Biomedical subjects
P Rush
Publications and source records attributed to P Rush.
Identification of a protein kinase activity that phosphorylates connexin43 in a pH-dependent manner.
The carboxyl-terminal (CT) domain of connexin43 (Cx43) has been implicated in both hormonal and pH-dependent gating of the gap junction channel. An in vitro assay was utilized to determine whether the acidification of cell extracts results in the activation of a protein kinase that can phosphorylate the CT domain. A glutathione S-transferase (GST)-fusion protein was bound to Sephadex beads and used as a target for protein kinase phosphorylation. A protein extract produced from sheep heart was allowed to bind to the fusion protein-coated beads. The bound proteins were washed and then incubated with 32P-ATP. Phosphorylation was assessed after the proteins were resolved by SDS-PAGE. Incubation at pH 7.5 resulted in a minimal amount of phosphorylation while incubation at pH 6.5 resulted in significant phosphorylation reaction. Maximal activity was achieved when both the binding and kinase reactions were performed at pH 6.5. The protein kinase activity was stronger when the incubations were performed with manganese rather than magnesium. Mutants of Cx43 which lack the serines between amino acids 364-374 could not be phosphorylated in the in vitro kinase reaction, indicating that this is a likely target of this reaction. These results indicate that there is a protein kinase activity in cells that becomes more active at lower pH and can phosphorylate Cx43.
Guidelines for critical care and the elderly: the search continues.
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Granulomatous tophaceous gout mimicking tuberculous tenosynovitis: report of two cases.
Granulomatous inflammation in a tissue specimen raises concern about infection with Mycobacterium tuberculosis, atypical mycobacteria, certain fungi, Brucella species, and other infectious agents. Inflammatory disorders, such as sarcoidosis, crystal-associated arthritis, or foreign body reactions also are considered when granulomatous changes are seen on histological examination of a tissue specimen. We describe two cases of granulomatous tenosynovitis due to tophaceous deposits in patients with gout. In one case, tuberculous synovitis was considered the primary diagnosis until the diagnosis of gout was confirmed by examination of a tissue specimen with polarized light. In the second case, gout and tuberculosis were found in the patient's wrist joint. After antituberculous therapy was discontinued, he continued to have wrist synovitis and chronic drainage due to granulomatous tophaceous gout. The findings in this report suggest that gouty tenosynovitis can mimic tuberculous tenosynovitis and that gout should be considered in the differential diagnosis of granulomatous tenosynovitis, especially when acid-fast stains and cultures are negative for mycobacteria.
Childhood linear scleroderma: a possible role of thermography for evaluation.
Linear scleroderma is a rare, at times debilitating, disease with an unpredictable course. Currently, there is no satisfactory objective method for assessment of disease activity upon which to base therapeutic decisions. We evaluated 11 children with 18 linear scleroderma lesions (mean age 11.7 years, mean duration of disease 5.1 years) for disease severity and the presence of immunologic abnormalities, and attempted to correlate these results with thermography. Positive thermography was defined as warmer than surrounding skin or opposite limb by 0.5 degrees C. Six patients were thermography positive. Mean age, sex, disease duration and the presence of hypergammaglobulinemia and autoantibodies were similar in thermography positive and thermography negative patients. Six of 18 linear scleroderma lesions were thermography positive. All 3 new or expanding lesions were thermography positive. All 3 lesions that were resolving clinically were thermography negative. Three of 12 lesions that were clinically unchanged over a 6-month period were also thermography positive. In summary, thermography is a noninvasive test that appears to demonstrate active lesions in linear scleroderma. It is not influenced by previous soft tissue damage induced by linear scleroderma and may enable better monitoring of the effectiveness of proposed therapies.
Tender shins and steroid therapy.
To quantify previously described shin tenderness in patients receiving chronic steroid therapy, we studied 54 patients, 26 treated with steroid, by dolorimetry at 4 control, 4 "fibrositic," and 4 shin sites. To measure observer variation, assessments were done by 2 or 3 of 10 observers, one of whom examined each subject. The specific increase of tenderness at shin sites associated with steroid therapy was confirmed, with a mean (SD) threshold in the steroid group of 3.0 (1.7) kg, and in the control group 5.6 (2.4). Other effects which were not site specific were found. There was a 2.0 kg increase in control site tenderness associated with steroid therapy, and a similar general increase in tenderness in patients with lupus and in women, independent of steroid therapy, affecting control as well as fibrositic sites. Underlying mechanisms must act generally as well as being site specific.
Clofibrate myopathy: a case report and a review of the literature.
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Paramacular telangiectasis.
Forty six patients with paramacular retinal telangiectasis were reviewed; unilateral telangiectasis was present in 26 and bilateral disease was present in 20. Patients with unilateral macular telangiectasis had the more extensive vascular involvement associated with exudation and were more likely to have peripheral telangiectasis. Bilateral macular telangiectasis was associated with pigment epithelial changes and sub-retinal scars. Visual acuity was mildly reduced in the majority of patients; severe loss of vision was most frequent in patients with bilateral macular disease. The evolution of vascular changes was very slow and only 5 patients lost vision of two lines or more during an average period of 40 months. The high incidence of peripheral changes in unilaterally involved patients implies the possibility of a primary defect of the retinal vessels in these patients. There is evidence to suggest that there may be a primary defect of the retinal pigment epithelium in some patients with bilateral involvement.
Visual loss from retinal oedema in autosomal dominant exudative vitreoretinopathy.
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Distinguished nurse honoured by Queen. Irene Ballantyne-Heard, MBE of Sacred Heart Hospital.
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Prenatal diagnosis of 22q11.2 deletion when ultrasound examination reveals a heart defect.
PURPOSE: The incidence of 22q11.2 deletion syndrome is approximately 1 in 5,000 births, and accounts for 5-30% of all heart defects, making it one of the more common genetic conditions in the population. METHODS: We employed fluorescence in situ hybridization (FISH) to study the incidence of 22q11.2 deletions in fetuses with cardiac anomalies detected on ultrasound examination. RESULTS: Of 64 cases, 18 had visible chromosome anomalies. FISH testing for 22q11.2 deletion was performed on the remaining 46 cases, and five exhibited a 22q11.2 deletion. Three of the five had de novo deletions, one was maternally inherited, and one family declined testing. CONCLUSION: FISH analysis for 22q11.2 deletion should be performed on all fetuses with cardiac defects (excluding hypoplastic left heart and echogenic focus) and a normal G-banded karyotype.