PubMed Health⌕ Search

Biomedical subjects

A Singer

Publications and source records attributed to A Singer.

At least 73 records · Page 4Linked to original sources
PubMed1989

An explanation for the problem of false-negative cervical smears.

False-negative cervical cytology due to sampling error is a well-recognized problem. Forty-seven women with histologically proven cervical intraepithelial neoplasia (CIN) were studied. All had two cervical smears performed at a mean interval of 3 months. At the time of the second smear, cervicography, colposcopy and biopsy were performed. The area of acetowhite cervical lesions and of the total visible atypical transformation zone (ATZ) were measured from the cervical photographs. The 17 women in whom one or both smears showed no dyskaryosis were found to have a significantly smaller proportion of their ATZ affected by CIN. It is suggested that this finding can account for the sampling error which causes false-negative cervical cytology. New screening techniques, such as cervicography, may offer a method of detecting and assessing these relatively smaller cervical lesions.

Biopsy↗
PubMed1989

Cytological status and lesion size: a further dimension in cervical intraepithelial neoplasia.

Quantitative histological study of 84 laser cone biopsies showed a highly significant correlation between the grade of a cervical smear and the size of the lesion for all grades of cervical intraepithelial neoplasia (CIN) (CIN I P = 0.004; CIN II P = 0.0001; CIN III P = 0.003; total CIN P less than 0.0001); 10 of 34 (29%) of women with CIN III and mild dyskaryosis or less had significantly smaller lesions than 23 of 36 (63%) of women with CIN III and moderate or severe dyskaryosis. Repeat cytology identified as severe dyskaryosis all those with large CIN III lesions. Lesion size has been neglected in studies of the natural history of CIN and in the assessment of cytological screening, but offers an explanation for the apparent discrepancies between cytological, colposcopic and histological assessment of progression of CIN.

Biopsy↗
PubMed1989

Dynamic MR imaging of the liver with Gd-DTPA: initial clinical results.

Gd-DTPA was evaluated as a hepatic contrast agent for MR imaging. Twenty-six consecutive patients referred for suspected masses in the liver were studied at 1.5 T. Fourteen patients had hepatic metastases and one patient each had cholangiocarcinoma and multicentric hepatocellular carcinoma. Four patients had cavernous hemangiomas and the remainder had other benign lesions. Diagnoses were proved by biopsy, sonography, or radionuclide scintigraphy in 23 cases and by autopsy in one case. Precontrast scans were obtained by using standard pulse sequences. In addition, breath-hold scans were obtained before and after bolus administration of 0.1 mmol/kg Gd-DTPA by using a multislice T1-weighted gradient-echo pulse sequence with an ultrashort echo time. Mean lesion-liver signal difference/noise increased by 50% (p less than .01) in the immediate postcontrast phase. In two of 26 cases, multiple additional lesions as small as 3 mm were detected after contrast administration that were not seen before contrast administration. In no case was lesion-liver contrast worsened on scans obtained immediately after administration of contrast material. However, on delayed scans, detection of lesions worsened in some cases because of equilibration of contrast material between liver and lesion. These initial clinical results suggest that enhancement with Gd-DTPA is a practical method for improving lesion-liver contrast and has the potential to improve the accuracy of MR imaging in the liver. However, optimized fast imaging techniques are required for best results.

Contrast Media↗
PubMed1989

Possible cofactors in the etiology of cervical intraepithelial neoplasia. An immunopathologic study.

Previous work in our department demonstrated a reduction in the numbers of Langerhans' cells in cervical epithelium showing histologic changes of human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN). In conjunction with a localized reversal of the T4:T8 ratio of T-lymphocytes, that finding provides evidence of the association of epithelial immunosuppression with both HPV infection and CIN. To investigate whether that phenomenon occurs primarily because of HPV alone or might be caused by a cofactor (e.g., cigarette smoking, oral contraceptive use, chlamydial infection), we performed a study of the effect of those cofactors on the immune defenses of the cervical epithelium. In a study of Langerhans' cells we showed that infection with HPV type 16 and current cigarette smoking both exert effects that cause a reduction in those cells. That diminution of the major antigen-presenting cells in cervical epithelium may constitute a mechanism that explains the observed role of those agents in the etiology of cervical neoplasia.

Antigens, CD1↗
PubMed1989

The P300 event-related potential and regional cerebral blood flow in patients with Alzheimer's disease.

A number of studies have reported that an abnormal delay in the latency of the P300 event-related potential (ERP) is characteristic of the majority of patients with a dementing process. Another body of research suggests regional cerebral blood flow (rCBF) is significantly reduced in Alzheimer's disease (AD). No previous study has compared the effectiveness of these 2 measures in identifying the same patients with AD. Furthermore, most of the studies on which the above findings are based examined patients in the moderate to severe stages of the disorder. In this study we examined P300 latency and rCBF in 10 patients with mild to moderate Alzheimer's disease, and compared their responses with those of normal subjects of similar age. The P300 component was not evident in 2 of the patients: the remaining 8 had a latency within normal limits for their age. On the other hand, 8 of the patients had abnormally reduced rCBF. These results suggest rCBF measures may be useful for identifying AD in its early stages.

Aged↗
PubMed1988

Induction of anti-CD8 resistant cytotoxic T lymphocytes by anti-CD8 antibodies. Functional evidence for T cell signaling induced by multi-valent cross-linking of CD8 on precursor cells.

The effector function of most MHC class I allospecific CTL is inhibited by anti-CD8 mAb. In the present study, we report the surprising observation that multi-valent cross-linking of CD8 molecules on precursor cells by specific antibody actively induces the generation of CD8+ class I allospecific CTL whose lytic function is resistant to anti-CD8 antibody inhibition, and actively induces down-modulation of cell surface CD8 expression on these cells. In marked contrast, bi-valent cross-linking of CD8 inhibits the generation of CD8+ CTL from precursor cells and fails to induce down-modulation of cell surface CD8 expression. These results demonstrate that CD8 can transduce net positive signals, but only when the molecule is extensively cross-linked.

Animals↗
PubMed1988

Engagement of the CD4 molecule influences cell surface expression of the T-cell receptor on thymocytes.

The intrathymic differentiation process by which precursor cells derived from the bone marrow develop into immuno-competent T lymphocytes is poorly understood. Most thymocytes express both CD4 and CD8 accessory molecules, yet little is known about either the function of these molecules or the responsiveness of the CD4+8+ double positive thymocytes that bear them. Here, we address the possibility that CD4 engagement influences T-cell receptor (TCR) expression on developing thymocytes. We engaged CD4 molecules on murine thymocytes by in vivo injection of an anti-CD4 monoclonal antibody, which reduced the surface expression of CD4 on CD4+ thymocytes. More importantly, CD4 engagement also affected TCR expression on CD4+ thymocytes, but the effect on CD4+8+ double positive and CD4+8- single positive thymocytes was very different. CD4+8+ thymocytes responded to CD4 engagement by dramatically increasing surface expression of TCR, whereas CD4+8- thymocytes decreased surface expression of TCR. These results demonstrate that the effect of CD4 engagement on TCR expression is dependent upon the developmental state of the responding thymocyte, and, most interestingly, results in increased TCR expression by double positive thymocytes.

Animals↗
PubMed1988

Effect of cigarette smoking on cervical epithelial immunity: a mechanism for neoplastic change?

Langerhans' cells in cervical epithelium in colposcopic biopsy specimens were identified by immunocytochemical staining for S100 protein and T6 (CD1) antigen, and their density was quantified. Possible cofactors for the development of cervical neoplasia were examined for any effect on the cell counts per unit area. Current cigarette smoking was associated with a significant decrease in the Langerhans' cell population in both normal epithelium and lesions due to cervical intraepithelial neoplasia. Ex-smokers tended to have cell counts between those of smokers and non-smokers. There was a dose-response relation between number of cigarettes smoked daily and effect on cell counts. These findings of a local immunological effect of smoking on cervical epithelium may explain the means by which cigarette smoking contributes to the development of cervical neoplasia.

Cell Count↗
PubMed1988

IL-1 as a co-factor for lymphokine-secreting CD8+ murine T cells.

Immunologically important among the known biologic activities of IL-1 is its ability to function as a co-factor for responses mediated by lymphokine secreting CD4+ Th cells. In contrast to its known effects in CD4+ T cell responses, IL-1 is not known to play a role in CD8+ T cell responses. In the present study, we have assessed the ability of murine recombinant IL-1 to function as a co-factor for stimulating CD8+ T cells to secrete lymphokines such as IL-2. We found that, in conjunction with either Ag or mitogen, IL-1 is able to stimulate lymphokine-secreting CD8+ T cells. Furthermore, we found that, as a consequence of its stimulation of lymphokine-secreting CD8+ T cells, IL-1 is able to reconstitute MHC class I allospecific cytolytic T lymphocyte responses by cell populations depleted of both accessory cells and CD4+ T cells. These results demonstrate that the biologic activity of IL-1 is not restricted to CD4+ cell responses, and suggests that IL-1 can function as a co-factor for the stimulation of lymphokine-secreting Th cells regardless of their CD4/CD8 phenotype. If IL1 acts directly on lymphokine-secreting T cells or on the APC with which they interact is not yet certain.

Animals↗
PubMed1988

Evidence for involvement of dual-function T cells in rejection of MHC class I disparate skin grafts. Assessment of MHC class I alloantigens as in vivo helper determinants.

The present study further characterizes the cellular mechanisms involved in the in vivo rejection of MHC class I-disparate skin allografts. Previously, we demonstrated that class I-specific rejection responses could result from collaborations between distinct populations of lymphokine-secreting T helper (Th) and lymphokine-responsive T effector (Teff) cells. In the present study, we have assessed the possibility that class I-specific rejection responses could also result from a second cellular mechanism involving a single population of dual-function Th/Teff cells that would not have any further requirement for cell-cell collaboration. Our experimental strategy was to determine the ability of MHC class I-allospecific T cells, in response to class I allodeterminants expressed on skin grafts, to provide help in vivo for activation of helper-dependent Teff cells. We found that class I anti-Kbm1-allospecific T cells would reject bm1 skin allografts, but would not generate help for the activation of helper-dependent effector cells that were specific for third-party skin allografts (e.g., grafts expressing Kbm6, Qa1a, or H-Y allodeterminants). This failure of anti-Kbm1 T cells to provide help in response to bm1 skin allografts was not due to an inability of lymphokine-secreting anti-Kbm1 Th cells to recognize and respond in vivo to Kbm1 allodeterminants expressed on skin, since lymphokine-secreting anti-Kbm1 Th cells were specifically primed in animals engrafted with bm1 skin allografts. Nor was any evidence found that this failure was due to active suppression of anti-Kbm1 helper activity. Rather, we found that anti-Kbm1 T cells consumed nearly all of the helper factors they secreted. Taken together, these results are most consistent with the in vivo activity of dual-function Th/Teff cells that consume the lymphokines they secrete. Thus, this study demonstrates that MHC class I-disparate skin allografts can be rejected by two mechanisms, depending on the ability of the allospecific Teff cell to secrete helper lymphokines. MHC class I-disparate grafts can be rejected by (a) class I-allospecific Teff cells that are unable to produce lymphokine but are responsive to exogenous T cell help; and (b) class I-allospecific dual-function Th/Teff cells that are able to both produce and consume soluble lymphokine.

Animals↗
PubMed1988

Differentiation of Ia-reactive CD8+ murine T cells does not require Ia engagement. Implications for the role of CD4 and CD8 accessory molecules in T cell differentiation.

The present study was undertaken to assess the Ia differentiation requirements of CD8+ class II-allospecific CTL, whose CD8+ phenotype is apparently "discordant" with their MHC class II reactivity. To do so, we compared the effect of in vivo anti-Ia blockade on the differentiation of Ia-reactive CD8+ CTL with its effect on the differentiation of CD4+ T cells. We found that anti-Ia blockade did not detectably interfere with the differentiation of CD8+ Ia-reactive CTL, even though it arrested the differentiation of CD4+ T cells. Thus, the differentiation of CD4+ T cells is strictly dependent upon Ia engagement, whereas the differentiation of CD8+ T cells, even those with reactivity against MHC class II alloantigens, does not require Ia engagement. These results support the concept that Ia-reactive CD8+ T cells are conventional CD8+ CTL, probably selected by self-class I MHC molecules during differentiation, whose receptors fortuitously crossreact on MHC class II alloantigens. Taken together, the present data indicate an intimate relationship between CD4/CD8 expression with MHC class specificity during T cell differentiation and selection. We suggest that an active triggering role for CD4 and CD8 accessory molecules in T cell differentiation is best able to explain these observations.

Animals↗
PubMed1988

Cell surface expression of the amino-terminal domain of A kappa alpha. Recognition of an isolated MHC antigenic structure by allospecific T cells but not alloantibodies.

To evaluate the relationship between structure and function of the alpha 1 and beta 1 domains of class II MHC molecules, a strategy has been developed whereby isolated alpha 1 or beta 1 domains can be expressed on the surface of transfected mouse L cells as a part of a hybrid class II/class I molecule. The construction and expression of a chimeric class II/class I gene encoding the first two exons of A kappa alpha linked to the C2, TM and cytoplasmic exons of H-2Dd (A kappa alpha 1/DdC2) are described. High levels of A kappa alpha 1/DdC2 protein were detected on transfected L cells with a DdC2-specific mAb. An anti-Ia xenoantiserum specifically bound to A kappa alpha 1/DdC2-transfected L cells, although 12 different mAb reactive against I-A kappa alpha and an anti-Ia kappa alloantiserum did not bind these cells. However, alloreactive Ia kappa-specific CTL lines were able specifically to lyse cells expressing the hybrid A kappa alpha 1/DdC2 molecule. This indicates that the isolated A kappa alpha 1 domain preserves some of the structure of the native molecule and demonstrates the recognition by T cells of domain-specific A alpha allodeterminants.

Animals↗
PubMed1988

Intrathymic differentiation and tolerance induction of lymphokine-secreting Lyt-2+ T helper cells.

The present study has assessed thymic influence on the differentiation and recognition specificity of developing Lyt-2+ lymphokine-secreting T cells, and compared it with those of developing Lyt-2+ CTL. It was demonstrated that development of Lyt-2+ lymphokine-secreting Th cells requires an intrathymic differentiation step, and that peripheral Lyt-2+ lymphokine-secreting Th cells, unlike peripheral Lyt-2+ CTL, are profoundly tolerant to intrathymically expressed alloantigens. These data are interpreted as demonstrating that functionally distinct Lyt-2+ T cell populations are heterogeneous in their requirements for differentiation and/or activation.

Animals↗