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Biomedical subjects

T Yamano

Publications and source records attributed to T Yamano.

At least 73 records · Page 4Linked to original sources

Loss of serotonin-containing neurons in the raphe of patients with myotonic dystrophy: a quantitative immunohistochemical study and relation to hypersomnia.

Hypersomnia occurs frequently in patients with myotonic dystrophy (MyD). We performed a quantitative immunohistochemical study of serotonin (5-HT)-containing neurons linked to hypersomnia in the dorsal raphe nucleus (DRN) and the superior central nucleus (SCN) in 8 patients with MyD, 5 of whom showed hypersomnia, and in 12 age-matched controls. The densities of 5-HT neurons in the DRN and the SCN were significantly lower in MyD patients with hypersomnia than in MyD patients without hypersomnia and controls. These data suggest that the loss of 5-HT neurons of the DRN and the SCN is associated with the presence of hypersomnia in MyD.

Aged↗

Decreased type IV collagen of skin and serum in patients with amyotrophic lateral sclerosis.

OBJECTIVE: To study type IV collagen of skin and serum in patients with ALS. BACKGROUND: Collagen abnormalities of skin have been reported in ALS patients. However, little is known concerning type IV collagen in ALS. METHODS: We studied type IV collagen immunoreactivity of skin and measured serum levels of the 7S fragment of the N-terminal domain of type IV collagen (7S collagen) in patients with ALS and control subjects. RESULTS: The basement membrane as well as blood vessels of skin in ALS patients was weakly positive for type IV collagen as compared with those of diseased control subjects. This weak immunostaining became more pronounced as ALS progressed. The optical density for type IV collagen immunoreactivity in ALS patients was significantly lower (p < 0.001) than in diseased control subjects and was significantly decreased with duration of illness (r = -0.85, p < 0.01). Serum 7S collagen levels in patients with ALS were significantly decreased (p < 0.01) as compared with those in diseased and healthy control subjects and were negatively and significantly associated with duration of illness (r = -0.81, p < 0.001). There was an appreciable positive correlation between concentrations of serum 7S collagen and the density for type IV collagen immunoreactivity in ALS patients (r = 0.81, p < 0.02). CONCLUSIONS: These data suggest that a metabolic alteration of type IV collagen may take place in the skin of ALS patients and that the decreased levels of serum 7S collagen may reflect a decreased type IV collagen immunoreactivity of skin in patients with ALS.

Aged↗

Alterations of skin glycosaminoglycans in patients with ALS.

BACKGROUND AND OBJECTIVE: Collagen abnormalities of skin have been reported among patients with ALS. However, little is known concerning glycosaminoglycans of the skin in ALS. Our objective was to clarify morphologic and biochemical findings of skin glycosaminoglycans among patients with ALS. METHODS: We performed morphologic studies and biochemical analysis of glycosaminoglycans of skin from 8 patients with ALS, 6 patients with other neurologic or muscular diseases (control group A), and 7 patients without neurologic disorders (control group B). RESULTS: The wide spaces that separate collagen bundles reacted strongly with Alcian blue stain in skin from patients with ALS and stained more markedly as ALS progressed. Staining with Alcian blue was virtually eliminated by Streptomyces hyaluronidase. The content of hyaluronic acid was significantly higher (p < 0.001) among patients with ALS than in control groups A and B. There was a significant positive correlation between content of hyaluronic acid and duration of illness among patients with ALS (r = 0.88, p < 0.01). However, there was no significant difference in content of dermatan sulfate, chondroitin sulfate-4S, or chondroitin sulfate-6S between patients with ALS and control groups A and B. There was also an appreciable positive correlation between optical density of Alcian blue and content of hyaluronic acid among patients with ALS (r = 0.92, p < 0.01). CONCLUSIONS: The data suggest that a metabolic alteration of glycosaminoglycans related to the increased amount of hyaluronic acid may take place in the skin of patients with ALS.

Aged↗

Loss of catecholaminergic neurons in the medullary reticular formation in myotonic dystrophy.

OBJECTIVE: To clarify the possible relation between the extent of involvement of catecholaminergic neurons and the presence of alveolar hypoventilation in patients with myotonic dystrophy (MyD). BACKGROUND: Respiratory insufficiency has been reported frequently in MyD patients. Recent data support the hypothesis that this respiratory failure results from a primary dysfunction of the CNS. METHODS: The authors performed a quantitative immunoreactive study of tyrosine hydroxylase immunoreactive (TH+) neurons linked to hypoventilation in the dorsal central medullary nucleus (DCMN), the ventral central medullary nucleus (VCMN), and the subtrigeminal medullary nucleus (SMN)--where the autonomic respiratory center is thought to be located--in eight MyD patients and in 10 age-matched control subjects. Alveolar hypoventilation of the central type was present in three of the MyD patients but not in the remaining MyD patients or the control subjects. RESULTS: The densities of TH+ neurons of the DCMN, the VCMN, and the SMN in MyD patients with hypoventilation were significantly lower than in those without hypoventilation (p < 0.02, p < 0.01, and p < 0.01, respectively) and control subjects (p < 0.01, p < 0.01, and p < 0.01, respectively). CONCLUSIONS: These data suggest that the loss of TH+ neurons of the DCMN, the VCMN, and the SMN is associated with the presence of hypoventilation in MyD and may be an important feature of MyD.

Aged↗

8-(3-oxo-4,5,6-trihydroxy-3h-xanthen-9-yl)-1-naphthoic acid inhibits MAPK phosphorylation in endothelial cells induced by VEGF and bFGF.

Angiogenesis is regulated by various factors. In particular, VEGF and basic FGF are of much importance. We found that 8-(3-oxo-4,5,6-trihydroxy-3h-xanthen-9-yl)-1-naphthoic acid inhibited the binding of VEGF to KDR/Flk-1 (VEGF receptor-2) or Flt-1 (VEGF receptor-1) and that it inhibited the MAPK phosphorylation in HUVEC induced by VEGF or basic FGF but not by EGF. 8-(3-oxo-4,5,6-trihydroxy-3h-xanthen-9-yl)-1-naphthoic acid might be used as an inhibitor of VEGF and basic FGF signal transduction.

Journal Article↗

[Arterial infusion of SMANCS-Lipiodol for advanced hepatocellular carcinoma].

Twenty-four patients were treated with arterial infusion of SMANCS dissolved in Lipiodol. Twenty of these patients had HCC with the main trunks of portal vein occluded by tumor, and four patients had severe cirrhosis and multiple HCC. The actual dose of SMANCS administered each patient ranged from 4 to 6 mg. Side effects occurred in 50%. Severe side effects such as shock and shivering-chilliness were observed in 18%. The differences between the values of hepatic functional serum indexes obtained before and after treatment with SMANCS were small and transient. With regard to the therapeutic response of the arterial infusion of SMANCS, the mean survival time was approximately 2.8 months. It was suggested that the more effective administration of SMANCS was combination of the arterial infusion of SMANCS-Lipiodol with TAE at the level of the right hepatic artery of left hepatic artery for multiple HCC.

Antineoplastic Agents↗

[Evaluation by MR imaging of neoadjuvant intra-arterial infusion chemotherapy in uterine cervical cancer].

Eight patients with uterine cervical cancer received two or three courses of neoadjuvant chemotherapy, including 254-S i.v. and CDDP i.a. Transcatheter arterial embolization (TAE) was added for seven patients. The therapeutic efficacy was evaluated by MR imaging and postoperative histopathological examination. Three patients achieved a complete response (CR) and five others were evaluated as a partial response (PR) on MR imaging. On postoperative histology, three of eight showed CR or PR, which coincided with MR findings. Viable cancer cells were shown in five patients. To detect these viable tumors, dynamic MR imaging was indispensable. However, because of limited spatial resolution, the detection of small residual tumors was not easy using dynamic MR imaging.

Adenocarcinoma↗

Human colon cancer cells express the functional Fas ligand.

Fas ligand (FasL) belongs to the TNF superfamily. It is induced in activated lymphocytes and eliminates Fas-positive lymphocytes, resulting in the down-regulation of immune responses. FasL has also been detected in tissues other than lymphoid cells. We investigated the expression and function of FasL on human colon cancer cells. FasL mRNA was detected by RT-PCR in all six colon cancer cell lines tested and was not found on fibroblasts. FasL protein was detected in DLD-1, LoVo, HCT-116 and RPMI 4788 cells by immunohistochemical staining. DLD-1, LoVo and WiDr were cytotoxic against mouse T lymphoma cells which were transfected with human Fas receptor cDNA. The cytotoxicity was significantly enhanced by phorbol 12-myristate 13-acetate (PMA) and ionomycin. Our data suggest that the FasL expressed in human colon cancer cells may be regulated by endogenous factors in the microenvironment of the host and facilitates the escape from the host immune system.

Apoptosis↗

General equation of steady-state enzyme kinetics using net rate constants and its applicaiton to the kinetic analysis of catalase reaction.

The steady-state velocity equation is derived for the general reaction scheme containing n kinds of enzyme species connected by a network of reversible reaction steps. The general equation is represented by the net rate constants as well as the true rate constants of the individual reaction steps. Using a general equation, equations for simpler schemes can easily be derived. Furthermore, the velocity equation expressed by net rate constants is useful for understanding the dynamic state of any reaction be it simple or complex. The generality of the presented equation is tested in a complex reaction involving Bacillus stearothermophilus catalase I. In addition, the applicability of the general equation in analysing the reaction specificity and dynamic state of the reaction is shown.

Animals↗

Age-dependent susceptibility in mumps-associated hydrocephalus: neuropathologic features and brain barriers.

Central nervous system susceptibility to viral infection is often age dependent for unclear reasons. In this study, we examined the age-dependent susceptibility of the brain in mumps virus-induced hydrocephalus in hamsters, and evaluated the relationship between neuropathologic features and brain barriers using glial fibrillary acidic protein and zonula occludentes 1 (ZO-1) immunohistochemistry. In a group intracerebrally inoculated with mumps virus at 2 days of age, pathologic findings such as periventricular edema, ependymal cell loss, and ventricular dilation were more prominent and the distribution of mumps virus antigen was wider than in a group inoculated at 30 days of age. ZO-1-immunoreactive tight junctions in the hydrocephalic brains of the 2-day group were severely damaged in the choroid plexus and ependyma, and in white matter capillaries as early as 3 days after inoculation. These changes were not apparent in the hydrocephalic brains of the 30-day group. Prominent cortical dissemination of virus in the 2-day group was related to underdeveloped perivascular glial foot processes in brain parenchyma. Periventricular edema in the 2-day group was linked to ependymal and blood-brain barrier tight-junction permeability. Our results suggest that tight junctions in the early postnatal period are more immature and fragile than in the adult. We concluded that brain susceptibility in mumps virus-induced hydrocephalus is intimately related to the maturity of brain barriers.

Aging↗

Dissociation of DDVP-induced DNA strand breaks from oxidative damage in isolated rat hepatocytes.

Dichlorvos (DDVP)-induced DNA single strand breaks were investigated in isolated rat hepatocytes. In a dose-response study in hepatocytes from PB-treated rats (80 mg/kg i.p., for 3 days), 250 microM DDVP substantially reduced cellular non-protein sulfhydryl (NPSH) content, but had no detectable effect on DNA. At 500 microM, the increase in DNA single strand breaks was significant, with a slight increase in cellular lipid peroxidation. At doses over 1000 microM DDVP, cell death was accompanied with considerable lipid peroxidation, and DNA single strand breaks were evident. When the antioxidant N,N'-diphenyl-p-phenylene diamine (DPPD) was added or if the hepatocytes were incubated under air instead of 95% O2, lipid peroxidation and cell death were attenuated but DNA single strand breaks and reduction in NPSH content were not. On the other hand, ferrous iron-induced DNA single strand breaks, lipid peroxidation, and depletion of NPSH content were all attenuated by DPPD or by incubating the cells under air. With respect to the subcellular lipid peroxidation, DDVP caused a significant increase mainly in the microsomal fraction, whereas ferrous iron caused rapid and substantial increases in mitochondrial, microsomal, and nuclear fractions. There were more DNA single strand breaks caused by N-nitrosodiethylamine (NDEA), which becomes genotoxic after microsomal metabolism, in hepatocytes from PB-treated rats than in those from control rats. The number of these breaks was reduced by adding the cytochrome P450 inhibitor metyrapone. On the other hand, the effect of DDVP on DNA was not affected by modification of the cytochrome P450 status. These results suggest that lipid peroxidation induced by DDVP in isolated rat hepatocytes plays a significant role in its cytotoxicity but not in its genotoxicity.

Animals↗

A novel nonsense mutation in exon 1 and a transition in intron 3 of the lipoprotein lipase gene.

We examined the lipoprotein lipase (LPL) gene by single strand conformation polymorphism (SSCP) and by restriction fragment length polymorphism (RFLP) analysis in 106 patients with hypertriglyceridemia to screen for novel mutations and to study the contribution of LPL genetic defects in hypertriglyceridemia. We found a single incidence of a homozygous novel nonsense mutation (216G-->A; -14Tryptophan-->stop codon) in exon 1 and 6 cases heterozygous for a single transition (C-->T) at six bp upstream from splicing acceptor site of intron 3. These mutations were not found in 105 normolipidemic controls. The proband homozygous for the nonsense mutation in exon 1, a 74 year old woman, had mild hyperchylomicronemia and her post-heparin plasma showed no LPL protein. However, four heterozygous among family members did not demonstrate hypertriglyceridemia. The frequency of heterozygosity for the C-->T transition in intron 3 was significantly different from that in normolipidemic controls. Therefore, it was suggested that the mutation is involved in hypertriglyceridemia. All of the heterozygotes were men with 4 patients having impaired glucose tolerance or diabetes mellitus. These observations suggest that this polymorphism in intron 3 combined with other as yet undefined factors may be related to hypertriglyceridemia.

Adult↗

[Clonal analysis of hepatocellular carcinoma].

We investigated the cell clonality of 12 cases of female solitary hepatocellular carcinoma (HCC) that were associated with hepatitis virus infection. The clonal origin of HCC could be assessed by the method based on restriction fragment length polymorphism (RFLP) of X-chromosome-linked androgen receptor gene (AR) and phosphoglycerate kinase (PGK) gene, taking advantage of random inactivation of one of two X-chromosomes by methylation in females. We extracted DNA samples from both fresh and paraffin-embedded specimens of the same lesion as a source of DNA sample for polymerase chain reaction (PCR). Consequently, it was possible to use methylation-sensitive restriction enzymes and PCR to study differential methylation patterns among alleles of these genes for both DNA samples. The RFLPs of AR gene and PGK gene were found in eight of 12 cases and five of 12 cases, respectively. There were two cases which had no RFLPs in either AR gene or PGK gene. All cases of HCC which had RFLP in either AR gene or PGK gene demonstrated monoclonal origin of the tumor regardless of their histologic patterns.

Aged↗

The adverse effects of oral 2-mercaptobenzimidazole on pregnant rats and their fetuses.

The effects of oral 2-mercaptobenzimidazole (2-MBI) on pregnant Wistar rats were examined. In a preliminary dose-finding study, pregnant rats treated with 2-MBI over Days 7-17 of gestation showed reduction in maternal thymus weights with compound-related mortality at doses > or = 40 mg/kg. No adverse effects on fetuses were found at doses < or = 40 mg/kg. However, anasarca, cleft palate, and dilated lateral ventricles were present in all fetuses from the only survivor among the dams treated with 60 mg/kg of 2-MBI. In the teratology study, pregnant rats were treated with 2-MBI at doses of 0, 3.3, 10, and 30 mg/kg during the period of organogenesis (Gestation Days 7-17). In addition, pregnant rats of three groups were also treated with 60 mg/kg of 2-MBI for 3 or 4 days during specific periods of organogenesis (Days 7-10, 11-14, or 15-17 of gestation). Treatment on Gestation Days 7-17 resulted in reduced maternal thymus weights at doses of > or = 3.3 mg/kg. In addition to reduced fetal weights, visceral variations (kinked ureter and dilated renal pelvis) and delayed ossification were seen in the fetuses at doses > or = 10 mg/kg, and skeletal variations (rudimentary lumbar ribs) were seen at 30 mg/kg. In the fetuses from the dams treated with 60 mg/kg of 2-MBI, rudimentary lumbar ribs were seen mainly in the group treated on Days 7-10 of gestation, whereas kinked ureter and dilated renal pelvis were evident mainly in the group treated on Gestation Days 15-17.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗