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Biomedical subjects

M Muto

Publications and source records attributed to M Muto.

At least 127 records · Page 7Linked to original sources
PubMed1994

Phase I pharmacokinetic study of the hypoxic cell sensitizer etanidazole with carboplatin and cyclophosphamide in the treatment of advanced ovarian cancer.

PURPOSE: A Phase I study was undertaken to determine the maximum tolerated dose of the hypoxic cell sensitizer etanidazole which could be administered with carboplatin and cyclophosphamide, to determine whether adequate serum levels of etanidazole were achieved to allow for alkylating agent sensitization, and whether pretreatment with etanidazole altered carboplatin pharmacokinetics. METHODS AND MATERIALS: Patients received 2 g/m2 of intravenous etanidazole followed by a second dose of 4 g/m2 90 min later, followed by intravenous carboplatin (300 mg/m2) and cyclophosphamide (600 mg/m2) for four treatment cycles. Patients received an additional two cycles of carboplatin and cyclophosphamide without etanidazole. RESULTS: Two patients who received a total of 24 g/m2 of etanidazole developed Grade 1 neurotoxicity, and therefore etanidazole doses were not escalated further. The grade of granulocytopenia was worse after cycles with etanidazole than after those without (p = 0.03), but clinical outcome was not different. Etanidazole levels were adequate for alkylating agent sensitization (> 70 ug/ml) in all patients for the majority of the 7 h of testing. Pharmacokinetic data suggested t1/2 alpha and t1/2 beta for carboplatin were prolonged after pretreatment with etanidazole. CONCLUSION: Etanidazole, 2 g/m2 followed by 4 g/m2 90 min later, is safe and results in adequate serum levels for alkylating agent sensitization. Neurotoxicity appears to prevent dose escalation of etanidazole, and an interaction between etanidazole and carboplatin may have enhanced neurotoxicity in these patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Pseudoinvasion of vascular spaces: report of an artifact caused by cervical lidocaine injection prior to loop diathermy.

Cervical loop diathermy is a relatively new procedure performed by gynecologists to diagnose and treat squamous intraepithelial lesions. We report a case of pseudoinvasion of vascular spaces noted in an excisional biopsy of a high-grade squamous intraepithelial lesion of the cervix. The neoplastic epithelium was forced into the cervical stroma by injection of local anesthetic through the lesion prior to loop diathermy. The identification of this pseudovascular space invasion as artifact had important prognostic and therapeutic value. With the increasing use of loop diathermy and local anesthesia this type of artifact may be seen more commonly.

Adult↗
PubMed1994

Crossed fat embolism in a cow with tetralogy of Fallot.

A 10-month-old, female Holstein-Friesian cow with tetralogy of Fallot died during surgery for ameliorating pulmonary stenosis. Necropsy revealed no fracture of bones. Microscopically, fat emboli in the capillaries were detected in the brain, kidney, lung, adrenal gland and pituitary. In the kidney, many fat emboli were present in the glomeruli. No significant changes of the neurons were found throughout the brain, and perivascular hemorrhage and/or necrosis were rarely seen accompanying with fat emboli in the cerebral cortex. The trigger for fat embolism might be costectomy, and right-to-left shunt due to heart malformation might be attributed to crossed and systemic distribution of the fat emboli.

Animals↗
PubMed1994

A case report of surgical treatment of a dog with atrioventricular septal defect (incomplete form of endocardial cushion defect).

A 3-month-old female collie was diagnosed as having atrioventricular septal defect with ostium primum atrial septal defect (PASD). The diagnosis was made by echocardiographic observation of the PASD and goose-neck deformity on left ventriculogram. The PASD was treated surgically with a patch graft under cross-circulation cardiopulmonary bypass (CC). The PASD was identified above the ventricular septum after right atriotomy. The patch graft was sutured along the fibrous tissue of the tricuspid annulus on the ventricular side of the PASD to avoid injuring the conduction system. After the operation, cardiac function and renal output were well preserved, but the dog died 33 hr later. At postmortem examination, a mitral cleft was identified.

Animals↗
PubMed1993

Multiple pre-neoplastic events and clonal selection of radiation induced mouse thymic lymphomas shown by TCR gene rearrangements.

After split-dose irradiation, pre-lymphoma cells develop from a tumor-specific surface antigen TL-2+ thymocyte subpopulation. To analyze the clonality of pre-lymphoma cells, various numbers of TL-2+ thymocytes from a single irradiated mouse were intra-thymically injected to Thyl congenic recipient mice. The incidence of donor type thymic lymphoma(s) was subsequently examined in a group of recipient mice. We chose several lymphomas derived from a single donor mouse and analyzed the TCR gene rearrangements and V(D)J junctional diversity as genetic markers of clonality. These results indicate multiple initial neoplastic events and clonal selection into lymphoma.

Amino Acid Sequence↗
PubMed1993

Mouse germline transcript of TCR alpha joining region and temporal expression in ontogeny.

The genetic element 'T early alpha' (TEA) in humans is located immediately 5' to the most upstream joining segment (phi J alpha) of the TCR alpha chain locus. The TEA transcript is present early in thymocyte ontogeny and the TEA-associated deletion of the TCR delta locus (delta Rec/phi J alpha rearrangement) precedes V alpha/J alpha rearrangement. We detected a 1.8 kb transcript homologous to human TEA that is spliced to C alpha in mouse thymic lymphomas showing concomitant rearrangement and expression of TCR gamma, delta, beta, and alpha. The TEA expression was highest in day 17 fetal thymocytes and declined thereafter. This expression parallels the TCR delta gene expression which is preceded by TCR gamma expression, and followed by the expression of TCR beta and alpha genes.

Animals↗
PubMed1993

Inhibitory effect of azelastine, a potent antiallergic agent, on release of tumor necrosis factor-alpha from activated human peripheral blood mononuclear cells and U937 cells.

It is generally accepted that tumor necrosis factor-alpha (TNF-alpha) is a multifunctional cytokine which is involved in the regulation of inflammation as well as immunity. In the present study, we investigated whether azelastine, a potent antiallergic agent, affects release of TNF-alpha from peripheral blood mononuclear cells (PBMC) and U937 cell line in vitro. When human PBMC and U937 cells were stimulated by phytohemagglutinin (PHA) and 12-0-tetradecanoyl-phorbol-13-acetate (TPA), respectively, the cells released significant amounts of TNF-alpha as determined by TNF-alpha-specific enzyme immunoassay. TNF-alpha levels in the culture supernatant of PHA-stimulated human PBMC and TPA-activated U937 cells decreased in a dose-dependent manner when these cells were cultured in the presence of azelastine. This inhibitory effect of azelastine was obtained at concentrations where the drug produced no toxicity. Moreover, azelastine also inhibited release of TNF-alpha from U937 cells which were already activated by TPA. These results suggest that the inhibitory effect of azelastine on TNF-alpha release plays an important role in its antiallergic action in addition to inhibition and/or antagonism of histamine and leukotrienes, which has been previously reported.

Depression, Chemical↗
PubMed1993

Use of peripheral-blood progenitor cells abrogates the myelotoxicity of repetitive outpatient high-dose carboplatin and cyclophosphamide chemotherapy.

PURPOSE: Attempts to increase dose-intensity in clinical practice have been limited by cumulative hematologic toxicity despite the use of hematopoietic growth factors. To address this problem, we designed a study to determine whether four cycles of dose-intensive chemotherapy with carboplatin could be administered in the outpatient setting using granulocyte-macrophage colony-stimulating factor (GM-CSF) and peripheral-blood progenitor cells (PBPCs) that had been harvested before initiation of treatment. PATIENTS AND METHODS: An initial cycle (cycle no. 0) of cyclophosphamide 4 g/m2 followed by GM-CSF was used to mobilize PBPCs harvested by leukapheresis for 6 consecutive days. Cycles no. 1 through 4 consisted of outpatient carboplatin 600 mg/m2 and cyclophosphamide 600 mg/m2 followed by GM-CSF 5 micrograms/kg subcutaneously (SC) twice per day every 28 days. In cycle no. 1, PBPC were not reinfused to assess the effects of GM-CSF alone. In cycles no. 2 through 4, PBPCs were reinfused on day 3 in an outpatient setting. RESULTS: In eight assessable patients, the addition of PBPCs in cycle no. 2 resulted in a significant reduction in the median duration of thrombocytopenia less than 20,000/microL (6.5 v 1 day; P = .016), days to platelets more than 50,000/microL (20.5 v 15 days; P = .020), number of platelet transfusions (five v 1.5; P = .016), and duration of neutropenia (absolute neutrophil count [ANC] < 1,000/microL (7 v 2.5 days; P = .008) when compared with cycle no. 1. Dose-limiting hematologic toxicity, defined as more than 7 days of platelets less than 20,000/microL or ANC less than 500/microL, was observed in four of eight patients during cycle no. 1, but not during cycles no. 2, 3, and 4 of chemotherapy supported by PBPCs (a total of 19 cycles in eight patients). Five of eight patients completed all four cycles of high-dose therapy. Three patients did not complete four cycles due to late thrombocytopenia (n = 2) or tumor progression (n = 1). CONCLUSION: These results indicate a benefit of PBPCs in addition to GM-CSF in alleviating myelosuppression of dose-intensive chemotherapy. Initial collection of PBPCs may allow administration of repetitive cycles of high-dose chemotherapy with acceptable toxicity to outpatients at disease onset.

Adult↗
PubMed1993

Preliminary results of short-term combination immunosuppressions of mizoribine, azathioprine, and prednisolone with pretreatment to canine kidney transplantation.

Serial combinations of immunosuppressive drugs (mizoribine: Mi, azathioprine: Az, and prednisolone: Pr) were administered for renal heterotopic allotransplantation in 50 mixed-breed dogs and 4 beagle dogs. The dogs were randomly divided in 5 groups depending upon immunosuppressive protocols. All immunosuppressive protocols were started at 5 days prior to transplantation and discontinued on the eighth day after transplantation. The mean survival time for the allograft recipients in the group receiving Az and Pr [Az (2.5) & Pr group; Az dosage, 2.5 mg/kg once a day with Pr] was 16.2 +/- 2.4 days and in the group receiving Az, Mi, and Pr (Mi & Az & Pr group; Mi dosage, 5.0 mg/kg once a day with Az and Pr), it was 14.0 +/- 2.6 days. These results were significantly longer than the control group (mean survival time, 8.7 +/- 2.4 days; P < 0.01). There was no statistical difference in survival time between these two groups. Groups with combinations of Az and Pr had significant elevations of hepatic enzymes (ALT and ALP) during the 7 days of immunosuppressive treatment after kidney transplantation. The Mi & Az & Pr group had lower elevations of hepatic enzymes than groups with combinations of Az and Pr. The combination immunosuppression of Mi, Az, and Pr with pre-treatment for canine, kidney transplantation revealed relatively fewer side-effects for the liver and longer survival-time.

Alanine Transaminase↗
PubMed1993

[A study of myocardial disorders in an autopsy case of mitochondrial encephalomyopathy].

We report an autopsy case of a 19 year-old man with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) a subgroup of mitochondrial encephalomyopathy presenting cardiomyopathy. He had repeatedly suffered from transient unconsciousness, hemiplegia, hemianopsia and convulsion attacks since the age of 9, and he died of severe congestive heart failure. In laboratory findings, blood lactate and pyruvate were markedly increased. Skeletal muscle biopsy demonstrated numerously scattered ragged-red fibers with modified Gomori's trichrome staining. Enzymatic activities of the mitochondrial respiratory chain showed a marked decrease of NADH cytochrome c reductase (complex I). In postmortem examination, the heart was 310g in weight and had right ventricular dilatation. Microscopically, degenerated and scattered myocardial cells (ragged-red fibers), interstitial edema and microvascular hyperplasia were demonstrated in the myocardium. Under the electron microscope, abnormal mitochondria proliferated and myofibrils were unusually sparse. Immunohistochemical studies with specific antibodies against the mitochondrial electron transfer enzyme subunits revealed a reduction of immunoreactive materials for complex I in the myocardium. These results suggested the relationship of myocardial disorders and decreased activity of complex I in electron transfer enzymes in this patient.

Adult↗
PubMed1992

Novel TCR gene rearrangements and expression in radiation-induced thymic lymphomas.

Using the intrathymic (i.t.) injection assay with a B10.Thy 1 congenic donor-host combination, we previously demonstrated that the pre-neoplastic cells (thymic prelymphoma cells) exist in immature T cell subpopulations; mainly in CD4-CD8- double negative (DN) and CD4-CD8+ single positive (SP) thymocytes and to some extent in CD4+CD8+ double positive (DP) thymocytes. Most thymic lymphomas that developed from these prelymphoma cells showed concomitant TCR alpha, beta and gamma gene rearrangements and expression. In this lymphomas, two lymphomas also showed TCR delta gene rearrangements. This represents the intermediate stages of TCR gene rearrangement. Every lymphoma, however, expressed CD3-associated alpha beta TCR on the cell surface, but not gamma delta TCR. Novel rearrangements of V gamma 4 and J gamma 4-C gamma 4 segments with non-gamma elements were found respectively in a concerted and symmetrical fashion. Recombinase-mediated inter-chromosomal exchanges characteristic of thymic lymphomas may function in radiation-induced lymphomagenesis.

Animals↗
PubMed1992

[Neuronal migration anomalies. The magnetic resonance aspects of some types].

The authors investigated the value of magnetic resonance (MR) imaging in the evaluation of some types of neuronal migration anomaly. During pregnancy, a radial neuronal migration from germinal matrix to cortex occurs in the fetal brain, and 6 layers are formed. Infections, traumas, vascular factors can block the migration. Neuronal migration disorders are divided into 5 different classes: (1) agyria-pachigyria complex; (2) schizencephaly; (3) polymicrogyria; (4) unilateral megaencephaly; (5) heterotopia. In this study, 12 patients were evaluated with MR imaging: 5 had lissencephaly, 4 heterotopia and 3 schizencephaly (2 with open lips, and 1 with closed lips). MR imaging is the method of choice in these patients; indeed, characteristic morphologic and signal patterns allow the correct evaluation and diagnosis of neuronal migration anomalies in all cases.

Adolescent↗
PubMed1991

Characterization of thymic prelymphoma cells that develop during radiation-induced lymphomagenesis in B10 mice.

An intrathymic (i.t.) injection assay on B10.Thy-1 congenic mice was used to demonstrate that thymic prelymphoma cells developed first within mouse thymus 4 to 8 days after split-dose irradiation and were present in more than 63% of the test donor mice thymuses examined 21 and 31 days after irradiation. For the characterization of these thymic prelymphoma cells, thymocytes from B10.Thy-1.1 mice sampled 1 mo after irradiation were stained with J11d mAb and mAb against TL-2 (thymus-leukemia) antigen which is not expressed on normal thymocytes of the B10.Thy 1.2 and B10.Thy 1.1 strains but does appear on thymocytes of split-dose irradiated mice. These cells were sorted into subpopulations, samples of which were injected into recipient thymuses to determine which subpopulations contained thymic prelymphoma cells. Results showed that the prelymphoma cells were located in the J11d+TL-2+ cells. These prelymphoma cells were further characterized phenotypically as to their expression of the CD4 and CD8 antigens, which demonstrated that the thymic prelymphoma cells were present in the CD4-CD8- and CD4-CD8+ thymocyte subpopulations mainly and in the CD4+CD8+ subpopulation. The experiments on i.t. injection of a graded quantity of TL-2+ thymocytes from individual mice suggest that not all TL-2+ cells undergo neoplastic initiation and that prelymphoma cells may develop infrequently from one or more TL-2+ cells by genetic or epigenetic changes.

Animals↗