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Biomedical subjects
Publications and source records attributed to M Cross.
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The difficulty in direct detection of oxygen-derived free radicals (OFR) in the intact kidney has left uncertain the role of OFR in renal hypoperfusion injury. Salicylate hydroxylation was used as a sensitive method of estimating the extent of production of highly reactive hydroxyl radicals in renal ischaemia-reperfusion injury in the intact rat kidney perfused with recirculating cell-free medium. The reaction products were detected and quantified by HPLC with electrochemical detection. Hydroxyl radicals were detected as 2,5-dihydroxybenzoic acid (2,5-DHBA). Ischaemia for 15 min followed by reperfusion for 15 min caused more than a twofold increase in 2,5-DHBA concentration (to 2279 +/- 225 pg/g tissue weight) compared to controls (933 +/- 103, P < 0.001). Addition of 15 mM dimethylthiourea (DMTU) before induction of ischaemia prevented this increase. Induction of hypoxia for 15 min with continued perfusion (as a model of low-flow ischaemia) had no significant effect on hydroxyl radical formation. We conclude that significant quantities of hydroxyl radicals form in the absence of circulating leucocytes during reperfusion following ischaemia, but not during hypoxia in the perfused rat kidney.
The regulation of bombesin-stimulated phospholipase D (PLD) activity in Swiss 3T3 fibroblasts was examined. Increasing protein-tyrosine phosphorylation by using pervanadate to inhibit tyrosine phosphatases was found to stimulate protein kinase C (PKC)-independent [3H]phosphatidylbutanol ([3H]PtdBut) accumulation within 5 min, which continued to increase up to 30 min. The stimulation of PLD activity in response to submaximal [bombesin] could be decreased by approx. 50% by the tyrosine kinase inhibitor genistein, whereas pretreatment with genistein and the PKC inhibitor Ro-31-8220 completely abolished the generation of [3H]PtdBut in response to a maximal concentration of bombesin. The addition of guanosine 5'-[gamma-thio]triphosphate (GTP[S]) into permeabilized cells resulted in an increase in [3H]PtdBut, which was abolished by depletion of cellular ATP. The additional presence of 30 microM GTP[S] did not increase the stimulation of PLD activity by any [bombesin] tested, whereas it was synergistic with that stimulated in response to phorbol 12-myristate 13-acetate. These findings suggest that bombesin-stimulated PLD activity is indirectly regulated by G-proteins, possibly through a kinase intermediate. Furthermore, activation of protein tyrosine kinases is proposed to account for the PKC-independent arm of bombesin-stimulated PLD activity. No evidence was obtained for a form of PLD directly regulated by tyrosine phosphorylation.
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We report four patients with a mean age of 17 years (14 to 22) with external rotation injuries of the knee in slight flexion. Radiographs showed a small fragment in the area of the lateral femoral condyle. At operation, the fragment, consisting of the femoral insertion of the popliteus, was anatomically reduced and fixed. At a mean follow-up of 35 months all the knees had an excellent function score. An isolated lesion of the popliteus often presents as a tendon avulsion whereas major damage to the posterolateral corner of the knee involves combined ligamentous injuries. In patients with an acute haemarthrosis and lateral pain in a stable knee, the diagnosis of isolated avulsion of the popliteus tendon should be suspected. Arthroscopy with special attention to the lateral gutter is indicated. We advise anatomical reduction and fixation of the fragment to prevent possible long-term effects on other posterolateral structures.
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Protection against hypoxic injury by supraphysiological glycine and alanine concentrations was investigated in the isolated perfused rat kidney (IPRK). 23Na NMR detects consistent increases in total renal Na in IPRK during hypoxic perfusion. Increasing the concentration of glycine and alanine to 5 mM each produced a 34% (p < 0.001) reduction in the increase in total renal Na following 30 minutes of hypoxia compared to a matched control group supplemented with 5 mM each of serine and glutamine. There was also a trend (p = 0.067) to improvement in the fractional excretion of sodium (FENa) in the glycine plus alanine treated group. Hypoxic alterations of other physiological parameters were not prevented by supraphysiological glycine plus alanine. This suggests that monitoring total renal Na is a more sensitive method of defining renal injury and protection than monitoring changes in FENa, fractional excretion of potassium (FEK) and inulin clearance.
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A new survey reveals the changing shape of human resource departments. Why call in management consultants? Shirley Giles reports. The standard payroll system is being challenged by moves towards integrated payroll and personnel programs. Barbara Millar examines staff support schemes. Trusts are tightening up on relocation packages.