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Biomedical subjects

R Murata

Publications and source records attributed to R Murata.

At least 73 records · Page 4Linked to original sources
PubMed1995

Histopathological evaluation of gastric mucosal environments in peptic ulcer using the endoscopic 5-point gastric biopsy method.

Although a strong association has been established between chronic Helicobacter pylori infection and peptic ulcers, the role of H. pylori is not necessarily causative because there are many patients infected with H. pylori who do not develop peptic ulcer. Therefore, we studied the relationship between the gastric mucosal environment and the development of peptic ulcers. We examined 165 endoscopic biopsy specimens from the gastric mucosa of 33 patients with peptic ulcers using the 5-point gastric biopsy method. The follow-up biopsies done within 3 weeks were well correlated with the first biopsy samples. We also reviewed the clinicohistopathological findings of 2250 endoscopic biopsy specimens from 450 patients with active gastric and/or duodenal ulcers. Over 90% of the patients with duodenal ulcer, with or without gastric ulcer, had no fundic gland atrophy, and a high incidence of intestinal metaplasia and pyloric mucosal atrophy was found in the patients with gastric ulcer. These findings suggest that patients with concomitant active gastric and duodenal ulcers exhibit severe atrophic changes in the antral mucosa but not in the fundic mucosa.

Adult↗
PubMed1995

Manganese chloride treatment does not protect against acute radiation injury of skin or crypt cells.

Metallothionein (MT), the synthesis of which can be induced by metalloelement administration, is a known radical scavenger. This study investigated the possible protective effect of MT against acute radiation injury. Manganese chloride (10 mg of manganese/kg) was administered intraperitoneally to male C3H/He mice 24 h prior to irradiation. The paw of each mouse was irradiated locally, and the acute skin reaction was scored daily and averaged. Acute radiation injury of the small intestine was studied using an LD50/8 assay and a gut microcolony assay after abdominal irradiation. An LD50/8 value represents the radiation dose required to kill 50% of animals within 8 days. The number of microcolonies per tissue section was counted 3.5 days after irradiation. The level of MT in the liver, skin and intestine was determined by a modified 203Hg-binding assay. Acute skin reaction was not prevented by manganese pre-administration. The LD50/8 values of manganese-pretreated and control mice were 19.4 and 18.4 Gy, respectively. However, the difference was not significant. The number of microcolonies was not significantly different for these two groups in the dose range of 13-19 Gy. The level of MT in the skin and intestine was not increased by administration of manganese, although a sixfold increase was observed in the liver. In conclusion, manganese chloride treatment of mice 24 h prior to irradiation did not significantly protect skin and small intestine against acute radiation injury, because such a treatment did not result in increased levels of MT in the skin and small intestine.

Animals↗
PubMed1995

Subacute sclerosing panencephalitis aggravated during the intraventricular interferon administration therapy.

Human lymphoblastoid interferon-alpha was given by intraventricular administration via an Ommaya reservoir to a woman who entered Jabbour stage III at the age of 25 years. The first dose was of 150,000 IU, and daily doses were gradually increased; the total dose over a 42-day period was 33,550,000 IU. The patient's neurological disability index score before this treatment was 56.3%, and 75% after interferon treatment ended. After other treatment for 6 months, the patient died. Results of the autopsy showed perivascular lymphocyte infiltration in the cerebrum and brain stem, with diffuse gliosis and demyelination. The virus was isolated from the frontal lobes, also. The interferon treatment may have been a factor in this patient's deterioration.

Adult↗
PubMed1995

Combined effects of buthionine sulfoximine and cepharanthine on cytotoxic activity of doxorubicin to multidrug-resistant cells.

We studied the potentiation of doxorubicin (DOX) activity in multidrug-resistant (MDR) cells by buthionine sulfoximine (BSO), a specific inhibitor of gamma-glutamylcysteine synthetase, and by cepharanthine (CE), which interacts with P-glycoprotein. The glutathione (GSH) of MDR cells was approximately 1.5-fold greater than that of the parental cell line. BSO reduced GSH content of MDR cells compared to that of the sensitive ones. The BSO treatment (50 microM) enhanced the effect of DOX by 1.8-fold, while CE caused a greater reversal of drug resistance. The combination of BSO with CE produced further potentiation of DOX activity in an antiproliferative effect. Pretreatment of cells with BSO did not alter the cellular accumulation of DOX in the absence or presence of CE. The addition of BSO (30 mM) to the drinking water of mice reduced the tissue levels of GSH in tumor cells, suggesting that the marked decrease in GSH might diminish the ability of that tumor to resist DOX. Combined administration of CE and DOX resulted in enhancement of DOX antitumor activity and prolongation of survival time. The survival of mice treated with BSO and CE as a supplement to DOX treatment was superior that of mice receiving DOX alone. These studies demonstrated that the combinations of BSO with CE may be useful for killing drug-resistant tumor cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Three-dimensional treatment planning for maxillary cancer using a CT simulator.

PURPOSE: The results of three-dimensional treatment planning using a computed tomography simulator were evaluated in patients with maxillary cancer. METHODS AND MATERIALS: Treatment planning was done in 25 patients using an x-ray simulator and plain x-ray films (1979-1982, group 1) in 34 patients using an x-ray simulator and computed tomography films (1983-1987, group 2), in 24 patients using a computed tomography simulator (1988-1992, group 3). The number of patients with Stage IV disease increased in the order of group 1 to group 3. RESULTS: The average radiation field was smallest in group 3 (66.5 cm2) followed by group 2 (67.4 cm2) and group 1 (72.9 cm2). A radiation dose of more than 30 Gy to the lens of the effected side was delivered to 13% of group 3, 44% of group 2, and 44% of group 1. The dose to the lens on the uneffected side was zero in 56% of group 1, 74% of group 2, and 96% of group 3. A long-term decrease in visual activity on the effected side occurred in 11% of group 3, 32% of group 2, and 44% of group 1. However, a significant increase in survival was only noted between groups 1 and 2, because the three population of patients were different. CONCLUSION: The three-dimensional treatment planning results in a better treatment than two-dimensional treatment planning as measured by complication rates and field sizes.

Aged↗
PubMed1994

Reoxygenation in the SCCVII tumor after KU-2285 sensitization plus single or fractionated irradiation.

PURPOSE: Because reoxygenation of solid tumors after irradiation with a hypoxic cell sensitizer has never previously been investigated, we assessed the reoxygenation in SCCVII tumors after treatment with KU-2285 plus single or fractionated irradiation. METHODS AND MATERIALS: KU-2285 (100 mg/kg) was injected intraperitoneally into C3H mice bearing 1-cm SCCVII tumors at 30 min before a single dose of 12 Gy or three fractions of 5 Gy at 12 h intervals. Changes of the hypoxic fraction (HF) were then evaluated by the paired survival curve method. RESULTS: Since the radiosensitizing effect of KU-2285 was relatively persistent, the HF was only evaluable after 6 h of irradiation. The HF of untreated SCCVII tumors was 9.1%. After treatment with KU-2285 and 12 Gy, the HF was 25% at 6 h, 32% at 12 h, 24% at 24 h, and 7.6% at 72 h. The HF was lower at 6 h than that after radiation alone, but was similar at later periods. After three fractions of 5 Gy with or without KU-2285, the HF was 33% at 6 h in both groups, while it was 12% and 13% at 24 h for tumors pretreated with KU-2285 and those receiving radiation alone, respectively. However, a sensitizing effect of KU-2285 was indicated by the downward shift of the survival curves for tumors irradiated after exposure to this agent. CONCLUSION: Reoxygenation occurred quite efficiently in tumors receiving KU-2285 and 12 Gy. After fractionated irradiation, however, reoxygenation was similar in the KU-2285-pretreatment and irradiation alone groups.

Animals↗
PubMed1994

Comparison of radiosensitizing effect of KU-2285 and SR-2508 at low drug concentrations and doses.

PURPOSE: Since the radiosensitizing effect of KU-2285 at relatively low dose levels is not known, we investigated its efficacy at such low concentrations or doses achievable in humans with oral administration of 0.3-1.0 g/m2. METHODS AND MATERIALS: KU-2285 was tested in comparison with SR-2508 at low concentrations (0.05-0.25 mM) in vitro by the cytokinesis-block micronucleus assay and by the colony formation assay, and at low drug doses (12.5-50 mg/kg) in vivo by the in vivo-in vitro assay and by the growth delay assay using SCC VII tumors in C3H/He mice. RESULTS: In the cytokinesis-block micronucleus assay, the sensitizer enhancement ratio (SER) for KU-2285 and SR-2508 was 1.43 and 1.17 at 0.05 mM, 1.75 and 1.27 at 0.10 mM, and 2.14 and 1.69 at 0.25 mM, respectively. In the colony formation assay, the SER for KU-2285 was also greater than that for SR-2508. In the in vivo-in vitro assay, the SER for KU-2285 and SR-2508 was 1.11 and 1.04 at 12.5 mg/kg, 1.21 and 1.04 at 25 mg/kg, and 1.26 and 1.18 at 50 mg/kg, respectively. In the growth delay assay at 50 mg/kg, no tumor regrowth was observed in four of the 18 mice treated with KU-2285 + 25 Gy, although the growth delay time for the remaining mice was similar to that for SR-2508 + 25 Gy. CONCLUSION: KU-2285 was more effective than SR-2508 both at low drug concentrations in vitro and at low drug doses in vivo. These promising findings suggest the potential superiority of KU-2285 over SR-2508 as a radiosensitizer for clinical use.

Animals↗
PubMed1994

KIN-804 vs. KU-2285 as a radiosensitizer for clinical use.

PURPOSE: The in vitro and in vivo effects of two promising hypoxic cell radiosensitizers, KIN-804 (KIN) and KU-2285 (KU), were compared using four types of assays, and the acute toxicity and pharmacokinetics of KIN were investigated to evaluate the clinical applicability of the compounds. METHODS AND MATERIALS: To evaluate the in vitro effect at low radiation doses (1-4.5 Gy), the cytokinesis-block micronucleus (MN) assay using SCCVII or EMT-6 cells and the chromosomal aberration (CA) assay using EMT-6 cells were performed. In addition, an in vivo-in vitro colony assay, a growth delay assay, and a pharmacokinetic study were performed using C3H mice bearing SCCVII tumors, and the LD50/7 was determined in ICR mice. RESULTS: In the in vitro MN assay, the sensitizer enhancement ratio (SER) at 0.1, 0.25, 1, and 5 mM with SCCVII cells, and at 1 mM with EMT-6 cells was respectively, 1.45, 1.61, 2.57, 4.22, and 1.96 for KIN, and 1.57, 1.62, 2.59, 5.66, and 2.21 for KU. In the in vitro CA assay, the SER at 1 mM was 1.78 for KIN and 1.79 for KU. In the in vivo-in vitro colony assay, the SER of KIN at 50, 100, and 200 mg/kg was 1.24, 1.30, and 1.45, respectively, while the SER of KU at 100 mg/kg was 1.41. In the growth delay assay, the growth delay time for 100 and 200 mg/kg of the drug plus 20 Gy of radiation was respectively, 16.5 and 19.1 days for KIN, and 18.9 and 24.0 days for KU. In all experiments, the sensitizing effect of KIN was almost equal to that of KU. The LD50/7 of KIN was 3.6 g/kg by intraperitoneal injection, while that of KU was 3.6 g/kg by intraperitoneal injection, and the pharmacokinetic study of KIN revealed a low uptake of the drug by the brain. CONCLUSION: Both KIN and KU had a definite sensitizing effect even at lower drug concentrations or doses, suggesting their potential usefulness in clinical radiotherapy.

Animals↗
PubMed1994

Characterization of a Rana catesbeiana lectin-resistant mutant of leukemia P388 cells.

Sialic acid-binding lectin (SBL-C) from Rana catesbeiana eggs inhibits the growth of tumor cells such as P388 and L1210 leukemia cells (K. Nitta et al., Cancer Res., 54: 920-927, 1994). Here we report the establishment of an SBL-resistant P388 variant cell line, RC-150. Both P388 and RC-150 cells were agglutinated by SBL-C; however, growth of RC-150 cells was unaffected by SBL-C. Cytoplasmic free Ca2+ concentration and transglutaminase activity of RC-150 cells were 0.5 (110 nM) and 3 times (0.62 nmol/mg/min) as high as those of P388 cells, respectively. Microvilli and microplicae were observed on the surface of P388 cells by scanning electron microscopy but were rarely seen on RC-150 cells. Dansylcadaverine-labeled SBL-C bound to both P388 and RC-150 cells. Binding of SBL-C to these tumor cells appears to be mediated by two species of wheat germ agglutinin-stained cell membrane sialoglycoproteins. Labeled SBL-C entered P388 but not RC-150 cells, suggesting that internalized SBL-C acts as an inhibitor of cell proliferation.

Agglutination↗
PubMed1994

Effects of an N-methyl-D-aspartate antagonist and a GABAergic antagonist on entorhinal tetanic responses during the early stages of amygdala kindling in rats.

Changes in synaptic potentials during each train stimulation (tetanic responses) have been suggested to intimately relate to the development of kindling. We examined the effects of an NMDA antagonist, carboxypiperazinephosphonate (CPP), and a GABAergic antagonist, picrotoxin, on entorhinal tetanic responses evoked by train stimuli (10 Hz, 100 pulses) at the developmental stage (seizure stage; 0-2) of amygdala kindling in conscious rats, to clarify the significance of facilitation in tetanic responses and the roles of NMDA and GABA receptors in the development of kindling. Facilitation of tetanic responses was noted as a progressive increase in both amplitude and duration of negative potentials in the tetanic responses, especially during the later half of train pulses (51-100). The negative potential area (mV x ms) of the averaged tetanic responses was used as an estimate of the magnitudes of excitatory synaptic activity in the tetanic responses, and correlated significantly (P < 0.001) with the duration of afterdischarges (AD). CPP (10 mg/kg) reversibly blocked AD in association with a significant decrease (P < 0.05) in the negative potential area. The CPP-sensitive component consisted of a slow negative potential with a duration longer than 60 ms and was greater in the later tetanic responses (51-100) than the earlier ones (1-50). Picrotoxin (2-3 mg/kg), which did not produce convulsions, significantly (P < 0.005) increased the negative potential area in the tetanic responses in association with a reversible decrease in the AD threshold. Although positive potentials ascribable to inhibitory synaptic activity were often negligible in the tetanic responses in controls, picrotoxin further decreased the positive potentials of tetanic responses, if any.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗
PubMed1994

[Clinical results of breast conservation therapy; a radiotherapeutical viewpoint].

Between November 1987 and March 1993, 244 breasts in 243 patients underwent breast conserving therapy at Kyoto University Hospital. Clinically, there were 159 stage I and 85 stage II tumors. Pathological staging showed 216 stage I, 24 stage II, and 4 stage III tumors. All except 10 tumors were invasive ductal carcinomas. Eleven tumors were margin--positive by histopathological examinations. As surgical treatment, quadrantectomy or wide excision with complete axillary dissection was performed. Radiation therapy consisted of 50 Gy delivered to the whole breast by opposed tangential fields over 5 weeks using 60Co gamma rays. For patients with a positive margin, boost electron irradiation was given to a total of 10 Gy. We used the CT simulator for individualized optimization of the tangential fields. Prompt and accurate determination of the tangential portals was possible by using the simulator to determine various parameters, including beam angle and the head rotation angle. During follow-up for 2-66 months (median, 20 months), unrelated death occurred in 2 patients and distant metastases developed in 5 patients (bone 4, lung 1). However, neither local recurrence nor symptomatic radiation pneumonitis has occurred. The cumulative survival rate and the disease--free survival rate at five years were 95.2% and 91.8%, respectively. These promising clinical results of breast conservation therapy encourage further clinical trials.

Breast Neoplasms↗
PubMed1994

Intraarterial infusion of autologous lymphocytes for the treatment of refractory lymphoedema. Preliminary report.

OBJECTIVE: To evaluate the results of the treatment of lymphoedema by intra-arterial infusion of autologous lymphocytes. DESIGN: Open study. SETTING: University Hospital. SUBJECTS: 13 patients with refractory lymphoedema. INTERVENTIONS: Lymphocytes were separated from the patient's own blood using a blood cell separator; about 100 cc of lymphocyte dominant blood separated from this blood was immediately infused into the proximal artery of the affected limb. Infusion was practiced once a week, and repeated 4 to 6 times. MAIN OUTCOME MEASURES: Change in size of the affected limb (defined as the difference between the affected limb and the normal limb after treatment), and softening of the edema (measured with a tension gauge). RESULTS: In all 13 patients there was softening of the affected hard limb followed by a reduction in the size of the limb (mean 64%), and the ache and sensation of heat in the limb lessened. The reduction in size was maintained in 9 of the 13 patients for three months, despite returning to their normal activities. CONCLUSION: Intra-arterial infusion of autologous lymphocytes is a promising treatment for refractory lymphoedema.

Adolescent↗
PubMed1993

Vertical transmission of hepatitis C virus (HCV) detected by HCV-RNA analysis.

The rate of transmission of hepatitis C virus (HCV) from patients with chronic hepatitis C to their children was studied. Of the 64 children with a parent with chronic hepatitis C, two (3%) had abnormal alanine aminotransferase (ALT) activities, six (9%) had anti-HCV detected by c100 ELISA, seven (11%) had anti-HCV detected by ELISA-II, and 21 (33%) had HCV-RNA by polymerase chain reaction (PCR). Anti-HCV detected by ELISA-II disappeared within six months in all six infants. Of the five children whose mothers were given a blood transfusion after the child's first birthday, none had anti-HCV or HCV-RNA. In the five families whose elder or eldest offspring had HCV-RNA, all of the younger offspring had HCV-RNA. The vertical transmission rate of HCV was low if judged by the presence of anti-HCV or abnormal ALT values, but the rate was high (33%) if judged by the presence of HCV-RNA.

Adolescent↗
PubMed1993

Enhancement of synaptic facilitation during the progression of kindling epilepsy by amygdala stimulations.

1. A quantitative analysis of facilitation during the kindling stimulation to the amygdala was conducted by measuring the area between the excitatory potential and the baseline in the averaged tetanic response recorded at the entorhinal cortex. The changes in facilitation were then compared with the development of electrographic afterdischarges (AD) and behavioral seizures in response to successive kindling stimulations. 2. Kindling train pulses (n = 99 or 100; duration: 0.5 ms; frequency: 10 Hz; intensity: AD threshold) were applied to conscious rats until at least one generalized seizure occurred or until 13 stimuli were delivered. 3. Facilitation of the entorhinal responses by kindling stimulation first occurred in the monosynaptic excitatory component and was then followed by a progressive increase in the polysynaptic component that was manifested as the later negative peaks. A clear progressive enhancement was observed in the facilitation by successive kindling stimulations, which also induced prolongation of the AD duration and progression of the seizure stages, indicating that activity-dependent enhancement of facilitation (EF) occurred during the progression of kindling epilepsy. 4. Quantitative analysis revealed that the EF that occurred with the progression of seizure stages was statistically significant (P < 0.001, Friedman test). The AD duration (r = 0.89) and the long-term potentiation (r = 0.85) of the entorhinal responses by single test amygdala stimuli showed a very good linear relation to the EF.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗