Biomedical subjects

T Arai

Publications and source records attributed to T Arai.

At least 199 records · Page 11Linked to original sources

PubMed2000

[Effects of intravenous nicardipine, prostaglandin E1, nitroglycerin, sodium nitroprusside, and epidural lidocaine on hepatic and renal blood flow during hypotensive anesthesia].

We studied the effects of intravenous nicardipine (NIC), prostaglandin E1 (PGE1), nitroglycerin (TNG), sodium nitroprusside (SNP) and epidural lidocaine (LID) on hepatic and renal blood flow during general anesthesia (nitrous oxide-oxygen-sevoflurane) in 46 female patients undergoing unilateral total hip arthroplasty. During operations, hepatic blood flow, glomerular filtration rate, renal plasma flow, and renal tubular injury were measured by R 15 ICG (15 minutes retention rate of indocyanine green), CCR (creatinine clearance), CPAH (para-aminohippuric acid clearance), and urinary excretion of NAG and beta 2-microglobulin. Significant elevation of R 15 ICG was observed in the hypotensive state in the TNG group and the elevation of R 15 ICG indicates that blood flow to the liver has decreased during hypotensive anesthesia. Urine volume in the PGE1 group was larger than that in the TNG, SNP or LID group. CCR in the PGE1 group was larger than that in the NIC, TNG or SNP groups. CPAH in the PGE1 group was larger than that in the SNP or LID group. The value of urine NAG in the TNG group was larger than that in the NIC or PGE1 group. The value of urine beta 2-microglobulin in the NIC group was larger than that in the PGE1 or SNP group. The results of urine volume, CCR, CPAH, urine NAG, and urine beta 2-microglobulin indicate that blood flow to the kidneys was greater in the PGE1 group as compared to other groups. This study indicates that prostaglandin E1 is the best hypotensive drug for hepatic and renal blood flow during hypotensive anesthesia.

Aged↗

PubMed2000

Ileosigmoid anastomosis with exclusion of transected ileal loop for intestinal fistula following total cystectomy of bladder cancer. Report of a case.

We report in this article a new technique of surgical treatment of enterocutaneous or enterovaginal fistula after total cystectomy for three cases of bladder cancer. The surgical outcome was successful in these patients, showing good performance status after this operation. It would seem that this technique is a good indication for enteric fistulas in the bottom of the pelvic cavity, which were difficult to be managed even under the control of total parenteral nutrition.

Abscess↗

PubMed1999

In vivo gene transfer of an extracellular domain of platelet-derived growth factor beta receptor by the HVJ-liposome method ameliorates bleomycin-induced pulmonary fibrosis.

A number of investigators have reported augmented expression of PDGF in lungs with idiopathic pulmonary fibrosis (IPF) or with other types of pulmonary fibrosis. To accomplish such a regulation of PDGF activity, we constructed an expression plasmid of the extracellular domain of PDGF receptor beta chain (XR), which lacks intracellular tyrosine kinase domain and transmembrane portions, and estimated the therapeutic effects of XR gene transfer through the trachea on bleomycin-induced lung fibrosis of C57BL/6 mice using the hemagglutinating virus of Japan(HVJ)-liposome method. The XR gene transfer ameliorated the increases in the wet weight and hydroxyproline content and the histopathologic changes of the lung induced by bleomycin. These findings suggest that PDGF plays a crucial role in the pathogenesis of pulmonary fibrosis, and that XR gene transfer using the HVJ-liposome method may limit the progression of pulmonary fibrosis.

Animals↗

PubMed1999

Functional changes of N-methyl-D-aspartic acid and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate channels in gerbil hippocampal CA1, in relation to postischemic enhancement of glutamate receptor-mediated responses.

Glutamate receptor-mediated responses have been reported to be enhanced in the postischemic CA1 pyramidal neurons before the appearance of delayed neuronal death, and the enhancement has been thought to be one of crucial factors leading postischemic CA1 pyramidal neurons to irreversible neuronal injury. In the present study, we examined what changes in functional properties of N-methyl-D-aspartic acid (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) channels are responsible for the enhanced postischemic glutamate receptor-mediated responses. Gerbils were subjected to 5-min ischemia to induce the enhancement of glutamate receptor-mediated responses and the hippocampal slices were prepared 3 h after ischemia. Single channel activities evoked by NMDA and AMPA were recorded from outside-out patches excised from the postischemic CA1 pyramidal neurons. The main conductance levels of NMDA and AMPA channels in the postischemic CA1 pyramidal neurons were not significantly different from those in control CA1 pyramidal neurons. The mean open time and the open-state probability of NMDA and AMPA channels significantly increased in the postischemic CA1 pyramidal neurons (NMDA channels: mean open time, 1.4-fold increase; open-state probability, 1.5-fold increase) (AMPA channels: mean open time, 1.3-fold increase; open-state probability, 1.8-fold increase). These findings indicate that the increases in the mean open time and the open-state probability of NMDA and AMPA channels are responsible for the enhancement of postischemic NMDA and non-NMDA receptor-mediated responses.

Animals↗

PubMed1999

Detection of silent myocardial ischemia patients by the spatial velocity electrocardiogram.

This study was designed to detect patients with type I silent myocardial ischemia (SMI) at rest by assessing the symmetry of the electrocardiographic (ECG) T wave using the spatial velocity electrocardiogram (SVECG). In this study, the ECG T waves in patients with SMI were symmetric compared with those in normal subjects, and the the c/a ratio in the SVECG-T wave as the index of degree of symmetry of the ECG T wave enabled us to diagnose 73% of these patients; the c/a ratio in the SVECG T wave was a useful index for detecting patients with type I SMI at rest.

Aged↗

PubMed1999

Decreased selective uptake of high density lipoprotein cholesteryl esters in apolipoprotein E knock-out mice.

Scavenger receptor BI (SR-BI) mediates the selective uptake of high density lipoprotein (HDL) cholesteryl esters (CE) by cells, i.e., the uptake of CE without degradation of HDL protein. Mice with attenuated expression of SR-BI, because of targeted gene mutation (SR-BIatt mice), have increased plasma HDL levels as a result of decreased selective uptake in the liver. To further evaluate the role of SR-BI in lipoprotein metabolism, compound apolipoprotein E knock-out (apoE0)/SR-BIatt mice were bred. Hepatic SR-BI protein was increased (2.3-fold) in apoE0 mice compared with wild type (wt) and was reduced significantly in apoE0/SR-BIatt mice. However, the plasma lipoprotein profile of apoE0 and apoE0/SR-BIatt mice was identical. This was explained by HDL turnover studies that revealed that the selective clearance of HDL CE by the liver and adrenal was already profoundly impaired in apoE0 mice compared with wt (28% of wt in liver). A similar decrease in selective uptake was seen when apoE0 HDL was incubated with isolated apoE0 hepatocytes. The results suggest that apoE plays a major role in the selective clearance of HDL CE by the liver and adrenal gland, possibly by facilitating the presentation of HDL to SR-BI at the cell surface.

Animals↗

PubMed1999

Cellular localization of adenosine A1 receptors in rat forebrain: immunohistochemical analysis using adenosine A1 receptor-specific monoclonal antibody.

Monoclonal antibodies were generated against the adenosine A1 receptor (A1R) purified from rat brain. In immunoblot analyses of purified or partially purified A1R preparations from rat brain, these antibodies recognized a solitary band, the size of which corresponded to that expected for A1R. These antibodies recognized not only the native form of A1R but also the deglycosylated form of A1R. Immunocytochemical analysis of Chinese hamster ovarian cells that were transfected stably with rat A1R cDNA showed that their cell bodies were stained intensely by these antibodies, whereas nontransfected Chinese hamster ovarian cells were not. These antibodies detected the A1R naturally present in the DDT(1)( )MF-2 smooth muscle cells. One of these antibodies (the 511CA antibody) was then used to examine the immunohistochemical distribution of A1Rs in rat forebrain. On light microscopy, A1R immunoreactivity was observed in the cerebral cortex, septum, basal ganglia, hippocampal formation, and thalamus. However, in some regions of the forebrain, regional differences in staining intensity were found as follows: In the cerebral cortex, the strongest immunoreactivity was found in the large pyramidal neurons of layer V. This immunoreactivity was detected in the pyramidal cell bodies, dendrites, and axon initial segments. In the hippocampus, A1R immunoreactivity was detected mainly in the stratum pyramidale. The pyramidal cells in fields CA2-CA3 of the hippocampus were stained more intensely or more clearly than those in field CA1 or the dentate gyrus. More intense A1R immunoreactivity of the apical dendrites was detected in field CA2 compared with other hippocampal fields and the dentate gyrus. Many interneurons of the hippocampus were stained by the 511CA antibody. The subcellular distribution of A1Rs in the forebrain was examined by using a digital deconvolution system and electron microscopy. In the cerebral cortex, the view obtained by removing the background haze by deconvolution revealed that the immunofluoresence-labeled A1Rs were distributed on the surfaces of the cell bodies and dendrites and in the cytoplasm of layer V neurons as small spots. In field CA1, immunoreactivity was detected in the areas surrounding pyramidal cells. Electron microscopy revealed the presence of A1R-immunoreactive products in both the presynaptic terminals and the postsynaptic structures. The specific cellular distribution of A1Rs is consistent with the physiological premise that endogeneously released adenosine exerts control over the excitability of forebrain neurons at both presynaptic and postsynaptic sites through A1Rs.

Animals↗

PubMed1999

Predominant germ-line mutation of the hMSH2 gene in Japanese hereditary non-polyposis colorectal cancer kindreds.

By means of PCR-SSCP and direct sequencing, we detected 12 germ-line mutations of hMSH2 or hMLH1 in 37 Japanese hereditary non-polyposis colorectal cancer (HNPCC) kindreds, of whom 15 satisfied the Amsterdam and 22 the Japanese criteria. The germ-line mutation detection rate of hMSH2 was much higher than that of hMLH1 (11/37 vs. 1/37). The total mutation detection rate of hMSH2 and hMLH1 in the Amsterdam criteria group was significantly higher than that in the Japanese criteria group (9/15 vs. 3/22). Furthermore, the mean age of the HNPCC patients in the mutation-positive group was lower than that in the mutation-negative one; the rates of both vertical transmission and multiplicity of tumors in the mutation-positive group were higher than those in the mutation-negative one. In addition, the number of patients with microsatellite instability-positive cancers in the mutation-positive group was higher than that in the mutation-negative one. Our results suggest firstly that the hMSH2 gene plays a much more important role than hMLH1 in the carcinogenesis of Japanese HNPCC patients, secondly that the rate of hMSH2 and hMLH1 mutations is high in the kindreds satisfying the Amsterdam criteria and thirdly that both the clinical phenotypes (early onset, vertical transmission and multiplicity of tumors) and the microsatellite instability status are important for the genetic screening of HNPCC.

Colorectal Neoplasms, Hereditary Nonpolyposis↗

PubMed1999

STAT3 activation is sufficient to maintain an undifferentiated state of mouse embryonic stem cells.

Embryonic stem (ES) cells can be maintained in an undifferentiated state in the presence of leukemia inhibitory factor (LIF). LIF acts through a receptor complex composed of a low affinity LIF receptor (LIFRbeta) and gp130. We reported that the intracellular domain of gp130 plays an important role in self-renewal of ES cells. In the present study, we examined the signaling pathway through which gp130 contributes to the self-renewal of ES cells. Mutational analysis of the cytoplasmic domain of gp130 revealed that the tyrosine residue of gp130 responsible for STAT3 activation is necessary for self-renewal of ES cells, while that required for SHP2 and MAP kinase activation was dispensable. Next, we constructed a fusion protein composed of the entire coding region of STAT3 and the ligand binding domain of the estrogen receptor. This construction (STAT3ER) induced expression of junB (one of the targets of STAT3) in ES cells in the presence of the synthetic ligand 4-hydroxytamoxifen (4HT), thereby indicating that STAT3ER is a conditionally active form. ES cells transfected with STAT3ER cultured in the presence of 4HT maintained an undifferentiated state. Taken together, these results strongly suggest that STAT3 activation is required and sufficient to maintain the undifferentiated state of ES cells.

Animals↗

PubMed1999

Dose-dependent transduction of vesicular stomatitis virus G protein-pseudotyped retrovirus vector into human solid tumor cell lines and murine fibroblasts.

We examined the transduction efficiency of a VSV-G (vesicular stomatitis virus G protein)-pseudotyped vector encoding beta-galactosidase (lacZ) into human solid tumor cell lines and murine fibroblasts, compared with that of an amphotropic vector carrying the same RNA sequence. The ratio of cells transduced with the VSV-G-pseudotyped vector corresponded closely to 1 - e(-m.o.i.), as predicted from a Poisson distribution of transduction to the entire cellular population, while this was not the case for the amphotropic vector. Here m.o.i. (multiplicity of infection) is defined as the ratio of input infectious units (titrated on the corresponding cell line) to the number of cells used for the transduction. At high m.o.i.s (values greater than 3), the VSV-G-pseudotyped vector transduced approximately 95% of the culture population of all cell lines examined. The transduction efficiency of the amphotropic vector, however, was not dose-dependent and reached a plateau or even decreased, especially at high m.o.i.; this may be attributable at least in part to the presence of envelope protein and noninfectious particles that compete for the receptor of infectious amphotropic virus. The copy number of integrated vector proviral DNA and the expression level of lacZ increased almost linearly with the dose of the VSV-G-pseudotyed vector, which could readily achieve multiple transduction of more than 10 copies per cell and afforded about 100-fold more transgene product than could be achieved with the amphotropic vector. These features of both the VSV-G-pseudotyped vector and the amphotropic vector were essentially unaffected by purification using centrifugation. These properties of the vector should be highly advantageous for gene transfer into entire populations of human tumor cell lines at a designed dosage.

Animals↗

PubMed1999

Metyrapone alleviates ischemic neuronal damage in the gerbil hippocampus.

Transient forebrain ischemia was induced in gerbils, and the effect of a pre-ischemic treatment with metyrapone (100 mg/kg) on delayed neuronal death in hippocampal CA1 neurons was evaluated. The effect of metyrapone on the ischemic release of amino acids in the CA1 region was also examined by microdialysis. Hippocampal slices were used for the evaluation of the hypoxia-induced intracellular Ca2+ increase by microfluorometry. The metyrapone treatment morphologically improved the damage provoked by 3 min of ischemia, although it did not alleviate the damage by 5 min. Ischemia for 3 min produced a 306% increase in the glutamate concentration in perfusates, and metyrapone suppressed the peak value to 42% of that in the control group. The extent of the increase in fluorescence intensity by intracellular Ca2+ was lower by 16% in slices from metyrapone-treated animals than in controls 600 s after induction of hypoxia. The removal of Ca2+ from the perfusion medium suppressed the hypoxic Ca2+ increase, and the increase was further reduced in slices pretreated with metyrapone. The increase in the level of endogenous glucocorticoids, which occurs in cerebral ischemia, may aggravate ischemic neuronal damage.

Amino Acids↗

PubMed1999

Sepsis facilitates brain serotonin activity and impairs learning ability in rats.

Sepsis often provokes various neurological disorders. Because many neurologic symptoms are caused by changes in neurotransmissions, we investigated the relationship between behavioral alterations and changes in activities of the monoaminergic systems in rats. Sepsis was induced by cecal ligation and puncture. A step-through passive avoidance test was used for the behavioral evaluation. Passive avoidance retention in animals subjected to learning immediately before the septic or sham operation was examined after 24 or 48 h. Retention performance in animals subjected to learning 24 h after the operation was also examined after a further 24 h. Plasma concentrations of amino acids were determined 24 h after the operation. The activities of the brain monoaminergic systems were evaluated by ratios of metabolites to monoamines. Marked damage was found in the septic rats in the blood analysis 24 h after the operation. The plasma concentrations of tyrosine and arginine in the septic rats were decreased to 69% and 70% of those in the sham-operated animals, respectively. Retention performance was impaired in the septic rats when they were subjected to learning 24 h after the operation, but it was not impaired when animals were subjected to learning before the septic operation. The brain concentration of serotonin was increased in the cerebral cortex, striatum, and hippocampus 48 h after the septic operation, but not after 24 h. The concentration of 5-hydroxyindoleacetic acid, a metabolite of serotonin, was increased in the above three regions both 24 and 48 h after the operation, but not in the hypothalamus. Facilitation of the serotonergic activity in the telencephalon and hippocampus is suggested to be involved in the impairment of learning ability in sepsis.

Animals↗

PubMed1999

Human MMH (OGG1) type 1a protein is a major enzyme for repair of 8-hydroxyguanine lesions in human cells.

8-Hydroxyguanine (8-OH-G) is the site of a frequent mutagenic lesion of DNA, produced by oxidative damage. MutM of E. coli and OGG1 of Saccharomyces cervisiae are known to possess 8-OH-G glycosylase activity and apurinic (AP) site lyase activity to repair 8-OH-G lesions. Recently, cDNA clones of human OGG1 homologues (hMMH) of four isoforms (type 1a, type 1b, type 1c, and type 2) were isolated. However, it is unknown whether expression of endogenous hMMH proteins actually occurs in mammalian cells. Here using hMMH type 1a-specific antibody and cells overexpressing tag-fused hMMH type 1a, we show the expression of hMMH type 1a protein in many types of human cells and show that endogenous hMMH type 1a protein has 8-OH-G glycosylase/AP lyase activity. Furthermore, we show that upon depletion of hMMH type 1a protein in a whole cell extract by its antibody, most of the AP lyase activity is lost, indicating that hMMH type 1a protein is a major enzyme for repair of 8-OH-G lesions in human cells.

Antibodies↗

PubMed1999

Characterization of the antiseptic-resistance gene qacE delta 1 isolated from clinical and environmental isolates of Vibrio parahaemolyticus and Vibrio cholerae non-O1.

The nucleotide sequence and mechanism of action were examined on the antiseptic-resistance gene qacE delta 1 that had been isolated from Pseudomonas aeruginosa, Vibrio parahaemolyticus and Vibrio cholerae non-O1. The nucleotide sequences of qacE delta 1 genes isolated from environmental isolates of V. cholerae non-O1 and V. parahaemolyticus differed by one base from that of the gene from P. aeruginosa. Escherichia coli C600 that harbored qacE delta 1 genes from several strains of Vibrio spp. exhibited low-level resistance to intercalating dyes. The resistance of E. coli cells with these genes to intercalating dyes, such as ethidium bromide, was mediated by an efflux system. Moreover, the activity of QacE delta 1 was inhibited in the presence of calcium channel blockers but not of calmodulin inhibitors. These results indicate that the qacE delta 1 gene can be function in E. coli and that the gene mediates resistance in a similar manner to the antiseptic-resistance gene smr.

Amino Acid Sequence↗

PubMed1999

Immunohistochemical localization of amyloid beta-protein with amino-terminal aspartate in the cerebral cortex of patients with Alzheimer's disease.

We investigated immunohistochemically the localization of amyloid beta-protein (Abeta) with amino-terminal aspartate (N1[D]) in brains of patients with Alzheimer's disease, diffuse Lewy body disease and Down's syndrome. A monoclonal antibody, 4G8, which recognizes the middle portion of Abeta, was used as a reference antibody to label the total Abeta deposits. Double staining with anti-Abeta(N1[D]) and 4G8 revealed that Abeta deposits in the subiculum and the neocortical deep layers often lacked N1[D] immunoreactivity, indicating N-terminal truncation of Abeta in these deposits. Abeta deposits in the neocortical superficial layers and the presubicular parvopyramidal layer always contained Abeta with N1[D]. Such regional as well as laminar differences in the distribution of Abeta beginning at N1[D] suggest that some local factors influence N-terminal processing of Abeta deposited in the brain.

Aged↗

PubMed1999

Effects of medium containing heparin and theophylline on capacitation and metabolic enzyme activities of ejaculated spermatozoa from dogs with asthenozoospermia.

The percentages of motile sperm (%MO), hyperactivated sperm (%HA), and acrosome-reacted sperm (%AR) of four beagle dogs with asthenozoospermia (AS) and five normal beagle dogs were determined during 7 h of incubation. The metabolic enzyme activities of the sperm was examined after 0 and 4 h of incubation. The sperm were incubated in canine capacitation medium (CCM) and CCM containing either 20 microg ml(-1) heparin (HE), 10 microg ml(-1) theophylline (TH) or 20 microg ml(-1) HE + 10 microg ml(-1) TH in glass tubes at 38 degrees C under 5% CO2 in air. The %HA and %AR were determined by counting the sperm exhibiting star-spin like movement and by the triple stain technique. The spermatozoa in HE + TH CCM were homogenized and centrifuged, and the metabolic activities of hexokinase, fructokinase, glucose-6-phosphodehydrogenase (G6PD), and pyruvate kinase in the sperm cytosol in the supernatant was measured with a spectrophotometer. The mean %MO and %HA values of both AS and normal dogs in the four types of CCM were highest in HE + TH CCM, with a mean %HA in HE + TH CCM of 78 +/- 5% (S.E.) after 7 h of incubation. However, there was little difference in %AR among the four types of CCM. The mean activities of the four enzymes in the sperm of AS dogs before incubation was significantly lower than in the sperm of normal dogs (P < 0.05, 0.01). However, after 4 h of incubation the activities of all enzymes in the sperm of both AS and normal dogs was clearly higher in HE + TH CCM than in the control CCM. These findings indicate that HE and TH in the medium are effective inactivating metabolic enzymes, maintaining longer sperm motility, and efficiently inducing HA even of the sperm of AS dogs.

Acrosome Reaction↗

PubMed1999

Decreased atherosclerosis in heterozygous low density lipoprotein receptor-deficient mice expressing the scavenger receptor BI transgene.

Scavenger receptor type B class I (SR-BI), initially identified as a receptor that recognizes low density lipoprotein (LDL), was recently shown to mediate the selective uptake of high density lipoprotein (HDL) cholesteryl esters in liver and steroidogenic tissues. To evaluate effects on atherosclerosis, transgenic mice with liver-specific overexpression of SR-BI (SR-BI Tg mice) have been crossed onto LDL receptor-deficient backgrounds. To induce atherosclerosis in a setting of moderate hypercholesterolemia, heterozygous LDL receptor-deficient mice (LDLR1) were fed a high fat/cholesterol/bile salt diet, and homozygous LDL receptor knock-outs (LDLR0) were fed a high fat/cholesterol diet. LDLR1/SR-BI Tg mice showed decreases in VLDL, LDL, and HDL cholesterol and a significant 80% decrease in mean lesion area in the aortic root compared with LDLR1 mice (female LDLR1 74, 120 micrometers(2) versus LDLR1/SR-BI Tg 12, 667 micrometers(2); male 25, 747 micrometers(2)++ versus 5, 448 micrometers(2), respectively). LDLR0/SR-BI Tg mice showed decreased LDL and HDL cholesterol but increased VLDL cholesterol and no significant difference in extent of atherosclerosis compared with LDLR0 mice. Combined data analysis showed a strong correlation between atherosclerotic lesion area and the VLDL+LDL cholesterol level but no correlation with HDL level. These studies demonstrate a strong anti-atherogenic potential of hepatic SR-BI overexpression. In mice with marked overexpression of SR-BI, the protective effect appears to be primarily related to the lowering of VLDL and LDL cholesterol levels.

Animals↗

PubMed1999

Argyrophilic glial inclusions in the midbrain of patients with Parkinson's disease and diffuse Lewy body disease are immunopositive for NACP/alpha-synuclein.

Argyrophilic glial inclusions occur in the midbrain of patients with Parkinson's disease (PD) and diffuse Lewy body disease (DLBD). These inclusions are immunohistochemically positive for NACP/alpha-synuclein but negative for tau protein. The results of the present study suggest that a primary degenerative process involves NACP/alpha-synuclein in PD and DLBD and that the process takes place not only in neurons but also in glial cells. Argyrophilic cytoplasmic inclusions, both glial and neuronal, in a variety of degenerative diseases may be grouped into two major categories; one related to aggregates of abnormally phosphorylated tau protein and the other to unusual accumulations of NACP/alpha-synuclein.

Aged↗