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Biomedical subjects

M Sakurai

Publications and source records attributed to M Sakurai.

At least 865 records · Page 48Linked to original sources

[The effect of methotrexate on intracellular nucleotide pools].

In a previous study, we showed that methotrexate (MTX) enhanced the intracellular production of ara-CTP. The study described in the present paper has elucidated the mechanism of this MTX-enhanced ara-CTP production, which occurs as a result of MTX reducing the intracellular dCTP pool, and the decreased dCTP pool then allowing activation of deoxycytidine Kinase. One of the mechanisms of synergistic interaction between 1-beta-D-arabinofuranosylcytosine (ara-C) and MTX might therefore be the stimulated phosphorylation of ara-C with MTX-activated deoxy-cytidine kinase. Using high-pressure liquid chromatography, the sequential changes occurring in the acid-soluble intracellular nucleotide pools of L1210 mouse leukemic cells were analysed after treatment with MTX (12mg/kg). At 3 hr after treatment with MTX a reduction of the dTTP pool to 46% of the control level was observed. The dCTP pool was also reduced to 36% of the control level after treatment with MTX. The levels of the dATP and dGTP pools were not significantly changed, at least during the observation period. Pyrimidine ribonucleotide pools were almost unchanged at 3 hr, but in the sequential changes observed in purine ribonucleotide pools after treatment with MTX, both diphosphate and triphosphate pools were seen to be on the decline, the reduction of triphosphate pools being especially marked. A decline in ATP and GPT to 24-30% of control levels was observed at 3 hr after treatment with MTX.

Adenosine Triphosphate↗

[Electrophysiologic study of paroxysmal supraventricular tachycardia].

Seventy patients (pts) with paroxysmal supraventricular tachycardia (PSVT) were examined by using electrophysiological techniques (EPS). At rest, 23 pts had the ECG evidence of W-P-W syndrome (group I) and 47 pts did not have (group II). In 20 pts of group I, PSVT could be induced by EPS. In 19 pts of them, the mechanism of PSVT was reentry using the accessory pathway (AP) retrogradely and the normal pathway (NP) antegradely, but only one showed the antidromic type (the former in reverse) of PSVT. Whereas in 45 pts of group II, PSVT could be induced reproduceably by EPS. In 31 pts of them, the mechanism of PSVT was reentry using concealed AP retrogradely and NP antegradely. In 13 pts, the mechanism was reentry within the AV node because dual pathways were found. In 11 pts, the reentrant beats conducted on the slow pathway (SP) antegradely, and on the fast pathway (FP) retrogradely. In 2 pts, reentrant beats conducted on the FP antegradely and on SP retrogradely. In one pt, PSVT was caused by sinus nodal or intraatrial reentry. Among 13 pts, in whom PSVT was caused by reentry using AP accompanied with dual pathways, the sudden change of the cycle length of PSVT were observed in 5 pts. PSVT which could only be induced by EPS in the laboratory were as follows: Af in 5, VT in 3 and sinus nodal reentrant tachycardia in one. In conclusion, in 65 pts of 70 pts with PSVT (93%), PSVT could be induced by EPS reproduceably. On the basis of EPS, the mechanism of PSVT was reentry involving AP in 29%, reentry involving concealed AP in 44%, AV nodal reentry in 19% and sinus nodal reentry in 1%.

Electrocardiography↗

[Fundamental and clinical studies on aspoxicillin in the field of pediatrics].

Fundamental and clinical studies were performed with aspoxicillin (ASPC), a new developed injectable broad penicillin, in pediatric infectious diseases, and the following results were obtained. Pharmacokinetics ASPC was administered to 2 cases at a dose of 20 mg/kg by one shot intravenous injection. The mean half-life (T 1/2) was 1.17 hours. The mean urinary excretion rate was 58.4% during 6 hours after ASPC treatment. In 3 cases of intravenous drip infusion with a period of 1 hour at a dose of 10 mg/kg (2 cases) and 20 mg/kg (1 case), the half-lives (T 1/2) were 1.7 hours, 3.5 hours and 1.0 hour, respectively. The urinary recovery rate during 6 hours after administration was 57.7%, 32.6% and 42.7%, respectively. At only one case treated with 10 mg/kg intravenous drip infusion, the half-life was prolonged and urinary excretion rate was lower than other 2 cases. Clinical study ASPC was administered 50-80 mg/kg/day for 4-8 days to 22 children comprising 6 tonsillitis, 2 bronchitis, 6 pneumonia and 8 urinary tract infections. Clinical efficacy was excellent in 13 cases, good in 8 cases and fair in 1 case, the total cure rate was 95%. As for the clinical response classified by diagnosis, the each efficacy rate of tonsillitis, bronchitis and pneumonia was 100%, and that of urinary tract infection was 87.5%. Clinical side effect and abnormal laboratory findings were not observed in any cases. From the above results, it was concluded that ASPC was one of the useful secure drug for treatment of infections in pediatric field.

Adolescent↗

[Clinico pathological study on prognostic factors of sarcoma].

A clinicopathologic study of 48 patients of sarcoma was performed. This malignant neoplasm principally of middle and late adults occurred most often in the body surface (58%). Forty-six patients were treated by surgery with wide or marginal or palliative resection. In two only biopsy was done. Adjuvant chemotherapy was added in 27 patients. Histological grading of surgical specimens was Stage I in 9, II in 16, III in 18 and IV in 5. The evaluation of prognosis showed that wide resection with lymph node dissection was most excellent procedure as the operative methods. Regarding histological grading, significant difference between Stage I + II and III + IV could be detected in the survival rates (p less than 0.05). The adjuvant chemotherapy used did not affect the prognosis.

Adolescent↗

[Modern trend in artificial joints].

When the bone and joint are destroyed by rheumatoid arthritis, fractures involving joint, bone tumor and osteoarthritis, surgical intervention is indicated to replace affected joint by artificial joint. In 1984, about 27,400 surgeries were done in Japan, including 12,000 endoprosthesis of femoral head and 9,400 total hip replacement. Materials used for artificial joint are stainless alloy, alumina-ceramic, polyethylene and silicon-rubber. Methalcrylate bone cement is frequently used to get anchoring between artificial joint and skeletal tissue, however, it has disadvantage in case of revision. Recently many designs of artificial joint without bone-cement have been developing. It has been elucidated that resistance at friction between ceramic and polyethylene is ten times lessened than metal and polyethylene. Polycentric architecture which is modified from simple ball and socket is known to be that wearing of artificial joint and bone structure is able to be decreased. Durability will be much improved by not only selecting a material but also by devising suitable design. Infection associated with implant should be strictly avoided by using clean operating room and prophylaxis with antibiotics.

Humans↗

[Pharmacokinetics and clinical evaluation of aztreonam in pediatrics].

Pharmacokinetics, in vitro, and in vivo effect of aztreonam (SQ 26,776, AZT), a newly synthesized monobactam antibiotic, were investigated in pediatric patients. The pharmacokinetics were studied in 12 children without renal or hepatic impairment, each of whom received single 10, 20 and 40 mg/kg intravenous doses of drug. Serial samples of serum and urine were assayed for AZT. Serum pharmacokinetics of AZT were described by an open, linear, two-compartment kinetic model. After intravenous administration, AZT was eliminated primarily by urinary excretion of unchanged drug (60.4%). The average biological half-lives of AZT in serum were 1.33 (10 mg/kg, n = 1), 1.69 +/- 0.40 (20 mg/kg, n = 8), and 1.51 +/- 0.61 (40 mg/kg, n = 3) hours. The antibacterial activity of AZT against E. coli and P. aeruginosa was equal or slightly stronger than that of CPZ, LMOX, and CTX. It had no antimicrobial activity against Gram-positive cocci. In vivo effect of AZT was evaluated in 13 children with various infections. The result was excellent in 7 cases, good in 1 case, fair in 3 cases and poor in 1 case, with effective ratio of 66.7%. Exanthema or elevation of GOT and GPT were noticed in 3 patients.

Adolescent↗

Natural killer (NK) and lymphokine-activated killer (LAK) cell activity in healthy volunteers with special emphasis on the familial incidence of cancer.

Natural killer (NK) and lymphokine activated killer (LAK) cell activities in 133 healthy volunteers were analyzed with regard to the volunteer's sex, age, smoking history and the familial incidence of cancer. None of these factors had any influence on NK and LAK cell activities. It was concluded that identifying individuals with increased risk of cancer development by examining NK and LAK activities would be difficult.

Adult↗

Clonogenic patterns of human pulmonary adenocarcinoma cell lines (PC-9, PC-13 and PC-14) and how they influence the results of test for chemosensitivity to cisplatin in the human tumor clonogenic assay.

The clonogenic patterns of three human pulmonary adenocarcinoma cell lines (PC-9, PC-13 and PC-14) were studied by human tumor clonogenic assay (HTCA), and factors which could influence the results of tests for the chemosensitivity of these tumor cells to cisplatin in HTCA were determined. The results showed that each tumor cell line had a characteristic clonogenic pattern. The time intervals for the cells to grow to the plateau phase varied from 9 to 16 days, depending on the cell line and number of cells plated. The number of cells plated could substantially influence the results of chemosensitivity tests. The percentage of surviving colonies increased markedly if too many cells (usually 5 X 10(4) or more/plate) were plated. For continuous exposure, the results of chemosensitivity tests were rather stable after 7 days of incubation in each cell line, especially when fewer than 2 X 10(4) cells/plate were plated. For 1-hour exposure, the incubation periods for the results to become stable varied from 7 to 16 days depending on the cell type, number of cells plated and drug concentration. It was stressed that for the correct evaluation of the chemosensitivity of cultured cell lines in HTCA, the clonogenic pattern of each tumor cell line should be checked in detail before further experiments are conducted. The higher the concentration and the longer the exposure time, the more strongly cis-diamminedichloroplatinum (CDDP) suppressed the colony growth in each of the three cell lines in HTCA, and it was recommended that CDDP should be used clinically in such a way as to maintain a high serum level of the active form of CDDP for a long time.

Adenocarcinoma↗

Transcatheter chemo-embolization effective for treating hepatocellular carcinoma. A histopathologic study.

A histopathologic study was done on livers from 14 patients who underwent surgery for hepatocellular carcinoma and who had been pretreated by a combination of intra-arterial embolization of Gelfoam (Upjohn) plus intra-arterial chemotherapy. This technique was effective as the excess vascularity of the tumor and the tumor bulk were reduced and resection was readily facilitated. For solitary tumors of less than 4 cm in diameter, this approach was particularly effective. As this combined treatment almost invariably leads to liquefaction and necrosis of the tumor, the likelihood of metastases is diminished.

Aged↗

High-resolution studies in patients with aniridia-Wilms tumor association, Wilms tumor or related congenital abnormalities.

We attempted to determine whether all cases of AWTA (anirida-Wilms tumor association) or any of the following groups of patients show 11p deletion: cases of Wilms tumor with congenital abnormalities other than aniridia, those without any congenital abnormalities, tumor itself in cases of Wilms tumor without constitutional 11p deletion and cases of aniridia or hemihypertrophy without Wilms tumor. We studied a total of 29 index patients including five cases of AWTA, four cases of Wilms tumor with various congenital abnormalities, 16 cases of Wilms tumor without other abnormalities, three cases of aniridia in one of which Wilms tumor developed later and a case of hemihypertrophy. In all five cases of AWTA and in a case of aniridia who later developed Wilms tumor, 11p deletion involving the p13 band was detected. The mother of the latter also showed an identical 11p deletion. The common segment of deletion was the middle part of the p13. Two possible hypotheses on the mechanism through which Wilms tumor might develop were evaluated, based on the distribution of break points. All other cases, including five with tumor culture, showed a normal karyotype.

Adolescent↗

Further study on a BF silent allele.

A family was found which indicated the existence of a silent allele (BF*QO) at the locus for complement factor B. Three generations with eight members were studied. Four individuals were considered to be heterozygous for B deficiency because of unusual segregation patterns of the BF electrophoretic variants and low levels of B. Haplotype study on the other HLA-linked markers supported the presumption. No unusual products were detected by immunoblotting after sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE).

Alleles↗

Cerebral neoplasms initially presenting with massive intracerebral hemorrhage.

In three patients, clinically silent brain tumors led to massive intracerebral hemorrhage. These patients represented 0.6% of 497 consecutive patients with primary or secondary brain tumors and 2.5% of 119 patients with hypertensive or spontaneous intracerebral hemorrhage. Examination by computed tomography and angiography provided no evidence suggestive of the presence of neoplasms. All three patients were surgically treated and the lesions were histologically confirmed to be metastatic bronchogenic carcinoma, metastatic clear-cell carcinoma and low-grade astrocytoma, respectively.

Adenocarcinoma↗

Nucleotide sequence of the insertion sequence found in the T-DNA region of mutant Ti plasmid pTiA66 and distribution of its homologues in octopine Ti plasmid.

The octopine tumor-inducing (Ti) plasmid pTiA66 has an insertion mutation in its T region (the DNA region incorporated into the plant genome) that results in the slow growth of crown gall tumors. These tumors exhibit hormonal autonomy different from that of the crown gall tumors caused by wild-type Ti plasmids. In the present study, the nucleotide sequences of both the DNA segment inserted into pTiA66 and its target site have been determined. The inserted segment is 2548 base pairs long and has 20-base-pair terminal inverted repeats. An 8-base-pair sequence at the target site is duplicated at both integration junctions. These structural features of the insert suggest that it is a bacterial insertion sequence (IS) element, which we have named IS66. Blot-hybridization analyses using IS66 probes revealed that genomes of octopine Ti plasmids contain at least three sequences homologous to IS66: two homologues are located in the virulence region and one is located between the left-hand (TL-DNA) and right-hand (TR-DNA) portions of T-DNA. The chromosome of Agrobacterium tumefaciens A66 also contains two sequences highly homologous to IS66. These results suggest that the mutant pTiA66 plasmid was generated by translocation of one of the sequences showing homology with IS66 into the T region. The fact that a sequence homologous to IS66 is present between TL-DNA and TR-DNA also suggests that the octopine T region was split into two portions, TL-DNA and TR-DNA, by translocation of IS66 or its relatives. Thus, IS66 may cause genetic and structural variations of the T region and the vir region of the octopine Ti plasmids.

Arginine↗