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Biomedical subjects

Y Hamada

Publications and source records attributed to Y Hamada.

At least 91 records · Page 5Linked to original sources

Stereoselectivity and species difference in plasma protein binding of KE-298 and its metabolites.

In vitro protein binding of KE-298 and its plasma metabolites, deacetyl-KE-298 (M-1) and S-methyl-KE-298 (M-2), was high in rat (>97%), dog (>89%) and human plasma (>99%), respectively. Human serum albumin (>93%) was the main protein involved in the binding to plasma proteins, while the binding to human serum globulins was low (16-33%). The binding of KE-298 and its metabolites in all species of plasma was stereoselective. The (+)-(S)-enantiomers of these compounds bound rat, dog and human plasma proteins to a greater extent than did the (-)-(R)-enantiomers, except that the case of KE-298 was opposite in rat plasma. The stereoselective plasma levels of these compounds in rats, dogs, or humans would likely be due to stereoselective differences in binding to plasma albumin. The protein binding of M-1 in adjuvant-induced arthritis rat plasma was >97%, and the stereoselectivity was similar to the case of normal rat plasma. KE-298 and its metabolites remarkably displaced [14C]warfarin, which bound on albumin in a solution of diluted rat serum albumin. Similarly, there was a displacement of [14C]warfarin in solutions of dog and human serum albumin, and concomitantly the displacement of [14C]diazepam. [3H]Digitoxin was not displaced by any of the enantiomers in each albumin solution. No stereoselectivity was found in displacement by enantiomers of the three compounds. These results suggest that stereoselective protein binding can be attributed to quantitative differences in binding to albumin rather than to the different binding sites.

Animals↗

Identification of collagen as a new fish allergen.

This study was intended to identify a high molecular weight allergen that had been detected in fish. Analyses by ELISA of five protein fractions prepared from bigeye tuna muscle showed that the high molecular weight allergen was contained in the myostromal protein fraction. Based on the results of SDS-PAGE, immunoblotting and amino acid analysis of the myostromal protein fraction, the high molecular weight allergen was judged to be collagen. Five of the eight patient sera used were found to react to the bigeye tuna collagen. In competitive ELISA inhibition experiments, the bigeye tuna collagen almost completely inhibited the IgE reactivity to the heated extracts from five species of fish, suggesting that collagen is commonly allergic regardless of fish species. However, no antigenic cross-reactivity was observed between collagens from fish and other animals.

Adolescent↗

Diurnal variations of post-exercise parasympathetic nervous reactivation in different chronotypes.

The purpose of this study was to investigate the diurnal variation and chronotype differences, i.e., in morning-types and evening-types, in post-exercise vagal reactivation. Twelve healthy male college students who were classified as morning-type (6) and evening-type (6), based on responses to a questionnaire, participated in this study. Postexercise vagal reactivation was assessed as the time constant of the beat-by-beat heart rate decrease for the first 30 sec after exercise (T30) at an intensity lower than the ventilatory threshold. The subjects performed 3-min cycle ergometer exercise at an intensity corresponding to 80% of the ventilatory threshold after a 1 min warm-up exercise in the morning (7:00 - 8:00) and evening (17:00 - 18:00) to obtain the T30. A significant interaction (chronotype-by-time) effect was found for T30. The morning value of the T30 in evening-type subjects was significantly larger than their evening value and the morning value in morning-type subjects. There was no significant interaction effect for heart rate and oxygen uptake during exercise. These results suggest that diurnal variation in post-exercise vagal reactivation is different between morning-type and evening-type, and post-exercise vagal reactivation in evening-type individuals is sluggish in the morning.

Adult↗

Dynamic sonography of hepatic tumors.

OBJECTIVE: Our objectives were to propose and evaluate a dynamic sonography protocol for the characterization of hepatic tumors. SUBJECTS AND METHODS: The subjects were 107 patients with focal liver lesions that initially had been found on conventional sonograms. The final diagnoses for the lesions were hepatocellular carcinoma in 60 patients, cholangiocellular carcinoma in six, metastatic carcinoma in 24, hemangioma in 10, and focal fat-spared region in seven. The pulse inversion harmonic imaging mode and a galactose-based contrast agent (Levovist) were used. Dynamic sonography was designed to obtain vascular-phase (composed of the arterial phase and the portal phase) images of the focal lesion and liver-parenchymal-phase images of the whole liver in a series obtained after a bolus injection of the contrast agent. RESULTS: If the whole-tumor or mosaic enhancement patterns (arterial phase) and/or the reticular enhancement (parenchymal phase) are regarded as positive findings for hepatocellular carcinoma, the sensitivity, specificity, and positive predictive value of dynamic sonography in our study were 92%, 96%, and 96%, respectively. If a ring enhancement (arterial to portal phase) or a clear defect (parenchymal phase) or both are regarded as positive findings for cholangiocellular carcinoma or metastasis, the sensitivity, specificity, and positive predictive value were 90%, 95%, and 88%, respectively. If puddle enhancement (portal phase) is regarded as a positive finding for hemangioma, the figures for sensitivity, specificity, and positive predictive value were 60%, 100%, and 100%, respectively. Also, the tumors that showed no focal sign in the liver parenchymal phase were all benign lesions, such as hemangiomas or focal fat-spared regions. CONCLUSION: Dynamic sonography in a protocol combining pulse inversion harmonic imaging and an IV bolus injection of the contrast agent proved to be an effective tool in characterizing liver tumors.

Adult↗

Aldose reductase inhibition ameliorates pupillary light reflex and F-wave latency in patients with mild diabetic neuropathy.

OBJECTIVE: The present study was conducted to investigate the effect of an aldose reductase inhibitor, epalrestat, on autonomic and somatic neuropathy at an early stage in type 2 diabetic patients by assessing the pupillary light reflex and minimum latency of the F-wave. RESEARCH DESIGN AND METHODS: A total of 30 diabetic patients with subclinical or mild diabetic neuropathy were randomly allocated to a control group (n = 15) and epalrestat (150 mg/day) group (n = 15). After 24 weeks, the pupillary light reflex test, cardiovascular autonomic function tests, and nerve conduction study were performed. RESULTS: The beneficial effect of epalrestat on the pupillary light reflex was observed in the minimum diameter after light stimuli (P = 0.044), constriction ratio (P = 0.014), and maximum velocity of constriction (P = 0.008). Among cardiovascular autonomic nerve functions, the ratio of the longest expiratory R-R interval to the shortest inspiratory R-R interval during deep breathing was significantly improved by epalrestat (P = 0.037). Minimum latencies of F-wave of median and tibial motor nerves were significantly shortened by epalrestat (P = 0.002 and P = 0.001, respectively); however, no significant effects were observed in motor or sensory nerve conduction velocity. CONCLUSIONS: These observations suggest that epalrestat may have therapeutic value at the early stage of diabetic neuropathy and that the pupillary light reflex and minimum latency of F-wave may be useful indicators of diabetic neuropathy.

Aldehyde Reductase↗

Homozygous serum amyloid P component-deficiency does not enhance regression of AA amyloid deposits.

Serum amyloid P component (SAP) is a common protein constituent of all types of amyloid deposits. Using SAP-deficient mice generated through gene targeting, we and others have shown that SAP significantly promotes amyloid deposition. It has been speculated that SAP protects amyloid fibrils from degradation by coating their exterior surface. To assess potential ways of treating individuals with amyloidosis, we examined the persistence of splenic AA amyloid fibrils in SAP-deficient and wild-type mice. No enhancement in the rate of regression of splenic AA amyloid was observed in the SAP-deficient mice relative to wild-type mice. These results present, for the first time, evidence that lack of SAP in AA amyloid deposits does not enhance regression of the deposits in vivo and suggest that dissociation of bound SAP from AA amyloid deposits would not significantly accelerate regression of the deposits in vivo.

Amyloidosis↗

Effect of coronary artery bypass grafting on native coronary artery stenosis. Comparison of internal thoracic artery and saphenous vein grafts.

BACKGROUND: The purpose of this study was to investigate the influence of coronary artery bypass grafting on the degree of stenosis of the native coronary artery. METHODS EXPERIMENTAL DESIGN: retrospective data analysis. SETTING: University hospital. PATIENTS: consecutive patients undergoing coronary artery bypass grafting (n=52). Bypasses using internal thoracic artery grafts (n=26) and saphenous vein grafts (n=37) to incompletely occluded coronary arteries were studied. INTERVENTIONS: coronary artery bypass grafting using internal thoracic artery or saphenous vein grafts. MEASURES: stenosis of the native coronary artery on angiography. RESULTS: Three recipient coronary arteries bypassed with internal thoracic artery grafts (12%) and 14 recipient coronary arteries bypassed with saphenous vein grafts (38%) showed progression of narrowing (p=0.024). Two recipient coronary arteries bypassed with internal thoracic artery grafts (8%) and 13 recipient coronary arteries bypassed with saphenous vein grafts (35%) showed total occlusion (p=0.016). Hypertension, hyperlipidemia, diabetes mellitus, and smoking history did not correlate with progression of stenosis of the native coronary arteries. Graft flow measured during surgery in the saphenous vein grafts was not significantly different between the group that exhibited progression of the native stenosis and the group that did not. CONCLUSIONS: Coronary artery bypass grafting with saphenous vein grafts may result in progression of stenosis of the recipient coronary artery. This is less likely after coronary artery bypass grafting with internal thoracic artery grafts. This difference may be due to the ability of the pedicled internal thoracic artery graft to regulate flow. Thus competitive flow in the native coronary artery is minimized. This has significant clinical implications.

Aged↗

The characteristics of screened patients with abdominal aortic aneurysm.

BACKGROUND: Screening for abdominal aortic aneurysm (AAA) has not yet been established in Japan. We therefore report the characteristics of a screened population and discuss the implications of screening using ultrasound in Japan. METHODS: The subjects in our screening group were composed of 4428 participants who were 60 years of age or older. Aneurysm was detected in 16 cases, 15 males and 1 female, the detection rate being 0.4% in total and 0.9% in the males. We compare the characteristics of screened patients (n = 16) with non-screened patients operated on for abdominal aortic aneurysm (n = 166). RESULTS: There were no significant differences in the mean age or in the female ratio between the screened and non-screened groups (71 vs 70 y/o, 6% vs 13%, respectively). Solitary iliac aneurysms were significantly (p < 0.05) more frequent in the screened than in the non-screened group (19% vs 3%). The size of aneurysm in the screened group was significantly (p < 0.05) smaller compared with the non-screened group. Sixty-three per cent of the screened group and only 8% of the non-screened group had an aneurysm less than 40 mm in size. Aneurysm was palpable in only 31% of those of the screened group. There were no significant differences between the groups in the frequency of arteriosclerotic risk factors such as hypertension, ischaemic heart disease, diabetes mellitus, peripheral vascular disease and smoking habits. Surgical treatment was selected in 7 out of 16 screened patients. The remaining 9 patients with small-sized abdominal aortic aneurysms have been carefully followed up. CONCLUSIONS: Screening for abdominal aortic aneurysm using ultrasound is advisable especially for male participants and for the detection of iliac aneurysms. This screening procedure is useful for early detection because the screened aneurysm is generally small-sized and impalpable.

Aged↗

KE-298 and its active metabolite KE-758 suppress nitric oxide production by murine macrophage cells and peritoneal cells from rats with adjuvant induced arthritis.

OBJECTIVE: To analyze the effects of KE-298 and KE-758 on lipopolysaccharide (LPS) induced nitric oxide (NO) production by the RAW264.7 murine macrophage cell line, and the effect of KE-758 on spontaneous NO production by peritoneal cells from rats with adjuvant induced arthritis. METHODS: The amount of NO was determined using Griess reagents. The proteins for inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) were detected by Western blot, then mRNA for interferon-beta (IFN)-beta, IFN regulatory factor-1 (IRF-1), and iNOS were detected by RT-PCR. Degradation of iNOS mRNA was analyzed using Northern blot. Nuclear factor-kappa B (NF-kappa B) in nuclear extracts was determined by EMSA. Adjuvant arthritis in rats was induced by inoculating heat killed Mycobacterium butyricum s.c. in the tail. RESULTS: KE-298 and KE-758 suppressed NO production by LPS activated RAW264.7 cells by inhibiting iNOS gene expression. Neither LPS induced NF-kappa B activation nor degradation of iNOS mRNA was affected by KE-758 treatment. LPS induced IFN-beta and IRF-1 gene expression were markedly suppressed by KE-758. In rats with adjuvant induced arthritis, enhanced NO and iNOS production by cultured peritoneal cells and the development of arthritis were suppressed by KE-758. CONCLUSION: KE-758 suppressed LPS induced iNOS gene expression by murine macrophage cells by inhibiting IFN-beta/IRF-1 expression. The potential of KE-758 to inhibit iNOS production might partly explain its efficacy on adjuvant induced arthritis in rats.

Animals↗

[Blood transfusion under cardiopulmonary bypass is a possible inducer for inflammation?].

To investigate that blood transfusion under cardiopulmonary bypass is a possible inducer for inflammation, a retrospective study was made with 20 adult patients who underwent coronary artery bypass grafting. The subjects were divided into two groups; transfusion group (group T) including 9 patients who received blood transfusion during cardiopulmonary bypass and the control group (group C) including 11 patients who did not undergo perioperative transfusion. Respiratory index as an indicator of respiratory functions was determined before and immediately after cardiopulmonary bypass, at the end of surgery and 4 hours thereafter. Cardiac index and arterial pressure were determined as the indicator of cardiac function. Moreover, interleukin 6 and 8 (IL-6 and IL-8), inflammatory cytokines were measured and compared between the two groups. The mean amount of blood transfusion was 2.1 units per individual of group T. The minimum value of hematocrit during cardiopulmonary bypass was significantly lower in group T (15.8 +/- 1.8%) than group C (19.1 +/- 1.4%), but the difference became not significant after cardiopulmonary bypass. There were no significant differences either in aortic pressure or cardiac index between two groups. The respiratory index at the end of surgery was higher in group T but the difference was not significant. Meanwhile IL-8 level at the end of cardiopulmonary bypass was significantly higher in group T (67.9 +/- 36 pg/ml) than group C (35.1 +/- 21 pg/ml). However, there was no difference in IL-6 level between the two. These results suggested that inflammation might be aggravated by an increase of IL-8 induced by blood transfusion.

Aged↗

[Right ventricular outflow tract reconstruction using a three-valved extracardiac conduit of expanded polytetrafluoroethylene vessel graft in the Ross operation: a pediatric case report].

A 16-year-old boy was diagnosed as having severe aortic regurgitation and moderate aortic stenosis due to congenital aortic bicuspid valve. A chest X-ray film showed the cardiothoracic ratio (CTR) of 64% and echocardiography revealed severe dilation of the left ventricular dimension with severe wall thickness. An electrocardiogram showed multiple ventricular arrhythmias. The patient underwent the Ross operation with the reconstruction between the right ventricle and the pulmonary arteries using a three-valved conduit which was made by an expanded polytetrafuloroethylene vessel graft. Ventricular arrhythmia disappeared just after the operation and left ventricular dimensions improved with the CTR of 53% except mild regurgitation of the neo-aortic valve three months later.

Adolescent↗

Cisplatin (CDDP) sensitizes human osteosarcoma cell to Fas/CD95-mediated apoptosis by down-regulating FLIP-L expression.

The mechanisms of escape from Fas/CD95-mediated apoptosis induced by immunosurveillance(NK cells and T cells) in tumor cells are correlated to tumorigenicity. Human osteosarcoma cell MG-63 constitutively expressed cell surface Fas antigen but was resistant to apoptosis by Fas stimulation. However, suboptimal dose of cisplatin(CDDP) could sensitize MG-63 cells to Fas-mediated apoptosis without up-regulation of cell-surface Fas antigen. Western blotting analysis showed that MG-63 cells constitutively expressed FLICE inhibitory protein long form(FLIP-L), which was a novel anti-apoptotic protein and had a potency of tumorigenicity. CDDP down-regulated FLIP-L in a time-dependent manner in MG-63 cells but did not influence expression of other anti-apoptotic molecules such as XIAP, c-IAP-1, c-IAP-2, FADD or pro-caspase-8. Moreover, antisense oligonucleotide to FLIP-L confirmed that down-regulation of FLIP-L induced sensitization to Fas-mediated apoptosis. These findings suggest that FLIP-L contributes to resistance to Fas-mediated apoptosis in MG-63 cells, and sensitization to Fas-mediated apoptosis by CDDP can be a new application of immune therapy.

Antineoplastic Agents↗

Different laterality between the thumb and index finger in human SII activities.

We compared the ipsilateral and contralateral evoked activities in the secondary somatosensory cortex (SII) of four human subjects. Magnetic cortical fields, evoked by electrical stimulation of the distal interphalangeal joint of either the thumb or the index finger, were recorded by an 80-channel whole head type magnetoencephalography system (MEG). We calculated the ratio of the equivalent current dipole (ECD) moment of the ipsilateral area to that of the contralateral area. The mean ratio for the thumb across the subjects was 0.43 +/- 0.13, while that for the index finger was 0.77 +/- 0.20 (mean +/- s.d). The ratio for the index finger was significantly higher than that for the thumb (p = 0.039, two tailed t-test). These results show that the cortical index finger area is activated more bilaterally than the thumb area.

Adult↗

Growth-stimulating effect of dienogest, a synthetic steroid, on rodent, canine, and primate mammary glands.

We observed hyperplasia of the mammary gland in female beagle dogs, but not in female rats and monkeys, in 91-day toxicity studies on dienogest. In order to elucidate a possible mechanism for its development and to account for this species difference, we determined the plasma level of growth hormone (GH) in dogs, rats, and monkeys treated orally with dienogest for 91 days. As a result, dogs with mammary hyperplasia showed a prominent, dose-dependent increase in their GH level; and, contrarily, rats and monkeys without the hyperplasia of this organ failed to show any such increase. These results were supported by evidence from immunohistochemical and morphometric analysis of the pituitary gland. In addition, dienogest and medroxyprogesterone acetate (MPA) stimulated the growth of canine mammary epithelial cells in the presence of estradiol in vitro, but had no effect on rat and human mammary epithelial cells incubated under the same conditions. In conclusion, dienogest with progestational activity caused proliferation of the mammary gland in beagle dogs by increasing the secretion of GH, as do other progestational compounds. This change may be partially dependent on the direct effect of the drug.

Animals↗

Edge thermal transport barrier In LHD discharges

In LHD discharges a significant enhancement of the global energy confinement has been achieved for the first time in a helical device with an edge thermal barrier, which exhibits a sharp gradient at the edge of the temperature profile. Key features associated with the barrier are quite different from those seen in tokamaks: (i) almost no change in particle (including impurity) transport, (ii) a gradual formation of the barrier, (iii) a very high ratio of the edge temperature to the average temperature, and (iv) no edge relaxation phenomenon. These features are very attractive in applying the thermal barrier to future reactor grade devices.

Journal Article↗

Aldose reductase inhibition prevents glucose-induced apoptosis in cultured bovine retinal microvascular pericytes.

The pathogenesis of pericyte loss, an initial deficit in the early stage of diabetic retinopathy, remains unclear. Polyol pathway hyperactivity has been implicated in the pathogenesis of diabetic retinopathy, and recent studies have suggested that apoptosis may be involved in pericyte loss. The present study was conducted to investigate whether high glucose induces apoptosis in cultured bovine retinal pericytes. The effect of an aldose reductase inhibitor, SNK-860, was also examined. After a 5 day incubation with various concentrations of glucose (5.5-40 m M) in the presence or absence of SNK-860, the cell viability and the percentages of dead cells were measured, and staining with the TUNEL method and Hoechst 33342, and DNA electrophoresis were performed. High glucose reduced the viability and increased the percentages of dead cells. TUNEL-positive cells were observed in pericytes under high glucose, but not in those under 5.5 m M glucose. In the staining of nuclei with Hoechst 33342, the percentage of apoptotic cells in total cells counted under high glucose was higher than that under 5.5 m M glucose. DNA electrophoresis of pericytes cultured with high glucose demonstrated a 'ladder pattern'. Hyperosmolarity also induced apoptosis in pericytes, but less than that by high glucose. SNK-860 inhibited the glucose-induced apoptosis in pericytes. These observations suggest that the pericyte loss in diabetic retinopathy involves an apoptotic process, and that the polyol pathway hyperactivity plays an important role in inducing apoptosis in pericytes by high glucose.

Aldehyde Reductase↗

Rotational Analyses of Several Infrared Bands of NH(2)Cl.

The high-resolution absorption spectra of several infrared bands of NH(2)Cl molecule have been observed and analyzed. Rotational lines of amino wagging and scissoring fundamental bands are split by about 0.2 cm(-1) through the amino inversion motion. The shape of the inversion potential and the barrier height are considered by comparing the results of the experimental observations and an ab initio MO calculation. The amino twisting band of amine molecule has been observed for the first time in the gas phase. The intensity of the transition seems to be induced through a Coriolis interaction with the intense amino wagging band. Copyright 2000 Academic Press.

Journal Article↗