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Biomedical subjects

K Inui

Publications and source records attributed to K Inui.

At least 271 records · Page 15Linked to original sources
PubMed1995

[Surgical treatment of apical invading lung cancer].

Operative technique and long-term results of seventeen patients with apical invading lung cancers were evaluated. External radiation therapy was administered preoperatively in all but one. Thirteen lobectomies, three wedge resections and one pneumonectomy were performed with combined resections of chest wall (and adjacent structures) 12, vertebra 3, brachicephalic vein 2, subclavian artery 1, lower part of brachial plexsus 3, sympathetic trunk 2 and phrenic nerve 1. Chest walls were reconstructed with marlex meshes in 5, the subclavian artery and one brachiocephalic vein were with artificial grafts. Operations were considered relative curative in 10, relative non-curative in 2 and absolutely non-curative in 5. Absolutely non-curative operations were due to cancer-positive stump of brachial plexus in the apex in four and metastatic lymph node invading aorta in one. Over all five-year survival rate was 35.3% and median survival was 20 months. Five-year survivals in patients with curative operations and non-curative operations were 60% and 0%, respectively, and the former was significantly higher. Surgical margin is a large factor for long-term result and invasion to the brachial plexus is thought to be a limiting factor for surgery.

Adult↗
PubMed1995

Specificity of p-aminohippurate transport system in the OK kidney epithelial cell line.

Substrate specificity of the p-aminohippurate (PAH) transport system was investigated in the OK kidney epithelial cells. PAH uptake by OK cells from the basal side was inhibited by beta-lactam antibiotics such as benzylpenicillin (PCG) and cefazolin. The inhibition of PAH uptake by PCG was competitive and the Ki value was calculated as 108.8 microM. Transcellular transport of PCG across OK cell monolayers occurred unidirectionally from the basal to apical side, and transcellular transport and basolateral uptake were inhibited by PAH, probenecid and beta-lactam antibiotics. The basolateral uptake of cefazolin and cefotiam was also inhibited by PAH and probenecid. The basolateral uptake of PAH and PCG were not affected by aliphatic dicarboxylates with 3 or 4 carbon atoms, but were strongly inhibited by those with 5 or 6 carbon atoms. The inhibitory effect became weaker for a longer dicarboxylate with 7 carbon atoms, then increased again with increasing number of carbon atoms. Such a pattern of inhibition by dicarboxylates is essentially the same with that observed in rat renal proximal tubules in situ. These findings suggest that the PAH transport system in OK cells has a substrate specificity similar to that in rat renal proximal tubules, which is involved in the active secretion of various organic anions including drugs.

Animals↗
PubMed1995

[Antegrade or retrograde blood cardioplegic method: comparison of postsurgical right ventricular function and conduction disturbances].

This study was undertaken to compare postsurgical right ventricular function and the occurrence of conduction disturbances after employing cold blood antegrade or retrograde cardioplegia during open heart surgery. Thirty-four patients were divided into AC (antegrade) and RC (retrograde) groups for the difference of route for delivery of cardioplegic solutions. Preoperative evaluation of cardiac and respiratory function revealed to be equal characteristics between the groups. Postoperatively, A-aDO2 and respiratory index (RI) as functional parameters of oxygenation capacity, LVSWI, RVSWI, dosage of dopamine and conduction disturbances were monitored at 0, 3, 6, 12 hours after termination of cardiopulmonary bypass and at extubation period. Although the recovery of respiratory function and left ventricular function were similar in both groups, temporal suppression of right ventricular function was indicated in RC group during early period after surgery, and then recovered to the same values of AC group within 3 hours. In RC group, several type of conduction disturbances were detected in 28 per cent of patients. But none of the persistent conduction disturbances were remained in all patients. We suggest retrograde coronary sinus perfusion may emerge as a valuable alternative to antegrade methods for delivery of cardioplegia.

Blood↗
PubMed1995

Transport of oral cephalosporins by the H+/dipeptide cotransporter and distribution of the transport activity in isolated rabbit intestinal epithelial cells.

Transport of cephalosporins was studied using isolated rabbit intestinal epithelial cells. Cephradine uptake by the cells was concentrative and was inhibited by the addition of glycylsarcosine. The accumulated cephradine was effluxed from the cells by the addition of a protonophore, carbonyl cyanide 4-trifluoromethoxyphenylhydrazone (FCCP). Amiloride, an inhibitor of the Na+/H+ exchanger, reduced the steady-state uptake of cephradine, suggesting that the exchanger contributes to the maintenance of an inward H+ gradient as a driving force. Cephradine uptake by ATP-depleted intestinal cells was actively driven by the inward H+ gradient and was inhibited by FCCP and glycylsarcosine. The distribution of cephradine transport activity along the small intestine and villus-crypt axis was also examined in the isolated cells, and the transport activity was higher in the upper parts of the intestinal segments and in villus cells. These results indicate that the uptake of oral cephalosporins by intestinal epithelial cells in concentrative and reversible and that the H+/dipeptide cotransporter and the Na+/H+ exchanger play an important role for the active uptake of these drugs. The activity of the H+/dipeptide cotransporter should be higher in upper segments and in villus cells of the small intestine.

Animals↗
PubMed1995

[A case of Mycobacterium avium disease presenting as a solitary pulmonary nodule and resected under a suspicion of lung cancer].

A 43 year old female smoker was admitted to our hospital for evaluation of solitary pulmonary nodule (SPN). She had no symptoms, and no past history or family history that might suggest compromised defense against pulmonary infections. Physical examination and laboratory findings including humoral and cell-mediated immunity revealed no abnormality. The chest radiography taken 2 years ago looked normal, but those on admission showed SPN in a left lower field. Computed tomography (CT) revealed solitary elipsoid nodule in S5. Because two trials of transbronchial biopsy, brushing and washing could not give any diagnostic findings, thoracotomy was performed under tentative diagnosis of lung cancer. The lesion was located in the outer portion of S5 and was found to consist of 2 elastic hard nodule surrounded by a atelectasis with inflammation. The nodule had supprative substance with several acid fast bacilli, and its intraoperative pathology revealed epitheloid cell granulomas. The lesion was resected completely. In a mean while, seventy smooth colonies grew on an Ogawa egg medium, which was identified as M. avium by the probe analysis using SNAP TEST. The final diagnosis of pulmonary M. avium disease was made, and the patient was administered RFP, EB, OFLX, and CAM in a outpatient clinic. Some discussions were also made about CT findings of pulmonary M. avium complex disease developed in patients without any predisposing conditions.

Adult↗
PubMed1995

[Comparison of postsurgical respiratory function employing either cold blood or crystalloid cardioplegia during open heart surgery].

This study was undertaken to compare postsurgical respiratory function after employing cold blood or cold crystalloid cardioplegia during open heart surgery. Fourty patients were divided into two groups for the difference of the cardioplegic solutions. Preoperatively, left ventricular stroke work index (LVSWI) and respiratory function test was evaluated. Postoperatively, A-a DO2 and respiratory index (RI) as functional parameters of oxygenation capacity, LVSWI and dosage of dopamine were monitored at 3, 6, 12, 18, 24 hours after cardiopulmonary bypass and at extubation period. The recovery of respiratory function and cardiac performance were superior in blood cardioplegia with a less accumulation of water in the pulmonary interstitium as a result of hemodilution effect.

Blood↗
PubMed1995

Cloning and characterization of a rat H+/peptide cotransporter mediating absorption of beta-lactam antibiotics in the intestine and kidney.

A complementary DNA (cDNA) encoding the rat H+/peptide cotransporter (PepT1) was isolated, and the transport characteristics of orally active beta-lactam antibiotics were assessed by measuring uptake into Xenopus oocytes expressing the rat PepT1. The rat PepT1 cDNA encoded a 710-amino acid protein with 77% identity to the rabbit PepT1. The message for rat PepT1 was approximately 2.9 kilobases and was found predominantly in the small intestine, whereas reverse transcription-polymerase chain reaction amplification revealed that the message was expressed both in the small intestine and in the kidney cortex. The 75-kDa protein was identified by translation of in vitro synthesized transcript of rat PepT1 cDNA by use of rabbit reticulocyte lysates and by Western blot analysis with a specific antibody against the rat PepT1. When expressed in Xenopus oocytes, rat PepT1 stimulated the uptake of ceftibuten (anion) and cephradine (zwitterion) in the presence of an inward H+ gradient, and the expressed uptake was inhibited by excess dipeptides. Kinetic analysis revealed that ceftibuten has 14-fold higher affinity for the rat PepT1 than cephradine. These findings suggest that the rat PepT1 mediates H(+)-coupled uphill transport of the oral beta-lactam antibiotics across the brush-border membranes of intestinal and renal proximal tubular cells.

Amino Acid Sequence↗
PubMed1995

[Krabbe disease (globoid cell leukodystrophy)].

Krabbe disease is an autosomal recessive inherited demyelinating disease, which is deficient in lysosomal enzyme, galactocerebrosidase. Pathophysiological characteristics of this disease are extreme demyelination in white matter and peripheral nerve, existence of globoid cells, absence of accumulation of main substrates, i.e. galactocerebrosidase in tissues and accumulation of psychosine. Molecular basis of this disease including isolation of a cDNA for human and murine galactocerebrosidase and cloning of genome of this gene are reviewed. The trial of gene therapy on twitcher, the mouse model of Krabbe disease, could break through on therapy on this progressive demyelinating disease.

Animals↗
PubMed1995

[The metabolism of radiolabelled GM1-ganglioside in cultured skin fibroblasts from controls and patients with GM1-gangliosidosis].

The metabolism of [3-3H-sphingosine] GM1-ganglioside was studied in cultured skin fibroblasts from control and patients with beta-galactosidase deficiency, primarily or secondarily. When dissolved in the medium with phosphatidylserine, GM1-ganglioside was efficiently taken up by cultured skin fibroblasts and transferred into lysosomes. A pulse-chase study revealed that [3-3H-sphingosine] GM1-ganglioside was metabolized to GM2-, GM3-ganglioside, ceramide, ceramide monohexoside, ceramide dihexoside and sphingomyelin. In a 20h pulse study, cell lines from patients with GM1-gangliosidosis of infantile, juvenile and adult types hydrolyzed 2 approximately 5%, 20 approximately 44% and 54 approximately 58% of the total endocytosed GM1-ganglioside respectively. These values were lower than in the control cells (62.2 +/- 5.43% (n=10). The hydrolysis rates of exogenous [3-3H-sphingosine] GM1-ganglioside in cultured skin fibroblasts from various types of GM1-gangliosidosis closely correlated to the clinical severity. This method is also useful to the diagnosis of impaired ganglioside metabolism.

Cells, Cultured↗
PubMed1994

Functional evidence for an apical ANP receptor in LLC-PK1 kidney epithelial cells.

The localization of natriuretic peptide receptors was studied in LLC-PK1 cell monolayers grown on a micro-porous membrane filter. The addition of alpha-human atrial natriuretic peptide (alpha-hANP) to the apical side of the cells produced a concentration-dependent increase in cyclic GMP (cGMP) formation, the extent of which was similar to that produced by the addition to the basolateral side. More cGMP was formed with alpha-hANP (1 and 100 nM) than with the C-type natriuretic peptide (100 nM). These findings indicate that the biologically active receptors with high efficacy for alpha-hANP are expressed in both the apical and basolateral membranes in LLC-PK1 cells.

Animals↗
PubMed1994

Functional and morphological abnormalities of mitochondria in human cells containing mitochondrial DNA with pathogenic point mutations in tRNA genes.

mtDNA with a point mutation in the tRNA(Ile) gene at nucleotide position 4269 found in a patient with fatal cardiomyopathy and mtDNA with a point mutation in the tRNA(Arg) gene at 10410 found in a patient with Alpers disease were transferred cytoplasmically to rho zero HeLa cells (HeLa cells lacking mtDNA) to determine whether these novel mtDNA mutations in the tRNA genes are responsible for the defects in mitochondrial respiration function observed in these diseases. Cybrid clones (clones of rho zero HeLa cells with mtDNA from the patients) were isolated, and respiratory function and morphology of the mitochondria of the cybrid clones containing wild-type mtDNA and mutant mtDNA predominantly were compared. The results showed that accumulation of mutant mtDNA at 4269 alone without defects in the nuclear genome was sufficient to produce a disease phenotype, while mutant mtDNA at 10410 was not related to pathogenesis and reflected one of the rare polymorphic sites of human mtDNA. Moreover, we found that mitochondria in living cells were significantly swollen only when they contained predominantly the pathogenic mutant mtDNA, suggesting that the functional abnormality of mitochondria induced by pathogenic mtDNA mutations in tRNA genes is always associated with their swollen structure.

Cardiomyopathies↗
PubMed1994

Facilitation of the arterial baroreflex by the ventrolateral part of the midbrain periaqueductal grey matter in rats.

1. The effects of stimulation of the ventrolateral part of the midbrain periaqueductal grey matter (PAG) on the arterial baroreflex were investigated in urethane-chloralose anaesthetized and artificially ventilated rats. 2. Both electrical and chemical stimulation of the ventrolateral PAG provoked hypotension, vagal bradycardia and marked facilitation of baroreflex vagal bradycardia (BVB), which was induced by stimulation of the aortic depressor nerve. The magnitude of ventrolateral PAG facilitation of BVB was 328 +/- 193% (n = 34) for electrical stimulation and 243 +/- 224% (n = 13) for chemical stimulation. Baroreflex hypotension was slightly augmented during either electrical or chemical stimulation of the ventrolateral PAG in vagotomized rats. 3. Stimulation of the nucleus raphe magnus (NRM) also provoked hypotension, vagal bradycardia and facilitation of BVB. The magnitude of BVB facilitation was 234 +/- 132% (n = 8) for electrical stimulation and 328 +/- 170% (n = 7) for chemical stimulation. After microinjection of kainic acid into the NRM region, baroreflex facilitation, as well as hypotension and vagal bradycardia, produced by ventrolateral PAG stimulation, was almost abolished. 4. In conclusion, the ventrolateral PAG, besides producing hypotension and bradycardia, facilitates arterial baroreflexes. These effects are exerted via the NRM, sharply contrasting with effects of the dorsal PAG.

Animals↗
PubMed1994

Bestatin transport in rabbit intestinal brush-border membrane vesicles.

The effect of papain treatment on bestatin uptake by rabbit intestinal brush-border membrane vesicles (BBMVs) was studied. Papain treatment of BBMVs effectively diminished aminopeptidase activity but not bestatin uptake by a H+/dipeptide cotransporter. Bestatin uptake by BBMVs was composed of two saturable components, and after papain treatment the high-affinity component disappeared while the low-affinity component was retained. These findings suggest that high- and low-affinity components represent bestatin binding to aminopeptidase and the true uptake by the H+/dipeptide cotransporter, respectively.

Adjuvants, Immunologic↗
PubMed1994

Krabbe disease: isolation and characterization of a full-length cDNA for human galactocerebrosidase.

Human galactocerebrosidase, the enzyme deficient in Krabbe disease, was purified, through several hydrophobic column steps and gel filtration, 22,650-fold from human lymphocytes. Using information on its N-terminal and internal amino acid sequences, and the polymerase chain reaction method, we cloned a full-length cDNA for the enzyme. The deduced amino acid sequence matched all amino acid sequences determined. The 3780 nucleotide sequence included 2007 nucleotides which encoded a single chain peptide of 669 amino acid residues with a 26 amino acid N-terminal signal peptide and six potential asparagine-linked glycosylation sites. The galactocerebrosidase cDNA detected an about 4 kb mRNA band material in human cultured skin fibroblasts. A nonsense mutation was found at codon 369 (GAA-->TAA) in the coding sequence of cDNA amplified from cultured skin fibroblast mRNA from a patient with typical Krabbe disease.

Amino Acid Sequence↗
PubMed1994

Diagnosis of carbohydrate-deficient glycoprotein syndrome by matrix-assisted laser desorption time-of-flight mass spectrometry.

Serum transferrin from patients with carbohydrate-deficient glycoprotein syndrome was analysed by matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF mass spectrometry). Abnormal molecular species with a defect of one or two oligosaccharide chains of 2200 Da were clearly identified. MALDI-TOF mass spectrometry will serve to diagnose this aetiologically unknown, metabolic disease.

Carbohydrate Metabolism, Inborn Errors↗