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Biomedical subjects

K Inoue

Publications and source records attributed to K Inoue.

At least 55 records · Page 3Linked to original sources

Usefulness of femoro(ilio)-axillar bypass surgery for the treatment of subclavian steal syndrome caused by aortitis syndrome.

In two patients with subclavian steal syndrome associated with aortitis syndrome, retrograde bypass grafting from the femoral or common iliac artery to the axillary artery resulted in the disappearance of symptoms. One patient, a 37-year-old female, was treated with a bypass from the left femoral artery to the left axillary artery with a 10-mm ring-supported double velour knitted Dacron graft. The other patient, a 54-year-old female, with the complication of moderate aortic regurgitation, was treated with a bypass from the left common iliac artery to the left axillary artery with an 8-mm EPTFE graft. These bypass grafts were angiographically confirmed to be patent after the operation. When changes in graft flow in different body positions (supine, sitting, and standing) were examined, using a transcutaneous Doppler flow meter, 5 years after the operation, resting graft flow to the upper extremities showed no consistent changes among the three different positions and was maintained in a stable condition, regardless of the patients' positions. Furthermore, graft flow increased while the left arm exercised. This finding, together with the clinical efficacy, indicates that this mode of retrograde bypass grafting may be effective in some selected patients with this complicated syndrome.

Adult

Protective effects of endothelin-1 on acute pancreatitis in rats.

Endothelin-1, a 21-residue peptide isolated from vascular endothelial cells, has a broad spectrum of actions. To clarify the involvement of endothelin-1 in acute pancreatitis, we examined the effects of endothelin-1 and its receptor antagonist BQ-123 on cerulein-induced pancreatitis in rats. Rats were infused intravenously with heparin-saline (control), endothelin-1 (100 pmol/kg/hr), cerulein (5 micrograms/kg/hr), or cerulein plus endothelin-1 for 3.5 hr. In another experiment, cerulein or cerulein plus BQ-123 (3 mg/kg/hr) was infused. Infusion of cerulein caused hyperamylasemia and pancreatic edema. Endothelin-1, when infused with cerulein, decreased the extent of pancreatic edema with a significant increase in the pancreatic dry- to wet-weight ratio. Histological changes induced by cerulein were markedly attenuated when endothelin-1 was given with cerulein. In contrast, endothelin-receptor blockade with BQ-123 further augmented pancreatic edema caused by cerulein. The extent of inflammatory cell infiltration was greater than BQ-123 was given with cerulein. Endothelin-1 or BQ-123 had no influence on hyperamylasemia. This study suggests that endothelin-1 has protective effects on experimental acute pancreatitis.

Acute Disease

Ductal adenocarcinoma of the pancreas associated with intratumoral calcification.

An invasive ductal carcinoma of the pancreas with intratumoral calcification is reported in a 59-yr-old female. The calcification was preoperatively demonstrated by ultrasonography and computed tomography. On the cut surface of the resected specimen of the pancreas tail, calcification was observed in the central part of the ductal adenocarcinoma. Although calcification is not uncommon in chronic pancreatitis or serous cystadenoma, mucinous cystadenoma/adenocarcinoma, solid and cystic tumor, and islet cell tumor, intratumoral calcification is uncommon in an ordinary ductal adenocarcinoma of the pancreas. For differential diagnosis from other conditions associated with calcification, careful examinations are necessary.

Calcinosis

Reduction of acetylcholine-activated current by low concentrations of extracellular adenosine 5'-triphosphate.

Effects of adenosine 5'-triphosphate (ATP) on ionic currents activated by acetylcholine (ACh) were investigated using rat pheochromocytoma PC12 cells and Xenopus oocytes expressing nicotinic receptors. In PC12 cells, ATP (10 nM to 1 microM) inhibited an inward current activated by ACh in not all but about 60% of cell batches. The ACh-activated current was also inhibited by ATP in Xenopus oocytes and, with a subunit combination of alpha 3 plus beta 4, the inhibition was observed at concentration as low as 100 fM. Uridine 5'-triphosphate (UTP) induced a similar inhibition of the ACh-activated current both in PC12 cells and Xenopus oocytes. These and other properties suggest that the current reduction by ATP is not mediated through conventional P2-purinoceptors.

Acetylcholine

D2 receptors in the ventrolateral striatum are involved in feeding behavior in rats.

To study the role of dopamine D1 and D2 receptors in the ventrolateral striatum in feeding behavior, a D1 receptor agonist (CY 208-243), a D1 receptor antagonist (SCH 23390), a D2 receptor agonist (quinpirole), and a D2 receptor antagonist [(-)-sulpiride] were perfused via a microdialysis probe into the ventrolateral striatum of rats fasted for 22 h. Then the rats were allowed to feed freely for 6 h. Sulpiride perfusion at a high concentration suppressed food and water intake significantly, whereas dopamine release and the levels of DOPAC and HVA were increased at all concentrations. In contrast, quinpirole perfusion at a high concentration increased food intake by 41%. Dopamine release and the levels of DOPAC and HVA were decreased at all concentrations. On the other hand, neither CY 208-243 nor SCH 23390 changed food intake or dopamine release, but both drugs decreased water intake. These results suggest that D2 receptors in the ventrolateral striatum have a more important role than D1 receptors in the feeding behavior of rats.

3,4-Dihydroxyphenylacetic Acid

Cerebellum of the adult reeler mutant mouse contains two Purkinje cell populations with respect to gene expression for the N-methyl-D-aspartate receptor channel.

Recent studies have identified five NMDA receptor subunits, which exhibit distinct cellular expressions in the normal rodent brain. The purpose of this investigation is to clarify the molecular-anatomical organization in the cerebellum of the reeler mutant mouse, in which various categories of the Purkinje cells are present as to the cell position and synaptic connectivity. In comparison with the distribution of the inositol 1,4,5-trisphosphate receptor mRNA, a molecular marker specific to the Purkinje cells, the epsilon 1 subunit mRNA of the NMDA receptor channel was found in the adjacent sections to be expressed in a subset of the Purkinje cells. In the rostrocaudal extent, the Purkinje cells expressing the epsilon 1 subunit mRNA were distributed preferentially in the rostral cerebellum, irrespective of the normal and heterotopic positions. In the mediolateral extent, they formed segregated cell clusters, interposed by epsilon 1 subunit mRNA-negative clusters. Hybridizing signals for the zeta 1 subunit mRNA were found in all the Purkinje cell population, whereas those for the epsilon 2, epsilon 3, and epsilon 4 subunit mRNAs were not detected in the cells. These findings suggest that the reeler cerebellum is topographically compartmentalized by two subpopulations of the Purkinje cells, one expressing the epsilon 1 and zeta 1 subunit mRNAs, and the other expressing the zeta 1 subunit mRNA alone.

Animals

Cloning and expression of a bovine glutamate transporter.

We have isolated a 3845 base-pair cDNA (BNGLUAS) encoding a bovine glutamate transporter (bovine GLAST) by screening a bovine retina cDNA library with an oligonucleotide probe corresponding to conserved regions of known glutamate transporters. The cDNA sequence predicted a protein of 542 amino acids and displayed 96% and 97% amino acid identity with the rat GLAST/GluT-1 and human GLAST, respectively. Expression of the bovine GLAST in Xenopus oocytes revealed Na(+)-dependent [14C]L-glutamate uptake and electrogenic glutamate uptake.

ATP-Binding Cassette Transporters

Neurogenic tumors of the mediastinum originated from the vagus nerve.

Thirty-nine patients with neurogenic tumors observed between 1974 to 1992 were reviewed. There were 32 patients with neurilemoma, one with neurofibroma, five with ganglioneuroma, and one with malignant neurilemoma. Two cases of neurilemoma originated from the vagus nerve, which is very rare. Surgical resection is recommended, not only to confirm the nature of the lesion, but also to prevent further growth and compression on adjacent structures. For benign encapsulated neurogenic tumors, resection is curative.

Ganglioneuroma

Ataxia with isolated vitamin E deficiency is caused by mutations in the alpha-tocopherol transfer protein.

Ataxia with isolated vitamin E deficiency (AVED) is an autosomal recessive neurodegenerative disease which maps to chromosome 8q13. AVED patients have an impaired ability to incorporate alpha-tocopherol into lipoproteins secreted by the liver, a function putatively attributable to the alpha-tocopherol transfer protein (alpha-TTP). Here we report the identification of three frame-shift mutations in the alpha TTP gene. A 744delA mutation accounts for 68% of the mutant alleles in the 17 families analysed and appears to have spread in North Africa and Italy. This mutation correlates with a severe phenotype but alters only the C-terminal tenth of the protein. Two other mutations were found in single families. The finding of alpha TTP gene mutations in AVED patients substantiates the therapeutic role of vitamin E as a protective agent against neurological damage in this disease.

Africa, Northern

Molecular characterization of proteins in protein-body membrane that disappear most rapidly during transformation of protein bodies into vacuoles.

During the post-germination growth of seeds, protein bodies fuse with one another and are converted to a central vacuole. To investigate this transition, protein-body membranes from dry seeds of pumpkin (Cucurbita sp.) were prepared and their protein components characterized. Five major proteins (designated MP23, MP27, MP28, MP32 and MP73) were detected in the protein-body membranes. A cDNA clone encoding both MP27 and MP32 has been isolated. The deduced precursor polypeptide was composed of a hydrophobic signal sequence, MP27 and MP32, in that order. A putative site of cleavage between MP27 and MP32 was located on the COOH-terminal side of asparagine 278, an indication that the post-translational cleavage may occur by the action of a vacuolar processing enzyme that converts proprotein precursors of seed proteins into the mature forms. Immunoelectron microscopic analysis showed that MP27 and MP32 were associated with protein-body membrane of dry pumpkin seeds. Among the five membrane proteins, MP27 and MP32 disappeared most rapidly during seedling growth. The degradation of MP27 and MP32 starts just after seed germination and proceeds in parallel with the transformation of the protein bodies into a vacuole.

Amino Acid Sequence

Specific binding of a synthetic peptide derived from an antibody complementarity determining region to phosphatidylserine.

We have established a series of monoclonal antibodies that bind to phosphatidylserine (PS). One mAb, PS4A7, showed a strict specificity for PS and distinguished the stereospecific configuration of its serine moiety. We determined the amino acid sequences of the heavy and light chain variable regions of PS4A7, and examined the reactivity of the synthetic peptides corresponding to the complementarity determining region (CDR) of the mAb with phospholipids. We found that a 12-amino acid synthetic peptide corresponding to the third CDR of the heavy chain (amino acid residues 93-102, referred to as CDR3-H) bound specifically to PS. Although the affinity of the peptide to PS was markedly lower, the peptide was shown to bind to 1,2-diacyl-sn-glycero-3-phospho-L-serine (PS), but not to 1,2-diacyl-sn-glycero-3-phospho-D-serine, showing a similar specificity to that of PS4A7. The specific binding of the CDR3-H peptide to PS was confirmed by ELISA and TLC-immunostaining assay. The interaction between the CDR3-H peptide and water-soluble PS-derivatives was investigated by inhibition of the ELISA. PS effectively inhibited the binding and phosphoserine showed a weak but significant inhibition, but no appreciable inhibition was observed with serine. These observations suggest that the CDR3-H peptide plays a major role in the interaction of PS4A7 with the phosphoserine residue of the PS molecule.

Amino Acid Sequence

Swimming endurance capacity of mice is increased by chronic consumption of medium-chain triglycerides.

The effect of chronic administration of medium-chain triglycerides (MCT) on swimming endurance (swim capacity) was investigated in male Std ddY mice. The mice were fed a diet containing 80 g MCT + 20 g long-chain triglycerides (LCT)/kg diet for 6 wk; mice fed diet containing 100 g LCT/kg diet were used as controls. After being accustomed to swimming, the mice were subjected to forced swimming every 2 d in the current water pool that we had developed, and the total swimming period until exhaustion was measured. The total swimming period was used as the index of swim capacity. The group fed MCT showed significantly greater swim capacity than the control group (89.5 +/- 2.5 vs. 80.2 +/- 2.0 min). In another experiment, after 4 wk of MCT diet consumption, significantly greater swim capacity was found in untrained mice. The major metabolic consequences of the adaptations of muscle to prolonged MCT administration during endurance training were higher activities of 3-oxo acid CoA-transferase (P < 0.01), citrate synthase (P < 0.1) and malate dehydrogenase (P < 0.1). These findings suggest that increases in the enzyme activities of the tricarboxylic acid cycle and ketone body utilization associated with the chronic administration of an MCT-containing diet enhance swim capacity in mice.

Animals

Phospholipid degradation in rat calcium ionophore-activated platelets is catalyzed mainly by two discrete secretory phospholipase As.

An "A1 type" phospholipase activity with serine-phospholipid preference was released by rat activated platelets. It was distinct from the secretory type II phospholipase A2 [Horigome, K., Hayakawa, M., Inoue, K., and Nojima, S. (1987) J. Biochem. 101, 625-631] and co-purified with the secretory lysophosphatidylserine-selective lysophospholipase activity [Higashi, S., Kobayashi, T., Kudo, I., and Inoue, K. (1988) J. Biochem. 103, 442-447]. Several lines of evidence indicated that a single protein was responsible for the phospholipase A1 and lysophospholipase activities. Marked accumulation of lysophospholipids was observed in rat calcium ionophore-activated washed platelets and both phospholipase A1/lysophospholipase and type II phospholipase A2 were shown to contribute to this phospholipid degradation. A selective inhibitor of type II phospholipase A2 reduced the phospholipid degradation and enhanced the clotting time and prothrombinase activity. These results indicate that secretory platelet phospholipases may play a role in regulation of blood clotting.

Animals

Carbachol and cholecystokinin enhance accumulation of nicotine in rat pancreatic acinar cells.

Nicotine is a possible risk factor for chronic pancreatitis and pancreatic cancer. To study the loci where nicotine might exert its effect, we examined interactions between nicotine and rat pancreatic acini. When pancreatic acini were incubated with [3H]nicotine, [3H]nicotine levels in pancreatic acini were increased in time-and dose-dependent manners, and the t1/2 for dissociation of [3H]nicotine was 63.8 min. At 4 degrees C, the association of [3H]nicotine was 33% of the association at 37 degrees C. Unlabeled nicotine had no significant effect on the accumulation of [3H]nicotine. In addition, surface-bound [3H]nicotine was not detected when acini were washed in a low-pH solution or when they were trypsinized. These results suggest that the accumulation of nicotine may be a biological phenomenon and that [3H]nicotine does not bind to surface receptors of acinar cells, but accumulates intracellularly. The addition of verapamil (0.1 mM) or 12-O-tetradecanoylphorbol-13-acetate (1 microM) had no effect on [3H]nicotine association, while 4-bromo-A23187 (2 microM) or EGTA (10 mM) significantly increased the accumulation of [3H]nicotine. Carbachol and cholecystokinin significantly enhanced the accumulation of [3H]nicotine in a dose-dependent manner. Taken together, the increasing effects of carbachol and cholecystokinin on the accumulation of nicotine may explain, at least in part, the mechanisms involved in the multiplicative effects of the combination of two risk factors, smoking habit and high-fat or high-protein diets, on human pancreatic diseases.

Animals

Sequential changes in the distribution of type I and III collagens in the infarct zone: immunohistochemical study of experimental myocardial infarction in the rat.

AIM: Ventricular remodeling following acute myocardial infarction is an important factor in prognosis. The healing process, involving changes in type I and III collagens, is one of the major factors in remodelling. We therefore examined sequential changes in type I and III collagens after experimental myocardial infarction. MATERIALS AND METHODS: Hearts were excised from 1 day to 10 weeks after permanent left coronary ligation in rats. Immunohistochemical staining with a polyclonal antibody to each collagen was performed by the avidin-biotin-peroxidase method. RESULTS: Type I collagen initially appeared in the peripheral zone of the infarct from 3 days after ligation, the extent of staining gradually increasing until it reached a maximal level on days 21-28, after which the distribution remained unchanged. Type III collagen appeared in the peripheral zone of the infarct from 3 days after ligation; the extent of staining reached the maximal level after 11-28 days, after which a slight decrease in the distribution was observed, although the staining did not entirely disappear. CONCLUSIONS: Type I collagen was a major factor in collagen matrix formation, especially in the relatively late phase. Type III collagen, however, contributed particularly to collagen matrix formation in the relatively early phase. This study improves current understanding of the time-dependent alterations in type I and III collagens involved in the healing process after coronary artery occlusion.

Animals