Characterization of Peptide 20–30 of Follicle Stimulating Hormone Receptor as an Antagonist of Receptor Activity: Significance of Charged Residues

We had previously reported the region (20–30) from follicle stimulating hormone receptor as being an immunodominant epitope and the smallest reported peptide capable of inhibiting hormone binding. We now report it to be an effective antagonist of ligand‐induced cAMP signalling as well. The region (20–30) of follicle stimulating hormone receptor has three charged residues, namely, E²², D²⁶ and R²⁹ that are specific to follicle stimulating hormone receptor and are conserved in mammals. This study aimed to verify whether the charged residues contribute to the activity of the follicle stimulating hormone receptor peptide (20–30). This was done using analogs of follicle stimulating hormone receptor peptide (20–30), each having an alanine substitution for a corresponding charged residue. The analog peptides displayed a loss of activity and could not inhibit hormone binding or the subsequent signal transduction. The ability of follicle stimulating hormone receptor peptide (20–30) to bind antipeptide antibodies against follicle stimulating hormone receptor peptide (9–30) was either decreased or abolished with the alanine substituted analog peptides of follicle stimulating hormone receptor peptide (20–30). The loss of function led us to verify whether there was a conformational change as well. CD spectral analysis did not reveal a significant change. These observations indicate that the charged aminoacids present in follicle stimulating hormone receptor peptide (20–30) are crucial for the observed follicle stimulating hormone antagonistic activity. This information could form the basis for the design of novel compounds capable of functioning as follicle stimulating hormone antagonists.     

Traumatic orbital third nerve palsy

We present a case series of three patients who developed acute traumatic orbital third nerve palsies. To our knowledge, reported cases have mainly been localised to the intracranial course of the nerve and often associated with visual impairment. Those in which the orbit is the site of injury are rare. Our case series highlights the importance of careful preoperative assessment of patients with orbital trauma (particularly when there is a coexisting fracture) and the need to assess ocular movements and pupillary reactions to distinguish between a neurogenic and soft tissue injury. Early diagnosis is helpful in deciding on the timing of the operation and enables patients to be given appropriate counselling to make sure that their expectations are realistic.     

The role of competing mechanisms on Lck regulation

Immunologic Research - Lck is a Src-related protein tyrosine kinase that associates with CD4 and CD8 molecules and is essential to T cell development and T cell activation. Regulatory mechanisms of...     

Mandibular Reconstruction: Overview

Introduction

Mandibular reconstruction has changed significantly over the years and continues to evolve with the introduction of newer technologies and techniques.

Purpose

This article reviews the history of oromandibular reconstruction, biomechanics of mandible, summarizes the reconstruction options available for mandible with defect classification, goals in reconstruction, the various donor sites, current reconstructive options, dental rehabilitation and persistent associated problems.

Summary

Oromandibular reconstruction, although a challenge for the head and neck reconstructive surgeon, is now reliable and highly successful with excellent long-term functional and aesthetic outcomes with the use of autogenous bone grafts and current reconstructive options. The ideal reconstruction would provide a solid arch to articulate with the upper jaw, restoring swallowing speech, mastication, and esthetics. Autogenous vascularized bone grafts in combination with microsurgical techniques have revolutionized mandibular reconstruction in oral cancer surgery. Current trends in mandibular reconstruction aim to achieve reestablishment of a viable mandible of proper form and maxillary mandibular relationship while decreasing the need for invasive autogenous graft procurement. However the optimal reconstruction of mandibular defects is still controversial in regards to reconstructive options which include the donor site selection, timing of surgery and method of reconstruction.

     

Vaccine-induced cytokine responses in a guinea pig model of pulmonary tuberculosis

Guinea pigs exposed to very small numbers of virulent tubercle bacilli by the respiratory route develop a disease which mimics many of the important features of the pathogenesis of human tuberculosis (TB), including the expression of strong protective immunity following vaccination with BCG. In order to elucidate the precise immunological mechanisms of vaccine-induced resistance in this model, both mRNA and protein assays for several guinea pig cytokines and chemokines have been developed. The coordinated expression of cytokine and chemokine mRNA and protein was examined in various leukocyte populations and in inflammatory cells and fluid collected following the induction of tuberculous pleurisy in BCG-vaccinated guinea pigs. Real-time RT-PCR assays revealed that the mRNA levels for IFNgamma, TNFalpha, and IL-8 rose over the first few days of TB pleuritis and then declined over the 9 days of the study. Injection of anti-TGFbeta on day 8 following pleurisy induction resulted in significant changes in cytokine mRNA levels and PPD-induced proliferation in pleural effusion lymphocytes taken 24h later. BCG vaccination induced significantly higher levels of bioactive TNFalpha protein in the supernatants of alveolar, peritoneal and splenic cells from BCG-vaccinated guinea pigs cultured in the presence of attenuated or virulent mycobacteria. In sharp contrast, following virulent challenge, all three cell types from BCG-vaccinated guinea pigs produced significantly less TNFalpha. Thus, BCG vaccination appears to modulate the potentially harmful effects of TNFalpha in this model of pulmonary TB. Levels of mRNA for IL-12p40 were upregulated by exposure of infected and uninfected macrophages to recombinant guinea pig (rgp)TNFalpha. The intracellular survival of mycobacteria was enhanced when endogeous TNFalpha activity was neutralized with anti-rgpTNFalpha antiserum. rgp RANTES (CCL5) upregulated mRNA levels for TNFalpha, IL-1beta, MCP-1 (CCL2), and IL-8 (CXCL8) in alveolar and peritoneal macrophages. These results illustrate the profound effects of prior vaccination with BCG on the cytokine and chemokine responses of distinct cell populations in the guinea pig following exposure to attenuated and virulent strains of M. tuberculosis.