Role of NOD2 Receptor in Immune Response to Staphylococcus Aureus

Staphylococcus aureus, a gram-positive, commensal bacterium, causes several opportunistic diseases and infections in humans. Furthermore, some strains of S.aureus have developed resistance to antibiotics such as methicillin and pose a health risk. Pattern Recognition Receptors (PRRs) on host immune cells recognize specific components of S.aureus cell wall and mount an immune response against the bacteria. One such PRR is the Nuclear Oligomerization Domain 2 (NOD2) receptor which is present in the cytosol of host immune cells. NOD2 recognizes Muramyl-Dipeptide (MDP), a component of the peptidoglycan cell wall of several bacteria including S. aureus. The binding of MDP to NOD2 allows the activation of host immune response by secretion of pro-inflammatory cytokines and antimicrobial compounds. The exact mechanism of binding of bacterial components to the NOD2 receptor is unknown. This study aims to utilize a S.aureus mutant library to screen for bacterial mutants that either fail to bind to NOD2 or show higher binding to NOD2 when compared to wild type bacteria. Commercially available Human Embryonic Kidney cells transfected with a mouse NOD2 gene (HEK-BLUE mNOD2) will be treated with wild type or mutant bacterial components from the S.aureus mutant library. Binding of bacterial components to NOD2 will be detected using a colorimetric assay and quantified by absorbance at 650nm. This screen will enable us to determine the bacterial components that are essential to NOD2 binding and may also shed light on ways by which S.aureus evades host immune responses

Role of color doppler ultrasonography in high risk pregnancies: a retrospective study

Background: Numerous adverse perinatal outcomes are associated with high-risk. The usage of doppler ultrasound bids a non-invasive way to study the fetal and maternal circulation and guide the clinical management. Objective of this study was to investigate the role of color doppler ultrasonography in effective management of high-risk pregnancies.Methods: A retrospective record-based study was carried out Department of obstetrics and gynecology. Record of antenatal women who belonged to the age group of 20-30 years with singleton pregnancy of gestational age of 26 weeks to term and presence of one of the high-risk factors were included in the study. The risk factors which were considered are pregnancy-induced hypertension (PIH), diabetes, anemia, oligohydramnios. Doppler study of umbilical artery was done. Epi-info 7 was used for analysis.Results: A total of 140 cases were studied in which high-risk pregnancy was most common in the age group of 20-25 years. The most common high-risk factor in pregnancy was PIH which accounted for 50% of cases. Out of 140 cases high-risk pregnancies, 40% of cases resulted in intrauterine growth restriction (IUGR). 43% of cases, umbilical artery findings were abnormal.Conclusions: Color doppler can be used as most effective for fetal surveillance in high-risk pregnancy cases. Most importantly it helps in guiding early intervention and improving fetal outcome

Elevated Baseline Serum Fibrinogen: Effect on 2-Year Major Adverse Cardiovascular Events Following Percutaneous Coronary Intervention.

BackgroundElevated fibrinogen is associated with short-term major adverse cardiovascular events (MACE) after percutaneous coronary intervention, but the relation with late MACE is unknown.Methods and resultsBaseline demographics and 2-year MACE were recorded among subjects undergoing nonemergent percutaneous coronary intervention. A total of 332 subjects (66.6±19.5 years, 69.9% male, 25.3% acute coronary syndrome) were enrolled. Two-year MACE (periprocedural myocardial infarction 9.0%, rehospitalization 6.3%, revascularization 12.7%, non-periprocedural myocardial infarction 4.5%, stent thrombosis 0.9%, stroke 1.8%, and death 0.6%) were associated with higher fibrinogen (352.8±123.4 mg/dL versus 301.6±110.8 mg/dL; P<0.001), longer total stent length (40.1±25.3 mm versus 32.1±19.3 mm; P=0.004), acute coronary syndrome indication (38.7% versus 17.8%; P<0.001), number of bare-metal stents (0.5±1.1 versus 0.2±0.5; P=0.002), and stent diameter ≤2.5 mm (55.8% versus 38.4%, P=0.003). No relation between platelet reactivity and 2-year MACE was observed. Fibrinogen ≥280 mg/dL (odds ratio [OR] 3.0, confidence interval [CI], 1.6-5.4, P<0.001), total stent length ≥32 mm (OR 2.2, CI, 1.3-3.8, P<0.001), acute coronary syndrome indication (OR 4.1, CI, 2.3-7.5, P<0.001), any bare-metal stents (OR 3.2, CI, 1.6-6.1, P<0.001), and stent diameter ≤2.5 mm (OR 2.0, CI, 1.2-3.5, P=0.010) were independently associated with 2-year MACE. Following a landmark analysis excluding periprocedural myocardial infarction, fibrinogen ≥280 mg/dL remained strongly associated with 2-year MACE (37.0% versus 17.4%, log-rank P<0.001).ConclusionsElevated baseline fibrinogen level is associated with 2-year MACE after percutaneous coronary intervention. Acute coronary syndrome indication for percutaneous coronary intervention, total stent length implanted, and use of bare-metal stents or smaller-diameter stents are also independently associated with 2-year MACE, while measures of on-thienopyridine platelet reactivity are not

Bombay phenotype Oh blood group: two case reports. Acute puerperal uterine inversion and term pregnancy in labour

Mrs. A, 30 years, para 3 with three live children was an unbooked emergency admission on 6 April 2007 with history of severe postpartum haemorrhage (PPH). She was in a state of shock with hypotension, tachycardia, pallor due to anaemia. Examination revealed the uterine inversion, uterus visible as a fleshy red mass protruded outside the vaginal introitus. Puerperal uterine inversion was reduced by vaginal manual reposition under observation through a mini laparotomy incision. She was transfused 4 units of O positive blood. On the second postoperative day she had signs and symptoms of a haemolytic transfusion reaction (HTR). She developed jaundice, haematuria and worsening anaemia. She was later detected to be Bombay Oh phenotype. Total 6 units of Bombay phenotype blood was transfused in a couple of days. Case 2: Mrs. R, 22 years primigravida, term gestation was admitted in labour in government maternity hospital/Osmania medical college, Hyderabad on 26 July 2007. A resident from Mahaboob Nagar district of Andhra Pradesh, unbooked emergency admission in labour, had severe anaemia with 4 gms Hb%. Her blood group was diagnosed as Bombay phenotype. She was given a vaginal delivery and transfused with compatible Oh Bombay blood obtained from Red Cross, Warangal, Andhra Pradesh

Loss of DNA Mismatch Repair Imparts a Selective Advantage in Planarian Adult Stem Cells

Lynch syndrome (LS) leads to an increased risk of early-onset colorectal and other types of cancer and is caused by germline mutations in DNA mismatch repair (MMR) genes. Loss of MMR function results in a mutator phenotype that likely underlies its role in tumorigenesis. However, loss of MMR also results in the elimination of a DNA damage-induced checkpoint/apoptosis activation barrier that may allow damaged cells to grow unchecked. A fundamental question is whether loss of MMR provides pre-cancerous stem cells an immediate selective advantage in addition to establishing a mutator phenotype. To test this hypothesis in an in vivo system, we utilized the planarian Schmidtea mediterranea which contains a significant population of identifiable adult stem cells. We identified a planarian homolog of human MSH2, a MMR gene which is mutated in 38% of LS cases. The planarian Smed-msh2 is expressed in stem cells and some progeny. We depleted Smed-msh2 mRNA levels by RNA-interference and found a striking survival advantage in these animals treated with a cytotoxic DNA alkylating agent compared to control animals. We demonstrated that this tolerance to DNA damage is due to the survival of mitotically active, MMR-deficient stem cells. Our results suggest that loss of MMR provides an in vivo survival advantage to the stem cell population in the presence of DNA damage that may have implications for tumorigenesis

Identification of karyopherin β as an immunogenic antigen of the malaria parasite using immune mice and human sera

A differential immunoscreening of the λgt11 Plasmodium falciparum genomic expression library was carried out using anti-P. yoelii sera (convalescent-phase mouse sera) and immune sera collected from healthy adults, to identify novel cross-reactive and possibly protective antigens of the parasite. One clone, with an insert size of 1132 bp that reacted strongly with both the sera was selected. The insert was found to be a part of the P. falciparum karyopherin β (PfKβ) homologue. RT-PCR and Northern blot analysis confirmed the expression of PfKβ in the blood stages of the parasite. The ~110 kDa protein was localized in the cytoplasm at the ring and trophozoite, and in the parasitophorous vacuole at the schizont stage. Two large fragments of PfKβ representing the N- and C-terminal halves were expressed in E. coli. The recombinant proteins were highly immunogenic in mice, and also found to be the target for immune response in natural infections of Plasmodium spp. Anti-sera against the protein showed a low level of anti-parasitic activity. Immunization with recombinant PfKβ fragments was only partially protective against a heterologous challenge infection in mice. Our results show that the parasite releases a highly immunogenic, cytoplasmic protein into the host which may not contribute to the development of protective immunity

Eustachian valve endocarditis: Rare case reports and review of literature

Eustachian valve endocarditis (EVE) is a distinctly rare and underdiagnosed entity. We report 2 new cases caused by vancomycin resistant Staphylococcus aureus and Staphylococcus hominis diagnosed on transesophageal echocardiography (TEE). Although, 63% of Eustachian valve endocarditis is caused by Staphylococcus aureus, we report the first case of vancomycin resistant Staphylococcus aureus and first case related to implantable venous access systems. EVE is now seen more commonly in elderly population with diverse microbial cultures and antibiotic sensitivities. TTE is the first modality for investigation of EVE, however a negative TTE does not preclude the diagnosis, as only 88% of cases were diagnosed on TEE