Reactivation of Latent Tuberculosis in Cynomolgus Macaques Infected with SIV Is Associated with Early Peripheral T Cell Depletion and Not Virus Load.

PLoS One. 2010;5(3):e9611

Authors: Diedrich CR, Mattila JT, Klein E, Janssen C, Phuah J, Sturgeon TJ, Montelaro RC, Lin PL, Flynn JL

HIV-infected individuals with latent Mycobacterium tuberculosis (Mtb) infection are at significantly greater risk of reactivation tuberculosis (TB) than HIV-negative individuals with latent TB, even while CD4 T cell numbers are well preserved. Factors underlying high rates of reactivation are poorly understood and investigative tools are limited. We used cynomolgus macaques with latent TB co-infected with SIVmac251 to develop the first animal model of reactivated TB in HIV-infected humans to better explore these factors. All latent animals developed reactivated TB following SIV infection, with a variable time to reactivation (up to 11 months post-SIV). Reactivation was independent of virus load but correlated with depletion of peripheral T cells during acute SIV infection. Animals experiencing reactivation early after SIV infection (<17 weeks) had fewer CD4 T cells in the periphery and airways than animals reactivating in later phases of SIV infection. Co-infected animals had fewer T cells in involved lungs than SIV-negative animals with active TB despite similar T cell numbers in draining lymph nodes. Granulomas from these animals demonstrated histopathologic characteristics consistent with a chronically active disease process. These results suggest initial T cell depletion may strongly influence outcomes of HIV-Mtb co-infection.

PMID: 20224771 [PubMed - in process]

Cutaneous leukocytoclastic vasculitis due to anti-tuberculosis medications, rifampin and pyrazinamide.

Allergy Asthma Immunol Res. 2010 Jan;2(1):55-8

Authors: Kim JH, Moon JI, Kim JE, Choi GS, Park HS, Ye YM, Yim H

Anti-tuberculosis drugs frequently result in cutaneous adverse reactions, including pruritus, maculopapular exanthems, and urticaria. However, anti-tuberculosis drug-associated cutaneous leukocytoclastic vasculitis (CLV) has been rarely reported. We describe a case of CLV induced by rifampin and pyrazinamide. A 38-year-old male had been diagnosed with pulmonary tuberculosis two months ago and then he started standard anti-tuberculosis therapy with isoniazid, rifampin, ethambutol, and pyrazinamide. Purpuric lesions developed in the extremities after 1.5 months of anti-tuberculosis medication; the lesions progressively spread over the entire body. Histopathology of the purpuric skin lesion was consistent with leukocytoclastic vasculitis. The skin lesion improved after cessation of anti-tuberculosis medications and treatment with oral corticosteroids and antihistamines. Anti-tuberculosis drugs were rechallenged one at a time over 3 days. Purpura recurred on the right forearm and forehead after taking 300 mg of rifampin. The skin lesion disappeared after taking oral prednisolone. Finally, 1,500 mg of pyrazinamide was readministrated, and then purpuric lesions recurred on both forearms. This report describes a case of leukocytoclastic vasculitis secondary to rifampin and pyrazinamide therapy.

PMID: 20224679 [PubMed - in process]

Preventive effects of mycobacteria and their culture supernatants against asthma development in BALB/c mice.

Allergy Asthma Immunol Res. 2010 Jan;2(1):34-40

Authors: Han ER, Choi IS, Eom SH, Kim HJ

PURPOSE: Live Mycobacterium bovis Bacille Calmette-Guérin (BCG) has a suppressive effect on asthma, but its use in clinical practice may be limited due to adverse reactions. To develop a product that is effective for suppressing asthma with minimal adverse reactions, we investigated whether the heat-killed body or culture supernatants of mycobacteria could also prevent asthma development. METHODS: Female BALB/c mice were treated with live BCG, the heat-killed body, or culture supernatants of BCG or Mycobacterium tuberculosis intraperitoneally, while sensitizing and provoking with ovalbumin. Then they underwent a methacholine bronchoprovocation test, and the peribronchial inflammatory cell numbers and cytokine levels in splenocyte culture supernatants were assessed. RESULTS: The airway sensitivity to methacholine decreased significantly after treatment with not only live BCG (30.8 versus 10.0 mg/mL, P<0.001) but also with the culture supernatant (BCG, 23.0 mg/mL, P<0.05; M. tuberculosis, 20.5 mg/mL, P<0.05). In contrast, heat-killed mycobacteria did not effectively decrease airway sensitivity. The peribronchial eosinophil counts and the goblet cell proportions in total epithelial cells decreased significantly in most of the groups. The interferon-gamma/interleukin-5 ratios increased significantly in most of the treatment groups except for the heat-killed groups, and were significantly related to airway sensitivity (r=0.312, P<0.01) and peribronchial eosinophil counts (r=-0.416, P<0.001). Interleukin-17A level was inversely related to airway sensitivity (r=-0.212, P<0.05) and was significantly lower in the live BCG group than in the control (137+/-20 versus 308+/-57 pg/mL, P<0.05). CONCLUSIONS: BCG and mycobacteria culture supernatants may effectively prevent the development of asthma associated with altered Th1/Th2 cytokines and interleukin-17A levels.

PMID: 20224676 [PubMed - in process]

A Report of Iliac Muscle Abscess Due to Mycobacterium bovis After Bacillus Calmette-Guerin Therapy for Bladder Cancer.

South Med J. 2010 Mar 10;

Authors: Talluri SK, Marigowda L, Besur S, Talluri J, Forstall GJ

Bacillus Calmette-Guerin (BCG) vaccine is traditionally used for vaccination against tuberculosis. BCG vaccine contains live attenuated strain of Mycobacterium bovis. Intravesical BCG is also effective in treatment of transitional cell carcinoma of the urinary bladder. Complications after intravesical BCG immunotherapy are extremely rare. We report an iliac muscle abscess due to M bovis that developed 4 years after intravesical BCG therapy for bladder cancer. Infection with M bovis, though rare, should be considered in patients with prior BCG therapy for bladder cancer.

PMID: 20224496 [PubMed - as supplied by publisher]

New and improved tuberculosis diagnostics: evidence, policy, practice, and impact.

Curr Opin Pulm Med. 2010 Mar 10;

Authors: Pai M, Minion J, Steingart K, Ramsay A

PURPOSE OF REVIEW: The aim is to summarize the evidence base for tuberculosis (TB) diagnostics, review recent policies on TB diagnostics, and discuss issues such as how evidence is translated into policy, limitations of the existing evidence base, and challenges involved in translating policies into impact. RECENT FINDINGS: Case detection continues to be a major obstacle to global TB control. Fortunately, due to an unprecedented level of interest, funding, and activity, the new diagnostics pipeline for TB has rapidly expanded. There have been several new policies and guidelines on TB diagnostics. However, there are major gaps in the existing pipeline (e.g. lack of a point-of-care test) and the evidence base is predominantly made up of research studies of test accuracy. SUMMARY: With the availability of new diagnostics and supporting policies, the next major step is translation of policy into practice. The impact of new tests will depend largely on the extent of their introduction and acceptance into the global public sector. This will itself depend in part on policy decisions by international technical agencies and national TB programs. With the engagement of all key stakeholders, we will need to translate evidence-based policies into epidemiological and public health impact.

PMID: 20224410 [PubMed - as supplied by publisher]

Thoracic empyema: current opinions in medical and surgical management.

Curr Opin Pulm Med. 2010 Mar 10;

Authors: Lee SF, Lawrence D, Booth H, Morris-Jones S, Macrae B, Zumla A

PURPOSE OF REVIEW: Empyema is defined as pus in the thoracic cavity due to pleural space infection and has a multifactorial underlying cause, although a majority of them are post-bacterial pneumonia caused by tuberculosis or by infection following penetrating chest injuries or surgical procedures. It is still associated with significant morbidity and mortality in adults and children despite optimal management according to current guidelines. Historically, empyema management has been empirical, but more recent data are leading to more focused management guidelines. RECENT FINDINGS: The number of therapeutic agents licensed for intrapleural use or undergoing clinical trials in the management of empyema continues to expand, although their use is currently controversial and probably best limited to trials and specialist centers. Although their use is limited by availability, ultrasound and guided aspiration is the investigation of choice in suspected empyema. It is safer, more sensitive, provides more information, and, in the case of guided-drainage, is more likely to be effective. Finally, there is a growing body of literature that supports very early involvement of thoracic surgeons in empyema management. An emerging question for the future is whether some or indeed all patients with empyema should now bypass medical thoracostomy and proceed directly to video-assisted thoracoscopic surgery for both acute and chronic empyemas. SUMMARY: A summary of the most recent opinions and results in thoracic empyema management is outlined. Treatment of empyema can be summarized as appropriate antibiotic therapy combined with medical or surgical pleural space drainage, management of any underlying factors, with further surgery indicated for chronic disease.

PMID: 20224409 [PubMed - as supplied by publisher]

Treatment Outcomes and Survival Based on Drug Resistance Patterns in Multidrug-resistant Tuberculosis.

Am J Respir Crit Care Med. 2010 Mar 11;

Authors: Kim DH, Kim HJ, Park SK, Kong SJ, Kim YS, Kim TH, Kim EK, Lee KM, Lee SS, Park JS, Koh WJ, Lee CH, Shim TS

RATIONALE: Few large-scale studies have investigated multidrug-resistant tuberculosis (MDR-TB) treatment outcomes relative to drug-resistance patterns. OBJECTIVE: To assess the impact of additional drug resistances on treatment outcomes and long-term survival in a large HIV-negative MDR-TB cohort. METHODS: Treatment outcomes and long-term survival of MDR-TB patients newly diagnosed or retreated in 2000-2002 were retrospectively analyzed based on drug-resistance patterns after 5-8 years of follow-up. RESULTS: Of 1,407 MDR-TB patients, 75 (5.3%) had extensively drug-resistant TB (XDR-TBre) by the revised definition, 159 (11.3%) had ofloxacin-resistant pre-XDR-TB (pre-XDR-TBo), and 117 (8.3%) had second-line injectable drug (SLID)-resistant pre-XDR-TB (pre-XDR-TBs). XDR-TBre patients showed the lowest treatment success rate (29.3%) and the poorest long-term survival, and XDR-TBre was more strongly associated with long-term mortality than XDR-TB as originally defined (HR, 3.15; 95% CI, 2.06â4.83; P < 0.001 vs HR, 2.15; 95% CI, 1.49â3.09; P < 0.001). Patients with either form of pre-XDR-TB showed poorer cumulative survival than those with ofloxacin-susceptible/SLID-susceptible MDR-TB (P < 0.05 for each comparison). Although streptomycin susceptibility did not affect the treatment outcomes of pre-XDR-TB patients, streptomycin-resistant pre-XDR-TB was more strongly associated with long-term mortality than ofloxacin-susceptible/SLID-susceptible MDR-TB (HR, 2.17; 95% CI, 1.22â3.84; P < 0.008 for pre-XDR-TBo; and HR, 2.69; 95% CI, 1.40â5.16; P = 0.003 for pre-XDR-TBs). CONCLUSION: The revised XDR-TB definition is appropriate for defining MDR-TB patients with the poorest outcomes. Both pre-XDR-TBo and pre-XDR-TBs were independently associated with poor long-term survival in MDR-TB patients. SM susceptibility was linked to better survival in pre-XDR-TB patients.

PMID: 20224066 [PubMed - as supplied by publisher]

CD4 and CD8 T Cell Responses to Mycobacterial Antigens in African Children.

Am J Respir Crit Care Med. 2010 Mar 11;

Authors: Tena-Coki NG, Scriba TJ, Peteni N, Eley B, Wilkinson RJ, Andersen P, Hanekom WA, Kampmann B

RATIONALE: The current tuberculosis vaccine, Bacille Calmete Guèrin (BCG), does not provide adequate protection against TB disease in children. Further, more efficacious TB vaccines are needed for children with immunodeficiencies such as HIV infection, who are at highest risk of disease. OBJECTIVES: To characterise mycobacteria-specific T cells in children who might benefit from vaccination against TB, focusing on responses to antigens contained in novel TB vaccines. METHODS: Whole blood was collected from 3 groups of BCG-vaccinated children: HIV-seronegative children receiving TB treatment (n=30), HIV-infected children (n=30) and HIV-unexposed healthy children (n=30). Blood was stimulated with Ag85B and TB10.4, or PPD, and T cell cytokine production by CD4 and CD8 was determined by flow cytometry. The memory phenotype of antigen specific CD4 and CD8 T cells was also determined. MEASUREMENTS AND MAIN RESULTS: Mycobacteria-specific CD4 and CD8 T cell responses were detectable in all 3 groups of children. Children receiving TB treatment had significantly higher frequencies of antigen-specific CD4 T cells, compared with HIV-infected children (p=0.0176). No significant differences in magnitude, function or phenotype of specific T cells were observed in HIV-infected children, compared with healthy controls. CD4 T cells expressing IFN-gamma, IL-2 or both expressed a CD45RA(-)CCR7(-)CD27(+/-) effector memory phenotype. Mycobacteria-specific CD8 T cells expressed mostly IFN-gamma in all groups of children; these cells expressed CD45RA(-)CCR7(-)CD27(+/-) or CD45RA(+)CCR7(-)CD27(+/-) effector memory phenotypes. CONCLUSIONS: Mycobacteria-specific T cell responses could be demonstrated in all groups of children, suggesting that the responses could be boosted by new TB vaccines currently in clinical trials.

PMID: 20224065 [PubMed - as supplied by publisher]

North Korea. New tuberculosis lab hailed as breakthrough in health diplomacy.

Science. 2010 Mar 12;327(5971):1312-3

Authors: Stone R

PMID: 20223956 [PubMed - in process]

The Mycobacterium tuberculosis origin of replication and the promoter for immunodominant secreted antigen 85B are the targets of MtrA, the essential response regulator.

J Biol Chem. 2010 Mar 11;

Authors: Rajagopalan M, Dziedzic R, Al Zayer M, Stankowska D, Ouimet MC, Bastedo DP, Marczynski GT, Madiraju MV

Efficient proliferation of Mycobacterium tuberculosis (Mtb) inside macrophage requires that the essential response regulator MtrA becomes optimally phosphorylated. However, the genomic targets of MtrA have not been identified. We show by chromatin immunoprecipitation and DNase I footprinting that the chromosomal origin of replication, oriC, and the promoter for the major secreted immunodominant antigen Ag85B, encoded by fbpB, are MtrA targets. DNAse I footprinting analysis revealed that MtrA recognizes two direct repeats of GTCACAgcg-like sequences and that MtrA~P, the phosphorylated form of MtrA, binds preferentially to these targets. The oriC contains several MtrA motifs, and replacement of all motifs or of a single select motif with TATATA compromises the ability of oriC plasmids to maintain stable autonomous replication in wild type and MtrA overproducing strains, indicating that the integrity of the MtrA motif is necessary for oriC replication. The expression of the fbpB gene is found to be down-regulated in Mtb cells upon infection when these cells overproduce WT MtrA but not when they overproduce a non-phosphorylated MtrA, indicating that MtrA~P regulates fbpB expression. We propose that MtrA is a regulator of oriC replication and that the MtrA's to affect apparently unrelated targets, i.e. oriC and fbpB, reflect its main role as a coordinator between Mtb's proliferative and its pathogenic functions.

PMID: 20223818 [PubMed - as supplied by publisher]

A heterodimer of EsxA and EsxB is involved in sporulation and is secreted by a Type VII secretion system in Streptomyces coelicolor.

Microbiology. 2010 Mar 11;

Authors: Akpe San Roman S, Facey PD, Fernandez-Martinez LT, Rodriguez C, Vallin C, Del Sol R, Dyson PJ

An esx locus, related to the multiple esx loci of Mycobacterium tuberculosis, is conserved in all sequenced Streptomyces genomes where it is associated with the developmental regulatory gene bldB. Here we demonstrate that the esxBA operon, comprising part of the locus, has a novel morphogenetic function in the model species S. coelicolor. This operon encodes two proteins belonging to the WXG-100 superfamily that can form a heterodimer and are secreted in the absence of signal sequences. A mutation in esxBA results in a delay in sporulation, with eventual development of aerial hyphae with chains of abnormally-sized spore compartments with irregular DNA contents. During early sporulation, expression of the operon is elevated in a bldB mutant. Other genes in the locus, notably SCO5734 and SCO5721, encode components of a Type VII secretion system. Disruption of either of these genes prevents secretion of EsxAB but has no effect on sporulation. To explain the morphogenetic function of EsxAB, we propose that the heterodimer sequesters a regulator of expression of genes involved in nucleoid organisation during sporulation.

PMID: 20223806 [PubMed - as supplied by publisher]

Single Nucleotide Polymorphisms in Cell Wall Biosynthesis-Associated Genes and Phylogeny of Mycobacterium tuberculosis Lineages.

Infect Genet Evol. 2010 Mar 8;

Authors: Chuang PC, Chen YM, Chen HY, Jou R

To investigate specific single nucleotide polymorphisms (SNPs) of different lineages of Mycobacterium tuberculosis, cell wall biosynthesis-associated genes encoding antigen 85 complex (fbpA, fbpB, and fbpC) and mannosyltransferase (pimB) were analyzed. Genetically diversified and predominant M. tuberculosis and M. bovis genotypes identified in Taiwan (26 Beijing and 44 non-Beijing) were included in the study. Sequence analyses revealed that nine novel SNPs were found within main lineages of M. tuberculosis complex, including East-African-Indian (EAI), Beijing, Central-Asian (CAS), Bovis, and one lineage containing Latin American and Mediterranean (LAM), Haarlem and T. Specifically, a SNP in pimB codon 270 was identified in EAI, fbpA codon 156 in ancestral Beijing, fbpB codon 238 in modern Beijing, fbpA codon 4 and fbpC codon 158 in CAS, fbpA codon 311 in M. bovis and an additional SNP in fbpB codon 140 in M. bovis-BCG, and pimB codon 107 in other spoligotypes lineages including an additional SNP in fbpC codon 103 in LAM. In addition, we proved that isolates with spoligotype shared type (ST) no. 523 (carrying all 43 spacers), designated as unknown lineage in an international spoligotyping database (SpolDB4), belong to an early ancestral Beijing sublineage. Accordingly, a phylogenetic tree was constructed using those SNPs, and an evolutionary hypothesis for lineages of M. tuberculosis was proposed. These novel lineage-specific SNPs will be informative genetic markers in molecular epidemiological and evolutionary studies of M. tuberculosis.

PMID: 20223296 [PubMed - as supplied by publisher]

Adverse reactions during biological therapy for psoriasis: Results of a survey of the Spanish Psoriasis Group.

Actas Dermosifiliogr. 2010 Mar;101(2):156-163

Authors: Sánchez-Regaña M, Dilmé E, Puig L, Bordas X, Carrascosa JM, Ferran M, Herranz P, García-Bustinduy M, López Estebaranz JL, Alsina M, Rodríguez MA, Ribera M, Fernández-López E, Moreno JC, Belinchón Romero I, Vidal D

BACKGROUND: Biologic therapies have been a major breakthrough in the treatment of psoriasis because they are more selective and have a better short-term and medium-term safety profile. There are reliable data to support both the efficacy and the safety of these drugs. However, it is always useful to report the clinical experience of dermatologists who are experts in the use of biologic agents to treat psoriasis, particularly with regard to their safety. MATERIAL AND METHODS: We present the results of a survey administered to the members of Spanish Psoriasis Group and based on a series of questions referring to the clinical safety of these agents. A total of 988 patients treated with efalizumab, infliximab, etanercept, and adalimumab were reported by 15 members of the group. RESULTS:There was a particularly high proportion of reactions (34%) to infliximab infusions. Blood test abnormalities were detected in 13.25% of patients and infections in 12.24%, with one case of pulmonary tuberculosis. Attention is drawn to the adverse effects profile of efalizumab: de novo arthritis in 5.8% and rebound in 20.9% of patients. CONCLUSION: The safety data provided by our study should be taken into account in view of the large number of patients recruited by dermatologists experienced in the use of this type of therapy.

PMID: 20223158 [PubMed - as supplied by publisher]

Roles of an anti-tuberculosis medication and surgery in patients with tuberculous otitis media.

Acta Otolaryngol. 2010 Mar 12;

Authors: Kwon M, Choi SH, Chung JW

Conclusion: The standard treatment for tuberculous otitis media (TOM) without complications consists of anti-tuberculosis (anti-TB) medication, with which we experienced good treatment outcomes. However, surgery is required for recovery of anatomy and hearing function. Objective: To determine the clinical characteristics of TOM that might optimize diagnosis and to evaluate the differences in clinical courses between patients treated with and without surgery. Methods: We analyzed 14 patients (16 ears) who had been diagnosed and treated for TOM. Radiologic findings, laboratory data, and audiometry results were also evaluated. Patients were divided into a chemotherapy group and a surgery group according to treatment modality. Results: Temporal bone CT (TBCT) showed total occupation of the tympanic cavity by soft tissue and little evidence of ossicular erosion. In the chemotherapy group, dry ears were obtained in all but one patient (14 ears) after treatment. Normalized tympanic membrane (TM) was found in 50% in the chemotherapy group and in 75% in the surgery group. The air-bone gap (ABG) changed from 40.3 +/- 2.5 dB to 47.0 +/- 19.2 dB in the chemotherapy group and from 35.2 +/- 7.6 dB to 30.2 +/- 11.4 dB in the surgery group. After treatment, ABG improved by > 10 dB in one ear in the chemotherapy group and in four ears in the surgery group.

PMID: 20222848 [PubMed - as supplied by publisher]

The role of biopsy in the diagnosis of infections of the central nervous system.

Ir Med J. 2010 Jan;103(1):6-8

Authors: Jansen M, Corcoran D, Bermingham N, Keohane C

CNS infections require prompt appropriate therapy, but do not usually require tissue biopsy for diagnosis. We performed a 5 year audit of CNS infections which required brain or spinal biopsy to determine or confirm a diagnosis of CNS infection. Sixteen cases were identified in which clinical, radiological or additional investigations including culture, serology or PCR for the suspected specific infective agents were not diagnostic. 6 (37.5%) were bacterial abscesses presenting as space-occupying intracerebral lesions with a differential diagnosis of neoplasm. There were 3 (18.7%) cases of toxoplasmosis and 2 (12.5%) cases of aspergillosis. There was one case (6.2%) of herpes simplex encephalitis, one cysticercosis and one progressive multifocal leucoencephalopathy, all biopsied as possible neoplasms. There were 2 (12.5%) cases of spinal tuberculosis, one multifocal, mimicking neurofibromatosis. This review highlights the usefulness of targeted biopsy in the rapid diagnosis of CNS infections. It also emphasizes the lack of specificity of 'negative' culture and serology in certain cases, especially in the setting of immune-compromise.

PMID: 20222384 [PubMed - in process]

Tubercular dactylitis (spina ventosa).

Postgrad Med J. 2009 Dec;85(1010):699-700

Authors: Patra SR

PMID: 20075411 [PubMed - indexed for MEDLINE]

Secondary lymphoid organs are dispensable for the development of T cell mediated immunity during tuberculosis.

Eur J Immunol. 2010 Mar 10;

Authors: Day TA, Koch M, Nouailles G, Jacobsen M, Kosmiadi GA, Miekley D, Kuhlmann S, Jörg S, Gamradt P, Mollenkopf HJ, Hurwitz R, Reece ST, Kaufmann SH, Kursar M

Tuberculosis (TB) causes 2 million deaths per year, yet in most cases the immune response successfully contains the infection and prevents disease outbreak. Induced lymphoid structures associated with pulmonary granuloma are observed during TB in both humans and mice and could orchestrate host defense. To investigate whether granuloma perform lymphoid functions, mice lacking secondary lymphoid organs (SLO), were infected with Mycobacterium tuberculosis (MTB). As in wild-type mice, granuloma developed, exponential growth of MTB was controlled, and antigen-specific T-cell responses including memory T cells were generated in the absence of SLO. Moreover, adoptively transferred T cells were primed locally in lungs in a granuloma-dependent manner. T-cell activation was delayed in the absence of SLO, but resulted in a normal development program including protective subsets and functional recall responses that protected mice against secondary MTB infection. Our data demonstrate that protective immune responses can be generated independently of SLO during MTB infection and implicate local pulmonary T-cell priming as a mechanism contributing to host defense.

PMID: 20222088 [PubMed - as supplied by publisher]

MYBBP1A: a new Ipr1's binding protein in mice.

Mol Biol Rep. 2010 Mar 11;

Authors: Cai L, Pan H, Trzci&#x144;ski K, Thompson CM, Wu Q, Kramnik I

Infection with mycobacterium tuberculosis (MTB) can cause different outcomes in hosts with variant genetic backgrounds. Previously, we identified an intracellular pathogen resistance 1 (Ipr1) gene with the role of resistance of MTB infection in mice model. However, until now, its binding proteins have been little known even for its human homology, SP110. In this study, the homology for mouse Ipr1 in canines was found to have an extra domain structure, h.1.5.1. And 30 potential candidate proteins were predicted to bind canine Ipr1, which were characterized of the interacting structure with the h.1.5.1. Among them, MYBBP1A was verified to bind with both Ipr1 and eGFP-Ipr1 in mouse macrophage J774A.1 clone 21 cells using co-immunoprecipitation method. And with the constructed high-confidence Ipr1-involved network, we suggested that Ipr1 might be involved in apoptosis pathway via MYBBP1A.

PMID: 20221700 [PubMed - as supplied by publisher]

Active Pulmonary Tuberculosis Case Detection and Treatment Among Floating Population in China: An Effective Pilot.

J Immigr Minor Health. 2010 Mar 11;

Authors: Li X, Zhang H, Jiang S, Wang J, Liu X, Li W, Yao H, Wang L

China has more and more floating population because of reform and opening-up. As one of the high burden countries in tuberculosis (TB) control in the world, China has to face more challenges about the TB case detection and treatment among floating population in China. Aim to evaluate the effect of case detection and treatment of the Floating Population TB Control Pilot Project from Global Fund Round Five (GFR5) TB Control Program in China. During October 2006 to September 2008, the pilot project was implemented gradually in 60 counties in Tianjin, Shanghai, Jiangsu, Zhejiang, Fujian, Shandong and Guangdong. All quarterly reports of the pilot project were collected, and these materials were summarized and analyzed. In seven coastal provinces, 19,584 active pulmonary TB (PTB) cases were registered among floating population in 2 years. Among the active PTB cases, 87.2% were 15-45 years old, and 62.8% were male. In second year, 15,629 active PTB cases were registered, and the overall registration rate was 68 per 100,000 people. DOT treatments were provided for 18,125 active PTB cases in 2 years, and overall DOT treatment rate was 92.6%. There were 3,955 active PTB cases registered in first year, and the overall cure rate was 86.0%. Through the implementation of the pilot project, the TB case detection and treatment among floating population have been enhanced in pilot areas of China. The useful experience and results from the pilot project have been being gradually generalized nationally.

PMID: 20221695 [PubMed - as supplied by publisher]

Expression of PE_PGRS 62 protein in Mycobacterium smegmatis decrease mRNA expression of proinflammatory cytokines IL-1beta, IL-6 in macrophages.

Mol Cell Biochem. 2010 Mar 11;

Authors: Huang Y, Wang Y, Bai Y, Wang ZG, Yang L, Zhao D

The pathogenesis of tuberculosis causing Mycobacterium bovis is largely due to its successful entry and survival in macrophages. Previous research indicated that mycobacteria-specific PE_PGRS genes code for cell surface proteins which may have role in mediating interactions with macrophages. In this study, we expressed PE_PGRS 62 gene in a non-pathogenic fast growing Mycobacterium smegmatis strain and found that the recombinant Mycobacterium smegmatis decreased macrophages livability in a dosage-dependent manner and time-dependent manner, compared with parental strain containing the vector only. To explore whether PE_PGRS 62 modulates the gene expression profile of macrophages, we stimulated macrophages by the M. smegmatis strain expressing PE_PGRS 62 as well as the control strains, followed by real-time RT-PCR assay for the mRNA expression level of IL-1beta, IL-6, and iNOS. The results showed that the expression of IL-1beta, IL-6 in macrophages were down-regulated by stimulation with the M. smegmatis strain expressing PE_PGRS 62 compared to the control strains (P < 0.05). In contrast, there were no measurable differences in the expression of iNOS. Overall, we demonstrated that PE_PGRS 62 protein altered the immune environment of the host cells, which suggest that the pathogenic PE_PGRS 62 protein altering the immune mechanism maybe involved in the pathogenesis of mycobacterial disease.

PMID: 20221673 [PubMed - as supplied by publisher]