Biomedical subjects

T Oikawa

Publications and source records attributed to T Oikawa.

At least 163 records · Page 9Linked to original sources

PubMed1992

Okadaic acid is a potent angiogenesis inducer.

Okadaic acid, which is a non-12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoter and an inhibitor of protein phosphatases 1 and 2A, induced angiogenesis in the chorioallantoic membrane of the chick embryo. Its potent angiogenic activity was dose-dependent. The minimum effective dose was 5 fmol/egg and the effective dose for 50% induction was 90 fmol/egg. These results indicated that okadaic acid exhibits angiogenic activity one order of magnitude stronger than that of TPA (reported previously). Moreover, the time-course of angiogenesis induction by okadaic acid was much slower than that by TPA. The difference is consistent with the time-courses of other biochemical and biological activities and also various gene expressions induced by okadaic acid and TPA, indicating that the difference in the time-course is associated with their mechanisms of action. We conclude that okadaic acid induces angiogenesis through a different pathway than does TPA, indicating the existence of a new mechanism of angiogenesis induction.

Animals↗

PubMed1992

[Immunocytochemical studies on the pancreatic endocrine cells in the Japanese newt (Cynopus pyrrhogaster)].

Pancreatic endocrine cells were examined by light and electron microscopic immunocytochemistry to discuss the co-localization of peptides in one cell type. A cells were irregular in shape with an occasional long cytoplasmic process, and contained glucagon-immunoreactive granules with various contours. These granules were 160-300nm in diameter with various density, and also immunoreactive to anti-human pancreatic polypeptide (PP) serum. A part of them were further immunoreactive to anti-somatostatin serum. B cells were round to elliptical in shape, and often aggregated around the capillaries. Granules of B cells were round to irregular in shape, 270-410 nm in diameter, and immunoreactive to anti-insulin serum. D cells were irregular in shape with meager cytoplasm, and contained somatostatin-immunoreactive granules. These granules were ovoid or teardrop in shape, 140-250nm in longitudinal diameter, and immunoreactive to both anti-somatostatin and anti-human PP sera. PP cells were round to spindle-shaped, and contained human PP-immunoreactive round granules 150-35nm in diameter. These findings reveal the existence of at least 4 types of endocrine cells secreting glucagon, insulin, somatostatin, and PP, respectively, in the newt pancreas, and suggest the co-localization of some of these peptides in one cell type.

Animals↗

PubMed1992

Effects of inline filtration on delivery of gentamicin at various flow rates.

The effects of inline filtration on delivery of gentamicin (GM) in the pediatric field were studied. The filter sets (Pall 0.20 micron. JMS 0.20 micron, and IVEX 2.022 micron) were studied using a simulated system. 10 mg of GM was injected into the system containing 5% dextrose in water (flow rate: 50 ml/hr, 10 ml/hr and 2 ml/hr) with horizontal and vertical settings of the inline filters. In case of 50 ml/hr, delivery of GM of Pall showed nearly the same delivery pattern as compared with no filter setting. However, JMS and IVEX 2 showed little differences. In case of 10 ml/hr and 2 ml/hr those differences became more significant. Delivery of GM was influenced by the priming volume of the filters, increasingly so at slow flow rates. Filter settings also influenced the delivery of GM. Furthermore, with regards to the results of the Vitamin K2 delivery and the technetium radiotracer method, JMS and IVEX 2 filters were observed to have some stagnation of drugs in the filter. Not only priming volumes of the filters affect delivery of drugs, filter designs also have an influence. The use of the inline filters is important in the pediatric field, but their charactaristics for drug delivery pattern should be considered.

Drug Contamination↗

PubMed1992

Inhibition of angiogenesis by staurosporine, a potent protein kinase inhibitor.

The effect of staurosporine, a potent inhibitor of protein kinases, on embryonic angiogenesis was studied in an in vivo assay system involving chorioallantoic membranes of growing chick embryo. Staurosporine inhibited embryonic angiogenesis in a dose-related manner, the ID50 value being 71 pmol/egg. Staurosporine dose-dependently suppressed the proliferation of vascular endothelial cells, an important event involved in the angiogenesis process. The IC50 value was 0.88 nM. In contrast, staurosporine did not affect the migration of vascular endothelial cells. These results suggest that staurosporine affected embryonic angiogenesis probably by inhibiting endothelial cell proliferation. In addition, these results might support the notion that certain protein kinase(s) could be implicated in induction of angiogenesis and also that staurosporine would be a useful compound for studying a mode of action of angiogenesis occurring in various diseases, including tumor development.

Alkaloids↗

PubMed1992

[Inhibition of neovascularization and tumor growth by dexamethasone].

It has been proposed that angiogenesis inhibitors should be used for the treatment of diseases accompanied by an uncontrolled angiogenic response, particularly such disease occurring during progressive growth of solid tumors. In this study, the antiangiogenic effect of dexamethasone (DEX) was studied in a system using chorioallantoic membranes (CAM) of fertilized eggs and rabbit corneas. First, DEX was examined for its effect on embryonic angiogenesis using 4, 5 day old CAMs of chick embryos. After the shell and shell membrane was removed, an EV pellet with or without DEX was placed within a silicon ring. Two days later, the antiangiogenic response was evaluated by measuring the avascular zone of the CAM beneath the pellet. When the CAM showed an avascular zone of 3 mm or more in diameter, the response was scored as positive. DEX showed potent antiangiogenic activity and produced an avascular zone in 100% of CAMs at the highest dose tested. (250 ng/egg). Next, inhibitory effect of vascularization and tumor growth by local implant of DEX was observed in a rabbit cornea assay. An intra-corneal pocket extending to within 1 mm of the limbus was used to house a 1-mm3 piece of glioma. In the treatment group, DEX-containing EV pellet was inserted between the limbus and glioma. Ten days after the implantation of glioma and EV pellet, vascular response and tumor growth was evaluated. For morphologic studies, the excised corneas were fixed with formaldehyde fixative and sectioned for light microscopy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Cloning and expression of the Erwinia herbicola tyrosine phenol-lyase gene in Escherichia coli.

The tyrosine phenol-lyase (TPL) gene of Erwinia herbicola was cloned and expressed in Escherichia coli, and the complete nucleotide sequence of the gene determined. The TPL gene comprises 1368 bp, encoding 456 amino acids which have 90% amino acid identity with TPL from Citrobacter freundii. After replacing the 5'-flanking region of the TPL gene with the E. coli lac promoter, TPL protein could be hyperproduced constitutively in E. coli without induction by L-tyrosine.

Amino Acid Sequence↗

PubMed1992

[Effect of meropenem on fecal flora in children].

Meropenem (MEPM, SM-7338), a novel parenteral carbapenem antibiotic, was examined for its effect on intestinal flora in children. Seven children with infectious diseases (3 male and 4 female children of age's ranging from 4 months to 8 years and 9 months weighing from 7.3 to 23.0 kg) were treated with MEPM at doses ranging 10.3 to 40.5 mg/kg 3 or 4 times a day for 6 to 12 days. Before, during and after the treatment, identities and numbers of various bacteria contained in 1 g of feces were determined and fecal beta-lactamase activity and Clostridium difficile D-1 antigen were also assayed. Changes in fecal flora during MEPM treatment was somewhat different depending on cases. Regarding Enterobacteriaceae among aerobes, all of 7 cases exhibited moderate or pronounced reductions in Escherichia coli. Some of the cases exhibited the tendency to increase in Klebsiella oxytoca. Enterobacter cloacae and Citrobacter freundii. E. coli which was reduced during the treatment increased rapidly after the treatment in 5 out of 7 cases, and the initial bacterial counts were restored. Diverse strains were observed within the genus Enterococcus, while the overall bacterial counts of this genus exhibited the tendency to increase during the treatment. As a result, no significant change in total aerobe count was observed in any case except 1 case where Enterococcus count was somewhat reduced. Among anaerobes, major bacteria such as Bacteroides, Bifidobacterium, Eubacterium and Peptococcaceae exhibited tendencies to decrease in some cases during the antibiotic treatment. Two infants and 1 child exhibited significant decreases in total anaerobe counts. In most of the cases, such changes in major anaerobes were transient and bacterial counts recovered to their initial values rapidly after completion of the treatment. In no cases, glucose non-fermentative Gram-negative bacilli or fungus became predominant. Although C. difficile D-1 antigen was observed in 4 cases, its changes had no relationship with characteristics of feces. C. difficile was not detected in any of the cases. MEPM was detected in feces in 4 cases being treatment, in concentrations ranging from 0.35 to 66.0 micrograms/g. Fecal MEPM levels were very low except in 1 case in which beta-lactamase was negative. From these results, effects of MEPM on intestinal flora in children were relatively minor compared to other new beta-lactam drugs. However, a care should be taken to minimize diarrhea and bacterial turnover when a prolonged use of the antibiotic, was practiced because of potential significant effects on intestinal flora.

Age Factors↗

PubMed1992

Familial juvenile nephronophthisis and renal transplantation in two siblings.

Familial juvenile nephronophthisis (FJN) is a hereditary renal disease, characterized by a juvenile onset and the development of medullary cysts and progressive renal damage. The pathogenesis of FJN remains unknown, and at present, no rational therapy other than renal transplantation is available. We describe two cases in siblings in whom there were no extrarenal complications, such as retinopathy or central nervous system involvement. Both patients display juvenile onset of the disease and end-stage renal failure. The brother received a kidney from his father, and the sister received a kidney from her mother. Recurrence of the underlying disease has not so far been found in the transplanted kidney.

Adolescent↗

PubMed1992

[The influence of cefprozil on intestinal bacterial flora].

Cefprozil (CFPZ, BMY-28100), a new oral cephalosporin antibiotic, was studied for its effect on the intestinal bacterial flora in pediatric patients. The subjects were children admitted for infections (2 males and 2 females, 9 months to 6 years 3 months old, weighed 4.3 to 19.0 kg). CFPZ granule was orally administered at a dose between 10.0 to 11.6 mg/kg, 3 doses daily, over 4 to 14 days. The feces from these children were collected before, during and after administration, and bacteria were identified and counted. CFPZ concentration, beta-lactamase activity were also assayed. Bacterial flora in feces during CFPZ administration showed some variance, but no significant change was observed in main aerobes and anaerobes. And in no case, glucose nonfermentative Gram-negative bacilli or fungi were found dominant. beta-Lactamase activity was positive in the feces in all cases. CFPZ concentrations were not detectable in feces before, during and after administration. The above results suggest that CFPZ is a drug with little influence on the intestinal bacterial flora in children.

Administration, Oral↗

PubMed1992

[The influence of cefdinir on the intestinal bacterial flora].

The influence of cefdinir (CFDN), a new oral cephalosporin, on the intestinal bacterial flora was studied in tetra-contaminated mice and in pediatric patients. CFDN in fine granules was administered at a dose of 10 mg/kg once a day for 5 consecutive days to mice contaminated with 4 different species of organism: Escherichia coli, Enterococcus faecalis, Bacteroides fragilis and Bifidobacterium breve. No remarkable changes were observed in the fecal viable cell counts except that decreases in E. coli counts were observed on the day 3 to 5 after starting administration. The subjects in pediatric study were 7 children with infections, 3 boys and 4 girls, with their ages from 6 months to 12 years 7 months. Their body weights ranged from 5.5 to 29.2 kg. CFDN fine granules was administered at each dose of 3.0 mg/kg to 3.7 mg/kg, 3 times a day for 4 to 14 days. During the administration of CFDN, some variations were observed in the pattern of changes in the fecal bacterial flora between subjects. Although Enterobacteriaceae and total counts of anaerobes were markedly decreased in 2 cases, total counts of aerobes were unchanged in the 2 cases, whereas main aerobes and anaerobes except enterococci hardly varied in the other cases. There was no case in which glucose non-fermenting Gram-negative rods and fungi became predominant species continually. Although Clostridium difficile and C. difficile D-1 antigens were detected in 1 and 4 cases, respectively, no relationship was found between the number of C. difficile and the characteristics of the feces. With regard to the drug sensitivities of bacteria isolated from feces before and after administration of CFDN, higher levels of resistance were found in some bacteria such as Enterococcus and Bacteroides during or after administration than before administration. CFDN was detected in fecal samples from 2 cases during administration with concentrations ranging between 0.99-254 micrograms/g. High value of CFDN was found in a case with low beta-lactamase activity in feces, in which marked decrease of Enterobacteriaceae and total counts of anaerobes was observed. The above results suggest that CFDN is considered to be a drug with relatively small influence on the intestinal bacterial flora. But as high concentrations of drugs were detected in feces under some circumstances, our attention will be required. Particular care is also required for the occurrence of diarrhea and microbial replacement during continuous, long-term administration of the drug.

Animals↗

PubMed1992

[Prednisolone and aspirin therapy for habitual abortion associated with anti-cardiolipin antibody].

Anti-phospholipid antibody syndrome (APS) is characterized by thrombocytopenia, thrombosis and/or abortion. Steroid and aspirin therapy has been reported useful for habitual abortion associated with APS. Eleven patients, whose prior pregnancies resulted in habitual abortion (41 abortions), were received a intentional prednisolone (40 mg/day) and aspirin (81 mg/day) therapy before further pregnancies and both agents were decreased gradually. We maintained prednisolone (10-15 mg/day) and aspirin (40.5 mg/day) during pregnancy period. After the treatment, the outcome of pregnancy was successful in 7 of 10 pregnancies. The weight of newborn infants ranged from 1980 to 2980 g and apgar score ranged from 4 to 9 points. No side effect was observed, and fetal malformation and/or adrenal insufficiency was not recognized in any infants. In conclusion, an intentional prednisolone plus aspirin therapy is useful to prevent habitual abortion in patient with APS.

Abortion, Habitual↗

PubMed1992

[Morphological and immunohistochemical quantitative analysis of dysplasia in ulcerative colitis. 1. Histological mapping specimen and morphological quantitative analysis].

Mapping specimens of 6 cases of ulcerative colitis included adenocarcinoma invaded into submucosa (invasive carcinoma) were made and Index value of Nucleus-Gland (ING) of invasive carcinoma, severe and moderate dysplasia in ulcerative colitis was measured and compared with one another. Large intestinal carcinoma invaded into submucosa, colonic adenoma and normal mucosa were examined as the control. Spatial relations of invasive carcinoma and dysplasia in ulcerative colitis were also examined. Severe and moderate dysplasia as well as large intestinal carcinoma invaded into submucosa showed significantly higher values of ING than adenoma (P less than 0.01). Invasive carcinoma and severe dysplasia of ulcerative colitis showed significantly higher values of ING than moderate dysplasia (P less than 0.01). Severe dysplasia was located around the portion of of invasive carcinoma of ulcerative colitis. Severe dysplasia falls into the same category with invasive carcinoma of ulcerative colitis because of the same value of ING and spatial translation each other. Moderate dysplasia was defined as borderline lesion because of the mean value of ING between severe dysplasia and adenoma.

Adenocarcinoma↗

PubMed1992

[Morphological and immunohistochemical quantitative analysis of dysplasia in ulcerative colitis. II. Immunohistochemical quantitative analysis].

Mapping specimens of 6 cases of ulcerative colitis included adenocarcinoma invaded into submucosa (invasive carcinoma) were made and immunohistochemical quantitative analysis of ras p21, an oncogene product and secretory component were examined in invasive carcinoma, severe and moderate dysplasia of ulcerative colitis. Large intestinal carcinoma invaded into submucosa, colonic adenoma and normal mucosa were examined as the control. Index values of Staining Density (ISD) and of Staining Gland (ISG) of ras p21 demonstrated significantly higher values in invasive carcinoma, severe and moderate dysplasia of ulcerative colitis than adenoma (P less than 0.01). ISG of secretory component in moderate dysplasia and adenoma showed significantly high value compared with severe dysplasia and invasive carcinoma of ulcerative colitis (P less than 0.05). The collective evidence indicates that severe dysplasia falls into the same category with invasive carcinoma of ulcerative colitis and may be defined as carcinoma in situ. Moderate dysplasia was also defined as carcinoma in situ or borderline lesion.

Adenocarcinoma↗

PubMed1991

Eponemycin, a novel antibiotic, is a highly powerful angiogenesis inhibitor.

Eponemycin, a novel antibiotic, was examined as to its anti-angiogenic activity in an in vivo assay system involving chorioallantoic membranes (CAMs) of growing chick embryos. Eponemycin powerfully inhibited angiogenesis in the CAMs. This powerful inhibition was dose-dependent, the inhibitory activity becoming detectable at a dose of 7.5 fmol/egg and the ID50 value being 250 fmol/egg, suggesting that eponemycin exhibits more potent anti-angiogenic activity than Ch 55, a synthetic retinoid, which had been the strongest angiogenesis inhibitor identified so far. To determine which event(s) in the angiogenesis process was affected by eponemycin, experiments were conducted using systems involving cultured vascular endothelial cells. Eponemycin effectively inhibited both the proliferation and migration of endothelial cells, indicating that the antibiotic affected these two important events during angiogenesis, resulting in effective inhibition of angiogenesis. These results strongly suggest that eponemycin could be a promising candidate as an angiogenesis inhibitor for the control of aberrant angiogenesis occurring in different diseases such as tumor development and diabetic retinopathy.

Allantois↗

PubMed1991

Re-transformation of non-transformed hybrids between c-myc-activating mouse plasmacytoma cells and normal fibroblasts by transfection with activated c-Ha-ras but not c-myc.

In a mouse plasmacytoma S194, c-myc oncogene is rearranged with Ig gene by chromosomal translocation and is consequently activated. We previously reported that transformation of phenotype and expression of rearranged c-myc were repressed in independently isolated hybrid clones, I-1 and IV-10, between S194 and normal fibroblasts. In order to investigate the relationship between transformation of phenotype and oncogene expression, transcriptionally enhanced c-myc or activated c-Ha-ras was transfected into I-1 or IV-10I, a subclone of IV-10. Transfectants expressing high levels of c-myc were found to retain the non-transformed phenotypes. On the other hand, transfectants expressing activated c-Ha-ras showed the transformed phenotypes. These results suggest that enhanced expression of c-myc is not sufficient for re-transformation of the non-transformed hybrid clones between c-myc-activating plasmacytoma cells and normal fibroblasts, but expression of activated c-Ha-ras could diminish or overcome the tumor-suppressive activity of normal fibroblasts.

Animals↗

PubMed1991

Angiogenic factor of a rat mammary tumor cell line (RMT-1) (I). Secretion of two distinct angiogenic factors into serum-free conditioned medium by RMT-1 cells.

Serum-free conditioned medium of a rat mammary tumor cell line RMT-1, established from a rat mammary carcinoma induced by 7,12-dimethylbenz[a]anthracene (DMBA), produced the complete angiogenic response in both rabbit cornea and chick embryo chorioallantoic membrane assays. The angiogenic activity in the RMT-1 conditioned medium was separated into two fractions on a column of heparin-Sepharose; one was eluted with 0.1 M NaCl and the other with 0.5 M NaCl, which are referred to hereafter as rAF-1 and rAF-2, respectively. These two angiogenic factors were further purified separately by FPLC on a Superose 12 column. The partially purified rAF-2 had an apparent Mr of 30,000-50,000 and seemed to exhibit mitogenic activity toward Balb/c 3T3 cells, while the partially purified rAF-1, with an apparent Mr of 10,000-30,000 did not have a mitogenic effect on these cells. Both rAF-1 and rAF-2 were resistant to heat and acid treatment, and exhibited trypsin sensitivity, suggesting that they are heat and acid stable peptides. The two angiogenic factors did not stimulate the proliferation of cultured vascular endothelial cells. These results suggest that RMT-1 secretes two distinct angiogenic factors into the medium and that these two secretable angiogenic factors participate cooperatively in the induction of the angiogenic response produced by a DMBA-induced rat mammary tumor in vivo.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1991

Chromosome translocation and c-MYC activation by Epstein-Barr virus and Euphorbia tirucalli in B lymphocytes.

Dual exposure to Epstein-Barr virus and purified 4-deoxyphorbol ester derived from the plant Euphorbia tirucalli induced a high frequency of chromosomal rearrangements in human B lymphocytes in vitro. Rearrangements most commonly affected chromosome 8, the chromosome most often showing structural changes in Burkitt's lymphoma (BL) cells. E tirucalli is indigenous in parts of Africa where BL is endemic and may be an important risk factor for the disease.

B-Lymphocytes↗

PubMed1991

Metalloselenonein, the selenium analogue of metallothionein: synthesis and characterization of its complex with copper ions.

We used an automated peptide synthesizer to produce a peptide, metalloselenonein, that contains selenocysteine residues substituted for all cysteine residues in Neurospora crassa copper metallothionein. Metalloselenonein binds 3 mol of Cu(I) per mol. This adduct shows a broad absorption band between 230 and 400 nm and a fluorescence band at 395 nm, which can be attributed to copper-selenolate coordination. The circular dichroism spectrum of the copper-metalloselenonein complex shows a positive band around 245 nm attributable to asymmetry in metal coordination.

Amino Acids↗