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Biomedical subjects

A Weiss

Publications and source records attributed to A Weiss.

At least 343 records · Page 19Linked to original sources

Intrathoracic Hodgkin's disease. A case presentation with multiple pulmonary nodules in the absence of mediastinal or hilar node disease.

Patients with Hodgkin's disease (HD) most commonly present with peripheral lymph node enlargement. The finding of pulmonary parenchymal involvement is usually associated with hilar and/or mediastinal adenopathy; such instances are felt to represent spread to the lung by contiguity. Noncontiguous spread to peripheral lung parenchyma in the absence of hilar or mediastinal node involvement has rarely been reported. This is the first documented case report in a 32-year-old woman with nodular sclerosing HD. The unusual clinical presentation in this patient was associated with the histologic detection of vascular invasion in the lymph node and open-lung biopsy specimens.

Adult↗

Mitoxantrone in malignant lymphoma.

Two phase II trials of mitoxantrone (Novantrone; dihydroxyanthracenedione) in refractory malignant lymphoma have been conducted. In the first of these, mitoxantrone, 5 mg/m2, was given weekly for six weeks and in the second, 14 mg/m2 was administered every three weeks. The first trial was conducted by the Southeastern Cancer Study Group (SECSG) and the second was a multicenter trial sponsored by Lederle Laboratories. Of the 51 patients entered in the SECSG trial, 28 could be evaluated for response and 43 for toxicity. WBC nadirs below 4.0 X 10(9)/litre were recorded in 25 patients. Three partial responses and no complete responses were obtained. These results contrast with those of the single dose every three weeks study in which 96 patients were entered and 69 of these were evaluated for response. Responses were obtained in 30 patients (4 complete, 26 partial). Side-effects on this three-weekly dose regimen were minimal. WBC nadirs below 4.0 X 10(9)/litre occurred in 85 patients. Twenty-three patients experienced at least mild nausea and vomiting and 15 had at least mild alopecia. These preliminary data indicate that mitoxantrone has significant activity in malignant lymphoma. All of the responding patients had received extensive prior therapy, many of them with anthracyclines in combination or as single agents. The higher response rate to mitoxantrone given at 14 mg/m2 every three weeks suggests that careful consideration should be given to dose schedule when this drug is examined further in phase III trials.

Alopecia↗

A comparison of shock avoidance learning in headless cockroaches in leg-lifting and lowering task.

Headless cockroaches were trained either to lift or to lower the prothoracic leg to avoid electric shocks. The learning process in both cases was very distinct. However, the learning performance in the lifting was better than in the lowering task. The reason for this poorer learning in the lowering task is due to the unconditioned leg raising movement of the animals to electric shocks. This unconditioned response affects the headless cockroaches avoid shocks in the lifting task by escape learning, whereas they avoid shocks in the lowering task by true avoidance learning. Injection of 30 microliter of Ringer's solution has no significant effect on the learning process in the lifting task. In the lowering task, however, Ringer's solution impairs the learning ability considerably. Crude extract of corpora cardiaca strongly inhibits the learning of both tasks.

Animals↗

Pertussis toxin is required for pertussis vaccine encephalopathy.

A mouse model for encephalopathy induced by pertussis immunization has been described; it has features that closely resemble some of the severe reactions, including seizures and a shock-like state leading to death, occasionally seen after administration of Bordetella pertussis (whooping cough) vaccine. Susceptibility to encephalopathy maps to genes of the major histocompatibility complex and correlates as well with the genetic regulation of the level of antibody response to bovine serum albumin. In this study we have investigated which bacterial determinant is responsible for the encephalopathy. Two lines of evidence implicate pertussis toxin as the active bacterial component. Single-site mutants of B. pertussis with single affected virulence factors were tested. A mutant that produces a defective pertussis toxin had greatly diminished capacity to induce encephalopathy, whereas a hemolysin- and adenylate-cyclase-deficient avirulent mutant had the same activity in the mouse model as a virulent strain. Purified pertussis toxin plus bovine serum albumin was tested and found to induce the lethal encephalopathy, demonstrating that the toxin was the critical constituent of B. pertussis responsible for encephalopathy.

Adenylate Cyclase Toxin↗

Characterization of two adhesins of Bordetella pertussis for human ciliated respiratory-epithelial cells.

Bordetella pertussis, the causative agent of whooping cough, adheres specifically to human ciliated respiratory-epithelial cells. In order to identify the adhesins of Bordetella, we tested mutant strains, each deficient in one of several bacterial virulence factors, for the ability to adhere to single, human ciliated cells in vitro. Loss of adherence was associated with lack of secretion of either of two surface antigens: filamentous hemagglutinin or pertussis toxin. These strains regained adherence if both components were present in the assay system (i.e., the missing protein was supplied exogenously). In this instance, both bacterial components were found bound to the surface of all the Bordetella strains tested as well as to cilia. We hypothesize that filamentous hemagglutinin and pertussis toxin, two naturally secreted surface antigens, act in concert as adhesins of Bordetella for human cilia.

Adhesiveness↗

Acquired immunodeficiency syndrome: epidemiology, virology, and immunology.

Acquired immunodeficiency syndrome indicates opportunistic infection or unusual malignancy associated with a marked deficiency of cell mediated immunity in the absence of any other cause of the immune defect. This review examines epidemiology, virology, and immunology associated with this disorder. The syndrome appears to be caused by infection of at-risk individuals by a retrovirus that has tropism for a specific population of T lymphocytes.

Acquired Immunodeficiency Syndrome↗

Filamentous hemagglutinin and pertussis toxin promote adherence of Bordetella pertussis to cilia.

Bordetella pertussis adheres specifically to the cilia of respiratory epithelial cells. This ability to adhere is characteristic of virulent organisms. In order to define the contribution of various virulence factors of B. pertussis to the process of adherence, mutants deficient in single virulence factors were tested for the ability to adhere to rabbit cilia in vitro and in vivo. Two protective antigens were found to be critical to the process of adherence: filamentous hemagglutinin and pertussis toxin.

Animals↗

Murine model for pertussis vaccine encephalopathy: role of the major histocompatibility complex; antibody to albumin and to Bordetella pertussis and pertussis toxin.

A mouse model for pertussis immunization encephalopathy has been described with features that closely resemble the severe adverse reactions occasionally seen after pertussis vaccine administration,m including seizures and a shock-like state leading to death. These reactions are produced with nearly one hundred percent efficiency provided that the mice immunized with Bordetella pertussis have 1) the appropriate major histocompatibility (H-2) genotype, 2) have been sensitized to bovine serum albumin (BSA), and 3) that the injected B. pertussis contained sufficient amounts of pertussis toxin. Antibody titres were measured in mice with haplotypes H-2d.s.k. that are highly susceptible to encephalopathy as well as in H-2b mice, that are totally resistant. Mice with H-2d.s.k. haplotypes were high responders to BSA, while H-2b (B10) mice were non-responders to BSA. Both H-2d and H-2b mice responded well to B. pertussis. Encephalopathy was induced in resistant H-2b mice with B. pertussis and passively administered anti-BSA antiserum, but not with B. pertussis and anti-(T,G)-A--L antibody. This indicated that B. pertussis and anti-BSA were absolutely required for development of encephalopathy. Encephalopathy could be induced in mice decomplemented with cobra venom factor and given BSA and B. pertussis. Several single-site mutants of B. pertussis affecting single virulence factors were induced with transposon Tn5. One of these mutants, BP357, deficient in pertussis toxin production, had a greatly reduced encephalopathic potential in the mouse model compared to the virulent strain BP 338, or to BP348, an adenylate cyclase and hemolysin double mutant, or to BP 349, a hemolysin mutant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylate Cyclase Toxin↗

The antigen receptor on a human T cell line initiates activation by increasing cytoplasmic free calcium.

A monoclonal antibody to the antigen-receptor on the T cell line Jurkat induces substantial increases in [Ca++]i. Ca++ ionophores can substitute for this antibody in activation by increasing [Ca++]i to levels comparable with those seen with the antigen-receptor antibody. Stimulation with either the antigen-receptor antibody or a Ca++ ionophore leads to the appearance of the same phosphoproteins. These results suggest that the antigen-receptor initiates T cell activation by increasing [Ca++]i.

Antibodies, Monoclonal↗

Activation of a human T cell line: a two-stimulus requirement in the pretranslational events involved in the coordinate expression of interleukin 2 and gamma-interferon genes.

In the resting state, the T3-positive, human T cell line Jurkat does not synthesize detectable amounts of either interleukin 2 (IL 2) or gamma-interferon (IFN-gamma). Activation of Jurkat as measured by the secretion of substantial amounts of both lymphokines requires two distinct signals. One signal is produced by the phorbol ester, phorbol myristate acetate, and the other by either phytohemagglutinin or antibodies to T3. To elucidate the molecular events by which these activation signals lead to the synthesis of IL 2 and IFN-gamma activity we used cDNA probes to follow the appearance of IL 2 and IFN-gamma-specific transcripts after activation of Jurkat. These studies demonstrate that both signals are required for the appearance of IL 2 or IFN-gamma-specific transcripts and that the appearance of IL 2 and IFN-gamma RNA is coordinate with regard to a) the signals required for their production, b) the kinetics of their appearance, and c) the inhibition of their appearance by cyclosporin A. These studies suggest that distinct T cell-activation signals may operate through a common regulatory pathway involved in the expression of both IL 2 and IFN-gamma genes.

Antibodies, Monoclonal↗

T cell activation: differences in the signals required for IL 2 production by nonactivated and activated T cells.

Soluble antibodies against the T3/antigen receptor complex alone are not sufficient to induce proliferation and interleukin 2 expression by T lymphocytes. An additional requirement is the presence of accessory cells (AC). In this model, AC provide at least two functions required for T cell activation: 1) the surface interaction of T3 antibodies with Fc receptors on the AC surface and 2) the production of soluble mediators such as interleukin 1 (IL 1). In the experiments reported here, these stimuli are represented by T3 antibodies immobilized onto Sepharose beads and by recombinant IL 1. In this study we investigated differences in activation requirements in resting and activated T cells. Resting T cells were represented by AC-depleted peripheral blood mononuclear cells (PBMC) or the T cell line Jurkat, which phenotypically resembles a resting T cell. Activated T cells were represented by T cell clones and the T cell line HUT 78, which express the activation molecules Ia and the IL 2 receptor (Tac). In resting cells, activation required the presence of three different signals: perturbation of the T3/antigen receptor complex by T3 antibodies, surface redistribution of T3/antigen receptor complexes, and presence of IL 1. In contrast, activated T cells require only perturbation and redistribution of T3/antigen receptor complexes and not IL 1 for the induction of proliferation or IL 2 production. Possible mechanisms of intracellular signaling for these stimuli are discussed.

Antibodies, Monoclonal↗

Symptomatology of adopted and nonadopted adolescents in a psychiatric hospital.

This study compared the symptomatology and diagnoses of adopted and nonadopted adolescents in a psychiatric hospital. Data were gathered from the hospital charts of adolescents who already had been discharged from the hospital. Contrary to expectations, adoptees were no more likely than nonadoptees to have received personality disorder diagnoses, nor were they more likely to be hospitalized as the result of antisocial behavior. However, in comparison with nonadopted adolescents, the adopted adolescents were younger upon admission to the hospital, significantly less often diagnosed psychotic, and significantly more often diagnosed adjustment reaction. It was suggested that adopted adolescents may be less likely than nonadopted adolescents to require severe or prolonged pathology in order to be admitted to a psychiatric hospital. It was also suggested that the antisocial symptomatology so frequently observed in adopted children in mental health settings does not account for the hospitalizations of those receiving inpatient treatment.

Adjustment Disorders↗

Pharmacological characterization of a new highly effective synthetic thrombin inhibitor.

The most potent synthetic reversible thrombin inhibitor described so far, N alpha-(2-naphthylsulfonylglycyl)-4-amidinophenylalanine piperidide (Ki = 6 nmol/l), was studied with respect to its pharmacodynamics and pharmacokinetics in mice, rats and rabbits. In mice the LD50 was 54 mg/kg i.v. and greater than 800 mg/kg p.o. Prolongation of bleeding time in mice and reduction of mean arterial blood pressure in rats were seen only at doses above the antithrombotically effective doses. After i.v. injection in rabbits the plasma half-life was estimated to be about 9 min. Subcutaneous injection resulted in measurable inhibitor plasma levels for 4 h. Administration of high does into the duodenum did not give antithrombotically effective plasma levels. The ligature of the functional and nutritive hepatic vessels prolonged the half-life of the thrombin inhibitor, whereas renal excretion seems to be of minor importance. A dose-dependent antithrombotic effect was shown in venous stasis-induced thrombosis in rabbits.

Animals↗

Requirement for the coexpression of T3 and the T cell antigen receptor on a malignant human T cell line.

The association between T3 and the T cell antigen receptor was examined using the T3 bearing T cell leukemic line Jurkat. A monoclonal antibody, C305, was produced, which reacted with idiotypic-like determinants expressed on Jurkat. The molecule with which this antibody reacted was a disulfide-linked heterodimer of 90 kD, composed of polypeptides of 42 and 54 kD. Thus, C305 reacted with a molecule with characteristics of the putative T cell antigen receptor described by others. A series of mutants of Jurkat, induced with ethyl methane sulfonate or radiation, was selected for T3 or antigen receptor negativity. In every instance, there was a concomitant loss of both T3 and the antigen receptor as assessed by quantitative absorption, indirect immunofluorescence, and antibody plus complement-mediated cytotoxicity. The absence of antigen receptor molecules was confirmed on diagonal gels, excluding the possibility that conformational changes of the antigen receptor on such T3-negative mutants were responsible for the failure of such mutants to react with C305. Moreover, in a mutant that expressed a marked decrease in the level of T3 expression, there was a comparable decrease in the expression of antigen receptor determinants. These results suggest that there is an obligate requirement for the coexpression of T3 and the T cell antigen receptor. Furthermore, attempts to activate such mutants with the lectin phytohemagglutinin suggested that the expression of T3 and/or the antigen receptor was required for activation of these cells.

Animals↗

Nutritional support in a general urological service.

A nutritional support team was used in the assessment and management of patients on a general urological service. Indications for nutritional evaluation included history of weight loss, anorexia, significant infection, chronic neoplastic disease, trauma or major surgery. The fat and protein status of the patient was assessed by anthropomorphic and laboratory determinations. The patient then was categorized as having mild, moderate or severe degrees of nutritional depletion. Deficiencies in vitamins, trace elements or essential fatty acids were not noted. Caloric and protein needs were calculated by multiplication of the basal energy expenditure by a metabolic activity factor, which was derived from the degree of illness or stress. Nutritional support was provided by enteral feedings via oral, nasogastric or jejunal feeding tubes and/or intravenous hyperalimentation via peripheral or central venous nutrient lines. During a 6-month interval nutritional consultation was requested for 50 patients, who represented 7 per cent of the urological admissions. Nutritional support was provided for patients who had obstructive uropathy with or without neoplasms, radiation cystitis, sepsis, urinary fistulas, mental depression, end stage renal disease or neurological dysfunction. In patients in whom urological treatment controlled the disease nutritional support maintained the weight, and stabilized serum albumin and lymphocyte counts. We concluded that a nutritional support program has a significant and, often, unappreciated role in the management of urological patients.

Aged↗