PubMed Health⌕ Search

Biomedical subjects

K Inoue

Publications and source records attributed to K Inoue.

At least 793 records · Page 44Linked to original sources
PubMed1998

Genotype-phenotype correlation of patients with multiple endocrine neoplasia type 2 in Japan.

BACKGROUND: Multiple endocrine neoplasia type 2 (MEN 2) is a hereditary syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and hyperparathyroidism. MEN 2 is caused predominantly by germ-line mutations of the RET proto-oncogene. This study aimed to clarify the genotype-phenotype correlation in MEN 2 patients in Japan in order to modify the clinical management according to the genotype. METHODS: Constitutive DNA of 64 MEN 2 patients (48 kindreds) were searched for mutations at exons 10, 11, 13, 14 and 16 of the RET proto-oncogene using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), direct sequencing and restriction enzyme digestion. The clinical characteristics of the patients were obtained from a previous nationwide questionnaire survey. RESULTS: Overall, 62 (96.9%) out of 64 patients had a germ-line point mutation at the hot spots. MTC and pheochromocytoma occurred equally in every genotype except C630S. Specific genotype had a correlation between tumor size and age at the operation for MTC or extent of MTC, i.e. C618S developed late onset type of MTC as compared with that of C634R, C634Y and M918T. Small MTC in C634R may be less aggressive than those in C634Y and M918T. CONCLUSIONS: DNA testing has good clinical implications for the management of patients with MEN 2 and the timing and operative procedures of thyroidectomy can be modified according to the genotype.

Adrenal Gland Neoplasms↗
PubMed1998

Swimming capacity of mice is increased by oral administration of a nonpungent capsaicin analog, stearoyl vanillylamide.

Intravenous injection of stearoyl vanillylamide (C18-VA), a nonpungent capsaicin (CAP) analog, enhances adrenaline secretion significantly and as effectively as CAP in rats. Because swimming capacity was enhanced by CAP in mice due to CAP-induced adrenal catecholamine secretion, we investigated the effects of oral administration of C18-VA on swimming capacity using an adjustable-current water pool. Male Std ddY 6-wk-old mice were fed a commercial diet for this study and one group was orally administered C18-VA via a stomach tube. Treated mice were able to swim longer before exhaustion than the control mice (62.9 +/- 5.6 vs. 49.6 +/- 7. 0 min, P < 0.05). The swimming capacity of two groups administered C18-VA (0.02 and 0.033 mmol/kg) was significantly greater than that of those administered vehicle alone, (P < 0.05). Substance P concentration in cerebrospinal fluid, which is involved in pain transmission and is the first direct measure of pungency, was not affected by C18-VA administration. In an experiment examining the effects of C18-VA on serum adrenaline concentration, adrenaline was significantly greater in C18-VA treated mice than in controls at 2-h post-dose (C18-VA group, 26.09 +/- 2.82; control group 13.29 +/- 0. 96 microg/L, P < 0.01). In a separate study free fatty acids in serum were elevated in treated mice at 2-h post-dose (P < 0.01). While serum glucose concentration was not affected. These results suggest that C18-VA increased swimming capacity of mice via adrenaline release, independent of pungency. In addition, the present study suggests the usefulness of its application to humans.

Animals↗
PubMed1998

Induction of apoptosis by phosphatidylserine.

Treatment of Chinese hamster ovary (CHO) cells with phosphatidylserine (PS) caused cell death in a dose-dependent manner. Other phospholipids, such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidic acid, had no effect on cell viability. The cells incubated with PS became round and underwent a dramatic reduction of cellular volume while maintaining the membrane containment of cellular contents. The PS-treatment induced chromatin condensation and extensive DNA fragmentation, with a pattern characteristic of internucleosomal fragmentation on agarose gel electrophoresis. These results indicate that PS-treatment induces apoptosis of CHO cells. This apoptosis-inducing activity was highly specific for PS, and neither of the synthetic PS analogs 1,2-diacyl-sn-glycero-3-phospho-D-serine (D-PS) and 2,3-diacyl-sn-glycero-1-phospho-L-serine induced apoptosis. Analysis using fluorescence-labeled phospholipids showed that both PS and D-PS were taken up equally and then transported to intracellular membranes, suggesting that the PS-specific induction of apoptosis was not the result of its specific internalization. These observations suggest that certain molecules which may recognize the stereo-specific configuration of PS are involved in the apoptotic process triggered by PS.

Animals↗
PubMed1998

Induction of metallothionein isoforms in rat hepatoma cells by various anticancer drugs.

The induction of metallothionein (MT) isoforms (MT-1, -2) by anticancer drugs was investigated in cultured rat hepatoma H4 II E C3 cells. The steady-state expression of MT-1 mRNAs was higher than that of MT-2 mRNAs. During incubation of the cells with various anticancer drugs, namely, adriamycin, epirubicin, cis-diamminedichloroplatinum(II) (CDDP), and cis-diammine(1, 1-cyclobutyldicarboxylato)platinum(II), both MT-1 and MT-2 mRNAs were coordinately inducible: the levels of isoMT mRNA reached a maxim of approximate by 6-fold at 3 h. Immunofluorescent studies revealed that the cytosolic fluorescence in the cells exposed to 1 microM CDDP for 48 h was more intensified than that in the untreated cells. Transfer of antisense oligonucleotides resulted in marked reduction of isoMT mRNA, and upon exposure to 5 microM CDDP for 48 h, the viabilities of these cells dropped to 25.8% of the controls. These results indicate that anticancer drugs are potent inducers of MT isoforms in hepatoma cells and that a decrease in cellular MTs enhances the susceptibility of hepatoma cells to CDDP. Thus, we conclude that endogenous MTs play a role in determining the sensitivity or resistance of cancer cells to clinically important anticancer agents.

Animals↗
PubMed1998

Secondary structures of synthetic peptides corresponding to the first membrane-contact portion of normal band 3 and its deletion mutant (Southeast Asian ovalocytosis).

The conformations of synthetic peptides corresponding to the first membrane-contact portion from Tyr390 to Lys430 of band 3 (band 3-1a) and the counterpart portion of South-East Asian ovalocytosis (SAO) band 3 (band 3-1b) in lipid bilayers were examined by means of circular dichroism (CD), Fourier transform infrared (FTIR) spectroscopy as well as a proteolytic digestion method. The CD and FTIR studies showed that band 3-1a and band 3-1b in a membrane lipid bilayer cannot assume an alpha-helix rich structure but instead assume a beta-structure rich conformation. The proteolytic digestion experiments demonstrated that the cleavage sites of Tyr392 and Phe423 were common to both the model and erythrocyte membranes. Taken together with our previous work, which indicated that the first membrane-contact portion was the portion embedded in the erythrocyte membrane without tight lipid-peptide interactions [Hamasaki et al. (1997) J. Biochem. 122, 577-585], we imply herein that the first membrane-contact portion of band 3 by itself can not assume the ordinary alpha-helix conformation in the membrane lipid bilayers. A proteinase-resistant portion, from Ser402 to Phe423, was observed when liposomes containing band 3-1a were digested with proteinase K, while no proteinase-resistant core portion was found in the case of band 3-1b (DeltaAla400-Ala408). This suggests the crucial role of the deleted portion, from Ala400 to Ala408, in the interaction of the first membrane-contact portion of band 3 with a membrane lipid bilayer.

Amino Acid Sequence↗
PubMed1998

Cutaneous reinnervation of the rectus abdominis musculocutaneous flap after chest wall reconstruction: development of herpes zoster in the transplanted musculocutaneous flap.

We report a patient in whom herpes zoster developed in the transplanted rectus abdominis musculocutaneous flap 14 months after a chest wall reconstruction for recurrent breast cancer. Based on the distribution of the varicella zoster virus spreading along the sensory nerve fibers, we concluded that the virus spread along the reinnervated sensory nerves from the dorsal ganglia, through the intercostal nerves, and into the flap skin. It is suggested that this finding demonstrates the pathway of reinnervation into the transferred musculocutaneous flap on the chest wall.

Abdominal Muscles↗
PubMed1998

Tensile load and the metabolism of anterior cruciate ligament cells.

It generally is recognized that tensile load plays a major role in maintaining the homeostasis of the anterior cruciate ligament fibers, but its detailed mechanism remains a matter of controversy. The effect of cyclic tensile load on the metabolism of the anterior cruciate ligament were investigated experimentally using cultured cells from the anterior cruciate ligament of rabbits. Using culture plates with flexible rubber bases, a cyclic tensile load was applied to the cultured cells for 24 hours, and the changes in shape, alignment, and metabolism of the cells were analyzed. Under the cyclic tensile load, the shape of the cells from the anterior cruciate ligament changed to spindle and aligned perpendicularly to the direction of the tensile load. The cyclic tensile load also caused an increase in collagen synthesis by the cells from the anterior cruciate ligament, which was predominant in Type I. The cells from the synovium showed similar changes in shape and alignment under the cyclic tensile load, but no significant change was observed in cell metabolism. These observations suggest that the application of cyclic tensile load on the anterior cruciate ligament cells is an important factor in the regulation of collagen synthesis in the anterior cruciate ligament.

Animals↗
PubMed1998

A new deleted allele in the human cytochrome P450 2A6 (CYP2A6) gene found in individuals showing poor metabolic capacity to coumarin and (+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride (SM-12502).

The S-oxidation of (4)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride (SM-12502) and the 7-hydroxylation of coumarin are primarily catalyzed by cytochrome P450 2A6 (CYP2A6). The activities of SM-12502 S-oxidase and coumarin 7-hydroxylase were investigated with liver microsomes from 20 human individuals. Liver microsomes from individual H16 showed the lowest activities of both enzymes. The expression of CYP2A6 protein was not detectable in liver microsomes from individuals H4, H5, H7, H8, H12 and H16. CYP2A6 mRNA was hardly detectable in the liver of the individual H16. A new SacI-restriction fragment length polymorphism showing the lack of a 2.6 kb fragment was found in two of forty genomic DNA preparations from individuals H16 and No. 594, using CYP2A6 cDNA as a probe. This deletional 2.6 kb fragment was isolated from a genomic library prepared from one individuals showing normal coumarin 7-hydroxylase activity and was sequenced. This fragment contained a CYP2A6 gene region from 319 bp upstream of a putative exon 6 to a SacI site in exon 9, indicating that this region was deleted in the two individuals in this study. We also demonstrated by polymerase chain reaction analysis that the exon 8 of CYP2A6 gene was deleted in individuals H16 and No. 594. These results indicate that the reduced activity of SM-12502 S-oxidase and no activity of coumarin 7-hydroxylase are caused by the lack of CYP2A6 mRNA and CYP2A6 protein caused by the CYP2A6 gene deletion.

Aryl Hydrocarbon Hydroxylases↗
PubMed1998

Hepatic infarction following percutaneous ethanol injection therapy for hepatocellular carcinoma.

We report on two patients who developed hepatic infarction after undergoing percutaneous ethanol injection therapy (PEIT) for hepatocellular carcinoma (HCC). In both cases, liver function parameters deteriorated immediately after the ethanol injection, and enhanced computed tomography images showed a wedge-shaped avascular low-density area due to hepatic infarction. In one patient, PEIT was performed for a nodule treated with transcatheter arterial infusion (TAI) using a suspension of styrene maleic acid neocarzinostatin (SMANCS) 4 weeks before. In the other patient, TAI with SMANCS had been carried out 14 months previously for a different nodule in the same segment where the nodule treated with PEIT was located. When PEIT is used for patients with HCC who have previously undergone TAI, especially with SMANCS, PEIT may induce hepatic infarction.

Antineoplastic Agents↗
PubMed1998

Developmental expression and substrate specificities of alfalfa caffeic acid 3-O-methyltransferase and caffeoyl coenzyme A 3-O-methyltransferase in relation to lignification.

The biosynthesis of monolignols can potentially occur via two parallel pathways involving free acids or their coenzyme A (CoA) esters. Caffeic acid 3-O-methyltransferase (COMT) and caffeoyl CoA 3-O-methyltransferase (CCOMT) catalyze functionally identical reactions in these two pathways, resulting in the formation of mono- or dimethoxylated lignin precursors. The activities of the two enzymes increase from the first to the sixth internode in stems of alfalfa (Medicago sativa L.), preceding the deposition of lignin. Alfalfa CCOMT is highly similar at the amino acid sequence level to the CCOMT from parsley, although it contains a six-amino acid insertion near the N terminus. Transcripts encoding both COMT and CCOMT are primarily localized to vascular tissue in alfalfa stems. Alfalfa CCOMT expressed in Escherichia coli catalyzes O-methylation of caffeoyl and 5-hydroxyferuloyl CoA, with preference for caffeoyl CoA. It has low activity against the free acids. COMT expressed in E. coli is active against both caffeic and 5-hydroxyferulic acids, with preference for the latter compound. Surprisingly, very little extractable O-methyltransferase activity versus 5-hydroxyferuloyl CoA is present in alfalfa stem internodes, in which relative O-methyltransferase activity against 5-hy-droxyferulic acid increases with increasing maturity, correlating with increased lignin methoxyl content.

Amino Acid Sequence↗
PubMed1998

Molecular composition of the 16S toxin produced by a Clostridium botulinum type D strain, 1873.

The 16S toxin was purified from a Clostridium botulinum type D strain 1873 (D-1873). Furthermore, the entire nucleotide sequences of the genes coding for the 16S toxin were determined. It became clear that the purified D-1873 16S toxin consists of neurotoxin, nontoxic nonhemagglutinin (NTNH), and hemagglutinin (HA), and that HA consists of four subcomponents, HA1, HA2, HA3a, and HA3b, the same as type D strain CB16 (D-CB16) 16S toxin. The nucleotide sequences of the nontoxic components of these two strains were also found to be identical except for several bases. However, the culture supernatant and the purified 16S toxin of D-1873 showed little HA activity, unlike D-CB16, though the fractions successively eluted after the D-1873 16S toxin peak from an SP-Toyopearl 650S column showed a low level of HA activity. The main difference between D-1873 and D-CB16 HA molecules was the mobility of the HA1 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Therefore it was presumed that the loss of HA activity of D-1873 16S toxin might be caused by the differences of processing HA after the translation.

Amino Acid Sequence↗
PubMed1998

Dopamine releases endothelium-derived relaxing factor via alpha 2-adrenoceptors in canine vessels: comparisons between femoral arteries and veins.

1. We investigated the role of vascular smooth muscle alpha-adrenoceptor subtypes in the vasoconstrictor response of femoral arteries and veins to dopamine and whether the vasoconstriction is modified by endothelium-dependent relaxation mediated via the activation of alpha 2-adrenoceptors in ring preparations of femoral arteries and veins from mongrel dogs. 2. Dopamine contracted both arteries and veins in a dose-dependent manner and this contraction was inhibited by pretreatment with phentolamine or prazosin. Pretreatment with yohimbine shifted the dose-response curve for dopamine to the right in femoral veins, but not in arteries. 3. Phenylephrine contracted femoral arteries and veins in a dose-dependent manner and this contraction was inhibited by pretreatment with prazosin. 4. Clonidine produced a bell-shaped dose-response curve in femoral veins and this curve was shifted upwards by pretreatment with NG-nitro-L-arginine (L-NNA). In contrast, femoral arteries were not affected by clonidine. NG-Nitro-L-arginine potentiated contractile responses to dopamine in both veins and arteries. This potentiation was inhibited by yohimbine or by the removal of the endothelium in both arteries and veins. 5. These results suggest that dopamine contracts femoral arteries via stimulation of alpha 1-adrenoceptors and contracts femoral veins via stimulation of both alpha 1- and alpha 2-adrenoceptors and that these contractions are attenuated by the vasodilator action of dopamine via alpha 2-adrenoceptor-mediated release of endothelium-derived relaxing factor.

Adrenergic alpha-Agonists↗
PubMed1998

Effect of obstructive jaundice on neutrophil chemotactic activity: an in vivo assessment in zymosan-induced peritonitis model in rats.

The effect of obstructive jaundice on local neutrophil accumulation in response to inflammatory stimulus was investigated in rats. Obstructive jaundice was produced by bile duct ligation for 7 days. Zymosan (200 mg) was injected intraperitoneally and 4h later myeloperoxidase activity in the peritoneal fluid was measured to quantify neutrophil recruitment. Zymosan-induced neutrophil recruitment was significantly greater (more than two-fold) in bile duct-ligated rats than in sham-ligated or normal animals. Depletion of peritoneal cells significantly suppressed neutrophil recruitment after zymosan injection in all three groups, with no significant differences between the groups. In normal rats, replacement of their peritoneal cells by those from bile duct-ligated rats did not enhance zymosan-induced neutrophil recruitment. In contrast, bile duct-ligated rats treated with peritoneal cell replacement from normals showed significantly increased neutrophil recruitment after zymosan injection. In vitro neutrophil chemotaxis in response to formyl-Met-Leu-Phe was significantly enhanced in bile duct-ligated rats, compared with that in sham-ligated animals. The results suggest that local neutrophil recruitment in response to inflammation may be enhanced in obstructive jaundice and that increased neutrophil chemotactic activity, not macrophage activity, may play a prime role in the mechanism.

Animals↗
PubMed1998

Perinatal management of congenital complete atrioventricular block: report of nine cases.

BACKGROUND: The addition of fetal ultrasonography has allowed the prenatal diagnosis and observation of congenital complete atrioventricular block (CCAVB). Thus, the management of the affected fetuses should be modified accordingly. METHODS: The medical records were reviewed to identify patients with CCAVB, and clinical and laboratory data were collected. RESULTS: Nine patients with CCAVB, diagnosed prenatally, were identified. The gestational age at the time of diagnosis ranged from 18 to 38 weeks (median, 25 weeks). The gestational age and birthweight ranged from 29 to 41 weeks and from 1420 to 4075 g, respectively. An accompanying congenital cardiac anomaly was noted in three cases, including one with polysplenia syndrome. The heart rate at birth ranged from 30 to 80 bpm. In three neonates, isoproterenol was given for bradycardia. One fetus with hydrops fetalis associated with complex heart disease was treated with maternally administered digoxin, with resolution of the fluid accumulation. A permanent pacemaker was implanted in six cases: two within 1 day of birth; two during the neonatal period; one at 51 days; and the other at 2 years and 11 months of age. There were no deaths or major complications and all have remained well beyond their infancy. CONCLUSIONS: With the improvement of diagnostic methodology, more cases with CCAVB, including those with complex heart disease, could be diagnosed during fetal life. Their outcome has been steadily improving with the advances in perinatal management, pacemakers and implant techniques, irrespective of associated structural cardiac defects.

Abnormalities, Multiple↗
PubMed1998

[Real time observation of binding of measles virus to Vero cells and neutralization of measles virus by human immunoglobulin using optical biosensor--a new real time diagnosis system for viral infections].

An optical biosensor to monitor molecular intractions was developed. This system made possible to observe reactions with a few minutes. We tried to apply this system for rapid diagnosis of viral infections. Measles virus propagated in our laboratory and crude rabbit anti-measles antiserum were used. A commercially available human immunoglobulin was used as a representative of patient sera. A crude rabbit anti-measles antiserum was fixed on the reaction surface of aminosilane coated cuvette, and specific binding of measles virus to this antibody was monitored. Specific purified IgG antibody was known to give as high sensitivity as the conventional culture method. But the sensitivity by crude antibody was found to be 1/10 in the sensitivity. This might be caused by the masked effects on specific antibody to the contaminated high amounts of non-specific proteins. None purified polyclonal antisera for most of the viruses are commercially available, and 10-20 times highly concentrated antibody solutions could be used for this titrations. Estimated anti-measles antibody titer of the commercial available human immunoglobulin by biosensor system was found to be the same as that by the conventional culture method. It was suggested that 1 X 10(3) virus particles/ml in the test solutions could be detectable and titerable by using commercially available specific anti-viral antibody in real time, and the viral infections could be diagnosed within an hour.

Animals↗
PubMed1998

Gene expression and cell cycle arrest mediated by transcription factor DMP1 is antagonized by D-type cyclins through a cyclin-dependent-kinase-independent mechanism.

A novel 761-amino-acid transcription factor, DMP1, contains a central DNA binding domain that includes three imperfect myb repeats flanked by acidic transactivating domains at the amino and carboxyl termini. D-type cyclins associate with a region of the DMP1 DNA binding domain immediately adjacent to the myb repeats to form heteromeric complexes which detectably interact neither with cyclin-dependent kinase 4 (CDK4) nor with DNA. The segment of D-type cyclins required for its interaction with DMP1 falls outside the "cyclin box," which contains the residues predicted to contact CDK4. Hence, D-type cyclin point mutants that do not interact with CDK4 can still bind to DMP1. Enforced coexpression of either of three D-type cyclins (D1, D2, or D3) with DMP1 in mammalian cells canceled its ability to activate gene expression. This property was not shared by cyclins A, B, C, or H; did not depend upon CDK4 or CDK2 coexpression; was not subverted by a mutation in cyclin D1 that prevents its interaction with CDK4; and was unaffected by inhibitors of CDK4 catalytic activity. Introduction of DMP1 into mouse NIH 3T3 fibroblasts inhibited entry into S phase. Cell cycle arrest depended upon the ability of DMP1 to bind to DNA and to transactivate gene expression and was specifically antagonized by coexpression of D-type cyclins, including a D1 point mutant that does not bind to CDK4. Taken together, these findings suggest that DMP1 induces genes that inhibit S phase entry and that D-type cyclins can override DMP1-mediated growth arrest in a CDK-independent manner.

3T3 Cells↗
PubMed1998

PET study of pointing with visual feedback of moving hands.

This study was conducted to determine where in the human brain visual feedback of hand movements is processed to allow accurate pointing. Regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET) and H2 15O in nine normal volunteers while performing one control and two reaching tasks. In all tasks, visual stimuli were presented on a head mounted display (HMD). A target board was placed in front of the subjects bearing six red light-emitting diodes (LEDs) aligned on a circle with a green LED at its center. The center green LED and one of the six red LEDs, randomly selected, were repeatedly switched on and off, alternatively. In the control task, subjects were instructed to gaze at the lit LED. In the two reaching tasks, the reaching with visual feedback (RwithF) task and the reaching without visual feedback (RwithoutF) task, they had to point to the lit red LED with their right index fingers. In the RwithF task, their right hands were visible on the HMD before touching the target, whereas in the RwithoutF task, they were not visible. For each subject, subtraction images of each reaching task minus the control and the RwithF task minus the RwithoutF task were calculated after transformation of PET images into the standard brain shape with an adjustable computerized brain atlas. These subtraction rCBF images were then averaged among the subjects, and significant changes of rCBF were identified. Significant increases in rCBF not only in the RwithF task minus control image but also in the RwithF task minus the RwithoutF task image were observed in the supramarginal cortex, the premotor cortex and the posterior cingulate cortex of the left hemisphere, the caudate nucleus and the thalamus of the right hemisphere, and the right cerebellum and vermis. These results indicate that the supramarginal cortex, the premotor cortex, and the posterior cingulate cortex of the left hemisphere and the cerebellum are involved in integrating visual feedback of hand movements and execution of accurate pointing.

Adult↗