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Biomedical subjects

P D Arkwright

Publications and source records attributed to P D Arkwright.

35 records · Page 2Linked to original sources
PubMed2000

Clinical course of patients with major histocompatibility complex class II deficiency.

The clinical course of 10 children who have been diagnosed with major histocompatibility complex (MHC) class II deficiency (bare lymphocyte syndrome) in the UK over the past eight years is described. They have had a generally poor prognosis, with only two of the 10 still alive despite eight attempts at bone marrow transplantation in six patients. Overwhelming viral infection was the predominant cause of death. Alternative transplant strategies or novel therapies are required for these patients.

Bone Marrow Transplantation↗
PubMed2000

TGF-beta(1) genotype and accelerated decline in lung function of patients with cystic fibrosis.

BACKGROUND: Polymorphisms in transforming growth factor (TGF)-beta(1) associated with variations in cytokine levels are linked to fibrosis in a number of tissues. However, the contribution of this cytokine to organ fibrosis in patients with cystic fibrosis is presently unclear. This study was undertaken to examine the association between TGF-beta(1) gene polymorphisms and the development of pulmonary dysfunction in patients with cystic fibrosis. METHODS: Polymorphisms in the TGF-beta(1) gene defining amino acids of codons 10 and 25 were determined by ARMS-PCR using DNA stored on 171 Caucasian patients who were homozygous for the DeltaF508 mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Clinical information on the patients was obtained from medical records. RESULTS: Patients with cystic fibrosis of a TGF-beta(1) high producer genotype for codon 10 had more rapid deterioration in lung function than those with a TGF-beta(1) low producer genotype. The relative risk of accelerated decline in forced expiratory volume in one second (FEV(1)) to 50% predicted and forced vital capacity (FVC) to 70% predicted of patients with a high producer genotype was 1.74 (95% CI 1.11 to 2. 73) compared with 1.95 (95% CI 1.24 to 3.06) for those with a low producer genotype. DISCUSSION: TGF-beta(1) genotypes may have a role in mediating pulmonary dysfunction in patients with cystic fibrosis. Further work is required to determine whether inhibition of TGF-beta(1) activity in these patients may slow disease progression.

Adolescent↗
PubMed1998

X linked lymphoproliferative disease in a United Kingdom family.

X linked lymphoproliferative disease (XLP; Duncan's disease) is a rare disorder affecting boys and characterised by a defective immune response to Epstein-Barr virus caused by a mutation in a gene located at chromosome Xq25. Three siblings with XLP in a single UK family are reported and the variation in phenotypic expression of the disease in these siblings described. One of the siblings with life threatening fulminant infectious mononucleosis was successfully treated by chemotherapy, followed by bone marrow transplantation using an unaffected brother as the donor. A healthy baby boy recently born into the family was identified as carrying the defective maternal X chromosome using molecular genetic linkage analysis. This family illustrates the extent of present understanding of this often fatal condition.

Bone Marrow Transplantation↗
PubMed1998

Dietary management of atopic eczema: is this justified?

The role of food allergens in triggering atopic eczema remains controversial. Certain foods can cause acute hypersensitivity reactions, which are more common in atopic individuals, but this does not necessarily imply that these allergens cause or trigger eczema. This article discusses the evidence for and against dietary intervention as a treatment for patients with atopic eczema.

Allergens↗
PubMed1996

Infantile nephrotic syndrome and atopy.

Nephrotic syndrome presenting in the 1st year of life is often associated with a very poor prognosis for normal renal function. A small proportion of patients, particularly boys, presenting after the first 3 months of life with idiopathic-type, steroid-sensitive nephrosis, have a much better prognosis and may achieve sustained remission. We describe three boys with infantile idiopathic nephrotic syndrome of the mesangial proliferative glomerulonephritis type who went into complete remission. The patients, their first-degree relatives or both suffered from atopy (eczema, asthma or hayfever). This is the first report linking infantile nephrotic syndrome and atopy. The literature linking idiopathic nephrotic syndrome and atopy is reviewed, and the implications of our findings discussed.

Anti-Inflammatory Agents↗
PubMed1995

Short communication: selective placental transport of maternal IgG to the fetus.

During pregnancy there is a dramatic reduction in the serum levels of agalactosyl IgG (G0IgG) in both normal women and those with rheumatoid arthritis. In order to determine if a similar reduction in G0IgG were apparent in fetal serum, a comparison of the galactose content of IgG from nine paired samples of umbilical vein or fetal blood and peripheral maternal serum, at gestational ages ranging from 16-41 weeks was performed. The full-term maternal IgG samples were highly galactosylated, so confirming previous observations of reduced G0IgG levels during pregnancy. In addition every paired sample of fetal IgG had a higher level of galactosylation than the corresponding maternal IgG. Therefore, during pregnancy there is both a reduced biosynthesis of the G0IgG glycoform by the mother, and a restriction of its transport across the placenta. The ratio of estimated G0IgG in fetal and maternal serum was found to be related to changes in IgG transport, and in particular the active transport of IgG1 across the placenta during gestation. Our data suggest that the placental IgG transport mechanism is either carbohydrate independent by discriminating for IgG1, or is carbohydrate dependent selecting for highly galactosylated IgG glycoforms. This study emphasizes the need for further investigations on the biological function of G0IgG in normal physiological states, in addition to disease states, such as juvenile and adult rheumatoid arthritis, where elevated G0IgG levels correlate with disease activity.

Arthritis, Rheumatoid↗
PubMed1994

Suppression of allogeneic reactivity in vitro by the syncytiotrophoblast membrane glycocalyx of the human term placenta is carbohydrate dependent.

Immunosuppressive factors isolated from trophoblast are known to block both innate and major histocompatibility complex (MHC)-dependent cell-mediated immune responses in vitro and, in some cases, in vivo. We investigated the biochemical nature of these factors, which is presently unknown. Immunosuppressive activity, assessed by inhibition of two-way MLR, was extracted from term syncytiotrophoblast microvilli using 3 M KCl. The activity resisted both extensive pronase digestion and heating to 90 degrees C for 1 h, demonstrating that intact membrane proteins were not required. Although purified protein-linked oligosaccharides released by hydrazinolysis from the syncytiotrophoblast membrane were themselves inactive, they blocked the immunosuppressive activity of the KCl extract. After pronase digestion, the activity could be fractionated by TSK 55S gel filtration, followed by C18 reverse-phase chromatography. Sequential exoglycosidase digestion of hydrazine-released sugars of the active fraction demonstrated that it contained neutral N-linked oligomannose and hybrid oligosaccharides, which normally make up < 3% of the total syncytiotrophoblast-derived protein glycan library. These glycopeptides of the active fraction were associated with membrane phospholipid micelles. The possible mechanism by which incompletely processed N-linked oligosaccharides expressed by a variety of syncytiotrophoblast membrane glycoproteins may block allogeneic reactivity when presented as polyvalent sugar groups is discussed.

Carbohydrate Metabolism↗
PubMed1993

Pre-eclampsia is associated with an increase in trophoblast glycogen content and glycogen synthase activity, similar to that found in hydatidiform moles.

Pre-eclampsia is a placental disorder, but until now, biochemical details of dysfunction have been lacking. During an analysis of the oligosaccharide content of syncytiotrophoblast microvesicles purified from the placental chorionic villi of 10 primigravid women with proteinuric pre-eclampsia, we found an excess of glycogen breakdown products. Further investigation revealed a 10-fold increase in glycogen content (223 +/- 117 micrograms glycogen/mg protein), when compared with controls matched for gestational age at delivery (23 +/- 18 micrograms glycogen/mg protein) (P < 0.01). This was confirmed by examination of electron micrographs of chorionic villous tissue stained for glycogen. The increase in glycogen content was associated with 16 times more glycogen synthase (1,323 +/- 1,013 relative to 83 +/- 96 pmol glucose/mg protein per min) (P < 0.001), and a threefold increase in glycogen phosphorylase activity (2,280 +/- 1,360 relative to 700 +/- 540 pmol glucose/mg protein per min; P < 0.05). Similar changes in glycogen metabolism were found in trophoblast microvesicles derived from hydatidiform moles. Glycogen accumulation in villous syncytiotrophoblast may be a metabolic marker of immaturity of this cell which is unable to divide. The implications of these findings with regard to the pathogenesis of pre-eclampsia are discussed.

Adult↗
PubMed1984

Free and sulfate-conjugated catecholamines during exercise in man.

The study examined the plasma concentration of free and sulfate-conjugated norepinephrine (NE) and epinephrine (E) at rest and after vigorous bicycle exercise. Free and total catecholamines were measured by a modified radioenzymatic assay using external standards. This assay was less costly and, in subjects with normal renal function, plasma levels were highly comparable to those obtained using internal standards. Exercise was associated with a predictable rise in plasma free NE and E concentration, which correlated with the hemodynamic changes, and a significant decrease in the levels of catecholamine sulfate conjugates. There was an inverse relationship between the degree of conjugation and the free levels of NE and E both at rest and after exercise. This suggests that the degree of conjugation is another factor determining the concentration of free amines in plasma.

Adult↗
PubMed1984

Plasma calcium and cortisol as predisposing factors to alcohol related blood pressure elevation.

Mechanisms by which alcohol consumption might cause hypertension were examined in 30 pairs of healthy drinking (greater than 275 g ethanol per week) and teetotal men closely matched for age and obesity. Both systolic and diastolic blood pressures were significantly higher in the drinkers. Plasma calcium levels correlated with diastolic blood pressures (r = 0.51, P = 0.004) in drinkers only. After adjusting for plasma albumin, diastolic pressures increased by 6.9 mmHg for each 0.1 mM increment of plasma calcium. It is proposed that regular alcohol consumption predisposes to hypertension by facilitating calcium accumulation in cells involved in blood pressure regulation. In the combined population of drinkers and teetotallers plasma cortisol correlated positively with diastolic pressure (r = 0.35, P = 0.012) and negatively with plasma potassium (r = -0.38, P = 0.006); this suggests a role for the pituitary/adrenal axis as a significant determinant of blood pressure differences between healthy subjects.

Adult↗
PubMed1983

Alcohol, personality and predisposition to essential hypertension.

The nature of the relationship between alcohol, personality and blood pressure levels was examined in 491 working men who completed detailed questionnaires which included Eysenck's personality inventory. Alcohol had an effect on systolic blood pressure levels independent of all other factors studied. However, in 152 non-smoking moderate to heavy drinkers (greater than 18 g ethanol per day) the extroversion/introversion trait was the most significant predictor of systolic blood pressure levels, and in introverted drinkers the prevalence of hypertension (greater than or equal to 140 mmHg systolic or greater than or equal to 90 mmHg diastolic) was three times that of extroverted drinkers and nine times that of teetotallers. This association between introversion and 'hypertension' was not seen in drinkers who also smoked cigarettes. The interactions between environmental stimuli (alcohol, smoking) and presumably genetically determined personality characteristics may have an important bearing on concepts of essential hypertension and point to new approaches for investigation.

Adult↗
PubMed1983

Adrenal and sympathetic nervous activity in subjects with "low' and "high' normal blood pressure.

Possible adrenal and autonomic mechanisms contributing to the onset of essential hypertension were studied in 18 men selected from the upper and lower extremes of blood pressure distribution within a larger population. In eight of the nine pairs of subjects, who were matched for age and obesity, those with higher pressure had significantly higher resting levels of both free adrenaline and noradrenaline sulphate in plasma than their lower pressure counterparts. The higher pressure group showed a positive correlation between diastolic blood pressure and both free and total noradrenaline levels (r = 0.77, P less than 0.05, and r = 0.81, P less than 0.01, respectively). In those with lower pressure, systolic blood pressure correlated closely with plasma adrenaline (r = 0.92, P less than 0.001). Increased adrenal medullary activity and altered autonomic tone appear to be features of the higher range of normal blood pressure and may precede the onset of essential hypertension.

Adrenal Medulla↗
PubMed1982

Effects of alcohol use and other aspects of lifestyle on blood pressure levels and prevalence of hypertension in a working population.

The relationship between alcohol consumption and blood pressure was studied in 491 males, ages 20-45 years, who volunteered to complete a health questionnaire and submit to standardized measurements of blood pressure, heart rate and body size. Average weekly alcohol consumption correlated with systolic pressure (r = 0.18) but not diastolic pressure. Systolic pressure increased progressively with increasing alcohol consumption, with no obvious threshold effect. In moderate and heavy drinkers (53% of the population studied), the prevalence of systolic hypertension (greater than or equal to 140 mm Hg) was four times that of teetotalers. The effect of alcohol on systolic blood pressure was independent of the effects of age, obesity, cigarette smoking and physical activity. Ex-heavy drinkers had blood pressures similar to those of teetotalers, suggesting that the effect of alcohol is reversible. Cigarette smokers had lower diastolic pressures than nonsmokers, an effect independent of obesity. The linear correlation between alcohol consumption and systolic blood pressure and the lower blood pressures in exdrinkers suggest a cause-and-effect relationship. The results indicate that alcohol ranks close to obesity as a potentially preventable cause of hypertension in the community.

Adult↗
PubMed1982

The pressor effect of moderate alcohol consumption in man: a search for mechanisms.

Thirty pairs of drinking and nondrinking men, matched for age and weight, were drawn from a working population in which a close relationship between alcohol consumption and blood pressure had been demonstrated. In this smaller sample, men who drank an average of 408 ml of ethanol/week had higher supine (126.9 +/- 2.3 mm Hg) and standing (113.3 +/- 2.5 mm Hg) systolic and supine diastolic blood pressure (75.5 +/- 2.2 mm Hg) than nondrinkers (117.5 +/- 2.0, 107.4 +/- 2.2 and 68.9 +/- 1.8 mm Hg, respectively). Resting plasma concentrations of free and sulfated norepinephrine and epinephrine, renin activity, angiotensin II, aldosterone and cortisol were similar in drinkers and nondrinkers. To investigate differences that may arise when sympathoadrenal activity was stimulated, the subjects underwent a series of standardized physiologic stresses: isometric hand grip, mental arithmetic, cold pressor testing, standing and bicycle exercise. Blood pressure and heart rate responses were similar in drinkers and nondrinkers, although the differences in blood pressure between the two groups tended to become smaller after certain stresses. No differences in the plasma levels of free or conjugated catecholamines were apparent after these stresses. Plasma renin activity increased only after bicycle exercise, and this was similar in both groups. Plasma cortisol levels did not increase. The higher blood pressure in drinkers, therefore, cannot be explained by increased activity of the sympathoadrenal and renal pressor mechanisms.

Adult↗
PubMedDate not supplied

Syncytiotrophoblast membrane protein glycosylation patterns in normal human pregnancy and changes with gestational age and parturition.

The fetally derived syncytiotrophoblast in the placenta form the major interface with the maternal circulation. Cell surface N-linked oligosaccharides are known to influence cell-cell interactions in a variety of ways. The N-linked oligosaccharide component of the human syncytiotrophoblast membrane has been purified from term placentae, and its biochemical structure analysed. Ninety-five per cent of structures were complex N-linked oligosaccharides, with the remaining 5 per cent being of the oligomannose type. Seventy-two per cent of oligosaccharides were sialylated; 50 per cent having two or more sialic acid residues. Such a population of N-linked oligosaccharides would be expected to provide a surface which inhibits interactions between trophoblast and maternal leukocytes. The temporal changes in syncytiotrophoblast N-linked oligosaccharides from the end of the second, and through the third trimester (25-41 weeks) were analysed, as were the changes which occur during parturition. There was no change in the degree of sialylation of these structures. The only significant change was a 37 per cent decrease in core fucosylation of complex N-linked sugars during gestation (P less than 0.005). Women delivered by caesarean section at term, had significantly higher levels of fucosylation (equivalent to women with a gestational age of 31-36 weeks), than those who laboured at term. Present knowledge of core fucosylation of N-linked oligosaccharides is discussed in relation to trophoblast functioning.

Carbohydrate Sequence↗
PubMedDate not supplied

Alcohol and blood pressure in a working population.

1. The association between alcohol consumption and blood pressure was studied in 491 Government employees. The men, aged 21-45 years, volunteered to complete a health questionnaire and submitted to standardized measurements of blood pressure, heart rate and body size. 2. Average weekly alcohol consumption correlated with systolic pressure (R = 0.18, P less than 0.001) but not with diastolic pressure. Systolic pressure increased progressively with increasing alcohol consumption with no obvious threshold effect. An effect of alcohol was seen independent of age, obesity (Quetelet's index) or cigarette smoking. 3. Results indicate that alcohol ranks close to obesity as a preventable cause of essential hypertension in the community.

Adult↗