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Biomedical subjects

E Clark

Publications and source records attributed to E Clark.

At least 19 recordsLinked to original sources
PubMed1999

Activation of the Drosophila C3G leads to cell fate changes and overproliferation during development, mediated by the RAS-MAPK pathway and RAP1.

The cellular signal transduction pathways by which C3G, a RAS family guanine nucleotide exchange factor, mediates v-crk transformation are not well understood. Here we report the identification of Drosophila C3G, which, like its human cognate, specifically binds to CRK but not DRK/GRB2 adaptor molecules. During Drosophila development, constitutive membrane binding of C3G, which also occurs during v-crk transformation, results in cell fate changes and overproliferation, mimicking overactivity of the RAS-MAPK pathway. The effects of C3G overactivity can be suppressed by reducing the gene dose of components of the RAS-MAPK pathway and of RAP1. These findings provide the first in vivo evidence that membrane localization of C3G can trigger activation of RAP1 and RAS resulting in the activation of MAPK, one of the hallmarks of v-crk transformation previously thought to be mediated through activation of SOS.

Amino Acid Sequence↗
PubMed1999

Antidepressant effects of nicotine in an animal model of depression.

Epidemiological studies indicate a high incidence of cigarette smoking among depressed individuals. Moreover, individuals with a history of depression have a much harder time giving up smoking. It has been postulated that smoking may reflect an attempt at self-medication with nicotine by these individuals. Although some animal and human studies suggest that nicotine may act as an antidepressant, further verification of this hypothesis and involvement of nicotinic cholinergic system in depressive symptoms is required. Flinders Sensitive Line (FSL) rats have been proposed as an animal model of depression. These rats, selectively bred for their hyperresponsiveness to cholinergic stimulation, show an exaggerated immobility in the forced swim test compared to their control Flinders Resistant Line (FRL) rats. Acute or chronic (14 days) administration of nicotine (0.4 mg/kg s.c.) significantly improved the performance of the FSL but not the FRL rats in the swim test. The effects of nicotine on swim test were dissociable from its effects on locomotor activity. Moreover, the FSL rats had significantly higher [3H]cytisine binding (selective for the alpha4beta2 nicotinic receptor subtype) but not [125I]alpha-bungarotoxin binding (selective for the alpha7 subtype) in the frontal cortex, striatum, midbrain and colliculi compared to FRL rats. These data strongly implicate the involvement of central nicotinic receptors in the depressive characteristics of the FSL rats, and suggest that nicotinic agonists may have therapeutic benefits in depressive disorders.

Alkaloids↗
PubMed1999

Characteristics of rural dust events shown to impact on asthma severity in Brisbane, Australia.

Wind erosion in arid inland Australia leads to dust plumes which can pass over populated coastal areas in Eastern Australia, such as Brisbane. Such events can lead to concerns about respiratory health problems because they significantly increase the fine particle component of atmospheric aerosols. This paper examines the particulate characteristics of 11 dust events in Brisbane and associations with daily diary records (peak expiratory flow, symptoms) of people with asthma, and hospital emergency attendances for asthma during a number of seasons between 1992 and 1994. These dust events are frequently, but not always, characterised by higher particulate levels and higher ratios of fine to coarse particulates. The results indicate that a number of dust events were significantly associated with changes in asthma severity, but general relationships could not be determined. Given that the phenomenon of wind-blown dust is not isolated to the Australian continent, these findings raise important questions about the effects of wind-blown dust in other parts of the world.

Adolescent↗
PubMed1999

Mapping of sugar and amino acid availability in soil around roots with bacterial sensors of sucrose and tryptophan

We developed a technique to map the availability of sugars and amino acids along live roots in an intact soil-root matrix with native microbial soil flora and fauna present. It will allow us to study interactions between root exudates and soil microorganisms at the fine spatial scale necessary to evaluate mechanisms of nitrogen cycling in the rhizosphere. Erwinia herbicola 299R harboring a promoterless ice nucleation reporter gene, driven by either of two nutrient-responsive promoters, was used as a biosensor. Strain 299RTice exhibits tryptophan-dependent ice nucleation activity, while strain 299R(p61RYice) expresses ice nucleation activity proportional to sucrose concentration in its environment. Both biosensors exhibited up to 100-fold differences in ice nucleation activity in response to varying substrate abundance in culture. The biosensors were introduced into the rhizosphere of the annual grass Avena barbata and, as a control, into bulk soil. Neither strain exhibited significant ice nucleation activity in the bulk soil. Both tryptophan and sucrose were detected in the rhizosphere, but they showed different spatial patterns. Tryptophan was apparently most abundant in soil around roots 12 to 16 cm from the tip, while sucrose was most abundant in soil near the root tip. The largest numbers of bacteria (determined by acridine orange staining and direct microscopy) occurred near root sections with the highest apparent sucrose or tryptophan exudation. High sucrose availability at the root tip is consistent with leakage of photosynthate from immature, rapidly growing root tissues, while tryptophan loss from older root sections may result from lateral root perforation of the root epidermis.

Journal Article↗
PubMed1999

Reproduction of lesions of postweaning multisystemic wasting syndrome in gnotobiotic piglets.

Neonatal gnotobiotic piglets were inoculated with tissue homogenates and low- and high-passage cell culture material to determine if the lesions of the newly described porcine postweaning multisystemic wasting syndrome (PMWS) could be reproduced. For this, 17 3-day-old gnotobiotic piglets were inoculated intranasally with pelleted chloroform-treated, filtered extracts from cell cultures, filter-sterilized homogenates of lymphoid tissue from PMWS-affected piglets, or control materials. Piglets were maintained in germ-free isolators for up to 5 weeks after infection prior to euthanasia and collection of samples for analysis. All piglets inoculated with the viral inocula developed lesions typical of PMWS, including generalized lymphadenopathy, hepatitis, nephritis, interstitial pneumonia, myocarditis, and gastritis. Porcine circovirus (PCV), as well as porcine parvovirus (PPV), was detected in tissues by virus reisolation, polymerase chain reaction analysis, or immunohistochemistry. All infected piglets developed moderate to high titers of antibody to PCV and moderate titers to PPV. No lesions, virus, or virus-specific antibodies were detected in sham-inoculated or uninoculated control piglets. These studies demonstrate that the lesions of PMWS can be experimentally reproduced in gnotobiotic piglets using filterable viral agents derived from pigs with PMWS and provide an experimental basis for further investigation into the pathogenesis and control of this emerging infectious disease in swine.

Animals↗
PubMed1998

"U" curve association of blood pressure and mortality in hemodialysis patients. Medical Directors of Dialysis Clinic, Inc.

BACKGROUND: Hypertension may play an important role in the pathogenesis of the excess cardiovascular and cerebrovascular (CV) morbidity observed in hemodialysis patients (HD). However, the optimal blood pressure (BP) range for HD patients has not been defined. We postulated that there is a "U" curve relationship between BP and CV mortality. To explore this hypothesis we studied 5,433 HD patients in Dialysis Clinic Inc., a large not-for-profit chain, over a five year period. METHODS: Cox regression, with fixed and time-varying covariates, was used to assess the effect of systolic blood pressure (SBP) and diastolic blood pressure (DBP), pre- and post-dialysis, on CV mortality, while adjusting for age, gender, ethnicity, primary cause of end-stage renal disease, Kt/V, serum albumin, and antihypertensive medications. RESULTS: The overall impact of BP on CV mortality was modest. Pre-dialysis, neither systolic nor diastolic hypertension were associated with an increase in CV mortality. Post-dialysis, SBP > or = 180 mm Hg (RR = 1.96, P < 0.015) and DBP > or = 90 mm Hg (RR = 1.73, P < 0.05) were associated with increased CV mortality. Low SBP (SBP < 110 mm Hg) was associated with increased CV mortality, pre- and post-dialysis. CONCLUSIONS: The results suggest the presence of a "U" curve relationship between SBP post-dialysis and CV mortality in HD patients.

Adult↗
PubMed1998

Candida albicans endocarditis associated with a contaminated aortic valve allograft: implications for regulation of allograft processing.

A patient developed Candida albicans endocarditis and fungemia after undergoing aortic valve replacement with an allograft. The allograft had been found during tissue bank processing to be contaminated with C. albicans, but it was culture-negative for C. albicans after routine disinfection with an antifungal-containing antimicrobial solution. Comparison of the preimplantation and postimplantation C. albicans isolates revealed remarkable genetic similarity, but antifungal susceptibility testing showed that the postimplantation isolate was more resistant to fluconazole and amphotericin B than the preimplantation isolate, suggesting emergence of resistance after disinfection. Implantation of a contaminated heart valve allograft can occur despite disinfection during processing and can result in endocarditis in the recipient. Antimicrobial disinfection protocols that include antifungal drugs may be ineffective. Current U.S. Food and Drug Administration regulations do not require companies to specify details concerning allograft processing. Additional measures may be required to prevent tissue bank release of allografts contaminated with C. albicans or other pathogens.

Aortic Valve↗
PubMed1998

Isolation of circovirus from lesions of pigs with postweaning multisystemic wasting syndrome.

Postweaning multisystemic wasting syndrome (PMWS), an apparently new disease, has been recognized in swine herds in western Canada. Young pigs with this disease have progressive weight loss, tachypnea, dyspnea, and jaundice, accompanied by interstitial pneumonia, lymphadenopathy, hepatitis, and nephritis. We examined more than 400 pigs from more than 70 herds in Alberta, Saskatchewan, and Manitoba with cases of PMWS. A small virus was isolated from a range of tissues from 8 of 8 affected pigs examined. The agent was identified as a circovirus-like virus using electron microscopy, immunohistochemical staining with porcine and rabbit immune serum, and in situ hybridization. Immunohistochemical examination of tissues from more than 100 affected pigs has revealed widespread viral antigen, often contained in circovirus-like inclusion bodies, in lesions from numerous organs. Although Koch's postulates remain to be fulfilled, these results demonstrate a high degree of association between the presence of the circovirus-like virus and PMWS in affected swine.

Alberta↗
PubMed1997

Relative expression and stability of a chromosomally integrated and plasmid-borne marker gene fusion in environmentally competent bacteria.

A xylE-iceC transcriptional fusion was created by ligatinga DNA fragment harboring the cloned xylE structural gene from the TOL plasmid of Pseudomonas putida mt-2 into the cloned iceC gene of Pseudomonas syringae Cit7. This fusion construct was integrated into the chromosome of Pseudomonas syringae Cit7 by homologous recombination. Both cis-merodiploid strain Cit7m17 and marker exchange strain Cit7h69 produced the XylE gene product, catechol2,3-dioxygenase. Strain Cit7m17, in which XylE was influenced by transcription initiated by the amp promoter on pBR322, exhibited XylE activity in stationary phase at levels about 45 times higher than strain Cit7h69, permitting detection of 10(7) Cit7m17 cells in the spectrophotometric assay and 10(3) cells in HPLC measurements. The stability of xylE in both Cit7m17 and Cit7h69 was compared with maintenance of xylE in several plasmid-borne constructs in P.aeruginosa, Erwinia herbicola, and Escherichia coli. Only the xylE-iceC fusion in the chromosome of Cit7h69 and Cit7m17was stable in plate assays over the course of these studies. Even though strain Cit7h69 stably expressed xylE, the low level of expression precludes its use in direct spectrophotometric or HPLC assays as a means for detecting cells in environmental samples. However, expression of xylEin Cit7h69 is sufficient for identification of colonies harboring this marker gene which is useful in laboratory plate assays, and as a marker gene system for the detection of environmentally-competent strains chromosomally taggedwith xylE for use in autecological studies.

Bacterial Outer Membrane Proteins↗
PubMed1997

Lack of effect of antenatal indomethacin on fetal cerebral blood flow.

OBJECTIVE: Our purpose was to investigate fetal cerebral blood flow and the incidence of intraventricular hemorrhage in patients undergoing tocolysis with either indomethacin or magnesium sulfate at < 30 weeks' gestation. STUDY DESIGN: Consenting patients at < 30 weeks' gestation with preterm labor were randomized to receive indomethacin or magnesium sulfate tocolysis. Magnesium sulfate was administered intravenously with an 8 gm loading dose given over the first hour, 4 gm over the second hour, and then a maintenance infusion of 2.5 gm per hour. The infusion was continued for approximately 12 hours after the cessation of uterine contractions. Patients randomized to receive indomethacin were given an initial dose of 50 to 100 mg orally or per rectum, followed by 25 to 50 mg orally every 4 to 6 hours for 24 to 48 hours. Oral tocolytic agents were not used after successful tocolysis. Betamethasone was administered to all patients. Patients underwent fetal cerebral Doppler studies during tocolytic therapy and at least 24 hours after completion of the treatment. RESULTS: Twelve patients were randomized to receive indomethacin and twelve patients were randomized to receive magnesium sulfate. Twenty-one fetuses underwent cerebral Doppler studies in triplicate during and after therapy. The mean gestational age at tocolysis was 27.5 +/- 1.9 weeks for the indomethacin group and 26.4 +/- 1.6 weeks for the magnesium sulfate group (p = 0.14). The middle cerebral artery resistance index for fetuses during indomethacin treatment was 0.73 +/- 0.09, whereas the resistance index after therapy was 0.75 +/- 0.05 (p = 0.49). The resistance index during magnesium sulfate tocolysis was 0.79 +/- 0.04 and after therapy it was 0.76 +/- 0.04 (p = 0.18). There was no significant difference in the resistance index between the groups on or off therapy. In addition, the incidence of intraventricular hemorrhage was similar in both groups. CONCLUSION: These results suggest that indomethacin does not significantly affect fetal cerebral blood flow. If antenatal indomethacin in the preterm fetus increases the risk of intraventricular hemorrhage, it would appear to be by another mechanism.

Adolescent↗
PubMed1997

Childhood traumatic brain injury: neuropsychological status at the time of hospital discharge.

The present study examined the status at the time of hospital discharge of 22 children who had sustained moderate to severe closed head injuries. Despite an average length of stay of 46 days, on average the children performed significantly below normal on cognitive, memory, and motor tests. The children who did the worst were those who sustained their injuries riding in a vehicle, as opposed to being hit by a vehicle while walking or riding a bicycle. No reliable associations were found between neuroimaging data and cognitive measures; however, children whose scans showed more diffuse severe injury (e.g. white matter hemorrhages) performed more poorly than those who did not. Of further importance were detailed morphometric analyses of tissue quantity and ventricular volume that showed significantly increased ventricle to brain ratios (VBR) over a 3 to 4 week period following injury.

Anticonvulsants↗
PubMed1997

The incidence and nature of fibrous continuity between the sphenomandibular ligament and the anterior malleolar ligament of the middle ear.

The purpose of this study was to determine the structural interrelationship between the temporomandibular joint (TMJ) and the middle ear, in terms of fibrous continuity between the sphenomandibular ligament (SML) of the mandible and the anterior malleolar ligament (AML) of the middle ear. Thirty-seven specimens of the TMJ and middle ear were obtained from adult human cadavers. The temporal bone, petrotympanic fissure, mandibular fossa, and middle ear were dissected en bloc, fixed, sectioned, stained, and observed microscopically. Of the 37 specimens, 67.6% had a continuity of the SML through the fissure passing near the malleus of the middle ear. The AML was present at the fissure in 64.9% of the specimens, with 58.3% passing through and not stopping at the fissure. Results indicated a fibrous continuity between the SML and the AML. Structural differences between the two ligaments were also noted. The SML contained randomly arranged fibrous connective tissue with numerous interposed blood vessels. The AML had a smooth arrangement of fibers within the connective tissue, and few blood vessels were apparent. The clear anatomic relationship observed strongly supports the contention of a functional interrelationship between the TMJ and the middle ear.

Aged↗
PubMed1996

Malignant tumors missed at laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy (LC) is now the treatment of choice for gallstone disease. The wide acceptance of LC resulted in increased cholecystectomy rates and entailed specific drawbacks such as missed malignant tumors of other organs. PATIENTS AND METHODS: The prospective follow-up of patients who underwent LC was studied, and all patients treated for malignant disease were included regarding a history of LC. RESULTS: Of 838 LCs performed, 5 patients underwent reoperation for missed carcinoma of the pancreas (n=2) and the right colon (n=3). Two other patients with carcinomas of the pancreas and the right colon had a history of LC performed elsewhere. All 7 patients (median age 72 years) complained of recent atypical pain at the time of the LC. Five tumors were resected (2 palliatively); 2 patients died. CONCLUSIONS: This study emphasizes the necessity of making a careful semiological analysis of the pain and associated symptoms before performing an LC.

Aged↗
PubMed1996

Children and adolescents with traumatic brain injury: reintegration challenges in educational settings.

Changes in federal law have paved the way for students with traumatic brain injury (TBI) to receive special educational services. Although not all students with TBI need special education, many will need careful planning for reintegration into the classroom. The present article presents information about the range of services that need to be considered for these students and the problems that can affect students' academic and social functioning. Characteristics that distinguish this group of students from peers with special learning needs are highlighted and specific suggestions are made to help educators work more effectively with these students when they return to school. A case study is used to highlight the issues discussed.

Adolescent↗
PubMed1996

Interventions for students with traumatic brain injury: managing behavioral disturbances.

The present article provides information about the behavioral sequelae that are commonly seen in children and adolescents following a traumatic brain injury (TBI) and ways that educators can begin to address these problems. Because, for the most part, behavioral interventions have not been empirically validated for use with TBI populations, this article focuses on the unique needs of these students and the factors that should be considered in designing intervention strategies. Emphasis is placed on the cognitive sequelae of TBI that can cause further behavioral problems and interfere with interventions (e.g., impaired attention, executive function, reasoning and problem solving, and learning and memory).

Behavior Therapy↗