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Biomedical subjects

O Tanaka

Publications and source records attributed to O Tanaka.

At least 109 records · Page 6Linked to original sources
PubMed1994

Localization of mRNAs for three novel members (beta 3, beta 4 and gamma 2) of phospholipase C family in mature rat brain.

In mature rat brain, PLC beta 3 mRNA was detected weakly only in the pituitary gland and the cerebellar Purkinje and granule cells whereas PLC beta 4 mRNA was expressed intensely in the olfactory mitral cells, thalamic nuclei, medial habenula, pituitary gland and cerebellar Purkinje and granule cells. The beta 4 mRNA was also detected discretely in large neurons of presumably cholinergic nature, scattered rather evenly throughout the caudate putamen and diagonal band, although no significant expression was seen in the medium spiny neurons in the caudate putamen, and the hippocampal pyramidal cells and dentate granule cells. PLC gamma 2 mRNA was localized only in the Purkinje and granule cells in the vermal portions of lobules IX and X of the cerebellum, and in the adenohypophysis.

Aging↗
PubMed1994

Contribution of RGD sequence to neuronal migration in developing cerebral cortex.

The RGD sequence (Arg-Gly-Asp) is known to bind integrins and the synthetic RGD tripeptide inhibits cell adhesion and migration of cultured neuronal cells. However, it is not known whether migration of neuronal precursors in vivo during the cortical histogenesis of the mammalian telencephalon depends on the RGD sequence. To examine this possibility, the RGD peptide was injected into the telencephalic vesicle of mouse embryos. A hypoplastic cortical plate was induced and histological analysis and BrdU-immunohistochemistry revealed that the RGD sequence is involved in neuronal migration and proliferation in the telencephalon during formation of the cortical plate.

Amino Acid Sequence↗
PubMed1994

Transgenic mice overexpressing human vasoactive intestinal peptide (VIP) gene in pancreatic beta cells. Evidence for improved glucose tolerance and enhanced insulin secretion by VIP and PHM-27 in vivo.

Vasoactive intestinal peptide (VIP), a 28-amino acid peptide hormone, plays many physiological roles in the peripheral and central nervous systems. It has been proposed that endogenous VIP released from VIP-containing nerves is involved in the regulation of the secretory function of the endocrine pancreas. To test this hypothesis in vivo, we produced transgenic mice carrying the human VIP/peptide histidine methionine 27 (PHM-27) gene under the control of insulin promoter. In immunohistochemical analyses of islets, all the islet beta cells of transgenic mice were intensely stained for both VIP and PHM-27, consistent with the fact that these two peptides are encoded in a single mRNA (Itoh, N., Obata, K., Yanaihara, N., and Okamoto, H. (1983) Nature 304, 547-549). VIP was efficiently secreted from isolated transgenic islets in vitro. The blood glucose assays in free-fed mice indicated that the transgene lowered the blood glucose levels of transgenic mice (128 +/- 4 mg/dl) by about 20% below control levels (155 +/- 6 mg/dl). In the glucose tolerance test, at 60 min after glucose administration, the transgenic blood glucose levels (129 +/- 12 mg/dl) were much lower than control levels (175 +/- 13 mg/dl). The transgenic serum insulin levels at 15 min after glucose administration were 2.5-3.0-fold higher than control levels. The transgene was also effective in ameliorating glucose intolerance of 70% depancreatized mice. These results indicate that VIP and PHM-27 produced from the transgenic beta cells efficiently enhance glucose-induced insulin secretion from beta cells by an autocrine mechanism. These results also suggest that genetic manipulation of islet beta cells by the human VIP/PHM-27 gene or delivery of VIP to beta cells may ultimately provide a valuable approach to enhancing insulin secretion in clinical diabetes.

Animals↗
PubMed1994

Different characteristics of hepatoid and non-hepatoid alpha-fetoprotein-producing gastric carcinomas: an experimental study using xenografted tumors.

The characteristics, including metastatic potential, of 5 xenografts of alpha-fetoprotein (AFP)-producing gastric carcinomas in nude mice, designated TSG1, TSG3, TSG11, TSG17 and TSG20, were examined. Of these xenografts, TSG1, TSG11 and TSG20 were regarded as hepatoid adenocarcinomas based on their morphological resemblance to hepatocellular carcinoma, frequent immunoreactivity for liver-cell markers, and excessive production of AFP with a high concanavalin A (Con-A)-binding property of hepatic type. On the other hand, TSG3 and TSG17 tumors showed the features of poorly differentiated medullary adenocarcinoma with scattered AFP-positive cells consistent with low AFP levels in mouse sera, and negative immunoreactivity for other liver-cell markers. Ultrastructurally, these tumors were composed of undifferentiated cells with a little adenocarcinomatous differentiation. Moreover, the AFP produced by TSG3 and TSG17 tumors had an extremely high Con-A nonbound fraction (80% to 90%), which was different from that of the hepatic or yolk-sac types. Therefore, both TSG3 and TSG17 tumors were regarded as non-hepatoid, poorly differentiated adenocarcinomas which could be differentiated from any types of AFP-producing gastric carcinoma. Furthermore, cells from hepatoid adenocarcinoma strains (TSG1, TSG11 and TSG20) injected into the spleens of nude mice produced liver metastases in all the mice examined, whereas cells from non-hepatoid carcinoma strains (TSG3 and TSG17) produced few or no liver metastases. Our data show that some non-hepatoid AFP-producing gastric carcinomas have lower liver-metastasizing potential than hepatoid AFP-producing gastric carcinomas.

Adenocarcinoma↗
PubMed1994

Patterns of lymphatic spread in thoracic esophageal cancer.

BACKGROUND: The cervical nodes have been excluded from the category of regional nodes in cases of thoracic esophageal cancer in the present TNM classifications. METHODS: One hundred and forty-one patients with thoracic esophageal cancer who had undergone extensive radical lymphadenectomy were included in the study. The patterns of early lymph node metastasis from the disease, in terms of lymph node metastases from the intramural tumors or those found in patients with a single metastatic node, were studied. Prognostic significance of the removal of the positive nodes also was examined in relation to the metastatic sites. RESULTS: Of the 47 patients with intramural cancer, only 21% had nodal metastases confined to the mediastinum, 11% had positive cervical nodes, and 23% had jumping metastases to the extramediastinal nodes. Of the 31 patients with a single metastatic node, 61% showed metastasis in a jumping fashion, and 19% had a positive node in the neck. Seventy-four (79.6%) of the 93 patients with vessel invasion also had lymph node metastases, whereas 20 (41.7%) of the 48 patients without vessel invasion had metastases to the lymph nodes (P < 0.001). The 5-year projected survival rate for patients with positive cervical nodes was 27%, with no significant difference in survival rate compared with that for patients with metastatic nodes in the mediastinum or the abdomen. The number of involved nodes was related significantly to outcome: The 5-year survival rates for the 45 patients with negative nodes the 66 patients with one to four positive nodes were 71.8 and 34.2%, respectively (P < 0.01), whereas none of the 27 patients with five or more positive nodes survived more than 3 years after the operation (P < 0.001). CONCLUSIONS: The cervical nodes should be included in the category of regional nodes in cases of thoracic esophageal cancer on the basis of the patterns of early lymph node metastases and the prognostic significance of a lymphadenectomy for metastases to these nodes.

Abdomen↗
PubMed1994

Pancreatic beta-cell replication and amelioration of surgical diabetes by Reg protein.

We previously isolated from a rat regenerating islet cDNA library a gene named Reg, which is expressed in regenerating islets but is not expressed in normal islets. Here we examined the effect of rat Reg protein on pancreatic beta-cell replication using both 90% depancreatized rats and isolated islets. The depancreatized rats that received i.p. administration of recombinant rat Reg protein (1 mg/kg per day) for 2 months showed amelioration of the surgical diabetes, as evidenced by a significant decrease in blood glucose with an increased beta-cell mass in the residual pancreas. In isolated rat islets, Reg protein (18-180 nM: 0.3-3 micrograms/ml) significantly increased [3H]thymidine incorporation into the nuclei of beta cells. These results indicate that Reg protein is a growth factor for pancreatic beta cells and also suggest that the administration of Reg protein could be used as another therapeutic approach for diabetes mellitus.

Animals↗
PubMed1994

Transgenic mouse model of hemifacial microsomia: cloning and characterization of insertional mutation region on chromosome 10.

The 643 transgenic mouse line carries an autosomal dominant insertional mutation that results in hemifacial microsomia (HFM), including microtia and/or abnormal biting. In this paper, we characterize the transgene integration site in transgenic mice and preintegration site of wildtype mice. The locus, designated Hfm (hemifacial microsomia-associated locus), was mapped to chromosome 10, B1-3, by chromosome in situ hybridization. We cloned the transgene insertion site from the transgenic DNA library. By using the 5' and 3' flanking sequences, the preintegration region was isolated. The analysis of these regions showed that a deletion of at least 23 kb DNA occurred in association with the transgene integration. Evolutionarily conserved regions were detected within and beside the deleted region. The result of mating between hemizygotes suggests that the phenotype of the homozygote is lethality in the prenatal period. These results suggest that the Hfm locus is necessary for prenatal development and that this strain is a useful animal model for investigating the genetic predisposition to HFM in humans.

Animals↗
PubMed1994

Ontogeny of alpha-crystallin subunits in the lens of human and rat embryos.

The distribution of alpha A- and alpha B-crystallin in the developing lens of human (Carnegie stages 13 to 23) and rat embryos (embryonic days E11 to 18) was examined immunohistochemically. In a human embryo at stage 13, the lens placode was already immunoreactive to alpha B-crystallin, but not to alpha A-crystallin. At stage 15, the lens vesicle was intensely immunoreactive both to alpha A- and alpha B-crystallin. From stages 16 to 23, the lens epithelial cells and fiber cells were immunoreactive to alpha A- and alpha B-crystallin. In rat embryos, alpha A-crystallin appeared in the lens pit at E12, and alpha B-crystallin appeared in the elongating lens fiber cells at E14. From E15 to E18, the lens epithelial cells and fiber cells were immunoreactive to alpha A-crystallin. The lens fiber cells were also immunoreactive to alpha B-crystallin, but the epithelial cells were not. These findings suggest that alpha B-crystallin appears earlier than alpha A-crystallin in the human lens, but at a later period than alpha A-crystallin in the rat lens. alpha B-Crystallin was not detected in the epithelial cells of the rat lens, but was persistently present in the epithelial cells of the human lens.

Animals↗
PubMed1994

Embryonic growth impaired by maternal hypoglycemia during early organogenesis in normal and diabetic rats.

The effect of maternal hypoglycemia on early organogenesis was studied in normal and diabetic rats. Female Wistar rats were made diabetic by an intravenous injection of streptozotocin (45 mg/kg) 2-3 weeks before conception. On day 9.5 or 10.5 of embryo development, both control and diabetic dams received saline or Actrapid human insulin (400 mU/rat) intraperitoneally after 19-h starvation. The fasting plasma glucose levels in diabetic dams decreased from approximately 23 to 8 mM. Hypoglycemia as low as 3.5 mM was maintained for 60 min in insulin-treated mother rats. Pregnancy was terminated on day 11.6 of embryo development. A significant growth retardation was found in diabetic embryos as compared with normal embryos. Maternal hypoglycemia lowered the DNA content in normal but not diabetic embryos, while the teratogenic effect of maternal hypoglycemia was not pronounced in either normal or diabetic embryos. These data may suggest that maternal hypoglycemia in vivo in early pregnancy influences the embryogenesis but not teratogenesis of rat embryos.

Animals↗
PubMed1994

Augmentation of 5-fluorouracil cytotoxicity by epidermal growth factor in a newly established human signet-ring cell carcinoma of the stomach in culture.

A cell line designated TSG6 was established from a signet-ring cell gastric carcinoma developed in a 57-year-old female patient. The TSG6 cells had well preserved the features of signet-ring cell carcinoma based on morphology. The cells exhibited both epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) immunoreactivities, and also secreted EGF. Moreover, the growth of TSG6 cells was stimulated in the presence of exogenous EGF. These results suggest that the possible presence of an EGF/EGFR autocrine growth mechanism is expressed in the TSG6 cells. The simultaneous treatment with EGF and 5-fluorouracil (5-FU) produced a nearly 2.4-fold enhancement of 5-FU cytotoxicity against TSG6 cells. A bromodeoxyuridine/DNA flow cytometry analysis revealed that EGF augmented 5-FU cytotoxicity by inducing the accumulation of S phase cells which might be more susceptible to 5-FU. Moreover, we found that the incorporation of 5-FU into the TSG6 cells was increased with the addition of EGF. These data indicate that EGF may be a potent agent as a biological response modifier for 5-FU against the tumors which express the EGF/EGFR autocrine mechanism, and that the TSG6 cell line is useful in furthering our understanding of the interaction between anticancer drugs and EGF.

Carcinoma, Signet Ring Cell↗
PubMed1994

Improvement of gas exchange following endobronchial instillation of an exogenous surfactant in an infant with respiratory failure by postoperative pulmonary haemorrhage.

We administered surfactant to a 5-month-old infant with respiratory failure due to right pulmonary haemorrhage accompanied by oedema following abdominal surgery. These pathological conditions were probably precipitated by disseminated intravascular coagulation and intra-operative excessive administration of fluids, respectively. Endobronchial instillation of the exogenous surfactant (120 mg) after selective intubation of the right bronchus produced a dramatic improvement of gas exchange 30 min after treatment and of chest X-ray findings at 6 h post-treatment. This case on an infant indicates that administration of surfactant may be one of promising therapeutic approaches to respiratory failure due to pulmonary haemorrhage.

Biliary Atresia↗
PubMed1994

Diterpenoid glycosyl esters from Phlomis younghusbandii and P. medicinalis roots.

From the roots of Phlomis younghusbandii collected in Tibet, new furanolabdane-type diterpenoid glycosides named phlomisosides III and IV were isolated together with a known sweet furanolabdane-type diterpenoid glycoside, phlomisoside I. The structure of the common aglycone of phlomisosides III and IV, which we have named phlomisoic acid, was established as 15,16-epoxy-8,13(16),14-labdatrien-19-oic acid by MS and NMR spectroscopy. Phlomisosides III and IV are tasteless and the structures of these were determined to be the beta-D-xylopyranosyl(1-->2)-beta-D-glucopyranosyl and the alpha-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranosyl ester of phlomisoic acid by chemical and spectroscopic methods, respectively. The diterpenoid glycoside constituents of the roots of P. medicinalis collected in Tibet were also elucidated, and baiyunoside and phlomisosides II and III were isolated and identified.

Carbohydrate Sequence↗
PubMed1994

Tissue transmigration of CZON (Cosmosin) to middle ear mucosa, maxillary sinus mucosa, and palatine tonsils.

The concentration of CZON was determined by HPLC in surgical patients with chronic otitis media, sinusitis, and tonsillitis. One gram of CZON was injected intravenously prior to surgery. The time course of the mean tissue CZON level was as follows: In the middle ear mucosa, 3.7 micrograms/g at 15 min, 7.2 micrograms/g at 30 min, and 2.9 micrograms/g at 1 hr (the half life: 21.3 min). In the maxillary sinus mucosa, 10.5 micrograms/g at 15 min, 11.8 micrograms/g at 30 min, and 2.8 micrograms/g at 1 hr (the half life: 17.5 min). In the tonsils, 14.9 micrograms/g at 15 min, 9.3 micrograms/g at 30 min, and 2.0 micrograms/g at 1 hr (the half life: 13.2 min). The concentration was high in the maxillary sinus mucosa and the tonsils, but was low in the middle ear mucosa. In the formers the transfer ratio reached its peak 15 to 30 min after administration, but in the latter the peak was reached 30 to 60 min after administration. The order of the transfer ratio at each region was above 25%. The tissue concentration exceeded the MIC80s of frequent isolates from these infections. CZON is considered to be a highly useful drug in the treatment of these infections.

Adolescent↗
PubMed1994

Clinical implications of cervical lymph node metastasis patterns in thoracic esophageal cancer.

OBJECTIVE: The authors attempt to clarify the clinical implications of cervical lymph node metastases from thoracic esophageal cancers. SUMMARY BACKGROUND DATA: Cervical lymph node metastases from thoracic esophageal cancer have been considered to be incompatible with curative resection. However, recent studies have demonstrated that cure is achievable in patients with such metastases. METHODS: Patterns of esophageal cancer metastasis to the cervical nodes and long-term results after tumor resection were investigated in 23 patients undergoing bilateral cervical lymphadenectomy for treatment of thoracic esophageal cancer. RESULTS: The number of positive nodes per patient was significantly greater (p < 0.05) in lower esophageal cancers (median: 15) than in upper or mid esophageal cancers (median: 2.5). Simultaneous metastases to three nodal regions (the neck, mediastinum, and abdomen) were significantly more common (p < 0.001) in lower esophageal tumors (88.9%) than in upper and mid esophageal lesions (7.1%). Although the overall 5-year survival rate was 16.5%, long-term survival was achieved only in patients with upper or mid esophageal cancer.

Adult↗
PubMed1994

Mechanisms of the development of trazodone withdrawal symptoms.

Three cases developed withdrawal symptoms of trazodone despite gradual discontinuation of therapeutic doses of the drug. This report suggests that effects of trazodone and its metabolite m-chlorophenylpiperazine on the serotonergic system, which may result in noradrenergic rebound after discontinuation, and short half-lives of these compounds are involved in the development of these symptoms. From a clinical point of view, we suggest that trazodone should be tapered off at a very slow rate.

Adult↗
PubMed1994

Adverse effects of zotepine and their relationship to serum concentrations of the drug and prolactin.

Adverse effects of zotepine, an antipsychotic drug, and their relationship to serum concentrations of the drug and prolactin were investigated in 28 schizophrenic in-patients. The daily dose was 100 mg during the first week and 200 mg during the next 3 weeks. Adverse effects were evaluated by the UKU Side Effect Rating Scale (21 items). The mean (+/- SD) total UKU score at the end of the study was 3.1 +/- 2.5, indicating mild adverse effects. The scores of psychic adverse effects at 2 weeks and total adverse effects at 3 and 4 weeks were significantly higher in nonresponders than in responders (p < 0.05). Furthermore, there was a significant inverse correlation between percent improvement in total Brief Psychiatric Rating Scale (BPRS) scores and total UKU scores at 4 weeks (p < 0.05). These results suggest a relationship between poor clinical response and increased adverse effects during zotepine treatment. Only the scores of akathisia at 2 weeks showed a significantly positive correlation with serum zotepine concentrations (p < 0.05). No correlation was found between prolactin response and neurological adverse effects.

Adolescent↗
PubMed1994

Flow cytometric analysis of early steps in development of adriamycin resistance in a human gastric cancer cell line.

We have established a low-level adriamycin (ADM)-resistant human gastric cancer cell line (MKN45R) from the parental cell line (MKN45) by exposure to stepwise increases of ADM concentration (final concentration, 0.026 microgram/ml). The purpose of this study was to identify the early steps in the development of ADM resistance in MKN45R by flow cytometric (FCM) analysis. Comparison of the concentration required for 50% growth inhibition, determined by a tetrazolium-based colorimetric assay, showed that MKN45R was about 2.6-fold more resistant to ADM than MKN45. However, the inhibition index values were 89.5% for MKN45 and 86.4% for MKN45R, respectively, showing that ADM was judged to be "effective" against both cell lines. On the other hand, cell kinetic analysis by FCM revealed that the increase of the ratio of G2M accumulation induced by ADM treatment was significantly lower (P < 0.01) in MKN45R. Moreover, the efflux of ADM estimated by FCM analysis was significantly increased (P < 0.05) in MKN45R even though there was no significant increase of P-glycoprotein expression. These results suggest that although ADM was still effective based on a standard drug sensitivity test, the cancer cells were already acquiring resistance to ADM as judged from FCM analysis. Moreover, the mechanism of this ADM resistance is considered to be independent of P-glycoprotein expression. Thus, FCM analysis is useful for detecting the early steps in the development of drug resistance of cancer cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗