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Biomedical subjects

A Singer

Publications and source records attributed to A Singer.

At least 253 records · Page 14Linked to original sources
PubMed1986

Ia+ murine epidermal Langerhans cells are deficient in surface expression of the class I major histocompatibility complex.

Murine epidermal Langerhans cells were analyzed with fluorescence microscopy and multicolor flow cytometry for the surface expression of major histocompatibility complex (MHC) class I and class II antigens. Langerhans cells of H-2k haplotype were identified in situ or in epidermal-cell suspensions by their surface expression of the MHC class II determinants I-Ak and I-Ek. More than 90% of class II-positive Langerhans cells in epidermal-cell suspensions expressed no or barely detectable amounts of MHC class I antigens. Quantitation by flow cytometry revealed that H-2k Langerhans cells expressed only 1.6-3.3% as much H-2Kk as did class II-negative keratinocytes in the same epidermal-cell suspensions. By fluorescence microscopy, class I MHC antigens were not detectable on Langerhans cells in situ when analyzed on sheets of intact epidermis. The deficient expression of class I MHC permitted highly purified Langerhans cell populations to be isolated from epidermal cell suspensions by treatment with anti-class I MHC monoclonal antibody and complement. It is likely that the uniquely low cell-surface expression of class I MHC antigen by Langerhans cells has relevance to both immune responses in the skin as well as to mechanisms of skin allograft rejection. In addition, it is conceivable that regulation of class I MHC expression on antigen-presenting cells in general is an important but hitherto unrecognized mechanism of immune regulation.

Animals↗
PubMed1986

Histological and immunocytochemical study of cervical intraepithelial neoplasia (CIN) with associated HPV 6 and HPV 16 infections.

Histological and immunocytochemical features of cervical intraepithelial neoplasia (CIN) associated with HPV 6 and HPV 16, either singly or in combination, were studied in 48 cases. Features of HPV infection (koilocytosis, binucleation, multinucleation, giant irregular nuclei and individual cell dyskeratosis) were present in high prevalence in both HPV 6 and HPV 16 associated CIN. Abnormal mitoses seemed to be a good indicator of CIN and were present in about 50% of cases of CIN associated with either HPV 6 or HPV 16 infection. This finding provides no support for the view held by some investigators that associated HPV 16 infection can be predicted by the presence of abnormal mitoses. Expression of HPV antigen was shown in about 40% of cases with a slight, but not significantly, higher prevalence in cases of combined HPV 6 and HPV 16 infection. Conventional histology and immunocytochemistry could not distinguish CIN associated with HPV 6 from CIN associated with HPV 16 infection.

Antigens, Viral↗
PubMed1986

Management of invasive cancer of the cervix.

Cancer of the cervix has an increasing prevalence and mortality in younger women. The disease is changing in its natural history and our concepts of management will have to undergo a similar change. This discussion is directed towards a more rational approach to the management of the early cancer.

Adenocarcinoma↗
PubMed1985

Characterization of antigen-specific, Ia-restricted, L3T4+ cytolytic T lymphocytes and assessment of thymic influence on their self specificity.

The goals of the present study were: (a) to generate antigen-specific L3T4+ cytolytic T lymphocytes (CTL), (b) to determine their major histocompatibility complex (MHC) restriction specificity, and (c) to assess the influence of thymic MHC determinants on their self specificity. We found that L3T4+ CTL specific for either trinitrophenyl (TNP)-modified self determinants or minor histocompatibility antigens could be generated from Lyt-2- responder T cells provided that the response cultures were supplemented with supernatants rich in helper factors. Such antigen-specific L3T4+ CTL were Ia-restricted by the criteria that they lysed only Ia+ target cells and that their lysis of Ia+ target cells was specifically inhibited by anti-Ia monoclonal antibodies. The relative frequency of L3T4+ pCTL was found to be only 5-10% of the total anti-TNP pCTL present in the spleens of normal mice. Finally, we utilized radiation bone marrow chimeras to assess the influence of the thymic haplotype on the self-Ia specificity of L3T4+ CTL. Both bulk culture and limiting dilution experiments revealed that the self-Ia specificity of L3T4+ anti-TNP CTL from F1----parent and A----B allogeneic chimeras was not markedly skewed toward the haplotype of the chimeric thymus. These results contrast with those obtained previously for L3T4+ anti-TNP Th cells and demonstrate that in the radiation bone marrow chimera model of T cell differentiation, the self specificity of Th cells but not pCTL is markedly influenced by the haplotype of the chimeric thymus.

Animals↗
PubMed1985

Both L3T4+ and Lyt-2+ helper T cells initiate cytotoxic T lymphocyte responses against allogenic major histocompatibility antigens but not against trinitrophenyl-modified self.

This study characterizes the T helper (Th) cells that initiate primary cytotoxic T lymphocyte (CTL) responses against allogeneic and trinitrophenyl (TNP)-modified self class I major histocompatibility (MHC) determinants. We show that two distinct Th cell subsets participate in allospecific CTL responses: (a) an L3T4+,Lyt-2- class II-restricted Th cell population, and (b) an L3T4-,Lyt-2+ class I-restricted Th cell population. Both of these T cell subpopulations were shown to function in allospecific CTL responses as helper cells by their ability to show synergy with allospecific CTL precursors. Thus, primary class I allospecific CTL responses represent an immune response involving not only L3T4+ Th cells, but Lyt-2+ Th cells as well. One of the necessary functions performed by both L3T4+ and Lyt-2+ Th cell populations in allospecific CTL responses was found to be the secretion of interleukin 2. Finally, despite the many similarities between anti-allo- and anti-TNP-CTL responses, anti-TNP-CTL responses were found to be mediated by only L3T4+ Th cells, not by Lyt-2+ Th cells. Consequently, Lyt-2+ Th cells appear to be a helper cell population that is primarily involved in MHC-specific immune responses.

Animals↗
PubMed1985

Increased risk of cervical neoplasia in consorts of men with penile condylomata acuminata.

19 (76%) of 25 women who had been the sole sexual consorts, for at least 1 year, of men with pre-existing penile condylomata acuminata had similar lesions of the lower genital tract. 9 (36%) of the women had an abnormal cervix as judged by cytology, colposcopy, and histology, and 7 (77%) of these 9 had associated human papillomavirus (HPV) infection detected by DNA/DNA hybridisation. None of 20 women in an age-matched control group had cytological or colposcopic evidence of cervical epithelial atypia. It is suggested that penile HPV infection in a male partner places a woman at risk of cervical neoplasia.

Adult↗
PubMed1985

Correlation of intrathymic tolerance with intrathymic chimerism in neonatally tolerized mice.

T cell tolerance to alloantigens can be induced in neonatal mice by the injection of semiallogeneic adult spleen cells. The thymus of neonatally injected mice rapidly becomes specifically unresponsive to the alloantigens expressed by the injected cells, even though the level of chimerism in the thymus of such mice is reportedly marginal compared with that of the periphery. In this report, we have studied the immune reactivity and degree of chimerism in the thymuses of 24 neonatally injected mice. In 13 older mice, the proliferative response of the thymocytes from individual mice to the injected alloantigen varied from strong reactivity to complete tolerance. Interestingly, analysis by flow microfluorometry of the same thymocytes for the presence of the inoculated alloantigen revealed an inverse correlation. That is, the thymuses which had a greater degree of chimerism were tolerant and those with fewer or no detectable cells were partially or totally reactive. The thymuses of 11 younger neonatally injected mice were invariably tolerant to both the MHC and Mls alloantigens of the F1 inocula. Analysis by flow microfluorometry of the thymocytes of these mice revealed that significant numbers of F1 cells reside in the thymuses of mice injected as neonates with semiallogeneic cells. These cells represent a possible source of specific tolerogen for thymocytes during their intrathymic differentiation.

Aging↗
PubMed1985

Human papillomavirus types 6 and 16 in multifocal intraepithelial neoplasias of the female lower genital tract.

Five women with multifocal intraepithelial neoplasia of the lower genital tract were investigated for the presence of human papillomavirus (HPV) infection by the method of DNA-DNA hybridization which detects the viral DNA. The DNA sequences of HPV types 6 and 16 were detected in each of the five patients and in each of the areas biopsied: cervix, vagina and vulva. DNA sequences of both viral types were also found in vulval intraepithelial neoplasia grades I-III and in cervical intraepithelial neoplasia grades I and III. The detection of HPV DNAs in multifocal lesions suggests a possible common aetiology for the lower genital tract intraepithelial neoplasias.

Adult↗
PubMed1985

Prevalence of human papillomavirus type 16 DNA sequences in cervical intraepithelial neoplasia and invasive carcinoma of the cervix.

The frequency of human papillomavirus (HPV) type 16 in premalignant and malignant lesions of the cervix was investigated and compared with the detection of HPV type 6. In cervical intraepithelial neoplasia (CIN) grades I-III HPV 6 was detected in 28% and HPV 16 in 62% of patients whereas 90% of malignant lesions contained HPV 16 only. In the CIN lesions there was an increase in HPV 16 detection as the severity of disease increased while the level of detection of HPV 6 decreased. Only three (18%) of the cervices that were colposcopically and histologically normal contained HPV genomes; although two of these three women had either a history of genital warts or a sexual partner with penile warts.

Adolescent↗
PubMed1985

Comparison of prevalence of human papillomavirus antigen in biopsies from women with cervical intraepithelial neoplasia.

Human papillomavirus antigen was found in 39 (16%) of 253 colposcopic biopsies from a group of women at high risk for cervical cancer who had been examined in the early 1970s. Immunohistochemical evidence of papillomavirus infection was found in 20 (30%) of 67 cervical intraepithelial neoplasia lesions infected with wart virus from these patients. When these results were compared with results of a similar study carried out in the early 1980s there was no significant difference in the prevalence of human papillomavirus antigen in cervical intraepithelial neoplasia lesions infected with wart virus from women who had been examined over a decade apart.

Adolescent↗
PubMed1985

Plasma fibronectin in systemic lupus erythematosus: relationship to clinical activity, DNA binding and acute phase proteins.

Plasma fibronectin was measured by ELISA in 25 samples from 22 patients with systemic lupus erythematosus (SLE). The mean fibronectin level for the entire patient group (654 micrograms/ml) was greater than that of normal controls (450 micrograms/ml), with highest levels observed in the subgroup of patients with severe disease activity (838 micrograms/ml) followed by those with moderate disease activity (732 micrograms/ml) (p = .04). Fourteen patients with other rheumatic disease had a mean fibronectin level of 407 micrograms/ml. Decreases in fibronectin levels corresponded to clinical improvement and reductions in DNA binding. Although elevated fibronectin levels did not correspond to any specific pattern of organ system involvement, fibronectin levels seem to parallel disease activity in certain patients. Future longitudinal studies of plasma fibronectin in SLE may further define its role as an indicator of disease activity.

Acute-Phase Proteins↗
PubMed1985

Generation of primary murine CTL specific for allogeneic and xenogeneic MHC determinants upon stimulation with murine L cells transfected with class I genes.

This communication describes in vitro culture conditions that permit the use of MHC gene-transfected L cells as stimulators of primary CTL responses. The use of L cells as stimulators usually results in the generation of "nonspecific" anti-L cell cytotoxicity too great to permit visualization of antigen-specific CTL responses. This study demonstrates that the generation of such anti-L cell cytotoxicity can be abrogated by strategies that prevent the in vitro activation of self-Ia-restricted TH cells. These maneuvers allowed the use of L cell transfectants as stimulators of allospecific and xenospecific CTL precursors in primary in vitro mixed lymphocyte reaction cultures.

Animals↗
PubMed1985

Human papillomavirus.

Whilst papillomaviruses mainly induce epithelial proliferations in man and in different animal species, the association of this group of viruses with malignant tumours has become increasingly evident. Despite the heterogeneity of human papillomavirus (HPV), only a small number are identified within carcinomas, implying a different, oncogenic potential for different HPV types.

Adult↗
PubMed1985

Lyb-5+ B cells can be activated by major histocompatibility complex-restricted as well as unrestricted activation pathways.

It has previously been demonstrated that B cells can be activated through two distinct T helper (Th) cell-dependent pathways, one requiring both carrier-hapten linkage and MHC-restricted T-B interaction and the other requiring neither. In addition, it has been shown that different B cell subpopulations exist and that these subpopulations differ in their activation requirements. Previous studies demonstrated that resting B cells containing an Lyb-5+ subpopulation were activated by MHC-unrestricted T cell signals, whereas resting Lyb-5- B cells were activated only through MHC-restricted T-B interaction. It was suggested that this difference resulted from the ability of Lyb-5+ but not Lyb-5-B cells to respond to soluble MHC-unrestricted Th signals. Because Lyb-5+ B cells were responsive in these previous experiments to MHC-unrestricted Th signals, it could not be determined whether Lyb-5+ B cells were also responsive to MHC-restricted Th signals. Consequently, the present study was undertaken to directly address the question of whether Lyb-5+ B cells can be activated under appropriate conditions by MHC-restricted as well as unrestricted T cell-B cell interactions. It was found that unprimed normal B cells (containing Lyb-5+ and Lyb-5-B cells) but not unprimed xid-defective populations (Lyb-5- only) can be activated by cloned KLH-specific and MHC-restricted Th cells in response to either high or low concentrations of TNP-KLH. The IgM response of Lyb-5+-containing B cells to a high concentration of antigen (10 micrograms/ml) was MHC unrestricted, whereas the IgM response of unprimed Lyb-5+ B cells to a low concentration of antigen (0.001 micrograms/ml) was MHC restricted. Thus, unprimed Lyb-5+ B cells can be activated through both MHC-restricted and unrestricted pathways. It was further demonstrated that the activation requirements of Lyb-5+ and Lyb-5- B cells differed even for MHC-restricted B cell activation.

Animals↗