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S Humphreys

Publications and source records attributed to S Humphreys.

At least 19 recordsLinked to original sources
PubMed1991

Characterization of functional calcitonin gene-related peptide receptors on rat lymphocytes.

Calcitonin gene-related peptide (CGRP), a vasoactive neuropeptide present in peripheral neurons, is released at local sites of inflammation. In these studies specific high affinity adenylyl cyclase linked CGRP receptors were characterized on rat lymphocytes. The distribution, affinity, and specificity of CGRP receptors was analyzed by radioligand binding. 125I-[His10]CGRP binding to rat lymphocytes was rapid, reaching equilibrium by 20 to 30 min at 22 degrees C, and dependent on cell concentration. The dissociation constants, Kd, for the CGRP receptor on purified T and B lymphocytes are 0.807 +/- 0.168 nM and 0.387 +/- 0.072 nM and the densities are 774 +/- 387 and 747 +/- 244 binding sites/cell, respectively. Competition binding studies determined that rat CGRP inhibits 125I-[His10]CGRP binding to lymphocytes with the highest affinity (Ki = 0.192 +/- 0.073) followed by human CGRP and the CGRP receptor antagonist CGRP8-37. 125I-[His10]CGRP binding to rat lymphocytes was not inhibited by the neuropeptides substance P, calcitonin, or neuropeptide Y. Lymphocyte CGRP receptor proteins were identified by affinity labeling by using disuccinimidyl suberate to covalently cross-link 125I-[His10]CGRP to its receptor. Specifically labeled CGRP binding proteins visualized by SDS-PAGE analysis had molecular masses of 74.5 and 220 kDa. A third high molecular mass protein band which did not penetrate the gel was also observed. In functional studies, CGRP stimulated a rapid, sustained increase in cAMP with an ED50 of approximately 8 pM. In experiments comparing optimal concentrations of isoproterenol, a beta 2-adrenergic agonist, and CGRP, intracellular cAMP elevation after isoproterenol treatment returned to basal levels by 30 min, whereas cAMP was still elevated at 60 min after CGRP treatment. The response to CGRP was specific in that it could be completely blocked by CGRP8-37. The presence of high affinity functional CGRP receptors on T and B lymphocytes provides evidence for a modulatory role for CGRP in regulating lymphocyte function.

Adenylyl Cyclases↗
PubMed1991

The osteodystrophy of congenital erythropoietic porphyria.

Congenital erythropoietic porphyria (CEP) is a rare disorder of heme biosynthesis that results in the production of large quantities of photoactive porphyrins. The clinical syndrome is dominated by extreme photosensitivity with mutilation of light exposed extremities and hemolytic anemia. Bone disease has been occasionally noted, but is not well characterised. We describe a man with CEP who developed bone pain and spinal crush fractures at the age of 22. Skeletal radiographs revealed features typical of other severe hemolytic anemias, but in addition there was loss of the terminal phalanges of the hand as a result of photomutilation. Spinal bone density (assessed by DPA) was reduced and at the hip bone density was at the lower limit of normal. The metacarpal cortical bone density was 2.9 standard deviations below normal. Biochemical and histological studies accelerated bone turnover. Although the serum 250H vitamin D concentration was very low (because of light avoidance) there was no evidence that the bone disease was a consequence of this. Treatment for one year with clodronate and a high transfusion regime was associated with small reductions in serum alkaline phosphatase and urine hydroxyproline excretion, but there was no improvement in bone mineral density. We conclude that CEP has a distinctive osteodystrophy comprising osteolysis of light-exposed extremities and a high turnover type of osteoporosis. Privational vitamin D deficiency may also occur. The effect upon bone of the new therapies for CEP should be considered.

Alkaline Phosphatase↗
PubMed1990

Monoamine synaptic structure and localization in the central nervous system.

The monoamines dopamine, noradrenaline, adrenaline, and serotonin as well as the diamine histamine have a widespread distribution in the central nervous system within synaptic terminals and nonsynaptic varicosities. In certain regions of the central nervous system the monoamines are contained in varicosities that have no synaptic specialization associated with them, suggesting a possible neuromodulatory role for some of the monoamines. The majority of monoamine labelled structures are synaptic terminals which are characterized by the presence of small, clear vesicles (40-60 nm) and large, granular vesicles (70-120 nm) within the terminal. A third population of vesicles--small, granular vesicles--which are visible only after histochemical staining, are probably the equivalent of the small, clear vesicles present after either autoradiographic or immunohistochemical labelling. Most monoamine containing terminals contact dendrites and dendritic spines and, less frequently, neuronal somata and other axons. Both asymmetrical and symmetrical membrane specializations are associated with monoaminergic terminals; however, asymmetrical contacts are the most frequent type found. These ultrastructural results indicate that monoamine containing terminals and varicosities in general share many common morphological features, but still have diverse functions.

Animals↗
PubMed1990

Hyperparathyroid bone disease in diabetic renal failure.

Hyperparathyroid bone disease is a common complication of end stage renal failure, particularly in patients on maintenance haemodialysis. Several studies have, however, shown a near absence of hyperparathyroid bone disease in diabetic patients who have been receiving haemodialysis for periods of up to 4 years. We have studied biochemical indices of mineral metabolism in 54 consecutive pre-dialysis patients with moderate to severe renal impairment. Deteriorating renal function was associated with developing hypocalcaemia and hyperphosphataemia. Hypocalcaemia was strongly related to increased severe alkaline phosphatase activity (p less than 0.001), suggesting the development of hyperparathyroidism. Five patients with hypocalcaemia and increased alkaline phosphatase were studied in detail. All had elevated serum concentrations of parathyroid hormone and histological signs of hyperparathyroidism on bone biopsy. Three of the patients had low serum 25 hydroxyvitamin D levels with associated osteomalacia, the other 2 patients were notable for their long duration of renal failure. In the long-term (greater than 4 years) we also observed the development of hyperparathyroidism in a small group of diabetic patients maintained on haemodialysis. We conclude that diabetic patients are not uniquely protected against renal osteodystrophy. Although the prevalence of hyperparathyroidism may be lower in diabetic patients than in those with other types of renal disease, the same factors which predispose to bone disease in non-diabetic patients (long duration of renal failure, low serum 25 hydroxyvitamin D and long periods on haemodialysis) also operate in the diabetic population.

Adult↗
PubMed1989

The relationship of plasma acetate with glucose and other blood intermediary metabolites in non-diabetic and diabetic subjects.

In investigating the interrelations of plasma acetate with glucose metabolism, we established that fasting plasma acetate levels (mmol/l) were greater in the diabetic than non-diabetic individuals (p less than 0.001). Plasma acetate and glucose levels correlated in all subjects (non-diabetic and diabetic) as a whole (rs 0.28, p less than 0.0001) and in the diabetics alone (rs 0.35, p less than 0.001). After i.v. glucose (20 g/m2 body surface area), plasma acetate levels increased further in the diabetic and non-diabetic individuals. Plasma acetate also increased when non-diabetic individuals consumed 75 g oral glucose. Moreover, while plasma acetate levels had returned to fasting values by 90 min in the non-diabetic subjects after oral and i.v. glucose, levels remained elevated in the diabetics after i.v. glucose. The K rate constant of glucose elimination after i.v. glucose in the diabetics correlated negatively with acetate values at many time points. In the non-diabetics, changing acetate and glucose levels after oral glucose also correlated at multiple time points. These results suggest that the plasma acetate level is influenced by variations in glycaemia and provide further evidence for an impaired rate of acetate metabolism in diabetes.

Acetates↗
PubMed1989

The femoral head in osteonecrosis. A quantitative study of osteocyte population.

The occurrence of osteonecrosis following renal transplantation is well recognised but its pathogenesis remains unknown. We have quantified the number of empty osteocytic lacunae in the subchondral bone of femoral heads from a control group of patients, and compared these with femoral heads from a group of renal transplant recipients without evidence of overt osteonecrosis. There is a significant increase in empty osteocytic lacunae in renal transplant patients. We conclude that loss of osteocytes precedes other manifestations of osteonecrosis.

Adrenal Cortex Hormones↗
PubMed1989

Change in plasma acetate levels in diabetic subjects on mixed high fiber diets.

When 10 diabetic (five insulin-dependent) subjects with reasonable glycemic control were randomized from their usual (U) diet (about 30 g fiber/day) between two different but isocaloric high fiber diets, each sequentially over 6 wk [HF (55 g fiber/day) and HFS (55 g fiber/day with sucrose taken as 15 g three times daily, with meals)], plasma acetate (mmol/L) increased by 35% on both high fiber diets from 0.21 +/- 0.06 (SD) to 0.28 +/- 0.10 (HF) and 0.30 +/- 0.10 (HFS) (both p less than 0.01). This was higher than the random weekly variation in plasma acetate levels of 11% in six other glycemically stable diabetic patients. When the acetate value was expressed as acetate/glucose, i.e., relative to the fasting glucose level (since fasting levels of acetate and glucose consistently positively correlate), the increase was about 80%. Fasting plasma non-esterified fatty acid (NEFA) levels fell during the high fiber diets and correlated negatively with the fasting acetate level (rs -0.51, p less than 0.005). The fall in NEFA and rise in acetate levels appeared greatest with the sucrose-supplemented meals. These results suggest increased exogenous contribution to the plasma acetate level from increased colonic fermentation of dietary fiber and raise the possibility of using such measurements in the assessment of compliance to high fiber diets. The fall in NEFA levels associated with raised plasma acetate levels may contribute to the beneficial effects on glycemic control observed with the high fiber diets.

Acetates↗
PubMed1988

Plasma acetate levels in response to intravenous fat or glucose/insulin infusions in diabetic and non-diabetic subjects.

We measured plasma levels of acetate, glucose, insulin, fatty acids and 'ketone bodies' (KB), during fat infusion and continuous simultaneous infusion of insulin and glucose according to a computerized algorithm to maintain fasting euglycaemia and derive indices of tissue insulin sensitivity (hyperinsulinaemic euglycaemic clamping HEC). (i) Plasma acetate levels (mmol/l) approximately doubled (0.14 +/- (SEM) 0.02 to 0.25 +/- 0.02, p less than 0.01) during INTRALIPID infusion in 7 non-diabetic individuals while total 'ketone bodies' and non-esterified fatty acids (NEFAs) increased 10-fold. (ii) Early in the HEC, plasma acetate levels decreased as did NEFAs in 13 non-diabetic (0.17 +/- 0.01 to 0.12 +/- 0.01, p less than 0.001) and 9 diabetic (0.22 +/- 0.02 to 0.15 +/- 0.01, p less than 0.005) individuals. However while acetate levels later rose to fasting values in the non-diabetics, they remained low in the diabetics. NEFA levels were low throughout the clamp but glucose flux was increased as judged from the glucose infusion even with maintained euglycaemia. The change in acetate values during the second hour of the clamp correlated with neither BMI nor two indices of insulin sensitivity (glucose metabolic clearance rate and steady state glucose infusion rate). These results accord with acetate production from glucose and fat oxidation, via acetyl CoA. The differing metabolism of acetate in the second hour of clamping between diabetics and non-diabetics may reflect altered post-receptor glucose metabolism with the onset of diabetes.

Acetates↗
PubMed1988

Mucoepidermoid carcinoma of the larynx in a child.

Laryngeal carcinoma in childhood is rare and most commonly classified as squamous cell carcinoma. Although mucoepidermoid carcinoma of the larynx has been noted in adults, it has not previously been reported in a child. A 13-year-old boy presented to our department with an epiglottic mass which was determined histologically to be mucoepidermoid carcinoma. A total epiglottectomy was performed and one year postoperatively the child is without disease.

Adolescent↗
PubMed1986

Soft tissue chondroma--a study of 15 tumours.

Fifteen cases of soft tissue chondroma have been reviewed. This lesion shows an equal sex incidence and occurs predominantly in middle-aged individuals. The majority arise in the hands and feet. Histologically these tumours are largely composed of adult-type hyaline cartilage, but in all cases foci show nuclear atypia and pleomorphism. In cartilaginous lesions of the axial skeleton or large limb bones this would probably have led to a diagnosis of well differentiated chondrosarcoma. Despite these worrying features none of the seven cases for which follow-up information is available recurred. The importance of recognizing the benign nature of these little-known tumours is stressed. The differential diagnosis of soft tissue cartilaginous tumours is briefly discussed.

Adolescent↗
PubMed1986

Urinary albumin excretion in pregnancy.

Urinary albumin excretion during pregnancy has been studied using a sensitive radioimmunoassay. One hundred pregnant women attending a high-risk antenatal clinic and 14 normal pregnant women were investigated serially, during pregnancy and post-partum. The normal subjects showed a small but significant rise in albumin excretion in the third trimester, which was sustained pre-delivery and in the first postnatal week. Twenty-six women were classified as having mild pre-eclampsia and 44 as having chronic hypertension without evidence of superimposed pre-eclampsia. In neither group was there evidence of proteinuria by conventional testing, nor was the median albumin excretion different from normal antenatally; in the first week after delivery a significant increase was observed, but this regressed to normal 6 weeks later. Eight patients developed severe pre-eclampsia, of whom one had evidence of underlying renal disease. Three presented with proteinuria already established. In the remaining five patients, the shift from normal to high albumin excretion occurred rapidly, usually preceded by a rise in uric acid and a decrease in the platelet count. These data suggest that proteinuric pre-eclampsia, as defined by relatively insensitive routine laboratory measurement, is not preceded by a phase of increasing albumin loss which can be detected by more sensitive assays.

Albuminuria↗
PubMed1986

Fibroma of tendon sheath: a clinicopathologic study.

Thirteen cases of fibroma of tendon sheath have been reviewed. This lesion presents predominantly in middle-aged adults, particularly men, and usually arises in the dermis and subcutis of the extremities, most especially the hands. Histologically these tumours are always well circumscribed and may be lobulated. They are largely composed of interlacing bundles of hyalinised, hypocellular fibrous tissue with occasional more cellular areas. A constant feature is the presence of slit-like vascular channels. They are benign lesions with little tendency to recur and, although becoming more generally recognised are not yet familiar to dermatologists.

Adolescent↗
PubMed1986

Early avascular necrosis of the femoral head. Report of a case and review of the literature.

The clinical and pathological findings in a case of early avascular necrosis of the femoral head following renal transplantation are described. Regions of subchondral bone distant from the principal lesions showed increased numbers of empty osteocytic lacunae. This has been quantified and it is suggested that a loss of osteocytes is perhaps one of the earliest lesions leading to established avascular necrosis.

Adult↗
PubMed1985

Mortal factors in type 2 (NIDDM) diabetes mellitus.

Five years after entry into a study prospective from diagnosis of non-insulin-dependent (Type 2) diabetes, 17 patients were known to be dead and 197 alive. On analysis of 136 patients (12 deaths) in whom there was complete information from clinical, metabolic and hormonal examination both before and 1 yr after start of treatment, an index of liability to death within this first 5 yr was calculated, to separate best the dead from the living. One index value correctly ascribed 83% of the dead and 90% of the living (89% of all predictions correct; Youden's "J" value = 0.73). Estimates from the less complete data on the other 78 patients (5 deaths) did not alter the predictive factors. Prediction is more successful with non-cardiac than with cardiac deaths. Five factors contributed to the predictive index for death. One was a long duration of symptoms as recalled at diagnosis. The other 4 factors all came from the 1-yr review (no death then). These were (a) greater glucose intolerance, as expressed by the KG rate constant for disappearance of i.v. injected glucose from the blood (more useful than fasting glucose concentration); (b) higher systolic blood pressure (more useful than diastolic); (c) less obesity, as expressed by the Body Mass Index, and (d) higher fasting blood glycerol concentration. As expected, hyper-glycaemia (as reflected in the KG value) is important, but adrenergic factors may contribute to (a), (b) and (d). From these results earlier diagnosis of this type of diabetes could well be associated with an improved outlook, and in addition this alone might ameliorate the other factors, but measures to normalise them post-diagnosis also require testing.

Blood Glucose↗
PubMed1977

Organization and polysaccharides of sponge aggregation factor.

Aggregation factor, the macromolecular complex which mediates species-specific aggregation of dissociated sponge cells, was isolated from several species, partially characterized, and visualized by electron microscopy. All factors were large fibrous complexes with a backbone and side chains or arms. In some factors, the backbone is linear. In others it is circular and the complex appears as a sunburst with arms extending like rays from the circle. The size and location of the polysaccharide chains have been studied using purified preparations of Microciona prolifera. "Sunbursts" treated with ethylenediaminetraacetate (EDTA) for 4 weeks at 0 degrees C dissociate into 3 protein- and polysaccharide-containing components. Sodium dodecyl sulfate does not cause the sunburst to dissociate nor does it inhibit dissociation in the presence of EDTA suggesting that dissociation is not due to hydrolytic enzymes. The dissociation products were fractionated on a 977-A pore size micropore glass column. Fifteen percent of the material is excluded and appears in the electron microscope as the central circle of the sunburst. Digestion of the circles with 10(-3) M dithiothreitol (DTT) and 0.5 mg/ml proteinase K for 72 h at 37 degrees C produces 2 polysaccharide chains of 65,000 and 6,000 daltons as fractionated and sized on a 233-A pore size micropore glass column using Pharmacia dextrans as standards. The included fractions of the EDTA-treated material are subunits of the arms which contain 70% of the polysaccharide. A single polysaccharide of 6,000 daltons as measured on 233-A size glass beads and Sephadex G-75 is released from these subunits by proteinase digestion. Pharmacia dextrans are used as standard on both columns. We calculate that there would be four 65,000-dalton chains and one hundred 6,000-dalton chains per circle and fifty 6,000-dalton chains per arm. The third component of the EDTA-treated preparation is partially included on the column. It appears as linear fibrils in the electron microscope and contains polydisperse polysaccharides of several-hundred-thousand daltons. It may be an impurity since there is apparently less than 1 of the large polysaccharide chains per sunburst.

Animals↗