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Biomedical subjects

E A Walker

Publications and source records attributed to E A Walker.

At least 19 recordsLinked to original sources
PubMed1996

Mechanism of action and cloning of epoxide hydrolase from the cabbage looper, Trichoplusia ni.

The majority of the JH III epoxide hydrolase activity in last stadium day 3 (gate 1) wandering Trichoplusia ni was membrane bound with approximately 9% of the activity found in the cytosol. Both the microsomal and cytosolic JH epoxide hydrolases were stable, retaining 30% of their original activity after incubation at 4 degrees C for 15 days. 18O-labeled water underwent enzyme catalyzed regioselective addition to the least substituted C10 position of JH III. In multiple turnover reactions with JH epoxide hydrolase in 97.9% 18O-labeled water, only 91.3% 18O incorporation was observed. This is consistent with an SN2 reaction likely involving a carboxylate in the active site of JH epoxide hydrolase. The DNA amplification cloning of a fragment of a putative T. ni epoxide hydrolase is reported. The deduced amino acid sequence shares 67% similarity to the rat microsomal epoxide hydrolase.

Amino Acid Sequence↗
PubMed1996

Molecular analysis of two functional homologues of the S3 allele of the Papaver rhoeas self-incompatibility gene isolated from different populations.

The S3 allele of the S gene has been cloned from Papaver rhoeas cv. Shirley. The sequence predicts a hydrophilic protein of 14.0 kDa, showing 55.8% identity with the previously cloned S1 allele, preceded by an 18 amino acid signal sequence. Expression of the S3 coding region in Escherichia coli produced a form of the protein, denoted S3e, which specifically inhibited S3 pollen in an in vitro bioassay. The recombinant protein was ca. 0.8 kDa larger than the native stigmatic form, indicating post-translational modifications in planta, as was previously suggested for the S1 protein. In contrast to other S proteins identified to date, S3 protein does not appear to be glycosylated. Of particular significance is the finding that despite exhibiting a high degree of sequence polymorphism, secondary structure predictions indicate that the S1 and S3 proteins may adopt a virtually identical conformation. Sequence analysis also indicates that the S1 and S3 proteins may adopt a virtually identical conformation. Sequence analysis also indicates that the P. rhoeas S alleles share some limited homology with the SLG and SRK genes from Brassica oleracea. Previously, cross-classification of different populations of P. rhoeas had revealed a number of functionally identical alleles. Probing of Western blots of stigma proteins from plants derived from a wild Spanish population which contained an allele functionally identical to the Shirley S3 allele with antiserum raised to S3e, revealed a protein (S3s) which was indistinguishable in pI and Mr from that in the Shirley population. A cDNA encoding S3s was isolated, nucleotide sequencing revealing a coding region with 99.4% homology with the Shirley-derived clone at the DNA level, and 100% homology at the amino acid level.

Alleles↗
PubMed1996

In vivo apparent pA2 analysis in rats treated with either clocinnamox or morphine.

Experiments tested the hypothesis that loss of agonist potency or effectiveness following irreversible antagonist or chronic agonist treatment may result from affinity changes at mu opioid receptors. Apparent affinity of naltrexone or nalbuphine for mu opioid receptors was measured in vivo in rats treated with either a single dose of the irreversible antagonist clocinnamox or repeated doses of morphine. Apparent affinity of each antagonist was estimated from its potency as an antagonist of discriminative stimulus or rate-decreasing effects of morphine in rats trained to discriminate 3.2 mg/kg morphine and saline. In control rats, apparent pA2 values for naltrexone and nalbuphine were 7.5-7.6 and 5.3, respectively. In clocinnamox-treated rats, apparent pA2 values for naltrexone were 7.2-7.7, suggesting that clocinnamox treatment did not alter affinity of naltrexone for sites through which morphine exerts behavioral effects. In rats treated repeatedly with morphine, apparent pA2 values for nalbuphine were 5.1-5.3, suggesting that repeated morphine treatment did not alter affinity of nalbuphine for these sites. The observation that neither clocinnamox nor repeated morphine treatment altered in vivo affinity estimates for naltrexone or nalbuphine, respectively, suggests that the reductions in agonist potency produced by these treatments do not result from changes in affinity at mu opioid receptors.

Animals↗
PubMed1996

Factors related to dissociation among patients with gastrointestinal complaints.

OBJECTIVES: Several recent reports have suggested that the process of dissociation is independently associated with several distressing conditions such as psychiatric diagnoses, somatization, current psychological distress, and past sexual and physical victimization. These studies, however, have not taken into account possible shared variance between these variables. Is dissociation uniquely related to each of these outcomes or do they, as a group, have common underlying factors that account for the relationship with dissociation? METHOD: As part of a larger study of gastroenterology clinic patients with irritable bowel syndrome and patients with inflammatory bowel disease (n = 103), we used stepwise multiple regression to select the factors most associated with dissociation, while controlling for the effects of other variables. Variable domains included demographics, psychiatric diagnoses, personality factors, functional disability, and trauma history. These domains as well as individual variables within these domains were systematically evaluated for their unique contribution to the prediction of dissociation as measured by the Dissociative Experiences Scale (DES). RESULTS: The best multivariable model for estimating dissociation magnitude included severe child sexual abuse, perceived physical disability, and lifetime dysthymia, alcoholism, and generalized anxiety disorder. These factors accounted for 37% of the variance in DES score and increased the correct classification of patients as either low-, middle-, or high-level dissociators. CONCLUSIONS: Dissociation among this convenience sample of IBS and IBD patients is a long-term coping pattern that is associated primarily with past sexual trauma, chronic emotional distress, alcoholism, and physical disability. Prospective studies are needed to test whether these findings also occur in other more generalizable samples.

Adolescent↗
PubMed1996

The relationship of current psychiatric disorder to functional disability and distress in patients with inflammatory bowel disease.

Although prior theories about psychiatric disorders causing inflammatory bowel disease (IBD) have largely been discredited, these same disorders have at times been associated with functional gastrointestinal symptoms such as those found in irritable bowel syndrome. Since functional gastrointestinal symptoms can also occur in patients with organic pathology, we hypothesized that a current psychiatric disorder might amplify or produce additional gastrointestinal symptoms in patients with organic gastrointestinal diseases such as IBD, leading to additive functional disability and decreased quality of life. This pilot study evaluated a sequential sample of 40 IBD patients using the NIMH Diagnostic Interview Schedule, structured interviews for functional gastrointestinal symptoms, and prior episodes of emotional, physical, and sexual abuse as well as self-report measures of personality and disability. We compared IBD patients with and without a current psychiatric disorder while controlling for disease severity. Eight patients with major depression were treated with antidepressants. Patients with a current psychiatric disorder had significantly higher 1) mean number of lifetime psychiatric diagnoses, 2) prevalence rates of prior sexual and physical victimization, and, 3) mean numbers of both gastrointestinal and other medically unexplained symptoms despite no differences in severity of IBD. Significant and trend level differences were apparent on several measures of functional disability. A regression analysis showed that number of psychiatric diagnoses, number of functional gastrointestinal symptoms, and dissociation scale scores significantly discriminated the groups. Treatment of current major depression decreased functional disability despite no objective changes in gastrointestinal disease severity. It was concluded that the presence of a current psychiatric disorder appears to alter the perception of disease severity in patients with IBD. Nonrecognition of the psychiatric disorder may lead to unnecessary and aggressive interventions for IBD patients such as medication changes, invasive testing, or surgery. The presence of a current psychiatric illness also appears to be associated with increased functional disability. Psychiatric evaluation and treatment, therefore, have an important role in the ongoing management of IBD patients with distressing gastrointestinal symptoms not directly attributable to their IBD.

Activities of Daily Living↗
PubMed1996

Assessing abuse and neglect and dental fear in women.

Little is known about how specific life stressors, such as sexual, physical and emotional abuse and neglect, might be factors in the establishment or maintenance of dental fears or might affect routine dental treatment. The authors collected data from 462 female members of a large urban health maintenance organization about their dental fear and histories of childhood and adult traumas. According to these data, a history of trauma appears to be significantly associated with elevated dental fear, although multiple factors play a major role in the establishment and maintenance of these phobias.

Adolescent↗
PubMed1996

Chronic pelvic pain and gynecological symptoms in women with irritable bowel syndrome.

Chronic pelvic pain and irritable bowel syndrome are common disorders, yet very little is known about their comorbidity. As part of an epidemiological study of patients with irritable bowel syndrome or irritable bowel disease we inquired about a history of chronic pelvic pain and related gynecological problems, and hypothesized that distress associated with either of these conditions was additive in women with both syndromes. A medically trained interviewer evaluated a sequential sample of 60 women with irritable bowel syndrome and 26 women with inflammatory bowel disease in an urban gastroenterology clinic using the National Institute of Mental Health Diagnostic Interview Schedule, the Briere Child Maltreatment Interview (emotional, physical and sexual abuse), and a structured interview to elicit a lifetime history of chronic pelvic pain that was distinct from the history of bowel distress. Chronic pelvic pain was reported in 21 (35.0%) of the irritable bowel syndrome patients vs. 4 (13.8%) of the inflammatory bowel disease group (p < 0.05). Compared to women with irritable bowel syndrome alone, those with both irritable bowel syndrome and chronic pelvic pain were significantly more likely to have a lifetime history of dysthymic disorder, current and lifetime panic disorder, somatization disorder, childhood sexual abuse and hysterectomy. Logistic regression showed that mean number of somatization symptoms was the best predictor of a history of both irritable bowel syndrome and chronic pelvic pain compared either to inflammatory bowel disease or irritable bowel syndrome alone. Many women with irritable bowel syndrome may have a history of chronic pelvic pain as well. The high rates of psychopathology associated with irritable bowel syndrome and chronic pelvic pain independently are even higher in women with both syndromes, and women who present with either irritable bowel syndrome or chronic pelvic pain should probably be evaluated for both disorders.

Adult↗
PubMed1995

Assessment of documented foot examinations for patients with diabetes in inner-city primary care clinics.

BACKGROUND: The established guidelines for a diabetes foot examination include assessing circulatory, skin, and neurological status to detect problems early and reduce the likelihood of amputation. OBJECTIVE: To determine documented adherence with guidelines for foot examinations. SETTING: Four clinics in underserved areas. METHODS: Charts of 350 diabetic patients, identified by billing code, were reviewed for foot examination documentation. A documented foot examination was defined as assessing at least two of the three components of a foot examination. The review determined the periodicity and prevalence of foot examinations, referrals to a podiatrist or vascular surgeon during a 2-year period, and risk factors for foot complications. Stepwise logistic regression was used to determine whether risk factors for foot complications predicted foot examination status. RESULTS: The patients had a mean age and duration of diabetes of 57.7 and 8.8 years, respectively; 86% were black or Hispanic. There was no indication of foot examination or referral for 55.7% of the patients during the 2-year period. Patients with foot care referrals were more likely to have foot examinations by their primary care providers (P = .0001). There was almost a fourfold increase in the odds that patients with diagnosed peripheral vascular disease had foot examinations, with twofold greater odds for each 25-year increase in age. CONCLUSIONS: Populations at risk of diabetic complications are unlikely to have foot examinations in their primary medical care, but having peripheral vascular disease increases the likelihood. Efforts are needed to improve adherence to foot examination guidelines for patients with diabetes from underserved populations.

Ambulatory Care Facilities↗
PubMed1995

Medical and psychiatric symptoms in female gastroenterology clinic patients with histories of sexual victimization.

Several recent retrospective reports have associated prior sexual victimization and long-term medical sequelae such as increased medical clinic utilization and reports of physical symptoms. However, methodological constraints have limited the generalizability of these findings. Our study was designed using structured interviews with a sequential sample of 89 female gastroenterology clinic patients, who were classified by severity of sexual trauma and studied for differences in lifetime psychiatric diagnoses, physical abuse, and medically unexplained symptom patterns. Compared with the 46 women who had experienced less severe or no prior sexual trauma, the 43 patients with severe victimization had significantly higher life-time and current rates of several selected psychiatric disorders as well as significantly higher mean numbers of lifetime psychiatric disorders, medically unexplained physical and anxiety symptoms, greater harm avoidance and dissociation scores, and increased functional disability. A logistic regression showed that the main predictors of a history of severe sexual abuse were the number of medically unexplained symptoms, adult physical abuse, and lifetime dysthymic disorder. We concluded that women with prior severe sexual trauma episodes may express medically unexplained physical symptoms as part of the long-term adaptation to their victimization.

Adaptation, Psychological↗
PubMed1995

Psychiatric diagnoses, sexual and physical victimization, and disability in patients with irritable bowel syndrome or inflammatory bowel disease.

We compared 71 patients with irritable bowel syndrome (IBS) and 40 patients with inflammatory bowel disease (IBD) using structured interviews for psychiatric, gastrointestinal and sexual/physical victimization histories, as well as self-reported measures of personality, functional disability and dissociation. IBS patients had significantly higher lifetime prevalence rates of major depression, current panic disorder, and childhood sexual abuse. Despite the absence of organic pathology, IBS patients had significantly higher numbers of medically unexplained physical symptoms and disability ratings equal to, or greater than, those of patients with severe organic gastrointestinal disease.

Adult↗
PubMed1995

Buprenorphine antagonism of mu opioids in the rhesus monkey tail-withdrawal procedure.

The apparent in vivo dissociation constant (KA) and relative efficacy values for alfentanil, etonitazene, morphine, and nalbuphine were determined by comparing the effects of these agonists in the presence of buprenorphine with the effects of these agonists alone in the rhesus monkey tail-withdrawal procedure. Initial time course studies of buprenorphine alone indicated that 3.2 and 10 mg/kg produced increases in tail-withdrawal latencies when studied with 48 degrees C water for 48 hr. No increases in tail-withdrawal latency were found with either dose studied with 55 degrees C water. Buprenorphine produced dose-dependent shifts to the right for the antinociceptive effects of alfentanil, etonitazene, morphine and nalbuphine 72 hr after administration and decreased the maximal effects of morphine in 48 degrees C water and those of alfentanil and etonitazene in 55 degrees C water. Buprenorphine administration decreased the receptors available for agonist interaction to approximately 2%. The average apparent in vivo dissociation constant (KA) values for alfentanil, etonitazene, morphine and nalbuphine were 3.3, 0.073, 60 and 31 mg/kg, respectively. High efficacy estimates were determined for alfentanil (149-203) and etonitazene (174-203), whereas lower efficacy estimates were determined for nalbuphine (57) and morphine (17). The apparent in vivo dissociation constant of a pseudoirreversible antagonist (KB) value for buprenorphine averaged 0.15 mg/kg across agonists, temperatures and buprenorphine doses. These data extend and emphasize the significance of in vivo estimates of affinity and relative efficacy for drug classification.

Alfentanil↗
PubMed1994

Cloning and expression of a distinctive class of self-incompatibility (S) gene from Papaver rhoeas L.

We present the identification, cloning, and characterization of a self-incompatibility (S) gene from Papaver rhoeas that has no significant homology to any previously reported gene sequences, including S genes from other species. This result suggests that a different self-incompatibility mechanism may be operating in this species and has important implications for the evolutionary relationships between the S genes. The S1 cDNA was cloned by using an oligonucleotide based upon N-terminal amino acid sequence data from stigmatic proteins that show complete linkage with the S1 gene. The single-copy gene has been expressed in Escherichia coli to test biological activity. Although the recombinant S1 protein (S1e) is not processed in the same way as the protein produced in the plant, it exhibits, in vitro, the specific pollen inhibitory activity expected of an S gene product; pollen carrying the S1 allele is inhibited, whereas pollen not carrying S1 is not inhibited. These results provide definitive demonstration that the product of a cloned S gene has S-specific pollen inhibitory activity.

Alleles↗
PubMed1994

In vivo apparent pA2 analysis for naltrexone antagonism of discriminative stimulus and analgesic effects of opiate agonists in rats.

Six opiate agonists were characterized by in vivo apparent pA2 analysis with respect to their discriminative stimulus, rate-decreasing and analgesic effects, by using the antagonist naltrexone. In drug discrimination experiments, rats were trained to discriminate 3.2 mg/kg of morphine from saline under a fixed-ratio 15 schedule of food reinforcement. In analgesia experiments, rat's tails were immersed into 55 degrees C water and latency for tail withdrawal was measured. Naltrexone (0.01-1.0 mg/kg) antagonized discriminative stimulus effects of all agonists, rate-decreasing effects of etorphine, morphine, fentanyl, buprenorphine and GPA 1657 [(1)-B-2'-hydroxy-2,9-dimethyl-5-phenyl-6,7-benzomorphan] and analgesic effects of etorphine, morphine, buprenorphine and GPA 1657. Analgesic effects of fentanyl and nalbuphine were not tested. Naltrexone apparent pA2 values across the three behavioral measures were etorphine (7.2-7.4 mol/kg), fentanyl (7.3-7.4 mol/kg), morphine (7.5-8.4 mol/kg), GPA 1657 (7.0-7.3 mol/kg), buprenorphine (7.5-7.7 mol/kg) and nalbuphine (7.7 mol/kg). Apparent pA2 values averaged 7.5 mol/kg and slopes of the naltrexone Schild regressions were not different from unity, suggesting that the measured behavioral effects of these agonists are mediated by mu opioid receptors. Nalbuphine also was used as an antagonist in the tail-withdrawal assay. The apparent pA2 values for nalbuphine were etorphine (4.9 mol/kg), morphine (5.9 mol/kg), GPA 1657 (5.7 mol/kg) and buprenorphine (5.5 mol/kg). Slopes of the Schild regressions differed, suggesting that nalbuphine's modest analgesic effects may have prevented proper conditions for an accurate Schild analysis.

Analgesia↗
PubMed1994

In vivo determination of mu opioid receptor turnover in rhesus monkeys after irreversible blockade with clocinnamox.

In a warm-water tail withdrawal antinociception assay performed at 45, 50 and 55 degrees C in the rhesus monkey, the irreversible opioid antagonist clocinnamox at a dose of 0.1 mg/kg s.c. produced an acute rightward shift of the dose-response curves of the selective mu opioid agonists alfentanil and morphine at all tested temperatures. In addition, clocinnamox depressed the maxima of the dose-response curves for both agonists at 50 and 55 degrees C. Analysis of these data according to Furchgott as modified by Black and Leff showed that clocinnamox acutely decreased mu opioid receptors available for alfentanil by 88%; receptor numbers returned to control levels with a half-life of 6.3 days. Assessment of receptor population changes after clocinnamox administration with either alfentanil or morphine gave essentially identical results: 2 to 4 weeks after clocinnamox, the receptor population not only returned to preclocinnamox levels, but actually showed an overshoot. In contrast, apparent values of alfentanil affinity; its efficacy, e; the theoretically obtainable maximum effect of the mu opioid antinociceptive system, Em; and the stimulus-response transducing factor, n; did not change significantly over time. Alfentanil showed a 29-fold higher affinity than morphine, the respective KA values being 0.84 mg/kg for alfentanil and 24 mg/kg for morphine. The efficacy of alfentanil was always 2- to 3-fold higher than that of morphine for any temperature tested, the efficacies of both mu opioid agonists being higher at lower temperatures.(ABSTRACT TRUNCATED AT 250 WORDS)

Alfentanil↗
PubMed1993

The relationship of chronic fatigue to psychiatric illness in community, primary care and tertiary care samples.

This paper reviews the psychiatric disorders associated with the symptom of fatigue in community, primary care and tertiary care samples. In each of these subsamples, studies using structured psychiatric interviews and operational diagnostic criteria are compared and contrasted. In summary, in community, primary care and tertiary care populations, there was a high association between the symptom of fatigue and affective and anxiety disorders. The prevalence rates of affective illness went up linearly in patients with fatigue as one moved from community to primary care and tertiary populations. The fact that fatigue is a common symptom in the community and is associated with significantly higher medical utilization when associated with affective and anxiety disorders may explain the increased association between this symptom and affective illness in primary and tertiary care.

Chronic Disease↗
PubMed1993

Psychiatric disorders and medical care utilization among people in the general population who report fatigue.

OBJECTIVE: To study the prevalence of fatigue in the general population and its association with psychiatric disorders, somatization, and medical utilization. SETTING: The public-use data tape from the 1984 National Institute of Mental Health Epidemiologic Catchment Area Study. PARTICIPANTS: Household sample of 18,571 subjects. INTERVENTIONS: Structured psychiatric interviews were reviewed to study the prevalence of complaints of current and lifetime fatigue and their relationship to selected psychiatric disorders. RESULTS: Fatigue has high current (6.7%) and lifetime (24.4%) prevalences in the general population. Medically unexplained fatigue also has high current (6.0%) and lifetime (15.5%) prevalences. When compared with those reporting no current fatigue, subjects who reported current (one-month) fatigue were significantly more likely to have experienced current and lifetime episodes of major depression, dysthymic disorder, panic disorder, and somatization disorder. They also had significantly higher mean numbers of lifetime and current DSM-III psychiatric diagnoses, medically unexplained physical symptoms (not just fatigue-related symptoms), and visits to health care providers than did patients without current episodes of fatigue. CONCLUSIONS: The high prevalence of fatigue in the general population appears to be significantly associated with increased lifetime and current risk for affective, anxiety, and somatoform disorders, as well as increased utilization of medical services. These data suggest that assessment of both medical and psychological health may be essential for the proper care of patients with fatigue.

Adult↗