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Biomedical subjects

T Ohta

Publications and source records attributed to T Ohta.

At least 307 records · Page 17Linked to original sources
PubMed1999

Chromosome-determined zinc-responsible operon czr in Staphylococcus aureus strain 912.

A novel operon, czrAB (zinc-responsible genes), was identified in the chromosome of Staphylococcus aureus. The operon consists of two genes, czrA and czrB. The czrA gene, coding for an 11.5 kDa protein, was homologous to cadC, arsR of S. aureus plasmid pI258 and smtB of Synechococcus PCC7942. The czrB, coding for a 36 kDa membrane spanning protein, was homologous to the czcD gene, cobalt, zinc and the cadmium-resistant factor of Bacillus subtilis and Alcaligenes eutrophus. In the presence of zinc (0.1-10 mM), the transcription of czrAB was enhanced in a concentration-dependent manner. Other heavy metals, such as cobalt, copper, manganese and nickel showed no effect on czrAB expression. The disruptant of the czrB gene became sensitive to zinc ion (MIC, 2 mM; MBC, 10 mM), and the complementation with the plasmid recovered the resistance to zinc at the same concentration as a parental strain (MIC, 5 mM; MBC, 20 mM). The disruptant accumulated intracellular zinc up to 0.4 mg per g dry weight of the organism, while that of the parental strain was 0.25 mg per g dry weight. The findings indicated that the novel operon czrAB should play a role in the transportation of zinc across the cell membrane to maintain the proper intracellular concentration.

Amino Acid Sequence↗
PubMed1999

Expression of nerve growth factor in hepatolithiasis.

AIMS/BACKGROUND: Nerve growth factor (NGF) has recently been shown to influence the survival and function of non-neuronal inflammatory cells, possibly through its activity as a colony-stimulating factor. It may also play an important role in acute inflammation and tissue repair. However, no prior report has focused on NGF in chronic inflammatory diseases of the gastrointestinal and biliary tracts. The aim of this study was to examine the expression of NGF in hepatolithiasis. METHODS: Twenty-six liver specimens resected from 22 patients with intrahepatic calcium bilirubinate stones and from 4 patients with intrahepatic cholesterol stones were examined immunohistochemically. RESULTS: The 22 patients with calcium bilirubinate stones demonstrated NGF immunoreactivity associated with surrounding inflammatory cells that was localized to the epithelia of proliferative peribiliary glands in the ductal wall. However, neither the surface lining of the bile duct nor hepatocytes expressed detectable NGF immunoreactivity. In the cholesterol stones cases in contrast, peribiliary glandular elements and inflammatory cell infiltration were less extensive than those observed in cases of calcium bilirubinate stones, and NGF immunoreactivity was not noted. CONCLUSIONS: These observations suggest that proliferative peribiliary glands express NGF protein in chronic proliferative cholangitis. This is characteristic of intrahepatic calcium bilirubinate stones.

Adult↗
PubMed1999

Effect of gene conversion on polymorphic patterns at major histocompatibility complex loci.

The pattern of polymorphisms at MHC loci was studied by computer simulations and by DNA sequence analyses, with special reference to synonymous and non-synonymous divergence among alleles. A model of overdominance plus short-term selection was simulated for a gene family with allelic and non-allelic gene conversion. It was found that the ratio of non-synonymous-to-synonymous divergence among alleles decreases as the non-allelic conversion becomes more frequent. On the other hand, the ratio of synonymous divergence at the antigen recognition site to that at non-coding region increases by non-allelic conversion. By comparing such a pattern with the observed values of mammalian genes, it is suggested that non-allelic conversion is less frequent in human genes than in genes of other mammals. A quantitative analysis on the patchwork pattern was attempted by using identity excess among nucleotide sites of a gene. Comparison of simulation results with DNA data analysis shows that the rate of allelic conversion is high.

Animals↗
PubMed1999

Genetic abnormalities in Prader-Willi syndrome and lessons from mouse models.

Prader-Willi syndrome is a multigenic disorder with developmental and neurobehavioural abnormalities. There are multiple genetic causes, although all ultimately involve the loss of paternally derived gene expression of chromosome region 15q11-q13. Multiple imprinted genes expressed only from the paternal allele have been identified in the specific region of human chromosome 15q associated with Prader-Willi syndrome and in the syntenic mouse chromosome 7C region, including a novel polycistronic gene (SNURF-SNRPN) that encodes two independent proteins. The latter genetic locus may play a key role in Prader-Willi syndrome and the evolution of imprinting in this domain, because it is uniquely involved with mutations in the imprinting process and balanced translocations in this syndrome. Indeed, based on the co-localization of SNURF and SNRPN within the imprinting control region critical to Prader-Willi syndrome, evolutionary arguments would suggest that this genetic locus is a prime candidate for mutations producing the failure-to-thrive phenotype of neonates with this syndrome and of corresponding mouse models. Hence, the SNURF-SNRPN gene may encode a paternally derived postnatal growth factor.

Angelman Syndrome↗
PubMed1999

Mutations affecting the ability of the Escherichia coli UmuD' protein to participate in SOS mutagenesis.

The products of the SOS-regulated umuDC operon are required for most UV and chemical mutagenesis in Escherichia coli, a process that results from a translesion synthesis mechanism. The UmuD protein is activated for its role in mutagenesis by a RecA-facilitated autodigestion that removes the N-terminal 24 amino acids. A previous genetic screen for nonmutable umuD mutants had resulted in the isolation of a set of missense mutants that produced UmuD proteins that were deficient in RecA-mediated cleavage (J. R. Battista, T. Ohta, T. Nohmi, W. Sun, and G. C. Walker, Proc. Natl. Acad. Sci. USA 87:7190-7194, 1990). To identify elements of the UmuD' protein necessary for its role in translesion synthesis, we began with umuD', a modified form of the umuD gene that directly encodes the UmuD' protein, and obtained missense umuD' mutants deficient in UV and methyl methanesulfonate mutagenesis. The D39G, L40R, and T51I mutations affect residues located at the UmuD'2 homodimer interface and interfere with homodimer formation in vivo. The D75A mutation affects a highly conserved residue located at one end of the central strand in a three-stranded beta-sheet and appears to interfere with UmuD'2 homodimer formation indirectly by affecting the structure of the UmuD' monomer. When expressed from a multicopy plasmid, the L40R umuD' mutant gene exhibited a dominant negative effect on a chromosomal umuD+ gene with respect to UV mutagenesis, suggesting that the mutation has an effect on UmuD' function that goes beyond its impairment of homodimer formation. The G129D mutation affects a highly conserved residue that lies at the end of the long C-terminal beta-strand and results in a mutant UmuD' protein that exhibits a strongly dominant negative effect on UV mutagenesis in a umuD+ strain. The A30V and E35K mutations alter residues in the N-terminal arms of the UmuD'2 homodimer, which are mobile in solution.

Bacterial Proteins↗
PubMed1999

rpoS function is essential for bgl silencing caused by C-terminally truncated H-NS in Escherichia coli.

From evolutionary and physiological viewpoints, the Escherichia coli bgl operon is intriguing because its expression is silent (Bgl(-) phenotype), at least under several laboratory conditions. H-NS, a nucleoid protein, is known as a DNA-binding protein involved in bgl silencing. However, we previously found that bgl expression is still silent in a certain subset of hns mutations, each of which results in a defect in its DNA-binding ability. Based on this fact, we proposed a model in which a postulated DNA-binding protein(s) has an adapter function by interacting with both the cis-acting element of the bgl promoter and the mutated H-NS. To identify such a presumed adapter molecule, we attempted to isolate mutants exhibiting the Bgl(+) phenotype in the background of hns60, encoding the mutant H-NS protein lacking the DNA-binding domain by random insertion mutagenesis with the mini-Tn10cam transposon. These isolated mutations were mapped to five loci on the chromosome. Among these loci, three appeared to be leuO, hns, and bglJ, which were previously characterized, while the other two were novel. Genetic analysis revealed that the two insertions are within the rpoS gene and in front of the lrhA gene, respectively. The former encodes the stationary-phase-specific sigma factor, sigma(S), and the latter encodes a LysR-like DNA-binding protein. It was found that sigma(S) is defective in both types of mutant cells. These results showed that the rpoS function is involved in the mechanism underlying bgl silencing, at least in the hns60 background used in this study. We also examined whether the H-NS homolog StpA has such an adapter function, as was previously proposed. Our results did not support the idea that StpA has an adapter function in the genetic background used.

Bacterial Proteins↗
PubMed1999

Confocal microscopy in cornea guttata and Fuchs' endothelial dystrophy.

AIMS: To report the appearances of cornea guttata and Fuchs' endothelial dystrophy from white light confocal microscopy. METHODS: Seven eyes of four consecutive patients with cornea guttata were prospectively examined. Of the seven eyes, three also had corneal oedema (Fuchs' dystrophy). In vivo white light tandem scanning confocal microscopy was performed in all eyes. Results were compared with non-contact specular microscopy. RESULTS: Specular microscopy was precluded by corneal oedema in one eye. In the remaining six eyes, it demonstrated typical changes including pleomorphism, polymegathism, and the presence of guttae appearing as dark bodies, some with a central bright reflex. In all seven eyes, confocal microscopy revealed the presence of round hyporeflective images with an occasional central highlight at the level of the endothelium. Changes in cell morphology and size were readily appreciated. CONCLUSION: By comparison with specular microscopy, the hyporeflective images with an occasional central highlight seen on confocal microscopy are consistent with the presence of guttae. Confocal microscopy may confirm the diagnosis of cornea guttata and Fuchs' endothelial dystrophy by demonstrating the presence of guttae. This technique is especially valuable in cases of corneal oedema, where specular microscopy may fail to visualise the endothelium. However, specular microscopy should remain the method of choice to evaluate the endothelium, principally because it is easier to use.

Adult↗
PubMed1999

Confocal microscopy in the iridocorneal endothelial syndrome.

AIMS: To report the appearances of iridocorneal endothelial (ICE) syndrome from real time, white light confocal microscopy. METHODS: Three consecutive patients, each with ICE syndrome, were examined prospectively. Corneal specular and confocal microscopic examinations were performed in all three patients. In the first patient, a penetrating keratoplasty was performed and the cornea was examined by light and scanning electron microscopy. No surgery was performed in the remaining two patients. RESULTS: In the first patient corneal oedema prevented endothelial specular microscopy. Confocal microscopy performed before penetrating keratoplasty successfully revealed abnormal epithelial-like endothelial cells. Histological examinations of the cornea following penetrating keratoplasty revealed the presence of multilayered endothelial cells with epithelial features (microvilli). In the remaining two patients, specular microscopy showed the presence of ICE cells with typical dark/light reversal. Confocal microscopy demonstrated groups of endothelial cells with epitheloid appearances. In all three patients, the contralateral endothelial appearance was normal by specular and confocal microscopy, except for moderate endothelial polymegathism in one patient. Epithelial-like endothelial cells were characterised by prominent nuclei on confocal microscopy. CONCLUSIONS: The application of confocal microscopy indicates that the ICE syndrome is characterised by epitheloid changes in the endothelium. Confocal microscopy may be used to diagnose the ICE syndrome by demonstrating epithelial-like endothelial cells with hyperreflective nuclei. This technique is especially of value in cases of corneal oedema, since specular microscopy may fail to image the endothelium in such cases.

Aged↗
PubMed1999

Allopurinol increases ear swelling and mortality in a dinitrofluorobenzene-induced contact hypersensitivity mouse model.

The immunomodulatory effects of allopurinol were investigated in a mouse contact hypersensitivity model. Allopurinol caused a time- and dose-dependent lethal effect in dinitrofluorobenzene (DNFB)-sensitized mice. Furthermore, allopurinol markedly increased ear swelling in the remaining mice. In contrast, TMX-67, a newly synthesized xanthine oxidase/xanthine dehydrogenase (XOD/XDH) inhibitor, had almost no effect on DNFB-sensitized mice. Allopurinol reduced both the spleen weight and white blood cell count in DNFB-sensitized mice without affecting the T cell subset of splenocytes. The production of interferon (IFN)-gamma, in the splenocytes of DNFB-sensitized mice was reduced by allopurinol administration. Death due to allopurinol was much lower in the non-sensitized mice than in the DNFB-sensitized mice. These findings indicate that allopurinol may interact with DNFB to enhance its toxicity and allopurinol might also modulate or enhance the inflammatory effect of DNFB. Also, DNFB may cause metabolic alterations via inflammation, leading to enhanced allopurinol toxicity.

Allopurinol↗
PubMed1999

Favorable life-style modification and attenuation of cardiovascular risk factors.

In order to develop an effective counseling system for prevention of cardiovascular diseases, the association of a favorably changed life-style with improved risk factors was examined. Participants were 7,321 office workers aged 30-69 years from in and around Nagoya city. The age-adjusted odds ratio (OR) and its 95% confidence interval (CI) were calculated to assess the likelihood of risk factor improvement by favorable life-style modifications during a 3-year period. Those who began to eat breakfast and increased their vegetable intake normalized their previously abnormal diastolic blood pressure with more than twice the likelihood (adjusted OR [95% CI] 2.89 [1.29-6.46] and 2.60 [1.18-5.75], respectively). 'Began to eat breakfast' was also significantly associated with normalized total cholesterol (TC) (1.84, [1.05-3.21]). 'Stopped eating till full' significantly normalized the body mass index (2.03; [1.25-3.28]), uric acid (1.65; [1.07-2.52]) and TC (1.43; [1.04-1.97]). Those who started regular exercise significantly normalized their high-density lipoprotein-cholesterol (HDL-C) abnormality with 1.69-times the likelihood (1.69; [1.24-2.29]) and those who began to walk briskly also improved their TC abnormality (1.85; [1.19-2.89]). HDL-C was normalized with 2.55-times the likelihood in those who quit smoking (2.55; [1.68-3.86]). Because favorable life-style modifications can attenuate abnormal cardiovascular risk factors, then proper advice on specific risk factors should be routinely given at each health check-up in order to prevent the onset of cardiovascular diseases in subsequent years.

Adult↗
PubMed1999

Levels of soluble cell adhesion molecules in patients with angiographically defined coronary atherosclerosis.

Adhesion molecules on the endothelial cell membrane play an important role in the pathogenesis of atherosclerosis. Levels of soluble forms of cell adhesion molecules are reportedly elevated in patients with peripheral artery vessel disease and in patients with an atherosclerotic aorta. The present study investigated the association of serum levels of soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble intercellular adhesion molecule 1 (sICAM-1), and soluble P-selectin (sP-selectin) with coronary heart disease (CHD) and the extent of coronary atherosclerosis, and examined the influence of serum levels of lipids, lipoproteins and apolipoproteins (apo) in subjects with (n=52, M/F:43/9) and without (controls, n=40, M/F:25/15) angiographically proven coronary atherosclerosis. After controlling for age and gender, levels of sVCAM-1 (least squares mean +/- std error: 565+/-36 ng/ml vs 540+/-41 ng/ml, ns), sICAM-1 (261+/-17ng/ml vs 247+/-19ng/ml, ns), and sP-selectin (142+/-8ng/ml vs 149+/-10 ng/ml, ns) in patients with coronary atherosclerosis were not different from those in controls, as assessed by an analysis of covariance. After also adjusting for body mass index, hypertension, diabetes mellitus, and smoking by a multiple logistic function analysis, the association of sVCAM-1, sICAM-1, and sP-selectin with CHD was still not significant. Levels of sVCAM-1, sICAM-1, and sP-selectin were also not related to the extent of coronary atherosclerosis as judged by the number of stenosed vessels. However, inverse (p<0.05) relationships were observed between sVCAMs and serum levels of HDL3-cholesterol, apo A-II, and lipoprotein containing apo A-I and A-II, between sICAMs and levels of apo A-II and Lp A-I/A-II (Lp A-I/A-II), and between sP-selectin and lipoprotein containing only apo A-I. In conclusion, serum levels of soluble VCAM-1, ICAM-1, and P-selectin were not related to CHD or the extent of coronary atherosclerosis, but were inversely related to serum levels of high-density lipoprotein-related lipoproteins.

Apolipoproteins↗
PubMed1999

Combined effects of probucol and benzafibrate on lipoprotein metabolism and liver cholesteryl ester transfer protein mRNA in cholesterol-fed rabbits.

Probucol decreases and bezafibrate increases plasma high density lipoprotein-cholesterol (HDL-C) levels in humans. This study was performed to determine whether the HDL-C-lowering effects of probucol could be reversed by treatment with bezafibrate in hypercholesterolemic rabbits. Forty-nine normolipidemic Japanese White rabbits were divided into 5 groups [group 1: normal chow; group 2: 0.2% cholesterol (Ch) diet; group 3: 0.2% Ch and 1% probucol diet; group 4: 0.2% Ch and 1% bezafibrate diet; group 5: 0.2% Ch and 1% probucol plus 1% bezafibrate diet] and treated for 8 weeks. Plasma lipids, cholesteryl ester transfer protein (CETP) activity in the lipoprotein-deficient plasma fraction, CETP mRNA in liver tissue and plasma drug concentrations were investigated. Serum total cholesterol (TC) increased after the rabbits in groups 2, 3, 4 and 5 were fed Ch, but overall, no significant differences were observed in serum TC and triglyceride (TG) among these groups. Serum HDL-C levels increased (p<0.01) in the bezafibrate-treated group, but a significant (p<0.05) reduction in HDL-C was observed in both the Ch + probucol (group 3) and Ch + probucol plus bezafibrate (group 5) groups; no significant difference was observed between groups 3 and 5. Significant correlation (p<0.01) was found between serum low density lipoprotein cholesterol (LDL-C) levels and plasma probucol concentrations in groups 3 and 5, but no correlation was found between plasma concentrations of probucol/bezafibrate and serum HDL-C levels. CETP activity in the lipoprotein-deficient plasma fraction increased in the Ch-, Ch + probucol-, and Ch + probucol and bezafibrate-fed groups (groups 2, 3 and 5, respectively), whereas a significant reduction in this activity was observed in the Ch + bezafibrate-fed group (group 4). An analysis of covariance showed that the CETP activity responded more sensitively to drug treatment than did the serum HDL-C level. CETP mRNA in liver tissue was assessed by Northern blotting at 8 weeks, but no changes were observed among the 5 groups. Probucol decreased and bezafibrate increased serum HDL-C levels, through CETP activity without affecting liver CETP mRNA levels, and the decrease in HDL-C levels produced by probucol could not be reversed by bezafibrate.

Animals↗
PubMed1999

A note on the correlation between heterozygosity and recombination rate.

Mechanisms responsible for the correlation between heterozygosity and recombination rate have been thought to be background selection and selective sweep. In addition to these two, diversity enhancing selection and/or gene conversion is suggested to be contributing to the correlation, by surveying some examples of highly polymorphic loci that tend to locate in high-recombination regions.

Gene Conversion↗
PubMed1999

Effects of various kinds of dietary amino acids on the hepatotoxic action of D-galactosamine in rats.

The protective effects of various kinds of dietary amino acids against the hepatotoxic action of D-galactosamine (GalN) were examined. Male Wistar rats fed with 20% casein diets containing 10% or 5% amino acid for one week were injected with GalN (800 mg/kg body weight), and the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities, the hepatic glycogen concentration, and the serum glucose-level were examined 20 hours after the injection. In the groups with the 10% amino acid diets, activities of AST, ALT, and LDH in serum of 10% L-glutamine (Gln), 10% L-asparagine (Asn), and 10% L-serine (Ser) groups were significantly lower than those of the control group, and in the groups with the 5% amino acid diets, those activities of 5% L-histidine (His), 5% L-tyrosine (Tyr), 5% L-lysine (Lys), and 5% L-glycine (Gly) groups were also lower than those of the control group. The concentration of liver glycogen of 10% Gln-, 10% Asn-, and 10% Ser- groups and those levels of 5% His-, 5% Tyr-, 5% Lys-, and 5% Gly-groups were also significantly higher than that of the control group. As a result, it was found that some kinds of dietary amino acid such as L-Ser, L-Asn, L-His, L-Lys, L-Tyr, and L-Gly, in addition to L-Gln were effective to protect the rats from GalN-induced injury.

Alanine Transaminase↗
PubMed1999

Insulinoma with hyperproinsulinemia during hypoglycemia and loss of expression of vacuolar-type H(+)-ATPase (V-ATPase) in the tumor tissue.

Hypoglycemia with a low serum immunoreactive insulin (IRI) level and serum immunoreactive C-peptide (IRC) level was found in a 74-yr-old female. Although a fasting test induced hypoglycemia, the responses of IRI and IRC during the fasting test, and the results of a glucose tolerance test, glucagon test, and secretin test did not indicate the presence of an insulinoma. However, the serum proinsulin level before the fasting test was 130.5 pmol/L (N: 3.0-10.0 pmol/L), and this high level was maintained throughout the test. Soon after surgical enucleation of the tumor, the patient's blood glucose levels increased. Postoperatively, the hypoglycemic status resolved, and the serum proinsulin levels returned to normal (2.8 pmol/L). Histopathological studies revealed a typical insulinoma. Immunohistochemical studies by the recently developed method for vacuolar-type H+ (V-ATPase), which is responsible for acidification of the intracellular compartments in eukaryotic cells, showed that normal islets stained positive, but not the tumor. This finding indicates that the insulin-secretory granules in the insulinoma cells existed in a microenvironment in which V-ATPase activity had been lost. This suggests that the reduced activity of V-ATPase on the endomembrane of the insulin-secretory granules in insulinomas may result in loss of the acidic microenvironment and impaired conversion of proinsulin by converting enzymes.

Aged↗
PubMed1999

Modification of mutagenic activities of pro-mutagens by glyco-ursodeoxycholic acid in the Ames assay.

Mutagenicity, co-mutagenicity and anti-mutagenicity of glycoursodeoxycholic acid (GUDCA) were examined by the Ames assay using Salmonella typhimurium strain TA98 with S9. As pro-mutagens, 2-aminoanthracene (2AA), Benzo[a]pyrene (BaP), 3-amino-1-dimethyl-5H-pyrido[4, 3-b]indole (Trp-P-2), 2-amino-3-methylimidazo[4, 5-f]quinoline (IQ) and 2-amino-3, 4-dimethylimidazo[4, 5-f]quinoline (MeIQ) were used. In addition to these pro-mutagens, blue-chitin extracts of human gallbladder bile (BCE) collected from the cholecystectomized patients with cholelithiasis were used in order to investigate the role of GUDCA on mutagen(s) actually existing in human bile. It was found that GUDCA did not show mutagenicity in this test system. Concerning the modification of mutagenic activities of pro-mutagens, GUDCA showed the different directions. GUDCA acted as co-mutagen, since it enhanced the mutagenic activities of 2AA and BaP. But, acted as anti-mutagen, since it suppressed the activities of Trp-P-2, IQ and MeIQ, all of which were classified as heterocyclic amines. GUDCA also suppressed the mutagen(s) in human bile. Because of the use of blue-chitin absorbed method for testing bile mutagenicity, the chemicals involved were considered to be heterocyclic amines and other polycyclic compounds. In these we suspect the bile mutagens are heterocyclic amines. Further examination should be directed towards the investigation into the mechanism of anti-mutagenic effects of GUDCA on mutagen(s) actually existing in human bile.

Anthracenes↗
PubMed1999

New bipolar diathermy forceps with automatic dripping and flushing--technical note.

A new bipolar diathermy forceps system was developed to solve the problems of constant, pressure-limited flow rate, and one-sided irrigation. A roller pump, activated synchronously by pressing a foot switch, feeds dripping and flushing solution to the target tissue via the tip at both ends of the forceps. This system is volume-limited. Continuous compression of the foot switch first activates the flushing function, which continues for less than 1 second, during which time bleeding spots can be detected. The flow then changes automatically to the dripping function to suppress tip burning and prevent damage to the surrounding tissues from heat and current leakage. Repeated pressing of the foot switch initiates the jet irrigation function (continuous high flow rates), allowing irrigation of hematomas and removal of excess debris.

Electrocoagulation↗