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Biomedical subjects

H Yoshida

Publications and source records attributed to H Yoshida.

At least 847 records · Page 47Linked to original sources
PubMed1997

Stereoselective disposition and chiral inversion of KE-298, a new antirheumatic drug, in rats.

The present study was an attempt to elucidate the relationship between stereoselective pharmacokinetics and protein binding of KE-298 and its active metabolites, deacetyl-KE-298 (M-1) and S-methyl-KE-298 (M-2). Metabolic chiral inversion was also investigated. The levels of unchanged KE-298 in plasma after oral administration of (+)-(S)-KE-298 to rats were lower than those of (-)-(R)-KE-298, whereas the levels of M-1 and M-2 after administration of (+)-(S)-KE-298 were higher than after (-)-(R)-KE-298. In vitro, rat plasma protein binding of (+)-(S)-KE-298 was lower than that of (-)-(R)-KE-298. In contrast, the binding of (+)-(S)-M-1 and (+)-(S)-M-2 was higher than that of (-)-(R)-M-1 and (-)-(R)-M-2. Displacement studies revealed that the (+)-(S) and (-)-(R)- enantiomers of KE-298 and their metabolites bound to the warfarin binding site on rat serum albumin. These results suggested that the stereoselective plasma levels in KE-298 and its metabolites were closely related to enantiomeric differences in protein binding attributed to quantitative differences in binding to albumin rather than to the different binding sites. Unidirectional chiral inversion was detected after oral administration of either (-)-(R)-KE-298 or (-)-(R)-M-2 to rats both yielding (+)-(S)-M-2.

Animals↗
PubMed1997

Pharmacokinetics and safety of the novel amino-3-hydroxy-5-methylisoxazole-4-propionate receptor antagonist YM90K in healthy men.

YM90K is a novel, selective and competitive alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor antagonist with neuroprotective properties, and it is currently under development for the intravenous treatment of stroke and other conditions of acute neuronal degeneration. The safety and pharmacokinetics of YM90K in healthy men was investigated after single doses up to 36 mg and repeated doses of 24 mg given by intravenous infusion over 3 hours. YM90K was well tolerated in healthy men and induced only mild changes in kidney function markers. Unchanged plasma drug concentration reached a near steady state during 3-hour infusion and rapidly decreased in a biphasic manner after the completion of infusion. YM90K showed linear pharmacokinetics. In the repeated-dose study, no significant differences were observed in pharmacokinetics of YM90K between the first and fifth dose. Unchanged urinary drug excretion was as high as 63.2% to 78.3% of the dose, most of which was excreted within 1 hour after the completion of infusion. YM90K is thought to be excreted mainly by renal tubular secretion. YM90K showed neither significant adverse reactions nor severe abnormalities in physical and laboratory examinations of the study participants and demonstrated safety and pharmacokinetic profiles compatible with clinical use.

Adult↗
PubMed1997

Orthotopic ossification of the spinal ligaments of Zucker fatty rats: a possible animal model for ossification of the human posterior longitudinal ligament.

Ossification of the posterior longitudinal ligament is a human genetic disease in which pathological ectopic ossification of the spinal ligaments develops. This leads to myelopathy or radiculopathy due to compression of the spinal cord. In this study, we investigated the histological features of orthotopic ossification of the spinal ligaments of senile Zucker fatty rats. A remarkably high incidence of orthotopic ossification was observed mainly in the thoracic spinal ligaments as compared with controls. The histopathological findings were similar to those for ossification of the human posterior longitudinal ligament. Bone morphogenetic proteins and activins, which exert their effects by way of specific type-I and type-II serine/threonine kinase receptors, play important roles in the formation of bone and cartilage. In the spinal ligaments of Zucker fatty rats, bone morphogenetic protein receptors and activin receptors were immunohistochemically detected around the ossified foci in a manner similar to that previously shown for the ossified tissue from patients who had ossification of the posterior longitudinal ligament. Thus, bone morphogenetic proteins and activin receptors might play important roles in orthotopic ossification of the spinal ligaments of Zucker fatty rats as well as in ossification of the posterior longitudinal ligament of humans. In addition, bone morphogenetic protein-receptor-IA was expressed in the nonossified ligament, suggesting that the spinal ligaments, of the rats may have a predisposition to orthotopic ossification. In the controls, no expression of bone morphogenetic protein receptors or of activin receptors was observed. In conclusion, there is a great degree of similarity between orthotopic ossification of the spinal ligaments of Zucker fatty rats and ossification of the posterior longitudinal ligament of humans. Thus, the rats provide a useful animal model for the study of ossification of the human posterior longitudinal ligament.

Activin Receptors↗
PubMed1997

The role of cellular immunity both in the induction and effector phases of experimental allergic blepharoconjunctivitis (EAC) in rats.

In allergic conjunctivitis, the early phase reaction has been studied extensively both in humans and animals. Although cellular infiltration is the main feature of the late phase reaction, the role of cellular immunity remains unclear. The purpose of this study was to elucidate the role of cellular immunity both in the induction and effector phases of experimental allergic blepharoconjunctivitis (EAC). To analyse the involvement of cellular immunity in the induction phase, 6-8-week-old male Lewis rats were immunized with ovalbumin (OVA) emulsified with complete Freund's adjuvant (CFA), incomplete Freund's adjuvant (IFA), TiterMaxR (TM), aluminum hydroxide [Al(OH)3], or without any adjuvant. Three weeks after immunization, the rats were challenged with OVA by eye drops, and 24 hr later they were euthanized and their eyes, including the lids, blood, and lymph nodes were harvested for analysis of disease and immune responses. The results indicated that adjuvants were necessary to induce disease as well as both cellular and humoral immunity. Al(OH)3, CFA and TM induced stronger disease and cellular immunity than IFA. The intensity of disease correlated with that of cellular immunity. To further investigate the involvement of cellular immunity in EAC, lymph node cells collected from immunized rats were adoptively transferred into naive syngeneic recipients that were challenged 4 days later with OVA. EAC developed in the recipients of lymph node cells that were also stimulated in culture with OVA. These recipient rats developed cellular infiltration in the lid and conjunctiva, in a dose-dependent manner. These results suggest that cellular immunity played a major role in the development of EAC, both in the induction and effector phases.

Adjuvants, Immunologic↗
PubMed1997

Sparing effect of hemiparesis on palindromic rheumatism.

A male patient with palindromic rheumatism developed left hemiplegia. Since then, joint symptoms have not been observed in paretic limbs, although palindromic rheumatism has developed consistently in the nonparetic side. It could be speculated that neural rather than mechanical factors participate in the sparing of joint inflammation. This is the first report of the sparing effect of hemiparesis on palindromic rheumatism.

Bone and Bones↗
PubMed1997

Response of the extramedullary lung plasmacytoma with pleural effusion to chemotherapy.

An elderly patient with extramedullary lung plasmacytoma and subsequent pleural effusion is described. The presence of abnormal plasma cells in the pleural fluid led to diagnosis. Histologically similar conditions such as multiple myeloma and solitary myeloma of bone were ruled out by clinical evaluation. These neoplasms usually occur in the head and neck area and are not characterized by paraprotein accumulation. Few cases in the lung have been reported. We describe a case of extramedullary plasmacytoma of the lung with plasmacytoma-induced pleural effusion and the presence of monoclonal paraprotein in both the serum and urine. Chemotherapy with melphalan was effective in reducing the size of the plasmacytoma, and pleurodesis was used to manage the pleural effusion.

Aged↗
PubMed1997

New retinoids and arsenic compounds for the treatment of refractory acute promyelocytic leukemia: clinical and basic studies for the next generation.

All-trans retinoic acid (ATRA) is a potent differentiation drug for acute promyelocytic leukemia (APL) and is now incorporated into first-line therapy. However, ATRA resistance has become a major clinical problem. This limitation has prompted the development of alternative agents with desirable pharmacologic properties. We describe (1) our recent clinical trial using the new synthetic retinoid Am80 to overcome acquired resistance to ATRA and (2) basic in vitro effects of arsenic trioxide, a possible alternative to ATRA, on APL cells. A total of 19 APL patients who had relapsed after ATRA-induced complete remissions (CRs) received 6 mg/m2 Am80 p.o. daily until CR; 11 (58%) patients achieved a CR between days 20 and 58 (median day 37). The in vitro sensitivity to Am80, based on PML immunostaining, correlated well with the clinical effect in all patients tested. All three patients whose blasts were sensitive to Am80 in vitro despite a poor response to ATRA achieved CRs. Thus, Am80 might be an effective compound for the treatment of refractory APL and is a promising alternative retinoid. Since arsenic compounds have reportedly induced CRs in APL patients in China, we studied the in vitro effect of arsenic and other metal ions on myeloid leukemia cell lines. The effects of arsenic were limited mainly to APL cells, and the arsenic concentration was critical for the APL cell line NB4: 1 microM As3+ induced time-dependent apoptosis, whereas 0.1 microM As3+ allowed partial NB4 cell differentiation. Arsenic trioxide was equally effective when used on ATRA-resistant NB4 cells. Among the clinical leukemia samples tested, the in vitro cytotoxic effects of As3+ were observed selectively in APL cells, regardless of their ATRA sensitivity. These data suggest that APL cells are sensitive to As3+ and that As3+ acts on APL cells via a different pathway to ATRA.

Antineoplastic Agents↗
PubMed1997

The specific expression of tenascin in the synovial membrane of the temporomandibular joint with internal derangement: an immunohistochemical study.

The expression of tenascin (TN) in the tempormandibular joint (TMJ) disc and synovial membrane was examined in 18 human TMJ samples from patients with internal derangement of the TMJ and ten control specimens by an immunohistological technique using paraffin-embedded tissue and specific anti-human TN monoclonal antibody (RCB-1). The expression of TN was observed in all 28 samples, but it was limited to the walls of blood vessels, the perineurium, and the surface of the TMJ disc. The expression of TN was diffuse in the stroma of mildly hypertrophic synovial membranes and focal in the surface of severely hypertrophic synovial membranes. The clinical symptoms of internal derangement of the TMJ are thought to be related to the degree of synovitis. The present study demonstrates that TN is expressed specifically in the portion of the TMJ synovial membrane affected with internal derangement.

Adult↗
PubMed1997

Assessment of hand-arm vibration exposure among traffic police motorcyclists.

The aims of this study were (1) to evaluate subjective symptoms in the hand-arm system of all traffic police motorcyclists of a city located in the central part of Japan and (2) to assess their hand-arm vibration exposure associated with traffic police motorcycle riding. The study population consisted of 119 motorcycling traffic policemen and 49 male controls. By means of a questionnaire, information on the occupational history and the presence of subjective symptoms in the hand-arm system of all subjects was obtained. Vibration was measured on the handlebars of the representative motorcycles and on the hands of the riders. The 4- and 8-h energy-equivalent frequency-weighted acceleration as well as the lifetime vibration dose were calculated for all police motorcyclists. The prevalence of finger blanching in the traffic police motorcyclists was 4.2%, but none of the controls had this symptom. The rates of finger numbness (19.3%), finger stiffness (16.0%), shoulder pain (13.4%), and shoulder stiffness (45.4%) were significantly higher among police motorcyclists as compared with controls. The root-mean-square (rms) frequency-weighted acceleration on the handlebars of police motorcycles was in the range of 2.2-4.9 m/s2 rms. The computed 4- and 8-h energy-equivalent frequency-weighted acceleration values were 2.8-4.5 and 2.0-3.2 m/s2 rms, respectively. A pattern of increasing percentage prevalence with increasing cumulative vibration dose was noticed. The subjects with a lifetime vibration dose of more than 20.1 m2 h3 s-4 (in scale) showed significantly higher prevalence rates for symptoms in the fingers and shoulders as compared with the control group. As occupational vibration exposure of traffic police motorcyclists might be considered a risk factor for the development of symptoms in the hand-arm system of the riders, its evaluation and control is needed for prevention methodology evolution.

Adult↗
PubMed1997

Effect of uncoupling NO/cGMP pathways on carbachol- and CCK-stimulated Ca2+ entry and amylase secretion from the rat pancreas.

Nitric oxide (NO) production reportedly regulates guanosine 3', 5'-cyclic monophosphate (cGMP) formation and Ca2+ influx in pancreatic acini. We have investigated the functional roles of the NO/cGMP messenger system in rat pancreatic acini. In dispersed acini, the levels of amylase secretion, cytosolic [Ca2+]([Ca2+]i), NO synthase, and cGMP were measured. The NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 0.01-100 microM) had no effect on amylase secretion induced by various concentrations of carbachol, cholecystokinin octapeptide (CCK-8) or the high affinity CCK agonist, JMV-180. Similarly, L-NAME up to 100 microM did not affect the changes in Ca2+ spiking evoked by these secretagogues; nor was Ca2+ entry, refilling or oscillation altered by L-NAME. Sub- and supramaximal concentrations of these secretagogues did not change NO synthase activities compared with basal levels. While sodium nitroprusside (SNP), a NO donor, caused a 9.4-fold increase in cGMP levels compared with basal levels, carbachol, CCK-8 and JMV-180 had no effect. In addition, the guanylate cyclase inhibitor LY 83583 (10 nM to 10 microM) altered neither amylase secretion nor Ca2+ signaling induced by these secretagogues. These findings indicate that the stimulatory action of carbachol or CCK-8 is not mediated by NO or cGMP. To investigate whether cGMP stimulates pancreatic secretion we showed that both SNP and a cell-permeant cGMP analog at 0.1-1 mM stimulated amylase secretion and Ca2+ transients to a level equal to 10-15% and 13-24%, respectively, of those observed with maximal concentrations of secretagogues. The guanylate cyclase activator guanylin (1-10 microM), which increased cGMP levels 2.4-fold compared with basal levels, elicited a small amount of amylase secretion and a small Ca2+ transient. In conclusion, exogenous NO is capable of increasing endogenous cGMP, which results in a modest increase in the [Ca2+]i transient and pancreatic amylase secretion. However, the NO/cGMP system does not appear to be involved significantly in the mediation of Ca2+ signaling and amylase secretion stimulated by carbachol and CCK-8.

Amylases↗
PubMed1997

Early presence of endothelial-like cells on the flow surface of porous arterial prostheses implanted in the descending thoracic aorta of the dog.

The purpose of this study was to investigate early arterial graft healing and its sources in porous Dacron prostheses after very short implantation periods in the dog, using extensive histologic examination of serial sections. Preclotted Dacron prostheses 6 cm long and 8 mm in diameter were implanted in the descending thoracic aorta (DTA) of 14 dogs, and retrieved at 7 days (n = 6), 10 days (n = 4), and 14 days (n = 4). The flow surface was assessed for thrombus coverage, endothelial-like cell (ELC) coverage, and the number of microvessel ostia. Where an ELC island was identified under the stereomicroscope, full-wall longitudinal tissue samples were taken, and embedded in resin for light microscopy study of 6-microns, H&E-stained serial sections to determine general healing and interstitial tissue presence. If there was more than one ELC island, another full-wall sample was taken and embedded in paraffin for staining with laminin, collagen IV, and smooth muscle alpha-actin antibodies, and PTAH. All grafts were patent with very little thrombus. Islands of endothelial-like cells were found for each time period, and on all 14-day grafts. Endothelial-like cell coverage was highest at 14 days. On 7- and 10-day grafts, cells proved to be endothelium were found in the middle of the flow surface, unconnected to either pannus or perigraft tissue ingrowth. Healing occurs as early as 7 days in porous knitted Dacron grafts. The source at periods earlier than 10 days appears to be cells from the blood stream.

Animals↗
PubMed1997

Effects of triolein or oleic acid on lymphatic recovery of docosahexaenoic acid given as ethyl ester and their intramolecular distribution in lymph triglyceride of rats.

Effects of oleic acid or triolein on lymphatic recovery of docosahexaenoic acid (DHA) given as an ethyl ester were examined in rats with cannulated thoracic ducts. Lymphatic recovery of ethyl DHA given with oleic acid or triolein was significantly higher than in rats given ethyl DHA alone. DHA distributed almost exclusively at the 1- and 3-position of triglyceride in lymph collected at 0-3 h after the administration, when it was given with oleic acid or triolein. A small part of DHA distributed at the 2-position when ethyl DHA was the sole fatty acid given. Oleic acid given as free acid or triolein with ethyl DHA was a major fatty acid at the 2-position. Intramolecular distribution of DHA and oleic acid in lymph triglyceride was similar when ethyl DHA was given with oleic acid or triolein.

Absorption↗
PubMed1997

Assessment of regional sympathetic nerve activity in vasospastic angina: analysis of iodine 123-labeled metaiodobenzylguanidine scintigraphy.

With the use of iodine 123-labeled metaiodobenzylguanidine (123I-MIBG) scintigraphy, this study evaluated regional sympathetic nerve activity in vasospastic angina. Twenty male patients with left anterior descending coronary artery spasm and 18 male patients with normal coronary arteries as a control group were studied. All patients underwent quantitative 123I-MIBG scintigraphy and atropine stress 123I-MIBG scintigraphy. Both groups showed a similar heterogeneous 123I-MIBG uptake in the left ventricle. However, the regional washout rate in patients with coronary artery spasm was significantly reduced in all three territories compared with that in the control group. In vasospastic angina, the regional washout rate in the left anterior descending coronary artery territory was significantly reduced as compared with the other two regions. After intravenous injection of 1 mg atropine, the regional washout rate in the three regions significantly increased in both groups, but the regional differences between the two groups disappeared. The current study demonstrated that cardiac sympathetic nerve activity in vasospastic angina was suppressed, especially in the territory of the spasm-induced coronary artery, probably because of the enhanced parasympathetic nerve activity.

3-Iodobenzylguanidine↗
PubMed1997

Increased secretion of hepatocyte growth factor by eutopic endometrial stromal cells in women with endometriosis.

OBJECTIVE: We evaluated the secretion of hepatocyte growth factor by eutopic endometrial stromal cells in vitro. DESIGN: Eutopic endometrial stromal cells were isolated and the culture supernatants were collected after 48 hours of incubation. The secretion of hepatocyte growth factor was analyzed by ELISA. SETTING: Department of Obstetrics and Gynecology of Tohoku University Hospital. PATIENT(S): Specimens of endometrium in the proliferative phase were excised from 11 patients who were undergoing laparoscopy for infertility. Six of the patients had endometriosis and five did not. None of the patients had received hormonal treatment before surgery. RESULT(S): Hepatocyte growth factor secretion was found to be increased significantly in cultured endometrial stromal cells from the infertile patients with endometriosis compared with those without endometriosis. CONCLUSION(S): The secretion of hepatocyte growth factor was up-regulated in eutopic endometrial stromal cells from patients with endometriosis. An increase in hepatocyte growth factor production may be characteristic of endometriosis and may be involved in the pathophysiology of this disease.

Adult↗
PubMed1997

The role of ERCP in biliary atresia.

BACKGROUND: It is not easy to discriminate between infantile hepatitis and biliary atresia in spite of several diagnostic tests including laboratory analyses, ultrasound, and hepatobiliary scans. ERCP is the most useful procedure for visualization of the extrahepatic biliary system, but ERCP is still an uncommon procedure in children. METHODS: ERCP examination was performed in 52 infants with biliary atresia (10 with infantile hepatitis, 5 with congenital biliary dilatation, 3 with paucity of intrahepatic bile duct, 2 with duodenal atresia, and 1 with postoperative jaundice of hepatoblastoma) aged from 8 days to 300 days (mean, 71 days). RESULTS: ERCP was successful in 47 with biliary atresia, in 9 with infantile hepatitis, and 10 with another disease. Liver biopsy was performed in 1 infant with hepatitis in whom the cannulation failed; in 9 with hepatitis in whom the cannulation was successful, exploratory laparotomy could be avoided. The ERCP findings in 46 patients with biliary atresia (excluding 1 in whom evaluation could not be performed because of poor x-ray quality) were classified into four patterns. CONCLUSIONS: A success rate of ERCP examinations in infants was 88%, so ERCP is recommended to make a correct decision regarding the need for surgery in cholestatic disorders.

Biliary Atresia↗
PubMed1997

Detection of tumor thrombus in children using color Doppler ultrasonography.

Color Doppler ultrasonography (CDUS), which provides information regarding both the tissue and the blood flow simultaneously in real time, is a relatively new and noninvasive technique for the evaluation of organ perfusion. The authors investigated the usefulness of CDUS in the detection of tumor thrombus in 34 children who had malignant tumor (21 neuroblastomas, 2 Wilms' tumors, 5 hepatoblastomas, 2 rhabdomyosarcomas, and 4 others) who underwent CDUS between April 1992 and March 1995 in our department. The CDUS showed tumor thrombus in four patients (11.8%). Three thrombi (in one patient each with neuroblastoma, Wilms' tumor, and hepatoblastoma) were situated in the inferior vena cava, and one (in a patient who had hepatoblastoma) in the portal vein. Each tumor thrombus was monitored and followed up using CDUS every month during the entire clinical course; two of the four thrombi remained despite intensive treatments. The authors have found CDUS to afford rapid and noninvasive detection of tumor thrombus, and it proved useful not only in the detection of tumor thrombus but also in its follow-up in these children who had malignant tumor.

Child, Preschool↗
PubMed1997

Pressure stimulates proliferation and DNA synthesis in rat intestinal epithelial cells.

Effects of intraluminal pressure on cultured intestinal epithelial cells were assessed by measuring cell proliferation and DNA synthesis after exposure to various pressures. Pressures of 40 to 120 mm Hg promoted cell proliferation and DNA synthesis. Pressure-induced DNA synthesis was further enhanced by the addition of interleukin-2, suggesting the regulation of intestinal epithelial growth by pressure in coordination with cytokines. Pretreatment with either a phospholipase C inhibitor or protein kinase C inhibitor significantly inhibited DNA synthesis promoted by pressure and interleukin-2. This study demonstrates a novel mechanism whereby pressure regulates cell growth in intestinal epithelial cells, possibly via activation of phospholipase C and protein kinase C.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗