Search PubMed⌕ Search

Biomedical subjects

D McCarthy

Publications and source records attributed to D McCarthy.

At least 37 records · Page 2Linked to original sources
PubMed1999

NSAID-related gastrointestinal complications.

Despite the common induction of gastrointestinal (GI) complications by nonsteroidal anti-inflammatory drugs (NSAIDs), many aspects of pathogenesis and management remain controversial. The most important complications are bleeding and perforation arising in the esophagus, stomach, and duodenum due to NSAID effects on platelets and on a variety of mucosal lesions. Complications arise from preexisting peptic ulcer, NSAID-induced ulcers and erosions, and other lesions (not caused by NSAIDs) caused to bleed by NSAID-induced platelet dysfunction. Much confusion has arisen from the umbrella term "NSAID gastropathy" used to embrace a variety of pathogenetically distinct mucosal lesions. Failure to discriminate among the different forms of NSAID injury has hampered clinical investigation. This article offers general guidelines for prevention of NSAID complications, but there remain many unresolved issues, including the role of Helicobacter pylori infection. The best approach to management is to remove or reduce exposure to NSAIDs whenever possible. The newer NSAIDs (e.g., cyclo-oxygenase [COX]-2-selective inhibitors) have a much lower risk of endoscopic ulcers and minimal platelet effects, which are likely to translate into lower risk of GI complications. However, this benefit on clinical outcome remains to be established.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

N-terminal and C-terminal modifications affect folding, release from the ribosomes and stability of in vitro synthesized proteins.

Important aspects of translation are release and folding of the synthesized protein into its three-dimensional structure. Studies from our group indicated that during in vitro protein synthesis a large portion of full-length polypeptides apparently accumulated as peptidyl-tRNA on ribosomes. We have also shown that some proteins though released in biologically active form may be inactivated without being degraded. These experiments were carried out by coupled transcription/translation using an Escherichia coli extract in which eukaryotic or prokaryotic test proteins were synthesized from their coding sequence inserted into specific plasmids. Experiments described here were designed to analyze the effects of N-terminal and C-terminal modifications of the coding sequence on the ribosomal release/termination process and on the stability of the newly synthesized protein. Elimination of the leader sequence in two proteins tested, mitichondrial rhodanese and bacterial beta-lactamase, caused an increase in the percentage of polypeptides released from the ribosomes relative to total synthesis. Conversely, an N-terminal extension such as a histidine-lag impaired the ribosomal release process. Also, a hydrophobic N-terminal modification of the synthesized protein reduced release of newly formed protein from the ribosomes. A C-terminal extension of the coding sequence for rhodanese by one amino acid decreased the percentage released polypeptide and furthermore affected the stability of the in vitro formed protein. We propose that a regulatory mechanism exists by which N-terminal and C-terminal sequences of a newly synthesized protein have feed-back effects on the termination factor-mediated release and on the stability of the native three-dimensional structure.

Cell-Free System↗
PubMed1999

Persons and their copies.

Is cloning human beings morally wrong? The basis for the one serious objection to cloning is that, because of what a clone is, clones would have much worse lives than non-clones. I sketch a fragment of moral theory to make sense of the objection. I then outline several ways in which it might be claimed that, because of what a clone is, clones would have much worse lives than non-clones. In particular, I look at various ideas connected with autonomy. I conclude that there is no basis to the claim that, because of what a clone is, clones would have much worse lives than non-clones. I therefore reject the claim that cloning human beings is morally wrong.

Cloning, Organism↗
PubMed1999

The effect of nutritional supplements on food intake in patients undergoing radiotherapy.

PURPOSE/OBJECTIVES: To describe the effect of nutritional supplements on food intake in patients undergoing radiotherapy. DESIGN: Experimental prospective. SAMPLE: 40 newly diagnosed patients with cancer beginning external beam radiation therapy. METHODS: Weekly dietary counseling and recording of total daily dietary intake for three days a week for four weeks. One half of the subjects were randomly assigned to ingest a liquid nutritional supplement between meals and at bedtime. MAIN RESEARCH VARIABLES: Total daily protein and caloric intake, food-derived protein and caloric intake, and supplement-derived protein and caloric intake. FINDINGS: Subjects ingesting nutritional supplements between meals significantly increased their total caloric and protein intake above that of controls and did not reduce their food-derived caloric or protein intake compared to controls. CONCLUSIONS: Nutritional supplements can be used to increase total caloric and protein intake without causing a significant reduction in food intake. IMPLICATIONS FOR NURSING PRACTICE: In this patient sample, supplements were not substituted for food intake. Further research is needed to determine the effects of supplements on appetite in patients with advanced cancer.

Adult↗
PubMed1998

Nonsteroidal anti-inflammatory drug-related gastrointestinal toxicity: definitions and epidemiology.

Nonsteroidal anti-inflammatory drug (NSAID)-associated gastrointestinal (GI) toxicity is a broad topic encompassing symptoms as well as severe GI complications. GI bleeding and perforation are the 2 overlapping components that account for the majority of deaths and disability associated with these drugs. Abnormal gastric endoscopic profiles as well as symptoms such as heartburn, pain, and dyspepsia are common in NSAID users, but no correlation has been found between these factors and the occurrence of the more severe complications; therefore, neither symptoms nor endoscopic observations can necessarily be considered reliable predictors of future outcomes. Confounding factors can increase the risk of complications, and specific NSAIDs vary in the magnitude and type of risk attending their use. Recent studies have focused on the contribution of nonprescription NSAIDs to total complications, and combined with evidence suggesting that the risk is greatest during the first month of NSAID use, it is apparent that NSAID toxicity is an acute as well as a chronic problem.

Age Factors↗
PubMed1998

Reactivation of thermally inactivated pre-beta-lactamase by DnaK, DnaJ, and GrpE.

To understand the role of the 23-amino acid signal sequence in the folding and stability of beta-lactamase, the precursor and a mutant beta-lactamase with a 19-amino acid signal sequence deletion were synthesized in vitro using an Escherichia coli cell-free coupled transcription/translation system. Approximately 30% of the newly synthesized full-length precursor and 60% of the deletion mutant polypeptides were terminated and released from the ribosomes as active enzyme. Activity of the pre-beta-lactamase, but not the mutant, was unstable at 37 degrees C, suggesting that the signal sequence causes the enzyme to unfold. This inactivation was independent of ATP. Pre-beta-lactamase activity was stabilized by lowering the temperature to 30 degrees C. Furthermore, addition of the molecular chaperones DnaK/J and GrpE, in the presence of ATP and Mg2+, restored the activity of the temperature-inactivated precursor. The precursor formed a stable complex with DnaK and GrpE. Both ATP and DnaJ were required for recovery of enzymatic activity, indicating that DnaJ may bind transiently to the complex. These results suggest that the signal sequence of the pre-beta-lactamase causes a temperature-dependent unfolding of the synthesized enzyme and that DnaK/J and GrpE interact with unfolded pre-beta-lactamase to promote refolding of the protein into its native, enzymatically active conformation.

Adenosine Triphosphate↗
PubMed1998

Generation of a nude mouse tumor model for in vivo replication of human cytomegalovirus.

Human cytomegalovirus (HCMV) is a common opportunistic infection resulting in retinitis in 15%-40% of AIDS patients. Several anti-HCMV therapies are currently available, and new treatments are in various stages of development. An HCMV animal model involving in vivo infection of human cells without the dependence on human fetuses or multiple surgical procedures has been developed. A human glioblastoma cell line that is permissive for HCMV replication (U373MG) was adapted to grow as a subcutaneous tumor in nude mice. These tumors arise in approximately 7 days and grow progressively. An evaluation of HCMV DNA replication demonstrated an increase in the accumulation of HCMV DNA within infected tumors from 48 to 168 h after infection. Immunohistochemical analysis showed focal areas of HCMV infection in which expression of immediate-early and late antigens was detected. In addition, it was demonstrated that ganciclovir inhibited HCMV DNA replication in vivo in a dose-dependent manner.

Animals↗
PubMed1998

Complement-binding anti-Jka not detectable by DiaMed gels.

BACKGROUND: An anti-Jka was not detectable by the DiaMed-ID Micro Typing System but was strongly reactive when tested using other indirect antiglobulin test (IAT) methods. However, it was detectable in the DiaMed-ID system when the recommended diluent ID-Diluent 2, was replaced by other low ionic Strength saline (LISS) solutions. This led us to believe that the problem lay with the ID-Diluent 2. METHODS: The anti-Jka was investigated using various low ionic strength diluents in the IAT against both polyspecific and monospecific antiglobulin reagents. We tested the ID-Diluent 2 for its ability to inhibit complement activation, and bind calcium. RESULTS: The anti-Jka was shown to be a 'complement-only' binding antibody that reacted in all IATs performed except when tested with ID-Diluent 2. The ID-Diluent was shown to prevent haemolysis of ABO lytic antibodies, and further testing shows that it binds calcium. CONCLUSION: The use of a diluent which prevents haemolysis and binds calcium in an IAT system that contains anti-complement as well as anti-IgG must be questioned.

Aged↗
PubMed1996

The diagnosis of iron deficiency in patients with rheumatoid arthritis and anemia: an algorithm using simple laboratory measures.

OBJECTIVE: Anemia of chronic disorders (ACD) and iron deficiency are common features in rheumatoid arthritis (RA), but may be difficult to distinguish without marrow sampling, which is invasive, time consuming, and expensive. We sought simple laboratory measures that identified patients with absent marrow iron stores (iron deficiency). METHODS: 45 anemic patients with RA underwent marrow sampling in addition to a complete blood count and serum ferritin and iron saturation measurements. RESULTS: 47% of patients had iron deficiency. These patients had significantly lower mean corpuscular volume (MCV), serum ferritin, and iron saturation. A 3 step algorithm was developed using these laboratory variables to identify iron deficiency. This algorithm correctly classified 94% patients with iron deficiency and 85% with ACD. CONCLUSION: Our study demonstrates that iron deficiency may be reliably identified by measuring serum ferritin, MCV, and iron saturation in many patients with RA, thereby avoiding the trauma and expense of marrow sampling.

Adult↗
PubMed1995

Synthesis and characterization of an aryl-azidoparoxetine. A novel photo-affinity probe for serotonin-transporter.

Paroxetine is an effective antidepressant drug and potent serotonin (5-HT) uptake inhibitor. It selectively labels 5-HT transporter on platelets and neurons. We report here the synthesis of an aryl-azido derivative of paroxetine, which is a novel photoactive and irreversible ligand for the [3H]paroxetine binding site on the platelet 5-HT transporter. The compound inhibited [3H]paroxetine binding (IC50, 55 nM) and 5-HT uptake (IC50, 12 nM) at equilibrium conditions and inactivated 10-20% of [3H]paroxetine binding sites upon irradiation at 320 nm. SDS-PAGE of platelet protein extract labelled with the radioactive analogue of the synthesized probe revealed the presence of four radioactive bands of which the 71-kDa one was the most prominent.

Affinity Labels↗
PubMed1995

Whole body autoradiography of CCK-8 in rats.

Rats were given i.v., intranasal or intraperitoneal doses of CCK-8 (sulfated) labelled with 125I-labeled Bolton and Hunter reagent. Radioactivity was found mainly in the liver, kidney, and the intestinal contents. No radioactivity was detected in the brain. In animals dosed i.v., specific localization occurred in the tissue of the pyloric region of the stomach, and in the pancreas. Label persisted within the pyloric region of the stomach for longer than 30 min, in spite of the reported half-life of CCK-8 in plasma of approximately 1 min. Intranasal and intraperitoneal doses had limited bioavailability. The binding to the sites in the pyloric region of the stomach, which required systemic delivery, may have identified receptors associated with appetite control.

Administration, Intranasal↗
PubMed1995

Comparison of the effects of hydrophobicity, amphiphilicity, and alpha-helicity on the activities of antimicrobial peptides.

Multiple linear regression was used to quantify the dependence of the antimicrobial activity of 13 peptides upon three calculated or experimentally determined parameters: mean hydrophobicity, mean hydrophobic moment, and alpha-helix content. Mean hydrophobic moment is a measure of the amphiphilicity of peptides in an alpha-helical conformation. Antimicrobial activity was quantified as the reciprocal of the measured minimal inhibitory concentration (MIC) against Escherichia coli. One of the peptides was magainin 2, and the remainder were novel peptides designed for this study. The multiple linear regression results revealed that the amphiphilicity of the peptides was the most important factor governing antimicrobial activity compared to mean hydrophobicity or alpha-helix content. A better regression of the data was obtained using ln(1/MIC+constant) as the dependent variable than with either 1/MIC or ln(1/MIC). These results should be useful in designing peptides with higher antimicrobial activity.

Amino Acid Sequence↗