Genetic polymorphisms of equine microsatellite loci: TKY16, TKY19 and TKY21.
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Biomedical subjects
Publications and source records attributed to S Mashima.
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Determinants of the electrocardiographic voltage are reviewed with formulation of certain parameters. The dipole moment of a single fiber and consequently, a possible maximal moment of the double layer of the activation wave front are estimated as 0.21 mA.cm per unit area (cm2). The longitudinal activation of parallel fibers produces much stronger double layer than the transverse activation across fibers. Without any loss of the electrical force of fibers, a normal ventricle of 200 g in weight would create a possible maximal QRS area of 350 microV.sec in a surface lead. The normal endo- to epicardial ventricular activation is predominantly transverse with respect to fiber orientation and rather inefficient in electrogenesis. It is implied that abnormalities in ventricular conduction may possibly improve the effectiveness of myocardial generator.
The possible contribution of localized conduction delay and abnormal action potentials to ventricular fibrillation (VF) was studied by applying an anisotropic cardiac computer model to clinical cases of the Brugada-type electrocardiogram (ECG), which shows right bundle branch block (RBBB), a normal QT interval, ST-segment elevation, and late r' in leads V1 and V2. The anisotropic heart model was composed of 50,000 discrete units with a spatial resolution of 1.5 mm and was mounted in a human torso model. The longitudinal/transverse conduction velocity ratio was 3:1. For the normal ECG, a conduction velocity of 0.75 m/s was required. In the abnormal area of the right anterior epicardial wall, the conduction velocity was set at 0.2 m/s, with decreasing action potential amplitude and 10% prolonged action potential duration. The ECG features of ST-segment elevation and Brugada-type right bundle branch block pattern were simulated. The action potential duration was able to change dynamically with coupling interval of stimulation, with a ratio of 9% for normal ventricular muscle and 50% for Purkinje fibers. Five successive stimuli were applied to the left lateral epicardium 300 ms after the first sinus excitation, and sustained VF was induced with the transmural conduction delay at the right anterior ventricle as a block increasing the vulnerability. At the initiation of VF, reentry circuits were shown around the border zone of the right epicardium and were very heterogeneous around the conduction delayed area and septal area. In an area with the characteristics of nontransmural conduction delay, sustained VF was prevented, and the pattern of transient right bundle branch block appeared on the simulated ECG and body surface potential maps. The late r' wave was calculated in the precordial leads and right anterior site on the body surface potential maps. These results suggest that increased multipolarity in the border zone between the Purkinje fibers and delayed conduction area in the right ventricle might play an important role as a functional block for the persistence of VF.
A genomic clone isolated from an equine genomic library probed with an oligonucleotide (CAG)10 showed high sequence similarity to the human F18 gene and was tentatively named equine F18 gene. Because the human F18 gene is expressed in many tissues, we examined whether this equine clone was also expressed in equine tissues. The cDNA encoding equine F18 was obtained by the reverse transcriptase-polymerase chain reaction (RT-PCR) from equine thymus. The nucleotide sequence of the equine F18 cDNA (1940 bp) was determined and contained both the ATG initiation codon and a poly(A) sequence. The cDNA sequence contained sequence homologous to exon 3 of human F18 gene and a new exon that is not found in the human F18 gene. The equine F18 gene contains a CAG repetitive sequence (CRS) that is translated into a polyglutamine tract. The CRS was analyzed for polymorphism by PCR: four and two different alleles were observed with unrelated east-Asian and thoroughbred horses, respectively. The equine F18 gene was mapped to Xq29.1 by fluorescence in situ hybridization. The human F18 gene is also X-linked. These data strongly supported the conclusion that the clone contains the equine homologue of the human F18 gene.
Body surface Laplacian maps (BSLMs) have been previously reported to provide enhanced capability in localizing and resolving multiple spatially separate myocardial events. However, only a few studies have been reported on the clinical applications of BSLM. To test the clinical utility of BSLMs, BSLMs and body surface potential maps (BSPMs) during ventricular depolarization for complete right or left ventricular bundle branch block (CRBBB or CLBBB) were studied in ten patients in each group. As a control group, ten healthy subjects were also studied using the same procedure. One hundred and twenty-eight electrodes were placed uniformly over the entire chest and back of the subjects. BSLMs were computed from recorded potentials, using a numerical algorithm. The BSLMs showed multiple and more localized positive and negative activities compared with the BSPMs. In healthy subjects, the BSLMs showed multiple areas of positive activity overlying the RV, LV, and the RV outflow, and negative activity corresponding to RV free-wall breakthrough and LV anterolateral breakthrough sites, whereas the BSPMs could not separate RV and LV activities. In the patients with CRBBB, the BSLMs showed more localized areas of activity corresponding to the LV apex breakthrough and LV lateral breakthrough, and separated LV lateral and posterior activation. In the patients with CLBBB, the BSLMs showed multiple RV activation, and propagating activation of LV from lateral to posterior. The BSLMs appear to provide enhanced capability in detecting multiple ventricular electrical events associated with normal and abnormal conduction and a more detailed activation sequence of both ventricles in healthy subjects and in the patients with CRBBB and CLBBB. BSLM may provide an important alternative to other imaging modalities in localizing cardiac electrical activity noninvasively.
For clinical utilization of extracorporeal liver perfusion as an artificial liver assist device, we examined the possibility of long-term xenoperfusion of the pig liver by the continuous administration of prostaglandin E1 (PGE1) and insulin. After a 3-hr perfusion period, pig livers that were xenoperfused with human blood exhibited a drastic decrease in the perfusate volume, a progressive elevation of the hepatic artery pressure, a gradual deterioration of bile production, and a marked increase in the release of creatine kinase-BB component. The continuous administration of PGE1 (25 microg/hr) and insulin (1 U/hr) significantly improved these derangements (P<0.05) and allowed stable perfusion for up to 9 hr. This manipulation also inhibited leukocyte aggregation in the graft, the characteristic perfusate hemolysis, and acceleration of ketogenesis. Histological examination revealed that the interlobular edema and hemorrhage, characteristics of tissue injuries in xenogeneic hyperacute rejection, were markedly alleviated in the PGE1 and insulin-treated group. This study clarifies the finding that the combined administration of PGE1 and insulin is effective for long-term xenogeneic extracorporeal liver perfusion, with the graft viability well maintained.
The ventricular gradient vector was determined in normal persons and in cases with left and right bundle branch block (BBB) by means of the best fit method from body surface potential mapping data. Similar measurements were also made in cases with artificial ventricular pacing and the G vector during sinus rhythm was compared with that of the paced beats. Results indicated that the magnitude of the G vector in cases with BBB was smaller than in normal persons. The directional change in the G vector was found to be along the direction of the QRS change in the majority of cases with left BBB. In right BBB, the direction of the G change was variable but the angle between the QRS change was less than 90 degrees on average. Following right ventricular pacing a small increase of the G magnitude was observed acutely, which was opposite in direction to the QRS change. Possible mechanisms are discussed. The G changes in left and right BBB are considered to be based on certain chronic processes, different from those involved in the acute immediate effect of altered activation.
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The onset of warm ischemia and reperfusion injury in the liver was investigated in a canine model through changes in parenchymal markers [isozyme class V of lactate dehydrogenase (LDH) and alanine aminotransferase (ALT)], endothelial markers [purine nucleoside phosphorylase (PNP) and hyaluronic acid clearance], and the liver metabolism (ketone body ratio) in warm ischemia induced by inflow occlusion using Pringle's maneuver and subsequent reperfusion. In this in vivo model, a PNP assay system and a model were designed so as to exclude the influence of wide localization of PNP possibly originating in erythrocytes or the intestine, and to discriminate between PNP of endothelial cells and that of parenchymal cells in the liver. After 45 min of warm ischemia, reperfusion resulted in damage only to endothelial cells, as seen by significant increase in PNP alone (3.6 +/- 0.1 U/liter at the end of warm ischemia to 6.8 +/- 0.5 U/liter at 5 min after reperfusion, P < 0.01) and significant decrease in hyaluronic acid clearance compared to the 30-min warm ischemia group in which no increase in either marker for parenchymal and endothelial cells was noted. By contrast, after 60 min of warm ischemia, reperfusion resulted in damage to parenchymal cells along with damage to endothelial cells, as seen by significant increases in LDH(V) and ALT (93 +/- 4 U/liter and 32 +/- 2 IU/liter at the end of warm ischemia to 239 +/- 17 U/liter and 165 +/- 27 IU/liter at 5 min after reperfusion, respectively), as well as a marked increase in PNP and deterioration of hyaluronic acid clearance compared to the 45-min warm ischemia group. Reperfusion after 120 min of warm ischemia did not show recovery of metabolic function of the liver as evaluated by hepatic mitochondrial redox state. It is suggested that a time lag occurs in the onset of injury between parenchymal cells and endothelial cells and that endothelial cells are temporally earlier in failing than parenchymal cells when the liver is exposed to short-term warm ischemia and subsequent reperfusion.
Hepatic xenografts can tolerate hyperacute rejection owing to their lower susceptibility to humorally mediated injury. We investigated the possibility of long-duration xenoperfusion without immunologically controlling natural antibodies or complements. Pig livers were perfused for 9 h with human blood (Group 1) or pig blood (Group 2). Physiological conditioning and administration of prostaglandin E1 and insulin was characteristic of our system. The portal vein and hepatic artery pressure and bile production did not significantly differ between the two groups. Despite a gradual decrease throughout the perfusion, overall oxygen consumption was significantly higher in Group 1. Liver enzymes were released at higher levels in Group 1. Histological examination revealed intact hepatic architecture in Group 2, while in Group 1 interlobular morphology was severely damaged by endothelial disruption, although hepatic sinusoidal architecture was preserved. It is concluded that, despite biochemically and histologically confirmed tissue injury, graft viability was well-maintained in xenoperfusion even without immunological manipulations.
To investigate the clinical significance of endothelin (ET), natriuretic peptides, and the renin-angiotensin-aldosterone system in pediatric liver transplantation, we measured plasma levels of ET, atrial and brain natriuretic peptides (ANP, BNP), aldosterone, and plasma renin activity in 18 patients (aged 0.5-12 yr; median 1 yr) undergoing living-related liver transplantation due to congenital biliary atresia and severe liver cirrhosis. Before transplantation, the plasma ET level (28.9 +/- 2.5 [mean +/- SEM] pg/mL) was increased compared with that of healthy children (10-18 pg/mL), but decreased during the anhepatic phase (22.5 +/- 1.6 pg/mL). It increased again after reperfusion and remained at high levels in the early postoperative period (postoperative day 3, 27.8 +/- 3.0 pg/mL). Plasma levels of ANP and BNP and aldosterone and plasma renin activity were also high before surgery. Plasma ANP and BNP did not change significantly during surgery. After transplantation, plasma BNP significantly increased, and plasma ANP tended to increase. Plasma aldosterone increased markedly during the anhepatic phase, although plasma renin activity decreased. After transplantation, plasma aldosterone and plasma renin activity both decreased to within normal levels. Mean arterial blood pressure increased gradually after reperfusion and surgery (postoperative day 3, 35.7 +/- 5.2% increase). No substantial differences in these variables occurred between the younger (< or = 1.0 yr, n = 9) and older patients (> 1.0 yr, n = 9). These results suggest that ET production in the cirrhotic liver is augmented and ET, natriuretic peptides, and the renin-angiotensin-aldosterone system all play some role in the circulatory regulation during perioperative periods of pediatric liver transplantation.
The protective effect of a novel prostacyclin (PGI2) analog, OP-2507, on mesenteric circulation was investigated in a canine warm ischemia model. In 20 mongrel dogs, the entire portion of the intestine supplied by the superior mesenteric artery (SMA) and drained by the superior mesenteric vein (SMV) was completely isolated, maintaining the blood and lymph vessels intact. Sixty or 120 min of complete warm ischemia (WI) of the intestine was induced by clamping SMA and SMV, followed by reperfusion for 120 min. Animals were divided into five groups (each n = 4): group 1, sham operation; group 2, 60 min WI; group 3, 120 min WI; group 4, 60 min WI with PGI2 analog administration; group 5, 120 min WI with PGI2 analog administration. The analog was administered at a rate of 6 micrograms.kg-1.h-1 immediately after laparotomy until the end of the observation period. Mean arterial pressure, SMA blood flow (SMABF), SMV pressure were monitored and total mesenteric vascular resistance (TMVR) was calculated. To evaluate the endothelial activation, endothelin, which is secreted from the endothelium under hypoxic stress, was assayed from blood samples of SMV. None of the animals showed significant changes in mean arterial pressure. In groups 2 and 3, SMABF decreased significantly to less than 60% of preoperative value (15 ml.kg-1.min-1) and TMVR significantly increased from 8.1 and 7.3 mm Hg.ml-1.kg.min before WI to 14.0 and 16.4 mm Hg.ml-1.kg.min after 120 min reperfusion, respectively, resulting in delayed hypoperfusion. In contrast, in groups 4 and 5, SMABF increased to over 100% of preoperative level, while TMVR declined from 7.8 and 8.4 mm Hg.ml-1.kg.min before WI to 6.2 and 6.3 mm Hg.ml-1.kg.min after 120 min reperfusion. After 60 min reperfusion, SMABF and TMVR showed a significant difference between the treated and nontreated groups. Only in group 3, high endothelin concentrations (over 20 pg/ml) were observed even after 120 min reperfusion. It was concluded that the PGI2 analog was able to suppress the endothelial activation and the disturbance of mesenteric circulation caused by WI and reperfusion.
The absolute potential value of Wilson's central terminal was calculated at 2 msec intervals during a cardiac cycle in 60 clinical cases. Starting from the body surface potential data at 128 thoracic locations, the effect of immersion of the body into an infinite conductor on the surface potential was calculated to obtain values with reference to zero potential at infinity. The conductivity of the outside medium was then made to approach zero. Comparison of the result with the original map showed nearly a constant shift of the potential, corresponding to the voltage of Wilson's terminal. In addition, the cardiac vector was calculated as the first approximation of the cardiac electromotive force and the lead vector of Wilson's terminal was obtained in order that the scalar product of the cardiac vector and the lead vector approximated the observed voltage of Wilson's terminal. The results indicate that the voltage of the Wilson electrode depended on the surface voltage with a peak value near the maximal QRS force in most of the cases. The peak voltage of Wilson's terminal was either positive or negative, and was 0.15 mV in absolute value on average. Voltage variations of Wilson's terminal during a cardiac cycle were 0.20 mV as an average of all cases. The voltage of Wilson's terminal also depended on the direction of the equivalent cardiac vector. The lead vector of Wilson's terminal was found to be directed superiorly in most of the cases. The average magnitude of the lead vector of Wilson's terminal was 0.097 omega/cm, which corresponded to about 1/4 of that of lead I.
The aim of this study was to assess the incidence of myocardial infarction among persistent perfusion defects in dipyridamole-stress thallium scintigraphy by inspecting autopsied hearts and to evaluate whether the regional thallium activity of a scintigraphic defect can predict the presence of infarction. Autopsied hearts were compared with dipyridamole myocardial scintigrams undertaken during life in 27 patients (mean age 85 +/- 8 years). The time interval from stress testing until death was 428 +/- 351 days. Regional thallium uptake of delayed perfusion defect was calculated on the short axis images. The grade of regional myocardial fibrosis in autopsy specimens was also quantified to correlate with the corresponding regional thallium uptake. In 6 of 15 (40%) regions with persistent defects on the scintigram, myocardial infarction was not found at autopsy. Regional thallium-201 uptake of delayed defects < 50% diagnosed infarction with a sensitivity of 82% and a specificity of 80%. A linear correlation (r = -0.67) was observed between percent thallium-201 uptake and the degree of myocardial fibrosis. In conclusion, perfusion defects at 4-hour imaging in dipyridamole-stress testing may overestimate the presence of myocardial infarction and regional thallium-201 activity is helpful in distinguishing between defects with and without infarction.
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Despite the developments in methods of various examinations in the field of arrhythmias, standard 12 leads ECG still gives the basis for interpretations of arrhythmias. The standard ECG is often the only information available in a particular patient. In practice, 12 lead ECG reflects new findings obtained from more detailed examinations. This paper includes topics on the timing and configuration of P&QRST complex.