Search PubMed⌕ Search

Biomedical subjects

W M McDonnell

Publications and source records attributed to W M McDonnell.

At least 19 recordsLinked to original sources
PubMed1997

Immunization.

Immunization is undergoing important changes, with improved vaccines replacing less immunogenic or less safe vaccines, new vaccines for common diseases such as chickenpox and hepatitis A infection, and improved immunization schedules. Immunization is also being transformed by basic work in molecular medicine. Vaccines made of DNA are being developed as a form of gene therapy that use the patient's own cellular machinery to make foreign proteins that stimulate an immune response. Currently immunization is used to protect patients prior to exposure to an infectious agent or during the incubation phase after exposure, but before disease has occurred. New technologies are being investigated to induce the immune system to fight infections that have already produced chronic disease such as acquired immunodeficiency syndrome and chronic hepatitis B virus infection.

Humans↗
PubMed1996

Identification of bilirubin UDP-GTs in the human alimentary tract in accordance with the gut as a putative metabolic organ.

The initial identification of traditionally hepatic enzymes expressed in the gut has led to the hypothesis that the gut may function as a metabolic organ. The UDP glucuronosyltransferases (UDP-GTs) play an important role as phase II metabolizing enzymes. Previously members of this family have been identified in the gut by non-isoform specific immunoreactivity, and a small amount of bilirubin glucuronosyltransferase activity was detected in the colon. Recent reports of gut transplantation to reverse the metabolic defect in Gunn rats raised further interest in the expression and distribution of human bilirubin (UDP-GTs (HUG Br 1 and HUG Br 2) in the human alimentary tract. The availability of molecular genetic probes for HUG Br 1 and HUG Br 2 permits the screening of the alimentary tract for the presence of isoform specific message. RNA samples extracted from pinch biopsy specimens of buccal mucosa, esophagus, stomach body, antrum, duodenum, and colon were analyzed for expression of HUG Br 1 and HUG Br 2. HUG Br 1 hybridization was detected in duodenum > colon, whereas HUG Br2 hybridization was detected in duodenum > esophagus > colon. Immunoreactivity data confirmed the presence of HUG Br 1 protein at low levels in the duodenum, whereas the less abundant HUG Br 2 protein was below the limits of detection of isoform specific anti-peptide antibodies. Bilirubin specific reactivity was demonstrated in duodenal samples but not antrum samples, consistent with the molecular genetic data. The presence of functional bilirubin UDP-GT isoforms in human alimentary tract supports the notion that the gut may function as a metabolic organ and may have diagnostic and therapeutic implications for disorders of bilirubin metabolism.

Adult↗
PubMed1996

DNA vaccines.

Explore the source record for details and available documents.

DNA↗
PubMed1996

Nicotine effects on prostaglandin-dependent gastric slow wave rhythmicity and antral motility in nonsmokers and smokers.

BACKGROUND & AIMS: Mechanisms of antral hypomotility with smoking are unknown. Slow wave disruption, which may be prostaglandin dependent, inhibits gastric motility. This study tested if nicotine reproduces motor effects of smoking and assessed the role of slow wave disruption in inducing hypomotility and the prostaglandin dependence of dysrhythmic responses. METHODS: Electrogastrography and antroduodenal manometry were performed in 9 nonsmokers and 9 smokers during transdermal nicotine treatment (14 mg). Studies were repeated after administration of 150 mg indomethacin daily for 3 days to test prostaglandin requirements of nicotine responses. RESULTS: Antral migrating motor complex periodicity and fasting and fed motility indices, not different in the groups under control conditions, decreased similarly in nonsmokers and smokers with nicotine. Tachygastria (> 4.5 cycle/min) increased from 2% +/- 2% to 16% +/- 3% of recording time, and arrhythmias (frequency instability index) increased from 0.5 +/- 0.1 to 1.1 +/- 0.2 cycle/min with nicotine in nonsmokers (P < 0.05), which normalized with indomethacin. Electrogastrography results were unchanged in smokers. CONCLUSIONS: Nicotine evokes antral hypomotility in nonsmokers and smokers but evokes prostaglandin-dependent gastric dysrhythmias only in nonsmokers. Smokes show desensitization to nicotine-stimulated dysrhythmias. Thus, slow wave disruption is not essential to inhibit motor activity. This provides a model for the motor and myoelectric effects of smoking.

Adolescent↗
PubMed1996

Massive secretory diarrhea and pseudo-obstruction as the initial presentation of Crohn's disease.

We report large-volume secretory diarrhea and intestinal pseudo-obstruction in a man whom ultimately proved to have Crohn's disease that responded to sulfasalazine and steroids with resolution of all his symptoms. Although this is an unusual presentation, Crohn's disease should be included in the differential diagnosis in patients whose initial symptoms are intestinal pseudo-obstruction and secretory diarrhea.

Anti-Inflammatory Agents↗
PubMed1995

Misuse of veterinary phenylbutazone.

Phenylbutazone is a nonsteroidal anti-inflammatory drug that was commonly prescribed for the treatment of arthritic conditions; it is no longer available for use in humans because of its numerous side effects, including aplastic anemia. We describe a horse trainer who developed gastric ulcers and renal insufficiency as a result of taking veterinary phenylbutazone. A review of the literature reveals a pattern of abuse by those who work with and around animals. When appropriate, patients who work around animals should be questioned about illicit phenylbutazone consumption.

Acute Kidney Injury↗
PubMed1995

Effects of smoking on interdigestive gastrointestinal motility.

The effect of smoking on interdigestive gastrointestinal motility is little studied but may play a role in gastrointestinal morbidity. We studied gastroduodenal motility in 10 volunteers (five smokers and five nonsmokers) using a water-perfused pressure catheter. A pH probe was placed in the duodenal bulb. Baseline motility was recorded until phase III of the migrating-motor complex had occurred in the stomach three times in order to record two complete cycles of MMC activity. Subjects then began smoking until phase III activity occurred again (mean duration of smoking 117 min). During the control period, all subjects had normal MMC cycles and there were no differences between smokers and nonsmokers. While smoking, no gastric phase III was observed in any subject and gastric motility was markedly reduced. In seven of 10 subjects, smoking did not prevent the occurrence of normal duodenal phase III activity. Three subjects had no duodenal phase III activity during smoking. The duodenal pH profile did not change during smoking and motilin levels continued to fluctuate in conjunction with phase III activity. In conclusion, smoking abolished phase III activity in the stomach without affecting the plasma motilin cyclic fluctuations or duodenal bulb pH. In contrast, smoking has little effect on duodenal motility.

Adult↗
PubMed1995

High efficiency prokaryotic expression and purification of a portion of the hepatitis C core protein and analysis of the immune response to recombinant protein in BALB/c mice.

Hepatitis C virus (HCV) produces chronic persistent liver infection in 1-2% of the U.S. population and is the leading cause of end stage liver disease in patients presenting for liver transplantation at our center. Efforts to cure persistent HCV infection are frequently unsuccessful, so the development of a HCV vaccine is a high priority. HCV envelope proteins are hypervariable so production of a recombinant surface antigen vaccine such as is available for hepatitis B is not likely to confer widespread, high level protective immunity. As the most highly conserved structural protein in the HCV genome, the core protein is one reasonable target for vaccine production. Presented here are data on the manufacture of recombinant core protein containing partial carboxy terminus deletions in an effort to increase the efficiency of core expression. The maltose binding protein (MBP) and glutathione S-transferase (GST) protein prokaryotic expression systems were used to study two different constructs, expressing the first 140 and 163 amino acids of the core region. Deletion of the 23 amino acids (aa) from aa141-163 led to a marked increase in the efficiency of protein production from < 1 to 3-4 mg/liter for both systems studied. Protein purification was accomplished using affinity chromatography (MBP) or inclusion body isolation (GST) as determined by SDS-PAGE gels and immunotransblot with HCV core protein-specific monoclonal antibody. Finally, the immune response to recombinant protein was assessed in BALB/c mice using a MBP HCV core fusion protein and an ELISA developed using GST HCV core protein as a target. In all mice of this strain, serum anti-HCV core antibody titer increased to 10(-4), two logs above background, following immunization in conjunction with Freund's complete adjuvant. These results represent an encouraging first step toward production of a core protein vaccine. Recombinant core protein is a useful tool to study the immune response to core protein and may be useful to further study the epidemiology and biology of the HCV virus.

3T3 Cells↗
PubMed1995

Sequence analysis of the hepatitis C virus (HCV) core gene suggests the core protein as an appropriate target for HCV vaccine strategies.

Hepatitis C virus (HCV) is a major healthproblem with a prevalence of 1% in the United States population, and a significant percentage of infected patients progress to chronic liver disease and cirrhosis. Interferon therapy has demonstrated that the immune system can be modulated to alter the acute course of the disease, but long-term treatments remain elusive. Prevention of hepatitis C infection is therefore an important strategy to mitigate the impact of this disease. Initial attempts at vaccination have focused on recombinant envelope vaccines, which have shown an ability to protect against very low titre challenges of HCV in chimps. The need for vaccines capable of protecting against higher titre challenges has led to the search for alternative vaccine strategies. The most highly conserved structural protein in the HCV genome is the core protein, and vaccine strategies targeting the core protein have been proposed to increase vaccine efficacy. The variability of HCV core sequences and genotypes in the Ann Arbor patient population are not known, and the present study was undertaken to assess the theoretical feasibility of developing a HCV core vaccine by excluding promiscuous core (C) gene variability as a mechanism of vaccine failure. Results of nucleotide and deduced amino acid sequence analysis from 13 of 14 patients studied reveal a 93% nucleotide and 96.4% amino acid core sequence homology in the C gene regions studied. Genotype analysis revealed four of 14 to be type 1a and nine of 14 to be type 1b with one infection not being sufficiently characterized to determine genotype. These results demonstrate a sufficiently high degree of conservation of HCV core sequences in our patient population to permit design of a vaccine directed against core protein.

Amino Acid Sequence↗