Diarrhoea due to cryptosporidium infection in thalassaemia major.
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Adult↗
Biomedical subjects
J Porter
Publications and source records attributed to J Porter.
Screening for prolonged incubation of HTLV-I infection in British and Jamaican relatives of British patients with tropical spastic paraparesis.
OBJECTIVE: To compare the prevalence of antibody to and proviral DNA of the retrovirus HTLV-I in relatives of 11 British patients with tropical spastic paraparesis who had migrated from Jamaica before they developed symptoms, and to examine factors possibly related to transmission of HTLV-I. DESIGN: Migrant, family study. Antibody state was determined by several methods and confirmed by western blotting; the polymerase chain reaction was used to detect proviral DNA. SETTING: Britain and Jamaica. SUBJECTS: All available first degree relatives: those born and still resident in Jamaica (group 1); those born in Jamaica who migrated to Britain (group 2); and index patients' children who were born and resident in Britain (group 3). All had been breast fed and none had had blood transfusions. RESULTS: Of the 66 living relatives, 60 were traced. Seroprevalence among those born in Jamaica (irrespective of current residence) was 22% (10/46; 95% confidence limits 9 to 34%) compared with zero among British born offspring (0/14) and was higher in group 2 at 33% (7/21; 12 to 55%) than in group 1 at 12% (3/25; 0 to 25%). (Patients in group 1 had the greatest mean age.) Proviral DNA was not detected in any subject negative for HTLV-I antibody, making prolonged viral incubation in those negative for the antibody unlikely. CONCLUSION: In this sample factors related to place of birth and early residence were more important in transmission of HTLV-I than maternal or age effects. In areas with a low to moderate prevalence policies of preventing mothers who are carriers of the virus from breast feeding would be premature.
Base Sequence↗
Epidemic alert: malaria infections in travellers from West Africa.
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Africa, Eastern↗
Detection of interleukin 1 beta but not tumor necrosis factor-alpha in cerebrospinal fluid of children with aseptic meningitis.
Tumor necrosis factor-alpha and interleukin 1 beta have been shown to be mediators of meningeal inflammation in animal models of bacterial meningitis. The presence of both cytokines in cerebrospinal fluid (CSF) of patients with bacterial meningitis has been documented recently. In this study, we measured concentrations of interleukin 1 beta and tumor necrosis factor-alpha in CSF samples from 36 patients with nonbacterial (aseptic) meningitis, 13 of whom had culture-proved enteroviral meningitis, and from 14 control patients. None of the samples from patients with aseptic meningitis and from the controls had detectable tumor necrosis factor activity in CSF. Thirty-two (89%) of 36 patients with aseptic meningitis had detectable interleukin 1 beta in CSF (mean +/- SEM, 48 +/- 11 pg/mL). These concentrations were significantly smaller than those previously reported in patients with bacterial meningitis (944 +/- 128 pg/mL). Only 2 of the 14 control patients had detectable CSF interleukin 1 beta concentrations of 21 and 42 pg/mL. A significant correlation was evident between interleukin-1 beta concentrations and white blood cell counts in the CSF of patients with aseptic meningitis. Our data suggest that the initial events of CSF inflammation in children with aseptic meningitis are different than those in patients with bacterial meningitis, and the participation of these two cytokines, especially tumor necrosis factor-alpha, is less critical to the process.
Adolescent↗
Novel 3-hydroxy-2(1H)-pyridinones. Synthesis, iron(III)-chelating properties, and biological activity.
The synthesis of a range of novel bidentate and hexadentate ligands containing the chelating moiety 3-hydroxy-2(1H)-pyridinone is described. The pKa values of the ligands and the stability constants of their iron(III) complexes have been determined. The stability constant of the iron(III) complex of one of the hexadentate ligands is comparable to that of desferrioxamine B. The distribution coefficients of the ligands and their iron(III) complexes were also determined. One of the novel hexadentate compounds has been shown to markedly enhance iron(III) excretion from both hepatocytes and iron-overloaded mice.
Animals↗
What is morally distinctive about genetic engineering?
It sometimes seems that genetic engineering is suspect, both to its practitioners and to the general public, because it is perceived as being somehow unnatural. This essay argues, on the basis of an analysis of two senses of "natural," that there is nothing distinctively morally problematic about genetic engineering, at least on the grounds of its alleged unnaturalness. It does not follow that we cannot distinguish among morally legitimate and morally suspect uses of genetic engineering. But these distinctions can and should be drawn on the basis of the same considerations that enter into the evaluation of particular uses of any other medical procedure.
Ethical Analysis↗
Dominant-negative mutants of a platelet-derived growth factor gene.
Using site-directed mutagenesis of a PDGF-A cDNA clone, we identify two domains that are required to generate stable, mitogenically active PDGF-AA homodimers. Alteration of the tetra-basic amino acid sequence (Arg84-Arg-Lys-Arg to Arg-Ser-Asn-Gly) results in the formation of stable pro-PDGF-A homodimers that lack mitogenic activity. Substitution of serine for Cys129 destabilizes PDGF-A subunits within the cell. Genes incorporating either the processing lesion or the cysteine substitution suppress wild-type PDGF-A gene expression in a trans-dominant fashion. Suppression occurs because the mutant PDGF subunits dimerize with wild-type subunits to form inactive or unstable heterodimers. Suppression is exerted across phylogenetic boundaries; thus, the mouse PDGF-A chain mutants inhibit the activity of the wild-type Xenopus PDGF-A. The cysteine mutant gene suppresses expression of PDGF-B (c-sis), as well as PDGF-A. The processing mutant gene, however, suppresses only PDGF-A. Dominant-negative mutations of PDGF and other growth factors which, like PDGF, function as dimers may prove useful for creating animals models of growth factor deficiency disease states and for revealing the function of growth factors during early embryonic development.
Amino Acid Sequence↗
Randomized comparison of routine vs highly selective use of Doppler ultrasound and biophysical scoring to investigate high risk pregnancies.
OBJECTIVE: To compare routine versus highly selective use of Doppler ultrasound and biophysical scoring in higher risk pregnancy. DESIGN: A pragmatic randomized trial. SETTING: St James's University Hospital, Leeds. SUBJECTS: 500 pregnant women at high risk of intrauterine growth retardation or still birth. INTERVENTIONS: Regular monitoring with biophysical profile assessment and Doppler velocity waveform recording in umbilical and uteroplacental arteries. Results immediately available to clinicians. MAIN OUTCOME MEASURES: Gestational age at delivery, obstetric intervention rates and short-term neonatal morbidity. RESULTS: Risk factors were distributed very evenly between the 250 patients in the study and control groups respectively. A total of 902 biophysical profile and Doppler assessments were done in the 250 study group patients and only in 12 patients in the control group. In the study group, absent end-diastolic flow was found in only 2.7% of all 902 measurements. A persistently abnormal biophysical score was always associated with absence of end-diastolic flow. The mean gestational age at induction of labour was statistically and clinically similar in the two groups and there was no overall statistically significant difference in intervention rates between the two groups. There was a statistically significant lower frequency of depressed 5-min Apgar scores in the study group. Serious neonatal morbidity was also statistically significantly more common in the control group than in the study group. CONCLUSIONS: The use of Doppler ultrasound in higher risk pregnancies does not lead to an increase in iatrogenic preterm delivery. The total rate of positive tests on Doppler ultrasound is very low and persistently abnormal biophysical scores are unlikely to be found in patients where umbilical end-diastolic blood flow is present. Surrogate measures for fetal damage seem to be improved when clinicians have access to Doppler ultrasound assessments.
Adult↗
Crucial role of pancreatic ductal collagenase injection for isolation of pancreatic islets.
We have been stressing the advantage of stationary digestion because of its simplicity and reproducible high yields of viable islets. In the present study optimal conditions of stationary in vitro collagenase digestion in mice and rats were examined. We also compared two possible routes for collagenase injection; ductal (PD) and portal venous (PV) based on subsequent islet yield and ability to reverse diabetes in rats. Three parameters which affect the quality of digestion are 1) collagenase concentration, 2) incubation time and 3) digestion temperature. Suitable conditions were easily determined and reproducible high yield of islets could be consistently obtained. The islets from one mouse pancreas (approximately 200 islets) could consistently restore normoglycemia in one STZ-induced diabetic mouse and the islets from one rat pancreas (500-600 islets) can restore normoglycemia in 5-6 STZ-induced diabetic mice within a couple of days. Islet yield in the PD method was greater than that in the PV method, and insulin release from PD islets in response to high glucose was well preserved after 24 hours of culture when compared to PV islets. The ability to restore normoglycemia in STZ-induced diabetic mice was well preserved when transplanting 100 PD islets as compared with the same number of PV islets. The PD islets revealed a well preserved structure with healthy endocrine cells, while the PV islets showed a dilated capillary network and distorted endocrine cell continuity. Histological examination of digested tissue following PD injection showed the complete destruction of pancreatic exocrine tissue, as well as mechanical separation and digestion of interstitial tissue between the islets and exocrine tissue, with the islet being preserved selectively intact.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Gamma-irradiation as a tool to reduce immunogenicity of islet allo- and xenografts.
Sensitivity of pancreatic endocrine cells to gamma-irradiation and alteration of islet immunogenicity by irradiation were examined. Syngeneic, allogeneic (DBA/2) and xenogeneic (rat) islets were irradiated and transplanted at varying doses (8, 24, 40, 80 and 160 Gy) into streptozotocin-induced diabetic B6AF1 mice. In an isograft model, late loss of graft function was observed in some animals given 200 24-Gy-irradiated islets. However, larger numbers (400-500) of islets given 40 Gy irradiation did not show reversal of normoglycemia. With higher doses (80 or 160 Gy) significant early as well as late graft loss was observed. In an allograft model, the irradiated islet allografts survived beyond controls. Marked prolongation was achieved with a broad range of irradiation doses between 8 Gy and 120 Gy with 30-90% of recipients maintaining normoglycemia over 50 days. Late loss of graft function was observed between 78 and 180 days with a dose over 24 Gy. Increasing dose resulted in a better allograft survival rate in the early postoperative period, but tended to curtail longterm survival. In an xenograft model, irradiation of islets with 8 to 24 Gy led to prolongation of graft survival. Maximum graft prolongation was achieved with 24 Gy. Higher doses were much less effective and, in some recipients, caused shortening of graft survival.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Aerosol delivery of liposome metaproterenol sulfate.
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Aerosols↗
Preparative-scale synthesis and reversed-phase purification of a gonadotropin-releasing hormone antagonist.
The preparation of "Nal-Glu" antagonist (Ac-D-Nal-D-Cpa-D-Pal-Ser-Arg- D-2-amino-5-oxo-5-(4-methoxyphenyl)pentanoic acid-Leu-Arg-Pro-D-Ala-NH2) was accomplished in two steps: (i) preparation of [Ac-D-Nal1, D-Cpa2, D-Pal3, Arg5, D-Glu6, D-Ala10]-GnRH via standard solid-phase synthetic techniques and (ii) acylation of anisole (Friedel-Crafts) by the glutamic acid residue in position 6. The preparative-scale, reversed-phase high-performance liquid chromatographic (HPLC) purification of the crude "Nal-Glu" antagonist employs first a triethylammonium phosphate (TEAP) (pH 2.25)-acetonitrile solvent system, followed by an HPLC-based desalting procedure, yielding the acetate salt of the peptide. This repetitive process of purification in TEAP-acetonitrile, followed by counter-ion exchange with 0.5% acetic acid-acetonitrile is highly reproducible and allows large amounts of a given peptide to be purified efficiently in a batchwise fashion. The procedure described for the synthesis, purification and characterization of the "Nal-Glu" antagonist is presented as a model for the multi-gram synthesis and purification of peptides to be used in clinical investigations.
Amino Acid Sequence↗
Aerobic fitness in patients with fibrositis. A controlled study of respiratory gas exchange and 133xenon clearance from exercising muscle.
Aerobic fitness was evaluated in 25 women with fibrositis, by having them exercise to volitional exhaustion on an electronically braked cycle ergometer. Compared with published standards, greater than 80% of the fibrositis patients were not physically fit, as assessed by maximal oxygen uptake. Compared with matched sedentary controls, fibrositis patients accurately perceived their level of exertion in relation to oxygen consumption and attained a similar level of lactic acidosis, as assessed by their respiratory quotient and ventilatory threshold. Exercising muscle blood flow was estimated by 133xenon clearance in a subgroup of 16 fibrositis patients and compared with that in 16 matched sedentary controls; the fibrositis patients exhibited reduced 133xenon clearance. These results indicate a need to include aerobic fitness as a matched variable in future controlled studies of fibrositis and suggest that the "detraining phenomenon" may be of relevance to the etiopathogenesis of the disease.
Adult↗
Successful treatment of experimental diabetes by sequential transplantations of multiple-donor pancreatic islet allografts.
Fifty hand-picked islets were freshly prepared from DBA/2 mice and transplanted four times into a streptozotocin-induced diabetic B6AF1 mouse without immunosuppression. Blood sugar levels decreased progressively and all recipients became normoglycemic after the 4th grafting. Four repeated transplantations at 2-4-day or 14-day intervals restored normoglycemia for more than 200 days in virtually all recipients. However, a majority of recipients given four transplantations of 50 DBA/2 islets at 7-day intervals or four transplantations of 100 DBA/2 islets at 4-day or 14-day intervals acutely rejected their grafts. When handpicked islets were freshly prepared from each of four histoincompatible donors (DBA/2, DBA/1, A.SW, and C3H) and sequentially transplanted four times (islets from one donor for each transplantation) into diabetic B6AF1 recipients, virtually all recipients maintained normoglycemia for more than 200 days regardless of the number of islets per grafting or intervals between transplantations. Since the purity of human islet preparations to date has been at the level of crude-digested islets, crude islets were used in sequential transplantation. Four transplantations of approximately 50 crude islets prepared from each of four donors achieved marked prolongation of graft survival. In sharp contrast, transplantation of 250-500 single-donor crude islets or four sequential transplantations of DBA/2 50 crude islets resulted in acute graft rejection.
Animals↗
Oral iron chelators: prospects for future development.
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Administration, Oral↗
The gonadotropin-releasing hormone pituitary receptor interacts with a guanosine triphosphate-binding protein: differential effects of guanyl nucleotides on agonist and antagonist binding.
Binding of the GnRH agonist [DAla6,NMe-Leu7,Pro9Net]GnRH to bovine anterior pituitary membranes is inhibited by guanyl nucleotides. The effect of guanyl nucleotides is temperature dependent, in that significant binding inhibition is observed when the receptor-hormone interaction is measured at 37 C, and no inhibition is seen at 4 C. Micromolar concentrations of the nonhydrolyzable GTP analog 5'-guanylylimidodiphosphate [Gpp(NH)p] displace the bound agonist in a dose-dependent manner, with half-maximal displacement occurring in a concentration range of 0.1-0.5 microM, and maximum displacement occurring at a concentration of 50 microM Gpp(NH)p. At a concentration of 50 microM, the other nucleotides GTP and GDP inhibit binding to a lesser extent, while GMP, cGMP, 5'-adenylylimidodiphosphate [App(NH)p], ATP, and cAMP have no effect on the binding. At 37 C, Gpp(NH)p reduces the affinity of the agonist by a factor of 6 and increases its dissociation rate. In the presence of Gpp(NH)p at 37 C, there is also a 2-fold increase in the total number of binding sites. Under the same conditions as those used for the agonist, there is no displacement of the bound antagonist [Ac-D2Nal1,4ClDPhe2,D3Pal3,DLys6,Lys8,D Ala10]-GnRH by doses up to 50 microM Gpp(NH)p. The modulation of the binding of the agonist, but not that of the antagonist, by guanyl nucleotides is characteristic of receptors that are coupled to GTP-binding proteins. Thus, the GnRH receptor appears to be coupled to a GTP-binding protein that may play a role in the mechanism of action of GnRH at the pituitary.
Animals↗
American perceptions of the British National Health Service: five myths.
This article explores five strong beliefs, or myths, held by Americans about the British National Health Service: (1) the NHS is socialized medicine; (2) widespread rationing occurs; (3) NHS patients have to face long waiting times; (4) the NHS does not offer free choice of provider; and (5) private medicine is taking over. The authors explore how ethnocentricity and American values have shaped these five myths, and argue that these cultural biases limit the ability of Americans to objectively evaluate the NHS and prevent them from learning from the British system.
Attitude to Health↗
Effect of gamma-irradiation on mouse pancreatic islet-allograft survival.
Elimination or inactivation of lymphoid tissue in the pancreatic islet preparation achieves prolongation of islet-allograft survival. In this study we examined the effect of gamma-irradiation on mouse islet-allograft survival. In a B6AF1 isograft model, irradiation up to 2400 rad did not induce deterioration of islet function over 200 days, but greater doses caused cessation of graft function between 83 and 186 days. When DBA/2 crude islets were transplanted into B6AF1 recipients, all nonirradiated allografts were acutely rejected. Marked prolongation of allograft survival was achieved by islet irradiation with doses between 800 and 12,000 rad. With higher doses, significant numbers of allografts survived beyond the controls, but many lost function between 78 and 180 days, with none surviving greater than 200 days. Irradiation with 16,000 rad caused acute radiation damage. Because most secondary islet allografts in recipient mice that lost primary islet-graft function between 84 and 195 days survived greater than 100 days, late functional loss was probably due to the radiation injury. Combined use of recipient treatment with cyclosporin A and graft irradiation (2400 rad) achieved prolongation of DBA/2 islets in B6AF1 mice.
Animals↗