PubMed Health⌕ Search

Biomedical subjects

A Takao

Publications and source records attributed to A Takao.

At least 19 recordsLinked to original sources
PubMed2002

Pharmacokinetics and disposition of rosuvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, in rat.

1. The pharmacokinetics and disposition of rosuvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, were investigated following single administration of (14)C-rosuvastatin in the Sprague-Dawley rat. 2. Following oral administration of (14)C-rosuvastatin at 1, 5 and 25 mg kg(-1), the C(max) and AUC of the radioactivity in the plasma increased more than the increase in dose ratio. 3. Excretion of radioactivity was 98.0% of the dose in the faeces and 0.4% in the urine up to 168 h after oral administration in the intact rat, and was 55.1% in the bile and 0.5% in the urine up to 48 h post-dosing in the bile duct-cannulated rat. The unchanged compound mainly accounted for the radioactivity in the bile and faeces. 4. In the tissue distribution study, the concentration of the radioactivity in the liver was markedly higher than those in the other tissues, and the radioactivity concentration ratios of the liver to the plasma were between 8 and 25 up to 48 h after oral administration. The liver-specific distribution of rosuvastatin was similarly recognized in whole-body autoradiography. 5. Metabolic profiling studies indicated that rosuvastatin would not be metabolized by CYP enzymes. 6. These results clarified that rosuvastatin selectively distributed in the liver - the target organ - and was excreted in the bile mainly as the unchanged compound.

Animals↗
PubMed2001

3beta-hydroxy-delta5 -C27-steroid dehydrogenase deficiency: diagnosis and treatment.

The aim of this study was to evaluate the effects of bile acid treatment and to obtain further information about the pathway of bile acid biosynthesis in a patient with 3beta-hydroxy-delta5-C27-steroid dehydrogenase/isomerase (3beta-HSD) deficiency by gas chromatography-mass spectrometry. Results showed that at 2 months of age, 3beta-hydroxy-5-cholen-24-oic acid (3.0 micromol/mmol Cr, 7.9%) was detected in the urine in essentially the same relative amount as 3beta,7alpha-dihydroxy- and 3beta,7alpha,12alpha-trihydroxy-5-cholen-24-oic acids (3.7 micromol/mmol Cr, 9.8%) during ursodeoxycholic acid treatment combined with prednisolone. As a result, diagnosis was delayed until 18 months of age. One month later with substitution of chenodeoxycholic acid treatment, urinary 3beta,7alpha-dihydroxy- and 3beta,7alpha,12alpha-trihydroxy-5-cholen-24-oic acids decreased significantly, and subsequent improvement of liver dysfunction was accelerated. Chenodeoxycholic acid treatment is useful in 3beta-HSD deficiency. However, in the diagnosis of this disease in early life, it should be noted that the acidic pathway may be the major route for bile acid biosynthesis in the neonatal period. Diagnosis of 3beta-HSD deficiency may have been delayed by administration of ursodeoxycholic acid, resulting in prolonged diagnostic investigation in this child with cholestasis. Further, use of prednisolone may have been contraindicated.

3-Hydroxysteroid Dehydrogenases↗
PubMed2001

[Sexual function in men with lower urinary tract symptoms].

PURPOSE: Recently there have been several alternatives not only to improve symptoms but to retain an acceptable quality of life as well as to reduce the complications. Therefore the objective of this study was to evaluate quantitatively and qualitatively the degree of erectile dysfunction in the population of men with lower urinary tract symptoms (LUTS). MATERIALS AND METHODS: Total 252 men with LUTS were investigated using the International Prostate Symptom Score (I-PSS) and sexual function inventory (SFI) consisting of sexual drive, erection and ejaculation. Spearman's rank order correlation was used to determine the degree of any correlation between age, the total I-PSS, the individual I-PSS questions and the various sexual function scores. RESULTS: 208 patient data were available for analysis. There were poor function patients in 67.8% for sexual drive, in 46.2% for erection and in 47.1% for ejaculation. On the other hand, 24% considered their sexual drive to be a big or medium problem, 20.7% for erection and 18.3% for ejaculation. Overall, 27.4% of the men were mostly or very dissatisfied with their sex life. There was a significant correlation between a patient's age and his score for each of the three sexual variables (p < 0.05). Furthermore, a significant correlation was noticed between the total I-PSS and the SFI score (p < 0.05). It might be suggested that the more symptomatic a patient for LUTS, the poorer his sexual function will be. CONCLUSIONS: About 20% men with LUTS are bothered by their sexual symptoms. Erectile dysfunction in dependent of age and the extent of LUTS. Consideration of the high population of erectile dysfunction in men with LUTS is necessary to the treatment of their urinary symptoms.

Adult↗
PubMed2001

[Septic shock due to pyonephrosis-calculosa: a case report].

A 69-year-old female was admitted to hospital with the complaint of high-grade fever and clouding of consciousness. Physical examination and laboratory data revealed septic shock, disseminated intravascular coagulation and multiple organ failure. Ultrasonography demonstrated left hydronephrosis and a cystic mass in peri-renal fatty tissue. KUB showed a left ureteral stone. A diagnosis of septic shock due to pyonephrosis-calculosa and peri-renal abscess was considered. A left nephrectomy, endotoxin removal therapy and continuous hemodiafiltration was performed. Thereafter all morbidities improved. A nephrectomy and intensive treatment are the good alternative method for such a case.

Aged↗
PubMed2000

Complete sequence and characterization of chick ventricular myosin heavy chain in the developing atria.

We isolated five complementary DNA (cDNA) clones, encoding the chick ventricular myosin heavy chain (MyHC) by reverse transcription polymerase chain reaction (RT-PCR). The entire cDNA consists of 5995 nucleotides with the 52 bp 5'-untranslated region and the 129 bp 3'-untranslated region. The complete cDNA encodes 1937 amino acids. Expression of the chick ventricular MyHC gene was also studied by Northern blot analysis. This gene continued to be strongly expressed in the ventricle during cardiac development. On the other hand, its expression was moderate in the early embryonic atria, and was down-regulated during development. In the adult atria, this gene was expressed at very low levels. To determine the localization of the ventricular MyHC protein, an immunohistochemical study was performed. The ventricular MyHC was present in early embryonic atrial myocytes. During development, the expression of this protein in the atrial myocytes was down-regulated, but continued to be present in the atrial conduction system. Our results indicate that the ventricular MyHC appears in the primary atrial myocardium and is then localized in the conduction cells of the atria.

Animals↗
PubMed2000

Evidence for the expression of neonatal skeletal myosin heavy chain in primary myocardium and cardiac conduction tissue in the developing chick heart.

We isolated a neonatal skeletal myosin heavy chain (MHC) cDNA clone, CV11E1, from a cDNA library of embryonic chick ventricle. At early cardiogenesis, diffuse expression of neonatal skeletal MHC mRNA was first detected in the heart tube at stage 10. During subsequent embryonic stages, the expression of the mRNA in the atrium was upregulated until shortly after birth. It then diminished, dramatically, and disappeared in the adult. On the other hand, in the ventricle, only a trace of the expression was detected throughout embryonic life and in the adult. However, transient expression of mRNA in the ventricle was observed, post-hatching. At the protein level, during the embryonic stage, the atrial myocardium was stained diffusely with monoclonal antibody 2E9, specific for chick neonatal skeletal MHC, whereas the ventricles showed weak reactivity with 2E9. At the late embryonic and newly hatched stages, 2E9-positive cells were located clearly in the subendocardial layer, and around the blood vessels of the atrial and ventricular myocardium. These results provide the first evidence that the neonatal skeletal MHC gene is expressed in developing chick hearts. This MHC appears during early cardiogenesis and is then localized in cardiac conduction cells. Dev Dyn 2000;217:37-49.

Amino Acid Sequence↗
PubMed2000

Infant leukemia suggestive of natural killer cell precursor origin followed an unusual clinical course.

We report a patient with infant leukemia showing the rare phenotypes of CD2+, CD4+, CD7+, CD56+, CD3-, CD5- who followed an unusual clinical course. The patient was a 3-month-old girl who was admitted because of unusual purpura looking like a black ring. On admission WBC count was 85.8 x 10(9)/l and bone marrow aspiration revealed a nucleated cell count of 112.0 x 10(9)/l with 70.8% atypical lymphocytes. On the 3rd hospital day, the WBC count decreased by about 1/5 without chemotherapy and partial remission was obtained. But about 3 weeks later, the WBC count increased again and she died. Based on surface marker analysis, genotypic analysis and autopsy, we diagnosed infant leukemia suggestive of natural killer (NK) cell precursor origin.

Antigens, CD↗
PubMed2000

Behavior of smooth muscle cells during arterial ductal closure at birth.

To determine which part of the smooth muscle cells (SMCs) of the ductus arteriosus (DA) contribute to duct closure after birth, we looked for areas in which SM2 myosin heavy chain (MHC) mRNA expression, which is associated with contraction of smooth muscle, and apoptosis could be detected in the DA during development. In situ hybridization revealed that the SM2 MHC mRNA was strongly positive in the longitudinally oriented SMCs and inner layer of the circularly oriented SMCs just before birth. Apoptotic cells were detected in the SMCs of the DA from 1 day after birth. Histochemical analysis using terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) revealed significant numbers of TUNEL-positive nuclei in the longitudinally oriented SMCs and the inner layer of the circularly oriented SMCs. Masson-stained sections showed that the TUNEL-positive area in the DA was replaced by connective tissue from 1 day after birth. These results suggest that the increase in the SM2 MHC mRNA expression and the induction of apoptosis are present at the same site in the media of the DA. Therefore, the SMCs in this area may play an important role in duct constriction and remodeling of the vessel wall after birth.

Animals↗
PubMed1999

Novel mechanism associated with an inherited cardiac arrhythmia: defective protein trafficking by the mutant HERG (G601S) potassium channel.

BACKGROUND: The congenital long-QT syndrome (LQTS) is an inherited disorder characterized by a prolonged cardiac action potential and a QT interval that leads to arrhythmia. Mutations in the human ether-a-go-go-related gene (HERG), which encodes the rapidly activating component of the delayed rectifier current (IKr), cause chromosome 7-linked LQTS (LQT2). Studies of mutant HERG channels in heterologous systems indicate that the mechanisms mediating LQT2 are varied and include mutant subunits that form channels with altered kinetic properties or nonfunctional mutant subunits. We recently reported a novel missense mutation of HERG (G601S) in an LQTS family that we have characterized in the present work. METHODS AND RESULTS: To elucidate the electrophysiological properties of the G601S mutant channels, we expressed these channels in mammalian cells and Xenopus oocytes. The G601S mutant produced less current than wild-type channels but exhibited no change in kinetic properties or dominant-negative suppression when coexpressed with wild-type subunits. To examine the cellular trafficking of mutant HERG channel subunits, enhanced green fluorescent protein tagging and Western blot analyses were performed. These showed deficient protein trafficking of the G601S mutant to the plasma membrane. CONCLUSIONS: Our results from both the Xenopus oocyte and HEK293 cell expression systems and green fluorescent protein tagging and Western blot analyses support the conclusion that the G601S mutant is a hypomorphic mutation, resulting in a reduced current amplitude. Thus, it represents a novel mechanism underlying LQT2.

Animals↗
PubMed1999

A mitochondrial DNA mutation cosegregates with the pathophysiological U wave.

In a family with long QT syndrome (LQT2), some individuals who did not harbor the HERG mutation had a prolonged QTU interval on electrocardiograms after exercise. It may be determined or modified by other gene(s) or factor(s). The sequence analysis of mtDNA in these individuals of this family showed a candidate pathogenic mutation at 3394 in the ND1 gene. The cybrids (mutation at 3394) showed significantly reduced NADH-CoQ reductase (complex I) activity and O2 consumption to normal levels. These inhibitory effects on respiratory function may result in the depletion of ATP and could possibly produce an increase in Ca2+ concentration in cytosol, and it may lead to the prolongation of the QTU intervals on electrocardiograms. Therefore, we stated that the 3394 mutation in the ND1 gene is pathogenic and could be the cause of prolongation of the QTU intervals or modification of the phenotypes of not only congenital but also so-called "acquired drug-induced long QT syndrome."

Adolescent↗
PubMed1999

A randomised dose-comparison trial of granisetron in preventing emesis in children with leukaemia receiving emetogenic chemotherapy.

This randomised study was performed to assess the anti-emetic efficacy and tolerability of two-dose regimens of granisetron in children with leukaemia. 49 children with leukaemia were treated with three consecutive courses of high-dose methotrexate or cytarabine regimen. During the first course, patients were evaluated regarding the emetogenicity of each regimen. They were randomised in a crossover manner to receive 20 or 40 micrograms/kg of granisetron before the second and third course of chemotherapy. Neither emesis nor severe appetite loss were observed in over 80% of patients within the first 24 h in all treatment groups. There was no significant difference in the anti-emetic efficacy between the two-dose regimens of granisetron. However, complete protection was achieved less frequently on days 2 and 3. Older children and girls appeared to be less well protected. No adverse events attributable to granisetron were observed. Granisetron dose regimens of 20 and 40 micrograms/kg are, comparably, well tolerated and effective in controlling chemotherapy-induced emesis in the first 24 h, though this protection fails thereafter, particularly in older patients and girls.

Adolescent↗
PubMed1999

In vitro responses to antigen stimulation: comparison between human lung parenchyma resected from asthmatic patients and non-asthmatic patients.

BACKGROUND: The airway of asthmatic patients is hyperresponsive to various stimuli in vivo. There are, however, only a few reports that compared the in vivo responsiveness of asthmatic patients and non-asthmatic subjects to those of lung parenchyma in vitro. OBJECTIVES: To compare the contractile response, release of various chemical mediators, and responsiveness to drugs in samples of lung parenchyma excised from asthma patients with those of non-asthmatic subjects. METHODS: Human lung parenchymal strips were subjected to passive sensitization with sera of 5+ RAST titer to mites. The strip was suspended in a magnus bath containing a buffer solution. Parenchymal contraction was induced by PGF2 alpha. After washing, the baseline concentrations of thromboxane B2 (TXB2), leukotriene (LT), and histamine were measured in each bath and then contraction was induced by the addition of a mite antigen. The concentrations of TXB2, LT, and histamine were measured after contraction. The inhibitory effects of TXA2 synthetase inhibitor (DP-1904) and TXA2 receptor antagonist (AA-2414) were also evaluated in both tissue samples. RESULTS: There were no significant differences between lung parenchymal tissues of asthmatic and non-asthmatic patients with regard to PGF2 alpha-induced contraction, antigen-induced contraction, release of chemical mediators, and the response to drugs. CONCLUSION: Unlike the response in vivo, there are no differences in the response to stimuli in vitro between lung parenchymal tissues of asthmatic and non-asthmatic patients.

Aged↗
PubMed1999

Inhibitory effects of azelastine hydrochloride in alcohol-induced asthma.

BACKGROUND: Alcohol-induced bronchoconstriction is due to high blood concentrations of acetaldehyde, a metabolic product of ethanol, which lead to the release of histamine from basophils and mast cells. OBJECTIVE: We examined the inhibitory effects of azelastine hydrochloride, which inhibits histamine release and blocks H1 receptors, in alcohol-induced asthma. METHODS: Subjects were 13 Japanese asthmatic patients. We measured the change in FEV1 after ingestion of 30 g of pure ethanol. Blood ethanol, acetaldehyde, histamine, leukotriene C4 (LTC4), and thromboxane B2 (TXB2) concentrations were also measured. Alcohol challenge test was repeated in responders after administration of azelastine for 1 week at 4 mg/day. RESULTS: Of 13 asthmatic patients, five (38.5%) tested positive during an ethanol challenge test, represented by a fall more than 20% in FEV1. The responders had a high blood ethanol, and showed a rise in blood acetaldehyde and histamine concentrations, but not in LTC4 or TXB2. After azelastine treatment, there was no significant fall in FEV1 among responders. Neither the rise in blood ethanol nor blood acetaldehyde levels were blunted by treatment with azelastine, but the rise in blood histamine was blunted by this treatment. CONCLUSION: Our results suggest that antihistamine agents may be effective against alcohol-induced asthma by both blocking H1 receptors and inhibiting histamine release.

Acetaldehyde↗
PubMed1999

Abscess forming ability of streptococcus milleri group: synergistic effect with Fusobacterium nucleatum.

The abscess forming abilities of "Streptococcus milleri" strains (Streptococcus constellatus, Streptococcus anginiosus, and Streptococcus intermedius) isolated from dentoalveolar abscesses and the synergistic effect of Fusobacterium nucleatum co-inoculated with the isolates were examined on a mouse subcutaneous abscess model. Five days after inoculation, all S. milleri strains formed abscesses, which showed less pathological spread to surrounding connective tissues than those formed by Staphylococcus aureus 209P strain and were similar to those by F. nucleatum ATCC25586. When each S. milleri strain and F. nucleatum were co-inoculated, abscess sizes and each bacterial number recovered from abscesses increased in comparison to those treated by bacterial mono-inoculation of each S. milleri strain or F. nucleatum alone. The strongest synergistic effect was observed in the combination of S. constellatus and F. nucleatum. In a time course experiment with this combination, the recovery of S. constellatus subsequently decreased after the decrement of F. nucleatum, and it appeared that the association with F. nucleatum maintained the bacterial number of S. constellatus in the abscess. The cell-free supernatant of F. nucleatum had a tendency to increase the abscess size caused by S. constellatus in this model. When S. constellatus was cultured with F. nucleatum culture supernatant in vitro, growth enhancement in the early phase was observed. Furthermore, the phagocytic killing of S. constellatus by human polymorphonuclear leukocytes (PMNs) was significantly suppressed and the PMN membranes appeared to be injured by addition of the F. nucleatum culture supernatant. These results suggest that the pathogenicity of S. milleri strains in odontogenic infections may be enhanced by the co-existence of F. nucleatum.

Abscess↗
PubMed1999

Unique expression patterns of myosin heavy chain genes in the ductus arteriosus and uterus of rabbits.

In smooth muscle tissue, two smooth muscle myosin heavy chain (MHC) isoforms (SM1, SM2) and two non-muscle MHC isoforms (NMA, NMB) have been identified. The purpose of our study was to clarify whether smooth muscle MHC mRNA expression reflects the physiological and functional state of the muscle. We studied the expression pattern of MHC mRNAs, using the S1-nuclease mapping procedure, in functionally and morphologically changeable organs; the ductus arteriosus (DA) during development (25 and 29 days of gestation, and from 3-day-old neonates) and uteri from virgin, day-10 pregnant (P10) and day-29 pregnant (P29) rabbits. The results demonstrated that SM2 expression was greater in the fetal DA than in the fetal aortic and pulmonary arteries, but that it decreased significantly following closure of DA. In the gravid uterus, SM1 expression was significantly (P<0.05) strong compared to other MHC mRNAs from virgin to P10 rabbits. During pregnancy, NMB expression showed a tendency to increase until P10, and after P10, SM2 expression increased dramatically and NMB expression decreased to give almost a mirror image of the SM2 expression. Smooth muscle type (SM1, SM2) was significantly (P<0.05) strong compared to non-muscle type expression (NMA, NMB) at P29. These data suggest that smooth muscle MHC mRNA, especially SM2 expression reflects the physiological and functional state of the smooth muscle.

Animals↗
PubMed1998

Phenotypic discordance in monozygotic twins with 22q11.2 deletion.

We report on male monozygotic twins with 22q11.2 deletion and discordant phenotypes. The twins had twin-to-twin transfusion syndrome. Twin 1, the smaller of the pair, had Tetralogy of Fallot, a characteristic facial appearance, swallowing dysfunction, anal atresia, short stature, and mental retardation, whereas twin 2 had a characteristic facial appearance but no other signs of the 22q11 deletion syndrome. Fluorescence in situ hybridization analysis showed a microdeletion on chromosome 22q11.2 in both twins. Zygosity analysis gave a probability of monozygosity greater than 99.999%. These observations indicate that environmental factors or postzygotic events play a role in the phenotypic variability in the twins.

Abnormalities, Multiple↗
PubMed1998

Situs variation and cardiovascular anomalies in the transgenic mouse insertional mutation, inv.

The inv mouse was reported as a novel strain with situs inversus Yokoyama et al., '93), and a few cases with heterotaxy were found in homozygotes. The original report by Yokoyama et al. described the location of the heart and the stomach using the index of arrangement of body structure. We newly examined 40 homozygous offspring for phenotypes of visceroatrial situs and the incidence of cardiovascular anomalies making use of morphological details defined in each organ structure. According to the arrangement of each organ, which ranged from the almost complete form of situs inversus to left isomerism, visceroatrial situs was classified into four categories: Situs inversus (4 cases), "variation type" of situs (17 cases), "abdominal heterotaxy" (15 cases), and visceroatrial heterotaxy (4 cases). In offspring with situs inversus, only one had aortic stenosis (25%). Seven with the "variation type" of situs had cardiovascular anomalies, such as aortic stenosis, endocardial cushion defect, and posterior vena cava interruption (41%). All 15 offspring with "abdominal heterotaxy" had anomalies of the posterior vena cava, and three of them also had tetralogy of Fallot. The remaining four with visceroatrial heterotaxy had endocardial cushion defect, which was associated with outflow tract anomaly in two cases (i.e. tetralogy of Fallot in one case and transportation of the great arteries in the other). These results revealed that visceroatrial heterotaxy frequently occurred in the inv homozygotes, especially in the abdomen, and often showed a propensity to left isomerism with posterior vena cava interruption.

Animals↗