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Biomedical subjects

A Singer

Publications and source records attributed to A Singer.

At least 109 records · Page 6Linked to original sources

Subpopulations of Langerhans' cells in cervical neoplasia.

Multiple markers were used to count Langerhans' cells in the cervix. In the normal cervix, thymocyte antigen (T6) and adenosine triphosphatase (ATPase) demonstrated the largest population of Langerhans' cells. MHC Class II positive cells were equivalent to 60%, and S100 positive cells were equivalent to 35% of T6 or ATPase positive cells. Whereas Langerhans' cells demonstrated by T6, ATPase, and MHC Class II antigen were evenly distributed throughout the epithelium, the S100 positive cells were seen predominantly near lymphocytic aggregates and capillaries. In human papillomavirus infection and cervical intraepithelial neoplasia the numbers of T6, ATPase, or MHC Class II positive Langerhans' cells were reduced by 60% but the S100 positive cells were almost completely depleted. These findings suggested that there were different subpopulations of Langerhans' cells in the cervical epithelium. The depletion of Langerhans' cells, particularly the selective depletion of the S100 positive subpopulation, might cause a localized immunodeficiency that impairs immune surveillance and the cell-mediated immune response to human papillomavirus infection and cervical intraepithelial neoplasia.

Adult

Lymphocyte phenotypes in cervical intraepithelial neoplasia and human papillomavirus infection.

Lymphocyte phenotypes in cervical mucosa were studied using a panel of monoclonal antibodies. T lymphocytes were predominant both within the epithelium and in the subepithelial stroma. In the normal cervix, both the T4+ (helper/inducer) and T8+ (suppressor/cytotoxic) subsets were present in a ratio similar to that in the peripheral circulation. In human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN) there was depletion of intraepithelial lymphocytes, especially of T4+ subset, with reversal of the ratio of T4+ to T8+ subsets to less than one. In contrast, there was no significant reduction in the number of lymphocytes in the subepithelial stroma. Tac+ (antigen primed and clonal expanding) lymphocytes were absent both within the epithelium and in the subepithelial stroma. These findings support our suggestion that there is a localized immunodeficiency in HPV infection and CIN. The aetiological and therapeutic implications are discussed.

Adolescent

Tissue macrophage response in human papillomavirus infection and cervical intraepithelial neoplasia.

Tissue macrophages in the uterine cervix were studied immunocytochemically with monoclonal antibody (MoAb) 3.9 which reacts with the majority of macrophages, and E11 which is specific for the C3b receptor, CR1. Samples from five normal women, six with human papillomavirus (HPV) infection and 10 with cervical intraepithelial neoplasia (CIN) were tested. A small population of MoAb 3.9 positive and only occasional MoAb E11 positive macrophages were found in the normal cervix. In HPV infection and CIN there was a significant infiltration of MoAb 3.9 positive and MoAb E11 positive macrophages in both the epithelium and the stroma. The pattern of infiltration in these groups of women suggests that these macrophages were most likely to be functioning as the first line of defence against the spread of the virus infection, either through a direct anti-virus mechanism or non-specific phagocytosis.

Adult

Cisplatin, vincristine, methotrexate and bleomycin (POMB) as initial or palliative chemotherapy for carcinoma of the cervix.

Chemotherapy was given as initial therapy to 12 women with very advanced squamous cell carcinoma of the cervix and to 19 women with recurrent disease. They received a median of four courses of POMB which comprised vincristine 1.0 mg/m2 and methotrexate 300 mg/m2 followed by folinic acid rescue, bleomycin 30 mg as a 48-h infusion or intramuscular injection and cisplatin 100 mg/m2 as a 12-h infusion. Two of the 14 assessable patients with recurrent disease (14%) had a complete response with no disease found histologically in one, and seven (50%) had a partial response. Although the actuarial median survival of all 19 patients with recurrent disease was 8 months, five patients have remained free from tumour progression for a median of 17 months from start of chemotherapy. Six of the 10 assessable patients receiving initial chemotherapy (60%) had a complete response (confirmed histologically in two) and two (20%) had a partial response. Nine patients had additional treatment with radiotherapy and or surgery. Although only four of the patients remain disease-free at 61, 51, 7 and 4 months, all but two were initially FIGO stage IV. Although cisplatin-induced emesis is controllable and the side-effects of methotrexate can be avoided, the POMB regimen remains potentially toxic. The small number of patients with very advanced disease who are long-term survivors prompts us to study further the role of aggressive chemotherapy as the initial treatment of patients with visceral or nodal involvement from carcinoma of the cervix.

Adult

Natural killer cells in cervical intraepithelial neoplasia and human papillomavirus infection.

A semiquantitative immunocytochemical study of natural killer (NK) cells in cervical mucosa was performed by the immunoperoxidase technique using anti-Leu-7 and anti-Leu-11 monoclonal antibodies. NK cells were present in two of the five normal controls and five of six specimens showing human papillomavirus (HPV) infection. Of the 12 CIN studied, six were positive for both Leu-7 and Leu-11 staining and three were positive for Leu-11 alone. NK cells were found predominantly in the subepithelial stroma. The frequency and pattern of distribution of these cells were similar in all grades of CIN. The number of NK cells present was usually small but the degree of infiltration by Leu-11 positive cells was pronounced in two HPV infections and in one CIN 1. NK cells may have a role in surveillance against HPV infection and the development and progression of CIN.

Adult

Management of squamous atypia (borderline nuclear abnormalities): repeat cytology or colposcopy?

A prospective cytological, colposcopic and histological study was conducted in 44 women with cervical cytology showing borderline nuclear abnormalities insufficient for the diagnosis of dyskaryosis. Atypical squamous epithelium was found on colposcopy in 41 patients and cervical intraepithelial neoplasia (CIN) was diagnosed on histology in 33 patients (75%) including 10 with CIN 3. Repeat cytology obtained under colposcopic vision was negative in 12 (33.4%) patients with CIN. The high prevalence of CIN in smears showing only borderline nuclear abnormalities and the high false negative rate of repeat cytology indicate that colposcopy should be the first line of management for these patients.

Adult

Recognition requirements for the activation, differentiation and function of T-helper cells specific for class I MHC alloantigens.

The present review has focused on the specificity of the T-helper cell populations initiating MHC class I alloreactions. In contrast to conventional immune responses against soluble antigens, responses against membrane-bound class I alloantigens are initiated by two distinct antigen-specific T-helper cell populations that can be distinguished by their Lyt phenotype, MHC restriction specificity, antigen specificity, and requirement for thymically determined self-recognition. Alloresponses were shown to be a composite consisting of two distinct components: one mediated by L3T4+ Th cells and very similar to conventional self + X responses; and one mediated by Lyt2+ Th cells and unique to alloresponses against MHC class I antigens. As would befit an unusual Th cell population, the recognition/response spectrum of Lyt2+ Th cells was highly unusual and was found to be the basis for much of the uniqueness we attribute to immune alloreactions, including rapid rejection of tissue allografts in vivo.

Animals

An investigation of patients presenting with multiple physical complaints using the illness behaviour questionnaire.

The Illness Behaviour Questionnaire was used to determine whether three groups of patients who had presented with multiple symptoms in different treatment settings (Briquet's syndrome, post-viral fatigue syndrome, and a heterogeneous general practice group) could be differentiated from one another and from a mixed group of psychiatric patients on the basis of their abnormal illness behaviour. All groups completed a version of the Perley and Guze diagnostic criteria for Briquet's syndrome. The three groups presenting with multiple symptoms were more similar to each other than to the psychiatric patients. The results suggest that patients presenting with multiple symptoms include similar populations of patients who are poorly distinguished using current schemes of classification.

Adult

Evoked response potentials and regional cerebral blood flow in somatization disorder.

Somatization disorder (SMD) is a chronic condition characterized by multiple complaints which are not due to any apparent organic illness but frequently involve pain. This study employs computer-aided imaging technologies to examine brain function in thousandths of a second (event-related brain potentials) and over a number of minutes (regional cerebral blood flow). Fourteen patients with SMD and 14 normal controls were investigated. Results from both studies suggest that patients with SMD have a dysfunction in the processes of attention, compared to normal controls.

Adult

Recognition of cervical neoplasia by the estimation of a free-radical reaction product (octadeca-9,11-dienoic acid) in exfoliated cells.

The molar ratio between a diene-conjugated linoleic-acid isomer (18:2(9,11)) and the parent linoleic acid (18:2(9,12)), both esterified as phospholipids, was significantly different in exfoliated cells from normal cervices and from cervices with colposcopic and cytological evidence of precancer. The measurement may provide a simple and perhaps improved alternative to cytological screening.

Biomarkers, Tumor

Quantitative deoxyribonucleic acid analysis of patients with mild cervical atypia: a potentially malignant lesion?

Quantitative deoxyribonucleic acid (DNA) analysis of cervical biopsy material from 32 women with cytologic, colposcopic, and histologic evidence of mild cervical atypia consistent with cervical intraepithelial neoplasia I, reactive atypia, or human papillomavirus infection was carried out using flow cytometry and Feulgen microspectrophotometry. Evidence of aneuploidy, ie, neoplastic transformation, was demonstrated in all cases of cervical intraepithelial neoplasia I and 68% of cases with human papillomavirus-induced atypia. These results support the growing impression that human papillomavirus-induced cervical atypia should be regarded as a true precursor of cervical neoplasia, and emphasize the necessity to refer patients with mild atypia for definitive diagnosis and management.

Carcinoma in Situ

Recognition of MHC class I allodeterminants regulates the generation of MHC class II-specific CTL.

We have analyzed the signals influencing the generation of major histocompatibility complex (MHC) class II allospecific cytolytic T lymphocytes (CTL) and have found that the development of these CTL is actively regulated in primary in vitro cultures by Lyt-2+ T cells triggered in response to MHC class I alloantigens. Class II allospecific CTL can be readily stimulated in primary cultures, but the presence of a simultaneous class I MHC stimulus in these cultures causes a marked reduction of class II-specific CTL activation. This reduction can be prevented by adding to culture a dose of monoclonal anti-Lyt-2 antibody (in the absence of complement) that does not block the generation of class I-specific CTL. The role of MHC class I alloantigens in the regulation of class II allospecific responses illustrates that T cells recognizing class I and class II MHC antigens in mixed leukocyte cultures interact in a complex and nonreciprocal manner to influence the final effector T cell repertoire elicited by this complex immunogenic challenge.

Animals