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Biomedical subjects

A Sharp

Publications and source records attributed to A Sharp.

At least 55 records · Page 3Linked to original sources
PubMed1990

The bone marrow as an effector T cell organ in aging.

The idea that the bone marrow (BM) might function as a T cell effector organ and might constitute a compensating system to the decreased T cell compartment in aging was examined by carrying out an analysis of T cell functions in this tissue. The Thy1+ cells, which were found to increase in their proportions with age in the BM, were sorted out from the BM of young and old mice by flow cytometry and their proliferative response to Concanavalin A (conA) stimulation was measured. The sorted Thy1+ cells responded to conA at levels comparable to those of splenocytes, with the old BM showing a significantly lower response than the young. To determine whether cells of the intact BM behave in a similar pattern to the sorted cells, we measured the responses induced by conA in unseparated BM cells of both age groups. The results showed that the patterns of proliferative response in the intact BM cells were different than those observed in splenocytes and in the Thy1+ sorted cells. Hence, cells of the old BM manifested initially higher levels of proliferation preceding that of the young BM, yet the response was apparent for a shorter duration. When we measured the conA induced proliferation of the intact BM cells in the presence of colchicine, the number of BM cells entering the first mitotic cycle was higher in the old. Thus, it seems that there are more effector T cells in the old BM, yet their response to stimulation is of shorter duration. This conclusion was also supported by the assessment of cytotoxic T lymphocytes precursor (CTLp) frequency and of CTL function of the BM. CTLp was higher in the old BM following 3 days of incubation and lower following 7 and 9 days of incubation. The old BM cells showed a reduced CTL response at the proliferative phase when stimulated for 4-7 days, yet their effector cell reactivity was either equal or more efficient than the young. To determine whether some of the differences between the two age groups were due to regulatory effects of the BM microenvironment, BM cells from young and old donors were admixed with young mouse splenocytes and stimulated with conA. The conA induced response was enhanced up to tenfold under these conditions yet to the same extent in both age groups. Thus, it appears that the BM has the capacity to function as a T cell effector organ.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1990

In vitro analysis of age-related changes in the developmental potential of bone marrow thymocyte progenitors.

Mechanisms underlying the age-related decrease in the developmental capacity of thymocyte progenitors from the bone marrow (BM) were analyzed, focussing on interaction of these cells with the thymic microenvironment. We employed the experimental model in which mixtures of young and old mouse BM cells, congenic for the Thy-1 marker, were seeded onto fetal thymus (FT) explains depleted of self lymphocytes and the levels of Thy-1+ cells developing from each of the two donor types were measured. When cells from young and old BM donors were seeded simultaneously, in saturating quantities, a higher level of T cells developed from the young donors. To find out whether there were originally more thymocyte progenitors in the young BM, we carried out the competitive colonization under limiting dilution conditions and found that the advantage of the young had diminished under these conditions, thus suggesting that the age-related changes could not be related solely to quantitative differences. We then incubated the FT sequentially with old donor cells for 24 h, followed by young for an additional 48 h and found that the advantage of the young progenitors was eliminated. We thus established that the initial stage of colonization of the FT was important in determining the outcome of the subsequent development. The kinetics of simultaneous competition within the FT, however, revealed that the advantage of the young BM-derived cells became significant only from day 7 in organ culture, thus suggesting that sequential divisions of these cells were at a higher level than those of the old. Recolonization of FT explants by young or old BM-derived thymocytes obtained from the first colonization of the FT stroma showed a reduced, but still significant advantage for the young BM-derived cells over the old. Thus, we concluded that the old BM thymocyte progenitors manifested a qualitative disadvantage which became apparent during competitive colonization of the FT.

Aging↗
PubMed1989

Age related changes in hemopoietic capacity of bone marrow cells.

The effect of aging on the hemopoietic capacity of bone marrow (BM) cells was investigated. No difference was found in the incidence of colony forming units-spleen (CFU-S) and granulocyte-macrophage colony forming cells (GM-CFC) present in the BM of young (2-4 months) or old (24-30 months) mice. However, increased proliferation (x3) of the old BM cells was observed when cultured in the presence of L-cell conditioned medium. The cells were also cultivated over an adherent layer of a BM stroma cell line (14F1.1, endothelial-adipocytes) and the non-adherent cells removed and tested weekly. Cells originating from the old BM proliferated to a greater extent and produced more GM-CFC than those from the young. Differentiation into T-cells after colonizing fetal thymus explants was also measured and found to be reduced in both groups, though to a greater extent in the old. Thus, under the present experimental conditions, myeloid progenitors in the old BM manifest a more pronounced self renewal and differentiation capacity than the young while for the T-cell progenitors the situation is reversed.

Aging↗
PubMed1989

Times are a'changin.

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Allied Health Personnel↗
PubMed1989

Who's in charge?

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Connecticut↗
PubMed1988

Hypothalamic-pituitary gonadal axis in boys with primary hypothyroidism and macroorchidism.

Nine of 15 boys with severe long-standing primary hypothyroidism were found to have macroorchidism. All 15 patients had elevated thyroid-stimulating hormone levels. However, only those patients with testicular enlargement had striking elevations of serum prolactin and gonadotropin values. The response to gonadotropin-releasing hormone in our patients was blunted, in contradistinction to that of children with true precocious puberty. In spite of the elevated levels of luteinizing hormone, the serum testosterone levels were in the prepubertal range, explaining the lack of peripheral manifestations of androgenic effect. Improvement of testosterone secretion followed decreasing prolactin levels with bromocriptine administration, suggesting an inhibitory effect of prolactin on luteinizing hormone action at the Leydig cell. We conclude that testicular enlargement is the result of continuous follicle-stimulating hormone stimulation and that the term "true precocious puberty" is not appropriate in children with hypothyroidism and macroorchidism unless the hypothalamic-pituitary gonadal axis is shown to be at the pubertal stage.

Adolescent↗
PubMed1987

Nimodipine-treated subarachnoid hemorrhage associated with acute pseudo-obstruction of the colon.

Nimodipine is being used with increasing frequency in the prevention or treatment of vasospasm due to subarachnoid hemorrhage. Few side effects have been described. An acute pseudo-obstruction of the colon (Ogilvie's syndrome) in a patient treated with an intravenous infusion of nimodipine is reported. The possible relationship between this serious complication and the use of this drug is discussed.

Acute Disease↗
PubMed1987

Boondock medics.

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Alaska↗
PubMed1986

High-affinity antibodies to the 1,4-dihydropyridine Ca2+-channel blockers.

Antibodies with high affinity and specificity for the 1,4-dihydropyridine Ca2+-channel blockers have been produced in rabbits by immunization with dihydropyridine-protein conjugates. Anti-dihydropyridine antibodies were found to specifically bind [3H]nitrendipine, [3H]-nimodipine, [3H]nisoldipine, and [3H]PN 200-110 (all 1,4-dihydropyridine Ca2+-channel blockers) with high affinity, while [3H]verapamil, [3H]diltiazem, and [3H]trifluoperazine were not recognized. The average dissociation constant of the [3H]nitrendipine-antibody complex was 0.06 (+/- 0.02) X 10(-9) M for an antiserum studied in detail and ranged from 0.01 to 0.24 X 10(-9) M for all antisera. Inhibition of [3H]nitrendipine binding was specific for the 1,4-dihydropyridine Ca2+-channel modifiers and the concentrations required for half-maximal inhibition ranged between 0.25 and 0.90 nM. Structurally unrelated Ca2+-channel blockers, calmodulin antagonists, inactive metabolites of nitrendipine, and UV-inactivated nisoldipine did not modify [3H]nitrendipine binding to the anti-dihydropyridine antibodies. Dihydropyridines without a bulky substituent in the 4-position of the heterocycle were able to displace [3H]nitrendipine binding, but the concentrations required for half-maximal inhibition were greater than 800 nM. In summary, anti-dihydropyridine antibodies have been shown to have high affinity and specificity for the 1,4-dihydropyridine Ca2+-channel blockers and to exhibit dihydropyridine binding properties similar to the membrane receptor for the 1,4-dihydropyridine Ca2+-channel blockers.

Animals↗
PubMed1983

An anti-acetylcholine receptor monoclonal antibody cross-reacts with phosvitin.

Rabbit and mouse anti-Torpedo acetylcholine receptor antibodies cross-reacted partially with the highly phosphorylated protein, phosvitin. We have selected an anti-Torpedo acetylcholine receptor monoclonal antibody which binds specifically to phosvitin; this binding is inhibited by acetylcholine receptor. These findings suggest that a phosphorylated amino acid residue may be a part of the determinant on the acetylcholine receptor recognized by this monoclonal antibody.

Animals↗