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Biomedical subjects

H Nishimura

Publications and source records attributed to H Nishimura.

At least 397 records · Page 22Linked to original sources
PubMed1994

[Analysis of acute toxicity (LD50-value) of organic chemicals to mammals by solubility parameter (delta) (3). Acute dermal toxicity to rabbits].

Acute dermal toxicity (LD50-value) of organic chemicals to rabbits was analyzed by using solubility parameter (delta c), a thermodynamic parameter, of the chemicals. As it was observed in the previous studies with rats and mice, parabolic correlations were also established between logarithm of LD50-value (mmol/kg body weight, rabbits) and delta c of all the collected chemicals (n = 56, R = 0.498), alcohols (n = 19, R = 0.857), ketones (n = 7, R = 0.711), aldehydes (n = 7, R = 0.633) and aromatics (n = 20, R = 0.613). Introduction of molar volume (Vc) to the above equations did not improve the correlations. In the study, we assumed that chemicals absorbed dermally by the mammals similarly disturb the homeostasis, as in acute oral toxicities of organic chemicals to rats and mice. We successfully confirmed the theoretical equation regardless of species and routes of administration by establishing statistically significant correlations with all the collected chemicals, alcohols and aromatics. By analysis, we could determine the solubility parameter of 2.24 x 10(4) (J/m3)1/2 for the biological membrane (absorption site) of rabbits. As the dermal delta c-values which dip the LD50-values for rabbits are approximately the same as in acute oral toxicities with rats and mice, common deleterious effects and mechanism may be working at the common target sites. The regression curves of LD50-values of rabbits, however, are slightly higher than those of rats and mice, which may reflect the difference in amounts of the chemicals absorbed by the body.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1994

Serial transcranial Doppler flow velocity and cerebral blood flow measurements for evaluation of cerebral vasospasm after subarachnoid hemorrhage.

Serial transcranial Doppler (TCD) and cerebral blood flow (CBF) examinations were performed in 73 patients with subarachnoid hemorrhage (SAH) due to ruptured intracranial aneurysm to evaluate cerebral vasospasm. Twenty-six (35.6%) of the 73 patients developed ischemic neurological symptoms associated with cerebral vasospasm, which were reversible in all except four patients (5.5%) who demonstrated low-density areas associated with vasospasm on computed tomographic scans. In general, the flow velocities in the middle cerebral arteries began to increase soon after onset of SAH, reaching the maximum between days 8 and 10, subsequently decreasing gradually. There was no significant difference in the highest value and the time course of flow velocities between symptomatic vasospasm and asymptomatic vasospasm patients. Patients with symptomatic vasospasm demonstrated two typical time courses of flow velocities: rapid increases in flow velocities that preceded the clinical manifestations of vasospasm (16 patients, 61.5%), and no rapid increases in flow velocities despite the presence of ischemic symptoms (10 patients, 38.5%). In the latter, angiograms demonstrated vasospasm in segments distal to those evaluated by TCD examination. These results showed that the degree of cerebral vasospasm cannot be assessed only by the absolute flow velocities. CBF was measured two to 10 (mean 4.7) times within 3 weeks of SAH using the 133Xe intravenous injection method. The CBF value remained stable even during the period of major risk of vasospasm. However, the CBF was significantly lower in patients with symptomatic vasospasm on days 8, 9, 10, 13, 14, and 15, when compared with patients without symptomatic vasospasm.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

In vivo induction of IgG anti-DNA antibody by autoreactive mixed haplotype A beta z/A alpha d MHC class II molecule-specific CD4+ T-cell clones.

We characterized autoreactive T-cell clones derived from (NZB x NZW)F1 (B/WF1) mice. These autoreactive T-cell clones are shown to be CD4+ by immunofluorescence staining and to belong to Th2 type by cytokine release assay. Specificity analysis revealed the existence of mixed haplotype A beta z/A alpha d major histocompatibility complex (MHC) class II molecule-specific T-cell clones as well as A beta z/A alpha z- or A beta d/A alpha d-specific T-cell clones. Some but not all of the mixed haplotype A beta z/A alpha d-specific autoreactive T-cell clones showed strong activity to induce IgG anti-DNA antibody production upon transfer to young (4-month-old) B/WF1 mice, indicating that T cells with these specificities might be involved in B/WF1 autoimmunity.

Animals↗
PubMed1994

Low density lipoprotein receptors in rat adipose cells: subcellular localization and regulation by insulin.

The distribution of LDL receptors within subcellular compartments of isolated rat adipose cells and the effects of insulin on their expression have been assessed. By immunoblotting with specific anti-rat LDL receptor antibodies, LDL receptors were 2.3- and 4.5-fold enriched in endoplasmic reticulum-rich high-density microsomes (HDM) and Golgi complex-rich low-density microsomes (LDM), respectively, compared to plasma membranes (PM). This distribution was similar in cultured cells in which total receptors were increased 2.5-fold compared to freshly isolated cells. After correction for enzyme recoveries, LDL receptors were distributed approximately 4% in HDM, approximately 73% in LDM, and approximately 23% in PM. Insulin decreased total LDL receptors in adipose cells approximately 44%, with a 48% and 49% decrease in HDM and LDM, respectively, without any changes in PM. In contrast, insulin caused an increase of glucose transporters in PM while also decreasing glucose transporters in LDM. When adipose cells were depleted of potassium to inhibit receptor-mediated endocytosis, insulin again caused a decrease of LDL receptors in LDM but now increased LDL receptors in PM. Insulin increased the rate of LDL receptor synthesis approximately 24%, but decreased their half life approximately 40%. Thus, in isolated adipose cells the majority of LDL receptors appear to be located in an intracellular compartment that co-sediments with the Golgi complex rather than located in the PM. The LDL receptors localized in intracellular compartments seem to be functionally regulated as insulin acutely diminishes the number of receptors by apparently accelerating their rate of degradation through, as yet, incompletely determined mechanisms.

Adipose Tissue↗
PubMed1994

Quantitative mapping of regional cerebral blood flow using iodine-123-IMP and SPECT.

UNLABELLED: A method was developed to calculate functional images of regional cerebral blood flow (rCBF) from a single scan using SPECT following intravenous 123I-N-isopropyl-p-iodoamphetamine (IMP) infusion. METHODS: A two-compartment model that includes two parameters of rCBF and regional distribution volume of IMP (Vd) was employed to correct for clearance of IMP from the brain. Using a given input function and a fixed Vd value (30 ml/ml according to an analysis on dynamic SPECT data), a unique value of rCBF was calculated for each pixel of the SPECT image according to the table-look-up procedure. This technique was applied to 15 human subjects, and the calculated rCBF values were compared with those measured by PET. RESULTS: A set of simulation studies demonstrated an optimal SPECT midscan time at 30 to 40 min postinjection of IMP, providing the minimal error sensitivity to the individual difference of the input function (rCBF values with an accuracy of +/- 10%). Another set of simulation suggested validity of fixing the Vd values, i.e., errors in calculated rCBF values were around +/- 7% for a change of Vd of +/- 10%. The measured rCBF values obtained from 15 human subjects were independent on the SPECT scan time. The calculated rCBF values also agreed well with those obtained by the nonlinear least-squares fitting analysis that were obtained from the dynamic SPECT scan and the frequent arterial blood sampling and measurement of lipophilic fraction for each sample (0.54 + 0.88x, r = 0.86), suggesting the validity of the simplified procedures in this method. CONCLUSION: These observations suggested the validity of this method as a clinical tool for quantitative measurement of rCBF.

Amphetamines↗
PubMed1994

[Development of enzyme-linked immunosorbent assay for biliary apolipoprotein A-I and a diurnal change of apolipoprotein A-I concentration in human bile].

Enzyme-linked immunosorbent assay for measuring biliary apolipoprotein A-I was established. Utilizing this assay, a diurnal change of apolipoprotein A-I concentration in hepatic bile obtained from percutaneous transhepatic drainage was investigated. A biliary apolipoprotein A-I concentration changed from time to time, and correlations between apolipoprotein A-I and total protein concentration, cholesterol concentration and lithogenic index, r = 0.873, 0.863 and 0.567 respectively, were observed. Moreover, biliary total protein concentration was closely related with lithogenic index (r = 0.671). These data suggest that hepatic lithogenic bile may induce apolipoprotein A-I secretion into hepatic bile.

Apolipoprotein A-I↗
PubMed1994

[Angiomyolipoma of the anterior mediastinum--a case report].

An asymptomatic 22-year-old female showed an enlarged mediastinal shadow in a chest X-ray mass screening. Computed tomogram indicated a tumor with a CT-number of 7-8 in her left anterior mediastinum, adjacent to the pericardium. With MRI the tumor showed a low signal intensity of T1 weighted images and a high signal intensity of T2 weighted images. Thoracotomy revealed that the tumor was yellow-whitish, and had a size of 7 x 7 x 1 cm. It was histologically composed of fatty tissue, smooth muscle, and vascular tissue, and was diagnosed as angiomyolipoma. Although angiomyolipomas are often found in the kidney, they are very rare in the mediastinum and difficult to diagnose by image analysis.

Adult↗
PubMed1994

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↗
PubMed1994

[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↗
PubMed1994

[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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗