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Biomedical subjects

M S Pollack

Publications and source records attributed to M S Pollack.

At least 55 records · Page 3Linked to original sources

Meningeal involvement in early stage chronic lymphocytic leukemia.

Two patients with early stage chronic lymphocytic leukemia were found to have meningeal involvement. The diagnosis was confirmed by cerebral spinal fluid cytology in the first patient and by flow cytometric analysis in the second patient. Both patients responded well to intrathecal chemotherapy and cranial irradiation. Central nervous system infiltration by tumor cells has rarely been described in chronic lymphocytic leukemia but must be considered in all patients regardless of stage who present with lethargy, dementia, or focal neurologic signs.

Female↗

Magnetic resonance imaging in the evaluation of suspected osteonecrosis of the knee.

Magnetic resonance imaging (MRI) was performed on 19 patients with suspected or proven osteonecrosis of the knee. The results were compared to radionuclide and plain radiographic studies when possible. The patients were grouped into one of three categories: patients with disease predisposing them to osteonecrosis (e.g., systemic lupus erythematosus (SLE), steroid use, and renal transplants), older patients without risk factors with acute onset of symptoms,and patients with knee pain months or years following trauma. In six patients with symptoms and predisposing diseases, MRI was abnormal in four cases, all of whom had bilateral abnormalities. In the ten older patients with classical symptoms, MRI was abnormal in seven, and bilateral abnormalities were present in three patients. The three patients with a history of antecedent trauma had normal MRI studies. Two patients with history and scintigraphic evidence of osteonecrosis had negative MRI scans. MRI may be of value in patients with suspected or proven osteonecrosis of the knee by demonstrating bilateral disease in patients with unilateral symptoms, showing the extent of involvement, and establishing the presence or absence of bone marrow changes in patients with positive bone scans and negative plain films.

Humans↗

Defective antigen presentation and novel structural properties of DR1 from an HLA haplotype associated with 21-hydroxylase deficiency.

We have segregated DR1+ individuals into two categories according to whether or not their class II+ cells stimulated T lymphocyte clones specific for or restricted to DR1. In a majority of cases (87%), failure to stimulate was a property of cells having the B14;DR1 haplotype and/or nonclassical 21-hydroxylase deficiency. Absence of clonal proliferation could not be explained by release of an intercellular suppressor factor or by stimulator cell absorption of interleukin 2. Homozygous cells inheriting both stimulatory (DR1n) and nonstimulatory (DR1x) haplotypes did not successfully mediate clonal expansion, implying that a trans acting factor operates intracellularly to modify both DR1 alleles or their products. Other DR alleles did not appear to be affected as evidence by normal proliferative responses of T lymphocyte clones restricted to DR2 or DR7 and stimulated by DR1x,2 and DR1x,7 cells, respectively. By two-dimensional gel analysis, we have further identified a 50-kD surface glycoprotein contained in anti-DR immunoprecipitates of DR1x, but not DR1n or non-DR1 cellular lysates. This 50-kD structure had antigenic and peptide identity to DR alpha and beta chains but was resistant to dissociation under conditions that normally separate DR alpha and beta (8 M urea plus 5% 2-mercaptoethanol); boiling in sodium dodecyl sulfate was required to segregate the component polypeptides of the 50-kD heterodimer. We postulate that a product of a novel combinatorial association between constitutive chains of DR may interfere with or compete for normal T cell receptor recognition of DR1 as both an alloantigen and a restricting element. We further propose that gene abnormalities within the class III region of a haplotype associated with nonclassical 21-hydroxylase deficiency may extend into the DR subregion of the major histocompatibility complex with consequent aberrations in DR1 presentation.

Adrenal Hyperplasia, Congenital↗

Urachal carcinoma: evaluation with computed tomography.

The computed tomographic (CT) findings in 7 patients with urachal carcinoma were reviewed. Computed tomography was useful in establishing an initial diagnosis, determining the tumor extent, and visualizing tumor recurrence. The embryology, histology, and clinical course of urachal carcinoma are reviewed.

Abdominal Neoplasms↗

HLA typing used with cultured amniotic and chorionic villus cells for early prenatal diagnosis or parentage testing without one parent's availability.

Like fetal fibroblasts and amniotic fluid cells, cultured chorionic villus cells can also be HLA typed with selected typing sera after preincubation with gamma interferon to promote better antigen expression. A modified procedure now in use would also allow any of these cell types to be tested for the presence or absence of all known HLA A,B,C, and DR antigens with standard preplated typing trays. This procedure was used to confirm that an on-going pregnancy had resulted from the successful in vitro fertilization and implantation of an anonymous donor's ovum and could also be of major use in rape or artificial insemination cases when the identity of the possible father(s) is not known.

Amnion↗

The immunological detection of a 21-OH deficiency mutation HLA supratype.

Previous studies have shown that the late-onset and cryptic forms of 21-hydroxylase deficiency are highly associated with the HLA supratype HLA-B14,C4A2,C4B1/2,DR1. Since cells from a number of unrelated normal individuals from different ethnic backgrounds expressing the DR1 associated with this supratype failed to stimulate two different DR1-restricted T-cell clones that proliferated in the presence of most other DR1 cells, we decided to test the hypothesis that cells with this supratype express "abnormal" DR1 molecules that have been affected in some way by the chromosomal mutation responsible for B14,DR1-associated 21-hydroxylase deficiency (21-OH-defL). The results showed an association between "abnormal" DR1 and 21-OH-defL (elevated rates of 17 alpha-hydroxyprogesterone [17-OHP] increase and elevated peak 17-OHP values following ACTH stimulation). The presence of the B14,DR1 supratype can be used to predict the presence of "abnormal" DR1 and the clinical status of individuals not previously known to be 21-OH-defL carriers.

17-alpha-Hydroxyprogesterone↗

Pleural effusions in the postpartum period.

We report on the high frequency of pleural effusions in the immediate postpartum period. Forty-four out of 45 women whom we examined within 24-48 h after delivery showed evidence of pleural fluid. Under these circumstances, this pleural abnormality should not be considered an indicator of serious cardiopulmonary disease.

Adult↗

Epstein-Barr virus-associated B-cell proliferations of diverse clonal origins after bone marrow transplantation in a 12-year-old patient with severe combined immunodeficiency.

A 12-year-old boy with severe combined immunodeficiency who had been kept in a gnotobiotic environment since birth received bone marrow from a histoincompatible sibling in an attempt to reconstitute immunologic function. To prevent graft versus host disease, the donor's marrow was treated in vitro with monoclonal antibody and complement to remove alloreactive T cells. Eighty days after transplantation, the patient had a systemic illness characterized by fever, thrombocytopenia, gastrointestinal pain, and bleeding; he died on the 124th post-transplantation day. Postmortem examination revealed multiple tumor-like B-cell proliferations, recipient in origin, in numerous organs. Epstein-Barr virus (EBV) was isolated from the patient's pharyngeal secretions; EBV nuclear antigen was found in spontaneously transformed peripheral-blood lymphocytes, inflammatory cells from peritoneal fluid, and bone marrow cells; and EBV genomes were discovered in all tumor tissues. The donor's serum showed evidence of past EBV infection. Analysis of cellular immunoglobulin and immunoglobulin gene DNA from the tumors indicated both monoclonal and oligoclonal B-cell proliferations. These findings provide evidence for the evolution of EBV-induced polyclonal activation of B cells to oligoclonal B-cell proliferation and finally to monoclonal B-cell lymphoma.

B-Lymphocytes↗

Class II determinants recognized by TNP-specific cloned human T cell lines.

Cloned human T lymphocyte lines were generated against trinitrophenyl (TNP)-modified autologous cells from four different individuals. By examining the reactivity patterns of 58 of these T cell clones (TLC) on panels of HLA-typed antigen presenting cells and employing monoclonal antibodies (MoAb) for inhibition studies, we have demonstrated that TNP may be recognized in the context of different DR and DP associated determinants. We did not identify any TLC restricted by determinants associated uniquely with DQ. Determinants associated with the expression of DR1,2,4,5, and 7 as well as the supertypic specificities DRw52 (MT2) and DRw53 (MT3) functioned as restriction elements. In addition, at least two antigenically distinct regions of the DP4 molecule appeared to function in the presentation of TNP. One TNP-specific TLC recognized a determinant associated with the expression of DP4 while another recognized TNP in the context of a highly nonpolymorphic determinant on DP which was expressed on all stimulators tested. Monoclonal antibody blocking studies suggest that these two determinants lie on different portions of the DP molecule. These studies demonstrated that both polymorphic and relatively nonpolymorphic restriction determinants on DR and DP may function in the presentation of conventional antigen to autologous lymphocytes.

Antibodies, Monoclonal↗

Class II positive human dermal fibroblasts restimulate cloned allospecific T cells but fail to stimulate primary allogeneic lymphoproliferation.

Recently, a number of laboratories have shown that gamma interferon (IFN-gamma) is a potent modulator of HLA class II antigen expression in a variety of cell types ranging from classical antigen presenting cells to those not expected to participate in physiological antigen presentation such as fibroblasts. In order to examine the role of HLA class II expressing fibroblasts in antigen presentation, we established dermal fibroblast (FIB) strains from five HLA typed donors. After optimal preculture with IFN-gamma, class II positive FIB were fully competent to restimulate proliferative responses of two DR specific T cell clones and one DP specific T cell line. However, they failed to elicit strong primary allogeneic proliferation from fully DR mismatched fresh PBMC. This failure was not due to a direct suppressive effect of FIB and could not be corrected by exogenous IL1 or by factors contained in conventional mixed leukocyte culture supernatants.

Antigen-Presenting Cells↗

Human leukocyte antigen associations in basal cell carcinoma.

Basal cell carcinoma is the most common form of skin cancer and is one in which both host and environmental factors are thought to play a role in its pathogenesis. For an investigation of the role of human leukocyte antigen (HLA)-associated variations in genetic susceptibility, thirty-one patients with multiple basal cell carcinomas were typed for HLA-A, B, C, and DR antigens. Patients were compared with both local and appropriate ethnic group controls. No statistically significant association with HLA-A, B, or C antigens was noted in any group. However, a significant increase in HLA-DR1 was noted in non-Irish, non-Ashkenazi patients. A tendency toward a decrease in HLA-DR3 was also noted among patients of Irish or Ashkenazi Jewish descent. The role of HLA-associated genetic factors in this form of skin cancer needs further investigation.

Basal Cell Carcinoma↗

HLA and DR antigen frequencies in melanoma patients: possible relation to disease prognosis.

The frequency of HLA-DR5 was significantly increased in a large group of malignant melanoma patients (33.7% vs 20.5% for controls). The subgroup of patients with poor prognosis showed both a DR5 increase and a relative decrease in DR1. Although none of these differences was significant after correction for the number of antigens tested, similar findings have been made for other malignancies and further studies should be encouraged.

Gene Frequency↗