Professor A. J. E. Cave 1900–2001

Few have served the Zoological Society of London longer or more faithfully than Alexander Cave who died on 17 May at the great age of 100.
As a Fellow, his record is outstanding: Member of Council, Vice President, Silver Medallist of the Society, Honorary Research Associate; and withal, an unending stream of original papers on various aspects of comparative anatomy. Unending? Well, almost, for he was still being published in his 95th year. Nor should be forgotten the great volume of work that he did in refereeing papers for the Journal of Zoology – an onerous and time-consuming task that he dealt with meticulously.     

Discriminating between the activities of human cathepsin G and chymase using fluorogenic substrates

Cathepsin G (CG) (EC 3.4.21.20) and chymase (EC 3.4.21.39) are two closely-related chymotrypsin-like proteases that are released from cytoplasmic granules of activated mast cells and/or neutrophils. We investigated the potential for their substrate-binding subsites to discriminate between their substrate specificities, aiming to better understand their respective role during the progression of inflammatory diseases. In addition to their preference for large aromatic residues at P1, both preferentially accommodate small hydrophilic residues at the S1' subsite. Despite significant structural differences in the S2' subsite, both prefer an acidic residue at that position. The Ala226/Glu substitution at the bottom of the CG S1 pocket, which allows CG but not chymase to accommodate a Lys residue at P1, is the main structural difference, allowing discrimination between the activities of these two proteases. However, a Lys at P1 is accommodated much less efficiently than a Phe, and the corresponding substrate is cleaved by β2-tryptase (EC 3.4.21.59). We optimized a P1 Lys-containing substrate to enhance sensitivity towards CG and prevent cleavage by chymase and β2-tryptase. The resulting substrate (ABZ-GIEPKSDPMPEQ-EDDnp) [where ABZ is O-aminobenzoic acid and EDDnp is N-(2,4-dinitrophenyl)-ethylenediamine] was cleaved by CG but not by chymase and tryptase, with a specificity constant of 190 mM(-1)·s(-1). This allows the quantification of active CG in cells or tissue extracts where it may be present together with chymase and tryptase, as we have shown using a HMC-1 cell homogenate and a sputum sample from a patient with severe asthma.     

Sexual orientation and bias in self-reported BMI

Our objective was to determine if sexual orientation groups differ in accuracy of BMI (kg/m(2)) calculated from self-reported height and weight and if weight status modifies possible differences. Using gender-stratified multiple linear regression to analyze Wave III of the National Longitudinal Study of Adolescent Health (n = 12,197), we examined the association of sexual orientation with BMI calculated from self-reported height and weight (self-reported BMI), controlling for BMI calculated from objectively measured height and weight (objectively measured BMI) as well as demographic, health, and behavioral variables. We tested for effect modification of the relationship between sexual orientation and self-reported BMI by objectively measured BMI. The population underestimated their BMI (females: β = 0.87, P < 0.001; males = 0.86, P < 0.001). Sexual orientation groups differed little in their accuracy of reporting; only gay males had significant underreporting (β = -0.37, P = 0.038) relative to their heterosexual peers. We found no evidence of effect modification of the relationship of sexual orientation and self-reported BMI by objectively measured BMI. With the exception of gay males, sexual orientation groups are consistent in their underreporting of BMI thus providing confidence in most comparisons of weight status based on self-report. Self-reporting of weight and height by gay males may exaggerate the differences in BMI between gay and heterosexual males.     

Prolonged Oliguria with Survival in Acute Bilateral Cortical Necrosis

Survival is uncommon in cases of acute bilateral cortical necrosis. Three cases admitted to the renal unit at Newcastle have regained useful renal function after oliguric phases of 38, 46, and 120 days.Prolonged periods of intermittent dialysis are justified in patients in whom a firm diagnosis of acute cortical necrosis is made.     

Ceramide-Protein Interactions Modulate Ceramide-Associated Lipotoxic Cardiomyopathy

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