Biomedical subjects

M Yamamura

Publications and source records attributed to M Yamamura.

At least 91 records · Page 5Linked to original sources

PubMed1996

A human/mouse chimeric monoclonal antibody against intercellular adhesion molecule-1 for tumor radioimmunoimaging.

A mouse-human chimeric antibody for intercellular adhesion molecule-1 (ICAM-1) was established by using heavy chain loss mouse mutant hybridoma and human immunoglobulin expression vector. The HA58 hybridoma secreted anti-ICAM-1 monoclonal antibody (MoAb) (IgG1, kappa). The gene of the mouse variable region of heavy chain was amplified and cloned by the polymerase chain reaction technique directly from the HA58 hybridoma RNA. The variable region of heavy chain was joined with an expression vector which contains human gamma 1 constant gene. The expression vector was transfected into heavy chain loss mutant cells HA58-7, which produced only murine immunoglobulin light chains. The resultant chimeric MoAb HA58, chHA58, retained full-binding reactivity to ICAM-1 compared with murine HA58 parental antibody. The chimeric MoAb chHA58 showed little antibody dependent cell-mediated cytotoxic activity against cultured tumor cells. Biodistribution studies with 99mTc-labeled chHA58 in nude mice bearing human gastric carcinoma JRST cells demonstrated that the tumor-blood ratio was 1.55 at 18 h after injection, when the tumors were clearly visible in gamma scintigraphy. These data suggest that chHA58 may be of practical use for radioimmunoimaging of a wide variety of tumors.

Amino Acid Sequence↗

PubMed1996

Acute-phase plasma proteins in gastric cancer: association with metastatic potential and prognosis.

We evaluated the possibility that acute-phase plasma proteins such as alpha 1-antichymotrypsin (ACT) and immunosuppressive acidic protein (IAP) might be useful predictors of lymph node metastasis and prognosis in patients with gastric cancer. Both ACT and IAP levels generally increased according to the pTNM stage. Patients with both abnormal IAP and ACT levels showed a high risk of lymphatic and hepatic metastasis as well as peritoneal dissemination, with a resultant poor prognosis. Patients who had abnormal IAP levels with or without abnormal ACT levels had a significantly higher risk of lymph node metastasis, as well as more invasive tumors and a worse prognosis than those who had normal IAP levels with or without abnormal ACT levels. In combination group 4 [IAP(+) ACT(-) vs. IAP(-) ACT(+)] lymphatic metastasis was seen more often with isolated IAP(+) (76.4%) than with ACT(+) (52.9%) (p < 0.0045), especially in the subgroup of poorly differentiated adenocarcinoma (POR; p < 0.0177). However, this does not demonstrate that ACT(+) is a protective factor against lymphatic invasion, because the results of combination group 6 [IAP(-) ACT(+) vs. IAP(-) ACT(-)] show that isolated ACT(+) is also significantly related to lymphatic metastasis (p < 0.001). The same is true for the subgroup of signet ring cell carcinomas (p = 0.038), but it has not been tested versus the POR subgroup.

Acute-Phase Proteins↗

PubMed1996

[Effect of (-)-N-[(S)-hexahydro-l-methyl-2, 6-dioxo-4-pyrimidinylcarbonyl]-L-histidyl-L-prolinamide (TA-0910), a new TRH analog, on plasma levels of TSH and thyroid hormones in rats].

The stimulatory effect of TA-0910 on the secretions of thyroid-stimulating hormone (TSH) and thyroid hormones was investigated in male and female rats. Single intravenous administration of TA-0910 at 8.3 nmol/body acutely elevated the plasma TSH level, with delayed and moderate increases of T3 and T4 in plasma. Similar increments of plasma TSH and thyroid hormones were observed when TRH was injected at the dose of 0.83 nmol/body. Oral administration of TA-0910 at 2.75 mumol/body was equally potent or slightly more potent to secrete TSH than TRH at 0.275 mumol/body. The elevated TSH by TA-0910 decreased to the control level within 2 hr after intravenous injection or within 6 hr after oral administration; on the other hand, the higher levels of the thyroid hormones were retained for up to 4 and 6 hr after intravenous and oral administration, respectively. These findings indicate that TA-0910 and TRH stimulate the secretion of TSH and thyroid hormones by a similar manner and that the TSH-secreting activity of TA-0910 is lower by an order of magnitude compared with that of TRH.

Administration, Oral↗

PubMed1996

Effect of TA-0910, a novel thyrotropin-releasing hormone analog, on in vivo acetylcholine release and turnover in rat brain.

To examine the action of a novel thyrotropin-releasing hormone (TRH) analog, TA-0910 ((-)-N-[(S)-hexahydro-1-methyl-2,6-dioxo-4-pyrimidinylcarbonyl]-L- histidyl-L-prolinamide tetrahydrate), on the cerebral cholinergic systems, the release of acetylcholine (ACh) and choline in freely-moving rats and ACh accumulation in gamma-butyrolactone (GBL, a nerve impulse flow blocker)- and physostigmine-treated rats were examined. TA-0910 (0.1-1 mg/kg, i.p.) caused a marked dose-dependent increase in extracellular ACh levels and a decrease in choline levels in the hippocampus of freely moving rats. These effects were significantly stronger and longer-lasting than similar effects of TRH. TA-0910 (1, 3 mg/kg, i.p.) depressed the ACh accumulation in the cerebral cortex and hippocampus of GBL (1000 mg/kg, i.p.)-treated rats. Moreover, this analog (1, 3 mg/kg, i.p.) increased the accumulation rate of ACh in these regions in physostigmine (1 mg/kg, i.p.)-treated rats. TRH (30 mg/kg, i.p.) affected the ACh accumulation only in the hippocampus of the GBL-treated rats. These results suggest that TA-0910 not only enhances the release of ACh, but also accelerates the ACh turnover, i.e., ACh release and synthesis, at the cholinergic neuronal terminals in normal rats.

4-Butyrolactone↗

PubMed1996

Takayasu's arteritis associated with ulcerative colitis; genetic factors in this association.

Both ulcerative colitis and Takayasu's arteritis are though to be organ-specific immune-mediated inflammatory diseases. We present the rare case of a 23-year-old woman with a 4-year history of ulcerative colitis who developed Takayasu's arteritis one month after giving birth. She was found to carry the human leukocyte antigens (HLA)-B52 and DR2, which were previously noted to be associated with these inflammatory conditions in the Japanese population. The pathogenic relevance of this haplotype to the concomitant development of these two conditions is discussed.

Adult↗

PubMed1996

Carcinoid tumor of the gall bladder.

A classical carcinoid tumor, measuring 11 x 17 mm, was found in a 41-year-old woman in the neck of the gall bladder. The lesion infiltrated the muscular layer of the gall bladder wall. Histologically, the tumor was positive for only Grimelius and chromogranin A stains. In a literature search, approximately half of the tumors reported as gall bladder carcinoid tumor appear to be actually endocrine cell carcinomas, which are completely different from classical carcinoid tumors with respect to size, metastasis and prognosis. These carcinomas should not be termed as carcinoid tumors from both the clinical and histological points of view, and should be clearly distinguished from benign lesions when reported.

Adult↗

PubMed1996

Plasma M-CSF as an indicator of response to chemotherapy in adult T cell leukemia patients.

The plasma concentration of macrophage colony-stimulating factor (M-CSF) was measured in 10 patients with acute type adult T cell leukemia (ATL) during the clinical course before and after chemotherapy. M-CSF concentration decreased significantly when the patients achieved complete remission (CR) or partial remission (PR) (t-test: p = 0.0001). Five of the patients showed disease progression after several months of PR, and plasma M-CSF increased at that time (t-test: p = 0.0456). Thus, plasma M-CSF concentration appeared to accurately reflect the disease activity in ATL. In support of these results, all three ATL cell lines established from these patients secreted M-CSF in vitro after stimulation with phorbol myristate acetate (PMA) or concanavalin A (Con A). Plasma M-CSF concentration, however, increased transiently when the patients were febrile (t-test: p = 0.0001), even though their ATL condition was unchanged. Taken together, these results indicate that there are two sources of increased plasma M-CSF concentration in ATL; ATL cells themselves and normal parenchymal cells that cause this increase as the result of elevated body temperature due to inflammation.

Adult↗

PubMed1996

Features of the cytokines secreted by adult T cell leukemia (ATL) cells.

Adult T cell leukemia (ATL) cells show a mature helper-inducer T cell phenotype and are thought to secrete many kinds of cytokines in vivo, complicating the clinical features in these patients. In an attempt to specify the cytokines produced by ATL cells, we measured the cytokine concentration in the culture supernatants of three ATL cell lines, all of which were confirmed to be true peripheral blood ATL cell in origin. All these cell lines showed the same cytokine production profile, secreting IL1-alpha, IL1-beta, LD78(MIP-l alpha), TNF-alpha, IFN-gamma, and GM-CSF, but not secreting IL-1 alpha, IL-1 beta, IL-1 receptor antagonist (IL-1 Ra), IL-4, IFN-alpha, and G-CSF irrespective of the stimulatory agents used. Such limited cytokine production may indicate the specific origin of ATL cells within the helper-inducer T cell subtypes. Moreover, these results explain some of the unusual clinical features of ATL patients.

Adult↗

PubMed1996

Increased levels of interleukin-6 (IL-6) in serum and spontaneous in vitro production of IL-6 by lymph node mononuclear cells of patients with angio-immunoblastic lymphadenopathy with dysproteinemia (AILD), and clinical effectiveness of cyclosporin A.

Serum levels of cytokines and in vitro cytokine production by lymph node mononuclear cells (LNMC) were studied in four patients with angio-immunoblastic lymphadenopathy with dysproteinemia (AILD) or AILD-type T cell lymphoma. An increased level of serum interleukin-6 (IL-6) was detected on initial diagnosis in both of two patients examined. Spontaneous production of IL-6 by LNMC was detected in all four patients studied. Immunosuppressive therapy with cyclosporin A (CsA) was attempted in a 68-year-old man, who was refractory to intensive combination chemotherapy. The increased level of IL-6 in this patient decreased to normal within 3 weeks of CsA administration and the patient became symptom-free. One and a half months later, the IL-6 level gradually increased along with clinical exacerbation. We also measured serum levels of IL-1 alpha, IL-2, IL-4, IFN-alpha, gamma and TNF-alpha in parallel with IL-6, but these factors were only sporadically detected. IL-6 production by LNMC was stimulated by IL-2 but inhibited by CsA. These observations suggest that IL-6 is one of the important cytokines to be involved in the pathophysiology of AILD and CsA is a useful reagent for relieving symptoms.

Aged↗

PubMed1996

[A clinical evaluation of fluconazole in deep seated fungal infections associated with hematological disorders].

The effectiveness of fluconazole on deep seated fungal infections associated with hematological disorders was evaluated in a multicenter clinical study. The underlying diseases included acute myeloblastic leukemia, acute lymphocytic leukemia, malignant lymphoma, adult T cell leukemia, multiple myeloma and others. Fluconazole (FLCZ) was administrated 100-400 mg/day intravenously or orally to 79 patients with systemic fungal infections complicated with hematological disorders and it was possible to evaluate clinical efficacies in 60 patients. 27 patients were diagnosed as having determinate systemic fungal infections and 33 patients suspected fungal infections. The clinical efficacies were 81.5% (22/27) in patients with diagnosed fungal infections and 57.6% (19/33) in patients with suspected fungal infections. The overall clinical efficacy was 68.3% (41/60). No side effects such as gastrointestinal symptoms, vascular pain and renal dysfunction were observed in this study. As for abnormal laboratory test, transient increases in GOT, GPT, Al-P, LDH, serum Na, Cl and decrease in serum K were observed in 9 patients (11.4%). These results indicated that FLCZ has a high therapeutic efficacy on deep seated fungal infections in patients with hematological disorders.

Aged↗

PubMed1996

Changes in urinary enzyme activity and histochemical findings in experimental tubular injury induced by gold sodium thiomalate.

To elucidate the renal injury induced by gold treatment, we administered various doses of gold sodium thiomalate (GST) to Wistar rats and investigated alterations in the urinary enzyme activity, gamma-glutamyl transpeptidase (gamma GTP) and N-acetyl-beta-glucosaminidase (NAG) activity, and histochemical change of enzymes, gamma GTP, alkaline phosphatase (ALP) and acid phosphatase (ACP) activity in the renal tissue. The single administration of a large dose of gold salts induced acute tubular necrosis and enzyme leakage was detected histochemically without damage to the glomerulus. After chronic administration of small doses of gold salts, the urinary gamma GTP activities gradually increased, but urinary NAG activities did not. These findings suggested that the change in urinary enzyme activities, which leaked from inside of brushborder or lysosome, indicated the degree or localization of tubular damage, because renal tubules were selectively injured by gold salts.

Acetylglucosaminidase↗

PubMed1995

IL-7 in the cell-mediated immune response to a human pathogen.

The goal of the present study was to investigate the role of IL-7 in regulating immune responses to infection. Leprosy provides a model for understanding human immune responses to infection; the disease presents as a spectrum in which the clinical manifestations correlate with the levels of cell-mediated immunity to the pathogen, Mycobacterium leprae. To determine whether IL-7 is produced at the site of infection in leprosy, we used the PCR to measure IL-7 and IL-7R mRNA in skin lesions. IL-7 mRNA was more strongly expressed in the tuberculoid form of the disease, in which the infection is limited (mean cpm = 48 +/- 8; n = 11), as compared with the progressive lepromatous form (17 +/- 2; n = 11). IL-7R mRNA, both membrane-bound and soluble forms, were also more strongly expressed in tuberculoid lesions, although these differences were not as striking as those for IL-7. The cellular source of IL-7 included Ag-stimulated monocytes and IFN-gamma-induced keratinocytes. M. leprae-induced PBMC responses in tuberculoid patients involved up-regulation of IL-7 and IL-7R mRNA and was IL-7 dependent. In contrast, M. leprae did not induce IL-7 mRNA in lepromatous patients, and their T cell responses were weakly augmented by rIL-7. These data suggest that IL-7, produced at the site of disease, contributes to the cell-mediated immune response to human pathogens.

Base Sequence↗

PubMed1995

Quantitative determination of diol metabolites of CS-670, a new antiinflammatory agent, by capillary column gas chromatography-mass spectrometry.

CS-670(I), being developed as a non-steroidal anti-inflammatory agent, is a racemic prodrug. It has been found to be readily metabolized to active metabolites: trans and unsaturated mono-ols (trans-OH, unsaturated-OH). We report here a method for the quantitative determination of the eight diol stereoisomers excreted in urine after administration I. The diols were well separated and quantitated using capillary column GC-MS after a rather simple derivatization with diazomethane-trifluoroacetic anhydride. Sex differences in rats and species differences between rats and mice were observed in the metabolism of I: the trans-diols originating from trans-OH were predominantly excreted in male and female rat urine but the excretion rate was greater in the male rats; the cis-diols originating from cis mono-ol (cis-OH) were the major urinary metabolites in mice. The hydroxy groups were mainly introduced at the respective equatorial hydrogen atoms at the 4'-carbon of trans-OH and the 5'-carbon of cis-OH. The 4'- and 5'-hydroxy groups in the diols were in the cis conformation with respect to the original 2'-hydroxy group. As approximately 9% of the trans-diols were excreted in urine after administration of cis-OH to rats, the chiral inversion from cis-OH to trans-OH was suggested to occur through the saturated ketone intermediate.

Animals↗

PubMed1995

Effects of TA-0910, a novel orally active thyrotropin-releasing hormone analog, on the gait of ataxic animals.

The effects of TA-0910 (1-methyl-(S)-4,5-dihydroorotyl-L-histidyl-L- prolinamide), a new thyrotropin-releasing hormone (TRH: L-pyroglutamyl-L-histidyl-L-prolinamide) analog, on ataxia were compared with those of TRH given by oral administration. The ataxic models used were the Rolling mouse Nagoya (RMN) showing genetic dysfunction of the cerebellum and striatum, rats with chemical degeneration of the inferior olive induced by 3-acetylpyridine (3-AP, 40 mg/kg, i.p.) and rats with a lesion of the thoracic spinal cord induced by mechanical compression. TA-0910 (1, 3, 10 mg/kg per day) clearly showed ameliorating effects on all these ataxic models. The dose-dependent effect of TA-0910 (10 mg/kg per day) on the gait of RMN was sustained until 2 weeks after the end of its 2-week administration. TRH (100, 300 mg/kg per day) also showed ameliorating effects on ataxia in RMN and 3-AP-treated rats. The ameliorating action of TA-0910 on ataxia was 100-300 times more potent than that of TRH.

Administration, Oral↗

PubMed1995

Leukocytapheresis therapy, performed with leukocyte removal filter, for inflammatory bowel disease.

Leukocytapheresis (LCAP), performed with a leukocyte removal filter, was administered five times, at 1-week intervals, for 5 weeks of intensive therapy and five times, at approximately 1-month intervals, for approximately 5 months of maintenance therapy, to 13 patients with inflammatory bowel disease (IBD) diagnosed as ulcerative colitis (UC) in 8 and Crohn's disease (CD) in 5. Clinical and blood examinations showed no side effects in any of the patients. During the intensive therapy, excellent or moderate clinical response was recognized in 11 of the 13 patients (84.6%), of whom 6 had a dramatic response; the excellent or moderate clinical response continued throughout the maintenance therapy in 8 of the patients (61.5%). Flow cytometry showed that the patients who had improved generally had high values for percentages of HLADR+, HLADR+CD3+, and HLADR+CD8+ cells before the first LCAP, and that these values and the C-reactive protein levels and erythrocyte sedimentation rates had decreased to the normal range by the end of both intensive and maintenance therapy. In the patients who showed poor response, in contrast, all the above values had been at or near normal before the initial LCAP administration. The clinical improvement in the absence of any additional medical treatment suggests that LCAP has the capacity to influence the causal mechanism(s) of IBD and that IBD is strongly associated with the cell-mediated immune response.

Adolescent↗

PubMed1995

Ameliorating effect of clentiazem (TA-3090), a new Ca antagonist, on the impaired learning ability of poststroke SHRSP.

We investigated the influence of clentiazem (8-chloro-diltiazem, (+)(2S,3S)-3-acetoxy-8-chloro-5-[2-(dimethyl-amino)ethyl]-2,3-dihydro-2- (4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one maleate, TA-3090) and other Ca antagonists on the impaired learning ability in poststroke spontaneous hypertensive rats stroke prone (SHRSP) using a shuttle box. SHRSP were given 1% NaCl solution as drinking water until the development of stroke (poststroke SHRSP). Active avoidance task was started from the fourth day after the onset of stroke. Over a period of 20 sessions (15 trials/session/day), the mean avoidance rate of the poststroke SHRSP was significantly lower than that of the nonstroke control group that was not given the salt solution. Clentiazem (1, 3, and 10 mg/kg/day) administered orally for 23 days after the development of stroke increased the avoidance rate in a dose-dependent manner. Nimodipine (1 and 10 mg/kg/day) also increased the avoidance rate, but its effect was not dose dependent. We also investigated the influence of clentiazem and other Ca antagonists on the passive avoidance performance by mice using a light-dark box. Clentiazem (3, 10, and 30 mg/kg) and other Ca antagonists, nimodipine (1 mg/kg) and nicardipine (10 mg/kg), all failed to protect either CO2- or electroconvulsive shock (ECS)-induced avoidance deficit when administered orally 1 h before the acquisition or retention trial. These results may be explained by the possibility that the Ca antagonists may ameliorate the impaired learning ability in poststroke SHRSP through their improving effect on the cerebral circulation disturbance.

Amnesia↗

PubMed1995

Changing pattern of mental health utilization in Hachijojima.

We have reviewed retrospectively 229 patients interviewed by the mental health team in the Hachijojima since the establishment of our services in 1987. The 6 year observation period was classified into three chronological stages for the purposes of identifying any change in the utilization pattern of the mental health services of the island. The rate of schizophrenia was observed to have decreased from 48% in the first 2 years of the study period to 28% in the last 2 years; while that of other mental disorders increased yearly. Interestingly, an increasing number of patients were referred to our services by professionals in areas other than mental health (from 42 to 77%), and patients without any history of psychiatric treatment were more frequently seen (from 36 to 75%) in the later part of the study period. These changes suggest the importance of access to mental health services.

Adolescent↗

PubMed1995

Anti-ataxic effects of TRH and its analogue, TA-0910, in Rolling mouse Nagoya by metabolic normalization of the ventral tegmental area.

1. The mechanism of the anti-ataxic action of thyrotropin-releasing hormone (TRH) and its analogue. TA-0910, in the Rolling mouse Nagoya (RMN), an ataxic mutant mouse, has been investigated. 2. TRH (30 mg kg-1, i.p.) and TA-0910 (3 mg kg-1, i.p.) reduced the fall index (number of falls/spontaneous motor activity), an index of ataxia, 10-30 and 10-60 min after administration, respectively. 3. Relative local cerebral glucose utilization (LCGU) in the cerebellum and ventral tegmental area (VTA) of the rolling mouse was significantly smaller than that in normal animals. TRH (30 mg kg-1, i.p.) and TA-0910 (3 mg kg-1, i.p.) increased the relative LCGU value of the VTA but not of the cerebellum in rolling mice to the level of normal animals. 4. These results suggest that the ataxia of the rolling mouse may be due to dysfunction of the cerebellum and VTA, and that amelioration by TRH and TA-0910 could result from metabolic normalization of the VTA.

Animals↗