Granulysin expression increases with increasing clinical severity of psoriasis.

BACKGROUND: Psoriasis is an erythematosquamous dermatosis, which has strong expression of antimicrobial peptides (AMPs), imparting a high resistance to lesional skin infection. Granulysin is a proinflammatory AMP that has been found in some infection-resistant dermatoses. AIM: To assess granulysin expression in psoriasis. METHODS: Immunohistochemical expression of granulysin was assessed in lesional skin biopsies taken from 30 patients with psoriasis and 10 normal skin specimens from healthy controls (HCs) matched for age, gender and skin site. Granulysin expression was found to be high in 11 patients (36.7%), moderate in 10 (33.3%) and low in 9 (30%). A highly significant (P = 0.001) difference in granulysin expression between patients with psoriasis and HCs was found. There were also significant differences in granulysin expression between patients with low Psoriasis Area and Severity Index (PASI) (≤ 10) and those with high PASI (> 10) (P = 0.001), and between patients with early-onset (< 40 years of age) and those with late-onset (> 40 years of age) disease (P < 0.04). There was a significant (P = 0.001) positive correlation between granulysin expression and PASI (r = 0.84) and a significant (P = 0.02) negative correlation with age of onset (r = -0.38). Patients with psoriasis hadhigh granulysin expression, which increased with increased clinical severity of the disease. CONCLUSIONS: These findings suggest a role for granulysin in psoriasis pathogenesis, and may explain the triggering effect of skin infection in psoriasis. If the pathogenic role of granulysin is substantiated by further studies, granulysin may be a potential target for immunomodulatory therapy for psoriasis.

Interactions between Trichinella spiralis infection and induced colitis in mice.

Inflammatory bowel disease (IBD) is a chronic relapsing inflammation afflicting any part of the bowel wall as a result of a deregulated and inappropriate immune response. In recent years, experimental and clinical evidence has demonstrated that infection with parasitic worms could protect hosts from IBD. The aims of this study were to determine if the underlying mechanism of the host immune regulation inherent to Trichinella spiralis infection involves Foxp3-expressing regulatory T cells, and to gain insight about time-related interactions between intestinal nematode infection and induced colitis using an experimental model for ulcerative colitis. Mice were experimentally subjected to acetic acid-induced colitis, which was either preceded or followed by T. spiralis infection. Assessment of colitis was done by histopathological examination of the colon and determination of pentraxin 3 levels. Immunohistochemistry was done for demonstration of Foxp3-expressing regulatory T cells in colonic tissues. It was evident that T. spiralis infection ameliorated the severe inflammation induced by acetic acid, evidenced by amelioration of histopathological changes and diminution of pentraxin 3 levels. The amelioration was more pronounced when T. spiralis infection preceded the induction of colitis. Regarding the immunohistochemical staining of regulatory T cells, T. spiralis infection induced recruitment of Foxp3-expressing regulatory T cells to areas of inflammation. In conclusion, T. spiralis regulatory mechanism can improve inflammation of the colon through the 'inflammatory-regulatory' axis. Finally, it would be of great importance to apply these results to the development of new therapeutic approaches for the treatment of ulcerative colitis.

EGR-1 forms a complex with YAP-1 and upregulates Bax expression in irradiated prostate carcinoma cells.

In this study, we investigated the functional role of early growth response-1 (Egr1 gene) in the regulation of radiation-induced clonogenic inhibition and apoptosis in p53 wild-type and mutant prostate cancer cells 22Rv1 and DU145, respectively. 22Rv1 cells were more sensitive to irradiation compared with DU145 cells, and the sensitivity was enhanced by overexpression of EGR-1 in both cells. Dominant-negative EGR-1 mutant (dnEGR-1) or repressor of EGR-1, NGFIA binding protein 1 (NAB1), increased radioresistance of these cells. Significant activation of caspases 3 and 9 and Bcl2-associated X (Bax) with increased poly(ADP-ribose) polymerase (PARP) cleavage and cytochrome c release was observed in radiation-exposed EGR-1 overexpressing cells. Gel shift analysis and chloramphenicol acetyl transferase (CAT) reporter assays indicate that EGR-1 transactivates the promoter of the Bax gene. Interaction of EGR-1 and Yes kinase-associated protein 1 (YAP-1) through the WW domain of YAP-1 enhances the transcriptional activity of EGR-1 on the Bax promoter as shown by chromatin immunoprecipitation and reporter assays. Irradiation of PC3 cell xenografts that were treated with adenoviral EGR-1 showed significant regression in tumor volume. These findings establish the radiation-induced pro-apoptotic action of EGR-1, in a p53-independent manner, by directly transactivating Bax, and prove that alters the B-cell CLL/lymphoma 2 (Bcl-2)/Bax ratio as one of the mechanisms resulting in significant activation of caspases, leading to cell death through the novel interaction of EGR-1 with YAP-1.

Screening for glandular fever in patients with Quinsy: is it necessary?

Quinsy (peritonsillar abscess) is a common emergency seen in otolaryngology practice. These patients are often screened for glandular fever in addition to routine haematological tests. In our unit, we have screened 66 patients with quinsy for glandular fever over a period of 12 months. All these patients were screened for glandular fever by rapid immunoassay. Only one out of 66 patients was tested positive for glandular fever. Due to the extremely low incidence of glandular fever in quinsy patients, we do not see any relevance in screening for glandular fever in quinsy patients. Hence we recommend that routine screening for glandular fever in quinsy patients is an unnecessary invasive investigation for the patients and not cost effective for the hospital.

Leishmaniasis of the nasal cavity: a case report.

Establishing diagnosis of a granulomatous lesion of the nose is often difficult. Here we report a case of granulomatous lesion of the nose caused by Leishmania--an unlikely cause in the UK. The diagnosis and management of the case is discussed here.

HPLC method for amino acids profile in biological fluids and inborn metabolic disorders of aminoacidopathies.

Quantification of total and individual amino acids in biological fluids such as plasma, urine and cerebrospinal fluid has an important diagnostic implication in laboratory medicine. The present paper describes protocols for the assay of total amino acids by modified method based on dinitrophenyl and HPLC profile involving pre-column derivatization with o-pthalaldehyde (OPA) derivatization, respectively. The method, based on the alkylation of-SH groups prior to OPA derivatization of amino acids followed by reverse phase high performance liquid chromatography, provide a comprehensive profile of more than twenty amino acids (including-SH group containing) in a single run lasting about 45 minutes. The present study, apart from establishing the normal profile of amino acids in plasma of Indian sub population, also presents HPLC profile for some of the rare amino acidopathies.

Drosophila heterochromatin protein 1 (HP1)/origin recognition complex (ORC) protein is associated with HP1 and ORC and functions in heterochromatin-induced silencing.

Heterochromatin protein 1 (HP1) is a conserved component of the highly compact chromatin of higher eukaryotic centromeres and telomeres. Cytogenetic experiments in Drosophila have shown that HP1 localization into this chromatin is perturbed in mutants for the origin recognition complex (ORC) 2 subunit. ORC has a multisubunit DNA-binding activity that binds origins of DNA replication where it is required for origin firing. The DNA-binding activity of ORC is also used in the recruitment of the Sir1 protein to silence nucleation sites flanking silent copies of the mating-type genes in Saccharomyces cerevisiae. A fraction of HP1 in the maternally loaded cytoplasm of the early Drosophila embryo is associated with a multiprotein complex containing Drosophila melanogaster ORC subunits. This complex appears to be poised to function in heterochromatin assembly later in embryonic development. Here we report the identification of a novel component of this complex, the HP1/ORC-associated protein. This protein contains similarity to DNA sequence-specific HMG proteins and is shown to bind specific satellite sequences and the telomere-associated sequence in vitro. The protein is shown to have heterochromatic localization in both diploid interphase and mitotic chromosomes and polytene chromosomes. Moreover, the gene encoding HP1/ORC-associated protein was found to display reciprocal dose-dependent variegation modifier phenotypes, similar to those for mutants in HP1 and the ORC 2 subunit.

Expression of p67 (Munc-18) in adult human brain and neuroectodermal tumors of human central nervous system.

p67 (Munc-18), is a neuron-specific protein of 67 kDa, known for its ability to bind with syntaxin and also to copurify with neuronal cdc2-like kinase. Earlier, in situ hybridization and immunocytochemical analysis of rat trigeminal ganglion and hippocampal cells demonstrated the specific localization of p67 in nerve cells and its rich distribution in axons. In the present study, we have looked for p67 expression in normal human brain and various neuroectodermal tumors. Immunohistochemical and Western immunoblot analysis of normal human brain tissue using antibodies against the N- and C-termini of p67 demonstrated the specific localization of this protein in postmitotic neurons but not in glia. Among neuroectodermal tumors, expression of p67 was observed in 100% of the tumors of neuronal origin studied, especially in the mature neuronal cell population of these tumors. Western immunoblot analysis of non-neuronal neuroectodermal tumors failed to reveal the expression of this protein in majority of cases. However, in gliomas and meningiomas, mild cytoplasmic immunohistochemical staining of neoplastic cells was noted in 64.7% and 25% of cases, respectively. Observed mild immunohistochemical staining of these tumors could be due to immunoreactivity to low molecular weight degraded products of p67, as seen on Western blot. The findings suggest that p67, by virtue of its ability to be expressed in postmitotic neurons of adult human brain and in tumors of neuronal origin, may serve as a molecular tool to understand the growth and differentiation of the nervous system in general.