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Biomedical subjects

S Yamada

Publications and source records attributed to S Yamada.

At least 451 records · Page 25Linked to original sources

Augmentation of Ca2+-stimulated insulin release by glucose and long-chain fatty acids in rat pancreatic islets: free fatty acids mimic ATP-sensitive K+ channel-independent insulinotropic action of glucose.

Glucose augments Ca2+-stimulated insulin release from the pancreatic beta-cell in an ATP-sensitive K+ channel (K(ATP) channel)-independent manner. In studying the mechanisms underlying this action, we used rat pancreatic islets and examined the effects of exogenous free fatty acids (FFAs), which are precursors of long-chain acyl-CoA (LC-CoA), on KCl-induced Ca2+-stimulated insulin release. Myristate, palmitate, and stearate augmented insulin release induced by 50 mmol/l KCl in the presence of 2.8 mmol/l glucose. Added acutely, their potency was weak compared with that of glucose-induced augmentation. The FFA-induced augmentation became much greater, however, when islets were preincubated with FFAs under stringent Ca2+-free conditions (with 1 mmol/l EGTA) before the KCl stimulation. Under these conditions, 16.7 mmol/l glucose augmented 13-fold insulin release induced by 50 mmol/l KCl, whereas palmitate or myristate (both at a free concentration of 10 micromol/l) produced 5.8- and 5.2-fold augmentations. Effects of FFAs and glucose were concentration-dependent. The temporal profiles of augmentation induced by 11.1 mmol/l glucose and 10 micromol/l palmitate were similar. Glucose and palmitate caused almost identical augmentation patterns for the initial 10 min of stimulation; subsequently, glucose augmentation was better sustained than palmitate augmentation. This suggests the existence of a longer-term glucose-specific signaling moiety that cannot be mimicked by FFAs. Our results provide direct evidence that FFAs can mimic the K(ATP) channel-independent action of glucose. Taking these results together with previous results, we conclude that glucose augments Ca2+-stimulated insulin release, at least in part, by increasing malonyl-CoA and cytosolic LC-CoA. However, one or more other glucose-specific signaling molecules are required for the full expression of augmentation.

Adenosine Triphosphate↗

Elevated remnant-like lipoprotein particles in impaired glucose tolerance and type 2 diabetic patients.

OBJECTIVE: Impaired glucose tolerance (IGT) in association with insulin resistance is considered to be a risk factor for atherosclerosis. Thus, patients with IGT may have abnormal lipid and lipoprotein profiles. The purpose of this study was to investigate presence of remnant-type hyperlipoproteinemia in patients with IGT. RESEARCH DESIGN AND METHODS: Serum levels of remnant-like lipoprotein particles (RLP) were measured in 541 subjects (362 men and 179 women, age 53 +/- 7.9 years) who visited our health center for routine medical examinations. We measured RLP cholesterol (RLP-C) and RLP triglycerides (RLP-TG) using immunoaffinity gel containing monoclonal anti-human apoproteins A-I (H-12) and B-100 (JI-H) antibodies. After a 75-g oral glucose tolerance test, subjects were divided into three groups: normal, IGT, and type 2 diabetic. RESULTS: After matching for sex, age, and body weight, serum RLP-C in normal, IGT, and diabetic groups were 4.2 +/- 1.7, 6.2 +/- 3.4, and 6.2 +/- 4.2 mg/dl, respectively. The corresponding RLP-TG values were 16.7 +/- 9.2, 28.0 +/- 19.1, and 29.0 +/- 27.2 mg/dl. We found that RLP-C and RLP-TG values were significantly higher in the IGT and diabetic groups compared with the normal group (P < 0.001). In the same order, total serum cholesterol levels were 206 +/- 29, 205 +/- 34, and 206 +/- 34 mg/dl and LDL cholesterol levels were 127 +/- 27, 124 +/- 34, and 123 +/- 34 mg/dl, showing no marked difference in these groups. However, serum levels of triglyceride were higher in the IGT and diabetes groups (155 +/- 76 and 151 +/- 81 mg/dl vs. 106 +/- 41 mg/dl; P < 0.0001). Further, the incidence of remnant hyperlipoproteinemia in normocholesterolemic subjects was up to four times higher in IGT and diabetic groups compared with the normal group. CONCLUSIONS: High serum RLP-C and RLP-TG levels in IGT and diabetic patients may represent an increased risk of atherosclerosis in these patients.

Analysis of Variance↗

Plasma cell generation from B-lymphocytes via CD27/CD70 interaction.

To produce antibodies, the differentiation of B cells into antibody-secreting cells, plasma cells, is required. We describe that ligation of CD27, which belongs to the tumor necrosis factor receptor (TNFR) family and is a memory marker of B cells, yields crucial signals that positively control the entry of B cells into the pathway to plasma cells. The triggering via CD27 by CD27 ligand (CD70) on purified peripheral blood B cells yielded an increase in the number of plasma cells in the presence of interleukin-10 (IL-10). The differentiation into plasma cells by a combination of IL-10 and CD70-transfectants occurred in CD27+ B cells, but not in CD27- B cells. Moreover, the addition of IL-2 to the IL-10 and CD70-transfectants greatly induced the differentiation into plasma cells. In the presence of only IL-2, IL-4 or IL-6, CD70-transfectants did not promote the differentiation into plasma cells. On the other hand, CD40 signaling increased the expansion of a B cell pool from peripheral blood B cells primarily activated by IL-2, IL-10 and anti-CD40 mAb. These data demonstrate that CD27 ligand (CD70) is a key molecule to direct the differentiation of CD27+ memory B cells toward plasma cells in cooperation with IL-10.

Animals↗

[Adverse reactions to autologous peripheral blood stem cell transplantation in patients over 65 years old].

We compared the outcomes of autologous peripheral blood stem cell transplantation (auto-PBSCT) for two groups: one composed of 6 patients over 65 years of age, and the other, of 8 younger patients. Transfused CD34-positive cells and CFU-GM counts, days to achieve a neutrophil count of over 500/microliter after transplantation, days to achieve a platelet count of over 50,000/microliter, and blood transfusion times were similar in both groups. Organ toxicity also appeared similar in both groups, but no severe adverse reactions (WHO grade/4) were observed. Poor performance status due to advanced tumors improved in some patients after PBSCT. We concluded that PBSCT is tolerable in patients over 65 years of age and useful as salvage therapy.

Age Factors↗

The influence of frequent and excessive intake of glucose on microvascular aging in healthy mice.

OBJECTIVE: The purpose of this study was to verify the following working hypothesis. Even in healthy individuals with normoglycemic adaptability, microvascular aging caused by the accumulation of advanced glycosylation end products (AGEs) in vascular walls would occur, when the blood glucose level is maintained intermittently high due to frequent and excessive sugar intake for a prolonged period. METHODS: Male BALB/c mice were divided into four groups: the S group raised with glucose-enriched feed and the C group with ordinary feed, as well as the SG group with the glucose-enriched feed and special drinking water supplemented with 0.25% aminoguanidine (AG), and the CG group with ordinary feed and this special drinking water. After 6 months, a mouse dorsal skinfold chamber was mounted on the skin of the back for the intravital-microscopic observations of microvasculature. RESULTS: Blood glucose levels were within normal ranges in all four animal groups, indicating their saccharometabolism to be normal. An autofluorescent AGE-positive ratio in the S group was 71.4%, and that in the C group was 33.3%. Mean caliber of arterial microvessels was smallest in the S group. The SG and CG group showed the caliber larger than the groups without AG. Vascular lesion indices were significantly larger in the S group than those of the groups with AG. The indices were particularly small in the SG group. A decrease of amplitudes in thicker vessels and an increase of vasomotor frequencies in thinner ones were demonstrated in the S group. The features of vasomotion differed in the groups with and without AG. CONCLUSIONS: Microvascular aging was clearly noticed in the S group. It has been concluded that vasomotor inhibition was generated in addition to hypertrophy and fragility in arterial microvessels of the group. It is further concluded that AG protects blood vessels from hypertrophy and fragility, but it downregulates vasomotion.

Aging↗

In vivo measurement by [3H]Tamsulosin of alpha1 adrenoceptors in rat tissues in relation to the pharmacokinetics.

The present study was undertaken to simultaneously measure alpha1 adrenoceptors in rat tissues by [3H]tamsulosin in vivo. In vivo specific [3H]tamsulosin binding was observed in the prostate, vas deferens, aorta, submaxillary gland, spleen, heart, lung, and kidney after i.v. injection of the ligand but not in the cerebral cortex and liver. Specific [3H]tamsulosin binding in the kidney, lung, heart, and spleen was greatest at 3 min after i.v. injection and declined rapidly with the disappearance of [3H]tamsulosin from the plasma. On the other hand, [3H]tamsulosin binding in the prostate and aorta peaked at 10 to 60 min after i.v. injection, and a considerable level of specific binding in both tissues persisted up to 240 min. The most sustained binding of [3H]tamsulosin occurred in the submaxillary gland. In vivo specific [3H]tamsulosin binding in rat tissues was effectively inhibited by the coinjection of low doses of unlabeled tamsulosin, prazosin, and terazosin with the radioligand but not by relatively high doses of yohimbine and propranolol. Based on estimated ID50 values, in vivo inhibitory effect of tamsulosin compared with prazosin was 5 to 14 times greater in rat tissues except the spleen, which showed 1.6 times less potent than prazosin. From ratios of ID50 (spleen) to ID50 (submaxillary gland) or ID50 (prostate), tamsulosin was 9 and 19 times, respectively, greater than prazosin in selectivity of alpha1 adrenoceptors in the submaxillary gland and prostate versus the spleen, respectively, suggesting that tamsulosin binds to alpha1A subtype with higher affinity than alpha1B subtype in vivo. The present study suggests that [3H]tamsulosin is a useful radioligand for in vivo measurement of alpha1 adrenoceptors in rat tissues.

Adrenergic alpha-1 Receptor Antagonists↗

[Intraoperative assessment by laser-Doppler skin blood flowmetry of the efficacy of endoscopic thoracic sympathectomy].

We have investigated whether laser-Doppler (L-D) skin blood flowmetry on the finger could be useful for an intraoperative assessment of the efficacy of endoscopic thoracic sympathectomy (ETS) under general anesthesia. Subjects were 5 young adults receiving ETS for palmar hyperhidrosis. ETS was performed with the patients in the semi-sitting position under one lung ventilation. A pair of LDF probes were placed on the palmar side of the both second fingers. Palmar hyperhidrosis disappeared after ETS in all cases, but compensatory hyperhidrosis developed in the back of the body and the thigh. After completion of ETS on one side, the L-D skin blood flow increased to 267.6 +/- 211.1% on the side of ETS, and it increased in 2 other cases and decreased on the contrary in 3 cases on the other side. After ETS on both sides the L-D skin blood flow increased to 265.0 +/- 185.9% on the side of initial ETS and to 211.4 +/- 172.8% on the side of subsequent ETS. The initial EST induced reflex vasoconstriction on the finger of both sides and also on the toe. Spontaneous fluctuation and reflex vasoconstriction of the skin blood flow were still observed, although the periodicity of spontaneous fluctuation between the right and the left finger was lost in some of the cases. An increase in L-D skin blood flow on the side of ongoing ETS is useful for intraoperative assessment of ETS.

Adult↗

[A novel Lp(a) assay not affected by apo(a) size polymorphism].

Apo(a), the protein moiety of Lp(a), has size polymorphism that derives from the variable number of K4 type 2 repeats. We have developed three ELISA method with using monoclonal antibodies against the K4 type 2 repeats, the K4 type 5-protease domain, and the K5 protease domain of the apo(a) molecule. The commercial assay kits were correlated with the results from ELISA that utilized a monoclonal antibody against the K4 type 2 but indicated poor correlation with an ELISA method using anti Lp(a) K4 type 5-protease domain monoclonal antibody. Serum Lp(a) values were 1.8-fold overestimated by the commercial assay kits in samples with S4 type of the largest isoform, but our ELISA method in which the apo(a) K4 type 5-protease domain is used as labeled antibody and capture antibody was not affected by size polymorphism.

Antibodies, Monoclonal↗

[Comparison of 201Tl-SPECT and MRI using Gd-DTPA for glioma].

201Tl-SPECT was performed in 25 patients with a pathological diagnosis of glioma. The lesion-to-normal (L/N) ratio of the glioblastoma group (n = 7) was found to be higher than that of the low-grade glioma group (n = 7; Mann-Whitney U-test, p < 0.0167). 201Tl accumulation in the tumor corresponded to contrast enhancement on MRI in 95% of cases. An insufficient blood-brain barrier was considered to be the primary contributor to 201Tl accumulation. In five cases, there was a discrepancy between the extent of 201Tl accumulation and the Gd-DTPA enhanced area. In these cases, the area of 201Tl accumulation was larger than the area of Gd-DTPA enhancement. This may result from damage to the blood-brain barrier that is not severe enough to be detected with Gd-DTPA or from additional factors other than change in the blood-brain barrier. 201Tl-SPECT is able to demonstrate the extent of glioma more accurately than contrast-enhanced MRI.

Brain Neoplasms↗

[Saliva level of free-3-methoxy-4-hydroxyphenylglycol in patients with anxiety disorders].

The saliva level of free 3-methoxy-4-hydroxyphenylglycol (MHPG) in 16 outpatients with anxiety disorders was determined by gas chromatography-mass spectrometry. The anxiety level of the patients was scored by the Hamilton Anxiety Scale (HAS) before and after a one-week drug treatment with alprazolam. The saliva level of free-MHPG at the subjects' first visit to the hospital was significantly higher than that of the control subjects and was reduced by the one-week alprazolam treatment. The post-treatment level of MHPG in patients who showed good response to the treatment was significantly less than the pretreatment level, but there was no significant difference between pre- and post-treatment levels of MHPG in poor responders. There was no correlation between the MHPG level and the HAS score at the first hospital visit. The MHPG levels after the treatment correlated with the HAS scores. The reduction of the anxiety level as scored by the HAS correlated with the reduction of the MHPG level. These results indicate that the free saliva MHPG level may be a useful indicator for assessing not only the level of anxiety but also the response to drug treatment for anxiety in these patients.

Adult↗

[Blood flow velocity in the central retinal artery of exotoxin-induced uveitis in rabbits].

PURPOSE: Exotoxin-induced uveitis in rabbit eyes was established by intravitreal inoculation of staphylococcal enterotoxin B (SEB). Association between findings of pulsed Doppler assessments and histological features were evaluated. MATERIAL AND METHODS: Eyes of rabbits were unilaterally inoculated with 50 ng/kg of intravitreal SEB. Pupil diameter, blood flow velocity in the central retinal artery in both eyes and heart rate were measured using an ultrasonic diagnostic apparatus after inoculation. RESULTS: The pupil diameter and the mean blood flow velocity in central retinal arteries decreased and reached a trough 3-5 hours after the inoculation, then increased. Pulsatility index showed reciprocal fluctuations. Histological features at the early phase after inoculation revealed lymphocytic, plasmacytic, and polynuclear leukocytic infiltrations around the anterior chamber, limbal conjunctivae, ciliary body, and nerve fiber layer of the retina, followed by recovery after about 5 days. At the late phase, recurrent inflammations in the ciliary body and intravitreal space were observed in addition to invasion into the rod and cone layer. CONCLUSION: Early and late phase uveitis was established by intravitreal SEB. It is considered that the uveitis may be caused by two different regulatory mechanisms.

Animals↗

[Diagnosis of myocardial viability by exercise echocardiography].

This study determined whether the diagnosis of myocardial viability could be established on the basis of the contractile reserve during low level exercise with an ergometer using echocardiography. The study involved 22 patients with transmural old myocardial infarction who underwent exercise echocardiography, followed by coronary intervention after a mean 4 days. Exercise echocardiography was started from 50 W and stepped up by 25 W every 3 min up to a maximum of 150 W. Low level exercise was administered for 1 to 2 min at 50 W. A 16-segment model was used for the left ventricular wall motion, which was evaluated by five-grade scoring, ranging from normokinesis to dyskinesis. If patients showed improvement by one point or more in the score for segments of dyskinesis, akinesis, or severe hypokinesis on the exercise echocardiography, they were considered to have positive viability. The golden standard for the diagnosis of myocardial viability was that wall motion abnormalities before exercise echocardiography should be improved by one point or more after coronary intervention. Before exercise echocardiography, there were 152 segments showing wall motion abnormalities assessed as severe hypokinesis or more. After coronary intervention, improvement of the wall motion by one grade or more was found in 2 of the 18 segments (11%) for dyskinesis, in 38 of the 96 segments (40%) for akinesis, and in 22 of the 38 segments (58%) for severe hypokinesis; improvement for the segments of severe hypokinesis was significantly better than those for dyskinesis and akinesis. Out of 19 segments with akinesis before exercise echocardiography in which wall motion was improved during low level exercise, 16 segments (84%) showed improvement in wall motion after coronary intervention. Out of 77 segments with akinesis before exercise echocardiography in which no change or worsening was seen during low level exercise, 22 segments (29%) showed improved wall motion after coronary intervention. There were 38 segments with severe hypokinesis before exercise echocardiography; out of 12 segments in which wall motion was improved during low level exercise, 7 segments (58%) showed improved wall motion after coronary intervention. Out of 26 segments with severe hypokinesis before exercise echocardiography in which no change or worsening was seen during low level exercise, 11 segments (42%) showed improved wall motion after coronary intervention. Wall motion was improved after coronary intervention in 20 of 25 segments (80%) that showed the biphasic response, in 4 of 7 segments (57%) that showed improvement, in 14 of 43 segments (33%) that showed worsening, in 24 of 77 segments (31%) for no change; the biphasic response showed a significantly higher improvement compared to worsening or no change. If segments in which wall motion was improved during low level exercise are regarded as positive viability segments, occurrences of the sensitivity, specificity and diagnostic accuracy of myocardial viability were 50%, 84%, and 71%, respectively.

Echocardiography↗

A randomized comparative study of the Bandloop versus the standard loop for transurethral resection of the prostate.

PURPOSE: The Bandloop is a new electroresection loop that is broader than the standard loop and thickens from front to back. We compared the safety and efficacy of the Bandloop to the conventional loop electrode for transurethral prostatectomy. MATERIALS AND METHODS: A randomized prospective study was performed on 53 patients with lower urinary tract symptoms and estimated prostatic volume greater than 30 ml. on transrectal ultrasonography. The Bandloop was used in 25 cases (Bandloop group) and standard loop was used in 28 (standard group). Surgical outcomes, including International Prostate Symptom Score, resected prostatic weight, operative time, uroflowmetry, post-void residual urine, postoperative catheterization period, time to disappearance of macrohematuria, and serial changes of hemoglobin and urinalysis, between the 2 groups were compared. RESULTS: A total of 23 Bandloop and 28 standard loop cases were evaluable. There was no difference in preoperative estimated prostatic volume (mean 44.7 versus 47.8 ml.), resected prostatic weight (36.5 versus 29.4 gm.) or operative time (61 versus 60 minutes) between the 2 groups. The ratio of resected weight-to-estimated prostatic volume was significantly greater in the standard group (81.4% versus 61.9%). There was no difference in postoperative catheterization period (3.3 versus 3.4 days) or time to disappearance of macroscopic hematuria (5.0 versus 5.0 days). Postoperative changes in symptom score (-15.1 versus -15.9), maximum flow rate (11.8 versus 16.3 ml. per second at 12 weeks) and residual volume (-31.6 versus -48.6 ml. at 12 weeks) demonstrated no significant difference between the 2 groups. There was no difference in intraoperative and postoperative bleeding estimated by serial changes in serum hemoglobin and urinalysis after surgery. No patient had major complications or required transfusion. CONCLUSIONS: Transurethral prostatectomy using the Bandloop is as safe and effective in achieving subjective and objective improvements as standard transurethral prostatectomy. However, our randomized study indicates that the Bandloop offers no advantage compared to the standard loop electrode for transurethral prostatectomy.

Aged↗