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Biomedical subjects

A Sharp

Publications and source records attributed to A Sharp.

At least 19 recordsLinked to original sources
PubMed1999

Differential effects of CD4+ and CD8+ cells on lymphocyte development from human cord blood cells in murine fetal thymus explants.

The possibility that mature lymphocytes play a role in the regulation of human T cell development was studied in the experimental model of fetal thymus organ cultures (FTOC), by reconstituting lymphocyte-depleted murine fetal thymus (FT) lobe with cells isolated from human umbilical cord blood (CB). Cultures were incubated with human cytokines (IL-7, FLT-3 ligand and Steel Factor), or remained untreated. When CD4+, or CD8+ CB cells, were co-cultured with FT explants, they expanded and maintained their original phenotypic markers, with no significant effect of the cytokines. Cultures of human hematopoietic stem cells (CD34+) gave rise to CD4+CD8- cells, which were mainly CD3-, with no indication of further intermediate developmental stages. However, a limited number of CD4+CD8+ (double positive [DP]) cells were detected when the CD34- cells were co-cultured with CD4+ cells from the same CB samples. In contrast, FT with unseparated CB cells resulted in the different CD4/CD8 subsets, and their numbers increased in the presence of cytokines. The appearance of DP cells depended on the presence of either CD4+ or CD8+ cells in the cultured CB samples. Hence, DP cells were not detected when the CB was depleted of CD4+ and CD8- cells ("depCB") before culture, and they appeared when depCB were co-cultured with either CD4+ or CD8+ cells. In contrast, CD4+ cells inhibited the development of CD8+CD3+ cells, and this was most pronounced in the absence of the cytokines. There was no symmetrical down-regulatory effect of CD8+ cells on the development of CD4+CD3+ cells. Addition of IL-15 to the cytokine mixture led to an increased proportion of CD56+ cells in cultures of CD34+ cells. The presence of CD4+, and not CD8+ cells, interfered with this process. Our results thus imply differential effects of CD4+ and CD8+ cells on thymocytopoiesis.

ADP-ribosyl Cyclase↗
PubMed1998

Estrogen-receptor expression and function in thymocytes in relation to gender and age.

The expression of estrogen receptor (ER) in thymocytes was studied in young, middle-aged, and old (2, 12, and 24 months, respectively) female and male C57BL/6J mice. Western immunoblots prepared from the thymocytes of females of all age groups showed the presence of a 67-kD protein band, which has been associated with the apparent MW of denatured ER. Flow cytometry analysis of cells stained with a monoclonal anti-ER antibody (clone 13H2) disclosed ER expression in both females and males of all age groups. In vivo treatment with estradiol (E2) led to an increase in the specific activity of thymic creatine kinase (CK) in the female mice, whereas the male thymocytes responded with an increase in CK activity only on treatment with dihydrotestosterone (DHT). The data show no differences in ER expression between male and females, but the receptor appears not to be functional in males. Interestingly, when estradiol was applied to co-cultures of lymphoid-depleted fetal thymus (FT) explants and bone-marrow cells, or thymocytes, from young and old females, it resulted in increased cellularity of cultures containing cells of the young, and not those of the old. The proportion of CD4/CD8 phenotypes of the developing cells in these cultures was not affected by E2 treatment. These observations provide a new insight into ER expression and function in T-cell development in relation to gender and age.

Age Factors↗
PubMed1998

MHC-linked syngeneic developmental preference in thymic lobes colonized with bone marrow cells: a mathematical model.

Reconstitution of the T-cell compartment after bone marrow transplantation depends on successful colonization of the thymus by bone-marrow-derived progenitor cells. Recent studies compared the development of syngeneic and allogeneic bone-marrow-derived cells in co-cultures with lymphoid-depleted fetal thymus explants, leading to the discovery of MHC-linked syngeneic developmental preference (SDP) in the thymus. To determine the nature of cell interactions among the bone marrow and thymic elements that might underlie SDP, we analyzed this phenomenon by mathematical modeling. The results indicate that syngeneic mature T cells, responsible for inducing this preference, probably interfere both with the seeding of allogeneic bone-marrow-derived thymocyte progenitors in the thymic stroma and with their subsequent proliferation. In addition, the possibility of augmented death among the developing allogeneic thymocytes cannot be ruled out.

Bone Marrow Transplantation↗
PubMed1996

Population structure of the yellow-footed rock-wallaby Petrogale xanthopus (Gray, 1854) inferred from mtDNA sequences and microsatellite loci.

The yellow-footed rock-wallaby Petrogale xanthopus is considered to be potentially vulnerable to extinction. This wallaby inhabits naturally disjunct rocky outcrops which could restrict dispersal between populations, but the extent to which that occurs is unknown. Genetic differences between populations were assessed using mitochondrial DNA (control region) sequencing and analysis of variation at four microsatellite loci among three geographically close sites in south-west Queensland (P. x. celeris) and, for mtDNA only, samples from South Australia (P. x. xanthopus) as well. Populations from South Australia and Queensland had phylogenetically distinct mtDNA, supporting the present classification of these two groups as evolutionarily distinct entities. Within Queensland, populations separated by 70 km of unsuitable habitat differed significantly for mtDNA and at microsatellite loci. Populations separated by 10 km of apparently suitable habitat had statistically homogeneous mtDNA, but a significant difference in allele frequency at one microsatellite locus. Tests for Hardy-Weinberg equilibrium and microgeographical variation at microsatellite loci did not detect any substructuring between two wallaby aggregations within a colony encircling a single rock outcrop. Although the present study was limited by small sample sizes at two of the three Queensland locations examined, the genetic results suggest that dispersal between colonies is limited, consistent with an ecological study of dispersal at one of the sites. Considering both the genetic and ecological data, we suggest that management of yellow-footed rock-wallabies should treat each colony as an independent unit and that conservation of the Queensland and South Australian populations as separate entities is warranted.

Alleles↗
PubMed1995

Menopause is associated with a significant increase in blood monocyte number and a relative decrease in the expression of estrogen receptors in human peripheral monocytes.

PROBLEM: The clinical significance of the differential expression of estrogen receptor (ER) in human monocytes was evaluated. METHOD: Two color flow cytometry analysis was used on peripheral blood samples of young and postmenopausal females and postmenopausal females treated with estrogen replacement therapy. In addition, the monocyte and lymphocyte counts and the blood estrogen levels of each patient were determine. RESULTS: During menopause there is a significant decrease in the percentage of ER positive monocytes, and an increase in blood monocyte number, which declines following estrogen replacement therapy to values of the young. CONCLUSIONS: These findings suggest that estrogen modulates the monocyte numbers and its effects may be mediated through the ER in the monocytes.

Adolescent↗
PubMed1995

MHC-linked colonization of the thymus and thymocyte development: effects of mature T lymphocytes.

Effects of mature T lymphocytes on thymic colonization by lymphohemopoietic cells were investigated in an in vitro experimental model, using a variety of experimental strategies. Lymphoid-depleted fetal thymus (FT) explants (C57BL/Ka, Thy1.1, H-2b) were incubated with bone marrow (BM) cells from syngeneic (C57BL/Ka; SBM) and allogeneic (BALB/c, Thy1.2, H-2d; ABM) donors. Cocultures of FT with SBM and ABM, depleted of Thy1+ or of CD3+ cells, resulted in equal proportions of lymphocytes from both BM donors. When peripheral blood lymphocytes (PBL) from synegenic or semi-allogeneic donors (F1[C57BL/Ka x C57BL/6J], Thy1.1/Thy1.2); or F1[C57BL/Ka x BALB/c], Thy1.1/Thy1.2, respectively) were added to these cultures, the total lymphocyte count per thymic lobe decreased and a developmental preference of the SBM-derived cells, as compared to the ABM-derived cells, was noted. Cells of the PBL types were also observed in the cultures. Cocultures of FT with ABM and PBL showed reduced proportions of ABM-derived cells and occurrence of cells of the PBL type. Finally, FT explants partially depleted of lymphocytes by irradiation (6 Gy), were cocultured with PBL from either syngeneic or allogeneic donors. In the presence of syngeneic PBL, the total number of cells and the proportion of double-positive (CD4+CD8+) T cells were similar to those in the FT cultured by itself, whereas in the presence of allogeneic PBL these values were reduced. The study suggests that mature T lymphocytes may play a role in the developmental processes in the thymus, and points to MHC-linked selective effects.

Animals↗
PubMed1994

Colonization of the thymus by T cell progenitors: models for cell-cell interactions.

The early events of T-cell generation, i.e. seeding of bone marrow-derived progenitor cells onto the thymic stroma, involve a small fraction (up to 1%) of thymus cells and are not presently observable. However, these events are crucial in determining the outcome of thymic colonization. In previous studies we utilized an experimental in vitro model of thymic reconstitution by bone marrow cells to compare normal thymocyte development with the development in conditions of T-cell deficiency, and, in particular, in aging. These studies showed that progenitor cells from old donor bone marrow are deficient in their ability to colonize the thymus, in spite of their ability to divide earlier upon seeding. In this study we apply mathematical and computer modelling in order to analyse early T-cell development and the causes for the developmental disadvantage of old donor bone marrow cells. The results indicate that the competition for seeding niches in the thymic stroma determines the outcome of colonization.

Aging↗
PubMed1994

[Pyogenic liver abscess. Experience with 50 cases].

During the last years the diagnosis and treatment of pyogenic liver abscess has changed substantially. The aim of this work is to report a retrospective analysis of 50 patients aged 24 to 87 years old, that presented with a pyogenic liver abscess and were treated in the last 13 years. The sensitivity for diagnosis of ultrasound examination, CAT scan and angiography was 68, 89 and 75% respectively. The origin of the abscess was detected at the biliary tree in 46% and remained unknown in 38%. Thirty one patients were operated, 13 were subjected to percutaneous drainage and 5 were treated only with antimicrobials. Forty percent of patients had a septic complication and 4 (8%) died. Mean hospital stay was 31 days for operated patients and 21 for the rest. The abscess recurred in seven patients and two of these had a gallbladder carcinoma. It is concluded that percutaneous drainage is an alternative to surgical treatment that must be accompanied by a careful diagnostic workup.

Adult↗
PubMed1994

[Choledochocele. Report of a case and review of the literature].

We report a 29 years old man with a choledochocele or type III choledochal cyst, an extremely rare condition. This was found during a cholecystectomy using a transcystic intra operative cholangiogram. A transduodenal sphincteroplasty was performed. The cyst diameter was 1.5 cm approximately and two 1-2 mm stones were extracted from its lumen. The chemical composition of these was different from those located in the gallbladder. The postoperative period was uneventful and the patient remains asymptomatic.

Adult↗
PubMed1993

MHC recognition in colonization of the thymus by bone marrow cells.

The role of major histocompatibility complex (MHC) class I and II molecules in the process of colonization of the thymic microenvironment by lymphohemopoietic cells was analyzed in an in vitro experimental model. When lymphoid-depleted fetal thymus (FT) explants were cocultured with a mixture of bone marrow (BM) cells, from donors syngeneic and allogeneic to the FT, the cells syngeneic to the FT showed a developmental preference. Treatment of these cocultures with antibodies to MHC class I (H-2D, H-2K) or class II (I-E, I-A) molecules of the syngeneic cells led to preferential development of the allogeneic donor type cells. Incubation of either the FT or the BM cell inoculum with the antibodies prior to coculture indicated that the effect was exerted on the BM cells rather than on the thymic stroma.

Animals↗
PubMed1993

[Vascular compression syndrome of the duodenum. Report of 2 cases].

Two young female patients with the syndrome of vascular compression of the duodenum are reported. Both patients presented with a history of vomiting and weight loss. Barium examination of the gastrointestinal tract showed in both cases, marked stomach distention and obstruction of the third portion of the duodenum. In one patient, abdominal CT scan discarded other causes of extrinsic compression. Both patients were operated. The simpler and safer surgical procedure is the section of the Treitz ligament and duodenal liberation, which can be used in the majority of patients.

Adolescent↗
PubMed1992

Aging in the T lymphocyte compartment. A developmental view.

A decline in the capacity of bone marrow cells to differentiate to T lymphocytes was found when cells from young and old donors were seeded onto an alymphoid fetal thymus. A step-by-step analysis of cell-cell interactions of the lymphohemopoietic cells and the thymic stroma indicated an effect of age on a variety of cell differentiation parameters. These included a decrease in the affinity of bone marrow cells to the stroma, and in their capacity to compete with the thymic lymphoid resident cells on colonization of the thymus. There was a significant decrease in the ability of cells of old donors to replicate sequentially within the thymic microenvironment. There was a reduced capacity of bone marrow cells from aging mice to express a developmental preference after seeding onto a syngeneic fetal thymus in a mixture with cells from allogeneic donors. We addressed the question whether the aging thymus contains increased levels of immature cells that fail to differentiate in the involuted thymic microenvironment by seeding thymocytes from young and old donors onto the fetal thymic stroma. The values of T cells that developed from the old donor inoculum were lower under these conditions. Our studies suggest that at least some of the manifestations of aging in the T cell compartment are related to developmentally programmed events in the lymphohemopoietic cell compartment.

Aging↗
PubMed1991

Interactions of bone marrow cells from young and old mice with syngeneic and allogeneic thymic tissue.

Age-related changes manifested in MHC-linked recognition of bone marrow (BM) cells by the thymic stroma were studied in vitro model of thymus-BM chimeras. Fetal thymuses (FT) depleted of self-lymphocytes were colonized with BM cells from syngeneic and allogeneic donor mice. When cells from young (3-month-old) or old (24-month-old) donors syngeneic to the stroma were seeded in a mixture with cells of allogeneic young origins (C57BL/6J-Thy1.2 and ARK/J-Thy1.1 seeded onto C57BL/6J FT), the syngeneic cells showed an age-related developmental advantage. Accordingly, cells from the old syngeneic mice manifested a significantly reduced capacity to compete with allogeneic cells when compared with the young syngeneic cells. When allogeneic BM cells from young or old mice were seeded onto the thymic stroma in a mixture with BM cells from young donors syngeneic to that stroma (BALB/c-Thy1.2 mixed with C57BL/Ka-Thy1.1 seeded onto C57BL/6J or C57BL/Ka FT), the Thy1+ cells which developed were mainly of syngeneic origin. The age of the allogeneic cells had no significant effect on the results. However, when old allogeneic cells were mixed with old syngeneic cells, the developmental advantage of the syngeneic cells was not manifested. When seeding of allogeneic cells was followed 1 day later by seeding of syngeneic cells, the syngeneic advantage was eliminated, suggesting that the MHC-linked competition began during the first 24 hr of contact with the thymic tissue. When BM-derived thmocytes grown in FT explants were transferred onto second FT recipient explants of the same genotype as the first ones, the syngeneic advantage was abolished, suggesting either that the thymic microenvironment was modified as a result of colonization or that it induced a change in the BM cells. In this respect, the young allogeneic BM-derived thymocytes showed a significant advantage when compared with the old cells. Thus, the MHC-linked syngeneic preference in the early development of BM cells is also manifested in aging mice, yet at a level that is significantly reduced compared with that seen in the young mice.

Age Factors↗
PubMed1991

Thymocyte development in an in vitro constructed chimera of irradiated fetal thymus and lymphohemopoietic cells.

An in vitro model of irradiated thymus-BM chimera was constructed to analyze the developmental interactions of donor and recipient type thymocytes. The experimental system was based on exposing 14-day fetal mouse thymuses to graded doses of irradiation and then reconstituting them with cells from various lymphohemopoietic origins. Values of donor vs. recipient type cells in chimeric thymuses varied with radiation dose, cell inoculum size and time between irradiation and cell seeding. During an 11 day organ culture period, thymocyte progenitors differentiated in this thymic microenvironment and expressed T-cell surface markers. The pattern of expression of T-cell surface markers in these cultures was similar to that in intact fetal thymic explants.

Animals↗
PubMed1990

Biliary-tract cancer in Chile.

This epidemiological study in Chile shows a marked increase in biliary-tract cancer based on mortality data, from an age-adjusted rate (1970 world population) of 5.1 per 100,000 in 1970 to 12.0 per 100,000 in 1988. There is an increased risk of this cancer in all age groups but especially in young adults (15-44 years). The female ratio of 3:1 persists. The increase in biliary-tract cancer in 1970-1985 was particularly important for young women but occurred in all female age groups whereas in men it was mostly in the elderly (65 years and more) and less in the middle-aged (45-64 years); no changes were observed in young men. Regional differences have begun to be appreciated. One of the factors which may account for this impressive and unexpected increase is the remarkable decrease in cholecystectomy rates. Less than 20% of the 154% increase in biliary-tract cancer mortality in the period 1970-1985 could be attributed to population aging. Improvements in diagnostic methods did not appear to be an important contributing factor. Other factors that could affect this increase in the incidence to epidemic levels include: an increase in the prevalence of cholelithiasis, an increase in the number of typhoid carriers and possible environmental carcinogens.

Adolescent↗
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↗