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Biomedical subjects

W Ershler

Publications and source records attributed to W Ershler.

8 recordsLinked to original sources
PubMed1999

Bladder infection in the menopausal monkey.

PURPOSE: The highest incidence of urinary tract infection in females occurs in elderly women. This study was done to determine whether this is due to the declining immune response that occurs during advancing age, or the menopausal state in the aged. MATERIALS AND METHODS: Adult female monkeys (average age 19 years) were studied, half being subjected to bilateral oophorectomy to produce the menopause. In addition, old females (average age 29 years) already at menopause were studied before and after hormonal replacement with estradiol and progesterone. Bacterial adherence to vaginal cells was studied prior to and after urethral infection with E. coli. Plasma estradiol and progesterone levels were done, as well as white blood counts, plasma cytokine assays and serum antibody titers. RESULTS: Bacteriuria was not prolonged, nor was there a significant difference in bacterial adherence to vaginal cells due to menopause. Interleukin-1 levels were depressed after surgical menopause but not as much as found in the old menopausal females and this low level was not corrected by hormonal replacement. The initial interleukin-2 levels were higher after spontaneous menopause, but the increasing plasma levels seen in cycling animals after infection did not occur in the aged menopausal females following infection even after hormone replacement. The antibody titers to the E. coli infection showed a trend to a lessened response to infection after menopause but were not significantly decreased. CONCLUSIONS: The deficient Il-1, Il-2 and antibody response following infection was not corrected by hormone replacement and thus appears to be due to aging rather than lack of female hormones. These facts may be explained by the T cell senescence known to occur in aged individuals.

Age Factors↗
PubMed1996

Immune dysregulation in the aging human lung.

Aging has been associated with diminished lung function and increased susceptibility to lung infection. To determine whether changes suggestive of immune dysregulation and inflammation appear in the lungs of clinically normal individuals as a function of advancing age, we performed bronchoalveolar lavage (BAL) on discontinuous age groups (20-36, 45-55, and 65-78 yr old) of clinically normal volunteer subjects. We measured immunoglobulin (IgG, IgA, IgM), albumin, interleukin-6 (IL-6), and interleukin-10 concentrations in BAL fluid. Bronchoalveolar cell profiles, cell surface antigen expression, and superoxide anion production were also measured. A significant increase in total cell concentration, neutrophils, and BAL immunoglobulin content was observed in the oldest age group compared with the youngest age group. Mean lymphocyte subset (CD4+/CD8+) ratios were significantly increased in blood (2.6 +/- 0.4 versus 1.6 +/- 0.1; p<0.03) and to a greater degree in BAL (4.8 +/- 1.0 versus 1.9 +/- 0.2; p<0.01) for the oldest versus youngest age groups. Similarly, BAL-derived cells displayed significantly increased phorbol myristate acetate-stimulated release of superoxide anion (8.8 +/- 1.3 versus 4.5 +/- 0.7 nmol/5 x 10 5 cells/h; p<0.01) for the oldest versus youngest subject group, and mean BAL IL-6 concentrations were significantly elevated in the oldest age group (0.86 +/- 0.13 ng/ml) compared with the youngest age group (0.53 +/- 0.03 ng/ml; p<0.01). Our observations suggest that altered inflammatory cell profiles and low-grade inflammation exist in the lower respiratory tracts of many asymptomatic, clinically normal volunteers of advanced age.

Adult↗
PubMed1995

Interleukin-6 causes hypocholesterolemia in middle-aged and old rhesus monkeys.

BACKGROUND: Hypocholesterolemia is a risk factor for morbidity and mortality in older people. We have hypothesized that hypocholesterolemia in older people is due to the chronic effect of proinflammatory cytokines on lipoprotein metabolism. METHODS: To test the effects of the chronic administration of interleukin-6 (IL-6) on lipoprotein levels in middle-aged and old rhesus monkeys, five middle-aged and five old rhesus monkeys received a subcutaneous injection of recombinant human IL-6 (15 micrograms/kg) for 28 days. Lipid, apolipoprotein, and albumin levels were measured at 0, 28, and 42 days after injection. RESULTS: Total and HDL cholesterol levels fell by 16 and 23%, respectively, after IL-6 injections. The concentrations of apolipoproteins A1 and B also decreased. The changes in lipoprotein levels were accompanied by a decrease in albumin levels and body weight. Levels of lipids and plasma proteins returned toward normal 2 weeks after injections were stopped. There was no difference in response between middle-aged and older animals. CONCLUSIONS: Chronic IL-6 injections cause acquired hypocholesterolemia, hypoalbuminemia, and weight loss in nonhuman primates. These changes are similar to those seen in older persons with acquired hypocholesterolemia.

Aging↗
PubMed1988

Pathogenetic role of HIV infection in Kaposi's sarcoma of equatorial East Africa.

Thirty residents of north-central Tanzania with various forms of Kaposi's sarcoma (KS) were evaluated. The absolute number of peripheral blood OKT4 lymphocytes in patients and Tanzanian control subjects tended to be low (in comparison with healthy young American adults), and many had inverted T4/T8 ratios. Plasma polyclonal beta- and gamma-globulin concentrations were increased in many patients with KS and in control patients in Tanzania with chronic dermatopathies, but not in African hospital employees and patients undergoing elective surgery. Three of nine patients with locally aggressive KS possessed antibodies to human T-cell lymphotropic virus type III/lyphadenopathy-associated virus (HIV), but none had evidence of the acquired immunodeficiency syndrome (AIDS) or the AIDS-related complex. Three patients with disseminated, rapidly progressive KS and high HIV-antibody titers had an immunologic and clinical picture consistent with AIDS. Two of 13 patients with the classic plaque/nodular form of KS had low plasma titers of HIV antibody, but the significance of these serologic findings is not known. The evidence suggests that HIV plays a role in the pathogenesis of some cases of KS in East Africa, but most patients with KS in East Africa have no evidence of overt immunologic deficiency or HIV infection.

AIDS-Related Complex↗
PubMed1987

Role of the thymus and T-cells in slow growth of B16 melanoma in old mice.

Clinical observations suggest that tumors grow more slowly in aged subjects. To investigate the influence of age on tumor growth, we injected the same number of cultured B16 melanoma cells into C57BL/6 mice of various ages. B16 melanoma cells, inoculated s.c., grew more slowly in old (18-20-month-old) as compared to young (6-8-week-old) mice. In young tumor-bearing mice there was a significant increase in the number and the proliferative response to phytohemagglutinin and concanavalin A of splenic T-cells as compared to old tumor-bearing animals. There was no difference in the response of B-lymphocytes from old and young tumor-bearing mice to lipopolysaccharide. The positive association between T-cells and the rate of tumor growth was also suggested by the slower growth of melanoma cells in thymectomized or thymectomized and anti-theta antiserum-treated young mice. Finally, the age-associated difference in tumor growth could be transferred by spleen cells from old or young mice to thymectomized and lethally irradiated syngeneic young animals. Young mice with rapidly growing B16 melanoma tumors have increased numbers and proliferative responses of thymic-derived lymphocytes. It is likely that T-cells or their products facilitate the growth of B16 tumor cells.

Aging↗
PubMed1981

The use of serial bone scans in assessing response of bone metastases to systemic treatment.

The accuracy levels of serial radioisotope bone scans and conventional bone radiographs in assessing the response of bone metastases to systemic therapy were compared in 34 women with metastatic breast cancer. Each patient had measurable or evaluable nonosseous metastases, which were assessed independently of skeletal disease. The bone scan was found to be more accurate and sensitive indicator of the status of bone metastases than the radiograph. The bone scan correlated well with response of soft tissue or visceral disease, while the results of repeated bone radiographs were frequently misleading. With use of a digital model, it was possible to accurately measure the area of skeletal involvement of the bone scan, and from this derive quantitative criteria for response in bone metastases analogous to response criteria currently in use for soft tissue and visceral disease. It is suggested that serial quantitative bone scans be done, in preference to radiographs, to assess the response of bone metastases to systemic therapy.

Adult↗