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Biomedical subjects

A Kawaguchi

Publications and source records attributed to A Kawaguchi.

At least 55 records · Page 3Linked to original sources
PubMed2000

The effect of atorvastatin on serum lipids and lipoproteins in patients with homozyous familial hypercholesterolemia undergoing LDL-apheresis therapy.

The efficacy of atorvastatin, a new hydroxymethylglutaryl (HMG)-CoA reductase inhibitor, in reducing serum lipid levels, modifying lipoprotein composition, and suppressing cholesterol synthesis was evaluated in patients with homozygous familial hypercholesterolemia (homozygous FH) undergoing LDL-apheresis therapy. Atorvastatin was given in escalating doses (10, 20, and 40 mg/day) to nine patients with homozygous FH. Five of nine patients responded well to atorvastatin; four of these patients were receptor-defective and the remaining one was receptor-negative. The change in LDL-cholesterol in the receptor-defective patients averaged -20.6% compared to the baseline level at the highest dose of atorvastatin. Of five receptor-negative type patients, only one showed good response to atorvastatin therapy with a LDL-cholesterol reduction of 14.9%. Although the other four receptor-negative patients did not show a change in LDL-cholesterol, all of them exhibited a considerable increase in HDL-cholesterol. All patients showed reduced urinary excretion of mevalonic acid, suggesting that atorvastatin decreases LDL-cholesterol by inhibiting cholesterol biosynthesis even where LDL-receptor activity is not present. Atorvastatin also decreased serum triglycerides in both receptor-negative and defective patients, especially in the latter. As cholesterol level rebounds quickly after each apheresis procedure, a combination therapy using atorvastatin and apheresis may increase the efficacy of the apheresis treatment, improving cost-benefit effectiveness by reducing the frequency of the apheresis treatment.

Adolescent↗
PubMed2000

In vitro neurogenesis by progenitor cells isolated from the adult human hippocampus.

Neurogenesis persists in the adult mammalian hippocampus. To identify and isolate neuronal progenitor cells of the adult human hippocampus, we transfected ventricular zone-free dissociates of surgically-excised dentate gyrus with DNA encoding humanized green fluorescent protein (hGFP), placed under the control of either the nestin enhancer (E/nestin) or the Talpha1 tubulin promoter (P/Talpha1), two regulatory regions that direct transcription in neural progenitor cells. The resultant P/Talpha1:hGFP+ and E/nestin:enhanced (E)GFP+ cells expressed betaIII-tubulin or microtubule-associated protein-2; many incorporated bromodeoxyuridine, indicating their genesis in vitro. Using fluorescence-activated cell sorting, the E/nestin:EGFP+ and P/Talpha1:hGFP+ cells were isolated to near purity, and matured antigenically and physiologically as neurons. Thus, the adult human hippocampus contains mitotically competent neuronal progenitors that can be selectively extracted. The isolation of these cells may provide a cellular substrate for re-populating the damaged or degenerated adult hippocampus.

Adult↗
PubMed2000

Antagonistic activity of tamsulosin against human vascular alpha1-adrenergic receptors.

OBJECTIVE: To elucidate the vascular effect of tamsulosin hydrochloride (INN, tamsulosin), a selective alpha1A-adrenergic receptor antagonist, in humans, we examined the alpha1-adrenergic receptor antagonistic activity against blood vessels after oral intake of recommended and higher doses of the drug and evaluated the relation between its plasma concentrations and the effect. METHODS: Nine healthy men ranging in age from 21 to 38 years received tamsulosin (0.2 mg or 0.6 mg) or lactate capsule as a control after breakfast in a randomized crossover fashion. Seven hours after administration, their fingertip vasoconstrictor response to contralateral hand cooling and vasoconstrictor response of the dorsal hand vein to phenylephrine were examined, and blood samples for the measurement of plasma drug concentration were obtained. RESULTS: The fingertip vasoconstrictor response was significantly reduced and the infusion rate of phenylephrine producing a half-maximal constriction was significantly increased by 0.6 mg tamsulosin but not by 0.2 mg tamsulosin. There were significant positive correlations between plasma drug concentrations and the changes of these parameters. CONCLUSION: These results suggest that although the alpha1-adrenergic receptor-blocking effect of tamsulosin on blood vessels is relatively small, it is clearly correlated with plasma drug concentration and a higher dose of the drug could cause systemic adverse effects.

Administration, Oral↗
PubMed2000

Influence of losartan on alpha-adrenoceptor-mediated vasoconstrictor response in humans.

To evaluate the influence of losartan on alpha-adrenoceptor-mediated vasoconstrictor response, we examined dorsal hand vein constrictor response to phenylephrine (16-8,192 ng/min) and fingertip vasoconstrictor response to cold stimulation with and without pretreatment with losartan (50 mg/day) for 3 days in nine healthy men. The effect of coadministration of angiotensin II (Ang II) (0.3 ng/min) on the venoconstrictor response also was evaluated. Oral pretreatment with losartan alone influenced neither of the responses. The log of the infusion rate of phenylephrine producing half-maximal venoconstriction [log(ED50)] was 2.69 +/- 0.10 (mean +/- SEM) for control and 2.68 +/- 0.09 for losartan, and the reduction ratio of fingertip blood flow was 68.1 +/- 4.0% for control and 66.7 +/- 4.3% for losartan. Coadministration of Ang II, however, significantly enhanced the venoconstrictor response to phenylephrine [log(ED50): 2.43 +/- 0.09, p < 0.05 vs. control], and the pretreatment with losartan attenuated this effect [log(ED50): 2.60 +/- 0.11]. These findings indicate that the alpha-adrenoceptor-mediated vasoconstrictor response is not influenced by losartan; however, it is enhanced by exogenous Ang II, and losartan attenuates the enhanced response, in healthy human subjects.

Adult↗
PubMed2000

Fluctuations of lamellar structure prior to a lamellar-->gyroid transition in a nonionic surfactant system

Fluctuations of lamellar structure prior to a lamellar-->gyroid transition in a nonionic surfactant-water system has been investigated by means of small-angle x-ray scattering (SAXS) and differential scanning calorimeter measurements. For large DeltaT (DeltaT=T-T(LG), where T is the temperature and T(LG) the lamellar-->gyroid transition temperature) in the lamellar phase, the SAXS profiles can be described by a Caille correlation function for undulating lamellar structure. Approaching the temperature to the T(LG), an excess diffuse scattering grows at the lower Q (Q is the magnitude of scattering vector) side of the first lamellar peak. Highly oriented lamellar samples revealed that the excess diffuse scattering arises from in-plane density fluctuations. We attribute this diffuse scattering to the perforation fluctuation layer (PFL) structure and we show that the PFL is an equilibrium structure. At T(LG), the PFL transformed to the gyroid phase through a transient ordered structure having a rhombohedral symmetry.

Journal Article↗
PubMed2000

Intravascular free tissue factor pathway inhibitor is inversely correlated with HDL cholesterol and postheparin lipoprotein lipase but proportional to apolipoprotein A-II.

To elucidate the distribution and clinical implications of tissue factor pathway inhibitor (TFPI) concentrations, we measured TFPI levels consisting of preheparin free, lipoprotein-bound (Lp-bound), and endothelial cell-anchor pools in 156 patients with coronary artery disease (average age, 61.2+/-9.1 years; range, 32 to 78 years) by heparin infusion (50 IU/kg) and compared them with the preheparin TFPI levels of 229 healthy subjects (average age, 59. 6+/-9.4 years; range, 41 to 80 years). The patients had lower preheparin free TFPI and lower HDL cholesterol (HDL-C) levels than the healthy subjects with equivalent Lp-bound forms (free TFPI, 15. 9+/-6.5 versus 19.2+/-8.1 ng/mL). In a partial correlation analysis, the preheparin free TFPI levels were shown to be inversely correlated with the HDL-C concentrations in both the patients (r=-0. 454, P<0.001) and the healthy subjects (r=-0.136, P<0.05). As determined by comparison of preheparin and postheparin plasma, the patients generally showed preheparin free TFPI <10%, Lp-bound TFPI at 30%, and endothelial cell-anchor TFPI at 60%. When the patients were divided into 4 categories by their LDL cholesterol (LDL-C, 130 mg/dL) and HDL-C (40 mg/dL) levels to specify their coronary risks, the low-HDL-C groups had significantly increased preheparin and postheparin free TFPI levels and decreased postheparin LPL levels, whereas the high-LDL-C groups showed increased levels of Lp-bound TFPI. In a partial correlation analysis, we found a proportional relation between postheparin free TFPI and apolipoprotein A-II (r=0. 5327) and between HDL-C and LPL (r=0.4906), whereas postheparin free TFPI was inversely correlated with HDL-C (r=-0.4280) and postheparin LPL (r=-0.4791). The inverse relationship between TFPI and LPL suggests that increased free TFPI concentrations as a compensatory response of the endothelium to prevent atherothrombotic processes compete with and displace LPL on endothelial surface, resulting in reduced LPL and low HDL-C.

Adult↗
PubMed2000

Bioactive constituents of Chinese natural medicines. V. Radical scavenging effect of Moutan Cortex. (1): Absolute stereostructures of two monoterpenes, paeonisuffrone and paeonisuffral.

The methanolic extract and the ethyl acetate-soluble and methanol-eluted fractions from Chinese Moutan Cortex, the roots of Paeonia suffruticosa ANDREWS, were found to exhibit scavenging effect on 1,1-diphenyl-2-picrylhydrazyl radical and superoxide anion radical generated by the xanthine-xanthine oxidase system. Two monoterpenes called paeonisuffrone and paeonisuffral were isolated from the ethyl acetate-soluble fraction. Their absolute stereostructures were elucidated on the basis of chemical and physiochemical evidence, which included the application of a modified Mosher's method and lipase catalyzed debenzoylation reaction.

Bepridil↗
PubMed2000

Failure of probucol to prolong survival in salt-loaded stroke-prone spontaneously hypertensive rats.

We examined the effect of probucol, a lipid-lowering agent with strong antioxidant properties, on neurological events and survival in stroke-prone spontaneously hypertensive rats (SHRSP). Rapid onset of stroke was induced by maintaining the animals on 1% NaCl solution in place of drinking water. Probucol (10 or 30 mg/kg/day), both of which doses are therapeutic in humans was given by gastric gavage once daily to salt-loaded SHRSP. Animals receiving vehicle were used as controls. Probucol did not influence the elevation of blood pressure. Although probucol did not improve the survival rate of salt-loaded SHRSP, 30 mg/ kg/day of probucol slightly but significantly delayed the development of neurological events (p=0.0235 by generalized Wilcoxon test). However, a high dose of probucol (100 mg/kg/day) did not change the survival or neurological events of salt-loaded SHRSP. These results suggest that probucol may be protective against the development of neurological events, but is not preventive for the progression of stroke in SHRSP.

Animals↗
PubMed2000

A case study on support for students' thinking through computer-mediated communication.

This is a case study on support for thinking through computer-mediated communication. Two graduate students were supervised in their research using computer-mediated communication, which was asynchronous and written; the supervisor was not present. The students' reports pointed out there was more planning and editing and low interactivity in this approach relative to face-to-face communication. These attributes were confirmed by their supervisor's report. The students also suggested that the latter was effective in support of a production stage of thinking in research, while the former approach was effective in support of examination of thinking. For distance education to be successful, an appropriate combination of communication media must consider students' thinking stages. Finally, transient and permanent effects should be discriminated in computer-mediated communication.

Adult↗
PubMed2000

Amelioration of murine experimental colitis by inhibition of mucosal addressin cell adhesion molecule-1.

Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is an adhesion molecule that mediates recruitment of lymphocytes into the gut mucosa. Attenuation of excessive expression of MAdCAM-1 in the inflamed mucosa could be useful for treatment of inflammatory bowel diseases. The aim of this study was to investigate whether anti-MAdCAM-1 antibody has a prophylactic effect on experimental colitis induced by dextran sulfate sodium (DSS). Colitis was induced by orally feeding BALB/c mice 5% DSS (mol. wt. 5000). Mice were sacrificed at intervals up to 21 days after administration to evaluate the changes over time in intestinal damage. The infiltrating lymphocytes and their subpopulations, and the expression of cell adhesion molecules were determined by immunohistochemistry. In another set of experiments, the attenuating effect of i.p.-injected anti-MAdCAM-1 antibody on colonic lesions was evaluated on day 14. Significant histological damage with shortening of crypts was observed on day 14 in colonic mucosa of DSS-treated mice. Before mucosal inflammation had become significant, expression of MAdCAM-1 was already increased in the microvessels of lamina propria on day 7. Significant infiltration of beta7-integrin-positive T and B cells in the mucosa was then noted on day 14. Administration of anti-MAdCAM-1 antibody significantly reduced colonic injury as well as the infiltration of beta7-integrin-positive lymphocytes in the colonic mucosa. This antibody also was effective when given 7 days after the start of DSS treatment. In the present study, we demonstrated that anti-MAdCAM-1 antibody significantly ameliorates DSS-induced colitis, suggesting that MAdCAM-1 may be useful for control of inflammatory bowel diseases.

Animals↗
PubMed1999

CBP-dependent and independent enhancing activity of steroid receptor coactivator-1 in thyroid hormone receptor-mediated transactivation.

Full-length of steroid receptor coactivator-1 (F-SRC-1) has been shown to interact with thyroid hormone receptors (TRs) in a ligand-dependent manner and to stimulate receptor-dependent transcription. To identify functional domains of F-SRC-1, several internal deletion mutants of F-SRC-1 were constructed. Although in vitro pull down assay with TR showed interaction of all of these mutants with TR, lack of mid legion (amino acids 398-1172) lost enhancing activity of TR-mediated transcription in a transient transfection assay. However, F-SRC-1 mutant lacking CBP-interacting domain still preserved enhancing activity. Surprisingly, F-SRC-1 mutants also increased basal level of viral promoter activity depending upon their deleted region. Yeast activation function assay revealed that these F-SRC-1 mutants had intrinsic activation function when bound to DNA. Analyses of small fragments of F-SRC-1 identified three separable activation domains. In vitro binding assay showed that TBP and TFIIB bound to C-terminal half of F-SRC-1. These results suggest that F-SRC-1 can function via both CBP-dependent and independent manners using various sets of activation domains and that direct interactions between F-SRC-1 and TBP or TFIIB may not be important for CBP-independent transcription.

Animals↗
PubMed1999

Two cases of inflammatory bowel disease with multiple myeloma.

A significant increase has been reported in reticuloendothelial neoplasms in patients with inflammatory bowel diseases. We present two rare cases of multiple myeloma in patients with inflammatory bowel diseases. One was in a 58-year-old woman with ulcerative colitis, and the other was in a 59-year old woman with Crohn's disease. In both patients, multiple myeloma occurred during long-term observation of inflammatory bowel disease and during the inactive stage of intestinal inflammation. The multiple myeloma appeared to have resulted from monoclonal gammopathy of undertermined significance in both patients, and was diagnosed by characteristic serum and bone marrow findings. Our findings suggested that multiple myeloma should be particularly considered in women of middle or advanced age with ulcerative colitis or Crohn's colitis and serum monoclonal gammopathy.

Female↗
PubMed1999

Characteristic cardiovascular manifestation in homozygous and heterozygous familial hypercholesterolemia.

BACKGROUND: The aortic valve dysfunction of patients with homozygous familial hypercholesterolemia (FH) suggests that hypercholesterolemia affects not only coronary arteries but also the aortic valve. We studied the aortic root of patients with homozygous FH and those of patients with heterozygous FH to characterize the premature atherosclerotic lesions by using histopathologic specimens. METHODS AND RESULTS: The aortic roots of 10 patients with homozygous FH, age 9 to 58 years, were studied by cardiac catheterization with several angiographies. The aortic roots of 39 patients with heterozygous FH under age 60 years were also examined for aortic and mitral valvular functions by color Doppler echocardiography, and 30 normocholesterolemic patients with coronary artery disease were examined as control subjects. In addition, in 22 patients with FH and 20 control subjects, the internal diameter of the aortic annulus and the aortic ridge in cardiac cycles were measured. Of the 10 homozygotes with FH, 8 patients had aortic regurgitation demonstrated by aortography; 3 of them showed significant transvalvular pressure gradients. Stenotic changes of coronary ostia were observed in 8 of the 10 homozygotes with moderate coronary atherosclerosis. Of the 39 heterozygotes with FH, 10 patients had aortic regurgitation shown by Doppler echocardiography, as did only 1 of the 30 control subjects (P <.05). The average diameter and distensibility of the ascending aorta were significantly reduced in the heterozygotes compared with the control subjects. The surgically resected cusp specimens of aortic valves obtained from 1 homozygous and 1 heterozygous patient showed significant thickening of the cusp with foam cell infiltration. CONCLUSIONS: Premature atherosclerosis in FH had a characteristic distribution, affecting the aortic root dominantly. The involvement of the aortic valve indicating "hypercholesterolemic valvulopathy" was a peculiar feature of FH, especially its homozygous form, but was reminiscent of ubiquitous processes caused by hypercholesterolemia.

Adolescent↗
PubMed1999

Chronotherapy of high-dose 1,25-dihydroxyvitamin D3 in hemodialysis patients with secondary hyperparathyroidism: a single-dose study.

BACKGROUND: A high-dose oral intermittent vitamin D (pulse therapy) is widely used for the treatment of secondary hyperparathyroidism associated with kidney failure. However, hypercalcemia by vitamin D sometimes interrupts this treatment. Because serum calcium concentration possesses a circadian rhythm, a chronopharmacologic approach of vitamin D may have merit for avoidance of adverse reactions. METHODS: Six female secondary hyperparathyroidism patients receiving maintenance hemodialysis received a single oral dose of 2 microg 1,25-dihydroxyvitamin D3 at either 8 AM or 8 PM in a crossover design. Serum concentrations of ionized and total calcium, phosphate, and vitamin D3 were determined for a 48-hour period after administration. We also measured serum intact parathyroid hormone before and 48 hours after dosing as an index for efficacy. RESULTS: A single oral administration of the drug caused an increase in concentration of ionized calcium, serum calcium, and phosphate. However, the area under concentration-time curve from zero to 48 hours [AUC(0-48)] and peak concentration of these variables were markedly lower after dosing at 8 PM. Pre-dose concentrations of these variables were lower at night. The AUC(0-48) of serum vitamin D3 of the morning and night trials did not differ significantly. Reduction of intact parathyroid hormone concentration was also similar between the two trials. CONCLUSION: The administration of vitamin D3 at night may reduce the occurrence of hypercalcemia and hyperphosphatemia in patients with secondary hyperparathyroidism, whereas the pharmacokinetics and intact parathyroid hormone-lowering effect of the drug does not vary with dosing time.

Area Under Curve↗
PubMed1999

Low density lipoprotein particle diameter in young, nonobese, normolipidemic Japanese men.

BACKGROUND: prospective studies have demonstrated that a predominance of small, dense LDL particles (pattern B) precedes the clinical onset of coronary heart disease. Prevalence and characteristics of subjects with this LDL size abnormality were studied in young, nonobese, Japanese normolipidemic men. METHODS AND RESULTS: LDL peak particle diameter (PPD) was measured by continuous disc polyacrylamide gel electrophoresis in 223 nonobese normolipidemic men aged 18-20 years (mean+/-S.D. body mass index: 21.9+/-3.7 kg/m2, total cholesterol: 180+/-29 mg/dl, triglyceride: 62+/-34 mg/dl, HDL cholesterol: 58+/-12 mg/dl). Men with small LDL (PPD < 25.8 nm) were found in only 5.4% (n=12) whereas 197 men (88.3%) had a preponderance of large LDL (PPD 26.3 nm). As compared with men in a top tertile (PPD 27.5 nm) those in a low tertile (PPD < 26.9 nm) had higher serum levels of LDL cholesterol (120+/-31 vs 104+/-24 mg/dl), triglyceride (72+/-39 vs 49+/-16 mg/dl) and apolipoprotein (apo) B (84+/-21 vs 68+/-14 mg/dl), and lower HDL cholesterol (54+/-10 vs 60+/-12 mg/dl). They also had greater body mass index (23.2+/-4.6 vs 20.9+/-3.1 kg/m2) and percent body fat (21.5+/-7.7 vs 17.5+/-4.9%). LDL-PPD was positively correlated with HDL cholesterol (R=0.20, P=0.002) and was negatively correlated with apoB (R=0.34, P < 0.001), triglyceride (R=0.32, P < 0.001). percent body fat (R=0.26, P < 0.001), body mass index (R=0.24, P < 0.001), fat mass (R=0.23, P=0.001), total cholesterol (R=0.20, P=0.002). In multiple regression analysis, apoB, triglyceride, HDL cholesterol, apoAI and percent body fat explained 18% of LDLPPD variability. CONCLUSION: even in young, nonobese, normolipidemic men, LDL size appears to be associated with triglyceride-rich lipoprotein metabolism and body fat.

Adolescent↗
PubMed1999

Analysis of serum lipid levels in Japanese men and women according to body mass index. Increase in risk of atherosclerosis in postmenopausal women. Research Group on Serum Lipid Survey 1990 in Japan.

Relatively low serum lipid levels are thought to be an important factor contributing to the low incidence of ischemic heart diseases (IHD) in Japanese. It has been proven that obesity or overweight constitutes a basal condition for several risk factors in atherosclerosis. The purpose of this study is to obtain data on serum lipids and lipoprotein profiles in relation to body mass index (BMI), which will enable us to compare the nature and weight of metabolic risk factors in atherosclerosis between Japanese and people in Western countries. Data of total serum cholesterol, triglyceride, and HDL-cholesterol levels of Japanese men and women obtained from a large-scale survey in 1990 were analysed according to BMI for different age groups. Apolipoprotein A-I and B and Lp(a) were also measured in randomly selected samples and their contribution as a risk factor was estimated especially in postmenopausal women. The subjects in two age groups of men (20-39 and 40 59 years) and women (20 39 and 50-69 years) were graded into quintiles according to the BMI. The middle grades of BMI were 21.9-23.3 and 22.4-23.6 for younger and older men, and 20.0-21.1 and 22.2-23.6 for younger and older women, respectively. These values are much lower than those in Western populations, the border between the IVth and the top quintile almost corresponding to the average for Americans. Total cholesterol showed a tendency to shift into higher ranges in all age groups in both men and women as BMI increased, with the highest distribution remaining in the range of 160-199 mg/dl (4.2-5.2 mmol/l). The average cholesterol levels for the top quintile of BMI were still lower than most of the average values in Western populations. The distribution of cholesterol in higher ranges was much greater and the difference according to BMI was smaller in older women than in men. In both men and women, whether younger or older, about 90% of the subjects in the lower quintiles of BMI had triglyceride levels lower than 150 mg/dl. The distribution in the higher range of triglyceride was small in women, not only at younger ages but also in postmenopausal women at the top quintile of BMI. About 85% of the younger women with a middle grade of BMI had an HDL-cholesterol level higher than 50 mg/dl. The values in postmenopausal women were still higher than in men aged 40-59 years. Shift of the distribution curves of HDL-cholesterol according to BMI was similar in all groups and more remarkable than the change in triglyceride. The average HDL-cholesterol levels at the top quintile were almost comparable to the average values in Western countries; the difference in HDL-cholesterol levels between the two populations can mostly be explained by the difference in BMI. Smokers showed a slightly lower total cholesterol and significantly (3-4 mg/dl) lower HDL-cholesterol levels, although there was no difference in distribution of BMI between smokers and non-smokers. Relatively low total cholesterol levels even in smokers has probably contributed to the low incidence of IHD in spite of the high frequency of smoking in Japanese population. Mean Lp(a) levels showed a tendency to increase after age 40 in women. BMI itself did not have a correlation with serum Lp(a) levels. The distribution curve of Lp(a) shifted to higher levels as total cholesterol increased and the tendency was most remarkable in women around or after the menopause. It was remarkable in older women that as the total cholesterol or apo B level increased there was also an increased prevalence of abnormal ECG with a pattern of myocardial ischemia. Postmenopausal women seem to have a great risk of atherosclerosis regarding the lipid and lipoprotein profile even in the Japanese population.

Adult↗