Escape from immunotherapy: possible mechanisms that influence tumor regression/progression

Tumor escape is one major obstacle that has to be addressed prior to designing and delivering successful immunotherapy. There is compelling evidence to support the notion that immunogenic tumors, in murine models and cancer patients, can be rejected by the immune system under optimum conditions for activating adaptive and nonadaptive antitumor immune responses. Despite this capability, a large number of tumors continue to grow and evade recognition and/or destruction by the immune system. The limited success in current immunotherapeutic strategies may be due to a variety of reasons: failure of effector cells to compete with the growing tumor burden, production of humoral factors by tumors that locally block cytotoxicity, antigen/MHC loss, T-cell dysfunction, production of suppressor T cells—to name but a few causes for therapeutic ineffectiveness for the particular malignancy being treated. To optimize immunotherapy strategies, correction of immune-activating signals, eradication of inhibitory factors, and the evasion from newly developed immunoresistant tumor phenotypes need to be simultaneously considered

Hygrothermal performance of building envelopes in the tropics under operative conditions : condensation and mould growth risk appraisal

Poor indoor hygrothermal performance increases the risk of indoor moisture problems and deterioration due to mould growth, corrosion and damage to archival materials. Hence, proper control of indoor thermohygric intensity abates indoor moisture and its associated problems. This paper presents the results of envelopes hygrothermal performance assessments in a hot and humid climate building with varying operational profile between adjacent spaces. The case-studied building runs on 24hrs cooling mode in one part against natural and/or mechanical supply-exhaust fan means on the other. In-situ experiments were combined with hygrothermal analytical methods to assess the envelope thermal quality together with the operative conditions against condensation and mould growth risks. The results show that the building is overcooled leading to poor envelope hygrothermal performance with associated condensation and mould growth problems on non-airconditioned sides of the envelopes

Purification and biochemical characterization of a Ca2+- independent, thermostable and acidophilic α-amylase from Bacillus sp. RM16

Bacillus sp. RM16 was isolated from a hot spring in Karachi and screened for the production of α- amylase. The enzyme was obtained after 72 h cultivation of strain in Luria broth containing 1% starch (w/v). Enzyme Amy RM16 was purified to electrophoretic homogeneity by a series of sequential steps including precipitation with ammonium sulfate at 70% saturation, Q-Sepharose, Phenyl Sepharose and reversed phase chromatography. The purified enzyme is made up of a single polypeptide chain of 66 kDa as established by a combination of SDS-PAGE and zymographic analysis. In our experimental conditions, a total yield of 1.35% with specific activity of 6380U/mg was obtained providing 17 fold final purification of the enzyme. Biochemical characterization of the Amy RM16 such as optimum temperature and pH, substrate specificity and enzymatic susceptibilities towards different metal ions and inhibitors were also performed. Results of these studies revealed that, the enzyme is active at wide temperature range with optimum activity at 80°C and retained 85% of the activity for 3 h at 50°C and around 50% of remaining activity for 1 h at 80°C. The enzyme showed optimum activity at pH 5.0. On the other hand, Ca+2 and EDTA (1 to 5 mM) did not significantly affect the enzyme activity. The main substrate for the enzyme was found to be starch but it could also hydrolyze raw starch, dextrin, γ-cyclodextrin and pullulan.Key words: Ca2+-independent, Bacillus sp, thermostable α-amylases, low pH profile, enzyme, raw starch digestion, HPLC

Comparative analysis of case screening with varying cough duration and sputum samples for diagnosis of tuberculosis in patients attending the OPD at a tertiary care hospital at Srinagar, India

Research Question: Can we minimize cough duration and number of sputum samples in chest symptomatic patients for screening of TB?Objective: To evaluate cough of 3 weeks versus 2 weeks duration using two sputum samples versus three samples in chest symptomatic patients attending the OPD.Study Design: Hospital-based cross-sectional study.Materials and Methods: Outpatients (2810) with H/O cough of 3 weeks and 2 weeks duration were screened by subjecting them to sputum microscopy for tuberculosis using two sputum samples as well as three samples following standard procedure for sputum collection, staining and acid-fast bacillus (AFB) identification. Those on drugs were not included.Results: Using .2 weeks cough, sputum positivity rate was 12%, nearly as high as the sputum positivity among patients with .3 weeks cough, i.e. 14%. First sputum smear alone on an average could detect 91.8% cases, while the first two sputum smears could detect on an average 96% cases. The study showed that maximum number of cases was diagnosed by only two sputum smears and added diagnostic value of third specimen was small, i.e. 4%.High sputum positivity rate using .2 weeks cough with two sputum samples was seen.Conclusion: The sensitivity analysis of the study showed that using .2 weeks cough with two sputum samples gives almost similar values as .3 weeks cough with three sputum samples, but this needs further confirmatory results of culture sensitivity. Hence, using .2 weeks cough with two sputum samples as the diagnostic criteria for screening of cough patients for TB should be recommended as one way of improving efficient use of scarce resources

The sensitivity and specificity of the conventional symptoms and signs in making a diagnosis of acute appendicitis

Introduction: Simple appendicitis can progress to perforation, which is associated with a much higher morbidity and mortality. So, surgeons have therefore been inclined to operate when the diagnosis is probable rather than wait until it is certain. Objective: This study is designed to evaluate the sensitivity and specificity of clinical examination in the diagnosis of acute appendicitis.Methods: The study included 866 patients of acute appendicitis who had undergone appendicectomy with preoperative diagnosis of acute appendicitis. They were analyzed retrospectively. The parameters evaluated were age/gender, clinical presentation (signs and symptoms) and total white blood cell counts. The operative findings were recorded and the inflammation of the appendix was graded into normal, acutely inflamed and gangrenous.Results: Clinical diagnosis was made correctly in 807 (93.2%) of the patients. White blood cells count ranged from 3.70 to 45.30 /mm3 (mean 17.5353 /mm3). It wa

Chemical composition, cytotoxic activity and antimicrobial activity of essential oils of leaves and berries of Juniperus phoenicea l. Grown in Egypt

Hydrodistillation of berries and leaves of Juniperus phoenicea grown in Sinai yielded volatile oils in the yield of 0.36 and 1.96%, respectively. Using gas chromatography/mass spectrometry technique, fifty eight compounds were identified in berry oil representing 99.2% of the oil composition. α-Pinene was the major compound in berry oil (39.30%) followed by sabinene (24.29%). Berry oil composed mainly of monoterpenoids which amounted to 90.53%, of which 72.85% was monoterpene hydrocarbons. The sesquiterpenoids accounted for about 8% of the total oil composition. Leaf oil was composed of about 66 compounds representing 99.16% of the total composition of the oil. α-Pinene was the major constituent of leaf oil at concentration of 38.22%, followed by α -cedrol (31.23%). The monoterpene hydrocarbon was the predominant chemical group (41.29%) followed by the oxygenated sesquiterpenes (32.21%). Both oils showed very high cytotoxic activities against all cell line tested. They showed equal activities against brain (0.6 μg//ml) and cervix (5.0 μg//ml) human cell lines, while berry oil was slightly more active than leaf oil against lung (0.6 and 0.7 μ/ml, respectively), liver (0.7 and 0.9 μg//ml, respectively) and breast human cell lines (0.8 and 1. μg//ml, respectively). The antimicrobial activity and minimum inhibitory concentration (MIC) of leaf and berry oils were also determined. The oils showed high activity against most of the tested strains. Keywords: Juniperus phoenicea, Cupressaceae, essential oils, berries, leaves, antimicrobial, cytotoxic, GCMS analysis.African Journal of Traditional and Complementary Medicine Vol. 4 (4) 2007: pp. 417-42