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

Immunotherapeutic potential of DISC-HSV and OX40L in cancer

Several vectors, viral and bacterial, have been developed over the past few years for means of generating an effective anti-tumor immune response. We have developed and studied a “model for immunotherapy” using a viral vector DISC-HSV, which efficiently transduces various tumor cell lines and offers a useful vehicle for the further development of cell based vaccines. The immunotherapeutic potential of DISC-HSV encoding GMCSF was demonstrated in a number of murine carcinoma models, leading to complete regression of well established tumors in up to 70% of the mice. Moreover, the therapeutic potential of DISC-HSV-GMCSF was significantly enhanced when used in combination therapy with either OX40L or dendritic cells (DC), even in poorly immunogenic tumor model. The ability of this vector to accept large gene inserts, its good safety profile, its ability to undergo only a single round of infection, the inherent viral immunostimulatory properties and its ability to infect various tumor cell lines efficiently, make DISC-HSV an ideal candidate vector for immunotherapy. The DISC- CT-26 tumor model has been used to investigate these mechanisms associated with immunotherapy – induced tumor rejection. Although CTL induction, was positively correlated with regression, MHC class I down regulation and accumulation of immature Gr1+ myeloid cells were shown to be the main immuno-suppressor mechanisms operating against regression and associated with progressive tumor growth

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

The best stain for morphological study of human seminal fluid's smears.

Objectives:There is a high need for proper evaluation of the morphological features of human sperms. The importance of this lies in the field of andrology, male fertility and in vitro fertilization. The wet smears can give rough clue about the shape of the sperms, but it is neither accurate nor reproducible. This study aimed to determine the best stain which can be used for seminal fluid cytology.Methods: This study was conducted in Port Sudan, Red Sea State, Sudan in the period from October 2006 to September 2007. The total number of patients was 50. Samples which were collected from normospermic patients (NSP) were prepared by direct smear technique. Samples which were collected from oligospermic patients (OSP) and azoospermic patients (ASP) were prepared by direct smear technique and also by indirect smear techniques (concentration method). Smear samples were stained by freshly prepared Harris's Haematoxylin, Papanicolaou stain, May-Grunwald Giemsa stains (MGG), supra vital stain, Giemsa stain and leishman's stain.Results: In this study, the best stain was Harris's Haematoxylin (80% excellent for the head of sperm, 70% good for the neck, 59% excellent for the tail, 42% very good for cells in background). Harris's stainwas followed by papanicolaou stain and the third best stain was supra vital stain. MGG was better than Giemsa in staining of semen smears (75% good versus 25% good) in overall performance. The worst stain was Leishman's stain.Conclusion: Stained smears must be used for the morphological study of semen samples. Harris's Haematoxylin is the best stain for semen cytological features. Stains which used for the semen samples should befreshly prepared

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