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Biomedical subjects

S Yoshida

Publications and source records attributed to S Yoshida.

At least 883 records · Page 49Linked to original sources

A novel mutation Gly 1672-->Arg in type 2A and a homozygous mutation in type 2B von Willebrand disease.

Genetic materials from 16 unrelated Japanese patients with von Willebrand disease (vWD) were analyzed for mutations. Exon 28 of the von Willebrand factor (vWF) gene, where point mutations have been found most frequent, was screened by various restriction-enzyme analyses. Six patients were observed to have abnormal restriction patterns. By sequence analyses of the polymerase chain-reaction products, we identified a homozygous R1308C missense mutation in a patient with type 2B vWD; R1597W, R1597Q, G1609R and G1672R missense mutations in five patients with type 2A; and a G1659ter nonsense mutation in a patient with type 3 vWD. The G1672R was a novel missense mutation of the carboxyl-terminal end of the A2 domain. In addition, we detected an A/C polymorphism at nucleotide 4915 with HaeIII. There was no particular linkage disequilibrium of the A/C polymorphism, either with the G/A polymorphism at nucleotide 4391 detected with Hphl or with the C/T at 4891 detected with BstEII.

Arginine↗

Short-term clinical trial of 1-(1-[4-(3-acetylaminopropoxy)-benzoyl]-4-piperidyl)-3, 4-dihydro-2(1H)-quinolinone in patients with diabetic nephropathy. Possible effectiveness of the specific vasopressin V1 receptor antagonist for reducing albuminuria in patients with non-insulin dependent diabetes mellitus.

We investigated the role of arginine vasopressin (AVP) in the development of diabetic nephropathy and the effect of specific vasopressin V1 receptor antagonist of 1-(1-[4-(3-acetylaminopropoxy)-benzoyl]-4-piperidyl)-3, 4-dihydro-2(1H)-quinolinone (CAS 131631-89-5, OPC-21268) on albuminuria in patients with non-insulin dependent diabetes mellitus. Basal levels of AVP in diabetic patients showing microalbuminuria were significantly high compared to diabetics without any complications, suggesting that in those patients abnormally high amounts of AVP seem to be secreted. Three-week treatment with OPC-21268 demonstrated that albuminuria significantly decreased without affecting renal function. Increased secretion of AVP may induce proliferation of renal mesangial cells and modify blood flows in the glomerular capillaries. The present data suggest that OPC-21268 may be useful for preventing the development of diabetic nephropathy, although its long-term effects should be examined. In conclusion, AVP may play a crucial role in the pathophysiology of diabetic nephropathy and that OPC-21268 seems to prevent further progression of nephropathy in non-insulin dependent diabetes mellitus.

Albuminuria↗

Visceral fat accumulation and vascular complications associated with VMH lesioning of spontaneously non-insulin-dependent diabetic GK rat.

OBJECTIVE: We have reported that ventromedial hypothalamic (VMH) lesions induced marked hyperglycemia and a distinct reduction in pancreatic insulin content during short-term observation in male Goto-Kakizaki (GK) rats, an animal model for non-insulin-dependent diabetes mellitus (NIDDM) (Metabolism 43: 32-37, 1994). We investigated the long-term effect of VMH lesions on glucose metabolism, pancreatic insulin content, abdominal fat distribution and vascular complications in male GK rats. DESIGN: Metabolic and histological examinations in male GK rats during 16 weeks after making VMH lesions were compared to those in sham operated GK or Wistar rats. SUBJECTS: Eleven 9-week-old male GK rats and 4 male Wistar rats. VMH-lesions were made in 6 GK rats and sham operation were performed on 5 GK rats and 4 Wistar rats as controls. MEASUREMENTS: Food intake, body weight, and plasma glucose, insulin and lipid levels at 2 weeks interval after operation. Urinary protein and albumin levels at 15 weeks after operation. Measurement of pancreatic insulin content, mesenteric fat and abdominal subcutaneous fat weights, and histological examinations of kidney and aorta were performed after 16 weeks. RESULTS: Although food intake increased in VMH-lesioned GK (GK-VMH) rats compared with that in sham-operated GK (GK-sham) rats, the body weight of GK-VMH rats was significantly less than that of GK-sham rats. Plasma glucose was markedly elevated in GK-VMH rats from 2 through 16 weeks after operation, while it was only mildly increased in GK-sham rats. Plasma insulin levels were higher in GK-VMH rats one week after operation and thereafter tended to be lower compared to those in GK-sham rats. Plasma triglyceride levels were significantly increased in GK-VMH rats. The insulin content of pancreas at 16 weeks after operation was markedly decreased in GK-VMH rats. VMH lesions caused a significant 1.2-fold increase in mesenteric fat weight and a 1.3-fold higher ratio of mesenteric fat weight to subcutaneous fat weight in GK rats compared with sham-operated rats at 16 weeks after operation. The urinary excretions of protein and albumin in GK-VMH rats were greater than those in GK-sham rats. Histological examinations of the kidneys in GK-VMH rats revealed that the glomerular basement membranes were thicker than those of GK-sham rats. The descending aorta in GK-VMH rats also showed morphologic changes in the intima characteristic of an early stage of atherosclerosis. CONCLUSION: Male GK-VMH rats may be a useful animal model for non-obese NIDDM with visceral fat accumulation, which develops typical diabetic complications, including both microangiopathy and macroangiopathy.

Adipose Tissue↗

[Effect of superoxide production on nitric oxide release from the pulmonary vascular endothelium during reperfusion after warm ischemia].

It has been reported that reperfusion injury results in the diminished nitric oxide (NO) release from the pulmonary vascular endothelium. However, this mechanism is completely unknown. We examined the effect of superoxide dismutase (SOD) on NO release at reperfusion. A rabbit lung was perfused with Krebs-Henselit buffer in a recirculation system. Cyclic GMP (cGMP) content in the lung effluent from the left ventricle was assayed in a time-dependent manner. In the control group, the lung was immediately perfused without interventing ischemia. In the warm ischemia and reperfusion group, the lung was reperfused after 30 min of warm ischemia. In the SOD group, SOD (60,000 U and 120,000 U) was administered at reperfusion after warm ischemia. The cGMP release in the warm ischemia and reperfusion group significantly decreased compared with the control group. In the SOD group, cGMP release was reversed with increasing doses of SOD, and the cGMP content was significantly reversed at all time points with SOD administration of 120,000 U. The impairement of cGMP release by reperfusion injury was restored by SOD administration. This data suggests that NO release from the endothelium may be quenched by superoxide anion generated at reperfusion. In lung transplantation, efforts must be pursued to preserve the endothelial function such as NO pathway.

Animals↗

[Myocardial metastasis in the right ventricle from uterine cervical carcinoma with high 67Ga-citrate accumulation: a case report].

We report a case of high 67Ga-citrate accumulation with myocardial metastasis in the right ventricle from uterine cervical carcinoma. A 41-year-old woman was admitted to our hospital because of acute abdomen after operation and radiotherapy for uterine cervical carcinoma. On performing 67Ga-scintigraphy for differentiation from fever of unknown origin, we found significant 67Ga-citrate accumulation in the right ventricle. To the best of our knowledge, this is a rare case.

Adult↗

[A pediatric case of cerebral infarction following minor head injury presenting interesting neuroradiological findings].

We reported a case of juvenile cerebral infarction following minor head injury. The patient, a 12-year-old girl, developed right hemiparesis and aphasia almost immediately after having fallen from about 1 meter height during the exercise class at school. CT and MRI study showed lacunar lesions bilaterally and almost symmetrically in the paraventricular deep white matter on both sides. A new stroke area, responsible for the symptoms, was recognized about 24 hours later on CT scan just next to the lacuna of the left side. Although angiography revealed a rare anomaly of the right side aortic arch, associated with subclavian steal phenomenon, presumably of congenital in nature, no abnormality was found in the intracranial vessels. She made a rapid recovery during her hospital stay and showed no more than a slight motor weakness in her right upper extremity on discharge. The literature was reviewed on the embryology of the aortic arch and brachiocephalic arteries. We speculate that the lacunar lesions found bilaterally are dilated large normal Virchow-Robin space, and the pathogenesis of the stroke in this patient was discussed.

Cerebral Infarction↗

[Costal chondritis treated by resection of the entire costal arch].

A 68-year-old man had chronic pleural empyema, an alveolar fistula, and purulent perichondritis. The pericostal abscess extended beneath both sides of the costal arch and had a cutaneous sinus in the right hypochondrium, but it did not communicate with the cavity of the pleural empyema. In separated operations, the entire costal arch was resected and the alveolar fistula was closed with the pedunculate latissimus dorsal muscle. Neither tuberculosis bacilli nor tubercular granulomas were seen in resected specimens. The postoperative course was uneventful and the pericostal abscess healed, but the alveolar fistula recurred and the patient died of pneumonia 3 years and 6 months after the first surgery.

Aged↗

[A case of recurrent squamous cell carcinoma of cervix successfully treated with BOMP].

Combination chemotherapy consisting of bleomycin, vincristine, mitomycin C and cisplatin (BOMP) was applied to a case (57 years old) with recurrence of squamous cell carcinoma of the cervix. The patient with FIGO stage IIIb cervical carcinoma had been treated with radiotherapy seven years ago. She was affected by malignant pericardial effusion, and was treated with direct intrapericardial administration of cisplatin (20 mg). After instillation, ultrasonography and computed tomography showed the wall thickening of colon and marked ascites. Barium enema showed the circumferential narrowing and serrations of colon, and it was diagnosed to be carcinomatous peritonitis. She was treated with BOMP consisting of BLM (5 mg, i.m., days 1 - 5), VCR (1 mg, i.v., day 5'), MMC (8 mg, i.v., day 5), and CDDP (70 mg, d.i.v., day 5). After three courses of BOMP therapy, she achieved a complete response with few toxic effects and did not require special care. She has been free of disease for six months and her performance status is 0. This encouraging result warrants the use of this combination chemotherapy regimen in other patients with recurrent squamous cell carcinoma of the cervix.

Antineoplastic Combined Chemotherapy Protocols↗

[Evaluation of thin section CT scanning in the prone position of metastatic axillary lymph nodes for breast cancer].

A retrospective study was performed to determine whether thin section CT scanning in the prone position of the breast and the axilla yielded useful information regarding the status of axillary lymph nodes in patients with breast cancer. Thirty-six patients with breast carcinomas were scanned preoperatively from the supraclavicular regions to the breast in the prone position with 5 mm sections. Axillary lymph nodes measuring > or = 5 mm on the short axis were considered abnormal. Correlation with axillary dissection was obtained in all patients, giving a positive predictive value for axillary metastases of 83.3%, with 88.2% sensitivity, 84.2% specificity, and 88.8% negative predictive value. We concluded that thin section CT scan in the prone position was an accurate predictor of axillary lymph node involvement. We made a phantom with lymph node swelling to evaluate whether CT scanning with 5 mm sections was necessary for detecting 5 mm swollen lymph nodes. We scanned the phantom with 5 mm and 10 mm sections. Twelve radiologists counted the swollen lymph nodes on 5 mm section images and 10 mm section images of the phantom. The average number of miscounts was 1.1 (miscount rate 6.8%) on 5 mm section and 2.8 (15%) on 10 mm sections. We concluded that 5 mm section CT scanning is superior for detecting 5 mm lymph nodes.

Adult↗

[The future of the Japan Endocrine Society].

The Japan Endocrine Society as it ought to be is discussed. 1. Paradigms of endocrine research. The recent rapid progress of molecular biology brought about breakthroughs in endocrine research. The cloning of hormone cDNA, as well as their receptors, enables us to study the mechanisms of intracellular signal transduction in detail. Genomic DNA might be considered the basic structure of a signal transduction system (endocrine system). In other words, endocrine research at present is performed by a paradigm that reduces components of a system in its minimum elements-genomic DNAs. It might, however, be naive of endocrinologists to believe that they can completely understand the endocrine phenomena merely by analyzing the minimum elements of the system (DNA). It might be necessary to reconstruct the systems from minimum elements to the system of the whole body. 2. What the Japan Endocrine Society should be. The Japan Endocrine Society should be reorganized in order to meet with the rapid progress of science. The board of regents of the Japan Endocrine Society appointed a committee in 1993 to discuss the society as it ought to be. The board of regents has decided as follows. 1) The autumn meeting of the society will be abolished in 1998. 2) In place of the autumn meeting, meetings of related societies (such as the thyroid branch of the society and the neuroendocrine branch of the society) will be held in the autumn.

Endocrinology↗

Desensitization by cyclic AMP-dependent protein kinase of GABAB receptor expressed in Xenopus oocytes.

Involvement of cyclic AMP-dependent protein kinase in the desensitization of GABAB receptor expressed in Xenopus oocytes was studied. GABA produced an outward current in the presence of bicuculline, under voltage-clamp conditions. Baclofen mimicked the effect of GABA, thereby indicating that the response to GABA in the presence of bicuculline is mediated by stimulation of GABAB receptor. The GABAB receptor-mediated response was suppressed by dibutyric cyclic AMP and forskolin, but not by 1,9-dideoxy-forskolin, and the effect of dibutyric cyclic AMP was inhibited by H-8. Application of GABA for 1 min at 20-min intervals induced a reliable response, while that at 10-min intervals produced a desensitization. The desensitization was also partially prevented by H-8. Dibutyric cyclic GMP, 8-bromo-cyclic GMP and Na-nitroprusside did not affect the GABAB receptor-mediated response. Thus, cyclic AMP-dependent protein kinase, but not cyclic GMP-dependent protein kinase participates in desensitization of the GABAB receptor expressed in Xenopus oocytes.

Animals↗

STT3, a novel essential gene related to the PKC1/STT1 protein kinase pathway, is involved in protein glycosylation in yeast.

Mutations of genes involved in the STT1/PKC1 pathway in yeast show staurosporine and temperature sensitivities (stt) which are suppressed by the addition of 1 M sorbitol [Yoshida et al., Mol. Gen. Genet. 242 (1994) 631-640]. Among the stt mutants, stt3-2 shares this phenotype. The STT3 gene encodes a novel 718-amino-acid protein with significant homology to potential transmembrane proteins of Caenorhabditis elegans and mouse mandibular condyle (about 80% homologous and 60% identical). Unlike the STT1/PKC1 gene, STT3 is essential for cell growth irrespective of osmotic support. Pulse-chase experiments show that the sst3 mutants are defective in protein glycosylation. The stt3 mutants are sensitive to hygromycin B and resistant to sodium orthovanadate, whose phenotypes are common to those defective in protein glycosylation.

Alkaloids↗

Insulin prevents apoptosis of external granular layer neurons in rat cerebellar slice cultures.

Using the slice culture system of 9-day-old rat cerebellum, effects of insulin on cell death of developing granule neurons were examined. Apoptotic cells were observed after 3 days culture by the in situ nick end labeling technique. Insulin deprivation induced apoptosis of granule neurons largely in the external granular layer, but scarcely in the internal granular layer. Proliferation of external granular layer neurons during the early culture period was not affected significantly by the insulin deprivation. These results suggest that insulin may prevent apoptosis of premigratory granule neurons during the development of the cerebellar cortex.

Animals↗

Effect of methionine-deprived total parenteral nutrition on tumor protein turnover in rats.

BACKGROUND: Previous studies have shown that a methionine-lacking diet inhibited tumor growth in rats. The aim of this study was to determine how methionine free total parenteral nutrition (MTPN) can result in the inhibition of tumor growth on tumor protein metabolism in rats. METHODS: On day 0, AH109A rat ascites hepatoma cells were implanted subcutaneously into male Donryu rats (n = 68, body weight, 200-225 gm). On day 10, a catheter for total parenteral nutrition (TPN) was placed and either MTPN or standard TPN solution was given for 5 days. On day 15, 1-14C-leucine was infused continuously to measure tumor protein synthesis. Tumor proteolysis was calculated from tumor regional blood flow, using the 85Sr-microsphere injection method. RESULTS: 1) Tumor weight was reduced with MTPN. 2) MTPN did not affect tumor protein synthesis, probably because endogenous methionine production was increased with MTPN (87.3 +/- 13.5 mumole methionine/kg/hour vs. 218.6 +/- 29.5, P < 0.01); however, MTPN caused an increase of tumor proteolysis (2.68 +/- 0.53 mumole leucine/g/hour vs. 3.79 +/- 0.73, P < 0.05). CONCLUSION: The enhanced tumor protein breakdown contributed to the inhibition of tumor growth that was found with the rats given the methionine free diet.

Animals↗

Selective reduction of T cells bearing invariant V alpha 24J alpha Q antigen receptor in patients with systemic sclerosis.

A novel subset of T cells characterized by the expression of an invariant T cell antigen receptor (TCR) encoded by V alpha 24J alpha Q gene segments was investigated in patients with systemic sclerosis (SSc). Polymerase chain reaction analysis demonstrated that the V alpha 24 TCR repertoire was selectively used in CD4-CD8- double-negative T cells both in patients and in healthy individuals, while almost all families of TCR V alpha were expressed in single-positive T cell fractions. The V alpha 24+ double-negative T cells were increased by approximately fivefold in patients. However, sequence analysis clearly showed significant differences in the V alpha 24 TCR repertoire dominating in patients and healthy donors. In healthy individuals, the invariant V alpha 24J alpha Q was expanded and comprised 20-50% of the total TCR-alpha, while their selective reduction was observed in SSc patients who also showed expansion of invariant V alpha 24 TCR other than V alpha 24J alpha Q. Analogous to murine invariant V alpha 14J alpha 281 TCR, these results suggest that T cells with invariant V alpha 24J alpha Q TCR would function as regulatory T cells, whereas T cells bearing other invariant V alpha 24 TCR in SSc patients could be autoaggressive T cells in nature.

Asian People↗