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Biomedical subjects

K Imamura

Publications and source records attributed to K Imamura.

At least 91 records · Page 5Linked to original sources
PubMed1998

Does comorbidity affect the outcome of surgery? Total hip replacement in the UK and Japan.

OBJECTIVES: To assess the impact of comorbidity on the outcome of surgery in the UK and in Japan; to determine the predictive ability of a new measure of comorbidity, the Index of Co-Existent Diseases (ICED); and to see if its predictive power could be improved. DESIGN: Logistic regression using data from two retrospective cohorts with prospective outcome data collection. SETTING: Six hospitals (three teaching, three non-teaching) in the UK and 15 (12 teaching, three non-teaching) hospitals in Japan. STUDY PARTICIPANTS: Patients undergoing total hip replacement (THR) surgery in the UK (n = 268) and in Japan (n = 249). MAIN OUTCOME MEASURES: Serious complications before hospital discharge and change in three measures of general health status [basic activities of daily living (ADL); instrumental ADL; social activities]. RESULTS: The distribution of levels of comorbidity differed between the UK and Japan: none (26.1 versus 42.2%); mild (30.6 versus 43.0%); moderate (23.5 versus 12.0%); and severe (19.8 versus 2.8%). In the UK, the incidence of serious complications was higher in patients with moderate (27.0%) or severe (26.4%) comorbidity than in those with no (14.3%) or mild (13.4%) comorbidity (P<0.001). In contrast, no significant association was found in Japan. The relationship between comorbidity and change in health status was weak in the UK and non-significant in Japan. Logistic regression confirmed that comorbidity was a significant predictor of serious complications in the UK. The only other significant factor was surgical approach (anterior/antero-lateral; odds ratio 2.16, P<0.05). Attempts to improve the predictive power of the ICED by modifying its structure and by reclassifying complications was successful in achieving a linear (rather than dichotomous) relationship. The predictive power, however, was poor. CONCLUSIONS: Comorbidity is a significant determinant of serious complications following THR but not of changes in functional or health status. Comparisons of clinical performance using post-operative complications must take levels of comorbidity into account if they are to be meaningful. The ICED is of less validity in the UK and Japan than in its country of origin, the USA. Further work to develop better instruments for the UK and Japan is needed.

Activities of Daily Living↗
PubMed1998

Genetic analysis of non-insulin-dependent diabetes mellitus in KK and KK-Ay mice.

The KK mouse is considered suitable as a polygenic model for human non-insulin-dependent diabetes mellitus. To identify the quantitative trait loci (QTLs) responsible for hyperglycemia and impaired glucose tolerance in KK mice, linkage analysis using 97 microsatellite markers was carried out in a 192 F2 progeny, comprising 93 mice with the a/a genotype at the agouti locus (chromosome 2) and 99 mice with the Ay/a genotype, produced by a cross between a C57BL/6J female and a KK-Ay (Ay congenic) male. In F2 a/a progenies, we identified a QTL for fasting glucose levels on chromosome 6 (LOD score 6.0) and three loci with suggestive linkage on chromosomes 3, 5 and 14, but could not identify loci accounting for glucose tolerance and plasma insulin levels. In F2 Ay/a progenies, there were no loci with statistically significant linkage, but three suggestive loci were identified: a locus for fasting glucose on chromosome 9, and two loci for glucose tolerance on chromosomes 1 and 8. It would thus appear that. although the fasting glucose level is controlled by QTLs in KK mice, these QTLs may be masked by the strong hyperglycemic influence of the Ay allele. Suggestive loci accounting for glucose tolerance may interact with the Ay allele, since these loci were identified only in F2 Ay/a progeny. This is consistent with the finding that the impaired glucose tolerance in KK mice is moderate and becomes overt when associated with the Ay allele.

Alleles↗
PubMed1998

The cDNA cloning and molecular characterization of a snake venom platelet glycoprotein Ib-binding protein, mamushigin, from Agkistrodon halys blomhoffii venom.

The entire cDNA sequences of a novel snake venom platelet glycoprotein (GP) Ib-binding protein (BP) composed of an alpha/beta heterodimeric structure, termed mamushigin, from Agkistrodon halys blomhoffii were determined, that include the leader peptides (21/23 amino acid residues) and mature subunits (136/123 amino acid residues). The mature subunits of mamushigin are 37.5% identical, and showed a high degree of similarity (37.7-67.5% identity) with the respective subunits of group VII C-type lectins (19). The sequences of the leader peptides of the mamusigin subunits showed the highest similarity (alpha-73.9/beta-82.6%) with those of factor IX/X-BP from Trimeresurus flavoviridis, and the cleavage site residue in both proteins was the same Ala(-1). The GPIb-binding specificity of mamushigin is strongly supported by several lines of evidence, but mamushigin can directly aggregate normal platelets, similar to alboaggregin-B (AL-B) (1). This differs from other GPIb-BP's. In mamushigin-treated platelets, serotonin was not released, and flow cytometric analysis using a monoclonal antibody PAC-1 totally excluded platelet GPIIb/IIIa activation. Mamushigin enhanced platelet aggregation at low-shear stress, and this effect totally disappeared in the presence of GPIb-receptor blockers specific for von Willebrand factor binding, but not by GPIIb/IIIa-receptor blockers. At high-shear stress, mamushigin blocked platelet aggregation in a dose-dependent manner, as seen with other GPIb-BP's. This paper, therefore, describes the cDNA cloning and molecular characterization of mamushigin which has a different effect on platelet aggregation under different shear stress.

Agkistrodon↗
PubMed1997

Reduced activity in the extrastriate visual cortex of individuals with strabismic amblyopia.

In order to examine the relationship between reduced visual acuity in human strabismic amblyopia and the cortical activation pattern, we studied, by use of positron emission tomography (PET) and the H2(15)O bolus technique, changes in the regional cerebral blood flow (rCBF) induced by monocular visual stimulation of 8 individuals with this disorder. Individual amblyopic thresholds for monocular detection of the checkerboard pattern were employed as stimuli for both eyes during PET scans. Statistical analysis of subtracted images showed significant increases in rCBF (P < 0.05) by the stimulation of the sound eye localized bilaterally to Brodmann's areas (BAs) 17-19. The cortical response evoked by the amblyopic eye was significantly reduced (P < 0.05) in the ipsilateral BAs 18, 19. These results suggest that the reduction in contrast sensitivity (pattern vision) in amblyopia is coupled with deactivation in identifiable regions of occipital visual areas, including ipsilateral BAs 18,19.

Adult↗
PubMed1997

Increased cardiac sympathetic activity in patients with hypothyroidism as determined by iodine-123 metaiodobenzylguanidine scintigraphy.

Clinical manifestations of hypothyroidism, such as bradycardia, suggest decreased sympathetic tone. However, previous studies in patients with hypothyroidism have suggested that increased plasma noradrenaline (NA) levels represent enhanced general sympathetic activity. As yet, cardiac sympathetic activity (CSA) in hypothyroidism has not been clarified. To evaluate CSA in patients with hypothyroidism, iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy was performed in eight patients with hypothyroidism before therapy and in ten normal control patients. Planar images were obtained at 15 min and 4 h after injection of MIBG. The ratio of early myocardial uptake to the total injected dose (MU) and myocardial clearance of MIBG within 4 h p.i. (MC) were calculated. Plasma NA was also measured, and echocardiography was performed in all patients. Those patients with hypothyroidism in the euthyroid state after medical therapy were also evaluated in a similar manner. Left ventricular ejection fraction, measured by echocardiography, did not differ significantly between the groups. NA, MU and MC were significantly higher in patients with hypothyroidism than in controls, and all parameters were decreased after therapy. MC was well correlated with NA in hypothyroidism (r=0.86) before therapy. We conclude that CSA is increased in patients with hypothyroidism, in parallel with the enhanced general sympathetic activity.

3-Iodobenzylguanidine↗
PubMed1997

Ultrastructural changes during myocardial hypertrophy and its regression: long-term effects of nifedipine in adult spontaneously hypertensive rats.

Nifedipine (20 mg/kg/day) was given to 15-week-old spontaneously hypertensive rats for 20 weeks (SHR-N, n = 8). Comparison was done with sex-matched 15-week-old SHR (SHR-15, n = 7), untreated 35-week-old SHR (SHR-C, n = 10), 15-week-old normotensive Wistar-Kyoto rats (WKY-15, n = 15), and 35-week-old WKY (WKY-15, n = 5). Light and electron microscopic data on the subepicardial, middle and subendocardial layers and papillary muscles of the left ventricle were compared among the five rat groups. In SHR-N, blood pressure was significantly reduced by nifedipine, but was higher than in WKY-35 (199 +/- 11 mmHg vs 121 +/- 13 mmHg). The left ventricular weight/body weight ratio was much lower in SHR-N than in SHR-C, and was even below the baseline value in SHR-15. In addition, cardiac myocyte diameter was much smaller in each myocardial layer of SHR-N than in SHR-C, and was similar to the findings in SHR-15, but still larger than in WKY-35. The interstitial area ratio was markedly reduced in SHR-N and did not differ from that in SHR-15 or even WKY-15, while capillary density was significantly greater than in SHR-C and comparable to that in WKY-35. In SHR-C, large fibrotic foci were common, and many hypertrophic cardiac myocytes showed various degenerative changes including those of mitochondria and widening of the intermyofibrillar spaces. These changes were rarely seen in SHR-N. The intracellular volume ratio of myofibrils did not differ between SHR-N and WKY-35, but was significantly decreased in SHR-C, whereas that of mitochondria did not differ between SHR-N and SHR-C or WKY-35. These findings indicate that despite only a moderate suppression of hypertension, long-term nifedipine treatment caused regression of left ventricular hypertrophy, with cardiocyte hypertrophy, interstitial fibrosis, degenerative changes, and subcellular remodeling being reversed to the baseline levels in SHR-15. In addition, the capillary density was increased to that seen in WKY-35.

Animals↗
PubMed1997

A novel near infra-red spectrophotometry system using microprobes: its evaluation and application for monitoring neuronal activity in the visual cortex.

A novel near-infrared (NIR) spectrophotometry system with microprobes of optical transmitter and receivers (550 and 410 microm in diameter, respectively) has been developed. A three-dimensional profile of the signal source estimated in in vitro experiments showed two spindle-shaped regions around the respective probes, suggesting that the signal detected by the present system comes from a relatively restricted region around each probe. Next, we examined how the concentration of oxygen in inspired gas affected the NIR signals in the rat cerebral cortex in vivo. Calculated concentrations of oxyhemoglobin (HbO2) and deoxyhemoglobin (Hb) in the rat cortex changed in mirror-image fashion in response to the change in the O2 concentration in the inspired gas. Finally, NIR responses to visual stimulation were recorded from the striate cortex of conscious adult cats that had been monocularly deprived since the peak of the sensitive period. Corresponding to the results of previous electrophysiological studies, stimulation of the normal eye induced significant NIR signals, whereas that of the deprived eye evoked no response. These results indicate that this new NIR system can be applied to study changes in oxygen metabolism in relatively restricted regions following neuronal activation in the brain.

Animals↗
PubMed1997

Effects of monocular enucleation on receptor binding and innervation pattern of the noradrenergic system in the superior colliculus of the pigmented rat.

To examine visual activity-dependent regulation of the central noradrenergic (NAergic) system, we carried out in vitro autoradiography for alpha2-, beta-adrenergic and NMDA, non-NMDA glutamatergic receptors together with immunohistochemical analysis for dopamine beta-hydroxylase in the major central visual structures, including the lateral geniculate nucleus, superior colliculus (SC), and visual cortex of pigmented rats, that had received monocular enucleation. Beta-adrenergic receptor (beta-AR) binding in the SC contralateral to the enucleated eye was significantly decreased (82%, P < 0.01) following monocular deprivation started at P12 and continued for 2 or 11 weeks. No significant change in beta-AR binding was found in other structures examined. The number of varicosities in NAergic fibers was significantly increased following longer enucleation, i.e. for 11 weeks, in the contralateral SC (197%, P <0.001), whereas that in the ipsilateral SC was reduced (75%, P <0.001). Changes in alpha2-adrenergic, NMDA, and non-NMDA glutamatergic receptor binding were small in these animals. Changes in neither beta-AR binding nor innervation pattern of NAergic fibers were found in one-year-old rats that had received a comparable period of monocular enucleation. Furthermore, neither unilateral ablation of the visual cortex to reduce a different set of major afferents nor neonatal enucleation, which induced anatomical reorganization of the afferents, was found to be effective. These findings suggest that beta-AR binding and innervation pattern of NAergic fibers in the SC are modified only when massive imbalance of retinal afferent activity is imposed during a limited period in early postnatal life (i.e. the sensitive period).

Animals↗
PubMed1997

Reliability of a comorbidity measure: the Index of Co-Existent Disease (ICED).

The reliability of an established comorbidity index (the Index of Co-Existent Disease) was tested using retrospective data from the case notes of elderly patients who had undergone total hip replacement. Inter-rater reliability was examined twice, first with two raters (n = 39) and then with three (n = 49). Intra-rater reliability was assessed using one rater (n = 45). Reasons for any lack of reliability were explored. The inter-rater reliability of the ICED was moderate (kappa 0.5-0.6). While the Functional Severity index performed well (kappa 0.6-1.0), the Index of Disease Severity subindex was less reliable (kappa 0.4-0.5). Differences between raters had an impact on the observed association between comorbidity and serious post-operative complications. Intra-rater reliability was excellent (kappa 0.9). Several reasons why inter-rater reliability was only moderate were identified, mostly related to uncertainties in applying the ICED. The reliability of the ICED needs to be improved before it is used more widely with retrospective data. This might be achieved by further clarification of the instructions for its use.

Activities of Daily Living↗
PubMed1997

Total hip replacement. The preoperative health status of patients in Japan compared with England and the United States.

To explore the contribution of health care to the excellent health status enjoyed by the Japanese compared with other industrialized populations, the preoperative health status of a retrospective cohort of 256 patients who underwent total hip replacement in Japan was compared with 301 patients in England (and published data from the United States). Patients in Japan had less severe hip disease, less comorbidity (in particular, less cardiovascular disease), and were in better general health. This finding suggests that health care contributes little to explaining the better health of people in Japan compared with England and the United States.

Activities of Daily Living↗
PubMed1997

Effects of topical antiandrogen and 5-alpha-reductase inhibitors on sebaceous glands in male fuzzy rats.

The fuzzy rat, a genetic mutant between hairless and hairy albino rats, expresses androgen-dependent hypersecretion of sebum and hyperplastic sebaceous glands. Using this model for human acne, we examined the effects of inhibitors of human steroid 5 alpha-reductase isozymes, type I (MK 386) and type II (finasteride), and an androgen receptor blocker (RU58841) on regression of glandular and ductal hyperplasia. The above three agents, 1% weight volume, were dissolved into the vehicle (propylene glycol, alcohol and water) and applied on the backs of peripubertal male rats for 2 months. Control and castrate groups received vehicle alone. At 8 weeks, we examined the size the sebaceous glandular lobules and ducts in split epidermal preparations as well as in frozen sections of skin stained with osmium-potassium dichromate solution. The number of bromodeoxyuridine (BrdU)-positive cells was counted in the glandular lobes in split-skin tissues stained with BrdU immunochemistry. The results revealed that the sizes of both lobes and ducts in castrates were 40-60% smaller than in controls. RU58841 induced glandular and ductal regression equivalent to that in castrates. Finasteride induced a moderate degree of lobular and ductal reduction, whereas MK386 caused only ductal regression. Reduction of BrdU-positive cells in the sebaceous lobes was found in the skin treated with finasteride and RU58841. Serum concentrations of testosterone and dihydrotestosterone showed no significant changes in all drug-treated rats. The weight of the prostatic lobes was reduced significantly in rats treated with finasteride but not by the other two agents. RU58841 effectively counteracted endogenous androgens resulting in a suppression of growth of the sebaceous glands but not the prostate. This rodent model for androgen-dependent hyperplasia of the sebaceous glands is useful for the study of many pharmacological aspects comprising the rate of percutaneous absorption, stability and affinity to target organs of the testing compounds, and selection of adequate vehicle for topical application.

5-alpha Reductase Inhibitors↗
PubMed1997

Single and repeated intravenous toxicity studies of pamiteplase (genetical recombination) in rats and monkeys.

Single and repeated intravenous toxicity studies of Pamiteplase (genetical recombination) YM866, a novel recombinant human tissue-type plasminogen activator, were conducted. No animal died from toxic effects of YM866 after single administration to F344 rats, squirrel monkeys and cynomolgus monkeys. Male and female F344 rats were given YM866 intravenously for 4 weeks at doses of 0 (vehicle), 0.1, 0.3 and 1 mg/kg/day. An increase in platelet count, slight decreases in hemoglobin and hematocrit, increases in plasma phospholipids, total cholesterol and total protein, and liver weight were observed at 1.0 mg/kg. Histopathology revealed no changes in any organ except for hemorrhage at the injection sites. These changes recovered after 4 weeks of withdrawal. Male and female squirrel monkeys were given YM866 intravenously for 4 weeks at doses of 0 (saline), 0 (vehicle), 0.1, 0.3 and 1 mg/kg/day. Prolongation of coagulation time at the injection site was observed at 0.3 mg/kg or more. Subcutaneous hemorrhage and a transient decrease in locomotor activity were observed at 1 mg/kg. Prolongation of coagulation time at the injection site was considered to be related to the pharmacological action of YM866. The results show that the approximate single lethal dose of YM866 is more than 60 mg/kg in rats, and more than 10 mg/kg in squirrel monkeys and cynomolgus monkeys. The no-toxic-effect level of YM866 after repeated administration for 4 weeks in rats and squirrel monkeys is considered to be 0.3 mg/kg.

Animals↗
PubMed1996

Down-regulation of beta-adrenergic receptor following long-term monocular deprivation in cat visual cortex.

To examine how adrenergic receptor binding is modified by experimental manipulation of sensory afferent, we carried out binding experiments (membrane fraction and in vitro autoradiography) for both alpha 2- and beta-adrenergic receptors in the brain of cats which had been deprived of vision in one eye. In the cerebral cortex of control animals, beta-adrenergic receptor (beta-AR) binding was found to be higher in the occipital regions than in other regions, while alpha 2-AR binding was relatively uniform. Monocular deprivation throughout the postnatal sensitive period (1-7 month of age) significantly decreased beta-AR binding in the visual cortex and lateral geniculate nucleus. Scatchard plot analysis in the visual cortex showed ca. 50% reduction in Bmax and little change in Kd. No significant difference was found in alpha 2-AR binding following monocular deprivation. Similar extent of down-regulation in beta-AR binding was confirmed in all layers of visual cortex using autoradiography.

Animals↗
PubMed1996

Enhancement of mRNA expression of tissue-type plasminogen activator by L-threo-3,4-dihydroxyphenylserine in association with ocular dominance plasticity.

Tissue-type plasminogen activator (tPA) plays important roles in the regulation of synaptic plasticity in the hippocampus and cerebellum. We found that the expression of tPA mRNA in the visual cortex was increased significantly by the peripheral administration of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS; 100 mg/kg, i.p.), which we had previously shown to have a promotive effect on ocular dominance (OD) plasticity. When plasminogen activator inhibitor-1 (PAI-1; 100 muM in an osmotic minipump) was infused into the kitten visual cortex, OD plasticity was suppressed; i.e. a significantly large number of binocular cells was recorded in the PAI-1 infused cortex following monocular deprivation. These results, therefore, suggest that the PA system is involved in the promotive effect of L-threo-DOPS in OD plasticity.

Animals↗
PubMed1996

Repeated peripheral administration of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin alters the binding activities of 5-HT1A and 5-HT2 receptors in rat brain.

Repeated peripheral administration of 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (R-THBP) induced significant changes in the binding activities of serotonergic receptors in the rat brain. The increase in the hippocampus and the decrease in the visual cortex of [3H]8-hydroxy-N,N-dipropyl-2-aminotetralin ([3H]8-OH-DPAT) binding (5-HT1A binding site) were found to be significant following R-THBP administration (20 mg/kg, twice a day for 1 week). [3H]Ketanserin binding (5-HT2 binding site) was increased in the striatum and hippocampus, whereas it was decreased in the cerebellum and visual cortex. Scatchard plot analysis showed ca. 20% reduction in the Bmax of [3H]8-OH-DPAT and [3H]ketanserin binding in the visual cortex, and KD values for [3H]8-OH-DPAT and [3H]ketanserin bindings in the hippocampus were significantly reduced 51% and 66%, respectively. These differential changes in 5-HT binding might be involved in the central action of R-THBP.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1996

Regional activation of human cerebral cortex upon an adaptation in mirror drawing.

To elucidate cerebral regions involved in adaptation to mirror drawing, changes in regional cerebral blood flow were measured using positron emission tomography at different levels of adaptation. A significant signal in subtraction images was localized in left Brodmann's area 45 (ventral sub-region of Broca's area) in the initial phase of the mirror drawing. This activity decreased as adaptation proceeded, and a small cluster in area 19 of the medial extrastriate cortex became significantly active. An after-effect of ca. 30 min of mirror-drawing was also detected in the right area 21 of the temporal association cortex. The results first demonstrated visuo-cortical regions where neurons might change their activity to evoke plastic response to the inverted vision.

Adaptation, Psychological↗