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Biomedical subjects

Y Takeuchi

Publications and source records attributed to Y Takeuchi.

At least 73 records · Page 4Linked to original sources

Neurons in the hilus region of the rat hippocampus are depleted in number by exposure to alcohol during early postnatal life.

We have previously shown that exposing rats to a relatively high dose of ethanol during early postnatal life resulted in a deficit in spatial learning ability. This ability is controlled, at least in part, by the hippocampal formation. The purpose of the present study was to determine whether exposure of rats to ethanol during early postnatal life affected the number of specific neurons in the hippocampus. Wistar rats were exposed to a relatively high daily dose of ethanol between postnatal days 10 and 15 by placing them for 3 h each day in a chamber containing ethanol vapor. The blood ethanol concentration was about 430 mg/dl at the end of the exposure period. Groups of ethanol-treated (ET) rats, separation controls (SC), and mother-reared controls (MRC) were anesthetized and killed at 16 days of age by perfusion with phosphate-buffered glutaraldehyde (2.5%). The Cavalieri principle was used to determine the volume of various subdivisions of the hippocampal formation (CA1, CA2+CA3, hilus, and granule cell layer), and the physical disector method was used to estimate the numerical densities of neurons within each subdivision. The total number of neurons was calculated by multiplying estimates of the numerical density with the volume. There were, on average, about 441,000 granule cells in the granule cell layer and 153,000 to 177,000 pyramidal cells in both the CA1 and CA2+CA3 regions in all three treatment groups. In the hilus region, ET rats had about 27,000 neuronal cells. This was significantly fewer than the average of 38,000 such neurons estimated to be present in both MRC and SC animals. Thus, neurons in the hilus region may be particularly vulnerable to the effects of a high dose of ethanol exposure during early postnatal life.

Animals↗

Antibody-regulated neurotoxic function of cell-surface beta-amyloid precursor protein.

APP is a transmembrane precursor of beta-amyloid, and its mutations cause early-onset familial Alzheimer's disease. We report a toxic function of normal wild-type APP (wtAPP). Treatment of neuronal F11 cells, immortalized embryonic day 13 neurons, overexpressing wtAPP with anti-APP antibodies caused death. Death was not induced by antibody in parental F11 cells. Death by antibody occurred through cell-surface APP, not through secreted APP, in a pertussis toxin-sensitive manner and was typical apoptosis, not observed in primary astrocytes or glioma cells overexpressing wtAPP, but observed in primary cortical neurons. Cell-surface APP thus performs a toxic function as an extracellularly controllable regulator of neuronal death. This study provides a novel insight into the normal and pathological functions of cell-surface wtAPP.

Alzheimer Disease↗

Continuous estimation of systolic blood pressure using the pulse arrival time and intermittent calibration.

A continuous noninvasive method of systolic blood pressure estimation is described. Systolic blood pressure is estimated by combining two separately obtained components: a higher frequency component obtained by extracting a specific frequency band of pulse arrival time and a lower frequency component obtained from the intermittently acquired systolic blood pressure measurements with an auscultatory or oscillometric system. The pulse arrival time was determined by the time interval from QRS apex in electrocardiogram to the onset of photoplethysmogram in a fingertip beat-by-beat via an oximetric sensor. The method was examined in 20 patients during cardiovascular surgery. The estimated values of systolic blood pressure were compared with those measured invasively using a radial arterial catheter. The results showed that the correlation coefficients between estimated values and invasively obtained systolic blood pressure reached 0.97 +/- 0.02 (mean +/- SD), and the error remained within +/- 10% in 97.8% of the monitoring period. By using a system with automatic cuff inflation and deflation to acquire intermittent systolic blood pressure values, this method can be applicable for the continuous noninvasive monitoring of systolic blood pressure.

Adolescent↗

Tricuspid valve replacement after cardiac transplantation.

Tricuspid regurgitation, a fairly common finding after cardiac transplantation, is generally mild or moderate, and is not clinically significant. The etiology of tricuspid regurgitation is not entirely understood, and experience with valve replacement after cardiac transplantation is limited. We describe a case of progressively severe tricuspid regurgitation ultimately requiring tricuspid valve replacement. At operation, the ruptured chordae of the posterior part of anterior and septal leaflet with resulting partially flail leaflets were found. Examination of the papillary muscle showed origins of several of the ruptured chordae. Damage to the tricuspid subvalvular apparatus at endomyocardial biopsy appeared to be a possible cause. A 31-mm Carpentier-Edwards porcine valve was implanted. This was because replacement with a mechanical prosthesis would prevent future right-side heart catheterization and endomyocardial biopsy and in valve repair, the patient remains exposed to the risk of the recurrence of chordal rupture. We discuss proposed causes and choices in surgical technique.

Adult↗

Technical aspects of venous stenting in high-grade stenoses using a long guidewire between dual venous access sites.

We describe the technical benefits of the dual-access technique for venous stenting in high-grade stenosis. Stents were implanted successfully with this technique in all patients, although the preceding transfemoral interventions had failed. The dual-access technique is useful to facilitate the intervention when the stenoses are too severe to place the stent through just a single access point.

Aged↗

Aberrant chloroplasts in transgenic rice plants expressing a high level of maize NADP-dependent malic enzyme.

NADP-dependent malic enzyme (NADP-ME) is a major decarboxylating enzyme in NADP-ME-type C4 species such as maize and Flaveria. In this study, chloroplastic NADP-ME was transferred to rice (Oryza sativa L.) using a chimeric gene composed of maize NADP-ME cDNA under the control of rice light-harvesting chlorophyll-a/b-binding protein (Cab) promoter. There was a 20- to 70-fold increase in the NADP-ME activity in leaves of transgenic rice compared to that in wild-type rice plants. Immunocytochemical studies by electron microscopy showed that maize NADP-ME was mostly localized in chloroplasts in transgenic rice plants, and that the chloroplasts were agranal without thylakoid stacking. Chlorophyll content and photosystem II activity were inversely correlated with the level of NADP-ME activity. These results suggest that aberrant chloroplasts in transgenic plants may be caused by excessive NADP-ME activity. Based on these results and the known fact that only bundle sheath cells of NADP-ME species, among all three C4 subgroups, have agranal chloroplasts, we postulate that a high level of chloroplastic NADP-ME activity could strongly affect the development of chloroplasts.

Chlorophyll↗

Characterization of pectin methyltransferase from soybean hypocotyls.

Pectin methyltransferase (PMT) catalyzing the transfer of the methyl group from S-adenosyl-L-methionine (SAM) to the C-6 carboxyl group of galactosyluronic acid residues in pectin was found in a membrane preparation of etiolated hypocotyls from 6-d-old soybean (Glycine max Merr.). The enzyme was maximally active at pH 6.8 and 35-40 degrees C, and required 0.5% (w/v) Triton X-100. The incorporation of the methyl group was significantly enhanced by addition of a pectin with a low (22%) degree of methyl-esterification (DE) as exogenous acceptor substrate. The apparent Michaelis constants for SAM and the pectin (DE22) were 0.23 mM and 66 microg x ml(-1), respectively. Attachment of the methyl group to the carboxyl group of the pectin via ester linkage was confirmed by analyzing radiolabeled product from incubation of the enzyme with [14C]methyl SAM and the acceptor pectin. Size-exclusion chromatography showed that both enzymatic hydrolysis with a pectin methylesterase and a mild alkali treatment (saponification) led to the release of radioactive methanol from the product. Enzymatic hydrolysis of the product with an endopolygalacturonase degraded it into small pectic fragments with low relative molecular mass, which also supports the idea that the methyl group is incorporated into the pectin. The soybean hypocotyls were fractionated into their cell wall components by successive extraction with water, EDTA, and alkali treatment. Among the resulting polysaccharide fractions, high PMT activity was observed when a de-esterified polysaccharide derived from the EDTA-soluble fraction (the pectic fraction) was added as an alternative acceptor substrate, indicating that the enzyme may be responsible for producing methyl-esterified pectin in vivo.

Cell Wall↗

Evaluation of autonomic nervous function during upper gastrointestinal endoscopy using heart rate variability.

To investigate autonomic nervous function during upper gastrointestinal endoscopy, we analyzed R-R interval variability from electrocardiograms obtained during endoscopy. Holter electrocardiogram recordings were made before and after premedication, and during endoscopy. Time- and frequency-domain analyses of heart rate variability were performed in 54 subjects premedicated with scopolamine butylbromide (SB group) and in 66 subjects premedicated with glucagon (G group). To determine the effect of autonomic imbalance on arrhythmia generation during endoscopy, subjects with arrhythmias (A group) were compared with subjects without arrhythmias (N group). In the SB group, high frequency spectral power (HF power; 0.15 to 0.40 Hz), which reflects parasympathetic activity, decreased significantly after premedication, and decreased further during endoscopy (P < 0.01). Moreover, HF power before premedication or during endoscopy in the A group was significantly lower than that in the N group (P < 0.01). This study suggests that the measurement of HF power prior to endoscopy can identify subjects with reduced HF power. This should allow the prevention of cardiovascular complications related to premedication and endoscope insertion.

Adult↗

Extensive lymphopenia due to apoptosis of uninfected lymphocytes in acute measles patients.

Infection with measles virus induces a transient immunosuppression, which occasionally results in fatal opportunistic infections. To obtain fundamental information about the mechanism, we examined peripheral blood mononuclear cells (PBMC) from acute measles patients aged from infants to 35 years old, obtained at various times from incubation periods to 103 days after onset of rash, for the number of lymphocyte subsets by flowcytometry. The data were analyzed for relationships between aging of the patients and the severity of immunosuppression. In classical measles cases, infected lymphocytes detected as a minor population during the incubation period disappeared soon after onset of rash, whereas in the cases of serious illness, the infected cells persisted longer after the rash. At the onset of rash, remarkable lymphopenia had already occurred in all measles cases with reduction in cell numbers of CD4+ T cells, CD8+ T cells, B cells, neutrophils, and monocytes. In contrast, natural killer (NK) cells were increased in number and activated, which might be a response compensatory for the lymphopenia. Apoptosis-associated molecules such as CD95(Fas) and TNF-related apoptosis-inducing ligand-receptor (TRAIL-R) were highly expressed on the cell surface of most surviving non-infected lymphocytes, and DNA fragmentation was also observed upon incubation in vitro. These results suggested that the profound lymphopenia was primarily due to extended death of non-infected blood cells caused by apoptosis. The severity and duration of the lumphopenia were age-dependent; less severe in young children whereas much severer in infants under one year of age as well as adolescents and adults. From these results, it was suggested that remarkable lymphopenia due to apoptosis of uninfected cells is one of the principal causes for immunosuppression induced by measles virus infection, and is correlated with the age-dependent severity of the disease.

Acute Disease↗

Twenty-two-year follow-up of saphenous vein grafts in pediatric Kawasaki disease.

We describe 2 Kawasaki disease patients with excellent long-term patency of saphenous vein grafts, who underwent coronary artery bypass at age 7 and 9 years, respectively, and demonstrated normal growth during 22 years of follow-up. The grafts showed no deterioration and played an important role in coronary blood supply.

Child↗

Lower sternal splitting approach for off-pump coronary artery bypass grafting.

There are several ways to revascularize coronary arteries without cardiopulmonary bypass using a minimally invasive method. Currently, one of the most commonly used methods is minimally invasive direct coronary artery bypass (MIDCAB) through a left thoracotomy. Using this technique, however, only the left anterior descending and diagonal branch can be grafted. This article describes coronary revascularization of the left anterior descending artery or right coronary artery, or both, via a lower ministernotomy without a transverse cut, namely, the lower sternal splitting method. Through this approach, the left anterior descending, diagonal, and right coronary arteries can be revascularized using a single, minimally invasive approach without the risk of damaging the tissue around the intercostal space when the sternum is transversely divided.

Aged↗

Alcohol enhances characteristic releases of dopamine and serotonin in the central nucleus of the amygdala.

The amygdaloid complex (AMY) is implicated in emotional and motivational aspects of behavior, including the formation of positive reinforcement association. AMY may also associated with brain rewarding circuitry. In the present study, the effect of ethanol (EtOH) on the release of dopamine (DA) and serotonin (5-HT) was studied in the central amygdaloid nucleus (CeAMY), and projecting excitatory afferents to the ventral tegmental area (VTA), of freely moving Wistar rats by brain microdialysis. Within 20 min of i.p. injection of EtOH (2 g/kg), the levels of DA and 5-HT in the CeAMY dialysate increased over the baseline value by 270 and 160% (N = 6-7), respectively. Addition of EtOH (25, 50 and 100 mM) to the microdialysis perfusion medium for 1 h caused a 115-150% dose-related increase in the extracellular level of DA in the CeAMY. 100 mM EtOH-induced CeAMY DA release continued to increase for 1 h after the perfusion medium was returned to normal perfusion medium. In contrast, the CeAMY 5-HT level was increased only by the addition of 100 mM EtOH for 1 h to 130% for 80 min. The stimulation of the CeAMY by EtOH through the microdialysis membrane showed delayed responses of DA and 5-HT compared with the i.p. injection of EtOH. Overall, the present findings are not sufficient to conclude whether EtOH acts directly or indirectly on the major monoamine nerve cells in the CeAMY, but the degree of acute EtOH action affected the differences in time at the peak response on EtOH-induced DA and 5-HT releases in the CeAMY via VTA.

3,4-Dihydroxyphenylacetic Acid↗

Putaminal necrosis presenting with hemidystonia.

A 7-year-old female presented with putaminal necrosis associated with hemidystonia. Cranial magnetic resonance imaging revealed bilateral putaminal lesions appearing as hypointense signals on T(1)-weighted images and hyperintense signals on T(2)-weighted images. After a differential diagnosis of basal ganglial degeneration was made, putaminal necrosis was diagnosed. Low doses of levodopa (0.5 mg/kg daily) were administered, but her clinical signs worsened. Positron emission tomography scanning with [(18)F]-6-fluoro-L-dopa revealed asymmetric uptake and right-sided dominant decreases of [(18)F]-6-fluoro-L-dopa uptake of the putamen. On the basis of these findings, standard doses of levodopa (10 mg/kg daily) were administered, and her clinical signs improved. These results suggest that hemidystonia is associated with a disturbance of the dopamine system.

Antiparkinson Agents↗

A monoclonal antibody-based enzyme-linked immunosorbent assay of ursodeoxycholic acid 3-sulfates in human urine.

Sulfation of the 3-hydroxy group is assumed to be a major metabolic route of ursodeoxycholic acid (UDCA) which is used for treating various hepatobiliary diseases. We have developed a sensitive enzyme-linked immunosorbent assay (ELISA) for determining the total amount of nonamidated, glycine- and taurine-amidated ursodeoxycholic acid 3-sulfates (UDCA 3-Suls) using a newly established monoclonal antibody. In this study, 12 kinds of antibody-secreting hybridoma clones were generated by a fusion experiment between P3/NS1/1-Ag4-1 myeloma cells and the spleen cells from a BALB/c or an A/J mouse which had been immunized with a conjugate of nonamidated UDCA 3-Sul and bovine serum albumin. One of the monoclonal antibodies, Ba-10 (gamma2a, kappa), had suitable binding properties for clinical application, which was group-specific to the UDCA 3-Suls, and showed negligible cross-reactivities with various related bile acids including potentially interfering compounds, namely, the unconjugated UDCA, UDCA 7-N-acetylglucosaminide, the 3-sulfates of cholic acid, chenodeoxycholic acid and deoxycholic acid. The antibody Ba-10 allowed us to develop a sensitive competitive ELISA system whose measurable range was approximately 2-200 pg per assay. A serial dilution study indicated that the ELISA enables the direct measurement of the UDCA 3-Suls in human urine before and after the administration of exogenous UDCA. The daily urinary excretion rate of UDCA 3-Suls from healthy male volunteers (n = 5) was determined to be a mean of 131 +/- 61.2 (SD) microgram as the nonamidated UDCA 3-Sul equivalent.

Animals↗

Vitamin K(2) inhibits adipogenesis, osteoclastogenesis, and ODF/RANK ligand expression in murine bone marrow cell cultures.

Several lines of evidence suggest that vitamin K has nutritional and pharmacological effects against bone loss. To clarify effects of vitamin K on bone marrow cells, which contains progenitors of both osteoblasts and osteoclasts, we examined mouse bone marrow cell cultures in the presence of vitamin K(1) (K1) and menatetrenone (MK4), a vitamin K(2) with four isoprene units. Treatment with MK4 but not K1 inhibited the formation of adipocytes and stimulated alkaline phosphatase activity, an early differentiation marker of osteoblast. Although nuclear receptor PPARgamma2 plays a pivotal role in adipogenesis, MK4 had no effects on the expression of PPARgamma2 mRNA and PPARgamma2-dependent transcriptional activity. MK4 inhibited the expression of osteoclast differentiation factor (ODF)/RANK ligand and the formation of osteoclast-like cells induced by 1,25-dihydroxyvitamin D(3). These results suggest that MK4 specifically influences differentiation and functions of bone marrow cells to inhibit adipogenesis and osteoclastogenesis. At the expense of adipogenesis, MK4 might stimulate osteoblastogenesis in bone marrow cells. Therefore, MK4 may favor bone metabolism to spare bone mass as a compound that modulates cellular differentiation and functions in bone marrow in addition to as a nutrient factor.

Adipocytes↗