Histologic Remission (NANCY Index) is Superior to Endoscopic Mucosal Healing in Predicting Relapse Free Survival in Patients With Ulcerative Colitis in Clinical and Endoscopic Remission.

Background: Histologic activity is recognized as an important predictor of relapse in ulcerative colitis (UC) patients. Current treatment targets aim at mucosal healing; however, many patients continue to have histologic activity.

Goals: The aim was to assess histologic activity using the validated Nancy histologic index (NHI) score as a predictor of future relapse amongst UC patients in endoscopic and clinical remission.

Autophagy efficacy and vitamin D status: Population effects.

Toll-like receptor (TLR) 2/1 signalling is linked to autophagy through transcriptional actions of the 1,25-dihydroxyvitamin D (1,25(OH)D)-vitamin D receptor (VDR) complex. Population-specific effects have been reported for TLR2/1-VDR signalling. We hypothesized that population effects extend to autophagy and are influenced by vitamin D status.

Cdx-2 polymorphism in the vitamin D receptor gene (VDR) marks VDR expression in monocyte/macrophages through VDR promoter methylation.

Caudal-type homeobox protein 2 (CDX-2) is an intestine-specific transcription factor (TF), with a polymorphic binding site (Cdx-2, rs11568820, A/G) in the vitamin D receptor gene (VDR). The molecular mechanism underlying Cdx-2 association with conditions like osteoporosis, which depends on intestinal VDR expression and calcium absorption, is believed to be due to higher affinity of CDX-2 for the ancestral A allele compared to the G allele. However, it is unclear why the polymorphism is associated with diseases like tuberculosis, which is dependent on VDR expression in immune cells that do not express CDX-2.

Methylation of the Vitamin D Receptor (VDR) Gene, Together with Genetic Variation, Race, and Environment Influence the Signaling Efficacy of the Toll-Like Receptor 2/1-VDR Pathway.

Background: The disparity in prevalence of infectious diseases across the globe is common knowledge. Vitamin D receptor (VDR)-mediated toll-like receptor (TLR) 2/1 signaling produces antimicrobial peptides, which is critical as a first line of defense in innate immunity. Numerous studies disclosed the independent role of genetic polymorphisms in this pathway, vitamin D status or season and more recently epigenetics, as factors contributing to infectious disease predisposition.

Vitamin D Status and Its Consequences for Health in South Africa.

In this review, reports were retrieved in which vitamin D status, as assessed by serum 25-hydroxyvitamin D [25(OH)D] levels, was measured in South African population groups with varied skin colours and ethnicities. Healthy children and adults were generally vitamin D-sufficient [25(OH)D level >50 nmol/L] but the majority of those aged above 65 years were deficient. A major role for exposure to solar ultraviolet radiation (UVR) in determining 25(OH)D levels was apparent, with the dietary contribution being minor.

Vitamin D Status in South Africa and Tuberculosis.

According to the World Health Organisation South Africa has the third highest tuberculosis (TB) incidence in the world, with an estimated 60 % incident cases having both TB and HIV. The South African National Tuberculosis Association (SANTA) recognized the importance of nutrition in the prevention and management of TB by including feeding schemes in community outreach programs. Vitamin D enhances innate immunity against mycobacterial infection through the antimicrobial peptide, cathelicidin.

Regulation of the vitamin D receptor gene by environment, genetics and epigenetics.

The vitamin D receptor (VDR) plays a pivotal role as a mediator of 1α,25(OH)2D signalling. Besides its role in calcium homeostasis, ligand- bound VDR supports immunity and cell cycle control. While VDR regulates numerous genes across the genome, much remains to be learned about the regulation of the VDR gene itself.

Heat shock, with recovery, promotes protection of Nicotiana tabacum during subsequent exposure to Ralstonia solanacearum.

Host-pathogen interactions in plants are complex and potentially influenced by heat shock/stress (HS). Host HS proteins (HSPs) induced prior to bacterial exposure may facilitate the folding of newly synthesized defense proteins and promote incompatible host-pathogen interactions. We hypothesized that a non-lethal HS, with recovery, promotes protection of Nicotiana tabacum during subsequent exposure to avirulent soilborne necrotrophic pathogen Ralstonia solanacearum.

Vitamin D Receptor Gene Expression and Function in a South African Population: Ethnicity, Vitamin D and FokI.

Polymorphisms of the vitamin D receptor gene (VDR) have been associated inconsistently with various diseases, across populations of diverse origin. The T(f) allele of the functional SNP FokI, in exon 2 of VDR, results in a longer vitamin D receptor protein (VDR) isoform, proposed to be less active. Genetic association of VDR with disease is likely confounded by ethnicity and environmental factors such as plasma 25(OH)D3 status.

Vitamin D receptor gene methylation is associated with ethnicity, tuberculosis, and TaqI polymorphism.

The Vitamin D receptor (VDR) gene encodes a transcription factor which, on activation by vitamin D, modulates diverse biologic processes, including calcium homeostasis and immune function. Genetic variation involving VDR shows striking differences in allele frequency between populations and has been associated with disease susceptibility, including tuberculosis and autoimmunity, although results have often been conflicting. We hypothesized that methylation of VDR may be population specific and that the combination of differential methylation and genetic variation may characterize tuberculosis (TB) predisposition.

Langerhans cell density and high-grade vulvar intraepithelial neoplasia in women with human immunodeficiency virus infection.

Background: Decreased numbers of Langerhans cells (LCs) in the cervix of human immunodeficiency virus (HIV)-infected women are believed to contribute to the progression of human papilloma virus (HPV)-related squamous intraepithelial lesions. However, this impairment of local immunity has not been well studied in the vulva. The objective of this study was to compare the S100+ LC density in high-grade vulvar intraepithelial neoplasia (VIN) in HIV-positive and HIV-negative women.

Association of HLA-DR, -DQ, and vitamin D receptor alleles and haplotypes with tuberculosis in the Venda of South Africa.

The vitamin D receptor (VDR) and the human leukocyte antigen (HLA) class II complex affect innate and/or adaptive immunity against Mycobacterium tuberculosis. HLA-DRB1, HLA-DQB1, and VDR gene (VDR) polymorphisms were previously associated with tuberculosis (TB) and are here investigated as candidates for TB susceptibility in the Venda population of South Africa. Genomic DNA from 95 patients with pulmonary tuberculosis (PTB) and 117 ethnically matched, healthy controls were typed for HLA-DRB1, DRB3, DRB4, DRB5, DQB1, and VDR polymorphisms FokI, BsmI, ApaI, and TaqI using polymerase chain reaction-sequence specific primers (PCR-SSP).

HLA class II disease associations in southern Africa.

Southern Africa harbors several population groups representing a diversity of gene pool origins. This provides a unique opportunity to study genetic disease predisposition in these populations against a common environmental background. Human leukocyte antigen (HLA) association studies of these populations could improve knowledge on inter-population variation and HLA-related disease susceptibility.

Iron and iron chelating agents modulate Mycobacterium tuberculosis growth and monocyte-macrophage viability and effector functions.

Excess of iron promotes Mycobacterium tuberculosis infection, its replication and progression to clinical disease and death from tuberculosis. Chelation of iron may reduce M. tuberculosis replication, restore host defence mechanisms and it could constitute an application in the prevention and treatment strategies where both iron overload and tuberculosis are prevalent.

A rapid and reliable flow cytometric method for determining Hsp70 levels in tobacco protoplasts.

Current methods to determine heat shock protein (Hsp) synthesis or accumulation in plant cells, such as Western blotting and biometabolic labelling are either indirectly quantitative, labour-intensive or biohazardous. An optimal flow cytometric protocol was developed to measure the intracellular Hsp70/Hsc70 levels in tobacco protoplasts. After heat treatments, protoplasts were fixed in 2% paraformaldehyde-phosphate-buffered saline and dehydrated overnight in methyl cellusolve, followed by permeabilization with Triton X-100 (0.

Iron overload and tuberculosis: a case for iron chelation therapy.

Elevated levels of iron impair immune defence mechanisms, and specifically the macrophage function of innate immunity. Iron enhances Mycobacterium tuberculosis infection, M. tuberculosis replication, progression to clinical disease and death from tuberculosis (TB).

Vitamin D receptor polymorphisms and susceptibility to tuberculosis in West Africa: a case-control and family study.

Vitamin D receptor (VDR) gene polymorphisms have been implicated in susceptibility to tuberculosis (TB), but reports have been inconsistent. We genotyped the VDR single-nucleotide polymorphisms (SNPs) FokI, BsmI, ApaI, and TaqI in 1139 case patients and control subjects and 382 families from The Gambia, Guinea, and Guinea-Bissau. The transmission-disequilibrium test on family data showed a significant global association of TB with SNP combinations FokI-BsmI-ApaI-TaqI and FokI-ApaI that were driven by the increased transmission to affected offspring of the FokI F and ApaI A alleles in combination.

Salicylic acid-mediated potentiation of Hsp70 induction correlates with reduced apoptosis in tobacco protoplasts.

Background: Elevated temperatures jeopardize plant disease resistance, as mediated by salicylic acid (SA). SA potentiates heat-induced expression of the 70-kDa heat shock protein (Hsp70) in tomato cells. In mammalian cells, Hsp70 suppresses apoptosis.

Assessment of a simple, non-toxic Alamar blue cell survival assay to monitor tomato cell viability.

The Alamar Blue (AB) assay, which incorporates a medox indicator that changes colour or fluorescence in response to metabolic activity, is commonly used to assess quantitatively the viability and/or proliferation of mammalian cells and micro-organisms. In this study the AB assay was adapted for the determination of the viability of plant cells. Cell suspension cultures of tomato, Lycopersicon esculentum, L.

Differential basal synthesis of Hsp70/Hsc70 contributes to interindividual variation in Hsp70/Hsc70 inducibility.

The source of intraspecies variation in the expression of heat shock proteins (HSPs) remains unresolved but could shed light on differential stress tolerance and disease susceptibility. This study investigated the influence of variable basal HSP synthesis on differential inducibility of HSP synthesis. Basal and heat-induced synthesis of the major HSP families in peripheral blood monocytes from healthy donors (n = 42) were analysed using biometabolic labelling and densitometry.

Salicylic acid influences Hsp70/Hsc70 expression in Lycopersicon esculentum: dose- and time-dependent induction or potentiation.

Overexpression of heat-shock (HS) proteins (HSP) is often sufficient to protect against lethal environmental stresses. Anti-inflammatory salicylates potentiate the induction of the 70 kDa HSP (Hsp70) in mammals in response to HS and enhance thermotolerance. In plants, salicylic acid (SA) is a natural signalling molecule, mediating resistance in response to avirulent pathogens.

Differential regulation and expression of stress proteins and ferritin in human monocytes.

We investigated the regulation and expression of ferritin in human cells by exposing peripheral blood monocytes (PBM) to heat shock (HS), opsonized sheep red blood cells (RBC), and iron. Iron induced ferritin but had no effect on stress protein expression. HS did not induce ferritin, indicating that ferritin is not a heat shock protein (HSP), at least in human PBM.

Stress symposium in Johannesburg: plants versus humans.

On 18 February 1998, a 'Stress symposium' was held at the Rand Afrikaans University (RAU) in Johannesburg, South Africa. The meeting brought together people from both the plant and the human oxidative stress field, which was exemplified by a talk entitled 'Heat shock proteins in host-pathogen interactions: plants versus humans'. There were moments when it appeared as if the main difference between plants and humans was, as sung by Julos Beaucarne, that 'the human plant is the only one to be able to water itself.

Effects of iron deprivation on the pathology and stress protein expression in murine X-linked muscular dystrophy.

Duchenne muscular dystrophy (DMD) is caused by dystrophin deficiency, which results in muscle necrosis and the upregulation of heat shock/stress proteins (HSP). We hypothesized that reactive oxygen species, and in particular hydroxyl radicals (.OH), participate in muscle necrosis and HSP expression.