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Biomedical subjects

K Hirabayashi

Publications and source records attributed to K Hirabayashi.

At least 91 records · Page 5Linked to original sources
PubMed1993

Decrease in deoxyribonucleotide triphosphate pools and induction of alkaline-labile sites in mouse bone marrow cells by multiple treatments with methotrexate.

Methotrexate (MTX), an inhibitor of dihydrofolate reductase (DHFR), slightly induced micronuclei in bone marrow and peripheral blood cells, and this induction was enhanced by multiple treatments with the drug. Furthermore, we have suggested that the multiple-dose effect on the induction of micronuclei by MTX might be explained by intracellular accumulation of the drug, resulting in an enhancement of DHFR inhibition. An imbalance or decrease in the deoxyribonucleotide (dNTP) pool would be generated by this enzyme inhibition. Therefore, we attempted to determine the level of the dNTP pool in mouse bone marrow cells. The levels of three dNTPs (dTTP, dATP, dGTP) as determined by HPLC were only 1/10-1/40 of the levels previously found in mammalian cell lines, but dCTP levels could not be determined precisely because they approached the limits of detectability. The levels of dTTP, dATP and dGTP in mouse bone marrow cells 3 h after four injections of MTX (4 mg/kg/day) decreased to 21.2%, 47.0% and 38.1%, respectively, of those in the control group. The level of dTTP 3 h after four injections of 100 mg/kg of the drug decreased to almost 0%. The results of alkaline elution assays suggested that alkaline-labile sites were generated in mouse bone marrow cells 6 h after four injections of MTX (4 mg/kg). These findings suggest that the multiple-dose effects of MTX on micronucleus induction in mouse bone marrow cells may be explained by the decrease in the dNTP pool and subsequent generation of alkaline-labile sites (possibly apurinic/apyrimidinic sites).

Animals↗
PubMed1993

Immunohistochemical type distinction of alpha-fetoprotein in various alpha-fetoprotein-secreting tumors.

In order to clarify the histogenesis of alpha-fetoprotein (AFP)-secreting tumor tissues, formalin-fixed, paraffin-embedded serial sections of 148 tumors in various organs were examined by the peroxidase-antiperoxidase method for AFP, and paradoxical concanavalin A staining. Yolk sac-type AFP was found in yolk sac tumors, embryonal carcinomas, solid teratomas, (yolk sac) endodermal cell tumors, adenocarcinomas (stomach, ovary or lung) and metastatic liver cancers. Hepatic-type AFP was demonstrated in hepatocellular carcinomas, hepatoblastomas, solid teratomas and a stomach cancer. Yolk sac-type AFP was observed in the neighboring liver cells of metastatic liver cancers without relation to the type of AFP in primary cancers. The results from serum analyses of preoperative tumor-bearing patients (68 cases) were coincident with those from immunohistochemical stainings.

Female↗
PubMed1993

Characterization of two novel polysaccharides having immunological activities from the root of Panax ginseng.

Two acidic polysaccharides, called ginsenan S-IA and ginsenan S-IIA, were isolated from the root of Panax ginseng C. A. Meyer. They were homogeneous on electrophoresis and gel chromatography, and their molecular masses were estimated to be 5.6 x 10(4) and 1.0 x 10(5), respectively. Ginsenan S-IA is composed of L-arabinose: D-galactose: D-galacturonic acid in the molar ratio of 8:8:1, and ginsenan S-IIA is composed of L-arabinose: D-galactose: D-glucose: D-galacturonic acid in the molar ratio of 15:10:2:5, in addition to small amounts of O-acetyl groups. About a half (ginsenan S-IA) and about a quarter (ginsenan S-IIA) of the hexuronic acid residues exist as methyl esters. Reduction of carboxyl groups, methylation analysis, nuclear magnetic resonance and periodate oxidation studies indicated that their structural features include mainly alpha-1,5-linked L-arabino-beta-3,6-branched D-galactan type structural units. Both polysaccharides showed remarkable reticuloendothelial system-potentiating activity in a carbon clearance test and pronounced anti-complementary activity. These substances are the first examples having a relatively high content of both alpha-3,5-branched L-arabinose and beta-1,4-linked D-galactose units among the acidic arabinogalactans with activities on phagocytosis and anti-complement.

Arabinose↗
PubMed1993

Characterization of two acidic polysaccharides having immunological activities from the root of Panax ginseng.

Two acidic polysaccharides, named ginsenan PA and ginsenan PB, were isolated from the root of Panax ginseng C. A. Meyer. They were homogeneous on electrophoresis and gel chromatography, and their molecular masses were estimated to be 1.6 x 10(5) and 5.5 x 10(4), respectively. They are composed of L-arabinose: D-galactose: L-rhamnose: D-galacturonic acid: D-glucuronic acid in the molar ratios of 11:22:1:6:1 (ginsenan PA) and 3:7:2:8:1 (ginsenan PB), in addition to small amounts of O-acetyl groups. Almost all (ginsenan PA) and part (ginsenan PB) of the hexuronic acid residues exist as methyl esters. Reduction of carboxyl groups, methylation analysis, nuclear magnetic resonance and periodate oxidation studies indicated that their structural features include mainly both alpha-arabino-beta-3,6-galactan type and rhamnogalacturonan type structural units. Both polysaccharides showed remarkable reticuloendothelial system-potentiating activity in a carbon clearance test, pronounced anti-complementary activity and alkaline phosphatase-inducing activity in a dose dependent manner.

Animals↗
PubMed1993

[A field assessment of a community 'rehabilitation class' for home handicapped persons--focusing on participant social network].

The purpose of this study is to evaluate a community 'Rehabilitation class' for its effectiveness. A function of the 'Rehabilitation class' is the expansion of a participant's social network, and the following hypothesis was formulated: the reciprocal relationships of participant and class or staff members bring about psychological effectiveness and a change of their awareness, resulting in the expansion of social networks. Actual class activity, psychological aspects and social networks of twenty-six participants and twenty care takers, who responded to a questionnaire survey, were examined with respect to the above hypothesis. Those reporting having changed were compared to those reporting no change. The results were as follows: (1) Class activity was directed at developing relationships among participants, and while most of them were changed positively, it appeared that staff members were not sufficiently involved. (2) There were 23 participants in the 'changed' group. Most of their care takers and family were changed positively. Eleven reported receiving significant emotional support from other 'Rehabilitation class' members, and therefore their social networks appeared to have expanded generally. (3) The 'non changed' group consisted of 3 participants whose social networks did not appear to have expanded. (4) Social networks outside the home were not expanded for all participants, probably due to their reported receiving little social support from others outside family members, and because they had few social roles outside the home. Based on the above results, it is concluded that effective classes involve participants individually, and encourage the independent activity of participants, and that it is necessary to have networking with other organizations in community, and the 'Rehabilitation class' should be provided to smaller local regions.

Aged↗
PubMed1992

Influence of fibril length upon ePTFE graft healing and host modification of the implant.

Influence of fibril length (porosity) upon synthetic vascular graft healing has not been investigated in detail. The purpose of this study was to determine the dependence of neoendothelial healing, cellular response, and biocompatibility on the fibril length of expanded polytetrafluoroethylene (ePTFE) grafts with an internal diameter of 1.5 mm. ePTFE grafts of different fibril length, 20, 40, 60, and 90 microns, were implanted into the abdominal aorta of rats (n = 5 for each group). After 5 weeks, the implants were harvested and examined for neointimal and pseudointimal coverage by light microscopy and SEM. The hydroxyproline content of the implants was measured, and the distribution of collagen types was examined. The neointimal and pseudointimal coverage was related to the fibril length, and the neoendothelial healing was better on 60-microns and 90-microns grafts than on 20-microns and 40-microns grafts. The amount of hydroxyproline was also related to the fibril length, however, no significant difference could be observed between 60-microns and 90-microns grafts. Collagen types I and III were almost identically located in the middle portion of the implants. Our results demonstrate that the fibril length of ePTFE grafts affected neoendothelial healing and its affinity to collagen.

Animals↗
PubMed1992

Mechanism of induction of micronuclei and chromosome aberrations in mouse bone marrow by multiple treatments of methotrexate.

Methotrexate (MTX), an inhibitor of dihydrofolate reductase (DHFR), slightly induced micronuclei and this induction of micronuclei was enhanced by multiple treatments with the drug (Yamamoto et al., 1981; Hayashi et al., 1984; CSGMT/JEM.MMS, 1990). More micronuclei and chromosomal aberrations in mouse bone marrow cells were induced by multiple than by single treatment. The MTX level in mouse plasma and bone marrow showed little (or no) differences between single and quadruple treatments several hours after the injection(s). On the other hand, the DHFR activity in bone marrow cells 3 h after one and four injections was decreased to approximately 38 and 0%, respectively, of that in non-treated mice. Furthermore, the intracellular MTX level in the bone marrow cells (but not in total bone marrow) after four injections was about 10-fold higher than that after one injection. The amount of MTX bound to protein 3 h after four injections, as assayed by gel filtration (Sephadex G-25), was approximately 8-fold greater than after one injection. Therefore, the multiple-dose effects of MTX on the induction of micronuclei and chromosomal aberrations may be explained by the intracellular accumulation of MTX resulting in an enhancement of enzyme inhibition.

Animals↗
PubMed1992

Spontaneous fracture of the odontoid process in rheumatoid arthritis.

Six cases of spontaneous fracture of the odontoid process in rheumatoid arthritis are presented. Fifty-one patients with atlantoaxial subluxation in rheumatoid arthritis underwent surgery between 1981 and 1990. This included six patients (in 10%) who had subluxation accompanied by fracture of the odontoid without apparent trauma. The mean patient age was 58 years and all had a long history of rheumatoid arthritis. No trauma was considered to be the cause of the fracture. This is a fracture caused by erosion and osteoporosis of the odontoid process due to rheumatoid synovitis, aging and steroid therapy. In addition, another cause is a dynamic load produced from the instability accompanying atlantoaxial subluxation working on the odontoid in cervical extension. It is important remember that the odontoid process is susceptible to spontaneous fracture.

Aged↗
PubMed1992

A clinical study of degenerative spondylolisthesis. Radiographic analysis and choice of treatment.

Surgical treatment of degenerative spondylolisthesis in 27 patients by means of anterior lumbar interbody fusion and in 14 patients by means of posterior decompression yielded average degrees of recovery of 77% and 56%, respectively. Preoperative analysis of myelograms, and computed tomographies after myelography indicated that anterior shifting of the inferior articular process of the slipping vertebra was the main factor responsible for compression of the nervous tissue in the early stages of degenerative spondylolisthesis. Patients in these stages should be treated by anterior lumbar interbody fusion. In the later stages of degenerative spondylolisthesis, osteophytes on the superior articular processes of the lower vertebra were an additional factor in compression, and patients should be treated by posterior decompression. Computed tomographies after myelography provided the key images for identifying pathologic processes in degenerative spondylolisthesis and selecting appropriate surgical procedures.

Adult↗
PubMed1992

[Combination chemotherapy with 254-S, ifosfamide and peplomycin for advanced or recurrent cervical cancer].

From favorable results with 254-S, a new cisplatin analogue, single administration, we have conducted a clinical study to investigate the efficacy of combination of 254-S, ifosfamide and peplomycin, each of which has a different dose limiting factor. A total of 45 patients, including 22 patients with stage III and IV cervical cancer and 23 cases with recurrent cervical cancer, were treated with at least two courses of 254-S (100mg/m2, iv. Day 1), ifosfamide (1,500mg/body, iv. Day 1-5) and peplomycin (5mg/body, im. Day 1-6), and tumor response was evaluated clinically and by CT scanning. The response rate obtained in patients with advanced disease was 81.8% (PR = 17, CR = 1) and that in cases with recurrence was 60.9% (PR = 12, CR = 2). Myelosuppression was the dose limiting factor. In the 121 courses, grade 3 and 4 of leucopenia and thrombocytopenia were observed with an incidence of 44% and 32%, respectively and DIC occurred in 3 cases with poor PS though they recovered after reducing the 254-S dose to 80 mg/m2. The other toxicities were mild except for alopecia. Anaphylaxia was observed in a case at the second administration though the patient recovered in 15 minutes. There was no death. As to prognosis, a significant prolongation of survival period was observed in recurrent cases and 4 cases are alive (NED) after one and a half year. In the advanced cases, until now 3 cases of stage IV have died from the disease. We have concluded that this regimen is effective as a neoadjuvant chemotherapy for advanced cervical cancer and useful for the treatment of recurrent cervical cancer.

Adenocarcinoma↗
PubMed1992

[Sensitivity test for anti-tumor agents-3. MTT assay and its clinical effect].

MTT assay, a sensitivity test of anti-tumor agents was performed, and its clinical usefulness, was discussed. In 15 surgical specimens, the cell suspensions were prepared aseptically, and divided into three processing; namely, Papanicolaou (Pap) smears to confirm the malignant cells, MTT assay, and cell cultures in chamber slides. MTT assay was evaluated only when tumor cells in the chamber slide were observed 50% or more by Pap staining. Drugs judged to be effective were applied for patients, resulting in 64.2% of predictive accuracy in the sensitivity. Conclusions; 1) MTT assay was developed for sensitivity test of anti-tumor agents, 2) Strict assessment was carried out by the confirmation of cancer cells using chamber slides, 3) On clinical usefulness, predictability for the sensitivity was 64.2%, that for resistance was 100%, and over all predictability was 66.7% 4) MTT assay was useful for the determination of effective and for elimination of ineffective drugs.

Antineoplastic Agents↗
PubMed1992

[The effect of elastase on aminonucleoside nephrosis--on renal vascular system].

This study was performed to investigated the relationship between cross sectional areas of glomerular arterioles and glomerular volume in rats with puromycin aminonucleoside (PAN)-induced nephrosis, which is an experimental model of glomerular sclerosis. We also evaluated the effect of an anti-arteriosclerotic agent, elastase on these parameters. Six-week-old male Sprague-Dawley rats were divided into 3 groups; control, PAN-treated (70 mg/kg i.p.), or PAN+elastase-treated (5 mg/kg/day i. m.) group. After 12 weeks of experimental period, microvascular cast of the kidney was prepared, and the cross sectional areas of afferent and efferent arterioles as well as glomerular volume were measured using scanning electron microscopy. In the juxtamedullary glomeruli with minor abnormalities, the efferent arteriole was narrower in PAN-treated rats than in the control rats and the elastase-treatment partially corrected it (control 55.7, PAN 35.9, PAN+elastase 43.7 x 10 microns 2). On the other hand, the cross sectional area of afferent arteriole was not different among the 3 groups. In glomeruli showing sclerosis, the cross sectional area of efferent arteriole correlated positively with the glomerular volume. There results suggest that constriction of the efferent arterioles contributes to the development of glomerular sclerosis in PAN-induced nephrosis. In addition, elastase possibly inhibits this process and thereby protect glomeruli from sclerosis.

Animals↗
PubMed1992

[A case report of poststernotomy mediastinitis treated with the pectoralis major muscle flap after protracted wound irrigation].

A 8-year-old boy developed mediastinitis after direct closure of atrial septal defect. Methicillin-resistant Staphylococcus aureus (MRSA) was detected from the wound. Intermittent wound irrigation with povidone-iodine solution and vancomycin solution was protracted for two months. After the remission of MRSA infection, implantation of pectoralis major muscle flap was performed. Without recurrence of infection the wound was healed completely. Although pectoralis major muscle flap is an effective method of choice for mediastinitis, an appropriate timing of enforcing this method should be investigated hereafter.

Child↗
PubMed1992

[The clinical and pharmacokinetic evaluation of two-route chemotherapy with cisplatin and sodium thiosulfate in combination with angiotensin II].

Thirty-six courses of chemotherapy with cisplatin (CDDP) and sodium thiosulfate (STS) were performed in 31 patients with gynecologic cancer 2 weeks after operation under the hypertensive condition induced by angiotensin II (AT-II). One hundred-fifty mg of CDDP/body was intraperitoneally administered while the usual systolic blood pressure was increased to 130-140% by AT-II. The hypertension was maintained for 15 minutes after finishing CDDP infusion, then 8g of STS was intravenously infused immediately after the cessation of AT-II. The urinary Pt level measured 15 minutes after finishing CDDP infusion was extremely low at 1.37 +/- 0.47 micrograms/ml, in spite of the significantly high levels of plasma total Pt (7.83 +/- 0.85 micrograms/ml) and filtrable Pt (4.02 +/- 0.55 micrograms/ml). This suggests that, during renal vasoconstriction induced by AT-II, the renal blood flow as well as renal uptake of CDDP was decreased. Plasma filtrable Pt levels were measured at 15, 30, 60 and 120 minutes after intraperitoneal administration of CDDP. At 15 and 30 minutes a significantly higher blood concentration was found than in the control group (p less than 0.05). However, CDDP-induced toxicities of the bone marrow, liver, kidney and alimentary tract were not increased. The extreme vasoconstriction in the kidneys and other organs induced by AT-II might have protected these organs from the toxicities of CDDP despite the fact that STS infusion was delayed by 15 minutes after CDDP infusion. STS infused immediately after the cessation of AT-II could neutralize the CDDP preventing the occurrence of toxicities.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1991

A case of Caroli's disease with hepatolithiasis, choledocholithiasis, and cholangiocarcinoma.

A 48-year-old woman with Caroli's disease accompanied by hepatolithiasis, choledocholithiasis, and cholangiocarcinoma is reported. Magnetic resonance imaging was useful for the diagnosis of the cholangiocarcinoma. The relationship between cholangiocarcinoma and hepatolithiasis, choledocholithiasis, and chronic cholangitis in Caroli's disease is discussed.

Adenoma, Bile Duct↗
PubMed1991

Secretory expression of the human serum albumin gene in the yeast, Saccharomyces cerevisiae.

We have fused a cDNA gene encoding mature human serum albumin (HSA) to several secretory leader-encoding sequences. The hybrid genes were cloned into an episomal vector under the control of several yeast promoters and then introduced into yeast cells. The GAL1 promoter in combination with either the native HSA pre-sequence or a modified HSA pre-sequence gave the highest production of immunoreactive HSA, 90 mg/liter being reached in a shake flask culture. The invertase pre-sequence, the mating factor alpha 1 prepro-sequence, and the modified HSA pre-sequence directed accurate processing. In contrast, the chicken lysozyme pre-sequence and the native HSA pre-sequence directed incorrect processing. Episomal vectors were unstable within the host cells under non-selective culture conditions. To improve the plasmid stability, the hybrid genes were incorporated into an integrative vector. Transformants carrying multicopies of the plasmid integrated at the LEU2 locus stably secreted HSA. The highest yield of 65 mg/liter in a shake flask culture was obtained with the combination of the yeast glyceraldehyde-3-phosphate dehydrogenase promoter and the modified HSA pre-sequence. By constructing transformed strains containing multicopies of plasmids integrated at both the chromosome LEU2 and HIS4 loci, we have obtained a stable strain that continuously secretes as much as 85 mg HSA per liter of culture medium.

Amino Acid Sequence↗