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Biomedical subjects

K Murata

Publications and source records attributed to K Murata.

At least 271 records · Page 15Linked to original sources
PubMed1997

The 3.0 A projection structure of microsomal glutathione transferase as determined by electron crystallography of p 21212 two-dimensional crystals.

Two-dimensional crystals of rat microsomal glutathione transferase were grown during dialysis of detergent-solubilized enzyme after addition of a small amount of phospholipid. The crystals had two-sided plane group symmetry p21212 with a calibrated unit cell size of a=91.90 A, b=90.83 A. Electron diffraction patterns were recorded showing significant reflections extending to 3.0 A. A combination of these structure factor amplitudes with phases from high-resolution images following image processing was used to calculate a projection map of the protein. The asymmetric unit of the structure consists of three microsomal glutathione transferase molecules. The local 3-fold axis at the center of the trimer is delineated by six parallel alpha-helices, two from each monomer. The two helices differ significantly in their respective projection structure. The inner helical core of the trimer is partly surrounded by elongated domains with extensions towards the helices and which contain resolved density maxima at a spacing of 4 to 5 A. A well-defined strong peak is localized close to the elongated domain and at a distance of about 9.5 A from two of the inner helices.

Crystallization↗
PubMed1997

Heparan sulfate isomers in cerebral arteries of Japanese women with aging and with atherosclerosis--heparitinase and high-performance liquid chromatography determinations.

Composition of heparan sulfate (HS) isomers from unaffected and atherosclerotic cerebral arteries (isolated by autopsy) of Japanese women, of various ages, was studied. HS isomers were separated as disaccharide units by high-performance liquid chromatography after degeneration with HS and heparin lyases. Heparitinase facilitated differentiation of eight unsaturated disaccharides (deltaDi-S(HS)) of vascular HS isomers. The HS isomers in the cerebral arteries consisted of approximately half the total glycosaminoglycans (GAGs). Both HS (and GAGs) tended to increase with the processes of aging but decreased with the advancing development of atherosclerosis. The HS isomers consisted of a higher proportion of non-sulfated disaccharide, about 2/3 of the total HS, followed by mono-sulfated and bis-sulfated saccharides; in addition, heparin existed, albeit in minute amounts. The proportion of deltaDi-S(HS) rich in sulfate compared with HS isomers tended to increase with aging but most decreased during formation of the atheroma. Putative functions of HS isomers in cerebral arteries are discussed, based on the characteristic distribution of HS components.

Adolescent↗
PubMed1997

The three-dimensional structure of aquaporin-1.

The entry and exit of water from cells is a fundamental process of life. Recognition of the high water permeability of red blood cells led to the proposal that specialized water pores exist in the plasma membrane. Expression in Xenopus oocytes and functional studies of an erythrocyte integral membrane protein of relative molecular mass 28,000, identified it as the mercury-sensitive water channel, aquaporin-1 (AQP1). Many related proteins, all belonging to the major intrinsic protein (MIP) family, are found throughout nature. AQP1 is a homotetramer containing four independent aqueous channels. When reconstituted into lipid bilayers, the protein forms two-dimensional lattices with a unit cell containing two tetramers in opposite orientation. Here we present the three-dimensional structure of AQP1 determined at 6A resolution by cryo-electron microscopy. Each AQP1 monomer has six tilted, bilayer-spanning alpha-helices which form a right-handed bundle surrounding a central density. These results, together with functional studies, provide a model that identifies the aqueous pore in the AQP1 molecule and indicates the organization of the tetrameric complex in the membrane.

Animals↗
PubMed1997

Cloning of cDNA and estrogen-induced hepatic gene expression for choriogenin H, a precursor protein of the fish egg envelope (chorion).

A cDNA for choriogenin H (Chg H; formerly high-molecular weight spawning female-specific substances, or H-SF), a precursor protein of the inner layer subunits of egg envelope (chorion) of the teleost fish, Oryzias latipes, was cloned and analyzed. The clone consisted of 1913 bp and contained an open reading frame encoding a signal peptide of 22 aa and Chg H protein of 569 aa. The Chg protein possessed three potential N-glycosylation sites and Pro-X-Y repeat sequences in the first two-fifths of the N terminus. There were amino acid sequence similarities between Chg H and a gene product expressed in the liver of female winter flounder during vitellogenesis. Moreover, the amino acid sequence of Chg H is similar to that of ZP2 rather than ZP3 of zona pellucida of some mammals. Northern blot analysis indicated that gene expression for Chg H occurred only in the livers of spawning female fish and 17beta-estradiol-treated male fish, but not in the ovary of the spawning female fish. Gene expression for Chg H and Chg L (formerly low-molecular weight spawning female-specific substance, or L-SF) was induced and increased in parallel in the male fish liver after 17beta-estradiol treatment.

Amino Acid Sequence↗
PubMed1997

Microbial system for polysaccharide depolymerization: enzymatic route for gellan depolymerization by Bacillus sp. GL1.

A bacterium-producing polysaccharide lyase (gellan lyase) was isolated from soil samples and identified to be Bacillus sp. The lyase was purified from the culture fluid of the bacterium (designated Bacillus sp. GL1) grown in the presence of gellan as a carbon source. The purified gellan lyase depolymerized deacetylated gellan and gave a single oligosaccharide product with a molecular weight of 646, which was determined by fast atom bombardment mass spectrometry. The structure of the product was determined by the combination of mass spectrometry, HPLC analysis, and high-resolution proton nuclear magnetic resonance spectroscopy to be a tetrasaccharide of glucuronyl-glucosyl-rhamnosyl-glucose with unsaturated glucuronic acid at the nonreducing terminal. When incubated in cell extracts of Bacillus sp. GL1, the tetrasaccharide was first converted to trisaccharide without unsaturated glucuronyl residue, and the trisaccharide was then converted to hydrolyzed monosaccharides glucose and rhamnose. These results show that, in the bacterium Bacillus sp. GL1, gellan is first depolymerized to give a tetrasaccharide, a repeating unit in gellan molecule, by an extracellular gellan lyase and then the tetrasaccharide is hydrolyzed to monosaccharides by successive actions of intracellular exoglycosidases.

Bacillus↗
PubMed1997

Integration patterns of HTLV-I provirus in relation to the clinical course of ATL: frequent clonal change at crisis from indolent disease.

We examined human T-lymphotropic virus type I (HTLV-I) DNA integration in 68 patients with adult T-cell leukemia/ lymphoma (ATL) by Southern blotting using EcoRI, which does not cut within the 9 kb of the genome and probes for pX and gag-pol region of HTLV-I. We detected defective proviral integration as a monoclonal band of various sizes with the pX but not with the gag-pol probe, or a monoclonal band of less than 9 kb with the pX probe, in 20 patients (29.4%). These were designated defective (D) type. With both probes, a single band greater than 9 kb was detected in 34 (50.0%), designated complete (C) type, and two or more bands greater than 9 kb, were designated multiple (M) type, in 14 (20.6%). Advanced age, a high LDH value, and hypercalcemia were more frequent in D type patients. The median survival time (MST) was 6.8, 24.4, and 33.3 months, for D, C, and M types, respectively (log rank P = .006). Among 52 sequentially examined patients, the HTLV-I integration patterns changed in 4 (7.5%). In three of these four, the rearrangements of the T-cell receptor (TCR)b gene concomitantly changed, suggesting the appearance of a new ATL clone. Another patient had the same rearrangement of the TCRb gene, indicating clonal evolution. The HTLV-I integration pattern changed at crisis from indolent to aggressive ATL in three patients. These findings suggested that the HTLV-I integration patterns have clinical implications in ATL pathophysiology. In contrast to the clonal evolution characteristic of the multistep carcinogenesis of most human malignancies, the frequent clonal change of ATL at crisis is a peculiar phenomenon, probably reflecting the emergence of multiple premalignant clones in viral leukemogenesis as suggested in Epstein-Barr virus associated lymphomagenesis in the immunocompromised host.

Aged↗
PubMed1997

Relation of iodine-123 metaiodobenzylguanidine myocardial scintigraphy to endomyocardial biopsy findings in patients with dilated cardiomyopathy.

BACKGROUND: Iodine-123 metaiodobenzylguanidine (123I-MIBG) concentrates in adrenergic neurons and has been developed for evaluation of the sympathetic nervous system. Recent studies have demonstrated that the normal heart is clearly visualized by 123I-MIBG cardiac scintigraphy, whereas abnormal 123I-MIBG myocardial uptake and washout have been demonstrated in patients after myocardial infarction and in patients with congestive cardiomyopathy, long QT syndrome, and ventricular tachycardia. HYPOTHESIS: Based on evidence from recent studies, it can be hypothesized that 123I-MIBG uptake is related to histopathologic changes in the myocardium. METHODS: The relation of 123I-MIBG uptake to the histologic findings for the heart was studied in 24 patients with dilated cardiomyopathy (DCM). The study group did not include patients with complicating disorders that primarily affect the adrenergic nervous system. The 123I-MIBG uptake was visually assigned one of four grades using the two criteria of the mean score for six regional uptake grades (mean score) and the global score obtained by visual evaluation of the entire image (global score). The 123I-MIBG uptake score was also determined for the region at which the biopsy specimen was obtained (biopsy region score). The histologic findings were evaluated by assigning one of four grades for each of the following five factors: myocyte hypertrophy, myocardial fibrotic change, myocyte degeneration and necrosis, mononuclear cell infiltration, and myocyte disarray. The sum for all grades was defined as the total score, and the global score was also assigned to the overall histologic findings. RESULTS: All of the global, mean, and biopsy region scores for 123I-MIBG uptake correlated significantly with the global and total scores for the histologic findings. Among the histologic factors, myocyte degeneration showed score correlated with all global, mean, and biopsy region scores for the uptake. Myocyte hypertrophy was associated weakly with the 123I-MIBG uptake scores. CONCLUSION: These results indicate that 123I-MIBG uptake imaging is associated with histopathologic abnormalities in patients with DCM.

3-Iodobenzylguanidine↗
PubMed1997

Neurophysiological methods in occupational and environmental health: methodology and recent findings.

Neurophysiological measurement, a promising technique for assessment of the subclinical effects of occupational and environmental factors, is rapidly progressing following development of computer technology. The methods include measurement of evoked and event-related potentials, nerve conduction velocity, distribution of nerve conduction velocities, electrocardiographic R-R interval variability, and computerized static posturography. This paper provides an overview of these methods, except for evoked and event-related potentials, which have been reviewed previously by the authors, to evaluate the effects of occupational and environmental factors on the peripheral, autonomic, and cerebellar nervous systems. The available data indicate that these methods are sensitive, reliable, and easily applied in a field study. When conducting these measurements, controlling for confounding factors such as age, sex, height, skin temperature, alcohol ingestion, and neurologic diseases is necessary.

Electrophysiology↗
PubMed1997

Postural sway frequency analysis in workers exposed to n-hexane, xylene, and toluene: assessment of subclinical cerebellar dysfunction.

To clarify the effects of organic solvents on the postural balance system, 29 male sandal, shoe, and leather factory workers exposed to n-hexane, xylene, and toluene (solvent workers) were examined by computerized static posturography with sway frequency analysis. Concentrations of metabolites of solvents in urine samples taken from the workers in the morning before work ranged from 0.41 to 3.06 (mean, 1.20) mg/g creatinine (Cn) for 2,5-hexanedione, from 0.10 to 0.43 (mean, 0.19) g/g Cn for methylhippuric acid, and from 0.05 to 2.53 (mean, 0.37) g/g Cn for hippuric acid; estimated concentrations of n-hexane in workplace air ranged from 13 to 100 (mean, 40) ppm. Control subjects were 22 healthy males without exposure to solvents. With eyes open, postural sway with a frequency of 2-4 Hz in solvent workers was significantly larger than that in controls in the anteroposterior direction. With eyes closed, sway with a frequency of 0-1 Hz was significantly larger in solvent workers in the mediolateral and anteroposterior directions. Results of multiple regression analysis showed that with eyes open the 1- to 2-Hz and 2- to 4-Hz sways were related positively to 2,5-hexanedione and inversely with methylhippuric acid. The pattern of changes suggests that the vestibulocerebellar and spinocerebellar afferent systems are asymptomatically affected by n-hexane; the effect of n-hexane on the vestibulocerebellar system is possibly inhibited by xylene.

Cerebellum↗
PubMed1997

Asymptomatic primary pulmonary hypertension associated with liver cirrhosis.

We report a case of asymptomatic primary pulmonary hypertension associated with liver cirrhosis (type B) and portal hypertension found by chance during a preoperative Swan-Gantz catheterization study. Our experience suggests that the actual prevalence of primary pulmonary hypertension associated with liver cirrhosis may be greater than that previously reported. During the follow-up of liver cirrhosis with portal hypertension, we should consider primary pulmonary hypertension, even if the patient is free of symptoms, and a chest X-ray check may be necessary.

Catheterization, Swan-Ganz↗
PubMed1997

Liver cirrhosis with synchronous gas gangrene and spontaneous bacterial peritonitis due to E. coli.

We report a case of synchronous gas gangrene and spontaneous bacterial peritonitis associated with liver cirrhosis. The patient was a 52-year-old man who was being followed for decompensated liver cirrhosis. He experienced sudden onset lower abdominal pain with distension and pain in the left leg. A bullous lesion, with crepitation, later appeared in the thigh and showed air-bubbles on X-ray. Eschericia coli was cultured from ascites and the bullous lesions; there was associated gas gangrene. The patient died of bacteremia with disseminated intravascular coagulopathy 26 h after admission, despite receiving intensive care. We discuss the route of bacteria causing the spontaneous bacterial peritonitis and simultaneous gas gangrene.

Bacteremia↗
PubMed1997

Asymptomatic sequelae to acute sarin poisoning in the central and autonomic nervous system 6 months after the Tokyo subway attack.

Six to eight months after the Tokyo subway attack in March 1995, the neurophysiological effects of acute sarin poisoning were investigated in 18 passengers exposed to sarin (sarin cases) in the subways to ascertain the focal or functional brain deficits induced by sarin. The event-related and visual evoked potentials (P300 and VEP), brainstem auditory evoked potential, and electrocardiographic R-R interval variability (CVRR), together with the score on the posttraumatic stress disorder (PTSD) checklist, were measured in the sarin cases and the same number of control subjects matched for sex and age. None of the sarin cases had any obvious clinical abnormalities at the time of testing. The P300 and VEP (P100) latencies in the sarin cases were significantly prolonged compared with the matched controls. In the sarin cases, the CVRR was significantly related to serum cholinesterase (ChE) levels determined immediately after exposure; the PTSD score was not significantly associated with any neurophysiological data despite the high PTSD score in the sarin cases. These findings suggest that asymptomatic sequelae to sarin exposure, rather than PTSD, persist in the higher and visual nervous systems beyond the turnover period of ChE; sarin may have neurotoxic actions in addition to the inhibitory action on brain ChE.

Acute Disease↗
PubMed1997

Effects of occupational use of vibrating tools in the autonomic, central and peripheral nervous system.

OBJECTIVES: The objective of this study was to clarify the autonomic, central and peripheral nervous effects of vibrating-tool operation. METHODS: The ECG R-R interval variability (CVRR), including the C-CVHF, C-CVLF (two component CVs of the CVRR reflecting parasympathetic and sympathetic activities, respectively) and the power spectral densities (PSDHF and PSDLF) after autoregressive analysis, short-latency somatosensory evoked potentials (SSEP), distribution of nerve conduction velocities (DCV), and median and radial nerve conduction velocities (NCVs) were measured in 17 vibrating-tool operators and the same number of age-matched control subjects. Some of the operators complained of white finger even in summer as soon as they arrived at the cold workplace. DESIGN: The significance of the differences in neurophysiological data between the exposed and unexposed groups and the associations between these data in the former were investigated. RESULTS: The CVRR, C-CVHF and PSDHF were significantly lower in the vibrating-tool operators than in the matched controls. The N9-N13 interpeak latency of the SSEP, i.e., conduction time of the cervico-spinobulbar pathway, in the operators was significantly prolonged as compared with the controls; the faster velocities of the DCV and the NCVs were significantly slowed in the operators. The N9-N13 interpeak latency in the operators was significantly correlated with the C-CVHF. CONCLUSION: Complex stressors of local vibration, cold, noise and heavy work, seem to affect the cervico-spinobulbar, parasympathetic and peripheral nerve functions. Also, parasympathetic hypofunction may imply a consequence in brainstem pathology induced by cold exposure in addition to vibration.

Adult↗
PubMed1997

The influence of coronary collateral flow on the assessment of myocardial perfusion by videodensitometry.

OBJECTIVES: Coronary collateral flow often mitigates the effects of coronary artery obstruction and has a significant impact on the prognosis of patients with coronary artery disease. In the presence of variable degrees of coronary collateral flow, digital radiographic assessment of myocardial blood flow has not been quantitatively validated. METHODS: A distal coronary arterial collateral path was created into the left anterior descending coronary artery (LAD) bed in 8 anesthetized pigs. Both LAD and collateral paths were pump-perfused and corresponding flows measured. A number of commonly used digital indices and parametric images of myocardial perfusion were then extracted from the sequence of images filmed before and during the injection of contrast. Data were acquired at 5 levels of total flow (LAD flow + collateral flow): 100, 85, 70, 55 and 40% of maximally vasodilated, baseline flow. At each level of total flow, data were acquired at 4 levels of collateral flow ratios (collateral flow/total flow): 0, 10, 25 and 50%. RESULTS: Regional percent segment shortening, reflecting myocardial blood flow, decreased as total flow fell, and remained unaltered when coronary collateral ratio alone was altered without change in total flow. On the other hand, linear regression between total flow and digital indices at 10, 25 and 50% coronary collateral flow ratios, compared with 0%, showed a successive and significant downward displacement, documenting an underestimation of flow by all digital indices in the presence of collateral flow. CONCLUSIONS: In the absence of a collateral pathway and during maximal coronary vasodilation with adenosine, digital radiographic indices of myocardial perfusion, based upon indicator dilution theory, show a relatively good correlation with regional transmural myocardial blood flow. However, due to underestimation of total transmural blood flow, these indices have limited utility when myocardial perfusion is provided in part by a collateral pathway. The effect is probably related to an alteration in the regional vascular volume into which iodinated contrast is injected.

Adenosine↗
PubMed1997

Pharmacokinetic and pharmacodynamic study of imidaprilat, an active metabolite of imidapril, a new angiotensin-converting enzyme inhibitor, in spontaneously hypertensive rats.

The pharmacokinetics and pharmacodynamics (PK/PD) of imidaprilat, an active metabolite of imidapril, a new angiotensin-converting enzyme (ACE) inhibitor, were investigated. Imidapril was infused subcutaneously for 4 weeks via an osmotic pump implanted under the skin in the back of male spontaneously hypertensive rats (SHRs). Plasma concentration of imidaprilat, systolic blood pressure (SBP), and plasma ACE activity were determined periodically. The plasma concentration of imidaprilat increased in proportion to the infusion rates and was maintained for 4 weeks. The SBP and ACE activity did not decrease in proportion to the infusion rates due to the saturation of the pharmacologic effects, but these actions also were maintained for 4 weeks. The PK/PD of imidaprilat were not influenced by aging of SHRs. The antihypertensive action in subcutaneous infusion of imidapril was as potent as that in oral administration at the same dose, although the maximum plasma concentration of imidaprilat in subcutaneous infusion was one-eightieth times of that in oral administration. The action was also maintained 28 times longer than that in oral administration, indicating that subcutaneous infusion is useful as an administration route. Furthermore, good correlation between plasma imidaprilat concentration and SBP was observed in subcutaneous infusion, indicating that plasma concentration may be a useful marker of pharmacologic action.

Administration, Oral↗
PubMed1997

Pharmacokinetics and pharmacodynamics of a sustained-release biodegradable pellet containing imidapril, a new angiotensin-converting enzyme inhibitor in spontaneously hypertensive rats.

The pharmacokinetics and pharmacodynamics (PK/PD) of a sustained-release biodegradable pellet containing imidapril, a new angiotensin-converting enzyme (ACE) inhibitor, were investigated in comparison with those of an osmotic pump in male spontaneously hypertensive rats (SHRs). A pellet was prepared from copolymer of DL-lactic acid and glycolic acid by the melt-pressing technique. Imidapril was released in vitro from the pellet at an approximately zero-order rate and the release profile was similar to that of the osmotic pump. Imidapril was administered subcutaneously via a pellet or an osmotic pump implanted under the skin in the back of SHRs. Plasma concentrations of imidaprilat as an active metabolite of imidapril, plasma ACE activity and systolic blood pressure (SBP) were determined periodically. The plasma concentration of imidaprilat during the administration of a pellet was maintained for 4 weeks, and the plasma concentration profile was close to that of the osmotic pump. Both groups of pellet and osmotic pump significantly inhibited plasma ACE activity and reduced SBP for 4 weeks, and these action profiles were similar in both groups. In addition, in vivo release profile of the pellet was close to the in vitro release profile, and the in vivo release profiles of the pellet and the osmotic pump were similar to each other. From these results, it was found that the PK/PD of a biodegradable pellet were close to those of the osmotic pump, and it was shown that the pellet may be a useful system to maintain the plasma concentration of imidaprilat for a long time.

Angiotensin-Converting Enzyme Inhibitors↗