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81.
Bozue JA Parthasarathy N Phillips LR Cote CK Fellows PF Mendelson I Shafferman A Friedlander AM 《Microbial pathogenesis》2005,38(1):1-12
Carbohydrate analyses of whole-spore extracts have confirmed the presence of rhamnose in the spore of the fully virulent Ames strain of Bacillus anthracis. A gene cluster containing loci with high homology to the rhamnose biosynthetic genes, rmlACBD, was identified within the B. anthracis chromosome. The first gene of this cluster, rmlA, was inactivated by forming a merodiploid cointegrate using an internal fragment of the gene within the Ames strain of B. anthracis to construct the mutant strain Ames-JAB1. Carbohydrate analysis of spores from this mutant demonstrated the loss of rhamnose. When assaying for spore infection of macrophages, we detected a significant decrease in the recovery with the Ames-JAB1 strain compared to the recovery with the Ames wild-type strain. When pre-treating macrophages with cytochalasin-D, spores of the mutant were further hindered in recovery, indicating that the spores were not able to bind as well to the macrophages. However, in guinea pigs challenge experiments, no difference in virulence was observed between the mutant and wild-type strains. These results suggest that the incorporation of rhamnose into the spore coat of B. anthracis is required for optimal interaction with macrophages but is not required for full virulence in this animal model. 相似文献
82.
HPV DNA in plasma of patients with cervical carcinoma. 总被引:4,自引:0,他引:4
Narayanan Sathish Priya Abraham Abraham Peedicayil Gopalan Sridharan Subhashini John R V Shaji George Chandy 《Journal of clinical virology》2004,31(3):204-209
BACKGROUND: HPV DNA has been detected in metastatic tumour and HPV plasma viraemia may indicate a poor prognosis and a high risk for metastasis. OBJECTIVE: Detection of HPV DNA in plasma of patients with cervical carcinoma. STUDY DESIGN: A cross-sectional study was done, wherein cervical biopsies and plasma samples were collected from 58 women with invasive cervical carcinoma, 10 women with cervical intraepithelial neoplasia (CIN) and 30 control women in the same age range. Polymerase chain reaction (PCR) was employed to detect the presence of HPV DNA. Samples positive for HPV DNA were typed by restriction fragment length polymorphism (RFLP). To confirm that the HPV sequence in plasma was identical to that in tissue, sequencing was done on all the paired plasma and tissue samples. RESULTS: All the 30 paired cervical tissue and plasma samples from the controls were negative for HPV DNA. HPV DNA was detectable in cervical tissues of 55 (94.8%) of 58 patients with invasive cervical carcinoma and in all 10 patients (100%) with CIN and in eight (11.8%) of the total 68 plasma samples from patients. All eight plasma samples were from women with invasive cervical carcinoma with three each in stages IIIB and IV and one each in stages IIB and IB, respectively. Of the eight positive samples, seven were typed as HPV-16 and 1 as HPV-58. HPV types detected in cervical tissue and plasma pairs from these eight patients correlated as revealed by RFLP and sequencing. A patient with stage IB cancer had detectable HPV DNA in the external iliac lymph node, removed at Wertheims hysterectomy, which was histopathologically free of tumour. The HPV type in the node, was the same as that present in the paired tissue and plasma sample. CONCLUSIONS: HPV DNA is detectable in the plasma of patients with advanced cervical cancer. 相似文献
83.
Selvaraj P Chandra G Jawahar MS Rani MV Rajeshwari DN Narayanan PR 《Journal of clinical immunology》2004,24(5):523-532
The regulatory role of vitamin D receptor (VDR) gene variants of Bsm I, Apa I, Taq I, and Fok I polymorphisms on vitamin D(3)-modulated macrophage phagocytosis with live Mycobacterium tuberculosis and lymphoproliferative response to M. tuberculosis culture filtrate antigen (CFA) was studied in patients with pulmonary tuberculosis (n = 46) and in normal healthy subjects (NHS) (n = 64). Vitamin D(3) at a concentration of 1 x 10(-7) M enhanced the phagocytic potential of normal subjects who had a phagocytic index of less than 20%. This increase was seen in subjects with the genotypes BB (p = 0.017), AA (p = 0.016), tt (p = 0.034), and FF (p = 0.013) and the extended genotype BBAAtt (p = 0.034). Normal subjects with BBAAtt performed better phagocytosis than individuals with bbaaTT genotype (p = 0.034). Vitamin D(3) at 10(-9), 10(-8), and 10(-7) M concentrations suppressed the lymphoproliferative response to CFA antigen in normal subjects. This decreased lymphocyte response was observed in normal individuals with the genotypes BB (p = 0.0009), tt (p = 0.016), and FF (p = 0.008) and the extended genotype BBAAtt (p = 0.02). Addition of vitamin D(3) had no significant effect on macrophage phagocytosis and lymphoproliferative response to CFA in pulmonary TB patients. This may be due to the unresponsive nature of the cells to the action of vitamin D(3) or the downregulated VDR expression by virtue of the disease, which renders them inactive. The genotypes BB, tt, and the extended genotype BBAAtt may be associated with increased expression of VDR which in turn regulate the action of vitamin D(3) and modulate the immune functions to M. tuberculosis in NHS. 相似文献
84.
Dhir V Fort M Mahmood A Higbee R Warren W Narayanan P Wittman V 《Journal of immunotoxicology》2012,9(1):34-42
Human peripheral blood mononuclear cells (PBMC) are routinely used in vitro to detect cytokine secretion as part of preclinical screens to delineate agonistic and antagonistic action of therapeutic monoclonal antibodies (mAbs). Preclinical value of standard human PBMC assays to detect cytokine release syndrome (CRS) has been questioned, as they did not predict the "cytokine storm" that occurred when healthy human volunteers were given a CD28-specific super-agonist mAb, TGN1412. In this article, we describe a three-dimensional biomimetic vascular test-bed that can be used as a more physiologically relevant assay for testing therapeutic Abs. For developing such a system, we used TGN1412 as a model mAb. We tested soluble TGN1412 on various combinations of human blood components in a module containing endothelial cells grown on a collagen scaffold and measured cytokine release using multiplex array. Our system, consisting of whole leukocytes, endothelial cells, and 100% autologous platelet-poor plasma (PPP) consistently produced proinflammatory cytokines in response to soluble TGN1412. In addition, other mAb therapeutics known to induce CRS or first infusion reactions, such as OKT3, Campath-1H, or Herceptin, generated cytokine profiles in our model system consistent with their in vivo responses. As a negative control we tested the non-CRS mAbs Avastin and Remicade and found little difference between these mAbs and the placebo control. Our data indicate that this novel assay may have preclinical value for predicting the potential of CRS for mAb therapeutics. 相似文献
85.
LN Barlow-Mosha DS Bagenda PK Mudiope MC Mubiru LM Butler MG Fowler PM Musoke 《African health sciences》2012,12(3):249-258
Background
Access to pediatric antiretroviral formulations is increasing in resource-limited countries, however adult FDCs are still commonly used by antiretroviral therapy (ART) programs.Objective
To describe long-term effectiveness of using adult FDC of d4T+3TC+NVP (Triomune) in children for HIV treatment.Methods
Clinical, immunologic, and virologic outcomes of HIV-infected ART-naïve children aged six months to 12 years, were evaluated up to 96 weeks post-ART initiation.Results
From March 2004 to June 2006, 104 children were followed with a median age of 5.4 years, median CD4 cell percent and HIV-1 RNA were 11.0% (IQR 6.7–13.9) and 348,846copies/mL (IQR 160,941–681,313) respectively at baseline. Using Kaplan-Meir estimates, 75% of children had undetectable viral loads (<400copies/mL) at 96weeks of ART. Children with a baseline CD4 cell percent >15% were 3 times more likely to achieve viral load <400copies/mL than those with baseline CD4 cell percent <5% after adjusting for baseline age {aHR = 3.03 (1.10–8.32), p=0.03}; no difference was found among those with CD4 cell percent >5–14.9% and <5%.Conclusion
Treatment with generic adult FDC for HIV-infected Ugandan children led to sustained clinical, immunologic and virologic response during 96 weeks of ART. Early initiation of ART is key to achieving virological success. 相似文献86.
87.
The ability of pathogenic bacteria to sense and respond to periods of host stress is critical to their lifestyle. Adrenaline and norepinephrine are catecholamines that mediate acute host stress in vertebrates and invertebrates. Catecholamines are also used as environmental cues to enhance growth, motility and virulence of bacterial pathogens via specific binding receptors. Incidence of multidrug resistant and highly virulent bacterial pathogens is on the rise, and majority of the genes for antimicrobial resistance (AMR) and virulence are carried on horizontally transferable genetic elements. Conjugation machinery offers an efficient method for acquisition of AMR and virulence genes, which may be responsible for propelling the evolution of pathogenic bacteria. Here we show that norepinephrine (NE) at physiological concentrations enhances horizontal gene transfer (HGT) efficiencies of a conjugative plasmid from a clinical strain of Salmonella Typhimurium to an Escherichia coli recipient in vitro. Expressions of plasmid encoded transfer (tra) genes necessary for conjugation were also significantly upregulated in the presence of NE. Phentolamine, an α-adrenergic receptor antagonist, negated the effects of NE on conjugation more strongly than propranolol, a β-adrenergic receptor antagonist. This study for the first time provides evidence that innate mediators of acute host stress may influence evolution and adaptation of bacterial pathogens. 相似文献
88.
Sujata Narayanan Neeraj Agarwal Kristina Callis-Duffin Julia Batten 《The American journal of the medical sciences》2010,339(6):580-581
Sunitinib is an oral tyrosine kinase inhibitor, which is indicated for the treatment of renal cell carcinoma and gastrointestinal stromal tumors. The authors report the case of a patient who underwent treatment for renal cell carcinoma and noted additional benefit by improvement in his psoriatic skin lesions. This may be attributed to the antiangiogenic activity of sunitinib by inhibition of vascular endothelial growth factor receptors. 相似文献
89.
Suresh Narayanan Senthil Murugan 《Anatomical science international / Japanese Association of Anatomists》2018,93(2):307-310
Variations in the origins and the branching pattern of the carotid system of arteries are not uncommon. Here we report a rare case of higher bifurcation of the common carotid artery (CCA) (at the level of the greater cornu of the hyoid bone), thyrolinguofacial trunk (TLFT) originating from the CCA, superior laryngeal artery (SLA) arising from the external carotid artery (ECA) on the left side, and linguofacial trunk arising from the ECA on the right side. In the present case, the CCA and carotid bifurcation may have arisen from the second aortic arch. The ECA bud could have developed from parts of the first aortic arch and ventral aorta. Thus, the altered blood flow through these vessels due to high carotid bifurcation could have caused disproportionate growth and shift in the origins of the branches of the ECA. An understanding of the bifurcation of the CCA and the branching pattern of the ECA should prove useful to surgeons performing selective intra-arterial chemotherapy for head and neck cancer. 相似文献
90.
Sriram Krishnamurthy Parameswaran Narayanan Sivaprakasam Prabha Nivedita Mondal Subramanian Mahadevan Niranjan Biswal Sadagopan Srinivasan 《Indian Journal of Critical Care Medicine》2013,17(4):207-213