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Biomedical subjects

T Takano

Publications and source records attributed to T Takano.

At least 271 records · Page 15Linked to original sources
PubMed1996

Dopamine transporter gene polymorphism and psychiatric symptoms seen in schizophrenic patients at their first episode.

To investigate the possible role of the dopamine transporter (DAT) gene in determining the phenotype in human subjects, allele frequencies for the 40-bp variable number of tandem repeats (VNTR) polymorphism at this site were compared between 117 Japanese normal controls and 118 schizophrenic patients, including six subgroups: early-onset, those with a family history, and those suffering from one of the following psychiatric symptoms at their first episode: delusion and hallucination; disorganization; bizarre behavior; and negative symptoms. No significant differences were observed between the group as a whole or any subgroup of schizophrenic patients and controls. The results indicate that VNTR polymorphism in the DAT gene is unlikely to be a major contributor to any of the psychiatric parameters examined in the present population of schizophrenic subjects.

Adult↗
PubMed1996

Proton magnetic resonance spectroscopy of basal ganglia in chronic schizophrenia.

Proton spectra in the regions of the right and left basal ganglia were studied in 14 medicated patients with chronic schizophrenia using proton magnetic resonance spectroscopy (1H MRS). Ratios of N-acetyl-aspartate (NAA) to choline-containing compounds (Cho) were significantly reduced in the bilateral basal ganglia regions compared to normal subjects. The relative level of Cho was increased in the left basal ganglia region in comparison to normal subjects. This finding suggests the presence of disturbances in phospholipid metabolism in the basal ganglia. The level of NAA was decreased in the bilateral basal ganglia regions, which may indicate neuronal dysfunction. The 1H MRS study demonstrated dysfunctions in the basal ganglia regions in medicated patients with chronic schizophrenia.

Adult↗
PubMed1996

Insertion of the 70-kDa peroxisomal membrane protein into peroxisomal membranes in vivo and in vitro.

Biosynthesis and intracellular transport of 70-kda peroxisomal membrane protein (pmp70) has been studied in rat hepatoma, h-4-ii-e cells. Pulse-chase analysis showed that a newly synthesized 35S-PMP70 first appeared in the cytosolic fraction and was then transported into the peroxisomal fraction. The half-life of 35S-PMP70 in the cytosolic fraction was approximately 3 min. Integration of 35S-PMP70 into membranes occurred in the peroxisomal fraction and was completed within 30 min. No proteolytic processing of 35S-PMP70 was observed. An in vitro import system was reconstituted to characterize the insertion mechanism of PMP70 into peroxisomes. Peroxisomes isolated from rat liver were incubated at 26 degrees C with [35S]methionine-labeled in vitro translation products of PMP70 mRNA in the presence of the cytosolic fraction. The peroxisomes were reisolated and insertion of 35S-PMP70 into the membrane was analyzed using a Na2CO3 procedure. The binding and insertion of 35S-PMP70 were dependent on temperature and incubation time and was specific for peroxisomes. Pretreatment of peroxisomes with trypsin and chymotrypsin almost abolished the binding and insertion of 35S-PMP70. The translation products contained several truncated 35S-PMP70s. The NH2 terminally truncated 35S-PMP70s, with a molecular mass greater than 50 kDa, bound to and inserted into peroxisomal membranes, whereas truncated 35S-PMP70s smaller than 45 kDa did not. These results suggest that PMP70 is post-translationally transported to peroxisomes without processing and inserted into peroxisomal membranes by a specific mechanism in which a proteinaceous receptor and a certain internal sequence of PMP70 are involved.

ATP-Binding Cassette Transporters↗
PubMed1996

Regulation of fatty acid synthase expression by cholesterol in human cultured cells.

The regulation of fatty acid synthase (FAS) expression by sterols in a cultured human hepatoblastoma cell line, Hep G2, was studied. When cells were treated with compactin in a medium containing lipoprotein deficient serum, FAS mRNA level increased 1.6-fold. A squalene synthase inhibitor, TAN1607A, decreased both free and esterified cholesterol contents in Hep G2 cells and increased mRNA levels for FAS, HMG-CoA reductase, squalene synthase and LDL receptor. However, for the increment of FAS mRNA, a 10-fold higher concentration of this inhibitor was needed. These results demonstrate that the concentration of cellular cholesterol which regulates FAS expression is necessarily lower than the levels which regulate other sterol sensitive genes. FAS mRNA was also increased by an inhibitor of SREBP degradation as well as chenodeoxycholic acid. These results indicate that FAS mRNA expression is regulated by cholesterol and is mediated through SREBPs. The implications of the different modes of sterol regulation of FAS and LDL receptor expression are discussed.

Bridged Bicyclo Compounds, Heterocyclic↗
PubMed1996

High-performance liquid chromatographic determination of finasteride in human plasma using direct injection with column switching.

A fully automated column-switching high-performance liquid chromatographic (HPLC) method was developed for the quantification of finasteride [N-(1,1-dimethylethyl)-3-oxo-4-aza-5 alpha-androst-1-ene-17 beta- -carboxamide] in human plasma. Plasma samples were diluted with an equal volume of ethylene glycol-water (40:60, v/v), then the diluted sample (150 microliters) was injected into the HPLC system without clean-up. The analyte was retained on a pretreatment column, whereas plasma proteins and other endogenous components were washed out to waste. The analyte was transferred to the analytical column in the heart-cut mode and then detected at 210 nm. A quantification limit of 1 ng/ml was attained. There was a linear relationship between peak height and drug concentration in plasma in the range 1-50 ng/ml. This method was validated and applied to the assay of plasma samples to characterize pharmacokinetic parameters in clinical studies.

Biotransformation↗
PubMed1996

Spatial and temporal pattern of smooth muscle cell differentiation during development of the vascular system in the mouse embryo.

The initial phase of smooth muscle differentiation in the vascular system of the mouse embryo was observed immunohistochemically with monoclonal antibody against alpha-smooth muscle actin. Few smooth muscle cells were detected in the vascular system of the 9.5-day embryo, where only the dorsal aorta and umbilical artery showed signs of smooth muscle differentiation. In the 10.5-day embryo, smooth muscle cells were observed in the dorsal aorta, ventral aorta, omphalomesenteric artery and vein, umbilical artery and vein, internal carotid artery, aortic arches III and IV, and subclavian artery. The extent of smooth muscle differentiation varied among these vessels and among regions of a vessel. At 11.5 days of gestation, smooth muscle cells appeared in the basilar artery, vertebral artery, aortic arches VI, intersomitic artery, ductus venosus, and caudal artery. Smooth muscle cells were absent from the venous system characteristic of the embryo at the stages examined. Alpha-smooth muscle actin-positive cells were also observed in allantoic mesoderm in the placenta at 9.5 days, when the umbilical vessels were not surrounded by smooth muscle cells. Vascular smooth muscle cells appear to arise independently from mesenchyme at multiple sites in the vascular system.

Actins↗
PubMed1996

Seasonality of mortality in Sri Lanka: biometeorological considerations.

The seasonal variation of mortality in Sri Lanka was studied in relation to meteorological variables. Time series data of the total monthly number of deaths in men and women from 1976 to 1980 were analyzed by power spectrum analysis of the fast Fourier transformation method in the areas of Colombo (lowland area, altitude 7 m) and Nuwara-Eliya (highland area, altitude 1890 m), respectively. In the Colombo area, where the mean temperature was always high (mean, 27.5 degrees C), a seasonal variation in mortality of 6 months was validated by power spectrum analysis with peak times in June and November. These mortality peaks corresponded to those of the amounts of rainfall which also showed an identical predominant period of 6 months. In the Nuwara Eliya area, where the mean temperature was always low at about 15-16 degrees C, a seasonal variation of approximately 3 months was found in addition to the 6 months' periodicity. The comparison of the power spectrum pattern of mortality with those of meteorological variables suggested that the amount of rainfall was associated with the seasonal variation of mortality in the Nuwara-Eliya area. In conclusion, the seasonality of mortality in Sri Lanka, a typical tropical zone country, was related to seasonal variation in the amount of rainfall, or a humidity factor, but not to mean temperature.

Female↗
PubMed1996

Overexpression of nestin and vimentin in ependymal cells in hydrocephalus.

In order to elucidate the immunohistochemical features of hydrocephalic ependyma, immunohistochemical examination was undertaken in 11 normal, postmortem brains (age range, 11 weeks' postconception to 6 months after birth) and 12 hydrocephalic brains (three cases each of congenital aqueductal stenosis, Dandy-Walker malformation, Arnold-Chiari type II malformation and posthemorrhagic hydrocephalus) by using antisera to nestin, vimentin and glial fibrillary acidic protein (GFAP). In normal brains, nestin was predominantly expressed in neuroepithelial cells and radial glial fibers during the period of neuronal migration. Vimentin immunoreactivity was principally detected in immature ependymal cells and their basal fibers after the period of neuronal migration, then partly replaced by GFAP reactivity during late gestation. In hydrocephalus, the areas of ependymal disruption were covered with nestin- or vimentin-positive cells. Nestin and vimentin were also expressed in immature ependymal cells or their basal processes in anatomical regions such as the roof or floor plate of the fourth ventricle or the cerebral aqueduct, and the ventral part of the third ventricle. These results suggest that the overexpression of nestin and vimentin in hydrocephalus follows two patterns: a reactive pattern of proliferating immature glial cells associated with ependymal cell loss and an abnormal developmental pattern of immunopositivity associated with anatomical regions in the midline mesencephalon.

Brain↗
PubMed1996

True malignant histiocytosis developed during chemotherapy for mediastinal immature teratoma.

We report an autopsy case of true malignant histiocytosis that developed during chemotherapy for mediastinal immature teratoma. The patient was a 14-year-old boy who exhibited hepatosplenomegaly while receiving chemotherapy for a mediastinal immature teratoma that had been resected 11 months before. The spleen and liver of the excisional biopsy displayed infiltration of multinucleated giant atypical cells with prominent erythrophagia in massive aggregations. These atypical cells expressed CD68, alpha1-antitrypsin, alpha1-antichymotrypsin, lysozyme, and vimentin, suggesting that the tumor cells may have been derived from macrophages. Immunocytochemistry showed p53 expression in the tumor cells of the malignant histiocytosis, as well as in the elements of the immature teratoma. Direct sequence analysis showed the p53 mutation in the tumor cells of the immature teratoma to be a mutation at codon 175 (exon 5), whereas the mutation in the malignant histiocytosis occurred at codon 285 (exon 8), ie, polyclonality was exhibited and these features suggested that the malignant histiocytosis arose independently from the immature teratoma during the chemotherapy.

Adolescent↗
PubMed1996

Lipid islands in human gastric mucosa: morphological and immunohistochemical findings.

BACKGROUND & AIMS: Lipid islands are a common finding in the gastric mucosa, but their pathogenesis has not yet been established. The aim of this study was to investigate the morphology and immunophenotype of the various cells in lipid islands and to consider the possible mechanisms involved in the pathogenesis of these lesions. METHODS: Morphological and immunohistochemical investigations using antibodies against macrophages, smooth muscle cells, and lymphocytes were performed. Unfixed tissue was available for immunostaining for low-density lipoprotein (LDL) and oxidized LDL in one case. RESULTS: The lipid islands were composed of KP1-, KiM1p-, and cathepsin D-positive foam cells that were only weakly reactive for lysozyme. In cryostat sections, the foam cells were found to contain LDL and oxidized LDL. A few smooth muscle cells, plasma cells, lymphocytes, pericytes, fibroblasts, and Schwann cells that contained lipid droplets were also found. CONCLUSIONS: In gastric lipid islands, the presence of oxidized LDL, which is taken up by macrophages and smooth muscle cells via scavenger receptors, suggests that oxidized LDL is of key significance in the development and persistence of these lesions. Because the metabolism of LDL to oxidized LDL may occur by various mechanisms, various different initial conditions, including gastritis, may precede the development of lipid islands. Thus, anti-inflammatory treatment may be appropriate.

Foam Cells↗
PubMed1996

A placebo-controlled study of the effect of sour milk on blood pressure in hypertensive subjects.

A placebo-controlled study was conducted to test the effect of Calpis (Calpis Food Industry Co, Ltd, Tokyo, Japan) sour milk, i.e., a milk fermented with a starter containing Lactobacillus helveticus and Saccharomyces cerevisiae, on the blood pressure of 30 elderly hypertensive patients, most of whom were taking antihypertensive medication. Subjects were randomly assigned to two groups. One group ingested daily 95 mL of the sour milk for 8 wk, and the other group ingested the same amount of artificially acidified milk as a placebo for 8 wk. In the sour-milk group, systolic blood pressure decreased significantly 4 and 8 wk after ingestion, by 9.4 +/- 3.6 mm Hg (mean+/- SE, P < 0.05) and 14.1 +/- 3.1 mm Hg (P < 0.01), respectively. The diastolic blood pressure also decreased significantly, by 6.9 +/- 2.2 mm Hg (P < 0.01), by 8 wk after ingestion of the sour milk began. No significant changes in blood pressure were observed in the placebo group. The decrease in systolic and diastolic blood pressure in the sour-milk group tended to be greater than in the placebo group. No marked changes were observed in other indexes, including pulse rate, body weight, and blood serum variables in both groups.

Adult↗
PubMed1996

Antihypertensive peptides are present in aorta after oral administration of sour milk containing these peptides to spontaneously hypertensive rats.

Absorption of inhibitory peptides to angiotensin I-converting enzyme, L-valyl-L-prolyl-L-proline and L-isoleucyl-L-prolyl-L-proline, was studied in spontaneously hypertensive rats and normotensive Wistar-Kyoto rats after an oral administration of Calpis sour milk, which contains these peptides. Six hours after the administration of Calpis sour milk or saline to spontaneously hypertensive rats or normotensive Wistar-Kyoto rats, the blood pressure was measured and rats were killed. Abdominal aorta, lung, kidney, heart and brain were excised, homogenized and solubilized by detergent treatments. Angiotensin I-converting enzyme activity in the solubilized fractions from the abdominal aorta was significantly lower in spontaneously hypertensive rats given the sour milk than in the rats given saline. L-Valyl-L-prolyl-L-proline and L-isoleucyl-L-prolyl-L-proline were detected by HPLC in the heat-treated solubilized fraction from the abdominal aorta of spontaneously hypertensive rats given the sour milk. In contrast, the tripeptides were not detected in rats given saline, or in normotensive Wistar-Kyoto rats given the sour milk or saline. These data suggest that L-valyl-L-prolyl-L-proline and L-isoleucyl-L-prolyl-L-proline in the Calpis sour milk are absorbed directly without being decomposed by digestive enzymes, reach the abdominal aorta, inhibit the angiotensin I-converting enzyme, and show antihypertensive effects in spontaneously hypertensive rats.

Administration, Oral↗
PubMed1996

Increased female drinking in accordance with post-industrial urbanization in Japan.

We studied the relationship between living in an urban area and the alcohol-consumption habits of young mothers in light of the recent increase of the female drinking population in Japan, particularly among those from 20 to 39 years of age. We conducted a survey in four areas in and around Tokyo, each area representing a different level of urbanization. The study population consisted of 6418 mothers of 3-year-old children; an 84.9% response rate was obtained. Thirty-eight per cent of the respondents had drunk at least four units of alcohol (about 44 g of pure ethanol) during the most recent month. The proportion of current drinkers in a more-urbanized area was greater than that in a less-urbanized area, and this tendency was significant (P < 0.001). Current workforce participation was significantly positively associated with current drinking (P < 0.01). Younger age significantly increased chances of current drinking (P < 0.05). Effects of living in a more-urbanized area on current drinking of mothers of 3-year-old children after excluding the effects of workforce participation and age was significantly positive (P < 0.001). An increase in female drinking in Japan was considered to be due to acculturation associated with urbanization in a post-industrial society.

Adult↗
PubMed1996

Multicenter, double-blind study of intravenous milrinone for patients with acute heart failure in Japan. Japan Intravenous Milrinone Investigators.

OBJECTIVES: Milrinone is a phosphodiesterase F-III inhibitor with positive inotropic and vasodilating activities. We investigated the hemodynamic response and pharmacokinetics of intravenous milrinone in patients with acute heart failure. DESIGN: Double-blind studies: a prospective, multicenter, double-blind, dose-finding study and a placebo-controlled, double-blind, comparative study. SETTING: Patients with acute heart failure (pulmonary artery occlusion pressure of > or = 18 mm Hg), who were hospitalized in the cardiac care units of 33 institutes in Japan, were entered into the study. PATIENTS: Fifty-four patients with acute or decompensated heart failure in the dose-finding study and 52 patients in the placebo-controlled, double-blind, comparative study. INTERVENTIONS: The present multicenter study consisted of a double-blind, dose-finding study (50-micrograms/kg intravenous loading dose, followed by 0.25, 0.5, or 0.75 microgram/kg/min of a continuous infusion of milrinone for 6 hrs, n = 54), and a placebo-controlled, double-blind, comparative study (50-micrograms/kg loading dose, followed by 0.5 microgram/kg/min of a continuous infusion of milrinone vs. placebo treatment, n = 52). We investigated the effects on cardiovascular hemodynamics, subjective symptoms, physical findings, and the pharmacokinetics of intravenous milrinone in a total of 106 patients with acute heart failure. MEASUREMENTS AND MAIN RESULTS: In the double-blind, dose-finding study, dose-dependent inotropic/vasodilating hemodynamic effects were documented for percent changes in cardiac index (+21.2%, +25.8%, and +30.9%, respectively) and pulmonary artery occlusion pressure (-12.8%, -17.0%, -41.3%, respectively) vs. plasma drug concentration at the equilibrium state (6 hrs after starting continuous infusion; 97 +/- 13, 197 +/- 22, and 284 +/- 28 ng/mL, respectively). Throughout the 6-hr infusion period, subjective symptoms were improved in 40%, 46.2%, and 70% of patients, respectively, for the three continuous infusion rates (0.25, 0.5, and 0.75 microgram/kg/min). In the placebo-controlled, double-blind, comparative study, the milrinone group exhibited marked improvement in cardiovascular hemodynamics (pulmonary artery occlusion pressure: from 26 +/- 6 to 15 +/- 3 mm Hg; cardiac index: from 2.6 +/- 0.9 to 3.3 +/- 1.1 L/min/m2) within 15 mins after starting drug administration. However, the placebo group showed no significant hemodynamic changes. Subjective symptoms and physical findings of acute heart failure improved in 47.6% and 40%, respectively, of patients within 60 mins after starting milrinone. The placebo group, however, showed no improvement providing inotropic/vasodilating (both 0%). CONCLUSION: Continuous infusion of milrinone (0.25 to 0.75 microgram/kg/min) after a 50-micrograms/kg loading dose is effective for inotropic/vasodilating hemodynamic support in patients with acute or decompensated heart failure.

Acute Disease↗
PubMed1996

Genotypes of sarco(endo)plasmic reticulum Ca(2+)-dependent ATPase II gene in substrains of spontaneously hypertensive rats.

OBJECTIVE: To search for a genetic marker of the sarco(endo)plasmic reticulum Ca(2+)-dependent ATPase (SERCA) II gene in spontaneously hypertensive rats (SHRs) and to investigate differences in blood pressure and intracellular Ca2+ among some substrains of SHRs and Wistar-Kyoto (WKY) rats related to their SERCA II genotypes. DESIGN AND METHODS: The coding region of the SERCA II gene was sequenced in SHRs. Blood pressure and intracellular Ca2+ concentration ([Ca2+]i) in platelets were measured in substrains of SHRs and WKY rats with different SERCA II genotypes. RESULTS: A point mutation that provided restriction fragment length polymorphisms (RFLPs) by HindIII or Saul was found in the SERCA II gene. The polymerase chain reaction (PCR) products were digested by HindIII in SHR substrains and WKY-Kyoto rats, whereas they were digested by Saul in normotensive strains and SHR-Toho. Among SHR-Kyoto, SHR-Toho, WKY-Kyoto and WKY-Charles River, the substrains with the HindIII-digested SERCA II genotype showed slightly but significantly higher systolic blood pressure and augmented agonist-stimulated [Ca2+]i than those with the Saul-digested genotype. CONCLUSIONS: RFLPs were found in the SERCA II gene. In the substrain analysis of SHRs and WKY rats, higher blood pressure and increased [Ca2+]i were associated with the SERCA II genotype digested by HindIII. The SERCA II gene locus has the potential to contribute to the development of hypertension and abnormal intracellular Ca2+ metabolism in SHRs. These RFLPs in the SERCA II gene should be a useful genetic marker.

Animals↗