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Biomedical subjects

S M Hsu

Publications and source records attributed to S M Hsu.

At least 127 records · Page 7Linked to original sources
PubMed1984

Analysis of lymphocyte subsets in patients with aplastic anaemia.

Lymphocyte subsets have been measured in the blood of 28 patients with aplastic anaemia. The mean helper/inducer:suppressor/cytotoxic T lymphocyte ratio (1.24 +/- 0.74) was significantly decreased in the total population in comparison to mean ratios in a normal population (1.78 +/- 0.57) and in patients with other haematological diseases (1.82 +/- 0.92). A reversed ratio (less than or equal to 1) was present in a large proportion (53%) of aplastic patients, due both to an absolute deficiency of helper/inducer lymphocytes and an increase in suppressor/cytotoxic lymphocytes. Increased HLA-DR expression, evidence of lymphocyte activation, was present in seven of 12 patients evaluated and was confined to the suppressor/cytotoxic lymphocyte population. In the bone marrow, the percentage of lymphocytes was increased two-fold compared to normal bone marrow but the ratio of T cell subsets was not abnormal. Two of four patients evaluated after haematopoietic recovery following ATG treatment showed a return to normal of the T4/T8 ratio; in two others a low T4/T8 ratio persisted despite recovery. These results indicate that lymphocyte subset imbalance and lymphocyte activation are present in many patients with aplastic anaemia, either as a contributing factor or as a result of bone marrow failure.

Adolescent↗
PubMed1984

Continuous intravenous infusions of bromodeoxyuridine as a clinical radiosensitizer.

Twelve patients were treated with continuous intravenous (24-hour) infusions of bromodeoxyuridine (BUdR) at 650 or 1,000 mg/m2/d for up to two weeks. Myelosuppression, especially thrombocytopenia, was the major systemic toxicity and limited the infusion period to nine to 14 days. However, bone marrow recovery occurred within seven to ten days, allowing for a second infusion in most patients. Local toxicity (within the radiation field) was minimal, with the exception of one of four patients, who underwent abdominal irradiation. Pharmacology studies revealed a steady-state arterial plasma level of 6 X 10(-7) mol/L and 1 X 10(-6) mol/L during infusion of 650 and 1,000 mg/m2/d, respectively. In vivo BUdR uptake into normal bone marrow was evaluated in two patients by comparison of preinfusion and postinfusion in vitro radiation survival curves of marrow CFUc with enhancement ratios (D0-pre/D0-post) of 1.8 (with 650 mg/m2/d) and 2.5 (with 1,000 mg/m2/d). In vivo BUdR incorporation into normal skin and tumor cells using an anti-BUdR monoclonal antibody and immunohistochemistry was demonstrated in biopsies from three patients revealing substantially less cellular incorporation into normal skin (less than 10%) compared with tumor (up to 50% to 70%). We conclude that local and systemic toxicity of continuous infusion of BUdR at 1,000 mg/m2/d for approximately two weeks is tolerable. The observed normal tissue toxicity is comparable with our previous clinical experience with intermittent (12 hours every day for two weeks) infusions of BUdR. Theoretically, a constant infusion should allow for greater incorporation of BUdR into cycling tumor cells and thus, for further enhancement of radiosensitization.

Bone Marrow↗
PubMed1984

Phenotypic expression of non-Hodgkin's lymphomas in China.

Monoclonal antibodies were used to label malignant lymphomas obtained from 57 patients. On the basis of morphologic criteria, 18 lymphomas were the B-cell type, 10 were the T-cell type, and 6 were histiocytic; for 23 the type could not be determined. After monoclonal antibody labeling, 18 lymphomas of B-cell lineage were confirmed, 16 of the T-cell type were demonstrated, 6 were true histiocytic, and 17 were the null cell (non-T, non-B) type. Of the 16 lymphomas of T-cell lineage, 6 were lymphoblastic and 10 were the peripheral type. The percentages of cell types in the non-Hodgkin's lymphomas were as follows: B-cell, 31.5%; T-cell, 28%; null cell, 29%; and histiocytic, 10%. Of the 16 lymphomas of T-cell origin, 15 belonged to helper T-cell subsets (Leu1+, Leu4+, and Leu3a+), and the la marker was positive in all 16. Of the 18 B-cell lymphomas, 14 were kappa-positive and 4 were lambda-positive. Eleven were both B1- and kappa-positive, and 1 was kappa-positive but B1-negative. In the 4 cases that were lambda-positive, 2 were both lambda- and B1-positive. The results indicate that Leu4, Leu2a, Leu3a, and B1 are the most important markers to differentiate T-cell and B-cell lymphomas for pathologic classification. The findings also show a higher percentage of T-cell neoplasm in China as compared to that in Western countries.

Adult↗
PubMed1984

Phenotypic expression of B-lymphocytes. 2. Immunoglobulin expression of germinal center cells.

With a sensitive and specific immunohistochemical technique, immunoglobulin expression was examined in germinal centers with frozen and paraffin-embedded tissues. The majority of cells positive for surface immunoglobulin (IgM and IgD) were confined to the dark zone of the germinal center, while the cells positive for cytoplasmic immunoglobulin (IgM and IgG) were found in the light zone. There were considerable numbers of germinal center cells without identifiable immunoglobulin. The results, in conjunction with previous in vitro and in vivo B-cell activation studies, indicate that centroblasts (noncleaved cells) are formed during early stages of B-cell differentiation. Centroblasts further mature into centrocytes.

Antibody-Producing Cells↗
PubMed1984

Monoclonal antibodies to Müller's cells of the retina.

The immunohistologic properties of two monoclonal antibodies produced by hybridomas generated from bovine retinal S-antigen (S-Ag) immunized mice were investigated. These monoclonal antibodies demonstrated a low antibody titer to the original S-Ag preparation by the ELISA method. Immunohistologic studies using avidin-biotin-peroxidase complex (ABC) showed strong specific binding to the retinal Müller cells of all species tested (human, bovine, guinea pig and rat), a weaker binding to cell bodies and proximal component of the outer segments of the photoreceptor, but no apparent binding to the distal component of the outer segments of the photoreceptor cells.

Animals↗
PubMed1984

Phenotypic expression of B-lymphocytes. 1. Identification with monoclonal antibodies in normal lymphoid tissues.

Marker expression is highly variable among different stages of B-cell activation. In peripheral lymphoid tissues, architecturally and cytologically three or four types of B cells can be identified, thus allowing an investigation of cellular surface or cytoplasmic phenotypes. Mantle zone lymphocytes of follicles are phenotypically similar, if not identical, to peripheral blood B-lymphocytes and express the following markers: B1, B2, BA-1, HLA-DR, Leu 10, A1G3, Leu 8, and T200. The germinal center is composed of two main populations, centroblasts and centrocytes which express the following markers: B1, BA-2, J5, OKT9, HLA-DR, Leu 10, and T200. This phenotype is similar to that of activated B cells or pre-B cells. Although membranous OKT10 is present in cortical thymocytes, the presence of cytoplasmic OKT10 appears to be a useful marker for plasma cells, terminally differentiated B cells, which also express A1G3 and T200. This study also revealed that a subpopulation of T cells in the germinal center express different markers (A1G3-/Leu 8-) as compared with that of most T cells in the T-dependent zone (A1G3+/Leu 8+).

Animals↗
PubMed1983

Lectin histochemistry of malignant tumors. I. Peanut agglutinin (PNA) receptors in follicular lymphoma and follicular hyperplasia: an immunohistochemical study.

Peanut agglutinin (PNA) receptors were studied in 37 cases of reactive follicular hyperplasia and 66 follicular lymphomas, using the unlabeled peroxidase-antiperoxidase (PAP) method on paraffin embedded material. Based on the binding sites of the lectin, positively stained cells were easily recognized as either cytoplasmic receptor-positive (CR+) or surface receptor-positive (SR+) cells. In the lymph node specimens, CR+ cells corresponded to macrophage-histiocytes and possibly dendritic reticulum cells; SR+ cells corresponded to lymphoid cells. Three categories of CR+ cells were noted: large, medium, and small. The large CR+ cells were present in most germinal centers from reactive nodes, but were virtually absent in neoplastic follicles. Varying numbers of medium and small CR+ cells were seen in reactive as well as neoplastic follicles. SR+ cells were present in both follicular lymphoma (64%) and follicular hyperplasia (19%). In neoplastic follicles, SR+ cells were distributed uniformly throughout every follicle in the node revealing no relation to the orientation of the node. In reactive follicles, however, the occurrence of SR+ cells was not only infrequent, but also focal, and was often associated with the polarity of the follicles. The uniform distribution of SR+ tumor cells produced a characteristic staining pattern of neoplastic follicles which, along with the disappearance of the large CR+ cells, would provide an additional feature useful in the differential diagnosis of neoplastic from reactive follicles.

Adolescent↗
PubMed1983

Rearrangement and expression of immunoglobulin genes and expression of Tac antigen in hairy cell leukemia.

The origin and exact stage of differentiation of the neoplastic cells that comprise hairy cell leukemia have remained uncertain. As Ig heavy and light chain genes must both undergo a DNA rearrangement during B-cell development but rarely do so within other hematopoietic lineages, we examined these genes in this leukemia. The neoplastic cells of all eight cases demonstrated rearranged heavy and light chain genes and, in two cases examined, contained the corresponding mRNA for heavy and light chain Ig. Consistent with this B-cell genotype, all cases displayed cell surface HLA-DR and B-cell-associated antigens. Unexpectedly, all cases demonstrated cell surface Tac antigen, which previously had been restricted predominantly to select T-cell malignancies and activated T cells. Prior studies suggested that the anti-Tac monoclonal antibody recognized a peptide associated with the binding of interleukin 2 (T-cell growth factor) in such T cells. Immunoprecipitation with anti-Tac and NaDodSO4/polyacrylamide gel electrophoresis revealed an antigen on leukemic hairy cells with a Mr of 53,000-57,000, identical in size to the receptor on activated T cells. This apparent biphenotypic status might reflect a transformation-associated expression of the Tac antigen in this leukemia. Alternatively, hairy cell leukemia may be a malignancy of a unique stage of normal B-cell differentiation in which the Tac antigen is expressed.

Antibodies, Monoclonal↗
PubMed1983

Monoclonal antibodies directed against human lymphoid, monocytic, and granulocytic cells: reactivities with other tissues.

Monoclonal antibodies (MAbs) reactive with lymphoid cells are not necessarily specific for lymphoid tissues. Forty MAbs with varying degrees of specificity in lymphoid tissue were tested against a wide battery of nonlymphoid human tissues. Cross-reactivity was identified in 18 of 41 antibodies tested. Based on their reactivities, the MAbs were classified in three groups: (1) antibodies with wide reactivities in normal nonlymphoid tissues, i.e., anti-Leu 4, anti-Leu M1, OKT9, anti-HLA-Dr, anti-Leu M2, Mo-2 (Coulter), anti-Leu 7, BA-1, BA-2, BA-3, J5, and A1G3; (2) antibodies with limited reactivities in nonlymphoid tissues (one or two tissues), i.e., OKT6, anti-Leu 10, Mo-1 (BRL), Mo-2 (BRL); and (3) antibodies without cross reactivities in nonlymphoid tissues, i.e., anti-Leu 1, anti-Leu 2a, anti-Leu 3a, OKT3, OKT10, 3A1, anti-Leu 8, TA-1, Lyt 3, B1, B2, OKMo-1, anti-Leu M3, T200. The reactions can be attributed to the presence of a similar, if not identical, epitope in related or different molecules.

Antibodies, Monoclonal↗
PubMed1983

Lymphocyte subsets in normal human lymphoid tissues.

A series of B, T, natural killer (NK) cell, and monocyte-specific monoclonal antibodies was used to determine the localization of lymphocyte subpopulations in frozen tissue sections of human lymph node, spleen, tonsil, and thymus by means of an immunohistochemical technic. In thymus, most cortical thymocytes reacted with Leu 1, Leu 2a, Leu 3a, Leu 4, Lyt 3, OKT3, and OKT6 antibodies. Except for OKT6, Leu 2a, and Leu 3a, these antibodies also reacted with medullary thymocytes. The majority (70-80%) of medullary thymocytes reacted with Leu 3a and a smaller fraction (20-30%) with Leu 2a antibody. The staining pattern of thymic medulla approximates the staining pattern of peripheral T cells. In peripheral lymphoid tissues, the majority of cells in the paracortical region of lymph node and in the periarteriolar sheath of spleen stained with Leu 1, Leu 4, OKT3, and Lyt 3 antibodies. Staining with Leu 3a and Leu 2a identified 60-80% and 20-40% of total T cells, respectively, as defined by Lyt 3 positivity. In addition, a substantial number of Leu 3a+ and Leu 7+ cells were found in the germinal centers of secondary follicles. This finding supports the importance of these subsets of lymphocytes in regulation of the human immune response. Leu 2a+ cells were rare in tissues with prominent follicular hyperplasia, but appeared in considerable number in the red pulp of spleen. In the mantle zone of lymphoid follicles, the majority of lymphocytes were positive for IgM, IgD, and B1. Approximately 60-70% of these cells bore kappa chain and 30-40% lambda chain immunoglobulin. The extracellular substance in germinal centers was positive for B1, IgG, IgM, kappa, and lambda. The majority of germinal center cells appeared to contain no surface or cytoplasmic immunoglobulins. Small mononuclear cells bearing OKM1 marker were abundant in the marginal zone of white pulp and in the red pulp of spleen but, rarely were observed in other portions of lymphoid tissues. OKM1 also reacted with granulocytes. Leu 7+ (NK) cells were rare in the thymus, but frequent in the GC of secondary follicles. The distribution of Leu 7+ cells did not correspond to staining with Lyt 3 and Leu 2a.

Antibodies, Monoclonal↗
PubMed1983

Utility of monoclonal antibodies directed against B and T lymphocytes and monocytes in paraffin-embedded sections.

Monoclonal antibodies reactive with B and T lymphocytes, monocytes, and granulocytes were applied to B-5-, Bouin's-, or formalin-fixed paraffin-embedded sections. Most antigens were destroyed or masked by fixation or embedding procedures, or both. However, T200, an antigen present in all lymphoid and hematopoietic cells, and Leu M1, an antigen in granulocytes, were well preserved in formalin-fixed tissues. Leu 1 and BA-1, antigens present on T and B lymphocytes, respectively, were preserved in Bouin's-fixed specimens. With careful selection of fixatives, identification of some T and B lymphocytes and granulocytes by monoclonal antibodies in paraffin-embedded specimens is possible.

Animals↗
PubMed1983

Hairy cell leukemia: a B cell neoplasm with a unique antigenic phenotype.

A panel of B, T, and monocyte antibodies was used to study the phenotype of hairy cell leukemia. It was found that the neoplastic cells had monoclonal surface immunoglobulins and, in addition, reacted with B1, HLA-DR, Leu 10, and Tac. Most of the above markers are features of B cell lymphocytes. However, Tac is a monoclonal antibody normally reactive with activated T lymphocytes. All other antibodies reactive with T cells were negative. An additional unexpected finding was intranuclear reactivity in 4/5 cases with an antibody to TdT. TdT enzymatic activity was not demonstrable by biochemical assay. All five cases were nonreactive with monocyte antibodies. The findings support the concept that hairy cell leukemia is of B cell lineage but demonstrates an unusual phenotype not seen in other normal or neoplastic B lymphocytes.

Adult↗
PubMed1983

A comparison of ABC, unlabeled antibody and conjugated immunohistochemical methods with monoclonal and polyclonal antibodies--an examination of germinal center of tonsils.

Staining of lymphoid tissues with anti-immunoglobulin antibodies often is complicated by heavy interstitial staining and potential unwanted binding through Fc receptors. This problem is aggravated in the germinal center because of an unusually intense extracellular staining. In an attempt to examine a variety of staining methods, we found both poly- or monoclonal antibodies produced satisfactory results only if a suitable method was employed, such as a two-step or three-step avidinbiotin-peroxidase complex (ABC) method. Other staining technics for example, indirect conjugate or four-layer PAP methods, failed to provide a clean background. The use of F(ab')2 fragments did not significantly improve the staining quality, indicating that the role of the Fc receptors in inducing nonspecific staining is not significant in acetone-fixed frozen tissues. Germinal centers also were studied with a panel of monoclonal and polyclonal anti-Ig antibodies, and the results indicated that the number of surface or cytoplasmic Ig-positive cells in the germinal center is variable from one follicle to another. IgG+ cells are generally sparse (less than 10%) and are scattered in the light zone of follicles. IgA+ cells constitute about 0-10% of the total cell population and tend to be distributed randomly either in the dark or light zones. IgM+ and IgD+ cells may be scanty (less than 10%) or abundant (50-70%). The IgM+ and IgD+ cells tend to localize in the dark zone of the follicles. The results indicate that, depending on the stage of differentiation or transformation of the germinal center, s-Ig or c-Ig expression is highly variable.

Animals↗
PubMed1983

Terminal deoxynucleotidyl transferase in non-Hodgkin's lymphoma.

To investigate the specificity of terminal deoxynucleotidyl transferase (TdT) as a marker for lymphoblastic lymphoma in the non-Hodgkin's lymphomas, the authors assayed malignant cells from 142 patients with non-Hodgkin's malignant lymphoma, as well as cells from normal lymphoid tissue controls. Neoplastic cells from all 25 patients with lymphoblastic lymphoma were TdT positive. Of the remaining 117 patients with malignant lymphoma of other histologic subtypes, only one patient, with diffuse, large cell immunoblastic lymphoma, had TdT-positive cells. This patient's cells had positive results only by the enzyme assay and were TdT-negative by both immunofluorescence and immunoperoxidase assays. Of 56 patients whose cells were studied by both enzyme assay and an immunoassay method for TdT detection, a discordant result was obtained only on cells from the previously mentioned patient with large cell immunoblastic lymphoma. To determine the optimal immunoassay method, the authors studied malignant cells from 24 patients with non-Hodgkin's lymphoma for the presence of TdT by three different methods: immunofluorescence, peroxidase-antiperoxidase, and avidin-biotin-complex immunoperoxidase. Fifteen of the 24 patients had lymphoblastic lymphoma. The avidin-biotin-complex method produced superior staining, with no false-negative results. False-negative results were seen with both the immunofluorescence and peroxidase-antiperoxidase methods. Other advantages of the avidin-biotin-complex method included a marked decrease in background and non-specific staining and the ability to use higher dilutions of antisera.

Clinical Enzyme Tests↗
PubMed1983

Bromodeoxyuridine in tumors and chromosomes detected with a monoclonal antibody.

Using a monoclonal antibody to bromodeoxyuridine (BUdR) and immunohistochemistry, we measured the incorporation of this thymidine analogue into the DNA of human normal and malignant cells exposed in vivo. BUdR given as a constant intravenous infusion for 12 or 24 h daily for up to 13 d resulted in a steady-state plasma level of 10(-6) M during the infusion. We demonstrated extensive incorporation of BUdR into both normal skin, normal bone marrow, and malignant melanoma cells. In addition, this infusion of BUdR was adequate to identify sister chromatid exchanges from human marrow chromosomes exposed in vivo. Using this constant infusion, significant but reversible (acute) toxicity was observed with myelosuppression and skin photosensitivity. These techniques, which are considerably less cumbersome and time-consuming than the use of radioactive isotopes of thymidine, can be used for further human studies of cell kinetics and chromosomal replication in both normal and malignant cells.

Animals↗
PubMed1983

Histochemical studies on lectin binding in reactive lymphoid tissues.

Using the avidin-biotin-labeled peroxidase complex (ABC) method, the staining reaction of a panel of 12 biotin-labeled lectins was studied in formalin-fixed, paraffin-embedded reactive lymph nodes and tonsils. Varying degrees of lectin binding were observed in lymphoid cells and macrophage-histiocytes with Concanavalin ensiformis (Con A), Lens culinaris (LCA), Phaseolus vulgaris (PHA), Pisum sativum (PSA), Ricinus communis (RCA), and Triticum vulgaris (WGA) agglutinins, but no evidence of binding was observed with Dolichos biflorus (DBA), Bandieraea simplicifolia (BSA), Arachis Hypogaea (PNA), Glycine soja (SBA), Sophora japonica (SJA), and Ulex europaeus (UEA) agglutinins. Three major patterns of binding were seen: the reaction products occurred along the plasma membranes (membranous), were confined to one pole of the cell membrane (cap-like), or were present diffusely in cytoplasm (cytoplasmic). The cells showing membranous and cap-like staining patterns corresponded to the lymphoid cells, as did the cytoplasmic to plasma cell and macrophage-histiocytes. Cap-like staining was observed on the lymphocytes at B and T cell areas with all six lectins. Thus, the presence of cap-like staining may not be useful for discrimination between B and T cells. Membranous staining, in contrast, was limited to lymphocytes of follicles (B cells) with PSA and LCA, and to germinal center cells with PHA, WGA, Con A, and RCA also reacted with the membrane of T-cell. The cytoplasmic staining reaction of macrophage-histiocytes varied markedly from one lectin to the other. Our study indicates that the carbohydrate moiety of the cells retains their binding sites for lectins through routine processing, providing a means of valid retrospective studies. Furthermore, these observations suggest that each lectin, despite its identical inhibitory sugar, should be tested for its unique reaction pattern, which is not predictable from the data derived from cell suspension studies.

Histocytochemistry↗
PubMed1983

Antithymocyte globulin reacts with many normal human cell types.

Antithymocyte globulin (ATG) is frequently effective therapy for aplastic anemia. Its mechanism of action is often assumed to be upon a lymphocyte inhibitor of hematopoiesis. However, specificity for T lymphocytes would not be anticipated from consideration of the method of preparing ATG. In fact, using flow microfluorometry and fluorescence immunohistochemistry, we have found that ATG binds to virtually all circulating lymphocytes, granulocytes, and platelets, as well as to bone marrow cells. Extensive absorption of ATG with either granulocytes or lymphocytes does not eliminate reactivity with the opposite cells, indicating that ATG recognizes some distinct antigens on each cell type. Treatment of cells with ATG blocks the binding of monoclonal antibodies directed against either lymphocyte differentiation or histocompatibility antigens. ATG also binds to visceral tissues, including thymus and testis cell membranes and the nuclear and cytoplasmic components of tonsil, kidney, liver, breast, lung, and intestine. In vitro cytotoxicity of ATG was demonstrated for both T and non- T lymphocytes and platelets. Despite its name, ATG is not specific for a particular cell type, and it would be premature to conclude that its effect is mediated through a specific lymphocyte population.

Antigen-Antibody Reactions↗