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Biomedical subjects

T Matsui

Publications and source records attributed to T Matsui.

At least 397 records · Page 22Linked to original sources

Adenoviral gene transfer of phospholamban in isolated rat cardiomyocytes. Rescue effects by concomitant gene transfer of sarcoplasmic reticulum Ca(2+)-ATPase.

Phospholamban forms an integral part of the cardiac sarcoplasmic reticulum (SR) and regulates the activity of SR Ca(2+)-ATPase (SERCA2a). A number of studies have suggested a decrease in SERCA2a relative to phospholamban in heart failure. To test the hypothesis that changes in the relative abundance of phospholamban to SERCA2a could account for the pathophysiological abnormalities in Ca2+ handling observed in failing myocardium, we created a recombinant adenovirus designed to overexpress phospholamban (Ad.RSV.PL). In neonatal rat cardiomyocytes, Ad.RSV.PL increased the expression of phospholamban in a concentration-dependent fashion, reaching 280 +/- 43% at a multiplicity of infection (MOI) of 10.0 plaque forming units (pfu)/cell at 48 hours. The relationship between Ca(2+)-ATPase activity and [Ca2+] was shifted rightward in membrane preparations from cardiomyocytes infected with Ad.RSV.PL. Intracellular Ca2+ transients measured in the neonatal cells infected with Ad.RSV.PL (MOI, 10 pfu/cell) were characterized by (1) a significant prolongation of the relaxation phase (344 +/- 26 versus 710 +/- 56 milliseconds, P < .01), (2) a decrease in peak [Ca2+]i (967 +/- 43 versus 630 +/- 33 nmol/L, P < .01), and (3) an elevation in resting [Ca2+]i (143 +/- 14 versus 213 +/- 17 nmol/L, P < .05). Similarly, the time course of shortening was prolonged in myocytes infected with Ad.RSV.PL. These effects were partially restored by simultaneous transduction with an adenovirus carrying SERCA2a. Cardiomyocytes infected with Ad.RSV.PL had an abnormal frequency response: a decrease in peak [Ca2+]i and an increase in resting [Ca2+]i with increasing frequency. These findings indicate that adenovirus-mediated gene transfer of phospholamban modifies intracellular Ca2+ handling and the frequency response in cardiomyocytes. Our results suggest that alterations in the ratio of phospholamban to SERCA2a could account for the abnormalities in Ca2+ handling observed in heart failure and that overexpression of SERCA2a can largely correct these abnormalities.

Adenoviridae↗

Determination of endogenous peptides with in vitro ACE inhibitory activity in normotensive human plasma by the fluorometric HPLC method.

An in vitro degradation test of angiotensin (ANG) II or III in normotensive supine human plasma from 9 healthy male subjects confirmed the production of smaller ANG metabolites with angiotensin I-converting enzyme inhibitory activity. These metabolites were identified as ANG (3-8), ANG (5-8), and ANG (3-4), whose respective peptide concentrations were determined by our proposed naphthalene-2,3-dialdehyde (NDA)-HPLC method to be 64 +/- 9, 39 +/- 5, 176 +/- 22, and 197 +/- 35 fmol/ml of plasma.

Adult↗

Metabolic behavior of angiotensins in normotensive human plasma in the supine and upright postures.

The effect of activating the renin-angiotensin system on the metabolism of angiotensins (ANGs) in normotensive human plasma was investigated. In normotensive supine human plasma, four peptides with in vitro angiotensin I-converting enzyme (ACE) inhibitory activity which correspond to the sequence of ANG (3-8), ANG (4-8), ANG (5-8), and ANG (3-4) existed at a concentration of > 39 fmol/ml of plasma. When activating the renin activity by keeping upright in posture for 60 min, ANG II and the four peptides significantly increased as compared with the levels in the supine posture, except for ANG I. In particular, Val-Tyr corresponding to ANG (3-4) in the upright posture was about 4-fold more than the value in the supine posture, and was predominantly present (447 fmol/ml of plasma) as well as ANG I. As a result of in vitro degradation tests on ANGs, ANG (3-4) was produced from ANG I, and not from ANG II, III or (3-8), during the 30-min incubation.

Adult↗

An electrophysiological study of the effects of acute methylmercury chloride exposure on the function of the guinea pig cochlea.

The inner ear function of methylmercury chloride (MMC)-exposed guinea-pigs was examined in this study. Previous studies which investigated the function of the eighth cranial nerve and Corti-organ using cochlear microphonics (CM), compound action potential (CAP) and measurement of endocochlear potential (EP) reported ototoxicity following experimental exposure to MMC. In this report, the effect of MMC on the cochlea and the eighth cranial nerve were investigated systematically by measuring CM, action potential (AP), EP and K+ ion concentration of the endolymph. Guinea-pigs were injected with 5 mg/kg MMC (using 0.2% solution) twice a week for 1-3 weeks. The maximum output voltage of AP was decreased by injection of MMC (5 mg/kg x 6). A decrease in the CM maximum output voltage and the elevation of CM pseudothreshold was seen after MMC injection. Changes in EP during 3 min anoxia were observed, especially a decrease in the absolute value of the negative potential. The endolymph K+ ion concentration remained unchanged. These findings indicate that the diffusion potentials decreased and at the same time was reduced the maximum output voltage in CM induced by MMC injection (5 mg/kg x 6) in this experiment.

Action Potentials↗

[A case of advanced gastric cancer that responded to long-term administration of low-dose 5'-DFUR].

A 83-year-old female suffering from advanced gastric cancer with paraaortic lymph node metastases was administered low-dose 5'-DFUR (600 mg/day) orally. The primary tumor reduced in size fifty days after the start of the treatment, and the swelled lymph node disappeared on abdominal CT scan. Specimens obtained by endoscopical biopsy were highly susceptible to pathological degeneration of the cancer. Low-dose 5'-DFUR was effective both for the primary lesion of gastric cancer and for the lymph node metastases in this case.

Aged↗

[Short-term intensive treatment for acute myelogenous leukemia (excluding M3 subtype) in adults].

Thirty-two adults (median age 48 years) with acute myelogenous leukemia (excluding M3) have been treated with short-term intensive therapy (M90 therapy). After induction therapy with daunorubicin, cytosine arabinoside (araC), 6-mercaptopurine, prednisolone, mitoxantrone (MIT) and etoposide (VP16), three regimens of post-induction chemotherapy were conducted as short an intercycle time as possible. The first regimen was with MIT and VP16, the second with behenoyl-araC and aclarubicin and the third with VP16, araC, vincristine and vinblastine. No further therapy was given. Complete remission was achieved in 24 (75%) of 32 patients and 24% of all patients were projected to remain free of disease at 5 years. The median duration of the entire therapy was 120 days with a range of 95 to 157 days. Post-induction regimens resulted in severe myelosuppression and their toxicity included treatment-related death in one patient. The treatment results of this short-term therapy were comparable to a former treatment protocol, M84 therapy with a median duration of the entire treatment therapy of 515 days. To confirm the advantages of such short-term therapy, prospective randomized comparisons with conventional post-induction therapy may be required.

Aclarubicin↗

[The correlation between interleukin-10 and interferon-gamma produced by peripheral blood mononuclear cells stimulated by house dust mite antigen in atopic dermatitis].

The production of interleukin (IL)-10 and interferon (IFN)-gamma by peripheral blood mononuclear cells (PBMC) stimulated by house dust mite (HDM)antigen and concanavaln A (Con A) was measured in patients with atopic dermatitis (AD). The HDM-stimulated PBMC from AD patients revealed to produce significantly higher levels of IL-10 (12 h: 918.4 +/- 206.5, 24 h: 1252.5 +/- 145.8, 72 h: 1332.7 +/- 123.9 pg/ml) than those from normal control subjects (12 h: 231.1 +/- 139.0, 24 h: 585.7 +/- 196.2, 72 h: 813.5 +/- 181.8 pg/ml). Con A-stimulated AD-PBMC also showed significantly higher levels of IL-10 production than those from normal controls, although they were lower than the productions induced by HDM antigen. By contrast, the levels of IFN-gamma from AD PBMC stimulated with HDM or Con A, were significantly lower than those from normal controls. IFN-gamm production might be down-regulated by IL-10 in AD-PBMC. The overproduction of IL-10 seems to show that helper T type 2 (Th2) cells are rather dominantly activated than Th1 cells and Th2 cells might contribute to produce the cytokines in response to HDM antigen in AD patients.

Adult↗

Zinc enhancement of 17beta-estradiol's anabolic effect in osteoblastic MC3T3-E1 cells.

The anabolic effect of 17beta-estradiol in osteoblastic MC3T3-E1 cells was investigated. The cells were cultured for 3 days in the medium containing either vehicle or 17beta-estradiol (10(-11)-10(-9) M). 17beta-Estradiol significantly increased alkaline phosphatase activity and protein concentration in the cells. The steroid (10(-9) M) also significantly elevated the cell numbers and the cellular DNA content. The anabolic effect by 17beta-estradiol was blocked by the presence of dipicolinate (10(-3) M), a chelator of zinc ion, suggesting a role of cellular zinc in osteoblastic cell function. The presence of zinc sulfate (10(-5) M) or beta-alanyl-L-histidinato zinc (AHZ) (10(-5) M) significantly enhanced the 17beta-estradiol (10(-10) or 10(-9) M)-induced increase of alkaline phosphatase activity and protein concentration in the cells; the effect of AHZ was greater than that of zinc sulfate. The enhancement by zinc compounds was not based on the augmentation of osteoblastic cell numbers. The co-addition of cycloheximide (10(-6) M), an inhibitor of protein synthesis, completely blocked the zinc compound (10(-5) M)-induced enhancement of 17beta-estradiol's (10(-9) M) effect to increase alkaline phosphatase activity and protein concentration in the cells. Moreover, the anabolic effect of 17beta-estradiol together with or without zinc compounds was abolished by the presence of staurosporine (10(-8) M), an inhibitor of protein kinase C, or of okadaic acid (10(-7) M), an inhibitor of protein phosphatase. The present study demonstrates that the anabolic effect of 17beta-estradiol is enhanced by zinc-chelating dipeptide in osteoblastic MC3T3-E1 cells, and that the enhancing effect may involve protein synthesis and protein kinase activity.

3T3 Cells↗

Significance of MTG8 in leukemogenesis.

MTG8 is a counterpart gene of AML1 in acute myeloid leukemia with t(8:21) translocation. Most of the coding region of the MTG8 is fused with AML1 runt domain. In normal tissues, the MTG8 is highly expressed in brain, but not in hematopoietic tissues. MTG8 may be important in leukemogenesis as well as in AML1 truncation. The function of MTG8 is assumed to be as a transcription factor, because it possesses several features common to transcription factors; putative zinc finger motifs, serine/threonine/proline-rich sequences and a region similar to TAF110. In this paper, we report on the protein properties of the MTG8.

Acute Disease↗

[A case of isolated ACTH deficiency accompanied by generalized painful muscle cramp].

We report a patient who had generalized painful muscle cramps associated with isolated ACTH deficiency. A 68-year-old woman was hospitalized because of painful muscle cramps present for one year. Neurological examination revealed no abnormalities except for generalized painful muscle cramps. Serum electrolyte and CPK levels were normal. Serum ACTH and cortisol levels as well as urine 17-OHCS were low. An ACTH loading test employing insulin, TRH and LH-RH indicated isolated ACTH deficiency. Just after the muscle cramp, EMG revealed a low amplitude in the biceps muscle. Colon biopsy showed mild fibrosis and inflammatory cell infiltration in the lamina propria. Her muscle cramps improved markedly after two weeks of hydrocortisone replacement therapy and resolved after three weeks, suggesting that this symptom was closely related to isolated ACTH deficiency. Our case suggests that isolated ACTH deficiency may present with very similar clinical symptoms to Satoyoshi disease.

Adrenocorticotropic Hormone↗

Beclomethasone dipropionate administration via cecostomy in ulcerative colitis.

Beclomethasone dipropionate was administered via a cecostomy to four patients with active ulcerative colitis that was refractory to conventional glucocorticosteroid therapy. From a tube cecostomy, beclomethasone dipropionate solution was administered continuously throughout the day. Clinical manifestations, laboratory examinations, and endoscopic and/or radiographic findings markedly improved within 1-2 wk. A serial decrease in the index of disease activity was observed from the time administration began (mean score, 226.0) to 2 wk later (137.4 points). An excellent clinical response was recognized without any significant side effects, and the urgent need for total colectomy was avoided in all four patients.

Adult↗

[Findings of genetic changes in small intestinal carcinomas].

There is now good evidence that a series of genetic lesions in both dominant oncogenes and tumor suppressor genes are involved in the pathogenesis of human digestive tract carcinomas. Small intestinal carcinomas are very rare, accounting for only about 0.19% of all primary gastrointestinal malignant tumors in Japan, so there are few reports investigating genetic changes of small intestinal carcinoma. We analyzed 3 microsatellite loci and the status of K-ras and p53 genes isolated from tumors and surrounding normal tissue samples obtained during surgery. The polymerase chain reaction (PCR) technique used frequent genetic instability to assess differences between tumor and matched DNAs. Replication errors (RERs) were observed in 3 of the 29 cases (10%) of gastric carcinoma and in 11 of the 72 cases (15%) of colorectal carcinoma. None of the 13 (0%) esophageal carcinoma cases showed any RER, but 5 of 11 cases of small intestinal carcinoma (45%) had RERs, reflecting a significantly high incidence. None of the 11 small intestinal carcinoma cases exhibited K-ras gene mutations. Of 7 case amplified successfully by polymerase chain reaction (PCR) in exon 5-8 loci in p53 gene, 2 exhibited abnormally migrated bands in polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. It is thus clear that the genetic carcinogenesis in the small intestine is different from other parts of the digestive tract. These results suggest that genetic instability plays an important role in the pathogenesis of small intestinal carcinomas.

Adenocarcinoma↗

[Quantitative evaluation of diabetic gastrointestinal paresis by measuring transit time of the stomach and the digestive canal].

Our subjects comprised eighty six diabetes mellitus (DM) patients without severe complication. To evaluate gastrointestinal motility quantitatively, we measured gastric emptying time by acetaminophen (APAP) method using serum APAP value and oro-cecal transit time (OCTT) by lactulose hydrogen breath test in the subjects and normal controls (NC). Comparing DM patients and NC, mean APAP value was lower and mean OCTT was prolonged in the former. Analysing DM patients' background, patients with peripheral neuropathy had prolonged OCTT than patients without neuropathy did. Comparing patients with higher HbA1c levels and patients with normal HbA1c levels, mean APAP value, which was closer to normal levels, was higher in the former. Analysing symptoms, some of them were apparently related to abnormal gastrointestinal motility. From these results, it was concluded that measuring both gastric emptying and OCTT was a useful method to evaluate slight abnormal motility in DM patients.

Diabetes Mellitus↗

[Enteral nutrition and total parenteral nutrition in Crohn's disease; factors influencing induction of remission].

The aim of this study was to clarify factors influencing the induction of remission and to compare the short term remission rate of EN with that of TPN. From 1985 to 1992, 87 active patients treated for more than 4 weeks with EN and 71 active patients treated with TPN were analysed. Excluding the case with severe complications (abdominal abscess, external fistula, sub-ileus), 132 patients were divided to two groups (patients with remission and non-remission) based on clinical response to the treatment. Remission was defined as Crohn's disease activity index (CDAI) < 150 and ESR < 20 mm/hr after 4 weeks of treatment. Clinical characteristics and radiographic findings were compared between the two groups. Furthermore, a multiple logistic regression analysis was performed to clarify the relative importance of various clinical or radiographic factors associated with remission. Remission rate at four weeks with EN was 77% and that with TPN was 62%. By a multiple logistic regression analysis using 15 factors, which were significant by a single variable analysis, four factors (times of previous nutritional treatment, IOIBD, WBC, polyposis score of the colon) in EN cases and three factors (ESR, platelets, extent of Crohn's disease) in TPN cases were selected as independent prognostic factors after adjusting for the effect of other factors. Moreover, mode of therapy was not selected as a valuable factor. From the above mentioned results, it was concluded that EN and TPN were equivalent in the efficacy of short-term therapy and patients having had several previous nutritional therapy, high IOIBD score, high WBC count, severe cobblestoning of the colon were tended to be resistant to EN therapy and high ESR value, high platelet count, broader extent of Crohn's disease were tended to be resistant to TPN therapy. Both clinical and radiographic features are important prognostic factors in predicting response to nutritional therapy.

Adult↗

Inhibition of metastasis by a dialysable factor in fetal bovine serum in B16 melanoma cells.

Fetal bovine serum (FBS) supplemented to the culture medium inhibited the metastasis of B16BL6 melanoma cells in a dose-dependent manner. This metastasis-inhibiting activity was accompanied by growth-promoting activity, up to the concentration of 10% FBS. However, among the clones isolated from B16BL6 cells, there were clones in which FBS significantly inhibited the metastasis without promoting their growth. Dialysis (cutoff M.W. 8000 Da) removed the metastasis-inhibiting activity but not the growth-promoting activity from FBS. These results indicate that FBS has metastasis-inhibiting activity which is independent of growth-promoting activity, and that the metastasis-inhibiting activity is carried by molecules removed by dialysis.

Animals↗

The alpha3beta3gamma subcomplex of the F1-ATPase from the thermophilic bacillus PS3 with the betaT165S substitution does not entrap inhibitory MgADP in a catalytic site during turnover.

The hydrolytic properties of the mutant alpha3(betaT165S)3gamma and wild-type alpha3beta3gamma subcomplexes of TF1 have been compared. Whereas the wild-type complex hydrolyzes 50 microM ATP in three kinetic phases, the mutant complex hydrolyzes 50 microM ATP with a linear rate. After incubation with a slight excess of ADP in the presence of Mg2+, the wild-type complex hydrolyzes 2 mM ATP with a long lag. In contrast, prior incubation of the mutant complex under these conditions does not affect the kinetics of ATP hydrolysis. The ATPase activity of the wild-type complex is stimulated 4-fold by 0. 1% lauryl dimethylamine oxide, whereas this concentration of lauryl dimethylamine oxide inhibits the mutant complex by 25%. Compared with the wild-type complex, the activity of the mutant complex is much less sensitive to turnover-dependent inhibition by azide. This comparison suggests that the mutant complex does not entrap substantial inhibitory MgADP in a catalytic site during turnover, which is supported by the following observations. ATP hydrolysis catalyzed by the wild-type complex is progressively inhibited by increasing concentrations of Mg2+ in the assay medium, whereas the mutant complex is insensitive to increasing concentrations of Mg2+. A Lineweaver-Burk plot constructed from rates of hydrolysis of 20-2000 microM ATP by the wild-type complex is biphasic, exhibiting apparent Km values of 30 microM and 470 microM with corresponding kcat values of 26 and 77 s-1. In contrast, a Lineweaver-Burk plot for the mutant complex is linear in this range of ATP concentration, displaying a Km of 133 microM and a kcat of 360 s-1.

Adenosine Diphosphate↗