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Biomedical subjects

T Oikawa

Publications and source records attributed to T Oikawa.

At least 181 records · Page 10Linked to original sources

Immunocytochemical localization of an oviductal zona pellucida glycoprotein in the oviductal epithelium of the golden hamster.

The immunocytochemical localization of an oviductal glycoprotein associated with ovulated eggs was investigated. Using a monoclonal antibody, we studied three regions of epithelium in the golden hamster oviduct. The monoclonal antibody reacted with the oviductal epithelium throughout the fimbriae and isthmus. Intense binding was observed in the ampulla and isthmus, especially in the caudal isthmus. In addition, reactive materials were present in the ovarian bursal sac and lumen of the ampulla. At the ultrastructural level, the monoclonal antibody reacted specifically with putative secretory granules and Golgi apparatus of nonciliated cells in the oviductal epithelium. Other cellular organelles did not react. Quantitative data indicated that the immunolabelings were intense in the ampullar and isthmic cells but weak in the fimbrial cells. Lipid droplet-like granules of the fimbriae and lysosome-like vesicles of the isthmus did not react with the monoclonal antibody. In all cases, ciliated cells did not react with the monoclonal antibody. These results suggest that the glycoprotein is primarily produced and secreted by ampullar and isthmic secretory cells and is then accumulated in the ovarian bursal sac. These findings may provide insight into regional and cellular differences in secretion of the golden hamster oviduct.

Animals↗

Growth requirements and long-term subcultivation of bovine granulosa cells cultured in a serum-free medium.

We have developed an improved serum-free medium to optimize the cell growth of bovine granulosa cells. The cells on collagen-coated culture plates proliferated extensively in a nutrient medium supplemented with insulin, heparin binding growth factor-2 (HBGF-2), lipoprotein, and bovine serum albumin (BSA). The cell doubling time at logarithmic phase and final cell density at confluent cultures were equal to those of cultures grown in the presence of medium supplemented with optimal concentration (10%) of fetal bovine serum (FBS). Whereas HBGF-2 or insulin alone had a small mitogenic effect of granulosa cells, lipoprotein or BSA did not. When lipoprotein, BSA, or insulin was added together with HBGF-2, synergistic cell proliferation was observed in all combinations. Insulin or lipoprotein had an additive mitogenic stimulation of these cells in the presence of BSA. After granulosa cells were subcultivated in a serum-containing medium until three generations [8.5 cumulative population doubling level (CPDL)], subsequent subcultivation of the cells in a complete serum-free medium could be achieved up to six generations (14.4 CPDL). These results demonstrate that this serum-free medium can support the optimal cell growth and long-term subcultivation of bovine granulosa cells.

Animals↗

Effects of sodium butyrate on the rearranged c-myc expression in mouse plasmacytoma cells.

The expression of c-myc mRNA was examined after 4 h of sodium butyrate treatment in a mouse plasmacytoma (MPC) cell line (S194). Steady-state levels of rearranged c-myc mRNA were suppressed by the agent in S194 cells. Run-on assay demonstrated that the suppression of the rearranged c-myc mRNA in the MPC was correlated with the transcriptional downregulation of the gene. The suppression was also accompanied by the reduced DNase I sensitivity of the gene. These findings suggest that the rapid downregulation of c-myc mRNA by sodium butyrate is subject to regulation at the transcriptional level following the alteration of the DNase I sensitive chromatin structure in mouse plasmacytoma cells.

Animals↗

Antitumor effect of 22-oxa-1 alpha,25-dihydroxyvitamin D3, a potent angiogenesis inhibitor, on rat mammary tumors induced by 7,12-dimethylbenz[a]anthracene.

The effect of 22-oxa-1 alpha,25-dihydroxyvitamin D3 (22-oxa-1,25(OH)2D3) on the growth of autochthonous rat mammary tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) was examined on the basis of our previous finding that this synthetic vitamin D3 analog has a potent angiogenesis inhibitory effect. Two doses of 22-oxa-1,25(OH)2D3, 0.1 and 1 microgram/kg of body weight, due to the limited amount of the compound available, were used. The daily administration of 22-oxa-1,25(OH)2D3 at the dose of 1 microgram/kg/day resulted in significant inhibition of the growth of these mammary tumors at 1, 2 and 3 weeks after the administration of this agent, although the agent caused little or no regression of the tumors. After daily administration for 3 weeks, a significant antitumor effect was also observed in the group treated with 0.1 microgram/kg/day. Treatment with 22-oxa-1,25(OH)2D3 did not affect the serum calcium levels in the treated rats. The lower dose of 22-oxa-1,25(OH)2D3 neither affected weight gain nor caused a decrease in body weight, while the higher dose, although having some effect on weight gain, did not induce a decrease in body weight. There were no significant differences in the weights of adrenals, uteri and ovaries between the treated groups and controls. These results suggest that 22-oxa-1,25(OH)2D3 has a significant growth inhibitory effect on DMBA-induced autochthonous mammary tumors in rats, without producing severe side effects, including hypercalcemic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

9,10-Dimethyl-1,2-benzanthracene↗

Clinicopathological findings of bucillamine-induced nephrotic syndrome in patients with rheumatoid arthritis.

This paper describes pathological and clinical investigations of glomerular lesions in bucillamine-induced nephropathy by analyzing biopsy materials from 9 patients with rheumatoid arthritis (RA). There was no specific predisposition for nephrotic syndrome induced by bucillamine in clinical profiles related to age, onset, duration of disease, sex, activity and dose of bucillamine. In light-microscopic, electron-microscopic and immunofluorescent findings, the characteristic changes were similar to those of idiopathic membranous glomerulonephritis (MGN). After discontinuance of bucillamine, the nephrotic syndrome improved slowly with or without corticosteroid therapy. Results confirmed that the most common lesion of nephrotic syndrome associated with bucillamine therapy in RA is MGN. We recommend that corticosteroid therapy should be restricted to cases with severe proteinuria.

Anti-Inflammatory Agents, Non-Steroidal↗

[Clinicopathological study of nephropathy in patients with rheumatoid arthritis].

We carried out a retrospective study to investigate the clinical and pathological findings in 31 patients with rheumatoid arthritis (RA). In clinical findings, 17 patients showed nephrotic syndrome, five had isolated proteinuria, two had proteinuria and hematuria and seven had renal failure. In pathological findings, there were 16 patients with membranous nephropathy (MN), two with proliferative glomerulonephritis (DPGN), two with minor glomerular abnormality (MGA), six with amyloidosis, 2 with tubulointerstitial nephritis, and three patients had accompanying lupus nephritis. Eleven of 16 with MGN had been treated with gold, bucillamine or D-penicillamine, so they were diagnosed as drug induced MGN. In the other five patients, we could not decide which drugs induced the nephropathy. The 2 cases of MGA were associated with nephrotic syndrome and acute renal failure, which were caused by non-steroidal antiinflammatory drugs. There were two cases of non-Ig A DPGN, which was regarded as the native nephropathy in RA. The three cases with lupus nephritis were diagnosed as systemic lupus erythematosus by the criteria of the American Rheumatism Association (ARA). In conclusion, the nephropathy in patients with RA was varied and renal biopsy was a useful examination.

Adult↗

Mixed outbreak of Bordetella pertussis and Bordetella parapertussis in an apartment house.

From September through November of 1985, a mixed outbreak of Bordetella pertussis and Bordetella parapertussis occurred in an apartment house in Ashikaga City, Japan. Bacteriological and serological investigations were conducted on seven families, comprising 13 adults and 19 children, living in the same apartment house and having social contacts. For all the subjects, cultivation of nasopharyngeal mucus and measurement of pertussis agglutinin antibody, anti-PT antibody, and anti-F-HA antibody were performed. On the basis of the clinical, bacteriological or serological findings, seven children of three families (families A, B and C), including the first child patient (index case) of family A, were diagnosed as having infections caused by B. pertussis, or B. parapertussis or both. B. pertussis and/or B. parapertussis were isolated from six of the seven child patients. B. pertussis alone was isolated from three children (one in each family), and two of them had not been vaccinated. B. parapertussis alone was isolated from two children, while both bacteria were isolated from one child. Those three children from whom B. parapertussis was isolated were in family C, which was the last of the three families to develop symptoms of infection. Josamycin had been administered to two of the three children from whom B. parapertussis was isolated before the nasopharyngeal mucus specimen was collected. In one of the two children from whom only B. parapertussis was isolated, the significant elevation of anti-PT antibody titer was observed, which was indicative of a mixed infection with B. pertussis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Pharmacokinetics and clinical efficacy of flomoxef in neonates].

Clinical pharmacology and efficacy of flomoxef (FMOX) in neonates were investigated. And the following results were obtained. 1. Mean serum concentrations of FMOX at 30 minutes after administration were 24.3 micrograms/ml, 47.6 micrograms/ml, and 85.8 micrograms/ml at doses of 10 mg/kg, 20 mg/kg, and 40 mg/kg administered, respectively. 2. Mean serum half-lives of FMOX were 3.4 hours in 0-3 day-old neonates, and 2.6 hours in 4 day-old or older subjects. 3. A dose response was evident among different dose groups given 10 mg/kg, 20 mg/kg, and 40 mg/kg. 4. Urinary recovery rates of FMOX in the first 6 hours after administration ranged between 12.8 and 51.1%. 5. FMOX was effective in 7 out of 8 cases in which causative pathogens were identified. 6. Diarrhea was observed in 1 case as a side effect of the drug, but the symptom was relieved soon after the completion of the treatment. There was no case in which any abnormal laboratory results were observed. 7. FMOX has a broad spectrum of activities against Gram-positive and Gram-negative aerobes and anaerobes. It is stable against most of beta-lactamases. It was demonstrated to be highly effective in our study, and yet without any serious side effects. FMOX is therefore considered to be one of the useful agents of the first choice for the treatment of bacterial infections such as sepsis and urinary tract infections in neonates and infants.

Age Factors↗

[Influence of cefodizime on intestinal bacterial flora].

Effects of cefodizime (CDZM), a new injectable cephem antibiotic, on the intestinal bacterial flora were studied in tetra-contaminated mice and in pediatric patients. CDZM was intramuscularly administered at a dose of 100 mg/kg once a day for 5 consecutive days to mice contaminated with 4 different species of organisms: Escherichia coli, Enterococcus faecalis, Bacteroides fragilis and Bifidobacterium breve. For 3 species except E. faecalis, bacterial populations in feces were markedly reduced after the start of the treatment. Subjects in the pediatric study were 5 children with bacterial infections (4 boys and 1 girl) at ages from 7 months to 9 years 6 months and with their body weights ranging from 7.6 kg to 51.1 kg. CDZM was intravenously administered at a dose of 9.7 mg/kg to 23.0 mg/kg 4 times a day for 5 to 15 days. Although some variations in the fecal bacterial flora were noticed among these subjects during the treatment, populations of main aerobes and anaerobes such as Enterobacteriaceae, Enterococcus, Bacteroides, Bifidobacterium and Eubacterium decreased markedly in most cases. Glucose non-fermenting Gram-negative rods and fungi tended to increase during or after the administration of CDZM, and they were the most predominant species in some cases. Although these changes tended to return to predosing states after the cessation of the treatment with CDZM, attention must be paid to possible occurrences of diarrhea, superinfection or bleeding tendency when treatment with the drug is continued for long periods of time. Fecal concentrations of CDZM considered to be closely related to the changes of the intestinal bacterial flora showed pretty high values in all cases.

Animals↗

[The influence of cefpirome on intestinal bacterial flora].

Cefpirome (CPR, HR810), a new parenteral cephalosporin antibiotic, was studied for its effect on the intestinal bacterial flora in pediatric patients. The subjects were children admitted for infections (6 males and 3 females, 1 month to 5 years 1 month old, weighted 3.94 to 21.0 kg). CPR was intravenously administered at a dose between 19.0 to 40.0 mg/kg, 3 to 4 doses daily over 6 to 12 days. The feces from these children were collected before, during, and after administration, and bacteria were identified and counted. CPR concentration, beta-lactamase activity, and Clostridium difficile D-1 antigen were also assayed. Bacterial flora changes in feces during CPR administration showed some variance, but generally 5 cases out of the 9 showed a significant decrease in Enterobacteriaceae and Enterococcus faecalis among aerobic bacteria. The other 4 cases showed some transient decrease, but no significant change was observed. No significant changes were recognized for Enterococcus avium and Enterococcus faecium, and the total aerobic bacterial count decreased in a transient manner in only one patient. Regarding anaerobic bacteria, Bifidobacterium and Eubactrium revealed a significant decrease, a transient decrease or no change from case to case. Bacteroides showed little change in count. Consequently, the total anaerobic bacteria count did not reveal a large change aside from 1 case in which Bacteroides was not detected before administration and a significant decrease of other bacteria was noted. In no case, glucose nonfermentative Gram-negative bacilli or fungi were found dominant. Although C. difficile and C. difficile D-1 antigen were detected in 3 and 4 cases, respectively, there was no exact relationship between the number of C. difficile and the characteristics of the feces. CPR was detected in fecal samples from 6 cases during administration with concentrations ranging between 1.20 to 22.4 micrograms/g. High values of CPR tended to be found in specimens with low beta-lactamase activity in the feces. When drug sensitivities of the bacteria isolated from feces before and after administration were compared, higher levels of resistance were found in some bacteria such as Enterococci and Bacteroides during or after administration than before administration. The above results suggest that CPR is a drug with a relatively small influence on the intestinal bacterial flora in children, but a particular attention is required for diarrhea and microbial replacement during a continuous, long-term administration of the drug.

Bacteria↗

Regional differences in the ultrastructural features of secretory cells in the golden hamster (Mesocricetus auratus) oviductal epithelium.

The secretory cells of the golden hamster (Mesocricetus auratus) oviductal epithelium on the day of ovulation were observed by light and electron microscopy. In the fimbriae two types of secretory cells were observed: one possessed secretory granules with electron-lucent matrices, prominent protrusions and many electron-dense granules resembling lipid droplets, and the other possessed many secretory granules with moderately electron-dense, homogeneous matrices, occasionally containing an electron-dense area. The former type was only observed in the fimbrial epithelium, while the latter was present in both the fimbriae and the infundibulum. In the ampullary and isthmic cells many secretory granules with moderately electron-dense, homogeneous matrices were observed in the supranuclear area. Electron-dense areas were frequently observed in many secretory granules of the isthmic cells. Lysosome-like vesicles, partly filled with a dense substance and/or a finely granular substance, were observed in the infranuclear cytoplasm of the isthmic cells. Fusion between vesicles and secretory granules was frequently observed. These ultrastructural observations of the golden hamster oviduct reveal marked regional differences in the morphological features of secretory cells. These results may provide insight into regional and cellular differences in the function of the oviduct.

Animals↗

A novel angiogenic inhibitor derived from Japanese shark cartilage (I). Extraction and estimation of inhibitory activities toward tumor and embryonic angiogenesis.

Guanidine extraction and crude fractionation of Japanese shark cartilage by ultrafiltration on a molecular weight basis were conducted and the antiangiogenic activities were assayed as to the inhibitions of tumor and embryonic angiogenesis. Significant inhibition of angiogenesis was found, and there was a linear relationship between the results of the two assays. The inhibitory activities were concentrated in the fraction in the molecular weight range of 103 to 104, and were resistant to heat treatment.

Animals↗

Inhibition of angiogenesis by vitamin D3 analogues.

The effects of vitamin D3 and two analogues on embryonic angiogenesis were studied in 4.5-day-old chick embryo chorioallantoic membranes. The active metabolite of vitamin D3, 1 alpha,25-dihydroxyvitamin D3, and a synthetic vitamin D3 analogue, 22-oxa-1 alpha,25-dihydroxyvitamin D3, inhibited angiogenesis in a dose-dependent manner, the inhibition occurring in the picomolar range. In contrast, vitamin D3 was not effective. The results suggest that these two vitamin D3 analogues might be promising anti-angiogenic agents for controlling the angiogenesis which occurs in several pathological conditions, including tumor development.

Animals↗

Transcriptional down-regulation of the rearranged C-myc expression in murine cell hybrids between a plasmacytoma and a T-cell lymphoma.

Regulation of the rearranged and non-rearranged c-myc expression was studied in murine cell hybrids (SBWI and SBWII) between plasmacytoma (S194) and T-cell lymphoma (BW5147) cells. Expression of the rearranged c-myc of heterogeneous mRNA sizes (1.8 approximately 2.4 kb) was markedly down-regulated in these hybrids regardless of retention of the gene. On the other hand, expression of the non-rearranged c-myc (2.4 kb) was not significantly affected in these hybrids. Treatment of SBWI hybrid cells with cycloheximide enhanced the non-rearranged c-myc 2- to 4-fold but did not release the down-regulation of the rearranged c-myc at all, suggesting that the down-regulation of the rearranged c-myc in the hybrid cells was mainly at a transcriptional rather than a post-transcriptional level. This was supported by the results of nuclear run-on assay: the high level of run-on transcripts in S194 cells declined in SBWI hybrid cells comparable to the level in BW5147 cells. The rearranged c-myc was hemi-methylated in S194 cells and the pattern was the same in SBWI hybrid cells. Furthermore, down-regulation of the rearranged c-myc in the hybrid was also not restored by treatment with 5-azacytidine (5-AzaC), 12-O-tetradecanoylphorbol-13-acetate (TPA) or forskolin, suggesting no causative involvement of DNA methylation or protein phosphorylation in down-regulation. Higher DNase I sensitivity of the rearranged c-myc in S194 cells decreased to a similar extent to that of the non-rearranged c-myc after cell fusion with BW5147 cells. These results suggest that expression of the rearranged c-myc is down-regulated at the level of transcription in murine cell hybrids between a plasmacytoma and a T-cell lymphoma, probably by changing chromatin configuration around the gene from the open to the closed state.

Animals↗

Study of the differentiation of secretory cells in the golden hamster oviductal epithelium by use of a monoclonal antibody.

The ontogeny of an oviductal zona pellucida glycoprotein, designated ZP-0, in the golden hamster oviductal epithelium was investigated by means of light and electron microscopic immunolabeling studies using a monoclonal antibody. Light microscopic immunohistochemistry showed that ZP-0 appeared in the oviductal epithelium from 9.5 to 10.5 days after birth. At first, ZP-0 appeared in the Golgi region of the epithelial cells, and then increased in amount as development progressed to fill the supranuclear cytoplasm. Electron microscopic observations showed that rough endoplasmic reticulum and Golgi apparatus were well developed in non-ciliated cells of the ampullar and isthmic segments at 10.5 days after birth. Secretory granules appeared near the Golgi apparatus and markedly increased in number until 15.5 days after birth. Ultrastructural immunocytochemistry showed that ZP-0 appeared in the well-developed Golgi apparatus and then was stored within the secretory granules of developing secretory cells. ZP-0 was never present in the ciliated cells. These results indicate a coincidence between the beginning of ZP-0 biosynthesis and the morphological cytodifferentiation of secretory cells in the golden hamster oviduct during postnatal development. This leads us to the conclusion that ZP-0 is a possible differentiation marker of the golden hamster oviductal secretory cell.

Animals↗