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Biomedical subjects

J Inoue

Publications and source records attributed to J Inoue.

At least 109 records · Page 6Linked to original sources
PubMed1995

Novel zinc chelators with dual activity in the inhibition of the kappa B site-binding proteins HIV-EP1 and NF-kappa B.

Both HIV-EP1 (also called PRDII-BF1 or MBP-1), a zinc finger protein, and NF-kappa B, a Rel family protein, bind to kappa B site present in the enhancer of multiple cellular and viral genes involved in immune function and inflammatory response including HIV-1 LTR and human interferon beta gene. When cells are exposed to extracellular stimuli such as virus or phorbol ester, the activity of both HIV-EP1 and NF-kappa B is induced. Thus, kappa B site-directed transcription could be regulated by two distinct proteins in a cooperative way. Novel heterocyclic compounds comprising (dimethylamino)pyridine and histidine units, i.e., 1-4, have been designed and synthesized, aiming at inhibition of these kappa B site-binding proteins to discriminate their functions. These compounds exhibited remarkable zinc-binding capability as revealed by NMR study. Compounds 1 and 2 showed a marked inhibitory effect on the DNA binding activity of HIV-EP1 by removing zinc without interfering with the DNA binding activity of NF-kappa B. Since it has been demonstrated that zinc somehow influences the DNA binding of NF-kappa B, the effect of these heterocyclic compounds and their zinc complexes on NF-kappa B was examined. Zinc complexes of 3 and 4 exhibited the inhibitory effect on the DNA binding of NF-kappa B and/or homodimeric complexes of p50 and p65 subunits of NF-kappa B without affecting HIV-EP1. Thus, it became possible to inhibit either one of the two kappa B site-binding proteins without inhibiting the other.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1995

Determination of (+)- and (-)-nicardipine concentrations in human serum and their correlation with the antihypertensive effect after oral administration of racemic nicardipine.

Serum (+)- and (-)-nicardipine concentrations were determined after oral administration of racemic nicardipine, and the relationship between the concentration of each enantiomer and the percentage change in blood pressure was investigated. Serum concentrations of (+) and (-)-nicardipine were assayed separately by a method combining high-performance liquid chromatography (HPLC) with gas chromatography - mass spectrometry (GS-MS). Linear relationships were found with serum concentrations of 0.25-80 mg x ml(-1) for both enantiomers of nicardipine with correlation coefficients of greater than 0.999. A single oral dose of 40 mg racemic nicardipine was given to 15 patients with essential hypertension. Serum (+)-nicardipine concentration was 2-3 times higher than the concentration of (-)-nicardipine 1, 2, and 3 after drug administration. The logarithmically transformed value of the serum (+)-nicardipine concentration was inversely correlated with the percentage change in systolic blood pressure, the correlation being statistically significant 1 and 2 h after drug administration, and also inversely correlated with the percentage change in diastolic blood pressure 1, 2 and 3 h after drug administration. However, the logarithmically transformed value of serum (-)-nicardipine showed no significant correlations with the percentage change in either systolic or diastolic blood pressure.

Administration, Oral↗
PubMed1995

On the parameter estimation for diffusion models of single neuron's activities. I. Application to spontaneous activities of mesencephalic reticular formation cells in sleep and waking states.

For the Ornstein-Uhlenbeck neuronal model a quantitative method is proposed for the estimation of the two parameters characterizing the unknown input process, namely the neuron's mean input per unit time mu and the infinitesimal standard deviation per unit time sigma. This method is based on the experimentally observed first- and second-order moments of interspike intervals. The dependence of the estimates mu and ŝigma on the moments of the observed interspike intervals and on the neuronal parameters is clarified, and a comparison is made between the estimates based on the classical Wiener model and those yielded by the Ornstein-Uhlenbeck model. Comprehensive tables are included in which the displayed values of mu and ŝigma have been calculated in terms of physiologically realistic pairs of first- and second-order moments. Our method is finally applied to interspike interval data recorded from neurons in the mesencephalic reticular formation of the cat during hypothetical sleep, slow-wave sleep stage, and wake stage.

Animals↗
PubMed1995

Plasticity of myofibroblasts appearing in granulation tissues after acetic acid treatment. Effect of bFGF.

To clarify the origin of the myofibroblasts appearing in the healing process of the acetic acid-induced ulcer and effect of basic fibroblast growth factor (bFGF) on these myofibroblasts, we conducted an immunohistochemical study using antibody to intermediate filaments, desmin and vimentin. The binding sites of bFGF on the regenerative tissues were also studied by the radioautographic study of soluble compounds. As a result, the binding sites of bFGF were accumulated on the fibroblasts and myofibroblasts as well as on endothelial cells. The effect of CS23, acid-stable human recombinant bFGF was shown on distribution of myofibroblasts and regeneration of the microvascular system in the mucosal and submucosal layers.

Acetates↗
PubMed1995

Effect of basic fibroblast growth factor on reinnervation of gastric microvessels. Possible relevance to ulcer recurrence.

Basic fibroblast growth factor (bFGF) has well-established angiogenic and ulcer healing actions. bFGF has also been found to induce neural regeneration in the central nervous system. Thus, the present study was undertaken to clarify the effect of basic fibroblast growth factor on the regeneration of autonomic nerves in the granulation tissues following the induction of experimental gastric ulcer induced by acetic acid in rats. Rats were divided into control, acetic acid alone, and acetic acid plus acid-stable human recombinant basic fibroblast growth factor (CS23, 1 microgram/100 g body wt., every 12 hr for three days, or one or two weeks, through oral gastric intubation) groups. As a result, few autonomic nerves were recognized surrounding the newly formed arterioles and venules in the acetic acid alone group. In the CS23-treated group, the cholinergic, calcitonin gene-related peptide and vasoactive intestinal peptide-immunoreactive nerves were clearly recognized near the microvessels, but few adrenergic nerves were seen even after CS23 treatment. From these observations, basic fibroblast growth factor was suggested to promote the reinnervation of the newly formed microvessels.

Animals↗
PubMed1995

Epitope tagging.

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Amino Acid Sequence↗
PubMed1995

Autoradiographic demonstration of lansoprazole uptake sites in rat antrum and colon.

To investigate possible effects of lansoprazole other than its acid suppression through the parietal cell, uptake sites for lansoprazole were studied by autoradiography in rat antral and colon mucosa. Autoradiography was performed using two different methods, i.e., routine fixation and in vitro autoradiography on cryostat sections. Our results showed that the uptake sites for lansoprazole in the gastric antrum were located in the interstitial cells, including unmyelinated nerve fibers, whereas those in the colon mucosa corresponded to epithelial cells and some of the interstitial cells. With electron microscopy, the uptake sites for lansoprazole in the colon epithelial cells were seen exclusively near the apical plasma membrane. On the basis of these findings, lansoprazole may have effects on autonomic nerve and colon epithelial function as well as on acid secretion.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

Overlapping substrate specificities of benzaldehyde dehydrogenase (the xylC gene product) and 2-hydroxymuconic semialdehyde dehydrogenase (the xylG gene product) encoded by TOL plasmid pWW0 of Pseudomonas putida.

Two aldehyde dehydrogenases involved in the degradation of toluene and xylenes, namely, benzaldehyde dehydrogenase and 2-hydroxymuconic semialdehyde dehydrogenase, are encoded by the xylC and xylG genes, respectively, on TOL plasmid pWW0 of Pseudomonas putida. The nucleotide sequence of xylC was determined in this study. A protein exhibiting benzaldehyde dehydrogenase activity had been purified from cells of P. putida (pWW0) (J. P. Shaw and S. Harayama, Eur. J. Biochem. 191:705-714, 1990); however, the amino-terminal sequence of this protein does not correspond to that predicted from the xylC sequence but does correspond to that predicted from the xylG sequence. The protein purified in the earlier work was therefore 2-hydroxymuconic semialdehyde dehydrogenase (the xylG gene product). This conclusion was confirmed by the fact that this protein oxidized 2-hydroxymuconic semialdehyde (kcat/Km = 1.6 x 10(6) s-1 M-1) more efficiently than benzaldehyde (kcat/Km = 3.2 x 10(4) s-1 M-1). The xylC product, the genuine benzaldehyde dehydrogenase, was purified from extracts of P. putida (pWW0-161 delta rylG) which does not synthesize 2-hydroxymuconic semialdehyde dehydrogenase. The amino-terminal sequence of the purified protein corresponds to the amino-terminal sequence deduced from the xylC sequence. This enzyme efficiently oxidized benzaldehyde (kcat/Km = 1.7 x 10(7) s-1 M-1) and its analogs but did not oxidize 2-hydroxymuconic semialdehyde or its analogs.

Alcohol Oxidoreductases↗
PubMed1995

The force-velocity relationship of the ATP-dependent actin-myosin sliding causing cytoplasmic streaming in algal cells, studied using a centrifuge microscope.

When uncoated polystyrene beads suspended in Mg-ATP solution were introduced into the internodal cell of an alga Chara corallina, the beads moved along the actin cables with directions and velocities (30-62 microns s-1) similar to those of native cytoplasmic streaming. Bead movement was inhibited both in the absence of ATP and in the presence of CA2+, as with native cytoplasmic streaming. These results indicate that bead movement is caused by cytoplasmic myosin molecules attached to the head surface interacting with actin cables. The steady-state force-velocity relationship of the actin-myosin sliding that produces cytoplasmic streaming was determined by applying constant centrifugal forces to the beads moving on the actin cables. The force-velocity curve in the positive load region was nearly straight, and the implications of this shape are discussed in connection with the kinetic properties of the actin-myosin interaction in cytoplasmic streaming. It is suggested that the time for which a cytoplasmic myosin head is detached from actin in one cycle of actin-myosin interaction is very short. The Ca(2+)-induced actin-myosin linkages, responsible for the Ca(2+)-induced stoppage of cytoplasmic streaming, were shown to be much stronger than the rigor actin-myosin linkages.

Actins↗
PubMed1995

[Bone mineral density in postmenopausal elderly women with type 2 diabetes].

We measured lumbar bone mineral density (L2-4 MBMD) in the postmenopausal elderly diabetic women and made comparisons with age-matched controls in terms of the age, body mass index (BMI) and % BMD of age-matched. In addition we evaluated the correlation between BMD and menarche age, menopause age, HbA1c, serum calcium, serum phosphate, serum alkaline phosphatase (S-Alp) and the ratio of urine calcium to urine creatinine (UCa/Cr). Moreover we divided non-insulin dependent diabetic patients (NIDDM) into two groups; the high BMD group and the low BMD group. Serum Alp and the ratio of UCa/Cr were compared in these two groups. The relationships between regimen of therapy and BMD were also analyzed in female NIDDM. There were no significant differences of BMD and background factors between controls and NIDDM. The ratio of UCa/Cr in the high BMD group were significantly less than that in low BMD group (p < 0.05). BMD in NIDDM with retinopathy was lower, but not significantly, than that in NIDDM without retinopathy. The methods of therapy for NIDDM such as diet alone, an oral hypoglycemic agent and insulin did not influence BMD in elderly postmenopausal diabetics. These results indicated that BMD in elderly postmenopausal diabetics are dependent on UCa/Cr and retinopathy.

Aged↗
PubMed1995

[Development of Elderly Diabetes Impact Scales (EDIS) in elderly patients with diabetes mellitus].

To assess the quality of life (QOL) in elderly diabetic patients, 452 elderly outpatients aged over 60 years old who lived in 4 districts near our hospital were visited at home and of them were asked to follow 83 questionnaires concerning QOL by professional interviewers. Using the 37 questions about the impact of diabetes on elderly diabetic patients, we have developed the Elderly Diabetes Impact Scales (EDIS). The EDIS consisted of 6 subscales (burden of symptoms, burden of daily life, burden of diet therapy, burden of drug therapy, satisfaction, worry). Responses to questions were estimated with a 4-point multiple-choice assessment. The impact was rated from 1 (no impact, never worried, or very satisfied) to 4 (very burdened, always worried, or very dissatisfied) for each question and total EDIS scores were calculated by summing up the scores of the 37 questions. The internal consistency of the EDIS and its six subscales were of a satisfactory magnitude (0.66-0.88). There was also a significant correlation between the EDIS and PGC morale scales (r = -0.48, p < 0.001) and between the EDIS subscales and 3 moral components suggesting a convergent validity of the EDIS. The EDIS may be useful in evaluating the quality of life in elderly patients with diabetes mellitus.

Activities of Daily Living↗
PubMed1995

[Factors associated with increased diabetes burden in elderly diabetic patients].

To define the factors that determine the increased burden of diabetes in elderly diabetic patients, we examined the relationship between the Elderly Diabetes Impact Scales (EDIS) and physical or social factors in 383 elderly outpatients aged over 60 years old who answered QOL questionnaires by professional interviewers. The EDIS consisted of 6 subscales (burden of symptoms, burden of daily life, burden of diet therapy, burden of drug therapy, satisfaction, worry) and total EDIS scores were calculated by summing up the 4-point scores of 37 questions. The EDIS scores were highest in patients who received insulin therapy. In univariate analysis, high EDIS scores were significantly associated with high HbA1c, low Roken ADL score, and the presence of retinopathy or neuropathy. Among social factors, leisure activities, housework or jobs, social network, and positive social support were significantly associated with low EDIS scores, while negative social support was associated with high EDIS scores in elderly diabetic patients. Multiple linear regression analysis revealed that age (younger), sex (women), low ADL (or diabetic complications), insulin therapy, low positive social support, high negative social support, economical dissatisfaction, and the low adaptative feeling of diabetes were significant and independent determinants of a high burden in diabetic patients indicated by EDIS scores in Japanese elderly diabetic patients.

Activities of Daily Living↗
PubMed1995

[Burden of dietary therapy on elderly patients with diabetes mellitus].

As a part of a QOL study in elderly diabetes mellitus, we performed an interview conducted by professional interviewers on the sense of burden of dietary therapy in 383 elderly outpatients with diabetes mellitus aged over 60 years old. We used a scale on Burden of Dietary Therapy (BDT) that consisted of 7 questions (calorie restriction, dietary balance, regular dietary habits, restriction of favorite food, restriction of amounts of snacks, restrictions when eating out, burden of total dietary therapy). The sense of burden was rated from 1 (never burdened) to 4 (heavily burdened) for each question and the alpha coefficiency of the BDT scale was 0.80. Women, relatively younger elderly patients, hyperglycemic patients, or tablet-treated patients had higher BDT scale scores. The lower the positive family support scores and the higher the negative social support scores the greater was the BDT score. High BDT scores were significantly associated with low PGC moral scales (p < 0.001). The results suggest that the burden of dietary therapy could lower the quality of life in elderly patients with diabetes mellitus.

Aged↗
PubMed1995

Uptake site of lansoprazole, a proton pump inhibitor, in human fundic mucosa: possible relevance with fibroblast and Helicobacter pylori.

To clarify the mechanism of the effect of lansoprazole in the healing of human gastric ulcer, the uptake sites of lansoprazole were studied using endoscopically biopsied specimens from the margin of the gastric ulcer. The specimens were incubated in a medium containing 3H-lansoprazole for 5 or 15 min., postfixed with 1% osmic acid and embedded in Epon. The semithin or ultrathin sections were made and radioautographic emulsion films were applied by the wire-loop method. 30 days after the incubation, the sections were developed, fixed and observed by light and electron microscopy. As a result, the uptake sites of lansoprazole were accumulated on the fibroblasts located near the tip portion of the gastric mucosa and on the unmyelinated nerve fibers as well as on the parietal cells. Some of the uptake sites were also observed near the plasma membrane of the bacteria in the gastric lumen. From these observations, lansoprazole uptake sites were not only on the parietal cells but on the fibroblasts and the bacteria, suggesting that the effect of lansoprazole was exerted partly through the influence on the mesenchymal cells and Helicobacter pylori-related organisms.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

[Neoadjuvant chemotherapy of liver tumors metastasized by sigmoid colon cancer: a case report of CDDP/5-FU intraarterial infusion therapy followed by hepatectomy].

A case of liver tumors metastasized by Sigmoid colon cancer was treated with intrahepatic arterial infusion of CDDP (10 mg) and 5-FU (250 mg) via subcutaneously implanted reservoir. After 20 administrations of CDDP and 5-FU, the tumors in the right lobe of the liver disappeared, but those in the left lobe remained. Therefore left hepatectomy was carried out. Six months after the hepatectomy, a nodule recurrence was disclosed in the right lobe of the liver. With re-elevated serum CEA level, subsequent intrahepatic arterial infusion of CDDP and 5-FU the nodule size reduced with normalization of the serum CEA level.

Aged↗