Biomedical subjects

H Higuchi

Publications and source records attributed to H Higuchi.

At least 55 records · Page 3Linked to original sources

PubMed2001

[Awareness of the health and defecation tendencies among college students by location of domicile].

In order to compare the food habits and defecation tendencies by region, a questionnaire survey was conducted of 1722 college women (18-20 years of age) living in Sapporo (146), Sendai (183), Osaka (1214), and Kumamoto (179). (1) When questioned about food habits, less than 58.5% of the respondents in the four groups considered their food intake to be sufficient to maintain their health. In regard to knowledge about their food intake requirements, the positive response was the highest in Sendai (85.8%), followed by Kumamoto (58.2%) and Osaka (50.9%) with the lowest in Sapporo (41.1%) (p < 0.01, among the four groups). (2) The students in Sendai, Osaka, Kumamoto and Sapporo, 96.2%, 93.5%, 92.9% and 92.5%, respectively, considered that constipation could affect their health (p < 0.05, among four groups). The percentage of those with regular bowel movements every day, tended to decrease in the order of Osaka (22.2%), Sapporo (21.2%) and Sendai (20.8%), with the lowest in Kumamoto (12.3%). Bowel movements of less than three times a week were reported by 24.7% in Sapporo, 24.0% in Sendai, 23.2% in Osaka and 22.3% in Kumamoto (p < 0.01, among the four groups). (3) Of those who defecated every day, in terms of time of day, the percentage was high between waking and after breakfast, with the highest percentage in Kumamoto (72.8%) and the lowest in Sapporo (61.2%) (p < 0.05, among the four groups). For subjects that responded that they should have a bowel movement every day, the highest percentage was in Osaka (91.0%) and the lowest was in Sapporo (83.9%) (p < 0.05, among the four groups).

Adolescent↗

PubMed2001

Overview of studies on rat sperm motion analysis using a Hamilton-Thorne Sperm Analyzer--collaborative working study.

This collaborative study was conducted to determine the utility and sensitivity of nine sperm motion parameters generated by a Hamilton-Thorne Sperm Analyzer (HTM-IVOS) for detecting adverse effects of chemicals on sperm motion in rats. The efficacy of sperm motion parameters was investigated using nine reproductive toxicants: adriamycin, alpha-chlorohydrin (3 different studies were carried out), dinoseb, ethylene glycol monoethyl ether, 2,5-hexanedione, sulfasalazine, trimethyl phosphate, and ornidazole. The percentage of motile sperm (% motile sperm), the only parameter expressing the status of semen containing non-motile sperm, detected adverse effects on sperm motion in 9 out of 10 studies. However, weak effects on sperm motion were not detected by this parameter in 4 out of 7 studies in which sperm motion disorders were noted at medium or low dosages. The percentage of progressively motile sperm (% progressive sperm) and the sperm velocity parameters (average path velocity, straight line velocity, and curvilinear velocity) detected adverse effects on sperm motion in all studies. In 7 studies which noted sperm motion disorders at medium or low dosages, weak effects on sperm motion were detected by the % progressive sperm in 5 studies and by the sperm velocity parameters in 6 studies. In 10 studies, amplitude of lateral head displacement (ALH) did not detect adverse effects on sperm motion in 4 studies, and beat cross frequency (BCF) failed to detect adverse effects on sperm motion in 3 studies. Because ALH and BCF show the swimming pattern of spermatozoa as head movement, the characteristics of these parameters are different from the % progressive sperm and the sperm velocity parameters. Straightness (STR) and linearity (LIN), which are secondary parameters calculated from sperm velocity parameters, could not detect adverse effects on sperm motion when the sperm velocity parameters did not detect adverse effects. On the basis of these results, we concluded that the % progressive sperm and sperm velocity parameters are useful and sensitive indicators for detecting adverse effects on sperm motion. However, in the % progressive sperm, setting up a suitable threshold of VAP and/or STR is important to gain further sensitivity for detecting adverse effects on sperm motion. The % motile sperm is useful for assessment of sperm motion disorder, and ALH and BCF are useful for evaluating the swimming pattern of sperm. STR and LIN are not very useful for detecting adverse effects on sperm motion.

Animals↗

PubMed2001

Application of computer-assisted sperm analysis system to elucidate lack of effects of cyclophosphamide on rat epididymal sperm motion.

A computer-assisted sperm analysis (CASA) system was used to examine the motion of epididymal spermatozoa derived from cyclophosphamide (CP)-treated male rats. Male rats were orally dosed daily for 1 week with 20 mg/kg of CP. Males were euthanized or were mated 3 times with untreated females at 1 day, 3 weeks, and 8 weeks after the final treatment. Significant decreases in testicular and epididymal weights and epididymal sperm counts of the treated animals were noted after 8-week recovery. Histopathological morphometry of the testis revealed minimal damage to spermatogonia at 1 day after the final treatment and to spermatocytes after 3-week recovery in the CP-treated group. On Caesarian section, increased post-implantation losses were found in females mated with CP-treated males in matings starting 1 day and 3 weeks after the final treatment. On the other hand, none of the sperm motion parameters of treated males derived from the CASA system exhibited significant changes at any time points, although the spermatozoa of treated males at 1 day and 3 weeks after the final treatment were damaged at the DNA level, and the spermatozoa of males after 8-week recovery had been the target cells of CP when they were spermatogonia in the testis. It was thus found that damaged spermatozoa could exhibit no changes on their motion when the damage was confined to the nuclei, and that the effect of CP on sperm nuclei was reversible.

Animals↗

PubMed2001

Serum lipid peroxide and alpha-tocopherol concentrations and superoxide dismutase activity in captive bottle-nosed dolphins.

OBJECTIVE: To evaluate serum lipid peroxide (LPO) and alpha-tocopherol concentrations and superoxide dismutase (SOD) activity in captive bottle-nosed dolphins and to evaluate effects of storage on production of LPO in various marine fish. ANIMALS: 16 bottle-nosed dolphins. PROCEDURE: 8 dolphins (group A) were fed chub mackerel and herring (high fat) and arabesque greenling and banded blue-sprat (low fat); the other 8 dolphins (group B) were fed chub mackerel and Pacific saury (high fat) and shishamo smelt and Japanese horse mackerel (low fat). Each group had been on these respective diets for 3 years. Serum LPO and alpha-tocopherol concentrations, serum SOD activity, and superoxide production by neutrophils were measured. All types of marine fish were frozen at -20 C for 6 months, and concentrations of LPO were measured at various time points. RESULTS: Serum LPO concentrations in group-A dolphins were significantly higher than those in group B. Serum alpha-tocopherol concentrations and SOD activity in group A were significantly lower than those in group B. A significant negative correlation was found between serum LPO and alpha-tocopherol concentrations in all 16 dolphins. The LPO concentrations in mackerel and herring fed to group-A dolphins were higher than those of other fish. Concentrations of LPO in herring stored for 3 and 6 months at -20 C were higher than those in herring before freezing and in herring stored for 1 month. CONCLUSIONS AND CLINICAL RELEVANCE: Serum LPO and alpha-tocopherol concentrations in captive bottle-nosed dolphins may be strongly influenced by high amounts of polyunsaturated fatty acid and LPO found in marine fatty fishes. High concentrations of serum LPO, as found in group-A dolphins, were associated with decreased antioxidative states. Monitoring of serum LPO and alpha-tocopherol concentrations and serum SOD activity may be useful for the management of captive marine mammals.

Animals↗

PubMed2001

[Preliminary report: the effect of flumazenil on the hypnotic dose of propofol in ddY mice].

The present investigation dealt with the effect of simultaneous administration of flumazenil on the hypnotic activity of propofol using a behavioral model of ddY mice. The mixed solution of propofol and flumazenil was administered intravenously into the mice tail vein and the achievement of hypnosis was defined as the loss of the righting reflex. Flumazenil 0.2 mg.kg-1 significantly decreased the required dose of propofol for hypnosis (8.43 +/- 0.46 mg.kg-1) compared to the control group (10.55 +/- 0.55 mg.kg-1). The mixture with a pH-3.9 acetate buffer solution did not change the hypnotic dose of propofol (10.88 +/- 0.62 mg.kg-1). The results suggest that flumazenil might potentiate the hypnotic activity of propofol in ddY mice.

Acetic Acid↗

PubMed2001

[The effect of the decreased serum concentration of propofol induced by rapid fluid infusion on the spectral edge frequency 90 and median frequency].

The effect of decreased serum concentration of propofol induced by rapid infusion therapy on the EEG was assessed by spectral edge frequency 90% (SEF90) or median frequency (MF) during propofol anesthesia. The eight scheduled surgical patients were administered propofol with a constant rate, and the rapid infusion therapy with 10 ml.kg-1 of acetate Ringer's solution significantly decreased the serum concentration of propofol from 1.96 +/- 0.22 micrograms.ml-1 to 1.68 +/- 0.19 micrograms.ml-1 (approximately 17% reduction). Simultaneous monitoring of SEF90 and MF, however, demonstrated no change during investigation. These results suggest that the mild decrease of the concentration of propofol might not induce the significant change of EEG, or that the reduction of propofol concentration by infusion might be deceptive and produce no significant change in the concentrations of each pharmacological compartment.

Adult↗

PubMed2001

[Co-administration of nitrous oxide reduces the pressor response against oro-tracheal intubation during induction of anesthesia with propofol infusion at a low rate].

This study investigated the effect of co-administration of nitrous oxide on the cardiovascular changes during induction of anesthesia with propofol infusion at a low rate. Sixty patients undergoing general anesthesia were randomly allocated into two groups, and received the inhalation of 100% oxygen (group 1) or 60% nitrous oxide and oxygen (group 2) via face mask for 3 minutes before administration of propofol at 15 mg.kg-1.hr-1. After beginning of propofol infusion, patients inhaled each gas continuously and the loss of response to simple commands by the anesthesiologist was considered as hypnosis. The dose and time for achieving hypnosis were determined, and non-invasive blood pressure, heart rate and arterial oxygen saturation were recorded during induction of anesthesia. Cardiovascular changes during induction were not different between the two groups except mean and diastolic blood pressure immediately after oro-tracheal intubation [126 +/- 21 vs. 113 +/- 21 mmHg and 108 +/- 21 vs. 95 +/- 19 mmHg, respectively (mean +/- SD)]. The dose of propofol and the time for achieving hypnosis showed no significant difference (73 +/- 20 vs. 68 +/- 19 mg and 4.8 +/- 1.0 vs. 4.4 +/- 1.0 min, respectively). Almost all patients were sedated with inhalation of nitrous oxide before infusion of propofol, but no additive effect was observed with nitrous oxide and propofol. Co-administration of nitrous oxide during propofol infusion at a low rate was an effective method to avoid undesirable pressor responses against oro-tracheal intubation without causing adverse cardiovascular depression.

Adult↗

PubMed2001

[Hemodynamic changes during slow induction of anesthesia using propofol and the effect of cardiac output on the propofol concentration].

This investigation assessed the hemodynamic changes during the slow induction of anesthesia using propofol, and evaluated the effects of cardiac output (CO) and other factors on the hypnotic dose of propofol, the time for hypnosis and the plasma propofol concentration. We studied 26 scheduled surgical patients and induced anesthesia with continuous infusion of propofol at the rate of 15 mg.kg-1.hr-1. The required dose of propofol and time for hypnosis were determined and the plasma concentration of propofol was measured after the administration of propofol 2 mg.kg-1. Cardiac output was determined by dye densitometry using indocyanine green 4 times during induction and CO did not show any significant changes during induction of anesthesia. Multiple linear regression analysis demonstrated that in addition to the age and total body weight, CO determined at achieving hypnosis was significantly related to the plasma concentration of propofol. Cardiac output might affect the pharmacokinetics of propofol during induction of anesthesia.

Adult↗

PubMed2001

[The effect of halothane anesthesia on dopamine release induced by apomorphine or haloperidol--an in vivo microdialysis study in rats striatum].

Brain microdialysis was used to study in vivo releases and changes in dopamine (DA) concentration induced by neuroleptics in the rat striatum during halothane anesthesia. Rats were implanted with a microdialysis probe into the right striatum and allowed to move freely. After acquiring steady state of DA and metabolites concentrations, apomorphine 50 micrograms.kg-1 or haloperidol 200 micrograms.kg-1 was administered intraperitoneally with or without 1.5% halothane anesthesia for 1 h. Halothane anesthesia showed no effect on the decrease of DA induced by apomorphine, but halothane antagonized the increase of DA induced by haloperidol. Administration of haloperidol produced an increase in metabolites of DA and it was unchanged by halothane. Malignant syndrome is a well known complication caused by interaction of neuroleptics and anesthesia. The results of the present investigation suggest that the mechanism of malignant syndrome might be associated with the dopaminergic activity.

Anesthesia, Inhalation↗

PubMed2001

Bid antisense attenuates bile acid-induced apoptosis and cholestatic liver injury.

Bile acids cause liver injury during cholestasis by inducing hepatocyte apoptosis by both Fas-dependent and -independent mechanisms. However, the Fas-independent apoptosis also appears to be death receptor-mediated. Because death receptor-mediated apoptosis in hepatocytes requires proapoptotic Bcl-2 BH3 domain only protein Bid, we postulated that Fas-independent but death receptor-mediated bile acid cytotoxicity would be Bid-dependent. We used Fas-deficient lymphoproliferative (lpr) mouse hepatocytes for these studies, and inhibited Bid expression using an antisense approach. Glychochenodeoxycholate (GCDC) was used to induce apoptosis. Bid cleavage and translocation to mitochondria was observed in GCDC-treated cells as assessed by immunoblot analysis and confocal imaging of Bid-green fluorescent protein, respectively. Bid translocation to mitochondria was associated with cytochrome c release. A Bid antisense 2'-MOE modified oligonucleotide inhibited Bid expression in hepatocytes and markedly attenuated hepatocytes apoptosis by GCDC. Treatment of lpr mice with Bid antisense also ameliorated liver injury following bile duct ligation of the mice, a model of extrahepatic cholestasis. These results suggest that bile acid cytotoxicity is Bid-dependent despite the absence of Fas. Bid antisense therapy is a promising approach for the treatment of cholestatic liver injury.

Animals↗

PubMed2000

Microarray hybridization with fractionated cDNA: enhanced identification of differentially expressed genes.

Molecular indexing is a technique to select a subpopulation of cDNA by ligation of adapters to cDNA fragments digested by a class IIS restriction enzyme(s). By this technique, 3' end cDNA fragments are divided into 16 fractions by selective ligation of adapters and subsequent PCR amplification. Each fraction is used as a hybridization target for microarray hybridization. This fractionated target has a relatively lower nucleic acid complexity, including more fractions for rare transcripts, and is useful for their detection. In an experiment with mouse cerebellum and cerebrum RNA, analysis of a subset of candidate genes indicated that 10 times more differentially expressed genes were detected by this method than by the conventional method using the unfractionated target.

Animals↗

PubMed2000

Kheper, a novel ZFH/deltaEF1 family member, regulates the development of the neuroectoderm of zebrafish (Danio rerio).

Kheper is a novel member of the ZFH (zinc-finger and homeodomain protein)/deltaEF1 family in zebrafish. kheper transcripts are first detected in the epiblast of the dorsal blastoderm margin at the early gastrula stage and kheper is expressed in nearly all the neuroectoderm at later stages. kheper expression was expanded in noggin RNA-injected embryos and also in swirl mutant embryos and was reduced in bmp4 RNA-injected embryos and chordino mutant embryos, suggesting that kheper acts downstream of the neural inducers Noggin and Chordino. Overexpression of Kheper elicited ectopic expansion of the neuroectoderm-specific genes fkd3, hoxa-1, and eng3, and the ectopic expression of hoxa-1 was not inhibited by BMP4 overexpression. Kheper interacted with the transcriptional corepressors CtBP1 and CtBP2. Overexpression of a Kheper mutant lacking the homeodomain or of a VP16-Kheper fusion protein disturbed the development of the neuroectoderm and head structures. These data underscore the role of Kheper in the development of the neuroectoderm and indicate that Kheper acts as a transcriptional repressor.

Alcohol Oxidoreductases↗

PubMed2000

Viral fusogenic membrane glycoprotein expression causes syncytia formation with bioenergetic cell death: implications for gene therapy.

Viral fusogenic membrane glycoproteins (FMGs) are candidates for gene therapy of solid tumors because they cause cell fusion, leading to formation of lethal multinucleated syncytia. However, the cellular mechanisms mediating cell death after FMG-induced cell fusion remain unclear. The present study was designed to examine the mechanisms by which FMG expression in hepatocellular carcinoma cells lead to cell death. Transfection of Hep3B cells with the Gibbon Ape leukemia virus hyperfusogenic envelope protein (GALV-FMG) resulted in the formation of multinucleated syncytia that reached a maximum 5 days after transfection (100 nuclei/syncytia). The syncytia were viable for a period of 2 days and then rapidly lost viability by day 5. Mitochondrial dysfunction occurred in GALV-FMG-induced syncytia prior to loss of viability with loss of the mitochondrial membrane potential, cellular ATP depletion, and release of mitochondrial cytochrome c-GFP into the cytosol. The pan-caspase inhibitor, Z-VAD-fmk, did not prevent cell death. However, glycolytic generation of ATP with fructose effectively increased cellular ATP and preserved syncytial viability. These data suggest that expression of FMG in hepatoma cells results in the formation of multinucleated syncytia, causing mitochondrial failure with ATP depletion, a bioenergetic form of cell death with necrosis. This form of cell death should be effective in vivo and enhance the bystander effect, suggesting that FMG-based gene therapy deserves further study for the treatment of hepatocellular and other cancers.

Adenosine Triphosphate↗

PubMed2000

A mutant of the motor protein kinesin that moves in both directions on microtubules.

Molecular motors move directionally to either the plus or the minus end of microtubules or actin filaments. Kinesin moves towards microtubule plus ends, whereas the kinesin-related Ncd motor moves to the minus ends. The 'neck'--the region between the stalk and motor domain--is required for Ncd to move to microtubule minus ends, but the mechanism underlying directional motor movement is not understood. Here we show that a single amino-acid change in the Ncd neck causes the motor to reverse directions and move with wild-type velocities towards the plus or minus end; thus, the neck is functional but directionality is defective. Mutation of a motor-core residue that touches the neck residue in crystal structures also results in movement in both directions, indicating that directed movement to the minus end requires interactions of the neck and motor core. Low-density laser-trap assays show that a conformational change or working stroke of the Ncd motor is directional and biased towards the minus end, whereas that of the neck mutant occurs in either direction. We conclude that the directional bias of the working stroke is dependent on neck/motor core interactions. Absence of these interactions removes directional constraints and permits movement in either direction.

Amino Acid Substitution↗

PubMed2000

Protective effect of diltiazem against ischemia-induced decreases in regional myocardial flow in rat heart.

Diltiazem has cardioprotective properties following myocardial ischemic injury. However, there are controversial results regarding the beneficial effects of diltiazem on regional myocardial flow after ischemia. Therefore, we investigated the effect of diltiazem on changes in regional myocardial flow due to ischemia for different periods. Non-radioactive colored microspheres were used for this measurement in isolated rat heart. After 20 or 40 min of global ischemia and 40 min of reperfusion, regional myocardial flow was decreased, especially in the endocardial layer. The endocardial/epicardial ratio was also decreased. The decreases in endocardial flow and the endocardial/epicardial ratio were more remarkable after 40 min of ischemia than after 20 min of ischemia. Diltiazem (10(-6) M), which was administered 15 min before ischemia, prevented only the decrease in endocardial flow and endocardial/epicardial ratio after 20 min of ischemia, whereas it did not prevent that after 40 min of ischemia. Nifedipine (2x10(-6) M) did not exert a cardioprotective effect. These findings suggested that the effect of ischemia is marked in the endocardium and, also, that the protective effect of diltiazem is seen only during a decrease in endocardial flow following short-term and reversible ischemia.

Animals↗

PubMed2000

Processive movement of single 22S dynein molecules occurs only at low ATP concentrations.

We have analyzed the movement of single 22S dynein molecules from Tetrahymena cilia by using a nanometer measuring system equipped with optical tweezers. Statistical analysis proved that a single molecule of 22S dynein can move processively and develop force at low concentrations of ATP (<20 microM). The maximum force was approximately 4.7 pN, and the force-velocity curve was convex down. During force development, dynein molecules showed stepwise displacement of approximately 8 nm and frequently exhibited backward steps of approximately 8 nm. At higher concentrations of ATP (>/=20 microM) single molecules of 22S dynein were not observed to move processively. Twenty-two S dynein seems to switch over from a processive mode to a nonprocessive mode, sensing a subtle change of ATP concentrations. These observations indicate that the processivity, maximum force, and step size of dynein are similar to those of kinesin, but the ATP concentration-dependence, force-velocity relationship, and backward steps are clearly distinct from kinesin.

Adenosine Triphosphate↗

PubMed2000

Upregulation of brain somatostatin and neuropeptide Y following lidocaine-induced kindling in the rat.

Male Sprague-Dawley rats received a daily injection of 60 mg/kg of lidocaine (> 30 days). Twenty percent of rats developed convulsions (kindled rats) and remaining rats did not show convulsions (non-kindled rats). The level of immunoreactive somatostatin (IR-SRIF) in kindled rats was significantly increased in amygdala than that in non-kindled rats and control rats. Immunoreactive neuropeptide Y (IR-NPY) contents in kindled rats were significantly increased in amygdala, hippocampus, cortex and striatum compared to non-kindled and control rats. The expression of SRIF mRNA in kindled rats produced a significant increase in amygdala, while NPY mRNA in kindled rats showed an elevated expression in both amygdala and hippocampus. These results coincide with the previous findings with the elevated expression of SRIF and NPY mRNA in electrically and pharmacologically kindled models, suggesting the important role of these peptides in the kindling phenomenon.

Amygdala↗

PubMed2000

Biperiden hydrochlorate ameliorates dystonia of rats produced by microinjection of sigma ligands into the red nucleus.

It has been reported that the imbalance of anticholinergic and antidopaminergic activity of each neuroleptic drug correlates with the capacity to produce neuroleptic-induced acute dystonia (NAD) and the major focus of NAD is thought to be the striatum. Anticholinergic drugs are highly effective on NAD, but they are partially effective on neuroleptic-induced tardive dystonia and their effect on idiopathic dystonia is disappointing. Recently, it has been reported that the unilateral microinjection of sigma (sigma) ligands into the red nucleus induces torticollis of rats. This animal model appears to be a model of dystonia, but it is not clear whether it is suitable for NAD in man. To clarify this issue, we investigated the effect of an anticholinergic drug, biperiden hydrochlorate (BH), on this animal model. This study revealed that BH dose-dependently ameliorated dystonia of rats induced by two sigma ligands, whether each sigma ligand had dopaminergic affinity or not. This animal model of dystonia appears to be a model of NAD in man from the viewpoint of treatment-response. The results also suggest that not only dopaminergic and cholinergic systems but also sigma system, and not only the striatum but also the red nucleus, may play an important role in the pathophysiology of NAD.

Animals↗