Biomedical subjects

K Sakai

Publications and source records attributed to K Sakai.

At least 217 records · Page 12Linked to original sources

PubMed2000

Ionotropic glutamate receptors and expression of N-methyl-D-aspartate receptor subunits in subregions of human hippocampus: effects of schizophrenia.

OBJECTIVE: Multiple quantifiable biologic abnormalities have been localized to the hippocampus in schizophrenia. Alterations in glutamate-mediated transmission at N-methyl-D-aspartic acid (NMDA)-sensitive receptors in hippocampus have been implicated in the pathophysiology of the illness. The authors tested the hypothesis that glutamatergic transmission within and efferent from hippocampus is altered in schizophrenia. METHOD: The authors analyzed postmortem hippocampal tissue from individuals with schizophrenia and from healthy individuals. The tissue samples had been collected by two brain tissue banks, one in Maryland and the other in Melbourne, Australia. lonotropic receptor binding for the NMDA, kainate, and (3)H-amino-3-hydroxy-5-methylisoxazol-4-propionate (AMPA) receptors was quantified by using usual radioligand techniques. In situ hybridization autoradiography was used to quantify mRNA for the NMDA receptor subunits NR1, NR2A, and NR2B. RESULTS: Ligand binding to the ionotropic glutamate receptors (NMDA, kainate, and AMPA) did not differ significantly overall or in any subregion between the schizophrenia tissue and the healthy comparison tissue. The only exception was AMPA receptor binding in hippocampal subregion CA2, which was slightly but significantly less in schizophrenia. However, the level of mRNA for the NMDA receptor subunits NR1 and NR2B was significantly different between groups; in several hippocampal subregions, the level of NR1 mRNA was lower and the level of NR2B mRNA higher in schizophrenia. CONCLUSIONS: Because the NR1 subunit of the NMDA receptor is critical to full receptor activity, a reduction of NR1 in hippocampus in schizophrenia suggests a functional impairment in glutamatergic transmission at the NMDA receptor, resulting in reduced glutamatergic transmission within and possibly efferent from the hippocampus in schizophrenia. This defect could underlie a hypoglutamatergic state in regions of limbic cortex, consistent with published results from other lines of research in schizophrenia.

Adult↗

PubMed2000

Complement component 9 deficiency is not a susceptibility factor for SLE.

Almost all complement component 9 (C9) deficiency in Japan shows Arg95 Stop mutation of C9 gene. Therefore, we studied the prevalence of Arg95Stop mutation of C9 gene among 78 patients with SLE to elucidate the association of SLE and C9 deficiency. The Arg95Stop carrier frequency showed no significant difference between SLE patients and controls. Thus, C9 deficiency is not implicated in SLE susceptibility.

Complement C9↗

PubMed2000

Function of the small guanosine triphosphate-binding protein RhoA in the process of implantation.

The Rho family of small GTPases occupies a key position in the control of cell motility and morphology in response to extracellular stimuli. Rho proteins trigger the formation of contractile stress fibers, resulting in regulation of cell motility. We explored the expression and function of RhoA in human endometrium and decidua. RhoA immunoreactivity had a predominantly glandular epithelial distribution in the proliferative phase and midsecretory phase. In decidua, the expression of RhoA was more pronounced in the stromal cells as well as in the glandular epithelium. RhoA protein levels in proliferative phase and midsecretory phase endometrium as well as decidua were evaluated by immunoblotting; a single band of RhoA protein with a molecular mass of 21 kDa was detected in all cell lysates. Cultured human decidual cells were found to have few actin stress fibers. Decidual cells lost their actin stress fibers by the treatment with C3, an exoenzyme produced by Clostridium botulinum, whereas new actin stress fibers appeared in human decidual cells stimulated with lysophosphatidic acid (LPA). Mouse blastocysts became attached to cultured human decidual cells after embryos hatched from the zona pellucida. The majority of hatched blastocysts attached to human decidual cells within 24 h. Blastocysts attached to decidual cells exhibited extensive outgrowth after 48 h in culture. Treatment of decidual cells with C3 exoenzyme or LPA did not affect the rates of hatching and attachment of blastocysts, but outgrowth of embryos on decidual cells was inhibited by C3 exoenzyme treatment in a dose-dependent manner. Contrariwise, addition of LPA to decidual cells dose dependently increased the outgrowth of embryos on decidual cells. These findings suggest that RhoA in decidual cells is important for embryonic development and differentiation after attachment.

ADP Ribose Transferases↗

PubMed2000

Clonidine attenuates the carbachol-induced contractile and phosphatidylinositol responses of rat trachea.

Although clonidine is known to affect vascular smooth muscle, its effects on airway smooth muscle are not fully understood. This study was designed to examine the effects of clonidine on carbachol-induced contractile and phosphatidylinositol responses of rat trachea. Clonidine, at a dose of 100 microM or greater, attenuated carbachol-induced contraction and the accumulation of carbachol-induced inositol monophosphate (IP1). Clonidine also attenuated the accumulation of aluminium fluoride-induced IP1. The concentration-effect relationship of IP1 accumulation was similar to that of carbachol-induced contraction; r = 0.797, P < 0.001. These results suggest that clonidine attenuates contractile responses, at least in part, through the inhibition of phospholipase C (coupled with G-proteins) in phosphatidylinositol responses.

Aluminum Compounds↗

PubMed2000

Quantitative prediction of in vivo drug interactions between nevirapine and antifungal agents from in vitro data in rats.

We investigated the effects of ketoconazole (KCZ) and fluconazole (FCZ) on rat liver microsomal nevirapine (NVP) metabolism in vitro and on NVP plasma profiles in vivo in order to determine whether the in vivo drug interactions could be predicted quantitatively from the in vitro data. The Ki values of KCZ and FCZ for NVP 12-hydroxylation were 1.59 microm and 11.5 microM, respectively, indicating that KCZ inhibited this activity more strongly than FCZ in vitro. In contrast, FCZ orally pre-administered at 20 mg/kg to rats increased the area under the plasma concentration-time curve (AUC) of NVP 7.4-fold, whereas KCZ increased it 2.1-fold, compared to the vehicle. We next investigated the inhibitory potency and unbound concentrations of KCZ and FCZ in microsomal mixtures with or without rat albumin. In the presence of albumin, the inhibition by KCZ was greatly decreased. Further, the unbound fraction of KCZ was decreased dramatically to around 3%, whereas more than 90% of FCZ remained in unbound form. When the increase in the AUC for NVP was calculated based on the concentrations of unbound inhibitors in the portal vein, good agreement with the observed in vivo values was obtained.

Albumins↗

PubMed2000

Insight into acid-mediated asymmetric spirocyclization in the presence of a chiral diol.

Asymmetric spirocyclization based on intramolecular conjugate addition using a combination of a Lewis acid and an optically active cyclohexane-1,2-diol has been studied in connection with 1) the effect of substituents on the cyclohexane-1,2-diol and 2) the effect of substituents on the substrate. This reaction was found to be both thermodynamically and kinetically controlled under restricted conditions.

Acids↗

PubMed2000

Application of Rh-catalyzed cyclization to the formation of a chiral quaternary carbon.

Rh-Catalyzed cyclization was applied to the formation of a chiral quaternary carbon. It has become clear that the Rh-complex can discriminate between isopropenyl and 2-isopentenyl (or isopentyl) substituents, and the cyclization afforded 3,3,4-trisubstituted cyclopentanones with a chiral quaternary carbon in a stereoselective manner. The cyclization of 4-pentenals 6a, b by an achiral neutral Rh(PPh3)3Cl afforded 3,3,4-cis-trisubstituted cyclopentanones (+/-)-7a,b in 86-96%, and the cyclization by a cationic Rh[(R)-BINAP]CIO4 afforded 3,3,4-trans-trisubstituted cyclopentanones (-)-8a, b of 82-86% ee in 88-98% yields. The mechanism of stereoselection by Rh-complexes is also discussed.

Catalysis↗

PubMed2000

[Recent advances in tetrodotoxin research].

One century has passed since fugu toxin was named tetrodotoxin (TTX) by Tahara. Chemical problems such as crystallization of tetrodotoxin and subsequent structure determination were solved by research groups headed by Tsuda, Hirata, Woodward, and Mosher. The International Symposium on the Chemistry of Natural Products in Kyoto (1964) was well known as symposium which the structure of TTX was internationally clarified. Since the first isolation of toxin from taricha torosa (imori) as natural source except for fugu fishes, distribution of toxin in nature has been widely investigated. And, it was proved that toxin is not produced by fugu fishes, but rather is formed by sea bacteria (30 sp.) such as Alteromonas sp, Vibrio sp, Shewanella. However, it seems to be difficult to explain the tetrodotoxin accumulation at high concentration in fugu by only toxin production by bacteria. TTX analogues were isolated from natural origins such as crabs, fish, annelids, and algae. Based on the structure of these toxin analogues, the biosynthesis of toxin and the structure-activity relationship (Na+ channel) were proposed by Yasumoto-Yamashita. The findings of wide distribution of toxin in nature may be attributed to development of highly sensitive detection method for toxin. The interesting proposal for the biosynthesis and the structure activity, and the detection method for toxin are outlined in this review.

Alteromonas↗

PubMed2000

Efficacy of mitral valve replacement for patients with mitral regurgitation and a dilated left ventricle.

Mitral regurgitation is a significant complication of end-stage cardiomyopathy, and its existence predicts poor survival. In general, it is thought that mitral valve replacement (MVR) alone is ineffective; however, there are few detailed reports of the clinical course of patients who have undergone MVR. Five patients with mitral regurgitation whose preoperative left ventricular end-systolic volume index was more than 100 ml/m2 were studied. Although their prognosis late after MVR became poor, none of them died within 30 days of the operation. Postoperative cardiac catheterization was performed 6.3+/-1.1 months after surgery; the end-diastolic volume had reduced (before: 193+/-26 ml/m2; after: 166+/-34 ml/m2, p<0.05), but the end-systolic volume had not (before: 110+/-7 ml/m2; after: 112+/-32 ml/m2). The end-systolic wall stress was substantially elevated preoperatively (238+/-29 kdyne/cm2) and tended to increase after surgery (295+/-96 kdyne/cm2). All the patients were able to return to work at some stage postoperatively (their New York Heart Association functional class improved to I or II), but 3 of the 5 patients died suddenly of heart failure at 3.3+/-1.6 years after surgery and the New York Heart Association functional class of the others worsened to III again. Mitral valve surgery, including MVR, can manage severe end-stage heart disease with mitral regurgitation.

Adult↗

PubMed2000

Application of a newly developed photoluminescence glass dosimeter for measuring the absorbed dose in individual mice exposed to low-dose rate 137Cs gamma-rays.

A photoluminescence glass dosimeter, GD-301, was applied to the measurement of low absorbed doses in mice exposed to low-dose rate 137Cs gamma-rays. The dosimeter system consists of small rod-shaped glass chip detectors capable of embedded in the body of a mouse and an automatic readout device equipped with a standard detector irradiated with 137Cs gamma-source. The measured absorbed doses were compared with the "exposure" estimated by an ionization chamber and with the doses measured by a BeO:Na thermoluminescence system. The results clearly demonstrate the superiority of the glass dosimetry regarding simplicity of operation, stability of long-term dose accumulation and good detector uniformity, which allow accurate tissue dosimetry.

Animals↗

PubMed2000

Sensitization by wortmannin of heat- or X-ray induced cell death in cultured Chinese hamster V79 cells.

Here we found that wortmannin sensitized Chinese hamster V79 cells to hyperthermic treatment at 44.0 degrees C as determined either by colony formation assay or by dye exclusion assay. Wortmannin enhanced heat-induced cell death accompanying cleavage of poly (ADP-ribose) polymerases (PARP). Additionally, the induction of heat shock protein HSP70 was suppressed and delayed in wortmannin-treated cells. Heat sensitizing effect of wortmannin was obvious at more than 5 or 10 microM of final concentrations, while radiosensitization was apparent at 5 microM. Requirement for high concentration of wortmannin, i.e., order of microM, suggests a possible role of certain protein kinases, such as DNA-PK and/or ATM among PI3-kinase family. The sensitization was minimal when wortmannin was added at the end of heat treatment. This was similar to the case of X-ray. Since heat-induced cell death and PARP cleavage preceded HSP70 induction phenomenon, the sensitization to the hyperthermic treatment was considered mainly caused by enhanced apoptotic cell death rather than secondary to suppression or delay by wortmannin of HSP70 induction. Further, in the present system radiosensitization by wortmannin was also at least partly mediated through enhancement of apoptotic cell death.

Androstadienes↗

PubMed2000

Role of conserved histidine residues in D-aminoacylase from Alcaligenes xylosoxydans subsp. xylosoxydans A-6.

D-Aminoacylase from Alcaligenes xylosoxydans subsp. xylosoxydans A-6 (Alcaligenes A-6) was strongly inactivated by diethylpyrocarbonate (DEPC). An H67N mutant was barely active, with a kcat/Km 6.3 x 10(4) times lower than that of the recombinant wild-type enzyme, while the H67I mutant lost detectable activity. The H67N mutant had almost constant Km, but greatly decreased kcat. These results suggested that His67 is essential to the catalytic event. Both H69N and H69I mutants were overproduced in the insoluble fraction. The kcat/Km of H250N mutant was reduced by a factor of 2.5 x 10(4)-fold as compared with the wild-type enzyme. No significant difference between H251N mutant and wild-type enzymes in the Km and kcat was found. The Zn content of H250N mutant was nearly half of that of wild-type enzyme. These results suggest that the His250 residue might be essential to catalysis via Zn binding.

Alcaligenes↗

PubMed2000

Ascorbic acid stimulation of production of a highly branched ,beta-1,3-glucan by Aureobasidium pullulans K-1--oxalic acid, a metabolite of ascorbic acid as the stimulating substance.

The production of a highly branched beta-1,3-glucan by Aureobasidium pullulans K-1 in Czapek's medium has been found to be stimulated by ascorbic acid. When the culture supernatant, after removal of polysaccharide from the culture filtrate by ethanol precipitation, was concentrated, then added to a new medium and this strain was cultured in the medium, the polysaccharide production was stimulated the same as when L-ascorbic acid was added to the medium. The stimulating substance was partially purified from the supernatant, and was found to be oxalic acid; 0.03% oxalic acid was the most effective concentration for the stimulation of polysaccharide production. The stimulating substance, oxalic acid, was proved to be derived from ascorbic acid added to a medium in an experiment using L-[1-14C]ascorbic acid. We suggest that oxalic acid generated from the metabolism of ascorbic acid in cells of Aureobasidium pullulans K-1 participated in the stimulation of the polysaccharide production by ascorbic acid.

Ascorbic Acid↗

PubMed2000

Purification and characterization of nitrite-oxidizing enzyme from heterotrophic Bacillus badius 1-73, with special concern to catalase.

Nitrite-oxidizing enzyme I (NiOx I) was purified from a heterotrophic bacterium, Bacillus badius I-73. The enzyme was a homotetramer of a heme-containing peptide, and was similar to catalases from various sources in its N-terminal amino acid sequence. The purified enzyme also catalyzed H2O2 degradation. The nitrite oxidation reaction required ascorbic acid and oxygen. Successive H2O2 feeding could be substituted for ascorbic acid. These indicated that NiOx I is a catalase and nitrite was oxidized by a peroxidase-like reaction.

Amino Acid Sequence↗

PubMed2000

Steroid 5alpha-reductase inhibitory activity and hair regrowth effects of an extract from Boehmeria nipononivea.

The acetone extract of Boehmeria nipononivea showed both potent 5alpha-reductase inhibitory activity and hair regrowth promotion effects on mice. 5alpha-Reductase inhibitory activity-guided fractionation led to six active fatty acids: alpha-linolenic, linoleic, palmitic, elaidic, oleic and stearic acids. The extract of B. nipononivea, and alphalinolenic, elaidic and stearic acids exhibited a hair regrowth effect.

5-alpha Reductase Inhibitors↗

PubMed2000

Ulnar neuropathy caused by a lipoma in Guyon's canal--case report.

A 74-year-old female presented with a 3-month history of compression neuropathy of the right ulnar nerve in Guyon's canal. Magnetic resonance imaging and ultrasonography revealed the location of the mass lesion. Surgical exploration discovered a lipoma pressing against both the ulnar nerve and the ulnar artery. The mass was extirpated. The postoperative course was uneventful with good function recovery.

Aged↗

PubMed2000

Value of dynamic MR imaging in assessing endometrial carcinoma involvement of the cervix.

OBJECTIVE: The purpose of this study was to evaluate endometrial carcinoma involvement of the cervix using dynamic MR imaging compared with T2-weighted and contrast-enhanced T1-weighted MR imaging. SUBJECTS AND METHODS: In 42 patients with endometrial carcinoma, T2-weighted MR imaging using rapid acquisition with relaxation enhancement, dynamic MR imaging using gradient-echo sequences, and contrast-enhanced T1-weighted MR imaging using spin-echo sequences were performed before treatment. We evaluated patterns of enhancement in the cervix and tumor. In 39 of the 42 patients who underwent surgical treatment, we compared MR imaging findings with histologic results concerning cervical involvement. RESULTS: Enhancement of the cervical epithelium was greater than that of the tumor and cervical stroma on dynamic MR imaging in most patients. In assessing cervical involvement, the accuracy of T2-weighted, dynamic, and contrast-enhanced T1-weighted MR imaging was 85%, 95%, and 90%, respectively; no statistically significant difference was observed. False-positive cases on T2-weighted MR imaging were correctly identified as having no cervical involvement on dynamic MR imaging using the finding of continuous enhancement of the cervical epithelium. We found this finding to be reliable in assessing tumor involvement of the cervix. CONCLUSION: We believe that, in combination with T2-weighted MR imaging sequences, dynamic MR imaging is useful in assessing endometrial carcinoma involvement of the cervix.

Adult↗

PubMed2000

Effects of ovariectomy on parafollicular cells in the rat.

Changes in the parafollicular cells in the thyroid gland of ovariectomized rats were investigated to clarify the relationship between the secretory function of sex hormones and that of parafollicular cells. Compared with control rats, the ovariectomized rats exhibited decreases in 1) the number of parafollicular cells in the thyroid glands, 2) the number of secretory granules in the parafollicular cells, and 3) the area occupied by the Golgi complex. These results suggest that the lack of estrogen caused by ovariectomy reduces the synthesis and release of calcitonin in parafollicular cells, which may be one of the causes of osteoporosis.

Animals↗