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Biomedical subjects

L M Weiss

Publications and source records attributed to L M Weiss.

At least 325 records · Page 18Linked to original sources

Expression of Tac antigen by non-Hodgkin's lymphomas.

Anti-Tac is a monoclonal antibody that appears to recognize the interleukin-2 receptor. With the use of a frozen-section immunoperoxidase technic, a large series of non-Hodgkin's lymphomas were investigated for the presence of Tac-antigen on neoplastic cells. Approximately one-fourth of cases expressed the Tac antigen, including 27% of B-lineage lymphomas, 6% of the T-lineage lymphomas, and three of four cases of Ki-1-expressing lymphoma. The B-lineage lymphomas with the highest incidence of Tac antigen expression were the large cell lymphomas, both diffuse and follicular, where about one-half of cases expressed the Tac antigen. All major categories of lymphoma expressed Tac except plasma-cytoma/myeloma, small noncleaved cell (Burkitt's and non-Burkitt's), and lymphoblastic malignancies.

Antibodies, Monoclonal↗

Low-grade renal cell carcinoma. A clinicopathologic study of 53 cases.

Fifty-three low-grade renal cell carcinomas and oncocytomas were reviewed to assess the prognostic significance of nuclear grade (grade 1 versus grade 2), character of cell cytoplasm, size, and stage. Twelve of 46 patients (27%) with follow-up died of disease. Stage 4 disease (most often, extensive local spread) best predicted decreased survival. The survival of patients with stage 1, 2, and 3 tumors was similar; and renal vein invasion was not an adverse prognostic indicator. Size also appeared to predict patient survival; tumors greater than 10 cm metastasized at a higher rate than neoplasms 5 cm or less. We were unable to demonstrate statistically significant differences in survival between individuals with grade 1 and 2 neoplasms, nor were we able to demonstrate a statistically significant difference in survival on the basis of the character of the cell cytoplasm. However, there was a trend toward better survival for patients with granular cell carcinomas and oncocytomas as opposed to neoplasms with clear or mixed cell cytoplasm. Although the number of patients with granular cell carcinomas and oncocytomas is small, the data suggest that the distinction between low-grade granular cell carcinomas and oncocytomas adds little prognostic information.

Actuarial Analysis↗

Lymphocyte predominance Hodgkin's disease: a reappraisal based upon histological and immunophenotypical findings in relapsing cases.

The clinical, morphological and immunological findings in nine cases of relapsing lymphocyte predominance Hodgkin's disease (LPHD) are examined. Six patients had initial biopsies demonstrating nodular lymphocytic and/or histiocytic (L&H) LPHD; Leu-M1 was not expressed by any of the atypical cells in these cases. All six demonstrated one or more recurrences of nodular L & H LPHD; four are currently free of disease, one died of non-Hodgkin's lymphoma and another died of leukaemia. Two patients had initial biopsies demonstrating diffuse LPHD, with only rare multilobated atypical cells (L & H variants). Both patients had recurrences interpreted as mixed cellularity Hodgkin's disease, 10 and 15 years after initial therapy and both died with lymphocyte depleted Hodgkin's disease. The atypical cells in the initial biopsies and in subsequent recurrences failed to express Leu-M1, but did express leukocyte common antigen. The initial biopsy from the final patient was histologically interpreted as focal involvement by LPHD, but interfollicular Hodgkin's disease was considered after the Leu-M1 stain revealed additional atypical cells. The disease relapsed and the patient died with typical nodular sclerosing Hodgkin's disease. The pattern of the relapses supports the concept that the histological entity of LPHD may include several distinct clinicopathological subgroups.

Biopsy↗

Aging-associated changes in indices of thrombin generation and protein C activation in humans. Normative Aging Study.

In view of the known association of vascular disease with increasing age, we have conducted an analysis of hemostatic system activity with respect to perturbations induced by aging phenomena. We have utilized an immunochemical assay for prothrombin fragment F1 + 2 to quantify Factor Xa activity upon prothrombin in the plasma of 199 healthy males between the ages of 42 and 80. The levels of F1 + 2 in this population generally increased as a function of age (P less than 0.0001). The metabolic behavior of this marker was determined in 10 individuals greater than 65 yr of age with varying levels of F1 + 2, which ranged from 1.28 to 5.85 nM. The elevations in the concentration of this component were not due to diminished clearance of the fragment. Radio-immunoassays for fibrinopeptide A (FPA) and the protein C activation peptide (PCP) were subsequently employed to measure thrombin activity upon fibrinogen and thrombin-thrombomodulin activity upon protein C, respectively, in 82 members of this population ranging in age from 42 to 80. Significant positive correlations were again observed between increasing age and the level of F1 + 2 (P less than 0.0001) as well as FPA (P less than 0.01) and PCP (P less than 0.002). The results of this cross-sectional study indicate that many apparently normal males of increasing age with normal immunologic levels of antithrombin III and protein C exhibit a biochemical defect that denotes the presence of an acquired prethrombotic state.

Adult↗

Epstein-Barr viral DNA in tissues of Hodgkin's disease.

Tissue specimens from 21 cases of Hodgkin's disease were examined for the presence of Epstein-Barr virus (EBV) and cytomegalovirus DNA by molecular hybridization techniques. EBV DNA was detected in 4 cases, including 2 of 8 cases which had been previously shown to contain clonal immunoglobulin gene rearrangements. Two of the cases containing EBV DNA were of the nodular sclerosing type and had received prior therapy; the other 2 were classified as mixed cellularity Hodgkin's disease and had not received therapy before the biopsy tissue was obtained. Analyses of the terminal portions of EBV genomes indicated a monoclonal or oligoclonal proliferation of EBV-infected cells in the tissues studied. In contrast, none of the 21 cases had detectable cytomegalovirus DNA sequences. The identification of EBV DNA may reflect the proliferation of lymphoblastoid cells due to the reduced immune competence frequently noted in Hodgkin's disease or may indicate the presence of EBV genomes within Reed-Sternberg cells.

Adult↗

Non-Hodgkin's lymphoma containing both B and T cell clones.

We describe a patient in whom two lymph node biopsies removed 18 months apart disclosed histologic and immunophenotypic evidence of a non-Hodgkin's lymphoma containing neoplastic lymphocytes of both B and T type. Analyses of immunoglobulin and T cell receptor genes confirmed the presence of separate B and T cell clones. In addition, immunogenotyping revealed the possibility of a second B cell clone within the patient's tumor. Development of a multiclonal lymphoma in this patient may relate to the carcinogenic effects of chemotherapy or to a predisposition for neoplastic transformation of lymphocytes due to a previously diagnosed autoimmune condition. Another possible explanation is that the lymphoma implies the existence in this patient of a transformed lymphocyte-committed stem cell that is capable of generating both B and T lineage clones.

B-Lymphocytes↗

Clonal T-cell populations in pityriasis lichenoides et varioliformis acuta (Mucha-Habermann disease).

Patients with the skin disorder pityriasis lichenoides et varioliformis acuta (PLEVA) develop recurrent, self-healing papulonecrotic lesions that contain infiltrates of cytologically and antigenically normal T lymphocytes. DNA extracted from the lesions of 3 patients with PLEVA was analyzed for rearrangement of beta-T-cell receptor genes for the purpose of assessing the clonality of T lymphocytes within the tissues of this disease. Lesions from all 3 cases showed clonal gene rearrangements. In each of 2 cases from which two separate lesions were biopsied, identical rearrangements were found in specimens from both sites. DNA from a variety of inflammatory lesions obtained from patients with other types of skin diseases failed to show detectable rearrangements of beta-T-cell receptor genes. These results suggest that PLEVA represents a T-cell lymphoproliferative process, rather than an inflammatory disorder, as had been previously thought.

DNA Restriction Enzymes↗

Immunophenotypic criteria for the diagnosis of non-Hodgkin's lymphoma.

This study examines the immunohistologic profiles of a large series of histologically proven benign and malignant lymphoproliferative processes in order to define immunophenotypic criteria useful in the diagnosis of non-Hodgkin's lymphoma. Using a method of analysis relying solely on immunoarchitectural features of a given case, the authors were able to define immunologic criteria capable of differentiating benign from malignant lymphoid processes independent from conventional morphologic analysis. In general, these criteria involved identification of abnormal expression or loss of antigens in B- and T-lineage populations. Among B-lineage populations the following features were associated with malignant histology: 1) light-chain-restricted B lineage, 2) light chain -B lineage, 3) Leu-1+ B lineage, 4) L60+ B lineage, 5) 41H+, Ki-67+ B lineage, 6) loss of pan-B antigens, and 7) LFA-1-B lineage. Among T-cell populations outside the thymus, phenotypes associated with malignancy included 1) loss of pan-T antigens (including loss of the beta chain of the T-cell antigen receptor), 2) coexpression or loss of T-subset antigens, 3) Leu-6+ T-lineage, and 4) MB-1+ T lineage. Application of these criteria to a series of nearly 500 cases of lymphoma indicated that over 90% of B-lineage and about 80% of T-lineage neoplasms manifested immunophenotypic abnormalities that could distinguish them from benign, reactive lymphoid processes. It is concluded that immunophenotypic analysis of lymphoproliferative lesions is sufficiently sensitive and specific to confirm the histologic diagnosis of lymphoma in the vast majority of cases seen in clinical practice. Furthermore, in difficult cases or those with limited material or poor histology, immunophenotypic analysis may be the only means of making a definitive diagnosis.

Antibodies, Monoclonal↗

Necrosis in lymph nodes.

When necrosis is identified in a lymph node biopsy, various entities should be considered in the differential diagnosis. Neoplastic conditions, especially lymphoma and metastatic carcinoma, must first be excluded. Numerous benign conditions also cause necrosis in lymph nodes, and the presence or absence of granulomatous inflammation as well as other histologic features are useful in suggesting various possibilities. Clinical information is very important in the differential diagnosis, and lymph node culture or other tests are often required to determine a specific diagnosis.

Humans↗

"Well-differentiated" lymphocytic neoplasms. Immunologic findings correlated with clinical presentation and morphologic features.

The authors studied 48 cases of well-differentiated lymphocytic neoplasms using a panel of monoclonal antibodies applied to frozen sections. Forty-seven tumors expressed monotypic immunoglobulin, one or more B-lineage antigens, and Ia (HLA-DR) antigen. Proliferation centers expressed the T9 antigen and increased numbers of Ki-67-positive cells. One tumor was of T-cell origin, had a cytotoxic/suppressor cell phenotype, and showed anomalous loss of Leu-1 antigen. Immunophenotypic findings were correlated to the clinical presentation and morphologic features of each neoplasm. Sixteen tumors were associated with peripheral lymphocytosis (greater than 4000/cu mm), 13 biopsies were obtained from extranodal sites, 16 tumors had proliferation centers, and 11 neoplasms had plasmacytoid features. The authors found no absolute and few statistically significant immunologic differences between the B-cell tumors according to their clinical presentation or morphologic features. Tumors associated with peripheral lymphocytosis more commonly expressed the Leu-1 antigen (P less than 0.01) and IgD (P less than 0.01) and less frequently were stained by BA-2 (P less than 0.05) and OKT9 (P less than 0.05). Plasmacytoid neoplasms more frequently expressed the Tac (P less than 0.01) and T9 antigens (P less than 0.05), and all expressed kappa light chain (P less than 0.05). Extranodal neoplasms more commonly expressed IgM (P less than 0.01). In contrast to the markedly different clinical presentation and morphologic appearance these tumors may have, the immunologic data suggest that B-cell small lymphocytic neoplasms are relatively homogeneous. For an individual case, immunophenotype does not predict clinical presentation or morphologic features.

Aged↗

Discordant expression of CD3 and T-cell receptor beta-chain antigens in T-lineage lymphomas.

Using an immunoperoxidase technique that identifies both surface and cytoplasmic antigen expression, the authors examined 28 benign reactive lymphorproliferative lesions and 55 T-lineage lymphomas for reactivity with CD3 (Leu-4; T-cell receptor-associated antigen) and beta F1 antibodies, the latter recognizing nonpolymorphic determinants on T-cell receptor beta chains. Consistent with previous observations that these two antigens are co-expressed on the vast majority of thymocytes, peripheral blood T cells and tonsillar T cells, all 28 reactive lymphoproliferations showed essentially identical patterns of CD3 and beta F1 expression. In contrast, only 29 of 55 T-lineage lymphomas displayed coexpression of these antigens. Among 33 peripheral T-cell lymphomas, 11 cases showed CD3/beta F1 discordance (7 CD3+/beta F1-; 4 CD3-/beta F1+), and 5 showed absence of both these antigens. Nine of 22 T-lymphoblastic lymphomas showed CD3/beta F1 discordance (all CD3+/beta F1-), and 1 case was CD3-/beta F1-. These patterns of CD3/beta F1 expression, along with the patterns of CD2, CD4, CD5, CD7, and CD8 antigen expression in these neoplasms, indicate that T-cell lymphomas can manifest phenotypes not apparently reflective of normal T populations and suggest the presence of abnormal gene expression in these malignancies. The existence of aberrant phenotypes in T-cell neoplasia suggests caution in interpretation of investigations using T-lineage malignancies as models of normal T-cell biology. Finally, the identification of phenotypic abnormalities in T-lineage populations can be of great diagnostic usefulness in the delineation of benign versus malignant T-cell proliferations.

Antigens, Differentiation, T-Lymphocyte↗

Sinusoidal hematolymphoid malignancy ("malignant histiocytosis") presenting as atypical sinusoidal proliferation. A study of nine cases.

A number of cases of sinusoidal hematolymphoid malignancy ("malignant histiocytosis") in which early lymph node biopsies have not allowed clear separation from benign histiocytic disorders have been observed. Nine such cases in which only a follow-up lymph node biopsy documented their malignant nature are reported. Seven of the nine patients were under 21 years of age; there was an even sex distribution. All had localized or generalized lymphadenopathy and three had hepatosplenomegaly at initial presentation. Histologically, the initial lymph node biopsy specimens showed an atypical sinusoidal proliferation, often with hemophagocytosis, but without sufficient atypia to allow a diagnosis of malignancy. The analysis of the follow-up biopsies, performed from 6 weeks to 5 years after the initial biopsy, showed a progression in histology with an increase in atypia, a greater tendency to efface lymph node architecture, and a decrease in hemophagocytosis. All patients were treated with chemotherapy. Six patients ultimately died; at autopsy, these patients showed a pattern of organ involvement typical of what has been described for malignant histiocytosis.

Adolescent↗

Clonal T-cell populations in lymphomatoid papulosis. Evidence of a lymphoproliferative origin for a clinically benign disease.

Lymphomatoid papulosis is a chronic, clinically benign skin disorder that, when examined histologically, is seen to include numerous large, atypical lymphoid cells that display antigenic markers of T lymphocytes. To investigate the disparity between the clinical behavior of this disease and its malignant histologic appearance, we analyzed the DNA from skin lesions of six patients for rearrangements of beta and gamma T-cell receptor genes. Lesions from five of these patients showed between one and three clonal rearrangements for at least one T-cell receptor gene. Three separate biopsy specimens from a single patient showed different patterns of rearrangements for the beta gene in each specimen. Our results indicate that lymphomatoid papulosis is a clonal T-cell lymphoproliferative process that may possibly be multiclonal in origin. We conclude that this disease has both biologic and histologic features consistent with a malignant T-cell neoplasm despite its indolent course.

Adult↗

Primary pulmonary Hodgkin's disease. A clinicopathologic study of 15 cases.

Fifteen cases of primary pulmonary Hodgkin's disease are reported. This presentation of Hodgkin's disease occurred more frequently in women (2:1) and older individuals, and B symptoms were relatively common (7 of 13). The majority of patients had nodular lesions on chest radiographs. An unfavorable prognosis was linked to B symptoms, older age (greater than 60 years) and multiplicity and bilaterality of lung lesions. The histologic differential diagnosis is discussed, particularly in regard to Wegener's granulomatosis and non-Hodgkin's lymphomas.

Adult↗

Autologous pericardium versus a xenograft substitute in myocardial wound healing.

This study compared repair of myocardial wounds covered with autologous pericardium to healing of wounds covered with glutaraldehyde-preserved bovine pericardium in an experimental canine model. Right (RV) and left (LV) full thickness ventriculotomies were made and closed. In the control group (n = 12), the pericardium was closed over the wound; in the experimental group (n = 12), wounds were covered with bovine pericardium. Animals were sacrificed at 14, 21, 28, and 42 days. After excising the pericardium, 6 mm punch biopsies of normal RV, RV wound, normal LV, and LV wound were assayed for hydroxyproline (HPro). Both autologous and bovine pericardium became densely adherent to the wounds. Bovine pericardium was mildly adherent over unwounded areas, while autologous pericardium was usually free. Normal RV contained more than twice as much HPro as normal LV (5.4 +/- 0.57 micrograms/mg vs 1.7 +/- 0.35 micrograms/mg, P less than 0.0002). A gradual rise in HPro over time was seen in both groups, but this increase was statistically significant only at 42 days (P less than 0.05). There was no significant difference in HPro between wounds covered with autologous pericardium and those covered with bovine grafts (P = 0.13) at any of the sample times in this study. In this experimental canine model, the pericardium does not appear to play a prominent role in myocardial wound healing by contributing collagen-producing fibroblasts. Furthermore, the bovine pericardial xenograft becomes densely adherent to LV and RV incisions. In the clinical setting, such may make reoperation more hazardous when the heart has been previously incised or coronary bypass grafts have been constructed.

Animals↗