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Biomedical subjects

T Fujinami

Publications and source records attributed to T Fujinami.

At least 19 recordsLinked to original sources

Adenine-induced selective apoptosis toward HIV chronically infected cells in vitro.

A novel strategy for anti-HIV therapy is the clearance of the residual infected cells from the body. Here, we show that 6-aminopurine, adenine, induced selective apoptosis toward HIV-1 producing chronically infected MOLT4 cells (MOLT4/HIV) without augmentation of virus production, whereas the growth of uninfected MOLT4 was stimulated. This selective apoptosis did not occur with other adenine nucleotides or with other bases. The purine ring and the amino residue of adenine were responsible for the apoptosis induction and selectivity, respectively. In addition, adenine slightly but consistently reduced viable cell numbers and the production of virus in a fraction of HIV-1 chronically infected human peripheral blood mononuclear cells (PBMCs/HIV) at day 7. On the other hand, blastogenic response of normal PBMCs to PHA, PWM and Candida albicans were potentiated in the presence of adenine. These results indicated that the effect of adenine may be attributable to activation-induced selective apoptosis toward virus-infected cells.

Adenine↗

Aging and spectral characteristics of the nonharmonic component of 24-h heart rate variability.

To examine whether heart rate variability (HRV) during daily life shows power law behavior independently of age and interindividual difference in the total power, log-log scaled coarse-graining spectra of the nonharmonic component of 24-h HRV were studied in 62 healthy men (age 21-79 yr). The spectra declined with increasing frequency in all subjects, but they appeared as broken lines slightly bending downward, particularly in young subjects with a large total power. Regression of the spectrum by a broken line with a single break point revealed that the spectral exponent (beta) was greater in the region below than above the break point (1.63 +/- 0. 23 vs. 0.96 +/- 0.21, P < 0.001). The break point frequency increased with age (r = 0.51, P < 0.001) and beta correlated with age negatively below the break point (r = 0.39) and positively above the break point (r = 0.70). The contribution to interindividual difference in total power was greater from the differences in the power spectral density at frequencies closer to both ends of the frequency axis and minimal from that at -3.25 log(Hz), suggesting hingelike movement of the spectral shape at this frequency with the difference in total power. These characteristics of the 24-h HRV spectrum were simulated by an artificial signal generated by adding two noises with different beta values. Given that the power law assumption is fundamental to the analysis of dynamics through the log-log scaled spectrum, our observations are substantial for physiological and clinical studies of the heartbeat dynamic during daily life and suggest that the nonharmonic component of HRV in normal subjects during daily life may include at least two 1/fbeta fluctuations that differ in dynamics and age dependency.

Adult↗

Electron microscopic peritubular capillary lesions: a new criterion for chronic rejection.

Typical chronic rejection showing prominent glomerular and/or arterial lesions is less common in renal allograft patients treated with cyclosporin A (CsA). We investigated the value of peritubular capillary lesions as a criterion for chronic rejection in the CsA era. A total of 129 renal graft biopsies, taken from recipients showing graft dysfunction after more than 2 months post-operatively, were examined by electron microscopy, and peritubular capillary lesions were studied, especially multi-layered basement membrane lesions (MLPTC). Eighty-two biopsy specimens taken from non-transplantation patients were also studied as a control. Five biopsies (6%) showed mild and atypical MLPTC in the control group. Of the 129 allograft biopsies, MLPTC was seen in 55 (42.6%). The prevalence showed no significant relationship to the interval from operation to biopsy. MLPTC was either typical (n = 10) or incomplete (n = 45). Concomitant membrane disruption, edema and lymphocyte infiltration of the subendothelial space, reflecting acute cellular rejection, were occasionally noted in both groups. Incomplete MLPTC often developed within 1 yr after surgery, in association with acute rejection. It was found in 26-50% of biopsies at any time up to 5 yr post-operatively. The incidence of typical MLPTC was 5.7-12.8% over 1 yr post-operatively. These findings suggest that the development of chronic rejection is closely related to relapsing acute tubulo-interstitial allograft rejection which is often clinically silent. We concluded that MLPTC is useful as a specific criterion for chronic rejection.

Basement Membrane↗

Evaluation of left ventricular early diastolic performance by color tissue Doppler imaging of the mitral annulus.

A noninvasive assessment of left ventricular (LV) diastolic performance by tissue Doppler imaging was performed in 56 patients (8 patients with atypical chest pain, 42 with coronary artery disease with a previous myocardial infarction, and 6 without a previous myocardial infarction) who underwent cardiac catheterization. Mitral annular velocity (MAV) during early ventricular diastole was obtained by M-mode color tissue Doppler imaging at the posterior corner of the mitral annulus. In each patient, the negative peak of the first derivative of LV pressure decay (peak -dP/dt) and a time constant of LV relaxation (tau) were calculated from the LV pressure waves obtained by a catheter-tip micromanometer. LV end-systolic volume index was measured from contrast left ventriculography. MAV during early diastole was significantly correlated with tau (r = -0.73, p <0.001), peak -dP/dt (r = 0.58, p <0.001), and LV end-systolic volume index (r = -0.63, p <0.001). On multivariate regression analysis with MAV during early diastole, tau and LV end-systolic volume index were selected as prime determinants (r = 0.80, p <0.001). These findings suggest that MAV during early diastole has a direct relation to LV elastic recoil as well as to LV relaxation. MAV during early diastole gives important information regarding LV behavior in late systole to early diastole where LV early diastolic performance is determined.

Adult↗

Effects of trimebutine maleate on gastric motility in patients with gastric ulcer.

The effects of trimebutine maleate (TM), a prokinetic drug, on gastrointestinal motility in patients with gastric ulcer were investigated. Twenty patients with active gastric ulcers were allocated to two groups; 10 patients received a proton pump inhibitor alone (PPI group), given orally, and 10 patients received oral TM in combination with a PPI (PPI + TM group), each for a period of 8 weeks. Electrogastrography (EGG) and gastric emptying were measured before and after the treatment period. During the active ulcer stage, tachygastria (more than 0.06 Hz) or bradygastria (less than 0.04 Hz) in the EGG frequency were observed in 9 patients either before or after meals. During the healed ulcer stage, tachygastria or bradygastria was observed in 4 of 10 patients in the PPI group, while in the PPI + TM group, 1 patient had tachygastria and none had bradygastria. Postprandial dip (PD) was observed in 3 of the 20 patients during the active stage, while after treatment, PD was observed in 3 patients in the PPI group and in 6 patients in the PPI + TM group, respectively. Gastric emptying in the PPI group did not show any change between before and after treatment, while that in the PPI + TM group improved significantly after treatment. These results suggest that TM may have an ameliorative effect on abnormal gastric motility in patients with gastric ulcer.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Fractional removal rate of fat emulsion (K2) remains to be low in APOE3/3 phenotype subjects with serum triglyceride level above 180mg/dl.

The relation between fractional catabolic rate (K2) of an intravenously injected fat emulsion, Intralipid, and the level of serum triglyceride (TG) was evaluated to cast light on TG-rich lipoprotein metabolism in 182 subjects who were homozygotes for the most common form of apoE3/3. Both normolipidemic individuals and primary hyperlipidemic patients were included. To assess the influence of variation in the apoE phenotype on fat emulsion metabolism, 25 subjects with the apoE 4/3 phenotype and 21 with apoE 3/2 phenotype were also evaluated. In the apoE 3/3 subjects, K2 decreased with increasing TG level up to 180mg/dl, but above 180mg/dl, K2 remained at a constant level. This TG value was therefore concluded to be a cut off beyond which the TG-dependent decrease in K2 disappeared. No apparent correlation between K2 and serum TG was observed in subjects with apoE 4/3 or 3/2 phenotypes. In subjects with TG above 180mg/dl, presumably both accelerated synthesis and limited removal are involved in the development of their hypertriglyceridemia. Since K2 demonstrated little change with increase of TG over 180mg/dl in apoE 3/3 subjects, we concluded that the capacity to catabolize fat emulsion reaches a kinetic saturation. The TG value of 180mg/dl may be a physiological significance. The relation between K2 and TG was specific in apoE 3/3, as it was not observed in subjects having apoE 4/3 or 3/2 phenotypes.

Adult↗

Circadian rhythms of atrioventricular conduction properties in chronic atrial fibrillation with and without heart failure.

OBJECTIVES: We examined the circadian variations in atrioventricular (AV) conduction properties during atrial fibrillation (AF) by a technique based on the Lorenz plot of successive ventricular response (VR) intervals and analyzed their relations with clinical features. BACKGROUND: The VR interval in chronic AF shows circadian variation, which is attenuated in patients with an increased risk of death. Although the VR interval is determined by the dynamic processes in the AV node randomly stimulated by rapid atrial activity, the circadian variations of the AV conduction properties related to this mechanism are unknown. METHODS: In 48 patients with chronic AF, Lorenz plots were generated on overlapping sequential segments of 512 VR intervals in 24-h ambulatory electrocardiograms. For each scatter plot, the 1.0-s intercept of the lower envelope (LE1.0) of the plot and the degree of scatter above the envelope (root mean square difference from the envelope [scattering index]) were measured for estimating AV node refractoriness and concealed AV conduction, respectively. RESULTS: In all patients, a significant circadian rhythm was observed for the average VR interval, LE1.0 and scattering index, with an acrophase occurring at night. The mesor, amplitude and acrophase of LE1.0 and the scattering index closely and independently correlated with the corresponding rhythm variables of the average VR interval (partial r2 0.98, 0.86 and 0.68 for LE1.0 and 0.98, 0.92 and 0.92 for scattering index). The amplitudes of these measures were lower in patients with congestive heart failure (CHF) even after adjustment for the effects of age, duration of AF, medications, left atrial diameter and blood pressure (p < 0.01 for all). CONCLUSIONS: These results suggest that 1) both AV node refractoriness and the degree of concealed AV conduction during AF may show a circadian rhythm; 2) the circadian rhythms of these properties may independently contribute to the circadian variation of the VR interval; and 3) these circadian rhythms may be attenuated in patients with CHF.

Aged↗

Pregnant woman with transient diabetes insipidus resistant to 1-desamino-8-D-arginine vasopressin.

We encountered a pregnant woman with transient diabetes insipidus which developed during the third trimester. A hypertonic saline infusion study did not concentrate the osmolality of urine. Her laboratory data showed hypokalemia, hyperreninemia, an increased concentration of plasma aldosterone and an increased urinary excretion rate of prostaglandin E2, which resembled hyperprostaglandin E-syndrome. T1-weighted magnetic resonance imaging of the posterior pituitary gland revealed decreased intensity. Polyuria reached 4-6 L daily, and urine osmolality remained dilute despite a lapse of four days since treatment with intranasal 1-desamino-8-D-arginine vasopressin (dDAVP: 10-25 microg every 12 h). The patient was conservatively managed without medical treatment, then delivered in the 38th week of pregnancy without complication. The osmolality of the patient's urine was higher than that of the plasma when tested 3 days postpartum. The abnormality of magnetic resonance imaging of the posterior pituitary gland disappeared at 6 months after delivery. We consider that subclinical nephrogenic diabetes insipidus in our patient was exacerbated during pregnancy.

Adult↗

Platelet epidermal growth factor in thyroid disorders.

We evaluated the concentration of epidermal growth factor (EGF) in platelets, serum and plasma obtained from 47 patients with Graves' disease, 7 with hypothyroidism and 20 healthy subjects. The platelets of the subjects were collected from platelet rich plasma and lysed by freezing and thawing. Subsequently the platelet debris was treated with Triton X-100. The EGF concentration was determined by homologous radioimmunoassay. The concentration of EGF in the platelets in 14 patients with untreated Graves' disease was significantly higher than that in the healthy controls. After treating these 14 patients with antithyroid agents, the EGF concentration in the platelets decreased to the level of the healthy controls. The EGF concentration in the platelets in the 7 untreated hypothyroid patients decreased after replacement therapy with thyroxine. The mean volume of the platelets in the 14 patients with untreated Graves' disease was significantly larger than in the control and decreased after treatment with antithyroid agents. The serum and plasma levels of EGF in the 7 untreated hypothyroid increased after replacement therapy. In conclusion, thyroid function affected the concentration of EGF in the platelets of patients with thyroid disorders.

Adult↗

alpha-tocopherol protects the peroxidative modification of LDL to be recognized by LDL receptors.

BACKGROUND: Peroxidatively modified low-density lipoprotein (LDL) may contribute to the atherosclerotic process; therefore, protecting LDL against peroxidation may reduce or retard the progression of atherosclerosis. We evaluated the effect of alpha-tocopherol on copper-catalyzed LDL peroxidative modification. METHODS: The protective effects of alpha-tocopherol on copper-catalyzed LDL peroxidative modification were examined by measurement of the concentration of lipid hydroperoxides in LDL and by the provision of LDL cholesterol to lymphocytes via the LDL receptor-mediated pathway. RESULTS: The measurement of concentration of lipid hydroperoxides in LDL showed that alpha-tocopherol inhibited the peroxidative modification of LDL. Also, alpha-tocopherol preserved the ability of LDL to be recognized by LDL receptors in peripheral blood lymphocytes to the same extent as native LDL. CONCLUSION: These findings indicate that alpha-tocopherol may protect LDL against peroxidative modification, maintaining its ability to act as a ligand for LDL receptors in vivo.

Adult↗

Human cholesteryl ester transfer protein measured by enzyme-linked immunosorbent assay with two monoclonal antibodies against rabbit cholesteryl ester transfer protein: plasma cholesteryl ester transfer protein and lipoproteins among Japanese hypercholesterolemic patients.

Plasma cholesteryl ester transfer protein (CETP) concentrations were measured in Japanese subjects by an ELISA with two different monoclonal antibodies that were raised against rabbit CETP and cross-reacted against human CETP. Among 63 patients who consecutively underwent coronary angiography, the plasma CETP of 37 patients with luminal stenosis > or = 50% in their coronary arteries was not significantly different from that of the 26 patients with luminal stenosis < 50%. No other lipoprotein-related measurement except HDL-cholesterol differentiated the two groups. Among 40 hypercholesterolemic patients, no lipoprotein-related measurement other than LDL-cholesterol was found to positive correlate with the CETP. Before and after the treatment of 23 patients with simvastatin 5 mg a day for 4 weeks, plasma CETP markedly decreased in those whose pretreatment CETP was > or = 3 mg/L; no change was observed for those with lower pretreatment CETP. In the former group, negative correlation between CETP and HDL-cholesterol was demonstrated only in the posttreatment plasma.

Adult↗

HDL3 exerts more powerful anti-oxidative, protective effects against copper-catalyzed LDL oxidation than HDL2.

OBJECTIVE: To evaluate which HDL subfraction, HDL2 or HDL3 exerts the greater preventive effect on the Cu(2+)-induced LDL oxidation. METHODS: LDL was incubated for 6 h with 2.5 microM Cu2+ in phosphate-buffered saline alone, or in the presence of HDL2 or HDL3 at various protein concentrations. Each sample was subjected to agarose gel electrophoresis, and the amount of lipid hydroperoxide in each sample of LDL was measured. RESULTS: There was no significant difference in the levels of LPO between the LDL and LDL + HDL2 cases, whereas a significant reduction was apparent with LDL + HDL3. Both HDL2 and HDL3 significantly inhibited oxidative modification of LDL, as assessed by electrophoretic mobility, in a concentration dependent manner, but this effect was much more pronounced with HDL3. CONCLUSION: HDL3 may play an important role in the prevention of atherosclerosis in vivo, more effectively inhibiting oxidation of LDL than HDL2.

Antioxidants↗

Effects of dehydroepiandrosterone on proliferation of human aortic smooth muscle cells.

Dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) have been shown to be associated with the progression of coronary atherosclerosis in clinical and in vivo studies. However, the mechanisms responsible for the association have not been determined. In the present study, we found that DHEA influences the in vitro growth of vascular smooth muscle cells obtained from the human aorta (hASMC). The concentrations of DHEA ranging from 10(-8) M to 10(-6) M significantly stimulated the mitogenesis of hASMC in serum-free culture. On the other hand, 4 hrs of pretreatment with DHEA attenuated the fetal calf serum induced proliferative effect in a dose-dependent manner. However, the in vitro effects of DHEA on the mitogenesis observed in hASMC were not seen in rat-derived aortic smooth muscle cell lines (A10 cells). With respect to DHEAS, the hormone, at concentrations up to 10(-5) M did not affect the growth of either hASMC or A10 cells in vitro. The growth response of hASMC to DHEA in vitro was markedly affected by the culture conditions. The differential proliferative effects of DHEA on smooth muscle cells between rat and human are of interest. We conclude that the effects of DHEA on mitogenesis of hASMC may, at least in part, explain the association between DHEA and atherosclerosis.

Animals↗

Abnormal cyanide metabolism in uraemic patients.

BACKGROUND: We previously investigated the factors involved in uraemic neuropathy in patients undergoing regular haemodialysis and found a significant relationship between the severity of vibration sensation impairment and the patients' smoking habits. The administration of methylcobalamin markedly improved the severity of uraemic neuropathy in terms of vibration perception thresholds. We presumed that abnormal cyanide metabolism is involved in the development of uraemic neuropathy. METHODS: Serum levels of thiocyanate (SCN-), the detoxication product of cyanide, were determined in 12 patients with preterminal chronic renal failure (PCRF), 30 patients undergoing regular haemodialysis (HD patients), and 13 healthy volunteers as a control group. Nine of the 30 HD patients were smokers. In addition, in 10 HD patients without smoking habits and 10 non-smoking healthy volunteers, the proportion of each vitamin B12 analogue in total vitamin B12 was estimated. RESULTS: The mean serum SCN- level of the 12 PCRF patients (5.1 +/- 1.5 micrograms/ml) was significantly higher than that of the control (2.8 +/- 0.9 micrograms/ml) (P < 0.01). The mean SCN- level before haemodialysis in the 21 non-smoking HD patients was identical to that in the PCRF group, whereas the level in the nine smoking HD patients (7.2 +/- 1.8 micrograms/ml) significantly higher than that in the non-smoking subgroup (P < 0.01). In 16 HD patients with methylcobalamin treatment, serum SCN- levels were lower than in those without methylcobalamin treatment (4.5 +/- 0.5 micrograms/ml in non-smoking subgroup, P < 0.05). And in the methylcobalamin-treated subgroup (n = 5), the proportion of each vitamin B12 analogue in total vitamin B12 was normal. In the untreated subgroup (n = 5), the proportion of cyanocobalamin fraction (10.5 +/- 2.6%) was as high as the level in Leber's disease patients, while the proportion of methylcobalamin fraction was low. And the serum cyanocobalamin level was higher in the treated subgroup. CONCLUSION: In uraemic patients, cyanide detoxication capability is impaired because of a reduced SCN- clearance, and increased cyanocobalamin synthesis indicates elevation of cyanide pool, which would be related to the development of uraemic neuropathy. Methylcobalamin was considered to be utilized in cyanide detoxication process via cyanocobalamin synthesis.

Adult↗

Spectral characteristics of ventricular response to atrial fibrillation.

To investigate the spectral characteristics of the fluctuation in ventricular response during atrial fibrillation (AF), R-R interval time series obtained from ambulatory electrocardiograms were analyzed in 45 patients with chronic AF and in 30 age-matched healthy subjects with normal sinus rhythm (SR). Although the 24-h R-R interval spectrum during SR showed a 1/f noise-like downsloping linear pattern when plotted as log power against log frequency, the spectrum during AF showed an angular shape with a breakpoint at a frequency of 0.005 +/- 0.002 Hz, by which the spectrum was separated into long-term and short-term components with different spectral characteristics. The short-term component showed a white noise-like flat spectrum with a spectral exponent (absolute value of the regression slope) of 0.05 +/- 0.08 and an intercept at 10(-2) Hz of 4.9 +/- 0.3 log(ms2/Hz). The long-term component had a 1/f noise-like spectrum with a spectral exponent of 1.26 +/- 0.40 and an intercept at 10(-4) Hz of 7.0 +/- 0.3 log(ms2/Hz), which did not differ significantly from those for the spectrum during SR in the same frequency range [spectral exponent, 1.36 +/- 0.06; intercept at 10(-4) Hz, 7.1 +/- 0.3 log(ms2/Hz)]. The R-R intervals during AF may be a sequence of uncorrelated values over the short term (within several minutes). Over the longer term, however, the R-R interval fluctuation shows the long-range negative correlation suggestive of underlying regulatory processes, and spectral characteristics indistinguishable from those for SR suggest that the long-term fluctuations during AF and SR may originate from similar dynamics of the cardiovascular regulatory systems.

Adult↗

Comparative effects of volume loading on pulmonary venous flow in dogs with normal heart and with myocardial ischemia.

The influences of cardiac loading conditions and left ventricular performance on pulmonary venous flow are poorly understood. The authors studied the effects of volume loading on the pattern of pulmonary venous flow in normal and ischemic hearts. Thirteen anesthetized dogs were equipped with a transit-time ultrasonic flow probe around the left upper pulmonary vein. In 6 of the dogs, the left anterior descending artery was ligated to induce myocardial ischemia. The remaining 7 dogs had normal hearts. Heart rate was fixed at 110 beats/minute by right atrial pacing. Dextran was infused from the femoral vein until mean left atrial pressure increased 3 mm Hg above the baseline value in both groups. In normal heart, systolic pulmonary venous flow volume (SI) increased significantly, but early diastolic flow volume (DI) did not show a significant change during volume loading. The ratio of SI/DI increased significantly (1.12 +/- 0.34 vs 2.11 +/- 0.49, P < 0.05). After ligation of the left anterior descending artery, the SI and DI decreased significantly. The ratio of SI/DI did not show a significant change (0.88 +/- 0.32 vs 0.87 +/- 0.30, ns). In dogs with myocardial ischemia, volume loading caused increases in the SI and DI. However, no significant change was observed in the ratio of SI/DI (0.87 +/- 0.30 vs 0.97 +/- 0.36, ns). These findings demonstrate that left ventricular performance influences the alteration in pulmonary venous flow pattern that is caused by systemic volume loading.

Animals↗