Quinolone resistance mechanisms in Klebsiella pneumoniae.
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Anti-Infective Agents↗
Biomedical subjects
A Kitamura
Publications and source records attributed to A Kitamura.
[Characteristics of participants in community-based rehabilitation programs and their levels of independence in activities of daily living].
To clarify characteristics of participants in community-based rehabilitation programs provided by local municipalities (cities, towns, and villages) and effect of the program on their levels of independence in activities of daily living (ADL), a cross-sectional study was performed on 422 participants in 49 municipalities in Kochi Prefecture. 1. Mean age of participants was 68.3 +/- 9.0, and 77.7% of them were stroke patients. 2. The mean interval between disease onset and program participation was 40.4 months, and the mean duration of program participation was 54.5 months. 3. At the start of rehabilitation programs and at the time of the investigation (December 1993), about 90% of the participants had good levels of independence in ADL (Rank A and over according to the standard of the Ministry of Health and Welfare). 4. The frequency of rehabilitation programs and the presence of occupational therapists were positively associated with the improvement of levels of independence in ADL. In particular, the frequency of rehabilitation programs was associated with improvement of quality of life in self-supporting participants (Rank J2), and the presence of occupational therapists was associated with the improvement of ADL in semi-bed-ridden participants (Rank A). 5. After adjusting for age and sex, using multiple logistic regression analysis, type of diseases (non-stroke), hospital rehabilitation immediately after onset, higher levels of independence in ADL at the start of rehabilitation programs, and higher frequency of rehabilitation programs were significantly associated with improvements in levels of independence in ADL. Shorter interval between disease onset and program participation, and the presence of occupational therapists were also associated with improvements in levels of independence in ADL, although the relation did not reach statistical significance.
Activities of Daily Living↗
[The clinical usefulness and problem of combined spinal epidural needle].
The clinical usefulness of combined spinal-epidural needles, Portex Spinal/Epidural set (Pencil point tip type and Lancet point tip type), was evaluated on 30 patients undergoing orthopedic lower limb surgeries, hysterectomies or transurethral surgeries. In all the patients, the spinal-epidural needles were successfully inserted with paramedian approach without any problem. The time to appearance of cerebrospinal fluid in the spinal needle hub after removal of the stylet was 15-40 seconds, and no patient in both groups had postspinal headache. Following spinal anesthesia, the local anesthetics injected through the epidural catheter extended the analgesia in the range of 1-2 dermatomes higher in the Lancet point type group in comparison with Pencil point type group. It is possible that the hole in the dura may allow a transfer of local anesthetics into the subarachnoid space. The present study shows that combined spinal-epidural block is clinically useful, and the Pencil point type is safer than the Lancet point type.
Adult↗
Induction of the human gene for p44, a hepatitis-C-associated microtubular aggregate protein, by interferon-alpha/beta.
A hepatitis-C-associated microtubular aggregate protein, referred to as p44, has been identified as a cytoplasmic antigen in the hepatocytes of chimpanzees infected with hepatitis C virus. The production of p44 mRNA is markedly induced in the liver of chimpanzees infected with hepatitis C or hepatitis D virus. To examine the mechanism of this induction, we isolated a genomic clone for the human p44 protein and analyzed its structure. The human p44 gene spans approximately 14 kbp of DNA and consists of nine exons separated by eight introns. An interferon-stimulated response element, which confers inducibility by interferon-alpha/beta, was found in the promoter region of the gene. Northern-blot analysis revealed that the human p44 gene is inducible by interferon-alpha/beta, but not by interferon-gamma. Functional analysis demonstrated that the interferon-stimulated response element in the promoter region of the gene mediates the inducibility of the gene by interferon-alpha/beta. Thus, the human p44 gene is a member of the family of interferon-alpha/beta inducible genes. The protein p44 may be one of the mediators involved in the antiviral action of interferon.
Amino Acid Sequence↗
Inhibitory activity of chlorophyllin on the genotoxicity of carcinogens in Drosophila.
Antimutagenic activity of copper chlorophyllin against various carcinogenic mutagens was assayed with Drosophila genotoxicity tests, i.e., the wing spot test for detecting somatic cell mutations and the DNA repair test for detecting DNA damage. In these tests, Drosophila larvae were fed carcinogens together with chlorophyllin. Polycyclic aromatic compounds, including heterocyclic amines, polycyclic aromatic hydrocarbons, aromatic amines and aromatic nitro compounds, were subject to inhibition, with a few exceptions. The results support the view that chlorophyllin traps carcinogens by forming complexes, thereby inhibiting the absorption of these compounds from the digestive tract. Consistent with this mechanism, Sepharose-supported chlorophyllin in the feed inhibited the Trp-P-2-induced wing spot formation, while Sepharose itself was ineffective.
Animals↗
Serum total cholesterol and mortality in a Japanese population.
Although the relation between serum total cholesterol and coronary heart disease is well established, the relation with mortality from non-coronary disease is controversial. Inverse relations of serum cholesterol with hemorrhagic stroke and cancer have stimulated the examination of cholesterol-non-coronary mortality associations. The population surveyed is 12,187 men and women aged 40-69 years living in Yao City, a suburb of Osaka, who undertook baseline examinations between 1975 and 1984 and had no history of stroke and coronary heart disease at baseline. The subjects were followed on average 8.9 years until the end of 1988 using systematic mortality surveillance. During the follow-up, there were 343 deaths, comprising 170 cancer deaths (International Classification of Death 9th edition: ICD-9, 140-239), 21 coronary heart disease deaths (ICD-9, 410-414), 67 other cardiovascular deaths (ICD-9, 390-458 excluding 410-414), and 85 non-cardiovascular, non-cancer deaths. There was a significant inverse association of serum cholesterol with total and cancer mortality for men, and no significant association for women. The cholesterol-disease association, although not significant, was positive for coronary heart disease and other cardiovascular disease deaths, and inverse for non-cardiovascular, non-cancer deaths in both sexes. The inverse association of serum cholesterol with total and cancer mortality for men remained significant after controlling for age, job classification, hypertension category, usual alcohol intake, cigarette smoking, and relative weight index.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Comparison of inhibition of Escherichia coli topoisomerase IV by quinolones with DNA gyrase inhibition.
In order to examine the inhibitory activities of quinolones against topoisomerase IV, both subunits of this enzyme, ParC and ParE, were purified from Escherichia coli. The specific activity of topoisomerase IV decatenation was found to be more than five times greater than that of topoisomerase IV relaxation. Thus, the decatenation activity of topoisomerase IV seems the most relevant activity for use in studies of drug inhibition of this enzyme. Although topoisomerase IV was less sensitive to quinolones than DNA gyrase, the 50% inhibitory concentrations for decatenation were significantly lower than those for type I topoisomerases. Moreover, there was a positive correlation between the inhibitory activity against topoisomerase IV decatenation and that for DNA gyrase supercoiling. These results imply that topoisomerase IV could be a target for the quinolones in intact bacteria and that quinolones could inhibit not only supercoiling of DNA gyrase but also decatenation of topoisomerase IV when high concentrations of drug exist in bacterial cells.
4-Quinolones↗
Left ventricular mass and subsequent blood pressure changes among middle-aged men in rural and urban Japanese populations.
BACKGROUND: It has been suggested that echocardiographically determined left ventricular mass (LVM) is useful in the prediction of hypertension. To examine the relation between LVM and subsequent blood pressure (BP) change, a 6- to 8-year follow-up was conducted in adult Japanese men. METHODS AND RESULTS: LVM was determined by M-mode echocardiography using the American Society of Echocardiography formula among 354 normotensive men aged 30 to 59 years from a rural community (n = 193) and from urban companies (n = 161) in Japan between 1979 and 1983. BP was remeasured 6 to 8 years after baseline in 148 rural men (77%) and 127 urban men (79%). For men whose BP was remeasured, the mean +/- SD LVM index (LVM/body surface area [g/m2]) at baseline was 117 +/- 22 in rural men and 99 +/- 15 in urban men (the difference, P < .001). For both populations, LVM index was positively associated with age and physical activity but not with body mass index. Associations of LVM index with usual alcohol intake and initial BPs were generally weak. According to linear regression analyses after controlling for these covariates at baseline, a 20-g/m2 greater LVM index at baseline was associated with a 5 mm Hg increase in systolic and a 4 mm Hg increase in diastolic BP during the subsequent 6 to 8 years for urban men. A 1-mm greater average ventricular wall thickness was associated with a similar BP increase. For rural men, positive associations of LVM index with BP increase existed but were weak. The weaker association between LVM index and BP increase in rural compared with urban men was probably the result of effects of higher physical activity, leading to a larger left ventricular internal dimension. The increase in systolic and diastolic BPs over the 6 to 8 years of observation was significantly related to baseline LVM index in rural and urban men with a smaller internal dimension (rural men, < or = 49 mm; urban men, < or = 47 mm) but not in those with larger dimensions. CONCLUSIONS: An increased LVM index predicts subsequent BP increase in middle-aged normotensive men in the presence of a normal or small internal dimension.
Adult↗
High-density lipoprotein cholesterol and premature coronary heart disease in urban Japanese men.
BACKGROUND: The objective of this study was to examine the relation of high-density lipoprotein cholesterol (HDL-C) to coronary heart disease in Japanese men whose serum total cholesterol is low by Western standards. METHODS AND RESULTS: A prospective, observational study based on 7.7 years of follow-up for incidence of coronary heart disease and stroke was conducted. The subjects were 6408 middle-aged male workers aged 40 to 59 years at baseline in urban companies in Osaka, Japan, whose mean serum total cholesterol was 5.10 mmol/L. Mean HDL-C adjusted for age, total cholesterol, systolic blood pressure, alcohol intake, cigarette smoking, and body mass index was 1.27 to 1.28 mmol/L for men who developed coronary heart disease (n = 46) or definite myocardial infarction (n = 21) compared with 1.46 mmol/L for those free of cardiovascular disease (n = 6256; difference, P < .01). There was no significant difference in mean HDL-C between stroke cases (n = 33) and those free of cardiovascular disease. The incidence rates of coronary heart disease and definite myocardial infarction, adjusted for the other risk factors, were three to four times higher in the lowest HDL-C quartile (< 1.24 mmol/L) than the highest quartile (> or = 1.66 mmol/L), and there was a significant dose response for definite myocardial infarction. Serum total cholesterol was positively and significantly associated with coronary heart disease incidence. Furthermore, the inverse association for HDL-C was apparent among men with total cholesterol < 5.69 mmol/L (mean total cholesterol, 4.76 mmol/L) and men with total cholesterol > or = 5.69 mmol/L (mean total cholesterol, 6.26 mmol/L). CONCLUSIONS: Coronary heart disease incidence is inversely related to HDL-C in urban Japanese middle-aged men, whose mean total cholesterol (5.10 mmol/L) is relatively low.
Adult↗
[Study of the effects of a new vitamin D3 derivative on type II collagen-induced arthritis in an experimental rat model of rheumatoid arthritis].
The effects of a new derivative of vitamin D3, 22-oxa-1 alpha,25-dihydroxyvitamin D3 (OCT), on rheumatoid arthritis was investigated using collagen-induced arthritis in rat, as an experimental model of the disease. Peroral administration of OCT significantly suppressed the incidence of arthritis and inhibited hind-paw-swelling. The levels of IgM and IgG antibodies against Type II collagen in sera were found to decrease in the OCT treated-group. The production of immunoglobulin against Type II collagen from rat spleen cells was also decreased in this group. These immunological effects of OCT on collagen-induced arthritis were more remarkable than those of 1 alpha-hydroxyvitamin D3. These findings indicated that OCT may have a therapeutic value as an immunoregulatory agent for patients with rheumatoid arthritis through inhibition of the autoimmune response to Type II collagen.
Administration, Oral↗
Molecular cloning and sequence analysis of the cDNA for a human serine protease reponsible for activation of hepatocyte growth factor. Structural similarity of the protease precursor to blood coagulation factor XII.
Hepatocyte growth factor (HGF) is a potent mitogen for parenchymal liver cells, epithelial cells, and endothelial cells and may play an important role in liver regeneration following hepatic injury. HGF is homologous to plasminogen and is first synthesized and secreted as an inactive single-chain precursor and then activated to a heterodimeric form by endoproteolytic processing. Recently, a novel serine protease responsible for this processing (HGF activator) has been purified from fetal bovine serum (Shimomura, T., Ochiai, M., Kondo, J., and Morimoto, Y. (1992) Cytotechnology 8, 219-229). In this study, we purified HGF activator from human serum and determined its partial amino acid sequence. Based on the amino acid sequence, we have molecularly cloned the cDNA for human HGF activator. The nucleotide sequence of the cDNA revealed that HGF activator is derived from the COOH-terminal half region of a precursor protein of 655 amino acids and that the precursor consists of multiple putative domains homologous to those observed in blood coagulation factor XII. These domains may be involved in the conversion of the precursor to the active form of HGF activator.
Amino Acid Sequence↗
Comparative developmental toxicity and metabolism of nitrazepam in rats and mice.
This study was designed to evaluate the developmental toxicity of nitrazepam (NZ) in Sprague-Dawley rats and ICR mice and to determine the metabolic factors which modulate susceptibility to the developmental effects of NZ. Rats were treated orally with a single dose of NZ at 300 mg/kg on Day 12 of gestation. Mice received one dose of 300 mg/kg NZ via gavage between Days 9 and 14 of gestation. NZ administration resulted in a significant incidence of malformations in rats, while no evidence of teratogenic action was observed in mice. Pronounced species differences in the metabolism of NZ were observed. In rats, 7-acetylaminonitrazepam (AANZ) was detected as the major metabolite in plasma and embryos, whereas in mice, only small amounts of this product were found. The rate of N-acetylation of 7-aminonitrazepam (ANZ) to AANZ was 8.5-fold greater in rat liver cytosol than that in mouse liver cytosol. In contrast, the rate of deacetylation of AANZ to ANZ was 9-fold greater in mouse liver microsomes than that in rat liver microsomes. The developmental effects of authentic metabolites of NZ were studied in the two species. A single oral administration of 300 mg/kg ANZ to pregnant animals produced a significant incidence of malformations in rats, but not in mice. On the other hand, AANZ was teratogenic in both species. These results suggest that the difference in the susceptibility to NZ-induced teratogenicity between rats and mice may be related to differences in the levels of N-acetyltransferase and deacetylase, and that AANZ may be involved in the teratogenic mechanism.
Abnormalities, Drug-Induced↗
Renal fibroblasts are sensitive to growth-repressing and matrix-reducing factors from activated lymphocytes.
Various forms of nephropathy accompany interstitial fibrosis with lymphocytic infiltration. To probe the relationship between lymphocyte-derived factors and renal fibroblasts, we studied the effect of culture supernatant from lymphocytes stimulated by concanavalin A (ConASN) on the growth and matrix metabolism of rat kidney fibroblasts. 3H-thymidine incorporation and Northern analysis, respectively, revealed that ConASN repressed cell growth and the mRNA level of collagen type I, but dramatically elevated the steady-state expression of metalloproteinase transin/stromelysin. The growth inhibitor in ConASN was moderately heat-sensitive and less than 5 kD in molecular size, qualities that differed from those of transforming growth factor-beta (TGF-beta), IL-1 beta, IL-6, and tumour necrosis factor-alpha (TNF-alpha). The matrix regulatory factor in ConASN was highly heat-sensitive and more than 30 kD in size. Among several lymphokines tested, TNF-alpha produced the same effects as ConASN on the metabolism of extracellular matrix. We hypothesize that lymphocyte-derived factors have a significant role in the attenuation of renal fibrogenesis, as well as its progression, via inhibiting cell growth and matrix accumulation.
Animals↗
[The intracuff pressure changes in N2O gas-barrier cuff made of a special material].
During inhalation anesthesia using N2O, the intracuff pressure has been reported to increase due to diffusion of N2O into the cuff. The excessive intracuff pressure may produce ischemia of the tracheal mucosa. In this study, the changes in the intracuff pressure of endotracheal tube with a cuff made of a material with high N2O gas-barrier properties were compared with those of the normal endotracheal tubes. Forty adult patients (16 males and 24 females) were anesthetized with oxygen 2 l.min-1, N2O 4 l.min-1 and isoflurane under controlled ventilation and they were divided into the following three groups according to the type of the endotracheal tube used: the tube with a standard cuff made by PORTEX Co. Ltd; the tube with a profile cuff (high volume cuff) made by PORTEX Co. Ltd; the tube with gas-barrier cuff made by TERUMO Co. Ltd. The changes of each intracuff pressure were recorded continuously for 180 minutes after cuff inflation. A marked increase of the pressure was observed after inhalation of N2O in standard and profile cuff groups. In gas-barrier cuff group, there was a tendency of increasing cuff pressure without a statistically significant difference. The present study suggests that the use of a cuff with a material of high N2O gas-barrier properties would be effective to prevent increased intracuff pressure by N2O diffusion, and this would be especially useful during long anesthesia and hypotensive anesthesia.
Adult↗
Gene expression and regulation of HGF-SF.
Molecular cloning and characterization of cDNAs and genomic DNA for human HGF-SF revealed the expression pattern of the gene. Alternative use of splicing sites and processing/polyadenylation sites generates multiple mRNAs for human HGF-SF in a variety of tissues and cell lines. This alternative mRNA production may be regulated in a tissue-specific manner. Full-length HGF-SF is encoded by the 6.3 kb or 3.1 kb mRNA. A variant form of HGF-SF is encoded by the 1.5 kb mRNA which is generated by alternative splicing accompanied by the utilization of an alternative processing/polyadenylation site in an extra exon. The variant form consists of an N-terminal sequence and the first two kringles and acts as an antagonist of HGF-SF mitogenic activity. HGF-SF with a deletion of 5 amino acids in the first kringle is produced from an alternatively spliced mRNA. The deletion induces the change in the heparin-binding property of the protein. Analysis of responses of the HGF-SF mRNA during liver regeneration revealed that the HGF-SF gene is activated. The level of mRNA markedly increases in the rat liver, spleen and lung after administration of hepatotoxins. Characteristic regulatory elements, an IL6 response element and an NF-IL6 binding element, are present proximal to the major transcription initiation site in the human HGF-SF gene. These elements may be involved in the activation of the gene after liver injury. The potential autocrine role of HGF-SF in the acquisition of altered phenotypes was determined by introduction of the gene into target cells for HGF-SF. Autocrine production of the factor induces changes in cell properties from parental types to those obtained by the addition of exogenous factor.
Alternative Splicing↗
Gene cloning and characterization of a novel extracellular ribonuclease of Bacillus subtilis.
An extracellular nuclease gene of Bacillus subtilis was cloned in the same organism by detecting the amplified enzyme activity, which was secreted from the transformant cells on an RNA-containing agar medium. An open reading frame encoding 289 amino acids was identified within the cloned fragment. The transcriptional initiation site was determined by nuclease S1 mapping and the promoter region showed similarity to the conserved recognition sequences for the E sigma A and/or E sigma E RNA polymerases. The production of the nuclease by the B. subtilis transformants greatly depends on the liquid medium used. SDS/PAGE analysis of the purified enzyme showed two adjoining bands of molecular mass about 32 kDa, and the NH2-terminal amino acid sequence analysis suggested that the NH2-terminal portion of the nuclease was subjected to a limited proteolysis after or during secretion. The nuclease was uniquely characterized as a Mg(2+)-activated ribonuclease which hydrolyzes RNA apparently nonspecifically into oligonucleotides with 5'-terminal phosphate. The deduced amino acid sequence of this enzyme shows no obvious similarity with other nuclease sequences.
Amino Acid Sequence↗
Gene expression of metalloproteinase and its inhibitor in mesangial cells exposed to high glucose.
To clarify the roles of metalloproteinases and their inhibitor (TIMP) in diabetic glomerulopathy, we studied the effect of a high glucose concentration on the gene expression of metalloproteinase transin and TIMP as well as collagen type IV and laminin in cultured rat mesangial cells (MCs). In the high glucose group, collagen type IV, laminin, and TIMP mRNA levels were all elevated in a concentration-dependent manner, whereas transin expression was suppressed. Osmotic control of high glucose with mannitol selectively stimulated TIMP expression. We hypothesize that high glucose decreases matrix-degrading activity as well as increases matrix productivity in MCs.
Animals↗
The diagnostic significance of anti-type II collagen antibody assay in rheumatoid arthritis.
An improved enzyme-linked immunosorbent assay (ELISA) for the detection of anticollagen antibodies in human serum has been developed. With the use of this method, antibodies against native human Type II collagen were detected in 22.7% of sera from 480 patients with rheumatoid arthritis (RA). The antibodies were found to be collagen type specific, showing no reaction with human Type I and Type III collagens. The antibodies appeared in high incidence during the early phase of the disease, and RA patients with involvement of a single joint, mono-articular arthritis, were often positive for anti-Type II collagen antibodies. In most of these patients, anti-Type II collagen antibodies preceded the appearance of rheumatoid factors. The antibodies were all negative in sera from patients with gout, osteoarthritis (OA) and non-arthritic diseases. Thus, anti-Type II collagen antibody assay may have diagnostic significance for RA patients, especially those in whom laboratory and clinical findings provide only minimal help in diagnosis.
Adult↗