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J S Wilson

Publications and source records attributed to J S Wilson.

At least 37 records · Page 2Linked to original sources
PubMed2000

Alcohol up-regulates UDP-glucuronosyltransferase mRNA expression in rat liver and in primary rat hepatocyte culture.

The interactions between alcohol and cytochrome P-450 enzymes have been well investigated. However, the data regarding the effect of alcohol on the regulation of UDP-glucuronosyltranferase (UGT) activity are less clear. The aim of the present study was to determine the role of alcohol in the regulation of UGT mRNA expression by using whole animal and primary cultured hepatocytes. Chronic ethanol feeding of rats significantly increased the expression of liver UGT1A1 mRNA to 177% of control. The mRNA levels for UGT1A5, UGT2B1 and UGT2B3 were also enhanced, but did not reach statistical significance. In cultured hepatocytes, treatment with either ethanol or isopentanol significantly increased the expression of UGT1A1, UGT1A5, UGT2B1, and UGT2B3 mRNAs, but to different degrees. The induction of UGT1A1 and UGT2B1 mRNAs by ethanol or isopentanol was time-dependent and maximal changes occurred at 48 h. The expression of UGT1A6 mRNA was not significantly modified by either ethanol or isopentanol. In conclusion, ethanol and isopentanol have direct roles in the regulation of UGT.

Animals↗
PubMed2000

Magnetic resonance angiography is an accurate imaging adjunct to duplex ultrasound scan in patient selection for carotid endarterectomy.

PURPOSE: The purpose of this study was to evaluate the accuracy of magnetic resonance angiography (MRA) for categorizing the severity of carotid disease relative to duplex ultrasound scan and cerebral contrast arteriography (CA) to determine if MRA imaging could replace the need for cerebral angiography in cases of indeterminate or inadequate duplex scan imaging. METHODS: Seventy-four carotid bifurcations in 40 patients undergoing 45 carotid endarterectomies from 1996 to 1998 were imaged with duplex ultrasound scan; MRA (two-dimensional neck and three-dimensional intracranial, time-of-flight technique); and biplanar, digital subtraction cerebral arteriography. Studies were blindly reviewed by one reader who used established threshold velocity criteria for the duplex scan and the North American Symptomatic Carotid Endarterectomy Trial method for MRA and CA to determine the percentage of diameter reduction of the internal carotid artery (ICA). Disease severity was grouped into four categories (< 50%, 50%-74%, 75%-99% stenosis and occlusion), and the results of MRA and duplex ultrasound scan were compared with CA. RESULTS: Sensitivity, specificity, positive predictive value, and negative predictive value for detection of > 50% ICA stenosis were 100%, 96%, 98%, and 100% for MRA and 100%, 72%, 88%, and 100% for duplex ultrasound scan, respectively; similarly, for detection of > 75% ICA stenosis values were 100%, 77%, 76%, and 100% for MRA and 90%, 74%, 72%, and 91% for duplex ultrasound scan, respectively. Both MRA and duplex ultrasound scan accurately differentiated all cases of > 95% stenosis (n = 7) from occlusion (n = 4). Short length ICA flow gaps were present on MRA in all cases of 75% to 99% stenosis and one half of cases of CA-defined 50% to 74% stenosis. In patients with 50% to 74% stenosis, the mean angiographic stenosis was significantly greater when a flow gap was present on MRA (64% +/- 6%) versus no flow gap (57% +/- 7%) (P =.04). There was overall agreement among duplex ultrasound scan, MRA, and CA in 73% of carotids imaged. Of the 24% discordant results between MRA and duplex ultrasound scan, MRA correctly predicted disease severity in all cases, and inaccurate duplex ultrasound scan results were due to overestimation in 83% of cases. The operative plan was altered by CA findings in only one patient (2%) after duplex ultrasound scan and MRA. CONCLUSIONS: MRA can accurately categorize the severity of carotid occlusive disease. Duplex ultrasound scan facilitates patient selection for carotid endarterectomy in most cases, but adjunct use of MRA improves diagnostic accuracy for > 75% stenoses and may obviate the need for cerebral arteriography when duplex scan results are inconclusive or demonstrate borderline disease severity.

Aged↗
PubMed2000

Normal diffusing capacity in patients with PiZ alpha(1)-antitrypsin deficiency, severe airflow obstruction, and significant radiographic emphysema.

alpha(1)-Antitrypsin deficiency is usually suspected clinically in young adults with irreversible airflow obstruction that is out of proportion to their smoking history. Many patients with alpha(1)-antitrypsin deficiency receive an initial diagnosis of asthma or chronic bronchitis. Measurement of the diffusing capacity of the lung for carbon monoxide (DLCO) has been recommended as a way to help distinguish emphysema from asthma and chronic bronchitis. In this article, we describe four patients with severe alpha(1)-antitrypsin deficiency, each of whom had a repeatedly normal DLCO despite having a significant component of fixed airway obstruction and prominent panacinar emphysema on high-resolution CT scan (HRCT). Each patient also demonstrated significant bronchodilator responsiveness, and two patients received an initial diagnosis of asthma. Potential explanations for these findings are discussed. We report these findings to illustrate the limitations of DLCO in this setting. alpha(1)-Antitrypsin deficiency should be considered in patients with fixed airway obstruction that is out of proportion to their age and smoking history, regardless of their diffusing capacity and response to bronchodilators.

Adult↗
PubMed1999

Activation of pancreatic stellate cells in human and experimental pancreatic fibrosis.

The mechanisms of pancreatic fibrosis are poorly understood. In the liver, stellate cells play an important role in fibrogenesis. Similar cells have recently been isolated from the pancreas and are termed pancreatic stellate cells. The aim of this study was to determine whether pancreatic stellate cell activation occurs during experimental and human pancreatic fibrosis. Pancreatic fibrosis was induced in rats (n = 24) by infusion of trinitrobenzene sulfonic acid (TNBS) into the pancreatic duct. Surgical specimens were obtained from patients with chronic pancreatitis (n = 6). Pancreatic fibrosis was assessed using the Sirius Red stain and immunohistochemistry for collagen type I. Pancreatic stellate cell activation was assessed by staining for alpha-smooth muscle actin (alphaSMA), desmin, and platelet-derived growth factor receptor type beta (PDGFRbeta). The relationship of fibrosis to stellate cell activation was studied by staining of serial sections for alphaSMA, desmin, PDGFRbeta, and collagen, and by dual-staining for alphaSMA plus either Sirius Red or in situ hybridization for procollagen alpha(1) (I) mRNA. The cellular source of TGFbeta was examined by immunohistochemistry. The histological appearances in the TNBS model resembled those found in human chronic pancreatitis. Areas of pancreatic fibrosis stained positively for Sirius Red and collagen type I. Sirius Red staining was associated with alphaSMA-positive cells. alphaSMA staining colocalized with procollagen alpha(1) (I) mRNA expression. In the rat model, desmin staining was associated with PDGFRbeta in areas of fibrosis. TGFbeta was maximal in acinar cells adjacent to areas of fibrosis and spindle cells within fibrotic bands. Pancreatic stellate cell activation is associated with fibrosis in both human pancreas and in an animal model. These cells appear to play an important role in pancreatic fibrogenesis.

Actins↗
PubMed1999

Esophagopharyngeal acid regurgitation: dual pH monitoring criteria for its detection and insights into mechanisms.

BACKGROUND & AIMS: A valid technique for the detection of esophagopharyngeal acid regurgitation would be valuable to evaluate suspected reflux-related otolaryngologic and respiratory disorders. The aim of this study was to derive pH criteria that optimally define esophagopharyngeal acid regurgitation and to examine patterns of regurgitation. METHODS: In 19 healthy controls and 15 patients with suspected regurgitation, dual or quadruple pH sensors were used to monitor pharyngeal and esophageal pH. For each combination of the 2 variables, DeltapH and nadir pH, proportions of pH decreases that occurred during or independent of esophageal acidification were calculated to determine the likelihood that an individual pharyngeal pH decrease was a candidate regurgitation event or a definite artifact. RESULTS: Overall, 92% of pharyngeal pH decreases of 1-2 pH units and 66% of pH decreases of this magnitude reaching a nadir pH of <4 were artifactual. Optimal criteria defining a pharyngeal acid regurgitation event were a pH decrease that occurred during esophageal acidification, had a DeltapH of >2 units, and reached a nadir of <4 units in less than 30 seconds. Regurgitation occurred more frequently in subjects in an upright (32 of 35) than in a supine (3 of 35 events; P </= 0.0001) position and was more frequently abrupt (synchronous with esophageal acidification) than delayed (P </= 0.05). CONCLUSIONS: Accepted criteria for gastroesophageal reflux are not applicable to the detection of esophagopharyngeal acid regurgitation, and most regurgitation occurs abruptly and in upright position.

Adult↗
PubMed1999

Chronic pancreatitis: complications and management.

Chronic pancreatitis is characterized by progressive and irreversible loss of pancreatic exocrine and endocrine function. In the majority of cases, particularly in Western populations, the disease is associated with alcohol abuse. The major complications of chronic pancreatitis include abdominal pain, malabsorption, and diabetes. Of these, pain is the most difficult to treat and is therefore the most frustrating symptom for both the patient and the physician. While analgesics form the cornerstone of pain therapy, a number of other treatment modalities (inhibition of pancreatic secretion, antioxidants, and surgery) have also been described. Unfortunately, the efficacy of these modalities is difficult to assess, principally because of the lack of properly controlled clinical trials. Replacement of pancreatic enzymes (particularly lipase) in the gut is the mainstay of treatment for malabsorption; the recent discovery of a bacterial lipase (with high lipolytic activity and resistance to degradation in gastric and duodenal juice) represents an important advance that may significantly increase the efficacy of enzyme replacement therapy by replacing the easily degradable porcine lipase found in existing enzyme preparations. Diabetes secondary to chronic pancreatitis is difficult to control and its course is often complicated by hypoglycaemic attacks. Therefore, it is essential that caution is exercised when treating this condition with insulin. This paper reviews recent research and prevailing concepts regarding the three major complications of chronic pancreatitis noted above. A comprehensive discussion of current opinion on clinical issues relating to the other known complications of chronic pancreatitis such as pseudocysts, venous thromboses, biliary and duodenal obstruction, biliary cirrhosis, and pancreatic cancer is also presented.

Analgesics↗
PubMed1999

Laryngeal motion during exercise.

OBJECTIVE: To compare laryngoscopically observed changes in the larynx during exercise in persons with exercise-induced laryngomalacia (EIL) with changes in asymptomatic control subjects. STUDY DESIGN: Clinical study using a standardized exercise protocol. METHODS: Subjects exercised on an incremental ergometer: videotaped recordings of the larynx were obtained through the entire exercise; pulmonary function tests were completed before and/or immediately after the exercise. RESULTS: Laryngeal lumen size decreases during exercise in subjects with EIL. CONCLUSION: Subjects with EIL had a significant decrease in laryngeal lumen size during exercise compared with asymptomatic control subjects.

Adolescent↗
PubMed1999

Pancreatic stellate cells are activated by proinflammatory cytokines: implications for pancreatic fibrogenesis.

BACKGROUND: The pathogenesis of pancreatic fibrosis is unknown. In the liver, stellate cells play a major role in fibrogenesis by synthesising increased amounts of collagen and other extracellular matrix (ECM) proteins when activated by profibrogenic mediators such as cytokines and oxidant stress. AIMS: To determine whether cultured rat pancreatic stellate cells produce collagen and other ECM proteins, and exhibit signs of activation when exposed to the cytokines platelet derived growth factor (PDGF) or transforming growth factor beta (TGF-beta). METHODS: Cultured pancreatic stellate cells were immunostained for the ECM proteins procollagen III, collagen I, laminin, and fibronectin using specific polyclonal antibodies. For cytokine studies, triplicate wells of cells were incubated with increasing concentrations of PDGF or TGF-beta. RESULTS: Cultured pancreatic stellate cells stained strongly positive for all ECM proteins tested. Incubation of cells with 1, 5, and 10 ng/ml PDGF led to a significant dose related increase in cell counts as well as in the incorporation of 3H-thymidine into DNA. Stellate cells exposed to 0.25, 0.5, and 1 ng/ml TGF-beta showed a dose dependent increase in alpha smooth muscle actin expression and increased collagen synthesis. In addition, TGF-beta increased the expression of PDGF receptors on stellate cells. CONCLUSIONS: Pancreatic stellate cells produce collagen and other extracellular matrix proteins, and respond to the cytokines PDGF and TGF-beta by increased proliferation and increased collagen synthesis. These results suggest an important role for stellate cells in pancreatic fibrogenesis.

Actins↗
PubMed1999

Alcoholic pancreatitis and polymorphisms of the variable length polythymidine tract in the cystic fibrosis gene.

BACKGROUND: The observation that only a minority of alcoholics develops clinical pancreatic disease has led to a search for a predisposing factor to the disease. One possible predisposing factor is mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene as cystic fibrosis leads to pancreatic injury. We have recently demonstrated that 15 common CFTR mutations are not found in patients with alcoholic pancreatitis. Another common polymorphism of the CFTR gene has recently been implicated in the pathogenesis of idiopathic chronic pancreatitis, the 5T variant of the variable length polythymidine tract in intron 8 (the normal genotypes are 7T and 9T). The 5T variant inhibits transcription of exon 9 resulting in a CFTR protein lacking chloride channel activity. The aim of this study was to determine whether the 5T variant is associated with alcoholic pancreatitis. METHODS: Fifty-two patients with alcoholic pancreatitis were identified using standardized diagnostic criteria. Fifty alcoholics without pancreatitis were also studied as controls. Genomic DNA was extracted from peripheral blood leukocytes and the polythymidine tract of intron 8 was amplified by nested polymerase chain reaction using established primers. The polymerase chain reaction products were digested with MseI, separated by electrophoresis on 15% polyacrylamide gels and genotypes assigned by comparison with known positive controls. RESULTS: The 5T allele we found in only two patients with alcoholic pancreatitis (3.9% of th index group; 95% confidence intervals 0-10%) and in seven alco holic controls. Allele frequencies for 5T, 7T, and 9T in patients with alcoholic pancreatitis were 1.9%, 85.6%, and 12.5%, respectively These did not differ from the allele frequencies in alcoholic controls (7%, 79%, and 14% for 5T, 7T, and 9T, respectively). CONCLUSION: The 5T allele was not associated with alcoholic pancreatitis. Individual susceptibility to this disease remains unexplained.

Adult↗
PubMed1998

Metabolism of ethanol by rat pancreatic acinar cells.

It has been postulated that ethanol-induced pancreatic injury may be mediated by the oxidation of ethanol within the pancreas with secondary toxic metabolic changes, but there is little evidence of pancreatic ethanol oxidation. The aims of this study were to determine whether pancreatic acinar cells metabolize significant amounts of ethanol and, if so, to compare their rate of ethanol oxidation to that of hepatocytes. Cultured rat pancreatic acinar cells and hepatocytes were incubated with 5 to 50 mmol/L carbon 14-labeled ethanol (25 dpm/nmol). Ethanol oxidation was calculated from the production of 14C-labeled acetate that was isolated by Dowex ion-exchange chromatography. Ethanol oxidation by pancreatic acinar cells was demonstrable at all ethanol concentrations tested. At an intoxicating ethanol concentration (50 mmol/L), 14C-labeled acetate production (227+/-20 nmol/10(6) cells/h) approached that of hepatocytes (337+/-61 nmol/10(6) cells/h). Phenanthroline (an inhibitor of classes I through III isoenzymes of alcohol dehydrogenase (ADH)) inhibited pancreatic ethanol oxidation by 90%, but 4-methylpyrazole (a class I and II ADH inhibitor), carbon monoxide (a cytochrome P450 inhibitor), and sodium azide (a catalase inhibitor) had no effect. This study has shown that pancreatic acinar cells oxidize significant amounts of ethanol. At intoxicating concentrations of ethanol, pancreatic acinar cell ethanol oxidation may have the potential to contribute to pancreatic cellular injury. The mechanism appears to involve the class III isoenzyme of ADH.

Acetates↗
PubMed1998

Chronic ethanol administration causes oxidative stress in the rat pancreas.

There is increasing evidence implicating oxidative stress in the pathogenesis of both acute and chronic pancreatitis. Because ethanol is a major cause of pancreatitis in Western society, the aim of this study was to determine whether chronic ethanol administration results in oxidative stress in the pancreas. Twelve pairs of rats were fed a diet containing ethanol as 36% of calories or an isocaloric control diet for 4 weeks. Ethanol feeding resulted in a 46% increase in pancreatic malondialdehyde (p=0.006). In addition, total pancreatic glutathione was increased by 22% (p=0.005). These biochemical changes occurred in the absence of histologic evidence of inflammation or necrosis, implying that the observed oxidative stress is a primary phenomenon rather than part of an inflammatory response.

Animals↗
PubMed1998

Cystic fibrosis genotypes and alcoholic pancreatitis.

Pancreatitis and pancreatic insufficiency are associated with both cystic fibrosis and alcoholism. The pathogenesis of alcoholic pancreatitis is unknown, but only a minority of alcoholics develop pancreatitis, and it has been suggested that a genetic predisposition may play a role in this disease. Two observations led to the hypothesis that this genetic predisposition could result from mutations in the cystic fibrosis gene. First, the prevalence of cystic fibrosis mutations in the Caucasian population (approximately 5%) is similar to the prevalence of pancreatitis among heavy drinkers. Second, in both diseases, pancreatic duct damage is a prominent feature and has been postulated to be the initial site of injury. Therefore, the aim of this study was to determine whether an increased frequency of mutations in the cystic fibrosis gene occurs in alcoholic pancreatitis. The 15 most common cystic fibrosis mutations in a Caucasian community were sought in 24 subjects with alcoholic pancreatitis. None were homozygous or heterozygous for these mutations. These findings suggest that cystic fibrosis mutations are not a major genetic factor predisposing to pancreatic injury in alcoholics.

Cystic Fibrosis↗
PubMed1998

Cytochrome P4502E1 is present in rat pancreas and is induced by chronic ethanol administration.

BACKGROUND: The mechanisms responsible for the initiation of alcoholic pancreatitis remain elusive. However, there is an increasing body of evidence that reactive oxygen species play a role in both acute and chronic pancreatitis. In the liver, cytochrome P4502E1 (CYP2E1, the inducible ethanol metabolising enzyme) is one of the proposed pathways by which ethanol induces oxidative stress. AIMS: To determine whether CYP2E1 is present in the pancreas and, if so, whether it is inducible by chronic ethanol feeding. METHODS: Eighteen male Sprague-Dawley rats were pair fed liquid diets with or without ethanol as 36% of energy for four weeks. CYP2E1 levels were determined by western blotting of microsomal protein from both pancreas and liver. Messenger RNA (mRNA) levels for CYP2E1 were quantified using dot blots of total pancreatic RNA. RESULTS: CYP2E1 was found in the pancreas. Furthermore, the amount of CYP2E1 was greater in the pancreas of rats fed ethanol compared with controls (mean increase over controls 5.1-fold, 95% confidence intervals 2.4 to 7.7, p < 0.02). In the liver, induction by ethanol of CYP2E1 was similar (mean increase over controls 7.9-fold, 95% confidence intervals 5.2 to 10.6, p < 0.005). Pancreatic mRNA levels for CYP2E1 were similar in ethanol fed and control rats. CONCLUSIONS: CYP2E1 is present in the rat pancreas and is inducible by chronic ethanol administration. Induction of pancreatic CYP2E1 is not regulated at the mRNA level. The metabolism of ethanol via CYP2E1 may contribute to oxidative stress in the pancreas during chronic ethanol consumption.

Animals↗
PubMed1998

Periacinar stellate shaped cells in rat pancreas: identification, isolation, and culture.

BACKGROUND: The pathogenesis of pancreatic fibrosis is unknown. In the liver, stellate cells (vitamin A storing cells) play a significant role in the development of fibrosis. AIMS: To determine whether cells resembling hepatic stellate cells are present in rat pancreas, and if so, to compare their number with the number of stellate cells in the liver, and isolate and culture these cells from rat pancreas. METHODS: Liver and pancreatic sections from chow fed rats were immunostained for desmin, glial fibrillary acidic protein (GFAP), and alpha smooth muscle actin (alpha-SMA). Pancreatic stellate shaped cells were isolated using a Nycodenz gradient, cultured on plastic, and examined by phase contrast and fluorescence microscopy, and by immunostaining for desmin, GFAP, and alpha-SMA. RESULTS: In both liver and pancreatic sections, stellate shaped cells were observed; these were positive for desmin and GFAP and negative for alpha-SMA. Pancreatic stellate shaped cells had a periacinar distribution. They comprised 3.99% of all pancreatic cells; hepatic stellate cells comprised 7.94% of all hepatic cells. The stellate shaped cells from rat pancreas grew readily in culture. Cells cultured for 24 hours had an angular appearance, contained lipid droplets manifesting positive vitamin A autofluorescence, and stained positively for desmin but negatively for alpha-SMA. At 48 hours, cells were positive for alpha-SMA. CONCLUSIONS: Cells resembling hepatic stellate cells are present in rat pancreas in a number comparable with that of stellate cells in the liver. These stellate shaped pancreatic cells can be isolated and cultured in vitro.

Animals↗
PubMed1998

A Rorschach investigation of defensiveness, self-perception, interpersonal relations, and affective states in incarcerated pedophiles.

Rorschach protocols of 60 incarcerated men who met the Diagnostic and Statistical Manual of Mental Disorders (4th ed. [DSM-IV]; American Psychiatric Association, 1994) criteria for Pedophilia were compared to those of 60 incarcerated men with no history of sex offenses (matched for age, education, and race). Comprehensive System Rorschach variables (Exner, 1991) were selected based on both psychodynamic and cognitive-behavioral models of pedophilia. Pedophiles' Rorschachs (a) contained significantly more responses and were more likely to reveal signs of (b) anxiety and helplessness, (c) painful introspection, (d) distorted views of others, and (e) primitive dependency needs than the comparison group's Rorschachs. Like other incarcerated men, the pedophiles exhibited disturbances in self-worth (either poor self-esteem or excessive self-focus), tendencies to abuse fantasy and avoid emotionally tinged stimuli, and chronic oppositionality and hostility. Pedophiles possess many core personality features associated with Narcissistic Personality Disorders, but are less well defended against feelings of vulnerability and painful introspection than other incarcerated men. Like Antisocial Personality Disorder patients (Gacono & Meloy, 1994), our pedophiles and nonpedophile offenders showed signs of impaired attachment and, in the context of incarceration, failed narcissism.

Adult↗