Fatty acyl CoA-mediated inhibition of endoplasmic reticulum assembly.

The protein machinery that mediates homotypic fusion of mammalian endoplasmic reticulum (ER) membranes is becoming increasing well defined. However, little is known of how acylation of constituent membrane components might impact upon this event. This is particularly important as acylation has been shown to promote both fusion and fission of heterotypic membranes.

Aversive smoking for smoking cessation.

Background: Aversion therapy pairs the pleasurable stimulus of smoking a cigarette with some unpleasant stimulus. The objective is to extinguish the urge to smoke.

Objectives: This review has two aims: First, to determine the efficacy of rapid smoking and other aversive methods in helping smokers to stop smoking; Second, to determine whether there is a dose-response effect on smoking cessation at different levels of aversive stimulation.

15-epi-lipoxin A4-mediated induction of nitric oxide explains how aspirin inhibits acute inflammation.

The established model for the mechanism of action of aspirin is the inhibition of prostaglandin synthesis. However, this has never fully explained aspirin's repertoire of antiinflammatory properties. We found in acute pleuritis that aspirin, but not salicylate, indomethacin, or piroxicam, increased plasma nitric oxide (NO), which correlated with a reduction in inflammation.

Are false negative direct immnufluorescence assays caused by varicella zoster virus gE mutant strains?

Strains of Varicella zoster virus (VZV) have been described recently in which a single base mutation in the gE epitope abrogates binding of the 3B3 monoclonal antibody, which is widely used for virus detection in diagnostic laboratories. These strains, named VZV-MSP, are associated with a distinct phenotype in both in vitro culture and in SCID-hu mice. We investigated the possibility that negative direct immunofluorescence results, using the 3B3 antibody, where the presence of virus was confirmed by polymerase chain reaction (PCR) or tissue culture are due in some cases to the MSP strain of VZV.

Erythropoietin attenuates the tissue injury associated with hemorrhagic shock and myocardial ischemia.

Here we investigate the effects of erythropoietin (EPO) on the tissue/organ injury caused by hemorrhagic shock (HS), endotoxic shock, and regional myocardial ischemia and reperfusion in anesthetized rats. Male Wistar rats were anesthetized with thiopental sodium (85 mg/kg i.p.

Pseudo-precocious puberty caused by a juvenile granulosa cell tumour secreting androstenedione, inhibin and insulin-like growth factor-I.

We report a female child who presented at age 3.92 years with a 2-year history of consonant pubertal development caused by a large right-sided ovarian juvenile granulosa cell tumour (JGCT). Although JGCTs causing pseudo-precocious puberty have been previously described, they remain rare and endocrine data are often incomplete.

A plasmid immunization construct encoding urease B of Helicobacter pylori induces an antigen-specific antibody response and upregulates the expression of beta-defensins and IL-10 in the stomachs of immunized mice.

The objectives of this study were to investigate the efficacy of a prototype DNA immunization construct encoding the urease B subunit enzyme of Helicobacter pylori (H. pylori) for inducing adaptive and innate immune responses in mice immunized via intramuscular or subcutaneous routes and to further explore the adjuvant effects of the CpG motifs in the vector. Antibody, cytokine, and beta-defensin profiles were assessed in the stomachs of immunized animals: experiments were terminated 3 months after immunization because there was a significant increase in the anti-H.

Variations in lipid and apolipoprotein concentrations in human leg lymph: effects of posture and physical exercise.

We studied the variations in the concentrations of cholesterol, triglycerides, phospholipids, apolipoproteins (apos) (A-I, A-II, B, C-III, E), free glycerol and albumin in human prenodal leg lymph during the 24 h cycle. Lymph was collected continuously for up to 96 h from nine healthy males on a low-fat isocaloric diet. In three free-living subjects, all lipid and apolipoprotein concentrations underwent synchronous variations, rising during the night and decreasing during the day.

Increased risk of skin cancer associated with the presence of epidermodysplasia verruciformis human papillomavirus types in normal skin.

Background: Human papillomaviruses (HPVs) are found in normal skin and in benign and malignant skin conditions. Epidermodysplasia verruciformis (EV) HPV types are those most plausibly linked to the development of squamous cell carcinomas of the skin.

Objectives: To assess the risk of nonmelanoma skin cancer (NMSC) associated with the presence of EV HPV in normal skin in immunocompetent (IC) individuals and renal transplant recipients (RTRs).

The effects of treatment with antibodies to transforming growth factor beta1 and beta2 following spinal cord damage in the adult rat.

We recently showed axonal ingrowth into fibronectin (FN) mats implanted into the spinal cord. However, little axonal growth was found from FN mats into intact spinal cord. Previous research has shown that this is due in part to astrocytosis around an area of CNS damage.

p16INK4a and p14ARF tumor suppressor genes are commonly inactivated in cutaneous squamous cell carcinoma.

The p16(INK4a) and p14(ARF) tumor suppressor genes (TSGs) are encoded within the CDKN2A locus on chromosome 9p21 and function as cell cycle regulatory proteins in the p53 and RB pathways. Inactivation of these genes by genetic and epigenetic changes has been described in some human cancers, but their importance in cutaneous squamous cell carcinoma (SCC) has not been established. Our detailed examination of 40 cutaneous SCC revealed loss of heterozygosity of 9p21 markers in 32.

Role of peroxisome proliferator-activated receptor-gamma in the protection afforded by 15-deoxydelta12,14 prostaglandin J2 against the multiple organ failure caused by endotoxin.

Objective: The cyclopentenone prostaglandin 15-deoxydelta-prostaglandin J2 (15 d-PGJ2) exerts potent anti-inflammatory effects in vivo, which are in part due to the activation of peroxisome proliferator-activated receptor (PPAR)-gamma. Here we investigate the effects of 15 d-PGJ2 on the multiple organ injury/dysfunction associated with severe endotoxemia.

Design: Prospective, randomized study.

Nitric oxide and the gut injury induced by non-steroidal anti-inflammatory drugs.

Nitric oxide (NO) can protect the gastrointestinal tract from injury, including that provoked by non-steroidal anti-inflammatory drugs (NSAIDs). This protective profile of NO, which predominantly reflects actions on the microcirculation, is mimicked by NO donors. Moreover, the NO-donating agents know as the NO-NSAIDs or CINODs (cyclo-oxygenase-inhibiting nitric oxide-donating drugs) exhibit reduced gut injury in experimental models, which is considered to reflect these local beneficial actions of NO.

Endogenous ligands of PPAR-gamma reduce the liver injury in haemorrhagic shock.

We demonstrate here for the first time that the novel, potent peroxisome proliferator-activated receptor (PPAR)-gamma antagonist GW9662 (2-chloro-5-nitrobenzanilide) augments the degree of liver injury associated with haemorrhagic (haemorrhage for 90 min and resuscitation for 4 h), but not endotoxic (6 mg/kg E. coli endotoxin i.v.

C-myc oncoprotein expression and gene amplification in apocrine metaplasia and apocrine change within sclerosing adenosis of the breast.

Overexpression and/or amplification of c-myc oncogene are known to occur in human breast carcinomas, particularly those of high grade. Apocrine metaplasia (APM) is a common finding within fibrocystic change, and in some cases appears to be associated with an elevated risk of subsequent breast cancer. It has been suggested that apocrine metaplasia within sclerosing adenosis of the breast, also called apocrine adenosis (AA), has a premalignant potential.

Antipyretic therapy.

Antipyresis can be achieved by physical methods such as cooling the body with tepid water or by pharmacological means such as the administration of antipyretic drugs. The nonsteroid anti-inflammatory drugs (NSAIDs) including aspirin, have been used to combat fever since the end of the 19th century and the analgesic antipyretics, from about the same time. Most of the antipyretic analgesics such as acetanilide and phenacetin are no longer used in therapy because of their toxicity.

Successful treatment of childhood-onset Cushing's disease is associated with persistent reduction in growth hormone secretion.

Objective: Although Cushing's disease (CD) rarely occurs in childhood, affected children commonly fail to achieve predicted adult height. Hypercortisolaemia results in reduced GH secretion and GH-deficiency may persist or demonstrate delayed recovery after successful treatment of CD in adults. Whether recovery of spontaneous GH secretion occurs following treatment of childhood CD has yet to be established.

Standard and low-dose IGF-I generation tests and spontaneous growth hormone secretion in children with idiopathic short stature.

Objective: Abnormalities in the GH-IGF-I axis, consistent with GH insensitivity (GHI), have been reported in some patients with idiopathic short stature (ISS). The standard IGF-I generation test (IGFGT) has not demonstrated mild GHI in subjects with ISS. The aim of this study was to investigate the GH-IGF-I axis in ISS by performing standard and novel low-dose IGFGTs together with determination of spontaneous GH secretion.

Chondrocyte death during murine osteoarthritis.

Objective: To determine whether chondrocyte apoptosis occurs during the progression of osteoarthritis (OA) in the STR/ort mouse model of OA.

Methods: Serial cryostat sections were cut (10 microns) through the knee joint of young and old male STR/ort mice and graded for the severity of OA lesions. Age- and sex-matched CBA mice were used as controls.

Neuronal calcium sensor-1 is expressed by dorsal root ganglion cells, is axonally transported to central and peripheral terminals, and is concentrated at nodes.

Neuronal calcium sensor-1 (NCS-1) is a member of the EF-hand calcium-binding protein superfamily which has been implicated in the modulation of a number of neuronal functions. In this study we have examined the expression of NCS-1 in adult rat dorsal root ganglion (DRG) neurons. NCS-1 immunoreactivity was present in most DRG neurons, including many calcitonin gene-related peptide (CGRP) expressing ones.

Intracellular potentiation between two second messenger systems may contribute to cholera toxin induced intestinal secretion in humans.

Background: Cholera toxin (CT) acts on intestinal epithelial cells both directly and indirectly via activation of a secretory neural reflex. The reflex may release acetylcholine as one of its final neurotransmitters. This opens up the possibility of a third mechanism of action for CT, namely a synergistic interaction between two secretagogues acting on different second messenger systems within the epithelial cell.

Ligands of the peroxisome proliferator-activated receptor-gamma and heart failure.

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors that are related to retinoid, steroid and thyroid hormone receptors. The PPAR subfamily comprises of three members, PPAR-alpha, PPAR-beta and PPAR-gamma. There is good evidence that ligands of PPAR-gamma, including certain thiazolinediones, reduce myocardial tissue injury and infarct size.

Expression of vascular endothelial growth factor (VEGF)-C and VEGF-D, and their receptor VEGFR-3, during different stages of cervical carcinogenesis.

Cervical carcinogenesis has well-defined stages of disease progression including three grades of pre-invasive lesions--cervical intraepithelial neoplasia grades 1-3 (CIN 1-3)--and invasive cervical cancer. However, the biological properties of CIN lesions prone to develop invasive disease are not well defined. Recent observations suggest that early invasive disease spreads to regional lymph nodes in several tumour types and that growth factors (VEGF-C and VEGF-D) involved in new lymphatic vessel formation may play a crucial role in this process.