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Biomedical subjects

K Eguchi

Publications and source records attributed to K Eguchi.

At least 487 records · Page 27Linked to original sources
PubMed1988

Phenotypic analyses and concanavalin-A-induced suppressor cell dysfunction of intrathyroidal lymphocytes from patients with Graves' disease.

The expression of phenotypic markers and Concanavalin-A-induced suppressor activity was compared among mononuclear cells isolated from thyroid glands and peripheral blood of thionamide-treated patients with hyperthyroid Graves' disease and peripheral blood from normal subjects. Intrathyroidal lymphocytes were obtained by two different methods (TG-1 and TG-2 cells), gradient centrifugation of supernatants of minced thyroid tissue and overnight culture of thyroid debris after mechanical disaggregation and enzymatic digestion, respectively. The percentages of CD3+ cells (all mature T cells) among peripheral blood and TG-1 and TG-2 cells from Graves' patients were similar, but the percentages of B1+ cells (pan B cells) among the TG-1 and TG-2 cells were markedly increased compared to that in peripheral blood. The percentages of CD4+ cells among the TG-1 and TG-2 cells were significantly less than that in peripheral blood. The percentages of CD4+2H4+ cells among CD4+ cells in TG-1 and TG-2 cells also were significantly less than that in peripheral blood. The percentage of CD4+4B4+ cells among CD4+ cells in thyroid glands was markedly higher than that in peripheral blood. The percentages of CD8+ cells and CD8+CD11b- cells (cytotoxic T cells) in thyroid glands were significantly higher than those in peripheral blood from Graves' patients and peripheral blood from normal subjects. The CD8+CD11b+ cells were subdivided into two subpopulations on the basis of CD8 antigen density. The percentage of dull CD8+CD11b+ cells (natural killer cells) among TG-2 cells was lower than that in peripheral blood, but there was no significant difference in bright CD8+CD11b+ cells (suppressor-effector T cells) between thyroid glands and peripheral blood. The percent suppression induced by Concanavalin-A in both TG-1 and TG-2 cells was significantly decreased compared with that in peripheral blood. These results suggest that impairment of suppressor cell activity and an increased number of B cells exist in thyroid glands of patients with Graves' disease compared to those in peripheral blood. It, thus, appears likely that both B cell hyperactivity and suppressor T cell dysfunction may induce excess production of autoantibodies in the thyroid glands of such patients.

Adolescent↗
PubMed1988

In vitro cellular interactions among thyrocytes, T cells and monocytes from patients with Graves' disease.

In order to investigate the cellular interactions among thyrocytes, T cells and monocytes in thyroid glands from patients with Graves' disease, we determined alterations of HLA-DR antigen expression on thyrocytes and T cells, and the production of interferon-gamma during coculture of thyrocytes, T cells and monocytes obtained from patients with Graves' disease. Thyroid glands were obtained at operation from 17 patients with Graves' disease. When thyrocytes and autologous peripheral blood T cells were cocultured for 7 days, the percentage of HLA-DR antigen expression on thyrocytes was significantly increased by T cells and that on T cells was also significantly increased by thyrocytes. Addition of autologous monocytes to the mixtures of thyrocytes and T cells significantly increased the expression of HLA-DR antigens on both thyrocytes and T cells compared with mixtures without monocytes. In culture supernatants, interferon-gamma was detected in 4 of 14 cocultures of thyrocytes and T cells, in 5 of 10 cocultures of thyrocytes, T cells and monocytes, but not in any cultures of thyrocytes alone, T cells alone and T cells and monocytes. Induction of HLA-DR antigen expression on thyrocytes and T cells was blocked by addition of anti-interferon-gamma monoclonal antibody to the mixture. These results suggest that HLA-DR antigen positive thyrocytes are able to induce the HLA-DR antigen expression of T cells in the presence of monocytes, and the activated T cells are capable of producing interferon-gamma which acts on thyrocytes to induce and maintain the expression of HLA-DR antigens.

Adolescent↗
PubMed1988

The effects of cytokines, antithyroidal drugs and glucocorticoids on phagocytosis by thyroid cells.

The present study was undertaken to examine whether thyrocytes possess phagocytic activity and whether the phagocytic activity is influenced by cytokines, such as interleukin 1, 2 (IL 1, IL 2) and interferon-alpha, -beta, and -gamma (IFN-alpha, beta, and gamma), and drugs, such as methimazole and dexamethasone. Thyroid glands were obtained from patients with Graves' disease. Thyrocytes were prepared by collagenase digestion. Thyrocytes were pre-incubated in the presence or absence of cytokines and drugs at 37 degrees C for 20 h and were further incubated with fluoresceinated latex beads at 37 degrees C for 60 min. The number of phagocytic thyrocytes was determined by FACS IV. Phagocytosis of latex beads was indeed seen within thyrocytes and gradually increased in a time-dependent manner. The rate of phagocytosis in thyrocytes was extremely slow as compared with that in macrophages. Phagocytic activity was detected in thyrocytes from patients with Graves' disease and from normal thyroid tissue adjacent to thyroid cancer. Phagocytosis was inhibited by IL 1, but was enhanced by IL 2. Although the enhanced phagocytosis with IFN-beta was consistently seen, little effect was detected with IFN-alpha and -gamma. Both methimazole and dexamethasone markedly inhibited phagocytosis. These results indicated that thyrocytes had phagocytic properties and that their phagocytic activity was modulated by cytokines, antithyroidal drugs and dexamethasone.

Antithyroid Agents↗
PubMed1988

Treatment for small cell lung cancer--present status and future prospects.

Strategies for the treatment of small cell lung cancer (SCLC) were reviewed depending on the recent results of treatment. The development of new anti-cancer drugs are essential for the further improvement results of SCLC. However, the candidate of patient for phase II study of new anticancer drug is controversial. Intensified chemotherapy is essential in order to obtain long term survivors, however, the toxic death rate should be less than 5% of whole patients. The theory of non-cross resistant alternative chemotherapy has also been applied to the treatment of SCLC. The protocol study supported by grant-in-aid from the Ministry of Health and Welfare is now on-going by cooperative study. There are many discussions about the efficacy of combined modality in SCLC. However, present randomized trials gave clear answers about the priority of combined modality in SCLC. There are numerous biological studies about SCLC. These studies will contribute to improve the treatment results of SCLC.

Carcinoma, Small Cell↗
PubMed1988

Molecular weights of IgA-circulating immune complexes (CIC) in patients with IgA nephropathy: application of HPLC and solid-phase anti-C3 Facb EIA.

The detection of molecular weights of IgA-circulating immune complexes (CIC) in sera is described. Measurement of IgA-, IgG- and IgM-CIC in sera was also performed. Serum samples were obtained from nine patients with IgA nephropathy, nine patients with chronic proliferative glomerulonephritis without IgA deposits (PGN) and 19 healthy adults. Serum samples of these patients were subjected to high performance liquid chromatography (HPLC) and then divided into 50 fractions. Measurement of IgA-, IgG- and IgM-CIC in such fractions was performed using solid-phase anti-C3 Facb EIA. The levels of IgA-CIC in sera from patients with IgA nephropathy were significantly higher than those from patients with PGN or healthy adults. The peak values of molecular weights of IgA-CIC in sera from patients with IgA nephropathy ranged from 2.6 X 10(5) to 3.0 X 10(5) daltons (mean +/- SD; 2.9 +/- 2.0). It was suggested that the increase of IgA-CIC in sera from patients with IgA nephropathy may be mainly due to dimers and/or polymers.

Adult↗
PubMed1988

Synergy in antigen presentation by thyroid epithelial cells and monocytes from patients with Graves' disease.

The present study was undertaken to examine the ability of thyrocytes from Graves' patients to present purified protein derivative (PPD) to autologous peripheral blood T cells. Normal human thyrocytes which were pre-cultured with interferon-gamma were able to induce the proliferation of T cells in response to PPD antigen, but unstimulated thyrocytes failed to do. Thyrocytes from Graves' patients on which HLA-DR antigens were expressed have an ability to induce the proliferation of T cells. Thyrocytes from Graves' patients which were pulsed with PPD antigen for 4 h were capable of stimulating proliferation of the T cells. However, the stimulation index of T cells co-cultured with thyrocytes and PPD were significantly lower than that of T cells co-cultured with monocytes and PPD. Sub-optimal numbers of monocytes which by themselves were unable to support T-cell proliferation synergistically augmented antigen presentation by thyrocytes. These results suggest that cellular interactions among thyrocytes, monocytes and T cells may perpetuate immune or autoimmune responses in thyroid tissues from Graves' patients.

Adolescent↗
PubMed1987

Combined study of 1H-magnetic resonance imaging and depth-selected, EKG-gated 31P-magnetic resonance spectroscopy of the heart in vivo.

NMR is useful for both 1H-magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). We undertook to combine these two merits of NMR for in vivo characterization of living rat heart in wide bore (9 cm) superconducting magnet under high magnetic field (6.4 Tesla). Spatial resolution of 1H-MRI attained 0.1 mm by spin warp method. Then, depth-selected, EKG-gated 31P-MRS was performed, adjusting the detection area to cover the heart that was identified by the preceding 1H-MRI. Three evidences that 31P-SMR signal chiefly originated from the heart without cross talk of adjacent organs indicated that combination of 1H-MRI and in vivo 31P-MRS under high magnetic field in whole animal is promising for more accurate evaluation of cardiac muscle metabolism.

Animals↗
PubMed1987

A new antitumor antibiotic FR66973: clonogenic in vitro assessment of activity against human non-small cell lung carcinoma.

We have utilized a human tumor clonogenic assay (HTCA), as a disease-oriented drug screening model of new antitumor drugs, to test the antitumor activity of FR66973 and compared the activity with that of its analogous compound, mitomycin C. The overall in vitro response rate (defined as less than 50% survival of tumor colony forming units) for FR66973 against fresh tumor cells obtained from patients with non-small cell lung carcinoma (NSCLC) was 32%, 50% and 89% at 0.1, 1 and 10 micrograms/ml, respectively, which was superior to that of mitomycin C at the corresponding concentration. Our data suggest that FR66973 is a promising new drug against NSCLC. If phase I toxicities are not prohibitive, FR66973 may also have good activity against NSCLC in clinical phase II trial.

Adult↗
PubMed1987

Prognostic factors in non-small cell lung cancer: multiregression analysis in the National Cancer Center Hospital (Japan).

A total of 190 patients with unresectable non-small cell lung cancer (NSCLC) were analyzed retrospectively using eight pretreatment and three treatment-related prognostic factors in terms of influence on survival. All the patients received chemotherapy with or without chest irradiation, according to the protocol of phase II or phase III trials of the National Cancer Center Hospital Tokyo between April 1980 and December 1985. The eight pretreatment factors selected were performance status, sex, stage, age, histology, and metastasis to brain, bone or, liver. Three treatment-related factors were radiation therapy to the primary site, response to chemotherapy, and treatment period, before or after clinical administration of cis-diamminedichloroplatinum (II) (CDDP). Of the 190 patients, 71 (37.4%) were alive for more than 1 year, but only 17 patients (8.9%) survived 2 years after the initiation of chemotherapy. By univariate analysis, performance status 0-1, female, no metastasis to bone or liver, response to chemotherapy, and treatment period after CDDP were considered to be favorable prognostic factors. By multiregression analysis, performance status, sex, and treatment period after CDDP proved to be important factors for long-term survival. Consideration of these prognostic factors could enable the results of chemotherapy to be more accurately evaluated, and stratification of patients with advanced NSCLC based on performance status and sex before entry into a randomized controlled trial is recommended.

Adenocarcinoma↗
PubMed1987

Respiratory depression caused by either morphine microinjection or repetitive electrical stimulation in the region of the nucleus parabrachialis of cats.

In chloralose-urethane anesthetized, vagotomized, paralyzed and artificially ventilated cats, respiratory response to either repetitive electrical stimulation or microinjection of morphine in the rostral pons was studied by recording the phrenic nerve discharges. In the region of the nucleus parabrachialis (PBN) and its ventral reticular formation, electrical stimulation delivered in 20 successive expiratory periods caused the respiratory depression to last long after the termination of stimulation. This respiratory-depressant effect could be reversed by naloxone. By a single electrical stimulation delivered in most of these effective sites, a phasic phrenic excitation was consistently elicited in the period of both expiration and inspiration, and the reduction in expiratory duration could be observed when the stimulation was delivered in expiratory period. In the microinjection study of 2.66 nmol morphine in 0.1 microliter in the localized area of the dorsolateral portion of the PBN, a significant reduction in both respiratory outputs and the rate of increase in inspiratory activity could be induced within 1 min after the application. The respiratory depression thus caused by both methods was quite similar in several respiratory variables. Thus an involvement of the PBN region in long-lasting respiratory modulation mediated by endogenous opioid system is suggested.

Animals↗
PubMed1987

Relationship between positive sharp wave bursts and unitary discharges in the cat hippocampus during slow wave sleep.

In the cat hippocampus bursts of positive sharp waves (PSWs) appeared sporadically almost exclusively during slow wave sleep. The PSW burst was most often found in cell-rich areas in the CA1 and subiculum, and its occurrence was almost synchronized in different regions. An individual burst was usually composed of 3-5 PSWs of about 10 msec duration and showed a considerable fluctuation in amplitude. It was occasionally followed by a negative-going deflection of large amplitude and long duration (post-PSW negativity). The amplitude of PSWs and post-PSW negativity in the CA1 was high in the area giving a large sized-evoked response after stimulation of the contralateral CA3. The spike discharge rate during the burst was two or three times higher than that during the period just preceding the burst, but the discharge never occurred in the positive phase of the PSWs. During the initial part of the post-PSW negativity the high firing probability was maintained. Even when the PSW burst was not followed by a detectable post-PSW negativity, the firing probability during the period corresponding to the post-PSW negativity was still significantly higher than the pre-PSW period. It was suggested that the PSW bursts and post-PSW negativity were triggered off in cell-rich areas by diffuse excitatory inputs impinging possibly upon the hippocampal pyramidal cells and subicular principal cells. The rhythmic PSWs may be post-synaptic inhibitory potentials produced on the somata of those cells after activation of recurrent interneuronal circuits.

Animals↗
PubMed1987

Induction and repair of DNA lesions in cultured human melanoma cells exposed to a nitrogen-ion beam.

Induction and repair kinetics of DNA lesions after exposure to nitrogen ions (N-ions) were studied in comparison to those after 180 kVp X-rays. DNA lesions in human melanoma cells (HMV-I) irradiated with 95 MeV N-ions (0-6 Gy, l.e.t.D = 530 keV micron-1 or with X-rays (0.9 Gy) were assayed by alkaline elution. The N-ion r.b.e. for DNA lesion induction was approximately 0.7. About 85 per cent of the lesions induced by N ions were rejoined with a time-course similar to the rejoining of DNA lesions produced by X-rays. These lesions were considered to be induced by delta-rays around the N-ion tracks. The fraction of residual DNA lesions remaining after a 6 h post-irradiation incubation was higher for N-ions than for X-rays. Unlike the case for X-rays, DNA-protein crosslinks were included in the residual DNA lesions after N-ion irradiation.

Cells, Cultured↗
PubMed1987

Human tumor clonogenic assay for carcinoma of the lung. II. Factors that influence colony formation in soft agar.

The human tumor clonogenic assay (HTCA) has potential value for studies of both the chemosensitivity and biology of human tumors. However, many technical problems including low plating efficiencies and the preparation of sufficient numbers of viable cells remain. In this study, an improved method for disaggregation of solid tumors increased the yield of single cells. Consequently, more than 10 anticancer drugs could be tested in 94 of 168 specimens (56%). Removal of peripheral blood lymphocytes from cell suspensions derived from effusions also improved colony formation. Adequate growth for sensitivity testing (greater than 30 colonies/plate) was obtained in 122 cases (73%), inadequate growth for drug evaluation (5-29 colonies/plate) in 29 cases (17%), and no colony formation (less than 5 colonies/plate) in 17 cases (10%) of the 168 viable samples. The cloning efficiencies of cells derived from primary tumors (median 0.015%) were higher than those of cells derived from metastatic tumors (0.012%), and they varied with the location of the metastatic site. Cloning efficiencies varied markedly from specimen to specimen, and were unaffected by tumor histology, grade of differentiation, patient age, stage of disease, or prior chemotherapy. The HTCA is promising as a potential tool for studying the biology of tumors.

Agar↗
PubMed1987

Inhibitory effect of interferon-gamma on the response of human thyrocytes to thyrotropin (TSH) stimulation: relationship between the response to TSH and the expression of DR antigen.

Thyroid epithelial cells (thyrocytes) in autoimmune thyroid disease have been found to express DR antigens on their surfaces, and interferon-gamma (IFN gamma) induces DR antigen expression. This study was undertaken to determine the effect of IFN gamma on the response of human thyrocytes to TSH stimulation and the relationship between the response to TSH and the expression of DR antigen induced by IFN gamma, using monolayer cultures of Graves' thyrocytes. When confluent thyrocyte monolayers were incubated with TSH or Bu2cAMP (DBcAMP) for 7-9 days, T3 and thyroglobulin concentrations in the culture medium increased gradually in a dose-dependent manner. However, when TSH or DBcAMP was added after the cells had been cultured for 4 days with IFN gamma, T3 and thyroglobulin secretion in response to both 10 mU/mL TSH and 1 mM DBcAMP was significantly inhibited. The inhibition by IFN gamma was dose dependent and correlated with the number of DR antigen-positive thyrocytes present on the last day of culture. IFN alpha and -beta did not affect the response of thyrocytes to TSH or DBcAMP stimulation. These results suggest that DR antigen-positive thyrocytes fail to respond to TSH stimulation at a site located distal to cAMP formation.

Bucladesine↗