Chondrosarcoma of the arytenoids- a rare laryngeal malignancy

Even though laryngeal malignancies are the most frequent primary malignancies of the upper aero digestive tract except for oral cavity cancers, laryngeal chondrosarcomas are rare tumors, constituting less than 1% of all laryngeal tumors. We present a rare case of chondrosarcoma arising from the right arytenoid cartilage with sub glottic extension. The mode of presentation and management of the case is presented along with a review of the literature.     

Neurofibroma of the external ear - a case report

Neurofibromas are relatively common tumours of the nervous system, but only a few cases involving the external ear have been reported. We are reporting here a case of a 20-year-old female with neurofibroma of the external ear. The primary complaint was cosmetic deformity. There was partial occlusion of the external auditory canal. The swelling was excised by postauricular approach. Surgery resulted in an excellent functional and cosmetic outcome.     

Implication of BRCA2 -26G>A 5' untranslated region polymorphism in susceptibility to sporadic breast cancer and its modulation by p53 codon 72 Arg>Pro polymorphism

Introduction  

The absence of mutation or promoter hypermethylation in the BRCA2 gene in the majority of breast cancer cases has indicated alternative ways of its involvement, deregulated expression being one possibility. We show how a polymorphism in the 5' untranslated region (UTR) of BRCA2 can serve as one such factor. Based on the hypothesis that variants of genes involved in the same pathway can influence the risk provided for breast cancer, the status of p53 codon 72 polymorphism was also investigated and a possible interaction between the polymorphisms was examined.     

Combining off pump coronary artery bypass with mitral valve replacement

Background Conventional approach to combined coronary artery bypass grafting (CABG) and mitral valve replacement (MVR) is associated with longer cardiopulmonary bypass (CPB) and aortic cross clamp (ACC) time leading to high operative risk. Methods We conducted a retrospective review of nine consecutive patients undergoing coronary artery bypass grafting/mitral valve replacement combining the off pump technique with cardioplegic arrest. Elective intra aortic balloon pump (IABP) support was instituted in all cases. CABG was first done in all cases without cardiopulmonary bypass support. Mitral valve replacement was then done using conventional cardiopulmonary bypass and cardioplegic arrest using the superior septal approach. Results Nine consecutive patients underwent coronary artery bypass grafting with mitral valve replacement including three patients with acute myocardial infarction. Preoperative echocardiogram revealed a mean ejection fraction (EF) of 38.4 ± 6.0%. Intra aortic balloon pump was inserted in all patients preoperatively. The average number of grafts were 3.0 ± 0.7. Eight patients received bioprosthetic valve while one patient received mechanical prosthesis. The average length of stay in intensive care unit was 3.3 ± 0.5 days. There was no mortality. One patient had superficial wound infection. Conclusion The data suggest that the combined technique (off pump coronary artery bypass grafting and conventional mitral valve replacement) is a safe method to perform coronary artery bypass grafting/mitral valve replacement with minimal morbidity and mortality.     

RNASEK is required for internalization of diverse acid-dependent viruses

Viruses must gain entry into cells to establish infection. In general, viruses enter either at the plasma membrane or from intracellular endosomal compartments. Viruses that use endosomal pathways are dependent on the cellular factors that control this process; however, these genes have proven to be essential for endogenous cargo uptake, and thus are of limited value for therapeutic intervention. The identification of genes that are selectively required for viral uptake would make appealing drug targets, as their inhibition would block an early step in the life cycle of diverse viruses. At this time, we lack pan-antiviral therapeutics, in part because of our lack of knowledge of such cellular factors. RNAi screening has begun to reveal previously unknown genes that play roles in viral infection. We identified dRNASEK in two genome-wide RNAi screens performed in Drosophila cells against West Nile and Rift Valley Fever viruses. Here we found that ribonuclease kappa (RNASEK) is essential for the infection of human cells by divergent and unrelated positive- and negative-strand-enveloped viruses from the Flaviviridae, Togaviridae, Bunyaviridae, and Orthomyxoviridae families that all enter cells from endosomal compartments. In contrast, RNASEK was dispensable for viruses, including parainfluenza virus 5 and Coxsackie B virus, that enter at the plasma membrane. RNASEK is dispensable for attachment but is required for uptake of these acid-dependent viruses. Furthermore, this requirement appears specific, as general endocytic uptake of transferrin is unaffected in RNASEK-depleted cells. Therefore, RNASEK is a potential host cell Achilles’ heel for viral infection.Viral pathogens are quite diverse in their replication strategies; however, all viruses must enter cells to initiate their replication cycles. The first step involves binding of virus particles to the cell surface. Such interactions can involve attachment factors, which have low affinity but concentrate viruses on the surface of cells, and receptors that intricately interact with viral envelope glycoproteins, which, in addition to binding, promote other aspects of infection such as internalization. Although a plethora of receptors and pathways can be used, most viruses take advantage of the cellular endocytic machinery and penetrate from within the cytosol (reviewed in refs. 1–3). Clathrin-mediated endocytosis, macropinocytosis, and caveolin-mediated endocytosis are the best-studied forms of uptake used by viruses. Clathrin-mediated endocytosis is the most common mechanism used by small viruses, as clathrin-coated vesicles have a diameter of 60–200 nm and can be enlarged to fit even larger particles (4, 5). This pathway is constitutive on most cells, and some viruses use preexisting clathrin-coated pits for entry (e.g., dengue virus), whereas others induce the formation of these structures (e.g., influenza virus) (6, 7). Macropinocytosis is an actin-dependent endocytic process for the nonselective uptake of nutrients in response to receptor engagement. It is the predominant pathway for many larger viruses, including vaccinia virus, but is also used by others, including influenza virus under some conditions (8–10). It also remains unclear which pathways are used by some viruses, including Rift Valley Fever virus (RVFV) (11–13).The molecular mechanisms involved in these uptake mechanisms are complex and rely on key molecules and organelles that are essential for cellular viability, as these uptake mechanisms bring nutrients and other metabolites into the cytosol for cellular growth and survival. Indeed, these processes and proteins involved are highly conserved from yeast to humans (14, 15). Depending on the virus entry requirements, some viruses fuse within early endosomal vesicles, whereas others traffic to more acidic compartments or macropinosomes for entry. Because many viruses are dependent on these endosomal trafficking pathways for entry, much effort has been made in identifying the specific cellular genes required for viral entry (16). Therapeutics targeting entry are appealing because it is the first step in the infection cycle, and many viruses use common pathways; thus, inhibition may be broadly antiviral, rather than active against only a specific virus. Furthermore, many viruses have high mutation rates and rapidly evolve resistance to therapeutics targeting virally encoded genes. Conversely, therapeutics against host encoded targets would likely be more difficult for the virus to evade.Recent advances in functional genomic technologies have facilitated the use of unbiased genome-wide RNAi screens to identify cellular genes required for viral infection (17). Such approaches allow for the discovery of otherwise unknown genes that play essential roles in infection. We recently performed such screens in insect cells against two disparate insect-borne human pathogens: the flavivirus West Nile virus (WNV) and the bunyavirus RVFV (18, 19). These are both arthropod-borne human pathogens for which there are no vaccines or therapeutics. Furthermore, these viruses are quite divergent: WNV is a flavivirus that is a globally important cause of encephalitis (20), and RVFV is a bunyavirus that causes significant morbidity and mortality in livestock and humans in Africa (21). In our screens, there were only three genes that promoted infection by both viruses: dRAB5, dSTX7, and dRNASEK (CG40127). The functions of RAB5 and STX7 have been described, but little is known about ribonuclease kappa (RNASEK). Both RAB5 and STX7 are involved in endosomal transport and have roles in viral entry (22, 23). Both WNV and RVFV are enveloped RNA viruses that require an acidic compartment for entry (12, 13, 24). RNASEK is a single-copy, 137-aa protein conserved from insects to humans (25–27) with an unknown function. We set out to determine the role of RNASEK in viral infection and found that RNASEK is required for internalization of a diverse panel of viruses of medical concern.     

Subtle structural variation in azine/imine derivatives controls Zn2+ sensitivity: ESIPT-CHEF combination for nano-molar detection of Zn2+ with DFT support

Excited-state intra-molecular proton transfer (ESIPT)-active imine and azine derivatives, structurally characterised by XRD, and denoted L1, L2, L3 and L4, possess weak fluorescence. The interaction of these probes with Zn²⁺ turns ON the fluorescence to allow its nano-molar detection. Among the four ESIPT-active molecules, L2, L3 and L4 are bis-imine derivatives while L1 is a mono-imine derivative. Among the three bis-imine derivatives, one is symmetric (L3) while L2 and L4 are unsymmetrical. The lowest detection limits (DL) of L1, L2, L3 and L4 for Zn²⁺ are 32.66 nM, 36.16 nM, 15.20 nM and 33.50 nM respectively. All the probes bind Zn²⁺ (10⁵ M⁻¹ order) strongly. Computational studies explore the orbital level interactions responsible for the associated photo-physical processes.

Single crystal X-ray structurally characterised ESIPT-active weakly fluorescent imine and azine derivatives undergo Zn²⁺ assisted turn ON fluorescence.     

Double-blind, placebo-controlled, randomised phase II trial of IH636 grape seed proanthocyanidin extract (GSPE) in patients with radiation-induced breast induration.

BACKGROUND AND PURPOSE: Tissue hardness (induration), pain and tenderness are common late adverse effects of curative radiotherapy for early breast cancer. The purpose of this study was to test the efficacy of IH636 grape seed proanthocyanidin extract (GSPE) in patients with tissue induration after high-dose radiotherapy for early breast cancer in a double-blind placebo-controlled randomised phase II trial. PATIENTS AND METHODS: Sixty-six eligible research volunteers with moderate or marked breast induration at a mean 10.8 years since radiotherapy for early breast cancer were randomised to active drug (n = 44) or placebo (n = 22). All patients were given grape seed proanthocyanidin extract (GSPE) 100 mg three times a day orally, or corresponding placebo capsules, for 6 months. The primary endpoint was percentage change in surface area (cm(2)) of palpable breast induration measured at the skin surface 12 months after randomisation. Secondary endpoints included change in photographic breast appearance and patient self-assessment of breast hardness, pain and tenderness. RESULTS: At 12 months post-randomisation, > or =50% reduction in surface area (cm(2)) of breast induration was recorded in 13/44 (29.5%) GSPE and 6/22 (27%) placebo group patients (NS). At 12 months post-randomisation, there was no significant difference between treatment and control groups in terms of external assessments of tissue hardness, breast appearance or patient self-assessments of breast hardness, pain or tenderness. CONCLUSIONS: The study failed to show efficacy of orally-administered GSPE in patients with breast induration following radiotherapy for breast cancer.     

Scapulothoracic dissociation--A case report

Scapulothoracic dissociation (SCTD) is a rare clinical entity with fewer than 70 cases reported in English literature. The mechanism of injury is severe rotational force, which causes disruption of the shoulder girdle from the rest of chest wall. Frequently, SCTD produces massive blood loss as it involves major fractures of the upper extremity, disruption of muscle, brachial plexus, and vascular damage. This case report demonstrates classical radiological findings of SCTD with brachial plexus injury but with no associated vascular damage.