Biomedical subjects
Publications and source records attributed to W Cheng.
Neuronal intestinal dysplasia (NID) usually mimics Hirschsprung's disease, but rarely presents as neonatal enterocolitis. The authors report a case of colonic hyperganglionosis, which is a form of NID, presenting with postenterocolitis intestinal strictures. NID should be considered as a possible (although rare) cause of neonatal enterocolitis and may present with intestinal strictures.
OBJECTIVE: To determine whether alpha 1 adrenergic receptor mediated myocyte contractility and growth are depressed acutely after non-occlusive coronary artery narrowing, the left coronary artery was constricted in rats and mechanical behaviour, cytosolic calcium, and regulation of alpha 1 adrenergic receptors were examined in myocytes seven days later. METHODS: Coronary artery stenosis was surgically induced in rats and following the estimation of global cardiac performance myocytes were enzymatically dissociated and radioligand binding studies were performed. In addition, the isotonic contractile performance, cytosolic calcium transients and noradrenaline stimulated inositol phosphate generation in myocytes were measured in the presence of WB 4101 or after chlorethylclonidine treatment. RESULTS: Estimations of cell mechanics in vitro established that peak shortening was decreased by 36% and 18% in left and right ventricular myocytes of coronary stenosed rats. Time to peak shortening was prolonged by 29% in left and 20% in right myocytes, whereas velocity of shortening was decreased by 27% in left myocytes. These alterations were associated with increases in cell length and width, indicative of myocyte hypertrophy. In addition, coronary stenosis was accompanied by reductions in the expression of alpha 1a and alpha 1b receptor subtypes in myocytes. alpha 1 Adrenergic receptor density and noradrenaline stimulated phosphoinositol turnover were decreased by 30% and 34% in left myocytes. alpha 1a Adrenergic receptor subtype mediated cytosolic calcium concentration and myocyte mechanical performance were also impaired in left myocytes only. The alpha 1a adrenergic receptor subtype antagonist WB 4101 abolished noradrenaline stimulated inositol phosphate generation in myocytes, whereas chlorethylclonidine at large doses only partially inhibited this response. CONCLUSIONS: In conclusion, coronary narrowing leads to defects in the regulation of alpha 1 adrenergic receptors on myocytes which are coupled with attenuation in the transmission of signals, possibly affecting myocyte cell function and ongoing reactive cellular hypertrophy.
The electron-carrying cofactor NADP is formed by phosphorylation of NAD. A strategy for the isolation of NAD kinase mutants revealed two classes of temperature-sensitive mutations, nadF and nadG, mapping at min 13 and 72 of the Salmonella chromosome. Both mutant types grew on nutrient broth at both 30 and 42 degrees C but on minimal medium showed a temperature-sensitive growth defect which was not corrected by any of the single nutritional supplements tested. A nadF deletion mutant grew on nutrient broth but not on minimal medium. A double mutant with the nadF deletion and a nadG(Ts) mutation showed temperature-sensitive growth on all media. We propose that Salmonella typhimurium has two NAD kinases, one encoded by the nadF and one by the nadG gene. This is supported by the fact that temperature-sensitive mutants of both genes produce kinase activity with altered heat stability. Results suggest that either one of two NAD kinases is sufficient for growth on rich medium, but that both are needed for growth on minimal media. Enzyme assays show that the nadF gene is responsible for about 70% of total NAD kinase activity, and that the nadG gene dictates the remaining 30%. While testing nutritional phenotypes of nadF and nadG mutants, we found that the biosynthetic intermediate, quinolinic acid (QA) inhibited growth of nadF mutants on nutrient broth. This suggested that the NadG enzyme might be inhibited by QA. Enzyme assays demonstrated that QA inhibits the NadG but not the NadF enzyme. This suggests the existence of a regulatory mechanism which controls NADP levels.
To determine whether cardiac failure produced by chronic coronary artery stenosis was associated with the activation of myocyte cellular hyperplasia in the myocardium, the changes in number and size of left ventricular myocytes were measured in rats 3 months after surgery. The hypertrophied left ventricle was found to possess 44%, 32%, 49%, and 48% fewer mononucleated, binucleated, trinucleated, and tetranucleated myocytes, respectively. In contrast, the hypertrophied right ventricle contained 1.49 x 10(6) more myocytes as a result of a 2.1-fold, 1.4-fold, and 1.4-fold increase in mononucleated, binucleated, and tetranucleated myocytes. Myocyte cell volume was seen to increase 49% and 21% in left and right ventricular myocytes, respectively. The process of myocyte cellular hyperplasia in the right ventricular myocardium was accompanied by capillary proliferation, and these events were responsible for the parallel addition of newly formed cells and capillaries within the wall and mural thickening. Moreover, the in-series insertion of new myocytes contributed to right ventricular dilatation after coronary artery stenosis. In view of the fact that extensive myocardial damage and cell loss may have masked the phenomenon of myocyte cellular hyperplasia in the left ventricle, the presence of DNA synthesis in myocyte nuclei was evaluated at 3 days, 1 week, 2 weeks, 1 month, and 3 months after coronary artery stenosis. Bromodeoxyuridine (BrdU) labeling markedly increased in myocyte nuclei of both ventricles, reaching its peak at 1 and 2 weeks. BrdU labeling of nonmyocyte nuclei also increased but mostly at 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
Triglyceride synthesis by hepatocytes is currently thought to be the rate-limiting step for lipoprotein formation. In order to determine whether triglyceride and cholesteryl ester syntheses in hepatocytes are sensitive to physiological fluctuations of serum fatty acids, the fatty acid dependence of these pathways was examined. Uptake of various fatty acids and incorporation into triglyceride and cholesteryl esters were studied in isolated rat hepatocytes. Rates were determined under conditions of linear incorporation and related to the concentrations of total and unbound fatty acid in a mixture of fatty acids and albumin. The findings were: pathways for triglyceride and cholesteryl ester synthesis saturated at unbound fatty acid concentrations (or fatty acid albumin ratios) within the range of serum values and thus would be acutely modulated by fluctuations in serum fatty acids. Addition of cholesterol to the medium increased cellular cholesterol, but did not alter rates of cholesterol esterification, suggesting that endogenous cholesterol synthesis provided the needed substrate. Oleate, palmitate, and linoleate were comparable in their saturation kinetics and ability to support triglyceride and cholesteryl ester synthesis. Consequently, their binding affinity for serum albumin would determine their lipid-incorporation rates. On this basis, in humans, oleate would yield the lowest rates as it has the lowest unbound fatty acid at each fatty acid-albumin ratio. Stearate, in contrast to the other fatty acids, was poorly esterified into neutral lipids by hepatocytes. Poor hepatic metabolism of stearate most likely explains previous findings of a hypocholesteremic effect of diets high in stearate as compared to other saturated fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS)
From 1989 to 1990, an investigation was conducted in three villages in Junsan township, Hanyang County, Hubei Province. The results showed that the infection rates of local residents were 55.1%, 49.5% and 44.3%, respectively; the EPG were 5.6, 5.2 and 2.0, respectively; the relative transmission index (RTI) were 7.1%, being highest in the age group 30-39 years. The relative index of potential contamination (IPC) was 67.2% in the age group 20-49 years, this group was considered as the main transmission source in the population. In animal hosts buffaloes, pigs and dogs, the infection rates were 35.7%, 60.0% and 75.0%, respectively; MPG (miracidium per gram), 0.4, 0.4 and 80.4, respectively; RTI (relative transmission index), 38.6%, 7.7 and 46.6%, respectively. The infection rates of pigs and dogs were high in Huangshi village, while the infection rate of buffaloes was high in Chuangjiang village. These results coincided with the transmission of schistosomiasis in these villages. The results showed that dogs as the main transmission sources had important significance in the epidemiology of schistosomiasis and that buffaloes and pigs herd and fed in the snail-habitats could be heavily infected.
The possible limitation of left ventricular (LV) relaxation during diastole is a concern for clinicians and researchers utilizing dynamic cardiomyoplasty. This study was designed to evaluate the LV compliance at three different skeletal muscle tensions, in a normal heart and in a failing heart, created by propranolol infusion (11.6 mg/kg). A biventricular latissimus dorsi muscle (LDM) wrap was performed in 10 dogs. The LV pressure (Millar) and two minor axis dimensions (endocardial crystals) were measured. LV pressure-volume loops were constructed, and LV diastolic compliance was calculated. The measurements were obtained before wrap and after wrap at different LDM tensions with 0, 5, and 10 volts stimulation each time. These measurements were repeated after propranolol treatment. The results showed that LV diastolic compliance (dV/dP) was 1.79 before wrap and about 0.7 after wrap, and after propranolol, at various tensions and stimulations. LDM wrap decreased LV compliance significantly. LV compliance was not significantly affected by changing tension or voltage of stimulation in either the failing or the non-failing heart. The reduction in compliance may be an indication that LDM wrap causes a limitation of LV relaxation, which is one of wrap's deleterious effects.
Core I protein is a nuclear-encoded component of the ubiquinol-cytochrome c reductase complex of the mitochondrial respiratory chain. We have located the gene for the human core I protein in the p21 region of chromosome 3, just upstream of the COL7A1 gene which encodes type VII collagen. The core I gene, which has been sequenced in its entirety, is comprised of 10,417 base pairs, from the major transcription start site to the polyadenylation signal, and contains 13 exons. The predicted polypeptide contains 480 amino acids, of which the first 34 are predicted to constitute a typical mitochondrial leader peptide containing 6 positively charged arginine residues. The predicted human protein shows significant homology with core I protein from Saccharomyces cerevisiae, rather high homology (64% similarity, 46% identity) with the processing enhancing protein, which functions as core I protein in Neurospora crassa, and, surprisingly, highest homology with the small subunit of the mitochondrial processing peptidase of rat (74% similarity, 55% identity). The predicted human sequence is 87% identical to the reported bovine core I sequence predicted from cDNA cloning, up to residue 298, but the two predicted sequences are widely divergent after that point.
Dynamic cardiomyoplasty, the use of skeletal muscle to assist the heart, is a new therapy for the treatment of heart failure. However, the effects of cardiomyoplasty on biventricular function and the synchrony of ventricular contraction are not fully known. We assessed the efficacy of latissimus dorsi muscle (LDM) dynamic cardiomyoplasty in a chronic model of biventricular failure. Five dogs received doxorubicin (1 mg.kg-1.wk-1) for up to 12 weeks to induce heart failure and then underwent a biventricular cardiomyoplasty. After operation, the muscle was progressively stimulated according to an established protocol. When training was complete (10 weeks), radionuclide ventriculographic and catheterization data were obtained. Peak left ventricular (LV) systolic pressure and its first derivative were unchanged, whereas LV end-diastolic pressure decreased slightly with LDM assistance (11.0 +/- 1.6 to 9.6 +/- 1.5 mm Hg; p < 0.05). Right ventricular (RV) systolic pressure increased significantly with LDM assistance from 21 +/- 2 to 26 +/- 3 mm Hg (p < 0.05), whereas its first derivative and RV end-diastolic pressure were unchanged. Dynamic cardiomyoplasty significantly improved LV ejection fraction from 0.18 +/- 0.07 without LDM assistance to 0.31 +/- 0.05 with LDM assistance (p < 0.05); similarly RV ejection fraction increased from 0.32 +/- 0.07 to 0.45 +/- 0.06 with LDM assistance (p < 0.05). The temporal sequence of LV wall motion was assessed by phase analysis of the radionuclide ventriculograms. With skeletal muscle assistance, standard deviation ("spread") decreased from 31.6 +/- 17.4 to 20.0 +/- 15.4 degrees (p < 0.06), whereas skewness ("symmetry") was unchanged. Dynamic cardiomyoplasty improved both LV and RV ejection fractions without increasing diastolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Median sternotomy is the most commonly used incision in cardiothoracic surgery. Closure of this incision is usually performed with parasternal wires, but alternate techniques have been proposed to improve closure stability. This study compares biomechanical stability of standard wire (No. 5 stainless steel) with that of three types of band closure: 5-mm Mersilene ribbon, 5-mm stainless steel band, and 5-mm plastic band. Eight bisected cadaver sterna were reapproximated using each method of sternal fixation and tested for biomechanical stability using an MTS Bionix 858 Biomechanical Tester. Loads of 50, 100, 150, and 200 Newtons (1 Newton = 1 kg.m/s2) were applied as a distracting force across the closure. A linear regression line of displacement as a function of increasing load was determined for each closure method; the slope of this line is inversely proportional to fixation stability. Displacement and load correlated linearly for each closure (r = 0.99). Mean slopes were 0.012 mm/Newton (95% confidence limits, 0.0098 to 0.0142 mm/Newton) for No. 5 stainless steel wire, 0.014 mm/Newton (95% confidence limits, 0.0118 to 0.0162 mm/Newton) for plastic band, 0.017 mm/Newton (95% confidence limits, 0.0148 to 0.0192 mm/Newton) for Mersilene ribbon, and 0.017 mm/Newton (95% confidence limits, 0.0148 to 0.0192 mm/Newton) for 5-mm steel band. No. 5 stainless steel wire provided the most stable closure, although statistical significance was achieved only in comparison with Mersilene ribbon and stainless steel band (p < 0.05). The superior stability of stainless steel wire closure may be due to tightening of the wires by twisting, which results in more tension across the reapproximated sternal halves than with other methods.
Explore the source record for details and available documents.
To determine the effects of acute myocardial infarction on the regulation of angiotensin II (Ang II) receptors and contractile performance of left and right ventricular myocytes, coronary artery ligation was surgically induced in rats, and Ang II receptor density and affinity and the mechanical properties of surviving muscle cells were examined 1 week later. Physiological determinations of cardiac pump function revealed the presence of ventricular failure, which was associated at the cellular level with a depression in the velocity of myocyte shortening and relengthening, a prolongation of time to peak shortening, and a reduction in the extent of cell shortening. These abnormalities in single-cell function were more prominent in left than in right ventricular myocytes. Cellular hypertrophy was documented by increases in cell length and width, which were also greater in the spared myocytes of the infarcted left ventricle. Reactive hypertrophy was accompanied by a 1.84- and 1.85-fold increase in the density of Ang II receptors on left and right myocytes, respectively. On the other hand, the affinity of Ang II receptors for the radiolabeled antagonist was not altered. However, Ang II-stimulated phosphoinositol turnover was enhanced by 3.7- and 2.5-fold in left and right myocytes, respectively, after infarction. Ventricular myocytes were found to possess the AT1 receptor subtype exclusively. In conclusion, myocardial infarction leads to impairment in the contractile behavior of the remaining cells and to the activation of Ang II receptors and effector pathway associated with these receptors, which may be involved in the reactive growth adaptation of the viable myocytes.
The results of an experimental study in rats fed with Equisetum hyemale and hyperlipid food have proved that inhibiting effects on the elevation of triglyceride and cholesterol can be obviously observed in both high and low doses of Equisetum. The study also shows that Equisetum hyemale can antagonize the hyperlipemia in rats. The acute toxic test has proved its low toxicity.
In order to assess the left ventricular diastolic function of Heart Qi Insufficiency Syndrome (HQIS), apexcardiogram, ECG, electro-cardio-phonogram, impedance cardiogram were recorded and computerized simultaneously. A/D, PEP/LEVT, A/H were increased, while TRTI, DATI, HI, SV, CI reduced in 64 patients, 34 of them with coronary heart disease. The change was statistically significant. This study showed that DATI was more sensitive than PEP/LEVT in patients with HQIS, while there was no significant difference between abnormal ratio of them, overlapping of the two indices was showed. Replenishing Heart Mixture attained its therapeutic effect through improving abnormal left ventricular function. After treatment A/H, A/D, PEP/LEVT were reduced and DATI, SV, CI increased (P < 0.05-0.01). In experiment, HQIS was produced by acute myocardial ischemia in open-chest anesthetized dogs by left anterior descending coronary artery occlusion. It has been shown that dp/dtmax and T were more sensitive than dp/dtmax. Result of the clinical and the experimental study were consistent.
Type V collagen is a fibrillar collagen that is widely distributed in tissues as a minor component of extracellular matrix and is usually composed of one pro alpha 2 (V) and two pro alpha 1 (V) chains. In this report, recently isolated cDNA and genomic clones, which encode the pro alpha 1 (V) chain, are used as probes for hybridization to filter-bound DNA from a panel of human-mouse hybrid cell lines and for in situ hybridization to metaphase chromosomes. These studies establish the chromosomal location of the COL5A1 gene, which encodes the pro alpha 1 (V) chain, within segment 9q34.2----q34.3. These findings add to the previously characterized dispersion of collagen genes in the human genome, as this is the first example of a collagen locus on chromosome 9. In addition, these studies place COL5A1 near the locus for the genetic disorder, nail-patella syndrome (hereditary osteo-onychodysplasia), which also maps to 9q34.
To determine whether the overload associated with myocardial infarction and ventricular failure in rats is coupled with activation of DNA synthesis in the remaining left and right ventricular myocytes, flow cytometric analysis was performed on myocyte nuclei prepared from both ventricles 7 and 30 days after coronary occlusion. In addition, oral captopril was administered in separate groups of control and experimental rats to establish whether a relation existed between attenuation of ventricular loading and magnitude of DNA synthesis in myocytes. Results demonstrated that left ventricular failure and right ventricular dysfunction at 7 days after infarction were biventricularly associated with marked increases in the number of myocyte nuclei in the G2M phase of the cell cycle. In contrast, the fraction of nuclei in the G0+G1 phase decreased. In comparison with the earlier time point, the 30-day interval was characterized by a significant magnitude of cardiac hypertrophy, a moderate amelioration of ventricular pump function, and a decrease in the percentage of myocyte nuclei in the G2M phase in both ventricles. However, 30 days after infarction, the number of right ventricular myocyte nuclei in the S and G2M phases remained elevated with respect to control animals. Captopril therapy reduced the extent of ventricular loading and the population of myocyte nuclei in the cell cycle at 7 days. In conclusion, DNA synthesis in myocyte nuclei may represent an important adaptive component of the myocardial response to infarction.
The effects of cardiomyoplasty were evaluated with multiple-gated equilibrium radionuclide angiocardiography and catheterization in a canine model of chronic heart failure. Doxorubicin was administered to 12 dogs at a dose of 1 mg/kg/wk intravenously for 10 weeks. Left ventricular ejection fraction was reduced from a mean of 53.6% +/- 3.4% to 33.5% +/- 2.3% preoperatively. Two dogs died of presumed arrhythmia during this period. Cardiomyoplasty with the left latissimus dorsi muscle was performed on 10 dogs. The muscle was wrapped around both the left and right ventricles. Five dogs died of infection or arrhythmia after the operation. Postoperatively the muscle remained unstimulated for 2 weeks to allow adhesion to the heart. After this period, the latissimus dorsi muscle was conditioned by a progressive stimulation protocol. After the muscle was conditioned, multiple-gated equilibrium radionuclide angiocardiography studies showed that left ventricular global ejection fraction was 18.4% +/- 7.2% at 0 volts (nonstimulation), 26.2% +/- 3.7% at 5-volt stimulation (p less than 0.05), and 31.0% +/- 5.4% at 10-volt stimulation (p less than 0.05). Regional ejection fractions in low lateral, apical, and low septal regions at 5 volts and 10 volts were higher than those at 0 volts (p less than 0.05). Regional wall motion (percent radial shortening) of the low lateral region was higher than that during nonstimulation (p less than 0.05). Peak emptying rate was 2.07 +/- 0.95 end-diastolic counts per second at 0-volt, 3.10 +/- 0.67 at 5-volt, and 3.34 +/- 0.89 at 10-volt stimulation (p less than 0.05). Peak filling rate was 1.81 +/- 0.52 end-diastolic counts per second at 0-volt, 2.67 +/- 1.18 at 5-volt, and 3.11 +/- 0.65 at 10-volt stimulation (p less than 0.05). Cardiac catheterization data showed a nonsignificant increase in left ventricular rate of pressure rise with increasing voltage (1302 +/- 355 mm Hg/sec at 0 volts, 1450 +/- 413 mm Hg/sec at 5 volts, and 1568 +/- 455 mm Hg/sec at 10 volts). Left ventricular systolic pressures were unchanged. End-diastolic pressures decreased (11.2 +/- 1.48 mm Hg at 0 volts, 10.4 +/- 2.30 mm Hg at 5 volts, and 9.6 +/- 1.52 at 10 volts; p less than 0.05). These data show that cardiomyoplasty can improve indices of systolic and diastolic function in a canine model of chronic heart failure.
We have isolated overlapping cDNA clones from human and hamster libraries which comprise the entire coding sequences for the prepro-alpha 1(V) collagen chains of both species. The translated polypeptide has a signal peptide of 36 amino acids, a central triple helical domain of 338 uninterrupted Gly-X-Y triplets, and 266 amino acids which comprise the C-telopeptide and propeptide. The N-propeptide and telopeptide are comprised of 522 residues in humans and 524 residues in hamsters. The cDNA-derived pro-alpha 1(V) amino acid sequences exhibit a variety of structural features characteristic of fibrillar collagens. Pro-alpha 1(V) is found to be unique among fibrillar collagen chains, however, in lacking potential cross-linking lysyl residues in either telopeptide, and in possessing potential N-asparaginyl-linked carbohydrate attachment sites in its N-propeptide. Of particular interest is the strong homology found between the pro-alpha 1(V) and pro-alpha 1(XI) collagen chains in most domains, with the notable exception of a subdomain in the globular region of the N-propeptide. RNase protection analysis of RNA with a variety of pro-alpha 1(V) cDNA-derived riboprobes indicates a broad distribution of expression of the pro-alpha 1(V) chain in tissues and suggests that transcripts encoding the pro-alpha 1(V) chain and the putative pro-alpha 1'(V) chain are not products of the same gene.