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Biomedical subjects

K Hashizume

Publications and source records attributed to K Hashizume.

At least 37 records · Page 2Linked to original sources
PubMed2002

Diminution of early insulin response to glucose in subjects with normal but minimally elevated fasting plasma glucose. Evidence for early beta-cell dysfunction.

AIM: Systematic analysis of beta-cell function in Japanese health examinees. METHODS: In 938 Japanese health examinees (627 men and 311 women, mean age and body mass index, 54.0 years and 23.6 kg/m2, respectively), plasma specific insulin was measured at fasting and during a 75-g oral glucose tolerance test. The subjects were stratified into six groups based on fasting plasma glucose < or = 5.1 mmol/l, 5.2-6.0 mmol/l, 6.1-6.9 mmol/l, 7.0-7.8 mmol/l, 7.9-8.7 mmol/l, and > or = 8.8 mmol/l as the 1st, 2nd, 3rd, 4th, 5th and 6th groups, respectively. RESULTS: Distribution of fasting insulin showed a very modest 'inverted U' shape, with the peak in the 5th group. Progressive increase from the 1st toward the 5th group was significant. In contrast, the ratio of change in insulin to change in glucose from 0 to 30 min during the glucose tolerance test was greatest in the 1st group and progressively declined in the groups with higher fasting glycaemia. Difference in the ratio was most striking and highly significant between the 1st and 2nd groups. Distribution of the insulin to glucose ratio of subjects with normal glucose tolerance significantly overlapped with that of untreated patients with diabetes. CONCLUSIONS: In a Japanese population, (i) beta-cell starts to deteriorate during normoglycaemia with a minimal elevation of fasting plasma glucose, and (ii) there are glucose-tolerant subjects with beta-cell dysfunction.

Adolescent↗
PubMed2002

A novel synbiotic therapy dramatically improved the intestinal function of a pediatric patient with laryngotracheo-esophageal cleft (LTEC) in the intensive care unit.

To demonstrate the beneficial effects of synbiotic therapy (combined use of probiotics and prebiotics) in critically ill patients, we designed a new protocol for such therapy. Three agents were used as synbiotics: Bifidobacterium breve, Lactobacillus casei, and galactooligosaccharides. More than 1 x 10(9) of probiotic bacteria were contained in each 1.0 g pack. We administered 3.0 g per day of each agent to the patient.A critically ill 9-month-old girl with laryngotracho-esophageal cleft (type IV) was treated by our new synbiotic therapy. Abundant amounts of synbiotic bacteria were detected in the feces which suggests that these administered bacteria affected intestinal function in situ. Bowel movements resumed soon after the commencement of synbiotic therapy and considerable amounts of short chain fatty acids were detected in the feces. Growth of the patient was satisfactory under this treatment. Our new synbiotic therapy had a beneficial effect to improve intestinal function. We recommend synbiotic therapy for critically ill patients in intensive care units as an important immunonutritional therapy.

Abnormalities, Multiple↗
PubMed2002

Time-dependent potentiation of the beta-cell is a Ca2+-independent phenomenon.

When isolated rat pancreatic islets are treated with 16.7 mM glucose, a time-dependent potentiation (TDP) of insulin release occurs that can be detected by subsequent treatment with 50 mM KCl. It has been thought that TDP by glucose is a Ca2+-dependent phenomenon and only occurs when exposure to glucose is carried out in the presence of Ca2+. In contrast to this, we now demonstrate TDP under stringent Ca2+-free conditions (Ca2+-free buffer containing 1 mM EGTA). In fact, under these Ca2+-free conditions glucose caused an even stronger TDP than in the presence of Ca2+. TDP induced by glucose in the absence of extracellular Ca2+ was unaffected by inhibitors of protein kinase C (PKC). However, cerulenin or tunicamycin, two inhibitors of protein acylation, eradicated TDP without affecting glucose metabolism. The TDP by glucose was not associated with an increase in the cytosolic free Ca2+ concentration ([Ca2+]i) during subsequent treatment with high K+. Exposure of islets to forskolin under Ca(2+)-free conditions did not cause TDP despite a large increase in the cellular cAMP levels. In conclusion, glucose alone induces TDP under stringent Ca2+-free conditions when [Ca2+]i was significantly lowered. Protein acylation is implicated in the underlying mechanism of TDP.

Acylation↗
PubMed2002

[A case of atypical aortic coarctation with mitral and aortic regurgitation and ascending aortic dilatation].

A 67-year-old female presented with dyspnea on exertion as a chief complaint. Diagnosed as having severe mitral regurgitation, aortic regurgitation, dilatation of the ascending aorta and atypical coarctation due to aortitis syndrome, she underwent mitral valve replacement, aortic valve replacement, ascending aorta and hemiarch replacement and ascending aorta-abdominal aorta extraanatomical bypass in one stage. Pathologically, typical findings of aortitis syndrome were not observed in the wall of the ascending aorta and aortic valve, but cystic medionecrosis was noted in the wall of the ascending aorta. Follow-up observations are needed for the remaining aortic wall.

Aged↗
PubMed2002

[Experience with pyoktanin lavage for mediastinitis and prosthetic graft infection following thoracic aortic surgery].

Pyoktanin, a triphenylmethane dye, is known to have a potent bactericidal activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). We used pyoktanin for irrigating wounds in 2 cases of mediastinitis and prosthetic graft infection following thoracic aortic surgery. Case 1 is mediastinitis and prosthetic graft infection due to Staphylococcus epidermidis following Cabrol procedure. After irrigating the anterior mediastinum with 0.1% pyoktanin solution twice a day for 8 days, omental transposition was performed, which let to cure of the infection. Case 2 is mediastinitis due to methicillin-resistant Staphylococcus epidermidis following ascending aortic and aortic arch replacement for acute type A aortic dissection. After irrigating the wound with 0.1% pyoktanin solution twice a day for 14 days, the wound was closed primarily, which resulted in cure of the infection of the wound. Using pyoktanin at low concentrations for irrigating wound for a short period of time is considered permissible and effective for mediastinitis and prosthetic graft infection due to Gram-positive bacteria including MRSA.

Anti-Infective Agents, Local↗
PubMed2002

[Acute aortic regurgitation due to localized aortic dissection adjacent to the commissure of the aortic valve].

A 78-year-old male with a sudden loss of consciousness and chest pain was transferred to our hospital. He presented heart failure due to severe aortic regurgitation. Cardiac ultrasonography and computed tomography (CT) scanning did not lead to an established diagnosis of acute aortic dissection. Aortic valve replacement was performed 24 days after the onset of the disease. The surgical findings showed prolapse of the aortic valve due to localized dissection adjacent to the commissure of the aortic valve.

Acute Disease↗
PubMed2002

Expression of prolactin-related protein I at the fetomaternal interface during the implantation period in cows.

The bovine placenta secretes multiple molecules during implantation and placentation, many of which are produced by binucleate cells. In this study, production of prolactin-related protein I (PRP-I), a member of the non-classical prolactin-related family, was investigated during the implantation period in cows. Expression of bovine PRP-I (bPRP-I) in the placentome was examined during the preimplantation (days 17-19), implantation (days 20-25) and post-implantation (days 30-60) periods by immunohistochemistry, immunofluorescence and in situ hybridization. During the preimplantation period, both bPRP-I and bovine placental lactogen (bPL) were undetectable in trophoblastic cells. Both bPRP-I mRNA and protein appeared first at day 20 of gestation in trophoblastic binucleate cells and multinuclear cells that might migrate into the endometrium and fuse to epithelium; however, no bPL was detected in binucleate cells at this time. After implantation, on day 30, both bPRP-I and bPL were detected in binucleate cells and were co-expressed in the same cells. These data indicate that bPRP-I may play a role before implantation and that bPRP-I may be an excellent marker for trophoblastic cell differentiation, as well as a candidate for pregnancy diagnosis.

Animals↗
PubMed2002

Association of Dolichos biflorus lectin binding with full differentiation of bovine trophoblast cells.

Binucleate cells in ruminant placenta are differentiated from fetal mononucleate trophoblast cells and secrete many glycoproteins. This study characterized bovine placental binucleate cells in primary culture and a bovine trophoblastic cell line (BT-1) with an N-acetyl-galactosamine-binding lectin, Dolichos biflorus agglutinin (DBA). DBA specifically bound to the surface membrane and the cytoplasm of binucleate cells. Mononucleate epithelial cells and fibroblasts were free of DBA. DBA-positive binucleate cells corresponded to the fully matured cells, producing placental lactogen, and the cytoplasm was devoid of cytokeratin. Binucleate cells assumed a flattened shape on a collagen substratum in an extended culture, and entered a dedifferentiated state with a degranulation of placental lactogen. In these flattened cells, DBA reactions were attenuated in the cytoplasm. DBA binding in BT-1 was subsequently examined. BT-1 was derived from blastocysts produced in vitro and is trophectodermal as shown by the expression of cytokeratin. BT-1 was able to differentiate into placental lactogen-producing binucleate cells on a collagen gel substratum. Cytokeratin expression in BT-1 was downregulated with the differentiation into binucleate cells. However, DBA bound to neither mononucleate nor the differentiated binucleate cells in BT-1. These results indicate that binucleate cells in vivo but not binucleate cells derived from BT-1, specifically developed glycoconjugates recognized by DBA. The glycoconjugate expression was associated with fully differentiated cells. The onset of DBA binding in binucleate cells coincides with placental development, and binucleate cells differentiated from BT-1 cell cultures may reflect those cells at earlier stages of gestation.

Animals↗
PubMed2001

Size-related and size-unrelated functional heterogeneity among pancreatic islets.

Functional heterogeneity of pancreatic islets was systematically analyzed for the first time using freshly isolated single rat pancreatic islets. First, 60 islets were sequentially exposed to 3, 9.4, 15.6, and 24.1 mM glucose for 30 min each in incubation experiments: 36 (60%) responded in a concentration-dependent and 19 (32%) in an all-or-none manner, and 5 (8%) islets did not respond to high glucose. As a group, the larger the islet, the higher the beta cell glucose sensitivity. However, glucose-stimulated elevation of [Ca2+]i in the beta cell. insulin/glucagon ratio in the islet, and expression of glucose transporter 2, glucokinase, and pancreatic duodenal homeobox factor-1 in the beta cell were not significantly related to islet size. Second, 50 islets were stimulated with 16.7 mM glucose in perifusion. A biphasic insulin release was found in 39 (78%), and no or little first phase response in 11 (22%) islets, irrespective of the islet size. Nevertheless, when the response was plotted as a group, it was clearly biphasic. Islet size, insulin content and the amount of insulin release were positively correlated with each other. In conclusion, there are size-related and size-unrelated functional diversity among pancreatic islets. The reason for such heterogeneity remained to be determined.

Animals↗
PubMed2001

Kainic acid-induced substantia nigra seizure in rats: behavior, EEG and metabolism.

RATIONALE: In order to clarify the role of substantia nigra pars reticulata (SNr) upon the development of epileptic seizure, kainic acid (KA) was injected into a unilateral SNr. MATERIALS AND METHODS: Wistar rats weighing 250-350 g were used. A stainless-steel cannula and depth electrode were inserted stereotaxically into the left substantia nigra pars reticulata (SNr). At 7 days after surgery, 1.0 microg of KA was injected into the left SNr. Experiment 1: In eight rats, behavior and electroencephalograms (EEG) were continuously recorded for about 30 h, and intermittently monitored following 1 month. Experiment 2: Two hours after KA injection into SNr, rats demonstrated status epilepticus. Then, 100 microCi/kg of [(14)C]2-deoxyglucose (2-DG) was intravenously injected in seven rats, and the rats were processed for autoradiographic study. RESULTS: Changes in behavior and EEG: On EEG, a secondary generalized seizure status was observed at about 70 min after KA injection. In video, limbic seizure manifestations such as salivation were observed as a initial symptom and followed by rolling and generalized tonic seizures. [(14)C]deoxyglucose autoradiographic study demonstrated increased local cerebral glucose metabolism in the medial and lateral septal nucleus, substantia nigra, hippocampus, parietal cortex, piriform cortex, medial and lateral geniculate nucleus, anterodorsal, lateral and ventral nucleus of the thalamus, amygdala and midbrain reticular formation. SUMMARY: The result suggested that the substantia nigra played an important role in the secondary generalization in the substantia nigra seizure model due to the decreased function of the GABAergic projection system induced by an excessive epileptic excitation of SNr.

Action Potentials↗
PubMed2001

The role of hinge domain in heterodimerization and specific DNA recognition by nuclear receptors.

Four structural domains are characteristic of the members of the nuclear receptor superfamily. The hinge (D) domain which is located between the DNA binding (C) domain and the ligand binding (EF) domain, is less conserved among the nuclear receptors. In this study, we investigated the effects of the D domain on receptor function with regard to ligand binding, protein-protein interaction and DNA recognition. We found that EF domain of TR lacked T3 binding activity and additional D domain was required for its ligand binding. Using pull down assays and two-hybrid assays, we also demonstrated that the EF domain of TR did not dimerize with TR or RXR in solution, while the DEF domain was able to homo-and heterodimerize with RXR. In contrast, the RXR EF domain alone was able to heterodimerize with TR. The D domain of TR is required but that of RXR is not necessary for the interaction. We further demonstrated that the D domain was required for receptor specific DNA recognition. The ABC domain of vitamin D receptor (VDR) and TR(DEF) chimeric receptor could not bind to VDR response element (VDRE). Addition of own D domain of VDR to the ABC domain enables the chimeric receptor to bind VDRE and transactivate. The D domain of TR cannot substitute for that of VDR in context of specific DNA recognition. These data suggest that the D domain is important to maintain the integrity of the functional structure of the nuclear receptors.

Animals↗
PubMed2001

Impaired spreading of surfactant phospholipids in the lungs of newborn rats with pulmonary hypoplasia as a model of congenital diaphragmatic hernia induced by nitrofen.

In order to clarify the pathological outcome of congenital diaphragmatic hernia (CDH), we devised an animal model of CDH by administration of 2,4-dichlorophenyl-p-nitrophenyl ether (nitrofen) to pregnant rats, and determined the level and distribution of lung surfactant using the monoclonal antibody toward sphingomyelin and disaturated phosphatidylcholine (disat-PC). In control rats, the concentration of disat-PC was found to increase greatly from 16 to 18 days of gestation. Intragastric administration of nitrofen to pregnant rats at day 9 of gestation resulted in CDH in 42.7% of fetuses delivered after 20 days of gestation. In nitrofen-treated fetuses, the concentration of disat-PC in the lungs was lower than those in control fetuses, and surfactant apoprotein SP-A was similarly reduced in nitrofen-treated fetuses. However, the concentration of disat-PC in nitrofen-treated fetuses was higher than that in control fetuses at 18 days of gestation, indicating a synthetic potential of surfactant in nitrofen-treated fetuses comparable to that at the late stage of normal gestation. Immunohistochemical study with the antibody revealed that surfactant phospholipid was mainly in the form of intracellular granules in nitrofen-treated fetuses, probably causing the hypoplastic lungs and then CDH, in contrast to the uniform distribution on the pulmonary alveolar surface in control fetuses.

Amniotic Fluid↗
PubMed2001

Expression of dominant negative form of PAX4 in human insulinoma.

The paired-homeodomain transcription factor PAX4 is expressed in the early pancreas, but is later restricted to beta cells and not expressed in mature islets, suggesting an important role of PAX4 in differentiation and development of pancreatic islet. Here we show that PAX4 mRNA was highly expressed in human insulinoma tissues, whereas little if any mRNA was expressed in normal islets. Furthermore, this insulinoma associated expression of PAX4 mRNA was accompanied with expression of its novel variant form (PAX4v). PAX4v was generated by alternative splicing lacking the exon 7, and containing intact paired and homeo domain followed by novel 35 amino acids. PAX4v reversed the wild-type PAX4 mediated repression of the insulin promoter in cotransfection assays. PAX4v may play a role to antagonize the wild-type PAX4 function in human insulinoma. These data imply a role of PAX4 and PAX4v expression in tumorigenesis and development of insulinoma.

Amino Acid Sequence↗
PubMed2001

Expression of placental lactogen and cytokeratin in bovine placental binucleate cells in culture.

Binucleate cells are present in ruminant placenta and play an endocrine role in the production of many hormones during pregnancy. We isolated and cultured binucleate cells from bovine placenta at middle to late gestation and characterized these cells using immunofluorescence techniques. Enriched preparations of binucleate cells were obtained using Percoll density gradient centrifugation following collagenase digestion. Binucleate cells in culture preferentially attached to collagen-coated dishes rather than to noncoated plastic dishes. The cells gradually extended their edges on collagen substrata, and finally assumed a flattened morphology. Antibodies to placental lactogen (PL) and pregnancy-associated glycoprotein-1 (PAG-1) specifically stained the majority of round binucleate cells, but not the flat cells. We found that PL-positive binucleate cells were consistently devoid of cytokeratin. In contrast, cytokeratin was expressed in PL-negative binucleate cells as well as mononuclear epithelial cells. Furthermore, the PL-negative flat binucleate cells also developed intense cytokeratin networks in the cytoplasm. These results indicate that cytokeratin expression is inversely proportionate to that of PL in cultured binucleate cells. We conclude that downregulation of cytokeratin in binucleate cells is a function of the state of cellular differentiation.

Animals↗
PubMed2001

Intraoperative assessment of coronary artery bypass graft: transit-time flowmetry versus angiography.

BACKGROUND: Transit-time flowmetry has been used to assess graft status intraoperatively. This study examines the validity of this method by comparing its results with the findings of simultaneously performed graft angiography. METHODS: The left internal thoracic artery (LITA) anastomosed to the left anterior descending artery (LAD) was assessed intraoperatively with both transit-time flowmetry and graft angiography in 30 patients. The patients were stratified into two groups based on intraoperative angiographic findings. In 18 patients (group A), the LITA and the LAD were well filled with contrast medium and the anastomosis was widely patent. In the other 12 patients (group B), spastic LITA or LAD was observed. Postoperative angiography was also performed before discharge from the hospital. RESULTS: The mean graft flow was 44.0 +/- 25.4 mL/min in group A and 23.4 +/- 10.0 mL/min in group B (p = 0.0129). Diastolic-dominant flow pattern was observed in both groups, and the ratio of peak diastolic flow to peak systolic flow and the percent diastolic time-flow integral were not statistically different between the groups. The pulsatility index was almost the same between the two groups and was acceptable in both. Postoperative angiography revealed that all grafts were patent without spasm or anastomotic stenosis. CONCLUSIONS: LITA graft status is satisfactory when high graft flow with diastolic dominance is obtained. When there is vasospasm but no anastomotic problems, decreased graft flow with an acceptable pulsatility index and diastolic augmentation is observed.

Angiography↗
PubMed2001

Single vaginal ectopic ureter and renal hypoplasia associated with urogenital sinus and abdominal muscular hypoplasia-a novel subtype of prune-belly syndrome in a female child?

We report a rare case that can be classified as prune-belly syndrome in a female. This patient came to our attention during the 19th week of gestation when massive ascites was found by ultrasound and the mother was transferred to our hospital. After birth, it was demonstrated that the infant had complicated anomalies, including abdominal muscular hypoplasia, urogenital sinus, a single, right-sided vaginal ectopic ureter, and hypoplasia of the right kidney. A sibling had a right hypoplastic kidney and right vesicoureteral reflux. Considering the combination of anomalies and the family history of urinary tract disease, her anomalies could be attributed to a genetic mutation.

Choristoma↗
PubMed2001

Small-for-size grafts in living-related liver transplantation.

BACKGROUND: The problems associated with small-for-size grafts in living-related liver transplantation are not fully understood. STUDY DESIGN: A consecutive series of 79 patients underwent 80 living-related liver transplantation procedures, including one retransplant, at the University of Tokyo from January 1996 to January 2000. They were divided into two groups by graft size: graft weight/recipient standard liver volume ratios of 40% or less (n = 24), and more than 40% (n = 56). Preoperative status, mortality, morbidity, duration of hospital stay, and postoperative graft function were examined and compared between the groups. RESULTS: The rate of patients who were restricted to the intensive care unit preoperatively was comparable between the groups (33% versus 21%, p = 0.27). The mean standard liver volume ratios were 37% in the small graft group and 84% in the large group. Survival rates were 80% (5 of 24) for the small graft group, which was significantly lower than that for the large group (96%, 54 of 56, p = 0.02). The rate of acute rejection was comparable between the groups (33% versus 43%, p = 0.47). Vascular complication was observed in 17% of the small graft group patients and 23% of the large group (p = 0.77). No difference was observed in the frequency of bile leakage or bile duct stenosis (25% versus 21%, p=0.77). Hyper-bilirubinemia and elongation of prothrombin time persisted longer in the small graft group than in the large group (p < 0.0001 for both). CONCLUSIONS: Our surgical results may suggest that a graft weight ratio of 40% or less provides a lower chance of survival after living-related liver transplantation.

Adolescent↗