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Biomedical subjects

J Meyers

Publications and source records attributed to J Meyers.

At least 37 records · Page 2Linked to original sources
PubMed1992

Susceptibility to cell death is a dominant phenotype: triggering of activation-driven T-cell death independent of the T-cell antigen receptor complex.

The failure of Thy-1 and Ly-6 to trigger interleukin-2 production in the absence of surface T-cell antigen receptor complex (TCR) expression has been interpreted to suggest that functional signalling via these phosphatidylinositol-linked alternative activation molecules is dependent on the TCR. We find, in contrast, that stimulation of T cells via Thy-1 or Ly-6 in the absence of TCR expression does trigger a biological response, the cell suicide process of activation-driven cell death. Activation-driven cell death is a process of physiological cell death that likely represents the mechanism of negative selection of T cells. The absence of the TCR further reveals that signalling leading to activation-driven cell death and to lymphokine production are distinct and dissociable. In turn, the ability of alternative activation molecules to function in the absence of the TCR raises another issue: why immature T cells, thymomas, and hybrids fail to undergo activation-driven cell death in response to stimulation via Thy-1 and Ly-6. One possibility is that these activation molecules on immature T cells are defective. Alternatively, susceptibility to activation-driven cell death may be developmentally regulated by TCR-independent factors. We have explored these possibilities with somatic cell hybrids between mature and immature T cells, in which Thy-1 and Ly-6 are contributed exclusively by the immature partner. The hybrid cells exhibit sensitivity to activation-driven cell death triggered via Thy-1 and Ly-6. Thus, the Thy-1 and Ly-6 molecules of the immature T cells can function in a permissive environment. Moreover, with regard to susceptibility to Thy-1 and Ly-6 molecules of the immature T cells can function in a permissive environment. Moreover, with regard to susceptibility to Thy-1 and Ly-6 triggering, the mature phenotype of sensitivity to cell death is genetically dominant.

Animals↗
PubMed1992

Genome digestion is a dispensable consequence of physiological cell death mediated by cytotoxic T lymphocytes.

We examined virally transformed murine fibroblast clones as targets for cytotoxic T lymphocyte (CTL)-triggered lysis and genome digestion. Strikingly, while all clones were essentially equivalent in the ability to be lysed, one clone, SV3T3-B2.1, failed to exhibit genome digestion associated with CTL attack. Other aspects of the physiological cell death process, including loss of adhesion and nuclear envelope breakdown (lamin phosphorylation and solubilization), were not altered in this clone. The absence of genome digestion associated with CTL-induced cell death correlated with the absence of endodeoxyribonuclease activity in the nuclei of that clone. Characterization of the activity affected identifies a calcium-dependent, DNase I-like endonuclease of approximately 40 kDa, normally present constitutively in all cell nuclei, as the enzyme responsible for genome digestion associated with CTL-mediated cell death. These observations indicate that neither genome digestion per se nor its consequences [such as activation of poly(ADP-ribose) polymerase] are essential for cell death resulting from the triggering of this cell suicide process.

Animals↗
PubMed1991

DNA and RNA flow cytometric study in multiple myeloma. Clinical correlations.

Flow cytometric studies of cellular DNA and RNA content using the acridine-orange technique were conducted in 81 patients with multiple myeloma (MM). All patients were treated with the M-2 protocol and clinical response was evaluated according to the criteria of the Chronic Leukemia-Myeloma Task Force. Aneuploid DNA stemlines were found in 38.2% of untreated patients with a median DNA index (DNA-I) of 1.15 in marrow aspirates and 1.22 in biopsy specimens. The median percentage of cells with abnormal DNA content was 31.5 (aspirates) and 35 (biopsy specimens) and a positive correlation with the percentage of bone marrow plasma cells was observed. Significantly higher proliferation (S-phase) was found in marrow biopsy specimens as compared with marrow aspirates. Significantly higher RNA content (RNA index [RNA-I]) was observed in aneuploid versus diploid patients in biopsy material. There was no difference in response to the Memorial Hospital M-2 protocol between diploid and aneuploid patients. In patients with DNA-I greater than 1.15 remission duration was shorter as compared with DNA-I less than or equal to 1.15. Furthermore, no difference in cellular RNA content was noted between responders and nonresponders. This study demonstrates no correlation between cellular RNA content and response, as previously described for patients treated with vincristine, Adriamycin, and dexamethasone (VAD), but DNA aneuploidy appears to be an adverse prognostic factor in MM patients treated with the M-2 protocol. It also demonstrates that prognostic models for MM are not universal but depend on the chemotherapeutic regimen used.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Supportive care of the marrow transplant recipient: the Seattle Experience.

It is now almost 2 decades after the first successful human marrow transplants from HLA-identical siblings for the treatment of life-threatening hematologic diseases. Results have improved, especially for patients transplanted earlier in the course of disease. However, major problems remain in supporting patients through the transplant. More effective and less toxic conditioning regimens are needed. Acceleration of hematopoietic and immunologic reconstitution by use of various cytokines holds promise for decreasing infectious morbidity and mortality. Improved regimens to control acute and chronic GVHD and prevent opportunistic infections will play a major role in the advancement of supportive care of the marrow transplant recipient.

Anti-Infective Agents↗
PubMed1985

The influence of exercise training on the ventilatory threshold of patients with coronary heart disease.

Out of 156 patients with stable coronary heart disease randomized to either an exercise intervention group or a control group, 41 had complete gas analysis data. Continuous gas exchange data, including the ventilatory threshold, and selected heart rates were determined initially and at 1 year. The mean attendance for the exercise group was 2.2 +/- 0.7 days a week at an intensity of 60 +/- 9% of estimated peak oxygen uptake for 1 year of the study. Statistically significant differences (p less than 0.05) were observed between the exercise group (n = 19) and the control group (n = 22) for peak oxygen uptake (L/min), total treadmill time, and supine rest and submaximal heart rates after 1 year. The most remarkable change was a 16% increase in treadmill time. There was no difference between groups for the ventilatory threshold expressed either as an absolute oxygen uptake or as a percentage of peak oxygen uptake at 1 year. However, there was a significant correlation (r = 0.45; p less than 0.05) between the absolute change in peak oxygen uptake and the absolute change in the ventilatory threshold. These results indicate that a moderate exercise program is inadequate to alter the ventilatory threshold in patients with coronary heart disease and that changes in ventilatory threshold do not explain the increase in treadmill time that usually occurs.

Coronary Disease↗
PubMed1985

Design and use of double lumen right atrial catheters in bone marrow transplant recipients.

Bone marrow transplant recipients require central venous catheterization for a variety of fluids. They are also particularly susceptible to infection. Here we discuss the use of double lumen catheters to reduce the number of invasions necessary. We make particular reference to infection, neutropenia, prophylactic antibiotics, additional catheters, and presence of graft vs host disease.

Adolescent↗
PubMed1985

Autologous marrow transplantation in patients with acute nonlymphocytic leukemia in first remission.

Thirteen patients with acute nonlymphocytic leukemia underwent autologous bone marrow transplantation (ABMT) following high doses of cyclophosphamide and total body irradiation while in first complete remission. After marrow infusion four patients received human leukocyte interferon and nine received intravenous methotrexate. One patient died on day 16 of septicemia associated with severe gastrointestinal toxicity. In the remaining 12 patients the median day of achieving a circulating granulocyte level of 500/mm3 was 29 (range 15-94 days). Eight of 12 evaluable patients achieved a sustained platelet count of 20,000/mm3 or greater in a median of 44 days (range 12-116 days) and four patients did not achieve this level before death on days 116-396. One patient died on day 116 of interstitial pneumonitis secondary to cytomegalovirus. Eight patients relapsed 58-365 days after AMBT (median 335 days), and all have died. Three patients are alive and well without relapse 26-50 months after ABMT. This study demonstrated that poor engraftment was a frequent complication of ABMT when early posttransplant cytotoxic therapy was attempted. Relapse of leukemia and the number of long-term survivors in this small group of patients was not different from that expected following conventional therapy.

Acute Disease↗
PubMed1983

Phytohemagglutinin derived from red kidney bean (Phaseolus vulgaris): a cause for intestinal malabsorption associated with bacterial overgrowth in the rat.

Plant lectins or carbohydrate binding proteins interact with membrane receptors on cellular surfaces but their antinutritional effects are poorly defined. Studies were conducted to determine the effects of phytohemagglutinin, a lectin derived from raw red kidney bean (Phaseolus vulgaris), on small intestinal absorptive function and morphology, and on the intestinal microflora. Phytohemagglutinin was isolated in purified form by thyroglobulin-sepharose 4B affinity chromatography. Red kidney bean and phytohemagglutinin (6% and 0.5%, respectively, of dietary protein) were fed in a purified casein diet to weanling rats for up to 21 days. Weight loss, associated with malabsorption of lipid, nitrogen, and vitamin B12, developed in comparison with animals pair-fed isonitrogenous casein diets. Antinutritional effects of red kidney bean were reversible on reinstitution of a purified casein diet. An increase in bacterial colonization of the jejunum and ileum occurred in red kidney bean- and phytohemagglutin-fed animals. When antibiotics were included in the diet, malabsorption of [3H]triolein and 57Co-vitamin B12 in red kidney bean-fed animals was partially reversed and, in germ-free animals, purified phytohemagglutinin had no demonstrable antinutritional effect. Mucosal disaccharidase activity was reduced in red kidney bean- and phytohemagglutinin-fed animals, but intestinal mucosal morphology was unchanged. Dietary administration of phytohemagglutinin, alone or as a component of red kidney bean, caused intestinal dysfunction, which was associated with, and dependent upon, small intestinal bacterial overgrowth. Adherence of enteric bacteria to the mucosal surface was enhanced by phytohemagglutinin which may have facilitated small intestinal bacterial overgrowth.

Animals↗
PubMed1979

Increased integration of viral genome following chemical and viral treatment of hamster embryo cells.

Treatment of hamster embryo cells with diverse classes of chemical carcinogens enhances transformation by a carcinogenic simian adenovirus, SA7. Virus transformed foci selected from plates pretreated with 3-methyl-cholanthrene (MCA), methyl methanesulfonate (MMS) or 7,12-dimethylbenz[a]anthracene (DMBA) and established as cell lines in culture, contained equivalent amounts of SA7 viral genome. However, hamster embryo cultures treated with MMS or nickel sulfate had increased amounts of SA7 DNA integrated into cellular DNA when examined 2--9 days after chemical treatment and viral inoculation. An increased uptake of SA7 DNA was demonstrated in hamster cells treated with MMS during DNA repair synthesis in cells retricted in scheduled DNA synthesis by amino acid deprivation; addition of virus after the repair period did not result in an increased integration of viral DNA. These data suggest that enhancement of viral oncogenesis by chemical carcinogens or mutagens may be related to the formation of additional attachment sites in cellular DNA for insertion of viral DNA, thereby increasing the probability of viral transformation.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1979

Juvenile-onset obesity and deficits in caloric regulation in MSG-treated rats.

Caloric regulation and the development of obesity were examined in rats which had received parenteral injections of monosodium glutamate (MSG) as neonates. Rats were injected with either 2 mg/g or 4 mg/g MSG on alternate days for the first 20 days of life. Lee Indices of obesity were calculated at 22, 70, and 130 days of age. Animals in the 4 mg/g group were significantly more obese than controls at all three ages. However, both food intake and body weight of this group were significantly lower than those of controls. In adulthood, the ability to regulate caloric intake was tested by allowing animals access to diets of varying caloric densities. While control animals maintained relatively constant caloric intakes across dietary conditions, MSG-treated animals demonstrated an inability to respond to caloric challenges. Treated animals decreased caloric intake on a diluted diet and consumed more calories than controls when presented with a calorically dense diet. This inability to regulate caloric intake is compared with regulatory deficits observed in animals sustaining lesions of the ventromedial hypothalamus. The value of an animal model of juvenile-onset obesity is also discussed.

Aging↗