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Biomedical subjects

M Takeda

Publications and source records attributed to M Takeda.

At least 487 records · Page 27Linked to original sources

Linkage and haplotype analysis of familial early-onset Alzheimer disease in Japanese population.

Linkage and haplotype analysis of eleven early-onset Alzheimer disease (AD) families was performed in relation to D21S210 and microsatellite DNA polymorphisms localized on chromosome 14q24.3. Linkage analysis of eight informative families out of eleven early-onset AD families disclosed the highest LOD score of 3.45 (theta = 0.00) at D14S77, while the locus of beta/A4 amyloid protein precursor gene was formally excluded within 10 cM from D21S210, given the evidence of recombinations in five families. Transmission disequilibrium study between the patients and controls without dementia indicated significant differences at D14S43 (p = 0.0001) and D14S71 (p = 0.02). Association study between genotypes linked or related to onset of AD and those of control also revealed a significant difference at D14S43 (p < 0.05), suggesting the existence of linkage disequilibrium. Moreover, the haplotypes at D14S43 linked with the onset of AD indicated a significant relationship with the mean age at onset. These results support that the major locus of early-onset familial AD is located on 14q24.3, and its close linkage to D14S43 and the existence of allelic heterogeneity were suggested.

Age of Onset↗

Missense mutation of rhodopsin gene codon 15 found in Japanese autosomal dominant retinitis pigmentosa.

Heterozygous missense mutation in codon 15 of the rhodopsin gene was detected in a patient with autosomal dominant retinitis pigmentosa (ADRP), where a transition of adenine to guanine at the second nucleotide in codon 15 (AAT-->AGT), corresponding to a substitution of serine residue for asparagine residue (Asn-15-Ser) was detected. None of the remaining unrelated 42 ADRP, 24 autosomal recessive RP (ARRP) and 34 normal individuals had this alteration. Her funduscopic findings were sectorial in type similar to that of the patients with the same mutation found in an Australian pedigree (Sullivan et al., 1993). This study shows phenotypic similarities in patients with the same mutation of a different ancestry.

Amino Acid Sequence↗

Effects of SDZ ENA 713, novel acetyl cholinesterase inhibitor, on learning of rats with basal forebrain lesions.

1. The effects of SDZ ENA 713, a novel acetyl cholinesterase inhibitor, on rat learning was studied using a step-down avoidance paradigm. 2. Injection of ibotenic acid into the caudolateral part of the basal forebrain (BF) innervating cholinergic neurons to the cerebral cortex, resulted in an increase in the number of trials required to obtain 300-second-latency, and also a decrease in the latency period after attaining 300-second-latency. 3. It is shown that the BF-lesioned rats are impaired in both acquisition and retention of learning. 4. Intraperitoneal injection of 0.10-0.05 mg/kg/day SDZ ENA 713 to the BF-lesioned rats showed amelioration of the learning impairment, with a decreased number of trials required to obtain 300-second-latency as well as an increase in the latency time after repeated training. 5. These results indicate that SDZ ENA 713 improves acquisition and retention impairment in BF-lesioned rats, and that this drug may be useful for demented patients with cholinergic dysfunction, such as Alzheimer's disease.

Animals↗

The organization of neurofilaments accumulated in perikaryon following aluminum administration: relationship between structure and phosphorylation of neurofilaments.

Neurofilaments accumulated in perikarya and dendrites of anterior horn cells and Purkinje cells of rabbit treated by aluminum chloride were analysed with a variety of techniques. Four different monoclonal antibodies against phosphorylated and nonphosphorylated epitopes on neurofilament H subunit were used to compare phosphorylation state of these accumulated neurofilaments with that of axonal neurofilaments. Although immunoblotting revealed no significant difference in phosphorylation between control and aluminum-treated brains, accumulated neurofilaments were immunocytochemically more phosphorylated than control perikaryal or dendritic neurofilaments. With detailed analysis of cryothin-section immunogold labeling, accumulated neurofilaments were, however, significantly less phosphorylated than axonal neurofilaments. With quick-freeze deep etching, core filaments of accumulated neurofilaments are as dense as axonal neurofilaments but much less regularly aligned. Cross-bridges of accumulated neurofilaments were less frequent and more branched than those of axonal neurofilaments, and when examined with combined immunocytochemistry and deep etching, were less phosphorylated. These results suggest that there is a relationship between the phosphorylation and the structural organization of neurofilaments. The phosphorylation of neurofilament H subunit may be necessary for formation of frequent and straight cross-bridges and resulting regular alignment of core filaments.

Aluminum↗

An essential role of androgen-induced growth factor in glucocorticoid-dependent autocrine loop in Shionogi carcinoma 115 cells.

Androgen-induced growth factor (AIGF) is essential for the androgen-induced autocrine growth of a mouse mammary Shionogi carcinoma cell line (SC-3 cells). Because glucocorticoid and estrogen have been observed to weakly stimulate DNA synthesis in SC-3 cells, the expression of AIGF mRNA after stimulation with various concentrations of androgen, glucocorticoid, or estrogen was examined by Northern blot analysis. Testosterone, dexamethasone, and estradiol-17 beta (E2) induced AIGF mRNA expression, although the maximum AIGF mRNA expression levels induced by dexamethasone or E2 were lower than that by testosterone. Yet, diethylstilbestrol showed no induction, suggesting that the effect of E2 could be mediated through the androgen receptor. The induction levels of AIGF mRNA by each steroid hormone were correlated positively with hormone-induced DNA synthesis. In addition, the DNA synthesis induced by each steroid hormone was almost completely inhibited by AIGF antisense oligonucleotides, indicating that AIGF is an obligatory component in not only the androgen- but also the glucocorticoid-inducible autocrine loop in SC-3 cells.

Androgens↗

Characterization and localization of nitric oxide synthase in the human prostate.

OBJECTIVES: To characterize nitric oxide synthase (NOS), which catalyzes nitric oxide (NO) production, in the human prostate using biochemical and immunohistochemical techniques. METHODS: NOS catalytic assay and NOS immunohistochemistry were performed on histologically verified nonmalignant prostate tissue obtained from the peripheral and transition zones of seven radical prostatectomy specimens. RESULTS: Biochemical analysis revealed NOS activity in the human prostate, with a greater amount in the peripheral zone than in the transition zone (P < 0.01). In both prostate zones, NOS was immunohistochemically localized to nerve fibers and ganglia coursing throughout the smooth musculature of the stroma and to subepithelial nerve plexuses. NOS immunoreactivity was also localized to glandular epithelium. CONCLUSIONS: The presence, activity, and distribution of NOS were described in two regions of the human prostate. The present evidence implicates NO in the automatic innervation and physiology of the human prostate. It is proposed that NO may modulate smooth muscle tone and secretory functions in the human prostate, although functional studies are needed to support these hypotheses.

Amino Acid Oxidoreductases↗

Effects of nitric oxide on human and canine prostates.

OBJECTIVES: To determine whether nitric oxide (NO) is a mediator of prostatic smooth muscle activity. METHODS: Pharmacologic experiments using electrical field stimulation (EFS) were performed on strips of human and canine prostate. RESULTS: EFS alone elicited frequency-dependent contractions in preparations of human and canine prostates. The greatest contractile activity was achieved at 30 Hz. In the presence of 10(-5) M guanethidine (GUA) and 2 x 10(-6) M atropine (ATR), EFS elicited relaxation of canine prostate strips relative to baseline tension. A weak biphasic response consisting of initial relaxation and subsequent contraction relative to baseline tension was observed in the human prostate strips exposed to similar conditions. The smooth muscle activity observed in the presence of GUA plus ATR was attributed to nonadrenergic, noncholinergic (NANC) nerve transmission. 10(-4) M L-NG-nitroarginine methylester (NAME) significantly increased EFS-elicited NANC smooth muscle activity both in human and canine prostates. L-arginine, 10(-2) M, reversed the effect of L-NAME in human and canine prostates. Sodium nitroprusside, 10(-4) M, a donor of NO, caused relaxation of both human and canine prostates. The mean magnitude of the relaxant response/cross-sectional area in human prostate (2.64 +/- 0.4 g/cm2) was significantly greater than in the canine prostate (1.09 +/- 0.17 g/cm2) (P < 0.005). CONCLUSIONS: These results provide compelling evidence that NO plays a role in mediating contractile function of human and canine prostates.

Animals↗

Histopathological sequence of hepatic and renal lesions in rats after cessation of the repeated administration of CCl4.

The histopathological sequence of hepatorenal lesions in rats after cessation of the repeated administration of CCl4 (0.5 ml/kg, p.o., twice a week for 12 weeks) was examined. In the liver, cirrhotic lesions reduced rapidly after cessation of the CCl4-administration and collagen bundles surrounding the pseudolobules almost disappeared 12 weeks later. In contrast, in the kidney, vacuolation of epithelial cells in the proximal tubules disappeared rapidly but glomerular lesions progressed even after cessation of the CCl4-administration, and marked glomerulosclerosis developed 12 weeks later. Electron microscopically, marked expansion of the mesangial region due to increases of mesangial cells and matrix material, irregular thickening of the capillary basement membrane with mesangial interposition, and various degenerative changes in podocytes including deposition of small-sized droplets were observed.

Animals↗

Significance of epidermal growth factor receptor and c-erbB-2 protein expression in transitional cell cancer of the upper urinary tract for tumour recurrence at the urinary bladder.

An immunohistochemical study of the expression of epidermal growth factor receptor (EGFR) and c-erbB-2 protein was performed in fresh-frozen sections from 30 patients with transitional cell cancers (TCCs) of the upper urinary tract (15 renal pelvic cancers, 15 ureteral cancers) who underwent total nephroureterectomy. We followed them and examined whether TCC appeared in the urinary bladder. The follow-up period ranged from 116 to 2348 days (mean 666 days). The mean period until a secondary urinary bladder cancer appeared was 306 days (116-829 days). Thirteen of those 30 TCCs (43.3%) showed increased expression of EGFR, and 11 TCCs (36.7%) showed increased expression of c-erbB-2. In 12 of 30 patients (40.0%), a secondary urinary bladder cancer appeared after surgery. In only one of the ten patients (10.0%) whose tumours did not exhibit increased expression of either of these receptors the tumour recurred in bladder. On the other hand, in 11 of 20 (55.0%) patients whose tumours had increased EGFR and/or c-erbB-2 expression, secondary urinary bladder cancers recurred after surgery (P < 0.05). Thus, the recurrence rate of TCCs with increased EGFR and/or c-erbB-2 expression was significantly higher than that of tumours showing no increased expression of these receptors (P < 0.01). These results suggest that the immunohistochemical detection of the expression of EGFR and c-erbB-2 in urothelial cancers of the upper urinary tract might be a useful method for determining the likelihood of secondary bladder cancer recurrences.

Aged↗

Three ATP1 genes are present on chromosome II in Saccharomyces cerevisiae.

Chromosome fragmentation, ATP1 disruption, and Southern blot analyses of total DNAs and prime clones of chromosome II showed that three identical ATP1s are present, directing from the telomere to the centromere on the 35-55 kb far from the left telomere sequence of chromosome II. That is, the coding and 5'-, 3'-non-coding regions of ATP1 are repeated 3 times at approximately 7 kb intervals. These three ATP1s are expressed, and one and two ATP1s-disrupted strains, respectively, showed ca.70 and 40% decreases in their ATPase activities and alpha subunit contents, compared to those of the wild type, DC-5 or W303-1A strain, but could grow on glycerol.

Chromosome Mapping↗

Case report: intraglomerular metastasis with neoplastic cell interposition.

A case is described of an 88-year-old man with lung cancer, nephrotic syndrome, and renal dysfunction who died suddenly of an acute myocardial infarction and whose autopsy revealed many adenocarcinoma cells stacked within glomerular capillary lumina of his kidney, entering into basement membrane zones (ie, neoplastic cell interposition). In addition, glomeruli showed a lobular transformation, doubling of glomerular basement membrane, and electron dense deposits along the glomerular basement membrane. These changes were similar to those of membraneoproliferative glomerulonephritis. The association of intraglomerular metastasis and membranoproliferative glomerulonephritis-like lesions led the authors to speculate that the latter glomerular change might have provided an attractive opportunity for circulating tumor cells to be trapped and grow within the glomerular lumina. This mode of metastasis has not been well-recognized. The authors describe the experience, review the literature, and discuss its possible pathogenesis.

Adenocarcinoma↗

Visual evoked potentials (VEPs) in Parkinson's disease: correlation of pattern VEPs abnormality with dementia.

There has been some debate about abnormalities in visual evoked potentials (VEP) in Parkinson's disease (PD). To elucidate the mechanism underlying abnormal VEPs, we investigated the relationship between pattern-reversal VEPs elicited by large checks and mental functions in PD patients (n = 32), as compared with VEPs of age-matched control subjects (n = 22). The PD patients were divided into two groups: PD without dementia (nD-PD; n = 21) and PD with dementia (D-PD; n = 11). All patients but five of the nD-PD patients were being treated with anti-parkinsonian drugs. The D-PD patients showed significantly prolonged P100 latencies compared with both the nD-PD patients and controls (p < 0.01 and p < 0.01, respectively). The PD patients treated with levodopa had significantly longer P100 latencies than the other PD patients. In PD patients, the P100 latency correlated significantly with illness duration (p < 0.05). There was also a significant negative correlation with P100 latency and Mini-Mental State Examination (MMSE) score (p < 0.05). The MMSE score did not correlate with illness duration in PD patients. These findings suggest that the VEPs abnormality elicited by large checks is related to dementia independent of progression of the illness, and that a nondopaminergic neurotransmitter system may play a role in the development of VEPs delay elicited by large checks.

Aged↗

CMV viraemia demonstrated in the serum of a patient with cytomegalovirus pneumonia.

We attempted to demonstrate the expression of cytomegalovirus (CMV) particles in the serum of an acute lymphocytic leukaemia patient with CMV pneumonia. The serum sample was applied to an affinity column coupled with human monoclonal antibody C23 which recognizes the envelope glycoproteins of CMV virus and neutralizes the viral activity. The DNA obtained from each fraction was amplified by double polymerase chain reaction (PCR) and analysed by gel electrophoresis. Bands were clearly observed in the eluted fraction. These results strongly suggest that CMV particles exist in the sera of patients with CMV pneumonia.

Base Sequence↗

Nitric oxide synthase in dog urethra: a histochemical and pharmacological analysis.

1. To examine the presence of nitric oxide synthase (NOS) activity in female dog urethra, pharmacological experiments were performed using electrical field stimulation (EFS), guanethidine, atropine, NG-nitro-L-arginine methyl ester and L-arginine, NOS immunohistochemistry using specific anti-NOS antibody, and reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining were also performed. 2. EFS caused frequency-dependent contractions in all urethral preparations, but in the presence of guanethidine and atropine, EFS caused significant relaxation in the proximal urethra and was without effect on the distal urethra. 3. In the presence of guanethidine, atropine, and NG-nitro-L-arginine methyl ester, small contractions to EFS were re-established in the proximal urethra, but not in the distal urethra. NG-nitro-D-arginine methyl ester had no such effect. 4. In the presence of guanethidine, atropine, and NG-nitro-L-arginine methyl ester, the addition of L-arginine, restored the EFS-elicited relaxant responses previously seen with guanethidine and atropine alone in the proximal urethra (at 30 Hz; 12.89 +/- 5.27% to -2.44 +/- 4.43%, mean +/- s.e., P < 0.05). D-Arginine had no such effect. 5. In the distal urethra, the addition of NG-nitro-L-arginine methyl ester and then L-arginine had no effect on responses to EFS in preparations treated with guanethidine and atropine. 6. Sodium nitroprusside caused relaxation in both the proximal and distal urethra. The relaxant responses per cm2 cross sectional area in the proximal and distal urethra were 1.23 +/- 0.29, and 2.02 +/- 0.54 g cm-2 cross sectional area (mean +/- s.e.), respectively: there was no significant difference between them. 7. Both NOS and NADPH diaphorase-positive neurones were present in dog urethra, the densities of both being higher in the proximal urethra than in the distal urethra. 8. These results show that female dog urethra possesses NOS nerves and that endogenous NO may play a role in relaxation in the proximal but not the distal urethra.

Adrenergic Agents↗

Analysis of PrPc mRNA by in situ hybridization in brain, placenta, uterus and testis of rats.

An amyloid-like isoform of a 33- to 34-kD glycoprotein, termed as the scrapie prion protein (PrPsc), plays a critical role in transmissible spongiform encephalopathies of animals and humans. It has even been suggested to present the responsible infectious agent. This protein is a posttranslationally modified form of the cellular isoform of prion protein (PrPc). Hitherto, little has been known about the functions of PrPc. In order to examine the localization of PrPc mRNA in rat tissues, the in situ hybridization technique was performed. In rat brain, PrPc mRNA was predominantly localized within pyramidal cells of the hippocampus, large neurons of the thalamus and neocortex, and Purkinje cells of the cerebellum. In the placenta, not only PrPc mRNA was localized to a subpopulation of decidual cells at the highest levels, it was also expressed in the amnion and mesodermal layer of the yolk sac. Furthermore, PrPc mRNA was also expressed in the myometrium of the uterus and seminiferous tubule in the testis. However, signals were not obtained in the lung, spleen, liver of prenatals and other fetus tissues. The distribution of rat PrPc mRNA portrayed the levels which were different among the various types of cells, suggesting that its expression may be regulated in a tissue-specific manner.

Animals↗

Early development of encephalomyocarditis (EMC) virus-induced orchitis in Syrian hamsters.

Lesions associated with encephalomyocarditis (EMC) virus in the testes of Syrian hamsters were investigated. Histopathologic changes were first detectable by light microscopy at 3 days postinoculation (DPI). Immunohistochemically, virus antigens were detected in the cytoplasm of germ cells and Sertoli cells in some seminiferous tubules beginning at 2 DPI. The following ultrastructural changes were observed: 1) swelling of mitochondria and dilatation of endoplasmic reticulum in germ cells, 2) large number of residual bodies in seminiferous tubules, 3) aggregates of virus-like particles in the cytoplasm of degenerated cells and tubular lumen, 4) condensation of cytoplasm and dilatation of endoplasmic reticulum in Sertoli cells, and 5) degenerative changes in capillary endothelial cells.

Animals↗

Effects of brain-derived neurotrophic factor on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonism in monkeys.

The effects of intrathecal infusion of brain-derived neurotrophic factor (BDNF) were examined in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced parkinsonian model in monkeys. Nine Japanese monkeys were divided randomly into three groups, an untreated control (n = 3), a BDNF group (n = 3), and a non-BDNF group (n = 3). Animals in the BDNF group received continuous intrathecal infusion of 10 ml of cell culture medium containing 10 micrograms of BDNF protein; the non-BDNF group received intrathecal infusion of the same culture medium without BDNF. To induce parkinsonian syndromes, a total of 1 mg/kg 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine was administered intravenously to each monkey in both the BDNF and non-BDNF groups. The neurological signs in the monkeys were monitored for 2 weeks and were scored according to the monkey parkinsonism rating scale; histological changes in the substantia nigra were evaluated after the 2-week observation period. The BDNF-treated animals remained asymptomatic during the 1st week and showed mild parkinsonism during the 2nd week, whereas the non-BDNF group showed typical parkinsonian syndrome during the 1st week, with deterioration in the 2nd week. Histological damage in the substantia nigra correlated well with the clinical features. Severe neuronal cell loss in the substantia nigra was observed in animals with severe parkinsonism (those in the non-BDNF group), whereas significantly less damage was observed in this region in the BDNF group.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗