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Biomedical subjects

K Inui

Publications and source records attributed to K Inui.

At least 199 records · Page 11Linked to original sources
PubMed1997

Inhibition of PAH transport by parathyroid hormone in OK cells: involvement of protein kinase C pathway.

We have previously shown that the p-aminohippurate (PAH) transport system in OK kidney epithelial cell line is under the regulatory control of protein kinase C. Parathyroid hormone (PTH) could activate protein kinase C, as well as protein kinase A, in OK cells. In the present study, the effect of PTH on PAH transport was studied in OK cells. PTH inhibited the transcellular transport of PAH from the basal to the apical side, as well as the accumulation of PAH in OK cells. Basolateral PAH uptake was inhibited by PTH in a dose- and time-dependent manner. Protein kinase A activators did not affect the transcellular transport or the accumulation of PAH. The PTH-induced inhibition of the accumulation of PAH was blocked by a protein kinase C inhibitor staurosporine. These results suggest that PTH inhibits the PAH transport in OK cells and that the messenger system mediated by protein kinase C, not protein kinase A, plays an important role in the regulation of PAH transport by PTH.

1-Methyl-3-isobutylxanthine↗
PubMed1997

Recognition of beta-lactam antibiotics by rat peptide transporters, PEPT1 and PEPT2, in LLC-PK1 cells.

PEPT1 and PEPT2 are H(+)-coupled peptide transporters expressed preferentially in the intestine and kidney, respectively, which mediate uphill transport of oligopeptides and peptide-like drugs such as beta-lactam antibiotics. In the present study, we have compared the recognition of beta-lactam antibiotics by LLC-PK1 cells stably transfected with PEPT1 or PEPT2 cDNA. Cyclacillin (aminopenicillin) and ceftibuten (anionic cephalosporin without an alpha-amino group) showed potent inhibitory effects on the glycylsarcosine uptake in the PEPT1-expressing cells. Other beta-lactams, such as cephalexin, cefadroxil, and cephradine (aminocephalosporins), inhibited modestly the PEPT1-mediated glycylsarcosine uptake. Except for ceftibuten, these beta-lactams showed much more potent inhibitions on the glycylsarcosine uptake via PEPT2 than via PEPT1. Comparison of the inhibition constant (Ki) values between cefadroxil and cephalexin suggested that the hydroxyl group at the NH2-terminal phenyl ring increased affinity for both PEPT1 and PEPT2. It is concluded that PEPT2 has a much higher affinity for beta-lactam antibiotics having an alpha-amino group than PEPT1 and that substituents at the NH2-terminal side chain of these drugs are involved in the recognition by both peptide transporters.

Animals↗
PubMed1997

[The studies of extracorporeal shock wave lithotripsy (ESWL) for pancreatic ductal stones].

30 patients with main pancreatic duct stones were treated by ESWL. In 18 of 22 patients who had not previously undergone endoscopic pancreatic sphincterotomy (EPST) or endoscopic sphincterotomy (EST), the stone fragments disappeared after ESWL. The fragments were removed endoscopically in the remaining 4 cases. Complete clearance was achieved in 8 cases with endoscopically unextractable stones by ESWL. After the ESWL procedure, absolute relief from pain was reported by in 19 of 22 patients with abdominal complaints. Serum amylase levels decreased significantly, and dilatation of the main pancreatic duct (MPD) was reduced. In the medium-term follow-up period, pancreatic exocrine function and endocrine function had a possibility to be preserved. One case of pancreatic cancer and one case of an intraductal papillary tumor of the pancreas were found, indicating that careful observation is necessary even after complete removal of pancreatic stones. In cases of Santorini duct dominant, multiple stones, or stricture of the MPD, ESWL should be combined with EPST and endoscopic stenting for preventing recurrence of acute pancreatitis and pancreatic stones. In conclusion, ESWL is the first choice of treatment for pancreatolithiasis and useful procedure and the limited complications.

Adult↗
PubMed1997

Characterization of stably transfected kidney epithelial cell line expressing rat H+/peptide cotransporter PEPT1: localization of PEPT1 and transport of beta-lactam antibiotics.

We established stably transfected LLC-PK1 cells expressing the rat H+/peptide cotransporter PEPT1 (designated LLC-rPEPT1) and examined membrane localization and uptake by rat PEPT1 of oral beta-lactam antibiotics. The LLC-rPEPT1 cells expressed a novel PEPT1 protein with an apparent molecular mass of 75 kdaltons, which was found in rat intestinal membranes. The cell surface biotinylation of LLC-rPEPT1 cell monolayers grown on membrane filters showed that PEPT1 was localized predominantly on the apical membranes and, to a lesser extent, on the basolateral membranes. The amount of [14C]glycylsarcosine uptake in LLC-rPEPT1 cell monolayers was 3-fold greater from the apical, than from the basolateral side, which suggested that rat PEPT1 expressed on both membranes was functionally active. LLC-rPEPT1 cells grown on plastic dishes transported differently charged oral cephalosporins such as ceftibuten (divalent anion lacking an alpha-amino group) and cephradine (zwitterion with an alpha-amino group) in the presence of an inward H+ gradient, whereas those transfected with the vector alone did not have transport activity. Kinetic analysis revealed that the LLC-rPEPT1 cells had much higher affinity for ceftibuten than for cephradine. Di- and tripeptides and bestatin, a dipeptide-like antineoplastic drug, potently inhibited the uptake of these cephalosporins. These results suggest that the LLC-rPEPT1 cells serve as a useful model with which to analyze the mechanisms involved in membrane targeting and substrate recognition by rat PEPT1.

Animals↗
PubMed1996

Cholesterol modulates organic cation transport activity and lipid fluidity in rat renal brush-border membranes.

The role of cholesterol in organic cation transport was studied in rat renal brush-border membranes. H+ gradient-dependent uptake of the organic cation tetraethylammonium in brush-border membrane vesicles was stimulated by cholesterol enrichment in a dose-dependent manner. The dissipation rate of the H+ gradient, a driving force for organic cation transport in brush-border membranes, was reduced by cholesterol enrichment. Tetraethylammonium uptake in the absence of H+ gradient was also stimulated by cholesterol enrichment. These findings indicate that cholesterol modulates tetraethylammonium uptake by affecting the intrinsic activity of the organic cation transporter and the H+ gradient dissipation rate. Therefore, cholesterol content should be an important determinant for organic cation transport in renal brush-border membranes.

Animals↗
PubMed1996

cDNA cloning and functional expression of a novel rat kidney organic cation transporter, OCT2.

A cDNA encoding a novel organic cation transporter, designated as OCT2 was isolated from the rat kidney. The rat OCT2 cDNA (2,205 bp) had an open reading frame encoding for a 593-amino acid protein (calculated molecular mass of 66 kDa) which shows 67% identity with the rat OCT1. Northern hybridization and reverse transcription-PCR analyses revealed that the rat OCT2 mRNA transcript was expressed predominantly in the kidney, at higher level in the medulla than in the cortex, but this transcript was not detected in the brain, heart, lung, liver, small intestine or spleen. When expressed in Xenopus oocytes, rat OCT2 stimulated the uptake of tetraethylammonium, and the uptake was markedly inhibited by the presence of cimetidine, procainamide and quinidine. These findings suggest that OCT2 is responsible for the transport of cationic drugs in the kidney.

Amino Acid Sequence↗
PubMed1996

Molecular cloning and tissue distribution of rat peptide transporter PEPT2.

A cDNA encoding rat H(+)- coupled peptide transporter PEPT2 was isolated. The cDNA encoded a protein of 729 amino acids with 48% amino acid identity to the rat PEPT1. The mRNA expression of rat PEPT2 was predominant in the kidney. When expressed in Xenopus oocytes, rat PEPT2 stimulated the uptake of bestatin, a dipeptide-like drug.

Amino Acid Sequence↗
PubMed1996

Immuno-localization of H+/peptide cotransporter in rat digestive tract.

In the mammalian digestive tract, small peptides are absorbed by a H+-coupled peptide transport system. Using an antibody against the rat H+/peptide cotransporter (PepT1), we examined the localization of PepT1 immunohistochemically along the rat digestive tract. PepT1 was detected in the small intestine (duodenum, jejunum, and ileum), but not in the esophagus, stomach, colon, or rectum. PepT1 was especially enriched in the villi, where it was localized in the brush border of the absorptive epithelial cells. PepT1 was not detected in the mucus-secreting goblet cells or less-differentiated epithelial cells in the crypts. These observations show that PepT1 is specific to the brush border of the differentiated absorptive epithelial cells and suggest that H+-coupled uptake of small peptides and peptide-like drugs occurs at the apical membrane of these cells in the small intestine.

Animals↗
PubMed1996

Expression of epidermal growth factor and its receptor in rabbits with ischaemic acute renal failure.

Urinary immunoreactive epidermal growth factor (EGF) levels decrease, and renal immunoreactive EGF levels increase in rats with ischaemic acute renal failure (ARF). We investigated the immunohistochemical localization of EGF and EGF receptor in rabbits with ischaemic ARF to clarify the significance of renal EGF. Male New Zealand White rabbits underwent right nephrectomy prior to a 60 min renal artery clamp. At 3, 6, 24, 48, 72 and 96 h after ischaemia, serum urea nitrogen and serum creatinine were determined. Guinea pig anti-rabbit EGF antibody and monoclonal anti-EGF receptor antibody were used for the primary incubation. EGF was immunolocalized to the ascending limb of Henle and the distal convoluted tubule in the normal right kidneys. However, in the post ischaemic left kidneys at 6, 24, 48 and 72 h, immunoreactivity of EGF was associated with proximal tubules. In the normal kidneys, antibody to EGF receptor reacted with distal tubules and collecting ducts. In the ischaemic kidneys, EGF receptor was localized in the basolateral membrane in the proximal tubules. The expression of EGF and EGF receptor in renal tubules may play an important role in repair following ischaemic renal damage.

Acute Kidney Injury↗
PubMed1996

Resection of primary pulmonary hemangiopericytoma: a report of two cases.

We report herein the cases of two patients who underwent resection of a primary pulmonary hemangiopericytoma. The first patient was a 58-year-old man found to have a mass-like shadow of about 5 cm in diameter in the right hilum by a routine chest X-ray. Subsequent magnetic resonance imaging (MRI) showed a probable mediastinal tumor, and surgery was performed. Postoperative pathological examinations confirmed the diagnosis of pulmonary hemangiopericytoma. The second patient was a 21-year-old woman found to have a mass-like shadow of about 2 cm in diameter in the left middle lung field. As a preoperative diagnosis could not be made, exploratory surgery was performed and the left S6 segment was excised. A definitive diagnosis of pulmonary hemangiopericytoma was established postoperatively by pathological examination. Primary pulmonary hemangiopericytoma is an extremely rare type of tumor, with only 36 cases having been reported in the Japanese literature to date, including out 2 cases. A discussion following the case reports examines the sex, age, initial manifestations, sites, and methods of surgery employed in these 36 cases.

Adult↗
PubMed1996

The infeasibility of using ten-ring irradiated grafts for tracheal allotransplantation even with omentopexy.

In our previous study, we demonstrated that high-dose 60Co irradiation was able to prevent rejection of canine tracheal allografts. To determine the maximum possible length of these grafts, in the present study we attempted to transplant five-ring and ten-ring tracheal allografts in two groups of five dogs each. Either five or ten rings were excised from donor tracheas and irradiated with 100,000 cGy of 60Co. The irradiated tracheal grafts were transplanted to replace either five- or ten-ring sections of the mediastinal tracheas removed from the recipient dogs. The grafts were covered with omental pedicles and no immunosuppressants were used. Graft incorporation was achieved in four of the five dogs in the five-ring groups, and three of these dogs survived for more than 700 days. However, four of the five animals in the ten-ring group died from tracheostenosis accompanied by ischemia within 3 weeks. These findings demonstrate the impossibility of performing ten-ring tracheal allotransplantation using irradiated grafts, even with omentopexy.

Animals↗
PubMed1996

Allele frequencies of intragenic, and 5' and 3' markers of the dystrophin gene in Japanese families afflicted with Duchenne or Becker muscular dystrophy.

Using the polymerase chain reaction method (PCR), we examined the allele frequencies and heterozygosities of 7 polymorphic sites (pERT87, and CA polymorphisms in the 5' and 3' regions) of the dystrophin gene in 20 Japanese Duchenne muscular dystrophy and Becker muscular dystrophy (DMD or BMD) families consisting of 36 males, including 23 cases of DMD and BMD, and 28 females. The allele frequencies of three primer and enzyme sets in the pERT87 locus were well comparable to those in the previously reported Japanese female cases but different from in other countries. The frequencies of 5' markers of the dystrophin gene in Japanes were different from the reported Caucasian frequencies. As for 5'DYS-I and 5'DYS-II, the numbers of alleles in our cases were less than in Caucasians, and the heterozygosities of all three markers (5'DYS-I, II and III) were lower than in Caucasians. However, the 3'CA polymorphisms showed almost the same frequencies and heterozygosities as in Caucasians. All of our females showed a heterozygous pattern for at least one locus, with the combination of the seven markers. The usefulness of linkage analysis involving PCR methods with these intragenic, and 5' and 3' markers of the dystrophin gene in the carrier and prenatal diagnosis of DMD and BMD was confirmed by the successful prenatal diagnoses in 15 fetuses, the exception being one case considered to have a new mutation.

Alleles↗
PubMed1996

Alzheimer-type pathology in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS).

A 53-year-old Japanese woman with a point mutation in mitochondrial DNA (tRNALeu(UUR), nt3243) consistent with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) and Alzheimer-type brain pathology is reported. This woman had suffered myopathy and psychosis without any clinical evidence of, stroke-like episodes during the last 10 years of her life, and had died after an accident. At autopsy 30 h post mortem, a part of the brain was snap frozen for biochemical and histochemical studies, and the remaining part was processed for a routine examination and electron microscopy. In the brain there were no ischemic lesions. Instead, primitive/diffuse senile plaques were found throughout the brain, predominantly in the frontal and temporal lobes, while Alzheimer neurofibrillary tangles were found only in the parahippocampal gyrus. These plaques were positive for beta-protein and mostly negative for tau protein, ubiquitin, neurofilaments, alpha-choline acetyltransferase, and acetylcholinesterase. Mutations in codon 331 of the ND2 gene as well as codons 693, 713 and 717 of the beta-amyloid precursor protein gene, known to be responsible for some cases of familial Alzheimer disease, were not found. Furthermore, coincidental Down syndrome was ruled out by chromosome analysis. The results suggest a possible correlation between this mitochondrial DNA abnormality and Alzheimer-type pathology.

Alzheimer Disease↗
PubMed1996

Surgical treatment for invasive thymoma, especially when the superior vena cava is invaded.

BACKGROUND: We analyzed the operative outcome of extensive surgery for invasive thymoma, especially in those with thymomas invading the superior vena cava, the left innominate vein, or both. METHODS: We treated 41 patients with invasive thymoma, including 34 stage III, 5 stage IVa, and 2 stage IVb thymomas. Thirty-eight patients received radiotherapy preoperatively or postoperatively. In 12 patients with invasion of the superior vena cava or innominate vein, we performed angioplasty, reconstruction, or both. RESULTS: The overall 5-year survival rate was 77% and the 10-year survival rate was 59%. In the stage III group, there was a significant difference between those with complete and those with incomplete resection. Ten of 12 patients who had angioplasty with or without reconstruction of the superior vena cava or innominate vein survived without recurrence of the tumors. CONCLUSION: Angioplasty and vascular reconstruction are recommended because successful treatment for invasive thymomas depends on complete resection of the tumors.

Adolescent↗
PubMed1996

A newly developed solution enhances thirty-hour preservation in a canine lung transplantation model.

Ischemia and reperfusion cause the production of oxygen free radicals. These damage grafts or disrupt normal vascular homeostatic mechanisms, with a parallel reduction in endothelial nitric oxide and adenosine 3',5'-cyclic monophosphate levels. We hypothesized that lung preservation failure may be related to these events. To improve lung preservation, we prepared a new ET-Kyoto solution, which contains N-acetylcysteine (a radical scavenger), nitroglycerin (to elevate the nitric oxide level), and dibutyryl adenosine 3',5'-cyclic monophosphate (to elevate the adenosine 3',5'-cyclic monophosphate level) and examined its efficacy in a canine single-lung transplantation model. Lungs were flushed with new ET-Kyoto solution (group I, n = 9), basal ET-Kyoto solution (group II, n = 6), basal ET-Kyoto solution plus ethanol and propylene glycol (solvents of nitroglycerin; group III, n = 6), or low-potassium dextran glucose solution (group IV, n = 6), and stored at 4 degrees C for 30 hours. After left single-lung transplantation, the right main bronchus and right pulmonary artery were ligated and the functions of the transplanted lung were assessed for 6 hours. Arterial oxygen tension was significantly higher in group I than in groups II, III, and IV (p < 0.05). Peak inspiratory pressure and wet-to-dry lung weight ratio were significantly lower in group I than in groups II and IV (p < 0.01). Histologic and ultrastructural studies showed better preservation in group I than in groups II, III, and IV. We conclude that the new ET-Kyoto solution provides enhanced 30-hour lung preservation.

Animals↗