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Biomedical subjects

M Shoemaker

Publications and source records attributed to M Shoemaker.

14 recordsLinked to original sources
PubMed2001

Is nausea associated with chronic hepatitis C infection?

OBJECTIVES: Hepatitis C virus is a common chronic infection that is widely associated with symptoms of fatigue and pain in the right upper quadrant. Nausea may be an underrecognized symptom. This study was designed to study the frequency of nausea in patients with hepatitis C virus infection compared to controls. METHODS: A cross-sectional study design with consecutive outpatients was used. Three groups were administered a dyspepsia and a previously validated Nausea Profile questionnaire. Univariate and multivariate analysis was performed. RESULTS: A total of 64 hepatitis C virus (HCV) patients, 53 liver disease controls (LC), and 64 normal controls (NC) were studied. An increased period prevalence of nausea was found in HCV patients 43% versus 29.7% in NC and 18.9% in LC (p = 0.009). There was an increased frequency of fatigue and abdominal pain in HCV patients over 1 month compared to LC and NC combined (p = 0.0001 and 0.0065 respectively). The Nausea Profile score revealed statistically higher total scores and higher subscale scores in the HCV group compared to controls. The total NP score expressed as a percentage of the maximum was 27% in HCV versus 12.7% for LC and 9.2% for NC (p = 0.0005). The odds of nausea using logistic regression were 2.1 CI (1.0-4.5) in HCV patients compared to controls (p = 0.05). Using linear regression, higher Nausea Profile scores were found to be independently associated with the diagnosis of HCV (.0005), fatigue (p = 0.0003), and abdominal pain (p = 0.0001). CONCLUSIONS: HCV infection is associated with an increased risk for nausea. The strong association between abdominal pain and nausea may be a clue to the etiology of nausea in these patients. Further etiological studies are needed.

Abdominal Pain↗
PubMed2001

Inhibition of CYP3A4 in a rapid microtiter plate assay using recombinant enzyme and in human liver microsomes using conventional substrates.

Cytochrome P450 inhibition studies are performed in the pharmaceutical industry in the discovery stage to screen candidates that may have the potential for clinical drug-drug interactions. A 96-well microtiter plate assay using recombinant cytochrome P450 (Supersomes) has been used to increase the overall throughput. The IC(50) values for the inhibition of CYP3A4 by 52 new chemical entities (NCEs) were determined using the Supersomes assay with resorufin benzyl ether as a substrate, and the data were compared with those obtained in human liver microsomes (HLM) using midazolam as a substrate. Among the 52 compounds tested, 25 showed IC(50) values within a 5-fold difference in the two assays. For all compounds that showed a >5-fold difference, the IC(50) values in the Supersomes assay were lower than those obtained in HLM, except for one compound. Further studies suggested that this discrepancy was not related to difference in protein concentrations between the two assays. In addition, the IC(50) values for 16 compounds with a wide range of inhibition potency were determined in HLM using testosterone and dextromethorphan as substrates. The results showed an 80 to 93% match within a 5-fold difference between the three probe substrates. However, for certain compounds including ketoconazole, there were substrate-dependent differences in the inhibition. The results suggest that the difference between the Supersomes and HLM could be partially attributed to differences in the substrate used, and to metabolism by other cytochrome P450s present in the HLM but not in the Supersomes. Furthermore, multiple CYP3A4 substrates should be used to improve the reliability of estimating potential drug-drug interaction of NCEs.

Cytochrome P-450 CYP3A↗
PubMed1999

Characterization of NAD:arginine ADP-ribosyltransferases.

NAD:arginine mono-ADP-ribosyltransferases catalyze the transfer of ADP-ribose from NAD to the guanidino group of arginine on a target protein. Deduced amino acid sequences of one family (ART1) of mammalian ADP-ribosyltransferases, cloned from muscle and lymphocytes, show hydrophobic amino and carboxyl termini consistent with glycosylphosphatidylinositol (GPI)-anchored proteins. The proteins, overexpressed in mammalian cells transfected with the transferase cDNAs, are released from the cell surface with phosphatidylinositol-specific phospholipase C (PI-PLC), and display immunological and biochemical characteristics consistent with a cell surface, GPI-anchored protein. In contrast, the deduced amino acid sequence of a second family (ART5) of transferases, cloned from murine lymphoma cells and expressed in high abundance in testis, displays a hydrophobic amino terminus, consistent with a signal sequence, but lacks a hydrophobic signal sequence at its carboxyl terminus, suggesting that the protein is destined for export. Consistent with the surface localization of the GPI-linked transferases, multiple surface substrates have been identified in myotubes and activated lymphocytes, and, notably, include integrin alpha subunits. Similar to the bacterial toxin ADP-ribosyltransferases, the mammalian transferases contain the characteristic domains involved in NAD binding and ADP-ribose transfer, including a highly acidic region near the carboxy terminus, which, when disrupted by in vitro mutagenesis, results in a loss of enzymatic activity. The carboxyl half of the protein, synthesized as a fusion protein in E. coli, possessed NADase, but not ADP-ribosyltransferase activity. These findings are consistent with the existence at the carboxyl terminus of ART1 of a catalytically active domain, capable of hydrolyzing NAD, but not of transferring ADP-ribose to a guanidino acceptor.

ADP Ribose Transferases↗
PubMed1998

Abnormal properties of creatine kinase in Alzheimer's disease brain: correlation of reduced enzyme activity and active site photolabeling with aberrant cytosol-membrane partitioning.

The report shows that Alzheimer's disease (AD) brain creatine kinase (CK) is modified such that the nucleotide binding site of CK is blocked and that abnormal partitioning of CK between the soluble and pellet fractions occurs. First, CK activity was 86% decreased in AD brain homogenates in comparison to age-matched controls. Secondly, over a 23.5 fold greater 32P photoincorporation of [alpha 32P]8N3ATP was observed into CK of control vs. AD samples. Also, a 7.4-fold increase of enzyme induced 32P incorporation was observed in controls vs. AD samples by incubation with [gamma 32P]ATP. Thirdly, Western blot analysis showed that CK copy numbers in the AD homogenate were decreased by less than 14% in comparison to controls. However, analysis showed that control supernatant and pellet fractions contained 10.3 and 0.4 times the CK copy number found in the corresponding AD fractions. 32P incorporation by both photolabeling and enzyme catalyzed incorporation of radiolabel followed CK activity and not CK copy number. Further, [alpha 32P]ADP and [gamma 32P]ATP incorporated 32P into control brain and purified brain CK equally well, indicating that a mechanism different from gamma-phosphoryl transfer is involved in the enzymatic incorporation of radiolabel. Also, the level of abnormal partitioning of CK into AD brain pellet correlated with the decreased [32P]8N3GTP photolabeling and abnormal partitioning of beta-tubulin, a protein known to be aberrantly modified in the AD brain. This indicates that a common chemistry is affecting both CK and tubulin in AD.

Alzheimer Disease↗
PubMed1998

22-Mb integrated physical and genetic map based on YAC/STS content spanning the interval DXS1125-DXS95 in human Xq12-q21.31.

A YAC/STS map has been assembled spanning 22 Mb across Xq12-q21.31, between markers DXS1125 and DXS95. In addition to the landmark loci for the X-inactivation center XIST and the ATRX, ATP7A, phosphoglycerate kinase, POU3F4, and choroideremia genes, the candidate disease gene regions for torsion dystonia 3 and two X-linked mental retardation syndromes are included. Also, the human voltage-dependent anion channel gene (HVDAC1) has been placed near DXS986. The current map incorporates 211 YACs from five different libraries, formatted with 185 STSs that comprise 26 genetic linkage markers, 60 newly-developed YAC-end STSs, and eight ESTs. The multiple clone coverage and average resolution of one STS per 120 kb provide resources for disease gene searches and are facilitating complete sequencing of the region.

Base Sequence↗
PubMed1996

The experience of being a male student nurse.

Although schools of nursing market their programs to all segments of society, men are underrepresented in schools of nursing. The purpose of this study was to identify male students' perceptions of the motivational factors, barriers and frustrations encountered in becoming a nurse. Eighteen students attended one of four focus groups representing one associate program, two baccalaureate programs and one diploma program. The students' belief that society perceived nursing as a feminine profession was an underlying thread that related to many of their perceptions and feelings. The most influential support people noted were immediate family, especially wives. The participants also believed that high school counselors were of no assistance in choosing nursing as a career. Even though the schools of nursing were perceived as supportive, the participants had feelings of isolation and self-doubt.

Adult↗
PubMed1994

A study and model of the role of the Renshaw cell in regulating the transient firing rate of the motoneuron.

This study sought to investigate the role of the Renshaw cell with respect to transient motoneuron firing. By studying the cat motoneuron and Renshaw cell, several low-order lumped parameter models were developed that simulate the known characteristics of the injected input current vs. firing rate. The neuron models in the Renshaw cell inhibition configuration were tuned to fit experimental data from cat motoneurons. Models included both linear versions and those with sigmoidal nonlinearities. Results of the simulation indicate that the motoneuron itself provides the adaptation seen in its firing rate and that the Renshaw cell's role is primarily to fine-tune the motoneuron's adaptation process.

Action Potentials↗
PubMed1992

Identification of the guanine binding domain peptide of the GTP-binding site of glucagon.

Glucagon, a peptide hormone synthesized and secreted by alpha islet cells, regulates glucose homeostasis by several mechanisms. Using [gamma 32P]8N3GTP, a proven photoaffinity probe for GTP, a specific nucleotide binding site on human glucagon was detected that showed preference for GTP. Half-maximal saturation of photoinsertion into the polypeptide hormone was at 8-12 microM with either [alpha 32P]8N3GTP or [gamma 32P]8N3GTP. GTP protected photolabeling with an apparent kd of 15 microM, whereas ATP was less effective as a protector, exhibiting an apparent kd of about 30 microM. Maximal protection by GTP and ATP was over 90%. UTP, CTP, GDP, ADP, GMP, AMP, guanosine, adenosine, guanine, and adenine were much less effective protectors, indicating that binding is specific for purine nucleoside triphosphates, particularly GTP. Mg2+ at 150 microM enhanced photoinsertion (twofold), whereas at 2-10 mM, it inhibited photoinsertion. Both Ca2+ and Zn2+ at 0.2 mM decreased photoinsertion about 45%. Purification of chymotryptic and tryptic digests of photolabeled glucagon by reverse-phase high performance liquid chromatography (HPLC) revealed that the N-terminal peptide, HSQGTF, was the only peptide region covalently photomodified by [32P]8N3GTP. GTP, if present during photolysis, greatly reduced both photoinsertion into glucagon and the amount of radiolabeled peptide recovered on HPLC. The specificity of binding to the N-terminal region is suggestive of a physiological role for a glucagon-GTP complex in the mechanism of action of this hormone.

Adenine↗
PubMed1990

Variables associated with weight loss and improvements in glycemic control in type II diabetic patients in behavioral weight control programs.

Because weight loss is difficult to achieve, it would be helpful to determine whether there are subgroups of obese type II diabetic patients who benefit most from participation in a behavioral weight loss program. We studied 178 obese patients with type II diabetes, who participated in a 12-20 week behavioral weight loss program and were followed for 1 year after the program to determine whether age, gender, percent overweight, medication, duration of diabetes or fasting glucose were related to weight loss and/or to the magnitude of improvement in glycemic control experienced with weight loss. Gender was the only variable related to weight loss; males lost more weight and had greater decreases in percent overweight than females. The variable most strongly related to improvement in glycemic control was pretreatment fasting glucose level; patients with higher initial glucose levels experienced the greatest improvements in control. There was no evidence to support the belief that patients on insulin have poorer weight losses or that patients with long-duration diabetes benefit less from weight reduction than those with recent-onset diabetes.

Behavior Therapy↗
PubMed1986

Differences in phosphate metabolite levels in drug-sensitive and -resistant human breast cancer cell lines determined by 31P magnetic resonance spectroscopy.

31P magnetic resonance spectra of perfused human breast cancer cells with the phenotype of pleiotropic drug resistance exhibit striking differences in the levels of phosphate metabolites from the wild-type, drug-sensitive parent cell line. Resistant cells demonstrated elevated levels of phosphocreatine and depressed levels of phosphomonoesters, phosphodiesters, and diphosphodiesters. These differences may reflect significant alterations in the control of bioenergetic metabolism between drug-resistant and -sensitive cells.

Breast Neoplasms↗
PubMedDate not supplied

Peritonsillitis: abscess or cellulitis?

Peritonsillitis encompasses both cellulitis and abscess. To determine the distinguishing factors for cellulitis and abscess, we reviewed 29 patients, 15 with cellulitis and 14 with abscess. Common presenting complaints included dysphagia, trismus, drooling, voice change and fever. Unilateral tonsillar enlargement was usually present, and uvular deviation was noted in 10 of 29 patients. The mean ages of patients with abscess was 15.0 years, and that of patients with cellulitis was 10.8 years. The two groups differed significantly by age (P = 0.02), and discriminant analysis showed age, dysphagia and drooling to be discriminators for abscess patients, while bilaterality or fever were not. Trismus was a discriminator for cellulitis patients. Etiology for abscess included Group A and non-Group A beta-hemolytic streptococci, Group D streptococcus, alpha-streptococcus, anaerobic diphtheroids and coagulase-negative staphylococci. The etiology of the cellulitis was Group A and non-Group A beta-hemolytic streptococci and Streptococcus pneumoniae. Peritonsillitis appeared to increase in frequency. On presentation patients with cellulitis are similar to patients with abscess. Abscess is more likely in adolescents. Recommended therapy is intravenous penicillin and prompt drainage for patients failing to respond.

Adolescent↗