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Biomedical subjects

S Yamada

Publications and source records attributed to S Yamada.

At least 577 records · Page 32Linked to original sources

Plasma vitronectin concentrations in patients with chronic hepatitis C treated with interferon alpha.

Plasma vitronectin concentration was measured in 60 patients with chronic hepatitis C before and after interferon alpha treatment. The plasma pretreatment levels of vitronectin in the interferon non-responders was significantly lower than those in the interferon sustained and transient responders, but the levels were not different in the latter two groups. After interferon therapy, the plasma levels of vitronectin were significantly increased in all three groups, and they were correlated with the albumin levels. Absolute changes of plasma vitronectin before and after interferon treatment were significantly related to initial levels, but they were not related to those of albumin or alanine aminotransferase levels. The values of sensitivity and specificity for plasma vitronectin in the sustained responder and non-responder were 45% and 95% for each. These results suggest that chronic hepatitis C patients with low levels of plasma vitronectin may have a weak response in interferon therapy.

Alanine Transaminase↗

A novel pentasaccharide sequence GlcA(3-sulfate)(beta1-3)GalNAc(4-sulfate)(beta1-4)(Fuc alpha1-3)GlcA(beta1-3)GalNAc(4-sulfate) in the oligosaccharides isolated from king crab cartilage chondroitin sulfate K and its differential susceptibility to chondroitinases and hyaluronidase.

Novel sulfated tetrasaccharide structures containing 3-O-sulfated GlcA were isolated recently from king crab cartilage chondroitin sulfate K [Sugahara, K., Tanaka, Y., Yamada, S., Seno, N., Kitagawa, H., Haslam, S. M., Morris, H. R., & Dell, A. (1996) J. Biol. Chem. 271, 26745-26754]. In this study, we prepared a series of oligosaccharides from the same source after exhaustive digestion with testicular hyaluronidase and determined the structures of a pentasaccharide, two hexasaccharides, and two heptasaccharides by means of fast atom bombardment mass spectrometry and 500-MHz 1H-NMR spectroscopy. All the oligosaccharides had the following hitherto unreported structures including a novel glucuronate 3-O-sulfate: GlcA(3S)(beta1-3)GalNAc(4S)(beta1-4)GlcA(3S)(beta1-3)GalNAc( 4S)(beta1-4)GlcA(beta1-3)GalNAc(4S), GlcA(3S)(beta1-3)GalNAc(4S)(beta1-4)GlcA(3S)(beta1-3)GalNAc( 4S)(beta1-4)GlcA(3S)(beta1-3)-GalNAc(4S), GlcA(3S)(beta1-3)GalNAc(4S)(beta1-4)(Fuc alpha1-3)GlcA(beta1-3)GalNAc(4S), GlcA(3S)(beta1-3)-GalNAc(4S)(beta1-4)(Fuc alpha1-3)GlcA(beta1-3)GalNAc(4S)(beta1-4)GlcA(beta1-3)GalNAc (4S), and GlcA(3S)(beta1-3)GalNAc(4S)(beta1-4)GlcA(3S)(beta1-3)GalNAc( 4S)(beta1-4)(Fuc alpha1-3)GlcA(beta1-3)GalNAc(4S), where 3S or 4S represent 3-O- or 4-O-sulfate, respectively. Furthermore, the three latter structures contained a novel combination of both 3-O-sulfated and 3-O-fucosylated GlcA residues. The pentasaccharide with 3-O-fucosylated GlcA at the internal position remained totally resistant to chondroitinase AC-II, whereas it was degraded by chondroitinase ABC into a disaccharide unit containing GlcA(3S) derived from the nonreducing side and a trisaccharide unit containing fucose from the reducing side.

Animals↗

Oral administration of KW-5092, a novel gastroprokinetic agent with acetylcholinesterase inhibitory and acetylcholine release enhancing activities, causes a dose-dependent increase in the blood acetylcholine content of beagle dogs.

Acetylcholine (ACh) was detected in the blood and plasma of beagle dogs using a specific, sensitive radioimmunoassay. The mean basal ACh contents in the blood and plasma of beagle dogs were 451 +/- 65 and 83.5 +/- 12.3 pg/ml (+/- SEM, n = 7), respectively, and were lower than the contents in humans reported previously by our laboratory. Oral administration of KW-5092 (10-30 mg/kg), a gastroprokinetic agent with acetylcholinesterase (AChE) inhibitory and ACh release enhancing activities, caused a dose-dependent increase in the ACh content of both the blood and plasma, as well as several behavioral side effects due to peripheral cholinergic stimulation. The size of the increase in the plasma ACh content at each dose of KW-5092 was greater than that in the blood, indicating that KW-5092 caused the increase in the blood ACh content through elevation of the plasma ACh content, by inhibition of AChE and facilitation of ACh release. These results demonstrate that the blood ACh of beagle dogs is present mainly in the blood cells and to a lesser degree in the plasma, and that KW-5092 increased the blood ACh content mainly by increasing the plasma ACh concentration.

Acetylcholine↗

Contemporaneous bilateral pallidotomy.

To investigate the effects of bilateral posteroventral pallidotomy (PVP) for Parkinson's disease (PD), the authors reviewed the technique and neurological outcome in a number of patients who had undergone bilateral pallidotomy. The authors have previously reported the outcome of PVP in 25 bilateral and 25 unilateral surgeries, rating the patient's postural stability, speech, and total Unified Parkinson's Disease Rating Scale scores. A second, separate group of 23 patients who underwent contemporaneous bilateral PVP were evaluated for early onset idiopathic PD, levodopa failure syndrome, and severe bilateral dyskinesia as well as akinetic "off" states. Cognitive and psychological studies were reviewed in 10 patients who demonstrated preoperative impairments in spatial recognition and memory. Following surgery there were significant improvements in these cognitive deficits and no deficits were incurred by surgery. Published reports regarding bilateral operations for PD have emphasized the risks of speech and cognitive deficits. This study shows bilateral PVP to be effective, particularly in patients with bilateral symptoms, including disabling dyskinesia. Additionally, bilateral PVP does not cause additional cognitive or speech deficits. The techniques and indications as well as outcomes and complications are presented and discussed in this report in light of their controversial nature.

Journal Article↗

Fluorimetric assay of 1 alpha,25-dihydroxyvitamin D3 in human plasma.

The first fluorimetric method for assaying plasma 1 alpha,25-dihydroxyvitamin D3 [1,25-(OH)2D3] is described. Lipid extracts from human plasma were successively purified by a Bond Elut NH2 column and a normal-phase HPLC column, and the 1,25-(OH)2D3 fractions obtained were fluorescence-labelled with 4-[2-(6,7-dimethoxy-4-methtyl-3-oxo-3,4-dihydroquinoxalyl)et hyl]-1, 2,4-triazoline-3,5-dione (DMEQ-TAD). The fluorescent adducts of 1,25-(OH)2D3 were analyzed by HPLC on a reversed-phase column, after extensive elimination of the degradation products of excess reagents, by a Bond Elut PSA column followed by a normal-phase HPLC column. The intra- and inter-assay coefficients of variation were within 10% in both assays. The analytical recoveries of standard 1,25-(OH)2D3 added to plasma were quantitative. The present fluorimetric assay was compared with the established radioreceptor assay (RRA) used in measuring plasma 1,25-(OH)2D3 concentration. The regression analysis of the data afforded a relationship y = 1.049x - 2.657 and a correlation coefficient (r) of 0.900.

Adult↗

Abeta1-40 but not Abeta1-42 levels in cortex correlate with apolipoprotein E epsilon4 allele dosage in sporadic Alzheimer's disease.

Apolipoprotein E (ApoE) epsilon4 allele is established to be a risk factor for the development of late-onset Alzheimer's disease (AD) which is associated with increased frequency of senile plaques and extent of amyloid angiopathy. In a recent report, we demonstrated that ApoE epsilon4 dosage correlates with an increase in A beta1-40 but not A beta1-42/43-immunoreactive plaques. In the present study, we sought to confirm this relationship at a biochemical level by using a sensitive ELISA to measure the amounts of A beta1-42/43 and A beta1-40 in cerebral cortex in 36 cases of sporadic AD. We found that dosage of ApoE epsilon4 allele correlated significantly with cortical A beta1-40 levels, while levels of A beta1-42 showed no significant association with genotype. These results parallel our immunohistochemical findings and suggest that A beta1-40 may play a key role in the pathogenesis of late-onset sporadic AD.

Aged↗

Effect of combination treatment of 15 cGy total body irradiation and OK-432 on spontaneous lung metastasis and mitogenic response of splenocytes in mice.

We investigated whether the combination treatment of 15 cGy total body irradiation (TBI) and a streptococcal preparation, OK-432, synergistically suppresses spontaneous lung metastasis and augments phytohemagglutinin (PHA) and concanavalin A (Con A) responses of splenocytes in WHT/Ht mice. TBI with 15 cGy was carried out 20 days after subcutaneous injection of squamous cell carcinoma cells into a hind leg. Lung colony number was counted 40 days after tumor injection. For PHA and Con A responses, mice were killed 4 hr after 15 cGy TBI. The combination treatment of 15 cGy TBI and OK-432 was most effective when OK-432 was administered 2 days before 15 cGy TBI. The combination treatment decreased the lung colony number to 29.9% of the control number. OK-432 slightly increased the PHA and Con A responses, and 15 cGy TBI did not increase them. However, when these two were combined, the PHA and Con A responses were significantly increased to 393% and 278% of the control levels, respectively. It was suggested that TBI and OK-432 acted synergistically in suppressing the lung metastasis and mitogenic response of splenocytes.

Animals↗

Pretreatment with activated protein C or active human urinary thrombomodulin attenuates the production of cytokine-induced neutrophil chemoattractant following ischemia/reperfusion in rat liver.

We investigated the role of anticoagulant in the ischemia/reperfusion injury of the liver, using activated protein C (APC), active human urinary thrombomodulin (UTM), and factor Xa blocked at the active site (DEGR-Xa). Liver ischemia was induced in male Wistar rats by occlusion of the portal vein with a microvascular clip for 30 minutes. Each anticoagulant was injected intravenously 10 minutes before clamping the portal vein. Serum concentrations of cytokine-induced neutrophil chemoattractant (CINC) were determined by enzyme-linked immunosorbent assay. The serum levels of CINC increased significantly following reperfusion, reaching a peak in 6 hours, and then decreasing gradually to control levels by 24 hours. CINC levels in rats pretreated with APC (500 U/kg), UTM (3,000 TMU/kg), or DEGR-Xa (10 mg/kg) peaked 3 hours following reperfusion and decreased rapidly to baseline level within 6 and 12 hours, respectively. These peak values were significantly lower than those observed in untreated rats (P < .01). Expression of CINC transcripts in liver tissue of untreated rats was evaluated by Northern blot analysis and peaked 3 hours following reperfusion. Pretreatment with these anticoagulants significantly decreased the expression of CINC messenger RNA transcripts as compared with untreated animals. Myeloperoxidase activity and the number of neutrophils accumulated into the liver 24 hours following ischemia/reperfusion were also significantly decreased in animals pretreated with these anticoagulants. In addition, correlations between the peak values of liver enzymes and serum CINC levels were found to be significant (P < .001). The inactive derivative of factor Xa, a selective inhibitor of thrombin generation, inhibited ischemia/reperfusion-induced increases in the serum concentration and messenger RNA transcript quantities of CINC. The inactive factor Xa also reduced hepatic accumulation of neutrophils after ischemia/reperfusion. These results indicate that the release of CINC is likely related to the hepatic microcirculation disturbance induced by microthrombotic occlusion following ischemia/reperfusion.

Animals↗

High-performance liquid chromatographic separation of microcystins derivatized with a highly fluorescent dienophile.

Microcystins are potent hepatotoxins produced by cyanobacteria, and are also tumor promoters as well as potent inhibitors of the catalytic subunits of protein phosphatases 1 and 2A. In order to establish a physicochemical method for individual detection and determination of trace amounts of microcystins, we developed a derivatization method for fluorescence (FL) and chemiluminescence (CL) detection, in which a highly fluorescent dienophile, DMEQ-TAD (4-[2-(6,7-dimethoxy-4-methyl-3-oxo-3,4-dihydroquinoxalinyl) ethyl]-1,2,4-triazoline-3,5-dione), was used as the labeling reagent. DMEQ-TAD reacted smoothly with the conjugated diene of the Adda moiety to give 2 stereoisomers of the adducts. As a result of the extensive experiments, the following reaction conditions were optimized for the labeling: sample amount, 10 micrograms; reaction solvent, DMF:acetonitrile (1:1); reaction time, 15 minutes; reaction temperature, 70 degrees C; amount of DMEQ-TAD used relative to that of microcystin, 80 equivalent. The resulting 6 adducts from microcystins-LR, -YR, and -RR can be separated from one another using the following reversed phase HPLC conditions in combination with a clean-up using ODS silica gel: column, Cosmosil 5C18-AR (150 x 4.6 I.D. mm); mobile phase, methanol:0.05M phosphate buffer (pH 3) (1:1); flow rate, 1.0 ml/min; detection, FL lambda ex 370 nm, lambda em 440 nm. The detection limits of the DMEQ-TAD derivatives were estimated to be 100 and 500 pg for LR, and 65 and 2,500 pg for RR using FL and CL detections, respectively; and the detection behavior was different from that of the Dns-Cys derivatives, which were more sensitive to CL than FL.

Bacterial Toxins↗

Correlation of expression levels of P-glycoprotein with resistance to adriamycin in a renal adenocarcinoma cell line.

We have demonstrated that low-level expression of P-glycoprotein (PGP), detectable by reverse transcriptase polymerase chain reaction (RT-PCR) assay and flow cytometric assay, is an important factor in multidrug resistance (MDR) in ACHN cancer cells. In this study, we established a subline highly resistant to adriamycin (ACHN/ADM) from ACHN cells, and determined the correlation between PGP levels and MDR levels using ACHN/ADM cells and their parent ACHN cells. The ACHN/ADM cells showed overexpression of PGP, and sensitivity to antitumor agents was lower than that found in ACHN cells. Intracellular accumulation of ADM in ACHN/ADM cells was approximately half the amount of its accumulation in ACHN cells. Sensitivity to ADM in ACHN/ADM cells was enhanced by chemosensitizers with an increase in intracellular ADM accumulation. These results indicate that PGP levels correlate with MDR levels and suggest that chemotherapy using chemosensitizers might be effective in the treatment of renal cancers with overexpression of PGP.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Resection of liver metastasis from alpha-fetoprotein-producing early gastric cancer: report of a case.

We herein present a case of resected synchronous solitary liver metastasis from alpha-fetoprotein (AFP)-producing early gastric cancer. A 61-year-old woman, who was diagnosed at a routine medical checkup as having early gastric cancer with a liver tumor, came to our hospital for surgery. Her serum AFP level was high at 910 ng/ml. An examination was performed to determine whether the liver tumor was primary hepatocellular carcinoma or metastasis from early gastric cancer. She had no evidence of either a hepatitis B or C virus infection, and her liver function was normal. A biopsy specimen from the gastric cancer predominantly revealed moderately differentiated adenocarcinoma, but a focally trabecular pattern compatible with AFP-producing gastric cancer was also observed. Preoperatively, it was concluded that the liver tumor was metastasis from an AFP-producing early gastric cancer. We thus performed distal gastrectomy and a posterior segmentectomy of the liver. Her serum AFP level decreased to the normal range within 2 weeks after the operation. An immunohistological examination revealed that AFP-positive cells were present in both the gastric cancer and liver tumor. One year after the operation, there was no sign of recurrence.

Adenocarcinoma↗

Longitudinal study on factors related to the course of vibration-induced white finger.

Follow-up surveys were conducted in 1982 and 1988 to investigate factors affecting the course of vibration-induced white finger (VWF). Subjects were 353 patients, aged 40 to 70 at the start of the 1982 survey, who were receiving treatment for hand-arm vibration syndrome. Between 1982 and 1988, the attacks of VWF decreased, while numbness and pain in the hand changed slightly. Finger skin temperature showed a tendency to increase, but recovery time in nail compression tests was unchanged. Vibration perception threshold and grasping power tended to become worse. Of the 177 patients with VWF in 1982, 55 (31%) had no VWF in 1988. The improvement in VWF depended on its severity assessed by the frequency of attacks, the extent of the affected finger phalanges and the Stockholm vascular (V) stage at the start of the 1982 survey. The improvement was observed in 46% of the 1V (mild) stage cases, against only 17% of the 3V (severe) stage cases. Patients in the 2V (moderate) and 3V stages had lower finger skin temperature than those without VWF (the 0V stage). Patients with milder VWF seemed more likely to improve. Continued use of vibratory tools was found to be an unfavourable factor for improvement of VWF. Age, smoking and drinking habits, and medical complications showed no significant effects on the course of VWF.

Adult↗

Combined effects of hand-arm vibration and noise on temporary threshold shifts of hearing in healthy subjects.

OBJECT: To investigate whether hand-arm vibration and noise have a combined effect on temporary threshold shift (TTS) of hearing among healthy subjects. METHOD AND DESIGN: Nineteen healthy subjects with an average age of 25.7 (SD 7.7) years were exposed to vibration (30 m/s2, 60 Hz), noise [90 dB(A)] and both, respectively. The subject's right hand was placed on the plate of a vibrator and the right ear exposed to noise via headphones. Subjects were exposed to vibration and/or noise for 3 min and after a 1-min pause the exposure was repeated five times. Hearing thresholds at 1, 4 and 6 kHz were measured during the time periods before, between (during pauses) and after exposure. RESULTS: Exposure to vibration alone caused almost no hearing threshold changes at every frequency tested. But exposure to noise or a combination of vibration and noise caused a significant increase in TTSs at 4 and 6 kHz. Moreover, exposure to a combination of vibration and noise caused significantly higher TTSs than exposure to noise at 4 and 6 kHz. CONCLUSION: The present results demonstrate the combined effects of hand-arm vibration and noise can enhance exposure to hand-arm vibration and noise can enhance the TTS of hearing more than noise exposure, though hand-arm vibration alone may hardly affect TTS.

Adult↗

Brain pharmacokinetics and in vivo receptor binding of 1,4-dihydropyridine calcium channel antagonists.

Brain pharmacokinetics of 1,4-dihydropyridine (DHP) calcium channel antagonists and their in vivo receptor binding in mice were characterized. The area under the concentration vs time curve (AUCbrain) for [3H]nifedipine, [3H]nimodipine and [3H]PN 200-110 in mouse brain after intravenous injection was higher than that for [3H]amlodipine. Brain/plasma concentration ratios (AUCbrain/AUCplasm) for [3H]nimodipine and [3H]PN 200-110 were 3 to 5 times higher than those for [ H]nifedipine and [3H]amlodipine. Further, brain/heart concentration ratios (AUCbrain/AUCheart) for [3H]nifedipine, [3H]nimodipine and [3H]PN 200-110 were about 20 times higher than the ratio for [3H]amlodipine. A significant amount of specific binding in particulate fractions of mouse brain was detected in vivo by intravenous injection of [3H]nifedipine, [3H]nimodipine and [3H]PN 200-110 but not [3H]amlodipine. These data suggest that [3H]nifedipine, [3H]nimodipine and [3H]PN 200-110 are more extensively taken up into brain from plasma than [3H]amlodipine and bind to the receptor sites in brain parenchymal cells in a significant amount in vivo. In conclusion, the present simultaneous measurement of pharmacokinetics and in vivo receptor binding in mouse brain suggests an usefulness of calcium channel antagonists such as nimodipine in the pharmacotherapy of brain diseases.

Animals↗