bluuebunny/crossref_metadata_2025_split huggingface dataset:
Renal cells activate the platelet receptor CLEC-2 through podoplanin
Authors: Christou Charita M. , Pearce Andrew C. , Watson Aleksandra A. , Mistry Anita R. , Pollitt Alice Y. , Fenton-May Angharad E. , Johnson Louise A. , Jackson David G. , Watson Steve P. , O'callaghan Chris A. 
Published: March 2008

We have recently shown that the C-type lectin-like receptor, CLEC-2, is expressed on platelets and that it mediates powerful platelet aggregation by the snake venom toxin rhodocytin. In addition, we have provided indirect evidence for an endogenous ligand for CLEC-2 in renal cells expressing HIV-1. This putative ligand facilitates transmission of HIV through its incorporation into the viral envelope and binding to CLEC-2 on platelets. The aim of the present study was to identify the ligand on these cells which binds to CLEC-2 on platelets. Recombinant CLEC-2 exhibits specific binding to HEK-293T (human embryonic kidney) cells in which the HIV can be grown. Furthermore, HEK-293T cells activate both platelets and CLEC-2-transfected DT-40 B-cells. The transmembrane protein podoplanin was identified on HEK-293T cells and was demonstrated to mediate both binding of HEK-293T cells to CLEC-2 and HEK-293T cell activation of CLEC-2-transfected DT-40 B-cells. Podoplanin is expressed on renal cells (podocytes). Furthermore, a direct interaction between CLEC-2 and podoplanin was confirmed using surface plasmon resonance and was shown to be independent of glycosylation of CLEC-2. The interaction has an affinity of 24.5±3.7 μM. The present study identifies podoplanin as a ligand for CLEC-2 on renal cells.
Oxidative folding competes with mitochondrial import of the small Tim proteins
Authors: Morgan Bruce , Lu Hui 
Published: March 2008

All small Tim proteins of the mitochondrial intermembrane space contain two conserved CX3C motifs, which form two intramolecular disulfide bonds essential for function, but only the cysteine-reduced, but not oxidized, proteins can be imported into mitochondria. We have shown that Tim10 can be oxidized by glutathione under cytosolic concentrations. However, it was unknown whether oxidative folding of other small Tims can occur under similar conditions and whether oxidative folding competes kinetically with mitochondrial import. In the present study, the effect of glutathione on the cysteine-redox state of Tim9 was investigated, and the standard redox potential of Tim9 was determined to be approx. −0.31 V at pH 7.4 and 25 °C with both the wild-type and Tim9F43W mutant proteins, using reverse-phase HPLC and fluorescence approaches. The results show that reduced Tim9 can be oxidized by glutathione under cytosolic concentrations. Next, we studied the rate of mitochondrial import and oxidative folding of Tim9 under identical conditions. The rate of import was approx. 3-fold slower than that of oxidative folding of Tim9, resulting in approx. 20% of the precursor protein being imported into an excess amount of mitochondria. A similar correlation between import and oxidative folding was obtained for Tim10. Therefore we conclude that oxidative folding and mitochondrial import are kinetically competitive processes. The efficiency of mitochondrial import of the small Tim proteins is controlled, at least partially in vitro, by the rate of oxidative folding, suggesting that a cofactor is required to stabilize the cysteine residues of the precursors from oxidation in vivo.
Biomolecular simulation: historical picture and future perspectives
Authors: van Gunsteren Wilfred F. , Dolenc Jožica 
Published: March 2008

Over the last 30 years, computation based on molecular models is playing an increasingly important role in biology, biological chemistry and biophysics. Since only a very limited number of properties of biomolecular systems are actually accessible to measurement by experimental means, computer simulation complements experiments by providing not only averages, but also distributions and time series of any definable, observable or non-observable, quantity. Biomolecular simulation may be used (i) to interpret experimental data, (ii) to provoke new experiments, (iii) to replace experiments and (iv) to protect intellectual property. Progress over the last 30 years is sketched and perspectives are outlined for the future.
Low-grade inflammation and arterial wave reflection in patients with chronic fatigue syndrome
Authors: Spence Vance A. , Kennedy Gwen , Belch Jill J. F. , Hill Alexander , Khan Faisel 
Published: March 2008

Some of the symptoms reported by people with CFS (chronic fatigue syndrome) are associated with various cardiovascular phenomena. Markers of cardiovascular risk, including inflammation and oxidative stress, have been demonstrated in some patients with CFS, but little is known about the relationship between these and prognostic indicators of cardiovascular risk in this patient group. In the present study, we investigated the relationship between inflammation and oxidative stress and augmentation index, a measure of arterial stiffness, in 41 well-characterized patients with CFS and in 30 healthy subjects. AIx@75 (augmentation index normalized for a heart rate of 75 beats/min) was significantly greater in patients with CFS than in control subjects (22.5±1.7 compared with 13.3±2.3% respectively; P=0.002). Patients with CFS also had significantly increased levels of CRP (C-reactive protein) (2.58±2.91 compared with 1.07±2.16 μg/ml respectively; P&lt;0.01) and 8-iso-prostaglandin F2α isoprostanes (470.7±250.9 compared with 331.1±97.6 pg/ml respectively; P&lt;0.005). In patients with CFS, AIx@75 correlated significantly with logCRP (r=0.507, P=0.001), isoprostanes (r=0.366, P=0.026), oxidized LDL (low-density lipoprotein) (r=0.333, P=0.039) and systolic blood pressure (r=0.371, P=0.017). In a stepwise multiple regression model, including systolic and diastolic blood pressure, body mass index, CRP, tumour necrosis factor-α, interleukin-1, oxidized LDL, high-density lipoprotein-cholesterol levels, isoprostanes, age and gender, AIx@75 was independently associated with logCRP (β=0.385, P=0.006), age (β=0.363, P=0.022) and female gender (β=0.302, P=0.03) in patients with CFS. The combination of increased arterial wave reflection, inflammation and oxidative stress may result in an increased risk of future cardiovascular events. Assessment of arterial wave reflection might be useful for determining cardiovascular risk in this patient group.
Pattern of skin and nail changes in chronic renal failure in Nepal: A hospital‐based study
Authors: AMATYA Beni , AGRAWAL Sudha , DHALI Tapan , SHARMA Sanjib , PANDEY Shyam Sunder 
Published: March 2008

ABSTRACTChronic renal failure, regardless of its cause, often produces specific dermatological abnormalities, which can develop long before failure manifests clinically. Our aim was to study the clinical pattern of skin and nail changes in chronic renal failure and also study the associations of these changes with age, sex, etiology and duration of the chronic renal failure. A total of 104 diagnosed cases of chronic renal failure were included in the study over a period of 1 year. Equal numbers of age‐ and sex‐matched individuals were taken as controls. The male : female ratio was 1.4:1. The mean duration of chronic renal failure was 19 ± 20 months. Among cases and controls, 72% and 16% had skin changes, respectively. Xerosis was the most common of the skin changes (28%), followed by hyperpigmentation (20%), pruritus (15%), infectious diseases (5%) and other skin changes (33%) in chronic renal failure patients. Abnormal nail changes were seen in 82% of the cases compared to only 8% of the controls. In the cases, white nail was most common followed by brown and half‐and‐half nail. Pruritus was significantly higher in the dialysis group whereas the nail changes were significantly higher in the non‐dialysis group. The skin and nail changes were common in chronic renal failure and manifested in various forms. Thus, thorough inspection of the integument might reveal markers of occult renal disease.
NON‐AUTONOMY OF HORMONE SECRETION IN PRIMARY HYPERPARATHYROIDISM
Authors: MURRAY T. M. , PEACOCK M. , POWELL D. , MONCHIK J. M. , POTTS J. T. 
Published: March 2008

SUMMARYParathyroid hormone (PTH) was measured by radioimmunoassay in the plasma of twenty patients with surgically proven primary hyperparathyroidism during intravenous infusions of calcium and/or EDTA. All patients studied showed significant increases in plasma PTH during induced hypocalcaemia and significant decreases in plasma PTH during induced hypercalcaemia. The secretion of para thyroid hormone was not autonomous in these patients with primary hyperparathyroidism, regardless of histological type, but varied with induced changes in serum calcium concentration. The presence of immunoreactive hormonal sub‐fragments in plasma seems the most likely explanation for the sharp contrast between our data and earlier studies. In spite of the difficulties presented by this complex pattern of hormonal metabolism, the radioimmunoassay for parathyroid hormone is clinically quite useful, particularly in the differential diagnosis of hypercalcaemia.
THE ROLE OF TRIIODOTHYRONINE (T3) IN THE MAINTENANCE OF EUTHYROIDISM IN ENDEMIC GOITRE
Authors: PHARAOH P. O. D. , LAWTON N. F. , ELLIS S. M. , WILLIAMS E. S. , EKINS R. P. 
Published: March 2008

SUMMARYSerum concentrations of triiodothyronine (T3), thyroxine (T4) and thyroid stimulating hormone (TSH) have been measured in subjects from an endemic goitrous area of New Guinea. An increase in TSH concentration and a decrease in T4 concentration was found in both goitrous and non‐goitrous subjects, both abnormalities being more frequent in the goitrous group. In the majority of subjects (93%) the T3 level fell within the normal range. Euthyroidism appears to be preserved in the iodine deficient state by the continued production of normal amounts of T3, the intrinsic metabolic activity of T4 being relatively unimportant.
AN ASSESSMENT OF THE METYRAPONE TEST
Authors: SHAHMANESH M. , HARTOG M. , CROOK D. 
Published: March 2008

SUMMARYThe degree of 11β‐hydroxylase inhibition produced during a 24 hr metyrapone test was assessed in sixteen normal subjects and seven patients with Cushing's syndrome using a urinary GLC method which distinguishes between 11‐deoxy‐corticosteroids and 11‐oxygenated corticosteroids. A doubling over basal values and a rise of total urinary corticosteroids of more than 10 mg in 24 hr was seen in all the fifteen normal subjects who achieved over 70% enzyme inhibition in at least one 24 hr period after the administration of metyrapone.All patients with Cushing's syndrome showed over 70% enzyme inhibition. On the basis of the test it was possible to distinguish between pituitary dependent Cushing's syndrome and that caused by an adrenal adenoma. A single patient with the ectopic ACTH syndrome showed a normal metyrapone response.The urinary GLC method provides a simple means of assessing the adequacy of enzyme inhibition produced by metyrapone.
SERUM TSH RESPONSES TO INTRAVENOUSLY AND ORALLY ADMINISTERED TRH IN MAN AFTER THYROIDECTOMY FOR CARCINOMA OF THE THYROID
Authors: FAIRCLOUGH P. D. , CRYER R. J. , McALLISTER J. , HAWKINS L. , JONES A. E. , McKENDRICK M. , HALL R. , BESSER G. M. 
Published: March 2008

SUMMARYFourteen patients whose thyroid glands had been ablated for carcinoma were given intravenous or oral thyrotrophin releasing hormone (TRH) at intervals after stopping replacement thyroid hormone. Despite continuing the TRH infusion, serum thyrotrophin (TSH) rose to reach a peak at 120 min after the start of the infusion, and then fell again towards the pre‐treatment values. Significant responses were seen by 4 days after stopping triodothyronine (T3), but progressively increased with longer intervals off T3. Oral TRH gave a similar pattern of responses. Patients maintained on thyroxine (T4) and changed to T3 4 weeks prior to treatment had smaller TSH responses to TRH than patients maintained continuously on T3. It would seem that: (1) TRH promotes TSH release faster than it promotes synthesis of new hormone under the conditions studied, and (2) that long‐term administration of T3 suppresses TSH secretion from the pituitary in response to TRH less than thyroxine. While it is possible to elevate the serum TSH levels of these patients with thyroid carcinoma into the rane normally seen in primary hypothyroidism by the use of TRH prior to administration of radioiodine without production of clinical symptoms of hypothyroidism, we do not yet know whether such elevation is of benefit in treatment.
OSTEOID MINERALIZATION DEFECT IN PRIMARY HYPERPARATHYROIDISM
Authors: BORDIER J. , WOODHOUSE N. J. Y. , SIGURDSSON G. , JOPLIN G. F. 
Published: March 2008

SUMMARYUsing a quantitative histological technique, four unselected patients with primary hyperparathyroidism were investigated and all were found to have a delayed or defective mineralization of osteoid, although their diet contained an adequate amount of vitamin D. This abnormality was most marked in the one patient with radiological bone disease. Mineralization of osteoid occurred during subsequent vitamin D administration, together with an improvement in 45Ca absorption by the gut; osteoclast numbers and serum acid phosphatase levels also increased.We suggest that (1) endogenous vitamin D deficiency and hyperparathyroidism frequently co‐exist, (2) vitamin D metabolism is abnormal in hyperparathyroidism, and (3) radiological loss of bone density and erosions in hyperparathyroidism are due to impairment of the process of bone repair, i.e. there is defective mineralization of the osteoid which is laid down by osteoblasts to fill the resorption lacunae.
THYROID FUNCTION IN EUTHYROID SUBJECTS WITH AUTONOMOUS THYROID NODULES
Authors: EVERED D. C. , CLARK F. , PETERSEN V. B. 
Published: March 2008

SUMMARYThe biochemical abnormalities in euthyroid subjects with autonomous thyroid nodules have been defined. Seven subjects have been studied in detail. None were hyperthyroid and conventional tests of thyroid function were normal. The characteristic abnormalities were noted on scanning. The absent response to TRH demonstrated that pituitary TSH suppression was present in all subjects. A moderate elevation of serum triiodothyronine (T3) concentration, 1.89‐3.07 ng/ml, was noted. It is concluded that autonomous nodules in the euthyroid subjects studied are associated with elevated T3 levels sufficient to produce pituitary suppression but not high enough to be associated with the clinical manifestations of hyperthyroidism.
TESTICULAR FUNCTION IN MYOTONIC DYSTROPHY OF CHILDHOOD
Authors: HAMILTON W. 
Published: March 2008

SUMMARYThe histological appearances of testicular tissue obtained from six cases of dystrophica myotonica are shown. These appearances ranged from near normal to complete atrophy and hyalinization of the seminiferous tubules.A method for the assessment of testicular steroid enzyme activity is proposed and has the advantage that preferential pathways of testosterone synthesis can be examined. Study of the enzyme activity in this testicular material showed that 17α‐hydroxylase is not an active testicular enzyme, that in three cases there was reduction in activity of the enzyme 17,20‐desmolase and in two cases there was reduced 17β‐reductase activity. Interstitium and tubules were not separately incubated in these experiments so that the defects observed cannot be associated with either tissue. However, since 17β‐reductase is normally more active in the tubules than interstitium, in the two cases where this enzyme was noted to be deficient, this could indicate failure of tubular enzyme activity.The studies indicate that the rate of testicular atrophy in dystrophia myotonica varies from case to case and is not age‐related.
THE EFFECT OF HYPOTHALAMIC LUTEINIZING HORMONE RELEASING HORMONE (LH‐RH) ON PLASMA GONADOTROPHIN LEVELS IN NORMAL SUBJECTS
Authors: FRANCHIMONT P. , BECKER H. , ERNOULD CH. , THYS CH. , DEMOULIN A. , BOURGUIGNON J. P. , LEGROS J. J. , VALCKE J. C. 
Published: March 2008

SUMMARYThe release of gonadotrophin following the injection of synthetic LH‐RH (Hoechst) was studied in various physiological and experimental circumstances.In the male, 25 μg of LH‐RH led to simultaneous release of FSH and LH prior to and during puberty. In adults, on the other hand, the same dose led only to an increase in LH while FSH levels remained unchanged. At higher doses there was FSH release and an increase in LH proportional to the amount of LH‐RH injected. When FSH was released the increase was clearly less than that of LH and often occurred considerably later.In the female, 25 μg of LH‐RH led to a clear‐cut release of FSH and a small release of LH prior to puberty. After the onset of puberty the degree of response was inverted: the increase in LH was greater than that of FSH. In normally menstruating women the FSH and LH response was greater during the luteal phase than during the preovulatory phase. Treatment with non‐sequential hormonal contraceptives blocked FSH and LH release normally produced by the injection of 50 μg of LH‐RH. There was no effect when a dose of 100 μg was injected.In post‐menopausal women, only LH rose following the administration of 25 μg of LH‐RH. After 5 days of treatment with 200 μg ethinyl oestradiol the same dose of LH‐RH led to simultaneous release of LH and of FSH.From the above studies it can be concluded that the secretory response of the gonadotrophins to LH‐RH is influenced by the endocrine equilibrium and more particularly by the interaction of the gonadal steroids which can alter the synthesis and/or the release of the pituitary gonadotrophins.
PERIPHERAL RESISTANCE TO THYROXINE: A CAUSE OF SHORT STATURE IN A BOY WITHOUT GOITRE
Authors: SCHNEIDER GEORGE , KEISER H. R. , BARDIN C. W. 
Published: March 2008

SUMMARYA euthyroid pubertal boy was investigated for short stature and was found to have an elevated serum thyroxine and delayed bone age. In spite of high thyroxine levels, there were no clinical signs of hyperthyroidism and kinetic studies revealed a normal rate of thyroxine metabolism. Plasma TSH levels were elevated but there was no goitre. Administration of up to 900 μg of triiodothyronine led to minimal changes in urinary hydroxyproline excretion, pulse rate and body weight. These observations indicate that this boy has a target organ insensitivity to thyroid hormones. When compared with other patients with this disorder, the studies further emphasize that this condition may have a variable clinical presentation. In addition, the extent of the target organ defect may not be evident from routine clinical and laboratory observations. The possible molecular basis of the defect is discussed.
THE LH RESPONSE TO LH‐RELEASING HORMONE IN CHILDREN WITH TRUE ISOSEXUAL PRECOCIOUS PUBERTY TREATED WITH CYPROTERONE ACETATE
Authors: KAULI R. , PRAGER‐LEWIN R. , KERET R. , LARON Z. 
Published: March 2008

SUMMARYFourteen girls and one boy with isosexual precocious puberty were submitted to LHRH stimulation tests, during and without therapy with cyproterone acetate. In addition, fourteen girls with isosexual precocious puberty not receiving any therapy were tested and served as controls.It was found that cyproterone acetate induces suppression of the responsiveness of the pituitary gland to secrete LH on LHRH stimulation. Daily oral therapy was found to be more effective than the regimen of intramuscular depot injections.These findings demonstrate that cyproterone acetate has an antigonadotrophic effect.
IODINE ORGANIFICATION DEFECT FOLLOWING TREATMENT OF THYROTOXICOSIS WITH ANTITHYROID DRUGS
Authors: HORTON P. W. , MILLAR W. T. , McLARTY D. G. , ALEXANDER W. D. 
Published: March 2008

SUMMARYTwo patients remained clinically euthyroid following treatment for thyrotoxicosis with antithyroid drugs in spite of persistently elevated thyroid radioiodine uptakes not suppressable by exogenous triiodothyronine. Perchlorate discharge tests showed a defect in the intrathyroidal organification of iodine. Circulating levels of thyroxine were normal. From our study of 105 patients treated for thyrotoxicosis with antithyroid drugs, apparent remission of thyrotoxicosis by this mechanism might occur in up to 2% of patients.
SPECIFIC CONTROL OF FOLLICLE STMULATING HORMONE IN THE MALE: POSTULATED SITE OF ACTION OF INHIBIN
Authors: BRAMBLE F. J. , HOUGHTON A. L. , ECCLES SHEILA S. , MURRAY M. A. F. , JACOBS H. S. 
Published: March 2008

SUMMARYSerum luteinizing and follicale stimulating hormone concentrations were related to gonadal function, as reflected by sperm count and serum testosterone concentrations, in a group of men studied over 10 years after surgical correction of bilateral crytorchidism in childhood.The results indicated that while all degrees of gonadal function occurred in these patients, the main adverse effect of crytorchidism was on spermatogenesis. In some of the patients with oligospermia and normal Leydig cell function there was an isolated increease f basal serum FSH concentrations, suggesting a specific iompairment of the testicular production of ‘inhibin’. Gonadotrophin releasing hormone (LHRH) tests in thesse patients were conpared to those in patients with normal basal gonadotrophins and to those with elevated basal LH and FSH concentrations. A selective exaggeration of the FSH response to expgenous LHRH in the group of patients with a monotropic elecation of FSH conventration suggests that ‘inhibnin’ modulates the secretion of FSH by an action on the pituitary rather than by modifying endogenous LHRH production by the hypothalamus.
FAILURE OF ADRENERGIC α AND β RECEPTOR BLOCKADE TO ELEVATE THE TSH AND PROLACTIN RESPONSE TO TRH IN HYPERTHYROIDISM
Authors: EPSTEIN S. , PIMSTONE B. L. , VINIK A. I. , McLAREN H. 
Published: March 2008

SUMMARYThe effects of adrenergic α and β receptor blockade on the thyrotrophin and prolactin responses to TRH were studied in groups of hyperthyroid patients who received either oral propranolol and phenoxybenzamine or intravenous propranolol and rogitine. The flat TSH and prolactin responses to TRH in the untreated hyperthyroid patients were not altered by oral or intravenous adrenergic α and β receptor blockade suggesting that catecholamines do not play a major role in the feedback suppression of TSH and prolactin in hyperthyroidism.
35S‐ANTITHYROID DRUG CONCENTRATION AND ORGANIC BINDING OF IODINE IN THE HUMAN THYROID
Authors: LAZARUS J.H. , MARCHANT B. , ALEXANDER W. D. , CLARK D. H. 
Published: March 2008

SUMMARY 35S‐methimazole (MMI), 35S‐carbimazole or 35S‐propylthiouracil (PTU) were given orally to fifty‐five patients at various times up to 12 h before surgical thyroidectomy. The amount of 35S radioactivity and labelled drug in thyroid and plasma samples was measured. Intrathyroidal inhibition of organic binding of iodine by MMI, carbimazole and PTU was measured after intravenous administration of 131I, 132I or 125I‐iodide. After administration of 35S‐carbimazole or 35S‐MMI the thyroid to serum (T/S) ratio of 35S radioactivity was greater in thyrotoxic glands than in non‐toxic adenoma tissue. 35S‐MMI was found in thyroid and plasma samples after administration of 35S‐carbimazole. The T/S 35S‐MMI was greater than 1 in most but not all patients. 35S radioactivity was also concentrated in the thyroid after administration of 35S‐PTU. In thyrotoxic glands there was an 80% inhibition of iodine organification in patients receiving MMI and 60% for those receiving PTU. It is suggested that carbimazole and MMI can be given once or twice daily in some patients but PTU would be less suitable for this dose schedule.Drug treatment of thyrotoxicosis using the thiocarbamide group of antithyroid drugs renders patients euthyroid after a variable period of administration. This variation in response may reflect individual differences, either in the nature of the disease process or in the response to antithyroid drugs.In this study we examine thyroidal levels of the thiocarbamide antithyroid drugs in thyrotoxicosis, non‐toxic goitre and ‘normal’ thyroid glands with particular emphasis on quantifying the effect of the drugs on inhibiting the organic binding of iodine within the gland.