BH3-domain mimetic compound BH3I-2' induces rapid damage to the inner mitochondrial membrane prior to the cytochrome c release from mitochondria.

The Bcl-2 family proteins are major regulators of cell survival and death in human leukaemia. BH3-containing peptides induce apoptosis by binding to the hydrophobic pocket of the anti-apoptotic proteins, such as Bcl-2 or Bcl-XL. A small cell-permeable compound, BH3I-2' (3-iodo-5-chloro-N-[2-chloro-5-((4-chlorophenyl)sulphonyl)phenyl]-2-hydroxybenzamide), has been recently reported to have a function similar to Bak BH3 peptide.

A Review of Environmental Noise and Mental Health.

The question of whether environmental noise exposure causes mental ill-health is still largely unanswered. This paper reviews the studies of environmental and industrial noise and mental ill-health published between 1993 and 1998 and suggests possibilities for future research. Recent community based studies suggest high levels of environmental noise are associated with mental health symptoms such as depression and anxiety but not with impaired psychological functioning.

Identification of post-translational modifications resulting from LHbeta polymorphisms by matrix-assisted laser desorption time-of-flight mass spectrometric analysis of pituitary LHbeta core fragment.

Metabolism of the human chorionic gonadotrophin (hCG)- and LHbeta-subunits (hCGbeta, LHbeta) terminates with the urinary excretion of core fragment (hCGbetacf, LHbetacf) molecules that retain antigenic shape and constituent N-linked carbohydrate moieties. We have previously demonstrated the resolved mass spectra of hCGbetacf, from which the carbohydrate moieties present at two N-linked glycosylation sites were identified. LHbetacf was subjected to the same mass spectrometric analysis.

A superoxide dismutase mimetic with catalase activity (EUK-8) reduces the organ injury in endotoxic shock.

Reactive oxygen species contribute to the multiple organ failure in endotoxic shock. Here, we investigate the effects of a salen-manganese complex, which exhibits both superoxide dismutase and catalase activity (EUK-8), on the circulatory failure, renal and liver injury and dysfunction caused by endotoxin in the anaesthetised rat. Endotoxaemia (6 mg/kg i.

Identification and quantification of antigens associated with HLA class I molecules on a bladder tumour cell line. Implications for vaccine design.

The aim of this study was to isolate and identify antigenic peptides associated with HLA class I molecules on a bladder tumour cell line. HLA-A1 molecules were purified using an immunobead-purification technique and following elution of nonapeptides associated with the complex, their HPLC profile was determined by Tandem mass spectrometry (MS/MS). Three peptides were identified namely: (1) P991 (VTDPGNLLY); (2) P1041.

Comparison of models of maternal age-specific risk for Down syndrome live births.

Objectives: To display and compare the different published formulae that specify the association between maternal age and the risk of a Down syndrome live birth.

Methods: Papers published since 1987 on the prevalence of Down syndrome live births in relation to maternal age were located using MEDLINE and the references given in other papers. The data series and the models fitted to them were plotted to obtain a visual idea of their similarities and differences.

The relationship between pituitary tumour transforming gene (PTTG) expression and in vitro hormone and vascular endothelial growth factor (VEGF) secretion from human pituitary adenomas.

Objective: Pituitary tumour transforming gene (PTTG) is a recently identified protooncogene, ubiquitously expressed in pituitary tumours at levels higher than those detected in normal pituitary. Although the precise function of PTTG protein is unknown, in vitro experiments have shown that it induces angiogenesis. In this study, we have examined the potential relationship between the level of PTTG expression and tumour phenotype, tumour size, in vitro pituitary hormone secretion and release of vascular endothelial growth factor (VEGF), a potent angiogenic factor.

Cardiac output, oxygen consumption and muscle oxygen delivery in submaximal exercise. Normal and low O2 states.

Cardiac output (Q) changes linearly with oxygen consumption (VO2) in normal subjects undertaking submaximal exercise (Q = A + B x VO2 where A is the y intercept and B the slope). If (hypothesis 1) the increase in cardiac output above the resting state represents the blood flow to exercising muscle (qm) and the increase in VO2 represents the oxygen consumption of exercising muscle (VO2m) then, where CaO2 is the arterial oxygen content, oxygen extraction, Em = 1/(B x CaO2). Secondly, exercising muscle venous oxygen content, CvO2m = CaO2 - 1/B.

Changes in summer temperature and heat-related mortality since 1971 in North Carolina, South Finland, and Southeast England.

Three climatically diverse regions were studied to determine the impact of temperature change on heat-related mortality from 1971 to 1997. Median regressions showed that May-August temperatures in North Carolina rose by 1.0 degrees C (95% CL 0.

Social and demographic predictors of parental consultation for child psychological difficulties.

Background: Results from previous studies examining determinants of parental consultation for child mental health provide inconsistent evidence concerning socio-demographic predictors. The aim of this study is to identify the sociodemographic predictors of parental consultation for child psychological difficulties.

Method: An epidemiological cross-sectional analysis was carried out using a sample of 5,913 children aged between 4 and 15 years from the Health Survey for England.

Winter mortality and its causes.

In the 1970s scientific research focussed for the first time on dramatic rises in mortality every winter, and on smaller rises in unusually hot weather. Following the recent decline in influenza epidemics, approximately half of excess winter deaths are due to coronary thrombosis. These peak about two days after the peak of a cold spell.

Role of DNA methylation in the suppression of Apaf-1 protein in human leukaemia.

Apaf-1 protein deficiency occurs in human leukaemic blasts and confers resistance to cytochrome-c-dependent apoptosis. Demethylation treatment with 5-aza-2'-deoxycytidine (5aza2dc) increased the sensitivity of the K562 leukaemic cell line to UV light-induced apoptosis in association with increased Apaf-1 protein levels. There was no correlation between Apaf-1 protein expression and Apaf-1 mRNA levels after the demethylation treatment.

Clinical and endocrine responses to pituitary radiotherapy in pediatric Cushing's disease: an effective second-line treatment.

Transsphenoidal surgery (TSS) is considered first-line treatment for Cushing's disease (CD). Options for treatment of postoperative persisting hypercortisolemia are pituitary radiotherapy (RT), repeat TSS, or bilateral adrenalectomy. From 1983 to 2001, we treated 18 pediatric patients (age, 6.

[Comparison of the pharmacologic effect of diacerein and a selective COX-2 inhibitor in the mouse induced-granuloma model].

Unlabelled: ANIMAL MODEL OF DEGENERATIVE JOIN DISEASE: A mouse model of joint disease with an induced granuloma has demonstrated that diacerein inhibits loss of hydroxyproline and proteoglycans in joint cartilage, an effect not observed with conventional nonsteroidal antiinflammatory drugs (NSAID) or with a specific inhibitor of cyclooxygenase-2 (COX-2). Specific COX-2 inhibitors could thus be beneficially combined with disease modifying osteoarthritis drugs DMOD such as diacerein. ANTIINFLAMMATORY EFFECTS OF COX-2: During the process of inflammation, COX-2 activity appears to occur at two specific time points, with a peak at 2 hours, associated with maximal activity of PGE(2) synthase (proinflammatory prostaglandin) and a second peak after 48 hours, associated with increased levels of PGD(2) and cyclopentenones (anti-inflammatory prostaglandins).

A novel, potent and selective inhibitor of the activity of inducible nitric oxide synthase (GW274150) reduces the organ injury in hemorrhagic shock.

An enhanced formation of nitric oxide (NO) by the inducible NO synthase (iNOS) may contribute to the pathophysiology of hemorrhagic shock. This study investigates the effect of a novel, potent and selective inhibitor of iNOS activity (GW274150) on the circulatory failure and the organ injury and dysfunction associated with hemorrhagic shock in the anesthetised rat. Hemorrhage (sufficient to lower mean arterial blood pressure to 45 mmHg for 90 min) and subsequent resuscitation with shed blood resulted (within 4 h after resuscitation) in a delayed fall in blood pressure, renal and liver injury and dysfunction as well as the pancreatic injury.

Dextran sulfate sodium-induced inflammation is enhanced by intestinal epithelial cell chemokine expression in mice.

Dextran sulfate sodium (DSS) induces an inflammatory bowel disease-like colitis in animals. To determine the contribution of epithelium to inflammation in the intestine, we examined the effects of DSS in transgenic mice that specifically secrete macrophage inflammatory protein-2 (MIP-2) from the intestinal epithelium. We first confirmed the production of MIP-2 from intestinal epithelial cells by Western blots in transgenic mice.

Fascin, an actin-bundling protein, modulates colonic epithelial cell invasiveness and differentiation in vitro.

In epithelial tissue, cell-matrix and cell-cell adhesive interactions have important roles in the normal organization and stabilization of the cell layer. The malignant conversion of epithelial cells involves alterations in the expression and function of these adhesion systems that enable a switch to a migratory phenotype in tumor invasion and metastasis. Fascin is an actin-crosslinking protein that is found in the core actin bundles of cell-surface spikes and projections that are implicated in cell motility.

The accuracy of three methods of age estimation using radiographic measurements of developing teeth.

The accuracy of age estimation using three quantitative methods of developing permanent teeth was investigated. These were Mörnstad et al. [Scand.

Actions of paracetamol on cyclooxygenases in tissue and cell homogenates of mouse and rabbit.

Background: Paracetamol is a potent analgesic and antipyretic drug, but has only weak anti-inflammatory activity. Unlike aspirin-like drugs, paracetamol does not damage the stomach mucosa or inhibit the aggregation of platelets. The analgesic action of paracetamol is on the central nervous system.

Modulation of mastication during experimental loosening of complete dentures.

Purpose: Suction is achieved when complete dentures are first fitted, but it fades during the months following insertion, when it is increasingly complemented by muscular denture control. The aim of this study was therefore to investigate the extent to which patterns of mastication are altered by experimental failure of physical retention.

Materials And Methods: Seven edentulous volunteers had maxillary replica dentures made, with fine tubes incorporated so that alternating positive and negative air pressure could be generated under the fitting surface.

The effect of veneering and heat treatment on the flexural strength of Empress 2 ceramics.

Objectives: The aims of the study were to test and compare the biaxial flexural strength and reliability of Empress 2 ceramics after heat treatment and the addition of the veneering material and to characterise their microstructures.

Methods: Forty disc specimens (2 x 14 mm) and forty disc specimens (1 x 14 mm) were produced by heat pressing in the EP 500 press furnace. Group 1 (2 x 14 mm Empress 2 core) was as heat pressed and group 2 (2 x 14 mm Empress 2 core) was subjected to the recommended firing cycles.