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Biomedical subjects

H Araki

Publications and source records attributed to H Araki.

At least 127 records · Page 7Linked to original sources
PubMed1997

Effects of the isocarbacyclin methyl ester clinprost incorporated into lipid microspheres, in focal ischemia of stroke-prone spontaneously hypertensive rats.

The effects of TTC-909, the isocarbacyclin methyl ester clinprost (CAS 88931-51-5), incorporated into lipid microspheres, on ischemia-induced decrease in norepinephrine (NE) contents in stroke-prone spontaneously hypertensive rats (SHR-SP) with an occluded middle cerebral artery (MCA) were examined. Occluding of MCA led to infarction limited to the cerebral cortex and also a severe decrease in NE contents in peripheral regions of the infarction. TTC-909 was injected immediately after MCA occlusion, and then daily for 6 consecutive days. As TTC-909 in a dose of 200 ng/kg significantly (p < 0.05) prevented decreases in NE contents, TTC-909 may have cytoprotective effects on neuronal damage related to ischemia in humans.

Animals↗
PubMed1997

[Clinical study on azithromycin in 10% fine granules and 100mg capsules in the field of pediatrics].

Azithromycin (AZM), a new oral macrolide antibiotic, in 10% fine granules or 100 mg capsules was given to pediatric patients to treat various infections. The following results were obtained in our studies of AZM for its antibacterial activities against clinical isolates, its pharmacokinetics, its efficacy, and its safety. 1. MICs of AZM, erythromycin (EM) and clarithromycin (CAM) were determined against a total of 57 strains all at 10(6) cfu/ml. Among Gram-positive cocci, MICs of AZM ranged from 0.78 to > 100 micrograms/ml against Staphylococcus aureus (20 strains), from 0.05 to 0.1 microgram/ml against Streptococcus pyogenes (11 strains), and from 0.0125 to 3.13 micrograms/ml against Streptococcus pneumoniae (10 strains). These MICs were similar to those of the other macrolides. Among Gram-negative bacilli, MICs of AZM were 0.05 micrograms/ml against Moraxella subgenus Branhamella catarrhalis (1 strain), from 0.78 to 3.13 micrograms/ml against Haemophilus influenzae (9 strains), 0.78 micrograms/ml against Haemophilus parainfluenzae (1 strain) and 6.25 micrograms/ml against salmonella sp. (1 strain). These values were similar to or lower than those of the other macrolides. Against Mycoplasma pneumoniae, MICs of AZM were < or = 0.0008 micrograms/ml in three strains. One strain of M. pneumoniae showed tolerance to AZM at MIC 25 micrograms/ml. The other agents exhibited higher MIC than AZM against this organism. 2. Plasma samples were collected from five patients receiving fine granules and four patients receiving capsules for drug level determination. The patients received AZM at 10.0 approximately 16.3 mg/kg body weight once daily for 3 days. Drug concentrations in plasma at two hours after Day 3 dosing were in a range between 0.02 and 0.19 micrograms/ml for fine granules and were in a range between 0.11 and 0.42 micrograms/ml for capsules. 3. Urine samples were collected from four patients receiving fine granules and four patients receiving capsules. Drug levels were determined to be 3 micrograms/ml at post-treatment 48 hours for fine granules and post-treatment 72 hours for capsules. Urinary excretion rates of AZM in three patients on capsules lied in a range between 4.69 and 10.17%. 4. Effectiveness of AZM in fine granules was evaluated in 128 patients having a total of 19 different infections. AZM was rated "excellent" in 51 patients, "good" in 63, "fair" in 8, "poor" in 6, resulting in an efficacy rate of 89.1%. Effectiveness of AZM in capsular form was evaluated in 23 patients with five different infections. AZM was found "excellent" in 13 patients and "good" in 10, resulting in an efficacy rate of 100%. 5. AZM in fine granules eradicated 45 strains of 54 in 8 different bacteria. AZM in capsules eradicated 9 strains of 10 strains in 6 different bacteria. 6. As for adverse reactions, one patient complained of eruption, one vomiting, one loose stool, five diarrhea, when administered with fine granular form of AZM. One patient on AZM capsules experienced urticaria and vomiting. 7. As for abnormal laboratory changes, three patients were found with decreased WBC, seven with increased eosinophil, two with increased GOT and GPT, one with increased GPT. They were all on fine granular form of AZM. As far as abnormalities found in patients administered with AZM in capsular form, two showed decreased WBC, one decreased WBC along with increased eosinophil, and three increased eosinophil.

Adolescent↗
PubMed1996

Relative selectivity for negative chronotropic and inotropic effects of a novel dihydropyridine derivative CD-832.

The effects of CD-832 [(4R)-(-)-2-(nicotinoyl-amino) ethyl 3-nitroxypropyl 1,4-dihydro-2,6-dimethyl-4,3-nitrophenyl, 3,5-pyridine dicarboxylate], a novel dihydropyridine derivative, on various guinea-pig myocardial preparations were compared with those of nifedipine, verapamil and diltiazem. CD-832 decreased the action potential duration of isolated papillary muscles without substantially affecting other parameters. In voltage-clamped single ventricular myocytes, CD-832 decreased the L-type Ca2+ current amplitude while having little effect on outward currents. CD-832 and other Ca2+ channel antagonists produced negative chronotropic effects in isolated right atrial preparations and negative inotropic effects in right ventricular papillary muscles, respectively, in a concentration-dependent manner. The potency order for the negative chronotropic effect was CD-832 > nifedipine > verapamil > diltiazem, while that for the negative inotropic effect was nifedipine > verapamil > or = CD-832 > diltiazem. The ratio, EC20 for negative inotropic effect divided by EC20 for negative chronotropic effect, which was considered to be an index of selectivity for negative chronotropic effect was highest for CD-832, the ratio for CD-832, nifedipine, verapamil and diltiazem being 5.4, 0.11, 0.25 and 0.37, respectively. These results indicate that CD-832 is an L-type Ca2+ channel antagonist with relative selectivity for a negative chronotropic effect rather than for a negative inotropic effect. This 'chrono-selective' cardiosuppressive effect of CD-832 could be of value in the treatment of cardiovascular diseases such as angina pectoris.

Action Potentials↗
PubMed1996

Rfc5, a small subunit of replication factor C complex, couples DNA replication and mitosis in budding yeast.

The inhibition of DNA synthesis prevents mitotic entry through the action of the S phase checkpoint. In the yeast Saccharomyces cerevisiae, an essential protein kinase, Spk1/Mec2/Rad53/Sad1, controls the coupling of S phase to mitosis. In an attempt to identify genes that genetically interact with Spk1, we have isolated a temperature-sensitive mutation, rfc5-1, that can be suppressed by overexpression of SPK1. The RFC5 gene encodes a small subunit of replication factor C complex. At the restrictive temperature, rfc5-1 mutant cells entered mitosis with unevenly separated or fragmented chromosomes, resulting in loss of viability. Thus, the rfc5 mutation defective for DNA replication is also impaired in the S phase checkpoint. Overexpression of POL30, which encodes the proliferating cell nuclear antigen, suppressed the replication defect of the rfc5 mutant but not its checkpoint defect. Taken together, these results suggested that replication factor C has a direct role in sensing the state of DNA replication and transmitting the signal to the checkpoint machinery.

Amino Acid Sequence↗
PubMed1996

Nitrooxy alkyl apovincaminate modulates GABA(A) receptor in rat neocortical neurones.

We investigated the effects of VA-045 ((+)-eburnamenine-14 carboxylic acid (2-nitroxyethyl) ester) on GABA(A) receptor-mediated Cl- currents in dissociated rat cerebral cortical neurones, using a nystatin-perforated patch recording configuration. At a holding potential of - 40mV, the external application of GABA evoked an inward Cl- current with an EC50 value of 5.6 x 10(-6)M. VA-045 increased the GABA response at GABA concentrations below 3.0 x 10(-6)M. The GABA response showed a time dependent decay consisting of fast and slow components and VA-045 significantly accelerated both components. The site of action for VA-045 was considered to be different from that for benzodiazepines or barbiturates.

Animals↗
PubMed1996

VA-045, a novel apovincamic acid derivative attenuates neuronal injury induced by hypoxia or by excitatory amino acids in cultures of rat cortices.

Effects of VA-045, a novel apovincaminic acid derivative, on neuronal damage induced by hypoxia or by excitatory amino acids (glutamate (Glu), N-methyl-D-aspartate and kainate) were examined in cultures of the rat cortices. The extent of cell injury was quantified by measuring lactic dehydrogenase activity released from the damaged cells into the culture medium. VA-045 at concentrations between 1 microM and 30 microM significantly attenuated this neuronal damage and exceeded those of vinpocetine. VA-045 had no significant binding affinity to Glu receptor subtypes. The cytoprotection of VA-045 does not seem to be the result of antagonism at Glu receptors. VA-045 inhibited lipid peroxide production in brain homogenates. Vitamin E also had this antioxidant effect, but did not attenuate the hypoxia-induced neuronal damage. A cAMP analogue and a phosphodiesterase (PDE) inhibitor also attenuated the hypoxia-induced neuronal damage. As VA-045 inhibits the activity of PDE, the effect of VA-045 may possibly relate to cAMP cascade. VA-045 may prove to be efficacious for the treatment of disorders related to cerebral neuronal injury.

Animals↗
PubMed1996

Neuroprotective effect of 4'-(4-methylphenyl)-2,2':6',2-terpyridine trihydrochloride, a novel inducer of nerve growth factor.

We have identified 4'-(4-methylphenyl)-2,2':6',2-terpyridine: trihydrochloride (SS701), which belongs to a family of a small unique neuroprotective agents. SS701 accelerated the production of nerve growth factor (NGF) in cultured astroglial cells, dose- and time-dependently. In in vivo studies, SS701, when administered 30 min after induced cerebral ischemia, neuroprotective effects on delayed neuronal death in Mongolian gerbils were evident. The neuroprotective effects of SS701 against ischemia-induced delayed neuronal death are attributed to stimulation of the production of NGF.

2,2'-Dipyridyl↗
PubMed1996

Imipenem and cephem resistant Pseudomonas aeruginosa carrying plasmids coding for class B beta-lactamase.

From October 1988 to January 1992, nine isolates of Pseudomonas aeruginosa carrying transferable plasmids encoding imipenem-hydrolyzing beta-lactamase (pI = c. 9.5) were recovered from nine different patients in a neurosurgical ward of a hospital in Japan. The beta-lactamase activities of the sonicated extracts from the transconjugants were inhibited by EDTA and this was partially reversible by the addition of zinc cation. The substrate specificity and pI of the beta-lactamase were similar to those of the metallo beta-lactamases from P. aeruginosa and Serratia marcescens TN9106. All strains were resistant to imipenem, carbenicillin and antipseudomonal cephems including ceftazidime, cefsulodin, cefpirome, while four and five strains were susceptible to piperacillin and aztreonam, respectively. Both low level imipenem resistance and high level cephem resistance were co-transferred with the production of metallo beta-lactamase, while resistance to piperacillin, aztreonam, and high level imipenem-resistance were not selected. Production of chromosomal cephalosporinase in piperacillin resistant strains was derepressed, and production of outer membrane protein of D2 was diminished in highly imipenem resistant strains. Six strains were isolated in 1991, and the amounts of antipseudomonal agents, especially imipenem, used in the neurosurgical ward increased markedly in this year. Only three of the nine isolates had the same serotype, pyocin type and phage type. Our results suggest that the repeated isolation of imipenem and cephem-resistant P. aeruginosa producing metallo beta-lactamase was related to the high usage of antipseudomonal beta-lactam antibiotics such as imipenem, and was exacerbated by the dissemination of a plasmid.

Anti-Infective Agents↗
PubMed1996

Severe gastrointestinal complications of dialysis-related amyloidosis in two patients on long-term hemodialysis.

Two patients undergoing long-term hemodialysis developed severe gastrointestinal complications due to dialysis-related amyloidosis (DRA). Case 1, a 68-year-old male on hemodialysis for 18 years developed marked gastric dilatation and severe paralytic ileus. Five years later he died of peritonitis. Autopsy showed extensive amyloid deposits in the muscle layers and blood vessels throughout the gastrointestinal tract. Case 2, a 56-year-old male on hemodialysis for 19 years, developed panperitonitis due to perforation of the sigmoid colon. The resected colon showed massive amyloid deposits in the muscle layers. In both cases, immunological studies revealed positive staining for antihuman beta2-microglobulin antibody. In long-term hemodialysis patients with gastrointestinal symptoms, gastrointestinal complications of DRA should be considered.

Aged↗
PubMed1996

Neuroprotective effect of TTC-909, an isocarbacyclin methyl ester incorporated in lipid microspheres, on hippocampal delayed neuronal death of stroke-prone spontaneously hypertensive rats.

TTC-909 is a newly developed isocarbacyclin methyl ester (TEI-9090) incorporated in lipid microspheres. The neuroprotective effect of TTC-909 was histologically examined in the pyramidal cell layer of the hippocampus CA1 subfield 7 days after transient forebrain ischemia using stroke-prone spontaneously hypertensive rats. TTC-909, given intravenously 10 min after the transient forebrain ischemia, dose-dependently protected against ischemia-related delayed neuronal death. The blood pressure remained unchanged following TTC-909 administration. This finding suggests that TTC-909 has a neuroprotective action on ischemic delayed neuronal death in the hippocampus.

Animals↗
PubMed1996

Intraovarian immunolocalization of steroidogenic enzymes in a Hokkaido brown bear, Ursus arctos yesoensis during the mating season.

Immunolocalization for four steroidogenic enzymes was performed on an ovary taken from a Hokkaido brown bear during the mating season. This specimen is considered to be in the follicular phase because of the presence of large follicles. In large follicles, cholesterol side-chain cleavage (P450scc) and 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) were immunolocalized in theca interna cells and granulosa cells. 17 alpha-hydroxylase/C17-C20 lyase cytochrome P450 (P450c 17) was immunolocalized in theca interna cells but not in granulosa cells. Aromatase cytochrome P450 (P450arom) was immunolocalized only in granulosa cells. In medium follicles, however, P450scc and 3 beta HSD were immunolocalized only in theca interna cells, and the immunoreactivity of P450arom was detected in neither theca interna cells nor granulosa cells. Immunoreactivities of P450scc, 3 beta HSD and P450c 17 but not P450arom were detected in interstitial cells. This study suggests that estrogen biosynthesis takes place through interrelation between theca cells and granulosa cells and is explained by the so-called two-cell mechanism. Furthermore, the granulosa cells in large follicles have the capability for pregnenolone and progesterone biosynthesis, and the interstitial cell in the bear ovary is also a steroidogenic site.

3-Hydroxysteroid Dehydrogenases↗
PubMed1996

Relation between the instrumental activities of daily living and physical fitness tests in elderly women.

A cross-sectional study was conducted to quantitatively evaluate the relationship between the instrumental activities of daily living (IADL) and various physical fitness tests in elderly women living at home. The study focused on the total population of those women aged 65 years and over living in Y Town, Hyogo Prefecture, Japan, who visited a nursing home for day services. A total of 128 subjects were divided into two groups: dependent in IADL group (n = 49) and independent in IADL group (n = 79). The magnitude of the relation was evaluated by the odds ratio (OR). The following tests showed a significant decrease in IADL: knee-raising test [age-adjusted OR = 4.23, 95% confidence interval (CI) 1.81-9.87], height (age-adjusted OR = 4.09, 95% CI 1.75-9.56), grip strength (age-adjusted OR = 3.68, 95% CI 1.57-8.60), sit-and-reach test (age-adjusted OR = 2.76, 95% CI 1.20-6.34), and standing on one leg with closed eyes (age-adjusted OR = 2.56, 95% CI 1.09-5.97). Multivariate analysis using Hayashi's quantification method I indicated that knee-raising was the test most highly correlated with decreased IADL. These results suggest that measurement of knee-raising ability, muscle strength of the lower extremities and flexibility of hip joint could be the most useful factors to assess the level of instrumental self-support ability.

Activities of Daily Living↗
PubMed1996

Effects of a new calcium antagonist, CD-832, on isoproterenol-induced myocardial ischemia in dogs with partial coronary stenosis.

Effects of CD-832 on isoproterenol (ISO)-induced myocardial ischemia were studied in dogs with partial coronary stenosis of the left circumflex coronary artery and findings were compared with those for nifedipine or diltiazem. In the presence of coronary artery stenosis, 3-min periods of intracoronary ISO infusion (10 ng/kg/min) increased heart rate and maximal rate of left ventricular pressure rise, which resulted in a decrease in percentage segmental shortening and ST-segment elevation of the epicardial electrocardiogram. After the control ISO infusion with stenosis was performed, equihypotensive doses of CD-832 (3 and 10 micrograms/kg/min, n = 7), nifedipine (1 and 3 micrograms/kg/min, n = 9) or diltiazem (10 and 30 micrograms/kg/min, n = 7) were infused 5 min before and during the second and third ISO infusion. Both CD-832 and diltiazem, but not nifedipine, significantly reduced the increase in heart rate induced by ISO infusion. In contrast to nifedipine, CD-832 (10 micrograms/kg/min) prevented the decrease in percentage segmental shortening from 32 +/- 12% to 115 +/- 26% of the control value (P < .01) and ST-segment elevation from 5.6 +/- 1.0 mV to 1.6 +/- 1.3 mV (P < .01) at 3 min after ISO infusion with stenosis. Diltiazem (30 micrograms/kg/min) also prevented the decrease in percentage segmental shortening from 34 +/- 14% to 63 +/- 18% of the control value (P < .05) and ST-segment elevation from 4.7 +/- 0.7 mV to 2.1 +/- 0.7 mV (P < .01) at 3 min after ISO infusion with stenosis. These data show that CD-832 improves myocardial ischemia during ISO infusion with stenosis and suggest that the negative chronotropic property of CD-832 plays a major role in the beneficial effects of CD-832.

Angina Pectoris↗
PubMed1996

Primary carcinoma of the gallbladder: role of external beam radiation therapy in patients with locally advanced tumor.

BACKGROUND/AIM: Several reports have demonstrated that occasional long-term survival might be obtained with external beam radiation therapy in patients with gallbladder cancer. However, there are few reports which evaluate the local effect of irradiation. The aim of our study was to investigate the local effect of radiation therapy. and to evaluate its role for locally advanced gallbladder cancer. PATIENTS AND METHODS: Twenty-two patients with locally advanced gallbladder cancer were treated with high-dose external beam radiation therapy. Tumor resection was performed in 5 patients, palliative surgery in 5, and the remaining 12 patients were treated by radiation therapy alone. RESULTS: Overall survival was 36% at 1 year, 18% at 3 years and 14% at 5 years. All but 2 patients developed local recurrence and died of disease at 1 to 99 months after radiation therapy. Among 17 patients who had not undergone tumor resection, partial response was obtained in 4 patients and no response in 13. Survival times in patients who achieved partial response were 14, 26, 47 and 99 months, whereas those of no response were 1 to 12 months with a mean of 4.8 months. Survival between these 2 groups (partial vs. no response) showed significant difference (p = 0.0008, logrank test). CONCLUSION: It is concluded that high-dose external beam radiation therapy could improve survival in some patients with unresectable gallbladder cancer.

Adenocarcinoma↗
PubMed1995

Dpb11, which interacts with DNA polymerase II(epsilon) in Saccharomyces cerevisiae, has a dual role in S-phase progression and at a cell cycle checkpoint.

DPB11, a gene that suppresses mutations in two essential subunits of Saccharomyces cerevisiae DNA polymerase II(epsilon) encoded by POL2 and DPB2, was isolated on a multicopy plasmid. The nucleotide sequence of the DPB11 gene revealed an open reading frame predicting an 87-kDa protein. This protein is homologous to the Schizosaccharomyces pombe rad4+/cut5+ gene product that has a cell cycle checkpoint function. Disruption of DPB11 is lethal, indicating that DPB11 is essential for cell proliferation. In thermosensitive dpb11-1 mutant cells, S-phase progression is defective at the nonpermissive temperature, followed by cell division with unequal chromosomal segregation accompanied by loss of viability.dpb11-1 is synthetic lethal with any one of the dpb2-1, pol2-11, and pol2-18 mutations at all temperatures. Moreover, dpb11 cells are sensitive to hydroxyurea, methyl methanesulfonate, and UV irradiation. These results strongly suggest that Dpb11 is a part of the DNA polymerase II complex during chromosomal DNA replication and also acts in a checkpoint pathway during the S phase of the cell cycle to sense stalled DNA replication.

Amino Acid Sequence↗
PubMed1995

Depolarization and hypoxia-induced cell damage in serum-free cultures of the rat cortex, and related extracellular glutamate changes.

Experiments were carried out to clarify the influence of K+-induced chronic membrane depolarization on cytotoxicity and changes in extracellular glutamate, as induced by hypoxia in serum-free cortical cultures. Excitotoxic cell death was examined by measuring lactic dehydrogenase (LDH) activity released into the culture medium. In culture grown in the presence of 25 mM K+, morphological injury occurred during a 4 h exposure to hypoxia, together with a substantial efflux of LDH. In hypoxic cultures, extracellular glutamate concentrations were elevated and these responses were absent in cultures grown in physiological medium (K+ = 5.4 mM), even with 16 h of hypoxia. In cultures at 25 mM K+, the cytotoxicity induced by hypoxia was attenuated by NMDA receptor antagonists, in a concentration dependent manner. We also examined the effects of excitatory amino acids, agonists of the main glutamate receptor classes (glutamate, NMDA, kainate, and AMPA). In both 5.4 nM and 25 mM K+ cultures, a dose dependent release of LDH was induced by a long exposure to glutamate receptor agonists, although the release of LDH in the 5.4 mM K+ was less than that in the 25 mM K+ cultures. Despite of the expression of the glutamate receptor in the 5.4 mM K+ cultures, hypoxic neuronal damage did not occur. These results suggest that when cultures grown in a chronically depolarizing environment are exposed to hypoxia, they are damaged by an excitotoxic mechanism in which the main cause seems to be the glutamate released into the medium at high extracellular levels.

Animals↗