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Y Kawabe

Publications and source records attributed to Y Kawabe.

At least 199 records · Page 11Linked to original sources

Reduction in the suppressor-inducer T cell subset and increase in the helper T cell subset in thyroid tissue from patients with Graves' disease.

The expression of surface markers associated with activation and characterization was compared among T cells in thyroid glands and peripheral blood of 10 patients with Graves' hyperthyroidism receiving chronic antithyroid drug therapy, in peripheral blood of 15 patients with untreated hyperthyroid Graves' disease, and in peripheral blood of 21 normal subjects using two-color flow cytometry. In the chronically treated Graves' disease patients, the percentage of activated T cells (HLA-DR+ T cells) among total T cells was significantly higher in thyroid tissue than in peripheral blood, and the increase in percent activated T cells was also significant among both helper/inducer T cell (CD4+ cell) and suppressor/cytotoxic T cell (CD8+ cell) subsets. The percentage of activated T cells in peripheral blood was not significantly different between chronically treated hyperthyroid Graves' patients and normal subjects, whereas the percentage of activated T cells in the peripheral blood from untreated hyperthyroid Graves' disease patients was significantly higher than that in normal subjects or chronically treated hyperthyroid Graves' patients. The percentages of CD4+ cells and CD8+ cells among total T cells were not different between thyroid tissues and peripheral blood in patients with chronically treated hyperthyroid Graves' disease. When CD4+ were further divided into helper T cells (CD4+2H4- cells) and suppressor-inducer T cells (CD4+2H4+ cells) using two-color flow cytometry, the percentage of helper T cells among CD4+ cells was significantly higher in thyroid tissue than in peripheral blood, resulting in an increased ratio of CD4+2H4- cells to CD4+2H4+ cells. The percentage of CD4+2H4+ cells in peripheral blood, however, was not significantly different among untreated and chronically treated Graves' disease patients and normal subjects. From the findings of abnormalities in intrathyroidal T cell subsets, we suggest that the decrease in the function of suppressor T cells within the thyroids of Graves' disease patients may be due to a decrease in CD4+2H4+ cells within thyroid tissue.

Adolescent↗

Dysfunction of suppressor T cells in thyroid glands from patients with Graves' disease.

To investigate the suppressor function of intrathyroidal (TG) T cells in Graves' disease, the percentage of suppressor T cell subsets and the suppressor function of TG and peripheral blood (PB) lymphocytes in Graves' disease were compared by determining the in vitro production of immunoglobulin G (IgG) in reconstituted mixtures of separated B, CD4+ (helper/suppressor-inducer T), and CD8+ (suppressor/cytotoxic T) cells. TG lymphocytes were obtained by gradient centrifugation of the supernatants of minced thyroid tissues. T Cells were separated by E-rosette formation, and CD4+ and CD8+ cell-rich populations were separated by a panning method using monoclonal anti-CD8 antibody. Mixtures of 5 X 10(4) B (PB1 or TG) cells, 2 X 10(4) CD4+ (PB or TG) cells, and 5 X 10(3) macrophages (PB or TG) were cultured with various numbers of CD8+ (PB) or CD8+ (TG) cells for 7 days with pokeweed mitogen, and IgG synthesis was determined by solid phase RIA. T cell subpopulations were quantitated by a direct immunofluorescence method using monoclonal anti-CD3, anti-CD4, and anti-CD8 antibodies. There was no difference in the percentages of CD8+ cells among total T cells between thyroid glands and peripheral blood from Graves' disease patients [mean PB, 39.8 +/- 9.8% (+/- SD); TG, 42.5 +/- 13.8%; n = 10]. IgG production by mixtures of B and CD4+ cells isolated from peripheral blood was not different from that by cells isolated from thyroid glands [mean PB, 1635 +/- 248 (+/- SE) ng/mL; TG, 1081 +/- 128 ng/mL; n = 19; P = NS]. The nonspecific suppressor activity of thyroid gland CD8+ cells was less than that of CD8+ (PB) cells [percent suppression of IgG production by mixtures of B (PB) and CD4+ (PB) cells, 12.5% vs. 57.0% (P less than 0.01); by mixtures of B (TG) and CD4+ (TG) cells, 5.8% vs. 38.9% (P less than 0.01)]. The suppressor-inducer function of CD4+ (TG) cells was also decreased compared with that of CD4+ (PB) cells. These results suggest that the impairment of suppressor cell activity may lead to excessive production of autoantibody in thyroid glands from patients with Graves' disease.

Adult↗

The metabolism of roxatidine acetate hydrochloride in rat and dog liver homogenates.

The metabolites were identified by gas chromatography-mass spectrometry (GC-MS). When an equimolar mixture of roxatidine acetate hydrochloride and its deuterated compound, labeled with ten deuterium atoms in the piperidine ring, was incubated with the 9000 X g supernatant (S-9) fraction of either rat or dog liver homogenate, the oxygenated metabolites of the piperidine ring such as the 3-hydroxypiperidine derivative (M1) and the 2-oxopiperidine derivative (M2) were isolated from rats but M2 was not isolated from dogs. These results suggested that the species differences in the metabolism of the piperidine ring in vitro are similar to that in vivo. The deuterium isotope effect (H/D) was 1.34 for M1 and 1.47 for M2 in rats, while the value for M1 in dogs was 1.69. On the other hand, the formation of these oxidative metabolites was inhibited by carbon monoxide in incubations using hepatic microsomes, suggesting that the reaction was catalyzed by cytochromes P-450.

Animals↗

The remarkable proliferation of helper T cell subset in response to autologous thyrocytes and intrathyroidal T cells from patients with Graves' disease.

We have studied cellular interactions among thyrocytes, intrathyroidal T cells and peripheral blood T cells from Graves' patients. In the autologous mixed lymphocyte reaction of Graves' patients, CD4+ cells were able to proliferate vigorously against autologous non-T cells, whereas CD8+ cells responded weakly to non-T cell stimulators. Furthermore, the proliferative response of the CD4+ 2H4+ suppressor-inducer T cell subset was increased like that of the CD4+ 2H4- helper T cell subset. In contrast to peripheral blood non-T cell stimulators, thyrocytes and intrathyroidal T cells had the ability to activate the CD4+ 2H4- helper T cell subset but were not able to cause proliferation both of CD4+ 2H4+ suppressor-inducer T cell and CD8+ suppressor/cytotoxic T cell subsets. The marked reduction in proliferative responses of CD4+ 2H4+ cells and CD8+ cells could not be attributed to a difference in kinetics or altered response to variable number of stimulator cells. On the basis of these findings, it is suggested that the concentration of the helper T cell subset may be progressively increased and suppressor circuits may be unable to be activated in thyroid tissues. These abnormalities in cellular interactions may induce the excessive production of autoantibodies.

Adolescent↗

Anterior neck dissection for carcinoma of the thyroid gland.

Anterior neck dissection, a regional neck dissection in which the internal jugular chain of nodes is dissected completely but the posterior triangle is left undisturbed, has been developed by us. Metastases of carcinoma of the thyroid to cervical lymph nodes were studied clinically and pathologically in 54 patients who had undergone therapeutic total neck dissections in order to determine selection guidelines for anterior neck dissections. If the 7 patients in whom nodes in the posterior triangle of the neck were palpable preoperatively were eliminated, there were 47 evaluable patients for this portion of the study. Nine (19%) of the 47 patients had nonpalpable but histologically positive nodes in the posterior triangle. If these patients were divided into 4 groups, I, II, III, and IV in which the number of palpable nodes in each was 1, 2, 3, and 4 or more, respectively, the incidence of microscopically positive nodes in each group was 1/20 (5%), 2/11 (18%), 2/8 (25%), and 4/8 (50%), respectively. Twenty-one evaluable anterior neck dissections were performed and followed from 4 to 9 years postoperatively. In 18 patients, there was a single palpable node and in 3 patients, there were 2 palpable nodes. No nodal recurrence has occurred in the necks with a single palpable node, but there has been one recurrence in the group with 2 palpable nodes. We conclude that anterior neck dissection is beneficial to patients with a single palpable node in carcinoma of the thyroid in reducing cosmetic disfigurement and preserving function.

Adolescent↗

[Histopathologic observation of anti-tumor effects of bleomycin and irradiation on cancers of the tongue].

Nine cases of squamous cell carcinoma of the tongue were treated by either intramuscular or local injections of total 60 to 200 mg of Bleomycin (BLM), and 7 cases by total doses of 1,200 to 5,320 rads of irradiation, followed by surgical removal of primary neoplasm. The histologic examination of the biopsied and surgical specimens from each case was done focussing on the antitumor effect of both treatments. In the cases with keratinizing component more than 25% in the biopsy specimens, the earliest change due to BLM was vacuolar degeneration of proliferating cells either at the base of superficial cancer epithelia or at the periphery of invading cancer foci. When the proliferating cancer cells disappeared, an appearance of invading cancer foci resembled to that of ectopic islands of normal squamous epithelium. These foci of differentiated squamous cell carcinoma gradually underwent morphological change into the so-called cancer pearls. Finally, the cancer pearls degenerated, leaving foreign bodies consisting of concreted keratin. The stromal reaction was characterized by the formation of granulation tissues accompanying significant numbers of foreign body giant cells. In the cases of lingual carcinoma with poor squamous differentiation, these processes were indistinct. Instead, the proliferating anaplastic cancer cells were markedly reduced and the remaining cancer cells transformed into large bizarre cells, probably at degenerative stage. On the histologic level, irradiation showed essentially similar antitumor effect to BLM, except for the rapid formation of concreted keratin bodies accompanying more abundant foreign body giant cells and the presence of irregular granulation tissues at different stages. We concluded that both BLM and irradiation had a powerful antitumor action on squamous cell carcinoma of the tongue. It is necessary, however, to establish an appropriate treatment modality through the more detailed histologic evaluation of a number of lingual cancer patients in consideration of the natural history of this neoplasm.

Adult↗

[Moderate dose methotrexate with citrovorum factor rescue therapy in the treatment of head and neck cancer].

A clinical trial of moderate dose methotrexate (MTX)-CF rescue was conducted in 12 institutions. Thirty-seven patients with head and neck carcinoma entered this trial, of which 32 were evaluable. MTX was administered 350 mg/m2 (500 mg/body) by i.v. drip over 6 hours. Three hours after completion of MTX infusion, CF rescue was started. There was no complete response in 32 patients. Nine patients showed partial response with the response rate of 28%. The response rates were 21% for the group of patients treated previously, and 75% for the group untreated previously. MTX concentration in plasma was determined at 6, 24, 48 and 72 hours after the initiation of MTX infusion, and the assay results revealed a safe range. GI disturbances were seen at the rates of 11 to 38%. Bone marrow suppression was mild and no renal toxicity was observed. We concluded that the moderate dose MTX-CF rescue therapy was useful for head and neck carcinoma. As a next step, we are planning to conduct a clinical trial of high-dose MTX.

Adult↗

[Experience with high-dose methotrexate therapy for malignant solid tumors].

Thirteen patients with malignant solid tumors, mainly osteogenic sarcomas, were treated by high-dose MTX therapy, 50-400 mg/kg, in a total of 72 cycles. It has been proved that this therapy was relatively safe provided careful clinical surveillance were assured. Of 8 patients with osteogenic sarcomas, 6 had no metastatic lesions on the chest X-rays before this therapy: three were alive without any evidence of disease for 18-25 months after high-dose MTX therapy. In some cases of other malignant solid tumors, particularly intracranial tumors, clinical efficacy was observed. Dose-time relationships, etc. should further be studied for more therapeutic efficacies of high-dose MTX therapy.

Adolescent↗

[A quantitative analysis of urinary 17-KS by GC-MS (author's transl)].

A quantitative analysis of seven components of 17-KS in human urine was successfully carried out by GCMS. The sample including deuterated 17-KS was introduced into TMS derivatives by BSTFA in pyridine. The derived TMS derivatives were analysed using the GC-MS system equipped with the column of 0.5% NPGS Chromosorb W AW DMCS, and the temperature was programmed from 180 degrees C to 240 degrees C at 3 degrees C/min. increment. Seven components were well separated, and each fraction was analysed by MS spectrum. Normal human urine was analysed by this method, the result of which is summarized in Table 3.

17-Ketosteroids↗

Late effects on the eye of conformation radiotherapy for carcinoma of the paranasal sinuses and nasal cavity.

Sixty patients with carcinoma of the paranasal sinuses and nasal cavity were treated with conformation radiotherapy technique (an improved moving-field technique). Only 28 were suitable for long-term follow-up with regard to eye complications. All patients receiving more than 5,800 rads in 6 weeks (1,700 reu in cumulative-radiation-effect dose) had strong panophthalmia with corneal ulceration within 2 years of radiotherapy. Of 21 eyes receiving 800--1,700 reu (2,800--5,400 rads in 6 weeks), 18 experienced visual disturbance from radiation cataracts and 3 equivocal changes at postirradiation intervals of 5 years. No patient receiving less than 800 reu (2,800 rads in 6 weeks) showed such complications.

Cataract↗