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Biomedical subjects

J Fujii

Publications and source records attributed to J Fujii.

At least 109 records · Page 6Linked to original sources
PubMed1996

[Legionella infection in occupational and environmental health].

Air condition systems are indispensable for amenity in the work environment. It is known that Legionella species are widely distributed in the water of cooling towers, and that the bacteria are responsible for community-acquired pneumonia (Legionnaires' disease) and for influenza-like symptoms (Pontiac fever). Furthermore, Legionella species are associated with building-related illness. In Japan, however, prevention and countermeasures are inadequate against legionellosis compared to those of Europe and the USA. This is because occupational and environmental medicine in Japan has not been based on a microbiological point of view, and that workplace inspections have not covered cooling towers. Therefore, Legionella species in the water of coolig towers have not been routinely monitored in the work environment. This review describes the microbiological characteristics of Legionella species, their habits in the environment, the source and route of infection, the pathogenesis, the symptoms and treatment of legionellosis, outbreaks of this disease throughout the world, and how to deal with this organism in the work environment to prevent legionellosis.

Environmental Health↗
PubMed1996

Increased plasma-soluble fibrin monomer levels in patients with disseminated intravascular coagulation.

Plasma-soluble fibrin monomer (SFM) level in patients with disseminated intravascular coagulation (DIC) was significantly higher than the level in patients with pre-DIC or in non-DIC patients, and the level in patients with pre-DIC was significantly higher than that in non-DIC patients. There was no significant difference in plasma SFM levels among various diseases underlying DIC. Plasma SFM level in patients with good outcome was significantly decreased after treatment for DIC. The sensitivity of fibrin degradation products and platelet number was high for DIC, but not for pre-DIC. The sensitivity of thrombin-antithrombin III complex, plasmin-plasmin inhibitor complex, and SFM was high for both DIC and pre-DIC. The specificity of these markers was also high. Receiver operating characteristic analysis suggests that plasma SFM level could be the most useful marker for the diagnosis of both DIC and pre-DIC.

Amino Acid Sequence↗
PubMed1996

Oxidative stress caused by glycation of Cu,Zn-superoxide dismutase and its effects on intracellular components.

It is now evident that the redox state of the cell is a pivotal determinant of the fate of cells. Extensive production of reactive oxygen species (ROI) causes necrotic cell death. Even transient or localized production of ROI may mediate a signal for apoptotic cell death, whereas small amounts of ROI function as an intracellular messenger of some growth stimulants. Accumulating evidence supports the concept that decreases in Cu,Zn-superoxide dismutase (SOD) activity causes apoptotic cell death in neuronal cells. Our data using mutant Cu,Zn-SOD related to familial amyotrophic lateral sclerosis (FALS) suggest that glycation itself and ROI produced from the glycated proteins are involved in many diseases, including diabetic complications. Glycation of important cellular components, including lipid, DNA and proteins, induces dysfunction of these components. Mutant proteins in patients with various hereditary diseases would be destabilized by the glycation reaction, as shown in the case of mutant Cu,Zn-SODs, thereby hyperglycaemic conditions would trigger the onset of some hereditary diseases such as FALS and Alzheimer's disease. Glycation, particularly of antioxidative enzymes, would enhance production of ROI, resulting in oxidative damage to the cells.

Amyotrophic Lateral Sclerosis↗
PubMed1996

Effect of a nitric oxide synthase inhibitor, S-ethylisothiourea, on cultured cells and cardiovascular functions of normal and lipopolysaccharide-treated rabbits.

Nitric oxide (NO) is synthesized from L-arginine by three isoforms of NO synthase (NOS). It is essential to suppress the function of the inducible isoform (macNOS) for amelioration of some inflammatory diseases in which the cytotoxic effect of NO is involved. S-Ethylsiothiourea (S-EIU) was reported to be a potent and specific inhibitor of macNOS. We also confirmed that it rather specifically inhibited the activity of the purified macNOS and the formation of nitrite by RAW264.7 cells compared to NG-monomethyl-L-arginine (L-NMA) and NG-nitro-L-arginine (L-NNA), the other isoforms being less effective. S-EIU suppressed the release of nitrite and lactate dehydrogenase from rat vascular smooth muscle cells treated with interleukin-1 beta and forskolin more potently than L-NMA or L-NNA. S-EIU also slightly suppressed internucleosomal DNA cleavage in pancreatic beta-cells induced by NO produced by macNOS. Intravenous administration of either S-EIU at 0.1 mg/kg/min or L-NMA at 1 mg/kg/min increased the blood pressure but decreased the heart rate in normal rabbits, while aminoguanidine at 1 mg/kg/min affected neither cardiovascular function. These inhibitors at these doses caused recovery of the blood pressure in lipopolysaccharide-treated rabbits that exhibited lowered blood pressure similar to that in the case of septic shock. Although S-EIU seemed not to be an adequate inhibitor for therapeutic use in vivo due to its side effects on cardiovascular functions, it is one of the most potent inhibitors of macNOS among reported inhibitors in vitro.

Animals↗
PubMed1996

The protective role of glutathione peroxidase in apoptosis induced by reactive oxygen species.

Selenium-dependent glutathione peroxidase (GPx) plays a protective role in oxidative stress-induced apoptosis. In this study, we demonstrated that MDBK cells, a bovine renal epithelial cell line, exhibited internucleosomal DNA fragmentation characteristic of apoptotic cell death under selenium-deficient conditions with lower doses of hydrogen peroxide (H2O2) than under selenium-supplemented ones. This was due to a decreased amount of GPx in the cells under selenium-deficient conditions, because other antioxidative enzyme activities were not affected by the selenium supplementation. Cumene hydroperoxide also induced DNA fragmentation in selenium-deficient cells but no ladder formation was observed. Flow cytometric analysis showed that selenium-deficient cells were less capable of scavenging intracellular peroxides after exposure to exogenous H2O2 than selenium-supplemented ones. In contrast, there was no difference in viability between selenium-supplemented and non-supplemented cells in cell survival after exposure to menadione, which activates the electron transport system and increases intracellular superoxide radicals. Clofibrate, a peroxisomal proliferator and an inducer of catalase (CAT), partially protected both Se-deficient and Se-supplemented cells from exogenous H202. We concluded that selenium-deficient cells were more easily brought to apoptotic cell death by peroxides, but not by superoxide radicals, than selenium-supplemented ones and that CAT could compensate for the depletion of GPx to a certain degree by scavenging H2O2.

Animals↗
PubMed1996

Effects of substitutions of the conserved histidine residues in human gamma-glutamyl transpeptidase.

gamma-Glutamyl transpeptidase possesses two histidine residues at positions 383 and 505 which are conserved in all mammalian and bacterial species. In order to elucidate the functions of these residues, we prepared mutants in which these residues were replaced by Ala. Kinetic analysis of the hydrolysis of L-gamma-glutamyl-p-nitroanilide indicated that substitution at His-383 decreased the Vmax value to 14% of that of the wild type, but had no effect on Vmax/K(m). In reactions involving glycylglycine as the acceptor substrate, the Vmax value of this mutant decreased to 38% with little alteration of Vmax/K(m) for L-gamma-glutamyl-p-nitroanilide as a gamma-glutamyl donor, but with a significant reduction of Vmax/K(m) for the acceptor. These results show that this substitution causes impairment of the step in which the free enzyme is regenerated from the gamma-glutamyl enzyme by water or an acceptor substrate. On the other hand, replacement of His-505 resulted in a decrease of the Vmax value for transpeptidation to about 10% of that of the wild type despite no substantial effect on the Vmax value for the hydrolysis reaction. However, this substitution did not affect Vmax/K(m) for the acceptor on transpeptidation. Thus, the formation of a non-productive enzyme-substrate complex with the acceptor substrate would decrease the Vmax value on transpeptidation. These results suggest that His-383 plays an important catalytic role in facilitating the degradation of the gamma-glutamyl-enzyme through hydrolysis or transfer of the gamma-glutamyl moiety to an acceptor. It was also shown that His-505 is important in the formation of a complex of the gamma-glutamyl enzyme with the acceptor substrate even though it plays no critical role in the catalysis. Although the pH-dependence profile and the van't Hoff plot for the ionic group responsible for enzyme activity were consistent with the requirement of a histidine residue, neither of the conserved histidines could be assigned as such an ionic group. This suggests that another histidine residue(s) might play an essential role in the enzyme function.

Alanine↗
PubMed1996

Induction of aldose reductase gene expression in LEC rats during the development of the hereditary hepatitis and hepatoma.

We examined age-related changes in the protein and the mRNA expression of aldose reductase in livers of Long-Evans with a cinnamon-like color (LEC) rats, which develop hereditary hepatitis and hepatoma with aging, using Long-Evans with an agouti color rats as controls. The levels of the protein and mRNA of aldose reductase increased after 20 weeks, at the stage of acute hepatitis, and were maintained at 60 weeks of age, while those of aldehyde reductase seemed to be constant at all ages. The expression of aldose reductase was marked in cancerous lesions in hepatoma-bearing LEC rat liver compared to uninvolved surrounding tissues. These results indicated that elevation of aldose reductase accompanied hepatocarcinogenesis and may be related to the acquisition of immortality of the cancer cells through detoxifying cytotoxic aldehyde compounds.

Aging↗
PubMed1996

Magnetic resonance imaging and histopathological study of brain lesions in rabbits given intravenous verotoxin 2.

When rabbits were given intravenously purified verotoxin 2 (VT2) at 5 microg/kg of body weight, they developed hemorrhagic diarrhea, flaccid paresis, an ataxic gait, an opisthotonic posture, and convulsions. To examine the effects of VT2 toxemia on the rabbit central nervous system, magnetic resonance imaging and ultrastructural studies were performed. At 24, 57, and 80 h after injection of VT2 into 12 rabbits, T2-weighted images of the central nervous system were obtained. The initial lesion was noted at 24 h in the hypothalamic areas of all experimental animals. At 57 h, the T2 value increased in the medulla of the cerebral hemisphere or the hippocampus, with a brain stem lesion in six rabbits (50%). The rabbits with the brain stem lesions, in which neurological signs were very severe, died within 6 days. Lesions in the cerebellar hemisphere and/or vermis were noted in four rabbits (33%) that survived more than 1 month. To better understand the pathogenesis of VT2 in these brain lesions, we examined the deterioration of the blood-brain barrier and cerebrospinal fluid-brain barrier by using horseradish peroxidase as a tracer. The tracer was detected by electron microscopy both in the subendothelial layer, including the basal lamina, and throughout the cytoplasm of the ependymal cell layer covering the ventricle after intravenous or intrathecal treatment with horseradish peroxidase. We also determined the localization of VT2 by immunoelectron microscopy and found that it was localized on edematous endothelial cells of capillaries, ependymal cells, and myelin sheaths. The present study suggests that VT2 was conveyed from the endothelial and ependymal cell layers and caused edematous changes in the rabbit brain.

Animals↗
PubMed1996

Examination of stability of anticonvulsants in a protease solution and assay of anticonvulsants in hairs.

For analyzing the concentrations of drugs in hairs, a new method of digestion of hairs with Biopurase, a protease obtained from Bacillus subtilis, was examined. The concentrations of drugs in hairs were then determined in order to examine the usefulness of the protease for the digestion of hairs. The stability of five anticonvulsants in the protease solution was maintained over a 12-h period. In the clinical tests, the concentrations of the drugs in hairs obtained from patients who were taking anticonvulsants for a long time were determined. The concentration of phenobarbital in hairs in 10 patients taking phenobarbital ranged from 194 to 5020 ng/10 mg with a mean of 578 ng/10 mg, and the concentration of phenytoin in hairs in 6 patients taking phenytoin ranged from 44 to 299 ng/10 mg with a mean of 115 ng/10 mg. From these results, the transfer of phenobarbital and phenytoin from circulating blood into hairs was confirmed, and the usefulness of Biopurase for the digestion of hairs was proved.

Anticonvulsants↗
PubMed1996

Abnormal Q wave, ST-segment elevation, T-wave inversion, and widespread focal myocytolysis associated with subarachnoid hemorrhage.

A 74-year-old Japanese woman with subarachnoid hemorrhage was admitted to our hospital. During her hospitalization, serial electrocardiograms showed the combination of abnormal Q waves, ST-segment elevation, and T-wave inversion, which strongly suggested acute myocardial infarction. However, postmortem examination revealed widespread focal myocytolysis of the myocardium which was unrelated to vascular distribution.

Aged↗
PubMed1996

Current status of antihypertensive therapy for elderly patients in Japan.

To assess how elderly Japanese hypertensive patients are treated by specialists, we conducted a cross-sectional survey. A total of 1,163 outpatients aged 50 years or older were studied. Hypertension was diagnosed in 939 of these patients, and 827 were receiving drug therapy. The average blood pressure during therapy was 143 +/- 16/81 +/- 10 mmHg. In patients aged 70 years or older, systolic blood pressure during antihypertensive therapy was significantly higher (p < 0.01) and diastolic blood pressure was significantly lower (p < 0.01) than the corresponding values in those aged 50 to 59 years or 60 to 69 years. The calculated mean blood pressures were similar in the different age groups. The rate of monotherapy in the patients aged 70 years or older was 58.8%, which was significantly higher (p < 0.01) than the rates of monotherapy in the other age groups. Calcium channel blockers were prescribed in about 80% of patients, irrespective of age or comorbidity. Of the patients receiving calcium channel blockers, 43.5% were treated with monotherapy. This rate significantly (p < 0.01) increased with advancing age. Diastolic blood pressures were significantly lower (p < 0.05) in patients with stroke and in those with ischemic heart disease, diabetes mellitus, or dyslipidemia, as compared with patients with no comorbidity. Among patients aged 70 years or older, the difference in systolic blood pressure between those with ischemic heart disease and those with no comorbidity was not significant. Blood pressure in elderly hypertensive patients was reduced to a level similar to that in younger patients. The target blood pressure was influenced by the presence of comorbidity. Furthermore, specialists showed a high preference for the use of calcium channel blockers in the management of hypertension.

Activities of Daily Living↗
PubMed1996

Involvement of glycation and oxidative stress in diabetic macroangiopathy.

Under diabetic conditions, the Maillard reaction facilitates the production of reactive oxygen species, and the activity of antioxidant enzymes such as Cu,Zn-superoxide dismutase is decreased, resulting in a remarkable increase of oxidative stress. The oxidative stress attacks DNA, lipids, and proteins and is also thought to be involved in the pathogenesis of diabetic complications, including the progression of macroangiopathy. Proliferation of smooth muscle cells (SMCs) is known to be associated with progression of macroangiopathy and is modulated by several growth factors. At least three mitogens for SMCs, platelet-derived growth factor (PDGF), fibroblast growth factor, and heparin-binding epidermal growth factor-like growth factor (HB-EGF), are known to be produced by SMCs themselves and are considered to be the most potent growth factors in the progression of macroangiopathy as seen in diabetes. HB-EGF, but not PDGF, is regulated at the transcriptional level by 3-deoxyglucosone (3-DG), a major and highly reactive intermediate in the glycation reaction. The induction seems to be triggered by the increase of reactive oxygen species produced by 3-DG. Taken together, glycation reactions under diabetic conditions may be highly associated with the pathogenesis of diabetic macroangiography by enhancing the gene expression of HB-EGF.

Animals↗
PubMed1996

Diversity of the synthetic-state smooth-muscle cells proliferating in mechanically and hemodynamically injured rabbit arteries.

Vascular smooth muscles contain at least three types of developmentally regulated myosin heavy-chain (MHC) isoforms; SM1, SM2, and SMemb. By investigating the expression of the three MHC isoforms, we previously demonstrated in rabbits that smooth muscles proliferating in the neointima of arterio- and atherosclerotic lesions regain an "embryonic" phenotype. In the present study, we examined if neointimal cells are morphologically similar to embryonal smooth muscles and if dedifferentiation of neointimal smooth muscles is a reversible process. Vascular injury was produced in rabbits either by endothelial cell denudation of the aorta or by poststenotic dilation of the carotid artery. We have demonstrated in this study that the proliferating neointimal cells expressed SM1 and SMemb, but not SM2, indicating smooth muscles of an "embryonic" phenotype. The dedifferentiation of neointimal smooth muscles was found to be reversible; at 4 to 8 weeks after injury, a majority of the cells reexpressed both SM1 and SM2, but not SMemb. By electron microscopy, we have revealed smooth-muscle phenotypes determined by MHC isoforms to correspond to the morphologic phenotypes as an increase in membranous organelles, and a decrease in myofilaments was associated with the reexpression of SMemb. Interestingly, we also found that in the medial wall at 4 to 8 weeks after ballooning injury, a number of SM1-negative cells proliferated rapidly, replacing normal smooth muscles. These cells were negative against SM1 and SM2 but positive for SMemb. These SM1-negative cells contained abundant membranous organelles and few myofilaments. These cells did not express SM1 or SM2 even after 8 weeks postinjury. We conclude from these results that the proliferating synthetic-type smooth muscles after vascular injury are composed of SM1-positive cells that are morphologically similar to embryonal smooth muscle and that maintain ability to redifferentiate, and SM1-negative cells that contain few myofilaments and remain dedifferentiated.

Age Factors↗
PubMed1996

[Differentiation of hypertrophic cardiomyopathy and hypertensive cardiac hypertrophy using the patterns of interventricular septum hypertrophy].

The patterns of interventricular septal hypertrophy were analyzed on two-dimensional echocardiograms to differentiate hypertrophic cardiomyopathy (HCM) from hypertensive cardiac hypertrophy. The control group comprised 110 patients without cardiovascular disease who were matched for age and gender with the hypertension group. The hypertension group comprised 110 patients with uncomplicated essential hypertension, and the HCM group comprised 32 patients in whom the wall thickness of the interventricular septum was 12 mm or more at the mid-portion and no underlying heart disease responsible for cardiac hypertrophy was detected. The interventricular septal thickness was measured both at the thickest portion within 15 mm distal to the aortoseptal junction (basal portion: B) and at the mid-portion (M) in the end-diastolic image on the left parasternal long-axis tomograms, and the B/M ratio was calculated in each patient. The B/M ratio was 1.07 +/- 0.16 in the control group, 1.19 +/- 0.18 in the hypertension group, and 0.83 +/- 0.12 in the HCM group. Compared with the control group, the B/M ratio was significantly high in the hypertension group (p < 0.05) and significantly low in the HCM group (p < 0.01). These results indicate that hypertrophy of the interventricular septum is dominant at the basal portion in hypertensive patients but at the mid-portion in patients with HCM.

Aged↗
PubMed1996

[Experimental production of tricuspid valve and papillary muscle lesions by premature ventricular contractions due to ventricular stimulation in rabbits].

Ventricular bigeminy or trigeminy can spontaneously occur in anesthetized rabbits forced into the supine position. Premature ventricular contractions (PVCs) of this type are characterized by a long coupling time and superimposition of the following P waves. Rabbits with PVCs of this type frequently develop peculiar mitral complex lesions which are detected by deposition of colloidal carbon. This study examined the effects on the tricuspid complex of artificial PVCs induced by left ventricular pacing in rabbits. Anesthetized rabbits were forced into the supine position under electrocardiographic monitoring. The animals were divided into those with spontaneous PVCs, those with artificial PVCs, and those without PVCs as controls. Colloidal carbon (1 ml) was intravenously injected into the animals the next day. All animals were sacrificed after 1 week. Tricuspid complex lesions were found in 2.0% of animals with spontaneous PVCs, in 17.6% of those with artificial PVCs, and in none of the controls. These results indicate that artificial PVCs induced by left ventricular pacing can cause peculiar tricuspid complex lesions.

Animals↗
PubMed1995

Characterization of cDNA and genomic DNA encoding SERCA1, the Ca(2+)-ATPase of human fast-twitch skeletal muscle sarcoplasmic reticulum, and its elimination as a candidate gene for Brody disease.

Genomic DNA and cDNA encoding human SERCA1, the Ca(2+)-ATPase of fast-twitch skeletal muscle sarcoplasmic reticulum (the ATP2A1 gene on chromosome 16p12), were isolated and characterized. The cDNA encodes 994 amino acids. The genomic DNA is 26 kb long and contains 23 exons, one of which can be alternatively spliced. The locations of each of the exon/intron boundaries are the same as those previously identified in the rabbit ATP2A1 gene. Brody disease is an inherited disorder of skeletal muscle, characterized by exercise-induced impairment of muscle relaxation. It has been postulated to result from a deficiency in SERCA1. In a search for the genetic basis of Brody disease, the coding sequence of the ATP2A1 gene in one Brody patient and the full-length sequences of two SERCA1 cDNAs in two other, unrelated Brody patients were compared with normal ATP2A1 sequences. In all three cases, the coding and splice junction sequences were normal, indicating that the forms of Brody disease manifested in these three patients are not caused by mutations in the coding or splice junction regions of the ATP2A1 gene.

Amino Acid Sequence↗
PubMed1995

Induction of nitric oxide synthase and concomitant suppression of superoxide dismutases in experimental colitis in rats.

Reactive oxygen species are thought to play an important role in some bowel diseases. In order to evaluate the participation of nitric oxide and superoxide in such diseases, we examined the expression of nitric oxide synthase (NOS) and superoxide dismutase (SOD) as well as their activities in whole excised colons of rats with colitis induced by intralumenal administration of 2,4,6-trinitrobenzenesulfonic acid. A marked increase in the inducible form of NOS mRNA was detected and NOS activity was coincidentally augmented in the group administered unbuffered TNBS (pH 1.0), in which severe inflammation was revealed by microscopic examination and myeloperoxidase activity of invading neutrophils in the tissues. The levels of the Mn- and Cu,Zn-SOD proteins as well as SOD activity were suppressed, although expression of the Mn-SOD mRNA was enhanced in colitis tissues. The elevation of NOS activity and the suppression of SOD activity occurred concomitantly at the stage of severe inflammation. This would increase peroxynitrite formation from superoxide and nitric oxide and enhance the tissue damage in experimental colitis.

Animals↗