Concentration and time-dependent amyloidogenic characteristics of intrinsically disordered N-terminal region of Saccharomyces cerevisiae Stm1.

Saccharomyces cerevisiae Stm1 protein is a ribosomal association factor, which plays an important role in preserving ribosomes in a nutrition-deprived environment. It is also shown to take part in apoptosis-like cell death. Stm1 N-terminal region (Stm1_N1-113) is shown to recognize purine motif DNA triplex and G-quadruplex. Circular dichroism (CD) spectra of Stm1_N1-113 (enriched in positively-charged Lysine and Arginine; negatively-charged Aspartate; polar-uncharged Threonine, Asparagine, Proline and Serine; hydrophobic Alanine, Valine, and Glycine) collected after 0 and 24 h indicate that the protein assumes beta-sheet conformation at the higher concentrations in contrast to intrinsically disordered conformation seen for its monomeric form found in the crystal structure. Thioflavin-T kinetics experiments indicate that the lag phase is influenced by the salt concentration. Atomic force microscopy (AFM) images collected for a variety of Stm1_N1-113 concentrations (in the range of 1-400 µM) in the presence of 150 mM NaCl at 0, 24, and 48 h indicate a threshold concentration requirement to observe the time-dependent amyloid formation. This is prominent seen at the physiological salt concentration of 150 mM NaCl with the fibrillation observed for 400 µM concentration at 48 h, whereas oligomerization or proto-fibrillation is seen for the other concentrations. Such concentration-dependent fibrillation of Stm1_N1-113 explains that amyloid fibrils formed during the overexpression of Stm1_N1-113 may act as a molecular device to trigger apoptosis-like cell death.

Durapain in symptomatic treatment of severe acute pain: a post-marketing, prospective, multicenter, observational study - PRIME study.

OBJECTIVE: To assess the effectiveness, overall tolerability, and gastrointestinal (GI) tolerability of Durapain (fixed dose combination of tramadol hydrochloride immediate release [50 mg] and diclofenac sodium sustained release [75 mg]) in symptomatic treatment of severe acute pain in physician's routine clinical practice. MATERIALS AND METHODS: In this prospective, multicenter, observational, post-marketing study, adult patients (aged 18-60 years) with severe acute pain were treated with tramadol hydrochloride/diclofenac sodium as per approved prescribing information. Evaluation was done at base-line, day 2, and day 5. Primary end point was pain intensity difference from baseline to day 5. RESULTS: A total of 351 patients (mean age 44.2 years; male 43%; female 57%) were included. The mean pain score was reduced from 9.2±1.09 at baseline to 2.8±1.73 at day 5 (p<0.0001). The number of patients with severe intensity of pain reduced from 100% at baseline to 18.3% at day 2 and 6.96% at day 5. According to the patient assessment, 68.36% of patients reported tolerability as "very good to good", whereas according to physician's assessment, "very good to good" tolerability was reported in 68.27% of patients. Five (1.43 %) patients discontinued the study because of adverse drug reaction. Five patients developed nine GI-related events of moderate intensity. Two patients developed three adverse reactions (burning sensation in urine, giddiness, and urine retention) other than GI events. No serious adverse drug reactions were reported during the study period. CONCLUSION: Tramadol hydrochloride/diclofenac sodium is an effective and well-tolerated treatment in Indian patients with severe acute pain. Treatment with tramadol hydrochloride/diclofenac sodium provides significant pain relief on day 2 and maintained until day 5 without any serious adverse reactions.

Cysticercus antibodies and antigens in serum from blood donors from Pondicherry, India.

The aim of the present study was to screen the serum of blood donors, which are apparently healthy and residing in Pondicherry or its neighboring districts of Tamil Nadu State, for specific detection of Cysticercus antigens and antibodies. A total of 216 blood samples were collected from blood donors at the Central Blood Bank, JIPMER Hospital, Pondicherry, India during January and February 2004. Enzyme-linked immunosorbent assay (ELISA) was used to demonstrate anti-Cysticercus antibodies and the Co-agglutination (CoA) was used to detect antigen in sera. 14 (6.48 %) males were positive for either anti-Cysticercus antibodies or antigens. Of these eight sera were positive for anti-Cysticercus antibodies and six were positive for antigens. Results of the present study show that serum Cysticercus antigen detection may be a useful adjunct to antibody testing for seroprevalence studies of cysticercosis in the community. The present study is the first kind of study, carried out to determine both cysticercal antibodies as well as antigens in the serum samples collected from the healthy blood donors.

Cysticercus antibodies and antigens in serum from blood donors from Pondicherry, India

O objetivo do presente estudo foi examinar o soro de doadores de sangue que são aparentemente saudáveis e residentes em Pondicherry ou seus distritos vizinhos do estado de Tamil Nadu, para a detecção específica dos antígenos e anticorpos de Cysticercus. Um total de 216 amostras de sangue foram coletadas de doadores de sangue do "Central Blood Bank, JIPMER Hospital", Pondicherry, Índia, durante janeiro e fevereiro de 2004. ELISA foi usado para demonstrar anticorpos anti-Cysticercus e co-aglutinação (CoA) foi utilizada para detectar antígenos no soro. 14 (6.48%) homens foram positivos para antígenos e anticorpos anti-Cysticercus. Destes, oito soros foram positivos para anticorpos anti-Cysticercus e seis positivos para antígenos. Os resultados do presente estudo mostram que a detecção de antígenos de Cysticercus no soro pode ser um adjunto útil para o teste de anticorpos para estudos de soroprevalência de cisticercose na comunidade. O presente estudo é o primeiro do tipo, realizado para determinar tanto anticorpos de Cysticercus como antígenos nas amostras de soro coletadas de doadores de sangue aparentemente saudáveis.

Functional laryngeal surgery - critical determinants of successful rehabilitation.

This study addresses the functional outcome and rehabilitative process in 30 partial laryngectomies carried out for laryngeal (22) und hypoorpharyngeal (8) cancers at the department of H/N Surgery, The kidwai Memorial Institute of Oncology. Bangalore, India from 1985-1995, Special emphasis is directed towards post-surgical convalescence after various partial laryngeetomy techniques which include 6 vertical laryngectomies (V L / VPL). 17 supraglottic laryngectomies (SG L), and 7 supracricoid laryngectomies with Cricohyoidepexy (CHP). Rehabilitative success was measured with respect to the ease of dccannulation, resumption of normal deglutition and speech analysis - both objectively using standard speech analytical equipment in a speech laboratory and subjectively using the services of blinded judges to score recorded speech of patients. The speech analysis indicate that past SGL speech was the superior most followed by V L and C H P in that order. Aspiration was deemed as minimal and inconsequential after V L/VPL followed by CHP;and SGL, in the order of severity;the extended modifications to resect the arytenoid and / or basE of tongue and / or piriform fossa faring worse than classic standard technique.

A lambda 3' enhancer drives active and untemplated somatic hypermutation of a lambda 1 transgene.

Somatic hypermutation is a highly regulated process that targets mutations to the rearranged Ig genes. Little is known about the cis-elements required for somatic hypermutation of the lambda light chain gene. We have studied somatic hypermutation of a rearranged lambda 1 transgene under the control of either a lambda 2-4 or kappa 3' enhancer. The mutations in the transgenes were analyzed by sequencing DNA amplified from hypermutating Peyer's patch B cells. The results indicate that the lambda 3' enhancer can drive active hypermutation of a lambda 1 transgene in Peyer's patch cells. The lambda 1 transgene under analysis carried two marked V lambda 2 genes immediately upstream that could serve as sequence donors in possible gene conversion events. There was no evidence of sequence transfer to the hypermutated lambda 1 gene, suggesting that gene conversion is not a major mechanism for somatic hypermutation in mice.

Oral facial digital syndrome.

We report a female infant with features suggestive of Oral Facial Digital Syndrome (OFDS) Type I and associated cerebellar anomalies with Dandy-Walker malformation which suggest OFDS Type VI. The phenotypic overlap in this child OFDS type I and TypeVI raises the question as to whether they represent separate genetic entities. This pattern of abnormalities appears to be unique.

Proteoglycan synthesis by normal and neoplastic human transitional epithelial cells.

Metabolically 35S-labeled proteoglycans were isolated from cell-associated matrices and media of confluent cultures of human normal transitional epithelial cells and HCV-29T transitional carcinoma cells. On Sepharose CL-4B columns, the cell-associated proteoglycans synthesized from both cell types separated into three identical size classes, termed CI, CII, and CIII. Normal epithelial cell C-fractions eluted in a 22:34:45 proportion and contained 64%, 64%, and 72% heparan sulfate, whereas corresponding HCV-29T fractions eluted in a 29:11:60 proportion, and contained 91%, 77%, and 70% heparan sulfate, respectively. Medium proteoglycans from normal cells separated into two size classes in a proportion of 6:94 and were composed of 35% and 50% heparan sulfate. HCV-29T medium contained only one size class of proteoglycans consisting of 23% heparan sulfate. The remaining percentages were accounted for by chondroitin/dermatan sulfate. On isopycnic CsCl gradients, proteoglycan fractions from normal cells had buoyant densities that were higher than the corresponding fractions from HCV-29T cells. DEAE-Sephacel chromatography showed that cell and medium associated heparan sulfate from HCV-29T cells was consistently of lower charge density (undersulfated) than that from normal epithelial cells. In contrast, the chondroitin/dermatan sulfate of HCV-29T was of a charge density similar to that of normal cells. These as well as other structural and compositional differences in the proteoglycan may account, at least in part, for the altered behavioral traits of highly invasive carcinoma cells.