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T Oikawa

Publications and source records attributed to T Oikawa.

At least 19 recordsLinked to original sources
PubMed1995

Reduced fidelity of DNA synthesis in cell extracts from chemically induced primary thymic lymphomas of mice.

To examine whether the fidelity of DNA synthesis is reduced in tumor cells, M13 mp2-based fidelity assays were carried out using 15 samples of whole-cell extracts from primary mouse thymic lymphomas induced by alkylating agents. We found that DNA synthesis activities of thymic lymphomas, detected as incorporation of [3H]TTP into acid-insoluble materials, were 2- to 10-fold higher compared to those of normal thymus. Furthermore, mutant frequencies in the forward mutation assay of DNA synthesis were increased 2- to 7-fold in cell extracts from thymic lymphomas compared to those from normal thymus. As the DNA polymerase beta (pol beta) activity was extremely high in the thymic lymphomas, we screened mutations in the pol beta gene to examine the possibility of involvement of mutated pol beta in reduction of the fidelity of DNA synthesis. Of 20 lymphomas, one case of point mutation (T to A) was found by reverse transcription-PCR single-strand conformation polymorphism analysis. These results suggest that the mutagenic DNA synthesis is involved in murine thymic lymphoma genesis, although mutation of the pol beta gene is not a major causal event.

Animals↗
PubMed1995

Differential expression of the T cell receptor/CD3 genes and their lymphoid-specific transcription factor genes in murine T cell x fibroblast and T cell x B cell hybrids.

We generated cell hybrids between mouse T cell lymphoma EL4 cells and mouse fibroblast B82 cells (BELIII and BELIV) to examine the expression of T cell receptor (TcR)/CD3 genes and their lymphoid-specific transcription factor genes, which are normally detected in EL4 cells. In BELIII and BELIV, expression of the TcR alpha, TcR beta and CD3 delta genes was extinguished, whereas expression of the CD3 epsilon gene was still detected. Expression of the (lymphoid enhancer binding factor 1) LEF-1 gene was extinguished and that of the GATA-3 gene was hardly detected in BELIII and BELIV. Ets-1 gene expression, observed not only in EL4 cells but also in B82 cells, was considerably reduced in BELIII and BELIV. A much higher level of PEBP2 alpha A gene expression was observed in B82 cells than in EL4 cells and was preserved in BELIII and BELIV. To examine whether reduced expression of these genes is also found in T cell x B cell hybrids, we generated an additional cell hybrid between EL4 cells and mouse plasmacytoma S194 cells (SELIII). Marked differences were observed in the expression of the TcR alpha, CD3 delta, LEF-1 and PEBP2 alpha A genes in BEL and SEL hybrids. Expression of the TcR alpha, CD3 delta and LEF-1 genes, which was extinguished in BELIII and BELIV, was detected in SELIII. PEBP2 alpha A gene expression, not detected in S194 cells, was considerably reduced in SELIII. Almost the sum of the chromosomes from the parental cells were retained by, and the presence of every gene was proven, in each cell hybrid. These results suggest that suppression of the expression of lymphoid-specific transcription factor genes may precede that of the TcR/CD3 genes in the cell hybrids, and that the presence of a different trans-acting negative regulatory mechanism(s) suppresses the expression of T cell specific genes in fibroblasts and B cells.

Animals↗
PubMed1995

Frequent expression of genes for receptor tyrosine kinases and their ligands in human pancreatic cancer cells.

Limited information is available concerning the involvement of growth factor receptors and their ligands in the pathogenesis of human pancreatic cancer. We analyzed 12 human pancreatic cancer cell lines by Northern blot analysis for the expression of 9 receptor tyrosine kinase (RTKs) and 6 growth factors. The effect of a monoclonal antibody (MAb) against transforming growth factor-alpha (TGF-alpha) on in vitro pancreatic cancer cell growth was also assessed, mRNA for EGF-R, c-erbB-2 and c-erbB-3 was expressed in 12 (100%), 12 (100%), and 7 (58%), respectively, of the cell lines examined. In addition, 8 (67%) cell lines expressed the c-met/receptor for hepatocyte growth factor. As for ligands, TGF-alpha mRNA was detected in 10 (83%) cell lines; MAb against TGF-alpha inhibited growth of the 2 cell lines examined. Furthermore, mRNA for amphiregulin (AR) was expressed in 10 (83%) cell lines. Coexpression of TGF-alpha, AR, and EGF-R was observed in 9 (75%) cell lines. These results support the concept that several specified types of RTKs and their ligands are closely involved in regulation of the growth of human pancreatic cancer cells.

ErbB Receptors↗
PubMed1995

Effect of Campylobacter rectus LPS on plasminogen activator-plasmin system in human gingival fibroblast cells.

The plasminogen activator (PA)-plasmin system is implicated in the degradation of the extracellular matrix in inflammation through activation of metalloproteases and prekallikrein. We examined the activation of the PA-plasmin system in human gingival fibroblast cells (Gin-1 cells) following treatment with lipopolysaccharide (LPS) from Campylobacter rectus, which is frequently detected at sites of periodontal disease. The C. rectus LPS stimulated the plasmin activity in the conditioned medium of Gin-1 cells in a time- and dose-dependent manner, and C. rectus LPS also stimulated the PA activity in the conditioned medium. The PA produced by Gin-1 cells was determined to be urokinase PA (uPA), as preincubation of Gin-1 conditioned medium with anti-uPA antiserum completely inhibited the PA activity while that with anti-tPA antiserum had no inhibitory effect. The concentration of PA inhibitor-1 (PAI-1) in the conditioned medium was decreased by the addition of C. rectus LPS. Therefore, the enhancement of plasmin activity in the conditioned medium was dependent on increased uPA activity via the decrease of the PAI-1 level of Gin-1 cells treated with C. rectus LPS. Furthermore, the conditioned medium of Gin-1 cells treated with C. rectus LPS showed significantly increased kallikrein activity, indicating the conversion of prekallikrein to kallikrein, which converts kininogen into kinin. These findings suggest that C. rectus LPS is a potent stimulator of inflammation of gingival tissue which acts through stimulation of the PA-plasmin system.

Campylobacter↗
PubMed1994

Stimulation of interleukin-6 production of periodontal ligament cells by Porphyromonas endodontalis lipopolysaccharide.

Interleukin-6 (IL-6), which is a multifunctional cytokine, has important roles in acute and chronic inflammation and may also be implicated in bone resorption. We examined the IL-6 production in periodontal ligament (PDL) cells which were treated with lipopolysaccharide (LPS) from several oral inflammatory pathogens. The LPS from Porphyromonas endodontalis, which was isolated from infected root canals and radicular cyst fluids, was more potent than the LPS from any other periodontal organisms examined. P. endodontalis LPS stimulated IL-6 release from PDL cells in a time- and dose-dependent manner. Northern blot hybridization analysis revealed that the IL-6 mRNA level in PDL cells was increased by P. endodontalis LPS. These results suggest that stimulation of the IL-6 release of PDL cells by P. endodontalis LPS may have a role in the progression of inflammation and alveolar bone resorption in periodontal and periapical diseases.

Blotting, Northern↗
PubMed1994

Production of endothelin-1 and thrombomodulin by human pancreatic cancer cells.

Analysis of bioactive substances produced by cancer cells is one approach to understanding the biological features of human cancer. One of these bioactive substances is endothelin (ET)-1, a peptide with potent vasoconstrictive activity produced by vascular endothelial cells. We have previously reported the production of ET-1 by several types of human cancer, especially pancreatic cancer cells. To elucidate whether these cancer cells might share biological characteristics with vascular endothelial cells, we investigated the production of three ET isoforms in pancreatic cancer cells, using a specific radioimmunoassay. Further, we also investigated whether these cells produce thrombomodulin (TM), another product of endothelial cells functioning as a modulator of procoagulant activity. ET-1 was detected in 11 of 12 pancreatic cancer cell lines (92%) while ET-2 and ET-3 were detectable in only one cell line. Gel filtration analysis confirmed the presence of ET-1. Moreover, TM was detected in the cell lysates of 11 of the 12 cell lines (92%) and it was released into the culture medium in the majority (58%) of these cell lines. TM mRNA was also detected in these cells. In addition, TM was demonstrated immunocytochemically along the cell surface. These results suggest that pancreatic cancer cells share two characteristics with endothelial cells: the production of ET-1 and TM.

Antibodies, Monoclonal↗
PubMed1994

Possible functional groups responsible for inhibition of in vivo angiogenesis by herbimycin A.

Six herbimycin A (HBM) derivatives were examined for their anti-angiogenic effects in a bioassay system involving chorioallantoic membranes (CAMs) of growing chick embryos on the basis of our previous observation that HBM is a potent angiogenesis inhibitor. 17-Cyclopropylamino-HBM dose-dependently inhibited embryonic angiogenesis. The ID50 value was 0.1 microgram (160 pmol) per egg and thereby lower than that of the parent compound HBM (ID50 = 0.15 micrograms (260 pmol) per egg). In contrast, 19-dimethylamino-, N-acetyl-, 2,3,4,5-tetrahydro- and 7-decarbamoyl-HBM at doses of 0.01-10 micrograms/egg failed to affect angiogenesis in CAMs. These results strongly suggest as follows: (1) C-19 position, amino group between positions C-1 and C-20 and carbamoyl group in C-7 are essential for the anti-angiogenic action of HBM; (2) HBM needs certain fixed conformation for expression of angiogenesis inhibition; (3) it is expected that the modification of C-17 with a suitable functional group results in increased anti-angiogenic potency of HBM--that is, a more potent angiogenesis inhibitor than the parent compound would be developed.

Allantois↗
PubMed1994

Three isoforms of platelet-derived growth factors all have the capability to induce angiogenesis in vivo.

Three isoforms of platelet-derived growth factors (PDGFs) composing of AA, AB, and BB chains all exhibited angiogenic activity in a dose-dependent manner in an in vivo assay system involving the chorioallantoic membrane of chick embryo. The order of potency as BB > AB = AA. They, however, failed to stimulate proliferation of vascular endothelial cells, suggesting that their effects are indirect. These data suggest that possibility that three PDGF isoforms are indirect angiogenic factors.

Animals↗
PubMed1994

Fine structure of the vomeronasal organ in the chinchilla (Chinchilla laniger).

Fine structure of the vomeronasal organ (VNO) was examined in the chinchilla (Chinchilla laniger) from a viewpoint of comparative anatomy. The VNO of chinchilla was a pair of tubular structure, about 6mm in length, and situated bilaterally along the base of the nasal septum. The VNO was encircled rostrally by the vomeronasal cartilage, but caudally by a bony capsule. The VNO communicated with the nasal cavity via a small pore at its rostral end, while it ended blindly at its caudal end. Its lumen was crescent to elliptical in a transverse plane, and lined medially with the vomeronasal sensory epithelium (VSE), but laterally with the vomeronasal respiratory epithelium (VRE). Jacobson's glands were tubulo-alveolar in type and distributed from the dorsolateral to the ventrolateral region of the VNO and opened with the duct to the lumen in the transitional region from the VSE to the VRE. Their secretions were periodic acid-Schiff (PAS)-positive but alcian blue (AB)-negative. The VSE consisted of sensory, supporting and basal cells. Supporting cells were characteristic of a large number of huge dense bodies in the perinuclear cytoplasm. The other ultrastructural features in sensory, supporting and basal cells of the VSE were similar to those in the previous reports. The VRE consisted of ciliated, non-ciliated and basal cells. Acinar cells of Jacobson's gland possessed two types of secretory granules. Secretory granules of one type were homogeneous and electronlucent, about 1,700nm in diameter, while granules of the other type were about 2,200nm in diameter, and various in electron density. The present findings suggest that the VNO is functionally active in the chinchilla.

Animals↗
PubMed1994

Matlystatins, new inhibitors of type IV collagenases from Actinomadura atramentaria. IV. Synthesis and structure-activity relationships of matlystatin B and its stereoisomers.

The first total synthesis of matlystatin B (1a), a low molecular weight inhibitor of type IV collagenases, was accomplished, and its absolute configuration was unambiguously determined. Furthermore, ten stereoisomers of 1a were synthesized, and the inhibition of the 92 kDa type IV collagenase and of other metalloproteinases by each stereoisomer was investigated.

Anti-Bacterial Agents↗
PubMed1994

Fabry-like laminated myelin body associated with IgA nephropathy.

We present the first female patient to exhibit Fabry-like myelin bodies in the glomerular epithelial cell in association with IgA nephropathy. This previously healthy 36-year-old woman presented with proteinuria and hematuria without skin lesions. Renal biopsy showed typical IgA nephropathy, with paramesangial deposits, mesangial proliferation and scattered myelin bodies. The leukocytic alpha-galactosidase A activity was abnormally low. She had no family history of Fabry's disease nor the characteristic features, such as skin lesion, neuralgia, or hypohidrosis. Fabry's disease is diagnosed from the renal biopsy findings and the activity of alpha-galactosidase A in leukocytes and/or fibroblasts. We diagnosed the present case with Fabry' disease and IgA nephropathy from these results.

Adult↗
PubMed1994

Renal complications during pregnancy in a patient with diabetes mellitus.

We present a 23-year-old woman with a 7-year history of insulin-dependent diabetes mellitus (IDDM) who became pregnant. At the 23rd week of pregnancy she exhibited the signs and symptoms (hypertension, edema, proteinuria) of both diabetic nephropathy and preeclampsia. A cesarean section was successfully performed. The proteinuria persisted for more than 3 months after delivery. Renal biopsy confirmed the diagnosis of diabetic glomerulosclerosis together with the renal findings attributable to preeclampsia. The rapid acceleration of diabetic nephropathy in this patient was attributed to preeclampsia. We therefore recommend that patients with DM be followed closely during pregnancy in an attempt to prevent the acceleration of renal damage by preeclampsia.

Adult↗
PubMed1994

[Effect of biapenem (L-627) on fecal flora in gnotobiotic mice and children].

Biapenem (L-627), a novel injectable carbapenem antibiotic, was studied with regard to its effect on mice inoculated with four types of bacteria and on the intestinal flora of pediatric patients. L-627 was given i.m., 40 mg/kg once daily for 5 consecutive days, to mice inoculated enterically with four types of bacteria (Escherichia coli, Enterococcus faecalis, Bacteroides fragilis, and Bifidobacterium breve). Except for a mild decrease in E. coli, there were no major fluctuations in viable bacterial counts in the feces during the treatment. Five children with bacterial infections (3 boys and 2 girls; ages: 1 month to 7 years and 7 months; body weights 4.62-21.8 kg) were given L-627 at 6.0 to 11.7 mg/kg 3 times daily for 7 to 11 days. Among aerobes, although Enterobacteriaceae such as E. coli tended to decrease remarkably in all patients, there was no major change in Enterococcus. Consequently, total aerobe counts did not change significantly in any patient. Among anaerobes, Bifidobacterium, Bacteroides, and Eubacterium, which are the predominant organisms in infants, decreased remarkably in some patients. One of the patients showed a marked decrease in total anaerobe count associated with a change in fecal characteristics (diarrhea). Glucose nonfermenting Gram-negative bacilli or fungi did not become predominant organisms in any patient. Recovery from these changes in the intestinal flora was noted promptly after terminating L-627 treatment. L-627 was detected in the feces of 4 patients during treatment. The fecal concentration ranged from 0.24 to 2.22 micrograms/g. Clostridium difficile was not detected in any patient. Although C. difficile D-1 antigen was observed in 2 patients, it bore no relationship to fecal properties. The results indicated that L-627 had relatively few effects on the intestinal flora compared to other new beta-lactam antibiotics.

Animals↗
PubMed1994

[Brain abscess ruptured into the lateral ventricle: the usefulness of treatment by intraventricular irrigation with antibiotics. A case report].

A case is reported of a brain abscess, which ruptured into the lateral ventricle and was treated using intraventricular irrigation with antibiotics. A 37-year-old man was suffering from a headache and high fever. Precontrast CT scan revealed a heterogeneous low density area in the left temporal lobe, and postcontrast CT scan showed a multilobular ring-like enhanced mass. Diagnosed as a brain abscess, intravenous administration of antibiotics was performed. On the sixth day the patient suddenly became drowsy. Postcontrast CT scan revealed an enhanced effect in the left lateral ventricular wall. Drowsiness was attributed to increased intracranial pressure and severe ventriculitis. Bilateral continuous ventricular drainage via the anterior horn of the lateral ventricle was performed. The drainage fluid from the left lateral ventricle was just like pus. Intraventricular irrigation with antibiotics between the bilateral anterior horns of the lateral ventricle, was performed in order to save the patient. The infusion fluid, Lactate Ringer's solution containing Cefazolin sodium, was infused into the right ventricle and CSF-like pus was drained from the left ventricle. The CSF reading gradually improved, and on the 14th day postoperatively irrigation was terminated. The postoperative course was uneventful. The diagnosis, treatment, and prognosis of patients with brain abscesses have improved dramatically as a result of more reliable methods of identifying infecting organisms, more effective antibiotic regimens, the development of microsurgical techniques and CT scan. However, despite these advances, the prognosis for brain abscess ruptured into the ventricle is usually very pessimistic.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Nephropathy in patients with primary antiphospholipid antibody syndrome].

Primary antiphospholipid antibody syndrome (APS) is characterized by abortion, thrombosis, thrombocytopenia and/or valvular disease and it is liable to complicate systemic lupus erythematosus (SLE). We carried out a study to investigate the clinical and renal pathological findings in five patients with APS, but not SLE. In the clinical findings, the patients had negative tests for proteinuria and hematuria, and their renal function and tubular function were within normal limits. In the light microscopic findings, three patients exhibited mild mesangial hypercellularity, and two had minor glomerular abnormalities. In immunofluorescent study, there were IgM and/or C3 depositions in the mesangial area in some cases, and in electron microscopic study, there were no special findings other than mesangial hypercellularity. In conclusion, nephropathy is a rare complication in patients with APS, unlike systemic lupus erythematosus.

Adult↗
PubMed1993

Extinction of expression of the PU.1/Sfpi-1 putative oncogene encoding a B-cell- and macrophage-specific transcription factor in somatic cell hybrids.

Several examples of extinction of cell type-specific gene expression have been observed following fusion of different cell types. Possible mechanisms of the extinction include loss of transcriptional activators and acquisition of repressor factors responsible for cell type-specific gene expression. In this study, we demonstrated the extinction of expression of the PU.1/Sfpi-1 putative oncogene encoding a B-cell- and macrophage-specific transcription factor when plasmacytoma cells are fused with embryonal carcinoma (EC) cells. The hybrid cells retained most chromosome complements from both parental lines including chromosome 2 on which the PU.1 gene is located. Therefore, extinction of PU.1 gene expression in the hybrids is not likely the result of chromosome segregation but rather due to a transacting negative factor(s) present in EC cells. On the contrary, expression of the PU.1 mRNA in plasmacytoma cells was not extinguished upon cell fusion with T-lymphoma cells, although the parental T-lymphoma cells did not express PU.1 transcripts. Hence, T-lymphoma cells seemed to be permissive to PU.1 gene expression, while EC cells were repressive. These results suggest that PU.1 gene expression which positively regulates some B cell- and macrophage-specific gene expression is a target of negative regulatory mechanisms during cell differentiation, and the regulatory mechanisms repressing PU.1 gene expression is different between EC cells and T-cells.

Animals↗