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K Obata

Publications and source records attributed to K Obata.

At least 73 records · Page 4Linked to original sources
PubMed1999

Arginine carboxypeptidase (CPR) in human plasma determined with sandwich ELISA.

There are two types of carboxypeptidases present in human blood, carboxypeptidase N (CPN) and arginine carboxypeptidase (CPR). CPR is generated during coagulation from a precursor (proCPR) which can be converted to the active form by trypsin in vitro. Since it is difficult to distinguish the two types of carboxypeptidases in human blood by the measurement of enzyme activity, we established a quantitative sandwich ELISA by which CPR can be quantitated. The amount of CPR in plasma, fresh serum and heated serum were essentially the same. Therefore the ELISA assay does not distinguish proCPR, activated CPR and inactivated CPR. With the ELISA method, CPR was quantitated in plasma from fifty patients with rheumatoid arthritis and eleven patients with severe hepatitis as well as healthy individuals. The amount of CPR in plasma obtained from patients with rheumatoid arthritis was not found to be lower than that of normal subjects. Furthermore, the patients who suffered severe hepatitis and had very low levels of CPR-total were fatal. This suggests that a decrease of CPR level might be a good indication of a patient's prognosis to death by hepatitis.

Antibodies, Monoclonal↗
PubMed1999

Immunohistochemical studies concerning cathepsin D in endometrial carcinomas.

OBJECTIVES: To study the prognostic value of immunohistochemical detection of cathepsin D and laminin in endometrial carcinomas. METHODS: Immunohistochemical staining of cathepsin D was performed on paraffin sections of 111 endometrial carcinomas, and laminin deposition was studied in 65 endometrial carcinomas. RESULTS: Of 111 tissue specimens, 55 showed a positive reaction for cathepsin D. The incidence of cathepsin D-positive staining increased with the extension of the primary tumor (p < 0.01). Patients with vessel invasion and pelvic lymph-node metastasis had a higher incidence of cathepsin D-positive staining than patients without these findings (p < 0.05). A favorable prognosis was obtained in a negative case of cathepsin D in comparison with a positive case (p < 0.01). Of 9 patients in whom laminin was detected in the cytoplasm of cancer cells, 5 showed poor prognoses and died from a primary disease. CONCLUSION: Cathepsin D and laminin status might represent possible prognostic factors.

Adult↗
PubMed1999

Effect of a novel immunosuppressant, FK 506, on autoimmune glomerulonephritis in Brown Norway rats.

Mercuric-chloride (HgCl2) induces a lymphoproliferative disorder and autoimmune glomerulonephritis in Brown Norway rats. The effects of a new immunosuppressant FK 506 on this model of glomerulonephritis were studied. Brown Norway rats were treated with HgCl2 according to a standard protocol (HgCl2 1 mg/kg s.c. 3 times/ week). Rats developed proteinuria at day 7, which reached a plateau level at day 14. On day 14, renal histology showed prominent mesangial cellular proliferation and the expansion of mesangial matrix. Electron microscopic study showed the effacement of visceral epithelial foot processes and the microvillous transformation of the visceral epithelium. Immunofluorescence study showed a strong linear staining for IgG and the adhesion molecule ICAM-1 in all glomeruli. Coadministration of FK 506 (1 mg/kg s.c. daily) prevented the appearance of proteinuria at day 14 (621.4 +/- 30.5 vs. 2.2 +/- 2.7 mg/day) and the morphological lesions. These findings suggest that FK 506 could be useful for the therapy of certain types of human glomerulonephritis.

Animals↗
PubMed1999

Effect of FK 506 in the treatment of autoimmune glomerulonephritis in Brown Norway rats.

Mercuric chloride (HgCl2) induces a lymphoproliferative disorder and autoimmune glomerulonephritis in Brown Norway (BN) rats. The effects of a new immunosuppressant, FK 506, on this model of glomerulonephritis were studied. BN rats were treated with HgCl2 according to a standard protocol (HgCl2 1 mg/kg s.c. 3 times/week). FK 506 was inoculated subcutaneously daily from day 15 to day 28. Animals were divided into 4 groups: group 1, rats were treated with normal saline alone and sacrificed on day 28; group 2, rats were treated with HgCl2 alone and sacrificed on day 14; group 3, rats were treated with HgCl2 alone and sacrificed on day 28, and group 4, rats were treated with HgCl2 and FK 506 (from day 15 to day 28) and sacrificed on day 28. Rats developed proteinuria by day 7, which reached a plateau level by day 14. On day 14, renal histology showed prominent mesangial cellular proliferation and the expansion of mesangial matrix. Electron microscopic study showed the effacement of visceral epithelial foot processes and the microvillous transformation of the visceral epithelium. Immunofluorescence study showed strong linear staining for IgG and the adhesion molecule ICAM-1 in all glomeruli. Treatment with FK 506 (1 mg/kg s.c. daily) resulted in a remarkable reduction in proteinuria on day 28 (493.5 +/- 48.3 vs. 24.4 +/- 13.5 mg/day) and an improvement in the morphological lesions. These findings suggest that FK 506 could be useful in the treatment of some human glomerulonephritides.

Animals↗
PubMed1999

Repeated ultrasonically guided needle biopsy of small subpleural nodules.

STUDY OBJECTIVE: To detect the significance of repeated ultrasonically guided needle biopsy (UGNB) for the diagnosis of nodular lesions </= 2 cm in diameter. DESIGN: Retrospective study to evaluate the diagnostic yield of UGNB. SETTING: University hospital, outpatients, and inpatients of the respiratory department. PATIENTS: One hundred seven cases with small nodular lesions </= 2 cm in diameter in contact with the pleura. Sixty-two of 107 cases were malignant, and the others were benign diseases. RESULTS: Initial UGNB identified 56% (35/62) of the malignant lesions and 16% (7/45) of the benign lesions, ie, 39% (42/107) of the total. In 35 of 65 cases that were not diagnosed by the initial UGNB, it was repeated. Diagnostic yields of the second UGNB were 68% (13/19) of the malignant cases, 25% (4/16) of the benign cases, yielding a total of 49% (17/35) in those reexamined. Furthermore, 51 of 65 patients with negative findings on the initial UGNB underwent fiberoptic bronchoscopy. The resulting diagnostic yields were 22% (5/23) from the malignant lesions and 18% (5/28) from the benign lesions, 20% (10/51) in total. Thus, among the malignant cases, the repetition of UGNB increased the definitive diagnostic yield from 56% (the initial UGNB) to 77%. In these small tumors, no serious complications were caused by the procedure. CONCLUSIONS: UGNB should be performed twice for a definitive diagnosis of small subpleural nodules before deciding on surgical biopsy or follow-up.

Biopsy, Needle↗
PubMed1999

Renin-angiotensin system component gene polymorphism in Japanese bronchial asthma patients.

The influence of renin-angiotensin system (RAS) component gene polymorphism in the pathogenesis of bronchial asthma was investigated in an association study involving 119 bronchial asthma patients and 208 control subjects. The selected RAS polymorphisms were angiotensinogen (Agt) T235/M235 and angiotensin I-converting enzyme (ACE) insertion/deletion (I/D). The control allelic frequencies of the Agt T235/M235 (0.84/0.16) and ACE I/D (0.63/0.37) in this study were similar to the previous reports in Japanese normal population. The allelic frequencies of the Agt T235/M235 (0.84/0.16) and ACE I/D (0.65/ 0.35) among the asthma patients were not significantly different from those among the control subjects. There was no association between severity of bronchial asthma and the selected RAS component gene polymorphism. From these data, we conclude that in the Japanese population, the RAS component gene polymorphism is not associated with increased risk for bronchial asthma.

Adult↗
PubMed1999

Molecular characterization of the genomic breakpoint junction in a t(11;22) translocation in Ewing sarcoma.

Polymerase chain reaction (PCR)-based nucleotide sequence analysis was performed in 12 cases of Ewing sarcoma on the cDNA and/or genomic DNA breakpoint regions of a t(11;22)(q24;q12), which joins the EWS gene located on chromosome 22 with the FLI1 gene located on chromosome 11, in order to understand the molecular mechanism of this translocation. Reverse transcriptase-PCR on total tumor cell RNA from the examined cases showed five types of EWS-FLI1 chimeric product, resulting from various junctions between EWS exon 7 or 10 with FLI1 exon 5, 6, or 8. Sequencing of the genomic fusion junctions of EWS-FLI1 in seven cases showing three types of the chimeric cDNA products revealed that most of the breakpoint junctions shared common nucleotide(s) from both genes, and that the breakpoints in EWS introns 7 and 10 clustered within 100 bp and 300 bp, respectively. All the junctions were found to be flanked by various oligomers, among which a consensus sequence, 5'-AGAAAARDRR-3', was found near the breakpoints of both genes in four cases, suggesting that these oligomers may have a functional significance in the genesis of t(11;22). In addition to these oligomers, sequences highly homologous to Alu repeats and/or eukaryotic topoisomerase II cleavage sites were located near, or flanked, or even encompassed, the breakpoints in most of the cases examined. Thus, these sequences may also mediate DNA double-strand breakage and rejoining to generate the t(11;22). Genomic sequence analysis of both EWS-FLI1 and FLI1-EWS chimeric genes in three of the seven cases demonstrated a deletion and duplication of both EWS and FLI1 sequences in two cases and no gain or loss in one case. The present findings suggest that multiple mechanisms may be operative for the break and rejoining of the fragments of chromosomes 11 and 22 in the genesis of t(11;22), and that some of these translocations are asymmetric at the molecular level.

Adolescent↗
PubMed1998

Novel breakpoints of the EWS gene and the WT1 gene in a desmoplastic small round cell tumor.

We report here a 15-year-old boy with an intraabdominal desmoplastic small round cell tumor (DSRCT). Cytogenetic analysis of the tumor cells showed the chromosomal translocation (11;22). Reverse-transcriptase polymerase chain reaction and sequencing analysis revealed a chimeric transcriptional message of the EWS gene exon 10 fused to the WT1 gene exon 8. The typical chimeric transcript seen in DSRCT is an in-frame fusion of EWS exon 7 to WT1 exon 8. The tumor in this case had a novel and longer chimeric transcript, which should be a potent transcription factor. Genetic analysis is a very powerful and specific aid in the differential diagnosis of small round cell tumors.

Abdominal Neoplasms↗
PubMed1998

Phosphorylation and spatiotemporal distribution of KW8 (NDRF/NeuroD2), a NeuroD family basic helix-loop-helix protein.

KW8, a NeuroD family basic helix-loop-helix protein, was initially cloned during the course of screening for the genes related to long term potentiation in rat hippocampal slice. Its homologue NDRF/NeuroD was also reported. In this report its phosphorylation and spatiotemporal distribution was studied. KW8 was expressed not only during embryonic and neonatal periods but also in adults. In adult, KW8 was expressed only in brain tissues, such as the cerebral cortex, hippocampus and cerebellum. Immunohistological studies revealed that KW8 was localized in the nuclei of neurons. On immunoblotting of rat brain tissue, COS-1 cells and Neuro2A cells overexpressing KW8, this protein was detected as several diffuse bands. Alkaline phosphatase treatment reduced the molecular weights of these bands. Metabolic labeling with 32Pi in COS-1 cells confirmed that the KW8 protein was phosphorylated in vivo. Some of the physiological functions of KW8 might be regulated by this phosphorylation. In yeast, the GAL4 fusion protein containing the C-terminal region of KW8 activated transcription of the reporter gene, suggesting that KW8 had transcriptional activity.

Age Factors↗
PubMed1998

Changes in extracellular glutamate and GABA levels in the hippocampal CA3 and CA1 areas and the induction of glutamic acid decarboxylase-67 in dentate granule cells of rats treated with kainic acid.

For the evaluation of glutamatergic and GABAergic transmission during seizures, rat hippocampal CA1 and CA3 areas were separately assessed by brain microdialysis, and extracelluar glutamate and GABA were measured through the course of the seizures after a systemic administration of kainic acid (KA). The generalized convulsion started at about 1.5 h and was suppressed by diazepam at 2 h after the KA treatment. In the CA3 area, extracellular glutamate started to increase soon after the KA injection and returned to the control level at about 1.5 h. A decrease and then slight increase of the extracellular glutamate level in CA3 followed the diazepam injection. In the CA1 area, in contrast, a long-lasting decrease of extracellular glutamate was observed. The extracellular GABA concentration in the CA3 area increased immediately after the systemic administration of KA and returned to the normal level at about 3.5 h. A second increase in the extracellular GABA in this area began at about 4.5 h after the KA treatment. In the CA1 area, an increase of extracellular GABA began at about 3.5 h after KA administration (much later than that observed in the CA3 area) and was maintained throughout the observation. In situ hybridization showed a transient expression of glutamic acid decarboxylase (GAD)-67 mRNA in the granule cell layer of the dentate gyrus at 4 and 6 h, whereas GAD65 mRNA was unaffected. GABA immunoreactivity in the same area and mossy fibers in the CA3 were increased most significantly at 8 h after administration of KA. The possible relation of GABA induction in mossy fibers with the delayed increase in extracellular GABA in CA3 was discussed.

Analysis of Variance↗
PubMed1998

Frequent PTEN/MMAC mutations in endometrioid but not serous or mucinous epithelial ovarian tumors.

Epithelial ovarian cancer comprises three major histological subtypes (serous, mucinous, and endometrioid), and it is becoming clear that the developmental pathways for these subtypes are fundamentally different. In particular, endometrioid ovarian cancers probably arise by the malignant transformation of ectopic endometrial implants called endometriosis and not the ovarian surface epithelium. The PTEN/MMAC gene on chromosome 10q23 is a tumor suppressor implicated in the pathogenesis of a wide variety of malignancies, but to date, somatic mutations in PTEN have not been identified in studies of predominantly serous ovarian cancers. In endometrial cancers, PTEN mutations are very common in tumors of the endometrioid type but have rarely been found in serous types, and we hypothesized that a similar histological subtype bias might be occurring in ovarian cancer. We have analyzed 81 ovarian tumors, including 34 endometrioid, 29 serous, 10 mucinous, and 8 clear cell tumors, for loss of heterozygosity (LOH) on 10q23 and for mutations in all 9 coding exons of PTEN. LOH was common among the endometrioid (43%) and serous (28%) tumors but was infrequent among the other histological subtypes. Somatic PTEN mutations were detected in seven (21%) of the endometrioid tumors, and in all informative cases, the mutation was accompanied by loss of the wild-type allele. One mucinous tumor without 10q23 LOH was shown to harbor two somatic PTEN mutations. In this tumor, the histological appearance of the mucinous areas was atypical, and the mucinous areas contained foci of endometrioid differentiation. The majority of tumors with PTEN mutations were grade 1 and/or stage 1, suggesting that inactivation of PTEN is an early event in ovarian tumorigenesis. No PTEN mutations were found among the serous or clear cell tumors. The identification of frequent somatic PTEN mutations in endometrioid ovarian tumors indicates that it plays a significant role in the etiology of this subtype. The absence of mutations in other histological subtypes is consistent with the hypothesis that epithelial ovarian cancers arise through distinct developmental pathways.

Adenocarcinoma, Clear Cell↗
PubMed1998

Influence of calcium on proliferation and phenotype alteration of cardiomyocyte in vitro.

An accelerated weight gain is noted in the heart of Ca-deficient, hypertensive chick embryos maintained in a shell-less culture in vitro. We previously observed that the Ca handling property of cardiomyocytes isolated from the shell-less embryo is altered, i.e., faster Ca uptake, suggesting a requirement for adequate Ca supply and/or proper Ca handling in embryonic cardiac development. In this study, we have examined the function of Ca on cardiomyocytes by analyzing the effects of 1) various Ca concentration in the culture medium (NCa, 1.8 mmol/ L; HCa, 2.8 mmol/L; LCa, 0.9 mmol/L), and 2) various modulators of Ca handling on cell proliferation and phenotype regulation in chick embryonic cardiomyocytes. The analytical parameters included cell number, DNA content, expression of cell cycle-specific and cardiomyocyte-specific proteins, and creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) enzyme activities. Cell number and total DNA were significantly larger (P < 0.01) in LCa cultures compared with those in NCa. The level of LDH was elevated (P < 0.01), but that of CPK was lowered in LCa. Expression of the G1-S-specific protein PCNA was raised, but that of the contractile proteins myosin and tropomyosin was substantially suppressed in LCa; in HCa, the cells did not proliferate as well, whereas the level of contractile proteins was higher. Thapsigargin, a sarcoplasmic reticulum (SR)-specific, Ca-ATPase inhibitor, simulated the effects of LCa by enhancing cell proliferation and lowering the expression of tropomyosin. These results suggest that culturing in low Ca concentration and inhibition of SR Ca pumping enhance myocardial cell proliferation and suppress sarcomeric protein expression, perhaps by inducing cellular de-differentiation. The in vitro effects of medium Ca concentration and Ca handling modulators on cardiomyocytes also suggest that the in vivo cardiomegaly of the SL embryos is a direct result of Ca-deficiency, and that Ca is important in the phenotype regulation of cardiomyocytes.

Animals↗
PubMed1998

Prenatally detected cystic neuroblastoma.

A case of adrenal cystic neuroblastoma (NB) detected by prenatal ultrasonography (US) is presented. The suprarenal mass initially showed pure cystic features on a variety of imaging studies such as US, computed tomography, and magnetic resonance imaging. Tumor markers were negative. The mass was suspected to be an adrenal hemorrhage rather than a NB. Three months later, although the diameter was unchanged, the thickness of the cyst wall seemed to have slightly increased. Surgical exploration revealed an adrenal cystic tumor and histology showed a NB in situ. Forty-five infants with prenatally detected NB were found in the English literature; about one-half of them were cystic NBs, and most had a favorable outcome.

Adrenal Gland Neoplasms↗
PubMed1998

Heterotopic pancreas of the esophagus associated with a rare type of esophageal atresia.

An infant with a rare type of esophageal/tracheal anomaly associated with heterotopic pancreas of the esophagus is herein reported. The upper pouch containing heterotopic pancreas reached 1.5 cm below the tracheal carina, and the distal esophagus connected to the trachea 2 cm above the tracheal carina and thus formed a partial duplication of the esophagus. Heterotopic pancreas of the esophagus is extremely rare, with only 7 cases previously reported. Here we report the combination of heterotopic pancreas and esophageal atresia with tracheoesophageal fistula.

Anastomosis, Surgical↗
PubMed1998

Dynamic regulation of the activated, autophosphorylated state of Ca2+/calmodulin-dependent protein kinase II by acute neuronal excitation in vivo.

Ca2+/calmodulin-dependent protein kinase II (CaMKII) has been implicated in various neuronal functions, including synaptic plasticity. To examine the physiological regulation of its activated, autophosphorylated state in relation to acute neuronal excitation in vivo, we studied the effect of electroconvulsive treatment in rats on CaMKII activity and in situ autophosphorylation levels. As early as 30 s after the electrical stimulation, a profound but transient decrease in its Ca2+/calmodulin-independent activity, as well as in the level of its autophosphorylation at Thr286(alpha)/Thr287(beta) measured by using phosphorylation state-specific antibodies, was observed in homogenate from hippocampus and parietal cortex, which was reversible in 5 min. In the later time course, a moderate, reversible increase, which peaked at around 60 min after the electrical stimulation, was observed in parietal cortex but not in hippocampus. The early-phase decrease was found to occur exclusively in the soluble fraction. In addition, partial translocation of CaMKII from the soluble to the particulate fraction seems to have occurred in this early phase. Thus, the activated, autophosphorylated state of CaMKII is under dynamic and precise regulation in vivo, and its regulatory mechanisms seem to have regional specificity.

Animals↗
PubMed1998

Dietary fiber, psyllium, attenuates salt-accelerated hypertension in stroke-prone spontaneously hypertensive rats.

OBJECTIVE: Although dietary fiber, psyllium seed husk (psyllium), is known to reduce blood glucose and lipid levels, the effect of psyllium on blood pressure elevation induced by salt ingestion has not been tested in human and rats. We observed the effect of psyllium on salt-accelerated hypertension in stroke-prone spontaneously hypertensive rats (SHRSP). METHODS: Forty male SHRSP (6 weeks of age) were divided into four groups: a plain laboratory diet (PL) group, groups receiving the PL diet substituted with 3% or 10% of psyllium, and a group fed the PL with 10% of cellulose. All those groups were given 0.5% salt water for drinking during the experiment. Urine and feces were collected during 24 hours with a metabolic cage on the 22nd and 29th days of experiment, and sodium and potassium were determined. On the 30th day of the experiment, five rats in each group were killed and heart weight was measured. RESULTS: Salt-accelerated hypertension was significantly attenuated in the SHRSP fed with 3% and 10% psyllium diets compared to those fed the PL and 10% cellulose diets (15th, 22nd, 29th day; 10% psyllium versus PL or 10% cellulose, P < 0.05, 29th day; 3% psyllium versus PL or 10% cellulose, P < 0.05). Ventricular weight was decreased in rats fed 3% or 10% psyllium diets. The amount of sodium, the amount of sodium/the intake of sodium and the sodium/potassium ratio in the feces were significantly increased in the groups on 3% and 10% psyllium diets both on the 22nd and 29th days of experiment compared with those on PL and 10% cellulose diets. CONCLUSIONS: The psyllium diet attenuated the salt-accelerated hypertension in SHRSP by a possible mechanism of increased fecal excretion of sodium absorbed into the psyllium.

Animals↗