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Biomedical subjects

S Spencer

Publications and source records attributed to S Spencer.

At least 19 recordsLinked to original sources

Paediatric renal transplantation in Ireland: 1980-1990.

Between 1980 and 1990, 862 renal transplants were performed at our unit. Forty-six of these were given to 38 children. The mean age of the children was 8.6 years. Reflux nephropathy accounted for 39% of the primary renal diseases, followed by congenital disorders (30%), and glomerulonephritis (16%). Seventy percent of the grafts were from cadaveric donors. The one year patient survival was 90%, and the one year graft survival 61%. Seven children received a second graft with a one year graft survival of 71%.

Adolescent

Cytomegalovirus infection as a complication of OKT3 therapy in kidney transplant recipients.

We compared the incidence of clinical CMV illness in 25 renal transplant recipients treated with OKT3 for steroid resistant cellular rejection with 88 renal transplant patients treated only with conventional immunosuppression (cyclosporin A and steroids). Nine (36%) patients in the OKT3 group developed CMV illness compared to (2.3%) amongst those treated conventionally (p < 0.0005). Patients who received OKT3 were divided into four groups according to the CMV antibody status of the donor and recipient. Six of the 9 episodes of CMV infection occurred in patients not previously exposed to CMV, who received a kidney from a CMV positive donor. Three (12%) of the patients treated with OKT3 died of CMV disease. A further 2 patients died of other causes giving an overall mortality in the OKT3 treated group of 20%. We concluded that when OKT3 therapy is used in association with donor/recipient CMV mismatch it is associated with a high CMV morbidity and mortality.

Adolescent

Does GAP-43 support axon growth by increasing the axonal transport velocity of calmodulin?

GAP-43 is a neuronal protein whose synthesis is elevated during developmental and regenerative axon growth. We propose that one consequence of this increased synthesis may be the delivery of calmodulin-like proteins to the distal portions of the growing axon at an increased velocity; this is because calmodulin, which is transported slowly in mature intact axons, can bind to GAP-43, which is transported rapidly. The release of calmodulin from GAP-43 would be regulated by phosphorylation by protein kinase C. Such a rapid carrier function could be important for allowing certain recently synthesized slowly transported proteins to reach the moving growth cone in time to support its function. This hypothetical carrier mechanism is consistent with the phosphorylation pattern, calmodulin binding, transport velocity, and growth-association of GAP-43, and suggests an explanation for the specific importance of newly synthesized GAP-43 in supporting axon growth.

Animals

Is cow's milk suitable for the dietary supplementation of rural Gambian children? 1. Prevalence of lactose maldigestion.

To define the age-related prevalence of lactose maldigestion (LM), 218 children aged 13-72 months from a rural Gambian village were studied using a lactose breath hydrogen test. There was a significant rise in LM from 21% to 76% between the 2nd and 3rd-5th years of life (p < 0.001). Only eight children had diarrhoea within 2 weeks before the test. Diarrhoea and abdominal discomfort followed in only seven children (3%). There was no difference in mean time of introduction of supplementary diet or cessation of breastfeeding between children aged 12-36 months with lactose digestion and LM. There was a greater proportion of children with normal lactose digestion than with LM in those still receiving breast milk (85% vs 15%), and a greater proportion of LM in the fully weaned group (63% vs 37%) (p < 0.001). There was no relation between weight-for-age or weight-for-height and the ability to digest lactose. The ability to digest lactose is lost in the majority of children during the 2nd year, coincident with the cessation of breastfeeding, but is not a major factor associated with growth failure thereafter.

Age Factors

Relation between magnesium and potassium concentrations in myocardium, skeletal muscle, and mononuclear blood cells.

Potassium and magnesium were measured in 26 cardiac surgery patients (right atrial appendage), 23 autopsy subjects (right atrial appendage, left ventricular free wall, and skeletal muscle), and 9 healthy volunteers (mononuclear blood cells) to determine whether there was a relation between these two ions in the tissues measured. In the cardiac surgery patients, the potassium and magnesium concentrations were 46.35 +/- 3.89 and 4.40 +/- 0.58 (mean +/- SD, mumol/g wet weight tissue), respectively, and were significantly correlated (r = 0.54, P = 0.005). In the autopsy group, the respective concentrations were: for right atrial appendage, 30.54 +/- 10.18 and 3.66 +/- 0.70 mumol/g (r = 0.38, P = 0.14); left ventricular free wall, 60.69 +/- 17.93 and 7.74 +/- 1.73 mumol/g (r = 0.92, P = 0.0001); and skeletal muscle, 93.05 +/- 20.49 and 8.64 +/- 2.06 mumol/g (r = 0.91, P = 0.0001). In the healthy volunteer group, the results for potassium and magnesium in mononuclear blood cells were 42 +/- 9.9 and 3.99 +/- 0.70 fmol/cell, respectively (r = 0.94, P = 0.0001). Thus, potassium and magnesium concentrations were significantly correlated in all the tissues measured.

Aged

Production of the neuronal growth-associated protein GAP-43 in a bacterial expression system.

GAP-43, a major protein of neuronal growth cones and certain presynaptic terminals, is a candidate for important functions in both axon growth and synaptic plasticity. To facilitate studies that may elucidate these functions, we have efficiently generated large quantities of GAP-43 by introducing a GAP-43 cDNA into a bacterial expression system driven by T7-RNA polymerase. Two constructs were expressed in this system: one (pT7Ava-GAP) produces a fusion protein in which the first 16 amino acids of GAP-43 are replaced by 11 amino acids of the phage T7 capsid protein; the other (pT7FL-GAP) produces full length GAP-43. After the bacteria were lysed, both products were soluble, and could be efficiently purified by HPLC chromatography on a C4 reversed-phase column. One liter of bacterial culture yielded 50 mg of purified fusion protein or 10 mg of complete GAP-43. When it was incubated with protein kinase C, the fusion protein was phosphorylated at the same single site (serine 41) that is phosphorylated in cultured neurons. The ability to produce large quantities of GAP-43 by this procedure should expedite future studies investigating its structure, posttranslational modification, and function.

Amino Acid Sequence

Transplantation of kidneys from pediatric cadaver donors to adult recipients.

Pediatric donors (less than 12 years old) are a potentially important source of kidneys for adult recipients. Previous reports of decreased graft survival and increased complication rates have made surgeons wary of using such kidneys. In 64 kidneys from younger donors transplanted to adult recipients the delayed graft function rate (41 versus 42%), and 2 and 3-year graft survival rates (67 versus 72% and 61 versus 65%, respectively) were similar to those seen with kidneys from adult donors. Kidneys from donors 24 months old or less experienced an 80% rate of graft loss at 1 year. When these kidneys are excluded the 1-year graft survival rate was similar to kidneys from older and younger donors (70 versus 77%). Mean serum creatinine at 1 year was similar in both groups (155 +/- 21 versus 151 +/- 10). Pediatric kidneys except those obtained from donors 2 years old or less are suitable for adult recipients. However, kidneys from very young donors may be more appropriate to pediatric recipients.

Adult

Patterns of uptake and problems presented at Well Woman clinics in Liverpool.

Well Woman clinics, at which all the staff are women, are provided on an open-access basis by Liverpool Health Authority. In 1986, uptake was low by women over the age of 55, by women from semi-skilled and unskilled manual households, and by women who did not have any formal employment. These, however, are the women who are at greatest risk of ill health. Almost half of the women attending had a vaginal problem or infection, and 40% were anxious or depressed. The clinics, however, are unable to treat any problems diagnosed, and over a third of women using the clinics were referred back to their general practitioner. The findings have important implications for the provision and continuity of primary and preventive care, not least because many women may be reluctant to take the problem which they present to Well Woman clinic doctors to their own (often male) general practitioner in a busy general surgery.

Adolescent

Epitope-specific binding of CD8 regulates activation of T cells and induction of cytotoxicity.

Functions of the CD8 molecule were examined to determine whether CD8 is merely a ligand-binding molecule and/or is involved in signal transduction. Using KT112 (anti-CD8 beta), CD8 was demonstrated to transduce an activation signal leading to cytotoxicity. Conformational changes of the CD8 molecule might be responsible for the activation, because (i) KT15 (anti-monomorphic CD8 alpha), but not antibodies specific for polymorphic CD8 alpha determinants, abrogated KT112 (anti-CD8 beta)-induced cytotoxicity without blocking the binding of KT112, whilst (ii) KT112 (anti-CD8 beta) inhibited KT15 (anti-monomorphic CD8 alpha)-mediated augmentation of proliferation triggered by a V beta 11-specific antibody without blocking the binding of KT15.

Animals

Brain natriuretic peptide-like immunoreactive innervation of the cardiovascular and cerebrovascular systems in the rat.

Atrial natriuretic peptide is a potent dilator of aorta and renal and cerebral arteries and inhibits sympathetic tone in the heart in several mammalian species. We examined the possibility that a molecule related to porcine brain natriuretic peptide (pBNP), which acts at the same receptor sites as atrial natriuretic peptide, might provide an alternative source of natriuretic peptide to the cardiovascular system in the rat. An antiserum against pBNP demonstrated profuse immunoreactive innervation of the heart, cerebrovascular tree, and renal arteries. pBNP-like immunoreactive fibers ran in bundles along the surface of the heart, innervating the atria most heavily and penetrating the ventricular myocardium along the coronary arteries. There was greater density of innervation of the right side of the heart compared with the left, particularly in the ventricles, suggesting a parasympathetic origin. The entire cerebrovascular tree was innervated by immunoreactive pBNP fibers, with the densest concentration of immunoreactive fibers along the surface of the internal carotid, middle cerebral, posterior communicating, and anterior cerebral arteries. The proximal renal arteries were not innervated, but as they approached the kidney, they were invested by bundles of immunoreactive pBNP fibers. These axons followed the major branches of the renal artery into the kidney parenchyma, running along the surface of the arterioles up to their entrance into the renal glomeruli. No immunoreactive innervation of the aorta or proximal brachiocephalic, subclavian, or carotid arteries was seen. A substance related to pBNP may serve as a neuromodulator regulating cardiac output as well as blood flow in certain vascular beds.

Animals