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Biomedical subjects

J Anderson

Publications and source records attributed to J Anderson.

At least 685 records · Page 38Linked to original sources

Biology of cloned cytotoxic T lymphocytes specific for lymphocytic choriomeningitis virus: clearance of virus and in vitro properties.

We have generated lymphocytic choriomeningitis virus-specific, H-2-restricted cytotoxic thymus-derived lymphocyte (CTL) clones. By using these reagents in several in vitro assays with infected target cells, we show that CTLs by themselves prevent the release of infectious virus into culture fluids and significantly lower the titers of infectious virus previously produced. This ability of cloned CTLs is not influenced by monensin. However, monensin does abrogate the ability of CTLs from spleens of mice primed 6 to 8 days previously with virus to kill virus-infected syngeneic targets. When tested for the participation of lymphokines in this system, the CTLs proliferate when reacted with syngeneic lymphocytic choriomeningitis virus-infected macrophages but fail to make interleukin-2. These CTLs make gamma interferon when reacted with syngeneic virus-infected targets. However, the production of interferon does not directly correlate with CTL-mediated killing. The number of H-2K and D molecules expressed on the target cell surface is not altered during the course of lymphocytic choriomeningitis virus infection. Electron microscopy shows finger-like projections of the CTL clone thrust into the infected cell and lesions bearing an internal diameter of approximately 15 nm in those membranes, illustrating the lytic process.

Animals↗

Subcellular localization of hypothalamic luteinizing hormone.

Ultracentrifugation and sucrose gradient separation techniques have been applied to study of the subcellular distribution of hypothalamic luteinizing hormone (LH). Subcellular particle-bound LH accounted for 42% of the total LH while cytoplasm contained 58% of the total immunoassayable LH in these extracts. 70% of particle-bound LH was present in the P2 fraction and most of the particle-associated LH was found in subfractions of P2 rich in synaptosomes but poor in myelin and mitochondria. While actual amounts of LH in the P3 and P4, the microsomal fractions, were relatively small, the concentration of LH, expressed as nanograms per milligram of protein was quite high. Both content and concentration of LH in the nuclear pellet, P1, were substantially lower. These findings provide further framework for speculation on the role of brain-based LH.

Animals↗

Malignant lymphoma in a colony of Macaca arctoides.

Malignant lymphoma occurred in six Macaca arctoides from a colony of 83 animals during a 30-month period. The cells of two neoplasms had T cell markers. Concurrent disease processes included atypical mycobacterial disease in four macaques and progressive multifocal leukoencephalopathy in one.

Animals↗

Effect of H1- and H2-receptor antagonists on sputum volume and lung function in patients with generalized bronchiectasis.

In a placebo-controlled trial, the effect was assessed of an histamine H1-receptor antagonist, terfenadine (60 mg twice daily) and an H2-receptor antagonist cimetidine (400 mg twice daily) on the sputum production, dyspnoea score and lung function of 12 adult patients with generalized bronchiectasis. Three of these patients had cystic fibrosis. Neither drug, whether given alone or in combination, had any demonstrable effect on any of the parameters measured. It is concluded that histamine plays no significant role in the bronchial hypersecretion occurring in bronchiectasis.

Adult↗

Antibody-complement-mediated cytotoxicity is enhanced by ribosome-inactivating proteins.

The antibody-mediated cytotoxicity of complement can be increased by the ribosome-inactivating proteins gelonin and PAP-S. Treatment of human lymphoid cells that express CALLA with an anti-CALLA monoclonal antibody, J5, and then with rabbit complement, leaves about 6% of the cells alive. The same treatment in the presence of a sublethal concentration of gelonin or PAP-S leaves only about 0.02 and 0.3% of the cells alive respectively. This synergistic effect has potential implications for the in vitro elimination of malignant cells or of immunocompetent cells from bone marrow before its transplantation.

Antibody-Dependent Cell Cytotoxicity↗

Monoclonal antibodies and bluetongue virus diagnosis.

A blocking enzyme linked immunosorbent assay (ELISA) is described for the detection of group specific antibodies to bluetongue virus (BTV). The test is based upon the interruption of the reaction between BTV antigen and a group specific monoclonal antibody raised against BTV by the addition of serial dilutions of either bovine or ovine test sera. The presence of group specific antibodies to BTV in the test serum, results in inhibition of the monoclonal antibody which is detected as a reduction in the expected optical density (OD) reading. The test is capable of the detection of antibodies to all 22 types of BTV but unlike the agar gel precipitin (AGP) test does not show cross-reactions with antibodies to epizootic haemorragic disease (EHD) viruses. Antibodies to cellular proteins which give rise to complications in the AGP test and indirect ELISA are not detected by this assay. Preliminary studies indicate that due to its high specificity and sensitivity, the blocking ELISA is an ideal alternative to the AGP test. The use of such a monoclonal antibody would also facilitate the standardization of diagnostic testing between laboratories.

Animals↗

Immunologic abnormality in a group of Macaca arctoides with high mortality due to atypical mycobacterial and other disease processes.

Of 54 Macaca arctoides, 44 died during the 2.5 years after their assignment to a common cage. Although early deaths were due to trauma, acute gastric dilatation, and shigellosis; latter deaths were the result of a variety of uncommon diseases including atypical mycobacterial disease, malignant lymphoma, protozoan encephalomyelitis, and other necrotizing and inflammatory lesions. Atypical mycobacterial disease due to Mycobacterium avium intracellular serotypes was the most frequent single disease agent recognized (33% [18 macaques]). This disease began in the ileum and large intestine with subsequent systemic involvement. An abnormality of host response to infective agents, in general, was indicated by the unusually high occurrence of this disease, as well as other disease processes. Morphologic evaluation of lymphoid organs revealed decreased cellularity of follicles and decreased numbers of plasma cells in all macaques, whereas T cell-dependent areas varied from hypocellular to hypercellular with 5 macaques with malignant lymphoma. The spontaneous erythrocyte rosette-forming subpopulation of T cells was decreased in peripheral blood, but was increased in lymph nodes containing atypical mycobacterial lesions. Serum immunoglobulin value decreased progressively in diseased macaques. A basic abnormality of T-cell subpopulations controlling other components of host response was suspected. Macrophages from lesions that contain mycobacterial organisms did not phagocytize latex beads normally in vitro, whereas monocytes in the blood of the same macaques were capable of in vitro phagocytosis.

Animals↗

Evidence for the superiority of immunosuppressive drugs and prednisone over prednisone alone in lupus nephritis. Results of a pooled analysis.

In an effort to clarify the role of immunosuppressive drugs in the management of lupus nephritis, we pooled data from all published clinical trials in which patients had been randomly assigned to receive either prednisone alone or prednisone plus cyclophosphamide or azathioprine. The pooled analysis showed that patients receiving immunosuppressive drugs had less renal deterioration (P = 0.006), were less likely to have end-stage renal disease (P = 0.023), and were less likely to die from kidney disease (P = 0.024) than patients receiving steroids alone. There were no significant differences with respect to deaths from nonrenal causes or overall mortality. When cyclophosphamide and azathioprine were considered separately, both were associated with a 40 per cent reduction in the rates of adverse renal outcomes, although because the treatment groups were smaller, many of these differences were not statistically significant. A power analysis showed that a study of 100 high-risk patients (development of renal insufficiency in 50 per cent) would be needed to prove that an immunosuppressive agent is 50 per cent superior to steroids alone in preventing renal deterioration. We conclude that immunosuppressive drugs and steroids together are more effective than steroids alone in treating lupus nephritis and that published trials have reached false negative conclusions because of small sample sizes.

Azathioprine↗

Does random blood glucose sampling outdate testing for glycosuria in the detection of diabetes during pregnancy?

A random blood glucose concentration was determined in 2403 pregnant women attending an antenatal clinic at between 28 and 32 weeks' gestation. The calculated 99% cut off values were 6.1 mmol/l (110 mg/100 ml) within two hours after a meal and 5.6 mmol/l (101 mg/100 ml) more than two hours after a meal. Patients with a blood glucose concentration in excess of these values were referred for a 75 g oral glucose tolerance test. Of 59 referred, four were found to have previously unsuspected but unequivocal diabetes mellitus and another four to have impaired glucose tolerance on the basis of the World Health Organisation's criteria. Screening all antenatal patients by randomly measuring blood glucose concentrations is not only cheap and efficient but also does not interfere with the routine of busy antenatal clinics.

Blood Glucose↗

Use of monoclonal antibody in a blocking ELISA to detect group specific antibodies to bluetongue virus.

An enzyme-linked immunosorbent assay (ELISA) in the form of a blocking test is described for the detection of group specific antibodies to bluetongue virus (BTV). The test relies upon interruption of the reaction between BTV antigen and a group specific murine monoclonal antibody against BTV by addition of serial dilutions of bovine or ovine test sera containing specific antibodies to BTV which inhibit binding of the monoclonal antibody to the BTV antigen. This is detected as a reduction in the optical density (O.D.) reading obtained with the monoclonal antibody alone. The test is capable of specific detection of antibodies to all 22 serotypes of BTV but, unlike the agar gel precipitin (AGP) test, does not show cross-reactions with antibodies to epizootic haemorrhagic disease of deer (EHD) viruses. Furthermore, antibodies to cellular proteins which complicate interpretation of the AGP test and the indirect ELISA are not detected in the blocking ELISA. The high sensitivity and specificity of the blocking ELISA make it an ideal alternative to the AGP test. The use of a monoclonal antibody would facilitate standardisation of diagnostic testing between laboratories.

Animals↗

Release of immunoreactive luteinizing hormone (LH) from rat hypothalamus-pars tuberalis explants.

A luteinizing hormone (LH)-like molecule has been described in the rodent central nervous system and has been shown to have immunologic, chromatographic, and biologic activity similar to that of pituitary LH. In this communication we report that a depolarizing stimulus, high potassium concentration in the presence of calcium, causes in vitro release of LH from hypothalamic explants containing the pars tuberalis. Release from other brain areas containing LH was not seen nor was release of LH, in vitro, significantly provoked from dorsal segments of the hypothalamus, thus suggesting that most, if not all, of the releasable LH from intact hypothalamic explants may come from cells of the pars tuberalis.

Animals↗