Biomedical subjects

S Yamada

Publications and source records attributed to S Yamada.

At least 505 records · Page 28Linked to original sources

PubMed1998

Xanthine oxidase inhibition attenuates kupffer cell production of neutrophil chemoattractant following ischemia-reperfusion in rat liver.

We investigated the effects of the xanthine oxidase inhibitor, BOF-4272, on the production of cytokine-induced neutrophil chemoattractant (CINC) following reperfusion injury in rat liver. Ischemia was induced for 30 minutes by portal vein occlusion. Animals were pretreated with intravenous injection of BOF-4272 (1 mg/kg) or heparin (50 U/kg) 5 minutes before vascular clamp. Both BOF-4272 and heparin limited increases in the chemoattractant compared with nonpretreated rats. Pretreatment with BOF-4272 plus heparin resulted in an additive effect. Most cells immunostained for chemoattractant were macrophages in sinusoids. In vitro chemoattractant production by Kupffer cells isolated from animals pretreated with heparin or BOF-4272 was significantly lower than by Kupffer cells from nonpretreated animals. Expression of transcripts in liver for chemoattractant peaked 3 hours after reperfusion in nonpretreated animals, while pretreatment with heparin or BOF-4272 significantly decreased chemoattractant mRNA levels. In vitro chemoattractant transcription and production could be induced in naive Kupffer cells by hypoxanthine and xanthine oxidase, but BOF-4272 prevented these increases. We conclude that Kupffer cells release chemoattractant in response to oxygen radicals reducible by xanthine oxidase inhibition.

Animals↗

PubMed1998

Successful surgical management of penetrating cardiac injury.

A 60-year-old Asian man who suffered penetrating thoracoabdominal injuries was admitted to our hospital in a state of shock. Because the results of a chest computed tomogram (CT) strongly suggested a left ventricular injury, an emergency thoracotomy was performed. A laceration of the left ventricle (3 cm) was sutured and was closed without cardiopulmonary bypass, and coexisting lacerations of the superior mesenteric artery (SMA) and small bowel were surgically repaired. During the procedure, cardiac arrest occurred, but the patient recovered without any apparent neurologic deficit. Postoperative examinations using echocardiogram, CT, and cardiac catheterization revealed a delayed rupture of the left ventricle. On the 28th day after surgery, he was transferred to another hospital for elective cardiac surgery. Primary management of penetrating cardiac injury is discussed in this report.

Abdominal Injuries↗

PubMed1998

Hemorrhage in pituitary adenoma: correlation of MR imaging with operative findings.

The aim of this study was to correlate MR imaging and operative findings of hemorrhage in pituitary macroadenomas. We retrospectively reviewed MR images of 113 surgically proven pituitary adenomas. All patients were examined on a 1.5-T MR system. The intensity of intratumoral cystic cavities was correlated with operative findings. In 15 patients with pituitary apoplexy, we determined relationship between interval of MR examination after apoplectic event and MR signal intensity. In 8 patients with repeated preoperative MR examination, we evaluated sequential changes of intratumoral hemorrhage. There were 54 cavities at surgery: 52 were hemorrhagic and 2 were nonhemorrhagic. Twenty-nine of 52 hemorrhagic cysts demonstrated high/low signal (H/L) fluid-fluid levels on T2-weighted image (T2WI). In 19 of them, two components could be separately seen at operation: the supernatant high-intensity area represented xanthochromic fluid, and the dependent low-intensity area represented liquefied hematoma. The H/L fluid-fluid level was observed predominantly in hematomas on MR images obtained after longer intervals. In patients with repeated MR examination, follow-up MR imaging revealed additional hemorrhage or new formation of fluid-fluid levels. It was surprising that 12 of 14 cysts preoperatively judged as nonhemorrhagic in fact contained hemorrhagic components. The preoperative MR images are well correlated to the operative findings in hemorrhagic pituitary macroadenomas. It proved that 52 of 54 cystic cavities had hemorrhagic component.

Adenoma↗

PubMed1998

A combination of preductal aortic coarctation and type B dissection: report of a case.

We present herein the case of a 39-year-old man found to have significant coarctation of the preductal aorta combined with a type B dissection, associated with Marfan's syndrome. This extremely rare pathological combination could be defined preoperatively only by a three-dimensional computed tomography scan. By means of selective cerebral perfusion, the coarctation was resected, and the total aortic arch was replaced with a Dacron graft.

Adult↗

PubMed1998

Changes in high K+-evoked serotonin release and serotonin 2A/2C receptor binding in the frontal cortex of rats with thioacetamide-induced hepatic encephalopathy.

Serotonergic systems were investigated in the frontal cortex of rats with thioacetamide (TAA)-induced acute hepatic encephalopathy (HE). Extracellular basal levels of 5-HT showed no difference between control and HE animals, whereas the levels of 5-HIAA were significantly increased in HE rats. Unlike basal levels, high K+-evoked 5-HT release was significantly higher in HE rats than controls. Bmax of (+/-)-1-(2,5-dimethoxy-4-[125I] iodophenyl)-2-aminopropane ([125I] DOI) binding, mainly labeling postsynaptic 5-HT2A receptors, was significantly decreased without any change in Kd in HE rats. These results suggest that there is no change in basal 5-HT release in the cortex of rats with TAA-induced HE despite the increase in intraneuronal 5-HT metabolism and in the size of releasable 5-HT pool, and that serotonergic neurotransmission via 5-HT2A receptor is altered in the brain area of rats with HE.

Acute Disease↗

PubMed1998

Mutations in the hepatocyte nuclear factor-1 alpha gene (MODY3) are not a major cause of early-onset non-insulin-dependent (type 2) diabetes mellitus in Japanese.

Maturity-onset diabetes of the young (MODY3), a monogenic subtype of non-insulin-dependent diabetes mellitus (NIDDM) with an early age of onset, is characterized by a primary defect in insulin secretion. Recently, it has been shown that mutations of the gene encoding the transcription factor hepatocyte nuclear factor-1 alpha (HNF-1 alpha) cause MODY3. Since NIDDM in Japanese is characterized by insulin secretory defects due to primary beta-cell dysfunction, we screened 60 Japanese nonobese subjects with early-onset NIDDM for mutations in this gene, 45 of whom had a first-degree relative with NIDDM. Direct sequencing of the ten exons and flanking introns of the gene in these subjects identified eight nucleotide substitutions including two amino acid changes, Ile-27-Leu and Ser-487-Asn, the frequencies of which were not significantly different in subjects with early-onset NIDDM and nondiabetic subjects. These results suggest that mutations in the HNF-1 alpha gene are not a major cause of early-onset NIDDM in Japanese.

Adolescent↗

PubMed1998

Right ventricular obstruction by tricuspid pouch in simple ventricular septal defect.

Tricuspid pouch sometimes causes subpulmonary obstruction in association with transposition of the great arteries, but rarely does so without transposition. A 5-year-old girl with isolated ventricular septal defect exhibited dynamic right ventricular outflow tract obstruction caused by pouches in the anterior and septal tricuspid leaflets. Echocardiography clearly demonstrated features of the tricuspid pouches. Ventricular septal defect closure resulted in disappearance of the tricuspid pouches and resolution of subpulmonary obstruction.

Child, Preschool↗

PubMed1998

Conversion of N-sulfated glucosamine to N-sulfated mannosamine in an unsaturated heparin disaccharide by non-enzymatic, base-catalyzed C-2 epimerization during enzymatic oligosaccharide preparation.

A novel disaccharide was isolated beside the predominant trisulfated disaccharide, delta HexA(2-O-sulfate)(alpha 1-4)GlcN(2-N-,6-O-disulfate) (delta HexA and GlcN represent 4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid and D-glucosamine, respectively) after treatment of porcine intestinal heparin with Flavobacterium heparinase. It accounted for 18% of total disaccharides. The structure was characterized by secondary ion mass spectrometry, enzymatic digestions, amino sugar analysis, and 500 MHz one- and two-dimensional 1H NMR spectroscopy as delta HexA(2-O-sulfate) (alpha 1-4)ManN(2-N-,6-O-disulfate), where ManN represents D-mannosamine. The C-2 epimerization from delta HexA(2-O-sulfate) (alpha 1-4)GlcN(2-N-,6-O-disulfate) to delta HexA(2-O-sulfate) (alpha 1-4)ManN(2-N-,6-O-disulfate) was also demonstrated to take place in vitro under very mild alkaline conditions. Hence, the latter compound is not a biosynthetic product, but is most likely an artifact generated by non-enzymatic, base-catalyzed C-2 epimerization during enzymatic preparation of heparin oligosaccharides. The present results warn that the formation of the C-2 epimerized compound has to be circumvented in the structural analysis of heparin/heparan sulfate.

Catalysis↗

PubMed1998

In vivo receptor binding of novel alpha1-adrenoceptor antagonists for treatment of benign prostatic hyperplasia.

New types of alpha1-adrenoceptor antagonists (tamsulosin, KMD-3213 and JTH-601) are currently receiving a great deal of attention, especially in terms of developing effective therapeutic agents to treat bladder outlet obstruction with less side effects, such as postural hypotension, in patients with benign prostatic hyperplasia (BPH). In vivo alpha1-adrenoceptor binding properties of these antagonists in prostate and other tissues of rats were examined. Intravenous injections of tamsulosin, KMD-3213 and JTH-601 inhibited dose-dependently in vivo specific [3H]tamsulosin binding in various tissues. Ratios of ID50(aorta) to ID50(prostate) of KMD-3213 and JTH-601 were greater than those of tamsulosin and prazosin. Further, the ratios of ID50(spleen) to ID50(submaxillary gland) of these drugs were greater than that of prazosin. Following intravenous injections of [3H]KMD-3213 in rats, the amount of specific binding in prostate was significantly greater than that of [3H]prazosin, but that in aorta or spleen was much smaller. Interestingly, [3H]JTH-601 showed little in vivo specific binding in aorta. These data suggest that KMD-3213 and JTH-601 exhibit higher affinity to alpha1-adrenoceptors in prostate and submaxillary gland than in vascular tissues in vivo.

Adrenergic alpha-Antagonists↗

PubMed1998

Ex vivo occupancy by tamsulosin of alpha1-adrenoceptors in rat tissues in relation to the plasma concentration.

At 0.5-12 h after oral administration of tamsulosin (2.3 micromol/kg) in rats, there was a significant decrease in specific [3H]prazosin binding in the prostate as compared to the control value. The greater decrease occurred in the submaxillary gland. The effect of tamsulosin was mainly due to a marked reduction of [3H]prazosin binding sites (Bmax) rather than to an increase in the dissociation constant (Kd). In contrast, there was only a slight decrease or no change in the [3H]prazosin binding in the spleen, heart, and cerebral cortex of tamsulosin-administered rats at 0.5-12 h. Oral administration of terazosin (21.7 micromol/kg) significantly increased Kd values for [3H]prazosin binding with little effect on Bmax values in the rat prostate at 3 and 6 h. The greater increases in Kd values were observed in the submaxillary gland, spleen and heart at 0.5-12 h. Terazosin had a slight effect on Kd values for the cerebral cortical [3H]prazosin binding. Tamsulosin was absorbed rapidly after oral administration at a dose of 2.3 micromol/kg in rats, and at 6 h, plasma concentration decreased markedly to approximately one-twentieth of the 0.5 h peak level. alpha1-Adrenoceptor occupancy was estimated as a percentage of decrease in Bmax values for [3H]prazosin binding in tissues of tamsulosin-treated rats compared with control rats. The alpha1-adrenoceptor occupancy by tamsulosin in the prostate and submaxillary gland occurred rapidly in parallel with the rise in plasma concentration of tamsulosin, and lasted for over 12 h despite the marked decrease in plasma concentration. Consequently, it is suggested that tamsulosin produces more selective and sustained occupancy in vivo of alpha1-adrenoceptors in the submaxillary gland and prostate of rats than in other tissues.

Administration, Oral↗

PubMed1998

Dopamine autoreceptors in rat nucleus accumbens modulate prepulse inhibition of acoustic startle.

Dopamine and 3,4-dihydroxy phenylacetic acid (DOPAC) levels in discrete regions and apomorphine- or (-)-sulpiride-induced changes in electrically evoked dopamine release from nucleus accumbens slices were assessed after testing prepulse inhibition of acoustic startle (PPI) in rats. Dopamine and DOPAC levels in the nucleus accumbens, but not in the striatum, correlated well with PPI (r = -0.64 for dopamine, r = -0.48 for DOPAC). Evoked dopamine release from the nucleus accumbens did not differ between the high-PPI (more than 60%) and the low-PPI (less than 40%) group. When slices were superfused with 1 microM apomorphine, the S2/S1 ratio in rats showing high PPI was 0.77 +/- 0.02 (mean +/- SEM, 66% of control), significantly smaller than in the low-PPI group (S2/S1 ratio = 0.97 +/- 0.08, 94% of control, p < 0.05). Moreover, (-)-sulpiride-induced increase in evoked dopamine release from the nucleus accumbens in the high-PPI group was inclined to be greater than in the low-PPI group. The results suggest that PPI differences between individuals may reflect the sensitivity of release-modulating dopamine autoreceptors in the nucleus accumbens.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1998

Biodosimetry of heavy ions by interphase chromosome painting.

We report measurements of chromosomal aberrations in peripheral blood lymphocytes from cancer patients undergoing radiotherapy treatment. Patients with cervix or esophageal cancer were treated with 10 MV X-rays produced at a LINAC accelerator, or high-energy carbon ions produced at the HIMAC accelerator at the National Institute for Radiological Sciences (NIRS) in Chiba. Blood samples were obtained before, during, and after the radiation treatment. Chromosomes were prematurely condensed by incubation in calyculin A. Aberrations in chromosomes 2 and 4 were scored after fluorescence in situ hybridization with whole-chromosome probes. Pre-treatment samples were exposed in vitro to X-rays, individual dose-response curves for the induction of chromosomal aberrations were determined, and used as calibration curves to calculate the effective whole-body dose absorbed during the treatment. This calculated dose, based on the calibration curve relative to the induction of reciprocal exchanges, has a sharp increase after the first few fractions of the treatment, then saturates at high doses. Although carbon ions are 2-3 times more effective than X-rays in tumor sterilization, the effective dose was similar to that of X-ray treatment. However, the frequency of complex-type chromosomal exchanges was much higher for patients treated with carbon ions than X-ray.

Aged↗

PubMed1998

Microsatellite instability in human mammary epithelial cells transformed by heavy ions.

We analyzed DNA and proteins obtained from normal and transformed human mammary epithelial cells for studying the neoplastic transformation by high-LET irradiation in vitro. We also examined microsatellite instability in human mammary cells transformed to various stages of carcinogenesis, such as normal, growth variant and tumorigenic, using microsatellite marker D5S177 on the chromosome 5 and CYl7 on the Chromosome 10. Microsatellite instabilities were detected in the tumorigenic stage. These results suggest that microsatellite instability may play a role in the progression of tumorigenecity. The cause of the genomic instability has been suggested as abnormalities of DNA-repair systems which may be due to one of the three reasons: 1) alterations of cell cycle regulating genes. 2) mutations in any of the DNA mismatch repair genes, 3) mutation in any of the DNA strand breaks repair genes. No abnormality of these genes and encoded proteins, however was found in the present studies. These studies thus suggest that the microsatellite instability is induced by an alternative mechanism.

Breast↗

PubMed1998

Effect of EPC-K1 on myocardial infarct size in a rat model with coronary artery occlusion and reperfusion.

1. The ability of EPC-K1 to improve myocardial infarction was evaluated in a rat model with coronary artery occlusion and reperfusion. 2. The myocardial infarct size was 30.5 +/- 1.7% by intravenous (i.v.) administration and 28.8 +/- 2.7% by intraduodenal (i.d.) administration of the saline EPC-K1 at doses between 1 and 10 mg/kg, i.v. and at doses between 50 and 200 mg/kg, i.d., reduced myocardial infarct size dose dependently. Significant reduction in myocardial infarct size was found at a dose of 10 mg/kg, i.v., and 200 mg/kg, i.d.

Animals↗

PubMed1998

Growth hormone stimulatory effects on osteoclastic resorption are partly mediated by insulin-like growth factor I: an in vitro study.

This study investigated the possible role in vitro of insulin-like growth factor I (IGF-I) as a mediator of the effects of growth hormone (GH) on osteoclastic resorption in an unfractioned rabbit bone cell model. After 4 days of rabbit bone cell culture, human GH (hGH) (50 ng/mL) and human IGF-I (hIGF-I) (50 ng/mL) significantly increased the formation of osteoclast-like cells with a lower level than parathyroid hormone (50 ng/mL) or VD3 (10(-8) mol/L). As well as parathyroid hormone and 1-alpha,25-dihydroxyvitamin D3, addition of hGH (1, 10, and 50 ng/mL) and hIGF-I (1, 10, and 50 ng/mL) stimulated the resorption activity of osteoclasts in terms of the percentage of dentin slice surface resorbed, number of lacunae per surface unit, and mean area of lacunae as compared to the control. When neutralizing antiserum against hIGF-I (4 micrograms/mL) was added at the start of culture, the stimulatory effects of hIGF-I and hGH on osteoclastic resorption activity were totally abolished. These results indicate that the effects of GH stimulation on osteoclastic resorption in vitro are mediated via local IGF-I secretion by stromal cells such as osteoblasts. As IGF-I receptors have recently been reported on rabbit osteoclasts, a direct action of IGF-I on mature osteoclasts could be envisaged. Further experiments will be required to determine the real level of IGF-I implicated in the stimulation of bone osteoclastic resorption.

Acid Phosphatase↗

PubMed1998

Receptor occupancy in myocardium, adrenal cortex, and brain by TH-142177, a novel AT1 receptor antagonist in rats, in relation to its plasma concentration and hypotensive effect.

PURPOSE: To study the relationship between angiotensin II (AII) receptor occupancy ex vivo in tissues plasma concentration and hypotensive effect of a novel AII receptor antagonist, TH-142177 and losartan in rats. METHODS: At 2, 8 and 24 hr after oral administration of TH-142177 and losartan in rats, AII receptors in myocardium, adrenal cortex and cerebral cortex were determined by radioligand binding assay using [125I]Sar1,Ile8-AII. Plasma concentrations of both drugs and metabolite in rats were also measured using validated HPLC assays. Further, systolic blood pressure (SBP) in conscious renal hypertensive rats treated orally with TH-142177 and losartan were measured by using a tail cuff plethysmographic method. RESULTS: Oral administration of TH-142177 (1.8 and 5.5 micromol/kg) and losartan (6.5 and 21.7 micromol/kg) in rats brought about dose-dependent decreases in [125I]Sar1,Ile8-AII binding sites (Bmax) in myocardium and adrenal cortex. The extent of receptor occupancy by both drugs in adrenal cortex was maximal at 2 hr later but that in myocardium at 8 hr later. Further, the receptor occupancy was more sustained in myocardium than adrenal cortex. The ex vivo binding affinity of TH-142177 for AII receptors in these tissues was roughly three times higher than that of losartan. Also, cerebral cortical [125I]Sar1,Ile8-AII binding was significantly reduced by oral administration of losartan but not by TH-142177. The time course of AII receptor occupancy by both drugs in adrenal cortex appeared to be in parallel with that of their plasma concentrations, while the time course in myocardium correlated with that of their hypotensive effects rather than plasma concentrations. CONCLUSIONS: TH-142177 produced a relatively selective and sustained occupancy ex vivo of AII receptors in myocardium and adrenal cortex of rats with approximately three times greater potency than losartan. Its time course of myocardial receptor occupancy was in parallel with that of hypotensive effect rather than plasma concentration.

Adrenal Cortex↗

PubMed1998

Intracellular calcium affects neutrophil chemoattractant expression by macrophages in rats with cerulein-induced pancreatitis.

Pancreatitis complicated with infection often results in the development of multiple organ failure. We investigated the role of altered intracellular calcium as a priming signal for cytokine-induced neutrophil chemoattractant expression in this process. Agents modulating cytosolic Ca2+ were utilized to study the in vivo and in vitro cytokine-induced neutrophil chemoattractant expression for macrophages in rats with cerulein-induced pancreatitis after intraperitoneal administration of lipopolysaccharide as a septic challenge. Pretreatment with the calcium channel blocker verapamil significantly reduced serum cytokine-induced neutrophil chemoattractant concentrations in rats with cerulein-induced pancreatitis after septic challenge. Lipopolysaccharide-stimulated in vitro cytokine-induced neutrophil chemoattractant (CINC) production by peritoneal macrophages was significantly enhanced by pretreatment with thapsigargin (an inhibitor of the endoplasmic reticulum-resident Ca2+-ATPase), but not by A23187 (a calcium-specific ionophore, extracellular Ca2+ influx). Pretreatment with U73122 (a phospholipase C inhibitor) inhibited lipopolysaccharide-stimulated but not basal cytokine-induced neutrophil chemoattractant production, while verapamil (a calcium channel blocker), TMB-8 (an inhibitor of calcium release from endoplasmic reticulum), and W7 (calmodulin antagonist) completely abrogated the chemoattractant production. Altered intracellular calcium, due to Ca2+ efflux from intracellular stores, may be involved in the "priming" of macrophages to release cytokine-induced neutrophil chemoattractant following triggering with lipopolysaccharide during acute cerulein pancreatitis.

Acute Disease↗

PubMed1998

Fatal hemorrhage in irradiated esophageal cancer patients.

Between 1980 and 1994, 423 patients with esophageal cancer were given curative radiation therapy. Of these patients, 31 died of massive hemorrhage and were used as the subjects of analysis in this study. The incidence of massive hemorrhage in all patients was 7% (31/423). In the 31 patients who died of massive hemorrhage, 27 had local tumors and two had no tumors at hemorrhage (two unknown cases). The mean time interval from the start of radiation to hemorrhage was 9.2 months. In 9 autopsy cases the origin of hemorrhage was a tear of the aorta in 5 cases, necrotic local tumor in 3 cases and esophageal ulcer in 1 case. The positive risk factors for this complication seemed to be excess total dose, infection, metallic stent, and tracheoesophageal fistula. Chest pain or sentinel hemorrhage proceeding to massive hemorrhage was observed in about half of the patients.

Aged↗