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Biomedical subjects

K Obata

Publications and source records attributed to K Obata.

At least 37 records · Page 2Linked to original sources
PubMed2001

Expression of HGF and cMet in the peripheral nervous system of adult rats following sciatic nerve injury.

Hepatocyte growth factor (HGF) exhibits neurotrophic properties on different types of neuron, including motor, sensory and parasympathetic neurons. We demonstrate that sciatic nerve ligation induces an increase of the HGF receptor, c-met, mRNA in the distal segment of the sciatic nerve to the ligation site and a delayed elevation in the proximal segment. Immunohistochemical analysis revealed co-localization of cMet and GFAP and indicates that Schwann cells express cMet in the sciatic nerve after injury. HGF mRNA was detected in the spinal cord and DRG, and nerve injury did not alter the expression. These data demonstrate that the expression of HGF and cMet in the peripheral nervous system shows the unique pattern of regulation following nerve injury.

Animals↗
PubMed2001

Role of FK506-binding protein 12 in development of the chick embryonic heart.

A cDNA encoding chicken FK506-binding protein 12 (FKBP12) was isolated and sequenced. The predicted amino acid sequence of the chicken protein shows high homology to those of FKBP12 proteins of other species ranging from human to frog. The possible role of FKBP12 in chick embryonic cardiac development was examined. Northern blot analysis revealed that FKBP12 mRNA is distributed widely in chick embryos, being especially abundant in the heart; the amount of FKBP12 mRNA in the embryonic heart decreased with time. Administration of FK506 to chick embryos at 7 to 9 days resulted in marked cardiac enlargement. FK506 also reduced the expression of myosin, induced a more elongated cell morphology, and impaired network formation in cultured chick embryonic cardiomyocytes. These results suggest that FKBP12 is important in the regulation of contractile function and phenotypic expression in chick cardiomyocytes during embryonic development.

Amino Acid Sequence↗
PubMed2001

Human biotin-containing subunit of 3-methylcrotonyl-CoA carboxylase gene (MCCA): cDNA sequence, genomic organization, localization to chromosomal band 3q27, and expression.

3-Methylcrotonyl-CoA carboxylase (MCCase; EC 6.4.1.4) is a mitochondrial biotin enzyme and plays an essential role in the catabolism of leucine and isovalerate in animals, bacterial species, and plants. MCCase consists of two subunits, those that are biotin-containing and non-biotin-containing. The genes responsible for these subunits have been isolated in soybean, Arabidopsis thaliana, and tomatoes, but not in mammals. In humans, MCCase deficiency has been thought to be a rare metabolic disease, but the number of patients with MCCase deficiency appears to be increasing with a wide range of clinical presentations, some that result in a lethal condition and others that are asymptomatic. In this report, we have isolated and carried out chromosomal mapping of the gene for the biotin-containing subunit (A subunit) of the human MCCase gene, MCCA. The cDNA predicts an open reading frame coding for a 725-amino-acid protein with mitochondrial signal peptide, biotin carboxylase, and biotin-carrier domains. The gene is composed of at least 19 exons and covers more than 70 kb of sequence on band q27 of chromosome 3. MCCA was abundantly expressed in mitochondria-rich organs, such as the heart, skeletal muscles, kidney, and liver. In exon 13, we observed a His/Pro polymorphism at codon 464 (an A to C transition at nucleotide position 1391 in the cDNA sequence). Then, we determined the DNA sequences of the 5' untranslated region and entire coding regions in two patients with MCCase deficiency, but no sequence substitution was detected, suggesting that the gene mutations might be in the non-biotin-containing subunit (B subunit) gene, MCCB, in these patients.

Amino Acid Sequence↗
PubMed2001

Clinicopathologic and immunohistochemical features and microsatellite status of endometrial cancer of the uterine isthmus.

To clarify the clinicopathologic, molecular, and immunohistochemical characteristics of uterine isthmic endometrial cancer (UIE), we examined 13 cases of UIE and compared them with 33 cases of endometrial cancer of the uterine corpus (UCE) with respect to clinicopathologic factors, the expression of p53, the estrogen receptor (ER) and the progesterone receptor (PR) status, DNA ploidy, and microsatellite instability (MSI). Five (38.4%) of the UIE patients had stage I, two (15.4%) had stage II, and six (46.2%) had stage III disease (FIGO 1988). Myometrial invasion was confirmed in 92.3% of the UIE patients, and these patients had a higher (p < 0.05) frequency of > 50% myometrial invasion (46.2%) than the patients with UCE (15.2%). Moreover, the UIE patients had a higher frequency of positive peritoneal cytology (p < 0.05) and pelvic lymph node metastases (p < 0.05). No UIE tumors exhibited MSI, and the tumors in these patients had a higher expression of p53 (p < 0.01), a lower expression of ER (p < 0.05) and PR (p < 0.05), and a higher frequency of DNA aneuploidy (p < 0.01) than the UCE tumors. These findings suggest that the UIE is clearly different from UCE in the clinicopathologic, immunohistochemical features, and microsatellite status.

Aneuploidy↗
PubMed2001

Development of a novel method for operating magnetic particles, Magtration Technology, and its use for automating nucleic acid purification.

Magnetic particles are useful for simple and efficient nucleic acid extraction. To achieve fully automated nucleic acid extraction and purification using magnetic particles, a new method for operating magnetic particles, Magtration Technology, was developed. In this method, magnetic separation is performed in a specially designed disposable tip. This enables high recovery of magnetic particles with high reproducibility. The features of this technology are (i) a simple mechanism for process control and (ii) flexible software to enable adaptation to commercially available reagents. Automated instruments based on Magtration Technology were developed and used for nucleic acid extraction. Total DNA, total RNA and plasmids were purified by Magtration Technology at an efficiency comparable to that of manual methods.

Journal Article↗
PubMed2001

[Dysmenorrhea].

Dysmenorrhea is commonly observed in women and it reduces their quality of life. Most of dysmenorrhea is based on the disease of endometriosis, uterine myoma, uterine anomalies etc. and some cases are functional. The functional dysmenorrhea arises from the underdevelopment of the uterine growth. There are many different factors for dysmenorrhea in endometriosis, which is the commonest disease with dysmenorrhea, and we have to perform various therapies for pain. Therefore, we discuss in this paper the control for the functional dysmenorrhea and the pain in endometriosis.

Analgesics↗
PubMed2001

Mutational analysis of BRCA1 and BRCA2 and clinicopathologic analysis of ovarian cancer in 82 ovarian cancer families: two common founder mutations of BRCA1 in Japanese population.

We analyzed genetic alterations in BRCA1 and BRCA2 genes among 82 ovarian cancer families in Japan. The clinical characteristics of BRCA-associated ovarian cancer patients were compared with cases carrying no mutations as well as with population controls. Using a direct sequencing method, 45 of the 82 ovarian cancer families were found to carry BRCA1 or BRCA2 germ-line mutations (40 with BRCA1 and 5 with BRCA2). In 24 independent mutations of BRCA1, 5 recurrent mutations were found and 2 of them, the L63X and Q934X mutations, were detected in seven and eight independent families, respectively. In addition, 16 mutations of BRCA1 and 3 mutations of BRCA2 have never been described previously. In consideration of clinicopathological features, there was a significantly higher proportion of tumors with serous adenocarcinoma and of cases of advanced stages in the BRCA1 or BRCA2 cases than in those of the controls. On the other hand, there were no differences of mean age at diagnosis between patients with BRCA1 or BRCA2 mutation and those of the controls. Our results indicate that the features of BRCA-associated ovarian cancer in Japan appear to be similar to those in Western countries, and the L63X and Q934X mutations of BRCA1 appear to be common founder mutations unique to the Japanese population.

Adolescent↗
PubMed2001

Localization of cathepsins G and L in spontaneous resorption of intervertebral discs in a rat experimental model.

To determine the involvement of cathepsins G and L in the mechanism of spontaneous resorption of herniated intervertebral discs, localization of these cathepsins in this process was examined immunohistochemically using a rat model of autologous transplantation of coccygeal discs. Rat coccygeal discs were resected and autotransplanted into the subcutaneous space of the skin of the back. Paraffin-embedded sections of intervertebral disc tissue, harvested at various post-transplantational periods, were immunohistochemically stained with antibodies for cathepsin G, cathepsin L, MMP-1, MMP-3 and ED-2. The number of positive cells was counted in each part of the transplanted discs. Immunolocalization of cathepsins G and L in various types of disc cells was first observed early in the post-transplantation period. From two days after the operation, histology showed invasion by granulation tissue, with many macrophages, in all sections. Subsequently, the number of macrophages in granulation tissue was observed to increase, along with a gradual increase in the percentage of cells positive for MMP-1 and MMP-3. In addition to the ability of cathepsins G and L to degrade major extracellular matrix components of intervertebral discs, cathepsin G is capable of activating latent pro-MMPs. The up-regulation of cathepsins G and L in the intervertebral disc tissue in this spontaneous resorption model suggests that these proteinases may be involved in degradation of extracellular matrix, leading to the natural resorption of herniated discs.

Journal Article↗
PubMed2000

Identification and characterization of 5' extension of mammalian agrin cDNA, the exons and the promoter sequences.

Agrin, which is secreted from motor neurons, is essential for the formation and maintenance of the vertebrate neuromuscular junctions. Here we show the complete N-terminal sequence of the mammalian cDNA required for the expression and secretion as well as the intron/exon structure and the 5'-flanking sequence required for basal promoter activity. The 5'-flanking region and the first exon are extremely GC rich and contain a CpG island. These features may account for hindrance in identification of the 5' end of the cDNA and the promoter region of the mammalian agrin gene.

Agrin↗
PubMed2000

Decreased locomotor activity in mice carrying transgenic Fyn tyrosine kinase.

We found that mice carrying constitutively active Fyn tyrosine kinase show low levels of spontaneous locomotor activity and that this activity increases when the mice are treated with the NMDA receptor antagonist MK-801. These findings indicate that the tyrosine phosphorylation of the NMDA receptors by Fyn participates in the control of locomotor activity.

Animals↗
PubMed2000

Pro-carboxypeptidase R is an acute phase protein in the mouse, whereas carboxypeptidase N is not.

Carboxypeptidase R (EC 3.4.17.20; CPR) and carboxypeptidase N (EC 3. 4.17.3; CPN) cleave carboxyl-terminal arginine and lysine residues from biologically active peptides such as kinins and anaphylatoxins, resulting in regulation of their biological activity. Human proCPR, also known as thrombin-activatable fibrinolysis inhibitor, plasma pro-carboxypeptidase B, and pro-carboxypeptidase U, is a plasma zymogen activated during coagulation. CPN, however, previously termed kininase I and anaphylatoxin inactivator, is present in a stable active form in plasma. We report here the isolation of mouse proCPR and CPN cDNA clones that can induce their respective enzymatic activities in culture supernatants of transiently transfected cells. Potato carboxypeptidase inhibitor can inhibit carboxypeptidase activity in culture medium of mouse proCPR-transfected cells. The expression of proCPR mRNA in murine liver is greatly enhanced following LPS injection, whereas CPN mRNA expression remains unaffected. Furthermore, the CPR activity in plasma increased 2-fold at 24 h after LPS treatment. Therefore, proCPR can be considered a type of acute phase protein, whereas CPN is not. An increase in CPR activity may facilitate rapid inactivation of inflammatory mediators generated at the site of Gram-negative bacterial infection and may consequently prevent septic shock. In view of the ability of proCPR to also inhibit fibrinolysis, an excess of proCPR induced by LPS may contribute to hypofibrinolysis in patients suffering from disseminated intravascular coagulation caused by sepsis.

Acute-Phase Proteins↗
PubMed2000

Postnatal development of a GABA deficit and disturbance of neural functions in mice lacking GAD65.

The 65-kDa isoform of glutamic acid decarboxylase (GAD65) is believed to play an essential role for GABA synthesis in the central nervous system. Using mice with targeted disruption of the GAD65 gene (GAD65(-/-) mice) we investigated the contribution of GAD65 to GABA synthesis in different brain areas during postnatal development and in adulthood. In the amygdala, hypothalamus and parietal cortex of GAD65(+/+) mice an increase of GABA levels was observed during postnatal development, most prominently between the first and second month after birth. This increase appeared to be dependent on GAD65, as it was delayed by 2 months in GAD65(+/-) mice and was not observed in GAD65(-/-) mice. Likely as a consequence of their GABA deficit, adult GAD65(-/-) mice showed a largely abnormal neural activity with frequent paroxysmal discharges and spontaneous seizures. They furthermore displayed increased anxiety-like behaviour in a light/dark avoidance test and reduced intermale aggression, as well as a reduced forced-swimming-induced immobility indicative of an antidepressant-like behavioural change. Adult GAD65(+/-) mice did not show behavioural disturbances except for a reduced aggressive behaviour that was comparable to that in GAD65(-/-) mice. We conclude that GAD65-mediated GABA synthesis may be crucially involved in control of emotional behaviour and indispensable for a tonic inhibition that prevents the development of hyperexcitability in the maturating central nervous system. Aggressive, and possibly other social behaviour may be especially prone to regulation through GAD65-mediated GABA synthesis.

Age Factors↗
PubMed2000

A case of biliary atresia with cystic dilatation of the extrahepatic bile duct and polysplenia syndrome.

A 79-day-old girl presented with jaundice and acholia. Laboratory findings disclosed elevated levels of bilirubin, transaminases, and gamma-glutamyl transferase. A chest X-ray film showed dextrocardia. A computed tomographic scan revealed a cystic mass at the porta hepatis, multiple spleens in the right side of the abdomen, and absence of the inferior vena cava. Under the diagnosis of biliary atresia (BA) (I-cyst) associated with polysplenia syndrome, a hepatic portojejunostomy was performed at 80 days of age. The postoperative course was uneventful, and the jaundice cleared. Although the occurrence of associated anomalies in BA is rare, polysplenia is most commonly seen, and its incidence is reported to be 2% to 10%. Patients with BA and polysplenia usually have a poor prognosis, however, this patient may have a good prognosis due to uneventful recovery from the jaundice.

Bile Duct Diseases↗