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Biomedical subjects

M Yamada

Publications and source records attributed to M Yamada.

At least 667 records · Page 37Linked to original sources
PubMed1998

Comparison of antiviral compounds against human herpesvirus 6 and 7.

Four classes of antiviral compounds were evaluated for inhibitory activity against two variants of human herpesvirus 6 (HHV-6A and -6B) and human herpesvirus 7 (HHV-7). These included: (1) a pyrophosphate analog, phosphonoformic acid (PFA); (2) beta-guanine analogs, 9-(2-hydroxyethoxymethyl)guanine (acyclovir or ACV), 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (ganciclovir or GCV) and 9-(4-hydroxy-3-hydroxy-3-hydroxymethylbutylyl)guanine (penciclovir or PCV); (3) acyclic nucleoside phosphonates, (S)-1-[(3-hydroxy-2-phosphonylmethoxy)propyl]cytosine [cidofovir or (S)-HPMPC] and its cyclic derivative (S)-cyclic-HPMPC (cHPMPC), 9-[[2-hydroxy-1-phosphonomethoxy)ethoxy]methyl]guanine (HPMEMG) and 9-[(2-phosphonylmethoxy)ethyl]-2,6-diaminopurine (PMEDAP), and the seven other related compounds; and (4) a series of benzimidazole ribonucleosides, including 2-bromo-5,6-dichloro-1-(beta-D-ribofuranosyl)benzimidazole (BDCRB). End-point inhibitory concentration (EPC) and 50% effective inhibitory concentration (EC50) values were determined by a dot-blot antigen detection method in cord blood mononuclear cells infected with HHV-6A, HHV-6B or HHV-7 at a multiplicity of infection of 0.004 CCID50/cell. (S)-HPMPC and cHPMPC had an EC50 value of approximately 0.3 microg/ml for HHV-6A, 1.2 microg/ml for HHV-6B and 3.0 microg/ml for HHV-7. These compounds were the most active of those tested against each virus. The EC50 value of GCV for HHV-6A was 0.65 microg/ml, 1.33 microg/ml for HHV-6B, and >7 microg/ml for HHV-7. The EC50 values of ACV and PCV were approximately 6-8 microg/ml for HHV-6A, 16-24 microg/ml for HHV-6B and 121-128 microg/ml for HHV-7. These drugs were the least active. The sensitivity of HHV-7 to the guanine analogs was different from HHV-6, suggesting a difference in selectivity of specific viral enzymes.

Antiviral Agents↗
PubMed1998

Modulation of chromatic difference in receptive field size of H1 horizontal cells in carp retina: dopamine- and APB-sensitive mechanisms.

Chromatic aspects of receptive field size in the H1 horizontal cell syncytium of the carp retina were investigated using spectral photostimuli (blue or red) presented in the form of either a pair of a small spot and annulus, or a narrow moving slit. In the light-adapted retina, the receptive field for the blue stimulus was found to be significantly smaller than that for the red, i.e. there was a chromatic difference in the receptive field size. During the course of dark adaptation, the overall receptive field size increased, but the chromatic difference decreased. Immediately after adaptation to bright light, the receptive field sizes were reduced significantly, but the chromatic difference increased, mainly due to a greater reduction in the receptive field for the blue stimulus. Application of dopamine (5 microM) to a dark-adapted retina gradually decreased the receptive field size for both colours, but the chromatic difference became larger, again due to a greater reduction in the receptive field size for the blue stimulus. 2-Amino-4-phosphonobutyrate (APB) applied to light-adapted retinae at a working concentration of 1 mM, greatly expanded the receptive field size and suppressed the chromatic difference due to the effect being greater for the receptive field for the blue stimulus. The effect of APB was slow and cumulative. On the other hand, intracellular injection of cGMP or dibutyryl-cGMP increased the chromatic difference in the receptive field size. It is suggested (i) that the chromatic difference in the receptive field size could be due to a cGMP-coupled, conductance-decreasing receptor mechanism activated by APB; and (ii) that the mechanism is associated with short-wavelength sensitive cone input to the H1 cells and operates in the light-adapted state of the retina.

Adaptation, Ocular↗
PubMed1998

Effect of macrophage colony-stimulating factor on mouse NK 1.1+ cell activity in vivo.

The effect of recombinant human macrophage colony-stimulating factor (rhM-CSF) on NK 1.1+ cell activity in vivo and in vitro was studied. An intravenous injection of rhM-CSF increased the numbers of NK 1.1+ cells in mouse spleen and blood and augmented the clearance of Yac-1 cells in vivo. Using a magnetic cell sorter (MACS), we purified NK 1.1+ cells from vehicle-injected and rhM-CSF-injected mouse spleen cells. More than 95% of the collected cells were NK 1.1 antigen-positive. NK 1.1+ cells purified from rhM-CSF-injected mouse spleen cells exhibited (a) higher cytotoxic activity against Yac-1 cells, (b) higher proliferative responsiveness to interleukin (IL)-2 and (c) a greater production of interferon (IFN)-gamma in response to IL-2 and IL-12 compared to cells purified from vehicle-injected mouse spleen cells in vitro. These results suggest that the administration of rhM-CSF increases NK 1.1+ cell numbers and activates the cells in vivo.

Animals↗
PubMed1998

Enhanced depressor and hyperemic responses to calcitonin gene-related peptide in spontaneously hypertensive rats.

Intravenous (i.v.) bolus injection of calcitonin gene-related peptide (CGRP) caused a depressor response, which was significantly larger in 12-week-old spontaneously hypertensive rats (SHR) than in Wistar-Kyoto rats (WKY). CGRP also caused decreases in carotid and hindquarter vascular resistance, the magnitude of which was larger in the carotid than the hindquarter. In both regions, the vasodilator response to CGRP was significantly larger in SHR than WKY. Plasma CGRP level was significantly lower in SHR than WKY. These results suggest that depressor and vasodilator responses to CGRP are enhanced in SHR and that decreased plasma CGRP level in SHR may contribute to the enhanced responses.

Age Factors↗
PubMed1998

Anxiolytic effects of low-dose clomipramine in highly anxious healthy volunteers assessed by frontal midline theta activity.

1. The appearance of Fm theta, the distinct EEG theta rhythm in the frontal midline area during performance of a mental task, reflects relief from anxiety in humans. 2. In the present study, the anxiolytic effects of low-dose clomipramine were examined by monitoring the Fm theta amount, the STAI scores and the plasma 5-HIAA concentration in 24 male university students with (Fm theta group, n = 12) and without (non-Fm theta group, n = 12) Fm theta. 3. Subjects were given placebo, 10 mg and 30 mg clomipramine in a double-blind crossover design. Blood samples were obtained, STAI scores were determined, and EEGs were recorded before and during the performance of an arithmetic addition task. The test was repeated twice: before and 3 hrs after drug administration. 4. In the non-Fm theta group, 10 mg clomipramine decreased the 5-HIAA concentration and state anxiety scores but increased the Fm theta amount, while 30 mg clomipramine slightly increased only the Fm theta amount. However, there were no differences in these items before and after clomipramine administration in the Fm theta group. 5. These results suggest that low doses of clomipramine such as 10 mg may exert anxiolytic effects during the acute phase of treatment in highly anxious humans.

Adult↗
PubMed1998

Stress-dependent antinociceptive effects of carbamazepine: a study in stressed and nonstressed rats.

1. The present study examined the antinociceptive effects of carbamazepine on the tail flick test in stressed and nonstressed rats. 2. Carbamazepine produced a bimodal antinociceptive effect in stressed rats, the first peak appearing 30 min and the second 4 h after injection. Antinociceptive effect was not observed in nonstressed rats. 3. The secondary, but not the initial, carbamazepine antinociception in stressed rats was blocked by naloxone (0.2 mg/kg, i.p.), an opioid receptor antagonist. 4. Caffeine (5 mg/kg, i.p.), an adenosine A1/A2 receptor antagonist, inhibited the both initial and secondary antinociceptive effects of carbamazepine in stressed rats. 5. Carbamazepine increased the antinociceptive effect induced by either i.p. or i.c.v. administration of N6-cyclohexyl adenosine (CHA), an adenosine A1 receptor agonist, in stressed rats, but decreased it in nonstressed rats. 6. These results suggest that the initial antinociceptive effect of carbamazepine in stressed rats may be produced via an activation of the adenosine A1 receptors, such as was produced by CHA. The secondary long-lasting antinociceptive effects of carbamazepine may be mediated by an activation of opioid systems. 7. Furthermore, the initial activation of the adenosine A1 receptors by carbamazepine may be a triggering factor for the subsequent long-lasting activation of the opioid system, which results in the antinociception effects.

Adenosine↗
PubMed1998

Modification of cataleptic responses to dopamine receptor antagonists after withdrawal from chronic cocaine or cocaine plus dopamine antagonist administration.

1. In mice pretreated chronically with cocaine (indirect dopamine agonist: 10 mg/kg, s.c. on alternating days for 15 days), haloperidol (dopamine D2 antagonist: 0.3 mg/kg i.p.) exerted an enhanced cataleptic response, but SCH23390 (dopamine D1 antagonist: 0.3 mg/kg i.p.) produced an attenuated response at 24 h, which converted to a supernormal response, when it was administered 15-60 days after withdrawal from cocaine. 2. A challenge dose of SCH23390 exhibited enhanced catalepsy when given 15 days, but not at 24 h, after the last pretreatment dose of SCH23390 (0.1-1.0 mg/kg s.c.). In contrast, haloperidol catalepsy was not affected by the SCH23390 pretreatment. 3. However, in animals chronically pretreated with haloperidol (0.1-1.0 mg/kg s.c.), a challenge dose of SCH23390 as well as haloperidol exhibited attenuated cataleptic effects at 24 h and normal cataleptic responses at 15 days after the last dose of the pretreatment regimen. 4. Challenge doses of haloperidol or SCH23390 given to mice 24 h after chronic cocaine pretreatment produced enhanced and attenuated cataleptic responses, respectively; however, these responses were no longer produced when haloperidol or SCH23390 was given to mice pretreated chronically with a combination of cocaine and either haloperidol or SCH23390. 5. The enhanced catalepsy produced by a challenge dose of SCH23390 (15-60 days after chronic cocaine) was further potentiated when it was administered to animals that had been pretreated chronically with a combination of SCH23390 and cocaine, but was antagonized in animals pretreated chronically with haloperidol and cocaine. In contrast, the degree of enhanced cataleptic responses produced by a challenge dose of haloperidol 30-60 days after pretreatment chronically with a combination of cocaine + SCH23390 was similar to that seen after chronic cocaine alone. However, this enhanced response was antagonized in animals that had been pretreated chronically with the combination of cocaine + haloperidol. 6. The results suggest that the coadministration of SCH23390 with cocaine was able to block indirectly dopamine D2 receptor inhibition (subsensitivity) induced during the early withdrawal period from chronic cocaine, despite the fact that by itself SCH23390 did not have an effect on haloperidol catalepsy. Accordingly, the stimulatory effects of dopamine D2 receptors by a single administration of cocaine may be mediated mainly by an indirect stimulation of dopamine D2 receptor function via its D1 receptor stimulating action. 7. The coadministration of SCH23390 with cocaine rather aggravate the subsensitive effect of dopamine D1 receptors (increased SCH23390 catalepsy) produced during long-term withdrawal period from chronic cocaine, but did not affect that of the dopamine D2 receptor. On the other hand, the coadministration of haloperidol with cocaine normalized both D1 and D2 receptor subsensitive effect. 8. These result suggest that a single administration of SCH23390 or haloperidol after long-term withdrawal periods from chronic cocaine may not be effective as antipsychotic drugs because of further aggravation of suppressive behaviors. These results also provide evidence that D2 receptor antagonists may be more effective as antipsychotic drugs than dopamine D1 receptor antagonist, since the coadministration of haloperidol with cocaine normalized the abnormal behaviors seen during early and long-term withdrawal periods from chronic cocaine.

Animals↗
PubMed1998

Risk factors of pneumonitis following chemoradiotherapy for lung cancer.

The purpose of this retrospective study was to identify risk factors associated with development of pneumonitis following chemoradiotherapy (CRT). We examined 60 patients (pts) who received CRT from May 1993 to August 1995. Factors evaluated included total radiation dose, field-size, irradiated site, type of chemotherapy, pulmonary fibrosis and treatment schedule (concurrent versus sequential). There were 17 pts (28.3%) who had > or = Grade 2 pulmonary toxicity. There was no significant relationship between total radiation dose, field-size > or = 200 cm2, pulmonary fibrosis or treatment schedule and risk of pneumonitis. In the sequential treatment group (22 pts), no relationship was noted between any factor and the risk of pneumonitis, while in the concurrent treatment group (38 pts), the incidence of pneumonitis was more frequent (53.8%) in patients with field-size > or = 200 cm2 than in patients with field-size < 200 cm2 (P < 0.05). In those who received concurrent treatment, including weekly CPT-11, pneumonitis was more frequent (56.3%) than in those without CPT-11 (13.6%, P < 0.01). When the lower lung field was included in the radiation site, the incidence of pneumonitis was 70% compared with 20% for other sites (P < 0.01). Multivariate analysis revealed a significant relationship between radiation site and the risk of pneumonitis (P = 0.0096). CPT-11 was significant (P = 0.038) only in the concurrent group. Pneumonitis was reversible in all but one pt by steroid therapy. Thus, irradiated site (included lower lung field) and concurrent CRT used with weekly CPT-11 were treatment factors significantly associated with a higher risk of pneumonitis following CRT.

Adult↗
PubMed1998

Fetal ventricular tachycardia in long QT syndrome.

We report a case of a fetus presenting intermittent ventricular tachycardia during mid-gestation, whose mother had long QT syndrome. The arrhythmia disappeared spontaneously, and the electrocardiogram of the baby after birth showed prolonged QTc. As far as we are aware, this is the first case in which ventricular tachycardia was documented during fetal life in a baby with long QT syndrome.

Adult↗
PubMed1998

Photodegradation products of methylprednisolone suleptanate in aqueous solution--evidence of a bicyclo[3.1.0]hex-3-en-2-one intermediate.

Two major photodegradation products of methylprednisolone suleptanate (sodium 11 beta, 17 alpha-dihydroxy-6 alpha-methyl-21-[[8-[methyl(2-sulfoethyl)amino]-1,8-dioxooctyl+ ++]oxy]-pregna-1,4-diene-3,20-dione) in aqueous solution irradiated with white fluorescent light at 2000 lux for 28 days at 25 degrees C were isolated by preparative high-performance liquid chromatography and characterized. Structures of the photodegradation products were determined as sodium 11 beta,17 alpha-dihydroxy-5 alpha, 6 alpha-dimethyl-21-[[8-[methyl(2-sulfoethyl)amino]-1,8-dioxoocty l]-oxy]-19-norpregna-1(10),3-diene-2,20-dione and sodium 1 beta, 11 beta-epoxy-17 alpha-hydroxy-6 alpha-methyl-21-[[8-[methyl(2-sulfoethyl)amino]-1, 8-dioxooctyl]oxy]-19 alpha-pregn-4-ene-2.20-dione. Formation of these compounds, especially the 1,11-epoxy analogue, strongly supports the existence of the bicyclo[3.1.0]hex-3-en-2-one intermediate in the photorearrangement of steroidal cross-conjugated dienones. The intermediate can account for all the major ketonic and phenolic products; these products are generated from the intermediate after subsequent transformations and/or further skeletal rearrangements. The 1,11-epoxy analogues were obtained from the prednisolone steroids in high yields by irradiation with a high-pressure mercury lamp.

Drug Stability↗
PubMed1998

In vitro study on intrathecal use of 5-fluoro-2'-deoxyuridine (FdUrd) for meningeal dissemination of malignant brain tumors.

We investigated 5-fluoro-2'-deoxyuridine (FdUrd) as a potential agent for intrathecal treatment of malignant brain tumors with meningeal dissemination. We examined the neurotoxicity of FdUrd in vitro using primary cultures of neurons from C57BL/6 mice (ED14). Tumoricidal activity was also studied in four glioma cell lines and one medulloblastoma cell line. In addition, thymidine phosphorylase (TPase) and thymidine kinase (TK), which are key enzymes for FdUrd metabolism, were measured in the cerebrospinal fluid (CSF) of 36 patients with brain tumors. The antitumor activity of FdUrd for murine glioma cells was approximately 20- to 200-fold higher than that of 5-fluorouracil (5-FU). Against human cell lines, it was 3- to 500-fold higher than that of 5-FU. The neurotoxic effect of FdUrd on cultured neurons was far less than that of 5-FU or 5-fluorouridine (FUrd). Cerebrospinal fluid contained no detectable thymidine phosphorylase in most patients with brain tumors. Several studies have indicated that FdUrd is rapidly converted to 5-FU in the presence of thymidine phosphorylase, so that a high dose of FdUrd must be administered to obtain good efficacy. However, a high dose FdUrd frequently cause severe toxicity. In contrast, the data obtained here suggest that no enzymatic conversion of FdUrd to 5-FU should occur in the CSF. In addition, FdUrd has an excellent antitumor activity and minimal neurotoxicity. We therefore conclude that intrathecal FdUrd is a potential therapy for CSF dissemination of malignant brain tumors.

Animals↗
PubMed1998

Oxygen toxicity induces apoptosis in neuronal cells.

1. A high oxygen atmosphere induced apoptosis in cultured neuronal cells including PC12 cells and rat embryonic cortical, hippocampal, and basal forebrain neurons associated with DNA fragmentation and nuclear condensation. 2. The sensitivity of CNS neurons to a high-oxygen atmosphere was the following order; cortex > basal forebrain > hippocampus. 3. Cycloheximide and actinomycin-D inhibited the apoptosis, indicating that it depends on new macromolecular synthesis. In contrast, cultured postnatal CNS neurons were resistant to oxidative stress. 4. Neurotrophic factors such as nerve growth factor (NGF), fibroblast growth factor (FGF), and epidermal growth factor (EGF) blocked the apoptosis induced by a high-oxygen atmosphere.

Animals↗
PubMed1998

Multiple endocrine neoplasia 2B with glaucoma associated with codon 918 mutation of the RET proto-oncogene.

PURPOSE: We report the first case of a 35-year-old Japanese man with multiple endocrine neoplasia (MEN) 2B de novo to be associated with primary open angle glaucoma. METHODS: DNA was extracted from the patient's circulating leukocytes, specimens of the resected cervical lymph nodes, the neuroma of the eyelid, and of the conjunctival epithelium. Mutation was assayed by PCR/restriction enzyme and direct sequencing. RESULTS: The glaucoma and MEN 2B were diagnosed at the same time, when the patient was 16 years old. The glaucoma was controlled by medical treatment. The codon 918 mutation (met918thr) in exon 16 of the RET proto-oncogene associated with MEN 2B was identified in all these tissues. CONCLUSION: This patient was found to have the germline mutation at codon 918 (met918thr) in the RET proto-oncogene. The association between the RET proto-oncogene and glaucoma remains unclear, since glaucoma is a rare manifestation of MEN 2B.

Adult↗
PubMed1998

Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretch.

To elucidate the molecular mechanisms whereby expanded polyglutamine stretches elicit a gain of toxic function, we expressed full-length and truncated DRPLA (dentatorubral-pallidoluysian atrophy) cDNAs with or without expanded CAG repeats in COS-7 cells. We found that truncated DRPLA proteins containing an expanded polyglutamine stretch form filamentous peri- and intranuclear aggregates and undergo apoptosis. The apoptotic cell death was partially suppressed by the transglutaminase inhibitors cystamine and monodansyl cadaverine (but not putrescine), suggesting involvement of a transglutaminase reaction and providing a potential basis for the development of therapeutic measures for CAG-repeat expansion diseases.

Animals↗
PubMed1998

SUR2 subtype (A and B)-dependent differential activation of the cloned ATP-sensitive K+ channels by pinacidil and nicorandil.

1. The classical ATP sensitive K+ (K(ATP)) channels are composed of a sulphonylurea receptor (SUR) and an inward rectifying K+ channel subunit (BIR/Kir6.2). They are the targets of vasorelaxant agents called K+ channel openers, such as pinacidil and nicorandil. 2. In order to examine the tissue selectivity of pinacidil and nicorandil, in vitro, we compared the effects of these agents on cardiac type (SUR2A/Kir6.2) and vascular smooth muscle type (SUR2B/Kir6.2) of the K(ATP) channels heterologously expressed in HEK293T cells, a human embryonic kidney cell line, by using the patch-clamp method. 3. In the cell-attached recordings (145 mM K+ in the pipette), pinacidil and nicorandil activated a weakly inwardly-rectifying, glibenclamide-sensitive 80 pS K+ channel in both the transfected cells. 4. In the whole-cell configuration, pinacidil showed a similar potency in activating the SUR2B/Kir6.2 and SUR2A/Kir6.2 channels (EC50 of approximately 2 and approximately 10 microM, respectively). On the other hand, nicorandil activated the SUR2B/Kir6.2 channel > 100 times more potently than the SUR2A/Kir6.2 (EC50 of approximately 10 microM and > 500 microM, respectively). 5. Thus, nicorandil, but not pinacidil, preferentially activates the K(ATP) channels containing SUR2B. Because SUR2A and SUR2B are diverse only in 42 amino acids at their C-terminal ends, it is strongly suggested that this short part of SUR2B may play a critical role in the action of nicorandil on the vascular type classical K(ATP) channel.

ATP-Binding Cassette Transporters↗
PubMed1998

Investigation of glucocorticoid-induced apoptotic pathway: processing of caspase-6 but not caspase-3.

Glucocorticoids (GCs) are essential therapeutic reagents for the treatment of lymphomas and leukemias. GCs cause cell death in certain types of lymphoid cells mediated by the process known as apoptosis. This cell death is completely inhibited by Bcl-2. Here we report that Bcl-2 and benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD-fmk), a broad spectrum caspase inhibitor, prevent loss of mitochondrial membrane potential (delta psi m) and the production of reactive oxygen species (ROS) caused by GC, while acetyl-Asp-Glu-Val-Asp-aldehyde (Ac-DEVD-CHO), an inhibitor of the caspase-3 family proteases, does not. This suggests that the inhibition by Bcl-2 and activation of some initiator caspases are upstream events of mitochondrial damage, whereas the activation of caspase-3 family proteases occurs downstream of mitochondrial changes. We also demonstrate that caspase-6 but not caspase-3 is cleaved and activated during GC-mediated apoptosis and that poly(ADP-ribose) polymerase (PARP), a substrate of caspases, also undergoes proteolysis. In addition, we provide the evidence that DNA fragmentation is markedly inhibited by Ac-DEVD-CHO, while cell death, assessed by the damage of the plasma membrane, is marginally inhibited or merely delayed.

Amino Acid Chloromethyl Ketones↗
PubMed1998

Efficient Fas-ligand gene expression in rodent liver after intravenous injection of a recombinant adenovirus by the use of a Cre-mediated switching system.

An adenovirus vector AxCALNFasL was constructed in order to transduce a gene for rat Fas-ligand, requiring co-expression of Cre recombinase for its expression. In the cosmid cassette, pAxCALNFasL, a stuffer DNA fragment flanked with two loxP sequences was placed between the promoter and Fas-ligand cDNA to prevent its expression in transfected 293 cells. COS-7 cells infected with AxCALNFasL alone did not induce apoptosis in cocultivated Jurkat cells, but the cells treated with AxCALNFasL and AxCANCre (an adenovirus expressing Cre recombinase with the CAG promoter) did. BALB/c mice injected with 10(9) plaque-forming units of AxCALNFasL and with different doses of AxCANCre, developed lethal acute liver failure. The number of the apoptotic hepatocytes increased dramatically with increased doses of injected AxCANCre, indicating that the level of transgene expression in the rodent liver appeared to be adjustable. Based on these observations, we conclude that vectors expressing a gene to produce cytotoxic substances can be constructed by the use of a Cre-mediated switching system. Our system also demonstrated that efficient expression of the toxic gene in the rodent liver was achievable by co-infection of adenovirus vectors carrying the target gene and Cre recombinase.

Adenoviridae↗