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Biomedical subjects

S K Oh

Publications and source records attributed to S K Oh.

At least 55 records · Page 3Linked to original sources
PubMed1990

Changes in thyrotropin receptor antibody after subtotal thyroidectomy in Graves' disease: comparison with the degree of lymphocytic infiltration in the thyroid.

To evaluate changes in TSH receptor antibody after surgery in Graves' disease and its relationship with the degree of lymphocytic infiltration, serial serum levels of TSH receptor antibody were measured before and after the subtotal thyroidectomy in 50 patients with Graves' disease. In 22 (44%) out of 50 patients, thyrotropin binding inhibitor immunoglobulin (TBII) levels gradually decreased and disappeared completely within 12 months after surgery (TBII disappearing group). Twenty-eight (56%) patients showed persistent TBII activity and their levels were not changed until 12 months after surgery (TBII persistent group). The changes of thyroid stimulating antibody (TSab) levels were very similar to those of TBII in both groups. The thyroidal lymphocytic infiltration was more prominent in the TBII disappearing group. The degree of the decrease of TBII levels after surgery correlated with the grade of thyroidal lymphocytic infiltration. There was no significant difference of TSH receptor antibody (both TBII and TSab) levels between the thyroid and peripheral venous blood. These data suggest that the persistence or disappearance of TSH receptor antibody after surgery may reflect the difference between patients in whom the thyroid is the major site of TSH receptor antibody and those in whom additional sites of TSH receptor antibody synthesis exist.

Adolescent↗
PubMed1990

Poorly differentiated carcinoma of the thyroid retrospective clinical and morphologic evaluation.

Five thyroid carcinomas showing clinically aggressive biologic behavior were retrospectively reviewed to evaluate the possible presence of morphologic differences from conventional thyroid carcinomas. They were originally diagnosed as follicular carcinomas, medullary carcinoma, papillary carcinoma, and mixed papillary and medullary carcinoma. There were three males and two females. The age at the time of initial diagnosis ranged from 36 years to 67 years (mean 56 years). The size of the tumor varied from 4.5cm to 10cm (mean diameter 7cm). One patient died of brain metastasis four years after the initial therapy and the other four patients are still alive with local recurrences and/or metastases to bone, spinal cord, lung, and buttock. Histologically these lesions are categorized into two different groups: insular variant and columnar cell variant. Insular variant was characterized by well-defined nests (insulae) that are composed of small, uniform cells, frequent tumor necrosis, and hyalinization of the stroma. Columnar cell variant was characterized by tall columnar cells with marked nuclear statification. All five cases stained positively for thyroglobulin and negatively for calcitonin. With the above clinical and histopathological findings, we interpreted these lesions as a poorly differentiated carcinoma, biologically in an intermediate position between well differentiated and anaplastic carcinomas. The rapid and often fatal outcome associated with these variants of poorly differentiated carcinoma warrants aggressive treatment at the time of diagnosis.

Adenocarcinoma↗
PubMed1989

Monoclonal antibody to SER immune suppressor detects polymeric forms of haptoglobin.

A series of monoclonal antibodies has been developed which is directed to a serum immunosuppressive factor, known as suppressive E-receptor factor (SER). SER, purified from the body fluids of cancer patients, is a polymeric form of haptoglobin, which is 100-1,000 times more potent an immunosuppressor than normal plasma haptoglobin and is immunochemically analogous to the neonatal form. Unlike the neonatal haptoglobin found in cord blood, SER, however, does not contain bound-hemoglobin. One group of monoclonal antibodies described in this study detects the polymeric forms of haptoglobin (SER) under non-denaturing conditions, but fails to recognize SER under the denaturing conditions of SDS-PAGE. A second group of monoclonal antibodies reacts only with the alpha subunit of haptoglobin but not with the beta subunit; in contrast, the commercially prepared polyclonal antisera to haptoglobin react with both the alpha and beta subunit. The average level of SER in normal human plasma (n = 19) was 1.0 micrograms/ml, regardless of age or sex. Since macrophages appear to secrete SER but do not synthesize haptoglobin, SER may represent an oxidized form of plasma haptoglobin generated from macrophages activated during an inflammatory response. These studies suggest that SER may be a negative feed-back regulator of immune response produced by activated macrophages.

Adult↗
PubMed1988

Role of a SER immune suppressor in immune surveillance.

A potent immunosuppressor factor, known as SER (suppressive E-receptor factor) has been identified in the body fluids of cancer patients. SER has been proven to be immunochemically analogous to the fetal form of haptoglobin. In this paper, we examine the role of SER immune suppressor in the immune surveillance mechanism of the host, using an affinity-purified SER. As shown in this study, SER, at microgram/ml concentrations, inhibits the T-cell proliferation induced with either monoclonal or polyclonal T-cell activators in vitro in human, and also inhibits the primary antibody response to T-dependent antigens in vivo in mice. Likewise, SER also inhibits the immunoglobulin synthesis of human B lymphocytes induced by a B-cell mitogen, pokeweed mitogen, in the presence of a tumour promoter, phorbol myristate acetate (PMA). In contrast to the T-dependent antibody response in vivo in mice or T-dependent mitogen response in vitro in human, SER does not interfere with the T-independent antibody responses to DNP-Ficoll or TNP-LPS in mice. SER also interferes with the natural killer cell function of human peripheral blood mononuclear cells. Although SER inhibits the phagocytic functions of human peripheral neutrophils, it requires at least 10-20 times the concentration of SER present in normal human plasma. Since this concentration of SER is attainable in the sera of solid tumour-bearing patients, highly elevated levels of SER could predispose the patients to microbial infections as well. This study demonstrates that purified SER manifests multi-faceted down-regulatory effects on the defence mechanism of hosts, thereby it could compromise the patients' cell-mediated immunity in vivo.

Animals↗
PubMed1987

An analogy between fetal haptoglobin and a potent immunosuppressant in cancer.

In spite of the numerous reports indicating the presence of humoral immunosuppressive factors in cancer patients, only a few of these factors have been biochemically identified. Furthermore, their role as effective immunosuppressors in vivo remains to be established. Our laboratory has attempted to isolate and identify the major immunosuppressive factor in the malignant effusions derived from ovarian and lung cancer patients. We have previously demonstrated that the Mr 52,000 immunosuppressive factor isolated from the ascites fluid of an ovarian cancer patient inhibited T-dependent immune responses in vivo and in vitro including the inhibition of E-rosetting. Thus, this immunosuppressive factor was named "suppressive E-receptor" (SER). Our current study demonstrates that this SER factor purified from malignant effusions derived from ovarian, lung, or head and neck cancer patients had a common component which dissociated equally into Mr 38,000-42,000 and 17,000-19,000 moieties on sodium dodecyl sulfate-polyacrylamide gel electrophoresis under vigorous reducing conditions. Electroelution of these two components followed by a limited amino acid sequence determination revealed these two components to have N-terminal amino acid sequences identical to the beta and alpha 2 subunits of normal adult haptoglobin. Immunoelectrophoresis of SER using a polyclonal antiserum to neonatal cord blood demonstrated that SER, unlike normal haptoglobin, has slower electrophoretic mobility than the normal adult haptoglobin. Western blotting analysis of SER separated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis under denaturing conditions failed to recognize a monoclonal antibody directed specifically to SER. However, this monoclonal antibody exclusively reacted with the SER separated by an analytical polyacrylamide gel electrophoresis gel under nondenaturing conditions while normal adult haptoglobins or purified but denatured haptoglobin obtained from the same malignant fluid as SER all failed to react with this antibody. Thus, SER appears to bear an additional epitope(s) that is absent in normal adult haptoglobin. Since the SER as well as the neonatal haptoglobin have at least 100 to 1000-fold more potent immunosuppressive activity than the normal adult haptoglobin, this additional epitope(s) present in SER may be responsible for the potent immunosuppressive property of SER.

Amino Acid Sequence↗
PubMed1987

Tumor regression and temporary restoration of immune response after plasmapheresis in a patient with recurrent oral cancer.

A major response to plasmapheresis is reported in a patient with advanced, recurrent squamous cell cancer of the oral cavity, similar to that previously reported in three of six comparable patients. Tumor regression followed temporary reduction of inhibition of normal lymphocyte response to phytohemagglutinin (PHA) by the patient's serum (from 99% to zero) and partial restoration of the patient's lymphocyte response (from 2% to 38% of control). The IgE level rose both overall and during some exchanges; this correlate of tumor response had been noted earlier. The tumor showed extensive necrosis, but the clinical effects were relatively short-lived and the patient died 11 weeks later. Biopsy specimens taken early in apheresis showed intense new infiltration of tumor by lymphocytes and monocytes; later biopsy specimens showed predominantly plasma cells with trapping and lysis of tumor cells. No other anti-cancer therapies had been used for 16 months before this trial, and no replacements were given other than saline and albumin.

Antigens, Surface↗
PubMed1987

Biological properties of suppressive E-receptor factor on lymphokine function.

A potent immunosuppressive factor isolated from malignant ascites fluids showed serological cross-reactivity with the E-receptor of human peripheral blood T lymphocytes. Thus, this factor was named suppressive E-receptor (SER) factor. In this study, we examined the effect of this immunosuppressor, SER, on lymphokine functions of human mononuclear cells participating in polyclonal T cell activation. SER is active at nanomolar concentrations in vitro and the inhibitory effect of SER was most pronounced when added at the initiation of stimulation with phytohemagglutinin or anti-T3 antibody. Concomitant with the inhibition on PHA-induced DNA synthesis, lymphocytes that were treated with SER failed to progress beyond G1 phase of cell cycle. These growth-arrested cells did expire after 7 days of culture in vitro. This anti-proliferative effect of SER was more easily demonstrated with normal lymphoid cells in culture than transformed cells or fibroblast cells. SER effectively interfered with the lympho-proliferative properties of interleukin 2 (IL 2) on human peripheral blood mononuclear cells and an IL 2-dependent murine cytotoxic T cell line. However, excess quantities of exogenous IL 2, especially when added in conjunction with IL 1, were able to partially overcome the ability of SER to inhibit T cell proliferation. In contrast to the inhibition on DNA synthesis of human lymphoblasts, expression of IL 2 receptor was only minimally inhibited by SER during the first 24 h of culture (24% inhibition at 12 h and 34% inhibition at 24 h) but it was followed by full expression of IL 2 receptor by 48 h. Thus, SER merely reduced the rate of expression of IL 2 receptor and was not able to inhibit the transcription of new message from activated T lymphocytes. Taken together, these studies indicate that SER acts as a noncytolytic anti-proliferative factor on immune responses that are mediated by T cells. SER appears to act on a relatively late event during T cell activation, perhaps on some portion of the DNA replication pathway.

Cell Line↗
PubMed1986

Modulation of E-receptor expression on activated T lymphocytes.

Our study indicated that the newly synthesized E-receptor, as measured with 125I-labeled monoclonal anti-E receptor antibody, on activated T lymphocytes were responsible for forming stable E-rosettes at 37 degrees C. Maximum induction of new E-receptor expression required at least 50 hr of culture with polyclonal T-cell activators, phytohemagglutinin, or phorbol myristate acetate. Polyclonal B-cell activator, lipopolysaccharide were not able to induce new E-receptor expression on the surface of T lymphocytes. The expression of the new E-receptor paralleled with the induction of Tac antigen expression. Interleukins 1 and 2 or Interferon-gamma were not able to initiate the induction of new E-receptors. However, a neuropeptide, endorphin exhibited biphasic effect on modulating the E-receptor expression, in the absence of polyclonal activators. As is the case with Tac antigen expression, induction of new E-receptor antigen may be a marker for activated T lymphocytes.

Animals↗
PubMed1985

Plasma exchange in six patients with advanced cancers of the head and neck.

Six patients with advanced squamous cell cancers of the head and neck, with serum IgA greater than or equal to 400 mg/dl and IgE less than or equal to 1000 IU/ml, underwent a trial of six 2-liter plasma exchanges over a 2-3-week period. Disease progressed in patients 1, 2, and 4, who died on days 44, 72, and 159. The tumor in patients 3 and 6 regressed significantly, repeatedly in patient 3 over each of four courses of apheresis. Tumor recurred in both patients after cessation of treatment, and they died at days 420 and 79. Patient 5, with inoperable disease, received full-dose radiotherapy immediately following the course of apheresis, and showed complete response in the primary lesion and a major response in the extensive lymph node metastases, dying on day 421 of apparently unrelated causes. Serum IgE in the three patients experiencing tumor regression rose paradoxically during plasmapheresis. Only patient 3 had an elevated level of soluble E-receptor suppressor factor prepheresis; the serum of patient 6 was lymphocytotoxic prepheresis but this activity decreased or disappeared during each of the exchanges studied. Controlled trials are now indicated.

Aged↗
PubMed1985

Quantification of soluble E-receptor in the serum of patients with various diseases and its accompanying in vitro immunosuppression in neoplasia.

Evidence in the literature indicates that soluble E-receptor in the serum may modulate T-dependent immune response. We have developed a solid-phase radioimmunoassay to measure the soluble form of E-receptor from various sources. The assay detects solubilized antigens derived from E-receptor-bearing T lymphocytes and not with non-E-receptor-bearing B lymphocytes. The sensitivity limit of the assay is 0.1 ng/ml of purified E-receptor antigen. Using this assay, one can show that the T-cell mitogen phytohaemagglutinin stimulated both lymphocytes and cells of the resting human T-cell lymphoma cell line Jurkat to shed or secrete E-receptor into the culture medium. Results of the radioimmunoassay performed on human sera indicated that some patients with Hodgkin's disease, melanoma, sarcoma, or acute or chronic lymphocytic leukaemia had elevated levels of this antigen in their serum, whereas normal human sera registered lower levels. Elevated levels of the soluble form of E-receptor in the serum were suggestive of an in vitro assessment of their immunosuppressive activity. These results indicate that activation of T-cell immunity in vivo may result in humoral immunosuppression.

Animals↗
PubMed1985

E receptor-related immunosuppressive factor in malignant pleural fluid and plasma: molecular mechanism of action on DNA-polymerase-alpha.

We previously purified a potent serum suppressor factor from malignant ascites fluid and showed that it had serologic cross-reactivity with E receptor of human T lymphocytes. We termed this factor "suppressive E receptor factor" (SER). Subsequent studies on SER showed that SER interfered with the production of interleukin 1 and 2 as well as interfering with their activities on target cells. However, SER was not directly cytotoxic to lymphocytes. In this study, we compared the inhibitor of DNA-polymerase (IDP) activity with the suppressive activity on phytohemagglutinin-induced DNA synthesis on intact cells. These two activities were closely correlated (with a linear correlation coefficient of 0.988) even with the whole plasmas derived from cancer patients. Fractionation and purification of IDP activity identified it with SER of a similar potency. Therefore, SER appeared to exhibit its potent immunosuppressive effect via its direct interference on DNA-polymerase activity. Furthermore, the DNA-polymerase inhibitory activity of SER appeared to be specific to DNA and it did not affect the RNA-polymerase activity. SER inhibition of DNA polymerase activity with respect to DNA primer as well as with the nucleotide substrate. Direct inhibition on DNA-polymerase-alpha activity may be one of the possible mechanisms of action of SER on lymphocyte proliferation.

Binding Sites↗
PubMed1984

Quantitation of serum suppressor factor, related to the erythrocyte receptor of human peripheral blood T lymphocytes as measured by radioimmunoassay.

A solid phase radioimmunoassay for a serum suppressor factor has been developed. The factor was previously purified from malignant ascites fluids and shown to be related to the sheep erythrocyte receptor of human peripheral blood T lymphocytes. This humoral suppressor factor has been termed suppressive E-receptor factor. Using this assay, it was demonstrated that both ascites fluids and sera derived from patients with solid tumors contain elevated levels of this factor compared to similar specimens from patients with a variety of nonmalignant diseases. The concentration of this SER factor does not correlate with serum immunoglobulin G levels but it does correlate with the ability of sera from individual patients to inhibit phytohemagglutinin-induced DNA synthesis by normal human peripheral blood T lymphocytes. Kinetically, this suppressive E-receptor factor directly competes with monoclonal antibody directed to the sheep erythrocyte receptor of human peripheral T lymphocytes and exhibits noncompetitive-type inhibition of DNA synthesis induced by phytohemagglutinin.

Antibodies, Monoclonal↗
PubMed1984

Suppression of tumor cell growth in vitro by a bone marrow factor.

A supernatant factor derived from monodispersed bone marrow cells was tested for its ability to inhibit the growth of tumor cell lines and freshly dispersed hemopoietic cells in vitro. The supernatant fluid from bone marrow cells was capable of inhibiting the mitogenic response of rat thymocytes to concanavalin A. It also was capable of inhibiting growth of HeLa cells, Sarcoma 180, EL-4, and BALB/c K3T3 tumor cell lines as measured by thymidine incorporation. The factor did not inhibit the growth of normal thymus cells, marrow cells, or WI-38-SV40, and F-46 tumor cell lines. From data derived from 51Cr release assays, the factor appears to be selectively cytoreductive. Bone marrow supernatant factor is stable to heat (100 degrees for 10 min) and trypsin digestion, but is sensitive to carboxypeptidase B digestion. Molecular weight estimation by gel filtration chromatography on a Sephadex G-75 column indicates its apparent molecular weight to be less than 12,000. Bone marrow supernatant factor appears to function across species and strain barriers.

Animals↗
PubMed1981

Purification and characterization of an immunosuppressive factor from ovarian cancer ascites fluid.

A nonspecific immunosuppressive factor present in malignant (ovarian carcinoma) ascites fluid has been purified by acid extraction from a high molecular weight (greater than 20000) complex followed by preparative isoelectric focusing on Bio-lyte media. It is an acidic protein (pI = 3.6) of mol. wt. 50000 to 52000 as estimated by gel filtration and composed of subunits of 25000 to 26000 estimated by sodium dodecyl sulfate polyacrylamide gel electrophoresis, under reducing conditions. It inhibits the phytohemagglutinin-dependent mitogenic response of normal peripheral blood lymphocytes by 50% at 2 microgram/ml concentrations in vitro and suppresses 80% of the plaque-forming cell response to sheep erythrocytes at 100 microgram per mouse in vivo. Its chemical identity with any of the known plasma proteins has not been established. Its failure to stain with periodic acid Schiff's reagent indicates its minimal content of carbohydrates. It is susceptible to tryptic and pronase digestion but insensitive to deoxyribonuclease and ribonuclease digestion. A smaller suppressive factor identified in the same fluid appears to be a lymphotoxin; it differs from the acid-extracted nonspecific suppressive factor in its lack of susceptibility to trypsin.

Acids↗
PubMed1981

Nonspecific immunosuppressive factors in malignant ascites: further characterization and possible relationship to erythrocyte receptors of human peripheral T cells.

Nonspecific suppressor factor has been purified from malignant human ascites through partial delipidation, ammonium sulfate precipitation, ACA-22 gel filtration followed by goat anti-human IgG immunoadsorbent chromatography. Molecular weight estimated by SDS-PAGE under mild reducing conditions is 50,000 and 25,000 under vigorous reducing conditions. It inhibits PHA, Con A, and PWM responses of peripheral lymphocytes by 50% at microgram concentrations per milliliter in vitro and inhibits plaque-forming cell response to SRBC at 100 microgram/mouse in vivo. It also inhibits 2-way mixed lymphocyte reactions and natural killer cell activities. It inhibits SRBC rosette formation of peripheral T cells and appears to be an erythrocyte receptor of peripheral T cells.

Animals↗