T-cell (thymus derived lymphocyte) counts or immunological functions, inbred C3H/He mice (8-10 weeks old) were injected subcutaneously with thyroxine for more than 3 months. After treatment for 3 months the mice were examined for peripheral T-cell counts, thymic incorporation of tritiated thymidine and rejection of tumour transplants. The number of T-cells was counted by the indirect immunoflourescence method using anti-thetaC3H serum after separation of lymphocytes on "Ficoll-Conray". It was revealed that the peripheral counts of both lymphocytes and T-cells were increased in the thyroxine treated group as compared with the control group, as was reported in the patients with Graves' disease. Thymic incorporation of tritiated thymidine was also found to be significantly increased in the thyroxine treated group. In addition, in order to study T-cell activity of the host, thyroxine treated and control mice were challenged with Ehrlich carcinoma cells at several concentrations (10(2), 10(4) and 2 x 10(6) per mouse). It was found that rejection of tumour transplants was significantly enhanced in the T-cell rich mice. Thus, it is possible that throxine affects peripheral T-cell counts and enhances immunological functions of the host.


Experimental studies on the nerve--sensory cell relationship during degeneration and regeneration in ampullar nerves of the frog labyrinth. The degeneration and regeneration of afferent and efferent nerves to the crista ampullaris in the frog were studied after transsection of the ampullar nerves. In some experiments one or both rostral ampullar nerves were simply divided and left in place. In other experiments the ampullar nerves to the horizontal and to the anterior vertical crista were divided and the branch to the former was brought into contact with the distal stump of the anterior vertical ampullar nerve. Sensory cells in the labyrinth survived total denervation for 1-2 weeks without regular signs of ultrastructural damage. The afferent synaptic structures in these cells were often preserved in the denervated stage. The afferent nerve fibres degenerated earlier than the efferent ones. Both type of fibres reinnervated the vestibular epithelium after division of the ampullar nerve. The fibres from a horizontal ampullar nerve could reinnervate a denervated anterior vertical crista, resulting in misdirected reflexes. About 40 days after division both function and morphological organization had been restored to normal.


[The influence of age on vestibular function]. Regular changes in vestibular responsitivity as a function of age are demonstrated with the maximum speed of the slow phase of caloric nystagmus. The clinical implication of this is that, when doing caloric tests, one should not switch for no reason from a once accepted temperature sequence, otherwise comparison with other tests becomes impossible. It rotation tests the best reactions are found in young people. The amplitude is a good parameter to detect age-factors in rotatory nystagmus.


[Models and experimentation. Vestibular adaptation]. In 1961, we have given the experimental proof that, in the frog, the excited or inhited electrical activity of the ampullar nerve produced by a copular deflection of long duration, showed a decline which was attributed to an "adaptation" of peripheral origin. We suggested that the "inverse phase" was due to this adaptation. Since then, many workers have showed that such an adaptation was to be found in the induced nystagmus by prolonged angular acceleration. The mathematical models constructed to explain the vestibular function have to take in account this response decline to coincide with the evolution of the slow phase velocity of the nystagmus, during the prolonged deflexions of the cupula produced by the clinical vestibular rotatory and caloric tests.