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Biomedical subjects

K Inui

Publications and source records attributed to K Inui.

At least 289 records · Page 16Linked to original sources
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↗
PubMed1994

An in vitro evaluation of prostaglandin E1 and I2 on hypothermic injury to immature myocytes.

The purpose of this study was to evaluate the functional and biochemical effects of Prostaglandin E1 (PGE1) and prostaglandin I2 (PGI2) on cardiac myocytes incubated under hypothermic conditions. Cardiac myocytes were isolated from neonatal rat ventricles and cultured for 4 days with MCDB 107 medium. Following this, 12.5 x 10(5) myocytes/flask were incubated at 4 degrees C for 24 h in media with PGE1, at concentrations of 0 M (group E0), 10(-9) M (group E1), 10(-8) M (group E2), 10(-7) M (group E3), or 10(-6) M (group E4); or with PGI2 at concentrations of 0 M PGI (group I0), 10(-9) M (group I1), 10(-8) M (group 12), 10(-7) M (group I3), or 10(-6) M (group I4). After hypothermic incubation, creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) were measured, and the myocytes were then cultured for 24 h at 37 degrees C to evaluate the recovery of the myocyte beating rate. Of the PGI2 groups, only group I2 recovered significantly more than the control group (group I0), at 47.9 +/- 28.5% (mean +/- SD) of the control, being the beating rate prior to hypothermic incubation, whereas it was 18.1 +/- 9.7% in group I0 (P < 0.025); however, there were no significant differences among the PGE1 groups. Moreover, the release of CPK and LDH was significantly suppressed in group 12 compared to the control, being 57.7 +/- 27.6 mIU/flask (P < 0.05) and 275.1 +/- 83.0 mIU/flask (P < 0.025), respectively, in group I2, and 96.8 +/- 38.3 mIU/flask and 439.6 +/- 147.1 mIU/flask in group I0. Again, no significant differences were observed among the PGE1 groups. In conclusion, PGI2 was found to have a direct cytoprotective effect on immature myocytes which suggests that PGI2 may promote cardiac preservation in the neonatal period.

Alprostadil↗
PubMed1994

Five-year results of a randomized clinical trial comparing modified radical mastectomy and extended radical mastectomy for stage II breast cancer.

A controlled cooperative study was carried out to assess the value of modified radical mastectomy for patients with stage II breast cancer. The data was analyzed from 11 institutions in the Shikoku District participating in a prospective clinical trial in which patients were randomly assigned either to a modified radical mastectomy group or an extended radical mastectomy group. These two groups of patients were similar to each other in terms of such background factors as age distribution, menopausal status, TNM classification, tumor size, location of the primary tumor, axillary nodal involvement, histological type, and estrogen receptor status. The median follow-up times in the modified and extended radical mastectomy groups were 4.7 and 4.5 years, respectively. The cumulative curves indicated no difference between the two groups in either disease-free survival or overall survival. The survival rates were classified according to the presence or absence of axillary nodal metastases. However, no significant difference was found between the two groups. These findings thus suggest that the routine removal of the grossly uninvolved major pectoral muscle and parasternal lymph nodes is not necessary in patients with stage II breast cancer.

Adenocarcinoma↗
PubMed1994

Arterial baroreflex inhibition by uterine distension in rats.

Arterial baroreflexes are inhibited during activation of some viscero-sensory receptors. The present study was designed to determine whether stimulation of mechanoreceptors of the uterus also inhibits the baroreflex bradycardia (BB). The aortic depressor nerve (ADN) was electrically stimulated to elicit BB in chloralose/urethane-anesthetized, succinylcholine-immobilized, and artificially ventilated rats. Hydraulic distension of the uterus with warm 0.9% NaCl solution was found to suppress BB with a threshold intra-uterine pressure of 25-100 mmHg. The inhibition was variably affected by successive transections of the hypogastric nerve (HgN) and the pelvic nerve (PN). In 6 rats out of the 16 tested, preceding transection of either HgN or PN (HgN, 4; PN, 2) abolished the inhibition, whereas in 8 rats the inhibition was not affected by preceding transection of either nerve but was abolished by subsequent transection of the other nerve (PN, 3; HgN, 5). In 2 rats, preceding HgN or PN section reduced the inhibition and subsequent PN or HgN section completed the withdrawal of the inhibition. Recording study confirmed that both the HgN and PN contain afferent fibers, signalling mechanoceptive information arising in the uterine wall. Electrical stimulation of the HgN as well as the PN remarkably suppressed the BB. In conclusion, uterine distension suppresses the BB and this inhibition is mediated by afferent fibers running in the HgN and PN with variable contributions among animals. The reflex suppression of BB due to uterine sensory activation may contribute to cardiovascular regulation during parturition.

Animals↗
PubMed1994

Baroreceptor inhibition of the locus coeruleus noradrenergic neurons.

The locus coeruleus is involved in the regulation of blood pressure. The present study was undertaken to address the question of how the blood pressure, in turn, changes the activity of the locus coeruleus neurons via the action of baroreceptors. In chloralose- and urethane-anesthetized rats, the central cut end of the aortic depressor nerve, which does not contain chemoreceptor afferents in this species, was stimulated electrically to excite baroreceptor afferents after bilateral vagotomy and sectioning of the carotid sinus nerve. Single train-pulse stimulation of the aortic depressor nerve provoked the inhibition of ongoing activity in 48% of locus coeruleus neurons tested, but 30% of them responded by excitation with subsequent inhibition. However, when the train-pulse stimulation was repeated with a frequency of 5 Hz, which is close to that of the heartbeat in the rat, all neurons were markedly inhibited. Another series of experiments was conducted in vagotomized and carotid sinus nerve-sectioned rats with intact aortic depressor nerves. When blood pressure was elevated by an intravenous injection of a pressor agent, methoxamine or angiotensin II, or by rapid blood loading, ongoing activities of all locus coeruleus neurons tested were suppressed. In contrast, intravenously injected nitroprusside, a depressor agent, increased the activity of locus coeruleus neurons. In rats with all nerves preserved, rapid blood loading markedly inhibited the activity of these neurons. Such inhibition was partially but significantly attenuated by bilateral sectioning of the aortic depressor nerves.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Omentoplasty for postpneumonectomy bronchopleural fistulas.

Postpneumonectomy fistula is one of the most serious complications in general thoracic surgery and remains difficult to manage. From 1984 to 1991, we successfully used pedicled omentum for the treatment of postpneumonectomy bronchopleural fistulas (omentoplasty) in five patients, four of whom had thoracic empyema. For bronchopleural fistulas without early postoperative infection, single-stage closure was performed which was then covered with pedicled omentum. Omentoplasty was performed successfully in patients with thoracic empyema, after open or closed drainage. Open thoracotomy was useful when closed drainage was ineffective. Even after open thoracotomy, closure of the wound was achieved. All five patients could be discharged. Omentoplasty was useful in the therapy of postpneumonectomy bronchopleural fistula even in the presence of thoracic empyema.

Aged↗
PubMed1994

A new method of real-time endoscopic measurement with an electric catheter.

A new method for measuring distances using electrically charged jets of water is described, and its precision examined. When combined with endoscopy, this method can be utilized to measured the lengths and areas of objects inside human body cavities. The apparatus used consists of a catheter with three metal needles at the tip, a personal computer, and a commercially available videoendoscopy system. To test the system, a regulated voltage was passed between the catheter tip and a wooden board, and two salt solutions of different concentrations were ejected at three different angles from the catheter to the board. The coordinates of the board were then computed from the amperages of the currents passing through the three jets of saline, and optical distortion was corrected using the computer. The length and area of an object could be measured rapidly by setting electrically the coordinates to match the endoscopic image. Lengths ranging from 10 to 50 mm were measured while varying the distance between catheter tip and board (10, 20, and 30 mm), as well as the angle formed by the catheter and the board (45, 60, and 90 degrees). The mean measurement error was less than 5.6% and accuracy was relatively independent of the angle between catheter and target.

Catheterization↗
PubMed1994

Purification and characterization of galactocerebrosidase from human lymphocytes.

Galactocerebrosidase was purified about 22,600-fold using several hydrophobic column and gel filtration steps with a 4.8% recovery, from human lymphocytes. Its specific activity was 1.54 x 10(5) nmol/h/mg with tritium-labeled galactocerebroside as the substrate in the taurocholate system. The optimal pH for galactocerebroside was 4.2 in the taurocholate system and 4.6 in the cholate system. The Km values for galactocerebroside were 5 microM in the taurocholate system and 25 microM in the cholate system. The molecular weight of the purified enzyme was estimated to be 90 kDa by sodium dodecylsulfate polyacrylamide gel electrophoresis and gel filtration. However, 70, 50, 40, and 30 kDa bands were also recognized on SDS-PAGE. The N-terminal amino acid sequences of the 70 kDa molecule and the three 50 kDa molecules were the same as that of the 90 kDa molecule. The N-terminal amino acid sequences of the 40 and 30 kDa molecules were unique. A monoclonal antibody raised against the purified enzyme effectively immunoprecipitated galactocerebrosidase activity, and an affinity column prepared with this monoclonal antibody bound the 90 and 50 kDa proteins. These results suggest that this enzyme is probably processed from the 90 kDa protein.

Amino Acid Sequence↗
PubMed1994

Immunochemical study of epidermal growth factor in rats with mercuric chloride-induced acute renal failure.

Urine contains high concentrations of epidermal growth factor (EGF), and EGF is a potent growth promoter for proximal tubular cells. In the present study, urinary and whole-kidney EGF levels were investigated in rats with mercuric chloride (HgCl2)-induced acute renal failure (ARF) using a specific radioimmunoassay for rat EGF to clarify changes in EGF after toxic injury. Male Wistar rats were given HgCl2 (2 mg/kg, subcutaneously) or saline. Serum urea nitrogen and creatinine levels were measured for 4 days after toxin administration. Forty-eight hours after toxic injury, urinary immunoreactive EGF levels in HgCl2-treated rats decreased significantly compared with control rats (1.62 +/- 0.15 versus 3.78 +/- 0.21 ng/mg creatinine; p < 0.01). Urinary immunoreactive EGF was at its lowest level 96 h after toxic injury (0.64 +/- 0.06 ng/mg creatinine; p < 0.001). Twenty-four hours after toxic injury, renal immunoreactive EGF levels increased significantly compared with control rats (22.04 +/- 2.12 versus 4.84 +/- 0.70 ng/g wet weight tissue; p < 0.001), and the increase persisted for as long as 48 h (13.36 +/- 1.61 ng/g wet weight tissue; p < 0.05). In summary, urinary immunoreactive EGF levels decreased and renal EGF levels increased in rats with HgCl2-induced ARF. These findings suggest that there is an impairment in the excretion of EGF in rats with HgCl2-induced ARF and that local paracrine production of EGF continues in ARF.

Acute Kidney Injury↗
PubMed1994

Effect of recombinant human adult T cell leukemia-derived factor on rat lung reperfusion injury.

The formation of reactive oxygen species (ROS) is a major factor responsible for reperfusion injury in lungs. Adult T cell leukemia derived factor (ADF), a polypeptide made of 104 amino acids, is induced by a variety of stresses including X-ray, ultraviolet, H2O2, and mitogen. ADF has a reducing activity, which catalyzes the proton transfer between thiol-radical of cystein-containing proteins. Furthermore, ADF has a protective activity of ROS which are formed by xanthine oxidase and other alternative pathways in vitro. Using a rat in vivo model of lung ischemia, we examined the protective effect of recombinant human ADF (rhADF) against ischemia reperfusion injury of the lung. Ischemia, lasting for 75 min, was induced in the left lung of rats at 23 degrees C. The lung was then reperfused. These animals were divided into two groups: group 1 (n = 6, treatment with normal saline) and group 2 (n = 6, treatment with 28 micrograms/g of rhADF). One minute after the beginning of reperfusion, arterial oxygen tension (PaO2) decreased significantly in both groups (p < 0.01), without any significant intergroup difference (55.5 +/- 9.8, 49.8 +/- 8.6 mm Hg, respectively). Twenty minutes after reperfusion, PaO2 was significantly higher (p < 0.05) in group 2 (113.0 +/- 8.1 mm Hg) than in group 1 (72.3 +/- 13.6 mm Hg). The wet/dry weight ratio was significantly higher in group 1 (7.31 +/- 0.54) than in group 2 (5.82 +/- 0.36). Histologically, lung injury tended to be milder in group 2 than in group 1. These results suggest that rhADF has a protective effect against ischemia reperfusion injury of the rat lung.

Animals↗
PubMed1994

Cloning, characterization, and chromosomal mapping of human aquaporin of collecting duct.

We recently cloned a cDNA of the collecting duct apical membrane water channel of rat kidney, which is important for the formation of concentrated urine (Fushima, K., S. Uchida, Y. Hara, Y. Hirata, F. Marumo, and S. Sasaki. 1993. Nature [Lond.]. 361:549-552). Since urine concentrating ability varies among mammalian species, we examined whether an homologous protein is present in human kidney. By screening a human kidney cDNA library, we isolated a cDNA clone, designated human aquaporin of collecting duct (hAQP-CD), that encodes a 271-amino acid protein with 91% identity to rat AQP-CD. mRNA expression of hAQP-CD was predominant in the kidney medulla compared with the cortex, immunohistochemical staining of hAQP-CD was observed only in the collecting duct cells, and the staining was dominant in the apical domain. Functional expression study in Xenopus oocytes confirmed that hAQP-CD worked as a water channel. Western blot analysis of human kidney medulla indicated that the molecular mass of hAQP-CD is 29 kD, which is the same mass expected from the amino acid sequence. Chromosomal mapping of the hAQP-CD gene assigned its location to chromosome 12q13. These results could be important for future studies of the pathophysiology of human urinary concentration mechanisms in normal and abnormal states.

Amino Acid Sequence↗
PubMed1994

Preventive effect of betamipron on nephrotoxicity and uptake of carbapenems in rabbit renal cortex.

The preventive effect of betamipron (N-benzoyl-3-propionic acid: BP) on the renal uptake and nephrotoxicity of carbapenems (panipenem and imipenem) was studied in rabbits. Panipenem, a new carbapenem antibiotic, induced nephrotoxicity at a dose of 200 mg/kg, i.v., but this was less severe than that caused by a single dose of imipenem or cephaloridine. Along with the significant reduction of nephrotoxicity, the uptake of these carbapenems in the renal cortex was remarkably inhibited by simultaneous treatment with BP (200 mg/kg, i.v.). These results suggest that BP reduces the nephrotoxicity of carbapenems through inhibiting the active transport of carbapenems in the renal cortex. Because of the low toxicity of BP (LD50 in the rat, more than 3,000 mg/kg, i.v.), it was concluded that BP might be a good candidate for reducing the nephrotoxicity induced by panipenem or imipenem.

Alanine↗
PubMed1994

Evaluation of immature cardiac myocyte viability after 24 hours of hypothermic preservation.

In this study, we evaluated cardiac myocyte viability and function under hypothermic conditions using three types of storage solutions; saline solution (SS), Euro-Collins solution (ECS) and MCDB 107 medium (MM). Cardiac myocytes were isolated from neonatal rat ventricles by collagenase dispersion and cultured for 4 days with MCDB 107 medium. A total of 12.5 x 10(5) myocytes/culture dish were used and the myocytes were incubated at 4 degrees C for 6, 12, 18 and 24 hrs in the various storage solutions. After each incubation time, CPK and LDH were measured in the storage solutions. The myocytes were then cultured in MCDB 107 medium and incubated for 24 hrs at 37 degrees C to evaluate the recovery of the myocyte beating rate. In group MM (n = 7), the recovery ratio of the myocyte beating rate was 99.2 percent of control (beating rate prior to hypothermic incubation) at 6 hours, 104.6% at 12 hrs and 44.8% at 24 hrs. Groups SS and ECS (n = 7 each) had significantly lower recovery ratios than the MM group (at 6 hrs: 74.3, 34.0; at 12 hrs: 61.0, 32.2; at 24 hrs: 0.0, 0.0 percent of control, respectively). Release of CPK and LDH in the MM group gradually increased and at 24 hrs was 28.6 IU/l and 93.6 IU/l, respectively. However, the SS group had significantly increased CPK and LDH values at 24 hrs (CPK: 66.9, LDH: 164.2). The ECS group showed the greatest increase in both markers (CPK: 317.5, LDH: 421.2). In summary, saline solution showed a beneficial effect on recovery of myocyte viability at 12 hours compared to Euro-Collins solution, however, MCDB 107 medium had the best overall protective effect on cultured myocytes. Accordingly, alternate hypothermic storage solutions, such as cell-culture medium, may have protective characteristics that are suitable for cardiac preservation.

Amino Acids↗
PubMed1994

[Palliative surgery of congenital heart disease in early infancy].

A total of 38 patients aged under 3 months with congenital heart disease (CHD) underwent palliative surgery between April, 1988 and March, 1993. The mean age at operation was 28.0 (range 1 to 87) days. Palliative procedures were: pulmonary artery banding (PAB) in 14 patients (IAA complex: 4, CoA complex: 6, AVSD: 2, TA: 2), Blalock-Taussig shunt (BTS) in 12 (TOF: 2, TGA: 1, AVSD: 1, PA-IVS: 3, PA-VSD: 3, PA-SV: 1, PA-AVSD: 1), Brock operation in 6 (PPS: 2, PA-IVS: 3, PA-SV: 1), Blalock-Hanlon operation (BH) with PAB in 2 (MA-SV: 2) and Norwood operation (NRD) in 4 (HLHS: 4). PAB of IAA or CoA complex was performed just after the repair of IAA or CoA. Overall operative mortality was 23% (PAB: 14.3, BTS: 8.3, Brock: 33.3, NRD: 100%). One week after PAB, pulmonary artery pressure (PAP) decreased significantly compared to the intraoperative PAP value after PAB (43.1 +/- 16.2, 32.3 +/- 9.0 mmHg, p < 0.05, respectively). Pulmonary artery index (PAI), which is an index of pulmonary artery growth, after BTS increased significantly compared to the preoperative value (mean follow-up interval: 22.1 months) (379.5 +/- 101.4, 159.3 +/- 51.2, p < 0.001, respectively). During Brock operation, balloon catheter was used in order to dilate pulmonary valve. One year after Brock operation, mean pressure gradient through the pulmonary valve 22.6 mmHg. Two-staged corrections of CHD will be performed both safely and successfully by effective palliations at the first stages in early infancy.

Cardiac Surgical Procedures↗
PubMed1994

Human P-glycoprotein as a multi-drug transporter analyzed by using transepithelial transport system.

To analyze the mechanism of drug transport, mechanism of inhibitors, and physiological substrates of human P-glycoprotein, we established a transepithelial transport system by introducing MDR1 cDNA into LLC-PK1, a pig kidney epithelial cell line. P-glycoprotein functions as a steroid transporter as well as a drug transporter as physiological functions. P-glycoprotein also transports MDR modulators such as cyclosporin A, FK506, and calcium channel blockers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗