Showing papers by "St Bartholomew's Hospital published in 1978"
TL;DR: An enkephalin analogue given intravenously to normal subjects raised serum prolactin and growth-hormone levels but lowered serum levels of luteinising hormone, follicle-stimulating hormone, cortisol, and corticotrophin.
361 citations
TL;DR: Patients with Crohn's disease who were in good health while taking azathiprine, 2 mg/kg body-weight/day, for at least six months were allocated either to a group in which azathioprine was continued or to one in which a control tablet was substituted.
330 citations
TL;DR: It is suggested that nitrous oxide interferes with the function of vitamin B12 in vitro and probably also in vivo when premixed 50% Nitrous oxide and 50% oxygen mixture ('Entonox') is given.
285 citations
TL;DR: Oral phenylethylamine challenge with amounts greater than those known to be present in a normal diet similarly gave rise to no adverse reaction in (-)-deprenyl-treated subjects; the reasons for this remain to be determined.
Abstract: After pretreatment with the selective monoamine oxidase B inhibitor, (-)-deprenyl, in doses sufficient for complete inhibition of the platelet enzyme, 4 normal and 6 parkinsoniam volunteers (2 receiving levodopa and 2 levodopa plus carbidopa) suffered no adverse pressor reaction ('cheese effect') after challenge with oral tyramine in amounts considerably greater than those likely to be encountered in a normal diet. Nor did the levodopa-deprenyl combination itself result in a pressor response. Normal human intestinal mucosa was shown predominantly to contain the deprenyl-insensitive A form of the enzyme, which presumably degraded administered tyramine in the deprenyl-treated volunteers; even those receiving the drug for prolonged periods manifested no 'cheese effect', suggesting that the A form remained uninhibited. Intestinal monoamine oxidase A was able to oxidise dopamine, whereas in human platelet or striatum the amine is a monoamine oxidase B substrate. Like tyramine, oral phenylethylamine challenge with amounts greater than those known to be present in a normal diet similarly gave rise to no adverse reaction in (-)-deprenyl-treated subjects; the reasons for this remain to be determined.
233 citations
TL;DR: In this review of tissue substitute materials, the historical development of the important systems is traced from the early 1900's and recommendations of systems having useful simulation properties are given.
Abstract: In this review of tissue substitute materials, the historical development of the important systems is traced from the early 1900's. Tabulations of the constituents, elemental compositions, specific gravities, and the photon and electron interaction characteristics of 64 materials are given together with recommendations of systems having useful simulation properties. Formulation and manufacturing procedures are described and possible future developments in both materials and phantom research are outlined.
228 citations
204 citations
TL;DR: In this paper, a radioimmunoassay for human β-endorphin in plasma and cerebrospinal fluid (C.S.F) was presented.
152 citations
TL;DR: There is an additive relative risk in subjects who possess two “high risk” HLA B alleles which has an important influence on the prevalence of the disease in sibships and possibly on the concordance rate in diabetic identical twins.
Abstract: The major genetic susceptibility to insulin dependent (Type 1) diabetes is determined by genes in the HLA chromosomal region. An increased relative risk for developing the disease is observed in subjects who are HLA A1, A2, B8, B18, B15, B40, CW3, Bfs, DW3, DW4, DRW3, DRW4 positive. There is an additive relative risk in subjects who possess two “high risk” HLA B alleles which has an important influence on the prevalence of the disease in sibships and possibly on the concordance rate in diabetic identical twins. There is also suggestive evidence that particular combinations of “high risk” HLA B alleles are associated with increased or persistent antibody production which may reflect enhanced or differential susceptibility. Certain factors (e. g. HLA B7, DW2 and DRW2) are associated with a significantly reduced risk and may exert a “protective” mechanism in Type I diabetes, by linkage disequilibrium with genes which reduce immune responsiveness. The significant increases and decreases in respect of the HLA B antigens are probably secondary to the corresponding HLA D and DRW associations which reflect a stronger linkage disequilibrium between the genes which determine these specificities and the putative genes which control susceptibility. Initial damage to the beta cells probably occurs a considerable time before the onset of symptoms and theoretically modification of the immune response early in the disease process may reduce the rate of beta cell destruction.
142 citations
TL;DR: The polyunsaturated fatty acids in the diet regulates the fatty acid composition of the liver endoplasmic reticulum, and this in turn is an important factor controlling the rate and extent of lipid peroxidation in vitro and possibly in vivo.
Abstract: The fatty acid compositions of the lipids and the lipid peroxide concentrations and rates of lipid peroxidation were determined in suspensions of liver endoplasmic reticulum isolated from rats fed on synthetic diets in which the fatty acid composition had been varied but the remaining constituents (protein, carbohydrate, vitamins and minerals) kept constant. Stock diet and synthetic diets containing no fat, 10% corn oil, herring oil, coconut oil or lard were used. The fatty acid composition of the liver endoplasmic reticulum lipid was markedly dependent on the fatty acid composition of the dietary lipid. Feeding a herring-oil diet caused incorporation of 8.7% eicosapentaenoic acid (C(20:5)) and 17% docosahexaenoic acid (C(22:6)), but only 5.1% linoleic acid (C(18:2)) and 6.4% arachidonic acid (C(20:4)), feeding a corn-oil diet caused incorporation of 25.1% C(18:2), 17.8% C(20:4) and 2.5% C(22:6) fatty acids, and feeding a lard diet caused incorporation of 10.3% C(18:2), 13.5% C(20:4) and 4.3% C(22:6) fatty acids into the liver endoplasmic-reticulum lipids. Phenobarbitone injection (100mg/kg) decreased the incorporation of C(20:4) and C(22:6) fatty acids into the liver endoplasmic reticulum of rats fed on a lard, corn-oil or herring-oil diet. Microsomal lipid peroxide concentrations and rates of peroxidation in the presence of ascorbate depended on the nature and quantity of the polyunsaturated fatty acids in the diet. The lipid peroxide content was 1.82+/-0.30nmol of malonaldehyde/mg of protein and the rate of peroxidation was 0.60+/-0.08nmol of malonaldehyde/min per mg of protein after feeding a fat-free diet, and the values were increased to 20.80nmol of malonaldehyde/mg of protein and 3.73nmol of malonaldehyde/min per mg of protein after feeding a 10% herring-oil diet in which polyunsaturated fatty acids formed 24% of the total fatty acids. Addition of alpha-tocopherol to the diets (120mg/kg of diet) caused a very large decrease in the lipid peroxide concentration and rate of lipid peroxidation in the endoplasmic reticulum, but addition of the synthetic anti-oxidant 2,6-di-t-butyl-4-methylphenol to the diet (100mg/kg of diet) was ineffective. Treatment of the animals with phenobarbitone (1mg/ml of drinking water) caused a sharp fall in the rate of lipid peroxidation. It is concluded that the polyunsaturated fatty acid composition of the diet regulates the fatty acid composition of the liver endoplasmic reticulum, and this in turn is an important factor controlling the rate and extent of lipid peroxidation in vitro and possibly in vivo.
129 citations
TL;DR: A suspension of isolated rat anterior pituitary cells, with viability of 90% was mixed with 0.5 g preswollen Bio-Gel P2 and packed into a column and ACTH in the fractions collected from the perfused column was measured by immunoassay and bioassay with well correlated results.
Abstract: A suspension of isolated rat anterior pituitary cells, with viability of 90% was mixed with 0.5 g preswollen Bio-Gel P2 and packed into a column. ACTH in the fractions collected from the perfused column was measured by immunoassay and bioassay with well correlated results (r = 0.84,P = 0.01). Cells were stimulated with 2–4-min pulses or crude stalk median eminence extract (SME) and responses were recorded as total ACTH released in excess of background. A log doseresponse curve was obtained over the range 0.0025–0.1 SME/ml (one SME = extract of 3–4 mg tissue/ml), giving a highly significant regression of response on dose (P < 0.01) with an index of precision of 0.164 ± 0.007 (mean ± SEM, n = 8). LH, as measured by immunoassay, was also released in response to SME. No significant ACTH release was seen with a cortex extract. ACTH elease was stimulated by 56 mM potassium ions; SMEstimulated ACTH release was dependent on calcium and magnesium ions and was inhibited by the presence of corticosterone (0.2 μg/ml)...
110 citations
TL;DR: The cell kinetics of the cartilage growth plate are outlined and discussed in terms of the probable levels of control on the system, but the evidence of cell Kinetics does not point unequivocally to any particular mechanism.
Abstract: The cell kinetics of the cartilage growth plate are outlined and discussed in terms of the probable levels of control on the system. Possible mechanisms of growth control at the cellular level are examined for (i) the rate of cell division in the proliferation zone, (ii) the command to differentiate that limits the size of the proliferation zone and (iii) the ageing process in the cartilage plate. the evidence of cell kinetics does not point unequivocally to any particular mechanism.
TL;DR: The clinicopathologic features of PCL differ from typical myeloma and resemble those of acute leukemia: patients with PCL have less bone disease but a much higher incidence of organomegaly and tissue infiltration as well as diffuse marrow involvement and more pronounced pancytopenia.
TL;DR: A direct, rapid, sensitive, and highly specific radioimmunoassay for plasma aldosterone has been developed using a Aldosterone conjugated to [125I]histamine as ligand and a highly specific ald testosterone antiserum.
Abstract: A direct, rapid, sensitive, and highly specific radioimmunoassay for plasma aldosterone has been developed using aldosterone conjugated to [125I]histamine as ligand and a highly specific aldosterone antiserum. This assay permits the direct measurement of plasma aldosterone without preliminary extraction or purification steps and hence allows a single technician t o assay 500 samples in a week. An excellent correlation was obtained between the results of the direct assay and the levels measured after paper chromatography (n = 43,r = 0.99, P< 0.001) or after extraction (n = 43, r = 0.99, P <). The coefficients of variation for intra-assay and inter-assay determinations of samples from a normal plasma pool were 7.6% and 9.3% respectively. (J. Clin. Endocrinol. Metab. 46: 105, 1978.)
TL;DR: In patients with a variety of diseases of the pituitary-adrenal axis, levels of beta hLPH follow immunoreactive ACTH levels, although the two are not always secreted on a 1:1 molar basis.
Abstract: A homologous RIA for human beta-lipotropin (beta hLPH) has been developed. At a final dilution of 1:24,000, the antiserum employed shows cross-reaction with beta hLPH but none with human beta-MSH (beta hMSH), and it is concluded that the antigenic determinant lies within the N-terminal 1-36 region of beta hLPH. With extraction of 3-ml plasma samples, the assay is sufficiently sensitive to measure circulating beta hLPH levels in normal individuals at 0900 h (25-200 pg/ml). There is a circadian variation with levels falling to (less than 20-80 pg/ml) at 2300 h. beta hLPH levels rise after metyrapone and after insulin-induced hypoglycemia, and fall after administration of dexamethasone. In patients with a variety of diseases of the pituitary-adrenal axis, levels of beta hLPH follow immunoreactive ACTH levels, although the two are not always secreted on a 1:1 molar basis.
TL;DR: The cardiac effects of artificial inflation of the lungs were studied during reflexly induced apnoea and bradycardia in anaesthetized dogs.
Abstract: 1. The cardiac effects of artificial inflation of the lungs were studied during reflexly induced apnoea and bradycardia in anaesthetized dogs.2. Reflex apnoea and bradycardia were induced (a) by stimulation of the larynx with water or by electrical stimulation of afferent fibres in the superior laryngeal nerve, or (b) by combined stimulation of the superior laryngeal nerve and carotid body chemoreceptors.3. During combined stimulation of the laryngeal and carotid body inputs, the activation of respiration normally evoked by chemoreceptor stimulation was inhibited whereas the chemoreceptor cardio-inhibitory reflex was facilitated leading to periods of temporary cardiac arrest.4. In spontaneously breathing animals and in those artificially ventilated, lung inflation invariably caused tachycardia.5. Rhythmic artificial inflation of the lungs during the apnoeic period produced by the laryngeal input or by a combination of the laryngeal and chemoreceptor inputs wholly or partly reversed the bradycardia. This occurred using lung inflation volumes within the range of the normal tidal volume and inflation pressures of less than 12 mmHg; the response was independent of the composition of the gas used for inflating the lungs, and occurred at constant P(a, O2) and P(a, CO2). Lung inflation carried out during a reflexly induced arrest of the heart immediately restarted the heart and was accompanied by an exaggerated sinus arrhythmia.6. Evidence is presented that the observed effects of artificial lung inflation are reflex in origin with the vagus nerves as the main afferent and efferent pathways.7. Electrical stimulation of the central end of the cut pulmonary branches of the thoracic vagosympathetic nerves also caused tachycardia and had the same effects as lung inflation in modifying the reflexly induced bradycardia.8. Some clinical implications of these results are discussed.
TL;DR: Deconvolution analysis of different regions of interest on gamma camera renography enables obstructive lesions causing impairment of nephron function to be distinguished from obstructives lesions which parenchymal function is unimpaired.
Abstract: Summary— Deconvolution analysis of different regions of interest on gamma camera renography enables obstructive lesions causing impairment of nephron function to be distinguished from obstructive lesions in which parenchymal function is unimpaired. Quantitation of isotope transit time through the parenchyma is a reliable method of diagnosing upper urinary tract obstruction.
TL;DR: Evidence for qualitative changes in the expression of the peptide ‘family tree’ is reported for the first time in the rhesus monkey, which has a fetal adrenal comparable with that of man.
Abstract: THE pituitary hormone adrenocorticotrophin (ACTH) belongs to a ‘family’ of peptides derived from a common ‘stem hormone’ (Fig. 1). Depending on the way in which the stem hormone is cleaved, the various peptides are expressed and it is possible that qualitative changes in the expression of the peptide ‘family tree’ may be responsible for the alteration in fetal adrenal function which precedes birth1. We now report evidence for such changes in the rhesus monkey, which has a fetal adrenal comparable with that of man.
TL;DR: Results from 10 mothers and their babies show the time-related passage of pethidine across the placenta and the elimination half-life of the drug from neonatal blood was 22.7h compared with 3h in the adult.
TL;DR: It seems likely that the TSH circadian rhythm is centrally determined and that free T3 levels are maintained more or less constant by variation in peripheral conversion from T4.
Abstract: Half-hourly blood samples were taken from six clinically euthyroid men over a continuous period of 24 h. Their concentrations of total thyroxine (T4), total triiodothyronine (T3), thyrotrophin (TSH) and prolactin (PRL) were assessed together with the degree of unsaturation of thyroid hormone binding proteins as determined by the thyroid hormone uptake test (THUT). Both T3 and T4 were also measured in urine samples collected serially during the same 24 h period. Significant circadian changes in serum TSH, THUT, serum and urine T4 and serum PRL were demonstrated in all subjects. TSH showed a reciprocal pattern to serum T4, with higher levels during the evening and at night than the daytime. This TSH pattern did not coincide with PRL secretion. Further studies on the same subjects did not show any significant effect of posture, corticosteroid or T4 administration upon circadian changes in TSH. There appeared to be no consistent circadian changes in serum or urinary T3. It seems likely that the TSH circadian rhythm is centrally determined and that free T3 levels are maintained more or less constant by variation in peripheral conversion from T4.
TL;DR: Log doseresponse curves for AVP and crude stalk median eminence extract (SME) were statistically significantly nonparallel and similar results were found for lysine vasopressin, arginine vasotocin (AVT), oxytocin, and human posterior lobe extract.
Abstract: The perfused isolated rat anterior pituitary cell column was used as a bioassay for corticotropinreleasing factor (CRF). The system responded to arginine vasopressin (AVP) in a dose-dependent manner with a minimum effective dose of 10-10 M. Log doseresponse curves for AVP and crude stalk median eminence extract (SME) were statistically significantly nonparallel (P < 0.05) and similar results were found for lysine vasopressin, arginine vasotocin (AVT), oxytocin, and human posterior lobe extract. Vasopressin and its analogs had no effect on LH release. Using RIA for AVP, SME was found to contain 10.83 ng (7.7–14.3 ng, n = 12) AVP, which could account for no more than 30% of its CRF activity. The CRF activity of both SME and AVP was totally quenched by incubation overnight with vasopressin antisera. Partial quenching was obtained with higher dilutions of the antisera. Vasopressin-stimulated ACTH release was affected in a similar way to SME-stimulated ACTH release by the presence of corticosterone (0.2 μg/ml)...
TL;DR: The role that the mitochondrially bound creatine kinase may play in the development of brain energy metabolism was studied in brain homogenates and the apparent K(m) and V(max.) values of the mitochondRIally bound rat brain creatine Kinase were determined in both directions.
Abstract: 1. The development of the total rat brain creatine kinase was studied in brain homogenates. Until approx. 14-15 days after birth, the activity remains less than one-third that of the adult activity (207+/-6 units/g wet wt. s.d.; n=3). Over the next 10 days the activity increases markedly to the adult value and thereafter remains essentially constant. 2. In the adult brain, approx. 5% (11.9+/-2.2 units/g wet wt. s.d.; n=5) of the total creatine kinase is associated with the mitochondrial fraction. This creatine kinase could not be solubilized by sodium acetate solutions of up to 0.8m concentration, whereas 66% of the hexokinase associated with brain mitochondria was released under these conditions. 3. Rat brain mitochondria incubated in the presence of various concentrations of creatine (1, 5 and 10mm) and ADP (100mum) synthesized phosphocreatine at rates of approx. 4.5, 11 and 17.5nmol/min per mg of mitochondrial protein. Atractyloside (50mum) or oligomycin (1.5mug/mg of mitochondrial protein) completely inhibited the synthesis of phosphocreatine. 4. The apparent K(m) and V(max.) values of the mitochondrially bound rat brain creatine kinase were determined in both directions. The V(max.) in the direction of phosphocreatine synthesis is 237nmol/min per mg of mitochondrial protein, with an apparent K(m) for creatine of 1.67mm and for MgATP(2-) of 0.1mm, and in the reverse direction V(max.) is 489nmol/min per mg of mitochondrial protein, with an apparent K(m) for phosphocreatine of 0.4mm and for MgADP(-) of 27mum. 5. The results are discussed with reference to the role that the mitochondrially bound creatine kinase may play in the development of brain energy metabolism.
TL;DR: The results of pulmonary function tests in 30 cases, and electron microscopic studies of cilia from epididymes and bronchial mucosa indicated that the basic abnormality might be malfunction of the microtubules which appeared to be ultrastructurally normal in most cases.
Abstract: Forty-five patients have been treated surgically for obstructive azoospermia. Fifteen underwent reversal of vasectomy and 40% of the wives became pregnant. Thirty had epididymovasostomy, and in only 2 (6.5%) did the sperm count become normal, although a few poorly motile sperms appeared in the ejaculate in a further 4 patients. Congenital abnormalities of the vasa in 7 cases and post-inflammatory blocks in 4 cases were examples of obstructive azoospermia due to well defined causes. However, in half of the patients (15 cases) the cause was obscure although it was associated with sinusitis, bronchitis or bronchiectasis (Young's syndrome). The results of pulmonary function tests in 30 cases, and electron microscopic studies of cilia from epididymes (10 cases) and bronchial mucosa (2 cases) indicated that the basic abnormality might be malfunction of the microtubules which appeared to be ultrastructurally normal in most cases. One case appeared to be associated with dietary deficiency, and correction of diet coincided with a successful result of surgery.
TL;DR: A polarisation fluoroimmunoassay for the determination of phenytoin levels in serum is described, which employs stable, non-radioactive reagents, requires no separation procedure, and involves only 1.25 microliter of serum.
TL;DR: Evidence was produced that immune-complex levels rise before the clinical detection of relapse, and it is suggested that the P.E.G.G.) assay could be a useful marker of disease progress.
TL;DR: In the studies comparing the effects of single oral doses of lergotrile (2 mg) and bromocriptine (2.5 mg) on GH and PRL secretion in patients with acromegaly and hyperprolactinemia, lergOTrile in the dose used has been found to have an earlier onset and shorter duration of action.
Abstract: The effects of the ergoline derivative, lergotrile mesylate, on the serum levels of PRL, GH, TSH, LH, FSH, cortisol, and blood sugar were studied in six normal males. The effects of lergotrile mesylate on the serum levels of GH and PRL were also studied in eight patients with acromegaly and in two with idiopathic hyperprolactinemia. In the normal subjects, 2 mg oral lergotrile lowered basal PRL levels after 90 min and markedly impaired the PRL response to TRH (200 micrograms iv); the mean peak value +/- SE was 8.3 +/- 1.1 micrograms/liter, compared to the control value of 66.6 /+- 11.3 micrograms/liter. Lergotrile raised serum GH levels in five of the six subjects to peaks of 8-49 micrograms/liter, compared to 2-8 micrograms/liter after placebo. In three subjects, the GH response to lergotrile was attenuated by the prior administration of the dopamine antagonist, metoclopramide (10 mg orally). Lergotrile had no effect on FSH and LH levels under basal conditions or after the gonadotrophin-releasing hormone (GnRH; 100 micrograms iv). Circulating TSH levels were unaltered basally but impaired after TRH. Blood sugar levels were unaltered; serum cortisol was elevated in five of six subjects; there was a brief depression of diastolic blood pressure, but no change in pulse rate. The side effects after lergotrile were variable, with drowsiness as a consistent feature. These actions are similar to those of bromocriptine (an ergot derivative treatment of hyperprolactinemia and acromegaly, to suppress PRL and GH secretion, and in parkinsonism. Therefore, it may be expected that lergotrile could fulfill these clinical uses; however, in the studies comparing the effects of single oral doses of lergotrile (2 mg) and bromocriptine (2.5 mg) on GH and PRL secretion in patients with acromegaly and hyperprolactinemia, lergotrile in the dose used has been found to have an earlier onset and shorter duration of action.
TL;DR: Evidence is provided from a reconstituted malate–aspartate cycle with brain mitochondria that increased C2 flux into the tricarboxylic acid cycle from pyruvate may inhibit the reoxidation of exogenous NADH.
Abstract: 1. The interrelationship of metabolism of pyruvate or 3-hydroxybutyrate and glutamate transamination in rat brain mitochondria was studied. 2. If brain mitochondria are incubated in the presence of equimolar concentrations of pyruvate and glutamate and the K+ concentration is increased from 1 to 20mm, the rate of pyruvate utilization is increased 3-fold, but the rate of production of aspartate and 2-oxoglutarate is decreased by half. 3. Brain mitochondria incubated in the presence of a fixed concentration of glutamate (0.87 or 8.7mm) but different concentrations of pyruvate (0 to 1mm) produce aspartate at rates that decrease as the pyruvate concentration is increased. At 1mm-pyruvate, the rate of aspartate production is decreased to 40% of that when zero pyruvate was present. 4. Brain mitochondria incubated in the presence of glutamate and malate alone produce 2-oxoglutarate at rates stoicheiometric with the rate of aspartate production. Both the 2-oxoglutarate and aspartate accumulate extramitochondrially. 5. Externally added 2-oxoglutarate has little inhibitory effect (Ki approx. 31mm) on the production of aspartate from glutamate by rat brain mitochondria. 6. It is concluded that the inhibitory effect of increased C2 flux into the tricarboxylic acid cycle on glutamate transamination is caused by competition for oxaloacetate between the transaminase and citrate synthase. 7. Evidence is provided from a reconstituted malate–aspartate (or Borst) cycle with brain mitochondria that increased C2 flux into the tricarboxylic acid cycle from pyruvate may inhibit the reoxidation of exogenous NADH. These results are discussed in the light of the relationship between glycolysis and reoxidation of cytosolic NADH by the Borst cycle and the requirement of the brain for a continuous supply of energy.
TL;DR: A simple fluoroimmunoassay for the determination of albumin levels in serum, urine and cerebrospinal fluid employs magnetisable particles to which antibodies to human serum albumin are covalently linked, and albumin labelled with fluorescein.