Search PubMed⌕ Search

Biomedical subjects

K Shimada

Publications and source records attributed to K Shimada.

At least 109 records · Page 6Linked to original sources
PubMed2001

Malfunction of circadian clock in the non-photoperiodic-diapause mutants of the drosophilid fly, Chymomyza costata.

The diel rhythmicity of adult eclosion was recorded in reciprocal F1 hybrids between the wild-type (Sapporo) and mutant (NPD) strains of Chymomyza costata and the functionality of central circadian clocks was checked in both strains by assessing diel and circadian patterns of the per gene mRNA abundance oscillations in fly heads using competitive polymerase chain reaction methodology. The previously detected mutations in the per coding region of the NPD strain (Shimada, Entomol. Sci. 2 (1999) 575) were found to be primarily neither responsible for the loss of the eclosion rhythm nor for the malfunction of the circadian clocks. While distinct diel and circadian rhythms in per mRNA abundance were found in the wild-type flies, the npd-mutants showed constant (arrhythmic) and low abundance of the per mRNA transcripts. Because the non-photoperiodism, arrhythmicity of adult eclosion and the malfunction of central circadian clocks all seem to result from a mutation in the autosomal npd locus, we hypothesize, that a product coded by this locus may represent a 'point of contact' between the circadian and photoperiodic time measurement systems in C. costata.

Journal Article↗
PubMed2001

Studies on neurosteroids XIV. Levels of dehydroepiandrosterone sulfate in rat brain and serum determined with newly developed enzyme-linked immunosorbent assay.

An enzyme-linked immunosorbent assay (ELISA) of dehydroepiandrosterone sulfate (DHEAS), one of the neurosteroids, has been developed for measuring its brain and serum levels in rats without deconjugation. 11 alpha-Hemiglutaryloxy-DHEAS was newly synthesized, conjugated with bovine serum albumin (BSA), and immunized to rabbits for the production of anti-DHEAS antibodies. A bridge-heterologous ELISA system employing the sequential saturation method exhibited a high sensitivity with a midpoint of 100 pg. Although the antibody significantly cross-reacted with epiandrosterone sulfate, it easily discriminated the unconjugated steroids and pregnenolone sulfate, which is reported to exist in the brain at a much higher level when compared with DHEAS. The brain homogenate or serum was treated with hexane to remove the lipophilic compounds and purified with an OASIS HLB cartridge. The DHEAS levels were then determined by ELISA. The overall recovery rate through the pretreatment was a satisfactory and constant (81.8 +/- 3.4% for brain, 89.3 +/- 3.0% for serum, mean +/- standard deviation). This ELISA afforded a satisfactory serial dilution study and recovery test. The intra- and inter-assay coefficients of variation were lower than 13%, which showed the precision of the proposed method. The applied method showed that DHEAS was not detected in some brain samples and its levels were much lower than those previously reported and than its serum levels.

Animals↗
PubMed2001

New lesions detected by intraoperative ultrasound during liver resection for hepatocellular carcinoma.

During liver resection for hepatocellular carcinoma (HCC), it is not uncommon for examinations by intraoperative ultrasound (IOUS) to detect small new lesions that were not found by preoperative examinations. Although a differential diagnosis is critical, it has not yet been established if IOUS is useful for this purpose with such small lesions. A total of 90 new lesions detected by IOUS in 79 liver resections were analysed. IOUS was performed on all of these cases and the features were recorded. The histologic characteristics of these 90 new lesions were checked by needle biopsy and their relations to the clinical data were analyzed. The IOUS pattern of the lesion was hypoechoic in 36 cases, hyperechoic in 49 and mosaic in 5. A total of 24 HCC lesions were detected and the incidences of malignancy for each type were 30.6%, 18.4% and 80.0%, respectively. Multiple regression analysis revealed that the IOUS features of the new lesions were the only significant factors in predicting the histology. IOUS should be mandatory in liver resection for HCC because it is useful for finding new lesions and might contribute to prediction of the histologic features.

Adult↗
PubMed2001

Silent and clinically overt stroke in older Japanese subjects with white-coat and sustained hypertension.

OBJECTIVES: We investigated whether white-coat hypertension is a risk factor for stroke in relation to silent cerebral infarct (SCI) in an older Japanese population. BACKGROUND: It remains uncertain whether white-coat hypertension in older subjects is a benign condition or is associated with an increased risk of stroke. METHODS: We studied the prognosis for stroke in 958 older Japanese subjects (147 normotensives [NT], 236 white-coat hypertensives [WCHT] and 575 sustained hypertensives [SHT]) in whom ambulatory blood pressure monitoring was performed in the absence of antihypertensive treatment. In 585 subjects (61%), we also assessed SCI using brain magnetic resonance imaging. RESULTS: Silent cerebral infarcts were found in 36% of NT (n = 70), 42% of WCHT (n = 154), and 53% of SHT (n = 361); multiple SCIs (the presence of > or =2 SCIs) were found in 24% of NT, 25% of WCHT and 39% of SHT. During a mean 42-month follow-up period, clinically overt strokes occurred in 62 subjects (NT: three [2.0%]; WCHT: five [2.1%]; SHT: 54 [9.4%]), with 14 fatal cases (NT: one [0.7%]; WCHT: 0 [0%]; SHT: 13 [2.3%]). A Cox regression analysis showed that age (p = 0.0001) and SHT (relative risk, [RR] [95% confidence interval, CI]: 4.3 [1.3-14.2], p = 0.018) were independent stroke predictors, whereas WCHT was not significant. When we added presence/absence of SCI at baseline into this model, the RR (95% CI) for SCI was 4.6 (2.0-10.5) (p = 0.003) and that of SHT was 5.5 (1.8-18.9) versus WCHT (p = 0.004) and 3.8 (0.88-16.7) versus NT (p = 0.07). CONCLUSIONS: In older subjects the incidence of stroke in WCHT is similar to that of NT and one-fourth the risk in SHT. Although SCI is a strong predictor of stroke, the difference in stroke prognosis between SHT and WCHT was independent of SCI. It is clinically important to distinguish WCHT from SHT even after assessment of target organ damage in the elderly.

Aged↗
PubMed2001

Modulation of coronary flow velocity reserve by gender, menstrual cycle and hormone replacement therapy.

OBJECTIVES: The purpose of this study was twofold: 1) to examine the relationship between menstrual cycle and coronary flow velocity reserve (CFVR) in young healthy women, and 2) to evaluate the effect of hormone replacement therapy by estrogen on CFVR in postmenopausal women, using transthoracic color Doppler echocardiography (TTCDE). BACKGROUND: Although the incidence of cardiovascular disease is lower in women before menopause compared with men, postmenopausal women have an incidence of coronary artery disease similar to that of men of the same age. This is mainly dependent upon estrogen deficiency. However, no clinical report has yet examined the effect of estrogen on CFVR, which is one index of coronary microcirculation. METHODS: We examined 15 male and both 15 premenopausal and 10 postmenopausal female healthy volunteers. We measured coronary flow velocity of the left anterior descending coronary artery at baseline and hyperemic conditions during adenosine triphosphate infusion by TTCDE and determined CFVR. Each premenopausal woman was studied two times (menstrual [M] and follicular [F] phases) in one menstrual cycle. Fifteen men were also studied at a time corresponding to women's menstrual cycle. The postmenopausal women were studied before and two hours after oral administration of conjugated estrogen (CE). RESULTS: Serum 17beta-estradiol level in premenopausal women increased in the F phase and decreased to the same levels as in men, as in the M phase and as in postmenopausal women (123 +/- 9 pg/ml vs. 28 +/- 6 pg/ml, 25 +/- 9 pg/ml and 19 +/- 11 pg/ml; p < 0.0001, respectively). The CFVR increased in the F phase compared with that in the M phase (4.8 +/- 0.4 vs. 3.7 +/- 0.8, p < 0.0001). We found that CFVR in men remained unchanged (3.7 +/- 0.6 vs. 3.8 +/- 0.5). After CE administration, CFVR increased compared with baseline in postmenopausal women (4.1 +/- 0.8 vs. 3.4 +/- 0.8, p < 0.005). CONCLUSIONS: In premenopausal women, CFVR determined by TTCDE varied during the menstrual cycle, and in postmenopausal women, CFVR increased after acute estrogen replacement.

Adult↗
PubMed2001

Involvement of BMP-2 signaling in a cartilage cap in osteochondroma.

This study describes the distributions of bone morphogenetic protein (BMP)-2 as well as mRNAs for BMP receptor type IB (BMPRIB). collagen types II (Col II) and III (Col III) in a growing "cartilage cap" of osteochondroma. In situ hybridization and immunohistochemical study were performed using histological sections obtained during surgery. BMP-2 was detected in mesenchymal cells in the outer fibrous layer and chondrocytes in the inner cartilaginous matrix, positive for Col III and Col II, respectively. BMPRIB mRNA was distributed in chondrocytes. This is the first study to provide observational evidence of the involvement of BMP-2 signaling in the pathogenesis of cartilage cap of osteochondroma. and suggests the role of BMP-2 in the growth of cartilage cap in osteochondroma.

Bone Morphogenetic Protein 2↗
PubMed2001

Different patterns of silent cerebral infarct in patients with coronary artery disease or hypertension.

The aim of the present study was to clarify the differences in the progression and the characteristics of silent cerebral infarcts (SCI) between patients with coronary artery disease (CAD) and hypertensive patients. Silent cerebral infarcts, a powerful prognostic indicator for stroke, are frequently found in patients with CAD and in hypertensives. However, the differences in the characteristics of SCI and related risk factors between CAD and hypertensive patients have not been thoroughly investigated. We evaluated the number of SCI and their distribution using brain magnetic resonance imaging (T1- and T2-weighted images) in 107 patients with CAD (validated by coronary angiography) and 101 hypertensive patients without history of clinical stroke. The prevalence of multiple SCI (three or more infarcts per person) in patients with CAD and with hypertension was significantly higher than in hypertensives without CAD (46% v 21%; P = .001), whereas that of patients with CAD without hypertension was intermediate (31%). The patients with multi- (two- or three-vessel) vessel diseases (VD) had a significantly higher prevalence of multiple SCI than the hypertensives and the no-stenosis or 1-VD group (68.1% in the 3-VD group, 52.0% in the 2-VD group, 26.8% in the 1-VD group, and 21.0% in the no-stenosis group). Multiple logistic regression analysis revealed that in the CAD group, the number of involved coronary arteries was an independent determinant of SCI (P < .005), whereas in the hypertensive group, age was an independent determinant of SCI (P < .005). When we investigated the distribution of SCI, in the CAD group, SCI in the deep perforator territory (the basal ganglia and the thalamus) were independently associated with the number of involved coronary arteries (P < .005), whereas SCI in the white matter were independently associated with age only (P < .005). In conclusion, SCI were more advanced in the patients with multivessel CAD than in the hypertensive patients, and were more common in patients with CAD and hypertension than in those without hypertension. Coronary atherosclerosis was independently and specifically associated with SCI located in the deep perferator territory but not of SCI located in the white matter. The CAD-atherosclerosis and hypertension may be independently involved in the pathologic process of SCI.

Arteriosclerosis↗
PubMed2001

Silent cerebral infarcts in basal ganglia are advanced in congenital protein C-deficient heterozygotes with hypertension.

Congenital protein C deficiency is now widely recognized as a genetic risk for venous thrombosis. However, it remains uncertain whether this condition also confers risk for arterial thrombosis. We evaluated the association of congenital protein C deficiency with hypertension and silent cerebrovascular disease using brain magnetic resonance imaging (MRI) (T1- and T2-weighted and proton density images) in a large family pedigree of protein C deficiency diagnosed by gene analysis, compared with 46 non-pedigree related control subjects with normal protein C levels (> or = 75%) who were selected from among 55 asymptomatic hypertensive subjects matched for age and cardiovascular risk factors. Of the 58 living subjects in this pedigree, we measured plasma protein C levels in 45 subjects, and found 2 cerebral infarctions in the 24 heterozygotic subjects, whereas there was no stroke in the 21 normal homozygotic subjects. We performed brain MRI in 14 asymptomatic hypertensive subjects without any cardiovascular disease and in two patients with cerebral infarction, and found 28 cerebral infarcts (two corresponded to the patients' neurologic deficits and 26 were silent). All were lacunar infarcts < 10 cm in size. A total of 25 silent lacunar infarcts were found in nine heterozygotic subjects, whereas only one was found in the seven normal homozygotic subjects (2.8 v 0.14 lacunes per person, P = .002). No advanced white matter hyperintense lesions in T2-weighted images were found in either group. The prevalence of silent lacunar infarcts in the heterozygotic subjects was also significantly higher than that in normal control subjects (1.0 per person, P = .01). Concerning the distribution of silent infarcts, the number of lacunes located in the basal ganglia was higher in the heterozygotic subjects (2.3 per person, P < .001) than in the seven normal homozygotic subjects (0.14 per person) or in the control group (0.28 per person), whereas the number of lacunes in the white matter was not different among the groups. In conclusion, congenital protein C deficiency may accelerate the progression of silent cerebral infarct formation in hypertension, particularly in the basal ganglia, and may be a potential risk for stroke or vascularly induced dementia.

Aged↗
PubMed2001

Quantitative analysis of tenascin in chordae tendineae of human left ventricular papillary muscle with aging.

A computer image analysis was done to investigate the distribution of tenascin and collagenous matrix components (collagen types I and III) in the chordae tendineae of the anterior cusp of the left ventricular papillary muscle, using confocal laser scanning microscopy in both a 20s age group and an 80s-90s age group. Tenascin and the collagenous matrix components showed marked accumulation in the 80s-90s age group with elastic fiber concentration being increased in the same region as that in the 20s age group. The highest content of intersurface layer staining with an anti-tenascin antibody and with anti-collagen type III in the inner layer was found in the 80s-90s age group. These content levels were low in each region in the 20s age group. The distribution and content of these extracellular matrix changes are related to the changes in mechanical performance of the cardiac muscle with age.

Adult↗
PubMed2001

Hepatic resection for hepatocellular carcinoma in the elderly.

BACKGROUND: Although the number of elderly people undergoing surgery for hepatocellular carcinoma (HCC) has increased because of the prolonged life expectancy rate, potential benefits of hepatectomy for elderly patients with HCC have not been fully delineated. STUDY DESIGN: Using medical records, surgical outcomes of HCC in 103 patients 70 years of age or older undergoing hepatic resection (older group) were clarified and compared with those of 283 patients younger than 70 years of age (younger group) in this retrospective study. Postresection prognostic factors were evaluated by multivariate analysis using Cox's proportional hazards model. RESULTS: There were no significant differences in postoperative complication, operative mortality, and overall hospital death rates between the two groups. Overall 3- and 5-year survival rates for the older group and the younger group were 51.0% versus 55.2%, and 42.2% versus 40.0%, respectively (p = 0.95). Disease-free 3- and 5-year survival rates for the older group and the younger group were 35.2% versus 37.6%, and 16.6% versus 24.2%, respectively (p = 0.66). Multivariate analysis revealed that the presence of liver cirrhosis and vascular invasion were independently significant factors of poor overall survival. CONCLUSIONS: Selected elderly patients with HCC benefited from resection as much as young patients, and age by itself may not be a contraindication to surgery. Postresection longterm prognosis in the elderly was determined by the presence of liver cirrhosis and vascular invasion.

Adult↗
PubMed2001

Effect of AVT antisense oligodeoxynucleotides on AVT release induced by hypertonic stimulation in chicks.

In birds, arginine vasotocin (AVT) and mesotocin (MT) are the neurohypophyseal hormones. AVT is known to be an avian antidiuretic hormone and is released from the neurohypophysis by dehydration or hyperosmotic stimulation. The purpose of this study was to determine whether the mechanism of AVT synthesis is related to the mechanism of hormone release from the neurohypophysis. Four-day-old chicks received an AVT antisense oligodeoxynucleotide (ODN) injection into the cerebral ventricle (icv). Following antisense administration, the chicks received hypertonic saline stimulation. Plasma levels of AVT and MT were measured by radioimmunoassays. In control birds, a hypertonic saline injection resulted in the increase of plasma AVT level. The administration of a high dose (50 microg) of antisense ODN inhibited the increase of plasma AVT level induced by the hypertonic saline stimulation. Plasma levels of MT did not change with the administration of hypertonic saline or antisense ODN. These results suggest that the mechanisms that regulate the secretion of AVT from the neurohypophysis may be coupled to the mechanisms that regulate the synthesis of AVT.

Animals↗
PubMed2001

Assessment of tear concentrations on therapeutic drug monitoring. II. Pharmacokinetic analysis of valproic acid in guinea pig serum, cerebrospinal fluid, and tears.

PURPOSE: To quantitatively describe the pharmacokinetics of valproic acid (VPA) in guinea pig serum (total [Cf+b] and free [Cf]), cerebrospinal fluid (CSF) [C]CSF and tears [C]T using a simple kinetic model, and to examine whether [Cf] and [C]CSF can be predicted by [C]T using the resulting pharmacokinetic parameters. METHODS: [Cf+b], [Cf], [C]CSF and [C]T were determined after bolus i.v. injection of 10 or 20 mg/kg VPA using GC/ECNCI/MS. RESULTS: [Cf+b] could be quantitatively described by a two compartment model with linear elimination kinetics. [Cf] was separately analyzed using multi-exponential equations. [C]CSF was analyzed using a simple kinetic model in which the CSF compartment is independently connected with the serum compartment by the apparent diffusion constants (KINCSF and KOUTCSF). [C]T was analyzed using the same simple kinetic model used for [C]CSF. The values of [C]CSF and [Cf] in the steady state can be represented by the following equations; [C]CSF = KINCSF/KOUTCSF x [Cf], [Cf] = KOUT/KINT x [C]T, and indicating that [Cf] and [C]CSF can be predicted by [C]T using the resulting pharmacokinetic parameters. CONCLUSIONS: The measurement of [C]T which can be collected non-invasively and estimated the pharmacokinetic parameters for [Cf], [C]CSF, and [C]T might be a very useful method for TDM of VPA.

Animals↗
PubMed2001

Adeno-associated virus-mediated transfer of endothelial nitric oxide synthase gene inhibits protein synthesis of rat ventricular cardiomyocytes.

We investigated whether nitric oxide (NO) synthase gene transfer could attenuate growth of cultured cardiac myocytes. First, we investigated the effects of exogenous NO and cGMP analog on protein synthesis of cultured neonatal rat cardiac myocytes. The NO donor 3-morpholino-sydnonimine-hydrochloride (SIN-1) and 8-bromo-cGMP caused concentration-dependent decreases in phenylephrine-stimulated incorporation of 3H-leucine into cardiac myocytes. We then transferred endothelial constitutive NO synthase (ecNOS) gene into cultured neonatal rat cardiac myocytes using adeno-associated virus (AAV) vectors. ecNOS gene transfer into cardiac myocytes induced 140 kD ecNOS protein expression and significantly increased cGMP contents of myocytes compared with control cells. ecNOS gene transfer inhibited 3H-leucine incorporation into cardiac myocytes in response to phenylephrine, which was significantly recovered in the presence of the NOS inhibitor N(G)-monomethyl-L-arginine acetate. These results indicate that endogenously generated NO by ecNOS gene transfer using AAV vectors inhibits the alpha-adrenergic agonist-induced cardiac protein synthesis at least partially via cGMP production.

Adenoviridae↗
PubMed2001

Identification of lipids as the main component of skeletal muscle Z-discs.

The existence of lipids in Z-discs of the vertebrate skeletal muscle was suggested by the results of microscopy using rhodamine 6G reagent, a fluorescent probe. After removal of lipids by treatment of myofibrils with 0.5% Trition X-100, intact configurations of Z-filaments composed of alpha-actinin were clearly visible under an electron microscope. These findings indicated that lipids were amorphous-matrix materials of the Z-disc. Lipids were proved to be the main component of Z-discs by their extraction from I-Z-I brushes with a mixture of methanol and chloroform and by analysing them. The total amount of lipids in Z-discs exceeded that of alpha-actinin and varied from 2.4 to 7.1 g per 100 g of myofibrillar proteins depending on the phenotype of skeletal muscle. The sum of the amounts of lipids and alpha-actinin was 4.5 g per 100 g of myofibrillar proteins in chicken pectoralis profundus muscle (fast type), while it was 10.1 g in chicken soleus muscle (slow type). Lipid classes were phospholipids, triacylglycerols, cholesterol and free fatty acids. Since the lipids extracted from I-Z-I brushes were hardly contaminated with those from the sarcoplasmic reticulum and mitochondria, their amounts and classes were considered to be characteristic of Z-discs. The lipids probably cement neighbouring Z-filaments electrostatically, reinforce the Z-disc structure, and play an important role in the force transmission of skeletal muscle myofibrils.

Actinin↗
PubMed2001

Effects of long-acting ACE inhibitor (temocapril) and long-acting Ca channel blocker (amlodipine) on 24-h ambulatory BP in elderly hypertensive patients.

In a prospective randomised cross-over study, we compared the effects of ACE inhibitor temocapril and calcium channel blocker (CCB) amlodipine on ambulatory blood pressure in 59 asymptomatic elderly hypertensive patients (mean age 69 years). This study was performed in a cross-over fashion after a 2-week placebo period and 4 to 8 weeks each of treatment with temocapril and amlodipine. Of those 59 hypertensive patients, three patients with side effects and 10 patients whose office BPs did not achieve the target BPs were excluded, and the remaining 46 were analysed in this study: they consisted of 30 dippers, with a night time reduction in systolic BP (SBP) > or = 10% and 16 non-dippers, with reduction by < 10%. At the baseline, there were no significant differences in the office, 24-h or daytime BPs between the two groups (dippers and non-dippers). Though the office BPs and daytime BPs were successfully controlled to the same levels with both treatments and in both dipping groups, the antihypertensive effects were stronger with the CCB than with the ACE inhibitor in the night time and morning, especially in non-dippers. We conclude that even though office BPs were controlled successfully to almost the same levels, there is a possibility that these long-acting drugs have differential antihypertensive effects on night time and morning BPs among hypertensive patients with different night time BP dipping statuses.

Aged↗
PubMed2001

Embryological consideration of drainage of the left testicular vein into the ipsilateral renal vein: analysis of cases of a double inferior vena cava.

The right gonadal vein (GV=testicular vein in men, ovarian vein in women) usually drains into the inferior vena cava (IVC) while the left gonadal vein drains into the left renal vein (RV). This anatomical difference induces relatively weak haemodynamics in the left testicular vein (TV) and is considered to be a cause of a left varicocele. In textbooks on embryology, it has been documented that bilateral supracardinal veins (=origin of right and left IVC) and the subcardinal sinus (=origin of RVs and GVs) symmetrically develop during early embryogenesis. However, persistence and regression of the right and left supracardinal veins, respectively, results in drainage of the left GV into the ipsilateral RV. A double IVC (DIVC) commonly originates from a failure of disappearance of the left supracardinal vein. Although there have been a considerable number of case reports on DIVC, little attention has been paid to the anatomy of the left GV in such cases. We report here an autopsy case, a 72-year-old Japanese man, with a DIVC. This case belongs to type BC of McClure and Butler's classification. In this case, it was observed that the right TV drained into the confluence of the right IVC with the ipsilateral RV, while the left TV drained into the left RV in spite of the presence of the left IVC. This case indicates that the embryonic anastomosis point between the subcardinal sinus and the supracardinal vein on the left side is different from that on the right side. Statistical analysis of many case reports of DIVC also suggests that the bilateral supracardinal veins tend to asymmetrically anastomose with the subcardinal sinus during embryogenesis. These data imply that drainage of the left GV into the ipsilateral RV leads to regression of the left supracardinal vein but also to asymmetrical anastomosis between the supracardinal veins and the subcardinal sinus.

Aged↗