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Biomedical subjects

S Tamura

Publications and source records attributed to S Tamura.

At least 397 records · Page 22Linked to original sources

[MECHOP-BM chemotherapy in the treatment of non Hodgkin's lymphoma].

Twenty patients with previously untreated advanced aggressive or relapsed or refractory non-Hodgkin's lymphoma were treated with the MECHOP-BM regimen (MCNU, etoposide, cyclophosphamide, adriamycin, vincristine, prednisolone, bleomycin and methotrexate). Of the 18 patients treated with the MECHOP-BM, the response rate was 78% and complete response (CR) was attained in 33%. Among these CR patients, one patient relapsed, but the other patients continued to show CR (59-243 days, medium 178 days). The most serious toxicity attributed to MECHOP-BM therapy was leukopenia. The mean white blood cell count dropped to 1,300/microliters, and only therapy could be useful in the treatment for patients with untreated aggressive and advanced stage of non-Hodgkin's lymphoma as well as salvage therapy of relapsed cases.

Adolescent↗

[Expression of rat type 2C alpha protein phosphatase in Saccharomyces cerevisiae cells].

In the course of a study to elucidate the physiological functions of type 2C protein phosphatase(PP2C), we investigated the effects of overexpression of the enzyme protein on the physiology of eukaryotes. In this study, we demonstrated that the overexpression of PP2C alpha caused a decreased growth rate and an increased UV-sensitivity of the yeast cells. We also showed that the expressed PP2C was phosphorylated by casein kinase II in the cells.

Animals↗

[The effects of prostaglandin E1 infusion during cardiopulmonary bypass on cardiac and renal function in the early postoperative period].

Postoperative complications after cardiac surgery are mainly caused by the detrimental effects of cardiopulmonary bypass (CPB) on hemodynamics and humoral factors. We studied the effects of prostaglandin E1 (PGE1) infusion on CPB induced organ failure. Twenty-four patients who underwent coronary bypass surgery with normal preoperative cardiac and renal function were divided into two groups. PG group (n = 11) was given PGE1 (0.03-0.05 microgram/kg/min) during CPB while the control group (n = 13) was not. Hemodynamic studies with the Swan-Ganz catheter and renal function tests including serum creatinine (Cr), serum beta 2-microglobulin (s-BMG) and urine beta 2-microglobulin (u-BMG) measurements were performed 24 hours after surgery. After CPB, alpha-adrenergic agent requirement was higher in the PG group than in the control group. In the PG group, the mean cardiac index was slightly higher and the mean left ventricular stroke work index was lower than in the control group. Although the mean systemic vascular resistance index was lower in the PG group, the mean pulmonary vascular resistance index was higher because of the vasoconstrictive action of alpha-adrenergic agents. These differences were seen only immediately after surgery; hemodynamic parameters in both groups were at the same level 3 hour postoperatively. Immediately after surgery, creatinine in the PG group was significantly lower than in the control group. While there was no significant differences in s-BMG between the two groups, u-BMG at 6 and 12 hours postoperatively in the PG group were significantly lower than in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Gastric DNA-binding proteins recognize upstream sequence motifs of parietal cell-specific genes.

Polymerase chain reaction amplification of cDNA from pig gastric mucosa demonstrated the presence of zinc-finger proteins called GATA-GT1, GATA-GT2, and GATA-GT3, each having zinc-finger sequences similar to previously characterized GATA-binding proteins. Subsequently, full-length cDNAs of GATA-GT1 and GATA-GT2 were obtained from rat stomach. The zinc-finger domains of GATA-GT1 and -GT2 were 66-86% identical on the amino acid level with each other and with other GATA-binding proteins. Potential protein kinase phosphorylation sites were present in the zinc-finger region. In contrast, regions outside the zinc fingers shared significantly lower similarities. GATA-GT2 was found to bind to the upstream sequence of the H+/K(+)-ATPase beta gene and to a sequence containing the GATA motif. GATA-GT1 and -GT2 were expressed predominantly in the gastric mucosa and at much lower levels in the intestine (GATA-GT2, also in testis), their tissue distributions being distinct from those of GATA-1, -2, or -3. These results clearly suggest that GATA-GT1 and GATA-GT2 are involved in gene regulation specifically in the gastric epithelium and represent two additional members of the GATA-binding protein family.

Amino Acid Sequence↗

Phosphorylation of Mg(2+)-dependent protein phosphatase alpha (type 2C alpha) by casein kinase II.

In this study we show that rat Mg(2+)-dependent protein phosphatase alpha (MPP alpha) expressed in Saccharomyces cerevisiae cells was phosphorylated on serine residues in vivo. The recombinant rat MPP alpha purified from Escherichia coli cells harboring an expression vector was phosphorylated in vitro by casein kinase II, but not by casein kinase I, to 1.5 mol phosphate per mol enzyme protein. Analysis by phosphopeptide mapping and amino acid analysis suggested that the sites of both in vivo and in vitro phosphorylation were the same and involved only serine residues. These results suggest that the rat MPP alpha expressed in yeast cells is phosphorylated by yeast casein kinase II in vivo. It is further proposed that the phosphorylation sites are located in the carboxyl terminal region of the enzyme molecule.

Amino Acid Sequence↗

Prognostic significance of transforming growth factor-alpha in human esophageal carcinoma. Implication for the autocrine proliferation.

BACKGROUND: The authors recently used immunostaining to demonstrate that patients with epidermal growth factor receptor (EGFR) overexpression have poor survival after surgery. However, the clinical significance of transforming growth factor (TGF)-alpha, one of the ligands of EGFR, has not been demonstrated in esophageal carcinoma. METHODS: Immunohistochemical study for TGF-alpha and EGFR was performed on 57 esophageal squamous cell carcinomas using monoclonal antibodies. RESULTS: TGF-alpha expression was positive in 35% of the tumors, and EGFR overexpression, defined as stronger staining in cancer cells than in normal epithelium, was positive in 43% of the tumors, according to the authors' arbitrary criteria. The incidence of TGF-alpha positivity was relatively higher in patients with the EGFR overexpression (EGFR+) than in the patients with non-overexpression (EGFR-). The survival rate was significantly lower in patients with TGF-alpha(+) than in those with TGF-alpha(-) (P < 0.01) and in patients with EGFR(+) than in patients with EGFR(-) (P < 0.01), respectively. Considering TGF-alpha and EGFR expression simultaneously, the survival rate of the patients with TGF-alpha(+)/EGFR(+) tumors was the lowest of the four subgroups, with statistically significant differences noted. These relationships between the immunoreactivities and survival curves were observed in the analysis within patients with node-positive disease. In addition, a multivariate statistical analysis demonstrated that TGF-alpha was the only significant variable, whereas EGFR and nodal status provided no additional information regarding postoperative survival. CONCLUSION: The results presented suggest that TGF-alpha may act as an autocrine growth factor through hyperproducing EGFR and that its expression and EGFR overexpression may prove useful as a valuable prognostic indicator for patients with esophageal carcinoma.

Carcinoma, Squamous Cell↗

Dephosphorylation of autophosphorylated Ca2+/calmodulin-dependent protein kinase II by protein phosphatase 2C.

It has been demonstrated that okadaic acid-insensitive protein phosphatases are involved in dephosphorylation of autophosphorylated Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) in rat cerebellar granule cells (Fukunaga, K., Rich, D. P., and Soderling, T. R. (1989) J. Biol. Chem. 264, 21830-21836). In the present study, recombinant rat protein phosphatase 2C (PrP-2C) expressed in Escherichia coli could dephosphorylate both Thr286/287 and Thr305/306 phosphorylation sites of CaM kinase II, which are responsible for the generation of Ca(2+)-independent activity and the inhibition of the total activity, respectively. The dephosphorylation of Thr286/287 and Thr305/306 was accomplished within 15 min at 0 degrees C and totally dependent on Mg2+. Phosphopeptide mapping of the CNBr-cleaved 32P-labeled CaM kinase II revealed that PrP-2C was relatively specific for dephosphorylation of Thr286/287 and Thr305/306 in the autophosphorylated CaM kinase II. These results suggest that PrP-2C has a role in the regulation of the Ca(2+)-independent activity of CaM kinase II in the neural cells.

Animals↗

Aromatase activity in human hepatocellular carcinoma. Relationship with the degree of histologic differentiation.

Human hepatocellular carcinomas (HCC) were examined aromatase activity, an enzyme that converts androgen into estrogen. Such activity was detected in all 13 specimens of HCC (mean activity, 120 fmol/30 min/mg microsomal protein). The activity tended to be lower in the HCC tissue than in the surrounding liver tissue (mean activity, 230 fmol/30 min/mg microsomal protein), although it was higher in the HCC tissue from three of eight patients with Edmondson's Grade 2 disease. This relationship was not found in the five with Grade 3 disease. On the whole, aromatase activity was significantly higher in specimens from patients with Edmondson's Grade 2 tumors than in the less differentiated Grade 3 type (P < 0.05). These observations suggested that aromatase activity was present in human HCC and was related to the degree of histologic differentiation.

Aged↗

Molecular cloning of a novel isotype of Mg(2+)-dependent protein phosphatase beta (type 2C beta) enriched in brain and heart.

Two complementary DNA (cDNA) clones (pTK-1 and -2) encoding two distinct isotypes of mouse Mg(2+)-dependent protein phosphatase beta (MPP beta-1 and -2, respectively) were isolated from a melanocyte cDNA library. Although mouse pTK-1 is orthologous to the rat cDNA (JW5) reported previously [Wenk, J., Trompeter, H.I., Pettrich, K.G., Cohen, P.T.W., Campbell, D.G., and Mieskes, G. (1992) FEBS Lett. 297, 135-138], pTK-2 is a novel cDNA clone. It was strongly suggested that the pTK-1 and -2 cDNAs are splicing variants of a single pre-mRNA. The difference in the amino acid sequences between MPP beta-1 and -2 was observed only at the carboxy-terminal regions. Both the recombinant MPP beta-1 and -2 expressed in Escherichia coli cells were immunoreactive to an anti-MPP beta antibody and exhibited Mg(2+)-dependent and okadaic acid-insensitive protein phosphatase activities with similar substrate specificities. Although the mRNA of MPP beta-1 was expressed ubiquitously in various mouse tissues, that of MPP beta-2 was expressed exclusively in brain and heart. These results suggest the difference in the physiological roles of these two enzyme isotypes.

Amino Acid Sequence↗

Comparison of postoperative results following terminal esophagoproximal gastrectomy and esophageal transection for esophageal varices.

The results of 44 terminal esophagoproximal gastrectomies (TEPG) and 53 esophageal transections (ET) for esophageal varices, performed during the period between January, 1975 and March, 1989, were retrospectively compared. The results examined prognosis, recurrence of esophageal varices and late postoperative complications. The 5-year survival rates for patients who underwent selective or prophylactic surgery were 85.9% following TEPG and 81.6% following ET. However, the 10-year survival rate for the former group was significantly lower than that for the latter group at 59.3% versus 70.0% (P < 0.05) because of the number of deaths due to hemorrhage and liver failure caused by anastomotic ulcers. The respective 5-year recurrence rates of varices for the TEPG and ET groups were 18.4% and 26.4%, respectively, while the 10-year recurrence rate for the former group was again significantly lower than that for the latter group at 27.1% versus 53.7% (P < 0.01). As for postoperative late complications, reflux esophagitis and/or anastomotic ulcers were found twice as frequently after TEPG as after ET. Thus, although TEPG was more effective for preventing variceal recurrence it left the potential for an anastomotic ulcer to develop, which was the dominant cause of death more than 5 years after surgery.

Adult↗

Specific cellular immune responses to pancreatic antigen in chronic pancreatitis and Sjögren's syndrome.

The specific cellular immune response to the partially purified pancreatic antigen was studied by the peripheral blood lymphocyte proliferation assay in patients with chronic pancreatitis, Sjögren's syndrome, and primary biliary cirrhosis. A significant positive result (stimulation index > 2.0) was observed in 7 of 21 patients with idiopathic chronic pancreatitis (33%; P < 0.05), 6 of 7 patients with Sjögren's syndrome-associated chronic pancreatitis (86%; P < 0.0005), and 6 of 11 patients with Sjögren's syndrome (55%; P < 0.01), compared to normal controls whose stimulation index was 0.94 +/- 0.28 (mean +/- SD; n = 14; range, 0.56-1.60). On the other hand, patients with alcoholic chronic pancreatitis (17%; n = 12), stone-related chronic pancreatitis (0%; n = 7), primary biliary cirrhosis-associated chronic pancreatitis (33%; n = 3), primary biliary cirrhosis (0%; n = 4), systemic lupus erythematosus (17%; n = 6), and autoimmune thyroiditis (0%; n = 6) showed no significant difference from normal controls. Furthermore, in patients with idiopathic chronic pancreatitis who had positive results, a lymphocyte proliferative response to the pancreatic antigen was observed in T cells, especially in the CD4+ T cell subpopulation. These results suggest that the pancreatic antigen plays a role in the pathogenesis of a part of idiopathic chronic pancreatitis and Sjögren's syndrome in association with T cell responses and, also, suggest that autoimmunity may be a possible etiological factor in chronic pancreatitis.

Animals↗

Molecular genetic study of a Japanese family with Lesch-Nyhan syndrome: a point mutation at the consensus region of RNA splicing (HPRTKeio).

Complete deficiency of hypoxanthine guanine phosphoribosyltransferase (HPRT) causes Lesch-Nyhan syndrome. A single nucleotide substitution of G to T at the 3'-end of intron 3 in the splicing consensus region has been identified in one allele of the HPRT gene from a mother predicted to be a heterozygous Lesch-Nyhan carrier. Utilizing a BfaI restriction site which was lost in the mutation as an indicator, family study showed that the mother and her only daughter were heterozygotes but the mother's sister did not have the mutant allele. The mutation generated splicing error and resulted in two types of abnormal mRNA. The major altered mRNA, named Type I, skipped the exon 4 and is predicted to produce a protein deleted of 22 amino acid residues. The other, Type II, having a 9-bp deletion at the 5'-end of exon 4, can result in a protein lacking 3 amino acids, from codon 107 to 109.

Base Sequence↗

Simple measurement of glycosaminoglycan produced by cultured fibroblasts using 4-methylumbelliferyl beta-D-xyloside.

A simple and rapid method was devised for measurement of glycosaminoglycan produced by cultured cells. 4-Methylumbelliferyl-beta-D-xyloside was added to the medium of the cultured cells. After incubation, glycosaminoglycan, which was produced from 4-methylumbelliferyl-beta-D-xyloside as a primer and secreted into the medium, was separated by proteinase digestion, trichloroacetic acid treatment and ethanol precipitation. The glycosaminoglycan, bearing a fluorescent moiety at the reducing terminal, was electrophoresed on cellulose acetate membrane, and then the fluorescent band visible on the membrane was extracted. The fluorescence of the band was measured, and from this the amount of glycosaminoglycan was estimated. Using this method, it was possible to quantify a very small amount of glycosaminoglycan with relatively high sensitivity without employing a radioisotope. This method was applied for determination of glycosaminoglycan produced by cultured fibroblasts from human uterine cervix, and also the effect of a hormone on glycosaminoglycan production. It was found that uterine cervical fibroblasts produced twice as much glycosaminoglycan as skin fibroblasts.

Carbohydrate Sequence↗

Positive association between serum zinc and apolipoprotein A-II concentrations in middle-aged males who regularly consume alcohol.

The relationship of serum zinc with serum concentrations of lipids and apolipoproteins was investigated in 464 male clerical workers aged 35-59 y. Subjects were divided into three groups, by drinking habits. Serum triglycerides, apolipoprotein (apo) A-I, and apo A-II in occasional (2-5 times/wk) and regular (> or = 6 times/wk) drinkers were higher than in non- or seldom (< 1 time/wk) drinkers, whereas serum zinc, total cholesterol (TC), and apo B were not different among groups. Significantly higher high-density-lipoprotein cholesterol (HDL-C) and HDL-C% (HDL-C/TC%) were observed in regular drinkers. Correlation analysis revealed that the serum zinc concentration was positively correlated with apo A-II only in the regular drinkers, and the relationship was significant even after body mass index, smoking habits, and frequency of physical exercise were adjusted for. The results suggest that the individual response of the apo A-II concentration to alcohol is associated with zinc nutritional status in regularly drinking middle-aged men.

Adult↗

Evidence for a new variant CYP2D6 allele CYP2D6J in a Japanese population associated with lower in vivo rates of sparteine metabolism.

A group of Japanese subjects were phenotyped for CYP2D6 activity by administration of sparteine and determination of urine metabolic ratios (MR). The CYP2D6 alleles from two subjects having a high MR, characteristic of slower rates of sparteine metabolism, were cloned in lambda EMBL3 and subjected to sequence analysis. One individual possessed a CYP2D6B allele, typically found in Caucasians, that is inactive due to an altered 3' splice recognition site and other potentially disruptive mutations. The second allele from this individual was identical to the wild type normal Caucasian CYP2D6 allele except for C188T and G4268C base differences in exons 1 and 9, respectively, that result in P34S and S486T amino acid substitutions. This allele was designated CYP2D6J. The second individual possessed two CYP2D6J alleles. PCR assays were performed to detect this allele and other alleles from a group of subjects exhibiting low rates of sparteine metabolism, i.e. with MRs > 1.5. Eleven CYP2D6J alleles were detected in 14 subjects exhibiting low rates of metabolism and including four individuals who were homozygous for this variant and had very low rates of sparteine metabolism (MRs > 2.5). In contrast, only two CYP2D6J alleles were found in 14 subjects having MRs of < 1.0. These data suggest that CYP2D6J encodes an enzyme having lower rates of sparteine metabolism.

Alleles↗