Search PubMed⌕ Search

Biomedical subjects

S Yamada

Publications and source records attributed to S Yamada.

At least 775 records · Page 43Linked to original sources

Acute immobilization stress reduces (+/-)DOI-induced 5-HT2A receptor-mediated head shakes in rats.

Acute immobilization stress induced by taping four limbs, applying tail pinch stress and electric foot shock stress immediately reduced the frequency of head shakes induced by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane ((+/-)DOI), a 5-HT2A/C agonist in rats. Immobilization stress due to the use of cylinder restraint and forced swimming did not affect 5-HT2A-mediated behavior. Acute immobilization stress did not affect [3H]ketanserin binding to the 5HT2A receptor in the prefrontal cortex and hippocampus. Presynaptic serotonergic lesions with 5,7-dihydroxytryptamine(5,7-DHT) did not affect the reduction in 5-HT2A-mediated behavior after acute immobilization stress. The decreases in head shake frequency after acute immobilization stress by taping were attenuated by pretreatment with diazepam (2.5 mg/kg IP): This attenuation was reversed by pretreatment with flumazenil (10 mg/kg IP). The reduction in (+/-)DOI-induced 5-HT2A-mediated behavior caused by stress may be related to a change in agonist affinity to the receptor or changes in other neurotransmitter systems or the effect of PI turnover.

Animals↗

Fulminant second-set allograft rejection and endoscopic findings following small bowel transplantation in the rat.

In the presensitized recipient who has been exposed to donor antigens, second-set rejection takes the form of severe hyperacute graft rejection. Second-set allograft rejection was studied following small bowel transplantation in the rat. Heterotopic intestinal grafting was performed from DA (RT1a) donors to PVG (RT1c) recipients 4 weeks after DA skin sensitization. The endoscopic images and histological specimens were compared with those of syngeneic and first-set rejected grafts. Endoscopically, diffuse erosions of the graft were detected from day 1. Mucosal necrosis progressed rapidly, and was accompanied by massive bleeding on days 3-5. These findings were similar to the course of severe necrotizing hemorrhagic enteritis. Histologically, interstitial edema and hemorrhage with massive infiltrations of neutrophils were manifested from day 1. Mesenteric vessels were completely occluded by thrombi on days 3-5. The grafted intestine had became totally necrotic by day 5. Microscopic findings strongly suggested that destructive graft necrosis was due to vascular damage caused by humoral factors. All the presensitized rats (n = 11) died showing systemic septic signs by day 11 after small bowel transplantation. We conclude that lethal hyperacute rejection occurred in presensitized recipients, even when the graft was transplanted heterotopically. Endoscopic evaluation is beneficial for the early diagnosis of graft rejection. Immediate graft removal should be mandatory as a rescue treatment in second-set rejection of the small intestine.

Animals↗

Clinical and laboratory characteristics in the families with diabetes and a mitochondrial tRNA(LEU(UUR)) gene mutation.

We identified three families having a mutation in the mitochondrial tRNA(LEU(UUR)) gene at bp 3243 in 300 patients with non-insulin dependent diabetes mellitus (NIDDM), who had first degree relatives of patients with NIDDM. We found six individuals with diabetes, one with impaired glucose tolerance (IGT), and five with normal glucose tolerance (NGT) among three families. Insulin secretory response to oral glucose load was impaired in six diabetics, but was normal in IGT and NGT, and the proportion of mutant DNA in the blood did not always associate with the severity of glucose intolerance. Furthermore, both gender and obesity may influence the clinical expression of diabetes in three pairs with an age-matched brother-sister relationship with similar high mutation rate in blood samples. Thus, although patients with mitochondrial gene mutation had a high frequency of diabetes, the proportion of mutant DNA evaluated by blood samples may not necessarily indicate glucose intolerance in the members with the mutation. Unidentified factors including gender, aging, and obesity may alter the clinical manifestation of diabetes.

Adolescent↗

Effects of VA-045 on peripheral and central circulation in anesthetized dogs.

1. The effects of VA-045, a novel apovincaminic acid derivative, vinpocetine, apovincaminic acid, brovincamine and nicergoline on peripheral and cerebral circulation were examined in anesthetized dogs. 2. Peripheral circulation: VA-045 induced a transient decrease in both blood pressure (BP) and heart rate (HR) andd an increase in vertebral arterial blood flow (VBF) without affecting femoral arterial blood flow (FBF) or carotid arterial blood flow (CBF). Vinpocetine had no effect on BP, HR, VBF, FBF or CBF. Apovincaminic acid decreased HR and increased VBF without affecting FBF, CBF or BP. Brovincamine increased VBF and decreased CBF without affecting BP or FBF. Nicergoline decrease BP without affecting VBF, FBA or CBF. 3. Cerebral circulation: VA-045 increased cerebral blood flow (CerBF) without affecting BP. Brovincamine also increased CerBF and decreased BP. The potency of VA-045 in increasing CerBF was stronger than that of brovincamine. Vinpocetine and apovincaminic acid had no effect on BP or CerBF. Nicergoline decreased BP but did not affect CerBF. 4. These findings indicate that VA-045 has a more selective vasodilative effect on the vertebral and cerebral arteries than the other reference drugs.

Anesthesia↗

A mutant of pseudorabies virus with deletion of glycoprotein gIII gene prepared from a Japanese isolate: it fails to agglutinate mouse erythrocytes.

A mutant with deletion of the glycoprotein gIII gene was produced from a Japanese isolate of pseudorabies virus (PrV) and characterized. Viral titers of the mutant propagated in PK-15 cells were always lower than those of the parental virus. The parental virus agglutinated BALB/c mouse erythrocytes, whereas the deletion mutant showed no hemagglutinating activity. Pigs inoculated with the parental virus produced not only neutralizing but also hemagglutination-inhibiting antibodies. On the other hand, the mutant induced high titers of neutralizing antibody comparable to the parental virus but no hemagglutination-inhibiting antibody in inoculated pigs, suggesting that glycoprotein gIII is an essential component for hemagglutination of PrV. Finally, no evidence that the deletion mutant lost virulence for mice was obtained.

Animals↗

Cytocidal infection of hog cholera virus in porcine bone marrow stroma cell cultures.

Porcine bone marrow stroma cell (BMSC) cultures producing cells of granulocyte-lineage were established. Hog cholera (HC) virus ALD and Alfort strains replicated in the porcine BMSC cultures showing distinct cytopathic effect (CPE). The differentiation of granulocyte-lineage cells in the cultures ceased after infection with HC virus. Polyclonal antibody against the ALD strain inhibited completely the development of CPE of the both ALD and Alfort strains. Monoclonal antibodies (mAbs) specific to the ALD strain inhibited CPE of the ALD strain, while CPE of the Alfort strain was not affected by those mAbs, suggesting that CPE induced in the BMSC cultures is due to HC virus.

Animals↗

Effects of radiotherapy on the cellular uptake of carbon-14 labeled L-methionine in tumor tissue.

In order to examine in vivo effects of irradiation on tumor uptake of L-[methyl-11C]methionine at a cellular level, the distribution of L-[methyl-14C]methionine (Met) in a rat AH109A tumor model was investigated using microautoradiography. Silver grain density of tumor cell layer decreased rapidly within the first day after 20 Gy of irradiation, and continued to fall during day 2. Grain density of granulation tissue was 25% of tumor cells and was unchanged after irradiation. Macrophages and necrotic tissue showed low grain density and a small post-irradiation decrease. One day after irradiation, tumor cell showed giant cell formation and decreased cell density per unit area. The number of grains was greater in giant tumor cells than in non-irradiated tumor cell. Rapid response of Met uptake by tumor cells without a significant uptake by granulation tissue and macrophages suggest that 11C-Met is a suitable tracer for monitoring tumor radiotherapy with positron emission tomography.

Animals↗

Selectin- and integrin-mediated T-lymphocyte rolling and arrest on TNF-alpha-activated endothelium: augmentation by erythrocytes.

The adhesive and hemodynamic forces that lead to lymphocyte rolling and arrest on activated endothelium and the biophysical role of various adhesion molecules and blood elements in this process are poorly understood. By quantifying their behaviour both in vivo and in vitro, we show here that erythrocytes facilitate selectin- and integrin-mediated rolling and binding of T-lymphocytes on tumor necrosis factor alpha-activated endothelium. The relative contribution of selectins and integrins to this process can be distinguished by using a simple mathematical expression of lymphocyte capture within the range of physiological shear stress. The need for selectin participation in lymphocyte capture increases with shear stress (> 1 dyn/cm2), and both beta 1 and beta 2 integrins act in synergy to produce adhesive drag on captured cells. These findings are potentially useful in developing strategies for intervening with T-cells in a variety of normal and pathological responses as well as for the delivery of genetically modified T-cells to their targets in vivo.

Animals↗

Study on brain interstitial fluid distribution and blood-brain barrier transport of baclofen in rats by microdialysis.

PURPOSE: This study was performed to examine the distribution in the brain interstitial fluid (ISF) and the blood-brain barrier (BBB) transport of baclofen in rats by a microdialysis technique. METHODS: Following an i.v. bolus administration and/or the constant i.v. infusion of baclofen to the microdialysis cannula-bearing anesthetized rats, the concentrations of baclofen in the hippocampal ISF, whole brain tissue, cerebrospinal fluid (CSF), and plasma were determined by high-performance liquid chromatography (HPLC). Data were kinetically analyzed to estimate the transport parameters, i.e., the influx clearance (CLin) from plasma to brain and the efflux rate constant (keff) from brain to plasma, and the steady-state volume of distribution in the brain (Vd). RESULTS: The concentrations of baclofen in ISF, whole brain tissue, and CSF at the pseudo-steady state were almost 30-fold lower than the plasma unbound concentration, suggesting the restricted distribution of baclofen in the brain. The estimated values of CLin and keff were 0.00157 +/- 0.00076 ml/min/g of brain and 0.0872 +/- 0.0252 min-1, respectively. The efflux clearance (CLout) calculated by multiplying keff by Vd (0.816 +/- 0.559 ml/g of brain) was 0.0712 +/- 0.0529 ml/min/g of brain, and it was significantly 40-fold greater than the CLin value and fully greater than the convective flow in ISF. Furthermore, no significant concentration gradient was observed between ISF and CSF. These results suggest that the CLout value mainly reflects the efflux clearance through the BBB. Additionally, the hippocampal ISF/plasma concentration ratio of baclofen was markedly increased by both systemic administration of probenecid and its direct instillation into ISF. CONCLUSIONS: The restricted distribution of baclofen in the brain ISF may be ascribed to the efficient efflux from the brain through the BBB which is regulated possibly by a probenecid-sensitive organic anion transport system.

Animals↗

Cyclic AMP-dependent modulation of vesicular monoamine transport in pheochromocytoma cells.

Cyclic AMP (cAMP) is well known to enhance tyrosine hydroxylase activity in PC12 cells. We were able to demonstrate, however, that the cellular dopamine level in PC12 was lowered by dibutyryl cAMP. Furthermore, the decrease in the cellular level of dopamine was accompanied by about a 10-fold increase in the medium. The aim of this work was to elucidate the effect of cAMP on catecholamine transport. Dibutyryl cAMP did not induce exocytotic release of norepinephrine but rather inhibited its uptake. As with forskolin and cholera toxin, physiological signaling molecules such as vasoactive intestinal polypeptide (VIP) and AMP, for which PC12 cells are known to have receptors linked to activation of adenylate cyclase, also inhibited norepinephrine uptake. The inhibitory effects of dibutyryl cAMP, VIP, and AMP were dose dependent, and EC50 values were estimated to be 100 microM, 10 nM, and 1.0 microM, respectively. The inhibition profile of dibutyryl cAMP over the time course of norepinephrine uptake was biphasic: inhibition became clearly detectable after the cytosolic pool of norepinephrine had been saturated. This profile is similar to that of reserpine. Nomifensine, however, inhibited uptake at a rather constant rate throughout the entire time course. The ATP-dependent serotonin uptake by digitonin-permeabilized cells was lowered to approximately 50% that of the control by dibutyryl cAMP treatment before permeabilization, indicating inhibition of vesicular monoamine transport. This effect was also dependent on a dibutyryl cAMP concentration with an EC50 of < or = 100 microM.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Synthesis of 25-hydroxyvitamin D3-26,23-lactone but not 24,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3 in opossum kidney cells treated with 1 alpha, 25-dihydroxyvitamin D3.

The pathway from 25-hydroxyvitamin D3(25[OH]D3) to 25-hydroxyvitamin D3-26,23-lactone (25[OH]D3-26,23-lactone) is important in the renal degradation of vitamin D metabolites. Our objective was to investigate the regulation of 25(OH)D3 metabolism in the opossum kidney (OK) cell line which has been used for studying the actions of the calcium-regulating hormones. While the untreated OK cells did not produce 25(OH)D3 metabolites, the synthesis of the lactone was increased dose-dependently by 20h pretreatment with 1 alpha,25-dihydroxyvitamin D3 (1,25[OH]2D3), peaked at 10(-7) M 1,25(OH)2D3, and decreased with higher concentrations. Little production of 24,25-dihydroxyvitamin D3 (24,25[OH]2D3) was observed after any dose of 1,25(OH)2D3. The increase in the production of lactone induced by 10(-7) M 1,25(OH)2D3 was detectable at 2 h, peaked between 4 and 24 h, and decreased gradually until 48 h. Its induction was inhibited by actinomycin D and cycloheximide, suggesting that de novo protein synthesis is required for such induction. After treatment with 10(-7) M 1,25(OH)2D3 for 20 h, 24-hydroxylase (24-OHase) mRNA was not detected in OK cells, but was found evident in COS-7 cells (a renal cell line). Moreover, the COS-7 cells treated with 10(-7) M 1,25(OH)2D3 metabolized 25(OH)D3 to 24,25(OH)2D3. These results indicate that 1,25(OH)2D3 stimulates the synthesis of 25(OH)D3-26,23-lactone in a dose- and time-dependent manner, but does not induce the gene expression or activity of 24-OHase in OK cells.

24,25-Dihydroxyvitamin D 3↗

Overhead work and shoulder-neck pain in orchard farmers harvesting pears and apples.

The effects of overhead work were studied by comparing orchard farmers' musculoskeletal symptoms while bagging pears with those same symptoms while bagging apples. The subjects were 52 Japanese female farmers, who were examined twice an evening in late June for bagging pears, and during another evening of late July for bagging apples, when each task had been almost finished. They were questioned about musculoskeletal complaints of stiffness and pain during each job, and examined for muscle tenderness and pain from joint movement. Arm elevation angles during the work were measured for each type of bagging. The prevalence of stiffness and pain in the neck and shoulder, muscle tenderness in the shoulder regions, and pain in neck motion were found to be significantly higher when bagging pears than apples. Musculoskeletal symptoms of parts other than the neck and shoulder did not differ between the two types of bagging. The working posture of elevating the arm more than 90 degrees was assumed to account for 75% of the time bagging pears, against 40% for bagging apples. Overhead work requiring arm elevation and head extension was considered to be closely related with shoulder-neck disorders among farmers.

Adult↗

New pathophysiology of Parkinson's disease revealed by posteroventral pallidotomy.

Since the failure of levodopa therapy to maintain long-term symptom relief in Parkinson's disease, posteroventral pallidotomy has seen a dramatic increase in use and interest. It has significantly reduced both the akinetic and hyperkinetic symptoms of Parkinson's disease while requiring most patients to maintain preoperative levodopa doses. Here we review the clinical results of over 300 posteroventral pallidotomies and pathophysiology of Parkinson's disease in relationship to different neurotransmitters and medical therapy.

Combined Modality Therapy↗

Stimulation of the globus pallidus in Parkinson's disease.

In 62 patients undergoing posteroventral pallidotomy (PVP) for the treatment of Parkinson's disease, we have demonstrated significant (p < 0.01) elimination of akinetic features and other symptoms during intraoperative stimulation trials in areas anterior to the PVP target (n = 30). Stimulation in anterior pallidal regions frequently resulted in an immediate reversal of akinetic states despite enforced abstinence of medications. The beneficial effects were achieved with as little as 0.25 V at 100 Hz. Stimulation at the PVP target site (n = 32) resulted in insignificant changes (p > 0.05).

Adult↗

The sulphated carbohydrate-protein linkage region isolated from chondroitin 4-sulphate chains of inter-alpha-trypsin inhibitor in human plasma.

Inter-alpha-trypsin inhibitor (ITI) in human plasma has a unique structural architecture composed of three polypeptide chains (H1, H2 and L chains), which are linked to each other through a chondroitin 4-sulphate chain. The structure of the carbohydrate-protein linkage region of the chondroitin 4-sulphate chain attached to the L chain was investigated. The peptide-chondroitin sulphate fraction was isolated by anion-exchange chromatography after exhaustive digestion with lysyl endopeptidase and then V8 protease. The chondroitin 4-sulphate chain was released from the peptides by beta-elimination using NaB3H4 and then digested with chondroitinase ABC. These treatments resulted in a single 3H-labelled hexasaccharide alditol fraction derived from the linkage region which had been associated with the L chain. Chemical and enzymatic analyses as well as fast-atom bombardment-mass spectrometry (FAB-MS) analysis revealed that the 3H-labelled hexasaccharide alditol had the following structure: delta HexA-alpha 1-3GalNAc(4-sulphate)beta 1-4GlcA beta 1-3Gal(4-sulphate)beta 1-3Gal beta 1-4Xyl-ol (where delta HexA is 4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid and Xyl-ol is xylitol). The structure contained the novel 4-sulphated Gal residue, which was previously demonstrated in a linkage hexasaccharide isolated from chondroitin 4-sulphate of rat chondrosarcoma (Sugahara et al., J. Biol. Chem., 263, 10168-10174, 1988) and of whale cartilage (Sugahara et al., Eur. J. Biochem., 202, 805-811, 1991). The above disulphated hexasaccharide alditol was the only component detected in the linkage region fraction of the chondroitin 4-sulphate chain of ITI, which implies some biological significance of this novel structure.

Alpha-Globulins↗

Four novel mutations in mucopolysaccharidosis type VII including a unique base substitution in exon 10 of the beta-glucuronidase gene that creates a novel 5'-splice site.

Mucopolysaccharidosis type VII (MPS VII), or Sly syndrome, is a lysosomal storage disorder caused by a deficiency in the enzyme beta-glucuronidase. Various clinical phenotypes of this autosomal recessively inherited disease have been described. Recent isolation and characterization of human beta-glucuronidase cDNA and the genomic sequences facilitate analysis of molecular defects underlying the different phenotypes, and eight mutations in the beta-glucuronidase gene have been described. This report summarizes studies characterizing four new mutations in two Caucasian patients with a severe form of MPS VII. Three are point mutations, resulting in two missense and one nonsense change, and one is a 38 bp deletion. The first patient was a compound heterozygote having P148S and Y495C alleles. The second patient was a compound heterozygote of W507X and a 38 bp deletion at position 1642-1679 in exon 10(1642 delta 38nt). The 38 bp deletion was caused by a single base change mutation in exon 10 that generates a new, premature 5' splice site. Expression of mutant cDNAs encoding each of the four mutations showed that all four resulted in a severe reduction of beta-glucuronidase activity, indicating that these mutations are responsible for the reduced enzyme activity in patient cells. These four previously undescribed mutations provide further evidence for the broad molecular heterogeneity in Sly syndrome.

Base Sequence↗

Structural analysis of a novel triphosphonoglycosphingolipid from the egg of the sea hare, Aplysia kurodai.

A novel phosphonoglycosphingolipid which contains three residues of 2-aminoethylphosphonate (2-AEP) was isolated from eggs of a sea gastropoid, Aplysia kurodai, and its structure was identified as follows. [see text] The major aliphatic components of ceramide were palmitic acid, stearic acid, 4-sphingenine, and 16-methyl-4-sphingenine. Antibodies which recognize 3-O-methylgalactose linked beta-glycosidically to phosphonoglycosphingolipids failed to react to the egg glycolipid. By comparing 1H-NMR spectra of native and HF-treated glycolipids, steric interactions of two residues of 2-AEP with ring protons of the glucose and the internal galactose were indicated.

Aging↗