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Biomedical subjects

C Burns

Publications and source records attributed to C Burns.

At least 37 records · Page 2Linked to original sources

Mutant cells that do not respond to interleukin-1 (IL-1) reveal a novel role for IL-1 receptor-associated kinase.

Mutagenized human 293 cells containing an interleukin-1 (IL-1)-regulated herpes thymidine kinase gene, selected in IL-1 and gancyclovir, have yielded many independent clones that are unresponsive to IL-1. The four clones analyzed here carry recessive mutations and represent three complementation groups. Mutant A in complementation group I1 lacks IL-1 receptor-associated kinase (IRAK), while the mutants in the other two groups are defective in unknown components that function upstream of IRAK. Expression of exogenous IRAK in I1A cells (I1A-IRAK) restores their responsiveness to IL-1. Neither NFkappaB nor Jun kinase is activated in IL-1-treated I1A cells, but these responses are restored in I1A-IRAK cells, indicating that IRAK is required for both. To address the role of the kinase activity of IRAK in IL-1 signaling, its ATP binding site was mutated (K239A), completely abolishing kinase activity. In transfected I1A cells, IRAK-K239A was still phosphorylated upon IL-1 stimulation and, surprisingly, still complemented all the defects in the mutant cells. Therefore, IRAK must be phosphorylated by a different kinase, and phospho-IRAK must play a role in IL-1-mediated signaling that does not require its kinase activity.

Cell Line, Transformed↗

Development and initial validation of a brief mental health outcome measure.

Using a combination of classical test theory and Rasch item analysis, we developed a short scale designed to measure the effectiveness of mental health treatment across a wide range of mental health services and populations. Item development for the scale was guided by literature review and interviews with senior clinicians and with patients. Using 3 different samples consisting of inpatients, outpatients, and nonpatients, we reduced our initial item pool from 81 to 10 items. The 10-item scale had an alpha of .96 and showed strong correlations with commonly used measures of psychological well-being and distress. Our results suggest that the scale appears to measure a broad domain of psychological health. The scale appeared to lack ceiling and floor effects, and it discriminated between inpatients, outpatients, and nonpatients, suggesting the scale has excellent potential to be broadly responsive to a variety of treatment effects. In addition, the new scale proved to be sensitive to treatment changes in a sample of 20 psychiatric inpatients. Overall, the initial data suggest that we have developed a brief, sensitive outcome measure designed to have wide application across psychiatric and psychological treatments and populations.

Adult↗

Characteristics of L-carnitine transport by lactating rat mammary tissue.

The transport of L-carnitine by lactating rat mammary tissue has been examined. L-carnitine uptake by rat mammary tissue explants isolated from lactating rats, 3-4 days post partum, was via both Na+-dependent and Na+-independent pathways. The Na+-dependent pathway, the predominant route for L-carnitine uptake, was a saturable process: the Km and Vmax were, respectively, 132 microM and 201 pmol/2 h/mg of intracellular water. The Na+-independent pathway, which was non-saturable, had a coefficient of 0.26 microl/mg of intracellular water/2 h. The Na+-dependent component of L-carnitine uptake by mammary tissue explants was cis-inhibited by D-carnitine and acetyl-L-carnitine, but not by choline or taurine. In contrast, the Na+-independent component of L-carnitine uptake was not affected by any of these compounds. The uptake of L-carnitine by mammary tissue isolated from lactating rats, 10-12 days post partum, was qualitatively similar to that by mammary tissue taken from rats during the early stage of lactation. However, L-carnitine uptake was quantitatively lower: this was attributable to a reduction in the Na+-dependent component of L-carnitine uptake. L-Carnitine efflux from rat mammary tissue taken from animals 3-4 days post partum, consisted of at least two components; a fast extracellular component and a slow membrane-limited component. Reversing the trans-membrane Na+-gradient did not stimulate L-carnitine efflux suggesting that the Na+-dependent L-carnitine carrier operates with asymmetrical kinetics. A hyposmotic shock, hence cell-swelling, increased L-carnitine efflux from mammary tissue explants.

Animals↗

Characteristics of L-glutamine transport by lactating mammary tissue.

The transport of L-glutamine by the lactating rat mammary gland has been investigated using rat mammary tissue explants and the in situ perfused rat mammary gland. L-glutamine uptake by both explants and the perfused mammary gland was via both Na(+)-dependent and Na(+)-independent pathways. It appeared that these pathways are situated on the blood-facing aspect of the mammary gland. L-glutamine uptake by both mammary preparations was markedly inhibited by 2-aminobicyclo[2,2,1]heptane-2-carboxylic acid in the absence of external Na+. This is consistent with L-glutamine uptake via system L. The Na(+)-dependent component(s) of L-glutamine uptake remains to be precisely identified. However, system A can be ruled out on the basis that L-glutamine was not inhibited by (methylamino)isobutyric acid. Mammary tissue concentrates L-glutamine with respect to both milk and plasma: we suggest that the Na(+)-dependent component(s) of L-glutamine uptake is responsible for generating the intracellular to extracellular concentration gradient.

Animals↗

A critique of the World Resources Institute's report "Pesticides and the immune system: the public health risks".

A recent World Resources Institute (WRI) report concluded that pesticides are a likely cause of immune suppression for millions of people throughout the world. The gravity of this conclusion motivated us to review the scientific evidence cited in the report. The predominant human evidence came from cross-sectional studies conducted in the former Soviet Union. These studies were difficult to evaluate due to incomplete reporting and had obvious limitations in terms of subject selection, exposure assessment,lack of quality control, statistical analysis, adequacy of the comparison group, and confounding. The toxicologic evidence was comprised mainly of acute high-dose studies in which the exposure conditions resulted in systemic toxicity. The relevance of these studies to effects at typical human exposure levels is questionable. We did not find consistent, credible evidence to support the conclusion of widespread pesticide-related immune suppression. Nonetheless, the WRI report is an important document because it focuses attention on a potentially important issue for future research and brings a substantial literature of foreign language studies to the attention of Western scientists.

Animals↗

Postmortem diagnosis of leukodystrophies.

Leukodystrophies are progressive disorders involving the development and maintenance of myelin in the central and peripheral nervous systems. Although relatively uncommon, leukodystrophic disorders may be undiagnosed or misdiagnosed during life, and may appear as "sudden death." In such instances, these victims may be referred to a forensic pathologist. In general, leukodystrophies are inherited in an autosomal recessive manner so that proper postmortem diagnosis by the forensic pathologist is extremely important to the decendant's family for future family planning.

Adrenoleukodystrophy↗

Applicability of telemedicine for assessing patients with schizophrenia: acceptance and reliability.

BACKGROUND: Telemedicine holds promise for providing expert psychiatric consultation to underserved populations, but has not been quantitatively studied in schizophrenia or any other major mental disorder. This study was conducted to assess the reliability and acceptance of video-conferencing equipment in the assessment of patients with schizophrenia. METHOD: We assessed reliability of the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive Symptoms (SAPS), and Scale for the Assessment of Negative Symptoms (SANS) under three conditions: (1) in person, (2) by videoconferencing at low (128 kilobits per second [kbs]) bandwidth, (3) by videoconferencing at high (384 kbs) bandwidth. All 45 patients met DSM-IV criteria for schizophrenia. All patients and the two interviewers rated various aspects of the study interviews against previous live psychiatric interviews. RESULTS: Total scores on both the BPRS and SAPS were assessed equally reliably by the three media. Total score on the SANS was less reliably assessed at the low bandwidth, as were several specific negative symptoms of schizophrenia that depend heavily on nonverbal cues. Video interviews were well accepted by patients in both groups, although patients in the high bandwidth group were more likely to prefer the video interview to a live interview. CONCLUSION: Global severity of schizophrenia and overall severity of positive symptoms were reliably assessed by videoconferencing technology. Higher bandwidth resulted in more reliable assessment of negative symptoms and was preferred over low bandwidth, although patients' and raters' acceptance of video was good in both conditions. Videoconsultation appears to be a reliable method of assessing schizophrenic patients in remote locations who have limited access to expert consultation.

Adult↗

Epidemiology of incident spinal fracture in a complete population.

STUDY DESIGN: Cross-section observational study of incident spinal fractures using an administrative data-base. OBJECTIVES: To identify and define all patients who have spinal fractures within a complete population. SUMMARY OF BACKGROUND DATA: The true incidence of spinal column and cord injury is not known. Previous studies have been institutional or practice based. Accurate information concerning the magnitude of the spinal injury population and their characteristics may provide more rational basis for public health decision making and resource allocation. METHODS: The study dates were April 1, 1981 to March 31, 1984. Using the Manitoba Health Services Insurance Plan database, all patients with ICD-9-CM coding of 805.x and 806.x (spinal column fracture with and without spinal cord injury) were identified. Incidence rates, age and gender distribution, and ambulatory and hospital contracts were identified. Hospital discharge abstracts were used to classify mechanisms of injury, associated injuries, and length of stay. RESULT: The annual incidence rate of spinal fracture was 64 per 100,000. Two thousand sixty-three patients were identified, with 944 being admitted to the hospital. There were two peaks of incidence occurring in young men and elderly women. Of the hospitalized patients, 182 had cervical injury, 286 had thoracic fracture, and 403 had injury in the lumbosacral spine Associated injuries occurred in 38% of hospitalized patients. Length of stay was an average of 38.5 days. Overall mortality was 41%. Neurologic injury occurred in 122 patients. CONCLUSIONS: Ambulatory care of spine injuries is more common than hospital care. Two peaks of incidence occur-in young men and elderly women. Future decisions for research, public health policy, and resource allocation can be based on these data.

Adolescent↗

Cognitive deficits in Machado-Joseph disease.

Cognitive function was examined in 6 patients with genetically confirmed Machado-Joseph disease (MJD) and 15 age- and ethnically matched controls using a series of subtests from the Cambridge Neuropsychological Test Automated Battery (CANTAB), a touch screen-based testing system previously validated in a number of movement and neurodegenerative disorders. The MJD patients had deficits in visual attentional function that were characterized by a slowing of the processing of visual information when task demands were high and an inability to shift attention to previously irrelevant stimulus dimensions to discriminate between complex stimuli. Tests of learning and visual memory were normal. These results demonstrate that specific cognitive deficits occur in patients with MJD, independent of motor dysfunction, and these deficits may reflect disruption to frontosubcortical pathways.

Adult↗

Mammographic phantom studies with synchrotron radiation.

PURPOSE: To explore the potential improvement in image contrast for breast imaging with use of monoenergetic photons. MATERIALS AND METHODS: The x-ray energy available from the National Synchrotron Light Source is from 5 to over 50 keV. A specific energy is selected with a tunable crystal monochromator. The object is scanned with a narrow beam of 80.0 x 0.5 mm. Mammography phantoms were imaged with plate and film as the imaging detectors. Phantom images were obtained at 16-24 keV and compared with images obtained with a conventional mammographic unit. RESULTS: Preliminary findings indicate improved image contrast of the monoenergetic images compared with that obtained from the conventional x-ray source, particularly at 18 keV and below. CONCLUSION: Pilot results are encouraging, and the authors presently continue to explore monoenergetic photon imaging with improved instrumentation, scatter rejection, and use of tissue samples.

Breast Neoplasms↗