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Biomedical subjects

C C Hsu

Publications and source records attributed to C C Hsu.

At least 217 records · Page 12Linked to original sources

Detection of B-lymphocyte (B-cell)-associated antigens on human leukemic lymphocytes. Masking of membrane antigens.

An indirect immunofluorescent technic has been used for rabbit antisera (anti-EP) that demonstrated complement-dependent cytotoxicity against human leukemic lymphocytes but not against normal blood lymphocytes. With the immunofluorescent technic, the antisera were found to react with 2--23% of normal blood lymphocytes. Simultaneous staining of normal cells with anti-EP and for surface immunoglobulins (SIg) on bone-marrow-derived B-cells showed that the proportions of stained cells were similar to percentages of cells stained by anti-EP alone or for SIg alone. The percentage of anti-EP reactive cells also approximated the percentages of cells reactive to a known antiserum to human B-cell associated, or Ia-like, antigens. The anti-EP reacted with lymphoblastoid cells from two B-cell lines lacking the Epstein-Barr viral genome. The antigens detected by anti-EP probably are B-cell-associated. The anti-EP intensely stained neoplastic cells of acute or chronic lymphocytic leukemia and lymphosarcoma-cell leukemia. Cells from two patients with chronic lymphocytic leukemia and from two patients with acute lymphocytic leukemia showed increased intensity of anti-EP staining and/or increased proportions of stained cells following overnight incubation in culture medium, compared with the preincubation samples. This observation suggests the presence of a "blocking component(s)" on cell surfaces, which interfered with anti-EP reactivity. After overnight incubation, the component might have been removed from the antigenic sites on cell surfaces. Further studies of leukemia lymphocytes using anti-EP for the cell-bound "blocking component" may reveal important pathogenetic mechanisms.

Antigens, Surface↗

Antisera against leukaemia-associated antigens on human lymphocytes.

Antisera were raised in rabbits against leukaemic lymphosarcoma (LSL) cells which carried surface markers of both thymus-derived T lymphocytes (T cells) and bone marrow-derived B lymphocytes (B cells). After absorption with leucocytes, erythrocytes and serum proteins from normal individuals, the antisera demonstrated significant complement-dependent cytotoxicity against leukaemic cells from patients with acute lymphoblastic leukaemia (ALL) (9/11), LSL (7/9) and chronic lymphocytic leukaemia (CLL) (9/12), with an antibody titre of 1:64 or greater. The antisera did not react with: (a) blood lymphocytes from clinically healthy individuals (0/23), patients with ono-lymphoproliferative disorders (0/8) and normal umbilical cords (0/3), (b) normal lymphocytes stimulated by pokeweed mitogen (0/7), allogeneic lymphocytes (0/3), fetuin (0/1), purified protein derivative (PPD) (0/2), and candida antigen (0/1); (C) normal marrow cells (0/3), (D) normal thymocytes (0/2) and (E) leukaemic cells from patients with acute myeloblastic (AML) (0/10) and chronic granulocytic leukaemia (CGL) (0/3). However, the antisera did react with lymphoblastoid cells from continuous B-cell lines derived from an AML patient and from a non-leukaemic individual and, to a lesser extent, with lymphocytes from patients with infectious mononucleosis. The antisera also reacted with lymphocytes from chronically infected tonsils. Cytotoxicity of the antisera against lymphoblastoid and tonsillar cells was inhibited by ALL and CLL cell-lysates; and, conversely, cytotoxicity against ALL cells was inhibited by the lymphoblastoid cell extract. In contrast, a cell lysate or extract from normal inhibited by the lymphoblastoid cell extract. In contrast, a cell lysate or extract from normal lymphocytes did not inhibit cytotoxicity toward lymphoblastoid, tonsillar or ALL cells. Cytotoxicity of the antisera was neutralized by a goat anti-rabbit IgG (GAR IgG). These results suggest that the antisera contained antibodies reactive with antigens possibly common to neoplastic lymphocytes, tonsillar cells, lymphoblastoid cells and some lymphocytes from patients with infectious mononucleosis.

Animals↗

Comparative inhibitory effects of serum on lymphocyte responses to mitogenic stimulation.

The effects of sera from pregnant women, human umbilical cords and nonpregnant healthy control individuals on human lymphocyte responses to phytohemagglutinin (PHA), pokeweed mitogen (PWM) and allogeneic lymphocytes (MLR) are described. Maternal sera invariably inhibited lymphocyte responses to PHA. In MLR and PWM-stimulated lymphocyte responses, however, some maternal sera had pronounced inhibitory effect while other maternal sera had none. Similar dissociation of inhibitory effects of lymphocyte responses to PHA and to PWM or in MLR was noted in some cord sera but not in the control sera we studied. The observations may reflect different serum factors impinging upon different lymphocyte subpopulations responsive to different mitogens. Preliminary attempts to relate the serum inhibitory effects to various serum components revealed that inhibition of MLR appeared to correlate with increases in alpha-2-globulins and beta-globulins. In contrast, inhibition of PHA responses was not similarly related to any one or two specific serum constituents.

Blood↗

Peripheral blood B-lymphocyte abnormalities associated with hyperthyroidism of Graves' disease.

Proportions of peripheral blood thymus-derived T lymphocytes (T cells) and bone-marrow-derived B-lymphocytes (B cells) were studied in twelve hyperthyroid patients and ninety-nine non-hyperthyroid control subjects including thirty-nine healthy individuals and sixty patients with various disorders. All hyperthyroid patients had Graves' disease and eight were untreated. The sheep erythrocyte (E)-rosetting technique was employed for enumeration of T cells and the immunofluorescent technique was used for identification of lymphocytes with surface immunoglobulins (SIg), a marker for B cells. The results showed that hyperthyroid patients had higher percentages of lymphocytes stainable for SIg, whereas their T-cell proportions were the same as our control values. In addition, approximately half or more of the fluorescein stainable lymphocytes reacted with each of the five antisera against individual heavy chain determinants, including the epsilon chain, indicating the presence of more than three Ig determinants on the same cell. The fluorescein-stainable cells did not form E rosettes. Blocking of the Fc receptor on lymphocytes by incubating the patients' cells with heat-aggregated human IgG or heated goat anti-bovine serum albumin (anti-BSA) failed to abolish the subsequent fluorescent staining of the cells. Incubation of patients' lymphocytes with non-fluorescent anti-epsilon inhibited the subsequent staining of cells with fluoresceinated anti-epsilon but not staining with fluoresceinated anti-mu or anti-gamma. Thus, the study revealed B-cell abnormalities associated with hyperthyroidism, manifested by the simultaneous presence of multiple Ig classes, including IgE, on a single B cell. Results of studies of incubation of the patients' plasmas with lymphocytes from health individuals and studies of SIg by overnight culture of the patients' lymphocytes with or without prior trypsinization suggested that the SIg was generated endogenously by the cell on which it resided.

Adult↗

Massive polyclonal hyperimmunoglobulinemia E, eosinophilia and increased IgE-bearing lymphocytes.

A patient (E.M.) with marked eosinophilia and hyperimmunoglobulin E (IgE) has been followed for 4 years. Peripheral blood eosinophilia reached levels in excess of 18,000 cells/mm3 and serum IgE concentration increased to more than 210,000 units/ml (about 0.48 mg IgE/ml). The IgE has both lambda and kappa light chains and is therefore considered polyclonal. The patient has an increase in peripheral blood lymphocytes which stain for surface IgE. Transfer of the patient's plasma (plasmsEM) to a rhesus monkey did not induce peripheral boood eosinophilia. The half life of IgEEM in a rhesus monkey was 2.2 days, which is similar to the half life of myeloma IgE in human subjects. The condition was not associated with defined morbidity except for mild persistent pruritus. Various studies revealed no evidence for atopic parasitic, immune deficiency or neoplastic disease.

Adult↗

In vitro production of IgE by lymphocytes from a patient with hyperimmunoglobulinaemia E, eosinophilia and increased lymphocytes carrying surface IgE.

The peripheral blood lymphocytes of a patient with massive hyperimmunoglobulinaemia E were used for in vitro studies. The serum IgE ranged from 140,000-210,000 u/ml. Peripheral blood lymphocytes had approximately 7% of cells staining for surface IgE. When these cells were cultured in vitro, IgE was produced as measured by the double antibody radioimmunoassay technique. The total IgE produced ranged from 140 to 484 units per 24 hr in different cultures. IgE production was greatest in the first 24 hr of culture and declined progressively thereafter. Some cultures still had measurable IgE at 48 hr. If the lymphocytes staining for surface IgE were the cells producing the IgE, it was estimated that between 1-7 and 2-8 molecules per cell per second were produced. No definite effect of concanavalin A, pokeweed mitogen or phytohaemagglutinin on in vitro IgE production could be demonstrated under the conditions of these experiments.

Cell Fractionation↗