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Biomedical subjects

T Shimokawa

Publications and source records attributed to T Shimokawa.

126 records · Page 7Linked to original sources

Isolation and storage of peripheral blood hematopoietic stem cells for autotransplantation into children with cancer.

Peripheral blood stem cells (PBSC) were collected for autotransplantation by a total of 46 continuous-flow leukaphereses in 17 children with various types of cancer in whom the stem-cell pool had been expanded by chemotherapy. As the cells collected by leukapheresis were contaminated with many visible cell clumps, platelets, and erythrocytes, they were separated from the platelet-rich plasma (PRP) by slow-speed centrifugation and fractionated on a discontinuous gradient of Percoll. All the hematopoietic progenitors (CFU-GM, CFU-GEMM) in the starting samples were recovered at the interface of 40% and 60% Percoll solutions largely free of other cellular components and with a substantial reduction in volume. The separation and freezing procedures could be completed within three hours after obtaining cells by leukapheresis. After their fractionation and storage, these PBSC were shown to be able to reconstitute normal hematopoiesis in ten children with poor prognosis leukemia or neuroblastoma for whom no HLA-compatible marrow donors were available and who had been subjected to marrow-ablative therapy. This separation procedure is simple, efficient, and readily available and can be used for children as a routine procedure for PBSC autotransplantation.

Adolescent↗

[Interstitial pneumonitis following high-dose MCNU].

We describe a 11-year-old boy with NHL, who developed interstitial pneumonitis following high-dose MCNU with autologous peripheral stem cell transfusion. Non-productive cough, malaise and progressive dyspnea on exertion were noticed 7 weeks after high-dose MCNU (600 mg/kg) treatment, and chest X-ray revealed a bibasilar reticular pattern. Arterial blood was hypoxemic and pulmonary function showed the development of a restrictive ventilatory effect and a reduced diffusing capacity for carbon monoxide (DLCO). Clinical Symptoms were resolved after 3 courses of m-PSL pulse therapy and 6 months prednisolone, but an isolated reduction in DLCO has been present. This case suggests that pulmonary toxicity is a dose limiting factor for MCNU treatment.

Antineoplastic Agents↗

Effect of dietary alpha-linolenate/linoleate balance on mean survival time, incidence of stroke and blood pressure of spontaneously hypertensive rats.

Following the suckling period, stroke-prone spontaneously hypertensive rats (SHR-SP) were fed semi-purified diets supplemented either with safflower seed oil (rich in linoleic acid) or with perilla seed oil (rich in alpha-linolenic acid). The mean survival time of male SHR-SP fed the perilla diet was longer than that fed the safflower diet by 17% (p less than 0.001) while the difference was 15% in female SHR-SP (p less than 0.05). The mean survival times of female SHR-SP were more than 40% longer than those of male SHR-SP in both dietary groups. Post-mortem examinations of brains revealed apoplexy-related symptoms as the major cause of the death in both dietary groups. The systolic blood pressure was lower by ca. 10% (21 mmHg) in the perilla group than in both the safflower group and conventional diet group. The eicosapentaenoate (20:5 n-3)/arachidonate (20:4 n-6) ratio of platelet phospholipids in spontaneously hypertensive rat (SHR), a measure of platelet aggregability, was much higher in the perilla group than in the safflower group. Thus, increasing the dietary alpha-linolenate/linoleate ratio resulted in an increased mean survival time of SHR-SP rats, possibly by lowering blood pressure and platelet aggregability.

Animals↗

Chromosome translocations involving band 7q35 or 7p15 in childhood T-cell leukemia/lymphoma.

In a chromosome study in childhood T-cell leukemia/lymphoma, we found t(7;11)(q35;p13) in 2 patients, t(7;14) (q35;q11) in one patient, and t(7;14)(p15;q32) in 1 patient. Southern blotting and in situ chromosomal hybridization studies in one patient with the t(7;11) demonstrated that both alleles of the T-cell antigen receptor beta-subunit gene (TCRB) were rearranged, and that one TCRB allele had relocated from 7q35 to the fusion point in band p13 of the involved chromosome 11 (11p-). These findings suggest that juxtaposition of TCRB with the putative oncogene tcl-2 located in band 11p13 may be a critical step toward development of this T-cell leukemia/lymphoma. In the other two translocations, all breakpoints were sites for lymphocyte function genes, ie, 7q35 for TCRB, 14q11 for T-cell antigen receptor alpha-subunit gene (TCRA), 7p15 for T-cell antigen receptor alpha-subunit gene (TCRG), and 14q32 for immunoglobulin heavy-chain gene (IGH). Thus, the findings in these cases allow us to expand the above hypothesis and propose that the juxtaposition of TCRB or TCRG with tcl-2, TCRA, or IGH through chromosomal translocation may activate a mechanism for the genesis of T-cell leukemia/lymphoma with these chromosome translocations.

Adolescent↗

Effect of clofibrate on lipid peroxidation in rats treated with aspirin and 4-pentenoic acid.

The in vivo hepatic lipid peroxide content of rats was increased by aspirin or 4-pentenoic acid (4-PA) administration but was decreased by clofibrate (CPIB) administration. The increase by aspirin or 4-PA treatment was depressed by simultaneous administration of CPIB. However, the in vitro formation of lipid peroxide in liver mitochondria and microsomes of rats treated with CPIB as well as aspirin and 4-PA was also elevated compared to that of control rats. The formation of lipid peroxide in mitochondria and microsomes of control rats in vitro was depressed by the addition of cytosols obtained from untreated (control), aspirin-treated, 4-PA-treated, and CPIB-treated rats, but was not depressed by the addition of albumin or heated cytosols. The most effective depression was obtained by the addition of cytosol obtained from CPIB-treated rats. In addition, glutathione peroxidase activity and nonprotein sulfhydryl content in cytosol obtained from CPIB-treated rats were elevated compared to those from control, aspirin, and 4-PA-treated rats. The results suggest that the action of CPIB may be mainly related to the increase of cytosolic glutathione peroxidase activity and nonprotein sulfhydryl content. Hepatic triglyceride and phospholipid contents of rats treated with aspirin or 4-PA were increased compared to those of control rats. These increases were also reversed by simultaneous administration of CPIB.

Animals↗

Effect of clofibrate on cholesterol metabolism in rats treated with polychlorinated biphenyls.

Serum and hepatic cholesterol content in rats treated with polychlorinated biphenyls (PCBs, KC-400) were increased compared to those of control rats. This increase of cholesterol content was reduced to control level by simultaneous administration of ethyl p-chlorophenoxyisobutyrate (CPIB). Also, when lecithin-cholesterol acyltransferase (LCAT) (EC. 2.3.1.43) activity was expressed as the net cholesterol esterification, the acyltransferase activity in rats treated with PCBs was elevated, while the elevated acyltransferase activity was brought to control level by simultaneous administration of CPIB. On the other hand, the amount of bile of rats treated with CPIB, PCBs and PCBs-CPIB was increased, but free and total cholesterol content in bile of these treated rats was decreased to 40-60% of those of control rats. Moreover, cytochrome P-450 content in liver microsomes of rats treated with CPIB, PCBs and PCBs-CPIB was increased. At the same time, cholesterol-metabolizing activity in liver microsomes of rats treated with CPIB, PCBs and PCBs-CPIB also was elevated. Similar results were obtained for drug metabolizing (aniline hydroxylation and aminopyrine N-demethylation) activity. In addition, the amount of bile acids excreted from rats treated with CPIB, PCBs and PCBs-CPIB was increased compared to that of control rats. These results suggest that hypercholesterolemia induced by oral ingestion of PCBs is recovered by CPIB treatment and that this hypocholesterolemic effect of CPIB may be related partly to the elevation of hepatic mixed function oxidase activity for cholesterol catabolism.

Animals↗

[Radiation decomposition of humic substances in landfill disposal leachate. TOC reduction and CO2 formation (author's transl)].

The leachate generated from landfill contains humic substances such as humic acid and fluvic acid. It shows, in general, high chemical oxygen demand (COD) and biological oxygen demand (BOD), and colors in dark brown. When the leachate collected on the No. 15 landfill in Tokyo Bay was irradiated by gamma-rays from a 60Co source in bubbling air, the total organic carbon (TOC) decreased with increasing dose and the brown color was bleached. The effects of pH, flow rate, and dose rate on the decrease of TOC, the variations of UV spectrum, and the formation of carbon dioxide by the irradiation were examined. The decreasing rate of TOC increased with an increase of the flow rate up to approximately 1l/min and showed a maximum value in the region of pH 4 approximately 6. It was also dependent on the dose rate and increased with a decrease of the dose rate. The radiation chemical yield, G(--TOC), reached 162 at low dose rate of 1.3 X10(4) rad/h. This result suggests that a radiation-induced chain reaction occurred. The amount of TOC decreased was almost equal to that of carbon dioxide formed. This result shows that the organic substances were decomposed by irradiation to carbon dioxide as a final product and it was ejected from the solution.

Carbon↗

Coherence resonance and discharge time reliability in neurons and neuronal models.

Neurons are subject to internal and external noise that have been known to modify the way they process incoming signals. Recent studies have suggested that such alterations have functional roles and can also be used in biomedical applications. The present work goes over experimental and theoretical descriptions of the response of neurons to white noise stimulation. It examines various forms of noise related behavior in a standard neuronal model, namely the leaky integrate and fire. This clarifies the conditions under which specific noise induced changes occur in neurons, and consequently can help in determining whether nervous systems operate under similar circumstances.

Action Potentials↗

Overview of clinical studies of childhood acute lymphoblastic leukemia for more than ten years by the Japanese Children's Cancer and Leukemia Study Group.

Since 1981, the Children's Cancer and Leukemia Study Group (CCLSG) has developed a series of protocols for treatment of acute lymphoblastic leukemia (ALL) in childhood. In the first randomized controlled study of the 811 protocol (1981-1983) a comparison of conventional daily 6-mercaptopurine and methotrexate with a pulsed regimen of the two drugs was performed. The superiority of the pulsed regimen was shown. In the next 841 protocol (1984-1987) a comparison of two drugs and three drugs during induction therapy was conducted. The three-drug regimen resulted in a significantly higher event-free survival (EFS) rate. In the 874 protocol (1987-1990) two regimens with or without cranial irradiation were randomly compared, and there was no significant difference between the two regimens for the standard-risk group. To further improve the EFS rate a risk group-directed protocol 911 was conducted starting in January 1991. Life-table analysis of serial CCLSG protocols revealed that the outcome of overall ALL has gradually improved with an increase of the EFS rate; 41.4% +/- 3.6% at 14 years for the 811 protocol, 51.3% +/- 3.5% at 11 years for the 841 protocol, 56.7% +/- 3.1% at 8 years for the 874 protocol, and 78.2% +/- 3.1% at 4 years for the more recent 911 protocol.

Antineoplastic Combined Chemotherapy Protocols↗