Biomedical subjects

C S Koh

Publications and source records attributed to C S Koh.

At least 91 records · Page 5Linked to original sources

PubMed1994

Tumor concentration and distribution of carcinoembryonic antigen measured by in vitro quantitative autoradiography.

UNLABELLED: One of the most critical factors in successful immunoscintigraphy and radioimmunotherapy is the local concentration and distribution of the target antigen. The purpose of this study was to evaluate the concentration and distribution of carcinoembryonic antigen (CEA) in various carcinomas. METHODS: In vitro quantitative autoradiography was performed in carcinomas of the stomach (32 cases), colon (20 cases), breast (29 cases) and lung (26 cases). Frozen tumor sections were incubated with varying concentrations of 125I-labeled monoclonal antibody (Mab) CEA-79.1 (IgG2a), which is specific for CEA. Digitized autoradiographic images from these sections were compared to adjacent H & E and immunoperoxidase-stained sections. Computer analysis of specific antibody binding quantitated the maximal value (Bmax), which is equal to the concentrations of CEA. RESULTS: Stomach cancer expressed CEA in 31 cases (97%). All colon cancer specimens exhibited CEA and breast cancer expressed CEA in 24 cases (83%). In adenocarcinoma of the lung, CEA was measured in all specimens. The concentration of CEA did not vary significantly among the pathologic types or among the various degrees of differentiation in each carcinoma. CEA was expressed homogeneously in adenocarcinomas of the colon and lung. However, CEA exhibited a heterogeneous distribution in a significant number of breast cancer (42%) and bronchogenic squamous-cell carcinoma (78%) specimens. CONCLUSIONS: CEA was expressed in most cases of stomach, colon, breast and lung carcinomas. These carcinomas, however, exhibited wide variation in the concentration and distribution of CEA expression. The concentration and distribution of CEA in a particular tumor type should be considered before undertaking tumor targeting methods.

Adenocarcinoma↗

PubMed1993

Radioimmunoscintigraphy of advanced gastrointestinal carcinomas employing I-131 labeled CEA-79 monoclonal antibody.

CEA-79 is a murine IgG2a type monoclonal antibody (MoAb) generated using purified CEA from culture supernatants of a human colon cancer cell line, LS174T. The association constant and immunoreactivity of the I-131 labeled CEA-79 ranged from 2.0 to 3.2 x 10(9) l/mole, and from 54 to 74%, respectively. The purpose of this study was to evaluate the feasibility of radioimmunoscintigraphy employing MoAb CEA-79 in patients with advanced gastrointestinal carcinomas. Two mgs of MoAb CEA-79 was labeled with 111 MBq (3 mCi) of I-131, and infused intravenously in 6 stomach cancer and 16 colon cancer patients. Out of 6 patients with stomach cancer, immunoscintigraphy was able to detect the tumors in 4 cases. However, immunoscintigraphy found out tumors in all patients with colon cancer. Moreover, 1 patient with stomach cancer and 2 patients with colon cancer showed increased uptake of MoAb in the tumor lesions despite normal serum levels of CEA. We could conclude that this antibody has a potential as a new imaging agent for the diagnosis of gastrointestinal carcinoma.

Adult↗

PubMed1993

Anti-lymphocyte antibodies and circulating immune complexes in the sera of patients with myelopathy associated with human T lymphotropic virus type-I.

We measured levels of circulating immune complexes in the human T-lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) by Raji cell assay and C1q binding assay using an enzyme-linked immunosorbent assay (ELISA). The levels of anti-lymphocyte antibody were also measured using normal donor peripheral blood T-lymphocytes. The levels of anti-lymphocyte antibodies were significantly higher in the sera of patients with HAM compared to controls (P < 0.01). The concentrations of immune complexes measured by Raji cell assay were also significantly higher in the HAM patients' sera than in controls. However, when levels of immune complexes were measured by C1q binding assay, there was no significant difference between HAM patients and controls. There was no significant difference in the levels of anti-lymphocyte antibodies and immune complexes between HTLV-I carriers and controls. Circulating immune complexes detected by the Raji cell assay did not include HTLV-I p-19 as detected by the indirect immunofluorescent method. Levels of anti-lymphocyte antibody were correlated with levels of circulating immune complexes as detected by the Raji cell assay in the sera of patients with HAM. These findings indicate that anti-lymphocyte antibodies and circulating immune complexes are present in the sera of HAM patients, and that the levels of complexes detected by Raji cell assay may reflect anti-lymphocyte antibody levels.

Adult↗

PubMed1993

Neurovascular permeability and fibrin deposition in the central neuraxis of Lewis rats with cell-transferred experimental allergic encephalomyelitis in relationship to clinical and histopathological features of the disease.

Abrupt increases in blood-brain barrier (BBB) permeability were detected by the dual-isotope technique, coinciding with evidence of activation of coagulation cascade, occurred 1 day prior to appearance of clinical neurological signs of experimental allergic encephalomyelitis (EAE) and in conjunction with initial detectable cell infiltration. Maximal increase of BBB permeability was observed on the first day of clinical signs, which was 2 days prior to maximum severity of clinical abnormalities and 1 day in advance of the greatest number of central nervous system (CNS) fibrin deposits and perivascular cellular infiltration. Returning of increased BBB permeability and CNS perivascular fibrin deposits to normal levels was demonstrated prior to complete remission of neurological signs. Considerable CNS perivascular cellular infiltrates, however, lasted after complete remission of neurological signs. These findings indicate that increased permeability of the BBB, in association with activation of the coagulation cascade, is the earliest expressions of immune effector activity of experimental allergic EAE.

Animals↗

PubMed1993

Immunoadsorption plasmapheresis for severe generalised myasthenia gravis.

Two patients with severe generalised myasthenia gravis of childhood were successfully treated with immunoadsorption plasmapheresis. One patient was a 5 year old girl and the other was a 12 year old girl. A dramatic improvement in bulbar symptoms and generalised muscle weakness was achieved without any side effects. Plasma exchange may also yield clinical improvement for myasthenia gravis, but the treatment is accompanied by the risk of viral infections and hypersensitivity reactions. Immunoadsorption plasmapheresis is an effective treatment for severe generalised myasthenia gravis of childhood and is superior to plasma exchange with respect to safety.

Child↗

PubMed1993

A strong association between thyrotropin receptor-blocking antibody-positive atrophic autoimmune thyroiditis and HLA-DR8 and HLA-DQB1*0302 in Koreans.

We investigated whether the associations between HLA alleles of patients with autoimmune hypothyroidism varied according to the presence or absence of TSH receptor-blocking antibody (TRBab). We analyzed the HLA-A, -B, -C, and -DR antigens by serotyping and the DQA1 and DQB1 genes using both enzymatic DNA amplification and sequence-specific oligonucleotide hybridizations. The patient population consisted of 47 Korean patients with atrophic autoimmune thyroiditis and 62 patients with goitrous autoimmune thyroiditis. The antigen frequency of HLA-DR8 was significantly increased in 23 atrophic autoimmune thyroiditis patients that were positive for TSH binding inhibitor immunoglobulin (TBII) compared to 136 controls [52% vs. 16%; chi 2 = 13.1; Pc (corrected P value) = 0.003]. This relative risk was 5.7; the etiological fraction was 0.43. HLA-DQB1*0302 was also increased in patients with TBII-positive atrophic autoimmune thyroiditis (24% vs. 7%; chi 2 = 11.2; Pc = 0.012; relative risk = 4.4; etiological fraction = 0.19). No specific DR antigens or DQB1 alleles were increased in either TBII-negative atrophic autoimmune thyroiditis or goitrous autoimmune thyroiditis. A significant decrease in the frequency of HLA-DR6 antigen was observed in both TBII-positive atrophic autoimmune thyroiditis (0% vs. 32%; chi 2 = 8.4; Pc = 0.03) and goitrous autoimmune thyroiditis (0% vs. 32%; chi 2 = 23.2; Pc < 0.001) patients. The frequency of the HLA-Cw1 antigen was significantly increased in all patient groups. We conclude that TRBab-positive atrophic autoimmune thyroiditis is immunogenetically different from both goitrous autoimmune thyroiditis and TRBab-negative atrophic autoimmune thyroiditis. It is possible that HLA-DR8 and/or DQB1*0302 may be related to the susceptibility genes involved in the production of TRBab in Koreans.

Adult↗

PubMed1993

Negative correlation between the conversion of thyrotropin receptor-bound blocking type thyrotropin receptor antibody to the stimulating type by anti-human IgG antibodies and the biological activity of blocking type thyrotropin receptor antibody.

It has been reported that receptor-bound blocking type TSH receptor antibody (TRAb) can be converted to the stimulating type by anti-human IgG antibodies. To evaluate the relationship between the conversion of receptor-bound blocking type TRAb to the stimulating type and the biological activity of blocking type TRAb, we compared converting activities of blocking type TRAb from 10 patients with primary nongoitrous hypothyroidism with both the doses of blocking type TRAb which show 50% inhibition of 125I-bTSH binding to the TSH receptor and those which show 50% inhibition of TSH-stimulated cAMP production in cultured rat thyroid cells (FRTL-5). The additions of anti-human IgG antibody to FRTL-5 cell-bound blocking IgGs resulted in the increase in cAMP production in a dose-dependent manner and the converting activities (percent increase of cAMP production) also depended on the doses of blocking IgGs. The converting activities were significantly correlated with the doses of blocking IgGs which showed 50% inhibition of 125I-bTSH binding to the TSH receptor (r = 0.71, p = 0.011). And these converting activities were also significantly correlated with the doses of blocking IgGs which showed 50% inhibition of TSH-stimulated cAMP increase (r = 0.81, p = 0.002), and were negatively correlated with thyroid stimulation blocking antibody activities (r = 0.58, p = 0.02). We have demonstrated that all cell-bound blocking type TRAb were converted to the stimulating type by anti-human IgG antibody and the degree of conversion was negatively correlated with the biological activity of blocking type TRAb.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Direct relationship between elevated free testosterone and insulin resistance in hyperprolactinemic women.

Women with hyperprolactinemia have been reported to have hyperandrogenemia and/or insulin resistance. However, little is known about the association of hyperandrogenemia and insulin resistance in these women. To investigate whether hyperandrogenemia and/or insulin resistance occur in hyperprolactinemic women, and to assess the relationship between them, we measured basal androgen level and both glucose and insulin levels after oral glucose administration in 20 hyperprolactinemic women and 7 female control subjects. Free testosterone level was higher and estradiol level lower in hyperprolactinemic women than in control subjects (p < 0.05), whereas dehydroepiandrosterone sulfate (DHEAS) and total testosterone levels were similar (p > 0.05). Both fasting glucose and insulin levels didn't differ in the two groups (p > 0.05). However, both serum glucose and insulin levels, after a 75 g glucose load, were significantly increased in hyperprolactinemic women, (p = 0.001, p < 0.001, respectively). In simple linear regression analysis in hyperprolactinemic women, only free testosterone level had a positive correlation with the incremental area under the insulin curve (insulin-IAU) (r = 0.47, p < 0.05). In multiple stepwise regression analysis, free testosterone level, mean blood pressure and DHEAS level were associated significantly with insulin-IAU (beta = 0.98, p < 0.0001; beta = 0.58, p = 0.002; beta = -0.67, p < 0.003, respectively). These results suggest that insulin resistance is closely related to elevated free testosterone level in hyperprolactinemic women.

Adult↗

PubMed1993

[Detection of interleukin-6 in serum and cerebrospinal fluid of patients with neuroimmunological diseases].

We quantitatively measured interleukin-6 (IL-6) levels in sera and cerebrospinal fluids (CSF) of patients with neuroimmunological diseases. Measurements were carried out by enzyme linked immunosorbent assay (ELISA) with anti-human IL-6 monoclonal antibody. The upper limit of IL-6 levels in the sera of normal controls was 15 pg/ml. Significant elevations of IL-6 levels were observed in the sera of patients with multiple sclerosis (MS) (212 +/- 320 pg/ml), Guillain-Barré syndrome (GBS) (90 +/- 62 pg/ml), myasthenia gravis (41 +/- 22 pg/ml), and polymyositis (119 +/- 72 pg/ml), when compared to those of controls (p < 0.05). The upper limit of IL-6 levels in the CSF of normal controls was 6.5 pg/ml. A significant elevation of IL-6 levels was observed in the CSF of patients with MS (131 +/- 307 pg/ml) (p < 0.05). However, no significant elevation of IL-6 levels was observed in the CSF of patients with GBS. The correlation indexes between CSF IL-6 and cell count, total protein levels, IgG levels in the CSF of MS patients were 0.776 (p < 0.001), 0.769 (p < 0.001) and 0.759 (p < 0.001), respectively. Serum IL-6 was not correlated with CSF IL-6 in MS patients. The elevated levels of IL-6 in the patients with these neuroimmunological diseases suggest that B-cells may be polyclonally activated in the sera of patients with these disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

B-Lymphocytes↗

PubMed1993

[A case of acute polyradiculoneuropathy following measles infection].

A 39-year-old man was admitted to our hospital because of diplopia, dysphagia, tetraparesis and urinary incontinence which developed six days after fever and general cutaneous rash had appeared. On neurological examination, total ophthalmoplegia, blepharoptosis, facial nerve palsy, bulbar palsy, and tetraparesis were observed, and the deep tendon reflexes were hypoactive or absent. The cerebrospinal fluid (CSF) showed albumin-cytological dissociation. serial complement fixation tests and enzyme-linked immunosorbent assays showed an elevation of antibody titers to measles virus in sera and CSF including serum IgM antibody. On the basis of findings, we diagnosed him as acute polyradiculoneuropathy following measles infection. After 3 sessions of immunoadsorption plasmapheresis his symptoms improved promptly. Marked improvement by immunoadsorption plasmapheresis suggested that immune-mediated mechanisms were involved in the pathogenesis of acute polyradiculoneuropathy following measles infection.

Acute Disease↗

PubMed1993

Clinical immunoscintigraphy of ovarian carcinoma using iodine-131-labeled 145-9 monoclonal antibody.

The monoclonal antibody (Mab) designated 145-9 recognizes CA125 antigen but binds to a different epitope than that recognized by OC125 antibody. This is a clinical study assessing the safety, kinetics and imaging sensitivity of Mab 145-9. Two milligrams of Mab were labeled with 111 MBq (3.0 mCi) of 131I and infused intravenously in 18 patients with ovarian carcinoma. Immunoscintigraphies were done at three, five, and seven days. There were no adverse reactions to the injection of this Mab. All immunoscintigraphies were considered positive. Immunoscintigraphy detected tumor lesions were confirmed in operative fields, in two patients with normal serum levels of CA125 and in four patients whose sonography and/or x-ray computed tomography showed negative findings. In five patients, immunoscintigraphy was repeated without any adverse reaction and revealed the progress of the carcinoma. Pharmacokinetic studies showed the steady-state volume of distribution (Vdss) to be 2772 +/- 466 ml (mean +/- s.d.), and clearance 51.3 +/- 12.7 ml/hr. In summary, immunoscintigraphies using 131I-labeled Mab 145-9 were done safely in patients with ovarian carcinoma. Preliminary results reveal a high sensitivity compared to radiological methods and tests currently in use.

Adult↗

PubMed1992

Concordance and localization of maximal vascular permeability change and fibrin deposition in the central neuraxis of Lewis rats with cell-transferred experimental allergic encephalomyelitis.

This study utilized Lewis rats and the cell-transfer form of experimental allergic encephalomyelitis (EAE) to focus on two central nervous system microvascular alterations known to be intimately associated with early clinical neurological signs of the disease, namely increased vascular permeability and deposition of fibrin. The main objective of the work was to define the degree of concordance and the anatomical localization of maximal vascular permeability change and fibrin deposition within the neuraxis of recipient rats during the earliest expression of clinical manifestations of the disease. Recipients were injected with predetermined doses of activated, myelin basic protein (MBP)-reactive syngeneic donor lymphoid cells and killed 6 or 7 days later when they exhibited the first clinical signs of disease. This experimental design allowed assessment of late occurring immune activities of a single population of MBP-reactive effector cells. Increased vascular permeability, expressed as mean extravascular blood equivalents (EVBE), attained maximum change, i.e., 16.04 +/- 5.07, within the lumbosacrococcygeal segment of the spinal cord (LSC). Maximal density of fibrin depositions, i.e., 192 +/- 94 deposits, also occurred within the LSC cord. The concordance of these two histoimmunopathological events, their tight linkage to early clinical signs of disease and the fact that both events attained maximal values within the LSC cord suggest that increased permeability and activation of the coagulation cascade may be prerequisite events for the expression of neurological signs of EAE.

Animals↗

PubMed1992

Evaluation of serum basal thyrotrophin levels and thyrotrophin receptor antibody activities as prognostic markers for discontinuation of antithyroid drug treatment in patients with Graves' disease.

OBJECTIVE: We evaluated whether antithyroid drug treatment could be terminated more appropriately when both the serum basal thyrotrophin (TSH) level and TSH receptor antibody activity have become normal. DESIGN: This was a prospective randomized study of patients with Graves' disease followed for a mean of 28 months after the withdrawal of antithyroid drug treatment. PATIENTS AND INTERVENTIONS: A total of 174 patients with hyperthyroid Graves' disease were entered consecutively into this study, 11 of whom were subsequently excluded. One hundred and sixty-three patients were divided randomly into two groups having different criteria for the discontinuation of the antithyroid drug. Group 1 consisted of 79 patients whose antithyroid drug treatment was discontinued if both their serum TSH level and thyrotrophin binding inhibitor immunoglobulin (TBII) activity normalized. Group 2 consisted of 84 patients who were treated for 24 months irrespective of their serum TSH level and TBII activity. All patients were treated initially with 400 mg/day of propylthiouracil followed by decreasing doses that maintained a euthyroid state. MEASUREMENTS: Serum basal TSH levels and TBII activities were measured using a radioimmunometric assay and a radioreceptor assay, respectively, every 2 months during the antithyroid drug treatment. RESULTS: The remission rate of Group 1 (51.9%) was not significantly different from that (63.1%) of Group 2. The mean duration of treatment in Group 1 was 10.2 +/- 4.5 months (range 5-24, median 10). Median duration of treatment in Group 1 was 14 months shorter than in Group 2. In Group 1, the relapse rate was independent of the duration of the treatment. Further, the mean duration of treatment in the relapsed patients was not significantly different from that for patients who went into remission (9.9 +/- 3.8 vs 10.7 +/- 5.7 months; P greater than 0.1). In Group 2, the relapse rate was dependent on the time when both the serum TSH level and TBII activity were normalized (chi 2 = 27.0, d.f. = 4; P less than 0.001). When both the serum TSH level and TBII activity were normalized, the relapse rate of Group 2 was not significantly different from that of Group I for treatment periods of 6-12 months (25 vs 24.2%, P greater than 0.1), 12-18 months (33.3 vs 40%, P greater than 0.1), and 18-24 months (46.2 vs 50%, P greater than 0.1). However, the relapse rate of Group 2 was significantly lower than that of Group 1 when there was only a 6-month treatment period (5.6 vs 42.9%, P less than 0.05). Of the clinical and laboratory parameters measured, male sex, change of goitre size during treatment, and TSH levels and TBII values at the end of treatment, were of prognostic significance in predicting a relapse. CONCLUSION: The present study suggests that antithyroid drugs treatment can be terminated more appropriately when both the serum TSH level and TBII activity are made normal, thus avoiding prolonged and unnecessary drug treatment.

Adult↗

PubMed1992

An autopsy case of Crow-Fukase (POEMS) syndrome with a high level of IL-6 in the ascites. Special reference to glomerular lesions.

A 58-year-old man developed polyneuropathy, organomegaly, gynecomastia, skin pigmentation, and multiple myeloma (IgG-lambda type). Although transient clinical improvement was obtained with prednisolone and cyclophosphamide, his general condition deteriorated progressively, and he died 3 years after onset. Lymph nodes showed angiofollicular hyperplasia, and the sural nerve revealed segmental demyelination. At autopsy, the glomeruli were enlarged and showed mild mesangial cell proliferation with segmental mesangiolysis and proliferation of endothelial cells forming abnormal vessels. The massive volume of ascites contained a high level of interleukin-6 (IL-6). IL-6, a multifunctional cytokine, may be the pathogenic factor which induces the various clinical symptoms and pathological features of Crow-Fukase (POEMS) syndrome.

Ascites↗

PubMed1992

Myalgia as the major symptom in systemic panniculitis (Weber-Christian disease).

A case of systemic panniculitis (Weber-Christian disease) presenting with myalgia as the main clinical symptom is reported. There was no laboratory or electromyographic evidence of myogenic disturbance. Biopsy of the painful muscle revealed nonspecific mononuclear cell infiltration in the epimysial fatty tissue, while the muscle fibers remained intact. Prednisolone was dramatically effective in alleviating the myalgia as well as the other signs of panniculitis. The present case may indicate that myalgia in systemic panniculitis is one manifestation of its systemic connective tissue involvement.

Adipose Tissue↗

PubMed1992

Allergic granulomatous angiitis and peripheral nerve lesion.

We examined 8 cases of allergic granulomatous angiitis (AGA). All cases showed peripheral nerve lesion, comprising damage of all myelinated fibers, which was more severe in larger ones. Immunofluorescent deposits of IgE were detected in the peripheral myelin. There was lymphocyte infiltration both around the endoneural capillaries and in the endoneurium, and an increase of endothelial cells. Nerve ischemia due to obstruction of the vasa nervorum, circulation insufficiency of the small vessels, or immunological abnormality through IgE may play a pathogenetic role in the peripheral neuropathy of AGA.

Child↗

PubMed1992

[A case of B-cell lymphoma with clinical and histological features of malignant histiocytosis].

A case of B cell lymphoma with clinical and histological features of malignant histiocytosis was described. A 57-year-old male was admitted to Shinshu University Hospital because of transverse myelopathy. Five months before admission, he noticed urinary disturbance, which progressed to urinary obstruction. The following month, bilateral muscular weakness appeared in his legs. A few days later he could not stand up, and was admitted to a local hospital. Neurological examination revealed sensory disturbances below the level of Th12 in all modalities, and marked weakness and hyperreflexia in the lower limbs. A spinal tumor was suspected. However, myelography showed no abnormality. The patient's condition worsened and he became bed-ridden in February 1990. He was transferred to Shinshu University Hospital for further evaluation. On admission he was poorly nourished with fever, anemia, hepatomegaly, and bilateral pretibial pitting edema. No lymphadenopathy was observed. Neurological examination showed total sensory loss below the level of Th12, spastic paraplegia, hyperreflexia in the legs, and urinary obstruction. Laboratory findings revealed an elevated erythrocyte sedimentation rate, increased CRP, pancytopenia, and hypoalbuminemia. Serum level of IgG, IgA, IgM, LDH, ALP, GPT and total bilirubin were increased. CSF and MRI imaging of the spinal cord were normal. Proliferation of atypical histiocytes with marked erythrophagocytosis, which is a characteristic pathological feature of malignant histiocytosis, was observed in peripheral blood and aspirated bone marrow. Immunoenzyme staining of bone marrow using monoclonal antibody L-26, which is a B-cell marker, revealed B-cell lymphoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Flow Cytometry↗

PubMed1992

[A case of Tolosa-Hunt syndrome accompanied by facial and vestibular nerve damage].

A 37-year old man, who had repeatedly suffered from transient ophthalmoplegia in his left eye at the age of 29 and 36, developed left painful ophthalmoplegia accompanied by ipsilateral facial nerve palsy in August, 1991. Neurological examination revealed involvement of the left oculomotor, trochlear, ophthalmic division of the trigeminal, abducens, facial and vestibular nerves. Gadolinium-enhanced MRI which was taken at the acute phase of the illness demonstrated markedly enhanced left cavernous sinus and adjacent thickened dura mater in the middle cranial fossa. At the remission phase after starting corticosteroid therapy, these enhanced lesions were no longer observed even in enhanced MRI studies. We diagnosed him as suffering from Tolosa-Hunt syndrome presently accompanied by facial and vestibular nerve damage because of his history of illness, confined lesion in the left cavernous sinus and steroid-induced remission. We concluded that Tolosa-Hunt syndrome may be accompanied by damage of other cranial nerves in its course and that repeated gadolinium-enhanced MRIs are necessary for diagnosis and observation of the patients.

Adult↗