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Biomedical subjects

A Singer

Publications and source records attributed to A Singer.

At least 37 records · Page 2Linked to original sources
PubMed1991

Disorganization and restoration of thymic medullary epithelial cells in T cell receptor-negative scid mice: evidence that receptor-bearing lymphocytes influence maturation of the thymic microenvironment.

In order to assess the possible role of lymphoid cells in the development of thymic epithelium, we compared the organization and maturation of thymic epithelium in scid mice lacking T cell receptor (TcR)-positive cells with that in scid mice containing TcR+ cells. Immunohistologic examination revealed that thymi from TcR- scid mice were deficient in thymic medullary epithelial cells recognized by the monoclonal antibody ER-TR5, and that the few thymic medullary epithelial cells present were not organized into discrete medullary areas. In contrast, thymi from scid mice containing TcR+ cells possessed ER-TR5+ thymic medullary epithelial cells and these cells were organized normally into discrete medullary regions. Thus, normal organization and maturation of thymic medullary epithelial cells did not occur in the absence of TcR+ cells, but did occur upon introduction of TcR+ cells. We conclude that lympho-stromal cell interactions in the thymus are not unidirectional, and that a symbiotic relationship exists between maturing epithelial cells and developing lymphocytes.

Animals↗
PubMed1991

Therapeutic dilemmas in management of cystine calculi.

The appropriate management of patients with cystine calculi necessitates a fundamental understanding of the pathophysiology of cystinuria and a working knowledge of the available therapeutic modalities. The following case reports and review of the literature serve to illustrate that successful treatment involves a multidimensional approach to eradication of calculi with long-term follow-up aimed at prevention.

Adult↗
PubMed1991

The use of cervicography in a primary screening service.

The cervicography and concurrent endocervical brush smear results obtained in 1162 women screened at the Marie Stopes Clinic were analysed. Colposcopy and biopsy results were obtained for positive cases. A comparison was made with a group of 1007 women attending the same clinic for routine cytology only. Nearly 10% of women who were screened by cervicography had a technically defective cervicogram, the main single reason being that the view was obscured by blood. Routine cytology was positive in 1%, while cervicography was positive in 13%, where positivity was defined as a result leading to a recommendation for colposcopy. The false positive rate for cervicography was 26%. Even after adjustment, this difference was highly significant (P less than 0.0001).

Acetates↗
PubMed1991

Hepatic schistosomiasis: report of two cases and literature review.

Two Filipino patients were referred for evaluation of abnormal liver enzymes. Both patients were known to come from regions endemic for Schistosoma japonicum. The clinical laboratory and radiological features of these patients are presented. We highlight the findings of radiologic evaluation, including magnetic resonance imaging (MRI). The epidemiology, clinical manifestations, diagnostic strategies including a comparison of the utility of ultrasound, computed tomography, and MRI are reviewed. The pathophysiology responsible for hepatic manifestations of schistosomiasis is reviewed. An increased influx to the United States of persons from regions endemic for schistosomiasis, such as South America, Southeast Asia, and the Philippines, will result in an increase in the prevalence of the disease in this country. The diagnosis of hepatic schistosomiasis will need to be considered in populations at risk for contracting this common worldwide problem.

Adult↗
PubMed1990

Inhibition of T cell receptor expression and function in immature CD4+CD8+ cells by CD4.

Most immature CD4+CD8+ thymocytes express only a small number of T cell receptor (TCR) molecules on their surface, and the TCR molecules they do express are only marginally capable of transducing intracellular signals. TCR expression and function was not intrinsically low in immature CD4+CD8+ thymocytes, but was found to be actively inhibited by CD4-mediated signals. Indeed, release of CD4+CD8+ thymocytes from CD4-mediated signals resulted in significant increases in both TCR expression and signaling function. These results suggest that, in CD4+CD8+ cells developing in the thymus, increased TCR expression and function requires release from CD4-mediated inhibition.

Animals↗
PubMed1990

Specific prolongation of MHC class II disparate skin allografts by in vivo administration of anti-IFN-gamma monoclonal antibody.

In vivo rejection of MHC class II disparate skin allografts has been thought to involve IFN-gamma-induced expression of MHC class II alloantigens because less than 3% of skin epidermal cells express MHC class II alloantigens constitutively. In our study we directly tested this hypothesis by examining the effect of in vivo administered anti-IFN-gamma mAb on rejection of MHC class II disparate skin allografts, and comparing its effect on rejection of MHC class I disparate skin allografts placed on the same individual mice. We found that anti-IFN-gamma mAb blocked the rejection of MHC class II disparate skin allografts, but had no effect on the rejection of MHC class I disparate skin allografts. These results demonstrate that endogenously produced IFN-gamma is critical for rejection of MHC class II disparate skin allografts, but not for rejection of MHC class I disparate skin allografts. Thus, this study strongly supports the concept that MHC class II rejection responses require IFN-gamma induced MHC class II expression on keratinocytes of the allograft.

Animals↗
PubMed1990

Novel post-translational regulation of TCR expression in CD4+CD8+ thymocytes influenced by CD4.

Expression of the multicomponent T-cell antigen receptor (TCR) complex on the surface of thymocytes is developmentally controlled. Most immature CD4-CD8- 'double negative' and CD4+CD8+ 'double positive' thymocytes express either no or few TCR on their surface, and maturation to CD4+CD8- or CD4-CD8+ 'single positive' thymocytes is accompanied by a dramatic increase in the number of surface TCR complexes. Although the initial appearance of TCR during differentiation results from rearrangement and initiation of transcription of TCR genes in the thymus, the mechanisms regulating the quantitative changes in TCR expression during intrathymic differentiation are unknown. Surface TCR levels in T-hybridoma cells can be quantitatively regulated by a series of post-translational processes, including sorting to alternative intracellular compartments and degradation, which ensure that only fully and correctly assembled receptor complexes are efficiently transported to the cell surface. Quantitative increases in TCR expression on the surface of CD4+CD8+ thymocytes occur in vivo in response to anti-CD4 antibody treatment. Here we present evidence that immature CD4+CD8+ thymocytes normally retain and degrade in the endoplasmic reticulum greater than 90% of some endogenously synthesized TCR chains, and that the increased surface TCR expression on immature CD4+CD8+ thymocytes induced by anti-CD4 is due to an increase in the escape of newly synthesized receptor chains from the endoplasmic reticulum, and is not due to increases in RNA levels, translation, or assembly. Post-translational mechanisms therefore control the levels of TCR complexes on CD4+CD8+ thymocytes, and these mechanisms can be modulated by signalling through CD4 surface molecules.

Animals↗
PubMed1990

Clonal deletion and clonal anergy in the thymus induced by cellular elements with different radiation sensitivities.

The present study demonstrates that immune tolerance can be achieved in the thymus both by clonal deletion and by clonal inactivation, but that the two tolerant states are induced by cellular elements with different radiation sensitivities. TCR engagement of self antigens on bone marrow-derived, radiation-sensitive (presumably dendritic) cells induces clonal deletion of developing thymocytes, whereas TCR engagement of self antigens on radiation-resistant cellular elements, such as thymic epithelium, induces clonal anergy. The nondeleted, anergic thymocytes can express IL-2-Rs but are unable to proliferate in response to either specific antigen or anti-TCR antibodies, and do develop into phenotypically mature cells that emigrate out of the thymus and into the periphery.

Animals↗
PubMed1990

[Treatment of acute myeloid leukemia in a special hematology unit].

Since 1984, 47 patients with untreated acute myeloid leukemia (AML) were hospitalized in a special hematology unit for aggressive chemotherapy. Complete remission was obtained in 68%, 15% died of complications of treatment (infections and bleeding) and 15% had refractory leukemia. The actuarial survival after 3 years for patients in remission was 43%. No patients with refractory leukemia lived more than 1 year. The actuarial remission at 3 years of 21 patients who received additional courses of aggressive chemotherapy (consolidation treatment) was 42%, as opposed to 11% in 11 patients who received maintenance treatment. The 47 patients received 108 courses of aggressive chemotherapy including 47 for induction of remission. During 86 courses (80%) the patients developed fever and in 33 blood cultures were positive; during 16 courses a fungal infection developed. The most common bacterial infection was by E. coli. During the first induction treatment 5 patients died of sepsis and 1 of cerebral hemorrhage. None died during consolidation therapy. During the year preceding the opening of the unit, 12 AML patients were treated on regular medical wards, and five (42%) achieved a complete remission, while 6 died of complications during the first course of induction chemotherapy. Our findings are in line with those of similar units, which indicates the importance of special nursing units for the treatment of acute leukemia.

Adolescent↗
PubMed1990

T cell receptor-negative thymocytes from SCID mice can be induced to enter the CD4/CD8 differentiation pathway.

In order to investigate the role of T cell receptor (TcR) expression in thymocyte maturation, we have analyzed thymocytes from C.B-17/SCID mice, which are unable to productively rearrange their antigen receptor genes and fail to express TcR. Despite this defect, SCID thymocytes are functional as they produce lymphokines and proliferate in response to a variety of stimuli. Phenotypic analysis revealed that thymocyte populations from young adult SCID mice resemble thymocyte populations from normal embryonic mice in that they are large, Thy-1.2+, CD4-, CD8-, TcR- and enriched in CD5lo, IL2R+ and Pgp1+ cells. However, other TcR- populations normally present in adult mice (i.e., CD4-CD8+ cells and CD4+CD8+ cells) are absent from the thymus of TcR- adult SCID mice. To understand the basis of the developmental arrest of TcR- SCID thymocytes at the CD4-CD8- stage of differentiation, we analyzed thymi from the occasional "leaky" SCID mouse which possesses small numbers of TcR+ thymocytes. We found that the presence of TcR+ cells within a SCID thymus was invariably associated with the presence of CD4+ and/or CD8+ SCID thymocytes. Interestingly, however, the CD4+/CD8+ SCID thymocytes were not themselves necessarily TcR+. That is, emergence of SCID thymocytes expressing CD4/CD8 was tightly linked to the presence of TcR+ cells within that SCID thymus, but the SCID thymocytes that expressed CD4/CD8 were not necessarily the same cells that expressed TcR. Finally, we found that the introduction into TcR- SCID mice of normal bone marrow cells that give rise to TcR+ cells within the SCID thymus promoted the differentiation of SCID thymocytes into CD4-CD8+ and CD4+CD8+ TcR- cells. These data indicate that TcR+ cells within the thymic milieu provide critical signals which promote entry of CD4-CD8-TcR- precursor T cells into the CD4/CD8 differentiation pathway. When applied to differentiation of normal thymocytes, these findings may imply a critical role for early appearing CD4-CD8- TcR (gamma/delta)+ cells in initiating normal thymic ontogeny.

Animals↗
PubMed1990

Case-control study of risk factors for cervical intraepithelial neoplasia in young women.

A case-control study of 497 women under age 40 diagnosed with cervical intraepithelial neoplasia (CIN) and 833 controls was done in the London area between 1984 and 1988 to examine whether known risk factors for invasive cervical cancer produced similar risks for CIN of different grades in young women. Cases of CIN III had a risk profile similar to that seen for invasive disease whereas CIN I cases were similar to the controls in all risk factors examined except a history of genital warts. Cases of CIN II were intermediate between the two. Among several indicators of sexual and reproductive behaviour, age at first childbirth and a history of multiple sexual partners were the strongest risk factors for CIN II and CIN III. Smoking had a strong and independent effect on the risk of CIN II and CIN III, but had only a limited effect for CIN I. Use of oral contraceptives was widespread in cases and controls, but length of use of oral contraceptives was not found to be a risk factor. A small protective effect of barrier contraception was observed.

Adolescent↗
PubMed1990

In vivo induction of antigen-specific transplantation tolerance to Qa1a by exposure to alloantigen in the absence of T-cell help.

A goal of transplantation immunology is to be able to induce antigen-specific tolerance in transplant recipients. In the present study we describe an in vivo model of antigen-specific transplantation tolerance to skin allografts using mice congenic at Qa1, a ubiquitously expressed class I-like molecule encoded to the right of H-2D. B6 mice are deficient in Qa1a-specific T-helper cells and only reject Qa1a disparate tail skin grafts when a second graft expressing additional helper determinants is also present. We report that animals initially engrafted with Qa1a disparate skin, in the absence of any source of additional help, are rendered tolerant to Qa1a disparate skin allografts despite the subsequent presence of inducer skin grafts expressing additional helper allodeterminants. The nonresponsive state is Qa1a-specific, because HY-bearing inducer grafts are rejected normally. In vitro, Qa1a-tolerant animals are specifically unable to generate anti-Qa1a T-killer cells, which provides the cellular basis for their failure in vivo to reject Qa1a skin allografts. Thus, initial exposure to Qa1a allodeterminants, in the absence of T-cell help, leads to a state of Qa1a-specific transplantation tolerance. This study suggests that antigen-specific transplantation tolerance may be induced by exposing naive T-killer cells to tissue alloantigens under conditions in which T-cell help is not generated.

Animals↗
PubMed1990

The problem of defining retirement among minorities: The Mexican Americans.

Using the 1979 Chicano Survey and four different operational definitions of retirement, we explored the effects of age, gender, health, birthplace, and lifetime work experience on the retirement of Mexican Americans. We found that correlates of retirement vary by the definition used. Frequent health limitations was associated with retirement defined by self-reported retirement or self-reported current work status, but not defined by respondents' self-described activities or receipt of retirement income. Operational definitions often used in discussions of timing and determinants of retirement, thus, poorly fit the lifetime work patterns and retirement process of Mexican Americans.

Aged↗
PubMed1990

Inverse correlation between steady-state RNA and cell surface T cell receptor levels.

The relationship between steady-state RNA and cell surface levels of T cell receptor (TCR) was examined in mature T cells and immature CD4+CD8+ double positive thymocytes. TCR is expressed at high levels on the surface of mature T cells and at much lower levels on double positive thymocytes. We demonstrate that in direct contrast to surface expression, TCR-alpha, -beta, CD3-delta, -epsilon, -gamma, and sigma RNA levels are much higher in the immature double positive thymocyte population than in mature T cells. These results demonstrate that quantitative differences in TCR surface expression in immature and mature T cells are not due to increases in TCR RNA levels.

Animals↗
PubMed1990

T cell subsets mediating rejection of established fetal pancreas grafts and failure to observe graft adaptation.

The present study has attempted to elucidate the cellular mechanisms by which long-term established fetal pancreas allografts are rejected. We used an experimental model in which H-2b nude mice were made hyperglycemic by streptozotocin treatment and then engrafted with allogeneic fetal pancreas grafts. These grafts were functional in that engrafted animals returned to near normoglycemia while all animals left unengrafted subsequently died. The fetal pancreas grafts were allowed to reside in the immunoincompetent nude host for 6-9 months prior to T cell reconstitution, at which time animals were reconstituted with either negatively selected CD4+ or CD8+ H-2b T cell subpopulations. We found that a 6-9 month residence in an immunoincompetent host did not lead to a change in the immunogenicity of fetal pancreatic grafts in that both CD4+ and CD8+ T cell subsets were capable of rejecting these long-term established fetal pancreas grafts. The finding that isolated CD8+ spleen T cell subpopulations, which are only activated by antigen-presenting cells of donor origin bearing MHC class I alloantigen, were capable of effecting graft rejection suggested that APC of donor origin persisted in these long-term fetal pancreas allografts.

Adaptation, Physiological↗