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Biomedical subjects

E Burke

Publications and source records attributed to E Burke.

At least 19 recordsLinked to original sources

Immunization with soluble BDC 2.5 T cell receptor-immunoglobulin chimeric protein:antibody specificity and protection of nonobese diabetic mice against adoptive transfer of diabetes by maternal immunization.

The BDC 2.5 T cell clone is specific for pancreatic beta-cell antigen presented by I-Ag7, and greatly accelerates diabetes when injected into 10-21-d-old nonobese diabetic (NOD) mice. The BDC 2.5 T cell receptor (TCR) has been solubilized as a TCR-IgG1 chimeric protein. All NOD mice immunized against BDC 2.5 TCR-IgG1 produced antibodies recognizing TCR C alpha/C beta epitopes that were inaccessible on the T cell surface. 56% of the mice produced antibodies against the BDC 2.5 clonotype that specifically blocked antigen activation of BDC 2.5 cells. We have used the adoptive transfer model of diabetes to demonstrate that maternal immunization with soluble TCR protects young mice from diabetes induced by the BDC 2.5 T cell clone.

Adoptive Transfer

The beta subunit of human rod photoreceptor cGMP-gated cation channel is generated from a complex transcription unit.

Human and bovine rod photoreceptor cGMP-gated cation channel consists of two subunits: alpha (63 kDa) and beta (240 kDa). The human beta subunit was shown to consist partly of sequence encoded by the cDNA clone hRCNC2b. Here we present the complete sequence of the human beta subunit and demonstrate that the previously reported human GAR1 gene encoding a glutamate-rich protein (hGARP) encodes its N-terminal portion. Using PCR, RNA blot and genomic DNA analysis, we provide evidence that the beta subunit is produced from a complex locus on chromosome 16 which is also capable of generating independent transcripts corresponding to GAR1 and the C-terminal two-thirds of the beta subunit. The results indicate that the beta subunit of the cGMP-gated cation channel is produced from an unusual locus consisting of more than one transcription unit.

Alternative Splicing

Tungiasis.

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Adult

Human Hsp60: bacterial expression, purification, development of monoclonal antibodies and a sandwich ELISA for quantitation.

Bacterial hsp60 proteins are major targets of immune responses during infection, and the highly conserved nature of bacterial and mammalian hsp60 has led to speculation that immune reactivity to these stress proteins may be a component of certain autoimmune diseases. We have developed recombinant proteins and monoclonal antibodies to facilitate further study of human hsp60 and its association with disease. The human hsp60 gene was expressed in Escherichia coli and a method for purification of the recombinant protein essentially devoid of E. coli GroEL was developed. Using the purified protein we have generated a number of monoclonal antibodies which are specific for human hsp60 and do not cross-react with its counterparts from E. coli and mycobacteria. A highly sensitive sandwich ELISA was developed to quantitate hsp60 levels and was used to study hsp60 accumulation in cells due to vaccinia virus infection and heat shock. This ELISA will be useful for monitoring hsp60 levels in body fluids or tissues during autoimmune reactions and/or inflammatory responses.

Animals

Prehospital thrombolysis in a rural community: short- and long-term survival.

In order to assess the feasibility and outcome of using prehospital thrombolysis in acute myocardial infarction in a rural community, we performed an open randomized study of patients with symptoms of acute myocardial infarction of less than 6 hours. One hundred and forty-five patients with acute myocardial infarction were allocated to receive IV streptokinase prehospital by means of a mobile coronary care unit (MCCU) (n = 43) or to receive IV streptokinase in hospital (n = 102). The mean delay time to treatment was 138 minutes (MCCU group) and 172 minutes (hospital group) (p less than 0.02). Reperfusion time was 88 minutes for the MCCU group and 92 minutes for the hospital group. Mortality at 14 days was 2.3% for the MCCU group and 11.7% for the hospital group (p less than 0.05). Six month mortality was 4.9% for the MCCU group and 17.3% for the hospital group (p = 0.03). Mortality at 1 year was 6.1% for the MCCU group and 20.0% for the hospital group (p = 0.04). There were no significant adverse events in either treatment group. Thus, prehospital thrombolysis by streptokinase is feasible and allows significant reduction in the delay time to treatment initiation. There are encouraging improvements in both short- and long-term survival with no apparent reduction in safety profile.

Adult

Cancer in relatives of survivors of childhood sarcoma.

Relatives of 88 long-term survivors of childhood sarcoma were examined for the familial cancer syndrome of sarcoma, breast cancer, and other neoplasms (Li-Fraumeni syndrome). Twenty-six of 402 close relatives developed cancer (expected, 23.8), including breast cancer in four mothers (expected, 3.1). Two sarcoma probands who developed second malignant tumors have multiple relatives with cancer and might have an inherited predisposition. An increased cancer risk and exceptional requirement for disease screening appear to be confined to first-degree relatives of a small fraction of children with sarcoma, notably probands with second cancers.

Adolescent

Milk-induced malabsorption in malnourished African patients.

Fifty malnourished rural African patients were randomly assigned to whole milk (50 g lactose/L), acidified milk (24 g lactose/L), or a commercial lactose-free diet (LFD) as a constant nasogastric infusion for 3 d, starting at 2 L/d and increasing to 3 L/d if tolerated. During the first 2 d mild symptoms of intolerance developed in 63% of patients on whole milk, 37% on acidified milk, and 54% on LFD whereas severe intolerance, necessitating withdrawal, was encountered in 22% receiving whole milk and none receiving LFD. Stool weights and fat excretion on day 3 were greater (P less than 0.02) in the remaining milk-fed patients whereas nitrogen balance remained strongly positive in all three groups. Eighty-seven percent of patients were methane producers, and high excretion rates were associated with better milk tolerance. The results suggest that although undiluted cow milk will not form a suitable tube feed for malnourished African patients, products such as acidified milk may prove cost effective.

Adult

HRT clinics.

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Aged

Asthma clinics.

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Ambulatory Care Facilities

Slow waves actively propagate at submucosal surface of circular layer in canine colon.

Colonic slow waves originate from pacemaker cells along the submucosal surface of the circular layer in the dog proximal colon. These events propagate in a nonregenerative manner into the bulk of the circular layer. Conduction velocities consistent with an active mechanism for slow-wave propagation in the longitudinal and circumferential axes of the colon have been reported. Experiments were performed using intracellular recording techniques on canine colonic muscles to determine the regenerative pathway for slow-wave propagation. In a thin band of muscle adjacent to the submucosal border of the circular layer, slow-wave amplitude was independent of distance from a pacing source, and events propagated at a rate of approximately 17 mm/s in the long axis of the circular fibers and 6 mm/s in the transverse axis of the circular fibers. These findings suggest that slow waves propagate in a regenerative manner in this region. Slow waves decayed as they conducted through regions from which the pacemaker cells had been removed with space constants of a few millimeters. Thus the integrity of the thin pacemaker region along submucosal surface is critical for propagation of slow waves and the organization of motility into segmental contractions.

Animals