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Biomedical subjects

S Yamaguchi

Publications and source records attributed to S Yamaguchi.

At least 685 records · Page 38Linked to original sources

[A case of idiopathic superficial siderosis of the central nervous system].

A 59-year-old man developed a staggering and wide based-gait in July 1990. Dysarthria, hearing loss, vexation and disturbance of memory appeared in January 1991. He consulted our clinic in May 1991, and cerebellar ataxia, neurogenic bladder, and cerebellar atrophy on brain CT were noted. Subsequently, he was followed as OPCA. Brain and spinal cord MRI (T2 and proton weighted images) revealed hypointensity on the surface of the Sylvian fissure, cerebellum, brainstem and spinal cord. We diagnosed this case as superficial siderosis because of the clinical course, i.e. cerebellar ataxia, dementia and sensorineural hearing impairment, and specific findings on MRI. We consider this case idiopathic superficial siderosis because the origin of the bleeding source was unknown. IMP-SPECT showed low perfusion in the cerebellum and frontal lobe where hemosiderin was heavily deposited. RI cisternography revealed a disturbance of CSF absorption even after 48 hours. The basic rhythm on EEG was slow alpha band with sporadic theta waves dominantly in the frontal lobe. His central conduction time on ABR and SEP was delayed, OKN was poorly elicited and ETT exhibited a staircase pattern. The physiological results as well as the clinical manifestations of the present case suggest that hemosiderin deposit on the surface of brain and spinal cord caused serious damage to the underlying structures.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Diseases↗

Dde I restriction fragment length polymorphism of the alpha 2-adrenoceptor gene does not correlate with blood pressure in the F2 generation obtained from crossing stroke-prone spontaneously hypertensive rats and Wistar-Kyoto rats.

OBJECTIVE: A pathogenetic role of altered alpha 2-adrenoceptors in essential hypertension has been suggested, based on studies in humans and animals. To examine the role of the alpha 2-adrenoceptor in genetically hypertensive rats, we compared the alpha 2-adrenoceptor genes of stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats by restriction fragment length polymorphism analysis using human alpha 2-adrenoceptor probes (alpha 2-C10) and Dde I restriction endonuclease, and conducted a genetic cosegregation study. METHOD: Five female WKY rats were bred with five male SHRSP. Eight pairs of F1 rats were mated in brother-sister pairs to yield an F2 population of 84 rats. Systolic blood pressure was determined by tail-cuff sphygmomanometry. Direct arterial blood pressure was taken under ether anaesthesia just before the rats were killed. Southern blots were performed using alpha 2C10 as a probe and the DNA from the F2 generation. RESULTS: A restriction fragment length polymorphism of the SHRSP allele of a 1.6-kb fragment and a WKY rat allele of a 0.9-kb fragment with a common band of 1.3 kb in SHRSP and WKY rats was found, as reported previously. The distribution of the genotype based on restriction fragment length polymorphism conformed to a 1:2:1 ratio in F2 rats, as expected for a Mendelian trait. There was no significant difference in the blood pressure of F2 rats with respect to alpha 2-adrenoceptor genotype. CONCLUSION: This study demonstrated that the alpha 2-adrenoceptor gene restriction fragment length polymorphism distribution is a Mendelian trait in the F2 rats of crossed SHRSP and WKY rats, but failed to show genetic cosegregation of this restriction fragment length polymorphism with blood pressure in this generation.

Alleles↗

[Significance of periventricular hyper-intensity in T2 weighted MRI on memory dysfunction and depression after stroke].

We studied the effect of periventricular hyperintensity (PVH) in T2 weighted MRI on memory function and post-stroke depression in 159 patients with cerebrovascular diseases. Memory function was assessed with Hasegawa's scale, and depressive state was estimated with Zung's self-rating depression scale. Patients showing diffusely distributed PVH had significantly low scores in memory function tests. Localized PVH around the anterior horns of the laterals ventricle was also associated with impaired memory function when the area of PVH was large. The incidence of post-stroke depression was high in patients with large PVH around the anterior horn in comparison with patients with PVH around the posterior horn. The severity of PVH around the posterior horn did not affect memory function and post-stroke depression. These findings suggest that memory dysfunction and post-stroke depression were accelerated by the diffusely or anteriorly distributed PVH.

Aged↗

[Pharmacokinetic studies on continuous intraportal 5-fluorouracil infusion].

Pharmacokinetics of 5-FU administered by continuous intraportal infusion were studied by infusing 5 mg/kg, 10 mg/kg, 20 mg/kg, and 40 mg/kg of 5-FU, respectively, into the ileocecal vein for an hour. Blood samples were collected from portal vein, femoral vein and liver, and small intestine specimens were obtained at proper intervals. The rabbits were sacrificed at 120 minutes from the start of 5-FU infusion. The results were as follows: Extremely high concentrations of 5-FU in the portal vein, femoral vein and liver tissue were observed in the 5-FU group infused with 40 mg/kg. This phenomenon was suggested to rely on the effect by which the 5-FU catabolic enzyme, dihydrouracil dehydrogenase, was saturated with a large inflow of 5-FU. FdUMP concentration of the liver was lower than that of the small intestine in all groups. These results suggest that a large dose of 5-FU infusion is effective to increase the FdUMP concentration in the liver with continuous intraportal 5-FU infusion.

Animals↗

A new communication system between hepatocytes and sinusoidal endothelial cells in liver through vascular endothelial growth factor and Flt tyrosine kinase receptor family (Flt-1 and KDR/Flk-1).

Hepatocyte Growth Factor (HGF)/Scatter Factor secreted from sinusoidal endothelial cells and Kupffer cells in liver activates the c-Met tyrosine kinase receptor expressed on hepatocytes. Here we report yet another possible communication system through a different ligand and tyrosine kinase receptor in an opposite direction. We isolated and determined the primary structure of the entire coding region of rat flt-1 (fms-like tyrosine kinase), a receptor for Vascular Endothelial Growth Factor (VEGF). Using rat flt-1 cDNA as a probe we found that the flt-1 mRNA was expressed at very high levels in sinusoidal endothelial cells in normal rat liver, but was hardly detectable in hepatocytes. The transcripts of another VEGF receptor KDR/Flk-1 structurally related to Flt-1 was also expressed specifically in sinusoidal endothelial cells. On the other hand, VEGF mRNA was expressed weakly in hepatocytes, but not in the nonparenchymal cell fraction. Furthermore, in an in vitro culture system, VEGF demonstrated a remarkably specific growth-stimulatory activity as well as maintenance activity on the sinusoidal endothelial cells. These results suggest that hepatocytes regulate the proliferation and survival of the sinusoidal endothelial cells in liver in a paracrine manner. Therefore two reciprocal communication systems, VEGF-Flt receptor family and HGF-Met receptor, may exist in hepatic tissue.

Amino Acid Sequence↗

[Cerebellar ataxia with hypogonadotropic hypogonadism and mental disturbance].

Cerebellar ataxia with hypogonadotropic hypogonadism is a rare condition. Both hypothalamic LHRH and pituitary gonadotropin deficiency may appear with cerebellar ataxia. In this report, a 19-year-old man who presented with progressive cerebellar ataxia and mental disturbance was found to have low plasma gonadotropin levels. No rise in gonadotropin was demonstrated after repeated stimulation with LHRH. Our findings suggested that the cause of hypogonadism was pituitary gonadotropin deficiency, or both hypothalamic and pituitary dysfunction. The endocrinological data and clinical features of our patient and all other reported cases suggest that the age of onset of the illness is related to the type of endocrinological abnormality: young-onset patients may have endocrine disturbances involving both the hypothalamus and the pituitary gland, which may be affected secondary to the hypothalamic disturbance, whereas adult-onset patients may show only hypothalamic disturbance.

Adult↗

[Solitary metastasis to residual ureter resulting from renal cell carcinoma after radical nephrectomy: report of a case].

A case of solitary metastasis to residual ureter from renal cell carcinoma is reported. In November, 1987, a 56-year-old male had undergone left radical nephrectomy with renal cell carcinoma (clear cell subtype, G2, Inf alpha). He was doing well until June in 1989 when macroscopic hematuria occurred. A tumor from residual ureter with a large blood clot was detected on cystoscopy. A malignant tumor from the residual ureter was suspected and it was extirpated. Histological diagnosis revealed the same findings as the primary renal tumor. No other metastasis was detected. Only 8 cases of ureteral metastasis from renal cell carcinoma after radical nephrectomy have been previously reported in the Japanese literature.

Carcinoma, Renal Cell↗

[A clinical study of the changes of bone lesions after parathyroidectomy in patients with secondary hyperparathyroidism].

We evaluated the changes of the bone lesions and their relative bone findings before and after parathyroidectomy in 23 patients with secondary hyperparathyroidism. Before the operation, all patients had bone and/or joint pain. In radiographic findings, subperiosteal bone resorption of the hand and a salt and pepper coloration of the skull were observed in all patients. Rugger jersey spine and the disappearance of the lamina dura were observed in about 90% of the patients. The bone mineral contents measured by single photon absorptiometry and digital image processing method had decreased in all of the patients compared with the mean values in sex- and age-matched controls. After the operation, the bone and/or joint pain had disappeared excluding three patients with recurrent hyperparathyroidism. The bone changes of the hand and the skull had improved in about 90% of the patients. However, the improvement rate was low in the vertebral and dental bone changes. The bone mineral contents increased significantly compared with the preoperative values. In recurrent cases, transient increase of the bone mineral contents was observed postoperatively. However, their values, were decreased gradually with the elevation of parathyroid hormone level. The evaluation of the bone lesions before and after parathyroidectomy not only indicates the effectiveness of the operation but also illustrates the function of the autotransplanted parathyroid tissues. We conclude that regular examination of the bone lesions after parathyroidectomy, paying attention to recurrent hyperparathyroidism and/or graft function, is mandatory.

Adult↗

Altered cerebral energy metabolism in Alzheimer's disease: a PET study.

UNLABELLED: In an effort to better understand the metabolic basis for the reported decreases in regional cerebral cortex glucose metabolism in patients with Alzheimer's disease, glucose utilization oxygen consumption and regional cerebral blood flow were examined. METHODS: Nine patients with Alzheimer's disease and nine age-matched normal controls were imaged using 18F-labeled deoxyglucose and 15O-labeled gases. RESULTS: Regional analysis of the cerebral metabolic rate of glucose (CMRglu), cerebral metabolic rate of oxygen (CMRO2) and cerebral blood flow (CBF) revealed that these values were significantly low in the frontal, parietal and temporal regions. The parietotemporal region had an abnormally high metabolic ratio (CMRO2/CMRglu), while the frontal, sensorimotor and occipital visual cortices had a metabolic ratio similar to that of the normal controls. CONCLUSIONS: These findings suggest that the abnormal parietotemporal metabolism in Alzheimer's disease involves a metabolic shift from glycolytic to oxidative metabolism. This impairment of glucose degradation may be the basis for synoptic dysfunction underlying the impairment observed in Alzheimer's disease.

Aged↗

Possible involvement of VEGF-FLT tyrosine kinase receptor system in normal and tumor angiogenesis.

A novel receptor-type tyrosine kinase gene flt (fms-like tyrosine kinase, flt-1) was isolated from human placenta cDNA library. Flt-1 receptor carries a ligand binding domain which contains seven immunoglobulin-like stretches. Further, Flt-1 tyrosine kinase domain is separated by an approximately 70 amino acid-insert region similar to the cases of Fms/Kit/PDGF-R (fms family). However, unlike the fms family members, Flt-1 insert region does not contain "Tyr-X-X-Met" motif, which is known to be important for signal transduction and for the binding of P13 kinase to the receptor. Thus, a unique structure of Flt-1 suggests that a signal transduction pathway from Flt receptor is different from that in the fms family. The expression of flt-1 gene is detectable in a variety of normal tissues, and cell fractionation studies indicate that the flt-1 mRNA is highly expressed in endothelial cell-enriched fraction. VEGF, which has recently been reported as a ligand for Flt-1 receptor, dramatically stimulated growth of endothelial cells in culture. Many human tumors were found to express VEGF mRNA but not Flt-1 message, suggesting a paracrine mechanism for tumor angiogenesis. Interestingly, VEGF could not stimulate proliferation of Flt-1-overexpressing NIH3T3 fibroblast cells. These results suggest that Flt-1 is an endothel-specific growth factor receptor and that the signal transducing pathway through Flt-1 receptor is inactive in the fibroblast background.

3T3 Cells↗

Molecular studies of mitochondrial acetoacetyl-coenzyme A thiolase deficiency in the two original families.

We describe mutations identified in stored skin fibroblast cell lines from two original probands (JB and JM), first reported with 2-methylacetoacetic aciduria, and shown later to have a deficiency of the K(+)-activated enzyme, mitochondrial acetoacetyl-coenzyme A thiolase (T2). JB is homozygous for a 4-base insertion (GCAG) which is derived mutation. The primary mutation is an AG/gt to AG/gc transition at the 5'-splice-junction site in intron 11. An alternative splice site 4 bp downstream (Ggcag/gt) is used which causes a frame shift and replaces 39 C-terminal residues by 70 nonfunctional residues. JM is homozygous for a mutation in the translation-initiation codon (ATG to AAG). By expression analyses the JB mutation (IVS11nt2) causes an unstable T2 polypeptide and the JM mutation (M1K) severely impairs T2 mRNA translation. The JB allele associates with Dutch ancestry (no consanguinity) and the JM allele with Chilean ancestry (distant consanguinity).

Acetyl-CoA C-Acetyltransferase↗

Monkey 3-deoxyglucosone reductase: tissue distribution and purification of three multiple forms of the kidney enzyme that are identical with dihydrodiol dehydrogenase, aldehyde reductase, and aldose reductase.

3-Deoxyglucosone (3DG) is a reactive intermediate in the glucose-mediated cross-linking of proteins. An enzyme catalyzing the reduction of 3DG is thought to prevent the damage to protein by the formation of 3DG. The NADPH-dependent enzyme activity was detected in the extracts of various monkey tissues, among which kidney exhibited the highest specific activity. One dimeric enzyme with subunit M(r) of 39,000 and two monomeric enzymes with M(r) of 38,000 and 34,000 were purified from monkey kidney. The dimeric enzyme exhibited high dihydrodiol dehydrogenase activity and was immunochemically identical to dimeric dihydrodiol dehydrogenase of monkey kidney. The two monomeric enzymes exhibited aldehyde reductase activity, but were clearly distinct from each other in substrate specificity, inhibitor sensitivity, and effect of sulfate ions. One enzyme was immunologically cross-reacted with human liver aldehyde reductase, whereas sequence data of digested peptides from the other enzyme revealed > 97% identity with human placental aldose reductase. Comparison of kinetic constants among the monkey kidney enzymes and aldoketo reductases from several mammalian tissues indicated that dimeric dihydrodiol dehydrogenase and aldose reductase exhibited higher catalytic efficiency for 3DG than did aldehyde reductase, carbonyl reductase, and monomeric dihydrodiol dehydrogenase.

Alcohol Oxidoreductases↗

Heparin sulfate in the stone matrix and its inhibitory effect on calcium oxalate crystallization.

The nature of the soluble stone matrix and its possible role in urinary stone formation was studied. For this purpose we performed two-dimensional cellulose acetate membrane electrophoresis of the glycosaminoglycans (GAGs) which were contained in the soluble stone matrix, substances adsorbed onto calcium oxalate crystals in vitro (crystal surface binding substances, CSBS) and urinary macromolecules (UMMs). The main GAG in the soluble stone matrix and CSBS was found to be heparan sulfate, whereas the UMMs contained various GAGs usually seen in urine. An inhibition assay showed the soluble stone matrix to have the strongest inhibitory activity among these macromolecular substances when inhibitory activity was expressed in terms of uronic acid concentration. It is suggested that the main GAG in the soluble stone matrix consists of heparan sulfate, which has a strong inhibitory activity on calcium oxalate crystal growth and aggregation and constitutes part of the CSBS.

Adult↗

In vivo flow visualization of induced saccular cerebral aneurysms in rats.

A surgical procedure to expose the arterial bifurcation at the base of the rat brain was developed without sacrificing the animal. Using this technique, visualization of flow in and around the induced cerebral aneurysm was achieved by detecting and following fluorescent particles in the blood stream. Cerebral aneurysms were produced by ligating one common carotid artery, inducing experimental hypertension and feeding them with beta-aminopropionitrile. Flow studies of the arterial bifurcation with an early aneurysmal formation showed that there were spiral flows proximal and distal to the bifurcation. This was the first direct visualization of the actual flow in and around cerebral aneurysms in a vital state. This technology can add further information on the development, growth and rupture of cerebral aneurysms.

Animals↗