Biomedical subjects

M Sano

Publications and source records attributed to M Sano.

At least 19 recordsLinked to original sources

PubMed1998

Activation of mitogen-activated protein kinases is not required for the extension of neurites from PC12D cells triggered by nerve growth factor.

Numerous studies with PC12 cells have suggested that the mitogen-activated protein (MAP) kinase pathway might play a major role in the neuronal differentiation that is induced by nerve growth factor (NGF). Cells of the PC12D subline extend neurites within several hours in response to NGF in the presence of inhibitors of the synthesis of RNA and protein. We examined the effects of a specific inhibitor 2-(2'-amino-3'-methoxyphenyl)-oxanaphthalen-4-one (PD98059) of the MAP kinase kinase (MEK)/MAP kinase pathway on the NGF-induced outgrowth of neurites in PC12D cells. The increase in MAP kinase activity in response to NGF was reduced by 80% upon treatment of PC12D cells with 50 microM PD98059, whereas the NGF-dependent formation of ruffles and the subsequent outgrowth of neurites were not blocked by PD98059 at this concentration. The outgrowth of neurites from conventional PC12 cells by NGF was suppressed by the addition of 50 microM PD98059 as reported by Pang et al. [L. Pang, T. Sawada, J. Stuart,S.J. Decker, A.R. Saltiel, Inhibition of MAP kinase kinase blocks the differentiation of PC12 cells induced by nerve growth factor, J. Biol. Chem. 270 (1995) 13585-13588]. In contrast, the rapid regeneration of neurites from PC12 cells primed with NGF, was not altered in the presence of the same dose of the inhibitor of MEK. It appeared, therefore, that the activation of the MAP kinase pathway was not necessarily required for the NGF-dependent extension of neurites. When PC12D cells were transfected with the dominant inhibitory Ha-ras Asn-17 gene, the induction of the mutant Ras protein led the suppression of the rapid outgrowth of neurites in response to NGF but not to dibutyryl cyclic AMP (dbcAMP). The result implies a direct involvement of Ras protein in the NGF-induced signal transduction that lead to the formation of neurites in PC12D cells. We can conclude that the activation of MAP kinase and selective gene expression are required for the differentiation of conventional PC12 cells to sympathetic neuron-like cells and that activation of Ras protein and, subsequently, of a MAP kinase-independent pathway might be involved in the extension of neurites from PC12D cells or in the regeneration of neurites from primed PC12 cells in response to NGF.

Animals↗

PubMed1998

NO is not involved in the simvastatin induced cell division and differentiation in PC12 cells.

Simvastatin, a potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor has been reported to inhibit cell division and induce neurite-like outgrowth in PC12 cells [Sato-Suzuki, I. and Murota, S., Neurosci. Lett., 220 (1996) 21-24]. In the present paper, we examined whether the induced nitric oxide (NO) in the simvastatin-treated PC12 cells is involved in the growth arrest and differentiation as reported in nerve growth factor (NGF) treated PC12 cells. Treatment of PC12 cells with simvastatin caused peripherin formation and enhanced NO production just like NGF-treated PC12 cells. Different from NGF, however, NO synthase inhibitors could not affect the growth arrest and differentiation in simvastatin-treated PC12 cells. In conclusion, NO had nothing to do with cell division and differentiation in simvastatin-treated PC12 cells.

Animals↗

PubMed1998

Distribution of cerebellar cortical lesions in multiple system atrophy: a topographic neuropathological study of three autopsy cases in Japan.

We investigated neuropathologically the distribution of the cerebellar cortical lesions in three Japanese autopsy cases of multiple system atrophy (MSA) using hemisphere specimens. The lesions were classified as mild, moderate or severe. The distribution of cerebellar cortical lesions in all three cases were uniform: the cerebellar cortical lesions were more conspicuous in the vermis than in the hemisphere. These neuropathological findings differ from the established theory that cerebellar lesions of MSA are more pronounced in the hemisphere than in the vermis. The degree of cerebellar cortical lesions in our cases increased in relation to the duration of the disease. Our pathological data may contribute to the morphological differential diagnosis in various neurodegenerative disorders including late cortical cerebellar atrophy. Our neuropathological findings may also make a contribution to the neuroradiological progress in the differential diagnosis of spinocerebellar disease.

Brain Mapping↗

PubMed1998

Biphasic activation of the JAK/STAT pathway by angiotensin II in rat cardiomyocytes.

This study was designed to demonstrate the characteristic pattern of angiotensin II-induced JAK/STAT (indicating just another kinase/signal transducer and activator of transcription) activation in cultured rat cardiomyocytes by comparing it with leukemia inhibitory factor (LIF)-induced activation. Angiotensin II (10(-7) mol/L) induced rapid phosphorylation of JAK2 and Tyk2, but not JAK1, and phosphorylated STAT1 and STAT2, but not STAT3, in the early stage up to 30 minutes. The time course of JAK/STAT activation by angiotensin II was apparently slower than that by LIF. Interestingly, angiotensin II phosphorylated STAT3 and rephosphorylated STAT1 in the late stage at 120 minutes. We also found that angiotensin II induced the formation of interferon-stimulating gene factor (ISGF) complexes biphasically, in the early stage at 15 to 30 minutes and in the late stage at 120 minutes, and that angiotensin II induced delayed activation of the sis-inducing factor (SIF) complex at 120 minutes. Formation of ISGF and SIF complexes in response to angiotensin II paralleled the phosphorylation pattern of STAT1 and STAT3 and was quite different from those obtained in response to LIF. The phosphorylation of STAT1 was suppressed by pretreatment with the angiotensin II type-1 (AT1) receptor antagonist CV11974, but the delayed addition of CV11974 failed to suppress phosphorylation of STAT3 at 120 minutes. In conclusion, angiotensin II-induced JAK/STAT activation in rat cardiomyocytes is biphasic and entirely different from LIF-induced activation.

Angiotensin II↗

PubMed1998

Differential adaptations of insulin-like growth factor-I, basic fibroblast growth factor, and leukemia inhibitory factor in the plantaris muscle of rats by mechanical overloading: an immunohistochemical study.

We investigated changes in several growth factors in the rat plantaris muscle produced by mechanical overloading by ablation of synergists using immunohistochemistry. At 1 and 3 days post surgery, the insulin-like growth factor-I (IGF-I) level was slightly increased in the cytosol and markedly increased in the invading cells of the extracellular space. Thereafter, the IGF-I immunoreactivity evoked by overloading rapidly decreased to the normal level. The level of leukemia inhibitory factor (LIF), which was not shown to change at 1 day post surgery, was increased in the cytosol at 3, 5, 7 and 10 days and at 2 weeks. Basic fibroblast growth factor (bFGF) immunoreactivity did not change during the entire period of overloading (1 day-3 weeks post surgery). These results indicate that the elevations of the levels of IGF-I and LIF show differential time course in the plantaris muscle subjected to functional overload. Furthermore, bFGF appears not to be related to the compensatory hypertrophy produced by overloading.

Adaptation, Physiological↗

PubMed1998

Androgen metabolism in cultured rat renal inner medullary collecting duct (IMCD) cells.

Although the stimulations of renal hypertrophy and renal erythropoietin production have been well-known androgen effects in the kidney, recent investigative progresses are further providing good evidences for androgen-regulated gene productions of key enzymes or local hormone substrates important to renal cell metabolisms and tubular functions in mouse or rat proximal tubules, respectively. It has been also reported that testosterone restores vasopressin receptors in medullary collecting ducts of the ageing rat and improves a urinary concentrating ability. Therefore in the present study we examined a metabolic pathway of androgens in cultured rat renal IMCD cells, which finally determine a urinary composition and volume. IMCD cells cultured from kidneys of male Wistar rats weighing about 200 g were incubated with serum-free culture media containing 4 nM [3H] testosterone or [3H] androstenedione for 2-48 h. Radioactive compounds in incubation media were then separated by reverse-phase high-pressure liquid chromatography (HPLC) and identified mainly on the basis of comparison of retention times of standard materials on HPLC. The main metabolites identified in testosterone or androstenedione incubation experiment were 5 alpha-dihydrotestosterone or 5 alpha-androstanedione, respectively. 5 alpha-Reductase inhibitor, MK 906, effectively inhibited the formations of these Ring A reduced metabolites. These results may suggest that rat renal IMCD cells possess 5 alpha-reductase activity, thereby converting androgens into their biologically active forms in vivo.

5-alpha Reductase Inhibitors↗

PubMed1998

Dementia as a predictor of adverse outcomes following stroke: an evaluation of diagnostic methods.

BACKGROUND AND PURPOSE: Although it is understood that dementia is a risk factor for adverse outcomes, little is known about the predictive validity of the numerous methods that have been proposed for its diagnosis. Thus, we performed the present study to assess the utility of a variety of diagnostic methods in the prediction of adverse outcomes following stroke. METHODS: We administered neuropsychological, neurological, and functional examinations to 244 patients (age, 71.7+/-8.5 years) 3 months after ischemic stroke. We diagnosed dementia using each of the following methods: (1) neuropsychological testing, requiring deficits in increasing numbers of cognitive domains, both with and without memory impairment, as well as functional impairment; (2) Mini-Mental State Examination (MMSE) score of <24; and (3) neurologists' clinical judgment. We then used survival analyses to investigate the ability of diagnoses based on those methods to predict death and recurrent stroke during long-term follow-up. RESULTS: Log-rank tests and Cox proportional hazards analyses, with recurrent stroke entered as a time dependent covariate, determined that all of the paradigms were significant predictors of mortality, but the performance of paradigms based on neuropsychological testing was superior to the use of the MMSE and clinical judgment, particularly when memory impairment was required. Log-rank tests determined that paradigms based on neuropsychological testing were the only significant predictors of recurrent stroke and performed best when memory impairment was required. CONCLUSIONS: Our results suggest that dementia diagnosis based on neuropsychological assessment and an operationalized paradigm requiring deficits in memory and other cognitive domains is superior to other conventional methods in its ability to identify patients at elevated risk of adverse outcomes following stroke.

Activities of Daily Living↗

PubMed1998

Cognitive function in nondemented older women who took estrogen after menopause.

Investigations of the effects of estrogen replacement on cognitive function in healthy older women have yielded disparate results. We evaluated the relationship between a history of estrogen use and cognitive test performance in 727 women participating in a large community-based study. Participants were followed longitudinally for an average of 2.5 years. Estrogen use history was obtained at baseline. Standardized tests of memory, language, and abstract reasoning were administered at baseline and at follow-up. Results indicate that women who had used estrogen replacement scored significantly higher on cognitive testing at baseline than nonusers, and their performance on verbal memory improved slightly over time. The effect of estrogen on cognition was independent of age, education, ethnicity, and APOE genotype. Results suggest that estrogen replacement therapy may help to maintain cognitive function in nondemented postmenopausal women.

Aged↗

PubMed1998

[A case of inflammatory pseudomotor of the lung suspected of being metastasis of thymoma].

An operated case of inflammatory pseudotumor of the lung is reported. A 27-year-old female was pointed out a coin lesion in the left lower lung field on chest X-ray and the size of mass increased. She had a history of thymomectomy for thymoma, and resection of right intrathoracic dissemination. Therefore operation was performed on suspicion of metastasizing thymoma. A partial resection including the mass with VATS was performed and histopathologic examination revealed inflammatory pseudotumor. The postoperative course was uneventful, and there has been no evidence of recurrence thereafter. In Japan, sixty-eight cases of inflammatory pseudotumor of the lung including our case have been reported in the literature.

Adult↗

PubMed1998

Antitussive effect of azelastine hydrochloride in patients with bronchial asthma.

To investigate the efficacy of azelastine hydrochloride (azelastine, CAS 79307-93-0, Azeptin) in suppressing cough, 22 bronchial asthma patients complaining mainly of cough were given the drug for four weeks. Peak flow rates (PEFR), pulmonary function tests, capsaicin cough threshold, and bronchial hyperresponsiveness were compared pre- and post-administration. After four-week's administration of azelastine (2 mg twice daily), cough decreased as demonstrated in a significant progressive improvement of cough points. The morning PEFR (1/min) was improved significantly at one week and two weeks post-administration. Changes were from 434 +/- 26.4 pre-administration to 461 +/- 25.8 at Week 1 (p < 0.05), 462 +/- 26.7 at Week 2 (p < 0.05), 452 +/- 22.5 at Week 3, and 462 +/- 20.8 at Week 4. The evening PEFR (1/min) showed 439 +/- 22.2 pre-administration, 454 +/- 21.4 at Week 1, 464 +/- 22.4 at Week 2, 457 +/- 19.3 at Week 3 and 467 +/- 17.8 at Week 4, improvement being significant at Week 1 (p < 0.05). Regarding pulmonary function tests no significant changes were observed. FVC (liter), FEV1 (liter), and FEV1/FVC (%) were 3.45 +/- 0.86, 2.68 +/- 0.52, and 83.6 +/- 5.93 pre-administration; and 3.48 +/- 0.21, 2.72 +/- 0.65, and 84.1 +/- 6.21 post-administration, respectively. The capsaicin cough threshold [Ccap (mumol/l)] showed significant improvement, changing from 5.95 (0.016-50.0) pre-administration to 19.7 (0.08-50.0) post-administration (p < 0.05). Conversely, an index of bronchial hyperresponsiveness, Dmin (mg/dl;U), showed no significant changes (14.9 +/- 5.2 vs. 19.7 +/- 5.3). These results suggest that azelastine inhibits cough in patients with bronchial asthma by increasing the level of the cough threshold without changing bronchial hyperresponsiveness.

Adolescent↗

PubMed1997

Serial brain CT in corticobasal degeneration: radiological and pathological correlation of two autopsy cases.

This report concerns serial brain computed tomography (CT) images in two patients with corticobasal degeneration (CBD). The diagnosis of CBD was confirmed by neuropathological examination. In one case, we obtained serial brain CT images for one year and five months, and in the other, for three years and four months. The CT images showed that the anterior portions of the cerebrum atrophied progressively with the length of the disease. This was also seen in the CT images with respect to the caudate nucleus. Regarding radiological and pathological correlations, we consider that the progressive atrophy of the anterior portions of the cerebrum, seen in brain CT images, is ascribed to neuronal loss and gliosis in the anterior portions of the cerebrum. We also believe that the observed caudate nucleus atrophy is due to loss of neurons and gliosis in this structure, and also to the fibrillary gliosis of the cerebral white matter. The progressive atrophy of the caudate nucleus detected in brain CT is a valuable feature for the neuroradiological diagnosis of CBD.

Aged↗

PubMed1997

Molecular cloning, expression, and sequence analysis of the endoglycoceramidase II gene from Rhodococcus species strain M-777.

Endoglycoceramidase (EGCase (EC 3.2.1.123)) is a hydrolase that hydrolyzes the linkage between the oligosaccharide and ceramide of various glycosphingolipids. This paper describes the molecular cloning and expression of EGCase II, one of the isoforms of EGCases. The gene encoding EGCase II was obtained by screening of a genomic DNA library from Rhodococcus sp. strain M-777 constructed in pUC19 with oligonucleotide probes deduced from a partial amino acid sequence of the enzyme protein. Recombinant Escherichia coli cells in which the EGCase II gene was expressed produced 14 units of the enzyme per liter of culture medium but did not produce sphingomyelinase. Recombinant EGCase II was a functioning enzyme with substrate specificity identical to that of the wild-type enzyme. Sequence analysis showed the presence of an open reading frame of 1470 base pairs encoding 490 amino acids. The N-terminal region of the deduced amino acid sequence had the general pattern of signal peptides of secreted prokaryotic proteins. Interestingly, the consensus sequence in the active site region of the endo-1,4-beta-glucanase family A was found in the amino acid sequence of EGCase II.

Amino Acid Sequence↗

PubMed1997

Multiple regulatory elements and binding proteins of the 5'-flanking region of the human estrogen-responsive finger protein (efp) gene.

The efp, a member of the RING finger family, was previously identified as an estrogen responsive gene. Here, we characterized basal promoter of the human efp gene. Transcription initiation site was found at position -60 G relative to the site for translation initiation, and TATA motif was absent. Deletion and mutation analyses of the 5'-flanking region using MCF-7 breast cancer cells indicated that the sequences located at -137 to -72 had the promoter activity for which an E-box (CACGTG) element at -110 to -105 was essential. EMSA showed that USF-1 bound to the E-box and that a protein-DNA complex was formed at the positive regulatory region (-137 to -110). Moreover, a strong negative regulatory region was present in -235 to -174. These findings suggest that the human efp promoter is regulated by multiple elements and their interacting factors, and the E-box near the transcription initiation site is essential for the basal promoter activity.

Base Sequence↗

PubMed1997

Post-initiation inhibitory effects of green tea catechins on 7,12-dimethylbenz[a]anthracene-induced mammary gland carcinogenesis in female Sprague-Dawley rats.

The dose-dependence of green tea catechin (GTC) effects on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary gland carcinogenesis were investigated in female Sprague-Dawley rats. Groups of 20 6-week-old rats were treated with dietary 1, 0.1 or 0.01% GTC for 2 weeks and then basal diet alone for 35 weeks. At the end of week 1, they received a 25 mg/kg body weight intragastric dose of DMBA. Further groups of 20 7-week-old rats each were given an intragastric dose of 25 mg/kg body weight DMBA, and starting 1 week after DMBA treatment they were placed on diet containing 1, 0.1 or 0.01% GTC or basal diet alone for 35 weeks. Control rats were given 1% GTC or basal diet alone. The final incidences and multiplicities of mammary tumors were not significantly different between the groups treated with GTC at the same time as DMBA, compared to the DMBA alone control group. On the other hand, the final multiplicities of mammary tumors in groups treated with 1% GTC (P < 0.05) or 0.01% GTC (P < 0.01), but not 0.1% GTC, after DMBA treatment were significantly decreased as compared to the control value. These results indicate that whereas GTC may inhibit mammary carcinogenesis in the post-initiation stage, the effect is weak and not dose-dependent.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1997

A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study.

BACKGROUND: There is evidence that medications or vitamins that increase the levels of brain catecholamines and protect against oxidative damage may reduce the neuronal damage and slow the progression of Alzheimer's disease. METHODS: We conducted a double-blind, placebo-controlled, randomized, multicenter trial in patients with Alzheimer's disease of moderate severity. A total of 341 patients received the selective monoamine oxidase inhibitor selegiline (10 mg a day), alpha-tocopherol (vitamin E, 2000 IU a day), both selegiline and alpha-tocopherol, or placebo for two years. The primary outcome was the time to the occurrence of any of the following: death, institutionalization, loss of the ability to perform basic activities of daily living, or severe dementia (defined as a Clinical Dementia Rating of 3). RESULTS: Despite random assignment, the baseline score on the Mini-Mental State Examination was higher in the placebo group than in the other three groups, and this variable was highly predictive of the primary outcome (P<0.001). In the unadjusted analyses, there was no statistically significant difference in the outcomes among the four groups. In analyses that included the base-line score on the Mini-Mental State Examination as a covariate, there were significant delays in the time to the primary outcome for the patients treated with selegiline (median time, 655 days; P=0.012), alpha-tocopherol (670 days, P=0.001) or combination therapy (585 days, P=0.049), as compared with the placebo group (440 days). CONCLUSIONS: In patients with moderately severe impairment from Alzheimer's disease, treatment with selegiline or alpha-tocopherol slows the progression of disease.

Activities of Daily Living↗

PubMed1997

Effects of tamoxifen, an antiestrogen, on rat prostate carcinogenesis by 3,2'-dimethyl-4-aminobiphenyl and testosterone do not support an estrogen role in testosterone promotion.

BACKGROUND: Our previous data suggest that estrogen plays an important role in rat prostate carcinogenesis, particularly in promotion by testosterone. Therefore, in the present experiment, effects of an antiestrogen, tamoxifen (TAM), were investigated. METHODS: Male F344 rats initially received 3,2'-dimethyl-4-aminobiphenyl (DMAB) at 50 mg/kg bw every 2 weeks for 20 weeks and then TAM in Silastic tubes was subcutaneously given alone or together with testosterone propionate (TP) for 40 weeks. RESULTS: TAM significantly suppressed prostate weights, suggesting an estrogenic action, but the development of preneoplastic and/or neoplastic lesions of the prostate or seminal vesicles in rats given DMAB alone or DMAB and TP was not altered. TAM reversed the suppression of development of ventral atypical hyperplasias by TP. CONCLUSIONS: These findings suggest that estrogen, which is derived from testosterone by the action of aromatase, is not involved in the strong promotion by TP of DMAB prostate carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1997

Predicting time to nursing home care and death in individuals with Alzheimer disease.

OBJECTIVE: To develop and validate an approach that uses clinical features that can be determined in a standard patient visit to estimate the length of time before an individual patient with Alzheimer disease (AD) requires care equivalent to nursing home placement or dies. DESIGN: Prospective cohort study of 236 patients, followed up semiannually for up to 7 years. A second validation cohort of 105 patients was also followed. SETTING: Three AD research centers. PATIENTS: All patients met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable AD and had mild dementia at the initial visit. INTERVENTION: Predictive features, ascertained at the initial visit, were sex, duration of illness, age at onset, modified Mini-Mental State Examination (mMMS) score, and the presence or absence of extrapyramidal signs or psychotic features. MAIN OUTCOME MEASURES: (1) Requiring the equivalent of nursing home placement and (2) death. RESULTS: Prediction algorithms were constructed for the 2 outcomes based on Cox proportional hazard models. For each algorithm, a predictor index is calculated based on the status of each predictive feature at the initial visit. A table that specifies the number of months in which 25%, 50%, and 75% of patients with any specific predictor index value are likely to reach the end point is then consulted. Survival curves for time to need for care equivalent to nursing home placement and for time to death derived from the algorithms for selected predictor indexes fell within the 95% confidence bands of actual survival curves for patients. When the predictor variables from the initial visit for the validation cohort patients were entered into the algorithm, the predicted survival curves for time to death fell within the 95% confidence bands of actual survival curves for the patients. CONCLUSIONS: The prediction algorithms are a first but promising step toward providing specific prognoses to patients, families, and practitioners. This approach also has clear implications for the design and interpretation of clinical trials in patients with AD.

Age of Onset↗

PubMed1997

Cloning, sequencing, and expression of Arthrobacter protophormiae endo-beta-N-acetylglucosaminidase in Escherichia coli.

The gene encoding endo-beta-N-acetylglucosaminidase from Arthrobacter protophormiae (Endo-A) was cloned, and its nucleotide sequence was determined. A single open reading frame consisting of 1935 base pairs and encoding a polypeptide composed of signal peptides of 24 amino acids and a mature protein of 621 amino acids was found. The primary structure of Endo-A exhibited significant homology with FO1F.10 gene product from Caenorhabditis elegans and weak homology with peptide-N4-(N-acetyl-beta-D-glucosaminyl)asparagine amidase from Flavobacterium meningosepticum and chitinase from Streptomyces olivaceoviridis. However, the enzyme had no significant homology with any previously reported endo-beta-N-acetylglucosaminidases. Transformed Escherichia coli cells carrying the 4.5-kb fragment expressed Endo-A activity. This enzyme activity was detected in the medium as well as in the periplasmic space of cells under the control of the Endo-A gene promoter. The recombinant Endo-A was efficiently isolated from the periplasmic space of the cells. N-terminal sequence analysis revealed that native and recombinant Endo-A have the same N-terminus. Recombinant and native Endo-A also showed very similar optimum pH profiles and transglycosylation activity.

Amino Acid Sequence↗