Biomedical subjects

T Hosoya

Publications and source records attributed to T Hosoya.

At least 37 records · Page 2Linked to original sources

PubMed2001

Abducens nerve enhancement demonstrated by multiplanar reconstruction of contrast-enhanced three-dimensional MRI.

We describe contrast enhancement of the cisternal portion of the abducens nerve and discuss its clinical significance. We examined 67 patients with ophthalmoplegia using contrast-enhanced 3-dimensional (3D) MRI with multiplanar reconstruction along the nerves and found 16 patients (ten men, six women), aged 10-73 years (mean 34.4 years), with contrast enhancement of the abducens nerve. Of the 36 patients who had an abducens palsy, 14 (39%) showed contrast enhancement. In the 16 patients, 23 abducens nerves enhanced; 13 were symptomatic and 10 asymptomatic at the time. The causes were disseminated tumour (1), an inflammatory process (3), trauma (2), ischaemia (2) and autoimmune diseases (8), such as the Miller Fisher syndrome, acute ophthalmoparesis, polyneuropathy and multiple sclerosis. Abducens and/or oculomotor nerve enhancement was the only abnormality on MRI in the patients with traumatic or ischaemic neuropathy or autoimmune diseases. There were 14 patients who recovered fully within 1-6 months after treatment, and resolution of the enhancement correlated well with recovery.

Abducens Nerve↗

PubMed2001

Virtual MR microscopy for unruptured aneurysm.

PURPOSE: This study was performed to evaluate the usefulness of virtual magnetic resonance microscopy (VMRM) for the diagnosis of cerebral aneurysms. MATERIALS AND METHODS: We reviewed 11 patients with unruptured aneurysms confirmed by angiography or surgical therapy. We evaluated the ability of VMRM to represent aneurysms and the findings of the form and neck of the aneurysms. RESULTS: VMRM revealed 17 aneurysms, one of which was not detected by MR angiography (MRA). One suspected aneurysm by MRA was denied by VMRM. Although VMRM did not clearly demonstrate either one giant aneurysm or distal middle cerebral artery, two aneurysms in the cavernous sinus were clearly visualized by VMRM. VMRM seems to be almost equivalent to computed tomography angiography when detecting aneurysms without additional radiation exposure. CONCLUSION: VMRM is found valuable not only to plan the microscopic surgical therapy, but to visualize aneurysms.

Aged↗

PubMed2001

Health-related quality of life among dialysis patients in Seattle and Aichi.

We used the 36-item Short-Form Health Survey to compare health-related quality of life (HRQOL) between 104 dialysis patients in Seattle, WA, and 2,178 patients in Aichi, JAPAN: Compared with Aichi patients, Seattle patients had lower scores on three scales related to physical HRQOL: Physical Functioning (PF; P = 0.03), Role-Physical (RP; P = 0.004), and Vitality (VT; P < 0.001). However, scores related to mental HRQOL were higher for Seattle patients compared with those of Aichi patients, which included scores for Role-Emotional (RE; P = 0.005) and Mental Health (MH; P < 0.001). Scores for Bodily Pain, General Health Perception, and Social Functioning did not differ significantly between the two groups. These differences persisted even after potential confounding factors were controlled for. However, after taking into account national norm data for the United States and Japan, differences in PF and VT disappeared, whereas differences in RP, RE, and MH persisted. These results suggest that the higher scores for PF and VT in Aichi patients were partly explained by the higher physical HRQOL of the Japanese general population. Although these data may not be representative of the total dialysis populations in the United States and Japan, they suggest potential differences in HRQOL between patients in the two countries. Additional research is needed to confirm these results and understand the factors associated with these differences. The findings suggest the need for further attention to the physical limitations of US dialysis patients and the mental health of Japanese dialysis patients.

Adult↗

PubMed2001

Effects of dantrolene and its derivatives on Ca(2+) release from the sarcoplasmic reticulum of mouse skeletal muscle fibres.

1. We analysed the effect of dantrolene (Dan) and five newly synthesized derivatives (GIFs) on Ca(2+) release from the sarcoplasmic reticulum (SR) of mouse skeletal muscle. 2. In intact muscles, GIF-0185 reduced the size of twitch contraction induced by electrical stimulation to the same extent as Dan. GIF-0082, an azido-functionalized Dan derivative, also inhibited twitch contraction, although the extent of inhibition was less than that of Dan and of GIF-0185. 3. In skinned fibres, Dan inhibited Ca(2+)-induced Ca(2+) release (CICR) under Mg(2+)-free conditions at room temperature. In contrast, GIF-0082 and GIF-0185 showed no inhibitory effect on CICR under the same conditions. 4. Dan-induced inhibition of CICR was not affected by the presence of GIF-0082, whereas it was diminished in the presence of GIF-0185. 5. GIF-0082 and GIF-0185 significantly inhibited clofibric acid (Clof)-induced Ca(2+) release, as did Dan. 6. Several Dan derivatives other than GIF-0082 and GIF-0185 showed an inhibitory effect on twitch tension but not on the CICR mechanism. All of these derivatives inhibited Clof-induced Ca(2+) release. 7. The magnitudes of inhibition of Clof-induced Ca(2+) release by all Dan derivatives were well correlated with those of twitch inhibition. This supports the notion that the mode of Clof-induced opening of the RyR-Ca(2+) release channel may be similar to that of physiological Ca(2+) release (PCR). 8. These results indicate that the difference in opening modes of the RyR-Ca(2+) release channel is recognized by certain Dan derivatives.

Animals↗

PubMed2001

Defective development of secretory neurones in the hypothalamus of Arnt2-knockout mice.

BACKGROUND: Within the basic region-helix-loop-helix (bHLH)-PAS family of transcription factors, Arnt and Arnt2 play unique roles; these two factors not only heterodimerize with themselves, but also with other members of this family and they act as transcription regulators which bind to specific DNA elements. Whereas Arnt is broadly expressed in various tissues, the expression of Arnt2 is known to be limited to the neural tissues. RESULTS: To elucidate the function of Arnt2 in detail, we cloned the mouse Arnt2 gene and its gene structure was determined. We subsequently generated germ line Arnt2 mutant mice by gene targeting technology. Heterozygous Arnt2 mice were viable, but homozygous Arnt2 gene knockout mice died shortly after birth. Histological and immunological analyses revealed that the supraoptic nuclei (SON) and the paraventricular nuclei (PVN) are hypocellular. Moreover, secretory neurones identified by the expression of neurosecretory hormone such as arginine vasopressin, oxytocin, corticotrophin-releasing hormone and somatostatin are completely absent in SON and PVN in the mutant Arnt2 mice. Consistent with these observations, prospective SON and PVN neurones which express Brn2 appeared around E13.5 in the mantle zone, but no neurones which expressed the neurosecretory hormones were found in the SON and PVN regions. CONCLUSIONS: These data show that the transcription factor Arnt2 controls the development of the secretory neurones at the later or final stages of differentiation rather than at the beginning stage. Strikingly similar observations have been reported with the Sim1 deficient mice. Taken together, our results demonstrate that Arnt2 is an indispensable transcription factor for the development of the hypothalamus, and suggest that Arnt2 is an obligatory partner molecule of Sim1 in the developmental process of the neuroendocrinological cell lineages.

Amino Acid Sequence↗

PubMed2001

Ganglioside as an endogenous growth suppressor for glomerular mesangial cells.

BACKGROUND: Glomerular mesangial cells potentially secrete many growth-modulating substances that could regulate mesangial cell proliferation. To date, however, the properties of such factors have not been fully evaluated. METHODS: For that purpose, conditioned medium (CM) from mesangial cells was used for cross-feeding experiments. Cell proliferation was evaluated by 3H-thymidine incorporation assay and direct cell counting. The growth-regulatory molecule was further characterized using biochemical techniques. RESULTS: Cross-feeding this CM to mesangial cells in vitro, despite stimulation with platelet-derived growth factor (PDGF), effectively suppressed the cells' synthesis of DNA in a dose-dependent manner. The inhibitory substance derived from mesangial cells was less than 3 kD in molecular mass, was heat stable, and was insensitive to proteinase K. After neuraminidase digestion, this inhibitory activity was lost. These data indicated that the inhibiting substance bore the typical features of gangliosides, which are multifunctional glycolipids that reside in cell membrane. Gangliosides were abundant in the CM from mesangial cells, as detected by metabolic radiolabeling and thin-layer chromatography (TLC). This result suggested that mesangial cells constitutively shed gangliosides. The growth suppressive activity in the CM was blunted when mesangial cells were pretreated with the ganglioside synthesis inhibitor d-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol-HCl (d-threo-PDMP; 20 micromol/L) in accordance with the decreased ganglioside content in cells. Finally, gangliosides isolated from CM of mesangial cells suppressed PDGF-induced DNA synthesis of mesangial cells. CONCLUSIONS: These results suggest that mesangial cells constitutively shed gangliosides that then suppress the division of these cells in an autocrine-like manner.

Animals↗

PubMed2001

Dialysis patients' preferences regarding cardiopulmonary resuscitation and withdrawal of dialysis in Japan.

The aim of this study is to show the preferences of Japanese dialysis patients for receiving cardiopulmonary resuscitation (CPR) in their current health status, if they were severely demented, or if they had terminal cancer and to determine their desires about continuing dialysis if they were severely demented or had terminal cancer. A questionnaire survey including the three scenarios was administered to 450 dialysis patients in 15 hospitals in JAPAN: Three hundred ninety-eight patients completed the questionnaires for a response rate of 88%. The majority of responding patients were men and were undergoing hemodialysis. Only 5% of the patients had discussed their preferences regarding CPR with their physicians, and 29%, with their family members. Forty-two percent of the patients answered that they would want to receive CPR if they experienced cardiopulmonary arrest in their current health status, and 12% answered in the affirmative if they were seriously demented or had terminal cancer. Eighteen percent of the patients would want to continue dialysis if they were demented, and 45%, if they had terminal cancer. Statistical analysis showed that more patients who were working tended to want to continue dialysis if they had terminal cancer than those who were not (53% versus 37%; P < 0.014). Patients' age and preferences did not statistically correlate. Preferences of Japanese dialysis patients for CPR and dialysis vary according to differences in health status, and only a minority would want to receive CPR for cardiopulmonary arrest even in their current health status.

Adult↗

PubMed2001

Analysis of the early blood kinetics of 99mTc-GSA and its verification: new one-compartment model and regression equation.

Technetium-99m-galactosyl human serum albumin (99mTc-GSA) is a radiopharmaceutical that binds to asialoglycoprotein receptors in the hepatocyte membrane; the level of 99mTc-GSA accumulation in the liver correlates well with the parameters of hepatic function tests. We hypothesized that the early blood kinetics of 99mTc-GSA could be described by a simple one-compartment model expressed as an offset + a monoexponential function (y=y0 +Ae(-alpha)t). The aims of this study were to assess the validity of this hypothesis using sequentially measured blood levels of 99mTc-GSA, which were approximated by a regression expression, and to analyse the regression equation. 99mTc-GSA levels were measured in blood samples collected from 30 patients with liver disease. From sequential changes in radioactivity up to 30 min after injection, a regression equation expressed as an offset+ a monoexponential function was calculated and evaluated by multiple correlation coefficients and absolute deviations (% error). The liver uptake rate 15 min after injection of 99mTc-GSA (liver uptake rate 15, UTR 15) was calculated from the regression equation in each case. The respective relationships of this parameter to the coefficient [A] and gradient [alpha] were evaluated. In all cases, the measured values of radioactivity in blood samples could be fitted to an offset + a monoexponential function. The validity of our hypothesis was supported by examining regression equations calculated from blood 99mTc-GSA levels. Analysis of the regression equations suggested a potential for a new index of hepatic functional reserve.

Algorithms↗

PubMed2001

Coordinate regulation of endothelin and adrenomedullin secretion by oxidative stress in endothelial cells.

To elucidate the significance of oxidative stress in the modulation of endothelial functions, we examined the effects of H(2)O(2) on the expression of two endothelium-derived vasoactive peptides, endothelin (ET) and adrenomedullin (Am), and their interaction. H(2)O(2) dose dependently suppressed ET secretion and ET-1 mRNA expression in bovine carotid endothelial cells (ECs). Menadion sodium bisulfate, a redox cycling drug, also decreased ET secretion in a dose-dependent manner. Catalase, a H(2)O(2) reductase, and dl-alpha-tocopherol (vitamin E) significantly inhibited H(2)O(2)-induced suppression of ET secretion. Downregulation of ET-1 mRNA under oxidative stress was regulated at the transcriptional level. In contrast, H(2)O(2) increased Am secretion (and its mRNA expression) accompanied by the augmentation of cAMP production. Am, as well as 8-bromo-cAMP and forskolin decreased ET secretion in a dose-dependent fashion. Furthermore, an anti-Am monoclonal antibody that we developed abolished H(2)O(2)-induced suppression of ET secretion at 6-24 h after the addition of H(2)O(2). H(2)O(2) increased the intracellular Ca(2+) concentration ([Ca(2+)](i)). Moreover, treatment with ionomycin, a Ca(2+) ionophore, and thapsigargin, an inhibitor of endoplasmic reticulum ATPase, decreased ET secretion dose dependently for 3 h. These results suggest that the production of ET was decreased via activation of the Am-cAMP pathway and by the elevation of [Ca(2+)](i) under oxidative stress. These findings elucidate the coordinate expression of two local vascular hormones, ET and Am, under oxidative stress, which may protect against vascular diseases.

Adrenomedullin↗

PubMed2001

Serum uric acid and renal prognosis in patients with IgA nephropathy.

BACKGROUND/AIMS: This study was designed to elucidate the clinical significance of serum uric acid (SUA) and the relationship between hyperuricemia and renal prognosis in IgA nephropathy. METHODS: The correlation between SUA and other clinical parameters were examined in 748 IgA nephropathy patients (432 males and 316 females). Among these patients, 226 (144 males and 82 females) who were followed for more than 5 years were examined for the relationship between hyperuricemia and renal prognosis. RESULTS: In IgA nephropathy, SUA correlated negatively with creatinine clearance (Ccr), and positively with urinary protein and tubulointerstitial damage. SUA was higher in patients with hypertension or diffuse proliferative glomerulonephritis. Hyperuricemia was a risk factor for renal prognosis, both in terms of serum creatinine (p = 0.0025) and Ccr (p = 0.0057). In 56 patients with normal Ccr at renal biopsy, the change of Ccr after more than 8 years was -22.3 +/- 20.8% in 13 patients with hyperuricemia, compared with +2.6 +/- 39.4% in 43 patients without hyperuricemia (p = 0.0238). Hyperuricemia was related independently to deterioration of Ccr (p = 0.0461). CONCLUSION: Hyperuricemia in IgA nephropathy is derived from both glomerular and tubulointerstitial damage, and correlated with hypertension. Hyperuricemia is a risk factor for renal prognosis in IgA nephropathy.

Adult↗

PubMed2001

Vitamin D receptor gene polymorphism detected by digestion with Apa I influences the parathyroid response to extracellular calcium in Japanese chronic dialysis patients.

BACKGROUND: To play its physiological role, 1,25(OH)2D3 must bind to a specific vitamin D receptor (VDR) in the nucleus. We have previously reported that VDR gene polymorphism influences the parathyroid function in patients with end-stage renal disease (ESRD). In the present study, we have investigated the relationship between the parathyroid responsiveness and VDR gene polymorphism, as detected by the Apa I restriction enzyme, by changing the concentration of Ca2+ in the dialysate. METHODS: 58 Japanese ESRD patients undergoing renal replacement therapy in our institution were evaluated. Genomic DNA was extracted from peripheral leukocytes and digested at the intron between exon 8 and exon 9 of the VDR gene using Apa I enzyme. Then alleles were classified into genotype A (undigested allele) and genotype a (digested allele). Extracellular ionized calcium ([Ca2+]e), serum phosphate, and intact parathyroid hormone (PTH) were measured before and after each hemodialysis (HD) session with dialysates having different concentrations of Ca2+ (1.5 or 1.25 mmol/l). The significance of differences in statistical analyses was defined within confidence limits of 5.0%. RESULTS: The AA, Aa, and aa genotypes were observed in 7/58 patients (12.1%), 23/58 patients (39.6%), and 28/58 patients (48.3%), respectively. The PTH reduction after HD with the 1.5-mmol/l Ca dialysate did not differ significantly between group AA+Aa and group aa. On the other hand, the PTH increase was significantly higher in group aa than in group AA+Aa after HD with the 1.25-mmol/l Ca dialysate (p = 0.0107), despite a similar PTH level before HD. Similarly, the percent increase of PTH after HD with the 1.25-mmol/l Ca dialysate was significantly higher (p = 0.0112) in group aa (50.2 +/- 9.4%) than in group AA+Aa (19.7 +/- 7.2%). There were no significant differences between the two groups in [Ca2+]e nor in serum phosphorus (Pi) before and after HD with either dialysate. Group AA+Aa and group aa did not show statistically significant differences in age, female/male ratio, ratio of diabetic nephropathy, or dialysis period. CONCLUSIONS: The study results showed that the patients in group aa were more sensitive to changes in [Ca2+]e than those in group AA+Aa. Moreover, they suggested that the VDR gene polymorphism may affect parathyroid responsiveness to changes in [Ca2+]e, which in turn may influence onset and progression of hyperparathyroidism in ESRD patients.

Alleles↗

PubMed2001

Association of angiotensinogen gene polymorphism with erythropoietin-induced hypertension: a preliminary report.

The association of the angiotensinogen (AGT) gene variation at codon 235, the T235 variant, with hypertension induced by erythropoietin (Epo) was investigated in patients with progressive renal disease requiring treatment for renal anemia with Epo. The subjects for the study were patients with renal diseases with serum creatinine concentration exceeding 2 mg/dl and a hematocrit (Ht) of less than 30%. During the run-in period, blood pressure was well controlled with an appropriate salt restricted diet and/or antihypertensive treatment. The patients were then given 6,000 IU of Epo once a week until the Ht rose by 5%. For the overall patient group, AGT gene polymorphism analysis revealed T235T (T/T) in 31 cases (61%), M235T (M/T) in 19 cases (37%), and M235M (M/M) in 1 case (2%). In response to treatment with Epo, hypertension (defined as an increase in mean blood pressure greater than 10 mmHg) was found in 11 cases (22%), all of who carried the homozygous T allele (T/T). On the other hand, the frequency of T/T in patients who did not develop hypertension was 50% (T/T:T/M=20:19 cases), indicating a significant difference (p=0.003 by Chi-square). Variables estimated to be associated with Epo-induced hypertension were the T allele, gender (male), and the degree of increase in Ht, in descending order. Our preliminary research indicates that individuals who carry two copies of the T allele, i.e., who are homozygous for T, are highly susceptible to development of hypertension when subjected to Epo. These results suggest that the AGT T235 variant may be the primary gene responsible for the development of Epo-induced hypertension.

Adult↗

PubMed2001

Association of Graves' disease with Evans' syndrome in a patient with IgA nephropathy.

A 20-year-old woman with IgA nephropathy was admitted to Jikei University Hospital for the treatment of rapid deterioration of renal function after receiving 131I-therapy against hyperthyroidism on October 23,1999, and hemodialysis was started. On admission, she was diagnosed as having Evans' syndrome in addition to known Graves' disease. Renal biopsy revealed end-stage renal damage, then, hemodialysis was maintained. Treatment for Evans' syndrome was also started and her general condition gradually improved. The present case implied that "Graves' disease" and "Evans' syndrome" could represent some of the manifestations of an underlying immunological disorder in the patient.

Adult↗

PubMed2001

S-15183a and b, new sphingosine kinase inhibitors, produced by a fungus.

In the course of our screening for inhibitors of sphingosine kinase, we found two active compounds in a culture broth of a fungus, Zopfiella inermis SANK 15183. The structures of the compounds, named S-15183a and b, were elucidated by a combination of spectroscopic analyses to be new azaphilone-type metabolites. S-15183a and b inhibited sphingosine kinase from rat liver with IC50 values of 2.5 and 1.6 microM, respectively. S-15183a also inhibited endogenous SPH kinase activity in intact platelets.

Blood Platelets↗

PubMed2001

Urinary type IV collagen excretion reflects renal morphological alterations and type IV collagen expression in patients with type 2 diabetes mellitus.

AIM: We tried to establish the significance of quantifying urinary type IV collagen (IV-C) excretion for the evaluation of renal involvement of type 2-diabetic patients. METHODS: Twenty patients (13 males and 7 females; age range 31 to 69 years) with type 2 diabetes mellitus had undergone renal biopsy and relationship between the severity of morphological alteration, IV-C expression and urinary IV-C excretion were examined. RESULTS: Urinary IV-C excretion significantly correlated with mesangial expansion score (p = 0.49, p < 0.05) and tubulointerstitial injury score (p = 0.56, p < 0.05). Furthermore, urinary IV-C excretion significantly correlated with both glomerular (r = 0.56, p < 0.01) and tubulointerstitial IV-C expression areas. Urinary protein excretion also correlated with mesangial expansion score and tubulointerstitial injury score. However, it did not correlate with the expression of IV-C in the kidney. CONCLUSIONS: These results suggest that urinary IV-C excretion reflects the pathogenetic process of diabetic nephropathy, which urinary protein excretion alone cannot do sufficiently. It can be concluded that urinary IV-C excretion could be a more useful marker for the evaluation of renal involvement of type 2-diabetic patients.

Adult↗

PubMed2000

The effects of sarpogrelate on cardiomyocyte hypertrophy.

Sarpogrelate was developed as an antiplatelet agent antagonizing 5-hydroxytryptamine (5-HT) receptors. It had been reported that 5-HT receptors were expressed in cardiovascular system, and that sarpogrelate had antihypertrophic effects in vascular smooth muscle cells. Cardiac hypertrophy is a major problem in cardiac diseases, so the present study was designed to elucidate the effects of sarpogrelate on cardiac hypertrophy. Cultured rat cardiomyocytes (MCs) and cardiac nonmyocytes (NMCs) were prepared by Percoll gradient and adhesion method and MCs were incubated with (MCs/NMCs) or without NMCs. As an index of protein synthesis of MCs, [3H]-leucine uptake into MCs and MCs/NMCs was measured. Sarpogrelate decreased [3H]-leucine uptake into MCs (maximum 62.6+/-20.6% of control at 10(-4)M, p<0.05 vs. control). Sarpogrelate also significantly attenuated angiotensin-II- and endothelin-1-induced [3H]-leucine uptake. These results indicated that sarpogrelate might have antihypertrophic effects and could be a useful aid for cardiovascular disease.

Angiotensin II↗

PubMed2000

A Drosophila homolog of LIM-kinase phosphorylates cofilin and induces actin cytoskeletal reorganization.

Mammalian LIM-kinases (LIMKs) phosphorylate cofilin and induce actin cytoskeletal reorganization. To elucidate the functional roles of LIMKs in vivo during developmental processes, we attempted to isolate the cDNA encoding a Drosophila homolog of LIMK (DLIMK) and identified two isoforms of DLIMK transcripts coding for proteins with 1235 and 1257 amino acids, possessing the structure composed of two LIM domains, a PDZ domain, a protein kinase domain, and an unusual long C-terminal extension. In situ hybridization analysis in Drosophila embryos detected the uniformly distributed DLIMK mRNA in stages 2 to 5. In vitro kinase reaction revealed that DLIMK efficiently phosphorylates Drosophila cofilin (twinstar) specifically at Ser-3, the site responsible for inactivation of its actin-depolymerizing activity. When expressed in cultured cells, wild-type DLIMK, but not its kinase-inactive form, induced changes in actin cytoskeletal organization. These observations suggest that the LIMK-cofilin signaling pathway for regulating actin filament dynamics is evolutionarily conserved between Drosophila and mammals.

Actin Depolymerizing Factors↗

PubMed2000

Preparation of Hydrophobically Modified Poly(amidoamine) Dendrimer-Encapsulated Gold Nanoparticles in Organic Solvents.

HAuCl(4) in aqueous solution was extracted to toluene or chloroform using a hydrophobically modified poly(amidoamine) dendrimer. Then, by reduction of Au(3+) ions with dimethylamineborane, gold nanoparticles in the size range of 2-4 nm were obtained in toluene or chloroform. It is suggested that gold nanoparticles are encapsulated by the dendrimer. Copyright 2000 Academic Press.

Journal Article↗