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Biomedical subjects

N Takeda

Publications and source records attributed to N Takeda.

At least 145 records · Page 8Linked to original sources
PubMed1999

Differential effects of troglitazone and D-chiroinositol on glucosamine-induced insulin resistance in vivo in rats.

Troglitazone and D-chiroinositol have been shown to exert antidiabetic effects by either potentiating or mimicking insulin action. We studied whether pretreatment with these compounds can prevent the deleterious effects of glucosamine on insulin action that may play an important role in hyperglycemia-induced insulin resistance. Normal Wistar rats were pretreated with troglitazone (100 mg/kg/d), D-chiroinositol (100 mg/kg/d), or placebo (saline) for 7 days. Glucosamine (50 micromol/kg/min) was then infused for 210 minutes, and a euglycemic glucose clamp was performed during the last 120 minutes. Pretreatment with troglitazone or D-chiroinositol had no effect on fasting plasma glucose or insulin or basal hepatic glucose output (HGO). Under the euglycemic-hyperinsulinemic (956+/-93 pmol/L) clamp condition, HGO in glucosamine-infused placebo-treated rats was not suppressed, but instead was increased over the basal level, indicative of hepatic insulin resistance. In contrast, HGO failed to increase during glucosamine infusion in rats pretreated with troglitazone but was not normally suppressed. This may indicate a partial improvement in the hepatic insulin resistance. D-Chiroinositol pretreatment had no effect on the glucosamine-induced increase in HGO. The glucose disposal rate (GDR) was 25% lower in rats infused with glucosamine versus saline-infused rats (25.5+/-2.5 v 34.1+/-2.0 mg/kg/min), indicative of peripheral insulin resistance. Pretreatment with D-chiroinositol (34.5+/-2.3 mg/kg/min) prevented the glucosamine-induced decrease in the GDR, indicating an improvement in peripheral insulin resistance. Troglitazone (25.2+/-3.3 mg/kg/min) was without effect. In conclusion, (1) in normal control rats, glucosamine infusion induced hepatic and peripheral insulin resistance; (2) D-chiroinositol, but not troglitazone, pretreatment prevented glucosamine-induced peripheral insulin resistance; and (3) troglitazone, but not D-chiroinositol, partially blocked the glucosamine-induced hepatic insulin resistance. D-Chiroinositol may provide a novel pharmacological approach to hexosamine-induced peripheral insulin resistance.

Animals↗
PubMed1999

Decrease in thromboxane A2 receptor expression by differentiation with dibutyryl cyclic AMP in 1321N1 human astrocytoma cells.

Thromboxane A2 (TXA2) receptor expression with its signaling was investigated in 1321N1 human astrocytoma cells differentiated with dibutyryl cyclic AMP (dbcAMP). The cells cultured in 0.5% fetal calf serum containing 0.5 mM dbcAMP for 3 days showed the star-shaped morphology, accompanied with the reduction of a TXA2 mimetic U46619-induced phosphoinositide hydrolysis and Ca2+ mobilization. Immunoblotting analysis revealed that human astrocytoma cells expressed phospholipase C (PLC)-beta1 and -beta3, but not PLC-beta2. The contents of PLC-beta1 and beta3 were not changed by the differentiation. The alpha subunit of Gq/ll bound to TXA2-receptor was reduced by the differentiation, determined by immunoblotting after immunoprecipitation with an anti-TXA2-receptor antibody. Scatchard analysis of the binding of [3H]SQ29548, a TXA2 receptor antagonist, to the membranes revealed that the maximum binding site was reduced by the differentiation. The expression of TXA2 receptor mRNA also was reduced by the differentiation, determined by reverse-transcribed-polymerase chain reaction. Although placental type of TXA2 receptor mRNA expression increased after the differentiation, endothelial type of TXA2 receptor mRNA expression slightly decreased. The results suggest that 1321N1 human astrocytoma cells differentiated with dbcAMP show impaired TXA2 receptor-mediated phosphoinositide hydrolysis and Ca2+ mobilization, due to the decrease in TXA2 receptor number.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1999

Mouse semaphorin H inhibits neurite outgrowth from sensory neurons.

Mouse semaphorin H (M-semaH) was structurally similar to semaphorin III/D, a mammalian homologue of collapsin 1 which was identified as a collapsing factor for sensory nerves. In this study we investigated the expression patterns of M-semaH mRNA and the protein binding sites in the trunk of mouse embryos. M-semaH mRNA was expressed in the mesenchymal tissues surrounding each dorsal root ganglia. These tissues include the caudal sclerotome and perinotochordal mesenchyme, which were thought to express factors repulsive to axons. M-semaH binding was detected on the spinal nerves. We further investigated, using in vitro co-culture assay, whether M-semaH acted as a chemorepulsive molecule on sensory axons. The results suggested that M-semaH was a candidate for a chemorepellent expressed in the mesenchyme surrounding the sensory ganglia, which is involved in the axonal guidance mechanism of sensory nerves in the trunk.

3T3 Cells↗
PubMed1999

Effects of long-term interferon-alpha treatment on glucose tolerance in patients with chronic hepatitis C.

BACKGROUND/AIMS: Interferon-a has been reported to acutely induce insulin resistance and glucose intolerance. The effects of long-term treatment with interferon-a on glucose metabolism remain unclear. METHODS: Thirty-two Japanese patients with chronic hepatitis C were given interferon-a (6x10(6)U/day) daily for 2 weeks and thereafter 3 times weekly up to 6 months. The patients received a 75-g oral glucose tolerance test before the treatment. Fifteen patients also had an intravenous glucose tolerance test for an assessment of insulin sensitivity with Bergman's minimal model. These tests were repeated 3 months after the treatment. RESULTS: Insulin sensitivity was not affected by the treatment (5.7+/-3.8 vs 5.2+/-3.8 10(-4) x min(-1) x mU(-1) x l , not significant) and a statistically significant but minimum decrease in area under the curve of plasma glucose (1012+/-332 vs 928+/-282 mmol x l(-1) x min, p<0.01) in a 75-g oral glucose tolerance test was noted. Acute insulin response to intravenous glucose tolerance tests (214+/-275 vs 294+/-334 mU x l(-1) x min, p<0.05) increased slightly. CONCLUSION: Contrary to the known acute metabolic effects, interferon-a therapy for 3 months in patients with chronic hepatitis C did not have deleterious effects on insulin sensitivity and glucose tolerance.

Adult↗
PubMed1999

Developmental localization of semaphorin H messenger RNA acting as a collapsing factor on sensory axons in the mouse brain.

Semaphorins/collapsins, a family of genes with a semaphorin domain conserved from insects through to mammals, are believed to be involved in axon guidance during neuronal development. We report the expression patterns of mouse semaphorin messenger RNAs. Among secreted semaphorins, mouse semaphorin H is structurally most similar to semaphorin III/D, the first semaphorin identified as a collapsing factor for sensory axons. However, its expression patterns apparently differ from those of semaphorin III/D. The messenger RNAs are distributed in the brain widely but unevenly during development, in particular, in the main olfactory bulb, hippocampus and pontine nucleus. In the trunk, the expression level is high in mesodermal tissues surrounding the dorsal root ganglia, while it is low in the spinal cord. Moreover, we examined whether this molecule has activity to collapse growth cones of sensory neurons, as well as semaphorin III/D. Mouse semaphorin H collapsed growth cones of sensory neurons of the dorsal root ganglion in a dose-dependent manner, and anti-neuropilin antibodies inhibited this activity. Taken together, these results suggest that mouse semaphorin H can function as a chemorepellent to guide sensory peripheral nerves, most likely via neuropilin as a receptor.

Amino Acid Sequence↗
PubMed1999

Relationship between drug delivery and the intra-arterial infusion rate of SarCNU in C6 rat brain tumor model.

The influences of the flow rate on the concentration and distribution of drug in the rat brains and brain tumors after intra-arterial (intra-carotid) administration of [3H]SarCNU (sarcosinamide chloroethyl-1-nitrosourea) were examined. Results obtained at three flow rates via intra-carotid route were compared to those obtained with intravenous administrations. Adult female Wistar rats bearing C6 brain tumor were randomized into four-groups. Groups 1 (G.1) to 3 (G.3) received intra-arterial injection and Group 4 (G.4) received intravenous administration of [3H]SarCNU. G.1 (slow infusion rate) was administered 1 ml of [3H]SarCNU solution over 60 min (0.017 ml/min), Group 2 (G.2; medium infusion rate): 0.2 ml over 5 min (0.04 ml/min), G.3 (fast infusion rate): 1 ml over 5 min (0.2 ml/min), and G.4 (intravenous infusion): 1 ml intravenously over 5 min. Quantitative autoradiographic method was used to measure the concentration and the distribution of [3H]SarCNU in the brain and the brain tumors. The tissue uptake constant of SarCNU in both viable (tumor tissue excluding necrosis) and peak regions (the area of tumor containing top 20% of the tracer concentration) of the intra-arterial injection groups were significantly higher (p < 0.0001) than those in the intravenous group. The mean concentrations of the viable tumor in the intra-arterial groups were 2.92 (G.1), 16.06 (G.2), and 20.8 (G.3) times higher than those of intravenous group. Between the intra-arterial groups, the mean concentration in the viable tumors of G.1 (slow flow rate) was significantly (p < 0.0001) lower than in G.2 and G.3. However, there was no significant difference between G.2 and G.3. In three intra-arterial groups the mean concentration delivery ratios of the brain tumors were high and ranged from 3.07 (G.3) to 3.87 (G.2), but there was no significant difference between them. Only G.4, intravenous group, showed significantly (p < 0.005) lower concentration delivery ratio, 1.26. These results suggest that higher infusion rate in the intra-arterial chemotherapy could have an effect not only on the streaming phenomenon which results in the brain toxicities, but also on the increase in the concentration and the sufficient distribution of a drug in tumors. By finding chemotherapeutic agents to which tumors show high sensitivity and using intra-arterial administration of these agents at more effective flow rate, better clinical results could be achieved in the treatment of patients with malignant brain tumors.

Animals↗
PubMed1999

Detection of hepatitis C virus RNA in the hearts of patients with hepatogenic cardiomyopathy.

We examined the Hepatitis C virus (HCV) genome in the myocardium and liver obtained at autopsy from seven patients with HCV-positive liver cirrhosis and hepatocellular carcinoma (HCC) by in situ hybridization and histopathological studies. The HCV virus genome was detected in the myocardium of one patient as well as in the liver in three out of seven patients. However, Epstein-Barr (EB) virus genome could not be detected in liver or myocardium. In the patient who showed positive reaction to HCV in myocardium, both serum HCV and Hepatitis B virus (HBV) antibodies were positive. It is unknown whether this was related to an immunological abnormality of the host or to an interaction between RNA and DNA viruses. In conclusion, we could identify the HCV genome in the myocardium of a patient with hepatogenic myocardosis.

Aged↗
PubMed1999

Differential changes in cardiac myofibrillar and sarcoplasmic reticular gene expression in alloxan-induced diabetes.

In order to examine the relationship between heart dysfunction and subcellular abnormalities as well as molecular mechanisms during the development of diabetes, we studied changes in cardiac performance, myofibrillar as well as sarcoplasmic reticular (SR) activities, and cardiac gene expression at different time intervals upon inducing diabetes in rats by an injection of alloxan (65 mg/kg; i.v.). Cardiac dysfunction was associated with a depression in myofibrillar Ca2+-stimulated ATPase and changes in myosin isozyme composition at 2-12 weeks of inducing diabetes. A reduction in SR Ca2+-uptake and Ca2+-pump (SERCA2) activities was evident at 10 days to 12 weeks of inducing diabetes. Alterations in cardiac function during 2-12 weeks of diabetes show a linear relationship with changes in myofibrils and SR membranes. Furthermore, alterations in cardiac function as well as myofibrillar and SR activities in 4 week diabetic animals were normalized upon treatment with insulin for 4 weeks. The steady-state mRNA abundance for alpha-myosin heavy chain in the heart was decreased at 2 and 3 weeks but was unchanged at 5 and 6 weeks, whereas mRNA levels for beta-myosin heavy chain remained elevated during 2-6 weeks after inducing diabetes. SERCA2 mRNA abundance in diabetic heart was significantly increased at 3 and 5 weeks but was unaltered at 2 and 6 weeks. These results support the view that heart dysfunction in diabetes may be a consequence of myofibrillar and SR abnormalities; however, defects in myofibrillar proteins, unlike those in the SR membranes, appear to be due to changes in their gene expression.

Animals↗
PubMed1999

Unilateral papilledema after bone marrow transplantation.

We describe a patient who developed unilateral papilledema after allogeneic BMT. This is a rare manifestation of pseudotumor cerebri, which results from elevated intracranial pressure caused by cyclosporin A. The papilledema usually involves the fundi bilaterally, but unilateral involvement has been described. Congenital anomalies, compression and adhesion of the optic nerve sheath are its causes. In this patient, the right optic fundus was spared although leukemic infiltration was present on this side and high-dose irradiation (72 Gy) was given. Although papilledema is a sensitive marker of elevated intracranial pressure, this sign may be masked by constriction of the optic sheath in patients who suffer from leukemic infiltration of the central nervous system and receive high doses of cranial irradiation.

Adult↗
PubMed1999

Aspergillus tracheobronchitis after allogeneic bone marrow transplantation.

We describe a patient who developed Aspergillus tracheobronchitis after BMT. She complained of progressive dyspnea on day +165 and her respiratory function deteriorated rapidly. Although neither early chest X-rays nor CT scans were negative, bronchoscopy revealed formation of a pseudomembrane around the bronchial walls. Based upon pathological and microbiological examinations, she was diagnosed as having invasive Aspergillus tracheobronchitis. Retrospectively analyzed, the Aspergillus circulating antigen detection tests became positive before clinical symptoms developed, and may be beneficial for early diagnosis of Aspergillus tracheobronchitis. This form of aspergillosis should be regarded as one of the serious complications after BMT.

Adult↗
PubMed1999

A complete deficiency of coagulation factor XIII A-subunit due to a novel compound heterozygote of Ser 413 Leu missense and an nt 389 (ins G) frameshift mutation.

Coagulation factor XIII consists of two A- and two B-subunits, and either gene mutation can cause a complete deficiency. In a newborn patient with persistent bleeding from the umbilical cord stump, the plasma A-subunit protein was not detectable. Direct PCR sequencing revealed an nt 389 (ins G) frameshift mutation in exon 4 resulting in a new stop codon and a Ser 413 Leu missense mutation in exon 10 in either allele. His mother and father were heterozygous for the nt 389 (ins G) and the Ser 413 Leu, respectively, with about 50% reduction of the plasma A-subunit proteins. In all family members examined only those with either mutation showed the reduced subunit A protein levels. Thus, this complete deficiency of factor XIII was due to a novel compound heterozygous mutation in the A-subunit gene.

DNA Transposable Elements↗
PubMed1999

Abnormalities of developmental cell death in Dad1-deficient mice.

BACKGROUND: Dad1, the defender against apoptotic cell death, comprises the oligosaccharyltransferase complex and is well conserved among eukaryotes. In hamster BHK21-derived tsBN7 cells, loss of Dad1 causes apoptosis which cannot be prevented by Bcl-2. RESULTS: To determine the role of Dad1 function in vivo, we prepared by gene targeting, mice harbouring a disrupted Dad1 gene. Homozygous mutants died shortly after they were implanted with the characteristic features of apoptosis. In an in vitro blastocyst culture system, Dad1-null cells displayed abnormalities which were comparable to those obtained in vivo. However, oligosaccharyltransferase activity was apparently retained even after the Dad1-null cells were destined to die. Some live-born heterozygous mutants displayed soft-tissue syndactyly. Mild thymic hypoplasia was also indicated in heterozygotes. CONCLUSION: These results suggest the involvement of the Dad1 gene in the acquisition of a common syndactyly phenotype, as well as in the control of programmed cell death during development.

Animals↗
PubMed1999

Rotation vector analysis of eye movement in three dimensions with an infrared CCD camera.

We have developed a new technique for analyzing the rotation vector of eye movement in three dimensions with an infrared CCD camera based on the following four assumptions; i) the eye rotates on a point; ii) the pupil edge is a circle; iii) the distance from the center of eye rotation to pupil circle remains unchanged despite the rotation; iv) the image of the eye by the CCD camera is projected onto a plane which is perpendicular to the camera axis. After taking digital images of voluntary circular eye movements, we first constructed a three-dimensional frame of reference fixed on the orbita of the subject wearing a goggle equipped with an infrared CCD camera, and determined the space coordinates of the center of eye rotation, the center of the pupil, and an iris freckle. We then took digital images of the eye movements during a saccade or vestibulo-ocular reflex (VOR) and analyzed the axis and angle of the eye movements by the trajectories of the center of the pupil and the iris freckle. Finally, Listing's plane of saccade and the gain and the phase of VOR were obtained. The suitability of this technique is examined.

Adult↗
PubMed1999

[Clinical analysis of patients with bacterial meningitis in childhood and reevaluation of rapid antigen detection methods].

Twenty-eight cases of bacterial meningitis during the recent ten years were analyzed retrospectively, and the following results were obtained. 1. Pathogens were as follows; H. influenzae 13 (46.4%), S. pneumoniae 8 (28.6%), S. agalactiae 4 (14.3%), E. coli 2 (7.1%), and L. monocytogenes 1 case (3.6%). 2. Twelve out of the thirteen H. influenzae cases were caused by serotype b (Hib), and 2 strains were beta-lactamase producer. Fifty percent of the S. pneumoniae cases were caused by penicillin-resistant strains. And all these resistant strains belonged to serotype 19 or 23. 3. Underlying diseases related to the onset of meningitis were found in 46% of the cases, and these consisted of CNS shunt operated 5, asplenia or polysplenia 2, Mondini's anomaly 1, sacral dermal sinus 1, and neonate 4 cases. 4. Prognosis of these cases were three deaths, four with neurologic sequelae, and twenty-one complete recoveries. 5. On admission, 85% (17/20) of the cases were diagnosed correctly by the rapid antigen detection. Sensitivity and specificity of the rapid antigen detection by using latex particle agglutination is 90% and 100% in the Hib cases, and 83% and 100% in the S. pneumoniae cases respectively. Moreover, the bacteriologically unknown 2 cases caused by parenteral partial treatment were also diagnosed by the detection of antigen in concentrated urine.

Antigens, Bacterial↗
PubMed1999

Changes in cardiac protein kinase C activities and isozymes in streptozotocin-induced diabetes.

To understand cardiac dysfunction in diabetes, the activity of protein kinase C (PKC) and protein contents of its isozymes (PKC-alpha, -beta, -epsilon, and -zeta) were examined in diabetic rats upon injection of streptozotocin (65 mg/kg iv). The hearts were removed at 1, 2, 4, and 8 wk, and some of the 6-wk diabetic animals had been injected with insulin (3 U/day) for 2 wk. The Ca(2+)-dependent PKC activity was increased by 43 and 51% in the homogenate fraction and 31 and 70% in the cytosolic fraction from the 4- and 8-wk diabetic hearts, respectively, in comparison with control values. The Ca(2+)-independent PKC activity was increased by 24 and 32% in the homogenate fraction and 52 and 89% in the cytosolic fraction from the 4- and 8-wk diabetic hearts, respectively, in comparison with control values. The relative protein contents of PKC-alpha, -beta, -epsilon, and -zeta isozymes were increased by 43, 31, 48, and 38%, respectively, in the homogenate fraction and by 126, 119, 148, and 129%, respectively, in the cytosolic fraction of the 8-wk diabetic heart. The observed changes in heart homogenate and cytosolic fractions were partially reversible upon treatment of the diabetic rats with insulin. The results suggest that the increased myocardial PKC activity and increased protein contents of the cytosolic PKC isozymes are associated with subcellular alterations and cardiac dysfunction in the diabetic heart.

Animals↗
PubMed1999

Changes in sarcolemmal PLC isoenzymes in postinfarct congestive heart failure: partial correction by imidapril.

We have examined the changes in quantity and activity of cardiac sarcolemmal (SL) phosphoinositide-phospholipase C (PLC)-beta(1), -gamma(1), and -delta(1) in a model of congestive heart failure (CHF) secondary to large transmural myocardial infarction (MI). We also instituted a late in vivo monotherapy with imidapril, an ANG-converting enzyme (ACE) inhibitor, to test the hypothesis that its therapeutic action is associated with the functional correction of PLC isoenzymes. SL membranes were purified from the surviving left ventricle of rats in a moderate stage of CHF at 8 wk after occlusion of the left anterior descending coronary artery. SL PLC isoenzymes were examined in terms of protein mass and hydrolytic activity. CHF resulted in a striking reduction (to 6-17% of controls) of the mass and activity of gamma(1)- and delta(1)-isoforms in combination with a significant increase of both PLC beta(1) parameters. In vivo treatment with imidapril (1 mg/kg body wt, daily, initiated 4 wk after coronary occlusion) improved the contractile function and induced a partial correction of PLCs. The mass of SL phosphatidylinositol 4,5-bisphosphate and the activities of the enzymes responsible for its synthesis were significantly reduced in post-MI CHF and partially corrected by imidapril. The results indicate that profound changes in the profile of heart SL PLC-beta(1), -gamma(1), and -delta(1) occur in CHF, which could alter the complex second messenger responses of these isoforms, whereas their partial correction by imidapril may be related to the mechanism of action of this ACE inhibitor.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Marked increase in plasma ACTH with tumor reduction after chemotherapy in ectopic ACTH syndrome.

We report on a case of rapid and marked hormone release as a result of rapid tumor reduction due to chemotherapy in a 36-year-old woman with ectopic ACTH syndrome due to small cell lung cancer. Treatment of the cancer with cisplatin and etoposide resulted in an 80% reduction in tumor size on computed tomographic scan within two weeks. Concurrently, plasma ACTH exhibited an unexpected and astonishing increase from 373 pg/ml before treatment to more than 1200 pg/ml. There were no biochemical characteristics observed in tumor lysis syndrome of solid tumors such as azotemia, increased LDH and hyperkalemia. The present case indicates that anticancer chemotherapy instituted in patients with ectopic ACTH syndrome could result in an acute increase of plasma ACTH and exacerbation of hypercortisolism, similar to tumor lysis syndrome, which is a potentially fatal complication following anti-cancer chemotherapy.

ACTH Syndrome, Ectopic↗