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H Nishimura

Publications and source records attributed to H Nishimura.

At least 415 records · Page 23Linked to original sources

Extragonadal germ cell tumor of retroperitoneal origin: report of two cases.

Two cases of primary extragonadal germ cell tumor of retroperitoneal origin are reported. One was a 26-year-old man complaining of back pain. He had a large retroperitoneal tumor with lung, liver and supraclavicular lymph node metastases. He was referred to us after being treated for malignant lymphoma. The serum AFP, beta-subunit of human chorionic gonadotropin (hCG-beta), CEA and CA-19-9 were elevated. The retroperitoneal disease was treated surgically and with radiotherapy. The pathological diagnosis was that of embryonal carcinoma and teratoma. The lung, liver and supraclavicular lymph node metastases disappeared completely after two courses of cisplatin-based chemotherapy. While further chemotherapy was postponed due to myelosuppression, the disease relapsed and was resistant to subsequent therapy. The patient died twelve months after he first saw us. The second case was that of a 36-year-old man complaining of edematous legs and external genitalia. He had an extensive retroperitoneal tumor with multiple pulmonary metastases. The serum AFP level was high. Suspected of having an extragonadal germ cell tumor, he was referred to us promptly. Cisplatin-based chemotherapy coupled with resection of residual retroperitoneal and pulmonary disease resulted in complete remission. The pathological diagnosis was that of possible embryonal carcinoma. Further chemotherapy was given as scheduled, using granulocyte colony-stimulating factor. The patient has been in complete remission for two years. The chemotherapeutic regimen and surgical policy in the treatment of the two patients were essentially same. Early diagnosis, adequate initial therapy and the use of granulocyte colony-stimulating factor may be relevant to the favorable prognosis in the latter case.

Adult↗

[Clinical significance of galactosyltransferase associated with tumor (GAT), a new tumor marker for ovarian cancer--with special reference to the discrimination between ovarian cancer and endometriosis].

We examined GAT, a newly developed tumor marker, in serum samples collected from 1,503 females in six institutions: 387 healthy females, 1,052 patients with gynecological diseases including 311 ovarian cancers, and 64 with nongynecological diseases. Based on the mean value + 2 SD for the healthy females, the cut-off value was set at 16 U/ml. The positive rate of GAT was 2.6% for the healthy females, 7.1% for patients with benign ovarian tumor, 5.6% for those with endometriosis, 47.9% for those with ovarian cancers, 9.3% for those with cervical cancer, and 13.3% for those with endometrial cancer. The false-positive rate of GAT for endometriosis was very low compared with that of the other markers such as CA 125, CA 602, CA 54/61, CA 72-4, STN, SLX examined in this study. The positive predictive value between ovarian cancer and endometriosis was the highest with GAT among the evaluated markers. In the cases in which the CA 125 (CA 602) value is relatively low, discrimination between ovarian cancer and endometriosis is difficult, because these cases include many patients with endometriosis. GAT showed the highest positive predictive value in such cases, so GAT proved to play a complementary role with CA 125 (CA 602). Combination assay with GAT and CA 54/61/CA 72-4/STN or SLX showed higher diagnostic efficiency between ovarian cancer and endometriosis. These results suggest the usefulness of GAT for discrimination between ovarian cancer and endometriosis.

Antigens, Tumor-Associated, Carbohydrate↗

[A case of coccidioidomycosis that was extirpated under thoracoscopy].

We report a case of coccidioidosis, which occurred in a 49-year-old Japanese man. He came back to Japan in 1994 after living in California in the U.S. for 2 years, and showed a round shadow in the left lower lung field on chest X-ray. A tumor was 1.4 cm in diameter and located in the left S8 showed by chest CT and the bronchography. It was extirpated under thoracoscopy. Histology of the tumor revealed chronic inflammation of the lung tissue, that contained a spherule of a diameter of 20-60 microns and endospores of a length of 2-6 microns. These structures were identified morphologically as coccidioides immitis. Only 3 cases of benign residual coccidioidal lesions have been reported in Japan including this case.

Chronic Disease↗

Factor IX Fukuoka. Substitution of ASN92 by His in the second epidermal growth factor-like domain results in defective interaction with factors VIIa/X.

Hemophilia B Fukuoka, a moderately severe bleeding disorder, is a naturally occurring mutant of factor IX. Plasma from our patient had 3% clotting activity even though 64% of factor IX antigen was present. The purified mutant protein was cleaved normally by factor Xla, factor VIIa-tissue factor complex, or RVV-X (factor X-activating enzyme from Russell's viper venom), yielding a two-chain factor IXa. Amino acid composition and sequence analyses of one of the lysyl endopeptidase peptides derived from factor IX Fukuoka revealed that Asn92 in the second epidermal growth factor (EGF)-like domain had been replaced by His. The active site of the factor IXa Fukuoka was normally competent for the incorporation of p-aminobenzamidine and for the hydrolysis of a synthetic substrate, N alpha-benzyloxycarbonyl-L-arginine p-nitrobenzyl ester. Factor Xa formation by factor IXa Fukuoka was only 8% of the normal factor IXa, even in the presence of polylysine, and only 0.2% of the normal in the system containing phospholipids, Ca2+, and factor VIIIa, thereby indicating a functional defect in interaction of the mutant with factors VIIIa/X. Furthermore, catalytic efficiency (kcat/Km) of factor IXa Fukuoka toward factor X in the presence of Ca2+, phospholipids, and factor VIIIa was only 2.3% of the normal factor IXa. These results suggest that an Asn-to-His substitution at position 92 in the second EGF-like domain of factor IX Fukuoka would have an untoward effect on the specific conformational state of factor IX for binding with factors VIIIa/X.

Adult↗

Glucose transporter recycling in rat adipose cells. Effects of potassium depletion.

Depletion of intracellular potassium (K+) induced a 4-fold increase in basal and 1 microM phorbol-12-myristate-13-acetate (PMA)-stimulated 3-O-methylglucose transport in rat adipose cells. K+ depletion had no effect on the maximum insulin (0.7 microM)-stimulated transport rate but enhanced the sensitivity to insulin 3-fold (EC50 = 0.05 versus 0.15 nM) by a mechanism that did not result from changes in the insulin receptor binding, autophosphorylation, or tyrosine kinase activity. Western blotting analysis revealed that K+ depletion induced a 2.2-fold increase in GLUT4 in plasma membranes from basal cells, enhanced the PMA-stimulated GLUT4 translocation by 4-fold, and increased the 5-fold insulin-stimulated GLUT4 translocation by 15%, indicating the presence of an inactive GLUT4 intermediate. The time course for insulin's stimulation of transport activity was accelerated by K+ depletion (t1/2 = 3 versus 1.5 min). Conversely, the reversal of transport activity, on removal of insulin, was delayed (t1/2 = 11 versus 22 min). The corresponding t1/2 values for the loss of GLUT4 were 22 min in control cells and 40 min in K(+)-depleted cells, again indicating the existence of an inactive intermediate. Photolabeling intact cells with the impermeant, exofacial photolabel 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis(D-mannos-4 - yloxy)-2-propylamine in the continuous presence of insulin revealed that K+ depletion had no effect on the GLUT4 externalization rate but halved the rate of internalization. K+ depletion elicited entirely analogous effects on the recycling of insulin-like growth factor II/mannose 6-phosphate receptor, strongly supporting the involvement of a coated pit mechanism in the recycling of GLUT4 transporters. An inactive conformation of GLUT4 has been detected in plasma membranes from insulin-stimulated cells, which is enhanced by K+ depletion, suggesting a limitation in the adipose cells' capacity to express active GLUT4 transporters.

3-O-Methylglucose↗

Use of bismannose photolabel to elucidate insulin-regulated GLUT4 subcellular trafficking kinetics in rat adipose cells. Evidence that exocytosis is a critical site of hormone action.

The subcellular trafficking of tracer-tagged GLUT4 between the plasma membranes and low-density microsomes of rat adipose cells has been studied. Cell-surface GLUT4 have been initially tracer-tagged in the insulin-stimulated state with the [3H]bismanose photolabel 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis-(D-mannos- 4-yloxy)-2- propylamine. The half-time for internalization of tracer-tagged GLUT4 when insulin is removed by collagenase treatment is similar to that observed for the decrease in immunodetectable GLUT4 in the plasma membranes and the decrease in glucose transport activity in the intact cells. In contrast, internalization of tracer-tagged GLUT4 also occurs when cells are maintained in the continuous presence of insulin even though the plasma membrane level of immunodetectable GLUT4 and glucose transport activity in the intact cells are unaltered. These data show, for the first time, that insulin has little, if any, effect on the rate constant for GLUT4 endocytosis, but instead, primarily increases the rate constant for exocytosis. Tracer-tagged GLUT4 that is returned to the low-density microsomes can be restimulated with fresh insulin to recycle to the plasma membranes and to a steady-state distribution level that is the same as that observed in cells that are maintained in the continuous presence of insulin. These data suggest that the cells' entire complement of GLUT4 is involved in the recycling process. Following insulin stimulation of adipose cells initially in the basal state, the increase in immunodetectable GLUT4 in the plasma membranes precedes the increase in accessibility of GLUT4 to exofacial 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis(D-mannos-4 -yloxy)-2- propylamine photolabeling, and this in turn precedes the increase in cellular glucose transport activity. Such time course data suggest that there may be plasma membrane intermediate states in the GLUT4 trafficking pathway. The kinetic properties of GLUT4 translocation and its recycling have been interpreted in terms of a subcellular trafficking model that identifies exocytosis, possibly involving-hypothetical "docking" and "fusion" steps, as the critical site of hormone action.

3-O-Methylglucose↗

Isolation and characterization of a thiamin pyrophosphokinase gene, THI80, from Saccharomyces cerevisiae.

The thi80 mutant of Saccharomyces cerevisiae (Nishimura, H., Kawasaki, Y., Nosaka, K., Kaneko, Y., and Iwashima, A. (1991) J. Bacteriol. 173, 2716-2719) shows markedly reduced activity of thiamin pyrophosphokinase (TPK; EC 2.7.6.2). We have isolated a DNA fragment carrying the THI80 gene from a yeast genomic library by its ability to complement constitutive synthesis of the thiamin-repressible acid phosphatase, encoded by the PHO3 gene, of thi80 mutant cells. On the other hand, the thi80 locus was found to be located 3.3 centimorgans proximal to the smp3 locus on the right arm of chromosome XV by genetic mapping analysis, and one more fragment bearing the THI80 gene trailing SMP3 gene was obtained by the plasmid eviction method. The nucleotide sequence of the overlapped region between the two isolated DNAs contained an open reading frame of 957 base pairs, encoding a 319-amino acid polypeptide with a calculated molecular weight of 36,616. When the intact THI80 open reading frame was expressed as a fusion protein carrying three vector-encoded amino acids at its N terminus in Escherichia coli lacking TPK, marked TPK activity was detected in the procaryotic cells, proving that the THI80 gene of S. cerevisiae encodes a structural gene of TPK. A gene disruption experiment demonstrated that the THI80 gene was essential for growth, and therefore, revealed that TPK is the only enzyme capable of synthesizing thiamin pyrophosphate in yeast. Studies of Northern blot analysis and the enzyme assay demonstrated that the THI80 gene expression is regulated mainly at the mRNA level by the intracellular thiamin pyrophosphate and requires the positive regulatory factors encoded by THI2 and THI3 genes. However, unlike thiamin-repressible acid phosphatase and the enzymes involved in thiamin synthesis of S. cerevisiae, TPK was found to be expressed constitutively at a low level and incompletely repressed by exogenous thiamin.

Amino Acid Sequence↗

Mixed haplotype A beta Z/A alpha d class II molecule in (NZB x NZW)F1 mice detected by T cell clones.

We have tried to demonstrate the existence of a mixed haplotype MHC class II molecule in (NZB x NZW)F1 (B/WF1) mice. When a large panel of keyhole limpet hemocyanin-specific T cell clones derived from B/WF1 mice was analyzed, several clones were shown to be restricted by a F1-specific A beta Z/A alpha d class II molecule. Autoreactive A beta Z/A alpha d-specific T cell clones were also obtained. The ability of the association and expression of A beta Z with A alpha d was confirmed by hybridoma and transfection experiments. Hybridoma cell lines created by fusion of NZW (H-2z) spleen cells with M12.C3 (a A beta d- variant cell line derived from M12.4.1 (H-2d) B lymphoma) cells expressed A beta Z determinants. Transfection of A beta Z genomic DNA to M12.C3 cells resulted in the expression of A beta Z determinants. These hybridoma cell lines and transfectants were able to stimulate A beta Z/A alpha d-specific T cell clones, suggesting the expression of A beta Z/A alpha d molecules on the cell surface. However, attempts to demonstrate the existence of mixed haplotype MHC class II molecules in B/WF1 mice by two-dimensional (nonequilibrium pH gradient gel electrophoresis/SDS-PAGE) gel electrophoresis analysis with the use of anti-class II mAb failed to demonstrate the existence of mixed haplotype A beta Z/A alpha d or A beta d/A alpha z class II molecules in B/WF1 mice. Analysis of mixture of TA beta Z cell and B/WF1 spleen cell lysates immunoprecipitated by anti-A beta Z mAb suggested that the amount of haplotype mixed A beta Z/A alpha d molecules in B/WF1 spleen cells is less than 1/10 that of haplotype matched A beta/A alpha pairs. Our results suggest that, although undetectable by biochemical analysis, small amounts of mixed haplotype A beta Z/A alpha d molecules exist in B/WF1 spleen cells. Also, T cell clones which recognize them exists in B/WF1 mice. Because autoimmune symptoms of B/WF1 mice are shown to be related to heterozygosity at the H-2 region, autoreactive T cell clones which recognize the mixed haplotype A beta Z/A alpha d class II molecule might be involved for the induction of autoimmunity in B/WF1 mice.

Animals↗

Kinetics of GLUT1 and GLUT4 glucose transporters expressed in Xenopus oocytes.

The predominant mechanism by which insulin activates glucose transport in muscle and adipose tissue is by affecting the redistribution of the facilitated hexose carriers, GLUT1 and GLUT4, from an intracellular site to the plasma membrane. A quantitative analysis of this process has been hampered by the lack of reliable determinations for kinetic constants catalyzed by each of these isoforms. In order to obtain such information, each transporter was expressed in Xenopus oocytes by the injection of mRNA encoding rat GLUT1 or GLUT4. Equilibrium exchange 3-O-methylglucose uptake was measured and the data fitted to a two-compartment model, yielding Km = 26.2 mM and Vmax = 3.5 nmol/min/cell for GLUT1 and Km = 4.3 mM and Vmax = 0.7 nmol/min/cell for GLUT4. Measurement of the abundance of cell surface transporters was accomplished by two independent protocols: photolabeling with the impermeant hexose analog 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis(D-mannos-4 -yloxy)-2-propylamine and subcellular fractionation of oocytes. Data obtained by either technique revealed that the ratio of plasma membrane GLUT1 to GLUT4 was about 4; this paralleled the relative maximal velocities for hexose transport, indicating that the turn-over numbers for the two isoforms were the same. Moreover, measurement of the concentration of exofacially disposed transporters with 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis(D-mannos-4 -yloxy)-2-propylamine allowed calculation of the turnover number to be about 20,000 min-1. These data indicate that, at low substrate concentrations, the catalytic efficiency of GLUT4 is significantly greater than GLUT1. Extrapolation to mammalian systems suggests that GLUT4 is responsible for virtually all of the hexose uptake in insulin-responsive targets, particularly in the presence of hormone.

3-O-Methylglucose↗

Lisinopril reduces cardiac hypertrophy and mortality in rats with aortocaval fistula.

We evaluated the effects of lisinopril (1 mg/kg per day) on hemodynamics, cardiac hypertrophy, and neurohumoral factors in Wistar rats with an abdominal aortocaval fistula. After 4 weeks of treatment, the results were compared with values obtained for untreated rats with a fistula and for sham-operated rats. Volume loading induced biventricular hypertrophy, hemodynamic signs of high-output heart failure (increased cardiac output, left ventricular end-diastolic pressure, and pulse pressure), and impaired renal function (decreased renal blood flow and kidney weight; increased blood urea nitrogen). Lisinopril did not affect these cardiorenal hemodynamics, but decreased left ventricular mass and mortality rate (both P < 0.05). Lisinopril attenuated the increase in plasma norepinephrine, and increased plasma renin activity (both P < 0.05). Thus, lisinopril reduced left ventricular mass and mortality in rats with high-output heart failure without changing the cardiorenal hemodynamics. Neurohumoral inhibition may play a role in the beneficial effects of lisinopril.

Angiotensin-Converting Enzyme Inhibitors↗

Distinction of mouse CD8+ suppressor effector T cell clones from cytotoxic T cell clones by cytokine production and CD45 isoforms.

Mouse CD8+ T cell clones could be subdivided into two subgroups by the pattern of cytokine production and CD45 isoforms that exactly corresponded with the functionally assigned cytotoxic (CTL) and suppressor (Ts) subsets. All the Ts clones invariably produced IL-10 after stimulation with immobilized anti-CD3, whereas none of CTL clones expressed mRNA of IL-10 by the same stimulation. All the CTL clones were positive for CD45RA Ag, a product of exon 4 of CD45 gene, whereas none of the Ts clones were positive for this Ag. The results are analogous to the situation within CD4+ T cell clones in which Th1 and Th2 subtypes can be distinguished by CD45 isoforms and cytokines they produce. Ts clones could suppress the proliferative responses of both Th1 and Th2 type CD4+ clones by the production of two different cytokines, IL-10 and IFN gamma, respectively, but none of the CTL clones could suppress the proliferation of CD4+ T cells. The participation of an additional nonspecific molecule in the suppression of antibody response is suggested.

Animals↗

[Magnetization transfer contrast imaging of the skeletal muscle in gradient recalled echo sequence].

The human midcalf muscle images were obtained using gradient recalled echo (GRE) sequence with and without magnetization transfer contrast (MTC) sequence. A significant decrease of relative signal intensity was observed in muscle with off-resonance irradiation. The percentage increase of signal intensity after dorsiflexion exercises was 55.6% and 29.0% for MTC-GRE and GRE sequence, respectively. MTC technique might be useful in improving contrast between many tissues as well as muscles.

Adult↗

[Evaluation of the invasion of esophageal cancer to the aorta by cine-MR imaging].

We examined the usefulness of cine-MR imaging for evaluation of the invasion of esophageal cancer to the aorta in 12 cases. We used the technique of field echo pulse sequence. When the low intensity stripe was recognized between the tumor and the wall of aorta, we interpreted it as negative finding of the direct tumor invasion. By using this criteria, 11 of the 12 cases (92%) of the esophageal cancer for aortic wall invasion were correctly diagnosed as compared with 75% correct diagnosis by conventional MR imaging.

Aorta↗

Preparation of anti-phosphoserine and anti-phosphothreonine antibodies and their application in the study of insulin- and EGF-induced phosphorylation.

We prepared antibodies against phosphoserine (P-Ser) and phosphothreonine (P-Thr) by immunizing rabbits with P-Ser or P-Thr conjugated to bovine serum albumin. The antibodies (anti-P-Ser and anti-P-Thr) were purified using P-Ser or P-Thr affinity columns. Anti-P-Thr was highly specific for P-Thr, while anti-P-Ser showed weak cross-reactivity with P-Thr. We showed that these antibodies can immunodetect serine/threonine phosphorylated insulin and epidermal growth factor (EGF) receptors and several proteins which are phosphorylated on serine/threonine residues in response to insulin or EGF stimulation. The antibodies will certainly provide a good tool for discovering novel kinases and substrates involved in signal transduction.

Animals↗

Somatic diversification and affinity maturation of IgM and IgG anti-DNA antibodies in murine lupus.

Molecular events occurring during the process of generation of pathogenic immunoglobulin (Ig)G anti-DNA antibodies in systemic lupus erythematosus (SLE) were studied using a newly established method. We analyzed the Ig variable (V) region gene sequence and DNA-binding activity of IgM and IgG anti-DNA monoclonal antibodies (mAb) from individual SLE-prone (NZB x NZW) F1 mice. The first event appeared to be clonal selection and expansion of IgM anti-DNA clones, in which several clones had intraclonal V gene mutations. Although the number of mutations was small, the mutated IgM clones were associated with an increase in DNA-binding activity. The somatic mutations located in complementarity-determining regions (CDR) and in framework regions (FR) of V genes were apparently related to changes in DNA-binding activity. IgG anti-DNA clones that progressively increased in number with aging had numerous somatic mutations in the V region genes and there was a pair of clones which showed an intraclonal accumulation of mutations, in association with increase in the DNA-binding activity. All these findings show that somatic mutations associated with affinity maturation of the V region begin immediately before isotype-switching from IgM to IgG of the clones that have been selected and expanded, in an antigen-driven manner and/or by other forces. We propose that further accumulations of intraclonal somatic hypermutation, in association with selection and expansion of high affinity IgG clones, may lead to formation of highly pathogenic anti-DNA antibodies.

Age Factors↗

Reduced renal arterial perfusion pressure stimulates renin release from domestic fowl kidneys.

Systemic hypovolemia and hypotension increase plasma renin activity (PRA) in fowl, but it is not clear whether this response is mediated directly by reduced renal arterial perfusion pressure (RAPP) or indirectly via renal nerves activated when systemic baroreceptors detect hypotension. To evaluate the influence of RAPP on renin release, arterial and renal venous blood samples were collected as RAPP was reduced step-wise from 108 mm Hg (control) to 71 and 47 mm Hg. PRA in systemic arterial (aPRA) and renal venous (vPRA) plasma was measured as the rate of fowl angiotensin I (ANG I) generation. Basal vPRA (2.47 +/- 0.6 ng x ml-1 x min-1) tended to be higher than aPRA (1.24 +/- 0.3 ng x ml-1 x min-1). When RAPP was reduced to 47 mm Hg both vPRA (4.35 +/- 0.6 ng x ml-1 x min-1) and aPRA (1.91 +/- 0.3 ng x ml-1 x min-1) increased significantly. Significant negative slopes (P = 0.01) were obtained when changes in aPRA or vPRA were regressed on RAPP. Mean systemic arterial pressure did not change during reductions in RAPP, nor did angiotensinogen concentrations differ when systemic arterial (472 +/- 30 ng/ml) and renal venous (460 +/- 27 ng/ml) plasma values were compared. Renal plasma flow was fully autoregulated as RAPP was reduced from 108 to 47 mm Hg; consequently, RAPP-induced increases in vPRA cannot be attributed to hemoconcentration of secreted renin. These results demonstrate that reductions in RAPP directly stimulate renin release from domestic fowl kidneys.

Angiotensin I↗

Aberrant retrotracheal goiter: report of a case.

A case of intrathoracic retrotracheal goiter in a 40-year-old woman is herein described. A computed tomographic scan, magnetic resonance imaging and endoscopical ultrasonography all confirmed the existence of a retrotracheal encapsulated lesion, which was suspected to be aberrant mediastinal goiter. Radioiodine scintigraphy, however, demonstrated little uptake in the mass. A large (7 x 6 x 4 cm), encapsulated adenomatous goiter was then easily removed via a right thoracic approach.

Adult↗