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Biomedical subjects

M Sugawara

Publications and source records attributed to M Sugawara.

At least 73 records · Page 4Linked to original sources

Evaluation of agonist selectivity for the NMDA receptor ion channel in bilayer lipid membranes based on integrated single-channel currents.

A new method for evaluating chemical selectivity of agonists to activate the N-methyl-D-aspartate (NMDA) receptor was presented by using typical agonists NMDA, L-glutamate and (2S, 3R, 4S)-2-(carboxycyclopropyl)glycine (L-CCG-IV) and the mouse epsilon1/zeta1 NMDA receptor incorporated in bilayer lipid membranes (BLMs) as an illustrative example. The method was based on the magnitude of an agonist-induced integrated single-channel current corresponding to the number of total ions passed through the open channel. The very magnitudes of the integrated single-channel currents were compared with the different BLMs as a new measure of agonist selectivity. The epsilon1/zeta1 NMDA receptor was partially purified from Chinese hamster ovary (CHO) cells expressing the epsilon1/zeta1 NMDA receptor and incorporated in BLMs formed by the tip-dip method. The agonist-induced integrated single-channel currents were obtained at 50 microM agonist concentration, where the integrated current for NMDA was shown to reach its saturated value. The obtained integrated currents were found to be (4.5 +/- 0.55) x 10(-13) C/s for NMDA, (5.8 +/- 0.72) x 10(-13) C/s for L-glutamate and (6.6 +/- 0.61) x 10(-13) C/s for L-CCG-IV, respectively. These results suggest that the agonist selectivity in terms of the total ion flux through the single epsilon1/zeta1 NMDA receptor is in the order of L-CCG-IV approximately = L-glutamate > NMDA.

Amino Acids, Dicarboxylic↗

Early mutation of precore (A1896) region prior to core promoter region mutation leads to decrease of HBV replication and remission of hepatic inflammation.

To evaluate the relationship between mutations and clinical courses, we investigated precore (preC) and core promoter (CP) mutations and serum HBV DNA levels in HBe-antibody-positive HBV carriers. Fifty-six asymptomatic carriers (ASC), 29 patients with chronic hepatitis who showed normal ALT levels for more than two years (CH-ASC), 31 patients with chronic hepatitis (CH), and 32 patients with hepatocellular carcinoma (HCC) were studied. Almost all patients (99.2%) had mutations in either CP or preC. Mutation only in preC (A1896) was present in 52.2% with ASC, 25.0% with CH-ASC, 16.1% with CH, and 8.0% with HCC, and was significantly higher in ASC (P < 0.01). The patients with only preC mutation showed low HBV DNA levels in each clinical stage. The mutation of preC (A1896) prior to the mutation of CP might control the replication of HBV, which leads to the remission of hepatitis.

Adult↗

Cardiac strangulation in a neonatal case: a rare complication of permanent epicardial pacemaker leads.

A newborn female underwent pacemaker implantation with epicardial pacing leads for the treatment of bradycardia caused by congenital atrioventricular block. At 10 months after pacemaker implantation, she was admitted with congestive heart failure. The epicardial leads were seen to encircle the heart, and myocardial ischemia was suggested. During cardiac catheterization she collapsed: emergency operation was performed, but she died on postoperative day 6.

Bradycardia↗

Effect of turgor pressure on outer hair cell motility.

The motor in the outer hair cell converts electrical energy directly into mechanical energy. There are two possible mechanisms for such a motor: one depends on changes in the membrane area ("area motor") and the other on changes in the stiffness ("stiffness motor"). These two mechanisms, which are not mutually exclusive, give different predictions on turgor pressure dependence of the amplitude. It was found that an increased pressure shifts the voltage dependence but does not change the amplitude of length changes. This observation is incompatible with a pure stiffness motor model. It was also confirmed that length changes are closely related to charge movements by monitoring the membrane capacitance. It can be concluded that hair cell motility is primarily based on area changes, and not changes in the elastic moduli.

Animals↗

Pontine atrophy in spinocerebellar ataxia type 6.

To investigate the clinical range of spinocerebellar ataxia type 6 (SCA6), we screened CAG repeat expansion in the voltage-dependent alpha 1A calcium channel gene (CACNL1A4) in 71 ataxic patients in 60 families; 54 patients in 43 families with hereditary ataxia and 17 sporadic patients. Thirteen patients with SCA6 were detected to have elongated CAG in CACNL1A4. Of these, 7 patients had been diagnosed as having hereditary cerebellar cortical atrophy, and 6 patients had been found to have sporadic occurrence. One patient showed distinct pontine atrophy with prominent horizontal or oblique gaze nystagmus which is an unusual feature in sporadic olivopontocerebellar atrophy. For the efficient screening of SCA6, we would propose testing CAG repeat expansion in CACNL1A4, in patients with one of two markers: (1) horizontal or oblique gaze nystagmus without other eye movement disorders, (2) pure cerebellar atrophy, even if occurrence is sporadic. We should note that the pontine atrophy could also be caused by CAG repeat expansion in CACNL1A4.

Adult↗

Crude protein content and amino acid composition in Taiwanese human milk.

Breast milk provides the essential nutrients for infants in readily available form. The content of nitrogen in human milk is of great importance because it relates to the growth of infants in the early stage, and the composition of nitrogenated compounds varies according to the lactational stage. Three-hundred-and-three human milk specimens were obtained from 240 healthy mothers living in two different districts in Taiwan, and 264 specimens were used for the analysis. The crude protein content, total and free amino acid compositions as well as urea content were evaluated using pooled milk samples according to different lactational stages and geographical location. The crude protein content decreased sharply from colostrum (2.51 g/100 mL) to mature milk (1.25 g/100 mL). Total amino acids account for 80-85% of the crude protein throughout the whole lactation period. Crude protein also contained 30 to 35 mg/ 100 mL urea and 41 to 48 mg/ 100 mL free amino acids as non-protein nitrogen components. The ratio of essential to non-essential amino acids remained constant throughout the lactation period in spite of a decline in amino acid content. The amino acid composition per 1 g of nitrogen varied during the lactation period. The differences of these lactational changing patterns of individual amino acids were probably reflected by variation of the protein composition during lactation. The sum of free amino acid content ranged from 43 to 50 mg/100 mL in Taipei and 40 to 45 mg/100 ml, in Kaohsiung. Although the variations of free amino acids during the lactation period differed among amino acids, glutamic acid predominated in mature milk while phosphoethanolamine was predominant in colostrum.

Adult↗

An improved genetic linkage map of rat chromosome 20.

BACKGROUND AND PURPOSE: Rat chromosome 20 is one of special interest because it contains some diabetogenic genes, such as a major histocompatibilitiy complex (MHC)-linked genetic components and quantitative trait loci. We studied rat chromosome 20, using the backcross progeny between BB/Wor and PVG.R23 rats, and confirmed the genetic linkage map by use of another backcross panel. METHODS: Backcross panels were done between BB/Wor and PVG.R23 rats, and BN and KZC rats. Length variations of simple sequence length polymorphism markers were analyzed by use of polymerase chain reaction (PCR) analysis. Alleles of RT1-Bb and RT1-Db were analyzed by use of the PCR-restriction fragment length polymorphism method. Genetic maps of rat chromosome 20 were constructed, using the Map Manager computer program. RESULTS: Fifty-two loci were mapped on rat chromosome 20. Genetic length was 57.9 cM, with average spanning of 1.11 cM between markers. The positions of RT1-N1, Tnf, and RT1-Bb into the MHC region were separated and confirmed by results of two backcross panels in our linkage studies. CONCLUSIONS: The genetic linkage map of rat chromosome 20 was improved, and was a useful tool for genetic analysis of a diabetogenic gene(s) and for producing MHC congenic strains.

Animals↗

Gnathostomiasis possibly caused by Gnathostoma malaysiae.

Gnathostomiasis is rarely reported in travelers, although the disease remains a major public health problem in Southeast Asia. A creeping eruption and Quincke's edema (slowly migrating erythema with pruritus) appeared in two Japanese men who had eaten raw freshwater shrimp in Myanmar. A Gnathostoma larva was found in subcutaneous tissue from one of the men. Four species causing human gnathostomiasis, G. hispidum, G. doloresi, G. nipponicum and G. spinigerum, can be distinguished based on the number of nuclei in intestinal epithelial cells of infected larvae, in cross-section. In G. hispidum, only a single large nucleus is found. Morphologically, our larva was initially identified as G. hispidum. However, since the number of epithelial cells was greater and the body width was larger than those of a "large-type" 3rd-stage larva of G. hispidum, the larva was then identified as a 3rd-stage larva of G. malaysiae, Miyazaki and Dun, 1965, as reported by Setasuban et al, (1991). Since no human cases caused by this species of Gnathostoma have previously been encountered, this appears to be the first report of gnathostomiasis due to G. malaysiae.

Animals↗

CDC45 and DPB11 are required for processive DNA replication and resistance to DNA topoisomerase I-mediated DNA damage.

The antitumor agent camptothecin targets DNA topoisomerase I by reversibly stabilizing a covalent enzyme-DNA intermediate. The subsequent collision of DNA replication forks with these drug-enzyme-DNA complexes produces the cytotoxic DNA lesions that signal cell cycle arrest and ultimately lead to cell death. Despite intense investigation, the character of the lesions produced and the repair processes that resolve the damage remain poorly defined. A yeast genetic screen was implemented to isolate conditional mutants with enhanced sensitivity to DNA topoisomerase I-mediated DNA damage. Cells exhibiting temperature-sensitive growth in the presence of the DNA topoisomerase I mutant, Top1T722Ap, were selected. Substitution of Ala for Thr722 increases the stability of the covalent Top1T722Ap-DNA intermediate, mimicking the cytotoxic action of camptothecin. Two mutants isolated, cdc45-10 and dpb11-10, exhibited specific defects in DNA replication and a synthetic lethal phenotype in the absence of DNA damaging agents. The accumulation of Okazaki fragments under nonpermissive conditions suggests a common function in promoting processive DNA replication through polymerase switching. These results provide a mechanistic basis for understanding the cellular processes involved in the resolution of DNA damage induced by camptothecin and DNA topoisomerase I.

Camptothecin↗

Effects of phosphatidylcholine/phosphatidylethanolamine composition in cholesteryl ester-micellar substrates on neutral cholesterol esterase activity.

The effect of phospholipid composition in cholesteryl ester (CE)-micellar substrates on neutral cholesterol esterase (N-CEase) activity was examined. N-CEase preparation was incubated with micelles composed of cholesteryl-[1-14C]-oleate, sodium taurocholate, and phosphatidylcholine (PC)/phosphatidylethanolamine (PE) at varying ratios (%PE:0 = PC only, 17, 33, 50, 66, 83). The activity increased dependently with the increase in PE content; the activity with the micelles containing the highest ratio of PE was 2.5-fold compared with the micelles consisting of PC only. Vmax with the micelles of 83, 66, and 50% PE was 3.1-, 2.7-, and 1.9-fold, respectively, compared with the micelles of PC only. Each micellar preparation was chromatographed through a Superose 6 column by the FPLC system. In 66 and 83% PE-containing micelles, PC, PE, CE, and part of sodium taurocholate eluted completely together in a single peak, whereas in micelles with 33 and 50% PE they eluted loosely together. The micelles with PC only or 17% PE formed PC-micelles without including CE and PE. It is concluded that PE plays a critical role in the formation of CE micelles with PC, and in the interaction with N-CEase. The CE-micelles with 66-83% PE serve as substrates for sensitive and reproducible N-CEase assay.

Adipose Tissue↗

Structures of mouse Rep-8 cDNA and genomic clones.

A mouse homologue of the human Rep-8 gene was cloned by PCR methods using degenerate oligonucleotide primers corresponding to highly conserved regions between human and mouse genes, and by the Marathon-Ready cDNA amplification method. The full-length mouse Rep-8 contains 1422 nucleotides and codes for a protein of 277 amino acids with a calculated mol. wt. of 31,519. The overall amino acid sequence homology between mouse and human Rep-8 proteins was 73%, and the overall nucleic acid sequence similarity was 65%. The predicted amino acid sequence of mouse Rep-8 has leucine zipper-like motifs in the N-terminal region, similar to the human Rep-8 protein. Rep-8 exists as a single-copy gene and is expressed in both the early and late embryonic stages of mouse development, suggesting that the Rep-8 gene product has an important role in embryogenesis. The genomic structure of the mouse Rep-8 gene was characterized extensively so that a gene targeting strategy could be used to develop an understanding of the biological function(s) of this interesting gene and its product.

Amino Acid Sequence↗

Longitudinal relationship between maternal depression and infant temperament in a Japanese population.

To investigate the relationship between maternal depression and infant temperament in a Japanese population, a prospective questionnaire survey was administered in the postpartum period. Postnatal depression was assessed by Zung's (1965) Self-Rating Depression Scale on two occasions (5 days and 12 months after delivery). At 6 months and 18 months after birth, infant temperament was assessed using the Revised Infant Temperament Questionnaire (RITQ; Carey & McDevitt, 1978) and the Toddler Temperament Scale (TTS; Fullward, McDevitt, & Carey, 1984), respectively. Of the five temperamental dimensions of the RITQ and TTS, "rhythmicity" and "attention span and persistence" showed reciprocal relationships with postnatal depression. Unidirectional effects of maternal depression on infant temperament were found for "frustration tolerance" and "fear of strangers and strange situations."

Adolescent↗

An equation to predict the changes in peak left ventricular pressure in hypertrophic obstructive cardiomyopathy after treatment: application to the administration of disopyramide.

A theoretical equation was derived based on the time-varying elastance model to predict theoretically the relationship between the delay in the onset of left ventricular outflow obstruction and the reduction in peak left ventricular pressure (LVP) caused by treatment in hypertrophic obstructive cardiomyopathy (HOCM). ECG, LVP, and other hemodynamic parameters were measured during catheterization at a constant heart rate with atrial pacing in 16 patients with HOCM before and after intravenous administration of disopyramide (1 mg/kg). After disopyramide administration, the duration between the R wave of the ECG and the onset of obstruction (T1) was prolonged significantly (from 117 +/- 30 to 155 +/- 32 ms, P < 0.0001), and peak LVP was reduced significantly (from 222 +/- 42 to 177 +/- 39 mmHg, P < 0.0001). The relation between the prolongation of T1 and the percent reduction in peak LVP was predicted well by the theoretical equation (coefficient of determination R2 = 0.926). Our model simplifies the therapeutic strategy for reducing the left ventricular outflow pressure gradient in patients with HOCM, which is to delay the time of onset of obstruction by some methods.

Adult↗

A noninvasive method of measuring wave intensity, a new hemodynamic index: application to the carotid artery in patients with mitral regurgitation before and after surgery.

Wave intensity (WI) is a new hemodynamic index, which is defined as (dP/dt)(dU/dt) at any site of the circulation, where dP/dt and dU/dt are the time derivatives of blood pressure and velocity, respectively. Arterial WI in normal subjects has two positive sharp peaks. The first peak occurs during early systole when a forward-traveling compression wave is generated by the left ventricle. The magnitude of this peak increases markedly with an increase in cardiac contractility. The second peak, which occurs towards the end of systole, is caused by generation of a forward-traveling expansion wave by the ability of the left ventricle to actively stop aortic blood flow. The interval between the R wave of the ECG and the first peak of WI (R-1st peak interval) and the interval between the first and second peaks (1st-2nd interval) are approximately equal to the preejection period and left ventricular ejection time, respectively. Using a combined Doppler and echo-tracking system, we obtained carotid arterial WI noninvasively. We examined the characteristics of WI in 11 patients with mitral regurgitation (MR) before and after surgery, and 24 normal volunteers. In the MR group before surgery, the second peak was decreased and the (1st-2nd interval)/(R-R interval) ratio was reduced, compared with the normal group (140 +/- 130 vs 750 +/- 290mmHg m/s3. P < 0.0083; 20.7% +/- 3.4% vs 26.7% +/- 2.8%, P < 0.083). There were no significant differences in the first peak between the normal group and the MR group before and after surgery. The second peak in the MR group was increased significantly (P < 0.016 vs before surgery) to 1,150 +/- 830mmHg m/s3 in the early period after surgery (stage I), and to 1,090 +/- 580mmHgm/s3 in the late period after surgery (stage II). These values did not differ significantly from that of the normal group. At stage I, the (R-1st peak interval)/ (R-R interval) ratio was increased from 13.4% +/- 2.7% to 20.6% +/- 5.6% (P < 0.016 vs before surgery). At stage II, this ratio decreased to 16.2% +/- 2.8% (P < 0.016 vs stage I). but was still significantly higher than that before surgery. The (1st-2nd interval)/(R-R interval) ratio increased significantly after surgery (P < 0.016 vs before surgery) to values (27.0% +/- 4.5% at stage I and 28.9% +/- 2.6% at stage II) which did not differ significantly from that of the normal group. The recovery of the second peak after surgery suggests that the left ventricle had recovered the ability to actively stop aortic blood flow. Wave intensity is useful for analyzing changes in the working condition of the heart.

Adult↗

Experimental application of microwave tissue coagulation to ventricular myocardium.

BACKGROUND: It is difficult to create transmural lesions in a beating, normothermic perfused heart. The aim of this study was to evaluate the effect of microwave tissue coagulation on a beating heart. METHOD: We used a microwave tissue coagulator that emits microwaves of 2,450 MHz. Studies were conducted on 30 mongrel dogs weighing between 9 and 13 kg, and microwave tissue coagulation was performed at the free wall of the left ventricle in a beating heart without cardiopulmonary bypass. RESULTS: Microwave tissue coagulation created transmural degenerated lesions in the left ventricle without risk of ventricular rupture. The lesion width of microwave ablation increased from 10 to 60 seconds. Histologic examinations revealed well-demarcated areas of heat degeneration consisting of coagulation necrosis and contraction band necrosis of the myocardium. The lesion healed to hard scar tissue, which was sharply demarcated from the normal myocardium. No animals had inducible ventricular tachycardia through programmed ventricular stimulation. CONCLUSIONS: Microwave ablation with a monopolar antenna created transmural lesions with only a few proarrhythmic events occurring during ablation.

Animals↗

Biocompatibility of a silicone-coated polypropylene hollow fiber oxygenator in an in vitro model.

BACKGROUND: A silicone-coated microporous hollow-fiber membrane oxygenator has been developed to prevent plasma leakage during long-term use. The objective of this study was to evaluate the biocompatibility of the oxygenator. METHODS: A silicone-coated oxygenator was compared with an uncoated oxygenator in an in vitro model of cardiopulmonary bypass. Simulated circulation was maintained for 6 h at 37 degrees C. RESULTS: Platelet counts decreased significantly (p < 0.05) and leukocyte counts tended to decline; however, the differences between groups were not significant. Concentrations of C3a increased significantly in both groups (p < 0.05), but levels were significantly less in the silicone-coated oxygenator (p = 0.008). In contrast, concentrations of C4a, beta-thromboglobulin, and granulocyte elastase increased significantly (p < 0.05), but the differences between groups were not significant. CONCLUSIONS: Silicone coating over a microporous hollow-fiber membrane may improve biocompatibility by reducing C3a activation.

Coated Materials, Biocompatible↗

Structure of depressive symptoms in pregnancy and the postpartum period.

BACKGROUND: The present study investigated the structure of depressive symptoms in the perinatal period. METHOD: The Zung Self-Rating Depression Scale (SDS) was administered to a total of 1329 women in early, middle and late pregnancy and 5 days, 1 month, 6 months, 12 months and 18 months after the delivery. RESULTS: A number of somatic items and the suicidal ideation item of the SDS made low contributions to the evaluation of the severity of depression, and as a consequence these were excluded in the principal component analysis. Three factors were interpretable as "Cognitive", "Affective insomnia" and "Attentional" emerged at all eight assessment points. The goodness-of-fit index (GFI) generated by confirmatory factor analyses (LISREL 7.20) proved sufficiently high on all eight occasions. LIMITATION: The present study investigated only one self-rating scale and the sample comprised Japanese mothers only. CONCLUSION: The three-factor model of the SDS in the perinatal period was derived from exploratory and confirmatory factor analyses. It is noteworthy that the same three-factor structure emerged at all eight collection points in the present study.

Adolescent↗