The link module from human TSG-6 inhibits neutrophil migration in a hyaluronan- and inter-alpha -inhibitor-independent manner.

TSG-6 protein (the secreted product of the tumor necrosis factor-stimulated gene-6), a hyaluronan-binding protein comprised mainly of a Link and CUB module arranged in a contiguous fashion, has been shown previously to be a potent inhibitor of neutrophil migration in an in vivo model of acute inflammation (Wisniewski, H. G., Hua, J.

Growth in disorders of adrenal hyperfunction.

Growth is disturbed by adrenal hypersecretion of androgens or cortisol. Androgen excess in virilizing adrenal tumours causes advanced growth and bone age. In 9 girls with virilizing tumours, mean heights at diagnosis and final heights were 1.

Effect of ozone and nitrogen dioxide on the permeability of bronchial epithelial cell cultures of non-asthmatic and asthmatic subjects.

Background: Although epidemiological as well as in vivo exposure studies suggest that ozone (O3) and nitrogen dioxide (NO2) may play a role in airway diseases such as asthma, the underlying mechanisms are not clear.

Objective: Our aim was to investigate the effect of O3 and NO2 on the permeability of human bronchial epithelial cell (HBEC) cultures obtained from non-atopic non-asthmatic (non-asthmatics) and atopic mild asthmatic (asthmatics) individuals.

Methods: We cultured HBECs from bronchial biopsies of non-asthmatics and asthmatics, and exposed these for 6 h to air, 10 to 100 parts per billion (p.

The GH-IGF-I axis in children with idiopathic short stature.

Idiopathic short stature (ISS) is a term used for children in whom the etiology of the short stature is undefined. Investigations of the growth hormone (GH)-insulin-like growth factor I axis have revealed several molecular and endocrinological defects in ISS patients. Abnormalities of GH secretion and action, although not frequent, will help to categorize some children with ISS.

Validation of a device to measure arterial pulse wave velocity by a photoplethysmographic method.

We aimed to validate a new method for measuring arterial pulsewave transit time and pulsewave velocity (a measure of arterial elasticity), based on the principle of photoplethysmography (PPG), and to compare transcutaneous values with those obtained by intra-arterial measurements. Three validation experiments are described. (a) PPG pulse wave delay times (defined as the time interval between the ECG R wave and the foot of the arterial pulse wave measured at the wrist or ankle) were compared to values obtained simultaneously from an established methodology (Doppler ultrasound).

Oxidative stress and cardiac microvascular structure in ischemia and reperfusion: the protective effect of antioxidant vitamins.

Reperfusion of the ischemic myocardium results in structural changes in the capillary bed, which may contribute to decreased microcirculatory flow ("no reflow"). This study was designed to correlate the endothelial cell shape changes with both oxidative stress and lipid peroxidation and to evaluate the beneficial potential of Trolox (a hydrophilic analogue of alpha-tocopherol) and ascorbic acid. Isolated buffer-perfused rat hearts were made ischemic for 45 min and then reperfused with 100 microM Trolox and/or 100 microM ascorbic acid.

Reaction of the spin trap 3,5-dibromo-4-nitrosobenzene sulfonate with human biofluids.

Using the spin trap 3,5-dibromo-4-nitrosobenzene sulfonate (DBNBS), an oxidant was previously detected in the plasma of patients with renal failure and the synovial tissue of rheumatoid arthritis patients. This oxidant has been shown to react with DBNBS to give a 3-line electron paramagnetic resonance (EPR) spectrum, previously assigned to the DBNBS radical cation (DBNBS*(+). However, confusion has arisen as to whether this paramagnetic species is indeed DBNBS*(+) or, rather, the DBNBS sulfite radical adduct (DBNBS-SO(3)*(-)).

Neonatal thyrotoxicosis and maternal infertility in thyroid hormone resistance due to a mutation in the TRbeta gene (M313T).

We report two unusual cases of resistance to thyroid hormone (RTH) in one family. The first case, a male infant, had clinical features of thyrotoxicosis in the neonatal period. In the fourth week of life weight gain was poor despite a daily intake of standard infant formula almost double the infant's estimated requirements.

Spontaneous growth hormone secretory characteristics in children with partial growth hormone insensitivity.

Objective: To investigate the characteristics of spontaneous GH secretion in four male children with short stature due to partial GH insensitivity. Their molecular defect consists of inclusion of a mutant intronic pseudoexon in the region of the GH receptor involved in homodimerization.

Subjects: The subjects were two pairs of brothers who were first cousins, aged 10.

Regulation of human glycoprotein hormone alpha-subunit gene transcription in LbetaT2 gonadotropes by protein kinase C and extracellular signal-regulated kinase 1/2.

Transcriptional activation of the human glycoprotein hormone alpha-subunit (alphaGSU) promoter in response to GnRH and phorbol-12-myristate-13-acetate (PMA) has been well characterized in alphaT3-1 gonadotropes but not investigated in the more differentiated LbetaT2 clonal gonadotrope. We have evaluated alphaGSU transcription in the more mature LbetaT2 cell line, using deletion and heterologous constructs of the alphaGSU promoter linked to a luciferase reporter gene. Basal alphaGSU-promoter activity was significantly less in LbetaT2 cells than in alphaT3-1 cells, but stimulation of transfected cells with GnRH and PMA resulted in similar increases in alphaGSU-promoter activity.

Endothelin content, expression, and receptor type in normal and diseased human gallbladder.

The aims of this study were to characterize the endothelin (ET) system in human gallbladder by determining (1) the tissue content of ET-1 and ET-2 by ELISA; (2) the expression of mRNA of the ET precursors preproendothelin-1, -2, and -3; and (3) mRNA expression for the ETA and ETB receptors. Median content of ET-1/2 was significantly reduced in severely inflamed gallbladders compared to gallbladders with mild inflammation. There was an inverse correlation between content of ET-1/2 and inflammation score.

Modulation of host antimicrobial peptide (beta-defensins 1 and 2) expression during gastritis.

Background: beta-Defensins are a newly identified family of antimicrobial peptides that are expressed by epithelia on mucosal surfaces where their production is augmented by infection or inflammation. Helicobacter pylori colonises the gastric epithelium causing persistent gastric inflammation leading to antral and corpus gastritis, and peptic ulcer disease.

Aims: To evaluate the role of beta-defensins in the innate immune response of the gastric epithelium to infection and inflammation, we have assessed mRNA expression and regulation of human beta-defensins 1 and 2 (hBD1, hBD2) by H pylori and proinflammatory stimuli.

Ligands of the peroxisome proliferator-activated receptor-PPAR-a reduce myocardial infarct size.

Background: This study was designed to investigate the effects of two, chemically distinct activators of PPAR-a (clofibrate and WY14643) in a rat model of acute myocardial infarction.

Material/methods: Male Wistar rats were anesthetized with sodium thiopentone (120 mg/kg i.v.

The Pastoral Pool: an evaluation of a new system of pastoral care provision.

Context: Medical students experience significant stress and stress-related problems. The benefits of support during training are described in this paper. Recently, student support systems have become increasingly stretched as medical schools merge, courses become modular and staff face increasing clinical and research pressures.

Support for students with academic difficulties.

Context: The human and financial costs of academic failure amongst medical students are extremely high. Often, remedial support is infrequently available or is available only for students failing their final examinations. We describe the design, implementation and preliminary evaluation of a remedial programme (RP) for students who experience academic difficulties.

Interactions between lipoteichoic acid and peptidoglycan from Staphylococcus aureus: a structural and functional analysis.

The cell wall of Gram-positive bacteria contains lipoteichoic acid (LTA) and peptidoglycan (PepG), which synergise to cause shock and organ failure in animals, and to activate human blood to release proinflammatory cytokines. The structural elements within LTA and PepG that are essential for the observed synergism are discussed.

1H and (13)C NMR spectroscopic analysis of human saliva.

We have explored the ability of high-resolution NMR techniques to (1) index salivary biomolecules and (2) provide valuable data regarding intra- and inter-subject variability in the concentrations of a series of components readily determinable by this technique (organic acids and malodorous amines). Experiments were conducted on 'whole' saliva samples collected from 20 patients, either randomly during their daily activities, or, for investigations involving the quantification of salivary biomolecules, immediately after they woke in the morning throughout a three-day period. These NMR techniques permitted us to detect greater than 60 metabolites, together with agents arising from dietary, oral health care product, and pharmaceutical sources.

Carboxy-PTIO, a scavenger of nitric oxide, selectively inhibits the increase in medullary perfusion and improves renal function in endotoxemia.

The acute renal failure associated with septic shock is associated with a high mortality despite dialytic therapies. Endotoxemia leads to marked changes in the distribution of intrarenal perfusion that may be independent of alterations in total renal blood flow or systemic hemodynamics. Modulation of this intrarenal redistribution may protect against acute renal failure.

Growth hormone replacement does not increase serum prostate-specific antigen in hypopituitary men over 50 years.

Objective: Epidemiological studies have shown an increased risk for prostate carcinoma in men with serum IGF-I in the upper part of the age-related reference range. Recombinant human GH (rhGH) is widely used in patients with GH deficiency, usually raising the serum IGF-I levels into the normal range: safety surveillance is therefore mandatory, with particular regard to neoplasia. The aim was to examine whether rhGH replacement in hypopituitary adults is associated with changes in serum prostate-specific antigen (PSA) as a surrogate marker of changes in prostatic growth.