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Biomedical subjects

K Wang

Publications and source records attributed to K Wang.

At least 361 records · Page 20Linked to original sources

Assembly of nebulin into the sarcomeres of avian skeletal muscle.

In developing muscle, relatively little is known about the synthesis and incorporation of the large actin binding protein, nebulin, into the sarcomere. To determine the temporal pattern of nebulin assembly into the myofibrils of differentiating skeletal muscle cells, myofibril assembly was examined by immunofluorescence microscopy. The distribution of nebulin was compared to other myofibrillar and cytoskeletal proteins (myosin, titin, actin, desmin, tubulin). At the onset of differentiation, we observed that nebulin is first seen in a diffuse distribution throughout the cytoplasm. At this time, muscle specific myosin and titin are also distributed in this manner. Myosin and titin become associated with the nascent myofibrils prior to the addition of nebulin. The mature striated pattern of myosin and titin also preceded the development of striations with nebulin. After nebulin becomes organized into a striated pattern, actin filaments separate across the A-band and form thin filaments of uniform length. These patterns of assembly suggest that nebulin is required for restricting the lengths of the thin filaments. We have employed the strategy of using ethyl methane sulfonate and taxol to perturb myofibril assembly to examine interactions critical for the addition of nebulin to the developing sarcomeres. The same temporal pattern of assembly seen in the normal cultures was observed in the ethyl methane sulfonate treated cultures, but at a much slower rate. In cultures treated with the microtubule stabilizing drug taxol, the amount of stress fibers and nascent I-bands was greatly diminished as previously reported by others; however, nebulin was found associated with myofibrils in a mature striated distribution. In addition, our results indicate that the taxol treated cultures contain remnants of the Z-line. These results suggest that nebulin assembly into the myofibril requires interactions or anchorage at the Z-line and within the A-band.

Animals↗

Concept of the homemade coronary stent: experimental results and initial clinical experience.

To defray the escalating cost of coronary stenting, we handmade a balloon expandable coil stent with stainless steel wire. Preliminary comparison with the Palmaz-Schatz stent showed that, when implanted in porcine iliac arteries, there was no difference in immediate angiographic results or in the degree of foreign body reaction at 6 wk. Subsequently, a total of 73 stents were implanted in 52 patients, either as a bailout device (54%) or for suboptimal angiographic results (46%). All but two implantations were successful. The postprocedural regimen consisted of heparin 1,000 IU/hr, aspirin 250 mg daily, and ticlopidine 500 mg daily. In-hospital complications were limited to two groin hematomas, one necessitating blood transfusion. Importantly, stent thrombosis was not observed. While 6-mo follow-up is pending, we already conclude that a balloon expandable coil stent can be handmade easily at low cost and implanted safely in patients.

Animals↗

Posttranscriptional regulation of connexin 32 expression in liver during acute inflammation.

Gap junctions mediate the communication between adjacent cells in tissues. In the liver, connexin 32 (Cx32) subunits make up the predominating gap junctions. The expression of Cx32 gene has been observed to be down-regulated in response to inflammatory states and during liver regeneration. In the present study we attempt to elucidate the molecular mechanisms underlying the down-regulation of the Cx32 expression during acute inflammation. A decrease in the level of Cx32 mRNA in rat liver occurred between 3 and 6 h after intravenous administration of bacterial lipopolysaccharide (LPS), simultaneously with the induction of an acute inflammatory response characterized by an increase in the level for beta-fibrinogen and a reduction of phosphoenolpyruvate carboxykinase mRNA. The reduction in Cx32 steady-state mRNA levels appears to occur at the posttranscriptional level, since the rate of degradation of this message seems to be higher than the rate of transcription of the gene. Degradation of Cx32 mRNA was blocked by the administration of actinomycin D, but not by cycloheximide, prior to injection of LPS. The stabilization of Cx32 message by actinomycin D correlated with the preservation of Cx32 on the cell surface, which otherwise disappears after administration of LPS alone. These results suggest that cellular communication via gap junctions could be regulated at the level of gene expression, by a posttranscriptional mechanism, during acute inflammatory states.

Acute Disease↗

Studies on the thermokinetic characterisation of actin polymerization and the effect of cisplatin.

The microcalorimetic measurement for studying the thermokinetic of actin polymerization in vitro was employed for the first time. The thermodynamic parameters of actin polymerization at 310.15 K are reported as delta Hm = 49.26 kJ/mol, delta Gm = 25.62 kJ/mol and delta Sm = 241.54 J/K.mol. The thermogram shows that polymerization of actin is a complicate process in which multistep reactions occur corresponding to exothermic and endothermic effects. Cisplatin, at lower concentration, affects the polymerization of G-actin resulting in a decrease of delta Hm; and, at higher concentration, induce the crosslinking and depolymerization of F-actin in the equilibrium system of G/F. The experimental results show that as the concentration of cisplatin increases, the sign of delta Hm changes from positive to negative, i.e. the magnitude and sign of delta Hm of actin polymerization depends on the concentration of cisplatin.

Actins↗

Natural history of bleeding peptic ulcers with a tightly adherent blood clot: a prospective observation.

BACKGROUND: The natural history of a bleeding peptic ulcer with a tightly adherent blood clot remains uncertain. Controversy exists concerning removal of such blood clots at the bleeding ulcer base. This article presents the natural history of a bleeding peptic ulcer with a tightly adherent clot and defines the characteristics of those requiring aggressive management. METHODS: Clinical parameters were analyzed to determine the independent predictors of rebleeding in these patients. One hundred one patients with bleeding peptic ulcers and tightly adherent blood clots were enrolled during a period of 12 months. RESULTS: Twenty-five patients (25%) rebled within 1 month. With a multivariate analysis, we found comorbid illness (odds ratio, 3.41), shock (odds ratio, 3.65), and initial hemoglobin at or below 10 gm/dL (odds ratio, 2.99) to be independent predictors of rebleeding. CONCLUSIONS: Most patients with a tightly adherent clot in an ulcer have an uneventful course. However, endoscopic therapy may prove to be beneficial in the subset of patients with independent predictors of rebleeding.

Blood Coagulation↗

Transgenic mdx mice expressing dystrophin with a deletion in the actin-binding domain display a "mild Becker" phenotype.

The functional significance of the actin-binding domain of dystrophin, the protein lacking in patients with Duchenne muscular dystrophy, has remained elusive. Patients with deletions of this domain (domain I) typically express low levels of the truncated protein. Whether the moderate to severe phenotypes associated with such deletions result from loss of an essential function, or from reduced levels of a functional protein, is unclear. To address this question, we have generated transgenic mice that express wild-type levels of a dystrophin deleted for the majority of the actin-binding domain. The transgene derived protein lacks amino acids 45-273, removing 2 of 3 in vitro identified actin interacting sites and part of hinge 1. Examination of the effect of this deletion in mice lacking wild-type dystrophin (mdx) suggests that a functional domain I is not essential for prevention of a dystrophic phenotype. However, in contrast to deletions in the central rod domain and to full-length dystrophin, both of which are functional at only 20% of wild-type levels, proteins with a deletion in domain I must be expressed at high levels to prevent a severe dystrophy. These results are also in contrast to the severe dystrophy resulting from truncation of the COOH-terminal domain that links dystrophin to the extracellular matrix. The mild phenotype observed in mice with domain I-deletions indicates that an intact actin-binding domain is not essential, although it does contribute to an important function of dystrophin. These studies also suggest the link between dystrophin and the subsarcolemmal cytoskeleton involves more than a simple attachment of domain I to actin filaments.

Actinin↗

The cost of coverage: rural health insurance in China.

China has undergone great economic and social change since 1978 with far reaching implications for the health care system and ultimately for the health status of the population. The Chinese Medical Reform of the 1980s made cost recovery a primary objective. The urban population is mostly protected by generous government health insurance. A high share government budget is allocated to urban health care. Rural cooperative health insurance reached a peak in the mid-1970s when 90% of the rural population were covered. In the 1980s rural cooperative health insurance collapsed and present coverage is less than 8%. The decline has been accompanied by reports of growing equity problems in the financing of and access to health care. This article is the first in a four-year study of the impact on equity of the changes in Chinese health care financing. The article examines the relationship between rural cooperative health insurance as the explanatory variable and health care expenditure, curative vs. preventive expenditure and tertiary curative care expenditure as dependent variables using a natural experimental design with a 'twin' county as a control. The findings support the hypothesis that cooperative health insurance will induce higher growth of health care expenditure. The findings also support the hypothesis that cooperative health insurance will lead to a shift from preventive medicine to curative medicine and to a higher level of tertiary curative care expenditure. The empirical evidence from the Chinese counties is contradicting World Bank health financing policies.

China↗

Early or delayed endoscopy for patients with peptic ulcer bleeding. A prospective randomized study.

The benefit of early endoscopy in the management of peptic ulcer bleeding remains controversial. In this study we looked at the role of early endoscopy in bleeding peptic ulcer patients with clear, "coffee grounds," or bloody nasogastric aspirate. A consecutive series of 325 patients with peptic ulcer bleeding were included (218 patients with clear aspirate, 77 patients with coffee-grounds aspirate, and 30 patients with bloody aspirate). They were randomized to receive early endoscopy (within 12 h of arrival at the emergency room) or delayed endoscopy (12 h after arrival at the emergency room). Early endoscopy did not benefit patients with clear or coffee-grounds aspirate. However, combined with endoscopic therapy, it did significantly benefit patients with bloody aspirate in reducing the need for blood transfusion (mean, 450 ml vs. 666 ml; p < 0.001) and hospital stay (mean, 4 vs. 14.5 days, p < 0.001). Early endoscopy and endoscopic therapy are not needed in bleeding peptic ulcer patients with clear or coffee-grounds nasogastric aspirate. However, early endoscopy and endoscopic therapy benefit patients with bloody nasogastric aspirate.

Aged↗

Gastric secretion in Chinese patients with cirrhosis.

The role of gastric secretion has been controversial in patients with cirrhosis. Except for studies of gastric secretion in cirrhotic patients who underwent a shunt operation, there is no report correlating gastric secretion with portal pressure in patients with cirrhosis. In this study, we evaluated gastric secretion in cirrhotic patients and correlated it with hemodynamic parameters. Within 12 months, 20 normal volunteers and 16 cirrhotic patients were enrolled. Gastric secretion was assessed in all patients, but portal pressure hemodynamic studies were performed only in cirrhotic patients. We found that the median basal acid output, maximal acid output, and basal pepsin output in the controls (1.41 mmol/h, 9.2 mmol/h, and 0.02 mg/h, respectively) and in the cirrhotic patients (0.6 mmol/h, 7.84 mmol/h, and 1.5 mg/h, respectively) were not statistically different. However, maximal pepsin output was lower in the cirrhotic patients (1.5 mg/h) than in the normal subjects (5.14 mg/h) (p < 0.05). Gastric secretion correlated poorly with hepatic venous pressure gradient (HVPG) and the presence of congestive gastropathy in cirrhotic patients. The severity of congestive gastropathy correlated poorly with HVPG. Helicobacter pylori has difficulty replicating in the stomach when HVPG is > 14 mm Hg. We conclude that patients with cirrhosis have a lower maximal pepsin output than that of the healthy subjects. Gastric secretion correlates poorly with HVPG and the presence of congestive gastropathy in patients with cirrhosis.

Aged↗

Local methylprednisolone inhibition of foreign body response to coated intracoronary stents.

BACKGROUND: When poly(organo)phosphazene coated metallic stents are implanted into normal coronary arteries of pigs a severe histolymphocytic and fibromuscular reaction is induced. Corticosteroids possess potent anti-inflammatory and immunosuppressive effects, they have been shown to decrease migration and functional capability of the cells of inflammation and they may stabilize lysosomal cell membranes. This study aims to evaluates the feasibility and efficacy of local corticosteroid delivery by implantation of methylprednisolone loaded coronary stents into coronary arteries of pigs. METHODS: Tantalum balloon expandable coronary stents were coated with poly(organo)phosphazene impregnated with 5 wt% methylprednisolone. Methylprednisolone release was calculated in vitro and then randomly either a methylprednisolone loaded stent or a plain polymercoated stent was implanted into the right coronary artery of 20 pigs. Quantitative coronary artery analysis was done before, immediately after and 6 weeks after stent implantation. The pigs were then killed and the stented arteries processed for histopathological and morphometric evaluation. RESULTS: In-vitro testing revealed that the methylprednisolone loaded stents, when incubated in physiological saline, released 96% of the drug within 24 h. Quantitative angiography of the implanted stents showed similar angiographic parameters in both treatment groups immediately after implantation, but, after 6 weeks of follow-up study the minimal luminal diameter of the stented arterial segment was considerably larger in the methylprednisolone-treated pigs than it was in the control pigs (2.74 +/- 0.34 versus 1.36 +/- 0.72 mm, P < 0.005) This angiographic finding was confirmed at post-mortem morphometry where the respective values for neointimal thickness were 0.99 +/- 0.28 and 1.74 +/- 0.84 mm (P < 0.02). CONCLUSIONS: Polymer coated stents can be loaded with methylprednisolone which inhibits the severe foreign-body reaction induced by the combination of overstretch injury and the poly(organo)phosphazene polymer coating of metallic stents.

Animals↗

Structured entry of radiology reports using World Wide Web technology.

Structured data entry--in which information is entered by using predetermined data elements and formats--has the potential to improve the radiology reporting process. The dependence on particular computer hardware and software platforms has posed a barrier to wider use of this approach. The World Wide Web (WWW), a client-server protocol for delivery of multimedia data via the Internet, was used to achieve platform-independent structured entry of radiology reports. A developmental system for structured entry of radiology reports, called SPIDER, incorporates a knowledge base of hierarchically organized concepts, a WWW server, and two specialized programs. The WebForm program transforms the system's knowledge into graphical WWW data-entry forms; the WebReport program converts data entered on these forms into outline-format reports. SPIDER received favorable evaluations from sonographers and physicians who used the system to record the results of several test cases. WWW technology can be used to achieve platform-independent entry of the results of radiologic procedures.

Artificial Intelligence↗

Metabolic profiles of minimally absorbed orlistat in obese/overweight volunteers.

To determine the metabolic profile of minimally absorbed orlistat in obese/overweight patients, an open-label, single-dose study was performed in eight obese/overweight volunteers between 23 and 68 years of age. Each subject received a single oral dose of 360 mg orlistat containing approximately 400 muCi of 14C-labeled orlistat. Serial blood samples were collected at specified times over 10 hours after administration of orlistat for determination of total radioactivity, unchanged orlistat, and major metabolites in the plasma. Urine samples were collected over 24 hours and analyzed to evaluate the urinary recovery of total radioactivity and the profile of orlistat metabolites in the urine. In addition, all fecal samples were collected and analyzed for total radioactivity. Urinary and fecal recovery of the administered dose of total radioactivity were 1.13 +/- 0.50% (24-hour data only) and 96.4 +/- 18.1% (n = 7), respectively. Maximum observed concentration (Cmax) and time to Cmax (tmax) values of plasma total radioactivity were 150 +/- 51 ng.eq/mL and 6.8 +/- 1.5 hrs, respectively. All these parameters obtained in obese/ overweight subjects were similar to those reported previously in healthy subjects. On the basis of the area under the concentration-time curve from 0 to 10 hours (AUC0-10), two major metabolites comprise a total of approximately 42% of the total radioactivity in plasma. The primary metabolite (M1) has a short half-life (approximately 2 hours), whereas the secondary metabolite (M3) disappeared at a slower rate. No strikingly apparent difference in the urinary metabolic profile was observed between two gender groups. It is concluded that the disposition of orlistat appears to be similar between normal and obese/overweight subjects. Of the minimal fraction of the dose that was absorbed systemically, the presence of two major metabolites accounts for approximately 42%.

Absorption↗

Local Angiopeptin Delivery Using Coated Stents Reduces Neointimal Proliferation in Overstretched Porcine Coronary Arteries.

BACKGROUND: Systemic administration of angiopeptin has been shown to inhibit myointimal thickening after arterial injury in several animal species. METHODS AND RESULTS: To explore to what extent high and long-lasting local concentrations of angiopeptin influence the healing process after vascular injury, tantalum balloon-expandable stents were first coated with a polymer loaded with angiopeptin 250 µg. Implantation of these stents in porcine coronary arteries resulted in tissue concentrations of 10.7 pg/ml wet weight in the stented arterial segment 24 hours after stent implantation, gradually declining to 2.0 pg/ml wet weight at day 8. Finally, 20 pigs were randomly treated with either an angiopeptin-loaded or a blank-coated stent. At baseline, the angiographic parameters were similar between both groups but, after 6 weeks, the minimal luminal diameter of the stented arterial segment was larger in the angiopeptin-treated pigs when compared to controls (2.20 +/- 0.57 mm vs 1.57 +/- 0.68 mm, p < 0.01) This angiographic finding was confirmed by post-mortem morphometry where the respective lumen area values were 1.00 +/- 0.54 mm2 and 0.43 +/- 0.28 mm2 (p < 0.01). CONCLUSION: Polymer coated stents can be loaded with angiopeptin, which after implantation in porcine right coronary arteries result in high local tissue concentrations gradually declining over more than 8 days. These high local concentrations inhibit myointimal proliferation induced by poly(organo)phosphazene coated overstretched stents.

Journal Article↗

Experimental Evaluation of a New Single Wire Stainless Steel Fishscale Coronary Stent (Freedomª).

Recent randomized clinical trials revealed a significant reduction in angiographic restenosis rates when adjunctive stenting was performed after conventional coronary balloon angioplasty. Current approved coronary stents are however hampered by their rigidity, limiting their trackability in tortuous vessels and furthermore, needing high pressure deployment for optimal vessel apposition. New coronary stents are currently under development, using more biocompatible metal alloys and/or designs which better align to the vessel wall at moderate deployment pressures. We evaluated the safety, efficacy, angiographic and histological effect of a new stainless steel fishscale designed stent (Freedomª, Global Therapeutics, Co., USA) in a porcine coronary and peripheral artery model. Implantation in the right coronary artery was successful in all 20 pigs. Control angiograms at 6 weeks follow-up demonstrated patent vessels and morphologic evaluation showed only a mild fibromuscular neointimal response resulting in an area stenosis of 28.7 +/- 0.18% and a mean neointimal hyperplasia of 0.18 +/- 0.25 mm. Comparison with the Palmaz-Schatzª coronary stent in a porcine peripheral artery model demonstrated similar quantitative angiographic and morphologic vessel analysis results. Also the morphometric data were comparable. Area stenosis: Palmaz-Schatz: 37 +/- 0.24%, Freedom: 21 +/- 0.14%, p = 0.07. Mean neointimal hyperplasia: Palmaz-Schatz: 0.33 +/- 0.24 mm, Freedom: 0.18 +/- 0.08 mm, p = 0.08. CONCLUSION: Freedom coronary stent implantation in a porcine model resulted in a high procedural success without subacute thrombotic occlusions, despite no further anticoagulation nor antiplatelet therapy. Six weeks histopathological and morphometric evaluation demonstrated only a mild fibromuscular neointimal hyperplasia.

Journal Article↗

Clinical and Angiographic Experience with Coronary Stenting Using Freedomª Stent.

The immediate safety and efficacy and the 6 month clinical and angiographic follow-up of a new fish-scale designed coronary coil stainless steel stent (Freedomª) was assessed by a prospective study. During 1995, 169 patients were treated on 177 vessels using 233 Freedom stents. Procedural indication for stenting was a bail-out situation in 79 vessels, a suboptimal angioplasty result in 62 vessels and a third restenosis after PTCA in 36 vessels. Procedural success was achieved in 170 vessels (96%); in 162 patients (96%). Subacute thrombotic occlusion occurred in one patient (0.6%). Acute myocardial infarction occurred in 7 patients (4.1%). Bleeding complications, necessitating blood transfusion occurred in 6 patients (3.6%). There were two non-stent related deaths. Recurrence of stent-related angina pectoris and/or a positive stress test occurred in 10 pts (6.4%). Elective control angiography at 6 months was performed in the first 85 patients. Stent restenosis of ³ 50% diameter stenosis was found in 14 patients (16.5%).

Journal Article↗