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Biomedical subjects

Y Matsuda

Publications and source records attributed to Y Matsuda.

At least 559 records · Page 31Linked to original sources

A novel skeletal drug delivery system using self-setting calcium phosphate cement. 7. Effect of biological factors on indomethacin release from the cement loaded on bovine bone.

The use of self-setting bioactive calcium phosphate cement containing indomethacin as a model drug in bovine bone was investigated by means of an in vitro drug release test, mercury porosimetry, and scanning electron microscopy (SEM). Calcium phosphate cements containing 2 and 5% indomethacin after being mixed with dilute phosphoric acid were applied to defect sites and the medullary cavity of bovine bone and transformed into hydroxyapatite. The in vitro drug release from the cement loaded on the defect site into a simulated body fluid (SBF) containing 2.5 mM Ca2+ and 1.0 mM HPO4(2+) or 0.1 M phosphate buffer at pH 7.25 and 37 degrees C continued for more than 3 weeks. The release profiles of the drug-loaded cements in phosphate buffer were linear using the Higuchi plot; however, that was not the case for SBF. The drug release in SBF was much lower than that in phosphate buffer. The total pore volume of the cement after the drug release test in SBF was lower than its initial value. However, the pore size of 0.1-0.01 microns after drug release in phosphate buffer was higher than that seen in SBF. The micropore distribution results suggested that hydroxyapatite crystallized from SBF and the pore volume in the cement decreased after drug release. However, in phosphate buffer it appeared to dissolve. The SEM observations for cements loaded on the bone after drug release in phosphate buffer suggested that there was a boundary layer between the cement and natural bone, but this was not the case in SBF, where the cement bonded with the natural bone. The drug release rates from the cement-loaded bone were significantly higher than those from cement loaded on the dissolution holder. The results suggested that cement formation and drug release were affected by the presence of protein from natural bone. The drug release rates from the cement loaded on the defective bone were slower than those from the medullary cavity.

Animals↗

Interspecific backcrosses provide an important new tool for centromere mapping of mouse chromosomes.

Centromere mapping of mouse chromosomes has been problematic due to a paucity of appropriate markers. As a result, the mapping of centromeres has most often relied on the use of Robertsonian chromosomes to mark chromosome ends. Many Robertsonian translocations have been shown to suppress recombination in pericentric regions; therefore, centromere mapping data generated by using Robertsonian chromosomes must be interpreted with caution. We have utilized a new tool for centromere mapping that is applicable to all mouse chromosomes (except the Y chromosome) and that potentially overcomes the inherent limitations of using Robertsonian translocations. Briefly, an interspecific backcross mapping panel was constructed from crosses of C57BL/6Ros and Mus spretus mice. The centromere of each chromosome was subsequently typed by in situ hybridization, using a major satellite probe that uniformly labels C57BL/6Ros centromeres but hybridizes only weakly to M. spretus centromeres. Genetic markers that were already known to map in the proximal region of each of the mouse chromosomes were then typed by segregation analyses of restriction fragment length polymorphisms. These studies have made it possible to align the interspecific genetic map of each of the mouse autosomes and the X chromosome with respect to the centromere. They also provide a basis for comparison with centromere mapping data generated previously by other means.

Animals↗

Spot mapping on the standard profile of restriction landmark genomic scanning (RLGS) of sorted chromosome 20 using methylation-insensitive enzyme.

We established the spot mapping system on a restriction landmark genomic scanning (RLGS) profile using sorted chromosome as RLGS material. In this mapping system, we can mapped RLGS spots physically, regardless of their polymorphism, using methylation-insensitive enzymes in all RLGS steps. Here, we report that we identified 28 spots derived from human chromosome 20 on an RLGS profile, and that number was in good agreement with the number predicted from the length of the chromosome 20.

Cell Line↗

Characterization of three different transgenic mouse lines that carry human poliovirus receptor gene--influence of the transgene expression on pathogenesis.

Three transgenic mouse lines, ICR-PVRTg1, ICR-PVRTg5, and ICR-PVRTg21, which are susceptible to poliovirus, have been established by introducing the human gene for poliovirus receptor (PVR) into the genome of mouse strain ICR. Genetic characterizations of the PVR gene were carried out on these mouse lines to define the approximate copy number, insertion site, and expression of the transgene in the central nervous system (CNS). The transgene was integrated in the chromosome 4, 12, and 13 of ICR-PVRTg1, ICR-PVRTg5 and ICR-PVRTg21 mice, respectively, and was stably transmitted to progeny mice. ICR-PVRTg1 appeared to have the most abundant copy numbers of the transgene and showed the highest level of PVR mRNA and membrane associated PVR protein in the CNS among the three mouse lines. Those in ICR-PVRTg21 and ICR-PVRTg5 were at intermediate and lowest levels, respectively. In the CNS, PVR mRNA was detected at high levels only in neurons of the spinal cord and brain stem where poliovirus can replicate, suggesting that the PVR mRNA expression confers cell specificity to poliovirus in the CNS. ICR-PVRTg1 and ICR-PVRTg5 showed the highest and the lowest sensitivity to poliovirus, respectively, whereas ICR-PVRTg21 was in-between. These results may suggest that poliovirus sensitivity of the mice is attributed to relative levels of PVR expression.

Animals↗

Aspartate aminotransferase-linked immunoglobulin complexes in serum of a patient with primary biliary cirrhosis.

A 51-year-old woman who had been treated for primary biliary cirrhosis (PBC) was admitted to our hospital for evaluation of unexplained, isolated, persistently increased aspartate aminotransferase (AST) activity. Results of laboratory tests on admission showed: AST 171 KU, alanine aminotransferase 28 KU, and anti-mitochondrial titer 1/1280. Results of hepatitis B surface antigen (HBs Ag) and hepatitis C virus antibody (HCV Ab; C100-3) assays were negative. Histology of a liver biopsy specimen was compatible with a diagnosis of PBC (stage III of Scheuer's classification). The molecular size of serum AST was estimated to be more than 500,000 by high-performance size-exclusion liquid chromatography. Electrophoretic analysis showed an abnormal band of AST between supernatant AST (sAST) and mitochondrial AST (mAST), which band was characteristic of AST-immunoglobulin complexes (AST-Ig). Ouchterlony double-diffusion and immunoprecipitation tests identified the immunoglobulin component as IgM. The presence of AST-Ig appeared to be responsible for the elevated serum AST.

Aspartate Aminotransferases↗

Left ventricular motion after bypass operation for coronary artery disease with collaterals.

Left ventricular ejection changes obtained from left ventricle roentgenograms were analyzed before and after coronary artery bypass grafting in 22 consecutive patients with chronic obstructive left anterior descending coronary artery disease receiving collaterals before surgical revascularization. The collateral vessels all disappeared after surgical revascularization. After operation, ejection changes of anterobasal, anterolateral and apical walls supplied by the left anterior descending coronary artery improved from 43.6% +/- 9.7% to 48.5% +/- 8.6% (p < 0.05), from 35.2% +/- 10.9% to 39.4% +/- 9.5% (p < 0.05), and from 46.0% +/- 10.6% to 50.0% +/- 8.7% (p < 0.05), respectively. The improvement in left ventricular wall motion did not appear to be related to the extent of preoperative collateralization. Thus, left ventricular wall motion was impaired in the area supplied by collaterals and was improved by myocardial revascularization. These results suggest that coronary blood flow, even through well-developed collaterals, may not be sufficient, which may produce chronic active ischemia and impaired left ventricular wall motion.

Aged↗

A family of McLeod syndrome, masquerading as chorea-acanthocytosis.

A man, aged 52, is reported to show (1) adult onset, (2) progressive orofacial dyskinesia and choreic movements of the extremities, (3) tongue biting, (4) denervation of the peripheral nerves, (5) acanthocytosis, and (6) increased serum creatine kinase, which are characteristic of chorea-acanthocytosis. The Kell blood group examination on erythrocytes disclosed that the propositus had McLeod phenotype, and his mother and one of his sisters were carriers of the McLeod phenotype. Thus, he was diagnosed as having McLeod syndrome. A criterion of exclusion of McLeod phenotype on erythrocytes should be added to the diagnostic criteria of chorea-acanthocytosis. Moreover, chronic neurogenic changes instead of myogenic changes were electromyographically and histopathologically verified in the muscle.

Acanthocytes↗

Do patients with Down's syndrome recognize Mickey Mouse?

In 47 patients with Down's syndrome who were too retarded to understand a conventional oddball paradigm, we studied event-related potentials (ERPs) by using task-irrelevant visual stimuli. As the patients had expressed interest in Disney cartoons and books, five pictures of Disney characters such as Mickey Mouse or Peter Pan were employed as the rare stimuli, and nine ordinary scenes such as mountains as the frequent stimuli. Five sets were constructed by intermingling each rare picture with nine frequent pictures, and each picture was presented on a TV screen. ERPs to the rare stimuli (N270-P380), which were different from the averaged waveforms to frequent stimuli and electrooculograms (EOGs), were clearly recorded in 35 out of 47 patients. Only 24 of these patients had ERPs using a conventional auditory oddball paradigm. The peak latencies in patients were significantly prolonged relative to age-matched normal controls, probably due to a slowed neural processing. The amplitude in patients was slightly larger than normal controls, probably due to the patients' greater interest or surprise when confronted with the Disney characters.

Adolescent↗

Myosin II is involved in transmitter release at synapses formed between rat sympathetic neurons in culture.

The presynaptic function of myosin II was studied at cholinergic synapses formed between rat superior cervical ganglion neurons in culture. Immunofluorescent staining showed that myosin II was colocalized with synaptophysin at the presynaptic nerve terminals. Antimyosin II antibody introduced into presynaptic neurons inhibited synaptic transmission. Transmission was also inhibited in a dose-dependent manner by two inhibitors of myosin light chain kinase: a peptide, SM-1, and an organic inhibitor, wortmannin. The inhibition produced by these agents was dependent on presynaptic activity. Extracellularly applied wortmannin also blocked synaptic transmission, but its effects were slower in onset. Wortmannin also decreased postsynaptic potentials and post-tetanic potentiation in intact superior cervical ganglia. These results suggest a model in which myosin light chain kinase phosphorylates myosin, and the resultant change in actin-myosin interactions is involved in neurotransmitter release.

Acetylcholine↗

Neuropathology of the near-term and midgestation ovine fetal brain after sustained in utero hypoxemia.

OBJECTIVE: The neuropathologic mechanisms of the ovine fetal brain in response to several hours of sustained hypoxemia with variable degrees of metabolic acidemia was investigated in both the preterm and near-term ovine fetus. STUDY DESIGN: Three groups of fetuses were studied in each of the near-term and midgestation groups: a hypoxic group, a control group, and an uninstrumented control group. Histopathologic studies were performed after a 40-hour recovery period after experimentation. RESULTS: Pathologic findings consisted of predominately white matter damage with some adjacent cortical necrosis but no selective neuronal injury. In the near-term group the hypoxia group fetuses demonstrated significantly higher white matter injury scores than did control group fetuses (p < 0.05). Periventricular white matter injury was the predominant pattern seen in the midgestation group. CONCLUSIONS: In spite of normalization of biophysical and biochemical parameters after hypoxemia both midgestation and near-term fetuses sustained pathologic changes. Presence or extent of injury did not correlate with the degree of hypoxemia or metabolic acidosis achieved.

Acidosis↗

Recovery of the ovine fetus from sustained hypoxia: effects on endocrine, cardiovascular, and biophysical activity.

OBJECTIVE: The purpose of this study was (1) to determine the ability of the ovine fetus to recover from a self-limiting asphyxial insult and (2) to monitor cardiovascular and biophysical activity as potential markers of such an insult or underlying neurologic impairment. STUDY DESIGN: Nineteen fetal sheep were studied (12 hypoxia and 7 control) at 0.9 of gestation during a 24-hour control period, up to 8 hours of either sustained hypoxemia or room air, and for a 40-hour recovery period. Fetal heart rate, blood pressure, electrocortical activity, electroocular activity, and breathing movements were monitored continuously. Fetal arterial blood was sampled at set times for blood gases, pH, lactate, and catecholamine levels. RESULT: Induced fetal hypoxemia resulted in a lactic metabolic acidosis that progressively worsened, with death occurring in three of the animals during the early recovery period. The remaining animals showed a rapid metabolic and endocrine normalization of values by 24 hours. Fetal cardiovascular and biophysical measurements likewise returned to control values during the early recovery period, although three animals had seizure-like activity. CONCLUSION: The near-term ovine fetus surviving a sustained asphyxial insult sufficient to induce neuropathologic change within the brain demonstrates a normalization of biophysical activity during the early period of recovery, although seizure-like activity may subsequently be evident.

Animals↗

Controlled drug release of highly water-soluble pentoxifylline from time-limit disintegration-type wax matrix tablets.

A pulsatile drug release system with a dry-coated tablet containing pentoxifylline was investigated for controlling drug release in the gastrointestinal tract. The system consisted of a core tablet with disintegrator and outer layer, which obtained compression from the ground mixtures of pentoxifylline and behenic acid. Drug release from a dry-coated tablet was investigated at 37 degrees C in JPXII 2nd fluid at pH 6.8. The drug release from the outer layer was fitted to the Cobby model. The drug release from the wax matrix increased significantly after tablet distintegration; therefore, the drug release profiles showed typical sigmoidal curves. The disintegration time depended on the weight fraction of the core tablet, and the drug release rate after disintegration increased with increasing drug concentration in the core tablet. The relationship between the time required for 50% drug release and the disintegration time was linear, indicating that the drug release rate was controlled by regulating the disintegration time.

Delayed-Action Preparations↗

Chemical stability of ethyl icosapentate against autoxidation. II. Effect of photoirradiation on oxidation kinetics.

The effect of ultraviolet (UV) or visible light (VIS) irradiation on the chemical stability of ethyl icosapentate [ethyl-(all-cis)-5,8,11,14,17-icosapentaenoate] (EPA) was investigated at 45 degrees C by means of HPLC and by measuring the peroxide value (POV). EPA was oxidized to peroxides after an induction period by photoirradiation, and the peroxide subsequently degraded to secondary products. The autoxidation of EPA followed consecutive reaction kinetics including an induction period, and the kinetic parameters of the oxidation were calculated based upon the consecutive reaction model by computer curve fitting. The results of the degradation rate constant, k, and the induction period obtained by HPLC showed that the radical and the peroxide formation rates are affected by UV, but not by VIS light irradiation. The formation rate constant of peroxide, k1, and its degradation rate constant to secondary products, k2, obtained from the POV under UV light irradiation, increased with irradiation intensity, during which the induction period decreased. On the other hand, k1, k2 and the induction period by VIS light irradiation did not change significantly. The relationship between the induction periods obtained by HPLC and POV and the UV light irradiation energy were superimposed in the plots, indicating that these parameters depended on the UV irradiation energy. The relationship between k1/k2 ratio and the UV irradiation energy suggested that the formation of secondary products was more remarkably accelerated by UV energy than that of peroxide.

Chromatography, High Pressure Liquid↗

The effect of some proteinase inhibitors on liquefaction of human semen.

This study examined the effect of some proteinase inhibitors on liquefaction of human semen. It revealed that a strong plasmin inhibitor, 6-amidino-2-naphthyl-6-guanidinobenzoate dihydrochloride (Fusan) showed a significant inhibition of liquefaction, while t-amino caproic acid (t-ACA) showed a weak retardation effect. In terms of sperm quality after liquefaction, Fusan (10 mM), ethyl diamine tetra-acetic acid (EDTA) and Urinastatin completely inhibited sperm motility. Fusan (1 mM) and Lima bean trypsin inhibitor (LBTI) decreased sperm motility significantly, while leupeptin and t-ACA had little effect. Leupeptin, LBTI, t-ACA and Fusan (1 mM) did not affect sperm speed. 50% inhibition of sperm motility was calculated to be approximately 1.7 mM of Fusan concentration. In addition, two inhibitors, Chymostatin and Phosphoramidon were also tested with each experiment and had no effect on liquefaction or on sperm motility and speed. These results strongly suggest that plasmin may play an important role in the liquefaction process of human semen.

Adult↗

Lysosomal enzyme replacement using alpha 2-macroglobulin as a transport vehicle.

Improvement of the delivery of exogenous enzymes is essential to achieve effective enzyme replacement therapy in lysosomal storage diseases. To test whether alpha 2-macroglobulin, an endogenous plasma protein, could serve as a transport vehicle of therapeutic agents to cells, alpha 2-macroglobulin and acid alpha-glucosidase or alpha-galactosidase A were coupled using two heterobifunctional cross-linking reagents. The alpha-glucosidase-alpha 2-macroglobulin conjugate was internalized and transported into lysosomes of acid alpha-glucosidase-deficient fibroblasts. The enzyme activity was stable after being taken up by the cells. Uptake of the conjugate resulted in the degradation of glycogen accumulated in lysosomes. The alpha-galactosidase A-alpha 2-macroglobulin conjugate was also internalized into the lysosomes of alpha-galactosidase A-deficient fibroblasts. Internalized alpha-galactosidase A-conjugate degraded globotriaosylceramide accumulated in lysosomes. The endocytosis of both conjugate was inhibited by alpha 2-macroglobulin-trypsin complex, indicating that the conjugates were endocytosed by an alpha 2-macroglobulin receptor system. These results showed the usefulness of alpha 2-macroglobulin as a transport vehicle of lysosomal enzymes for effective enzyme replacement.

Animals↗

Identification of renal natriuretic peptide receptor subpopulations by use of the non-peptide antagonist, HS-142-1.

1. The renal actions of natriuretic peptides are dictated by the distribution of guanylyl cyclase-linked (NPRA and NPRB) and non-guanylyl cyclase-linked (NPRC) receptors. Natriuretic peptide receptors have previously been distinguished on the basis of their differential affinity for peptide fragments and analogues; however, most of the available ligands are not fully selective. We have used the specific guanylyl cyclase-linked receptor antagonist, HS-142-1, to investigate the differential distribution of natriuretic peptide receptor subtypes in the human, bovine and rat kidney. 2. Specific, high affinity 3-([125I]-iodotyrosyl)-rat-ANP-(1-28)([125I]-rANP1-28) binding sites were identified in all three species, localized to glomeruli, inner medulla, intrarenal arteries and regions in the outer medulla corresponding to vasa recta bundles. Binding sites were also identified in the smooth muscle lining of the hilar region in the bovine and rat kidney. 3. In the rat, [125I]-rANP1-28 binding was inhibited by unlabelled peptide sequences with a rank order of potency (rANP1-28 > pCNP1-22 > C-ANP4-23). The glomeruli exhibited a heterogeneous population of binding sites, C-ANP4-23 and pCNP1-22 producing a significantly better fit to a two component inhibition curve compared to the single component curve for rANP1-28. 4. Competitive inhibition experiments with the receptor selective ligands, C-ANP4-23 and HS-142-1, suggested that, like the rat, human and bovine glomeruli possessed a heterogeneous population of binding sites, whilst those in the inner medulla and intrarenal arteries of all three species represented a homogeneous population. Rat glomeruli exhibited a high proportion (>80%) of the NPRc receptor subtype whereas in human and bovine glomeruli this receptor represented less than 20% of the total population, the majority of binding sites being HS-142-1-sensitive.5. C-ANP4-23 exhibited a significantly higher inhibitory potency for binding sites in rat glomeruli compared to those in human and bovine kidney whilst HS-142-1 was significantly more potent in the rat and bovine kidney compared to man. No evidence was found to suggest the presence of a renal NPRBreceptor subtype.6. The relative density, affinity and proportion of natriuretic receptor subtypes in the kidney exhibit significant species differences. HS-142-1 may be a valuable tool in further elucidating the localization and function of these receptors, but heterogeneity between species should be considered when selecting experimental models.

Adult↗

Successful thermal management of a totally implantable ventricular assist system.

Thermal management of the implantable ventricular assist system (VAS) is important not only from the pathophysiological point of view but also from the standpoint of system endurance. The heat distribution within the Baylor VAS was measured using different motor housing materials and environmental conditions. The temperature of the circulating water in the mock loop was set at 37 degrees and 42 degrees C. A polycarbonate motor housing was not a suitable material because of the high temperature development in the actuation system. An anodized aluminum housing demonstrated excellent heat conductivity. The surface temperature of this motor housing was 41.6 degrees C when immersed in circulating water at 42 degrees C. Heat conduction from the motor to the circulating blood revealed an effective thermal path. In the worst case, the heat flux of the motor to the circulating blood revealed an effective thermal path. In the worst case, the heat flux of the motor housing was calculated to be less than 0.062 W/cm2--an acceptable level for the surrounding tissues.

Equipment Design↗

In vitro and in vivo validation tests for total artificial heart.

Properly planned in vitro and in vivo studies are mandatory to validate blood pump performance. However, standard procedures for in vitro and in vivo tests of total artificial heart (TAH) performance still do not exist. At Baylor College of Medicine, standard tests procedures for performance validation of the totally implantable TAH have been established. In this paper, these in vitro tests protocols (performance mapping tests, accelerated endurance test, hemolysis test, flow visualization tests, etc.) are described as well as in vivo test procedures (TAH implantation procedure, including surgical technique, postoperative management and tests, etc.). In addition, pathological protocols are presented. In our experience, these procedures are very simple, easy to perform, and inexpensive. These protocols are proposed as standard in vitro and in vivo tests for a TAH.

Animals↗