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Biomedical subjects

A J Saunders

Publications and source records attributed to A J Saunders.

At least 37 records · Page 2Linked to original sources
PubMed1996

Effects of recombinant human growth hormone on renal function in children with renal transplants.

OBJECTIVE: To provide accurate measurement of renal function during treatment with recombinant human growth hormone (rhGH). METHODS: We measured glomerular filtration rate and effective renal plasma flow by clearance of inulin and para-aminohippuric acid before rhGH therapy, after 1 week, and then at 6-month intervals for up to 2 years of treatment in 16 children (mean (SD) age = 13.1 (2.2) years; glomerular filtration rate = 52 (27) ml/min per 1.73 m2). The mean (SD) time from transplantation was 6.5 (3.6) years. RESULTS: Linear growth velocity during rhGH therapy increased from 4.0 (1.8) to 8.8 (2.6) cm/yr (p < 0.0001). One child was withdrawn after 9 months because of abnormal glucose tolerance, and another child received a second renal transplant after 18 months. Glomerular filtration rate increased to 57 (29) ml/min per 1.73 m2 at 1 week (p = 0.004), remained improved at 6 months (63 (30); p = 0.013), but was not significantly better at 1 year (59 (33)). Effective renal plasma flow on day 1 was 237 (127) ml/min per 1.73 m2 and was unchanged on day 8 (244 (123)), at 6 months (271 (149)), and after 1 year (269 (157)). During the study there was no significant change in filtration fraction, blood pressure, or kidney volume, and excretion of microalbumin and N-acetylglucosaminidase was unaltered. There was one rejection episode per 14.8 patient-months in the year before treatment, 1 per 18.9 patient-months during the first year of treatment, and 1 per 13 patient-months during the second year of rhGH therapy. CONCLUSION: Treatment with rhGH improves growth in children with renal transplants. Glomerular filtration rate was increased after 1 week and 6 months of rhGH therapy but returned to baseline values thereafter. The data indicate the need for long-term follow-up of children with renal transplants who are receiving rhGH.

Adolescent↗
PubMed1995

Protein thermal denaturation, side-chain models, and evolution: amino acid substitutions at a conserved helix-helix interface.

Random mutant libraries with substitutions at the interface between the N- and C-terminal helices of Saccharomyces cerevisiae iso-1-cytochrome c were screened. All residue combinations that have been identified in naturally occurring cytochrome c sequences are found in the libraries. Mutants with these combinations are biologically functional. Enthalpies, heat capacities, and midpoint temperatures of denaturation are used to determine the entropy and Gibbs free energy of denaturation (delta GD) for the ferri form of the wild-type protein and 13 interface variants. Changes in delta GD cannot be allocated solely to enthalpic or entropic effects, but there is no evidence of enthalpy-entropy compensation. The lack of additivity of delta GD values for single versus multiple amino acid substitutions indicates that the helices interact thermodynamically. Changes in delta GD are not in accord with helix propensities, indicating that interactions between the helices and the rest of the protein outweigh helix propensity. Comparison of delta GD values for the interface variants and nearly 90 non-cytochrome c variants to side-chain model data leads to several conclusions. First, hydrocarbon side chains react to burial-like transfer from water to cyclohexane, but even weakly polar side chains respond differently. Second, despite octanol being a poor model for protein interiors, octanol-to-water transfer free energies are useful stability predictors for changing large hydrocarbon side chains to smaller ones. Third, unlike cyclohexane and octanol, the Dayhoff mutation matrix predicts stability changes for a variety of substitutions, even at interacting sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Design of a ruthenium-cytochrome c derivative to measure electron transfer to the initial acceptor in cytochrome c oxidase.

A ruthenium-labeled cytochrome c derivative was prepared to meet two design criteria: the ruthenium group must transfer an electron rapidly to the heme group, but not alter the interaction with cytochrome c oxidase. Site-directed mutagenesis was used to replace His39 on the backside of yeast C102T iso-1-cytochrome c with a cysteine residue, and the single sulfhydryl group was labeled with (4-bromomethyl-4' methylbipyridine) (bis-bipyridine)ruthenium(II) to form Ru-39-cytochrome c (cyt c). There is an efficient pathway for electron transfer from the ruthenium group to the heme group of Ru-39-cyt c comprising 13 covalent bonds and one hydrogen bond. Electron transfer from the excited state Ru(II*) to ferric heme c occurred with a rate constant of (6.0 +/- 2.0) x 10(5) s-1, followed by electron transfer from ferrous heme c to Ru(III) with a rate constant of (1.0 +/- 0.2) x 10(6) s-1. Laser excitation of a complex between Ru-39-cyt c and beef cytochrome c oxidase in low ionic strength buffer (5 mM phosphate, pH7) resulted in electron transfer from photoreduced heme c to CuA with a rate constant of (6 +/- 2) x 10(4) s-1, followed by electron transfer from CuA to heme a with a rate constant of (1.8 +/- 0.3) x 10(4) s-1. Increasing the ionic strength to 100 mM leads to bimolecular kinetics as the complex is dissociated. The second-order rate constant is (2.5 +/- 0.4) x 10(7) M-1s-1 at 230 mM ionic strength, nearly the same as that of wild-type iso-1-cytochrome c.

Animals↗
PubMed1993

Intracomplex electron transfer between ruthenium-65-cytochrome b5 and position-82 variants of yeast iso-1-cytochrome c.

We tested the idea that the aromatic ring on the invariant residue Phe-82 in cytochrome c acts as an electron-transfer bridge between cytochrome c and cytochrome b5. Ru-65-cyt b5 was prepared by labeling the single sulfhydryl group on T65C cytochrome b5 with [4-(bromomethyl)-4'-methylbipyridine][bis(bipyridine)]ruthenium 2+ as previously described [Willie, A., Stayton, P.S., Sligar, S.G., Durham, B., & Millett, F. (1992) Biochemistry 31, 7237-7242]. Laser excitation of the complex formed between Ru-65-cyt b5 and Saccharomyces cerevisiae iso-1-cytochrome c at low ionic strength results in rapid electron transfer from the excited-state Ru(II*) to the heme group of Ru-65-cyt b5 followed by biphasic electron transfer to the heme group of cytochrome c with rate constants of (1.0 +/- 0.2) x 10(5) s-1 and (2.0 +/- 0.04) x 10(4) s-1. Variants of iso-1-cytochrome c substituted at Phe-82 with Tyr, Gly, Leu, and Ile have fast-phase rate constants of 0.4, 1.9, 2.1, and 2.0 x 10(5) s-1 and slow-phase rate constants of 5.3, 3.5, 2.4, and 2.0 x 10(3) s-1, respectively. Increasing the ionic strength to 50 mM results in single-phase intracomplex electron transfer with rate constants of 3.8, 3.1, 3.0, 5.0, and 4.5 x 10(4) s-1 for the wild-type, Tyr, Gly, Leu, and Ile variants, respectively. These results demonstrate that an aromatic side chain at residue 82 is not needed for rapid electron transfer with cytochrome b5. Furthermore, two conformational forms of the complex are present at low ionic strength with fast and slow electron-transfer rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytochrome c Group↗
PubMed1993

Probing weakly polar interactions in cytochrome c.

Theoretical, statistical, and model studies suggest that proteins are stabilized by weakly polar attractions between sulfur atoms and properly oriented aromatic rings. The two sulfur-containing amino acids, methionine and cysteine, occur frequently among functional alleles in random mutant libraries of Saccharomyces cerevisiae iso-1-cytochrome c genes at positions that form a weakly polar aromatic-aromatic interaction, the wild-type protein. To determine if a weakly polar sulfur-aromatic interaction replaced the aromatic-aromatic interaction, the structure and stability of two variants were examined. Phenylalanine 10, which interacts with tyrosine 97, was replaced by methionine and cysteine. The cysteine was modified to form the methionine and cysteine analog, S-methyl cysteine (CysSMe). Proton NMR studies indicate that changing Phe 10 to Met or CysSMe affects only local structure and that the structures of sulfur-containing variants are nearly identical. Analysis of chemical shifts and nuclear Overhauser effect data indicates that both sulfur-containing side chains are in position to form a weakly polar interaction with Tyr 97. The F10M and F10CSMe variants are 2-3 kcal mol-1 less stable than iso-1-cytochrome c at 300 K. Comparison of the stabilities of the F10M and F10CSMe variants allows evaluation of the potential weakly polar interaction between the additional sulfur atom of F10CSMe and the aromatic moiety of Tyr 97. The F10CSMe;C102T variant is 0.7 +/- 0.3 kcal mol-1 more stable than the F10M;C102T protein. The increased stability is explained by the difference in hydrophobicity of the sulfur-containing side chains. We conclude that any weakly polar interaction between the additional sulfur and the aromatic ring is too weak to detect or is masked by destabilizing contributions to the free energy of denaturation.

Cysteine↗
PubMed1991

Pancreatic ascites presenting in infancy, with review of the literature.

We report a 4-month-old boy with massive ascites in whom a diagnosis of pancreatitis was made on a raised ascitic amylase level after two inconclusive laparotomies. He developed a pseudocyst which was managed with repeated percutaneous needle aspirations, nutrition being maintained intravenously. Endoscopic retrograde cholangiopancreatography (ERCP) demonstrated a congenital intra-pancreatic cyst. He thrived after operation drainage for recurrent pseudocyst, but repeat ERCP shows that the cyst in the head of the pancreas remains. Pancreatic ascites is rare in children and diagnosis is frequently delayed. A third of reported cases in childhood present in the first year of life. A search for the underlying cause should include an ERCP to demonstrate abnormalities of the pancreaticobiliary ducts.

Ascites↗
PubMed1988

Ureteric obstruction in stented renal transplants.

The use of renal stents in renal transplants is becoming increasingly popular and has been routine practice at this institution for the past 4 years. Despite this procedure, however, obstruction of the transplant ureter still occurs and we describe 7 patients who developed renal obstruction in the presence of a stented transplant ureter. The underlying causes of these findings are discussed together with suggested recommendations for optimum radiological assessment of transplant ureteric stents. The implication of these observations is that urine may flow down stented ureters between the ureter and the stent rather than down the stent lumen.

Adolescent↗
PubMed1987

Midgut malrotation diagnosed by ultrasound.

Ultrasound was used to demonstrate the abnormal orientation of the mesenteric vessels in six cases of midgut malrotation. Five of these patients were known to have an abnormality of rotation before the ultrasound scan. In one patient malrotation was predicted from the ultrasound scan and confirmed by a barium study and at operation.

Adult↗
PubMed1986

Anorexia nervosa and pancreatic ascites.

Acute alcoholic pancreatitis was undiagnosed in a patient with anorexia nervosa who subsequently developed pancreatic ascites and oedema, wrongly attributed to protein malnutrition alone. She became hyperphagic in an attempt to reverse the malnutrition and hence the abdominal swelling, indicating that the goal of attaining a thin shape was the major determinant of the eating disorder in this patient. Measurement of ascitic fluid amylase concentration should be carried out in all patients with unexplained ascites.

Adult↗
PubMed1985

Functional morphology of the piper Hyporhamphus ihi with reference to the role of the lateral line in feeding.

As a basis for understanding the function of the halfbeak of the piper Hyporhamphus ihi (Phillips), details of the structure and dimensions of the anterior lateral line on the head and lower jaw of the piper are described. The anterior lateral line is composed of a series of cranial canals; the supraorbital-postorbital canal; the suborbital canal; and the preopercular-mandibular canal which extends along the lower jaw. Each canal opens to the surface by a series of pores, and individual neuromasts exist in specialized regions of the canals between each of the pores. Piper are nocturnal plankivores and they possess the feeding structures and digestive tract suited to this diet. The hypothesis is proposed that they use the anterior lateral line system in prey detection, and this paper shows that the piper's elongate body form, swimming behaviour, and lack of a specialized visual system are all consistent with this hypothesis.

Animals↗
PubMed1985

Field and laboratory studies of the feeding behaviour of the piper Hyporhamphus ihi with reference to the role of the lateral line in feeding.

Piper school in large groups close to the water surface during daylight hours, whereas at night the schools break up and individual fish can be observed swimming slowly through the water. Analysis of gut contents indicates that during the day piper feed primarily on copepods, and terrestrial insects trapped on the water surface; after dark the demersal zooplankton which enter the water column form the major dietary component. Prey selectivity is evident in that certain groups present in the plankton are not found in the stomach contents of piper, and that the size of prey taken is biased towards the larger size classes of plankton. Laboratory experiments establish that piper are capable of locating prey in total darkness, and that under these conditions live prey are consumed in a higher proportion, and much more quickly than dead prey. These results strengthen the hypothesis that piper use their anterior lateral line to feed on zooplankton at night.

Animals↗
PubMed1985

Effect of blood glucose control on increased glomerular filtration rate and kidney size in insulin-dependent diabetes.

To investigate the relation between blood glucose control on the one hand and an increased glomerular filtration rate and enlarged kidneys on the other, we studied 12 patients with insulin-dependent diabetes and an increased glomerular filtration rate for a year after they were randomly assigned either to continuous subcutaneous insulin infusion or to unchanged conventional therapy. Glycemic control, measured by mean plasma concentrations of glucose and glycosylated hemoglobin, was rapidly and significantly improved (P less than 0.001) in the pump group but did not change in the conventional-treatment group. In the pump group, the glomerular filtration rate fell significantly in the study period (P less than 0.001) and became normal in four of the six patients. It did not change in the conventional-treatment group. There was no change in kidney volume in either group. At the end of a year, a return to conventional insulin treatment in the pump group resulted in both metabolic deterioration and a significant rise in the mean glomerular filtration rate toward base-line values. We conclude that in patients with established insulin-dependent diabetes, strict glycemic control normalizes the glomerular filtration rate, although the kidneys may remain enlarged.

Adult↗
PubMed1983

An assessment of the potential role of routine radionuclide thyroid scanning in the differentiation between solid and cystic lesions in the solitary thyroid nodule.

The value of the conventional 99mTc-pertechnetate scan, to differentiate cystic from solid solitary or dominant non-functioning nodules in the thyroid was investigated in 104 patients. Although these nodules are thought to be non-functioning, a low level of radioactivity can be detected in some of the nodules. The assessment was based on the level of radioactivity in the nodules. The nodules with higher activity were considered to have a higher probability of being solid. This diagnosis was confirmed either by ultrasound, or by histological examination, or both, and sensitivity and specificity evaluated with ROC curve analysis which reached 81% sensitivity with a specificity of 44%. The method was more reliable for larger than for smaller nodules reaching a sensitivity of 81% with a specificity of 84%. The results indicate that 99mTc-pertechnetate scanning can provide a useful procedure to distinguish between cystic and solid lesions in the thyroid.

Diagnosis, Differential↗