Analysis of human papillomavirus prevalence and TP53 polymorphism in head and neck squamous cell carcinomas

Head and neck squamous cell carcinoma is a disease associated with tobacco and alcohol abuse. There is evidence that the oncogenic human papillomavirus (HPV) may also be a risk for upper aerodigestive tract cancers. High-risk HPVs encode two early proteins, E6 and E7, that can bind to p53 and pRb, respectively, and induce its degradation or inactivation. The TP53 gene has a single polymorphism at codon 72 of exon 4 that encodes either arginine (Arg) or proline (Pro). The purpose of this study was to evaluate the role of HPV infection and TP53 polymorphism in head and neck cancer. We analyzed 50 tumors, as well swabs of oral mucosa from 142 control individuals, with a polymerase chain reaction technique. The prevalence of HPV in controls was 10.6% and in cancer specimens 16%. The frequency distribution of genotypes in controls was 50% Arg/Arg, 43% Arg/Pro and 7% Pro/Pro; in tumors, it was 52% Arg/Arg, 32% Arg/Pro, and 16% Pro/Pro. Contrary to the results of some studies on cervical cancer, no association between any TP53 genotype or allele and the development of head and neck cancer was observed, regardless of HPV status, except for the Pro/Pro genotype, which is associated with the absence of HPV. The arginine allele appears to protect against head and neck cancers. Also, the data showed that HPV infection results in no increased risk of developing head and neck tumors.     

Reversal or reduction of glutamate and GABA transport in CNS pathology and therapy

A dysfunction of amino acid neurotransmitter transporters occurs in a number of central nervous system disorders, including stroke, epilepsy, cerebral palsy and amyotrophic lateral sclerosis. This dysfunction can comprise a reversal of transport direction, leading to the release of neurotransmitter into the extracellular space, or an alteration in transporter expression level. This review analyses the role of glutamate and GABA transporters in the pathogenesis and therapy of a number of acute and chronic neurological disorders.     

Immunohistowax processing, a new fixation and embedding method for light microscopy, which preserves antigen immunoreactivity and morphological structures: visualisation of dendritic cells in peripheral organs

AIMS: To describe a new fixation and embedding method for tissue samples, immunohistowax processing, which preserves both morphology and antigen immunoreactivity, and to use this technique to investigate the role of dendritic cells in the immune response in peripheral tissues. METHODS: This technique was used to stain a population of specialised antigen presenting cells (dendritic cells) that have the unique capacity to sensitise naive T cells, and therefore to induce primary immune responses. The numbers of dendritic cells in peripheral organs of mice either untreated or injected with live Escherichia coli were compared. RESULTS: Numbers of dendritic cells were greatly decreased in heart, kidney, and intestine after the inoculation of bacteria. The numbers of dendritic cells in the lung did not seem to be affected by the injection of E coli. However, staining of lung sections revealed that some monocyte like cells acquired morphological and phenotypic features of dendritic cells, and migrated into blood vessles. CONCLUSIONS: These observations suggest that the injection of bacteria induces the activation of dendritic cells in peripheral organs, where they play the role of sentinels, and/or their movement into lymphoid organs, where T cell priming is likely to occur.     

Cytokines, allergy, and asthma

PURPOSE OF REVIEW: This review examines recent articles on the relationship of cytokines to allergy and asthma with particular emphasis on immune mechanisms involved in disease development in early life. RECENT FINDINGS: It was previously proposed that reduced microbial exposure in early life is responsible for a shift of the Th1/Th2 balance in the immune system towards the proallergenic Th2 response. This Th1/Th2 imbalance results in the clinical expression of allergy and/or asthma. In recent years, accumulating data from mice and humans have identified Th2 cytokines [interleukin (IL)-4, IL-13, and IL-5] as major contributors to allergy and asthma. Interestingly, the Th1 cytokine interferon-gamma has recently been shown to act concurrently with Th2 cytokines in maintaining the chronic inflammatory response in allergic diseases, particularly in asthmatic airways. Most recently, evidence suggests that suppression of T-regulatory cells may contribute to the underlying immune mechanisms involved in allergy and asthma. SUMMARY: An enhanced Th2 immune response and the elaboration of cytokines such as IL-4, IL-13, and IL-5 contribute to the induction of allergy and asthma. Interferon-gamma, a Th1 cytokine, acts in conjunction with Th2 (IL-4, IL-13, and IL-5) in maintaining chronic allergic inflammation. The mechanisms leading to an enhanced Th2 response are still controversial. Th2-dominated immune responses may result from immune suppression of T-regulatory cells as well as Th1 cells. Understanding early-life immune mechanisms responsible for atopic diseases, specifically how cytokines of T-regulatory cells act to balance the Th1 and Th2 immune response, continues to be a fruitful area of research.     

Interaction between KIR3DL1 and HLA-B*57 supertype alleles influences the progression of HIV-1 infection in a Zambian population

KIR and HLA loci are both highly polymorphic, and some HLA class 1 products bind and trigger cell-surface receptors specified by KIR genes. We examined whether KIR genes act in concert with HLA-B locus to control HIV-1 infection in a sample of Zambian patients. DNA samples from 88 Zambian patients with HIV-1 were examined. Patients were classified as either slow progressors (SP; n = 54) or rapid progressors (RP; n = 34) to AIDS. All were typed for HLA-B and KIR genes. Our results reveal an association between B*57 supertype (B*57s, which includes B*57 and B*58 alleles) and delayed progression to AIDS (p = 0.0007 by pc = 0.015; OR = 5.25). We also observed an increase incidence of Bw4-I80 in patients with slow progression (p = 0.001 by pc = 0.003, OR = 5). This increase was found to be secondary to B*57s. The presence of both KIR3DL1 and B*57S has a significant effect on progression to AIDS (p = 0.0008; OR = 5.61). B*57s genotypes with another HLA-B allele different from those in the trans position, which also had a specificity different to Bw4-I80 (Bw4-T80 or Bw6), was also greater in the SP than in the RP group (p = 0.00003; OR = 10.11). The presence of the inhibitory allele KIR3DL1 in combination with the HLA-B*57s alleles that contain the Bw4-I80 epitope, has a highly protective effect against progression to AIDS in Zambian patients.     

Twenty-four hour leukocyte adherence inhibition test in thyroid cancer patients

The effect of TG cell depletion taking place during 24 hour incubation on the leukocyte adherence inhibition phenomenon was investigated in patients suffering from cancer of the thyroid and healthy volunteers. The depletion coincided with the increase of the adherence inhibition if PPD was used as antigen in both groups, but the reaction to the tumour associated antigen could not be brought into relation with the depletion of TG cells.