Structural Basis For Human Anti-dna Antibody Specificity

Anti-DNA antibodies are hallmarks of SLE both in human and inbred lupus prone mice. The role of these antibodies in disease pathogenesis, particularly in glomerulonephritis has been documented. It is now well accepted that the genetic potential to generate anti-DNA antibodies also exists in the normal B cell immune repertoire. This genetic potential has been revealed by detection of anti-DNA antibodies in serum of normal individuals and by immortalizing DNA reactive B cells as hybridomas and as transformed cell lines. There is growing evidence that anti-DNA antibodies from the normal B cell repertoire and disease-associated anti-DNA antibodies share V region gene structures. Evidence for structural similarities includes the expression of normal monoclonal anti-DNA antibody idiotypes by lupus serum anti-DNA antibodies. Further direct evidence has been provided by sequence analysis of anti-DNA antibody genes. Thess studies showed that anti-DNA antibodies of either origin use no singular or simple mechanism for the generation of their specificity for DNA. It has been shown that VH and VL chain Ig germline genes in different combination can encode both normal and SLE anti-DNA antibodies and many of these genes can also be used by non DNA-binding antibodies. SLE anti-DNA antibodies are often somatically mutated and enriched with arginine residue(s) which could increase their affinity for DNA. In addition, the Ig V region of some anti-DNA antibodies are enriched with amino acids such as tyrosine, asparagine and glutamine which may also facilitate DNA-binding of these antibodies. It has also been suggested that heavy chains make a major contribution to DNA-binding in some anti-DNA antibodies based on the presence of common idiotype markers or motifs. One such motif YYGS, resides in the CDR3 region of KIM4.6 a natural human anti-DNA antibody heavy chain and is also expressed in more than 20% of human and murine anti-DNA antibodies and in the VH CDR2 region of some murine IgG anti-DNA antibodies.;The current study has explored the structural basis for DNA binding of human anti-DNA antibodies and in particular has focussed on the examination of the role of the heavy chain, the diversity region and the YYGS motif in conferring DNA specificity to the natural human monoclonal IgM anti-DNA antibody KIM4.6.;This study describes the generation and molecular characterization of Variants of KIM4.6 hybridoma which have lost their DNA binding property. The Ig V genes of three anti-Sm/RNP antibodies which either react with DNA or use genes related to KIM4.6 were also characterized. Gene manipulation techniques and a phage expression system or an in vitro transcription and translation system was used to further directly explore the role of YYGS motif in the DNA specificity of the KIM4.6 anti-DNA antibody.;This study revealed that: (1) the KIM4.6 heavy chain confers DNA specificity in this antibody, (2) the KIM4.6 D region YYGS motif is a necessary but not sufficient structural determinant in KIM4.6 reactivity to ds DNA but not ss DNA

RICING INSURANCE IN ORDER TO MINIMIZING THE EXPECTED LOSS IN WEALTH VIA OPTIMAL CONTROL

Abstract. In this paper we are interested in Pricing insurance in order to minimizing the expected loss inwealth via optimal control. The objective is to find the policy which maximizes the total wealth in company insurances. For this purpose, First, a dynamic model is introduced to describe the process of receiving premium and paying claims. Then, we introduce the premium variable as the problem control variable. Next, we define an appropriate objective function for the control variable and state variables in order to reduce expected losses and increase the wealth. In the end, one of the main variables is estimated by statistical methods and we solve the optimal control problem by PMP method and finally, numerical example are presented.Keywords: Optimal control, Premium, Dynamical systems, expected loss, Optimization

A review on the most important medicinal herbs native to Iran with anti-acetaminophen toxicity

Acetaminophen is an analgesic and anti- fever drug, which can be toxic in high doses and leads to hepatic and renal injury. Acetaminophen poisoning can cause many complications and injuries in the body including vomiting, diarrhea, malaise, shock, jaundice, and liver failure and in some cases will lead to myocardial and kidney damage. Against all toxic and destructive effects of drugs like acetaminophen, some compounds are found that can partially restrain poisoning of abuse such compounds. In this review article, medicinal plants native to Iran have been reported, which are used to protect acetaminophen toxicity. In this review study, searching the articles with key words such as acetaminophen, hepatotoxicity, herbs, extracts, and essential oils were used. Searching the articles was conducted through databases of income in Iran like Google Scholar, ISI January, MegaIran, and a number of other databases. Medicinal plants including green tea, turmeric, cress, dandelion, and capers are the most important medicinal plants against the toxicity of acetaminophen. It seems that pharmacological bioactive and antioxidants substances obtaining from plant and biological materials are anti- acetaminophen poisoning. © 2009-2016, JGPT

Prediction of Obsessive-compulsive Symptoms Based on Negative Affect, Rumination, and Dispositional Mindfulness

Obsessive-compulsive symptoms could be an important background for clinical disorder of OCD. The role of negative affect, rumination, and dispositional mindfulness has not been investigated in previous researches. Therefore, the purpose of this study was to study the relationship among negative affect, rumination, dispositional mindfulness with obsessive-compulsive symptoms. In a descriptive-correlational and crosses- sectional study, 283 students from University of Tabriz have selected by available sampling method during April through May 2017.Maudsley OCD inventory, Positive affect and negative affect scale (PANAS), Five Facet Mindfulness Questionnaire (FFMQ) and Rumination Scale of the Response Styles Questionnaire were used for collecting the data. Data were analyzed using Pearson correlation and multiple Regressions tests. The results showed that correlation between obsessive-compulsive symptoms and dispositional mindfulness was negative and significant, correlation between obsessive-compulsive symptoms and negative affect was positive and significant and correlation between obsessive-compulsive symptoms and rumination was significant. Also, negative affect, rumination, and dispositional mindfulness did able to predict the obsessive-compulsive symptoms. Dispositional mindfulness, negative affect, and rumination are the important determinants of obsessive-compulsive symptoms

A Double-Blind Randomized Trial Comparing the Effectiveness and Safety of Nifedipine and Isosorbide Dinitrate in Chronic Anal Fissure

Background: Chronic anal fissure is a common disease that is accompanied with pain and bleeding during defecation. Various surgical and non-surgical methods have been offered for the treatment of this condition. The aim of this randomised clinical study was to compare the effectiveness and safety of nifedipine and isosorbide dinitrate (ISDN) in the treatment of chronic anal fissure. Methods: This double-blind clinical trial study was performed on patients aged 20 to 60 years old in 2012 to 2013. The samples with a primary diagnosis of chronic anal fissure were enrolled from the patients admitted to public treatment at the educational Imam Ali Clinic, Shahrekord, Iran by researchers and general surgery specialists. The patients were randomised into two groups: nifedipine 0.3% (n = 35) or ISDN 0.2% (n = 35) applied three times a day for three weeks. The patients were examined on the 7th, 14th, and 21st days of treatment, and the symptoms including bleeding, pain, and healing status, as well as the side effects of the drugs, were assessed. Pain was evaluated using a visual analogue scale (VAS). Results: After 21 days of follow-up, complete healing was achieved in 77.1% (n = 27) of patients in the nifedipine group and 51.4% (n = 18) in the ISDN group (P = 0.05). The mean VAS of the pain on day 21 was 0.91 (SD 0.01) in the ISDN group and 0.45 +/- 0.78 in the nifedipine group, with a statistically significant difference (P = 0.038). The bleeding was similar in the two groups (P = 0.498). Conclusion: In view of the findings on healing status and pain in the patients, nifedipine may be significantly more effective in the treatment of chronic anal fissure than ISDN

Sequence homology: A poor predictive value for profilins cross-reactivity

BACKGROUND: Profilins are highly cross-reactive allergens which bind IgE antibodies of almost 20% of plant-allergic patients. This study is aimed at investigating cross-reactivity of melon profilin with other plant profilins and the role of the linear and conformational epitopes in human IgE cross-reactivity. METHODS: Seventeen patients with melon allergy were selected based on clinical history and a positive skin prick test to melon extract. Melon profilin has been cloned and expressed in E. coli. The IgE binding and cross-reactivity of the recombinant profilin were measured by ELISA and inhibition ELISA. The amino acid sequence of melon profilin was compared with other profilin sequences. A combination of chemical cleavage and immunoblotting techniques were used to define the role of conformational and linear epitopes in IgE binding. Comparative modeling was used to construct three-dimensional models of profilins and to assess theoretical impact of amino acid differences on conformational structure. RESULTS: Profilin was identified as a major IgE-binding component of melon. Alignment of amino acid sequences of melon profilin with other profilins showed the most identity with watermelon profilin. This melon profilin showed substantial cross-reactivity with the tomato, peach, grape and Cynodon dactylon (Bermuda grass) pollen profilins. Cantaloupe, watermelon, banana and Poa pratensis (Kentucky blue grass) displayed no notable inhibition. Our experiments also indicated human IgE only react with complete melon profilin. Immunoblotting analysis with rabbit polyclonal antibody shows the reaction of the antibody to the fragmented and complete melon profilin. Although, the well-known linear epitope of profilins were identical in melon and watermelon, comparison of three-dimensional models of watermelon and melon profilins indicated amino acid differences influence the electric potential and accessibility of the solvent-accessible surface of profilins that may markedly affect conformational epitopes. CONCLUSION: Human IgE reactivity to melon profilin strongly depends on the highly conserved conformational structure, rather than a high degree of amino acid sequence identity or even linear epitopes identity

Effect of home postpartum care on quality of life of low risk mothers

Background & Aim: Home care visits have unique advantages in many social problems and health complications such as psychologic complications and adverse birth outcomes. The aim of this study was to identify the effect of postpartum care at home on quality of life among low risk mothers. Methods & Materials: This interventional study was conducted in Akbarabad health center of Tehran University of Medical Sciences in 2010. A total of 200 mothers were randomly allocated in two intervention and control groups. Mothers in the ..

International Hospitals’ Performance Variables: A Comparative Study

Background: To define a series of variable that separates international hospitals from other ones is the main aim of this study.Materials and Methods: After choosing some countries in the worldwide, two hospitals, which were the leaders on international patients’ admissions, were selected for investigating their main indicators according to world health organization framework for demonstrating performance assessment to attract patients from the universe.Results: Under the first performance assessment dimension clinical effectiveness and safety, in chosen hospitals of Australia as Malaysia found (4), New Zealand (9), India (7) and Iran (1) indicator (s). The production efficiency and staff orientation dimensions concluded no difference in terms of quantity and type of indicators via countries. Next aspect as patient centeredness was consisted of 4 indicators in Australia, New Zealand (2), India (6) and Iran (5). Eventually, eight indicators asset from Australia, New Zealand (2), India (6) and Iran (6) for responsive governance.Conclusion: Although the variables of international hospital’s performance assessment were the same with others, these should be more highlighted for attracting worldwide patients and strongly recommends the international authority for quality assurance

International Hospital Performance Assessment: Developing a Questionnaire

Background: As there is no valid questionnaire for assessing international hospital performance from providers’ perspective, this study aimed to develop a reliable as well as valid questionnaire for Iranian hospitals.Materials and Methods: To develop the International Hospital Performance Assessment (IHPA) questionnaire, literature review did and comparative study conducted for extracting relevant items from twenty leader hospitals in all over the world. After that, to design the questionnaire and estimate its content validity index and ratio (CVI, CVR), 20 medical tourism experts selected. Then, questionnaire‘s construct validity (CVI & CVR) determined by using SPSS version 21 as well as exploratory factor analysis. Finally, reliability assessed by calculating Cronbach’s alpha coefficient.Results: The content validity of the questionnaire determined as (CVI= 0.85, CVR= 0.60). According to expert opinion 5 dimensions of the questionnaire selected from World Health Organization hospital performance framework, which were clinical effectiveness and patient safety, efficiency, patient centeredness, governance responsiveness and even staff orientation. Furthermore, results of exploratory factor analysis showed that the questionnaire contained 45 items and Cronbach’s alpha coefficient was 0.687.Conclusion: Results indicated that standard IHPA questionnaire with 45 items in 5 dimensions developed as a tool for measuring hospitals’ quality of care in Iran