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Biomedical subjects

J S Wilson

Publications and source records attributed to J S Wilson.

At least 73 records · Page 4Linked to original sources
PubMed1995

Effects of ethanol and protein deficiency on pancreatic digestive and lysosomal enzymes.

The pathogenesis of alcoholic pancreatitis is not fully understood. An increase in pancreatic digestive and lysosomal enzyme synthesis because of ethanol consumption could contribute to the development of pancreatic injury in alcoholics. This study aimed, firstly, to determine the effect of ethanol on the content and messenger RNA levels of pancreatic digestive enzymes and on the messenger RNA level of the lysosomal enzyme cathepsin B, and secondly, to examine the influence of concomitant protein deficiency (a known association of alcoholism and pancreatic injury) on these effects. A rat model of chronic ethanol administration was used in which rats were fed in groups of four, and for four weeks, protein sufficient and protein deficient diets with or without ethanol. Ethanol increased the pancreatic content of lipase but did not influence chymotrypsinogen or trypsinogen values. mRNA levels for lipase, trypsinogen, and chymotrypsinogen were raised in rats fed ethanol. Protein deficiency resulted in reduced tissue levels of lipase, chymotrypsinogen, and amylase but did not influence trypsinogen values. mRNA levels for proteases were increased in protein deficient rats, while those for lipase remained unaltered. Both ethanol and protein deficiency increased mRNA levels for cathepsin B. It is concluded that chronic ethanol consumption, in both protein sufficient and protein deficient states, increases the capacity of the pancreatic acinar cell to synthesise digestive and lysosomal enzymes.

Amylases↗
PubMed1995

Ethanol-induced alterations in messenger RNA levels correlate with glandular content of pancreatic enzymes.

Ethanol abuse is a well-known association of pancreatitis. The effects of chronic ethanol consumption on pancreatic digestive and lysosomal enzymes may be relevant to the pathogenesis of alcoholic pancreatitis, because pancreatic enzymes play an important role in the development of pancreatic injury. The aims of this study were to determine the effects of ethanol on gene expression and glandular content of pancreatic digestive enzymes and on gene expression of the lysosomal enzyme cathepsin B (known to be capable of activating trypsinogen). Pancreatic content and mRNA levels for lipase, trypsinogen, and chymotrypsinogen were determined in rats that were pair-fed a nutritionally adequate liquid diet with or without ethanol for 4 weeks. mRNA levels for the lysosomal enzyme cathepsin B were also assessed in this model. Ethanol significantly increased the content of lipase in the pancreas. There was a trend toward an increase in trypsinogen and chymotrypsinogen levels; however, these differences were not statistically significant. mRNA levels for lipase, trypsinogen, and chymotrypsinogen were raised in ethanol-fed rats. Ethanol feeding also increased mRNA levels for the lysosomal enzyme cathepsin B. Furthermore, there was a close, statistically significant correlation between changes in mRNA levels and tissue activities of pancreatic digestive and lysosomal enzymes after ethanol consumption. These results suggest that ethanol increases the capacity of the pancreatic acinar cell to synthesize digestive and lysosomal enzymes, thereby increasing the susceptibility of the gland to enzyme-related injury.

Acetaldehyde↗
PubMed1994

Intracellular response of neurons of the caudate nucleus and putamen to intrastriatal stimulation in cat.

The purpose of this research was to determine if the different functional areas of the striatum, as defined by corticostriate connections, have excitatory and/or inhibitory interconnections. In cats anesthetized with barbiturates, an intracellular recording electrode was angled at 45 degrees such that it (1) crossed all functional areas of the striatum in a single pass and (2) traversed perpendicular to intrastriatal axonal bundles and their terminal fields. > 95% of the neurons recorded intracellularly in the head of the caudate (Cd) nucleus responded to stimulation of the rostromedial striatum (limbic area) producing an initial excitatory response in all cases. Membrane hyperpolarization and inhibition followed the initial excitatory response in approximately half of the responsive neurons. As the recording electrode approached the stimulating electrode, latencies to response onset decreased and amplitudes of the initial excitatory responses increased. Stimulation of a single site produced responses in neurons found in all functional areas of the Cd nucleus. Based on the known topography of afferents to the striatum, these results cannot be explained by stimulation of fibers en passant. Therefore, we conclude that the limbic striatum is connected to other functional areas of the Cd nucleus by intrinsic excitatory and inhibitory circuits. We speculate that intrinsic circuits are a hidden layer of organization providing connectional plasticity by which the influence of an input on striatal neurons may be expanded or contracted beyond the anatomical limits of the afferent terminal field.

Animals↗
PubMed1994

Lipid intolerance does not account for susceptibility to alcoholic and gallstone pancreatitis.

BACKGROUND/AIMS: Hypertriglyceridemia is an established cause of pancreatitis and has been suggested as a predisposing factor in alcohol and gallstone-induced pancreatitis. The aims of this study were to determine fasting and postprandial triglyceride levels of alcoholics with pancreatitis, alcoholics without pancreatitis, patients with previous gallstone pancreatitis, patients with choledocholithiasis, and healthy controls. METHODS: Oral lipid tolerance studies were performed in the above groups. RESULTS: No relationship was found between alcoholic pancreatitis and hypertriglyceridemia, regardless of whether subjects were studied in the fasting state, after ingestion of fat, or after ingestion of fat with ethanol. Plasma triglyceride levels of alcoholics with pancreatitis remained similar to those of alcoholics without pancreatitis, but levels in both groups varied in relation to recent alcohol intake. Plasma triglyceride levels from both groups of alcoholics were greater than those of nonalcoholic healthy subjects. In addition, the previously reported association between postprandial hypertriglyceridemia and gallstone pancreatitis was not observed. CONCLUSIONS: Plasma triglyceride levels do not account for individual susceptibility to either alcoholic or gallstone pancreatitis.

Alcoholism↗
PubMed1994

Chronic ethanol consumption increases the fragility of rat pancreatic zymogen granules.

Intracellular activation of pancreatic digestive enzymes by lysosomal hydrolases is thought to be an early event in the pathogenesis of pancreatic injury. As ethanol excess is an important association of pancreatitis, experimental work has been directed towards exploring possible mechanisms whereby ethanol may facilitate contact between inactive digestive enzyme precursors and lysosomal enzymes. The aim of this study was to find out if chronic ethanol administration increases the fragility of rat pancreatic zymogen granules. Sixteen male Sprague-Dawley rats were pair fed ethanol and control liquid diets for four weeks. Zymogen granule fragility was then assessed in pancreatic homogenate by determination of (a) latency and (b) per cent supernatant enzyme after sedimentation of zymogen granules. Amylase was used as a zymogen granule marker enzyme. Latency was significantly reduced in pancreatic homogenates of ethanol fed animals suggesting increased zymogen granule fragility. In support of this finding, there was a trend towards increased supernatant enzyme after ethanol feeding. In conclusion, administration of ethanol increases the fragility of pancreatic zymogen granules in the absence of morphological evidence of pancreatic injury. It is proposed that zymogen granule fragility may play an early part in the pathogenesis of alcoholic pancreatitis by permitting contact between digestive and lysosomal enzymes.

Amylases↗
PubMed1994

Asbestos-induced pleural fibrosis and impaired exercise physiology.

To further assess the clinical significance of asbestos-induced pleural fibrosis, we performed cardiopulmonary exercise testing in 90 subjects who were exposed to asbestos. Of the 82 subjects without an abnormal resperate exercise, 35 had normal pleura, 33 had circumscribed pleural plaques, and 14 had diffuse pleural thickening. Interstitial fibrosis (International Labor Organization [ILO]. > or = 1/10) was present in 14 of 35 subjects with normal pleura, 13 of 33 subjects with circumscribed pleural plaques, and 2 of 14 subjects with diffuse pleural thickening. Although pleural fibrosis did not appear to be related to impaired respiratory function with exercise in our entire cohort, this finding was confounded by a higher proportion of interstitial fibrosis in subjects with normal pleura. In fact, among study subjects without asbestosis, significant decreases in gas exchange (higher VD/VT and increased alveolar-arterial oxygen pressure difference) were observed at maximal exercise among subjects with pleural fibrosis. Interestingly, neither a higher respiratory rate nor a lower VT/FVC ratio was observed among those with pleural fibrosis, suggesting that the mechanical effects of pleural fibrosis on the chest wall do not explain the increased VD/VT. Using multivariate analyses to control for potential confounders, regression models showed that pleural plaques (p = 0.04) and diffuse pleural thickening (p = 0.03) were independently associated with significant increases in dead space ventilation (VD/VT) with maximal exercise. These findings indicate that asbestos-induced pleural fibrosis is independently associated with decrements in gas exchange with maximal exercise and suggest that interstitial lung disease, not detected on the routine chest x-ray film, may be responsible for this abnormal response to exercise.

Asbestos↗
PubMed1994

Relief of superior vena cava syndrome due to fibrosing mediastinitis using the Palmaz stent.

Relief of superior vena cava (SVC) syndrome due to non-neoplastic mediastinal disease presents a formidable challenge. Long-term patency of surgically created bypass grafts has been poor, and the morbidity associated with these procedures is substantial. We report a case of SVC syndrome, caused by fibrosing mediastinitis, treated with Palmaz balloon expandable intravascular stents. Intravascular stents are a promising alternative for relief of non-neoplastic SVC obstruction.

Adult↗
PubMed1994

Aortic valve replacement in adults after balloon aortic valvuloplasty.

BACKGROUND: Percutaneous balloon aortic valvuloplasty is limited by a high risk of procedural morbidity, transient clinical benefit, and a high restenosis rate. The management of patients with symptomatic aortic valve restenosis after percutaneous balloon aortic valvuloplasty is unclear. We hypothesized that aortic valve replacement would produce superior midterm survival compared with repeat balloon aortic valvuloplasty or medication alone in patients with symptomatic aortic valve restenosis after prior balloon aortic valvuloplasty. METHODS AND RESULTS: Baseline clinical, echocardiographic, and hemodynamic data were collected on 165 patients who underwent percutaneous balloon aortic valvuloplasty as treatment for symptomatic degenerative calcific aortic stenosis. In 144 of these patients (87%), aortic valve replacement was originally considered to carry excessive risk. The survival of three subgroups was calculated during a median follow-up period of 3.9 years (range, 1 to 6 years). Ninety-four patients (57%) had no further mechanical intervention (subgroup 1-BAV), 31 patients (19%) developed symptomatic aortic valve restenosis and underwent a repeat balloon aortic valvuloplasty (subgroup 2-BAV), and 40 patients (24%) subsequently underwent aortic valve replacement (subgroup BAV+AVR). Follow-up was 99% complete. Patients in subgroup BAV+AVR tended to be younger and have a lower prevalence of coronary artery disease or mitral regurgitation. Only 1 patient (2.5%) suffered a perioperative death during aortic valve replacement. The probability of survival 3 years from the date of the last mechanical intervention was 13% for subgroup 1-BAV, 20% for subgroup 2-BAV, and 75% for subgroup BAV+AVR. At the conclusion of follow-up, only 2 patients had symptoms of congestive heart failure or angina after aortic valve replacement. CONCLUSIONS: Aortic valve replacement may be performed with a low mortality rate, excellent palliation of symptoms, and prolongation of survival in selected high-risk patients with a history of previous balloon aortic valvuloplasty.

Actuarial Analysis↗
PubMed1994

Complications related to percutaneous transvenous mitral commissurotomy.

Recent randomized studies have demonstrated that percutaneous transvenous mitral commissurotomy (PTMC) has similar efficacy compared to surgical commissurotomy. Compared with surgery, PTMC is associated with shorter hospital stays, reduced patient discomfort, and significantly lower costs. The challenge of PTMC remains to provide increased safety. The most serious risks of balloon commissurotomy include cardiac perforation and embolic stroke. The creation of severe mitral regurgitation also limits the effectiveness of the procedure and occasionally leads to the requirement for emergency mitral valve replacement. Since 1986, procedure-related mortality has ranged from 0-2.7% with lower mortality rates reported recently. The most frequent cause of procedure-related death has been left ventricular (LV) perforation. This is almost exclusively a complication associated with the double balloon technique, which requires LV guidewires. Cardiac perforation due to inadvertent atrial perforation during transseptal catheterization may occur with the Inoue technique as well, but this tends to be less severe and has not resulted in death. Embolic stroke has occurred in 1.1-5.4% of cases. The incidence of embolic events has been favorably influenced by routine preprocedure transesophageal echocardiography (TEE), eliminating patients with left atrial thrombi. Significant mitral regurgitation occurs in 3.3-10.5% of patients undergoing balloon mitral commissurotomy. Fortunately, mitral regurgitation infrequently requires emergency surgery (0.3-3.3% of cases). Iatrogenic atrial septal defects are usually of no clinical consequence. Their frequency has been reduced with the use of the Inoue balloon catheter system and they rarely require surgical repair.(ABSTRACT TRUNCATED AT 250 WORDS)

Catheterization↗
PubMed1994

Ethanol induced acinar cell injury.

Ethanol abuse is a well known association of pancreatitis. Research into the pathogenesis of alcoholic pancreatitis has generally followed two directions. Firstly, factors which may predispose alcoholics to pancreatitis have been examined. To date, these studies have been negative and the predisposing factor(s) remain unknown. The second approach has involved studies on the constant metabolic effects of ethanol on the pancreas which may render the acinar cell susceptible to digestive enzyme induced injury. Recently developed models of experimental pancreatitis have implicated intracellular activation of digestive enzymes by lysosomal enzymes as an early event. Using the Lieber-DeCarli model of ethanol administration to rats, a number of changes have been described in pancreatic acinar cells which may predispose the gland to autodigestion. These changes include: (1) increased glandular content of digestive enzymes as a result of increases in mRNA levels for these enzymes; (2) increased glandular content of the lysosomal enzyme cathepsin B (known to be capable of activating trypsinogen); (3) increased fragility of lysosomes possibly mediated by cholesteryl esters and fatty acid ethyl esters; and (4) increased fragility of zymogen granules. These effects of ethanol constitute a "primed" setting (the "Drinker's Pancreas") for autodigestion. Triggering factors for autodigestion in this setting have not yet been identified.

Animals↗
PubMed1994

An overview of extrapancreatic factors in the pathogenesis of alcoholic pancreatitis.

Although alcohol is likely to have direct effects on the subcellular integrity of the pancreas, other factors arising outside the pancreas may modulate or potentiate alcohol-induced damage. Among these factors are the hepatic metabolism of ethanol to acetaldehyde (via isoenzymes of ADH), the hepatic production of free radicals, the release of G.I. hormones, pancreatic ischemia (and reperfusion injury), hyperlipemia, diet and smoking. This article summarises what is known about these extrapancreatic factors. It is suggested that the pathogenesis of alcoholic pancreatitis is multifactorial but that many studies in this field are difficult to interpret because of methodological problems, particularly with regard to inadequate controls.

Acetaldehyde↗
PubMed1993

Smoking and alcoholic pancreatitis.

Only a small minority of alcoholics develop clinical evidence of pancreatitis. The reasons for this variation in individual susceptibility have not yet been defined. Recent studies have suggested that smoking may be a risk factor for the development of pancreatitis. However, there have been methodological problems with these studies regarding choice of controls and assessment of tobacco consumption. The present study was designed to determine whether smoking is a risk factor for pancreatitis in alcoholics. Tobacco consumption in alcoholics with pancreatitis was compared to that of alcoholics without pancreatitis (controls). Of 52 subjects with alcoholic pancreatitis, 86.5% were smokers compared with 87.2% of 47 alcoholic controls. Both daily and lifetime tobacco consumption in subjects with pancreatitis were less than those of alcoholic controls. Thus, there was no association between smoking and pancreatitis in this study. The previously described association between smoking and pancreatitis may be related to the high prevalence of smoking among alcoholics.

Adult↗
PubMed1993

Fatty acid ethyl esters increase rat pancreatic lysosomal fragility.

Recent studies indicate that altered lysosomal function may be involved in the early stages of pancreatic injury. Chronic consumption of ethanol has been shown to increase rat pancreatic lysosomal fragility. Fatty acid ethyl esters (nonoxidative products of ethanol metabolism) accumulate in the pancreas after ethanol consumption. The aim of this study was to determine whether the lysosomal fragility observed after ethanol could be mediated by fatty acid ethyl esters. Rat pancreatic lysosomes were incubated for 20 minutes at 20 degrees C with ethyl oleate (a representative fatty acid ethyl ester). Lysosomal stability was then assessed by determination of (1) latency (i.e., the percent increase in lysosomal enzyme activity after addition of Triton X-100) and (2) supernatant activity (i.e., the proportion of lysosomal enzyme remaining in the supernatant after resedimentation of lysosomes). N-acetyl glucosaminidase and cathepsin B were assayed as lysosomal marker enzymes. Lysosomes incubated with buffer alone were used as controls. Ethyl oleate at concentrations above 140 mumol/L increased pancreatic lysosomal fragility as demonstrated by decreased latency. Increased percentage of enzyme in the supernatant was observed at higher concentrations. These results suggest that increased pancreatic lysosomal fragility observed with ethanol may be mediated by fatty acid ethyl esters.

Acetylglucosaminidase↗
PubMed1992

Effects of ethanol, acetaldehyde and cholesteryl esters on pancreatic lysosomes.

Recent studies indicate that altered lysosomal function may be involved in the early stages of pancreatic injury. Chronic consumption of ethanol increases rat pancreatic lysosomal fragility. The aim of this study is to determine whether the lysosomal fragility observed after chronic ethanol consumption is mediated by ethanol per se, its oxidative metabolite acetaldehyde or cholesteryl esters (substances which accumulate in the pancreas after ethanol consumption). Pancreatic lysosomes from chow fed rats were incubated for 30 minutes at 37 degrees C with ethanol, acetaldehyde or phosphatidylcholine vesicles containing cholesteryl oleate. Lysosomal stability was then assessed by determination of: (a) Latency--that is, the per cent increase in lysosomal enzyme activity after addition of Triton X-100 and (b) Supernatant activity--that is, the proportion of lysosomal enzyme remaining in the supernatant after resedimentation of lysosomes. Acid phosphatase, N-acetyl glucosaminidase, beta-glucuronidase and cathepsin B were assayed as lysosomal marker enzymes. Lysosomes incubated with homogenising medium alone or equivalent volumes of phosphatidylcholine vesicles without cholesteryl oleate were used as controls. Cholesteryl oleate at concentrations of 15 and 20 mM increased pancreatic lysosomal fragility as shown by decreased latency and increased supernatant enzyme. In contrast, ethanol (150 mM) and acetaldehyde (5 mM) had no effect on lysosomal stability in vitro. These results suggest that increased pancreatic lysosomal fragility observed with ethanol may be mediated by cholesteryl ester accumulation rather than by ethanol or acetaldehyde.

Acetaldehyde↗