Search PubMed⌕ Search

Biomedical subjects

A Watanabe

Publications and source records attributed to A Watanabe.

At least 505 records · Page 28Linked to original sources
PubMed1994

Additive effects of cepharanthin in CDDP/hyperthermia combination therapy against transplantable human esophageal cancer in nude mice.

PURPOSE: Additive effects of cepharanthin in CDDP/hyperthermia combination therapy were evaluated. METHODS AND MATERIALS: Nude mice bearing a transplantable human esophageal cancer (ES0-2), classified histologically as a moderately differentiated squamous cell carcinoma, were treated with cepharanthin (20 mg/kg IP) in addition to cis-diamminedichloroplatinum(II) (CDDP; 4 mg/kg IP) and/or hyperthermia at 42 degrees C for 30 min, to determine the additive effects of cepharanthin. Furthermore, effects of cepharanthin on intratumoral concentration of CDDP were evaluated. RESULTS: Cepharanthin itself did not have an anti-tumor effect. This agent did not enhance the anti-tumor effect of CDDP alone, but enhanced the anti-tumor effects of both 42 degrees C hyperthermia alone, and combination therapy with CDDP and 42 degrees C hyperthermia. The concentration of CDDP in the tumors treated by 42 degrees C hyperthermia was slightly higher than in nonheated tumors. Cepharanthin did not affect the intratumoral concentration of CDDP, irrespective of whether hyperthermia was applied. CONCLUSION: Cepharanthin enhanced the effect of CDDP/hyperthermia combination therapy through thermoenhancing effect.

Alkaloids↗
PubMed1994

Effects of nitric oxide synthase inhibitors on N-methyl-D-aspartate-induced phase delay of circadian rhythm of neuronal activity in the rat suprachiasmatic nucleus in vitro.

Excitatory amino acid (EAA) receptors such as N-methyl-D-aspartate (NMDA) and non-NMDA receptors have been suggested to play an important role in the regulation of photic information from the retina to the suprachiasmatic nucleus (SCN). Therefore, we investigated the role of glutamate as a retinohypothalamic transmitter by analyzing the phase-resetting effects of NMDA and a non-NMDA agonist, (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), on the circadian rhythm of SCN firing activity. Nitric oxide (NO) production is believed to be an essential intermediate in NMDA-induced cGMP production in the CNS. Thus, we examined the effects of blockers of NO production on NMDA- or AMPA-induced phase delay of SCN activity rhythm. N-nitro-L-arginine methylester (L-NAME) blocked NMDA- but not AMPA-induced phase shift, indicating the involvement of NO synthesis in NMDA-induced phase changes. L-arginine but not D-arginine caused a phase delay, and L-NAME blocked L-arginine-induced phase delay. In addition, cotreatment with NMDA and L-arginine did not have an additive effect. These results suggest that NO production itself is involved in the phase change of SCN neuron activity, and NMDA-induced phase changes are also mediated via activation of NO synthesis in this nucleus.

Amino Acid Oxidoreductases↗
PubMed1994

Protein-synthesis inhibitor blocks (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-or substance P-induced phase shift of the circadian rhythm of neuronal activity in the rat suprachiasmatic nucleus in vitro.

The mammalian suprachiasmatic nucleus (SCN) has been identified as a circadian pacemaker. N-methyl-D-aspartate (NMDA), non-NMDA and substance P receptors have been suggested to be involved in handling of photic information in the SCN. In the Aplysia eyes, in which the circadian clocks are involved, serotonin- or cAMP-induced phase changes of the circadian rhythm were reported to be blocked by protein-synthesis inhibitors. Therefore, we investigated whether protein-synthesis inhibitor can block the non- NMDA receptor agonist (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrobromide (AMPA)- or substance P (SP)-induced phase changes of SCN activity rhythm. Although application of 10 microM cycloheximide alone during the early part of the subjective night did not cause phase change, it blocked both 10 microM AMPA- and 1 microM SP-induced phase delay. The present result suggests that protein synthesis may be required in the manifestation of AMPA- and SP-induced phase change of circadian clock.

Animals↗
PubMed1994

The effect of repeated administration of methamphetamine on dopamine uptake sites in rat striatum.

In this experiment, rats were injected intraperitoneally with 6 mg/kg methamphetamine (MAP) hydrochloride or the same volume of saline once daily for 14 days. Rats were decapitated after a 1-day, 4-day or 10-day withdrawal period. The number and affinity of [3H]mazindol binding sites in the striatum were measured. Their number in the MAP group decreased as compared with controls after a 1-day withdrawal period, but returned to the control level after a 4-day and 10-day withdrawal period. These results are believed to show that the decrease in dopamine uptake sites after repeated administration of MAP is transient and does not contribute to MAP-induced behavioral sensitization.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Observation of idiopathic full-thickness macular holes. Follow-up observation.

OBJECTIVES: To evaluate the long-term follow-up observation of idiopathic full-thickness macular holes, with emphasis on the incidence and process of disappearance. METHODS: The authors followed up 97 eyes with idiopathic full-thickness macular holes for a period ranging from 2 to 182 months (average, 66 months). RESULTS: Apparent disappearance of the hole was observed in six eyes. Although improvement in visual acuity of at least 2 lines resulted in all six eyes, visual acuity improved to 20/30 or better in those eyes in which macular holes disappeared within 24 months of the initial examination. CONCLUSION: The incidence of apparent disappearance of idiopathic full-thickness macular holes was low. Improvement in visual acuity was greater in those cases in which macular holes disappeared in a relatively short period of time.

Aged↗
PubMed1994

High-dose chemotherapy and blood stem cell autografts for children with first relapsed acute lymphoblastic leukemia: a pilot study of the Children's Cancer and Leukemia Study Group of Japan (CCLSG).

This study was performed to determine the value of high-dose chemotherapy and peripheral blood stem cell autografts (PBSCT) in the treatment of children with first relapsed acute lymphoblastic leukemia (ALL). Eighteen children underwent PBSCT during the second complete remission (CR) and had a minimum 10 month follow-up. The median age of the patients was 11 yr (range, 2-17 yr). Fifteen patients received the "MCVAC" regimen, one received high-dose MCNU+busulfan therapy, one received high-dose melphalan+VP-16, and one received melphalan+carboplatin+cytosine arabinoside+MCNU. None of these regimens included total body irradiation. Eight patients developed recurrence of the disease at 1 to 19 mo (median, 3 mo) after PBSCT. Patients in whom the first relapse occurred sooner, that is, within 16 mo of initial therapy, tended to have a better survival rate than those who developed relapse after 30 mo (six of seven survived versus four of 11; not significant). Although the preliminary data provided little conclusive information, it did suggest that incorporation of PBSCT in the salvage protocol of relapsed childhood ALL can be justified.

Adolescent↗
PubMed1994

Biphasic and differential expression of cytosolic glutamine synthetase genes of radish during seed germination and senescence of cotyledons.

Three structurally distinct cDNA clones for cytosolic glutamine synthetase (GS1) were isolated from libraries prepared from senescing radish cotyledons. Northern blot analysis showed that transcripts from two of the three genes encoding GS1, Gln1;1 and Gln1;3, accumulated in the cotyledons during both dark-induced and natural senescence. Transcripts from the last gene, Gln1;2, remained at a low level during both processes. Transcripts from all three Gln1 genes accumulated in cotyledons of germinating seeds. We infer from these findings that GS1 enzymes function in both germination and senescence to convert ammonium to glutamine to remobilize nitrogen from source to sink organs. We have also examined the pattern of expression of these genes in different tissues. All three genes are expressed in roots. A large amount of transcripts from Gln1;1 accumulated in hypocotyls. Whereas none were transcribed in flowers. During dark-induced senescence of cotyledons, application of inorganic nitrogen delayed chlorophyll degradation. Inorganic nitrogen enhanced the accumulation of Gln1;1 transcripts, but decreased those of Gln1;3. In contrast, application of glutamine promoted yellowing of cotyledons during the dark treatment, and slightly increased the amounts of transcripts from Gln1;3 but decreased those of Gln1;1. Transcription of the three Gln1 genes appears, therefore, to be differentially regulated in radish cotyledons during senescence and germination.

Amino Acid Sequence↗
PubMed1994

Hyperammonemia induced in rats by inhalation anesthesia with ether.

Transient hyperammonemia was observed in rats after inhalation anesthesia with ether. The elevation of blood ammonia concentration induced by ether anesthesia was greatest in carbon tetrachloride injured and indomethacin-treated rats, but not observed in phenobarbital-treated rats. The results suggest interaction between ether metabolism and ammonia metabolism in the liver.

Ammonia↗
PubMed1994

Involvement of vasoactive intestinal polypeptide in NMDA-induced phase delay of firing activity rhythm in the suprachiasmatic nucleus in vitro.

Glutamate has been reported to be involved in the transmission of photic information from the retina to the suprachiasmatic nucleus (SCN). Therefore, we investigated whether the application of N-methyl-D-aspartate (NMDA), a glutamate receptor agonist could, reset the circadian rhythm of SCN firing activity in vitro. Treatment with NMDA for 1 h between projected zeitgeber time (ZT) 13-14 produced a phase delay in a concentration-dependent manner. The NMDA-induced phase delay was antagonized by an NMDA-receptor antagonist, MK-801 (100 microM). The retinohypothalamic tract has been reported to make terminals on neurons possessing vasoactive intestinal polypeptide (VIP). Therefore, we investigated the effect of NMDA on VIP release from the SCN and on VIP immunoreactivity in the SCN. Application of NMDA for 15 min between ZT 13-15 increased release of VIP from the SCN. In contrast to release, the content of VIP in the SCN tissue was reduced by application of NMDA. Immunohistochemical analysis revealed that application of NMDA for 4 h or 1 h reduced VIP immunoreactivity in the SCN. To investigate the possibility that VIP released by NMDA could reset SCN neuronal activity, we examined the effects of VIP on the SCN neuronal activity rhythm. Co-treatment with VIP (1 microM) and gastrin-releasing peptide (1 microM) for 1 h between ZT 13-14 caused a phase-delay of SCN activity rhythm. These findings suggest that activation of NMDA receptors during early subjective night causes a phase delay of the SCN neuronal activity via facilitation of VIP release in this nucleus.

Animals↗
PubMed1994

Platelet 3H-paroxetine binding in control subjects and depressed patients: relationship to serotonin uptake and age.

3H-paroxetine is regarded as a better ligand for the serotonin (5-hydroxytryptamine; 5-HT) uptake site than 3H-imipramine. In the present study, platelet 14C-5-HT uptake and 3H-paroxetine binding were simultaneously measured in 12 control subjects. There was a significant positive correlation between the individual Bmax value for 3H-paroxetine binding and the Vmax value for 14C-5-HT uptake. Platelet 3H-paroxetine binding was also determined in 21 drug-free patients who satisfied DSM-III-R criteria for major depression and 21 control subjects. A negative correlation was found between the Bmax values for 3H-paroxetine binding with age in control subjects. There was no change in 3H-paroxetine binding in depressed patients compared with control subjects. Our results indicated that 3H-paroxetine was a good ligand for evaluating 5-HT uptake sites, and the influence of age ought to be taken into consideration in the study of 3H-paroxetine binding. The present study indicated that there was no change in 5-HT uptake sites in platelets from depressed patients.

Adult↗
PubMed1994

Effects of glycyrrhizin on hepatitis B surface antigen: a biochemical and morphological study.

Glycyrrhizin, a major component of a herb (licorice), has been widely used to treat chronic hepatitis B in Japan. This substance improves liver function with occasional complete recovery from hepatitis; its effects on the secretion of hepatitis B surface antigen (HBsAg) were examined in vitro. Glycyrrhizin suppressed the secretion of HBsAg and accumulated it dose-dependently in PLC/PRF/5 cells. Its action was further analyzed and determined in the HBsAg-expression system using the varicella-zoster virus. Glycyrrhizin suppressed the secretion of HBsAg, resulting in its accumulation in the cytoplasmic vacuoles in the Golgi apparatus area. HBsAg labeled with 35S-methionine and cysteine accumulated in the cells and its secretion was suppressed dose-dependently in glycyrrhizin-treated culture. The secreted HBsAg was modified by N-linked and O-linked glycans but its sialylation was inhibited dose-dependently by glycyrrhizin. Thus glycyrrhizin suppressed the intracellular transport of HBsAg at the trans-Golgi area after O-linked glycosylation and before its sialylation. HBsAg particles were mainly observed on the cell surface in the glycyrrhizin-treated culture but not in the untreated culture. This suggests that asialylation of HBsAg particles resulted in the novel surface nature of glycyrrhizin-treated HBsAg particles. We elucidated the unique mechanism of action of glycyrrhizin on HBsAg processing, intracellular transport, and secretion.

Antiviral Agents↗
PubMed1994

[Studies on respiratory infections in primary care clinic (V). The pattern of distribution on bacteria, Mycoplasma pneumoniae and virus isolated from patients with respiratory infections, who were seen in six private clinics, and clinical efficacy of ciprofloxacin and roxithromycin].

The pattern of distribution of bacteria, Mycoplasma pneumoniae and virus isolated from the same specimen recovered from the throat swab or the sputum of 479 patients with respiratory infections who were seen in six private clinics in Sendai City of Japan during the period from October to November in 1992 (period I) and from January to February in 1993 (period II) was documented. Of the 479 patients, 234 had acute pharyngitis, 145 had acute bronchitis, 96 had influenza, 21 had acute tonsillitis, 5 had acute pneumonia and 9 had other respiratory infections. One hundred (42.4%) strains of potential pathogen and one strain of M. pneumoniae were recovered from 236 cases in period I, and 66 (27.2%) strains of potential pathogen, one strain of M. pneumonae and 73 strains of Influenza virus (30.0%: 43 of type A Hong-Kong and 30 of type B) from 243 cases in period II. Of the 166 strains, major isolates were Staphylococcus aureus (56 strains), Streptococcus pneumoniae (12 strains), Streptococcus pyogenes (15 strains), Haemophilus influenzae (17 strains), Esherichia coli (4 strains), Klebsiella spp. (35 strains), Pseudomonas aeruginosa (4 strains) and Acinetobacter spp. (23 strains). Only one strain of S. aureus was resistant to methicillin (MIC: 50 micrograms/ml). None of S. pneumoniae was resistant to 1 microgram/ml of ampicillin. Ciprofloxacin was administered to 113 cases and roxythromycin to 220 cases by doctors in charge.(ABSTRACT TRUNCATED AT 250 WORDS)

Ciprofloxacin↗
PubMed1994

Porphyromonas gingivalis fimbriae induce a 68-kilodalton phosphorylated protein in macrophages.

The present study was performed to examine whether Porphyromonas gingivalis fimbriae induce specifically a protein kinase-mediated phosphorylated protein that is involved in the mechanism of signal transduction. The fimbriae induced a 68-kDa phosphorylated protein (pp68) in a dose-dependent manner in mouse peritoneal macrophages. A marked appearance of pp68 was observed 20 min after the initiation of fimbrial treatment. The fimbria-induced pp68 was inhibited dramatically by staurosporine, a potent inhibitor of protein kinase C. pp68 induction was also inhibited by H-7, a potent inhibitor of several types of protein kinase. However, the induction was not inhibited by HA-1004 and H-8, relatively high-affinity inhibitors of protein kinase A. Phorbol myristate acetate and 1-oleoyl-2-acetyl-sn-glycerol, activators of protein kinase C, were able to induce pp68 in mouse peritoneal macrophages. This protein was localized in the cytosolic fraction of fimbria-treated macrophages. pp68 also was induced in fimbria-treated human monocyte-like cells. Finally, we observed that gene expression of the fimbria-induced neutrophil chemoattractant KC was inhibited markedly by staurosporine.

Alkaloids↗
PubMed1994

N-methyl-D-aspartate induces phase shifts in circadian rhythm of neuronal activity of rat SCN in vitro.

The suprachiasmatic nucleus (SCN) acts as a pacemaker for mammalian circadian rhythms. Receptors for excitatory amino acids like N-methyl-D-aspartate (NMDA) and non-NMDA receptors have both been found to play an important role in the transmission of photic information from the retina to the SCN. Therefore, we investigated whether the application of glutamate receptor agonists could reset the phase of the circadian rhythm of SCN firing activity in vitro. Treatment with NMDA (0.1-10 microM) for 15 min or 1 h during the early part of the subjective night produced phase delay, whereas treatment during the late subjective night caused an advance in phase. The phase-response curve for NMDA was similar to that previously obtained in response to light pulses in vivo. Application of DL-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrobromide (AMPA) (1 or 10 microM), a non-NMDA-receptor agonist, also produced a dose-dependent phase delay of SCN activity. The NMDA-induced phase delay was antagonized by an NMDA-receptor antagonist MK-801. These findings suggest that both NMDA and non-NMDA receptors may be involved in the transmission of information to the SCN via the retinohypothalamic tract. In addition, both the advances and delays in phase caused by NMDA were potentiated by cotreatment with neuropeptide Y, whereas AMPA-induced phase delay was not potentiated by neuropeptide Y. This points to a functional link between NMDA and neuropeptide Y receptor-mediated mechanisms in the SCN.

Animals↗
PubMed1994

An ex vivo assay for estimating the antiviral state of hepatocytes.

An ex vivo antiviral assay was established which uses hepatocytes from mice given recombinant mouse interferon-beta (rmIFN-beta). Assay results were compared with results obtained with a 2',5'-oligoadenylate synthetase (2-5AS) assay. rmIFN-beta was intraperitoneally administered to C3H mice and the antiviral state of their liver parenchymal cells was evaluated in an in vitro cytopathic effect assay. In this assay, cells are infected with vesicular stomatitis virus (VSV) and surviving cells are determined colorimetrically. The antiviral state was measured as the resistance of hepatocytes to VSV infection with increasing doses of rmIFN-beta. The antiviral state correlated well with the dose-dependent increase in hepatic 2-5AS activity. This good correlation suggests that induction of 2-5AS mediates the antiviral action of interferon in liver tissue. This ex vivo assay could be a useful tool for estimating the ability of hepatocytes to resist hepatitis virus infection.

Animals↗
PubMed1994

Release profiles of phenytoin from new oral dosage form for the elderly.

Utilization of the solid mass containing phenytoin, sodium caseinate and microcrystalline cellulose (MCC) as a new dosage form for the elderly was studied. The solid mass was prepared by treatment of the powder mixture with high pressure steam at 115 degrees C for 10 min. The stability of phenytoin in the solid mass was confirmed by infrared spectroscopy and high performance liquid chromatography. The extent of swelling of the solid mass containing phenytoin was investigated by water absorption test and gel strength test, and the swelling property was almost independent of the presence of phenytoin. The release profile of phenytoin from the solid mass was determined under various conditions, and was found to be influenced by the extent of swelling and the swollen state. It was observed that the protein adsorption to the phenytoin crystal surface and the addition of digestive enzyme also affected the release profile. In water, the solid mass prepared from a ground mixture of phenytoin and MCC showed remarkable improvement of release profile of phenytoin.

Absorption↗