Low-level dynamic exercises for earlier cardiac rehabilitation: aerobic and hemodynamic responses. Three different kinds of low-level exercise (one arm and two leg exercises) and a low-level treadmill test were designed for patients recovering from acute myocardial infarction; noninvasive circulatory and aerobic responses to these activities were evaluated in healthy subjects. Exercise systolic pressure-rate product (X 10(-2)) were, respectively, 92 +/- 16, 98 +/- 10, 106 +/- 22 and 129 +/- 17 for the four activities studied. Exercise metabolic rates were 1.56 +/- 0.16, 1.99 +/- 0.22, 1.68 +/- 0.25 and 2.74 +/- 0.32 METS (multiples of the observed resting oxygen requirements). Additionally, arteriovenous oxygen difference, cardiac output, stroke volume, mean systemic and mean pulmonary pressures were measured in four coronary patients as they performed the leg exercises. It is hoped that this study will provide a basis for applying these different forms of exercise to patients recovering from an acute myocardial infarction, even when they are confined to bed, in order to advance the onset of cardiac rehabilitation. In a similar way, the new low-level treadmill test may be indicated for the same patients to assess the safety of discharging them from the hospital and permitting unsupervised ambulatory activity at home.


Pancreatic abscess following acute pancreatitis. Pancreatic abscess is probably the most serious complication of acute pancreatitis. During the ten-year period from 1966 to 1975, twenty-eight patients with pancreatic abscess following acute pancreatitis were treated by surgical drainage. A review of these cases revealed that there was a lull in the clinical course of the antecedent pancreatitis prior to the time of surgical drainage in 70% of the cases. Despite an aggressive surgical approach, there were major postoperative problems in 26 patients. Sepsis persisted in 14 patients. Major gastrointestinal hemorrhage occurred in seven, intra-abdominal bleeding in nine, and fistulization in 13. Fourteen patients died (a mortality of 50%). The operative treatment of pancreatic abscess must be aggressive and persistent. In addition to extensive drainage with soft sump drains, vigilance must be exercised to avoid pressure against bowel or major vessels. Reoperation should be considered if postoperative improvement is not sustained.


Acute massive hemorrhage from intestinal Crohn disease. Report of seven cases and review of the literature. Acute massive intestinal bleeding from Crohn disease occurred in 1.4% of 503 patients undergoing treatment at the New York Hospital-Cornell Medical Center over a 43-year period. Of the entire series, 31% had clinically evident rectal bleeding, while 13% had occult bleeding. Combined with previously reported series, onset of massive bleeding was not influenced by age of patient, duration of Crohn disease, use of corticosteroids, or activity of disease. Surgical therapy gave satisfactory results in patients with life-threatening hemorrhage.


Selective angiography. Inadequate guide for surgery in bleeding colonic diverticula. We describe a case of severe bleeding from left-sided colonic diverticula, 2 1/2 years following right-sided colectomy for massive rectal bleeding confirmed angiographically to be from the right part of the colon. This experience demonstrates that total abdominal colectomy with ileoproctostomy is the only way to ensure that there is no bleeding postoperatively from diverticula, regardless of angiographic findings.


[Interstitial pneumopathies in children treated for malignant diseases]. The authors report 21 cases of severe interstitial pneumonitis observed in 1974 in Paris, in children with malignancies, either solid tumours or leukemias. Twelve patients died. The incidence of these complications in children with intensive chemotherapy and the clinical symptoms which may reveal them are reviewed; the bad prognosis of measles in these patients is stressed. Radiological findings are described and the possible wrong diagnoses are listed. Among viral infections, measles is the severest and its diagnosis is often difficult. Pneumocystis carinii infection is frequent. The use of surgical pulmonary biopsy and other diagnostic procedures is discussed. The immune status of these patients has been studied, which revealed severe impairement of cellular immunity, including low lymphocyte count, while humoral immunity was not changed. Symptomatic treatment may include oxygen supply and mechanical respiratory help, dietary management, and attempts towards non specific immune system stimulation. Aetiologic treatment is essentially the treatment of Pneumocystis carinii, which is discussed. Diagnosis and treatment of pneumonitis in immunosuppressed patients being very difficult, emphasis is made on the prevention of this accident, including caution in the handling of chemotherapy protocols.


Immediate endoscopic diagnosis of upper gastrointestinal bleeding. Its accuracy and value in relation to associated pathology. Two hundred sixty-two patients with active upper gastrointestinal (GI) bleeding underwent panendoscopy between July 1970 and March 1973. There was 100% accuracy of endoscopic diagnosis as to the anatomical site of bleeding; the etiopathologic definition was 94.7% accurate. The series was divided into two groups, 116 with "liver disease" and 146 with "no liver disease." There were 107 patients with varices: 21 fell into no liver disease (small varices) and 86 into liver disease (39 small and 47 large varices). All had associated gastritis. Three endoscopic bleeding patterns were identified in the liver disease group. Only 27% of the patients in the liver disease group with varices (cirrhotics) had frank variceal hemorrhage, whereas 57% bled from hemorrhagic gastritis. The diagnostic unit provided early diagnosis, meaningful therapy, organized data gathering, and rough estimates of ultimate prognosis.


Human T lymphocyte colonies in agar: a comparison with other T cell assays in healthy subjects and cancer patients. Colonies of human lymphocytes with T cell characteristics will grow in agar from repeated mitotic divisions with phytohaemagglutinin (PHA) stimulation. The colonies comprise spheres of tightly-packed cells with up to 500-1,000 blast-like cells in each colony. 65% of cells from pooled colonies bound AET-treated sheep red cells. 1,100-2,500 colonies/10(6) peripheral blood lymphocytes developed when cell donors were healthy but lower numbers (350-1,000 colonies/10(6) lymphocytes) were detected in blood from cancer patients. Comparison with other non-specific assays of cell-mediated immunity showed that while 66% of cancer patients were anergic (to five recall antigens) and 78% exhibited depressed mitotic activity in standard cultures with low dose PHA, 100% of these patients revealed T cell colony formation below normal. It is suggested that further studies of T lymphocyte colony-forming cells in healthy people and in a number of disease states may significantly advance our understanding of mechanisms of cell-mediated immunity.


Effect of anti-inflammatory agent on L-glutamine-D-fructose-6-phosphate transaminase. The enzyme L-glutamineD-fructose-6-phosphate aminotransferase (EC 2.6.1.16) was isolated, partially characterized, and purified from the gastric mucosa of dogs. A new method, using 14C-fructose-6-phosphate, has been developed for the estimation of the enzyme activity. Several classes of standard anti-inflammatory agents including acetyl-salicylic acid, salicylic acid, flufenamic acid, phenyl-butazone, indometacin, mefenamic acid, oxyphenyl-butazone, antipyrine, aminophenazone, allopurinol, cortisol, and dimethylsulfoxide (DMSO) were found to be inhibitors of this enzyme. The property of inhibition of this amino-transferase could, thus, be used as a rapid in vitro test method for the primary screening of potential anti-inflammatory agents.


Lymphocytotoxic antibodies in SLE patients and their relatives. A search for lymphocytotoxic antibodies in 50 SLE patients and in 109 of their blood relatives revealed an incidence of cold-reacting antibodies of 80% and 39% respectively, as compared with 15% in 110 normal blood donors paired for age, sex, and racial origin. The antibodies were also present in 7 of 18 (39%) of the spouses of SLE patients. Lymphocytotoxic antibodies exhibited broad reactivity in all groups, although positive SLE sera showed a tendency to react with a wider variety of lymphocytes and to present higher titers than positive sera from the other groups tested.


Serum antibody in rheumatoid arthritis reactive with a cell-associated antigen. Demonstration by precipitation and immunofluorescence. A cell-free extract of human diploid B lymphocytes (Wil2) in continuous culture was used as the source of antigen in immunodiffusion to detect a precipitating antibody referred to as rheumatoid arthritis precipitin (RAP) in sera of patients with rheumatoid arthritis (RA). The prevalence of RAP was determined in various arthritides and other connective tissue diseases. It was found in 67% of patients with seropositive RA and in 62% of patients with Sjögren's syndrome associated with RA. But its frequency was lower in many other connective tissue diseases, including seronegative RA and Sjögren's syndrome without associated RA. Matching sera and synovial fluids from patients with seropositive RA were also studied. Differences in serum and synovial fluid RAP titers were demonstrated, but generally when RAP was present in serum, it was also present in synovial fluid and vice versa. Indirect immunofluorescence (IF) with Wil2 cells as substrate was used to demonstrate RAP and to determine morphologically the nature of the reactive cellular antigen. When cells were treated with commonly used fixatives, little or no staining with RAP positive sera was observed. This outcome was shown to be the result of the extreme solubility of the cellular antigen reactive with RAP. The antigen was retained best in a reactive form in Wil2 cells after fixation of cells with dry heat at 37 degrees C for 30 minutes, and it was demonstrated by IF staining as small round granules distributed in the nucleus and cytoplasm. IF was also employed to demonstrate that RAP is immunoglobulin belonging to IgG and IgM classes and not to IgA or IgD.


Lymphocyte populations in rheumatoid arthritis. For each of 28 patients with RA and 27 normal controls, the in vitro lymphocyte responses to PHA and to Con A were simultaneously determined on aliquots of the same cell preparation. In the case of RA lymphocytes, the response to Con A was abnormally low when compared with the simultaneous response to PHA (P less than 0.01). Cells capable of responding to PHA were specifically killed with BUdR. The cells remaining after this procedure showed a relatively greater response to Con A than did the original population. In the case of RA lymphocytes, this relative increase in the response to Con A was significantly less than normal (0.02 greater than P greater than 0.01). These results suggest that a lymphocyte subpopulation, responding principally to Con A, is relatively reduced in RA.


Autoantibodies in patients with chronic bronchitis. Antinuclear antibody (ANA) was found in low titre in 28% of a group of 50 patients with chronic bronchitis by MRC criteria and defined as "severe", that is having at least six infective episodes a year, a vital capacity of less than 70% of predicted and less than 30% reversibility of their airways obstruction after inhalation of isoprenaline. By contrast ANA was found in only 4% of age and sex matched non-bronchitic controls and in none of 28 patients with "less severe" chronic bronchitis in whom these three criteria of severity were not fulfilled. The presence of antinuclear antibody was unrelated to the duration of the disease, sputum volume or the presence of purulent sputum at the time of the study. Neither was it related to blood eosinophilia, respiratory function, smoking or the presence of bacterial precipitins in the patient's serum. These findings are important because they suggest that incidental chronic bronchitis, unless it is extremely severe, is unlikely to contribute substantially to the prevalence of antinuclear antibody found in certain other lung diseases. There was no significant increase in smooth muscle or "reticulin" antibodies in this series of patients.


Diagnostic features of the Favre-Goldmann syndrome. Extensive retinal vascular disease was noted in three patients from two families with Favre-Goldmann syndrome. In addition to classical features they had pronounced leakage from some retinal vessels. Vessels were either opaque ('sclerotic') or non-perfused. Cystoid macular oedema was a contributing cause of decreased vision. Two of the three patients showed a discrepancy on electroretinography between single-flash photopic amplitudes and flicker fusion frequency. This may be characteristic of Favre-Goldmann syndrome.


Pyrrolo[1,4]benzodiazepine antibiotics. Biosynthesis of the antitumor antibiotic 11-demethyltomaymycin and its biologically inactive metabolite oxotomaymycin by Streptomyces achromogenes. 11-Demethyltomaymycin, an antitumor antibiotic produced by Streptomyces achromogenes, and its biologically inactive metabolite oxotomaymycin are biosynthesized from L-tyrosine, DL-tryptophan, and L-methionine. The anthranilate part of 11-demethyltomaymycin is derived from tryptophan probably via the kynurenine pathway. The predominant loss of tritium from DL-[5-3H]tryptophan, during its conversion to 11-demethyltomaymycin and oxotomaymycin is interpreted to mean by NIH shift rules, that the main pathway to the 5-methoxy-4-hydroxy anthranilate moiety is through hydroxylation at C-8 prior to hydroxylation at C-7. The methoxy carbon is derived from the S-methyl group of methionine by transfer of an intact methyl group. The ethylideneproline moiety of 11-demethyltomaymycin is biosynthesized from tyrosine, without a 1-carbon unit from methionine. The results of biosynthetic feeding experiments with L-[1-14C, 3- or 5-3H]tyrosine are consistent with a "meta" or extradiol cleavage of 6,7-dihydroxycyclodopa as has also been demonstrated previously for anthramycin and lincomycin A. An experiment in which L-[1-14C, Ala-2,3-3H]tyrosine was fed showed that both the beta hydrogens of this amino acids are retained in 11-demethyltomaymycin. It has been demonstrated in cultures and washed cell preparations that 11-demethyltomaymycin is enzymatically converted to oxotomaymycin by an intracellular constitutive enzyme. Conversion of oxotomaymycin to 11-demethyltomaymycin by these same preparations could not be demonstrated. The enzymatic activity associated with the conversion of 11-demethyltomaymycin to oxotomaymycin is not limited to the 11-demethyltomaymycin to oxotomaymycin is not limited to the 11-demethyltomaymycin production phase, since trophophase cells and even cells from 11-demethyltomaymycin nonproducing cultures of S. achromogenes were equally active in converting 11-demethyltomaymycin to oxotomaymycin.


The effect of ethanol on ion transport in frog skin. Frog skin has been used as a model epithelial sodium-transporting system to study the effect of ethanol on ion transport. Treatment of the outside of frog skin with ethanol decreased the net sodium transport due to inhibition of 22Na+ influx. Ethanol did not alter sodium outflux when bathin the outside of the skin. The inhibition was in proportion to the concentration of ethanol, 0.25 M resulting in 50% inhibition. The chloride permeability of the skin was increased several-fold when the skin was exposed to ethanol in either bathing solution. With 0.4 M ethanol in the inner bathing solution, all the unidirectional fluxes of Na+ and C1- were increased. The movement of C1- was evaluated by comparison of C1- flux with urea flux, since urea is thought to move passively across frog skin via an extracellular (shunt) pathway. Chloride flux was increased to a greater extent than urea flux. These experiments indicate that ethanol affects chloride permeability beyond an increase in extracellular ion flow and independent of its effect of Na+ transport.


Pysicochemical studies of taste reception. V. Suppressive effect of salts on sugar response of the frog. The tast responses of frog to various kinds of sugars were measured quantitatively by use of the glossopharyngeal nerve activity under an appropriate condition where the water response was completely suppressed. The concentration dependences of response of frog tongue to D-fructose, D-glucose, and sucrose were almost the same, D-galactose, however, elicited a much larger response in comparison with the other sugars in the whole range of concentrations examined. The sugar response was suppressed extensively by the presence of small amount of salts in the stimulating sugar solution. The suppressive effects of NaCl, KCl, MgCl2, MgSO4, and K4Fe(CN)6 were examined with a fixed concentration of sugar. The results obtained with these salts, added in various concentrations, fell on a single curve when the data were plotted against the ionic strength in the stimulating solution. The present results were consistent with the notion that the taste receptor potential for salts or acids is attributable to a change in the phase boundary potential at the membrane-solution interface as proposed in the previous papers of this series.


Phytohaemagglutinin stimulation of rat thymus lymphocytes glycolysis. Glucose disappearance and lactate production by the rat thymocytes are stimulated significantly 45 min after addition of phytohaemagglutinin or concanavalin A and the stimulated rate is sustained for at least 8 h. Changes in the steady-state concentration of glycolytic intermediates that occur at non-equilibrium steps during the increased rate of glycolytic flux indicate that the glucose carrier, hexokinase and phosphofructokinase are potentially regulatory steps that undergo nearly simultaneous or tightly sequential activation following interaction of the cells with the mitogen.


Purification and physicochemical properties of superoxide dismutase from two photosynthetic microorganisms. Superoxide dismutase (EC 1.15.1.1) has been isolated and characterised from the blue-green alga Spirulina platensis and from aerobically-grown Rhodopseudomonas spheroides, a purple, non-sulphur bacterium. The former enzyme contains 1 gatom of iron and the latter 1 gatom of manganese per mol; both enzymes have a molecular weight of 37 000-38 000, being composed of two non-covalently joined subunits of equal size. Various spectral studies have been carried out including absorbance, circular dichroism and electron spin resonance. Catalytic activity has been studied as a function of pH and shows a decrease at alkaline pH values. The manganoenzyme is generally more stable to various potentially denaturing conditions and is resistant to inactivation by hydrogen peroxide. Amino acid compositions and N-terminal residue determinations are presented.


Membranes of Rhodopseudomonas sphaeroides. IV. Assembly of chromatophores in low-aeration cell suspensions. Chromatophore membrane formation was induced in low-aeration suspensions of Rhodopseudomonas sphaeroides and highly purified chromatophore preparations were isolated at various intervals between 4 and 18 h. The levels of several functional components associated with the isolated strucures were investigated. B-875, the light-harvesting bacteriochlorophyll complex associated with the reaction center, was preferentially inserted into the chromatophore membrane during the early stages of induction, and thereafter its levels reached a steady state; b- and c-type cytochromes were also maintained at essentially constant levels. In contrast, the levels of B-850, the accessory light-harvesting bacteriochlorophyll, together with its associated protein, continued to increase throughout the induction process. Increases in the levels of the major carotenoid component followed a similar course. These findings are consistent with a stepwise assembly mechanism for associated bacteriochlorophyll and protein components and suggest that separate regulatory mechanisms control the levels of functionally essential and accessory components within the membrane.


The serum sialyltransferase activity in alpha 1-antitrypsin deficiency. alpha 1-Antitrypsin phenotypes Pi M and Z, purified by the thiol-disulfide exchange procedure, were desialylated by treatment with neuraminidase covalently coupled to Sepharose and used as acceptors of sialic acid in an assay system for serum sialic acid transferase (CMP-N-acetylneuraminate:D-galactosyl-glycoprotein N-acetylneuraminyltransferase, EC 2.4.99.1) activity. Both asialoantitrypsins were equally effective as acceptors in contrast to native Pi Z antitrypsin which did not accept any sialic acid. Serum sialyltransferase activity was determined in 38 adult alpha 1-antitrypsin deficient individuals (Pi Z, MZ, FZ, SZ) with normal liver function and was found to be of the same magnitude as the activity in normal individuals (Pi M). Equal activities were also found in 5 Pi Z patients with cirrhosis of the liver. The results strongly argue against the concept that sialyltransferase deficiency provides the molecular basis for alpha 1-antitrypsin deficiency.


Chronic hepatotoxicity and intestinal bleeding in 1,2-dimethylhydrazine carcinogenesis in rats and mice. The long term administration of dimethylhydrazine to mice induces severe hepatotoxic damage. Parenchymal cell pleomorphism and necrosis were later associated with reticulin collapse and bile duct proliferation. Withdrawing the drug after 17 weeks was followed by some improvement in the parenchymal cells but there was a chronic proliferative response tending towards early cirrhotic changes. The rats appeared relatively resistant to the hepatotoxic effects but unlike the mice the colon tumors arising in these animals bled frequently and could result in profound anemia.


A new and simple method of quantifying the bleeding time. Disorders which produce an increase in blood loss after skin trauma do not necessarily result in a prolongation of the bleeding time. A standardized method to quantify this blood loss using the Coulter Counter model S (or other available haemoglobinometer) is reported. The need for and use of such a technique is illustrated by the investigation of primary or secondary haemostatic disorders and assessment of transfusion studies.


Short induction treatment in acute granulocytic leukemia. Short treatment with four cytostatics in acute granulocytic leukemia induced aplasia and reduction of total leukemic cells in 50 over 59 patients. Complete remission occured in 30 and 20 died with infectious complications during induction. Short induction treatment allowed a reduction of induction period and so a reduction of high risk period of induction before completion of complete remission.


Disorganized meridional rows in the lens epithelium of hypophysectomized frogs (Rana pipiens). Hypophysectomy of the frog Rana pipiens causes the disappearance of mitosis in the lens epithelium. The lens epithelium from animals hypophysectomized for ten months has been found to display a disorganization of the meridional rows. Experiments with mechanical and chemical injuries suggest that cell density may be involved in column disorganization.


[Blood flow distribution in the branches of frog mesentery arterial microvessels]. The blood flow distribution in 49 arterial branchings of the mesentery (R. temporaria) was investigated (D of the trunk = 25.7 + 0.0 mum). Linear rate was measured by the impulse digital chronometry of the intervals of the erythrocyte transit time. The geometric characteristics of the branching was determined in vivo, on photographs. An asymmetric structure of the investigated branching was shown; branch 1 had the inner initial cross-section which was 2.2 times greater than that of branch 2 and lesser turning angles (29 and 59 degrees). The blood flow in branch 1 was three times greater than the blood flow in branch 2; this was due to its greater inner initial cross-section and a higher linear rate. According to calculations, the blood flow resistance of the branch-turn was insignificant in the general blood flow resistance of branches; therefore the turning angle of the branches could not serve as an important regulator of the volume of the blood flowing in them. An experimentally revealed association between the blood flow in the branches, their radius and their turning angles is well described by equations of the "optimal" model of the vessel branching.


[Relationship between T- and B-lymphocyte cooperation and their syngeneity]. Cooperation efficiency of (CBA x C57BL/6) F1 thymocytes and CBA bone marrow cells in immune response to SRBC was compared with the syngenic combination of the same cells. Selectivity of interaction of the T- and B-lymphocytes of different origin was studied in incomplete cyclophosphamines (CBA x C57BL/6) leads to CBA chimerae, where donors were primed with SRBC and the recipients were either intact or tolerant to the given antigen. F1 T-cells proved to interact with the CAB-B-cells 10-15 times less effectively than with the syngenic B-cells. It is suggested that similarity between the antigenic structure of the cell membrane of the T- and B-lymphocytes, aiding their physical contact, increased the action efficiency of the T-mediator on the B-cell.


[Use of peritoneal macrophages labeled with Cr51 and cultivated in vitro as target cells for quantitative assessment of the cytotoxic activity of immune T-lymphocytes]. Peritoneal macrophages previously labeled in a suspension with 51Cr and grown in the form of a discontinuous monolayer on glass, pretreated with poly-l-lysin were used as target cells. This permitted to estimate the cytotoxic activity of immune lymphocytes by 51Cr release for the period of 4 and 20 hours of incubation with the target. 51Cr release from such a target incubated with normal lymphocytes for 20 hours did not exceed 10-20% of the maximum release. Application of a 2% solution of sodium dodecylsulfate ensured a 100 per cent solubilization of labeled macrophages growing on the glass surface, and permitted the cytotoxic effect to be determined by measuring the label remaining in the intact cells.


[A peculiarity in the humoral immunity of BALB/C mice with Rauscher leukemia]. There proved to be an increase in B-lymphocyte count (associated with increased synthesis of nonspecific immunoglobulins) in BALB/C mice highly sensitive to Rausher virus, after the administration of a relatively low dose of the virus. After the administration of the virus in combination with complete Freund's adjuvant in the spleen of mice, at the early periods of development of the disease, there were present normal cells synthesizing antibodies against the surface antigen of Rausher leukemia and leukemic cells with blocking antibodies adsorbed on their surface.


[Effect of trasyslol on the permeability of the histo-hematic barrier in ischemic myocardium]. Ligation of the descending branch of the left coronary artery caused an increase in the permeability of the histo-hematic barrier of the myocardium for sulfacyl-sodium in the ischemic area and in the region adjacent to it. Trasylol proved to decrease the permeability of the histo-hematic barrier of the myocardium in the mentioned area, without influencing the intact zone. Fluoresceine test demonstrated the presence of membranotropic effect of trasylol; the preparation had no effect on the osmotic stability of erythrocytes in vitro.


[Aggregated immunoglobulins as antigen-binding receptors of immune lymphocytes]. At the peak of the primary immune response to sheep erythrocytes there appeared in the spleen of mice rosette-forming cells (RFC) effectively inactivated with antibodies against aggregated mouse immunoglobulins and with the complex of polyadenylic-polyuridylic acids (poly-A, poly-U, respectively). These cells disappeared from the spleen on the 9th day after the primary immunization and were not revealed at the peak of the secondary immune response. When small splenic lymphocytes obtained on the 5th day after the immunization with sheep erythrocytes were incubated in vitro for 24 hours the total amount of the RFC inactivated by antibodies to the aggregated mouse immunoglobulin disappeared completely. These data can be considered as an indication of the existence at the peak of the primary immune response of rosette-forming cells having the antigen-antibody complexes in the capacity of the antigen-binding receptors.


[Cytotoxic and complement-binding activity of rabbit antisera against the cortex and cerebral white matter of rats and humans]. The cytotoxicity and complement-fixation activity of rabbit antisera against rat and human brain cortex and white matter was tested against mouse and rat thymocytes and bone marrow cells. The cytotoxic test proved to be more sensitive and accurate. The cytotoxins to rodent thymocytes were found in the antisera against human brain cortex only. At the same time cytotoxic antibodies were revealed both in the antisera rat brain cortex and white matter; but the former contained much more cytotoxic antibodies than the letter. After absorption with the same antigen the antisera against rat brain cortex lost their cytotoxic effect, but retained it in case of absorption with the white matter.


[Selective concurrent suppression of the process of rosette-forming cell accumulation during the immune response]. Repeated injections to mice of normal rabbit immunoglobulins preceding immunization with sheep erythrocytes inhibited the accumulation of rosette-forming cells (RFC) in the spleen, without influencing the proliferation of the antibody-forming cells and hemaggutinin production. Reduction of the RFC under these conditions occurred on account of B-cells whose antigen-binding receptors could be blocked by antibodies against the aggregated mouse immunoglobulins and a complex of polyadenylic-polyuridylic acids. Repeated injections of the competitive antigen enhanced the formation of the immunological memory to the second antigen. The problem of the origin of the immune rosette-forming B-cells and their influence on the formation on the immunological memory is discussed.


[NAG infection of grass frog (Rana temporaria) tadpoles]. Rana temporaria tadpoles (2250) were contaminated with three types of NAG vibrio cultures. Clinical, bacteriological and morphological examinations showed the larvae to be suffering from an acute infection during the first 2 days after the contamination. Then the vibrios persisted in the tadpole organism for a long time and were excreted in the feces.


[T- and B-lymphocyte content in the peripheral blood of healthy subjects]. It was revealed by the method of rosette-formation that the content T- and B-lymphocytes differed in human blood depending on the time of the day and the season. T-cells were at their maximum in the morning and B-cells -- in the evening. The percentage content of B-cells was greater in autumn than in winter.


[Cytogenetic effects of chloroquine in a culture of human lymphocytes]. Chloroquine added to human lymphocyte culture at the G1 stage had no influcence on the chromosome aberration level in the concentration of 15 mug/ml and suppressed the mitotic activity of the cells almost completely in the concentration of 60 and 100 mug/ml. At the G2 stage chloroquine in the concentration of 15 mug/ml had no cytogenetic effect and in the concentration of 100 mug/ml -- it increased the number of chromosome aberrations significantly.


Antibody-induced von Willebrand's disease: a newly defined inhibitor syndrome. A patient is described with clinical and laboratory evidence of von Willebrand's disease (VWD) in association with lymphosarcoma. He consistently had a bleeding time of over 20 min; factor VIIAHF, VIIAGN, and VIIVWF under 20%; and severe, diffuse hemorrhage, Following transfusion with cryoprecipitate, the patient had the expected rise in VIIAGN and VIIAHF. The patient's plasma contained an inhibitor which prevented aggregation of normal platelets by ristocetin, but which did not interfere with the measurement of VIIAGN or inactivate VIIAHF activity. The inhibitor was present in serum heated at 56 degrees C for 30 min, was present in a purified IgG fraction of serum, and was precipitated by anti-human IgG. The antibody did not interact directly with washed platelets, but appeared to interact with that portion of the factor VII protein that supports ristocetin aggregation (VIIIVWF). The data provide the first explanation for the pathophysiology of the acquired von Willebrand's syndrome.


Cell-mediated immunity in patients with carcinoma: correlation between clinical stage and immunocompetence. Cell-mediated immunity (CMI) was evaluated in 82 patients with non-lymphoid tumors by in vivo and in vitro methods. These included skin test with ubiquitous antigens, 2,4 dinitrochlorobenzene (DNCB) sensitization, determination of T and B peripheral blood lymphocytes, and lymphocyte response to phytohemagglutinin (PHA). The patients were divided into two groups: those with localized and those with disseminated disease (LD and DD). The patients with LD showed no significant differences in CMI when compared with normal controls. The patients with DD showed various defects in CMI when compared with controls and patients with LD. There were significant differences in the response to DNCB, and streptokinase-streptodornase (SK-SD) was the most discriminative of the skin-test antigens. The response to PHA was greatly depressed in patients with DD, whether in the presence of autologous or homologous plasma; in some patients a factor inhibiting to blastogenesis was detected in the serum. In patients with DD, a T-cell lymphopenia was observed. These data showed a correlation between immunocompetence and clinical stage.


Correlation of regional lymph node in vitro antitumor immunoreactivity histology with colorectal carcinoma. Lymph nodes from resected specimens of human colorectal carcinoma were investigated for in vitro lymphocyte cytotoxicity against primary cultures of autologous tumor cells. Regional lymph node lymphocytes were cytotoxic in 32 of 142 cases (23%). Altogether 200 nodes were examined and the cytotoxicity correlated directly with sinus histiocytosis, seen in 43 nodes from 35 cases, and with hyperplasia of B- and T-lymphocyte areas combined, seen in 92 nodes from 65 cases. Lymph nodes with combined B- and T-cell hyperplasia were significantly more common in cases of good tumor differentiation. The findings suggest that sinus histiocytosis and hyperplasia of both major lymphocyte populations are morphological expressions of in vitro antitumor immunoreactivity in the regional lymph node.


High terminal deoxynucleotidyl transferase activity in acute myelogenous leukemia. Although leukocytes from all 13 acute lymphoblastic leukemia patients examined had high terminal deoxynucleotidyl transferase (terminal transferase) activity (20 to 100 units/mg of cellular DNA, where 1 unit equals 1 nmole of nucleotide polymerized in 1 hr) and those from 21 acute myelocytic leukemia patients had low terminal transferase activity (0.2 to 2 units/mg of cellular DNA), the bone marrow and peripheral blood leukocytes from 2 patients with acute myelocytic leukemia, diagnosed on the basis of clinical features and the morphology, cytochemistry, and cytogenetics of the leukemic cells, had terminal transferase activity (39 to 52 units/mg of cellular DNA) equivalent to that found in leukemic lymphoblasts. These results bring under question the specificity of high terminal transferase activity outside of the thymus as a marker for leukemic lymphoblasts and, secondarily, the derivation of acute lymphoblastic leukemia cells in all cases from thymocytes. Perhaps malignant transformation in a pleuripotent stem cell with derepression of the genome for terminal transferase could account for high terminal transferase activity observed in certain leukemic cells.


Continuous culturing of murine splenic B-lumphocytes: synthesis and surface deposition of IgM and putative IgD molecules. A method for the continuous culturing of mouse splenic lymphocytes is described. The method utilizes rat-tail collagen-coated glass or plastic surfaces which enhance the adherence and proliferation of B-lymphocytes. The cultured cells are shown to synthesize IgM and putative IgD molecules which are deposited on the cell membrane. The majority of the cells possessed Fc receptors and C' receptors, while none of them seemed to possess theta-antigen. It is concluded that these cells are functionally active B-lymphoid cells.


Arenaviruses: purification and physicochemical nature. The arenaviruses are a group of enveloped viruses having as a unique morphological finding the presence in the virion of granules instead of a defined core. The viruses contain a single-stranded RNA genome, but appreciable amounts of ribosomal-like RNA and 4-6S RNA of host cell origin have been detected. Little information is available on the mode of replication of the viral nucleic acids. A virion-associated RNA-dependent RNA polymerase has been described and there is indirect evidence to suggest that host cell RNA or DNA participates in virus replication. However, the steps in viral RNA synthesis and expression have not yet been elucidated.Pichinde virus contains 2 glycoproteins and 2 polypeptides. Cells infected with Pichinde virus or LCM virus have been shown to produce 2 antigens detectable by immunodiffusion. Both antigens appear to be components of the virion, but the relation between the antigens detected by immunodiffusion and the polypeptides detected by polyacrylamide gel electrophoresis has not yet been clarified.


LCM virus infection of cells in vitro.

LCM virus infection of cells in vitro. Most mammalian cells cultivated in vitro can be infected with lymphocytic choriomeningitis (LCM) virus. In addition to infectious virus, the cells produce antigenic material that fixes complement in the presence of antibody and is precipitated by antiserum. Intracellular antigen can also be demonstrated by the immunofluorescence procedure. When infected cells are viewed with the electron microscope, viral structures are seen either budding from or in association with the cell membranes. Immunoelectron microscopy, immunofluorescence, and cytotoxicity tests reveal virus-specific antigens on the surface of intact cells. Virus multiplication may be succeeded by cytolysis. Two LCM virus-specific antigens (or antigenic groups) can at present be distinguished. One corresponds to the infectious virus; the other is the complement-fixing "soluble" antigen. This extractable complement-fixing activity is produced by infected cells and is also a structural component of the infectious virus. It is not represented on the surface of either the virion or the infected cell. The cytolytic potential of LCM virus varies and is dependent on its previous passage history. Cytolytic and "attenuated" variants are able to initiate persistent infection of Mus musculus.Together with infectious virus, particles are produced that temporarily protect cells against standard virus. They appear to be by-products of virus multiplication, not in the sense of deletion mutants but of virus structures insufficiently equipped for their own active or passive replication, though capable of interfering with infectious virus. No evidence has been found for the generation of "defective interfering" particles, though their presence has not yet been excluded.


Immune responses to LCM virus infection in vivo and in vitro. Mechanisms of immune-mediated disease. Both recovery and death of mice following acute infections with lymphocytic choriomeningitis virus appear to be mediated by a population of virus-specific thymus-derived (T) effector lymphocytes that possess lytic activity in vitro against virus-infected syngeneic fibroblasts. Whether recovery or death occurs is determined by the balance between two interdependent factors: (1) the extent of virus-induced modifications in the surfaces of cells comprising "target" tissues, and (2) the efficiency of the immune inductive process leading to the generation of effector T lymphocytes that recognize and destroy these modified cells.


Persistent LCM virus infection in the mouse. Immunity and tolerance. The initiation of persistent infections with the Traub strain of the LCM virus is dependent not only on the number of immunocompetent cells present in the infected animals but probably also on the fact that the virus depresses the development of the bone marrow cells and causes a pronounced immunosuppression at the T cell level. By analysing the events leading to the termination of the virus carrier state by adoptive immunization, it was clearly demonstrated that the cellular immunity provoked was solely responsible for the virus elimination. Furthermore, helper T cells were shown to be necessary for the production of antibodies, which also occurs in adoptively immunized mice. In view of this finding, further experiments were performed, which strongly indicated that neither LCM-primed B cells nor LCM-primed helper T cells are present in mice that are persistent virus carriers. Similarly, neither cellular immunity to the LCM virus nor the presence of enhancing factors or suppressor cells could be detected. It is concluded that C(3)H mice that are persistent virus carriers have developed a humoral as well as a cellular immunological tolerance to the LCM virus.


Neurobiology of LCM virus infection in rodents. In addition to the previously reported data on the retinal and cerebellar immunopathology following infection of neonatal rats with LCM virus, we have found that there are long-term effects on behavioural and neurological development. Rats were inoculated intracerebrally with the E-350 strain at different ages during the first 3 weeks after birth. Behavioural tests were initiated when the animals were either 3 months or 1 year of age. The behavioural consequences appear to be a long-term alteration in emotional reactivity such that the infected animals are less responsive than controls as assessed by these measures. No alterations were detected in animals infected after the first postnatal week. Complementing these data are the findings of a collaterally progressive lesion of the hippocampal dentate gyrus as well as a loss in total cell number in the forebrain (as assessed by DNA, RNA, and protein determinations) amounting to about 20% of the brain mass. These behavioural, histological, and biochemical data indicate that there are forebrain structures, most probably within the limbic system, that are susceptible at critical phases of development to the pathological consequences of infection with LCM virus.


The pathology of human Lassa fever.

The pathology of human Lassa fever. Pathological findings have been described in only a small number of cases of Lassa fever since the virus was first isolated in 1969. Morphologically, eosinophilic necrosis of hepatocytes was the most frequent finding and focal necroses, often extensive, were present in most cases. These findings are similar to the lesions previously described in Argentinian and Bolivian haemorrhagic fever. Focal interstitial pneumonitis, focal tubular necrosis in the kidney, lymphocytic infiltration of the splenic veins, and partial replacement of the splenic follicles by amorphous eosinophilic material have been described, but the significance of these findings is unclear. More detailed and sophisticated investigations are required in the future if pathogenetic mechanisms are to be unravelled.


Recent outbreaks of lymphocytic choriomeningitis in the United States of America. Lymphocytic choriomeningitis (LCM) has been rarely reported in the American literature since 1960. It is interesting that each of the 3 epidemics reported since then has been associated with exposure to hamsters. In 1973, 48 cases of LCM spanning the years 1971-1973 occurred at the University of Rochester Medical School associated with hamsters implanted with tumour tissues. These tissues were found to be LCM-positive, as in an earlier outbreak in 1965 at the National Institutes of Health. A nationwide outbreak of LCM occurred in late 1973 and early 1974 totalling at least 181 cases in 12 states; all were associated with pet hamsters from a single breeder in Birmingham, Alabama. He was an employee of a biological products firm whose tumour tissues were found positive for LCM and were also incriminated in the 1973 Rochester outbreak. The last outbreak occurred in a graduate school laboratory in New York State involving 7 individuals working with hamster tumours from the same Birmingham biological firm. The nationwide epidemic ended in middle April 1974 following removal of incriminated hamsters from pet shops throughout the country and voluntary cessation of distribution of hamsters from the incriminated breeder. The biological firm notified all laboratories of the possible contamination of tumours and has voluntarily stopped distribution of known positive tumours.


Some observations on hamster-derived human infection with lymphocytic choriomeningitis virus. The sequence of events leading to the diagnosis of recent outbreaks of hamster-borne lymphocytic choriomeningitis (LCM) in New York State is briefly reviewed. Some relevant experiments on persistent LCM infection of hamsters are described, including measurements of complement levels in the affected animals. Evidence is discussed which suggests that complement has an important role in eliminating free virus in the circulation by participating in virus neutralization.


Clinical and epidemiological patterns of Argentine haemorrhagic fever. The epidemiology of Argentine haemorrhagic fever (AHF) is closely related to cricetine rodents acting as natural hosts of Junin virus. The endemo-epidemic area, which has increased 5 times since the disease was first recognized 15-20 years ago, is located in a densely populated region of Argentina. It has been shown that the virus of LCM is active in humans and rodents of the AHF endemic area; this demonstrates the simultaneous presence of two arenaviruses pathogenic for man in a given geographic location.The disease is characterized by haematological, renal, neurological and cardiovascular changes. Electron microscopy and immunohistochemical studies have shown cytopathic changes, characteristic intracellular virus-like particles, and antigenic determinants of Junin virus in different organs from 9 cases of AHF. No deposits of immunoglobulins or C3 were found in the kidneys; in addition, an absence of fibrinogen and C3 in the hepatocytes and of immunoglobulins in the spleen was observed. These findings suggest a direct viral pathogenic action in the human disease.Ultrastructural and immunofluorescence studies in tissues of guinea-pigs inoculated with two strains of Junin virus revealed the presence of the same types of virus-like particles and antigenic determinants of Junin virus as were encountered in the human subjects with AHF.


Surveillance of Lassa fever in missionaries stationed in West Africa. To determine the distribution of Lassa virus in West Africa, a serological survey was undertaken. A number of mission hospital supplied sera from patients admitted with a history of fever and specimens were also collected in New York from missionaries who had experienced an unusual febrile illness while working in Africa. More cases of Lassa fever were detected among missionaries than among Africans, possibly because many African patients had left hospital before the complement fixation tests had become positive. Although most adults had fairly high fever and some were prostrated, fever was less severe in the children examined. In general the findings confirm that not all Lassa fever patients have the severe syndrome described in the original reports.


Lassa fever in Onitsha, East Central State, Nigeria in 1974. Three cases of Lassa fever occurred in Onitsha, East Central State, Nigeria, in January and February 1974. The first case was a 19-year-old Nigerian; the other 2 cases were German missionary physicians at St Charles Borromeo Hospital, Onitsha, one of whom cared for the patient who was the first case. Thus, 2 of the 3 cases were hospital acquired. Investigations failed to discover a village outbreak or the source of virus for the first case. A serosurvey of 258 hospital staff members and contacts of the 3 cases showed no other persons with antibody to Lassa virus. The absence of Lassa virus antibody in a high-risk group indicates a low or nonexistent level of past Lassa virus activity in southeastern Nigeria.


Use of the complement fixation (CF) test in Lassa fever surveillance. Evidence for persistent CF antibodies. A survey to detect individuals with antibodies to Lassa virus was undertaken among hospital personnel in the eastern and southern provinces of Sierra Leone late in 1974. Sera were evaluated by the complement fixation test. The data obtained showed that some contacts of Lassa fever patients in the 1972 epidemic had developed antibodies to the virus; individuals who had never reported being sick also showed evidence of infection, with significant CF antibody titres in their sera. Surviving Lassa fever patients from the 1972 epidemic still had easily measurable levels of persisting CF antibodies. The significance of these data is discussed; in addition it is recommended that the CF test should continue to be the method of choice in mass surveys for this virus disease until other tests can be developed.


Recent isolations of Lassa virus from Nigerian rodents. Rodents were trapped in the Benue-Plateau and North-Eastern States of Nigeria where Lassa fever had been reported in previous years. Eight Lassa virus strains were isolated from tissues and blood of rodents identified in the field as being of 3 different species: Mastomys natalensis, Rattus rattus, and Mus minutoides. All the infected rodents were collected in village habitats. These isolations indicate the presence of Lassa virus in wild rodents in Nigeria during periods when no human infections were evident.Prior studies in Sierra Leone have indicated that a single rodent species, M. natalensis, may be the important reservoir host of Lassa virus. Since the present study indicates that other rodent species may be involved as well, the ecology of Lassa virus may be more complicated than was heretofore supposed. In view of the importance of determining the geographic and species range of rodent hosts of Lassa virus, and because of the problems inherent in rodent identification under austere field conditions, it is urgent that further studies be conducted in the same areas of Nigeria to confirm these findings.


Viruses other than arenaviruses from West African wild mammals. Factors affecting transmission to man and domestic animals. At least thirty-seven different viruses have been isolated from wild mammals in West Africa since 1962. Some of these, including Lassa virus, are already known to cause serious human morbidity and mortality. Crimean haemorrhagic fever-Congo virus, Dugbe virus, Mokola virus, and a smallpox-like agent from a gerbil in Dahomey are briefly discussed. An account of social and ecologic factors affecting man, domestic animals, and their interaction with wild mammals is given.


The ecology of Praomys (Mastomys) natalensis in southern Africa. The only non-human host of Lassa virus so far identified is the multimammate mouse, Praomys (Mastomys) natalensis, but its precise role in the natural Lassa fever cycle remains to be determined. This species is also an important link in the plague cycle in southern Africa and is one of the commonest rodents of Africa. It is a prolific breeder and can be kept and bred easily in captivity. It is thus an excellent laboratory animal, although it needs to be handled with care because it is aggressive towards man and bites readily. The current status of knowledge of its taxonomy, ecology, distribution, and role as a disease vector is reviewed, but attention is drawn to the possibly disastrous consequences of attempting to eradicate a vector species before the natural cycle of the disease and the ecology of the vector are fully understood.


The biology, behaviour, and ecology of Mastomys natalensis in southern Africa. The multimammate mouse, Mastomys natalensis, is the most widespread and common rodent in Africa south of the Sahara. It is an ideal carrier of normally non-human diseases to the domestic environment, not only because of its semi-commensal habit but also because of a combination of other behavioural and ecological factors. Of these, the most important is an exceptionally high propagation rate.


Spontaneous diseases in a closed colony of Praomys (Mastomys) natalensis. In comparison with other rodents, the mastomys is unique as regards the patterns of neoplastic and non-neoplastic diseases that it develops, some of which may constitute suitable animal models for corresponding diseases of man. Among the spontaneous diseases commonly encountered in necropsies of 600 mastomys maintained in a closed colony were: (1) degenerative joint disease of diarthroses and interventricular disks, which develops regularly in the second year of life; (2) renal disease, a type of immune-complex glomerulonephritis, affecting approximately 80% of mastomys in the age bracket 18-36 months; (3) thymomas and thymic hyperplasia affecting 30% of mastomys by the time they are 2 years old or older; (4) a combination of thymoma and polymyositis in a mastomys showing serum-globulin reactivity, presumably auto-antibody against striated muscle; (5) beginning before the age of 1 year, replacement of the normal cell population of the lymphoid tissues by plasma cells, and intense plasma cell infiltration at many other organ and tissue sites; (6) haematopoietic neoplasms, without leukaemic blood, in 10% of mastomys; and (7) histamine-producing argyrophilic carcinoid tumours of the glandular stomach in approximately 60% of old male and 30% of old female mastomys. Additionally, other neoplasms not infrequently encountered in mastomys rarely occur in other rodent species; conversely some neoplasms commonly found in other rodents, including especially tumours of the lung and mammary gland and leukaemia, are rare or absent in mastomys.


Lassa virus infection in Mastomys natalensis in Sierra Leone. Gross and microscopic findings in infected and uninfected animals. Pathological examinations of 28 wild-caught Mastomys natalensis from Sierra Leone, 14 of which were positive for Lassa virus by tissue culture, are reported. The high frequency of neoplastic and degenerative diseases observed among older animals in closed colonies of M. natalensis were not observed in the wild animals studied. This is probably a reflection of the age distribution of the study population, since the life expectancy of wild Mastomys is less than a year. Inflammatory lesions were nonetheless identified, some of which were similar to those described in laboratory colonies. Frequent lesions were myocarditis (54%), myositis (32%), interstitial pneumonitis (50%), intercapillary glomerulosclerosis (36%), and acute nephrosis (14%). Follicular and nodular lymphoid hyperplasia were evident in the spleen (74%) and Peyer's patches (64%). Lymphoid cell accumulations were prominent in the salivary glands (36%), periportal hepatic region (25%), lungs (32%), perivascular regions (36%), and kidney (21%). Cytomegalic inclusion body sialoadenitis was common (25%). Coccidiosis was evident in the intestinal tract (25%), kidney (25%), and muscle (21%). One neoplasm, a parahepatic haemangioma, was observed histologically.Mean body weights and lengths for virus-positive animals (33 g and 9.2 cm) and virus-negative animals (54 g and 12.2 cm) showed that virus-positive animals were smaller in weight and shorter in length. Since the age of the animals could not be determined, these differences remain unexplained.In comparison with virus-negative animals, virus-positive Mastomys had higher frequencies of splenic follicular hyperplasia (82% against 50%), myocarditis (79% against 29%), perivascular lymphoid cell accumulation (57% against 7%), myositis (50% against 14%), and cytomegalic inclusion body sialoadenitis (36% against 14%). The frequency of lymphoid hyperplasia of Peyer's patches was high in both groups of animals (71% and 57%).The presence of Lassa virus, small size, myocarditis, and lymphoid perivasculitis appeared to be interrelated, but larger and better controlled studies are required to elucidate the relationship.


Problems of rodent control in rural tropical areas. Rodent control strategies, techniques, and research needs in rural tropical environments are reviewed and discussed with special reference to Mastomys natalensis, the possible reservoir of Lassa fever in West Africa.Public health rodent problems are far more serious and widespread in rural tropical areas than in developed countries. In the latter, only the commensal rodents constitute a major problem, whereas in rural tropical areas, native semidomestic species also serve as disease reservoirs and sources of infection to man. The success of rodent control programmes in developed countries depends in large part on the willingness and ability of people and governments to spend relatively large sums on research and control, on an acquired intolerance of people to rats and disease, and on a substantial economic base. These prerequisites are not usually to be found in rural tropical areas. Consequently, the rodent control techniques and programme organizations of developed countries are not directly applicable to such areas, even though the principles are the same. For this reason, it is suggested that a well-funded, integrated research and control programme should be undertaken in a known Lassa fever area, stressing public education, personnel training, and environmental management as well as rodenticidal approaches.


Evaluation of demographic parameters of native rodent populations and implications for control. The ecology of the multimammate mouse ,Mastomys natalensis, is reviewed and approximations are derived for the parameters governing population growth. By means of computer simulation, the relative importance of the timing of reproduction, the age class distribution or age structure of the population, the competition between Mastomys and Rattus, and the interaction with a predator are evaluated. Although each of these demographic or ecological factors modifies the fate of the Mastomys population, the greatest single impact results from a reproductive season that is divided into two parts rather than a single continuous reproductive season. Division into two parts, correlated with a similar distribution of rainfall, allows time for maturing of the young born early in the season and for production of young by them, thus adding to the momentum of population increase. The interaction of density-dependent factors controlling population growth, competition with another rodent, or predation by a Viverrid predator, may increase the growth rate of the Mastomys population or may depress population growth rate, even to the point of extinction. These simulation studies demonstrate the necessity for critical evaluation of the demographic parameters and ecological characteristics of a particular Mastomys population before an effective control programme can be designed. They also demonstrate, however, that if the programme is based upon sound ecological theory control can be effected.


Problems associated with the control of rodents in tropical Africa. As elsewhere in the world, rodents are responsible for very considerable economic losses in tropical Africa because of their depredations on both growing crops and stored food products. Unfortunately, few accurate data are available on the extent of these losses but there is evidence that they are considerable. The public health importance of rodents, both as reservoirs and vectors of disease in tropical Africa, is also great; plague, leptospirosis, murine typhus, and Lassa fever are among the diseases associated with rodent hosts. Scientifically based rodent control programmes have been carried out in very few areas of Africa and there is urgent need for studies and demonstrations on rodent control in both urban and rural areas. The problems likely to be encountered are reviewed and methods of control proposed.


Diagnosis of Lassa fever and the isolation and management of patients. The clinical spectrum of Lassa fever is described and discussed in terms of the possible pathophysiological events involved. Early diagnosis is essential to permit prompt isolation of the potentially infectious patient. Lassa fever may be suspected on clinical grounds, but specific early diagnosis depends upon isolation of the virus. Virus isolation is best accomplished from serum obtained during the first 2 weeks of illness. The patterns of viraemia and virus excretion described in this paper are useful guidelines for determining the duration of patient isolation. Problems encountered in the isolation, management, and transport of the patient with Lassa fever are discussed.


Handling patients with suspected Lassa fever entering Great Britain. A special isolation unit has been created at the Hospital for Tropical Diseases, London, for the reception of patients arriving in Great Britain from West Africa with suspected Lassa fever. The management of such patients and the operation of the unit are described. Experience during the first eighteen months of operation has been very satisfactory and valuable lessons have been learned concerning the diagnosis and treatment of Lassa fever and the nursing of patients.


Arenavirus chemotherapy--retrospect and prospect. Two groups of compounds, identifiable by structural similarity, have been found to interfere with the in vitro replication of arenaviruses. All 4 members of the benzimidazole group contain dipolar fused benzene and 5-membered nitrogen-containing rings and share potential chelating ability through the different bidentate structures formed with their side-chains. The biological activity of one of these compounds, metisazone, has been shown to depend on the presence of divalent metals of the first transition series, Cu(++) being the most effective. Furthermore, whereas metisazone inactivates cell-free virus, two other members of the group, HBB and 1,2-bis(5-methoxy-1H-benzimidazol-2-yl)-1,2-ethanediol, act intracellularly. The site of action of the fourth member, SKF 30097, is not known. Using murine lymphocytic choriomeningitis infections as an in vivo model, the bisbenzimidazole derivative has been found to increase life-span without interfering with virus replication. Medication with SKF 30097 or metisazone and copper (2(+)) sulfate did not significantly or reproducibly change the expected day of death of the animals. The amantadine compounds of the second group have unusual symmetric structures with a 10-carbon cage. The parent compound acts intracellularly, while the site of action of an octachloro derivative is not known. Medication with the parent compound, but not the derivative, shortened the interval between LCM infection and death of the mouse. Tissue culture and animal screening of the many available derivatives in these two groups may uncover compounds more efficacious than those already examined.


The meaning of persistent infections in nature. Viruses that cause persistent infections maintain themselves more effectively in nature than those causing acute and limited infections. There is a tendency for persistent viruses to evolve towards a state of minimal pathogenicity in the host. Vertical transmission, with integration of viral into host genome, represents the state of perfect parasitism.


Directions for future research on the pathogenesis of arenaviral infections. The pathogenesis of arenavirus infection is considered separately for the haemorrhagic fever (HF) syndrome and for lymphocytic choriomeningitis (LCM) virus infection of rodents. Experimental models of HF have received only limited study, mainly because of the virulence of the causal agents. Two useful models (Junin virus in guinea-pigs and Machupo virus in rhesus monkeys) are now available and an attempt is made to delineate crucial questions for future studies, including the physiology of shock, disseminated intravascular coagulation, immune mediation of disease, efficacy of antibody in treatment, and relative utility of attenuated and inactivated vaccines. Immunobiologic problems currently under investigation in LCM virus infection include the mechanism of immune destruction of infected tissues, the H-2 restriction of in vitro T-cell-mediated lysis of infected target cells, the transient immunodepression that accompanies acute primary LCM virus infection, and the mechanism of T-cell-mediated clearance of virus from infected tissues following adoptive immunization of persistently infected carrier mice.


The arenaviruses: some priorities for future research. In this paper Lassa virus is used as a model in pinpointing priorities for future research on the arenaviruses. Suggestions for specific investigations and public health measures cover the detection of Lassa virus infection, the pathology and therapy of the disease, and its prevention and control.


Adipose tissue cellularity in human obesity. All human obesity is characterised by adipocyte hypertrophy and when body weight exceeds 170 per cent of ideal, a maximum cell size of roughly twice normal is achieved. With greater severity, hyperplasia becomes increasingly manifest and when body weight exceeds 170 per cent of ideal, the degree of hyperplasia is well correlated with severity. Although severity and hypercellularity are often found in those with early onset of obesity, individuals can be found who are hypercellular but have had a later onset of obesity. Until the details of cellular development in man are more fully understood, the precise timing of 'critical' periods for cellular development must remain speculative.


Hidden' IgG antiglobulins in normal human serum. Hidden antiglobulins reacting with whole rabbit immunoglobulin were found by radioassay or indirect haemagglutination after gel filtration or ultracentrifugation of normal serum. Suprisingly, both the IgM and IgG antiglobulins were present in the same macroglobulin fractions. The IgG antiglobulins could be dissociated into 7S components by separating the serum under acid conditions. Antiglobulin activity was a function of the Fab region.


A double antibody solid phase assay for DNA autoantibodies for clinical use. DNA antoantibodies in serum will bind to antigen-coated polystyrene tubes and can be detected by radiolabelled anti-immunoglobulin. The method is quantitative, gives information on the antibody class and is not readily subject to interference by factors such as the size of the DNA, minor contamination of double-stranded with single-stranded DNA and the presence of materials which can combine "non-specifically" with the antigen. Double-stranded DNA gave good discrimination between SLE and rheumatoid arthritis but with single-stranded preparations approximately 40% of the RA patients showed elevated antibody values. Individual results obtained with the two antigens were compared and correlated with the Farr test and ANA titres. Surprisingly, a proportion of the SLE sera gave high background binding to  tubes coated with gelatine.


Acute energy deprivation in man: effect on cell-mediated immunological reactions. The effects of 10 days of total energy deprivation on lymphocyte functions and cell-mediated immunity was evaluated in fourteen healthy, normal-weighted males. Lymphocytes from seven of the subjects were tested in vitro. A significant depression was noted of the DNA synthesis after stimulation with pokeweed mitogen and PPD while there was no effect on the response to concanavalin A. No change was noted in the percentages and total numbers of circulating B and T lymphocytes and monocytes. The delayed skin reactivity following intracutaneous PPD and mumps antigen was not different from non-starving control subjects.


Rosette-formation with mouse erythrocytes. II. A marker for human B and non-T lymphocytes. Peripheral blood lymphocytes from healthy control subjects were studied for spontaneous rosette-formation with mouse erythrocytes. The mean percentage of mouse erythrocyte rosette-forming cells (MRFC) in sixty-three subjects was 7.4X3.5; after neuraminidase treatment olymphocytes the mean percentage of mouse erythrocyte rosette-forming cells(NMRFC) was 17.2X5.6. Thymus cell suspensions made only occasional rosettes with mouse erythrocytes. There was no effect of neuraminidase treatment of thymocytes on mouse erythrocyte rosette-formation. Double labelling experiments with other cell surface markers confirmed this binding of mouse erythrocytes to be a B-cell characteristic. Monocytes and granulocytes do not bind mouse erythrocytes. It appears that there is a distinct receptor for the binding of mouse erythrocytes on the surface of lymphocytes carrying surface immunoglobulins; neuraminidase treatment of lymphocytes permits this binding to occur also on virtually all the non-T cells B cells plus the third population cells).


In vitro response of bovine thoracic duct lymphocyte to phytohaemagglutinin following adult thymectomy. The effect of adult thymectomy on the thoracic duct lymphocyte population of yearling calves has been investigated. Four to 6 weeks after thymectomy animals showed significantly reduced thoracic duct lymphocyte concentrations when compared to non-thymectomized controls. In addition, phytohaemagglutinin responsiveness of thoracic duct lymphocytes, measured by (3H) thymidine uptake, was significantly decreased following adult thymectomy. However, this decreased response to PHA was not accompanied by a change in spontaneous isotope incorporation. It is concluded that adult thymectomy in the bovine probably leads to a reduction in the number of PHA responsive T cells in the thoracic duct lymph.


Stress ulcer: a continuing dilemma.

Stress ulcer: a continuing dilemma. The disease is painless and presents as a massive upper GI hemorrhage. Early diagnosis and rapid treatment are mandatory for patient survival. A variety of nonoperative treatment regimens are available, none demonstrating a clearcut superiority. Because the incidence of rebleeding is high, operative intervention is frequently required. The appropriate surgical procedure is unclear, although most surgeons perfer a generous subtotal gastrectomy with truncal vagotomy. Unquestionably, the best treatment is prevention.


[Clinical results of laser-coagulation in gastro-intestinal bleeding (author's transl)]. Endoscopic laser-coagulation was used 94 times in 14 patients to stop gastro-intestinal bleeding or coagulate potential bleeding sources during non-bleeding intervals. Lasting haemostasis was achieved in three cases of incomplete gastric erosion, one of gastric ulcer, one of duodenal ulcer and one of bleeding after antral rugectomy. It failed to stop severe arterial bleeding in a case of gastric carcinoma. Lasting haemostasis was achieved in six haemangiomas of the colon, one case of angiomatosis of the antrum with 62 individual sites, two of angiodysplasia of the colon, 17 lesions in Osler's disease of the oesophagus (2 cases), stomach (10) and duodenum (5). The procedure was performed in the course of diagnostic endoscopy with an argonion laser developed by the authors, which has a density of 0.7-1.3 W/mm2. No complications have been observed so far.


Inhibitory effect of 5-hydroxytryptophane on the induction of persistent estrus by androgen in the rat. Effects of monoamines or its precursors on the induction of persistent estrus by testosterone propionate (T.P.) were studied in Wistar strain female rats. Daily treatment with 5-hydroxytryptophane (5-HTP) for the first 10 days of life delayed the occurrence of persistent estrus in rats given T.P. at 4 days of age. The onset of persistent estrus occurred in this group of animals at 67.1+/-2.5 days of age compared with 45.1+/-1.4 days of age for the saline treated control group. The role of hypothalamic monoamines in contributing to the induction of persistent estrus by T.P. treatment of neonatal rats is discussed.


Effect of cortisol on the release and retention of labelled DNA in the thymus and spleen of mice. The lymphocytolytic effect of different doses of cortisol was studied in the thymus and spleen of mice previously injected with 3H-thymidine. The results indicate that in thymus the fraction of labelled cells was more resistant to cortisol than the unlabelled cell population. The release of DNA into the fraction of DNA soluble in 0.14 M NaC1 was delayed suggesting that cortisol controls indirectly the lymphocytolytic process. Up to 24 hours after administration of cortisol the loss of labelled spleen cells significantly exceeded the loss of unlabelled cells. The time course of the release of labelled DNA into the fraction of DNA soluble in 0.14 M NaC1 indicates that a fraction of labelled DNA was rapidly removed from the spleen after injection of cortisol.


Experimental coronary artery bypass operation. Myocardial blood flow, ventricular performance and regional myocardial function. Myocardial blood flow and ventricular function was studied in seven dogs with chronic myocardial ischemia before and after coronary bypass grafting. Restoring blood flow in an area of 25% of the anterior wall of the left ventricle did not significantly improve overall ventricular function. Assessment of intramyocardial pressure as an index of regional myocardial function revealed a consistent enhancement of myocardial contraction at rest, and under pharmacological stress of the heart.


Tryptophan hydroxylase in discrete brain nuclei: comparison of activity in vitro and in vivo. The increase of 5-hydroxytryptophan after treatment with the decarboxylase inhibitor Ro 4/4602 was 30 times greater in the raphe nuclei (which contain serotonergic cell bodies) than the hippocampus or caudate (which contain serotonergic terminals). Pretreatment with chlorimipramine reduced the 5-hydroxytryptophan accumulation in the median but not dorsal raphe. The large amount of tryptophan hydroxylase in cell bodies appears to be active in vivo. The serotonin rapidly turning over there may have a functional role.


Effect of aprotinin, EACA and heparin on growth and vasopeptide system of Murphy-Sturm lymphosarcoma. The effect of aprotinin, EACA and heparin on the growth of the transplanted rodent Murphy-Sturm lymphosarcoma and on several components of the tumor kinin-forming enzyme system was studied. Therapy was administered for 15 days, 3 times daily, one day after tumor transplant. Tumor weights and biochemical parameters (prekallikrein, kininogen and kininase) were measured on the 8th, 10th, 12th and 15th day of therapy. Both aprotinin and heparin significantly inhibited (p less than 0.01) tumor growth by the 15th day, compared to control, saline-administered animals. EACA did not affect the tumor growth rate at any time period. Tumor prekallikrein and kininogen levels were significantly higher (p less than 0.01) in the aprotinin-treated animals. Kininogen levels were higher in the EACA-treated tumors during the latter phase of growth. None of the agents affected the increase in tumor kininase activity that occured during the growth of the tumors. The tumor inhibition and biochemical data suggest the involvement of proteases in the neoplastic process.


Characteristics of B-lymphocyte colony growth in vitro. A cloning system in semisolid agar has been developed which supports colony formation by mouse B-lymphocytes. Colonies appear to be clones and colony cells synthesize immunoglobulin. Approximately one cell in 50 in the spleen or lymph nodes is capable of forming a colony and colony-forming cells appear to have the properties of B-lymphocytes. Colony formation is dependent on mercaptoethanol but the possible additional involvement of a specific B-lymphocyte regulatory factor has not been excluded.


Reactivation by glycerol and ethylene glycol of inactivated delta-aminolevulinic acid synthetase of Rhodopseudomonas spheroides. Reactivation effects by glycerol and ethylene glycol of inactivated ALA synthetase of R. spheroids were observed. Accompanying the reactivation of the inactivated enzyme, Km value for PLP decreased to levels similar to those of the freshly prepared enzyme.


Latency of taste nerve signals in frog (Rana catesbeiana). The latency of frog gustatory neural impulses to 1.0 M NaCl was a mean of 86 msec. Electrical stimulation of taste cell membranes produced gustatory neural impulses with the mean 5 msec latency. It is concluded that most of the 86 msec latency of taste nerve responses to 1.0 N NaCl is due to the latency of taste receptor potential following the onset of gustatory stimulation.


Elemental distribution of Na, P, Cl and K in different structures of myelinated nerve of Rana esculenta. Measurements of the distribution of Na, P, Cl and K were performed in different structures of the myelinated nerve. Whereas the axon shows a typical intracellular distribution pattern for Na, Cl and K, the interstitial space and the myelin sheath show a typical extracellular pattern. These measurements have demonstrated that Na is present in the myelin sheath close to the node of Ranvier.


The effects of neonatal vestibular stimulation on adult growth and emotional reactivity in BALB/c mice. Two experiments were conducted to determine the effects of neonatal vestibular stimulation on the subsequent development and behavior in BALB/c mice. No evidence appeared to suggest that neonatal vestibular stimulation alters either the growth pattern or the ontogenesis of emotional reactivity.


Portal hypertension and primary biliary cirrhosis. Portal hypertension has been regarded as an uncommon and late complication of primary biliary cirrhosis (PBC). 24 patients with PBC were investigated for portal hypertension. Esophageal varices were present in 20, 50, and 90% of the patients 1, 3, and 9 years, respectively, after the onset of pruritus and/or jaundice. Portal hypertension was responsible for gastrointestinal bleedings in 11 patients; bleeding was the first clinical manifestation of PBC in two of them. Wedged hepatic venous pressure was increased in all the patients with portal hypertension whether regenerative nodules were present or absent. Portacaval shunt was performed in five patients and was well tolerated in three of them. It is concluded that (a) portal hypertension is common in PBC; (b) the intrahepatic block is of the so-called postsinusoidal type, even in patients without regenerative nodules; (c) gastro-intestinal bleeding due to portal hypertension occurs in about half of the patients and may be the first manifestation of PBC; (d) portacaval shunt seems to be indicated when gastro-intestinal bleeding occurs in earlier stage of the disease.


High power argon laser treatment via standard endoscopes. I. A preliminary study of efficacy in control of experimental erosive bleeding. With minimal transmission loss a high power argon laser (10 w) was coupled to a waveguide consisting of a flexible, single, coated, quartz fiber encased in a protective polyethylene tube. This waveguide can be passed down the biopsy channel of any standard fiberoptic endoscope. An aiming light improves accuracy. Safety devices were developed to protect the subject and the operator. Each of 8 heparinized mongrel dogs had three superficial erosions created endoscopically in the fundal gland mucosa by a jet of warm 0.1 N HC1. In each animal two lesions were photocoagulated with the laser and the third was left as a control. The animals were killed at 0, 4, 7, 10, and 14 days, and the erosions were examined histologically. By 14 days all lesions were covered by normal surface epithelium. Parietal and chief cells had returned to untreated erosions at 14 days but not to all lasered lesions. Only rarely did the lasered lesions penetrate through the muscularis mucosae into the submucosa. High power argon laser photocoagulation is now feasible through standard endoscopes. These data are sufficiently promising to encourage further evaluation of laser photocoagulation in a variety of animal models.


Pathogenesis of bleeding colonic diverticulosis. The cause of bleeding was found in 8 of 10 cases of colonic diverticulosis associated with severe rectal hemorrhage by using arteriographic and microangiographic techniques to localize the site and serial histological sections to study the lesion. Strikingly consistent changes were identified. These are related to the characteristic angioarchitecture of colonic diverticula. These changes include asymmetric rupture of the vas rectum toward the lumen of the diverticulum precisely at its dome or antimesenteric margin; conspicuous eccentric intimal thickening of the vas rectum, often with medial thinning of duplication of the internal elastic lamina at and near the bleeding point; and general absence of diverticulitis. Control colonic diverticula demonstrated normal structures or, only occasionally, minimal eccentric intimal thickening in their associated vasa recta. This suggests that traumatic factors arising within the diverticular or colonic lumen induce asymmetric intimal proliferation and scarring of the associated vasa recta, predisposing to rupture and massive bleeding.


alpha-1-antitrypsin deficiency in liver disease: the extent of the problem. A prospective screening program was undertaken at the Royal Free Hospital, London, to ascertain the incidence of alpha-1-antitrypsin (AAT) deficiency in patients with liver disease. Quantitative determinations of serum alpha-1-antitrypsin were performed on 469 patients with hepatobiliary disease and 98 subjects with no known liver disease. Sera with low values of AAT were phenotyped. The homozygous state was rare and comprised only 1% of the patients with liver disease. All of the 5 homozygous deficient (ZZ phenotype) patients had a history of neonatal liver disease. Other phenotypes (partial deficiency) were found in 4.7% of patients with liver disease and 6.1% of subjects with normal liver function. Types of liver disease in the patients with other phenotypes were widely varied. Routine determination of serum AAT level and phenotype and special staining for AAT in liver biopsies in all adults with liver disease appears unnecessary. Investigation of possible AAT deficiency should be carried out, however, in children and young adults, in those with a history of neonatal liver disease, and possibly in all patients with liver disease of unknown aetiology.


Immunocompetent cells in man. IV. The inhibition of pokeweed mitogen-induced blastogenesis of normal human peripheral leukocytes by trypsin: a B-cell mitogen of mouse, but not of human, lymphocytes. Normal human peripheral blood lymphocytes were tested for their blastogenic response in vitro to trypsin. Although it has been shown by other investigators that mouse B lymphocytes are stimulated trypsin to undergo blastogenesis, we have shown that human lymphocytes are not stimulated by trypsin. Paradoxically, trypsin inhibits the response of human lymphocytes to pokeweed mitogen, a B-cell stimulat, without significantly affecting the response of these cells to phytohemagglutinin, a T-cell stimulant. These results serve to underline the functional dissimilarity of mouse spleen cells and human circulating lymphocytes, at least with respect to their blastogenic responses to mitogenic agents.


Heterogeneity of the protein moiety of carcinoembryonic antigens. N-terminal amino acid sequences were determined for the protein moiety of carcinoembryonic antigen (CEA) isolated from three colon cancers that had metastasized to the liver. The results showed that the polypeptide portion of CEA preparations isolated from different tumors are not identical. Furthermore, each CEA preparation appeared to be heterogeneous within itself, since multiple amino acid residues were recovered at most of the positions following stepwise cleavage of the protein moiety of CEA molecules by automatic Edman degradation.


Secondary cytotoxic cell response to lymphocytic choriomeningitis virus II. Nature and specificity of effector cells. The method described in the previous paper was used to induce secondary responses in spleen cells from CBA/H mice, pre-primed with lymphocytic choriomeningitis (LCM) virus by culturing them with LCM-infected peritoneal cells. The cytolytic effector cells thus generated have been characterized. Effector cells were sensitive to treatment with anti-theta ascitic fluid and complement. Separation procedures based on rosetting of certain categories of lymphocytes with sheep red cells through an Isopaque-Ficoll gradient indicated that effector cells lacked surface immunoglobulin and generally did not bear Fc receptors. Cytolytic activity was restricted by the H-2 gene complex. Killing had single-hit characteristics. All these results suggested that the cells from memory cultures mediating cytolysis were T cells. There was evidence for two T cell subsets, a major subpopulation directed against antigens on infected targets and a minor one directed against antigens on uninfected, H-2-compatible targets. Specificity was present at the infected cell:memory responder and killer:target levels between LCM virus (an arenavirus) and ectromelia virus (a poxvirus).


Preferential generation of killer or helper T-lymphocyte activity directed to the tumour-associated transplantation antigens. Induction of killer and helper T-cell activities towards transplantation antigens of two tumour cell lines was analysed in the allogeneic and syngeneic host combinations. The lymphoid cells from C57BL/6 mice immunized with allogeneic viable or mitomycin C-treated X-5563 plasmacytoma cells derived from C3H/He mice revealed both killer and helper T-cell activities against alloantigens, whereas cells from mice immunized with tumour cells killed by a freezing and thawing procedure revealed predominantly helper T-cell activity. On the other hand, when C3H/He mice were immunized with viable syngeneic X-5563 plasmacytoma or MM102 mammary tumour cells, the former generated preferentially killer T-cell activity, whereas the latter induced predominantly helper T-cell activity against tumour-associated transplantation antigens. Thus, immunization with transplantation antigen(s) does not always induce both helper and killer T-cell activities in parallel, but a certain antigenic system induces predominantly one type of T-cell response, thus indicating that two distinct subsets of helper and killer T cells against the transplantation antigen(s) can be raised independently without an absolute requirement of collaboration between these different T-cells subsets.


Helper T-cell kinetics and investigation of antigen receptor expression on early and memory T-helper cells. The subcutaneous application of soluble antigen resulted in generation of helper T lymphocytes in the draining lymph nodes, tested 4 days after priming in the adoptive transfer system. Four days later a specific helper T-cell population was detected in the spleen. B-cell activity could be demonstrated 4-5 days after helper T-cell activity in both organs. We investigated the early helper T-cell population and memory T cells with respect to differences in the expression of antigen receptors. No such differences could be detected, either by anti-immunoglobulin-coated Degalan columns or by an antigen-specific rosetting method.


Synergy between human T and B lymphocytes in their response to phythaemagglutinin and pokeweed mitogen. Human B- and T-lymphocyte preparations were isolated by separating T lymphocytes that formed rosettes with sheep erythrocytes from unrosetted B lymphocytes. Pokeweed mitogen stimulates the proliferation of both B- and T-lymphocyte preparations. In contrast, phytohaemagglutinin stimulates little or no proliferation of purified B lymphocytes although it stimulates the proliferation of T lymphocytes. Lymphoid preparations containing both T and B lymphocytes are more responsive to both mitogens than are either T- or B-lymphocyte preparations. This observation suggested synergy between T and B lymphocytes in the response of unfractionated lymphocytes to mitogens. The basis for this synergy was shown to be the capacity of T lymphocytes to facilitate the proliferation of B lymphocytes cultured with pokeweed mitogen or phytohaemagglutinin. The activity of T lymphocytes is not dependent upon their proliferation or attributable to their release of mitogenic factors. With regard to the clinical evaluation of immune function, our results indicate that the proliferative response of human lymphocytes to phytohaemagglutinin or pokeweed mitogen cannot be directly related to the percentage of T lymphocytes in the lymphoid preparation.


Interactions of murine leukemia virus (MuLV) with isolated lymphocytes. II. Infections of B and T cells with Friend virus complex indiffusion chambers and in vitro: effect of polyclonal mitogens. The infection of isolated B and T cells by a murine leukemia virus (Friend) MuLV-F) was studied both in vitro and in vivo with an implanted diffusion chamber system. Lymphocytes were obtained from pools of normal spleen cells by filtration of the cell suspension through a nylon-wool column. The purity for both Ig positive and theta-positive cells varied between 85% and 90% in the B-cell and T-cell fractions; both lymphocyte fractions responded very well to stimulation with their respective specific polyclonal mitogens, bacterial lipopolysaccharide (LPS) and concanavalin A (Con A). Lymphocytes were infected by incubating pelleted cells in 2-6 x 10(4) FFU MuLV for 1 h at 4 degrees C and were then cultured for 5-10 days. Cells releasing infectious MuLV were enumerated as infectious centers (IC). IC were really detectable in the cultures of infected B-cells but none were found in the T-cell cultures. Addition of LPS to the culture medium increased the number of IC in B-cell fractions up to 1,000-fold. Furthermore, in T-cell cultures with LPS, IC also appeared in number which approximately correlated with the contaminating Ig+ cells of the T-cell fraction. In contrast, Con A had no consistent effect on the infection of either B or T cells. In the absence of MuLV-F, mitogenic stimulation alone did not elicit any endogenous IC. In subsequent experiments, purified lymphocytes were infected in diffusion chambers in vivo. The number of IC in infected B cells increased 1,000-fold as compared to infection in tissue culture. The peak of infection at 10 days was followed by a slight decline. Infected cells were also found in diffusion chambers containing T-cell fractions; these IC had very similar kinetics to those in B-cell-containing chambers, but their number was 10 times lower, suggesting that the infected cells were B cells, which comprised about 10% of the T-cell fraction. The virus-related antigens were detectable by immunofluorescence on the membrane of cells recovered from B-cell-bearing chambers but not on cells from T-cell-bearing chambers.


Inflammatory cells in solid murine neoplasms. II. Cell types found throughout the course of Moloney sarcoma regression or progression. Regressing and progressing Moloney sarcomas, induced in BALB/c mice by the injection of cultured sarcoma cells (MSC)1, were sampled for histologic analysis and then disaggregated using mixtures of trypsin, collagenase and DNAse or collagenase and DNAse alone. The types of inflammatory cells (IC) found in resultant cell suspensions were determined 6, 11, 14 and 18 days post inoculation. Inflammatory infiltrates were composed almost exclusively of three cell types; neutrophils, T lymphocytes and macrophages. The extent to which each was found in tumors was related to the time post inoculation. Neutrophils were part of an early acute inflammatory response seen in both developing regressing and progressing sarcomas. The onset of regression was associated histologically with the appearance within tumors of a mononuclear inflammatory infiltrate. T lymphocytes and macrophages were the principal constituents. A higher percentage of T lymphocytes was recovered at all sampling times from regressing, compared to progressing, sarcomas. During development of the mononuclear inflammatory infiltrate there were relatively more large T cells in regressing, than in progressing tumors, and the percentage of macrophages was higher. Thereafter, the proportion of macrophages in the recovered cell population was approximately the same for both types of tumor. Such equality was more apparent than real, however, since IC were restricted to the peripheries of progressing sarcomas after the acute inflammatory phase, but continued to be found throughout regressing neoplasms. The effective ratio of macrophages and T lymphocytes to tumor cells therefore was much lower in progressing sarcomas than was suggested by percentage figures. The data presented support the concept that T lymphocytes are instrumental in causing the regression of Moloney sarcomas, possibly through interactions with macrophages.


Ocular pathology induced by the suckling mouse cataract agent. The eye disease caused by SMCA may be best characterized as an endophthalmitis, with early retinitis followed by subsequent posterior uveitis. Pathologic features of lens included: proliferation and abnormal posterior extension of lens epithelium, increased accumulation of lens capsule material, and production of aberrant lens substance. Cataractous change appears to be secondary to intraocular inflammation. In addition to the above pattern, in roughly 20 per cent of all cases, 3 weeks after inoculation, lens capsule is destroyed giving rise to a foreign body granulomatous reaction.


Improved voiding in response to electrical stimulation of the spinal cord of paraplegic dogs. Bipolar electrodes were inserted into the conus medullaris and attached to the proximal urethra of paraplegic dogs. Repeated stimulus trains were delivered to the spinal cord electrodes and the urethral electrodes in an attempt to improve voiding induced by cord stimulation. The results indicate that the increased outflow resistance which often accompanies electromicturition can be significantly overcome both by repeated spinal cord stimulation and by prestimulation of the proximal urethra.


[Chewing pads, a variant of knuckle pads]. Three young male patients with chewing pads are reported. Their tic-like habit of chewing on the dorsal aspects over the middle joints of fingers I-IV caused a pad-like thickening of soft tissue. These chewing pads are a variant of "false" knuckle pads. The importance of a medical history and dermatological inspection is stressed to avoid unnecessary diagnostic procedures. This harmless augmentation of soft tissue is commonly confused with rheumatoid disease of the fingers, sarcoidosis or pachydermoperiostosis. Patients should be informed of the true nature of their pads, as discontinuation of their chewing habit will resolve their problems.


Millisecond fading and recovery phenomena in fluorescent biological objects. Cytofluorometric signals derived from some frequently used fluorophores were studied during illumination times in the millisecond range. These rapid signals were recorded on a storage oscilloscope. The objects studied included (1) Berberine sulphate stained mast cell heparin, (2) Acriflavine-Feulgen stained DNA, (3) Acridine orange stained mast cell heparin, (4) Acridine orange stained DNA and (5) Fluorescein isothiocyanate-conjugated IgG in an antinuclear factor test. A new rapid fading phenomenon, appearing as an initial peak upon the familiar slowly declining fluorescence signal, is reported. This fading, which had a duration of about 10 ms, also showed a very rapid recovery. The influence of this phenomenon on fluorometric measurement techniques is discussed. The millisecond fading phenomenon occurred in all the fluorophores studied except Fluorescein isothiocyanate-conjugated IgG. In the case of acridine orange the phenomenon was present when the dye was bound to nuclear DNA but absent when the dye was bound to mast cell heparin. This suggests that the millisecond fading and recovery phenomenon may be used in fluorescent microprobe studies.


Histochemical characterization of the monoamine-containing cells of the adenohypophysis in the Chinese quail. The demonstration of biogenic amine-containing cell is classically performed by means of the formaldehyde-induced fluorescence technique after administration of the monoamine precursors, L-dopa or 5-hydroxytryptophan (5-HTP. The injection of these two two compounds rapidly leads to the formation of large amounts. The biochemical pathway evoked above   is studied in the avian adenohypophysis by two different methods involving enzyme...


Electrophysiological evidence for a topographical projection of the nasal mucosa onto the olfactory bulb of the frog. Three olfactory nerve branches respectively subserving either a medial, an intermediate, or a lateral region of the dorsal olfactory receptor sheet of the bullfrog Rana catesbeiana were electrically stimulated with bipolar platinum hook electrodes. Extracellular single unit responses from 93 second-order cells in different regions of the olfactory bulb were recorded with metal-filled glass micropipets. The excitatory responsiveness of each unit to the stimulation of each of the three nerve branches (response profile) was determined. Some units were sensitive to stimulation of each of the three nerve branches, thus suggesting a wide projection from the entire receptor sheet. On the other hand, other units were more selective. Of this latter group, units in the lateral bulb were excited by nerve branches subserving the more lateral regions of the receptor sheet; units in the medial bulb were excited by the nerve branches subserving the more medial regions of the receptor sheet. These data provide electrophysiological evidence for a topographical projection of the olfactory receptor sheet onto the olfactory bulb, and further suggest that the projections onto different bulbar cells vary in degree of localization.