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Biomedical subjects

I Kobayashi

Publications and source records attributed to I Kobayashi.

At least 91 records · Page 5Linked to original sources

Circulating interleukin-6 significantly correlates to thyroid hormone in acute myocardial infarction but not in chronic heart failure.

To investigate relationships between thyroid states and the cardiac endocrine system, we analyzed thyrotropin (TSH), thyroid hormone, plasma levels of interleukin-6 (IL-6) and brain natriuretic peptide (BNP) in 50 patients with chronic heart failure (CHF), in 30 patients with heart failure from acute myocardial infarction (AMI), and in 15 controls. Plasma levels of IL-6 and BNP in both CHF and AMI were significantly elevated, while free triiodothyronine (FT3) was significantly decreased compared to controls. FT3/free thyroxine (FT4) ratio was significantly decreased in CHF but not in AMI compared to controls. In CHF, diuretic treatment diminished circulating BNP but not IL-6, while diuretic treatment increased FT3/FT4 ratio. In AMI, FT3/FT4 ratio was significantly decreased 72 h compared to 12 h after the onset of AMI, while BNP and IL-6 were significantly increased 72 h compared to 12 h after the onset of AMI. In both CHF and AMI, BNP significantly correlated with FT4. On the other hand, significant correlations between IL-6 and FT3, and between IL-6 and FT3/FT4 ratio were detected in AMI but not in CHF. This preliminary study suggests that IL-6, BNP and thyroid hormone reflect ventricular dysfunction in both acute and chronic heart failure, and that IL-6 significantly relates to circulating thyroid hormone in AMI but not in CHF.

Aged↗

Improved dysgammaglobulinaemia in congenital rubella syndrome after immunoglobulin therapy: correlation with CD154 expression.

UNLABELLED: A boy with congenital rubella syndrome developed dysgammaglobulinaemia with elevated serum levels of IgM. CD154 was not induced on his peripheral blood mononuclear cells when rubella virus RNA was detected in his throat swabs and peripheral blood by reverse transcriptase polymerase chain reaction. Following intravenous immunoglobulin therapy, improvement of immunoglobulin abnormalities, disappearance of rubella virus and normalisation of CD154 expression were demonstrated. CONCLUSION: These findings implicate the efficacy of intravenous immunoglobulin therapy for dysgammaglobulinaemia in congenital rubella syndrome and a role of CD154 for a prolonged virus infection.

Antibodies, Viral↗

High-resolution CT findings of macrophage activation syndrome: a case report.

Macrophage activation syndrome (MAS) is a rare disorder characterised by benign, reactive, excessive, well-differentiated macrophage proliferation, secondary to an immune dysregulation in response to some triggering agents such as viral infection. We report a 3-year-old girl with MAS and pulmonary involvement. This is the first radiographic description of MAS on high-resolution CT.

Anti-Inflammatory Agents↗

Serum level of vascular endothelial growth factor is decreased by hormone replacement therapy in postmenopausal women without hypercholesterolemia.

The administration of hormone replacement therapy (HRT) to postmenopausal women (PMW) reportedly has beneficial effects on their levels of lipid and lipoproteins. Estrogen retards the development of atherosclerosis induced by a high-fat diet in animals. Although vascular endothelial growth factor (VEGF) may be involved in the development of atherosclerosis in humans, there is no information on effect of estrogen administration on VEGF level and lipid metabolism. We evaluated 64 healthy normotensive or hypertensive PMW before and during the administration of HRT (0.625 mg conjugated equine estrogen combined with 2.5 mg medroxyprogesterone acetate orally) daily for 6 months. All hypertensive PMW were well-controlled on antihypertensive drug therapy. According to their total cholesterol level at baseline, we divided the PMW with HRT (n=54) into a normocholesterolemic group (NC, total cholesterol <220 mg/dl, n=35) and a hypercholesterolemic group (HC, total cholesterol >/=220 mg/dl, n=19). We evaluated the serum levels of VEGF at baseline, and again at 3 and 6 months after starting HRT. HRT significantly (P<0.01) reduced the mean VEGF level from 31.5+/-4.3 pg/ml at baseline to 18.2+/-2.3 pg/ml after 6 months in the NC group. However, the VEGF levels in the HC group and the control group exhibited no significant change at either 3 or 6 months after starting HRT. In summary, HRT, using a combination of conjugated equine estrogen and medroxyprogesterone acetate, reduced the level of VEGF in normocholesterolemic PMW more effectively than in those with hypercholesterolemia.

Aged↗

(9-[4-acetyl-3-hydroxy-2-n-propylphenoxy) methyl]-3-(1H-tetrazol-5-yl)-4H-pyrido [1,2-a] pyrimidin-4-one), AS-35, inhibits leukotriene synthesis.

AS-35, (9-[4-acetyl-3-hydroxy-2-n-propylphenoxy) methyl]-3-(1H-tetrazol-5-yl)-4H-pyrido[1, 2-a] pyrimidin-4-one), was developed as a leukotriene (LT) receptor antagonist, which also inhibited IgE-mediated release of leukotrienes (LTs). We have investigated the action of AS-35 on the enzyme activities which are involved in the synthesis of LTC(4) and LTB(4) (LT-synthesizing enzymes); cytosolic phospholipase A(2) (cPLA(2)), 5-lipoxygenase (5-LO), leukotriene (LT)C(4) synthase and LTA(4) hydrolase. AS-35 dose-dependently inhibited IgE- and A23187-stimulated production of LTC(4) by up to 71.5-84.8% and that of LTB(4) by 48.3-49.2% at 2. 5x10(-5) M. The assays for cPLA(2)(-), 5-LO-, LTC(4) synthase- and LTA(4) hydrolase-activities revealed that the inhibition is attributable to suppression of cPLA(2), 5-LO and LTC(4) synthase but not LTA(4) hydrolase. We have also studied the action of AS-35 on the release of beta-hexosaminidase (beta-HEX) as a marker of preformed mediators. AS-35 had only weak inhibitory action on the release of beta-HEX. The results indicate that anti-allergic action of AS-35 is predominantly attributable to its inhibition of LT synthesis by suppressing three consecutive enzymes for LTC(4) synthesis.

Animals↗

Antimicrobial activity of gemifloxacin (SB-265805), a newer fluoroquinolone, against clinical isolates of Neisseria gonorrhoeae, including fluoroquinolone-resistant isolates.

Antimicrobial activity of gemifloxacin (SB-265805), a newly developed fluoroquinolone, to Japanese isolates of Neisseria gonorrhoeae was compared with those of various fluoroquinolones, including norfloxacin, ciprofloxacin, tosufloxacin, levofloxacin, sparfloxacin, and trovafloxacin. Among the fluoroquinolones tested, gemifloxacin was most active against N. gonorrhoeae isolates. The MIC90 values of gemifloxacin for 94 N. gonorrhoeae isolated from 1992 through 1993 and 100 isolated from 1996 through 1997 were 0.03 and 0.125 microg/ml, respectively. On the other hand, MIC90 values of the other fluoroquinolone for the 1992-1993 isolates and the 1996-1997 isolates ranged from 0.125 to 2 microg/ml and from 0.5 to 8 microg/ml, respectively. Gemifloxacin was also the most potent fluoroquinolone against 31 ciprofloxacin-resistant isolates with the ciprofloxacin MIC of 1 to 16 microg/ml, for which the gemifloxacin MIC50 and MIC90 values were 0.25 and 2 microg/ml, respectively. Moreover, the activity of gemifloxacin against fluoroquinolone-resistant gonococcal isolates containing multiple amino acid substitutions in both GyrA and ParC proteins was superior to those of the other compounds.

Amoxicillin↗

A defect in harmonin, a PDZ domain-containing protein expressed in the inner ear sensory hair cells, underlies Usher syndrome type 1C.

Usher syndrome type 1 (USH1) is an autosomal recessive sensory defect involving congenital profound sensorineural deafness, vestibular dysfunction and blindness (due to progressive retinitis pigmentosa)1. Six different USH1 loci have been reported. So far, only MYO7A (USH1B), encoding myosin VIIA, has been identified as a gene whose mutation causes the disease. Here, we report a gene underlying USH1C (MIM 276904), a USH1 subtype described in a population of Acadian descendants from Louisiana and in a Lebanese family. We identified this gene (USH1C), encoding a PDZ-domain-containing protein, harmonin, in a subtracted mouse cDNA library derived from inner ear sensory areas. In patients we found a splice-site mutation, a frameshift mutation and the expansion of an intronic variable number of tandem repeat (VNTR). We showed that, in the mouse inner ear, only the sensory hair cells express harmonin. The inner ear Ush1c transcripts predicted several harmonin isoforms, some containing an additional coiled-coil domain and a proline- and serine-rich region. As several of these transcripts were absent from the eye, we propose that USH1C also underlies the DFNB18 form of isolated deafness.

Adaptor Proteins, Signal Transducing↗

Moderate-intensity regular exercise decreases serum tumor necrosis factor-alpha and HbA1c levels in healthy women.

OBJECTIVE: To evaluate the effects of moderate-intensity regular exercise on serum levels of tumor necrosis factor-alpha (TNF-alpha) and glucose and lipid metabolism parameters. DESIGN: Longitudinal intervention study of a 5 month exercise training program (30-45 min/day, 4-5 days/week). SUBJECTS: Forty-one healthy Japanese women aged 41-69 y at baseline; 27 participants in the exercise program. MEASUREMENTS: Body mass index (BMI), waist-to-hip ratio (WHR), percentage body fat, and fasting levels for serum TNF-alpha, serum soluble TNF receptor p55 (TNF-RI) and TNF receptor p75 (TNF-RII), serum lipids, HbA1c, and serum insulin before and after exercise. RESULTS: In overweight to obese subjects, serum levels of TNF-alpha, TNF-RI and TNF-RII were significantly higher than those in lean subjects. There were significant correlations between log serum TNF-alpha and BMI, percentage body fat, WHR, HbA1c and log insulin. TNF-RI was significantly correlated with BMI, percentage body fat, WHR and HbA1c. TNF-RII was also associated with BMI, percentage body fat and WHR. However, the correlation between TNF-RII and HbA1c did not reach statistical significance. Neither TNF-RI nor TNF-RII was correlated with log insulin. In contrast, TNF-alpha, TNF-RI and TNF-RII were negatively correlated with HDL cholesterol. Regular exercise decreased BMI, percentage body fat, HbA1c, serum TNF-alpha, TNF-RI and TNF-RII and increased HDL cholesterol levels. In addition, exercise-induced change in serum TNF-alpha was independently correlated with changes in HbA1c and serum insulin, after being adjusted for the change in fat-free mass. CONCLUSION: Changes in serum TNF-alpha that occur with exercise may play an important role in improving glucose metabolism parameters.

Adult↗

The effects of water extracts of CagA positive or negative Helicobacter pylori on proliferation, apoptosis and connexin formation in acetic acid-induced gastric ulcer of rats.

AIM: To investigate the influence of water extracts of CagA-positive or -negative Helicobacter pylori on healing of chronic gastric ulcers and on connexin formation, proliferation and apoptosis, in acetic acid-induced chronic gastric ulcers in rats. METHODS: Acetic acid was used to induce chronic gastric ulcers in rats, and a water extract of H. pylori was given by mouth every day. Connexin 32 formation was assessed using Western blotting as previously described. The frequencies of proliferating cell nuclear antigen staining and of TdT-mediated dUTP-biotin nick end labelling were examined. RESULTS: In untreated rats, acetic acid-induced gastric ulcers healed after 14 days and the electrophoretic band corresponding to connexin 32 appeared 4 days after ulcer induction. Treatment with a water extract of H. pylori delayed ulcer healing, with the ulcers remaining unhealed even on the 14th day; healing was delayed more when treatment was with an extract of CagA-positive rather than CagA-negative H. pylori. Connexin 32 appeared earlier when treatment was with a CagA-negative rather than a CagA-positive extract, but in both cases later than in the untreated control group. Proliferating cell nuclear antigen labelling on the fourth day was seen in 14.5% +/- 1.6% of mucosal cells of control group, but in 35.9% +/- 1.4% and 36.5% +/- 1.4% of mucosal cells treated with either VacA(+)CagA(-) and VacA(+)CagA(+) H. pylori extract, respectively. Furthermore, extracts of both H. pylori strains, especially VacA(+)Cag(+) H. pylori promoted apoptosis. CONCLUSIONS: A water extract of H. pylori increased both proliferation and apoptosis, which are related to exacerbation and healing of ulcer as well as appearance of connexin 32.

Acetic Acid↗

A dynamic analysis of chest wall motions with MRI in healthy young subjects.

OBJECTIVE: The objective of this study was to analyse respiratory-related motion of the chest wall with non-invasive method. METHODOLOGY: Using magnetic resonance image (MRI), 30 sequential images (scanning time, 0.4 s per image) on sagittal, axial and coronal planes were obtained in nine healthy young subjects during quiet breathing (QB) and maximal deep breathing (MDB). The coronal planes were obtained in five of nine subjects during MDB. Ventilation was simultaneously measured with pneumotachometer. RESULTS: There was a linear correlation between instantaneous lung volume and lung cross-sectional area. Motion of the diaphragm and rib cage was also linearly related to instantaneous lung volume. The exception was lower anteroposterior (AP) diameter of the rib cage. The contribution of individual part of the chest wall motion to a unit lung volume change was assessed by slope (S) of the linear regression line. The S at the anterior diaphragm was significantly smaller than those at middle and posterior parts during MDB. The S of middle and posterior diaphragmatic motion was approximately five times that of AP motion of upper rib cage. The S of AP motion of upper rib cage was twice that of transverse motion during either QB or MDB. CONCLUSION: We concluded that dynamic MRI study with concurrent ventilation measurement is a simple and reliable method for evaluation of local chest wall motion, and that neither diaphragm nor rib cage works as a single functional unit during active ventilation.

Adult↗

Incidence of human papillomavirus 16 and 18 infection and p53 mutation in patients with oral squamous cell carcinoma in Japan.

The purpose of this study was to investigate the prevalence of human papillomaviruses (HPVs) 16 and 18 infection, and p53 mutation in oral squamous cell carcinomas (SCCs) in Japanese patients. Our results showed a higher incidence of HPV16 and 18 infections than previous studies because we combined the findings of a consensus polymerase chain reaction (PCR), restriction fragment length polymorphism by using the restriction enzyme digestion of the PCR products and Southern blot hybridization. Each HPV16 and 18 E6/E7 DNA was detected in 9 (20%) and 25 (54%) of 46 samples. The p53 mutation in the exons from 5 to 8 were detected in 20 out of 46 samples (43%) by a PCR-single strand conformation polymorphism analysis. There was a significant relationship between HPV16 and the p53 mutation (P =0.02) suggesting that HPV16 infection has a mutagenic effect in oral SCC. However, neither HPV infection nor p53 mutation influenced survival.

Adult↗

Comparison of gyrA and parC mutations and resistance levels among fluoroquinolone-resistant isolates and laboratory-derived mutants of oral streptococci.

Laboratory-derived fluoroquinolone-resistant mutants were obtained by serial passage of Streptococcus sanguis and Streptococcus anginosus isolates on agar containing increasing concentrations of old and new fluoroquinolones, ofloxacin and DU-6859a, respectively. Sequencing of an S. sanguis isolate exposed to DU-6859a showed that resistance was associated with two mutations in the quinolone resistance determining region (QRDR) of the gyrA gene (Ser83-->Phe; Glu87-->Lys), and with a mutation in the parC gene (Ser79-->Ile). However, different mutations in the gyrA gene (Ser83-->Tyr) and parC gene (Ser79-->Phe) were found in a S. sanguis isolate exposed to ofloxacin. A fluoroquinolone-resistant isolate, QR-95101, from a dental infection, had a single mutation in the gyrA gene (Ser83-->Phe) and in the parC gene (Ser79-->Phe). Two fluoroquinolone-resistant mutants, QS-701OFm and QS-701DUm, were obtained from S. anginosus QS-701, by exposure to ofloxacin and DU-6859a, respectively. These mutants showed a common substitution at codon 83 (Ser-->Phe) in the gyrA gene but had different substitutions at codon 87 (QS-701OFm, Glu-->Gln; QS-701DUm, Glu-->Lys). They also had different substitutions at codons 79 and 135 in the parC gene (QS-701OFm, Ser79-->Leu but no change at Glu135; QS-701DUm, Ser79-->Ile and Glu135-->Gln). The resistance levels of the DU-6859a-selected resistant S. sanguis mutant QS-951DUm to DU-6859a, ofloxacin, ciprofloxacin and norfloxacin were higher than those of the ofloxacin-selected resistant mutant QS-951OFm. However, ampicillin susceptibilities of these mutants were not different from the parental strains. In S. anginosus, the DU-6859a-selected fluoroquinolone-resistant mutant QS-701DUm was resistant to all the fluoroquinolones tested, while the ofloxacin-selected mutant QS-701OFm was resistant to three fluoroquinolones, but not DU-6859a. The results indicate that different fluoroquinolones select distinct mutations in the QRDR of the gyrA and parC genes in oral streptococci. The gyrA or parC mutation in oral streptococci may determine the levels of fluoroquinolone resistance.

Anti-Infective Agents↗

Interleukin 12 induces crescentic glomerular lesions in a high IgA strain of ddY mice, independently of changes in IgA deposition.

BACKGROUND: Our recently established high immunoglobulin (Ig)A inbred strain (HIGA) of ddY mice showed constantly high serum IgA levels, progressive mesangial sclerosis accompanied by IgA deposits, and elevated renal expression of transforming growth factor (TGF)-beta, mimicking IgA nephropathy. In the present study, we assessed the role of the immune system, especially of T cells, in this strain. METHODS: The in vitro production of interferon (IFN)-gamma, interleukin (IL)-4 and TGF-beta1 by splenic CD4+ T cells was assessed in HIGA mice at 14 and 28 weeks of age by comparison with age-matched C57BL/6 and BALB/c mice, T-helper (Th) 1, and Th2 prone controls respectively. Moreover, recombinant murine IL-12 was administered intraperitoneally to HIGA mice and serum IgA and renal lesions were analysed. RESULTS: The production of IFN-gamma by splenic CD4+ T cells was markedly upregulated in HIGA mice at both ages as compared with age-matched C57BL/6 and BALB/c mice. Although splenic CD4+ T cells from HIGA mice produced less IL-4 than those from BALB/c mice at both ages, the former produced significantly more IL-4 with age, which contrasted with the age-associated decrease in the latter. Moreover, TGF-beta1 production of these cells in HIGA mice was equal to or greater than that in the two groups of control mice at both ages. Daily intraperitoneal administration of IL-12 for 1 week significantly enhanced crescent formation with glomerular macrophage accumulation and interstitial cell infiltration, whereas it reduced the serum IgA level. CONCLUSIONS: In HIGA mice, Th1 is markedly upregulated from a young age and there is an age-associated Th2 increase with TGF-beta1 upregulation in helper T cells. The former may be related to the exacerbation of inflammatory renal lesions on IL-12 administration, while the latter may contribute to increased IgA production, leading to glomerular IgA deposition and progressive glomerulosclerosis in HIGA mice. The pathogenic role of T cell function and fluctuation of these subsets, especially the Th1/Th2 balance, is crucial to the immunopathological phenotype of the renal lesions in HIGA mice.

Animals↗

Evolution of sequence recognition by restriction-modification enzymes: selective pressure for specificity decrease.

Several type II restriction-modification (RM) gene complexes kill host bacterial cells that have lost them, through attack on the chromosomal recognition sites of these cells. Two RM gene complexes recognizing the same sequence cannot simultaneously enjoy such stabilization through postsegregational host killing, because one will defend chromosomal sites from attack by the other. In the present work, we analyzed intrahost competition between two RM gene complexes when the recognition sequence of one was included in that of the other. When the EcoRII gene complex, recognizing 5'-CCWGG (W = A, T), is lost from the host, the SsoII gene complex, which recognizes 5'-CCNGG (N = A, T, G, C), will prevent host death by protecting CCWGG sites on the chromosome. However, when the SsoII (CCNGG) gene complex is lost, the EcoRII (CCWGG) gene complex will be unable to prevent host death through attack by SsoII on 5'-CCSGG (S = C, G) sites. These predictions were verified in our experiments, in which we analyzed plasmid maintenance, cell growth, cell shape, and chromosomal DNA. Our results demonstrate the presence of selective pressure for decrease in the specificity of recognition sequence of RM systems in the absence of invading DNA.

Cell Division↗

Isolation and characterization of arsenate-sensitive and resistant mutants of Chlamydomonas reinhardtii.

Arsenate-sensitive and resistant mutants of Chlamydomonas reinhardtii were obtained by screening mutants generated by random insertional mutagenesis for growth in the presence of various concentrations of arsenate. The intracellular concentrations of arsenic in the mutants kept in the arsenate-containing medium were determined with an atomic absorption spectrophotometer. The intracellular levels of arsenic in the arsenate-resistant mutants were all lower than that of the parent strain CC425. Some of the arsenate-sensitive mutants, AS1 and AS3, showed obviously higher levels of arsenic than that of CC425, while other sensitive mutant, AS2, did not accumulate arsenic so much. Analysis of the chemical species of arsenic suggested that inorganic arsenic was converted to dimethylarsinic acid (DMAA) in CC425. However, DMAA was hardly detected in AS2. The mechanisms of the resistance to arsenate are discussed on its uptake and detoxification.

Animals↗