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Biomedical subjects

A Matsuda

Publications and source records attributed to A Matsuda.

At least 361 records · Page 20Linked to original sources

[Aspergillosis of the maxillary sinus in a patient with Ph1 positive acute lymphoblastic leukemia: a case report].

A 46-year-old woman was admitted to our hospital because of leukocytosis. A diagnosis of acute lymphoblastic leukemia (FAB: L2 type) was made by reviewing peripheral blood smear and bone marrow aspirate. Chromosome analysis showed the presence of Philadelphia chromosome. A combination chemotherapy with L-asparaginase, doxorubicin, vincristine, and prednisolone was started, but complete remission was not achieved. During a neutropenic period after combination chemotherapy with doxorubicin, vincristine, vinblastine, and VP-16, high fever and tender swelling of the right cheek were noticed. A diagnosis of maxillary sinusitis was made with tomography and CT scan of the maxillary sinus. Since culture of the aspirate from the maxillary sinus grew aspergillus, a diagnosis of aspergillosis of the maxillary sinus was made. Immediately after the intravenous administration of amphotericin B and the lavage of the sinus with amphotericin B was started, high fever subsided and clinical improvement was observed. Several regimens of chemotherapy failed to obtain hematological remission, she died of sepsis of Enterobactor cloacae without evidence or relapse of dissemination of aspergillosis after initial successful treatment. While a few cases with aspergillus maxillary sinusitis were reported in leukemic patients, the possible occurrence of this complication must be kept in mind in a severe neutropenic period after intensive chemotherapy. The combination of intravenous administration and local lavage of amphotericin B appeared to be an effective treatment in the Aspergillus maxillary sinusitis.

Amphotericin B↗

Imbalance of deoxyribonucleoside triphosphates, DNA double-strand breaks, and cell death caused by 2-chlorodeoxyadenosine in mouse FM3A cells.

The mechanism of the cytotoxic action of 2-chlorodeoxyadenosine in mouse FM3A cells was investigated. Imbalance of the dNTP pools occurred within 3 h of treatment with 20 microM 2-chlorodeoxyadenosine; the dATP and dGTP pools were depleted and the dTTP pool increased. 2-Chlorodeoxyadenosine added to the culture medium broke mature DNA strands, giving fragments of 100-200 kilobase pairs as found by orthogonal-field-alternation gel electrophoresis. DNA strand breaks, measured by this technique, were observed in the treated cells about 12 h after the addition. The cells also lost viability at about 12 h. Breaks in the single and double strands of DNA, as measured by alkaline and neutral filter elution, became evident 18 h after treatment with 20 microM 2-chlorodeoxyadenosine; there were as many single-strand breaks as would be caused by 130 rads of gamma-ray irradiation. Double-strand breaks were equivalent to those caused by 2180 rads of gamma-ray irradiation. Comparison of the ratio of single- and double-strand breaks caused by 2-chlorodeoxyadenosine to that following radiation suggested that 2-chlorodeoxyadenosine broke only double strands. Cycloheximide inhibited the breakage of DNA double strands and the cell death caused by this compound. Flow cytometric studies of cytostasis brought about by 2-chlorodeoxyadenosine in FM3A cells showed that cells accumulated in the earlier part of the S phase. 2-Chlorodeoxyadenosine decreased DNA synthesis more than RNA or protein synthesis. The breaks in double strands of DNA were probably important in the cell death caused by 2-chlorodeoxyadenosine. The intracellular dNTP imbalance may trigger these events.

Animals↗

Pharmacokinetics of bestatin and oral activity for treatment of experimental metastases.

Bestatin is a low molecular weight aminopeptidase inhibitor originally isolated from culture filtrates of Streptomyces olivoreticuli. The serum pharmacokinetics in mice are dependent on route of administration, with a short t1/2 (1.69 min t1/2 alpha and 12.8 min t1/2 beta), but a high initial serum level following i.v. administration. When administered via the i.p., s.c., i.m., or p.o. routes of administration, bestatin had serum t1/2 beta s of 8.56, 16.91, 19.25, or 15.4 min, respectively. The maximum area under the curve (concentration X time) occurred following i.v. and i.m. administration, with a lower level following p.o. or i.p. administration. Bestatin had therapeutic activity for experimental metastases, not only following i.v., i.p., and i.m. routes of administration but also following oral administration. Because of its brief serum t1/2, bestatin's therapeutic activity depends on aggressive (either daily or twice daily injection, especially following p.o. administration) and high-dose administration. Thus, the rate-limiting aspect of bestatin's therapeutic activity appears to be associated with its pharmacokinetics.

Administration, Oral↗

Induction of DNA double-strand breaks in Chinese hamster V79 cells by 2-chlorodeoxyadenosine.

2-Chlorodeoxyadenosine was found to induce DNA double-strand breaks as well as cell death in log-phase Chinese hamster V79 cells. The induction of DNA double-strand breaks, measured by a neutral elution technique, was observed after a 2-h incubation of the cells in the presence of 5 microM of 2-chlorodeoxyadenosine, but these breaks were almost rejoined by a subsequent 1-h incubation, even though this drug was present in the medium during incubation. This repair was prevented by the addition of nicotinamide, which is known to inhibit poly(ADP-ribose) synthesis that is strongly associated with the DNA ligation, but not prevented by the addition of 9-beta-D-arabinofuranosyladenine (araA), which is known to inhibit DNA polymerization. These results suggest that the repair of CdA-induced double-strand breaks is achieved by ligation alone without DNA polymerization. When 35 microM of cycloheximide and 1.3 mM of dibutyryl cAMP were added to the medium, it was found that the induction of double-strand breaks by 2-chlorodeoxyadenosine was suppressed, while the cytotoxicity of 2-chlorodeoxyadenosine measured by colony-forming ability was not interfered with. These results suggest that the induction of DNA double-strand breaks is not associated with the cytotoxicity of this drug.

2-Chloroadenosine↗

[Effects of total parenteral nutrition containing essential trace elements on their concentrations in rats].

Twenty-four rats were equally divided into 4 groups and maintained for 1 week as follows: Group A (normal control) with a synthetic normal diet and distilled water, group B with conventional total parenteral nutrition (TPN), i.e., TPN without essential trace elements (ETE), group C with TPN supplemented with a usual dose of ETE solution (TE-5), and group D with TPN supplemented with 3 times the usual dose of TE-5. Body weight, trace element concentrations in various tissues and certain blood biochemical parameters were determined in these rats. The results were as follows: 1) No significant differences in body weight were observed among the groups. 2) The iron concentrations in plasma and tibia decreased significantly in group B as compared with group A. The addition of TE-5 prevented these decreases, but dose-dependent increases in the concentrations of iron were observed in liver, spleen and kidney (groups C and D). 3) The zinc concentrations in plasma, whole blood, brain, heart, kidney and tibia decreased significantly in group B as compared with group A. The addition of TE-5 prevented these decreases dose-dependently (groups C and D). 4) The copper concentrations in plasma, whole blood, liver, spleen, kidney, testis and tibia decreased significantly in group B as compared with group A. The addition of TE-5 resulted in a tendency for these decreases to diminish (groups C and D). 5) The manganese concentrations of whole blood in group B decreased significantly as compared with group A. The addition of TE-5 caused the manganese concentrations of various tissues in groups C and D to increase significantly as compared with group A.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[The effect of the dosage and route of manganese administration on manganese concentration in rat brain].

We investigated the differences in manganese concentration and distribution in the brains of rats administered MnCl2 perorally, intravenously and intraperitoneally for one week. Forty two male Wistar rats were divided into eight groups, designated A to H. Groups A (n = 5) and B (n = 7) were maintained with synthetic diets, with 50 and 1000 mg manganese per kg diets, respectively. Groups C (n = 5), D (n = 5) and E (n = 5) were administered manganese intravenously with dosages of 0.088, 0.88 and 2.2 mg/kg.b.w./day, respectively. Groups F (n = 5), G (n = 5) and H (n = 5) were administered manganese intraperitoneally with dosages of 0.088, 0.88 and 2.2 mg/kg.b.w/day, respectively. Four brain regions (cerebrum, cerebellum, basal ganglia and the remainder) were analyzed by atomic absorption spectrophotometry for manganese. The manganese concentrations in basal ganglia were increased proportionally to the administration dosages in intravenous administration groups (C, D and E). At the highest dosage of manganese administration, manganese concentrations in cerebrum and basal ganglia were higher with intravenous administration of manganese than with intraperitoneal administration. In addition, manganese concentrations were hardly increased in peroral administration groups. Therefore, we suggested that basal ganglia are vulnerable to manganese exposure and that liver and intestine might play the important roles in the reduction of manganese accumulation in the central nervous system.

Animals↗

[Supplementation of essential trace elements during total parenteral nutrition--effects on trace element-deficient rats].

Thirty-one male SD rats, six weeks old, were fed a trace element-deficient diet for two weeks and then divided into three groups and maintained for 1 week as follows: group A with total parenteral nutrition (TPN) without supplementation of trace elements, group B with TPN supplemented with the following 5 trace elements ... iron, zinc, copper, manganese and iodine, and group C with a diet free of the above five trace elements. Another group of eight rats was fed a diet supplemented with the above five trace elements for three weeks as a control (group D). Feeding or TPN without supplementation of trace elements evoked microcytic hypochromic anemia and significant decreases in iron concentrations in plasma and tissues (groups A and C). Supplementation of trace elements in the TPN solution showed a tendency to cure anemia and a significant increase in the iron concentration in tibia (group B). Decreases in the zinc or copper concentrations in plasma and tissues during TPN without trace elements were prevented by supplementation of trace elements in the TPN solution (group B). The plasma zinc and copper concentrations correlated well with their levels in liver, kidney and tibia. Manganese deficiency was not recognized in this investigation (groups A and C), though supplementation of trace elements in the TPN solution increased tissue manganese concentration (group B). Feeding or TPN without supplementation of trace elements induced decreases in plasma triiodothyronine and thyroxine (groups A and C). Supplementation of trace elements in the TPN solution showed a tendency to increase plasma thyroxine (group B).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Changes in trace-element concentrations after intravenous injection of an essential trace-element preparation for parenteral use in rats].

This experiment was carried out to investigate the effects of intravenous injection of an essential trace-element preparation (TE-5) on iron, zinc, copper and manganese concentrations, and blood biochemical and hematological parameters in rats. The rats were treated by intravenous injection of TE-5 for 7 days and the following results were obtained: 1) Neither a 0.04 nor a 0.4 ml/kg/day injection of TE-5 affected the iron, zinc, copper and manganese concentrations in tissues. 2) At a higher dose (1.2 ml/kg/day), iron concentrations in liver and spleen, zinc concentrations in liver, kidney, tibia and plasma, copper concentrations in heart, kidney and whole blood, and manganese concentrations in brain, heart, spleen, kidney, femoral muscle, tibia and whole blood increased. 3) At the highest does (4 ml/kg/day), all rats died and iron, zinc, copper and manganese concentrations in tissues increased remarkably. 4) With injections of TE-5 (0.04-1.2 ml/kg/day), hemoglobin, hematocrit, alkaline phosphatase activity and blood urea nitrogen decreased slightly. These results suggest that iron, zinc, copper and manganese concentrations, and blood biochemical and hematological parameters are maintained at doses up to 0.4 ml/kg/day of TE-5, but that doses higher than that destroy homeostasis.

Animals↗

Effects of dietary treatment on serum insulin and proinsulin response in newly diagnosed NIDDM.

Serum proinsulin is disproportionately elevated both in the basal state and after an oral glucose load in non-insulin-dependent diabetes mellitus (NIDDM). However, there is no detailed information about the effect of glycemic control on this abnormality. We investigated the effect of glycemic control by dietary treatment on serum proinsulin level in the basal state and in response to an oral glucose load. Ten NIDDM patients (7 men and 3 women), aged 19-60 yr, with mean (+/- SD) body mass index of 28 +/- 6 kg/m2 (range 21-42 kg/m2) and normal renal and liver function were studied. Before and after dietary therapy (25-30 kcal/kg ideal body wt), 100-g oral glucose tolerance tests were performed. Proinsulin was measured with our proinsulin-specific antiserum, which recognizes the connecting site of the B-chain of insulin and C-peptide. After dietary treatment, fasting plasma glucose decreased from 197 +/- 35 to 113 +/- 18 mg/dl (P less than .001). Both serum insulin and proinsulin decreased (insulin from 15 +/- 8 to 10 +/- 4 microU/ml, P less than .02; proinsulin from 31 +/- 18 to 13 +/- 5 pM, P less than .02), and the molar ratio of proinsulin to insulin also tended to decrease (from 0.321 +/- 0.08 to 0.24 +/- 0.10, P less than .10). Insulin response to oral glucose increased after dietary treatment, whereas proinsulin response did not change, resulting in a significant decrease in the molar ratio of the area under the curve of proinsulin to insulin after glucose load (from 0.28 +/- 0.12 to 0.13 +/- 0.07, P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Synthesis and properties of oligodeoxyribonucleotides containing N6-methoxyadenine.

Oligodeoxyribonuclotides containing N6-methoxyadenine (mo6A), a promutagenic base, were synthesized. The Tm values and thermodynamic parameters for double strand formation of d(CCTGGTAmo6ACAGGTCC) have been measured. The order of the base-pair stability was A-T greater than mo6A-C approximately equal to mo6A-T greater than A-C.

Adenine↗

Quantifying manganese in lymphocytes to assess manganese nutritional status.

To clarify whether manganese nutritional status is better reflected by the manganese concentration in lymphocytes or in whole blood, we injected manganese solutions intravenously into manganese-deficient rats and determined manganese concentrations in lymphocytes, whole blood, and various tissues. The manganese concentrations in lymphocytes and tissues, but not in whole blood, were significantly less in manganese-deficient rats than in normal rats. These low values could be prevented by intravenous injection of manganese in a dose-dependent manner. These results suggest that, for assessment of manganese nutritional status, measurement of manganese in lymphocytes is better than that in whole blood.

Animals↗