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Biomedical subjects

R Murata

Publications and source records attributed to R Murata.

At least 19 recordsLinked to original sources
PubMed2004

Tumour-specific enhancement of thermoradiotherapy at mild temperatures by the vascular targeting agent 5,6-dimethylxanthenone-4-acetic acid.

The effect of combining the vascular targeting agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) with both radiation and hyperthermia treatments was investigated in a transplanted C3H mouse mammary carcinoma and a normal mouse tissue. Tumours were grown on the right rear foot of female CDF1 mice and treated when sized 200 mm3. The foot skin of non-tumour-bearing CDF1 mice was used to assess normal tissue damage. Radiation and hyperthermia were given locally to the tumour/skin of restrained non-anaesthetized animals. DMXAA (20 mg/kg) was dissolved in saline and injected intraperitoneally 1 h after irradiating and then heating started 3 h later. The endpoints were local tumour control within 90 days or the development of moist desquamation in skin between 11 and 23 days after treatment. The radiation dose (+/- 95% confidence intervals) producing local tumour control in 50% of treated animals was 53 (51-55) Gy for radiation alone. This value was significantly (Chi-squared test; p < 0.05) decreased to 47 (42-52) Gy by DMXAA and to 47 (44-51) Gy by heating (41.5 degrees C/60 min) 4 h after irradiation. Combining both DMXAA and heating further reduced this to 30 (26-35) Gy. When the heating temperature was decreased to 40.5 degrees C, the effect of the triple combination was decreased but was still significant compared with radiation + DMXAA or radiation + hyperthermia. However, this enhancement disappeared at 39.5 degrees C. Radiation damage of normal foot skin was not enhanced by combining DMXAA and hyperthermia at 41.5 degrees C. In conclusion, adding DMXAA to thermoradiotherapy at 40.5-41.5 degrees C significantly improved local tumour control without enhancing normal tissue damage. Thus, including a vascular targeting agent in a mild thermoradiotherapy treatment regimen is a useful approach that may lead to a re-evaluation of the use of hyperthermia in cancer treatment.

Animals↗
PubMed2002

Treatment of pure red cell aplasia after major ABO-incompatible peripheral blood stem cell transplantation by induction of chronic graft-versus-host disease.

This report concerns a case of long-lasting pure red cell aplasia (PRCA) with a duration of 178 days after major ABO-incompatible allogeneic peripheral blood stem cell transplantation (PBSCT). The patient needed red blood cell transfusion every week from day 54 following PBSCT. He showed no evidence of GVHD and the dose of cyclosporin A (CsA) was reduced rapidly from day 123, followed by the development of chronic GVHD around day 145. The patient no longer needed transfusions from day 167, the reticulocyte count began to increase on day 179, and antidonor isohemagglutinin titers became undetectable. Chronic GVHD induced by tapering of CsA thus appeared to be related to improvement in PRCA.

ABO Blood-Group System↗
PubMed2001

Combretastatin A-4 disodium phosphate: a vascular targeting agent that improves that improves the anti-tumor effects of hyperthermia, radiation, and mild thermoradiotherapy.

PURPOSE: To investigate the effect of combining the vascular targeting drug combretastatin A-4 disodium phosphate (CA4DP) with hyperthermia, radiation, or mild thermoradiotherapy in a transplanted C3H mouse mammary carcinoma. METHODS AND MATERIALS: The C3H mammary carcinoma was grown on the rear foot of female CDF1 mice and treated when at 200 mm(3) in size. CA4DP was dissolved in saline and injected i.p. Hyperthermia and/or radiation were locally given to tumors in restrained nonanesthetized mice. Tumor response was assessed using either a tumor growth or a tumor control assay. Mouse foot skin was used to assess normal tissue damage. RESULTS: CA4DP significantly enhanced thermal damage in this tumor model. This effect was independent of drug doses between 25-400 mg/kg, but was strongly dependent on the time interval between drug injection and heating, with the greatest improvement seen when CA4DP preceded the heating by 1 h or less. There was also a suggestion of a temperature dependency with a 1.9-fold increase in heat damage at 42.5 degrees C and a 2.6-fold increase at 41.5 and 40.5 degrees C. Heat-induced normal tissue damage was also enhanced by combining CA4DP with heat, but the degree of enhancement was less than that seen in tumors. CA4DP (25 mg/kg) significantly increased radiation-induced local tumor control and this was further enhanced by combining CA4DP with mild temperature (41.5 degrees C, 60 min) heating. CONCLUSIONS: CA4DP improved the anti-tumor effect of hyperthermia, especially at mild temperatures. More importantly, it also increased the tumor response to mild hyperthermia and radiation, which suggests that CA4DP may ultimately have an important application in clinical thermoradiotherapy.

Animals↗
PubMed2001

Contribution of serotonin to liver injury following canine small-intestinal ischemia and reperfusion.

Intestinal ischemia and reperfusion (I/R) has been shown to be associated with multiple organ damages. Serotonin (5-hydroxytriptamine; 5-HT), which is synthesized in the enterochromaffin cells in the intestine and stored in platelets, is known to play an important role in platelet aggregation and vasoconstriction and may ultimately enhance such organ injuries. The purpose of this study was to investigate the association between liver damage and 5-HT levels in the liver after intestinal I/R. The entire canine small intestine, isolated on a vascular pedicle that consisted of the proximal superior mesenteric artery and superior mesenteric vein, was subjected to 4-h ischemia by clamping these vessels and the marginal arteries supplying the proximal and distal ends of the small intestine. Hepatic blood flow, liver tissue blood flow, bile flow rate, and hepatic venous ketone body ratio (HVKBR) were measured before and at the end of intestinal ischemia and at 5, 15, and 30 min, and 1 and 2 h after reperfusion. 5-HT levels in plasma of the portal vein and hepatic vein were assayed at the same intervals. Time-matched, sham-operated animals served as controls. Intestinal I/R significantly decreased the liver tissue flow, bile flow rate, and HVKBR. Compared to those in controls, 5-HT levels in the portal vein and hepatic vein were markedly increased after reperfusion. Furthermore, intravenous administration of 5-HT receptor antagonists attenuated the liver dysfunction after intestinal reperfusion. These results suggest that intestinal I/R induces continuous disturbance of hepatic microcirculation, leading to liver dysfunction, and that 5-HT may be implicated as one of the mediators of liver dysfunction after intestinal I/R.

Animals↗
PubMed2001

Interaction between combretastatin A-4 disodium phosphate and radiation in murine tumors.

BACKGROUND AND PURPOSE: The ability of combretastatin A-4 disodium phosphate (CA4DP) to induce vascular damage and enhance the radiation response of murine tumors was investigated. MATERIALS AND METHODS: A C3H mouse mammary carcinoma transplanted in the foot of CDF1 mice and the KHT mouse sarcoma growing in the leg muscle of C3H/HeJ mice were used. CA4DP was dissolved in saline and injected intraperitoneally. Tumor blood perfusion was estimated using 86RbCl extraction and Hoechst 33342 fluorescent labelling. Necrotic fraction was determined from histological sections. Tumors were locally irradiated in non-anaesthetised mice and response assessed by local tumor control for the C3H mammary carcinoma and in vivo/in vitro clonogenic cell survival for the KHT sarcoma. RESULTS: CA4DP decreased tumor blood perfusion and increased necrosis in a dose-dependent fashion in the C3H mammary carcinoma, which was maximal at 250 mg/kg. The decrease in perfusion and induction of necrosis by CA4DP was more extensive in the KHT sarcoma. CA4DP enhanced radiation damage in both tumor types. In the KHT sarcoma this enhancement was independent of whether the drug was given before or after irradiating, whereas for C3H mammary carcinoma the enhancement was only significant when administered at the same time or after the radiation, with no enhancement seen if CA4DP was given before. These effects were drug-dose dependent. CA4DP did not enhance radiation damage in normal skin. CONCLUSIONS: CA4DP enhanced radiation damage in the two tumor models without enhancing normal tissue damage. These radiation effects were clearly consistent with the anti-vascular action of CA4DP.

Animals↗
PubMed2001

Improving local tumor control by combining vascular targeting drugs, mild hyperthermia and radiation.

Improvement in local control in a foot-implanted (200 mm3) C3H mouse mammary carcinoma by combining vascular targeting drugs, mild hyperthermia and radiation was investigated. The vascular targeting drug was flavone acetic acid (FAA; 150 mg/kg) intraperitoneally injected either 3 h before local tumor water-bath heating or 1 h after local tumor irradiation. For untreated tumors, the average (+/- 1 S.E.) tumor growth time (TGT; time to reach 5 x treatment volume) was 7.1 days (+/- 0.4). This was increased to 9.2 days (+/- 0.7) by using FAA. Heating also increased TGT, the effect being temperature and time dependent, and this heat response was further increased by FAA. The radiation dose (+/- 95% confidence interval) to control 50% of tumors (TCD50) 90 days after irradiation was 52 Gy (50-55) for radiation alone. This was decreased to 42 Gy (39-45) by FAA, 47 Gy (45-50) by heating (41.5 degrees C; 60 min) 4 h after irradiation, and to 28 Gy (22-35) by combining FAA and heat. Thus, vascular targeting drugs can improve the efficacy of mild hyperthermia and radiation.

Animals↗
PubMed2001

Comparative effects of combretastatin A-4 disodium phosphate and 5,6-dimethylxanthenone-4-acetic acid on blood perfusion in a murine tumour and normal tissues.

PURPOSE: To compare the ability of combretastatin A-4 disodium phosphate (CA4DP) and 5,6-dimethylxanthenone-4-acetic acid (DMXAA) to change tissue blood perfusion. MATERIALS AND METHODS: The tissues were a C3H mouse mammary carcinoma and various murine normal tissues, with perfusion measured using the 86RbCl extraction technique. RESULTS: CA4DP (250mg/kg; i.p.) reduced tumour perfusion to 34% of that seen in controls within 1 h of injection. It was maintained at this for at least 6 h, returning to control levels by 24 h. This decrease was dose-dependent. DMXAA (25mg/kg; i.p.) caused a 79% reduction in tumour perfusion 6h after injection; no recovery was observed even after 24 h. DMXAA showed no changes at doses below 10 mg/kg. Both CA4DP and DMXAA increased perfusion in the gut, kidney, bladder and lung, while decreasing splenic perfusion. CA4DP tended to decrease perfusion in muscle, while DMXAA increased liver perfusion. These changes in normal tissue perfusion were generally less than those changes seen in tumours. No significant changes were seen in skin. CONCLUSIONS: CA4DP and DMXAA produced a selective and significant reduction in tumour perfusion, but the pattern of change was different. These results suggest how these vascular targeting drugs should be combined with more conventional therapies.

Animals↗
PubMed2001

Hemadsorption expressed by cloned H genes from subacute sclerosing panencephalitis (SSPE) viruses and their possible progenitor measles viruses isolated in Osaka, Japan.

Most subacute sclerosing panencephalitis (SSPE) viruses, including our Osaka-1, -2, and -3 strains isolated in Osaka, have shown negative hemadsorption (HAD) by African green monkey red blood cells. This property has been thought to be characteristic of SSPE virus as compared to the positive reaction of the standard Edmonston strain of measles virus (MV). However, this assumption has become quite obscure because MV mutates frequently at the genetic level during its multiplication and also because recent field strains isolated by lymphoblastoid cell lines have shown negative HAD. To investigate the above issue, the nucleotide sequences of the hemagglutinin (H) genes from SSPE virus Osaka-1, -2, or -3 strains were compared to those of various MV field strains isolated in Osaka by Vero cells. The H gene sequences of three SSPE strains were relatively conserved without such biased hypermutation as had been observed in the matrix (M) gene of three SSPE strains. However, this analysis of the H gene sequence of the SSPE viruses enabled us to deduce possible progenitor MVs, which are in agreement with the deduction from the M gene analysis we reported previously. The HAD of Vero cells transfected with the cloned H cDNAs from the SSPE strains and their progenitors suggested that negative HAD of the SSPE viruses has been maintained as one of original properties of the progenitor MVs rather than having been acquired as an altered one during long-term persistent infection in the brains of patients with SSPE.

Amino Acid Sequence↗
PubMed2001

Mechanism of resistance to oxidative stress in doxorubicin resistant cells.

Doxorubicin (DOX) is an anthracycline drug widely used in chemotherapy for cancer patients, but it often gives rise to multidrug resistance in cancer cells. The purpose of this work was to study the effect of hydrogen peroxide in DOX-sensitive mouse P388/S leukemia cells and in the DOX-resistant cell line. Hydrogen peroxide induced a significant increase in dose- and time-response cell death in cultured P388/S cells. The degree of cell death in P388/DOX cells induced by hydrogen peroxide was less than that in P388/S cells treated with hydrogen peroxide. Parent cells exposed to 3 mM of hydrogen peroxide showed a loss of mitochondrial membrane potential correlated with cell death. Hydrogen peroxide at a concentration greater than 0.3 mM increased the intracellular Ca2+ of P388/S cells dose-dependently; however, no change following addition of hydrogen peroxide (0.3-1 mM) was observed in the resistant cells. Hydrogen peroxide (0.1 and 1 mM) treatment also induced the production of intracellular ROS in P388/S cells, while no such increase was produced by this substance in P388/DOX cells. Resistant cells also showed a significant level of glutathione (GSH) compared with the parent cells. In addition, N-acetyl-L-cysteine and reduced GSH antioxidants abolished death of P388/S cells caused by hydrogen peroxide. Therefore, it is believed that the reduced effect of oxidative stress towards the resistant cells may be related to an increase in intracellular GSH level.

Animals↗
PubMed2001

Improved tumor response by combining radiation and the vascular-damaging drug 5,6-dimethylxanthenone-4-acetic acid.

The interaction between 5,6-dimethylxanthenone-4-acetic acid (DMXAA) and radiation was investigated in two different mouse tumor models and a normal mouse tissue. C3H mouse mammary carcinomas transplanted in the feet of CDF1 mice and KHT mouse sarcomas growing in the leg muscles of C3H/HeJ mice were used. DMXAA was dissolved in saline and injected intraperitoneally. Tumors were irradiated locally in nonanesthetized mice, and response was assessed using tumor growth for the C3H mammary carcinoma and in vivo/in vitro clonogenic cell survival for the KHT sarcoma. DMXAA alone had an antitumor effect in both tumor types, but only at doses above 15 mg/kg. DMXAA also enhanced radiation damage, and again there was a threshold dose. No enhancement was seen in the C3H mammary carcinoma at 10 mg/kg and below, while in the KHT sarcoma, doses above 15 mg/kg were necessary. This enhancement of radiation damage was also dependent on the sequence of and interval between the treatments with DMXAA and radiation. Combining radiation with DMXAA at the maximum tolerated dose (i.e., the highest dose that could be injected without causing any lethality) of either 20 mg/kg (CDF1 mice) or 17.5 mg/kg (C3H/HeJ mice) gave an additive response when the two agents were administered simultaneously. Even greater antitumor effects were achieved when DMXAA was administered 1-3 h after irradiation. However, when administration of DMXAA preceded irradiation, the effect was similar to that seen for radiation alone, suggesting that appropriate timing is essential to maximize the utility of this agent. When such conditions were met, DMXAA was found to increase the tumor response significantly in the absence of an enhancement of radiation damage in normal skin, thus giving rise to therapeutic gain.

Animals↗
PubMed2001

[Seizures associated with fever in children of congenital adrenal hyperplasia].

We investigated seizures in 22 children with congenital adrenal hyperplasia (CAH), eight of whom had seizures associated with fever. The follow-up period was 5-18 years. The onset of seizures ranged from 1 to 4 years of age, and the total number of seizures was one to three in all cases. Four cases had seizures twice within 24 hours. None had seizures after 5 years of age. In two of the eight cases, the seizures may have caused by hypoglycemia or hyponatremia, in the remaining six they were considered to be febrile seizures. Three of them had first-degree relatives with febrile seizures. Electroencephalogram was recorded in five cases, with normal results in all of them. One case with febrile status developed localization-related epilepsy later. None showed developmental delay during follow-up. Although seizures in CAH have been ascribed to hypoglycemia and/or metabolic disorders (hyponatremia), our findings implicate unknown factors in the pathogenesis such as excess secretion of corticotropin releasing factor (CRF) under stress, prolonged elevation of CRF during fetus life and linkage between CAH and febrile seizures on the chromosome 6.

Adrenal Hyperplasia, Congenital↗
PubMed2001

[Acute myelogenous leukemia associated with disseminated intravascular coagulation and acute myocardial infarction at relapse].

A 71-year-old man with acute myelogenous leukemia (AML, M2) developed signs of chest oppression, and was diagnosed as having acute myocardial infarction (AMI). At the same time, his leukemia relapsed in association with disseminated intravascular coagulation (DIC). The patient's risk factors for AMI were hyperlipidemia, hyperglycemia, and a history of smoking. Coronary angiography showed occlusion of the circumflex branch. Percutaneous transluminal angioplasty (PTCA) was performed successfully, followed by administration of heparin. After chemotherapy, the patient's DIC improved and a second remission was attained. When elderly patients with AML show evidence of DIC, we should be aware of AMI as a possible complication. PTCA is a safe operation for such patients.

Aged↗
PubMed2000

Multiple duodeno-jejunal diverticula causing massive intestinal bleeding.

A case of massive intestinal blood loss from multiple duodeno-jejunal diverticula is described. A 39-year-old man was referred to our hospital because of recurrent bloody stool and worsening anemia. Upper and lower endoscopy, selective abdominal angiography, and radionuclide scanning were performed to seek the cause of the intestinal bleeding, but none of these studies revealed the source of bleeding. Small-bowel barium follow-through examination showed numerous diverticula in the distal duodenum and proximal jejunum. Excision of the duodenal diverticulum and resection of the involved portion of the jejunum cured the patient. On histopathological examination, an ulcerative lesion with an exposed vessel suggestive of the source of bleeding was seen in the resected duodenal diverticulum. Although duodeno-jejunal diverticula are rare, the importance of a careful search for this malformation in a patient with intestinal blood loss is stressed.

Adult↗
PubMed2000

Combretastatins novel vascular targeting drugs for improving anti-cancer therapy. Combretastatins and conventional therapy.

Combretastatins are a new class of compounds that appear to have anti-tumour activity as a result of specifically targeting the vasculature of tumours. The aim of this study was to investigate the potential of combretastatin A-4 disodium phosphate (CA4DP) to induce vascular effects in a C3H mouse mammary carcinoma, and to see if the anti-tumour response could be improved by combining the drug with conventional anti-cancer therapies. It was found that CA4DP (250 mg/kg) significantly decreased tumour perfusion within 30 minutes after injection and maintained this decrease for several hours, although there was a return to normal by 24 hours. Similar changes were seen in the tumours bioenergetic and oxygenation status. The drug also significantly increased tumour necrosis and had a small inhibitory effect on tumour growth. It was also able to enhance the tumour response to radiation and hyperthermia, when given at the same time or 30 minutes after the radiation and hyperthermia, respectively. Giving the drug 1 hour after cisplatin injection only resulted in a tumour response that was no greater than additive. These results confirm the anti-vascular effects of CA4DP and demonstrate its potential to enhance the anti-tumour activity of conventional therapy.

Animals↗
PubMed1999

Sequential MRI, SPECT and PET in respiratory syncytial virus encephalitis.

We report on a 3-year-old girl with respiratory syncytial virus (RSV) encephalitis manifested by disturbance of consciousness, conjugate eye deviation, anuria, truncal ataxia and intention tremor. T2-weighted magnetic resonance imaging (MRI) showed hyperintense areas in the cerebellar cortex. No lesion was detected in the cerebral cortex, pons or spinal cord. The hyperintense areas in the cerebellar cortex diminished with recovery from the clinical manifestations and had resolved 2 months after onset. The MRI lesions in the cerebellum were considered to be due to oedema. SPECT and positron emission tomography (PET), performed 3 months after onset, disclosed areas of hypoperfusion and hypometabolism at the same sites. One year after onset, MRI showed mild atrophy of the cerebellum. Hypoperfusion on SPECT and hypometabolism on PET remained. Neuroimaging showed that ataxia and tremor in this case were the result of cerebellitis. The patient has no neurological deficit except for mild truncal ataxia. This patient is a rare example of RSV encephalitis.

Brain↗
PubMed1999

Differences in target outline delineation from CT scans of brain tumours using different methods and different observers.

PURPOSE: To assess errors resulting from manual transfer of contour information for three-dimensional (3-D) target reconstruction, and to determine variations in target volume delineation of brain tumours by different radiation oncologists. MATERIALS AND METHODS: Images of 18 patients with intracranial astrocytomas were used for retrospective treatment planning by five radiation oncologists. In this study, the target outline was delineated on sequential CT slices by an experienced radiation oncologist. Thereafter, the target outline was manually reconstructed by five radiation oncologists onto an A-P or lateral scout film. The same target outline was also reconstructed as a projection using the Beam's-eye view capability on a CT simulator unit. The two target outlines were compared by encompassing each shape with the smallest rectangle. The manually-reconstructed radiation field was termed 'Field manually established on X-ray film (F-X)', and the automatically-established field was termed 'Field established by CT simulator (F-CT)'. In a second part of this study, four radiation oncologists defined contours from contrast enhanced CT images of nine patients with intracranial astrocytomas. The CT images of these nine cases included five pre-operative cases and four post-operative cases. Both gross tumour volume (GTV) and clinical target volume (CTV) were outlined on sequential CT slices. The target outlines for the four radiation oncologists were compared by identifying the smallest rectangular field surrounding the projection of these contours. The field established by each radiation oncologist was termed 'Field of target volume (F-TV)', and the overlapping portion of the four F-TVs for each case was termed 'Overlapped field of the target volume (Fo-TV)'. RESULTS: The average distance between the isocentres of F-X and F-CT was 0.6 +/- 0.4 cm (mean +/- SD). The average ratio of the area of F-X divided by the area of F-CT was 1.04 +/- 0.12. The area of F-X was wider than the area of F-CT for four of the five oncologists. The ratio of the area of F-TV divided by the area of Fo-TV was calculated. The average ratio was relatively greater for CTV (2.07 in pre-operative cases and 2.11 in post-operative cases) than for GTV (1.12 in pre-operative cases and 1.41 in post-operative cases). Among radiation oncologists, variations in the delineation of GTV were smaller than those of CTV. CONCLUSIONS: When using an X-ray simulator in treatment planning, errors resulting from the manual transfer of CT contour information to planar radiographs must be considered. When computer techniques are used to project contours onto radiographs errors resulting from individual variations when performing the contouring must be considered.

Astrocytoma↗