Dendritic Cell Activity Driven by Recombinant Mycobacterium bovis BCG Producing Human IL-18, in Healthy BCG Vaccinated Adults.

Science.gov (United States)

Szpakowski, Piotr; Biet, Franck; Locht, Camille; Paszkiewicz, Małgorzata; Rudnicka, Wiesława; Druszczyńska, Magdalena; Allain, Fabrice; Fol, Marek; Pestel, Joël; Kowalewicz-Kulbat, Magdalena

2015-01-01

Tuberculosis remains an enormous global burden, despite wide vaccination coverage with the Bacillus Calmette-Guérin (BCG), the only vaccine available against this disease, indicating that BCG-driven immunity is insufficient to protect the human population against tuberculosis. In this study we constructed recombinant BCG producing human IL-18 (rBCGhIL-18) and investigated whether human IL-18 produced by rBCGhIL-18 modulates DC functions and enhances Th1 responses to mycobacterial antigens in humans. We found that the costimulatory CD86 and CD80 molecules were significantly upregulated on rBCGhIL-18-infected DCs, whereas the stimulation of DCs with nonrecombinant BCG was less effective. In contrast, both BCG strains decreased the DC-SIGN expression on human DCs. The rBCGhIL-18 increased IL-23, IL-10, and IP-10 production by DCs to a greater extent than nonrecombinant BCG. In a coculture system of CD4(+) T cells and loaded DCs, rBCGhIL-18 favoured strong IFN-γ but also IL-10 production by naive T cells but not by memory T cells. This was much less the case for nonrecombinant BCG. Thus the expression of IL-18 by recombinant BCG increases IL-23, IP-10, and IL-10 expression by human DCs and enhances their ability to induce IFN-γ and IL-10 expression by naive T cells, without affecting the maturation phenotype of the DCs.

Dendritic Cell Activity Driven by Recombinant Mycobacterium bovis BCG Producing Human IL-18, in Healthy BCG Vaccinated Adults

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Piotr Szpakowski

2015-01-01

Full Text Available Tuberculosis remains an enormous global burden, despite wide vaccination coverage with the Bacillus Calmette-Guérin (BCG, the only vaccine available against this disease, indicating that BCG-driven immunity is insufficient to protect the human population against tuberculosis. In this study we constructed recombinant BCG producing human IL-18 (rBCGhIL-18 and investigated whether human IL-18 produced by rBCGhIL-18 modulates DC functions and enhances Th1 responses to mycobacterial antigens in humans. We found that the costimulatory CD86 and CD80 molecules were significantly upregulated on rBCGhIL-18-infected DCs, whereas the stimulation of DCs with nonrecombinant BCG was less effective. In contrast, both BCG strains decreased the DC-SIGN expression on human DCs. The rBCGhIL-18 increased IL-23, IL-10, and IP-10 production by DCs to a greater extent than nonrecombinant BCG. In a coculture system of CD4+ T cells and loaded DCs, rBCGhIL-18 favoured strong IFN-γ but also IL-10 production by naive T cells but not by memory T cells. This was much less the case for nonrecombinant BCG. Thus the expression of IL-18 by recombinant BCG increases IL-23, IP-10, and IL-10 expression by human DCs and enhances their ability to induce IFN-γ and IL-10 expression by naive T cells, without affecting the maturation phenotype of the DCs.

Rodent malaria: BCG-induced protection and immunosuppression

International Nuclear Information System (INIS)

Smrkovski, L.L.; Strickland, G.T.

1978-01-01

One dose of 10 7 viable units of Mycobacterium bovis, strain BCG, protected a significant number of Swiss mice from a primary challenge with 10 4 thoracic sporozoites of Plasmodium berghei. Immunization with irradiated sporozoites induced greater protection than that observed in BCG-treated animals. Mice treated with BCG and surviving a primary sporozoite challenge were not protected from rechallenge, whereas mice immunized with irradiated sporozoites and surviving initial challenge of sporozoites were solidly immune to further challenge. Immunizing mice with BCG and irradiated sporozoites simulataneously resulted in a synergistic effect of increased protection against a primary challenge of sporozoites only if the two immunogens were administered on the same day and if the mice were challenged 1 to 3 days later. Mice given BCG and irradiated sporozoites and surviving a primary challenge of sporozoites were unable to survive rechallenge. BCG given to mice previously immunized with irradiated sporozoites suppressed their protective immunity against sporozoite challenge

Systemic BCG-Osis as a Rare Side Effect of Intravesical BCG Treatment for Superficial Bladder Cancer

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S. Lukacs

2013-01-01

Full Text Available Intravesical Bacilli Calmette-Guérin (BCG immunotherapy is a commonly used treatment for superficial bladder cancer. Although the treatment is well tolerated in 95% of cases, life-threatening side effects including BCG sepsis can occur. This report describes the case of an 82-year-old man with a background of lung disease. He developed septic shock and type two respiratory failure after receiving the sixth installation of intravesical BCG (TICE strain immunotherapy for recurrent bladder Transitional Cell Carcinoma in situ. Despite the early initiation of broad spectrum antibiotics (tazocin and gentamicin, he remained pyrexial. There was a rapid deterioration, and on the second day of his admission, he developed type two respiratory failure secondary to Acute Respiratory Distress Syndrome (ARDS prompting transfer to Intensive Care for Bilevel Positive Airway Pressure (BiPAP Ventilation. The blood cultures taken before the induction of antibiotics results were negative. Increasing clinical suspicion of systemic BCG-osis prompted the initiation of antituberculosis therapy (ethambutol, isoniazid rifampicin and steroids. Following six days of BiPAP and anti-tuberculosis therapy in ITU, his condition started to improve. Following a prolonged hospital stay he was discharged on long term ethambutol therapy. BCG-osis is a well-known though rare side effect of intravesical BCG therapy. We would like to highlight the importance of having a low threshold for starting anti-TB treatment.

Invitro immune responses in children following BCG vaccination

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Vijayalakshmi V

2006-01-01

Full Text Available Introduction: There is still no consensus on the efficacy of BCG vaccine in the prevention of tuberculosis. This study therefore addressed the question of the magnitude of immunity afforded by BCG, by studying the effector mechanisms of protection in children. The main objectives were to assess the degree of immunity conferred by BCG vaccine in children and to identify the most immunogenic antigen(s of BCG by conducting in-vitro studies. Materials and methods: Children in the age-group of 1 to 10 years, were categorized: (A normal, and vaccinated with BCG during the first year, n=45, (B normal, without scar and with no evident history of vaccination, n=31: and (C children admitted in the hospital with a confirmed diagnosis of tuberculosis, n=31. Fractions of BCG were obtained by lysis, sonication, separation by gel chromatography, HPLC and confirmed by SDS-PAGE. In lymphoproliferative assays PBMC were cultured and stimulated with either Concanavalin-A or Tuberculin or the fractions of BCG. Stimulation indices (SI in lymphoproliferation, CD4/CD8 cells, levels of Interferon-γ (IFN- γ in the culture supernatants were measured by ELISA. Results: The vaccinated children displayed significantly high (P< 0.05 mean values of SI in LTT, CD4/CD8 cell ratio against the unfractionated, 67kDa fraction and BCG-CF Ags. While 100% of the vaccinated children had positive lymphoproliferation indices to BCG-CF, only 8.3% of the unvaccinated children were positive. Conclusion: Some of the components of BCG induced a strong Thl cell response in children. These immunogenic antigens were present in the whole cell lysate. The use of BCG vaccine for tuberculosis is worthwhile till a new vaccine is developed.

Bacillus Calmette-Guérin (BCG) Treatment Failures with Non-Muscle Invasive Bladder Cancer: A Data-Driven Definition for BCG Unresponsive Disease.

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Steinberg, Ryan L; Thomas, Lewis J; Mott, Sarah L; O'Donnell, Michael A

2016-04-27

Objective: To create the first data-driven definition for those unlikely to benefit from further BCG treatment. Materials and Methods: The database created for the Phase 2 BCG-Interferon- α 2B (IFN) study was queried and BCG failure patients were identified ( n  = 334). Full study protocols have previously been published. Separate models were constructed for analysis of patients with any CIS (pure or concomitant) and pure papillary disease. Variables considered included age, gender, stage, grade, tumor size and focality (for papillary only), number of prior BCG courses, and prior BCG failure interval. Results: Patients with recurrent CIS within 6 months of their most recent prior BCG course (HR 2.56, p  disease within 6 months (HR 1.82, p  = 0.02), ≥2 BCG failures (HR 1.54, p  = 0.03), and multifocal disease (HR 2.05, p  disease remained disease free in 38% of cases (24-51% 95% CI) at 2 years with low rates of progression. Conclusions: Patients who fail two courses of BCG with either persistent or recurrent multifocal papillary disease within 6 months or CIS within 12 months of their prior BCG should be considered BCG unresponsive. Recurrent T1 disease respond reasonably well to another course with low progression rates but further investigation is warranted.

Randomized trial of BCG vaccination at birth to low-birth-weight children

DEFF Research Database (Denmark)

Aaby, Peter; Roth, Adam Anders Edvin; Ravn, Henrik

2011-01-01

Observational studies have suggested that BCG may have nonspecific beneficial effects on survival. Low-birth-weight (LBW) children are not given BCG at birth in Guinea-Bissau; we conducted a randomized trial of BCG at birth (early BCG) vs delayed BCG.......Observational studies have suggested that BCG may have nonspecific beneficial effects on survival. Low-birth-weight (LBW) children are not given BCG at birth in Guinea-Bissau; we conducted a randomized trial of BCG at birth (early BCG) vs delayed BCG....

Cisticercosis diseminada: reporte de un caso en Perú

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Julio Maquera-Afaray

Full Text Available La cisticercosis es una enfermedad desatendida y endémica en el Perú que afecta comúnmente al sistema nervioso central (SNC, causando la neurocisticercosis (NCC. Sin embargo, son pocos los reportes de cisticercosis diseminada (CCD en el mundo. Se reporta el caso de un paciente varón de 82 años, natural del departamento de Junín, que presenta pérdida brusca del nivel de conciencia asociada a convulsiones tónico-clónicas generalizadas. La tomografía axial computarizada y la resonancia magnética nuclear cerebral mostraron múltiples lesiones de aspecto quístico con presencia de escólex en su interior y compatibles con NCC masiva; la resonancia magnética nuclear torácica, abdominal y pélvica permitieron evidenciar la diseminación multiorgánica de cisticercos. Aunque es poca la casuística y experiencia terapéutica en los casos de CCD, el paciente recibió tratamiento antiparasitario con albendazol y corticoides, logrando una evolución clínica favorable y sin complicaciones durante la hospitalización

Evitar o efeito da vacinação BCG na detecção de infecção por Mycobacterium tuberculosis com um teste sanguíneo Avoiding the effect of BCG vaccination in detecting Mycobacterium tuberculosis infection with a blood test

OpenAIRE

R. Diel; M Ernst; G Doscher; L Visuri-Karbe; U Greinert; S Niemann; A Nienhaus; C Lange

2007-01-01

O risco de progressão da infecção por Mycobacterium tuberculosis para tuberculose-doença é sobretudo elevado nos primeiros anos após a infecção, estimando-se que 50% dos casos de tuberculose-infecção desenvolvem doença nos dois anos seguintes. A investigação precoce dos contactos baseia-se neste facto, e o teste cutâneo de tuberculina tem sido largamente utilizado como a prova de rastreio, apesar da sua limitação na população vacinada com BCG, nas reacções cruzadas com micobactérias não tuber...

Cytochemical and biological properties of Mycobacterium bovis BCG.

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Slosárek, M

1977-01-01

It was the aim of the present communication to find a simple test for a reliable discrimination of Mycobacterium bovis BCG from Mycobacterium tuberculosis. A total of 26 BCG strains, out of them 10 Czechoslovak strains (2 lyophilized cultures of BCG of different batch, 6 strains isolated from abscesses of children after BCG-vaccination and 2 strains from fatal cases after BCG-vaccination) and 16 strains obtained from foreign laboratories, were used. Of the tested characteristics a combination of 3 tests, sensitivity to 1 microgram of 2-thiophene carbonylhydrazide (TCH), activity of 3 acylamidases (urease, nicotinamidase and pyrazinamidase) and a quantitative nitrate test, was found to be most advantageous. The Czechoslovak strains of Mycobacterium bovis BCG were fully sensitive to TCH, of the 3 acylamidases mentioned above only urease was positive and nitrate was reduced only little or not at all. On the other hand, strains of Mycobacterium tuberculosis were always resistant to TCH, had positive urease, nicotinamidase and pyrazinamidase and reduced nitrate very intensively.

BCG protects against tuberculosis irrespective of HIV status

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Faurholt-Jepsen, Daniel; Range, Nyagosya; PrayGod, George

2013-01-01

While BCG vaccine protects against severe tuberculosis (TB) in children, its effect against adult TB is questionable. Furthermore, it is not known if HIV co-infection modifies the effect of BCG. Among 352 pairs of Tanzanian TB cases and matched controls, the BCG scar was associated with a reduced...

Evolution and Strain Variation in BCG

KAUST Repository

Abdallah, Abdallah; Behr, Marcel A.

2017-01-01

BCG vaccines were derived by in vitro passage, during the years 1908–1921, at the Pasteur Institute of Lille. Following the distribution of stocks of BCG to vaccine production laboratories around the world, it was only a few decades before different

Another vaccine, another story: BCG vaccination against tuberculosis in India, 1948 to 1960 Outra vacina, outra história: a vacinação de BCG contra tuberculose na Índia, 1948 a 1960

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Niels Brimnes

2011-02-01

sofreram mais com problemas de recrutamento do que a mais "heroica" campanha de erradicação da varíola. E por último, a vacina de BCG foi contestada em círculos médicos e foi muito mais bem adaptada do que a vacina contra varíola como um veículo para articulação de preocupações sobre a modernização pós-colonial.

The efficacy of BCG TICE and BCG Connaught in a cohort of 2,099 patients with T1G3 non-muscle-invasive bladder cancer

NARCIS (Netherlands)

Witjes, J.A.; Dalbagni, G.; Karnes, R.J.; Shariat, S.; Joniau, S.; Palou, J.; Serretta, V.; Larre, S.; Stasi, S. Di; Colombo, R.; Babjuk, M.; Malmstrom, P.U.; Malats, N.; Irani, J.; Baniel, J.; Cai, T.; Cha, E.; Ardelt, P.; Varkarakis, J.; Bartoletti, R.; Spahn, M.; Pisano, F.; Gontero, P.; Sylvester, R.

2016-01-01

BACKGROUND: Potential differences in efficacy of different bacillus Calmette-Guerin (BCG) strains are of importance for daily practice, especially in the era of BCG shortage. OBJECTIVE: To retrospectively compare the outcome with BCG Connaught and BCG TICE in a large study cohort of pT1 high-grade

The efficacy of BCG TICE and BCG Connaught in a cohort of 2,099 patients with T1G3 non-muscle-invasive bladder cancer.

Science.gov (United States)

Witjes, J Alfred; Dalbagni, Guido; Karnes, Robert J; Shariat, Shahrokh; Joniau, Steven; Palou, Joan; Serretta, Vincenzo; Larré, Stéphane; di Stasi, Savino; Colombo, Renzo; Babjuk, Marek; Malmström, Per-Uno; Malats, Nuria; Irani, Jacques; Baniel, Jack; Cai, Tommaso; Cha, Eugene; Ardelt, Peter; Varkarakis, John; Bartoletti, Riccardo; Spahn, Martin; Pisano, Francesca; Gontero, Paolo; Sylvester, Richard

2016-11-01

Potential differences in efficacy of different bacillus Calmette-Guérin (BCG) strains are of importance for daily practice, especially in the era of BCG shortage. To retrospectively compare the outcome with BCG Connaught and BCG TICE in a large study cohort of pT1 high-grade non-muscle-invasive bladder cancer patients. Individual patient data were collected for 2,451 patients with primary T1G3 tumors from 23 centers who were treated with BCG for the first time between 1990 and 2011. Using Cox multivariable regression and adjusting for the most important prognostic factors in this nonrandomized comparison, BCG Connaught and TICE were compared for time to recurrence, progression, and the duration of cancer specific survival and overall survival. Information on the BCG strain was available for 2,099 patients: 957 on Connaught and 1,142 on TICE. Overall, 765 (36%) patients received some form of maintenance BCG, 560 (59%) on Connaught and 205 (18%) on TICE. Without maintenance, Connaught was more effective than TICE only for the time to first recurrence (hazard ratio [HR] = 1.48; 95% CI: 1.20-1.82; PTICE was more effective than Connaught for the time to first recurrence (HR = 0.66; 95% CI: 0.47-0.93; P = 0.019) with a trend for cancer specific survival (HR = 0.36; 95% CI: 0.14-0.92; P = 0.033). For time to progression and overall survival, Connaught and TICE had a similar efficacy. Compared to no maintenance therapy, maintenance BCG significantly reduced the risk of recurrence, progression and death, both overall, and disease specific, for TICE, but not for Connaught. We found that BCG Connaught results in a lower recurrence rate as compared with BCG TICE when no maintenance is used. However, the opposite is true when maintenance is given. As there is currently a BCG shortage, information on the efficacy of different BCG strains is important. In this nonrandomized retrospective comparison in over 2,000 patients, we found that BCG Connaught reduces the recurrence rate

BCG vaccination at birth and early childhood hospitalisation

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Stensballe, Lone Graff; Sørup, Signe; Aaby, Peter

2017-01-01

vaccination at birth would reduce early childhood hospitalisation in Denmark, a high-income setting. METHODS: Pregnant women planning to give birth at three Danish hospitals were invited to participate. After parental consent, newborn children were allocated to BCG or no intervention within 7 days of age......BACKGROUND: The BCG vaccine is administered to protect against tuberculosis, but studies suggest there may also be non-specific beneficial effects upon the infant immune system, reducing early non-targeted infections and atopic diseases. The present randomised trial tested the hypothesis that BCG......-protocol analyses. RESULTS: 4184 pregnant women were randomised and their 4262 children allocated to BCG or no intervention. There was no difference in risk of hospitalisation up to 15 months of age; 2129 children randomised to BCG experienced 1047 hospitalisations with a mean of 0.49 hospitalisation per child...

Effectiveness of BCG vaccination to aged mice

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Ito Tsukasa

2010-09-01

Full Text Available Abstract Background The tuberculosis (TB still increases in the number of new cases, which is estimated to approach 10 million in 2010. The number of aged people has been growing all over the world. Ageing is one of risk factors in tuberculosis because of decreased immune responses in aged people. Mycobacterium bovis Bacillus Calmette Guérin (BCG is a sole vaccine currently used for TB, however, the efficacy of BCG in adults is still a matter of debate. Emerging the multidrug resistant Mycobacterium tuberculosis (MDR-TB make us to see the importance of vaccination against TB in new light. In this study, we evaluated the efficacy of BCG vaccination in aged mice. Results The Th1 responses, interferon-γ production and interleukin 2, in BCG inoculated aged mice (24-month-old were comparable to those of young mice (4- to 6-week-old. The protection activity of BCG in aged mice against Mycobacterium tuberculosis H37Rv was also the same as young mice. Conclusion These findings suggest that vaccination in aged generation is still effective for protection against tuberculosis.

Role of fibronectin in intravesical BCG therapy for superficial bladder cancer.

Science.gov (United States)

Ratliff, T L; Kavoussi, L R; Catalona, W J

1988-02-01

Intravesical bacillus Calmette-Guerin (BCG) has been demonstrated to be effective both for prophylaxis and treatment of superficial bladder cancer. In order to identify the progression of events that result in BCG-mediated antitumor activity, studies were performed to evaluate the mechanism of binding of BCG within the bladder. Histological and quantitative studies in a mouse model revealed that BCG attached to the bladder wall only in areas of urothelial damage. Preliminary in vitro data showed that BCG attached to surfaces coated with extracellular matrix proteins. Further studies were then performed using purified extracellular matrix proteins to identify the proteins responsible for attachment. BCG were observed to attach to surfaces coated only with purified fibronectin (FN) but not to other purified proteins including laminin, collagen or fibrinogen. The attachment of BCG to purified FN in vitro was dose dependent and was inhibited by anti-FN antibodies. Moreover, BCG attachment in vivo to bladders with damaged urothelial surfaces was inhibited more than 95% by anti-FN antibodies, but binding was not affected by anti-laminin antibodies or preimmune serum. A survey of commercially available BCG vaccines (Pasteur, Tice, Glaxo, Connaught) showed that only Glaxo BCG did not attach to FN-coated surfaces. Glaxo BCG also was shown to express inferior antitumor activity suggesting that the absence of FN binding by Glaxo may have been associated with the absence of antitumor activity of the vaccine.

BCG: the only available vaccine against tuberculosis: review article

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Roghayeh Teimourpour

2017-01-01

Full Text Available Background: Despite advances in the vaccinology and chemotherapy in the past century, tuberculosis is still responsible for two million deaths every year. Emergence of multi-drug resistant strain and coinfection of TB-HIV make it a serious concern. Treatment and control of tuberculosis is a great health burden in every community. Active tuberculosis in children has very severe consequences especially those who are under 5-years-old, therefore vaccine indication should be taken. Bacille Calmette-Guérin (BCG is a live attenuated strain of Mycobacterium bovis that has been used for providing immunity or protection against tuberculosis (TB. In addition, BCG provides relative protection against leprosy and Buruli ulcer, it also can be used for treatment of bladder cancer. BCG is the most widely administered vaccine around the world. It has been given to over three billion individuals over the past decades. At first it was developed in 1908 at the Pasteur Institute in Lille by Albert Calmette and Camille Guérin. In fact BCG is a strain of Mycobacterium bovis that bear deletion in its genome following too long subculture in special media. Deletion in region of deletion 1 (RD1, a specific region of Mycobacterium bovis genome, has decreased pathogenicity of BCG strain. Following culture of BCG on different media since 1921 make genetic variation in the BCG strains that have specific characteristics. BCG should begin given to only immune-competent individuals and should not be administered to immunocompromised people. This vaccine is not effective in people formerly infected or sensitized with environmental mycobacteria. Previous meta-analysis studies indicate that BCG has variable range of protection from 0 to 80 percent against pulmonary TB, but is very effective against severe disseminated forms such as meningitis and miliary form of TB. Despite many research and develop new generation vaccine against TB, BCG vaccine still remains as the only

Determinants of BCG scarification among children in rural Guinea-Bissau

DEFF Research Database (Denmark)

Funch, Katarina M; Thysen, Sanne M; Rodrigues, Amabelia

2018-01-01

: Bandim Health Project (BHP) runs a Health and Demographic Surveillance System site in rural Guinea-Bissau. BHP provides BCG at monthly visits. We studied determinants for not developing a BCG scar using binomial regression models to obtain relative risks (RR). RESULTS: From May 2012 until October 2014......, BHP nurses vaccinated 2415 infants with BCG. We assessed BCG scar between 6 and 12 months of age for 2156 (89%) of these children and 2115 (98%) had developed a scar. In comparison, among 785 children BCG vaccinated elsewhere, 622 (79%) had a scar, the RR of not having a scar being 10.91 (7.......52-15.85) compared with children vaccinated by BHP....

Digestive juices action on the absorption and the oral BCG destination

International Nuclear Information System (INIS)

Mortatti, R.C.; Fonseca, L.

1986-01-01

The absorption and the biological routing of Mycobacterium bovis BCG vaccine following intragastric administration to mice was studied. A harmful action of gastric (GJ) and duodenal juices (DJ) on BCG cells in vitro was found. Treatment with GJ induced a significant decrease of the oxygen uptake and a moderate loss of viability as expressed by the number of colony-forming units (CFU) of BCG. Severe decreases of bacilli respiration and a notable fall of CFU counts were detected during DJ treatment. The biorouting of BCG cells was determined using carbon-14 labelled bacilli. The labelling was accomplished through a metabolic precursor of mycobacterial lipids, sup(14)C-glycerol. The levels of radioactivity recovered at the first day in the organs of mice receiving either gastric instillation of sup(14)C-BCG, sonically disrupted sup(14)-BCG or sup(14)C glycerol were very similar. Subsequently, sonicated sup(14)C-BCG and sup(14)C-glycerol were involved in a biological decay process, while the level of sup(14)C-BCG associated radioactivity remained stable in the organs from 6 to 24 days. Data on the biodecay from the small intestine and liver showed that absorptive events were fast enough to reach the highest level at 24 hours, dropping thereafter according to the complexity of the material given to the mice. In all instances, however, living BCG was not cultured from organs of mice given unlabelled BCG. The preceding data suggest that the great majority of BCG cells that passed the gut barriers were absorbed intact but not alive. (author)

Asociación de encefalomielitis diseminada aguda y síndrome de Guillain-Barré en un adulto

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Miguel A. Pagano

2011-06-01

Full Text Available La encefalomielitis diseminada aguda (EMDA y el síndrome de Guillain-Barré (SGB son reconocidas como entidades distintas, que afectan diferentes sectores del sistema nervioso, pero que comparten varias características tales como la patogenia autoinmune, el impacto sobre la mielina y el antecedente de infección viral o vacunación una a cuatro semanas previas al cuadro clínico. Se presenta un paciente varón de 41 años de edad que consultó por presentar fiebre, debilidad en miembros inferiores y somnolencia dos semanas posteriores a episodio agudo de gastroenteritis. Al ingreso se constató deterioro del sensorio (obnubilación hiperreflexia patelar, Babinski bilateral y vejiga neurogénica. Veinticuatro horas después desarrolló paraplejía flácida y arreflexia generalizada, requiriendo asistencia respiratoria mecánica por insuficiencia respiratoria. El líquido cefalorraquídeo mostró pleocitosis mononuclear e hiperproteinorraquia. El estudio electrofisiológico evidenció importante disminución de las velocidades de conducción en ambos nervios ciáticos poplíteos externos, compatible con polineuropatía desmielinizante. La resonancia magnética nuclear mostró imágenes compatibles con desmielinización en cerebro, protuberancia y segmentos medulares dorsales. Se realizó diagnóstico de ASEMDA-SGB e inició tratamiento con metilprednisolona e inmunoglobulina intravenosa. Evolucionó favorablemente, recuperando las funciones motoras, vesical y la sensibilidad, siendo capaz de deambular luego de seis meses. La asociación de EMDA y SGB (ASEMDA-SGB es una condición infrecuente, generalmente señalada como de mal pronóstico, en la cual un diagnóstico precoz y un rápido y enérgico tratamiento pueden mejorar substancialmente la evolución.

BCG strain S4-Jena: An early BCG strain is capable to reduce the proliferation of bladder cancer cells by induction of apoptosis

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Hermann Inge-Marie

2010-06-01

Full Text Available Abstract Background Intravesical immunotherapy with Mycobacterium bovis bacillus Calmette-Guérin has been established as the most effective adjuvant treatment for high risk non-muscle-invasive bladder cancer (NMIBC. We investigated the differences between the S4-Jena BCG strain and commercially available BCG strains. We tested the genotypic varieties between S4-Jena and other BCG strains and analysed the effect of the BCG strains TICE and S4-Jena on two bladder cancer cell lines. Results In contrast to commercially available BCG strains the S4-Jena strain shows genotypic differences. Spoligotyping verifies the S4-Jena strain as a BCG strain. Infection with viable S4-Jena or TICE decreased proliferation in the T24 cell line. Additionally, hallmarks of apoptosis were detectable. In contrast, Cal29 cells showed only a slightly decreased proliferation with TICE. Cal29 cells infected with S4-Jena, though, showed a significantly decreased proliferation in contrast to TICE. Concordantly with these results, infection with TICE had no effect on the morphology and hallmarks of apoptosis of Cal29 cells. However, S4-Jena strain led to clearly visible morphological changes and caspases 3/7 activation and PS flip. Conclusions S4-Jena strain has a direct influence on bladder cancer cell lines as shown by inhibition of cell proliferation and induction of apoptosis. The data implicate that the T24 cells are responder for S4-Jena and TICE BCG. However, the Cal29 cells are only responder for S4-Jena and they are non-responder for TICE BCG. S4-Jena strain may represent an effective therapeutic agent for NMIBC.

BCG and Adverse Events in the Context of Leprosy

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Renate Richardus

2018-04-01

Full Text Available BackgroundNotwithstanding its beneficial immunoprophylactic outcomes regarding leprosy and childhood TB, BCG vaccination may cause adverse events, particularly of the skin. However, this local hyper-immune reactivity cannot be predicted before vaccination, nor is its association with protection against leprosy known. In this study we investigated the occurrence of adverse events after BCG (revaccination in contacts of leprosy patients and analyzed whether the concomitant systemic anti-mycobacterial immunity was associated with these skin manifestations.MethodsWithin a randomized controlled BCG vaccination trial in Bangladesh, 14,828 contacts of newly diagnosed leprosy patients received BCG vaccination between 2012 and 2017 and were examined for adverse events 8 to 12 weeks post-vaccination. From a selection of vaccinated contacts, venous blood was obtained at follow-up examination and stimulated with Mycobacterium leprae (M. leprae antigens in overnight whole-blood assays (WBA. M. leprae phenolic glycolipid-I-specific antibodies and 32 cytokines were determined in WBAs of 13 individuals with and 13 individuals without adverse events after vaccination.ResultsOut of the 14,828 contacts who received BCG vaccination, 50 (0.34% presented with adverse events, mainly (80% consisting of skin ulcers. Based on the presence of BCG scars, 30 of these contacts (60% had received BCG in this study as a booster vaccination. Similar to the pathological T-cell immunity observed for tuberculoid leprosy patients, contacts with adverse events at the site of BCG vaccination showed elevated IFN-γ levels in response to M. leprae-specific proteins in WBA. However, decreased levels of sCD40L in serum and GRO (CXCL1 in response to M. leprae simultaneously indicated less T-cell regulation in these individuals, potentially causing uncontrolled T-cell immunity damaging the skin.ConclusionSkin complications after BCG vaccination present surrogate markers for protective

La Matriz BCG (Boston Consulting Group para la Gestión de Publicaciones Periádicas The BCG (Boston Consulting Group matrix for management of periodic publications

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Mª del Pilar Serrano Gallardo

2005-11-01

Full Text Available El marketing documental se ha de encargar de satisfacer las necesidades informativas de los usuarios de forma rentable para ellos y para el centro; para ello se ha de partir de un conjunto de herramientas técnicas que se conocen como el Marketing - Mix, y que abarcan el Producto, el Precio, la Distribución y la Comunicación. Dentro de las herramientas destinadas al producto se encuentra la matriz BCG (Boston Consulting Group, que está orientada a gestión, sobre la base de la situación del producto en el mercado. El objetivo del presente artículo es proponer una matriz BCG para la gestión de una publicación periódica enfermera en nuestro mercado.La matriz BCG se construye con dos variables: el Crecimiento del Mercado y la Tasa Relativa del Mercado, las cuales se han operacionalizado como Media de Crecimiento Anual en el número de suscripciones de tres revistas enfermeras (Rol de Enfermería, Metas de Enfermería y Nursing durante el último quinquenio y Media de Tirada Actual de las tres publicaciones. Se han utilizado datos ofrecidos por la Oficina para el Control de la Difusión (OJD. La matriz BCG puede constituirse como herramienta básica en la gestión de publicaciones, dado que tras determinar la situación del producto, se pueden establecer estrategias que ayuden o favorezcan el mejor posicionamiento posible del producto en el mercado.Documentary marketing has to address the information needs of the users in a manner that is cost-effective not only for them but also for the institution. To do this, a set of technical tools, known as Marketing- Mix, need to be used. These tools include the Product, Price, Distribution and Communication. Within the set of tools used for the Product, we find the BCG matrix (Boston Consulting Group, a tool aimed at the management of the product on the basis of where it is positioned in the market. The objective of this paper is to propose a BCG matrix for the management of a nursing periodic

Persistence of the immune response induced by BCG vaccination

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Blitz Rose

2008-01-01

Full Text Available Abstract Background Although BCG vaccination is recommended in most countries of the world, little is known of the persistence of BCG-induced immune responses. As novel TB vaccines may be given to boost the immunity induced by neonatal BCG vaccination, evidence concerning the persistence of the BCG vaccine-induced response would help inform decisions about when such boosting would be most effective. Methods A randomised control study of UK adolescents was carried out to investigate persistence of BCG immune responses. Adolescents were tested for interferon-gamma (IFN-γ response to Mycobacterium tuberculosis purified protein derivative (M.tb PPD in a whole blood assay before, 3 months, 12 months (n = 148 and 3 years (n = 19 after receiving teenage BCG vaccination or 14 years after receiving infant BCG vaccination (n = 16. Results A gradual reduction in magnitude of response was evident from 3 months to 1 year and from 1 year to 3 years following teenage vaccination, but responses 3 years after vaccination were still on average 6 times higher than before vaccination among vaccinees. Some individuals (11/86; 13% failed to make a detectable antigen-specific response three months after vaccination, or lost the response after 1 (11/86; 13% or 3 (3/19; 16% years. IFN-γ response to Ag85 was measured in a subgroup of adolescents and appeared to be better maintained with no decline from 3 to 12 months. A smaller group of adolescents were tested 14 years after receiving infant BCG vaccination and 13/16 (81% made a detectable IFN-γ response to M.tb PPD 14 years after infant vaccination as compared to 6/16 (38% matched unvaccinated controls (p = 0.012; teenagers vaccinated in infancy were 19 times more likely to make an IFN-γ response of > 500 pg/ml than unvaccinated teenagers. Conclusion BCG vaccination in infancy and adolescence induces immunological memory to mycobacterial antigens that is still present and measurable for at least 14 years in the

SIMULTANEOUS BCG AND SMALLPOX VACCINATION ON NEWBORN INFANTS

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Abdul Rivai

2012-09-01

Full Text Available Telah dikemukakan anggapan-anggapan yang terdapat dewasa ini tentang vaksinasi BCG dan cacar secara simultan. Telah dilakukan vaksinasi BCG dan cacar secara simultan pada 729 neonati dengan freeze dried Smallpox vaccine buatan dari Bio Farma dan freeze dried BCG vaccine Tokyo. Pencacaran dilakukan secara multiple puncture dan bifurcated needle dengan suntikan BCG dengan jarum dan spuit khusus intracutan dengan dosis 0,1 ml. Tuberkulin test dilakukan dengan PPD dari Kopenhagen dengan kekuatan 2 TU 9 minggu setelah vaksinasi. Dari 741 bayi yang diikut sertakan dalam survey, 12 menolak, 3 bayi tidak dapat dilakukan pemeriksaan pertama, 35 bayi belum diperiksa, pemeriksaan pertama telah dilakukan pada 691 bayi. Dari 406 bayi yang seharusnya sudah diperiksa untuk pemeriksaan kedua, 23 dapat dilakukan karena tidak dapat dijumpai atau meninggal. Telah dikemukakan bahwa pencatatan alamat yang jelas dan lengkap serta kesungguhan dalam melakukan home visits sangat penting untuk berhasilnya penyelidikan semacam ini. Dari hasil-hasil yang didapatkan sampai sekarang telah dapat diambil kesimpulan sementara, bahwa vaksinasi BCG dan cacar secara simultan memberikan hasil yang memuaskan, juga bila dibandingkan dengan hasil-hasil penyelidikan diluar negeri take pada pencacaran 99.4 percent, test tuberkulin dengan PPD 2 TU 9 minggu setelah vaksinasi memberikan indurasi lebih dari 5 mm pada 99.75 percent dan tidak menimbulkan komplikasi-komplikasi. Pelaksanaan vaksinasi BCG dan cacar dapat dilakukan oleh tenaga paramedis yang telah mendapat latihan khusus dan diawasi oleh dokter yang kompeten. Dianjurkan untuk melakukan follow up pada bayi-bayi yang diikut sertakan dalam survey ini.

Tuberculin reactivity in a population of schoolchildren with high BCG vaccination coverage

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Bierrenbach Ana L.

2003-01-01

Full Text Available OBJECTIVE: To investigate the influence of BCG vaccination or revaccination on tuberculin skin test reactivity, in order to guide the correct interpretation of this test in a setting of high neonatal BCG vaccination coverage and an increasing BCG revaccination coverage at school age. METHODS: We conducted tuberculin skin testing and BCG scar reading in 1148 children aged 7-14 years old in the city of Salvador, Bahia, Brazil. We measured the positive effect of the presence of one or two BCG scars on the proportion of tuberculin skin test results above different cut-off levels (induration sizes of > 5 mm, > 10 mm, and > 15 mm and also using several ranges of induration size (0, 1-4, 5-9, 10-14, and > 15 mm. We also measured the effects that age, gender, and the school where the child was enrolled had on these proportions. RESULTS: The proportion of tuberculin results > 10 mm was 14.2% (95% confidence interval (CI = 8.0%-20.3% for children with no BCG scar, 21.3% (95% CI = 18.5%-24.1% for children with one BCG scar, and 45.0% (95% CI = 32.0%-58.0% for children with two BCG scars. There was evidence for an increasing positive effect of the presence of one and two BCG scars on the proportion of results > 5 mm and > 10 mm. Similarly, there was evidence for an increasing positive effect of the presence of one and two scars on the proportion of tuberculin skin test results in the ranges of 5-9 mm and of 10-14 mm. The BCG scar effect on the proportion of results > 5 mm and > 10 mm did not vary with age. There was no evidence for BCG effect on the results > 15 mm. CONCLUSIONS: In Brazilian schoolchildren, BCG-induced tuberculin reactivity is indistinguishable, for results under 15 mm, from reactivity induced by Mycobacterium tuberculosis infection. BCG revaccination at school age increases the degree of BCG-induced tuberculin reactivity found among schoolchildren. This information should be taken into account in tuberculin skin test surveys intended to

BCG induced granulomatous prostatitis ; a case report

Energy Technology Data Exchange (ETDEWEB)

Moon, Min Hoan; Seong, Chang Kyu; Lee, Kyoung Ho; Kim, Seung Hyup [College of Medicine and the Institute of Radiation Medicine, Seoul National University, Seoul (Korea, Republic of)

2000-04-01

Granulomatous prostatitis was relatively uncommon until the introduction of intravesical BCG for the treament of bladder cancer. Since that time, there has been an increase in the number of cases of granulomatous prostatitis, but the domestic literature contains no report. We recently encountered a classic case of BCG induced granulomatous prostatitis and describe this case, including its radiologic findings. (author)=20.

Competitividad de las exportaciones argentinas de fruta a la Unión Europea : su análisis mediante los métodos del Boston Consulting Group (BCG) y la matriz refinada de Viaene Gellynck

OpenAIRE

Cohen, Gloria Virginia; Pena de Ladaga, Beatriz Susana; Gil Roig, José María

2000-01-01

p.409-419 En el presente trabajo se analizó el desempeño competitivo de las seis principales frutas exportadas por la Argentina (manzanas, peras, naranjas, mandarinas, limones y pomelos) en el mercado de importaciones de terceros países del Hemisferio Sur de la Unión Europea. Los métodos elegidos para medir el desempeño competitivo fueron el Boston Consulting Group (BCG) y la matriz refinada del BCG teniendo en cuenta a la modificación realizada por Viaene-Gellynck. Se trabajó con datos de...

BCG protects toddlers during a tuberculosis outbreak.

LENUS (Irish Health Repository)

Gaensbauer, J T

2009-05-01

In 2007, an outbreak of tuberculosis occurred in a toddler population attending two child care centres in Cork, Ireland. Of 268 children exposed, 18 were eventually diagnosed with active tuberculosis. We present the initial clinical and radiographic characteristics of the active disease group. Mantoux testing was positive in only 66% of cases. All cases were either pulmonary or involved hilar adenopathy on chest radiograph; there were no cases of disseminated disease or meningitis. 24% of the exposed children had been previously vaccinated with BCG, and no case of active disease was found in this group (p = 0.016), suggesting a profound protective effect of BCG in this population. Our experience provides evidence supporting a protective effect of BCG against pulmonary disease in young children.

BCG+MMC trial: adding mitomycin C to BCG as adjuvant intravesical therapy for high-risk, non-muscle-invasive bladder cancer: a randomised phase III trial (ANZUP 1301)

International Nuclear Information System (INIS)

Hayne, Dickon; Stockler, Martin; McCombie, Steve P.; Chalasani, Venu; Long, Anne; Martin, Andrew; Sengupta, Shomik; Davis, Ian D.

2015-01-01

Despite adequate trans-urethral resection of the bladder tumour (TURBT), non-muscle-invasive bladder cancer (NMIBC) is associated with high rates of recurrence and progression. Instillation of Bacillus Calmette-Guérin (BCG) into the urinary bladder after TURBT (adjuvant intravesical administration) reduces the risk of both recurrence and progression, and this is therefore the standard of care for high-risk tumours. However, over 30 % of people still recur or progress despite optimal delivery of BCG. Our meta-analysis suggests that outcomes might be improved further by using an adjuvant intravesical regimen that includes both mitomycin and BCG. These promising findings require corroboration in a definitive, large scale, randomised phase III trial using standard techniques for intravesical administration. The BCG + MMC trial (ANZUP 1301) is an open-label, randomised, stratified, two-arm multi-centre phase III trial comparing the efficacy and safety of standard intravesical therapy (BCG alone) against experimental intravesical therapy (BCG and mitomycin) in the treatment of adults with resected, high-risk NMIBC. Participants in the control group receive standard treatment with induction (weekly BCG for six weeks) followed by maintenance (four-weekly BCG for ten months). Participants in the experimental group receive induction (BCG weeks 1, 2, 4, 5, 7, and 8; mitomycin weeks 3, 6, and 9) followed by four-weekly maintenance (mitomycin weeks 13, 17, 25, 29, 37, and 41; BCG weeks 21, 33, and 45). The trial aims to include 500 participants who will be centrally randomised to one of the two treatment groups in a 1:1 ratio stratified by T-stage, presence of CIS, and study site. The primary endpoint is disease-free survival; secondary endpoints are disease activity, time to recurrence, time to progression, safety, health-related quality of life, overall survival, feasibility, and resource use

Diagnóstico de la infección micobacteriana diseminada: evaluación de un método sencillo y barato para países en desarrollo

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Fandinho F. C .O.

1998-01-01

Full Text Available Con el desarrollo de la epidemia del síndrome de inmunodeficiencia adquirida (sida, el aislamiento de micobacterias de la sangre se ha convertido en un problema habitual de los laboratorios clínicos. En el presente estudio se evaluaron dos métodos para aislar micobacterias en muestras de sangre de pacientes de sida: 1 la inoculación directa en un medio bifásico y 2 un método no comercializado de lisis por centrifugación. A cada uno de los 50 pacientes de sida con sospecha de enfermedad micobacteriana diseminada se le extrajeron tres muestras de sangre consecutivas a intervalos de 15 minutos. En 70 de 138 muestras de sangre obtenidas de 30 (60% pacientes se detectó crecimiento de micobacterias. A partir de estos cultivos, en 19 pacientes se aisló Mycobacterium tuberculosis y en 11 (37%, el complejo Mycobacterium avium. Los cultivos en que se utilizó el método de lisis por centrifugación fueron positivos en 54% de los pacientes, mientras que esta cifra se redujo a 44% en los cultivos en que se usó el método bifásico (P > 0,05. El porcentaje de muestras positivas al complejo M. avium fue mayor con el método de centrifugación por lisis (91% que con el de inoculación directa en medio bifásico (45,4% (P 0,05. La técnica no comercializada de centrifugación por lisis es barata, fiable y puede constituir un método alternativo para el diagnóstico de micobacteriemia en países en desarrollo.

SIMULTANEOUS SMALLPOX AND B.C.G. VACCINATION IN INDONESIA

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Nyoman Kumara Rai

2012-09-01

Full Text Available Vaksinasi cacar dan BCG mulai diberikan secara simultan di Jawa dan Bali pada bulan April 1972 vaksinasi cacar diberikan pada lengan kiri dan BCG pada lengan kanan. Secara berangsur-angsur prograi ini kemudian diperluas kedaerah luar Jawa-Bali, sehingga pada akhir tahun 1973 sudah mencakup seluruh Indonesia. Tenaga yang digunakan adalah para juru cacar yang sudah ada dalam rangka proyek pembasmian penyakit cacar yang dimulai tahun 1968, dan terdapat hampir disemua kecamatan diseluru Indonesia. Ide untuk menggabungkan kedua jenis vaksinasi ini yang kebetulan mempunyai target sam (anak2 0 - 14 thn  timbul setelah penderita cacar tidak dilaporkan lagi dibulan September 1971 (ternyata kemudian letusan cacar terakhir adalah dibulan Desember 1971. Sampai saat itu vaksina BCG dilakukan oleh petugas Puskesmas dan tenaga part timer. Ternyata target tidak pernah tercapa hal ini mungkin disebabkan oleh terbatasnya waktu yang tersedia untuk melakukan vaksinasi BCC sehingga para tenaga part timer tsb. hanya mampu mencakup daerah disekitar Puskesmas dan sekolah dasar. Sebelumnya telah diadakan dua trial; yang pertama diadakan di Bandung untuk melihat at tidaknya saling pengaruh mempengaruhi antara kedua jenis vaksin cacar dan BCG bila diberikan pat saat yang bersamaan, sedangkain trial kedua dilakukan untuk menilai kemampuan juru cacar dala melaksanakan vaksinasi BCG serta kesukaran! yang dijumpai dilapangan (masing2 didua kabupaten (Jawa Tengah, Timur dan Yogyakarta. Disamping keuntungan yang diperoleh dari penggabungan kedua jenis vaksinasi ini yakni penghematan tenaga, biaya dan waktu, dijumpai juga beberapa kesukaran antara lain pengumpulan anak2, supply vaksin BCG yang tidak teratur dll. Walaupun demikian, di Jawa dan Bali hasil vaksinasi BCG antara April 1972 sampai dengan April 1973 menunjukkan kenaikan out-put leb dari 4 kali lipat bila dibandingkan dengan out-put sebelum penggabungan, meskipun out-put prin vaksinasi cacar mempunyai tendensi menurun

Estimativa do risco de infecção tuberculosa em populações vacinadas pelo BCG Determining the risk of tuberculosis infection in BCG-vaccinated populations

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Gilberto Ribeiro Arantes

1992-04-01

Full Text Available A revacinação de escolares com BCG, capaz de restaurar a alergia remanescente de vacinação realizada nos primeiros meses de vida, porém incapaz de modificar a alergia devida à infecção pelo M. tuberculosis, possibilitaria a quantificação da parcela dessa população infectada pelo bacilo de Koch. Foi desenvolvida pesquisa com o objetivo de avaliar a aplicabilidade desses pressupostos na estimativa do risco de infecção tuberculosa em áreas sob elevada cobertura com BCG. A população de estudo foi constituída por escolares com 6 a 9 anos de idade freqüentando escolas municipais da zona leste da cidade de São Paulo, durante o primeiro semestre letivo de 1988. De 11.455 vacinados, apenas 7.470 foram submetidos ao teste tuberculínico, revacinados em seguida e retestados dez semanas depois. Destes, 3.314 tinham sido vacinados no primeiro trimestre de vida com meia dose e os demais 4.156 receberam dose plena acima dessa idade (75% no primeiro ano de vida, 20% no segundo e 5% no terceiro. A contagem dos infectados, pelo confronto dos resultados pré e pós vacinais em tabelas de correlação, foi realizada segundo os critérios do método original e modificação introduzida pelos autores, separadamente para os vacinados no primeiro trimestre de vida e após essa idade. O risco de infecção foi, respectivamente, 0,35% e 0,37% com o critério original e 0,45% e 0,49% com o modificado. O referencial médio disponível para a área estudada, estimado por outros métodos, foi 0,55%. As diferenças entre critérios e idades e destes com o referencial não foram significantes (P > 0,05. Os resultados sugerem que o método é aplicável para a estimativa do risco de infecção tuberculosa na idade escolar, em vacinados com BCG no primeiro ano de vida, com dose plena de vacina.The revaccination of schoolchildren can restore the residual allergy induced by vaccination in the first years of life but can not modify the allergy resulting from a

Ultraviolet susceptibility of BCG and virulent tubercle bacilli

International Nuclear Information System (INIS)

Riley, R.L.; Knight, M.; Middlebrook, G.

1976-01-01

To test the effectiveness of irradiating the upper air of a room with ultraviolet light at reducing the concentration of airborne tubercle bacilli, the susceptibility to the germicidal effects of ultraviolet light, Z, was determined for various mycobacteria. Virulent tubercle bacilli and bacille Calmette-Guerin (BCG) were susceptible to ultraviolet radiation, whereas Mycobacterium phlei had 10 times their resistance (Z, approximately one-tenth that for M. tuberculosis). The effectiveness against BCG of upper air ultraviolet irradiation in a room was tested directly by nebulizing BCG into the air of the room and monitoring its rate of disappearance. With one 17-watt fixture operating, the rate of disappearance increased 6-fold; with 2 fixtures operating (46 watts total), the rate of disappearance increased 9-fold. This implies that under steady-state conditions, the concentrations of airborne organisms with ultraviolet light(s) on would have been one-sixth and one-ninth, respectively. The increase in rate of decay of the airborne organism using 1 fixture was equivalent to 10 air changes per hour, whereas that using 2 fixtures was approximately 25 air changes per hour (range: 18 to 33 air changes per hour). These increments are less than those reported previously for Serratia marcescens, because the Z value for BCG is approximately one-seventh that for serratia. These findings with BCG are believed to be directly applicable to virulent tubercle bacilli

Oral polio vaccine influences the immune response to BCG vaccination. A natural experiment.

Science.gov (United States)

Sartono, Erliyani; Lisse, Ida M; Terveer, Elisabeth M; van de Sande, Paula J M; Whittle, Hilton; Fisker, Ane B; Roth, Adam; Aaby, Peter; Yazdanbakhsh, Maria; Benn, Christine S

2010-05-21

Oral polio vaccine (OPV) is recommended to be given at birth together with BCG vaccine. While we were conducting two trials including low-birth-weight (LBW) and normal-birth-weight (NBW) infants in Guinea-Bissau, OPV was not available during some periods and therefore some infants did not receive OPV at birth, but only BCG. We investigated the effect of OPV given simultaneously with BCG at birth on the immune response to BCG vaccine. We compared the in vitro and the in vivo response to PPD in the infants who received OPV and BCG with that of infants who received BCG only. At age 6 weeks, the in vitro cytokine response to purified protein derivate (PPD) of M. Tuberculosis was reduced in LBW and NBW infants who had received OPV with BCG. In a pooled analysis receiving OPV with BCG at birth was associated with significantly lower IL-13 (p = 0.041) and IFN-gamma (p = 0.004) and a tendency for lower IL-10 (p = 0.054) in response to PPD. Furthermore, OPV was associated with reduced in vivo response to PPD at age 2 months, the prevalence ratio (PR) of having a PPD reaction being 0.75 (0.58-0.98), p = 0.033, and with a tendency for reduced likelihood of having a BCG scar (0.95 (0.91-1.00), p = 0.057)). Among children with a scar, OPV was associated with reduced scar size, the regression coefficient being -0.24 (-0.43-0.05), p = 0.012. This study is the first to address the consequences for the immune response to BCG of simultaneous administration with OPV. Worryingly, the results indicate that the common practice in low-income countries of administering OPV together with BCG at birth may down-regulate the response to BCG vaccine.

Oral polio vaccine influences the immune response to BCG vaccination. A natural experiment.

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Erliyani Sartono

Full Text Available BACKGROUND: Oral polio vaccine (OPV is recommended to be given at birth together with BCG vaccine. While we were conducting two trials including low-birth-weight (LBW and normal-birth-weight (NBW infants in Guinea-Bissau, OPV was not available during some periods and therefore some infants did not receive OPV at birth, but only BCG. We investigated the effect of OPV given simultaneously with BCG at birth on the immune response to BCG vaccine. METHODS AND FINDINGS: We compared the in vitro and the in vivo response to PPD in the infants who received OPV and BCG with that of infants who received BCG only. At age 6 weeks, the in vitro cytokine response to purified protein derivate (PPD of M. Tuberculosis was reduced in LBW and NBW infants who had received OPV with BCG. In a pooled analysis receiving OPV with BCG at birth was associated with significantly lower IL-13 (p = 0.041 and IFN-gamma (p = 0.004 and a tendency for lower IL-10 (p = 0.054 in response to PPD. Furthermore, OPV was associated with reduced in vivo response to PPD at age 2 months, the prevalence ratio (PR of having a PPD reaction being 0.75 (0.58-0.98, p = 0.033, and with a tendency for reduced likelihood of having a BCG scar (0.95 (0.91-1.00, p = 0.057. Among children with a scar, OPV was associated with reduced scar size, the regression coefficient being -0.24 (-0.43-0.05, p = 0.012. CONCLUSIONS: This study is the first to address the consequences for the immune response to BCG of simultaneous administration with OPV. Worryingly, the results indicate that the common practice in low-income countries of administering OPV together with BCG at birth may down-regulate the response to BCG vaccine.

Reducing the activity and secretion of microbial antioxidants enhances the immunogenicity of BCG.

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Shanmugalakshmi Sadagopal

Full Text Available In early clinical studies, the live tuberculosis vaccine Mycobacterium bovis BCG exhibited 80% protective efficacy against pulmonary tuberculosis (TB. Although BCG still exhibits reliable protection against TB meningitis and miliary TB in early childhood it has become less reliable in protecting against pulmonary TB. During decades of in vitro cultivation BCG not only lost some genes due to deletions of regions of the chromosome but also underwent gene duplication and other mutations resulting in increased antioxidant production.To determine whether microbial antioxidants influence vaccine immunogenicity, we eliminated duplicated alleles encoding the oxidative stress sigma factor SigH in BCG Tice and reduced the activity and secretion of iron co-factored superoxide dismutase. We then used assays of gene expression and flow cytometry with intracellular cytokine staining to compare BCG-specific immune responses in mice after vaccination with BCG Tice or the modified BCG vaccine. Compared to BCG, the modified vaccine induced greater IL-12p40, RANTES, and IL-21 mRNA in the spleens of mice at three days post-immunization, more cytokine-producing CD8+ lymphocytes at the peak of the primary immune response, and more IL-2-producing CD4+ lymphocytes during the memory phase. The modified vaccine also induced stronger secondary CD4+ lymphocyte responses and greater clearance of challenge bacilli.We conclude that antioxidants produced by BCG suppress host immune responses. These findings challenge the hypothesis that the failure of extensively cultivated BCG vaccines to prevent pulmonary tuberculosis is due to over-attenuation and suggest instead a new model in which BCG evolved to produce more immunity-suppressing antioxidants. By targeting these antioxidants it may be possible to restore BCG's ability to protect against pulmonary TB.

Oral Polio Vaccine Influences the Immune Response to BCG Vaccination. A Natural Experiment

DEFF Research Database (Denmark)

Sartono, E.; Lisse, I.M.; Terveer, E.M.

2010-01-01

not receive OPV at birth, but only BCG. We investigated the effect of OPV given simultaneously with BCG at birth on the immune response to BCG vaccine. Methods and Findings: We compared the in vitro and the in vivo response to PPD in the infants who received OPV and BCG with that of infants who received BCG...... only. At age 6 weeks, the in vitro cytokine response to purified protein derivate (PPD) of M. Tuberculosis was reduced in LBW and NBW infants who had received OPV with BCG. In a pooled analysis receiving OPV with BCG at birth was associated with significantly lower IL-13 (p = 0.041) and IFN-gamma (p...... = 0.004) and a tendency for lower IL-10 (p = 0.054) in response to PPD. Furthermore, OPV was associated with reduced in vivo response to PPD at age 2 months, the prevalence ratio (PR) of having a PPD reaction being 0.75 (0.58-0.98), p = 0.033, and with a tendency for reduced likelihood of having a BCG...

Oral polio vaccine influences the immune response to BCG vaccination. A natural experiment

DEFF Research Database (Denmark)

Sartono, Erliyani; Lisse, Ida M; Terveer, Elisabeth M

2010-01-01

not receive OPV at birth, but only BCG. We investigated the effect of OPV given simultaneously with BCG at birth on the immune response to BCG vaccine. METHODS AND FINDINGS: We compared the in vitro and the in vivo response to PPD in the infants who received OPV and BCG with that of infants who received BCG...... only. At age 6 weeks, the in vitro cytokine response to purified protein derivate (PPD) of M. Tuberculosis was reduced in LBW and NBW infants who had received OPV with BCG. In a pooled analysis receiving OPV with BCG at birth was associated with significantly lower IL-13 (p = 0.041) and IFN-gamma (p...... = 0.004) and a tendency for lower IL-10 (p = 0.054) in response to PPD. Furthermore, OPV was associated with reduced in vivo response to PPD at age 2 months, the prevalence ratio (PR) of having a PPD reaction being 0.75 (0.58-0.98), p = 0.033, and with a tendency for reduced likelihood of having a BCG...

IL-18 Does not Increase Allergic Airway Disease in Mice When Produced by BCG

Science.gov (United States)

Amniai, L.; Biet, F.; Marquillies, P.; Locht, C.; Pestel, J.; Tonnel, A.-B.; Duez, C.

2007-01-01

Whilst BCG inhibits allergic airway responses in murine models, IL-18 has adversary effects depending on its environment. We therefore constructed a BCG strain producing murine IL-18 (BCG-IL-18) and evaluated its efficiency to prevent an asthma-like reaction in mice. BALB/cByJ mice were sensitized (day (D) 1 and D10) by intraperitoneal injection of ovalbumin (OVA)-alum and primary (D20–22) and secondary (D62, 63) challenged with OVA aerosols. BCG or BCG-IL-18 were intraperitonealy administered 1 hour before each immunization (D1 and D10). BCG-IL-18 and BCG were shown to similarly inhibit the development of AHR, mucus production, eosinophil influx, and local Th2 cytokine production in BAL, both after the primary and secondary challenge. These data show that IL-18 did not increase allergic airway responses in the context of the mycobacterial infection, and suggest that BCG-IL-18 and BCG are able to prevent the development of local Th2 responses and therefore inhibit allergen-induced airway responses even after restimulation. PMID:18299704

Viral booster vaccines improve Mycobacterium bovis BCG-induced protection against bovine tuberculosis.

Science.gov (United States)

Vordermeier, H Martin; Villarreal-Ramos, Bernardo; Cockle, Paul J; McAulay, Martin; Rhodes, Shelley G; Thacker, Tyler; Gilbert, Sarah C; McShane, Helen; Hill, Adrian V S; Xing, Zhou; Hewinson, R Glyn

2009-08-01

Previous work with small-animal laboratory models of tuberculosis has shown that vaccination strategies based on heterologous prime-boost protocols using Mycobacterium bovis bacillus Calmette-Guérin (BCG) to prime and modified vaccinia virus Ankara strain (MVA85A) or recombinant attenuated adenoviruses (Ad85A) expressing the mycobacterial antigen Ag85A to boost may increase the protective efficacy of BCG. Here we report the first efficacy data on using these vaccines in cattle, a natural target species of tuberculous infection. Protection was determined by measuring development of disease as an end point after M. bovis challenge. Either Ad85A or MVA85A boosting resulted in protection superior to that given by BCG alone: boosting BCG with MVA85A or Ad85A induced significant reduction in pathology in four/eight parameters assessed, while BCG vaccination alone did so in only one parameter studied. Protection was particularly evident in the lungs of vaccinated animals (median lung scores for naïve and BCG-, BCG/MVA85A-, and BCG/Ad85A-vaccinated animals were 10.5, 5, 2.5, and 0, respectively). The bacterial loads in lymph node tissues were also reduced after viral boosting of BCG-vaccinated calves compared to those in BCG-only-vaccinated animals. Analysis of vaccine-induced immunity identified memory responses measured by cultured enzyme-linked immunospot assay as well as in vitro interleukin-17 production as predictors of vaccination success, as both responses, measured before challenge, correlated positively with the degree of protection. Therefore, this study provides evidence of improved protection against tuberculosis by viral booster vaccination in a natural target species and has prioritized potential correlates of vaccine efficacy for further evaluation. These findings also have implications for human tuberculosis vaccine development.

Mycobacterium bovis endophthalmitis from BCG immunotherapy for bladder cancer

NARCIS (Netherlands)

Gerbrandy, S. J. F.; Schreuders, L. C.; de Smet, M. D.

2008-01-01

BACKGROUND: We report a patient who developed BCG endophthalmitis after BCG immunotherapy for bladder cancer. Comparison of this case with 2 other reported cases reveals a similar pattern of elderly, debilitated and immunocompromised patients with poor response to systemic antituberculous therapy in

An Analysis on BCG Growth Sharing Matrix

OpenAIRE

Mohajan, Haradhan

2017-01-01

In the 21st century, sustainable improvement of business faces various challenges for the global economic competition. But, these challenges can be overcome by the efficient business strategies. The Boston Consulting Group (BCG) helps the business organizations to develop their efficiency for the successful operation of their business activities. To develop the efficiency of marketing decision making, the BCG Matrix plays an effective tool for strategic planning of product performance in indu...

Neonatal BCG vaccination and atopic dermatitis before 13 months of age

DEFF Research Database (Denmark)

Thøstesen, Lisbeth Marianne; Kjaergaard, Jesper; Pihl, Gitte Thybo

2018-01-01

Studies have suggested that Bacillus Calmette-Guérin (BCG) vaccination may reduce the risk of allergic diseases, including atopic dermatitis. The Danish Calmette Study was conducted 2012-2015. Within 7 days of birth new-borns were randomised 1:1 to BCG or no BCG. Exclusion criteria were gestational...... in the control group (RR=0.90 (95% confidence intervals 0.80 to 1.00)). The effect of neonatal BCG vaccination differed significantly between children with atopic predisposition (RR 0.84 (0.74 to 0.95)) and children without atopic predisposition (RR 1.09 (0.88 to 1.37)) (test of no interaction, p=0.04). Among...... children with atopic predisposition, the number-needed-to-treat with BCG to prevent one case of atopic dermatitis was 21 (12 to 76). This article is protected by copyright. All rights reserved....

MRP8/14 induces autophagy to eliminate intracellular Mycobacterium bovis BCG.

Science.gov (United States)

Wang, Jinli; Huang, Chunyu; Wu, Minhao; Zhong, Qiu; Yang, Kun; Li, Miao; Zhan, Xiaoxia; Wen, Jinsheng; Zhou, Lin; Huang, Xi

2015-04-01

To explore the role of myeloid-related protein 8/14 in mycobacterial infection. The mRNA and protein expression levels of MRP8 or MRP14 were measured by real-time PCR and flow cytometry, respectively. Role of MRP8/14 was tested by overexpression or RNA interference assays. Flow cytometry and colony forming unit were used to test the phagocytosis and the survival of intracellular Mycobacterium bovis BCG (BCG), respectively. Autophagy mediated by MRP8/14 was detected by Western blot and immunofluorescence. The colocalization of BCG phagosomes with autophagosomes or lysosomes was by detected by confocal microscopy. ROS production was detected by flow cytometry. MRP8/14 expressions were up-regulated in human monocytic THP1 cells and primary macrophages after mycobacterial challenge. Silencing of MRP8/14 suppressed bacterial killing, but had no influence on the phagocytosis of BCG. Importantly, silencing MRP8/14 decreased autophagy and BCG phagosome maturation in THP1-derived macrophages, thereby increasing the BCG survival. Additionally, we demonstrated that MRP8/14 promoted autophagy in a ROS-dependent manner. The present study revealed a novel role of MRP8/14 in the autophagy-mediated elimination of intracellular BCG by promoting ROS generation, which may provide a promising therapeutic target for tuberculosis and other intracellular bacterial infectious diseases. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Not dead yet: the rise, fall and persistence of the BCG Matrix

OpenAIRE

Madsen, Dag Øivind

2017-01-01

The BCG Matrix was introduced almost 50 years ago, and is today considered one of the most iconic strategic planning techniques. Using management fashion theory as a theoretical lens, this paper examines the historical rise, fall and persistence of the BCG Matrix. The analysis highlights the role played by fashion-setting actors (e.g., consultants, business schools and business media) in the rise of the BCG Matrix. However, over time, portfolio planning models such as the BCG Matrix were atta...

Comparative Proteomic Profiling of Mycobacterium bovis and BCG Vaccine Strains

KAUST Repository

Gao, Ge

2013-09-01

BCG is the only licensed human vaccine currently available against TB. Derived from a virulent strain of M. bovis, the vaccine was thought to have struck a balance between reduced virulence and preserved immunogenicity. Nowadays, BCG vaccine strains used in different countries and vaccination programs show clear variations in their genomes and immune protective properties. The aim of this study was to characterize the proteomic profile on Mycobacterium bovis and five BCG strains Pasteur, Tokyo, Danish, Phipps and Birkhaug by Tandem Mass Tag® (TMT®)-labeling quantitative proteomic approach. In total, 420 proteins were identified and 377 of them were quantitated for their relative abundance. We reported the number and relationship of differential expressed proteins in BCG strains compared to M. bovis and investigated their functions by bioinformatics analysis. Several interesting up-regulated and down-regulated protein targets were found. The identified proteins and their quantitative expression profiles provide a basis for further understanding of the cellular biology of M. bovis and BCG vaccine strains, and hopefully would assist in the design of better anti-TB vaccine and drugs.

[Complete genome sequencing and sequence analysis of BCG Tice].

Science.gov (United States)

Wang, Zhiming; Pan, Yuanlong; Wu, Jun; Zhu, Baoli

2012-10-04

The objective of this study is to obtain the complete genome sequence of Bacillus Calmette-Guerin Tice (BCG Tice), in order to provide more information about the molecular biology of BCG Tice and design more reasonable vaccines to prevent tuberculosis. We assembled the data from high-throughput sequencing with SOAPdenovo software, with many contigs and scaffolds obtained. There are many sequence gaps and physical gaps remained as a result of regional low coverage and low quality. We designed primers at the end of contigs and performed PCR amplification in order to link these contigs and scaffolds. With various enzymes to perform PCR amplification, adjustment of PCR reaction conditions, and combined with clone construction to sequence, all the gaps were finished. We obtained the complete genome sequence of BCG Tice and submitted it to GenBank of National Center for Biotechnology Information (NCBI). The genome of BCG Tice is 4334064 base pairs in length, with GC content 65.65%. The problems and strategies during the finishing step of BCG Tice sequencing are illuminated here, with the hope of affording some experience to those who are involved in the finishing step of genome sequencing. The microarray data were verified by our results.

Recombinant Mycobacterium bovis BCG for immunotherapy in nonmuscle invasive bladder cancer.

Science.gov (United States)

Begnini, K R; Buss, J H; Collares, T; Seixas, F K

2015-05-01

In the past three decades, intravesical instillation of Mycobacterium bovis bacille Calmette-Guérin (BCG) has been used for treating bladder cancer and it still remains at the forefront of immunotherapy for cancer patients. Although BCG-based therapy is the most effective intravesical therapy for this kind of tumor and represents the only agent known to reduce progression into muscle invasive bladder cancer, BCG is ineffective in approximately 30-40 % of cases and disease recurs in up to 50 % of patients. Since that BCG is considered an effective vehicle for delivery of antigens due to its unique characteristics, the genetic manipulation of these mycobacteria has been appealing in the search for less toxic and more potent therapeutic agents for bladder cancer immunotherapy. Herein, we discuss current advances in recombinant BCG construction, research, concerns, and future directions to promote the development of this promising immunotherapeutic approach for bladder cancer.

Active suppression of in vitro reactivity of spleen cells after BCG treatment

International Nuclear Information System (INIS)

Orbach-Arbouys, S.; Poupon, M.F.

1978-01-01

It was found that spleen cells from mice injected i.v. with large doses of BCG responded to PHA stimulation less intensely than did normal spleen cells. It was shown that nylon wool column purified BCG treated T cells also had a low PHA reactivity. Unfractionated spleen cells, adherent cells or T-enriched populations from BCG treated mice, when added to normal T cells lowered their PHA reactivity. When the same BCG treated cell populations were added to tumor cells in vitro, they inhibited their growth. (author)

BCG vaccination in patients with severe combined immunodeficiency: complications, risks, and vaccination policies.

Science.gov (United States)

Marciano, Beatriz E; Huang, Chiung-Yu; Joshi, Gyan; Rezaei, Nima; Carvalho, Beatriz Costa; Allwood, Zoe; Ikinciogullari, Aydan; Reda, Shereen M; Gennery, Andrew; Thon, Vojtech; Espinosa-Rosales, Francisco; Al-Herz, Waleed; Porras, Oscar; Shcherbina, Anna; Szaflarska, Anna; Kiliç, Şebnem; Franco, Jose L; Gómez Raccio, Andrea C; Roxo, Persio; Esteves, Isabel; Galal, Nermeen; Grumach, Anete Sevciovic; Al-Tamemi, Salem; Yildiran, Alisan; Orellana, Julio C; Yamada, Masafumi; Morio, Tomohiro; Liberatore, Diana; Ohtsuka, Yoshitoshi; Lau, Yu-Lung; Nishikomori, Ryuta; Torres-Lozano, Carlos; Mazzucchelli, Juliana T L; Vilela, Maria M S; Tavares, Fabiola S; Cunha, Luciana; Pinto, Jorge A; Espinosa-Padilla, Sara E; Hernandez-Nieto, Leticia; Elfeky, Reem A; Ariga, Tadashi; Toshio, Heike; Dogu, Figen; Cipe, Funda; Formankova, Renata; Nuñez-Nuñez, M Enriqueta; Bezrodnik, Liliana; Marques, Jose Gonçalo; Pereira, María I; Listello, Viviana; Slatter, Mary A; Nademi, Zohreh; Kowalczyk, Danuta; Fleisher, Thomas A; Davies, Graham; Neven, Bénédicte; Rosenzweig, Sergio D

2014-04-01

Severe combined immunodeficiency (SCID) is a syndrome characterized by profound T-cell deficiency. BCG vaccine is contraindicated in patients with SCID. Because most countries encourage BCG vaccination at birth, a high percentage of patients with SCID are vaccinated before their immune defect is detected. We sought to describe the complications and risks associated with BCG vaccination in patients with SCID. An extensive standardized questionnaire evaluating complications, therapeutics, and outcomes regarding BCG vaccination in patients given a diagnosis of SCID was widely distributed. Summary statistics and association analysis was performed. Data on 349 BCG-vaccinated patients with SCID from 28 centers in 17 countries were analyzed. Fifty-one percent of the patients had BCG-associated complications, 34% disseminated and 17% localized (a 33,000- and 400-fold increase, respectively, over the general population). Patients receiving early vaccination (≤1 month) showed an increased prevalence of complications (P = .006) and death caused by BCG-associated complications (P vaccine has a very high rate of complications in patients with SCID, which increase morbidity and mortality rates. Until safer and more efficient antituberculosis vaccines become available, delay in BCG vaccination should be considered to protect highly vulnerable populations from preventable complications. Published by Mosby, Inc.

Deletion of zmp1 improves Mycobacterium bovis BCG-mediated protection in a guinea pig model of tuberculosis.

Science.gov (United States)

Sander, Peter; Clark, Simon; Petrera, Agnese; Vilaplana, Cristina; Meuli, Michael; Selchow, Petra; Zelmer, Andrea; Mohanan, Deepa; Andreu, Nuria; Rayner, Emma; Dal Molin, Michael; Bancroft, Gregory J; Johansen, Pål; Cardona, Pere-Joan; Williams, Ann; Böttger, Erik C

2015-03-10

Having demonstrated previously that deletion of zinc metalloprotease zmp1 in Mycobacterium bovis BCG increased immunogenicity of BCG vaccines, we here investigated the protective efficacy of BCG zmp1 deletion mutants in a guinea pig model of tuberculosis infection. zmp1 deletion mutants of BCG provided enhanced protection by reducing the bacterial load of tubercle bacilli in the lungs of infected guinea pigs. The increased efficacy of BCG due to zmp1 deletion was demonstrated in both BCG Pasteur and BCG Denmark indicating that the improved protection by zmp1 deletion is independent from the BCG sub-strain. In addition, unmarked BCG Δzmp1 mutant strains showed a better safety profile in a CB-17 SCID mouse survival model than the parental BCG strains. Together, these results support the further development of BCG Δzmp1 for use in clinical trials. Copyright © 2015 Elsevier Ltd. All rights reserved.

Tuberculosis: looking beyond BCG vaccines.

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Mustafa Abu S

2003-01-01

Full Text Available Tuberculosis (TB is an infectious disease of international importance and ranks among the top 10 causes of death in the World. About one-third of the world′s population is infected with Mycobacterium tuberculosis. Every year, approximately eight million people develop active disease and two million die of TB. The currently used BCG vaccines have shown variable protective efficacies against TB in different parts of the world. Moreover, being a live vaccine, BCG can be pathogenic in immunocompromised recipients. Therefore, there is an urgent need to develop new vaccines against TB. The comparative genome analysis has revealed the existence of several M. tuberculosis-specific regions that are deleted in BCG. The work carried out to determine the immunological reactivity of proteins encoded by genes located in these regions revealed several major antigens of M. tuberculosis, including the 6 kDa early secreted antigen target (ESAT6. Immunization with ESAT6 and its peptide (aa51-70 protects mice challenged with M. tuberculosis. The protective efficacy of immunization further improves when ESAT6 is recombinantly fused with M. tuberculosis antigen 85B. In addition, ESAT6 delivered as a DNA vaccine is also protective in mice. Whether these vaccines would be safe or not cannot be speculated. The answer regarding the safety and efficacy of these vaccines has to await human trials in different parts of the world.

Mitsuda's reactions: induced by BCG in the normal Rhesus ("Macacca mulatta"

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M. J. Pereira Filho

1955-12-01

Full Text Available The reversals of Mitsuda's reactions induced by BCG have been objected to based on the possiblem interference of other determination causes of the phenomenon: tuberculous primo-infections, communicants of unsuspected leprosy, revearsals due to other causes, such as anti-diphteric and anti-tetanic vaccination, etc. In order to study the problem, we have used Rhesus monkeys (Macaca mulatta, which were reared in isolation, in an attempt to avoid the referred to interferences. Prior to the experiments, all animals were tested and found negative to radiograph, tuberculin and lepromin tests and were then submitted to the application of BCG vaccine (from 1 to 3 days old, in different doses and by different via. At different times, after the application of BCG, they were again submitted to the radiographic, tuberculin and lepromin tests. In the tables I to IV the experiences were summarised. From the experiments, the following conclusions were reached: 1 - From 12 Rhesus that received BCG 11 showed reversals of the Mitsuda reaction (91.7%. 2 - These reverseals took place both in tests effected shortly after BCG (from 6 days to 2 months, and tests effected much later (from 7 to 12 months after BCG. 3 - Some differences were found in the results, according to the dosis and the application via of the BCG. a - The testicular and peritonela via (0,02g were the only that determined strong positive Mitsuda's reactions (+++. b - By oral via, animals that received high dosis (0.6g and 1.2 g, there resulted uniform and regular reversals, even though of low intensity (+; but from those who got small doses (0.2 g. one showed no reversals in all tests, and the other presented reversals in the 2nd and 3rd tests only, also with low positivity (+. 4 In the 2nd and 3rd Mitsuda's reactions in the same animals, positivity was always precocious (generally within 48 hours, one getting the impression that there occurs a sensibilization of the animal body by the antigen with

Mycobacterium bovis BCG mycobacteria--new application.

Science.gov (United States)

Kowalewicz-Kulbat, Magdalena; Pestel, Joël; Biet, Franck; Locht, Camille; Tonnel, André-Bernard; Druszczyńska, Magdalena; Rudnicka, Wiesława

2006-01-01

The polarized response of T helper-2 (Th2) lymphocytes to an allergen is considered to be the main cause of the pathogenesis of asthma. In this study, we asked a question whether M. bovis BCG mycobacteria which are known for the preferential stimulation of T helper-1 (Th1) immunity, diminish the effector functions of Th2 cells from allergic patients upon stimulation with a common house dust mite Der p-1 allergen. Our results allow a positive answer to this question. We demonstrate that BCG modulates the dendritic cell-dependent allergen presentation process and switches naive T lymphocytes towards an anti-allergic Th1 profile.

Estimativa do risco de infecção tuberculosa em populações vacinadas pelo BCG

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Arantes Gilberto Ribeiro

1992-01-01

Full Text Available A revacinação de escolares com BCG, capaz de restaurar a alergia remanescente de vacinação realizada nos primeiros meses de vida, porém incapaz de modificar a alergia devida à infecção pelo M. tuberculosis, possibilitaria a quantificação da parcela dessa população infectada pelo bacilo de Koch. Foi desenvolvida pesquisa com o objetivo de avaliar a aplicabilidade desses pressupostos na estimativa do risco de infecção tuberculosa em áreas sob elevada cobertura com BCG. A população de estudo foi constituída por escolares com 6 a 9 anos de idade freqüentando escolas municipais da zona leste da cidade de São Paulo, durante o primeiro semestre letivo de 1988. De 11.455 vacinados, apenas 7.470 foram submetidos ao teste tuberculínico, revacinados em seguida e retestados dez semanas depois. Destes, 3.314 tinham sido vacinados no primeiro trimestre de vida com meia dose e os demais 4.156 receberam dose plena acima dessa idade (75% no primeiro ano de vida, 20% no segundo e 5% no terceiro. A contagem dos infectados, pelo confronto dos resultados pré e pós vacinais em tabelas de correlação, foi realizada segundo os critérios do método original e modificação introduzida pelos autores, separadamente para os vacinados no primeiro trimestre de vida e após essa idade. O risco de infecção foi, respectivamente, 0,35% e 0,37% com o critério original e 0,45% e 0,49% com o modificado. O referencial médio disponível para a área estudada, estimado por outros métodos, foi 0,55%. As diferenças entre critérios e idades e destes com o referencial não foram significantes (P > 0,05. Os resultados sugerem que o método é aplicável para a estimativa do risco de infecção tuberculosa na idade escolar, em vacinados com BCG no primeiro ano de vida, com dose plena de vacina.

Estimativa do risco de infecção tuberculosa em populações vacinadas pelo BCG

Directory of Open Access Journals (Sweden)

Gilberto Ribeiro Arantes

1992-04-01

Full Text Available A revacinação de escolares com BCG, capaz de restaurar a alergia remanescente de vacinação realizada nos primeiros meses de vida, porém incapaz de modificar a alergia devida à infecção pelo M. tuberculosis, possibilitaria a quantificação da parcela dessa população infectada pelo bacilo de Koch. Foi desenvolvida pesquisa com o objetivo de avaliar a aplicabilidade desses pressupostos na estimativa do risco de infecção tuberculosa em áreas sob elevada cobertura com BCG. A população de estudo foi constituída por escolares com 6 a 9 anos de idade freqüentando escolas municipais da zona leste da cidade de São Paulo, durante o primeiro semestre letivo de 1988. De 11.455 vacinados, apenas 7.470 foram submetidos ao teste tuberculínico, revacinados em seguida e retestados dez semanas depois. Destes, 3.314 tinham sido vacinados no primeiro trimestre de vida com meia dose e os demais 4.156 receberam dose plena acima dessa idade (75% no primeiro ano de vida, 20% no segundo e 5% no terceiro. A contagem dos infectados, pelo confronto dos resultados pré e pós vacinais em tabelas de correlação, foi realizada segundo os critérios do método original e modificação introduzida pelos autores, separadamente para os vacinados no primeiro trimestre de vida e após essa idade. O risco de infecção foi, respectivamente, 0,35% e 0,37% com o critério original e 0,45% e 0,49% com o modificado. O referencial médio disponível para a área estudada, estimado por outros métodos, foi 0,55%. As diferenças entre critérios e idades e destes com o referencial não foram significantes (P > 0,05. Os resultados sugerem que o método é aplicável para a estimativa do risco de infecção tuberculosa na idade escolar, em vacinados com BCG no primeiro ano de vida, com dose plena de vacina.

Combined immunomodulating effects of BCG and Lentinan after intranasal application in guinea pigs.

Science.gov (United States)

Drandarska, Ivanka; Kussovski, Vesselin; Nikolaeva, Sascha; Markova, Nadya

2005-04-01

The ability of a Shiitake (Lentinus edodes) medical mushroom-derived bioactive polymer Lentinan (Ajinomoto, Japan) to modulate the immune response makes it a potential candidate for combination therapy with BCG, or as adjunct for BCG vaccination, especially in high-risk individuals. We studied the combined immune-potential effectiveness of intranasal application of Lentinan (at a dose of 1 mg/kg, three times at 2-day intervals), followed by administration of BCG (strain Sofia SL-222 at a dose of 1 x 10(8) CFU, once) in guinea pigs. Samples of broncho-alveolar lavage fluid, as well as tissue fragments of lungs, spleens and lymph nodes were obtained from four groups (combined treatment with Lentinan and BCG; only with Lentinan; only with BCG; control with saline) of animals at different intervals--1, 14 and 45 days after last treatment and were evaluated by several parameters (establishing the number, H2O2 and nitrite production, and killing ability against Mycobacterium tuberculosis and Staphylococcus aureus of alveolar macrophages; spleen index, BCG CFU in spleens and histomorphological observations). Our attention was focused both on local effects in lungs, and systematical effects in reticuloendothelial system. The results indicate that intranasal application of BCG alone, or in combination with Lentinan induced high level of alveolar macrophage activation. Pre-treatment with Lentinan enhanced the local immunohistological response to BCG in lung and reduced the generalized side effects.

Role of a bacillus Calmette-Guérin fibronectin attachment protein in BCG-induced antitumor activity.

Science.gov (United States)

Zhao, W; Schorey, J S; Bong-Mastek, M; Ritchey, J; Brown, E J; Ratliff, T L

2000-04-01

Intravesical Mycobacterium bovis bacillus Calmette-Gu*erin (BCG) is the treatment of choice for superficial bladder cancer. Previous studies showed that attachment of BCG to fibronectin within the bladder was necessary for mediation of the antitumor response. Further studies identified a bacterial receptor, fibronectin attachment protein (FAP), as an important mediator of BCG attachment to fibronectin. In vitro studies showed that a stable BCG/fibronectin interaction was dependent on FAP binding to fibronectin; however, no role for FAP in the attachment of BCG in vivo has been characterized. We now report the cloning of the M. bovis BCG FAP (FAP-B) and demonstrate an important role for FAP in the in vivo attachment of BCG to the bladder wall and in the induction of BCG-mediated antitumor activity. The predicted amino acid sequence for FAP-B shows 61% and 71% homology, respectively, with Mycobacterium avium FAP (FAP-A) and Mycobacterium leprae FAP (FAP-L). Rabbit polyclonal antibodies against Mycobacterium vaccae FAP (FAP-V) reacted with all 3 recombinant FAP proteins on Western blots. Functional studies show FAP-B to bind fibronectin via the highly conserved attachment regions previously identified for FAP-A and FAP-L and also to competitively inhibit attachment of BCG to matrix fibronectin. In vivo studies show FAP to be a necessary protein for the stable attachment of BCG to the bladder wall. Moreover, stable binding of BCG via FAP was shown to be necessary for the expression of BCG-induced antitumor activity. Our results demonstrate a biological role for FAP in the mediation of BCG-induced antitumor activity.

Celulitis por Microascus trigonosporus(anamorfo Scopulariopsis trigonospora

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DELIA CANLE CORTIÑAS

2013-06-01

Full Text Available Resumen: Microascus trigonosporus ( anamorfo Scopulariopsis trigonospora es un hongo filamentoso ubicuo que se encuentra en el suelo , plumas de aves, material vegetal e insectos. Aunque Scopulariopsis spp se consideran comúnmente hongos contaminantes , pueden causar ocasionalmente infecciones en humanos, en especial onicomicosis . Excepcionalmente se han descrito infecciones de piel, abscesos cerebrales, endocarditis ,sinusitis e infecciones diseminadas por Scopulariopsis spp , casi siempre en pacientes inmunodeprimidos . En los últimos años se han publicado un mayor número de casos de infecciones oportunistas por Scopulariopsis spp y otros hialohifomicetos multiresistentes. Todavía no está establecido cuál es el mejor régimen de tratamiento para las infecciones por Scopulariopsis spp. Presentamos un caso excepcional de celulitis por Microascus trigonosporus en un paciente con tratamiento prolongado con corticoides. Abstract: Microascus trigonosporus ( Anamorph Scopulariopsis trigonospora is a cosmopolitan filamentous fungus that inhabits soil, feathers ,plant material and insects. While Scopulariopsis is commonly considered as a contaminat fungus it may cause occasionally infections in humans ,especially onychomycosis .Skin lesions, brain abscess , endocarditis, sinusitis and disseminated infections due to Scopulariopsis species have been rarely reported , usually in immunocompromised patients . Over the last few years opportunistic infections by Scopulariopsis species and others multi-resistant hyalohyphomycetes have been increasingly reported . No clear treatment regimen for Scopulariopsis species infections has been established yet. We present a exceptional case of cellulitis due to Microascus trigonosporus in a patient with prolonged steroid therapy.

The relationship between nutritional and sociodemographic factors and the likelihood of children in the Dominican Republic having a BCG scar Relación entre los factores nutricionales y sociodemográficos y la probabilidad de que los niños de la República Dominicana tengan cicatriz de BCG

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Eddy Pérez-Then

2007-06-01

Full Text Available OBJECTIVES: To critically assess the prevalence among schoolchildren 6 to 9 years of age throughout the Dominican Republic of a bacille Calmette-Guérin (BCG vaccination scar, and to examine the relationship between nutritional and sociodemographic factors and the likelihood of having a BCG scar. METHODS: This correlational study used the database of the Second National Census on Height and Weight of Elementary School First Grade Students, which was conducted in the Dominican Republic August 2001-May 2002, to provide a critical assessment of BCG coverage nationwide. The Census information for the children included the presence of BCG scar, their nutritional status, and basic demographic data. We developed a new sociodemographic indicator, the "Rosa Index," to examine the potential influence of poverty and other environmental characteristics on scar presence. We used logistic regression models to predict the presence of a BCG scar. RESULTS: An overall BCG scar prevalence of 55.3% (85 644/154 887 was found. Malnourished children were less likely to have a BCG scar than were children with adequate nutritional status (odds ratio = 0.91; 95% confidence interval: 0.87, 0.95, P OBJETIVOS: Evaluar críticamente la prevalencia de cicatrices por la vacunación con el bacilo de Calmette-Guérin (BCG en niños de 6 a 9 años de la República Dominicana y examinar la relación entre los factores nutricionales y socioeconómicos y la probabilidad de tener cicatriz de BCG. MÉTODOS: Para este estudio correlacional se empleó la base de datos del II Censo Nacional de Talla y Peso en Escolares de Primer Grado de Básica, realizado en la República Dominicana entre agosto de 2001 y mayo de 2002, para evaluar críticamente el nivel de cobertura nacional de la vacunación con BCG. Entre la información censal de los niños estaban si tenían cicatriz de BCG, su estado nutricional y sus datos demográficos básicos. Se desarrolló un nuevo indicador sociodemogr

Features of General Reactive Potential of the Body in Infants with BCG lymphadenitis

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A.I. Bobrovitskaia

2014-11-01

Conclusions. When using BCG vaccine of Russian production, there is far less significant overload of blood flow by products of intoxication and inflammation, more pronounced body’s ability to respond to antigenic stimulus generalization and no risk of infection, especially in infants, compared with Danish BCG vaccine. For vaccination of infants against tuberculosis, it is advisable to use more refined, with high immunogenicity and less reactogenic BCG vaccine of Russian production. Despite the presence of complications when using BCG vaccine, protection of the body from the development of generalized forms of tuberculosis in young children is possible by vaccination in the neonatal period.

Vaccination of cattle with Mycobacterium bovis BCG by a combination of systemic and oral routes.

Science.gov (United States)

Buddle, Bryce M; Denis, Michel; Aldwell, Frank E; Martin Vordermeier, H; Glyn Hewinson, R; Neil Wedlock, D

2008-11-01

Mycobacterium bovis bacille Calmette-Guérin (BCG) vaccine delivered to calves by the subcutaneous (s.c.) or by the oral route in a formulated lipid matrix has been previously shown to induce similar levels of protection against bovine tuberculosis. The current study was aimed at determining whether a combination of delivering BCG by s.c. and oral routes would enhance levels of protection, compared to only one route of vaccination. Forty calves were randomly divided into four groups (10/group). Calves were vaccinated with 10(6)colony forming units (CFU) of BCG Pasteur by the s.c. route or orally with 10(9)CFU BCG incorporated into a lipid formulation. One group received a combination of BCG administered by both the s.c. and oral routes and a non-vaccinated group served as a control. The two groups of calves that received s.c. BCG produced strong IFN-gamma responses in whole blood cultures stimulated with bovine purified protein derivative (PPD) 3 weeks after vaccination. Cattle vaccinated just with oral BCG in a lipid matrix produced a strong IFN-gamma response 8 weeks after vaccination, and peaking at 11 weeks after vaccination. All calves were challenged by the intratracheal route with M. bovis 15 weeks after vaccination and were euthanized and necropsied to assess protection at 17 weeks following challenge. BCG given s.c. or orally induced significant and comparable levels of protection against the virulent challenge. Vaccination of cattle by a combination of s.c./oral routes did not enhance protection beyond that achieved by s.c. or oral vaccination alone. We conclude that vaccination of cattle with BCG by a combination of routes has no beneficial additive effects, compared to a single s.c. administration of BCG or BCG given orally in a lipid formulation.

Active Mycobacterium Infection Due to Intramuscular BCG Administration Following Multi-Steps Medication Errors

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MohammadReza Rafati

2015-10-01

Full Text Available Bacillus Calmette-Guérin (BCG is indicated for treatment of primary or relapsing flat urothelial cell carcinoma in situ (CIS of the urinary bladder. Disseminated infectious complications occasionally occur due to BCG as a vaccine and intravesical therapy.  Intramuscular (IM or Intravenous (IV administrations of BCG are rare medication errors which are more probable to produce systemic infections. This report presents 13 years old case that several steps medication errors occurred consequently from physician handwriting, pharmacy dispensing, nursing administration and patient family. The physician wrote βHCG instead of HCG in the prescription. βHCG was read as BCG by the pharmacy staff and 6 vials of intravesical BCG were administered IM twice a week for 3 consecutive weeks. The patient experienced fever and chills after each injection, but he was admitted 2 months after first IM administration of BCG with fever and pancytopenia. Unfortunately four month after using drug, during second admission duo to cellulitis at the sites of BCG injection the physicians diagnosed the medication error. Using handwritten prescription and inappropriate abbreviations, spending inadequate time for taking a brief medical history in pharmacy, lack of verifying name, dose and wrote before medication administration and lack of considering medication error as an important differential diagnosis had roles to occur this multi-steps medication error.

Immunotherapeutic effect of BCG-polysaccharide nucleic acid powder on Mycobacterium tuberculosis-infected mice using microneedle patches.

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Yan, Qinying; Liu, Houming; Cheng, Zhigang; Xue, Yun; Cheng, Zhide; Dai, Xuyong; Shan, Wanshui; Chen, Fan

2017-11-01

Polysaccharide nucleic acid fractions of bacillus Calmette-Guérin, termed BCG-PSN, have traditionally been used as immunomodulators in the treatment of dermatitis and allergic diseases. While the sales of injectable BCG-PSN have shown steady growth in recent years, no reports of using BCG-PSN powder or its immunotherapeutic effects exist. Here, BCG-PSN powder was applied directly to the skin to evaluate the immunotherapeutic effects on mice infected with Mycobacterium tuberculosis (MTB). In total, 34 μg of BCG-PSN powder could be loaded into a microneedle patch (MNP). Mice receiving BCG-PSN powder delivered via MNP exhibited significantly increased IFN-γ and TNF-α production in peripheral blood CD4 + T cells and improved pathological changes in their lungs and spleens compared to control group mice. The immunotherapeutic effect of BCG-PSN powder delivered via MNP was better than that delivered via intramuscular injection to some extent. Furthermore, MNPs eliminate the side effects of syringes, and this study demonstrated that BCG-PSN can be clinically administrated in powder form.

Up-date of the BCG code library

International Nuclear Information System (INIS)

Caldeira, A.D.; Garcia, R.D.M.

1990-01-01

Procedures for generating an up-date material library for the BCG code were established. A new library was generated by processing ENDF/B-IV data with the 89-1 version of the LINEAR, RECENT and SIGMA1 programs. The effect of library change in the neutron spectrum and effective multiplication factor of a fast reactor cell was analized. During the course of this study, an error was detected in the BCG code. Although localized in a narrow energy range, the discrepancies in neutron spectrum caused by the error were large enough to yield a difference of about 1% in the effective multiplication factor of the test cell. (author)

Tuberculosis vaccine strain Mycobacterium bovis BCG Russia is a natural recA mutant

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Böttger Erik C

2008-07-01

Full Text Available Abstract Background The current tuberculosis vaccine is a live vaccine derived from Mycobacterium bovis and attenuated by serial in vitro passaging. All vaccine substrains in use stem from one source, strain Bacille Calmette-Guérin. However, they differ in regions of genomic deletions, antigen expression levels, immunogenicity, and protective efficacy. Results As a RecA phenotype increases genetic stability and may contribute restricting the ongoing evolution of the various BCG substrains while maintaining their protective efficacy, we aimed to inactivate recA by allelic replacement in BCG vaccine strains representing different phylogenetic lineages (Pasteur, Frappier, Denmark, Russia. Homologous gene replacement was achieved successfully in three out of four strains. However, only illegitimate recombination was observed in BCG substrain Russia. Sequence analyses of recA revealed that a single nucleotide insertion in the 5' part of recA led to a translational frameshift with an early stop codon making BCG Russia a natural recA mutant. At the protein level BCG Russia failed to express RecA. Conclusion According to phylogenetic analyses BCG Russia is an ancient vaccine strain most closely related to the parental M. bovis. We hypothesize that recA inactivation in BCG Russia occurred early and is in part responsible for its high degree of genomic stability, resulting in a substrain that has less genetic alterations than other vaccine substrains with respect to M. bovis AF2122/97 wild-type.

Vitamin A supplementation and BCG vaccination at birth in low birthweight neonates

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Benn, Christine Stabell; Fisker, Ane Baerent; Napirna, Bitiguida Mutna

2010-01-01

OBJECTIVE: To investigate the effect of vitamin A supplementation and BCG vaccination at birth in low birthweight neonates. DESIGN: Randomised, placebo controlled, two by two factorial trial. SETTING: Bissau, Guinea-Bissau. PARTICIPANTS: 1717 low birthweight neonates born at the national hospital...... months of age for infants who received vitamin A supplementation compared with those who received placebo. RESULTS: No interaction was observed between vitamin A supplementation and BCG vaccine allocation (P=0.73). Vitamin A supplementation at birth was not significantly associated with mortality......: the MRR of vitamin A supplementation compared with placebo, controlled for randomisation to "early BCG" versus "no early BCG" was 1.08 (95% CI 0.79 to 1.47). Stratification by sex revealed a significant interaction between vitamin A supplementation and sex (P=0.046), the MRR of vitamin A supplementation...

Haematological profile of rats (Rattus norvegicus) induced BCG and provided leaf extract of Plectranthus amboinicus Lour Spreng)

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Silitonga, Melva; Silitonga, Pasar M.

2017-08-01

Plectranthus amboinicus Lour Spreng is a medicinal plant that has many benefits, such as an antioxidant, hepatoprotective and immunostimulan. Immune status can be seen from hematological profile. This study aims to investigate hematology profile on rats induced BCG and leaf extract of Plectranthus amboinicus. 24 male rats aged 3 months and weighing between 140-200 grams divided equally into six groups, P0, P1, P2, P3, P4 and P5. P0 as controle was given aquadest. The P1, P2, P3, P4 and P5 treatment groups were given 19 g / kg AEP + BCG, 31.5 g / kg AEP + BCG, 19g / kg AEP, 31.5 g / kg AEP and BCG consecutively. The BCG were used as antigen. The AEP was administered orally for 30 days and 100 µl BCG were intramusculary administered on day 14 th and day 21. On day 31st, the rats we decapitated and their blood were collected for hematology (leucocyte (WBC), Erythrocyte (RBC), thrombocyte (PLT) count, Haemoglobin (Hb), erythrocyte sedimentation rate (ESR), MCV, MHC, and MHCH analysis. Data were analyzed with ANOVA. WBC increased significantly in treatment AEP 31.5 g / kg bw, 31.5 g AEP / kg bw + BCG and so were only given BCG. RBC tend to increase in all AEP treatment but tends to increase again when given a BCG. Hb increased in treatment P1, P2, T3 and P4, but the improvement was significant only in treatment P1. While PLT increase significantly in all treatments compared to the controls. HCT did not show significant differences but all of them were in the normal range. EAP without BCG and with the addition of BCG lowered ESR significantly, whereas BCG alone increased the ESR significantly. MCV increased significantly only in the treatment of P1 and show the same pattern with the MHC and MHCH. The conclusion that Plectranthus amboinicus Lour a positive impact on blood profiles with and without BCG. Plectranthus amboinicus Lour managed blood profile when administered together with BCG

Successful Handling of Disseminated BCG Disease in a Child with Severe Combined Immunodeficiency

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Bacalhau, S; Freitas, C; Valente, R; Barata, D; Neves, C; Schäfer, K; Lubatschofski, A; Schulz, A; Farela Neves, J

2011-01-01

In high-burden countries, Mycobacterium bovis Bacillus Calmette-Guérin (BCG) vaccine is administered in newborn to prevent severe Mycobacterium tuberculosis infection. Because life-threatening disseminated BCG disease may occur in children with primary immunodeficiency, vaccination strategy against tuberculosis should be redefined in non-high-burden countries. We report the case of a patient with X-linked severe combined immunodeficiency (SCID) who developed disseminated BCG disease, highligh...

Strongyloides stercoralis y VIH: un caso de infección diseminada en una zona no endémica

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F. D. Rivero

2006-09-01

serrana de la provincia de Córdoba, Argentina, que acudió a la consulta por un cuadro respiratorio complicado debido a una neumocistosis, por lo que se le indicó tratamiento con trimetoprima-sulfametoxazol parenteral y prednisona. Pocos días después de la admisión, demostró marcado deterioro y en un nuevo análisis de esputo evidenció larvas filariformes de S. stercoralis, motivo por el cual recibió terapia oral con ivermectina (200 µg/kg/d. Paralelamente comenzó con intolerancia alimentaria y la instauración de un íleo, lo que llevó a su fallecimiento a los pocos días por falla multiorgánica. La evolución de su enfermedad al estadio de SIDA, la administración de esteroides para aminorar el grave compromiso respiratorio y la falla terapéutica, a pesar del tratamiento oral con ivermectina, incrementaron su deterioro en beneficio de la proliferación de larvas y lo condujeron a la muerte. Esta comunicación no sólo constituye el primer caso de estrongiloidiasis diseminada descrito en nuestro hospital, sino que además informa sobre una infección autóctona de esta helmintiasis poco frecuente en esta área, la que a veces puede ser subdiagnosticada. Asimismo, estos hallazgos ameritan el alerta de médicos y microbiólogos para la administración de terapias antiparasitarias por vías alternativas en casos de íleo y malabsorción, cuadros clínicos característicos de la hiperinfección por esta parasitosis.

[Mechanism of action of intravesical BCG. Biological bases and clinical applicability.

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Carballido, Joaquín A; Rodríguez Monsalve, María

2018-05-01

The therapeutic approaches developed around immune system modulation find the therapeutic contribution of intravesical Bacillus Calmette Guerin (BCG) for transitional cell bladder cancer an unquestionable example as a proof of concept of antitumor immunotherapy since more than 30 years ago. Intravesical immunotherapy for urothelial carcinomas is considered with periodic intravesical instillations schedules, and the one with longer historic development and wider diffusion is BCG in the form of suspension. BCG is a unique strain obtained from Mycobacterium bovis at the end of the first third of the XX century and represents the historically most successful immunotherapeutic modality of all tumors with a high level body of evidence. Currently, we even see an unpredictable development potential of this therapeutic modality based on immunomodulation related with activation or suppression of T lymphocytes by blocking the immune system checkpoints. This option is at this time a decisive step in the treatment of chemotherapy refractory metastatic urothelial carcinoma. Over the last years, there have been advances in the intimate mechanism of action of intravesical BCG, but there are many open questions that will only be answered from complex basic and translational research platforms. The objective of this review article is to try to translate the basic mechanisms currently implicated in the different phases of antitumor response of BCG in its routine use in clinical practice. Also, to analyze the future lines already active under clinical research with and without implications of the mechanisms of action of BCG. We describe the role of interactions basally established between urothelial tumor cells and cellular and molecular elements of the immune system of the patients with ulterior antitumor effector capacity. After intravesical BCG therapy and its interaction, we describe the various phases of its mechanism of action, namely fixation, internalization and triggering of

Successful Handling of Disseminated BCG Disease in a Child with Severe Combined Immunodeficiency

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Sílvia Bacalhau

2011-01-01

Full Text Available In high-burden countries, Mycobacterium bovis Bacillus Calmette-Guérin (BCG vaccine is administered in newborn to prevent severe Mycobacterium tuberculosis infection. Because life-threatening disseminated BCG disease may occur in children with primary immunodeficiency, vaccination strategy against tuberculosis should be redefined in non-high-burden countries. We report the case of a patient with X-linked severe combined immunodeficiency (SCID who developed disseminated BCG disease, highlighting the specific strategies adopted.

Surgical Complications of Bacille Calmette-Guérin (BCG) Infection in ...

African Journals Online (AJOL)

Surgical Complications of Bacille Calmette-Guérin (BCG) Infection in HIV infected children. J Karpelowsky, A Alexander, SD Peek, A Millar, H Rode. Abstract. Aim. Bacille Calmette-Guérin (BCG) immunisation is well established as part of the South African national expanded programme for immunisation (EPI). The World ...

Revaccination of Guinea Pigs With the Live Attenuated Mycobacterium tuberculosis Vaccine MTBVAC Improves BCG's Protection Against Tuberculosis.

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Clark, Simon; Lanni, Faye; Marinova, Dessislava; Rayner, Emma; Martin, Carlos; Williams, Ann

2017-09-01

The need for an effective vaccine against human tuberculosis has driven the development of different candidates and vaccination strategies. Novel live attenuated vaccines are being developed that promise greater safety and efficacy than BCG against tuberculosis. We combined BCG with the vaccine MTBVAC to evaluate whether the efficacy of either vaccine would be affected upon revaccination. In a well-established guinea pig model of aerosol infection with Mycobacterium tuberculosis, BCG and MTBVAC delivered via various prime-boost combinations or alone were compared. Efficacy was determined by a reduction in bacterial load 4 weeks after challenge. Efficacy data suggests MTBVAC-associated immunity is longer lasting than that of BCG when given as a single dose. Long and short intervals between BCG prime and MTBVAC boost resulted in improved efficacy in lungs, compared with BCG given alone. A shorter interval between MTBVAC prime and BCG boost resulted in improved efficacy in lungs, compared with BCG given alone. A longer interval resulted in protection equivalent to that of BCG given alone. These data indicate that, rather than boosting the waning efficacy of BCG, a vaccination schedule involving a combination of the 2 vaccines yielded stronger immunity to M. tuberculosis infection. This work supports development of MTBVAC use as a revaccination strategy to improve on the effects of BCG in vaccinated people living in tuberculosis-endemic countries. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Disseminated BCG infection in a patient with severe combined immunodeficiency

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Han, Tae Il; Kim, In One; Kim, Woo Sun; Yeon, Kyung Mo

2000-01-01

Disseminated mycobacterial infection after bacillus Calmette-Guerin (BCG) accination is a very rare disorder, occurring mostly in patients with immunologic eficiency. We report a case of disseminated BCG infection in a 16-month-old girl with severe combined immunodeficiency. Plain radiographs showed multiple osteolytic lesions in the femora, tibiae, humerus, and phalanges. Abdominal sonography and CT scanning revealed multiple nodules in the spleen, and portocaval lymphadenopathy

Disseminated BCG infection in a patient with severe combined immunodeficiency

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Han, Tae Il [Eulji University School of Medicine, Taejon (Korea, Republic of); Kim, In One; Kim, Woo Sun; Yeon, Kyung Mo [Seoul National University College of Medicine, Seoul (Korea, Republic of)

2000-06-01

Disseminated mycobacterial infection after bacillus Calmette-Guerin (BCG) accination is a very rare disorder, occurring mostly in patients with immunologic eficiency. We report a case of disseminated BCG infection in a 16-month-old girl with severe combined immunodeficiency. Plain radiographs showed multiple osteolytic lesions in the femora, tibiae, humerus, and phalanges. Abdominal sonography and CT scanning revealed multiple nodules in the spleen, and portocaval lymphadenopathy.

Long-term in vitro and in vivo effects of γ-irradiated BCG on innate and adaptive immunity

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Arts, Rob J W; Blok, Bastiaan A; Aaby, Peter

2015-01-01

were less strong than those induced by live BCG. γBCG vaccination in volunteers had only minimal effects on innate immunity, whereas a significant increase in heterologous Th1/Th17 immunity was observed. Our results indicate that γBCG induces long-term training of innate immunity in vitro. In vivo, γ......BCG vaccination is associated with a reduced mortality from nonmycobacterial infections. This is likely to be mediated by a combination of innate-immune memory ("trained immunity") and heterologous effects on adaptive immunity. As such, BCG could be used to boost host immunity...

[Mycobacterial bovis BCG cutaneous infections following mesotherapy: 2 cases].

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Marco-Bonnet, J; Beylot-Barry, M; Texier-Maugein, J; Barucq, J P; Supply, P; Doutre, M S; Beylot, C

2002-05-01

Infectious complications following mesotherapy are usually due to ordinary bacteria or atypical mycobacteria. We report two new cases of mycobacterial bovis BCG infections following mesotherapy. To our knowledge only one case has already been reported. A 52 year-old woman developed vaccinal MERIEUX BCG cutaneous abscesses following mesotherapy. Identification was made by a novel class of repeated sequences: Mycobacterial interspersed repetitive units. Despite prolonged anti-tuberculous therapy, complete remission was not obtained and surgical excision was performed. The second case was a 49 year-old man who developed a mycobacterial bovis BCG cutaneous abscess (Connaught) after mesotherapy, the regression of which was obtained with anti-tuberculous therapy. The severity of these two mycobacterial infections following mesotherapy illustrate the potential risks of mesotherapy. Identification is possible by molecular biology techniques (PCR and sequencing). The origin of this infection is unclear and therapeutic decision is difficult. Some authors recommend anti-tuberculous therapy but surgical excision may be necessary as in our cases.

BCG vaccine powder-laden and dissolvable microneedle arrays for lesion-free vaccination.

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Chen, Fan; Yan, Qinying; Yu, Yang; Wu, Mei X

2017-06-10

Live attenuated Bacille Calmette-Guerin (BCG) bacillus is the only licensed vaccine for tuberculosis prevention worldwide to date. It must be delivered intradermally to be effective, which causes severe skin inflammation and sometimes, permanent scars. To minimize the side effects, we developed a novel microneedle array (MNA) that could deliver live attenuated freeze-dried BCG powder into the epidermis in a painless, lesion-free, and self-applicable fashion. The MNA was fabricated with biocompatible and dissolvable hyaluronic acid with a deep cave formed in the basal portion of each microneedle, into which BCG powder could be packaged directly. Viability of BCG vaccine packaged in the caves and the mechanical strength of the powder-laden MNA did not alter significantly before and after more than two months of storage at room temperature. Following insertion of the MNA into the skin, individual microneedle shafts melted away by interstitial fluid from the epidermis and upper dermis, exposing the powder to epidermal tissues. The powder sucked interstitial fluid, dissolved slowly, and diffused into the epidermis in a day against the interstitial fluid influx. Vaccination with BCG-MNA caused no overt skin irritation, in marked contrast to intradermal vaccination that provoked severe inflammation and bruise. While causing little skin irritation, vaccination efficacy of BCG-MNAs was comparable to that of intradermal immunization whether it was evaluated by humoral or cellular immunity. This powder-laden and dissolvable MNA represents a novel technology to sufficiently deliver live attenuated vaccine powders into the skin. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of revaccination with BCG in early childhood on mortality: randomised trial in Guinea-Bissau.

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Roth, Adam Edvin; Benn, Christine Stabell; Ravn, Henrik; Rodrigues, Amabelia; Lisse, Ida Maria; Yazdanbakhsh, Maria; Whittle, Hilton; Aaby, Peter

2010-03-15

To determine whether BCG revaccination at 19 months of age reduces overall child mortality. Randomised trial, with follow-up to age 5. A health project in Bissau, Guinea-Bissau, which maintains a health and demographic surveillance system in an urban area with 90 000 inhabitants. 2871 children aged 19 months to 5 years with low or no reactivity to tuberculin and who were not severely sick on the day of enrollment. BCG vaccination or no vaccination (control). Hazard ratios for mortality. 77 children died during follow-up. Compared with controls, the BCG revaccinated children had a hazard ratio of 1.20 (95% confidence interval 0.77 to 1.89). Two hundred and fifty children were admitted to hospital for the first time between enrollment and the end of the study, with an incidence rate ratio for BCG revaccinated children versus controls of 1.04 (0.81 to 1.33). The trial was stopped prematurely because of a cluster of deaths in the BCG arm of the study. This increase in mortality occurred at a time when many children had received missing vaccinations or vitamin A or iron supplementation; the hazard ratio for BCG revaccinated children compared with controls was 2.69 (1.05 to 6.88) in the period after these campaigns. Throughout the trial, the effect of BCG revaccination on mortality was significantly different (P=0.006) in children who had received diphtheria-tetanus-pertussis (DTP) booster vaccination before enrollment (hazard ratio 0.36, 0.13 to 0.99) and children who had not received the booster before enrollment (1.78, 1.04 to 3.04). There was no overall beneficial effect of being revaccinated with BCG. The effect of BCG revaccination on mortality might depend on other health interventions. Trial registration Clinical Trials ICA4-CT-2002-10053-REVAC.

ESAT6 inhibits autophagy flux and promotes BCG proliferation through MTOR

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Dong, Hu, E-mail: austhudong@126.com [Department of Medical Immunology, Medical School, Anhui University of Science and Technology (China); Medical Inspection Center, Anhui University of Science and Technology, Huainan (China); Jing, Wu, E-mail: wujing8008@126.com [Department of Medical Immunology, Medical School, Anhui University of Science and Technology (China); Medical Inspection Center, Anhui University of Science and Technology, Huainan (China); Runpeng, Zhao; Xuewei, Xu; Min, Mu; Ru, Cai [Department of Medical Immunology, Medical School, Anhui University of Science and Technology (China); Yingru, Xing; Shengfa, Ni [Affiliated Cancer Hospital, Anhui University of Science and Technology (China); Rongbo, Zhang [Department of Medical Immunology, Medical School, Anhui University of Science and Technology (China); Medical Inspection Center, Anhui University of Science and Technology, Huainan (China)

2016-08-19

In recent years, increasing studies have found that pathogenic Mycobacterium tuberculosis (Mtb) inhibits autophagy, which mediates the anti-mycobacterial response, but the mechanism is not clear. We previously reported that secretory acid phosphatase (SapM) of Mtb can negatively regulate autophagy flux. Recently, another virulence factor of Mtb, early secretory antigenic target 6 (ESAT6), has been found to be involved in inhibiting autophagy, but the mechanism remains unclear. In this study, we show that ESAT6 hampers autophagy flux to boost bacillus Calmette-Guerin (BCG) proliferation and reveals a mechanism by which ESAT6 blocks autophagosome-lysosome fusion in a mammalian target of rapamycin (MTOR)-dependent manner. In both Raw264.7 cells and primary macrophages derived from the murine abdominal cavity (ACM), ESAT6 repressed autophagy flux by interfering with the autophagosome-lysosome fusion, which resulted in an increased load of BCG. Impaired degradation of LC3Ⅱ and SQSTM1 by ESAT6 was related to the upregulated activity of MTOR. Contrarily, inhibiting MTOR with Torin1 removed the ESAT6-induced autophagy block and lysosome dysfunction. Furthermore, in both Raw264.7 and ACM cells, MTOR inhibition significantly suppressed the survival of BCG. In conclusion, our study highlights how ESAT6 blocks autophagy and promotes BCG survival in a way that activates MTOR. - Highlights: • A mechanism for disruping autophagy flux induced by ESAT6. • ESAT6-inhibited autophagy is MTOR-dependent. • ESAT6-boosted BCG is MTOR-dependent.

Biomarkers in patients treated with BCG: an update.

Science.gov (United States)

Klap, Julia; Schmid, Marianne; Loughlin, Kevin R

2014-08-01

Bacillus Calmette-Guerin (BCG) instillations are the recommended treatment for non-muscle invasive bladder cancer but high recurrence and progression rates remain after treatment. Despite patients risk stratification, BCG effectiveness remains unpredictable. A close, invasive and expensive follow up is mandatory. To improve or even replace this heavy surveillance in this high risk population, validated biomarkers were developed. To identify the useful tools for the urologist in monitoring bladder cancer patients, we reviewed the literature focusing on plasma and urinary biomarkers of BCG-therapy outcome. Articles dated from 1988 to 2013 including specific keywords (urinary bladder neoplasm, biological markers, intravesical administration, recurrence) were examined and relevant papers were selected. Before treatment initiation, genetic polymorphisms of multiple agents (cytokines, matrix-metalloproteinases) were found to become very useful to tailor therapy and monitoring. Those biomarkers belong to personalized medicine which is a topic of great interest today, but still need to be validated in cohorts from different ethnicities. During instillations, cytokines (IL-2, IL-8, IL-6/IL-10) were reported to be reliable to determine treatment response and efficacy. Further studies are needed to confirm results and standardize thresholds. After treatment, UroVysion, the FDA-approved fluorescence in situ hybridization (FISH), appeared to be the most robust marker of all the clinical parameters reviewed; but is not yet validated for BCG-treated patients. No recommendations for everyday practice can be established today, but a combination of several markers and clinicopathological characteristics may be the future. As bladder cancer diagnosis and management are evolving, practicing urologists should be aware of and utilize bladder cancer markers in clinical practice.

Neonatal BCG-vaccination and atopic dermatitis before 13 months of age. A randomised clinical trial

DEFF Research Database (Denmark)

Thøstesen, Lisbeth Marianne; Kjaergaard, Jesper; Pihl, Gitte Thybo

2017-01-01

Studies have suggested that Bacillus Calmette-Guérin (BCG) vaccination may reduce the risk of allergic diseases, including atopic dermatitis. The Danish Calmette Study was conducted 2012-2015. Within 7 days of birth new-borns were randomised 1:1 to BCG or no BCG. Exclusion criteria were gestational...... in the control group (RR=0.90 (95% confidence intervals 0.80 to 1.00)). The effect of neonatal BCG vaccination differed significantly between children with atopic predisposition (RR 0.84 (0.74 to 0.95)) and children without atopic predisposition (RR 1.09 (0.88 to 1.37)) (test of no interaction, p=0.04). Among...... children with atopic predisposition, the number-needed-to-treat with BCG to prevent one case of atopic dermatitis was 21 (12 to 76). This article is protected by copyright. All rights reserved....

Auxotrophic recombinant Mycobacterium bovis BCG overexpressing Ag85B enhances cytotoxicity on superficial bladder cancer cells in vitro.

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Begnini, Karine Rech; Rizzi, Caroline; Campos, Vinicius Farias; Borsuk, Sibele; Schultze, Eduarda; Yurgel, Virginia Campello; Nedel, Fernanda; Dellagostin, Odir Antônio; Collares, Tiago; Seixas, Fabiana Kömmling

2013-02-01

BCG therapy remains at the forefront of immunotherapy for treating patients with superficial bladder cancer. The high incidence of local side effects and the presence of non-responder diseases have led to efforts to improve the therapy. Hence, we proposed that an auxotrophic recombinant BCG strain overexpressing Ag85B (BCG ∆leuD/Ag85B), could enhance the cytotoxicity to the human bladder carcinoma cell line 5637. The rBCG was generated using an expression plasmid encoding the mycobacterial antigen Ag85B to transform a BCG ∆leuD strain. The inhibitory effect of BCG ∆leuD/Ag85B on 5637 cells was determined by the MTT method, morphology observation and a LIVE/DEAD assay. Gene expression profiles for apoptotic, cell cycle-related and oxidative stress-related genes were investigated by qRT-PCR. Bax, bcl-2 and p53 induction by BCG ∆leuD/Ag85B treatment was evaluated by Western blotting. BCG ∆leuD/Ag85B revealed a superior cytotoxicity effect compared to the control strains used in this study. The results showed that the expression level of pro-apoptotic and cell cycle-related genes increased after BCG ∆leuD/Ag85B treatment, whereas the mRNA levels of anti-apoptotic genes decreased. Interestingly, BCG ∆leuD/Ag85B also increased the mRNA level of antioxidant enzymes in the bladder cancer cell line. Bax and p53 proteins levels increased following treatment. In conclusion, these results suggest that treatment with BCG ∆leuD/Ag85B enhances cytotoxicity for superficial bladder cancer cells in vitro. Therefore, rBCG therapy may have potential benefits in the treatment of bladder cancer.

Evolution of M. bovis BCG Vaccine: Is Niacin Production Still a Valid Biomarker?

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Sarman Singh

2015-01-01

Full Text Available BCG vaccine is usually considered to be safe though rarely serious complications have also been reported, often incriminating contamination of the seed strain with pathogenic Mycobacterium tuberculosis. In such circumstances, it becomes prudent to rule out the contamination of the vaccine seed. M. bovis BCG can be confirmed by the absence of nitrate reductase, negative niacin test, and resistance to pyrazinamide and cycloserine. Recently in India, some stocks were found to be niacin positive which led to a national controversy and closer of a vaccine production plant. This prompted us to write this review and the comparative biochemical and genotypic studies were carried out on the these contentious vaccine stocks at the Indian vaccine plant and other seeds and it was found that some BCG vaccine strains and even some strains of M. bovis with eugenic-growth characteristics mainly old laboratory strains may give a positive niacin reaction. Most probably, the repeated subcultures lead to undefined changes at the genetic level in these seed strains. These changing biological characteristics envisage reevaluation of biochemical characters of existing BCG vaccine seeds and framing of newer guidelines for manufacturing, production, safety, and effectiveness of BCG vaccine.

Neonatal BCG has no effect on allergic sensitization and suspected food allergy until 13 months.

Science.gov (United States)

Thøstesen, Lisbeth Marianne; Kjaer, Henrik Fomsgaard; Pihl, Gitte Thybo; Nissen, Thomas Nørrelykke; Birk, Nina Marie; Kjaergaard, Jesper; Jensen, Aksel Karl Georg; Aaby, Peter; Olesen, Annette Wind; Stensballe, Lone Graff; Jeppesen, Dorthe Lisbeth; Benn, Christine Stabell; Kofoed, Poul-Erik

2017-09-01

Vaccination with Bacillus Calmette-Guérin (BCG) is used in many countries as protection against tuberculosis. Studies have suggested that BCG may also have non-specific effects, reducing non-tuberculosis mortality, morbidity, and atopic manifestations. In this study, we evaluated the effect of neonatal BCG vaccination on allergic sensitization and suspected food allergy at 13 months of age. The Danish Calmette Study was conducted from 2012 to 2015 at three Danish hospitals. Within 7 days of birth, the 4262 newborns of 4184 included mothers were randomized 1:1 to BCG or to a no-intervention control group. Exclusion criteria were gestational age food allergy, resulting in a risk ratio comparing BCG-vaccinated children with control children of 0.91 (95% CI 0.71-1.16). Among 1370 blood samples, sensitization (Phadiatop Infant >0.35 kUA/L) was found in 55 of 743 (7.4%) children in the BCG group and 50 of 627 (8.0%) of the control group (risk ratio 0.94 [0.65-1.36]). In this randomized clinical trial, neonatal BCG had no significant effect on suspected food allergy or on sensitization at 13 months of age. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Neonatal BCG vaccination is associated with enhanced T-helper 1 immune responses to heterologous infant vaccines.

Science.gov (United States)

Libraty, Daniel H; Zhang, Lei; Woda, Marcia; Acosta, Luz P; Obcena, Anamae; Brion, Job D; Capeding, Rosario Z

2014-01-01

Neonatal Bacille Calmette Guérin (BCG) vaccination has been reported to have beneficial effects beyond preventing infantile tuberculous meningitis and miliary disease. We hypothesized that BCG vaccine given at birth would enhance T-helper 1 (Th1) immune responses to the first vaccines given later in infancy. We conducted a nested case-control study of neonatal BCG vaccination and its heterologous Th1 immune effects in 2-3 months old infants. BCG vaccination at birth was associated with an increased frequency of interferon-γ (IFN-γ) producing spot-forming cells (SFC) to tetanus toxoid 2-3 months later. The frequency of IFN-γ producing SFC to polioviruses 1-3 also trended higher among infants who received BCG vaccination at birth. The frequency of IFN-γ+/tumor necrosis factor-α (TNF-α)+CD45RO+CD4+ T-cells upon stimulation with phorbol myristate acetate (PMA)/Ionomycin was higher in 2-3 months old infants who received BCG vaccination at birth compared to those who did not. The circulating frequency of forkhead box P3 (FoxP3)+ CD45RO+ regulatory CD4+ T-cells also trended lower in these infants. Neonatal BCG vaccination is associated with heterologous Th1 immune effects 2-3 months later.

Prosthetic Joint Infection due to Mycobacterium bovis after Intravesical Instillation of Bacillus Calmette-Guerin (BCG

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Eric Gomez

2009-01-01

Full Text Available Intravesical instillation of Bacillus Calmette-Guerin (BCG is a treatment to prevent recurrence of superficial urothelial bladder carcinoma. Complications after bladder instillation of BCG have been reported including locally invasive and systemic infections due to dissemination of Mycobacterium bovis from the bladder. We present an uncommon case and literature review of prosthetic joint infection due to M. bovis after intravesical BCG treatment of bladder cancer.

BCG plus levamisole following irradiation of advanced squamous bronchial carcinoma. [Hard X Radiation

Energy Technology Data Exchange (ETDEWEB)

Pines, A.

1980-08-01

Fifty patients with inoperable squamous cell carcinoma of the bronchus were treated with radical radiotherapy. Afterwards, 16 patients received levamisole on 2 days per week and bacillus calmette guerin (B.C.G.) skin innoculations every two weeks;another 16 received the same dosage of levamisole but B.C.G. every 4 weeks; 18 patients were controls. Survival was better in the first group of patients only during the first two years of study (P = 0.02) but not later: metastases were fewer. Both B.C.G. and levamisole gave little discomfort when the dose was adjusted for each patient.

Bacille Calmette-Guérin (BCG) vaccination at birth and antibody responses to childhood vaccines. A randomised clinical trial

DEFF Research Database (Denmark)

Nissen, Thomas Nørrelykke; Birk, Nina Marie; Smits, Gaby

2017-01-01

) vaccination at birth, The Danish Calmette Study, we investigated the effect of BCG at birth on the antibody response to the three routine vaccines against DiTeKiPol/Act-Hib and Prevenar 13 in a subgroup of participants. METHODS: Within 7days after birth, children were randomised 1:1 to BCG vaccination...... children (178 BCG; 122 controls), almost all children (>96%) had antibody responses above the protective levels. Overall BCG vaccination at birth did not affect the antibody level. When stratifying by 'age at randomisation' we found a possible inducing effect of BCG on antibodies against B. pertussis......-protective levels in almost all children. No overall effect of neonatal BCG vaccination was observed....

Factors determining whether the parents accept BCG immunization of the new-born child in a high-income country

DEFF Research Database (Denmark)

Thybo Pihl, Gitte; Ammentorp, Jette; Kofoed, Poul-Erik

Introduction: A large prospective randomised clinical trial in Denmark is planned to test the hypothesis that compared to non-BCG-vaccinated infants, infants who are BCG vaccinated at birth experience less hospitalisations, use less antibiotics, and develop less atopic disease in early childhood......' Connors 'Decisional Conflict scale' to compare decisional conflicts for the parents that accept BCG vaccination and parents who do not accept the BCG vaccination of their newborn child....

Neonatal BCG vaccination is associated with enhanced T-helper 1 immune responses to heterologous infant vaccines

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Daniel H. Libraty

2014-01-01

Full Text Available Neonatal Bacille Calmette Guérin (BCG vaccination has been reported to have beneficial effects beyond preventing infantile tuberculous meningitis and miliary disease. We hypothesized that BCG vaccine given at birth would enhance T-helper 1 (Th1 immune responses to the first vaccines given later in infancy. We conducted a nested case-control study of neonatal BCG vaccination and its heterologous Th1 immune effects in 2–3 months old infants. BCG vaccination at birth was associated with an increased frequency of interferon-γ (IFN-γ producing spot-forming cells (SFC to tetanus toxoid 2–3 months later. The frequency of IFN-γ producing SFC to polioviruses 1–3 also trended higher among infants who received BCG vaccination at birth. The frequency of IFN-γ+/tumor necrosis factor-α (TNF-α+CD45RO+CD4+ T-cells upon stimulation with phorbol myristate acetate (PMA/Ionomycin was higher in 2–3 months old infants who received BCG vaccination at birth compared to those who did not. The circulating frequency of forkhead box P3 (FoxP3+ CD45RO+ regulatory CD4+ T-cells also trended lower in these infants. Neonatal BCG vaccination is associated with heterologous Th1 immune effects 2–3 months later.

Mycobacterium tuberculosis, but not vaccine BCG, specifically upregulates matrix metalloproteinase-1.

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Elkington, Paul T G; Nuttall, Robert K; Boyle, Joseph J; O'Kane, Cecilia M; Horncastle, Donna E; Edwards, Dylan R; Friedland, Jon S

2005-12-15

Pulmonary cavitation is fundamental to the global success of Mycobacterium tuberculosis. However, the mechanisms of this lung destruction are poorly understood. The biochemistry of lung matrix predicts matrix metalloproteinase (MMP) involvement in immunopathology. We investigated gene expression of all MMPs, proteins with a disintegrin and metalloproteinase domain, and tissue inhibitors of metalloproteinases in M. tuberculosis-infected human macrophages by real-time polymerase chain reaction. MMP secretion was measured by zymography and Western analysis, and expression in patients with pulmonary tuberculosis was localized by immunohistochemistry. MMP-1 and MMP-7 gene expression and secretion are potently upregulated by M. tuberculosis, and no increase in tissue inhibitor of metalloproteinase expression occurs to oppose their activity. Dexamethasone completely suppresses MMP-1 but not MMP-7 gene expression and secretion. In patients with active tuberculosis, macrophages express MMP-1 and MMP-7 adjacent to areas of tissue destruction. MMP-1 but not MMP-7 expression and secretion are relatively M. tuberculosis specific, are not upregulated by tuberculosis-associated cytokines, and are prostaglandin dependent. In contrast, the vaccine M. bovis bacillus Calmette-Guérin (BCG) does not stimulate MMP-1 secretion from human macrophages, although M. tuberculosis and BCG do upregulate MMP-7 equally. BCG-infected macrophages secrete reduced prostaglandin E2 concentrations compared with M. tuberculosis-infected macrophages, and prostaglandin pathway supplementation augments MMP-1 secretion from BCG-infected cells. M. tuberculosis specifically upregulates MMP-1 in a cellular model of human infection and in patients with tuberculosis. In contrast, vaccine BCG, which does not cause lung cavitation, does not upregulate prostaglandin E2-dependent MMP-1 secretion.

Tuberculin reaction and BCG scar

DEFF Research Database (Denmark)

Timmermann, Clara Amalie Gade; Biering-Sørensen, Sofie; Aaby, Peter

2015-01-01

rate ratio (MRR) comparing children with a BCG scar with those without was 0.42 (95% CI = 0.19; 0.93). There was a similar tendency for TST positivity: MRR = 0.47 (95% CI = 0.14; 1.54). For LBW children who had both a positive TST reaction and a scar, the MRR was 0.22 (95% CI = 0.05; 0.87). For NBW...

Clinical features and outcome of eleven patients with disseminated Bacille Calmette-Guerin (BCG) infection

International Nuclear Information System (INIS)

Al-Arishi, Haider M.; Frayha, Husn H.; Qari, Hussni Y.; Al-Rayes, H.; Tufenkeji, Haysam T.; Harfi, H.

1996-01-01

Disseminated BCG infection is a very rare complication of BCG vaccination. This study presents 11 patients with such complication. The underlying disease in eight of the 11 patients was primary immunodeficiency. Seven of these had severe combined immune deficiency (SCID) and one had isolated T-cell defect. Of the three remaining patients, one was healthy, one was diagnosed with mucocutaneous candidiasis and the third was diagnosed with leukocytoclastic vasculitis. Cutaneous nodular lesion, persistent fever, hepatosplenomegaly and pulmonary symptoms were common presenting features. All but one patient received antituberculous treatment. Four of 11 patients died because of extensive BCG disease. Three of these had SCID and one had T-cell deficiency. Patients with SCID who survived had bone marrow transplantation in addition to antituberculous chemotherapy. We conclude that a family history of immunodeficiency should be sought and if suggestive, BCG vaccine should be deferred until the immune status of the baby is clarified. In addition, early diagnosis is important for successful outcome. Bone marrow transplant on an emergency basis is the treatment of choice in patients with SCID and disseminated BCG infection, as immune reconstitution is essential to control infection in these patients. (author)

Oral vaccination of brushtail possums with BCG: Investigation into factors that may influence vaccine efficacy and determination of duration of protection.

Science.gov (United States)

Buddle, B M; Aldwell, F E; Keen, D L; Parlane, N A; Hamel, K L; de Lisle, G W

2006-10-01

To determine factors that may influence the efficacy of an oral pelleted vaccine containing Mycobacterium bovis bacille Calmette-Guérin (BCG) to induce protection of brushtail possums against tuberculosis. To determine the duration of protective immunity following oral administration of BCG. In Study 1, a group of possums (n=7) was immunised by feeding 10 pellets containing dead Pasteur BCG, followed 15 weeks later with a single pellet of live Pasteur BCG. At that time, four other groups of possums (n=7 per group) were given a single pellet of live Pasteur BCG orally, a single pellet of live Danish BCG orally, 10 pellets of live Pasteur BCG orally, or a subcutaneous injection of live Pasteur BCG. For the oral pelleted vaccines, BCG was formulated into a lipid matrix, and each pellet contained approximately 107 colony forming units (cfu) of BCG, while the vaccine injected subcutaneously contained 106 cfu of BCG. A sixth, non-vaccinated, group (n=7) served as a control. All possums were challenged by the aerosol route with a low dose of virulent M. bovis 7 weeks after vaccination, and killed 7-8 weeks after challenge. Protection against challenge with M. bovis was assessed from pathological and bacteriological findings. In Study 2, lipid-formulated live Danish BCG was administered orally to three groups of possums (10-11 per group), and these possums were challenged with virulent M. bovis 8, 29 or 54 weeks later. The possums were killed 7 weeks after challenge, to assess protection in comparison to a non-vaccinated group. The results from Study 1 showed that vaccine efficacy was not adversely affected by feeding dead BCG prior to live BCG. Feeding 10 vaccine pellets induced a level of protection similar to feeding a single pellet. Protection was similar when feeding possums a single pellet containing the Pasteur or Danish strains of BCG. All vaccinated groups had significantly reduced pathological changes or bacterial counts when compared to the non-vaccinated group

Overexpression of a Mycobacterium ulcerans Ag85B-EsxH Fusion Protein in Recombinant BCG Improves Experimental Buruli Ulcer Vaccine Efficacy.

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Bryan E Hart

2016-12-01

Full Text Available Buruli ulcer (BU vaccine design faces similar challenges to those observed during development of prophylactic tuberculosis treatments. Multiple BU vaccine candidates, based upon Mycobacterium bovis BCG, altered Mycobacterium ulcerans (MU cells, recombinant MU DNA, or MU protein prime-boosts, have shown promise by conferring transient protection to mice against the pathology of MU challenge. Recently, we have shown that a recombinant BCG vaccine expressing MU-Ag85A (BCG MU-Ag85A displayed the highest level of protection to date, by significantly extending the survival time of MU challenged mice compared to BCG vaccination alone. Here we describe the generation, immunogenicity testing, and evaluation of protection conferred by a recombinant BCG strain which overexpresses a fusion of two alternative MU antigens, Ag85B and the MU ortholog of tuberculosis TB10.4, EsxH. Vaccination with BCG MU-Ag85B-EsxH induces proliferation of Ag85 specific CD4+ T cells in greater numbers than BCG or BCG MU-Ag85A and produces IFNγ+ splenocytes responsive to whole MU and recombinant antigens. In addition, anti-Ag85A and Ag85B IgG humoral responses are significantly enhanced after administration of the fusion vaccine compared to BCG or BCG MU-Ag85A. Finally, mice challenged with MU following a single subcutaneous vaccination with BCG MU-Ag85B-EsxH display significantly less bacterial burden at 6 and 12 weeks post-infection, reduced histopathological tissue damage, and significantly longer survival times compared to vaccination with either BCG or BCG MU-Ag85A. These results further support the potential of BCG as a foundation for BU vaccine design, whereby discovery and recombinant expression of novel immunogenic antigens could lead to greater anti-MU efficacy using this highly safe and ubiquitous vaccine.

The immunological effects of oral polio vaccine provided with BCG vaccine at birth

DEFF Research Database (Denmark)

Jensen, Kristoffer Jarlov; Karkov, Hanne Sophie; Lund, Najaaraq

2014-01-01

BCG alone at birth, and subsequently randomised to have a blood sample taken at 2, 4 or 6 weeks post-randomisation. Excreted levels of cytokines (IL-2, IL-5, IL-10, TNF-α and IFN-γ) were measured from whole blood in vitro stimulations with a panel of recall vaccine antigens (BCG, PPD, OPV), mitogen...... prevalence of IFN-γ responses to PPD (prevalence ratio (PR): 0.84 (0.72-0.98)) and reduced IL-5 to PPD (PR: 0.78 (0.64-0.96)). No effects were observed for CPR, RBP, white blood cell distribution, or BCG scar prevalence. CONCLUSION: The results corroborate that OPV attenuates the immune response to co...

Organization of the BcgI restriction-modification protein for the cleavage of eight phosphodiester bonds in DNA

Science.gov (United States)

Smith, Rachel M.; Marshall, Jacqueline J. T.; Jacklin, Alistair J.; Retter, Susan E.; Halford, Stephen E.; Sobott, Frank

2013-01-01

Type IIB restriction-modification systems, such as BcgI, feature a single protein with both endonuclease and methyltransferase activities. Type IIB nucleases require two recognition sites and cut both strands on both sides of their unmodified sites. BcgI cuts all eight target phosphodiester bonds before dissociation. The BcgI protein contains A and B polypeptides in a 2:1 ratio: A has one catalytic centre for each activity; B recognizes the DNA. We show here that BcgI is organized as A2B protomers, with B at its centre, but that these protomers self-associate to assemblies containing several A2B units. Moreover, like the well known FokI nuclease, BcgI bound to its site has to recruit additional protomers before it can cut DNA. DNA-bound BcgI can alternatively be activated by excess A subunits, much like the activation of FokI by its catalytic domain. Eight A subunits, each with one centre for nuclease activity, are presumably needed to cut the eight bonds cleaved by BcgI. Its nuclease reaction may thus involve two A2B units, each bound to a recognition site, with two more A2B units bridging the complexes by protein–protein interactions between the nuclease domains. PMID:23147005

Neonatal BCG vaccination has no effect on recurrent wheeze in the first year of life

DEFF Research Database (Denmark)

Thøstesen, Lisbeth Marianne; Stensballe, Lone Graff; Pihl, Gitte Thybo

2017-01-01

Background: Recurrent wheeze (RW) is frequent in childhood. Studies have suggested that BCG vaccination can have nonspecific effects, reducing general nontuberculosis morbidity, including respiratory tract infections and atopic diseases. The mechanisms behind these nonspecific effects of BCG...... (relative risk, 1.07; 95% CI, 0.89-1.28). Supplementary analyses were made, including an analysis of baseline risk factors for development of RW. Conclusion: Neonatal BCG had no effect on the development of RW before 13 months of age....

Randomized trial of BCG vaccination at birth to low-birth-weight children: beneficial nonspecific effects in the neonatal period?

Science.gov (United States)

Aaby, Peter; Roth, Adam; Ravn, Henrik; Napirna, Bitiguida Mutna; Rodrigues, Amabelia; Lisse, Ida Maria; Stensballe, Lone; Diness, Birgitte Rode; Lausch, Karen Rokkedal; Lund, Najaaraq; Biering-Sørensen, Sofie; Whittle, Hilton; Benn, Christine Stabell

2011-07-15

Observational studies have suggested that BCG may have nonspecific beneficial effects on survival. Low-birth-weight (LBW) children are not given BCG at birth in Guinea-Bissau; we conducted a randomized trial of BCG at birth (early BCG) vs delayed BCG. In the period 2004-2008 we recruited 2320 LBW children in Bissau. The children were visited at home at 2, 6, and 12 months of age. With a pretrial infant mortality of 250 per 1000, we hypothesized a 25% reduction in infant mortality for LBW children. Infant mortality was only 101 per 1000 during the trial. In the primary analysis, infant mortality was reduced insignificantly by 17% (mortality rate ratio [MRR] = .83 [.63-1.08]). In secondary analyses, early BCG vaccine was safe with an MRR of .49 (.21-1.15) after 3 days and .55 (.34-.89) after 4 weeks. The reduction in neonatal mortality was mainly due to fewer cases of neonatal sepsis, respiratory infection, and fever. The impact of early BCG on infant mortality was marked for children weighing <1.5 kg (MRR = .43 [.21-.85]) who had lower coverage for diphtheria-tetanus-pertussis vaccinations. Though early BCG did not reduce infant mortality significantly, it may have a beneficial effect in the neonatal period. This could be important for public health because BCG is often delayed in low-income countries.

Boosting BCG-primed responses with a subunit Apa vaccine during the waning phase improves immunity and imparts protection against Mycobacterium tuberculosis.

Science.gov (United States)

Nandakumar, Subhadra; Kannanganat, Sunil; Dobos, Karen M; Lucas, Megan; Spencer, John S; Amara, Rama Rao; Plikaytis, Bonnie B; Posey, James E; Sable, Suraj B

2016-05-13

Heterologous prime-boosting has emerged as a powerful vaccination approach against tuberculosis. However, optimal timing to boost BCG-immunity using subunit vaccines remains unclear in clinical trials. Here, we followed the adhesin Apa-specific T-cell responses in BCG-primed mice and investigated its BCG-booster potential. The Apa-specific T-cell response peaked 32-52 weeks after parenteral or mucosal BCG-priming but waned significantly by 78 weeks. A subunit-Apa-boost during the contraction-phase of BCG-response had a greater effect on the magnitude and functional quality of specific cellular and humoral responses compared to a boost at the peak of BCG-response. The cellular response increased following mucosal BCG-prime-Apa-subunit-boost strategy compared to Apa-subunit-prime-BCG-boost approach. However, parenteral BCG-prime-Apa-subunit-boost by a homologous route was the most effective strategy in-terms of enhancing specific T-cell responses during waning in the lung and spleen. Two Apa-boosters markedly improved waning BCG-immunity and significantly reduced Mycobacterium tuberculosis burdens post-challenge. Our results highlight the challenges of optimization of prime-boost regimens in mice where BCG drives persistent immune-activation and suggest that boosting with a heterologous vaccine may be ideal once the specific persisting effector responses are contracted. Our results have important implications for design of prime-boost regimens against tuberculosis in humans.

Recombinant Mycobacterium bovis BCG producing IL-18 reduces IL-5 production and bronchoalveolar eosinophilia induced by an allergic reaction.

Science.gov (United States)

Biet, F; Duez, C; Kremer, L; Marquillies, P; Amniai, L; Tonnel, A-B; Locht, C; Pestel, J

2005-08-01

Allergic reactions occur through the exacerbated induction of a Th2 cell type expression profile and can be prevented by agents favoring a Th1 profile. Bacillus Calmette-Guérin (BCG) is able to induce high IFN-gamma levels and has been shown to decrease experimentally induced allergy. The induction of IFN-gamma is mediated by interleukin (IL)-12 known to be secreted upon mycobacterial infections and can be enhanced by IL-18 acting in synergy with IL-12. We evaluated the ability of a recombinant BCG strain producing IL-18 (rBCG) to modify the Th2 type responses in a murine model of ovalbumin (OVA)-dependent allergic reaction. Mice were injected intraperitoneally or intranasally with OVA at days 0 and 15 and exposed to an OVA aerosol challenge at days 29, 30, 31 and 34. At days 0 and 15, two additional groups of mice received OVA together with 5 x 10(6) colony forming units of either rBCG or nonrecombinant BCG. A time-course analysis of OVA-specific immunoglobulin (Ig)E, IgG1 and IgG2a levels indicated no significant difference between the three groups of mice. However, following in vitro stimulation with OVA, lymph node cells from rBCG-treated mice produced less IL-5 and more IFN-gamma than those of mice injected with nonrecombinant BCG. In addition, 48 h after the last OVA challenge, a strong reduction of bronchoalveolar eosinophilia was found in the rBCG-injected mice compared to the nontreated or nonrecombinant BCG-treated groups. These results indicate that the production of IL-18 by rBCG may enhance the immunomodulatory properties of BCG that suppress pulmonary Th2 responses and, in particular, decrease airway eosinophilia.

Human β-defensin 2 may inhibit internalisation of bacillus Calmette-Guérin (BCG) in bladder cancer cells.

Science.gov (United States)

Kim, Jung Hoon; Kim, Soon-Ja; Lee, Kyung Mee; Chang, In Ho

2013-10-01

To investigate whether secretion of human β-defensin 2 (HBD-2) is induced by bacillus Calmette-Guérin (BCG) and to determine whether HBD-2 affects BCG internalisation in bladder cancer cells. Reverse transcription-polymerase chain reaction analysis was used to determine whether HBD-2 mRNA increases after incubation with BCG. HBD-2 proteins in 5637 and T24 human bladder cancer cell lines were assayed by enzyme-linked immunosorbent assay. The internalisation rate was evaluated by double immunofluorescence assay and confocal microscopy to test the optimal dose of HBD-2 for BCG internalisation. We also investigated the difference in internalisation rates and cell viability between recombinant HBD-2 protein, anti-HBD-2 antibody, and HBD-2 plus anti-HBD-2 antibody pretreatments. BCG induced HBD-2 mRNA expression and HBD-2 production dose and time-dependently in bladder cancer cells and affected BCG internalisation. Pretreatment with recombinant HBD-2 protein lowered internalisation of BCG dose-dependently. Moreover, anti-HBD-2 antibody prevented the effect of HBD-2 on BCG internalisation in bladder cancer cells. The internalisation rate of BCG pretreated with anti-HBD-2 antibody was higher than that in the control in 5637 (P internalisation rate in cells pretreated with anti-HBD-2 antibody plus recombinant HBD-2 protein was higher than that in the control in 5637 (P internalisation, which plays an important role during the initiation and propagation of the immunotherapeutic response in bladder cancer cells. © 2013 The Authors. BJU International © 2013 BJU International.

Immunometabolic Pathways in BCG-Induced Trained Immunity

NARCIS (Netherlands)

Arts, R.J.; Carvalho, A.; Rocca, C. La; Palma, C.; Rodrigues, F.; Silvestre, R.; Kleinnijenhuis, J.; Lachmandas, E.; Goncalves, L.G.; Belinha, A.; Cunha, C.; Oosting, M.; Joosten, L.A.; Matarese, G.; Crevel, R. van; Netea, M.G.

2016-01-01

The protective effects of the tuberculosis vaccine Bacillus Calmette-Guerin (BCG) on unrelated infections are thought to be mediated by long-term metabolic changes and chromatin remodeling through histone modifications in innate immune cells such as monocytes, a process termed trained immunity.

Comparative performance of public and private sector delivery of BCG vaccination: evidence from Sub-Saharan Africa.

Science.gov (United States)

Wagner, Zachary; Szilagyi, Peter G; Sood, Neeraj

2014-07-31

The private sector is an important source of health care in the developing world. However, there is limited evidence on how private providers compare to public providers, particularly for preventive services such as immunizations. We used data from Sub-Saharan Africa (SSA) to assess public-private differences in Bacillus Calmette-Guérin (BCG) vaccine delivery. We used demographic and health surveys from 102,629 children aged 0-59 months from 29 countries across SSA to measure differences in BCG status for children born at private versus public health facilities (BCG is recommended at birth). We used a probit model to estimate public-private differences in BCG delivery, while controlling for key confounders. Next, we estimated how differences in BCG status evolved over time for children born at private versus public facilities. Finally, we estimated heterogeneity in public-private differences based on wealth and rural-urban residency. We found that children born at a private facility were 7.1 percentage points less likely to receive BCG vaccine in the same month as birth than children born at a public facility (95% CI 6.3-8.0; pprivate providers (as opposed to NGOs) where the BCG provision rate was 10.0 percentage points less than public providers (95% CI 9.0-11.2; pprivate for-profit facilities remained less likely to be vaccinated up to 59 months after birth. Finally, public-private differences were more pronounced for poorer children and children in rural areas. The for-profit private sector performed substantially worse than the public sector in providing BCG vaccine to newborns, resulting in a longer duration of vulnerability to tuberculosis. This disparity was greater for poorer children and children in rural areas. Copyright © 2014 Elsevier Ltd. All rights reserved.

Relative Efficacy of Uptake and Presentation of Mycobacterium bovis BCG Antigens by Type I Mouse Lung Epithelial Cells and Peritoneal Macrophages ▿

Science.gov (United States)

Kumari, Mandavi; Saxena, Rajiv K.

2011-01-01

Flow cytometric studies indicated that both peritoneal macrophages (PMs) and primary lung epithelial (PLE) cells isolated from mouse lungs could take up fluorescence-tagged Mycobacterium bovis BCG. BCG uptake in both cases was significantly inhibited by cytochalasin D, indicating active internalization of BCG by these cells. Confocal microscopy data further confirmed that BCG was internalized by PLE cells. BCG sonicate antigen (sBCG) had marked toxicity toward PMs but was relatively nontoxic to PLE cells. Accordingly, BCG sonicate antigen induced a significantly higher apoptotic and necrotic response in PMs compared to that in PLE cells. Both PMs and PLE cells exposed to BCG antigens and fixed thereafter could efficiently present antigens to purified BCG-sensitized T helper cells, as assessed by the release of interleukin-2 (IL-2) and gamma interferon (IFN-γ). If, however, PLE cells were fixed before exposure to BCG, antigen presentation was abrogated, indicating that the PLE cells may in some way process the BCG antigen. A comparison of efficacies of BCG-pulsed PLE cells and PMs to present antigen at various antigen-presenting cell (APC)/T cell ratios indicated that PMs had only marginally greater APC function than that of PLE cells. Staining with specific monoclonal antibodies indicated that the cultured PLE cells used for antigen presentation essentially comprised type I epithelial cells. Our results suggest that type I lung epithelial cells may present BCG antigens to sensitized T helper cells and that their performance as APCs is comparable with that of PMs. PMID:21646448

Evitar o efeito da vacinação BCG na detecção de infecção por Mycobacterium tuberculosis com um teste sanguíneo Avoiding the effect of BCG vaccination in detecting Mycobacterium tuberculosis infection with a blood test

Directory of Open Access Journals (Sweden)

R. Diel

2007-01-01

Full Text Available O risco de progressão da infecção por Mycobacterium tuberculosis para tuberculose-doença é sobretudo elevado nos primeiros anos após a infecção, estimando-se que 50% dos casos de tuberculose-infecção desenvolvem doença nos dois anos seguintes. A investigação precoce dos contactos baseia-se neste facto, e o teste cutâneo de tuberculina tem sido largamente utilizado como a prova de rastreio, apesar da sua limitação na população vacinada com BCG, nas reacções cruzadas com micobactérias não tuberculosas e na anergia cutânea em grupos específicos. Nos presentes estudos avalia-se a maior especificidade (no primeiro e a maior sensibilidade (no segundo de um novo teste sanguíneo na detecção de tuberculose- infecção. Este teste laboratorial feito em uma única amostra de sangue do doente baseia-se na libertação de gama-interferão das células T CD4 do indivíduo infectado quando expostas a antigenes micobacterianos. A libertação de interferão é fortemente estimulada por antigenes do Mycobacterium tuberculosis ausentes no M. bovis e na grande maioria das restantes micobactérias - conferindo especificidade ao teste. Estes antigenes ESAT-6/ CFP10 (early secretory antigenic target 6/ culture filtrated protein 10 reagem com o sangue do indivíduo infectado, levando à libertação de gama-interferão medido pelos métodos ELISA ou ELISPOT, dependendo do fabricante, respectivamente - Quantiferon Gold; Cellestis Limited, Austrália; e T-Spot.TB, Oxford Immunotec, UK. No primeiro estudo referenciado, 369 pessoas da academia de Polícia alemã foram avaliadas para o risco de tuberculose-infecção após o contacto com militar a quem foi diagnosticada tuberculose pulmonar com presença de bacilos ácido-alcool resistentes 3+ em exames de expectoração, com posterior cultura positiva para Mycobacterium tuberculosis. Foi efectuado teste de Mantoux a todos os contactos, e aos que apresentavam o teste positivo (induração = 5mm

Neonatal BCG vaccination has no effect on recurrent wheeze in the first year of life

DEFF Research Database (Denmark)

Thøstesen, Lisbeth Marianne; Stensballe, Lone Graff; Pihl, Gitte Thybo

2017-01-01

Background: Recurrent wheeze (RW) is frequent in childhood. Studies have suggested that BCG vaccination can have nonspecific effects, reducing general nontuberculosis morbidity, including respiratory tract infections and atopic diseases. The mechanisms behind these nonspecific effects of BCG...

Challenges to Improve the Stability and Efficacy of an Intravesical BCG Product

OpenAIRE

Hozouri, Hamidreza; Norouzian, Dariush; Nafissi-Varcheh, Nastaran; Aboofazeli, Reza

2014-01-01

The aim of this investigation was to improve the storage stability and survival rate of an intravesical BCG product, manufactured with an attenuated strain of Mycobacterium bovis (Pasteur strain 1173P2 of BCG) in the presence of sodium glutamate. Formulations with various concentrations of trehalose (a known protectant) were developed as liquid and lyophilized forms. Formulations were evaluated by different methods, including optical density measurement, safety assessment, skin reaction test,...

rBCG30-induced immunity and cross-protection against Mycobacterium leprae challenge are enhanced by boosting with the Mycobacterium tuberculosis 30-kilodalton antigen 85B.

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Gillis, Thomas P; Tullius, Michael V; Horwitz, Marcus A

2014-09-01

Leprosy remains a major global health problem and typically occurs in regions in which tuberculosis is endemic. Vaccines are needed that protect against both infections and do so better than the suboptimal Mycobacterium bovis BCG vaccine. Here, we evaluated rBCG30, a vaccine previously demonstrated to induce protection superior to that of BCG against Mycobacterium tuberculosis and Mycobacterium bovis challenge in animal models, for efficacy against Mycobacterium leprae challenge in a murine model of leprosy. rBCG30 overexpresses the M. tuberculosis 30-kDa major secretory protein antigen 85B, which is 85% homologous with the M. leprae homolog (r30ML). Mice were sham immunized or immunized intradermally with BCG or rBCG30 and challenged 2.5 months later by injection of viable M. leprae into each hind footpad. After 7 months, vaccine efficacy was assessed by enumerating the M. leprae bacteria per footpad. Both BCG and rBCG30 induced significant protection against M. leprae challenge. In the one experiment in which a comparison between BCG and rBCG30 was feasible, rBCG30 induced significantly greater protection than did BCG. Immunization of mice with purified M. tuberculosis or M. leprae antigen 85B also induced protection against M. leprae challenge but less so than BCG or rBCG30. Notably, boosting rBCG30 with M. tuberculosis antigen 85B significantly enhanced r30ML-specific immune responses, substantially more so than boosting BCG, and significantly augmented protection against M. leprae challenge. Thus, rBCG30, a vaccine that induces improved protection against M. tuberculosis, induces cross-protection against M. leprae that is comparable or potentially superior to that induced by BCG, and boosting rBCG30 with antigen 85B further enhances immune responses and protective efficacy. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Age at BCG administration during routine immunization.

African Journals Online (AJOL)

Age at BCG administration during routine immunization. R.D. Wammanda , M.J. Gambo and I. Abdulkadir. Department of Paediatrics,. Ahmadu Bello University Teaching Hospital,. Zaria. Correspondence to: Dr.R.D. Wammanda. Email: wammanda@yahoo.com. Summary. In Nigeria, as part of the National Programme on ...

Early BCG-Denmark and Neonatal Mortality Among Infants Weighing <2500 g: A Randomized Controlled Trial

DEFF Research Database (Denmark)

Biering-Sørensen, Sofie; Aaby, Peter; Lund, Najaaraq

2017-01-01

-Denmark” (intervention group; n = 2083) or “control” (local policy for LW and no BCG-Denmark; n = 2089) at discharge from the maternity ward or at first contact with the health center. The infants were randomized (1:1) without blinding in blocks of 24. Data was analyzed in Cox hazards models providing mortality rate...... ratios (MRRs). We had prespecified an analysis censoring follow-up at oral poliovirus vaccine campaigns. Results. Early administration of BCG-Denmark was associated with a nonsignificant reduction in neonatal mortality rate (MRR, 0.70; 95% confidence interval [CI], .47–1.04) and a 34% reduction (0......Background. BCG vaccine may reduce overall mortality by increasing resistance to nontuberculosis infections. In 2 randomized trials in Guinea-Bissau of early BCG-Denmark (Statens Serum Institut) given to low-weight (LW) neonates (mortality rates, we observed...

Development of Th1 Imprints to rBCG Expressing a Foreign Protein: Implications for Vaccination against HIV-1 and Diverse Influenza Strains

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Carl Power

2010-01-01

Full Text Available We demonstrate here that immunizing naïve mice with low numbers of recombinant Bacille Calmette-Guérin (rBCG expressing β-galactosidase (β-gal generates predominant Th1 responses to both BCG and β-gal whereas infection with high numbers generates a mixed Th1/Th2 response to both BCG and β-gal. Furthermore, the Th1 response to both BCG and β-gal is stable when mice, pre-exposed to low numbers of rBCG, are challenged four months later with high numbers of rBCG. Thus the Th1/Th2 phenotypes of the immune responses to β-gal and to BCG are “coherently” regulated. Such rBCG vectors, encoding antigens of pathogens preferentially susceptible to cell-mediated attack, may be useful in vaccinating against such pathogens. We discuss vaccination strategies employing rBCG vectors that are designed to provide protection against diverse influenza strains or numerous variants of HIV-1 and consider what further experiments are essential to explore the possibility of realizing such strategies.

IL-18 Does not Increase Allergic Airway Disease in Mice When Produced by BCG

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L. Amniai

2007-01-01

These data show that IL-18 did not increase allergic airway responses in the context of the mycobacterial infection, and suggest that BCG-IL-18 and BCG are able to prevent the development of local Th2 responses and therefore inhibit allergen-induced airway responses even after restimulation.

Improving the Immunogenicity of the Mycobacterium bovis BCG Vaccine by Non-Genetic Bacterial Surface Decoration Using the Avidin-Biotin System.

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Ting-Yu Angela Liao

Full Text Available Current strategies to improve the current BCG vaccine attempt to over-express genes encoding specific M. tuberculosis (Mtb antigens and/or regulators of antigen presentation function, which indeed have the potential to reshape BCG in many ways. However, these approaches often face serious difficulties, in particular the efficiency and stability of gene expression via nucleic acid complementation and safety concerns associated with the introduction of exogenous DNA. As an alternative, we developed a novel non-genetic approach for rapid and efficient display of exogenous proteins on bacterial cell surface. The technology involves expression of proteins of interest in fusion with a mutant version of monomeric avidin that has the feature of reversible binding to biotin. Fusion proteins are then used to decorate the surface of biotinylated BCG. Surface coating of BCG with recombinant proteins was highly reproducible and stable. It also resisted to the freeze-drying shock routinely used in manufacturing conventional BCG. Modifications of BCG surface did not affect its growth in culture media neither its survival within the host cell. Macrophages phagocytized coated BCG bacteria, which efficiently delivered their surface cargo of avidin fusion proteins to MHC class I and class II antigen presentation compartments. Thereafter, chimeric proteins corresponding to a surrogate antigen derived from ovalbumin and the Mtb specific ESAT6 antigen were generated and tested for immunogenicity in vaccinated mice. We found that BCG displaying ovalbumin antigen induces an immune response with a magnitude similar to that induced by BCG genetically expressing the same surrogate antigen. We also found that BCG decorated with Mtb specific antigen ESAT6 successfully induces the expansion of specific T cell responses. This novel technology, therefore, represents a practical and effective alternative to DNA-based gene expression for upgrading the current BCG vaccine.

Improving the Immunogenicity of the Mycobacterium bovis BCG Vaccine by Non-Genetic Bacterial Surface Decoration Using the Avidin-Biotin System.

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Liao, Ting-Yu Angela; Lau, Alice; Joseph, Sunil; Hytönen, Vesa; Hmama, Zakaria

2015-01-01

Current strategies to improve the current BCG vaccine attempt to over-express genes encoding specific M. tuberculosis (Mtb) antigens and/or regulators of antigen presentation function, which indeed have the potential to reshape BCG in many ways. However, these approaches often face serious difficulties, in particular the efficiency and stability of gene expression via nucleic acid complementation and safety concerns associated with the introduction of exogenous DNA. As an alternative, we developed a novel non-genetic approach for rapid and efficient display of exogenous proteins on bacterial cell surface. The technology involves expression of proteins of interest in fusion with a mutant version of monomeric avidin that has the feature of reversible binding to biotin. Fusion proteins are then used to decorate the surface of biotinylated BCG. Surface coating of BCG with recombinant proteins was highly reproducible and stable. It also resisted to the freeze-drying shock routinely used in manufacturing conventional BCG. Modifications of BCG surface did not affect its growth in culture media neither its survival within the host cell. Macrophages phagocytized coated BCG bacteria, which efficiently delivered their surface cargo of avidin fusion proteins to MHC class I and class II antigen presentation compartments. Thereafter, chimeric proteins corresponding to a surrogate antigen derived from ovalbumin and the Mtb specific ESAT6 antigen were generated and tested for immunogenicity in vaccinated mice. We found that BCG displaying ovalbumin antigen induces an immune response with a magnitude similar to that induced by BCG genetically expressing the same surrogate antigen. We also found that BCG decorated with Mtb specific antigen ESAT6 successfully induces the expansion of specific T cell responses. This novel technology, therefore, represents a practical and effective alternative to DNA-based gene expression for upgrading the current BCG vaccine.

Vaccination technique, PPD reaction and BCG scarring in a cohort of children born in Guinea-Bissau 2000-2002

DEFF Research Database (Denmark)

Roth, Adam Anders Edvin; Sodemann, Morten; Jensen, Henrik

2005-01-01

and scarring in Guinea-Bissau. In a cohort of children born in suburban Bissau from March 2000 to July 2002, we assessed a Mantoux test with Purified protein derivative (PPD) (SSI, 2 T.U.) at 2 (2689 children), 6 (N=2148) and 12 months (N=1638) of age, and BCG scar was assessed at 2 (N=2698) and 6 months (N......=2225) of age. In a subgroup of the children the vaccination technique was monitored by direct observation of post-vaccination wheal and route of administration. Three different types of BCG vaccine supplied by the local Extended Programme on Immunization were used. At 6 months of age the rate of PPD...... reactors (>1mm) after BCG vaccination was 25% and the rate of scarring was 89%. One BCG strain was associated with fewer PPD reactors (OR=0.54 (0.31-0.91)) and BCG scars (OR=0.13 (0.05-0.37)) and larger post-vaccination wheals produced more PPD reactions (OR 1.21 (95% CI 1.02-1.43)) and BCG scars (OR 1...

Assessment of safety and interferon gamma responses of Mycobacterium bovis BCG vaccine in goat kids and milking goats.

Science.gov (United States)

Pérez de Val, Bernat; Vidal, Enric; López-Soria, Sergio; Marco, Alberto; Cervera, Zoraida; Martín, Maite; Mercader, Irene; Singh, Mahavir; Raeber, Alex; Domingo, Mariano

2016-02-10

Vaccination of domestic animals has emerged as an alternative long-term strategy for the control of tuberculosis (TB). A trial under field conditions was conducted in a TB-free goat herd to assess the safety of the Mycobacterium bovis BCG vaccine. Eleven kids and 10 milking goats were vaccinated with BCG. Bacterial shedding and interferon gamma (IFN-γ) responses were monitored throughout the study. Comprehensive pathological examination and mycobacterial culture of target tissues were performed. BCG vaccine strain was only isolated from the draining lymph node of the injection site of a kid euthanized at week 8 post-vaccination. The remaining animals were euthanized at week 24. Six out of 20 showed small granulomas at the injection site. BCG shedding was not detected in either faeces or in milk throughout the study. All vaccinated kids showed BCG-induced IFN-γ responses at week 8 post-vaccination. BCG vaccination of goats showed no lack of biological safety for the animals, environment and public health, and local adverse reactions were negligible. Copyright © 2016 Elsevier Ltd. All rights reserved.

The value of counting BCG scars for interpretation of tuberculin skin tests in a tuberculosis hyperendemic shanty-town, Peru

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Saito, M.; Bautista, C. T.; Gilman, R. H.; Bowering, A.; Levy, M. Z.; Evans, C. A.

2010-01-01

SUMMARY SETTING The tuberculin skin test (TST) is widely used as a diagnostic or screening test for Mycobacterium tuberculosis infection and disease. A peri-urban shanty-town in the desert hills of south Lima, Peru, highly endemic for tuberculosis, and where bacille Calmette-Guérin (BCG) vaccine had been given in multiple doses until 1995. OBJECTIVE To analyze the effect of multiple BCG vaccines on TST in a community-based setting. DESIGN Point-prevalence survey of TST reactions of 572 people aged 6–26 years from 255 households. TST reactions were compared to the observed number of BCG scars and other potential risk factors (age, living with a TST-positive person, and contact with active tuberculosis). RESULT People with two or more scars had significantly larger reactions, even after adjusting for potential risk factors. The adjusted population attributable fraction of being TST-positive and having two or more BCG scars was 26%. CONCLUSION There is no demonstrated benefit of repeat BCG vaccination. We therefore recommend that physicians take into consideration the number of BCG scars when interpreting the TST and that programs give no more than one BCG vaccination. PMID:15260275

Intranasal boosting with an adenovirus-vectored vaccine markedly enhances protection by parenteral Mycobacterium bovis BCG immunization against pulmonary tuberculosis.

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Santosuosso, Michael; McCormick, Sarah; Zhang, Xizhong; Zganiacz, Anna; Xing, Zhou

2006-08-01

Parenterally administered Mycobacterium bovis BCG vaccine confers only limited immune protection from pulmonary tuberculosis in humans. There is a need for developing effective boosting vaccination strategies. We examined a heterologous prime-boost regimen utilizing BCG as a prime vaccine and our recently described adenoviral vector expressing Ag85A (AdAg85A) as a boost vaccine. Since we recently demonstrated that a single intranasal but not intramuscular immunization with AdAg85A was able to induce potent protection from pulmonary Mycobacterium tuberculosis challenge in a mouse model, we compared the protective effects of parenteral and mucosal booster immunizations following subcutaneous BCG priming. Protection by BCG prime immunization was not effectively boosted by subcutaneous BCG or intramuscular AdAg85A. In contrast, protection by BCG priming was remarkably boosted by intranasal AdAg85A. Such enhanced protection by intranasal AdAg85A was correlated to the numbers of gamma interferon-positive CD4 and CD8 T cells residing in the airway lumen of the lung. Our study demonstrates that intranasal administration of AdAg85A represents an effective way to boost immune protection by parenteral BCG vaccination.

Enhanced and enduring protection against tuberculosis by recombinant BCG-Ag85C and its association with modulation of cytokine profile in lung.

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Ruchi Jain

Full Text Available BACKGROUND: The variable efficacy (0-80% of Mycobacterium bovis Bacille Calmette Guréin (BCG vaccine against adult tuberculosis (TB necessitates development of alternative vaccine candidates. Development of recombinant BCG (rBCG over-expressing promising immunodominant antigens of M. tuberculosis represents one of the potential approaches for the development of vaccines against TB. METHODS/PRINCIPAL FINDINGS: A recombinant strain of BCG - rBCG85C, over expressing the antigen 85C, a secretory immuno-dominant protein of M. tuberculosis, was evaluated for its protective efficacy in guinea pigs against M. tuberculosis challenge by aerosol route. Immunization with rBCG85C resulted in a substantial reduction in the lung (1.87 log(10, p<0.01 and spleen (2.36 log(10, p<0.001 bacillary load with a commensurate reduction in pathological damage, when compared to the animals immunized with the parent BCG strain at 10 weeks post-infection. rBCG85C continued to provide superior protection over BCG even when post-challenge period was prolonged to 16 weeks. The cytokine profile of pulmonary granulomas revealed that the superior protection imparted by rBCG85C was associated with the reduced levels of pro-inflammatory cytokines - interleukin (IL-12, interferon (IFN-gamma, tumor necrosis factor (TNF-alpha, moderate levels of anti-inflammatory cytokine - transforming growth factor (TGF-beta along with up-regulation of inducible nitric oxide synthase (iNOS. In addition, the rBCG85C vaccine induced modulation of the cytokine levels was found to be associated with reduced fibrosis and antigen load accompanied by the restoration of normal lung architecture. CONCLUSIONS/SIGNIFICANCE: These results clearly indicate the superiority of rBCG85C over BCG as a promising prophylactic vaccine against TB. The enduring protection observed in this study gives enough reason to postulate that if an open-ended study is carried out with low dose of infection, rBCG85C vaccine in all

Heterologous Immunological Effects of Early BCG Vaccination in Low-Birth-Weight Infants in Guinea-Bissau

DEFF Research Database (Denmark)

Jensen, Kristoffer Jarlov; Larsen, Nanna; Biering-Sørensen, Sofie

2015-01-01

or -7/8, or purified protein derivative (PPD). RESULTS:  Among 467 infants, BCG significantly increased the in vitro cytokine responses to purified protein derivative of Mycobacterium tuberculosis (PPD), as expected. BCG was also associated with increased responses to heterologous innate stimulation...

Neonatal BCG has no effect on allergic sensitization and suspected food allergy until 13 months

DEFF Research Database (Denmark)

Thøstesen, Lisbeth Marianne; Kjaer, Henrik Fomsgaard; Pihl, Gitte Thybo

2017-01-01

BACKGROUND: Vaccination with Bacillus Calmette-Guérin (BCG) is used in many countries as protection against tuberculosis. Studies have suggested that BCG may also have non-specific effects, reducing non-tuberculosis mortality, morbidity, and atopic manifestations. In this study we evaluated...

The effects of BCG, cyclophosphamide and x-radiation on reticuloendothelial system and immune responsiveness in mice, 1

International Nuclear Information System (INIS)

Harada, Susumu

1978-01-01

The effects of BCG and x-radiation of sublethal dose on reticuloendothelial system (RES) were studied in mice. An attempt was also made to evaluate the action of BCG on the recovery of immune responsiveness in irradiated mice. Carbon clearance test and measurement of spread macrophage in peritoneal cells were used to assay the function of RES. The result of carbon clearance was in good accordance with the one of macrophage spreading test. Either intracutaneous or intravenous administration of BCG increased the activity of RES, and 3 to 5 weeks later, the functional levels of RES reached a maximum. When BCG was given intravenously, the highly increased level of phagocytic activity was obtained even one week after BCG injection. Whereas x-radiation of sublethal dose caused a marked reduction of the number of peritoneal cells, the decrease of RES activity was not found. Although x-radiation suppressed markedly the immune response to sheep red blood cells (SRBC), delayed type reactivity recovered quickly to a normal level. The production of plaque forming cells (PEC) in spleen also recovered within 2 weeks after x-radiation and thereafter increased rather, while PFC in the draining lymph node reduced markedly and its recovery was protracted. BCG inoculation in x-radiated mice could not increase the number of peritoneal cells while it increased the activity of RES and the immune responsiveness to SRBC. BCG inoculation made mice extremely susceptible to pseudomonas infection either 2 to 3 weeks after i.v. inoculation or 5 weeks after i.c. inoculation. But a marked resistance than normal controls was found 10 weeks after the i.c. inoculation of BCG. On the other hand, x-radiation caused a serious damage to protective activity against pseudomonas infection and no increase of resistance throughout experimental period. (auth.)

The Cyclic Di-GMP Phosphodiesterase Gene Rv1357c/BCG1419c Affects BCG Pellicle Production and In Vivo Maintenance.

Science.gov (United States)

Flores-Valdez, Mario Alberto; Aceves-Sánchez, Michel de Jesús; Pedroza-Roldán, César; Vega-Domínguez, Perla Jazmín; Prado-Montes de Oca, Ernesto; Bravo-Madrigal, Jorge; Laval, Françoise; Daffé, Mamadou; Koestler, Ben; Waters, Christopher M

2015-02-01

Bacteria living in a surface-attached community that contains a heterogeneous population, coated with an extracellular matrix, and showing drug tolerance (biofilms) are often linked to chronic infections. In mycobacteria, the pellicle mode of growth has been equated to an in vitro biofilm and meets several of the criteria mentioned above, while tuberculosis infection presents a chronic (latent) phase of infection. As mycobacteria lack most genes required to control biofilm production by other microorganisms, we deleted or expressed from the hsp60 strong promoter the only known c-di-GMP phosphodiesterase (PDE) gene in Mycobacterium bovis BCG. We found changes in pellicle production, cellular protein profiles, lipid production, resistance to nitrosative stress and maintenance in lungs and spleens of immunocompetent BALB/mice. Our results show that pellicle production and capacity to remain within the host are linked in BCG. © 2015 International Union of Biochemistry and Molecular Biology.

Manifestaciones cutáneas por choque séptico en una adulta

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Julio César González Aguilera

2015-05-01

Full Text Available Se describe el caso clínico de una adulta de 33 años de edad con antecedentes de asma bronquial, que fue ingresada en el Hospital General Universitario "Carlos Manuel de Céspedes", en Bayamo (Granma, por choque séptico a causa de una bronconeumonía bacteriana, además de disfunción orgánica y acidosis metabólica sostenida, que requerían el apoyo de drogas vasoactivas a altas dosis. También aparecieron lesiones diseminadas en la piel, principalmente en las áreas distales de las manos y los pies, con coloración violácea y necrosis isquémicas hacia los pulpejos de los dedos. En los hemocultivos se aisló el Staphylococcus aureus, y el tratamiento consistió en sostén hemodinámico, antimicrobianos de amplio espectro, corticoesteroides y curas de las lesiones cutáneas, que incluyó la escisión del tejido necrosado

[Construction and expression of recombinant Mycobacterium bovis BCG with the ompA-like membrane protein gene Loa22 of Leptospira interrogans serovar].

Science.gov (United States)

Li, Dao-kun; Bao, Lang; Zhang, Ying; Sun, Zhan

2010-03-01

To study the immunity of Loa22 from Leptospira interrogans serovar Lai strain 56601 by expressing its protein in BCG. Amplified the mature peptide of Loa22 gene from the genome of of Leptospira interrogans serovar Lai strain 56601 and constructed recombinant plasmid rpMV36l-1oa22 with the E. coli-BCG integrating shuttle plasmid pMV361 and the Loa22 mature peptide gene. The rpMV36l-1oa22 plasmid was transformed into BCG by electroporation. The rBCG bearing rpMV36l-1oa22 was induced by high temperature of 45 degrees C and expressed protein was identified by SDS-PAGE and Western Blotting. Fifth 6-week-old BALB/c mice were randomly divided into five groups, which were inoculated intraperitoneally two times at 0-day and 21-day with BCG, rBCG-pMV361, rI3CG-1oa22, Loa22 and killed whole-leptospires respectively. All animals were dislocated from cervical vertebra on the 14Ih day after the last immunization. The proliferative reaction of splenic lymphocyte in tuitro were tested by XTT. The rpMV36l-1oa22 plasmid was constructed successfully and transformed into BCG. The rBCG expressed a 19 X io specifical protein identified by SDS-PAGE and Western Blotting. The splenic lymphocyte proliferate activity (SI) in rBCG-ioa22 group in intro was significantly higher than those in BCG group and rBCG-pMV361 group. We explored the expressing feasibility of Loa22 in Mycobacterium bovis BCG. may therefore make further researches on the induction of protective immunity against human and animal leptospirosis.

Nonspecific effect of BCG vaccination at birth on early childhood infections

DEFF Research Database (Denmark)

Kjærgaard, Jesper; Birk, Nina Marie; Nissen, Thomas N

2016-01-01

BACKGROUND: Childhood infections are common and Bacillus Calmette-Guérin (BCG) vaccination at birth may prevent these via nonspecific effects. METHODS: A randomized, clinical multicenter trial. All women planning to give birth (n = 16,521) at the three study sites were invited during the recruitm......BACKGROUND: Childhood infections are common and Bacillus Calmette-Guérin (BCG) vaccination at birth may prevent these via nonspecific effects. METHODS: A randomized, clinical multicenter trial. All women planning to give birth (n = 16,521) at the three study sites were invited during...... during the first 3 mo....

Early BCG-Denmark and Neonatal Mortality Among Infants Weighing <2500 g: A Randomized Controlled Trial

DEFF Research Database (Denmark)

Biering-Sørensen, Sofie; Aaby, Peter; Lund, Najaaraq

2017-01-01

ratios (MRRs). We had prespecified an analysis censoring follow-up at oral poliovirus vaccine campaigns. Results. Early administration of BCG-Denmark was associated with a nonsignificant reduction in neonatal mortality rate (MRR, 0.70; 95% confidence interval [CI], .47–1.04) and a 34% reduction (0.......66; .44–1.00) when censoring for oral poliovirus vaccine campaigns. There was no reduction in mortality rate for noninfectious diseases, but a 43% reduction in infectious disease mortality rate (MRR, 0.57; 95% CI, .35–.93). A meta-analysis of 3 BCG trials showed that early BCG-Denmark reduced mortality...

Scar formation and tuberculin conversion following BCG vaccination in infants: A prospective cohort study

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Sara S Dhanawade

2015-01-01

Full Text Available Background: There is considerable variation in BCG scar failure rate on available data and correlation between BCG scar and tuberculin conversion remains controversial. Through this study we aimed to determine the scar failure rate and tuberculin conversion in term infants vaccinated with BCG within the first month. Materials and Methods: A prospective cohort study was conducted among 85 consecutive infants weighing >2 kg attending the immunization clinic of a medical college hospital. Fifteen subjects who could not complete the follow up were excluded. Total of 70 cases were analyzed. All babies were administered 0.1 ml of BCG and examined at 3 months (+1 week for scar. Tuberculin test was done with 5TU PPD. An induration of >5 mm was considered positive. Statistical analysis was done using Microsoft Excel and SPSS-22. Results: Out of the 70 infants, 41 (58.6% were males. Although majority (72.9% of infants were vaccinated within 7 days, only 18 (25.7% received BCG within 48 hours of birth. Sixty-four (91.4% had a visible scar at 12 weeks post vaccination representing a scar failure rate of 8.6%. Tuberculin test was positive in 50 (71.4%. The mean ± s.d. for scar and tuberculin skin test (TST reaction size was 4.93 ± 2.01 mm and 6.01 ± 3.22 mm, respectively. The association between scar formation and tuberculin positivity was highly significant (P < 0.001. There was significant correlation between scar size and TST size (r = 0.401, P = 0.001 Conclusions: Less than 10% of infants fail to develop a scar following BCG vaccination. There is good correlation between scar positivity and tuberculin conversion.

Outcome after BCG treatment for urinary bladder cancer may be influenced by polymorphisms in the NOS2 and NOS3 genes.

Science.gov (United States)

Ryk, Charlotta; Koskela, Lotta Renström; Thiel, Tomas; Wiklund, N Peter; Steineck, Gunnar; Schumacher, Martin C; de Verdier, Petra J

2015-12-01

Bacillus Calmette-Guérin (BCG)-treatment is an established treatment for bladder cancer, but its mechanisms of action are not fully understood. High-risk non-muscle invasive bladder-cancer (NMIBC)-patients failing to respond to BCG-treatment have worse prognosis than those undergoing immediate radical cystectomy and identification of patients at risk for BCG-failure is of high priority. Several studies indicate a role for nitric oxide (NO) in the cytotoxic effect that BCG exerts on bladder cancer cells. In this study we investigated whether NO-synthase (NOS)-gene polymorphisms, NOS2-promoter microsatellite (CCTTT)n, and the NOS3-polymorphisms-786T>C (rs2070744) and Glu298Asp (rs1799983), can serve as possible molecular markers for outcome after BCG-treatment for NMIBC. All NMIBC-patients from a well-characterized population based cohort were analyzed (n=88). Polymorphism data were combined with information from 15-years of clinical follow-up. The effect of BCG-treatment on cancer-specific death (CSD), recurrence and progression in patients with varying NOS-genotypes were studied using Cox proportional hazard-models and log rank tests. BCG-treatment resulted in significantly better survival in patients without (Log rank: p=0.006; HR: 0.12, p=0.048), but not in patients with a long version ((CCTTT)n ≧13 repeats) of the NOS2-promoter microsatellite. The NOS3-rs2070744(TT) and rs1799983(GG)-genotypes showed decreased risk for CSD (Log rank(TT): p=0.001; Log rank(GG): p=0.010, HR(GG): 0.16, p=0.030) and progression (Log rank(TT): p<0.001, HR(TT): 0.05, p=0.005; Log rank(GG): p<0.001, HR(GG): 0.10, p=0.003) after BCG-therapy compared to the other genotypes. There was also a reduction in recurrence in BCG-treated patients that was mostly genotype independent. Analysis of combined genotypes identified a subgroup of 30% of the BCG-treated patients that did not benefit from BCG-treatment. Our results suggest that the investigated polymorphisms influence patient response

Lipoproteins of slow-growing Mycobacteria carry three fatty acids and are N-acylated by apolipoprotein N-acyltransferase BCG_2070c.

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Brülle, Juliane K; Tschumi, Andreas; Sander, Peter

2013-10-05

Lipoproteins are virulence factors of Mycobacterium tuberculosis. Bacterial lipoproteins are modified by the consecutive action of preprolipoprotein diacylglyceryl transferase (Lgt), prolipoprotein signal peptidase (LspA) and apolipoprotein N- acyltransferase (Lnt) leading to the formation of mature triacylated lipoproteins. Lnt homologues are found in Gram-negative and high GC-rich Gram-positive, but not in low GC-rich Gram-positive bacteria, although N-acylation is observed. In fast-growing Mycobacterium smegmatis, the molecular structure of the lipid modification of lipoproteins was resolved recently as a diacylglyceryl residue carrying ester-bound palmitic acid and ester-bound tuberculostearic acid and an additional amide-bound palmitic acid. We exploit the vaccine strain Mycobacterium bovis BCG as model organism to investigate lipoprotein modifications in slow-growing mycobacteria. Using Escherichia coli Lnt as a query in BLASTp search, we identified BCG_2070c and BCG_2279c as putative lnt genes in M. bovis BCG. Lipoproteins LprF, LpqH, LpqL and LppX were expressed in M. bovis BCG and BCG_2070c lnt knock-out mutant and lipid modifications were analyzed at molecular level by matrix-assisted laser desorption ionization time-of-flight/time-of-flight analysis. Lipoprotein N-acylation was observed in wildtype but not in BCG_2070c mutants. Lipoprotein N- acylation with palmitoyl and tuberculostearyl residues was observed. Lipoproteins are triacylated in slow-growing mycobacteria. BCG_2070c encodes a functional Lnt in M. bovis BCG. We identified mycobacteria-specific tuberculostearic acid as further substrate for N-acylation in slow-growing mycobacteria.

Optimizing HIV-1-specific CD8+ T-cell induction by recombinant BCG in prime-boost regimens with heterologous viral vectors.

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Hopkins, Richard; Bridgeman, Anne; Bourne, Charles; Mbewe-Mvula, Alice; Sadoff, Jerald C; Both, Gerald W; Joseph, Joan; Fulkerson, John; Hanke, Tomáš

2011-12-01

The desire to induce HIV-1-specific responses soon after birth to prevent breast milk transmission of HIV-1 led us to propose a vaccine regimen which primes HIV-1-specific T cells using a recombinant Mycobacterium bovis bacillus Calmette-Guérin (rBCG) vaccine. Because attenuated live bacterial vaccines are typically not sufficiently immunogenic as stand-alone vaccines, rBCG-primed T cells will likely require boost immunization(s). Here, we compared modified Danish (AERAS-401) and Pasteur lysine auxotroph (222) strains of BCG expressing the immunogen HIVA for their potency to prime HIV-1-specific responses in adult BALB/c mice and examined four heterologous boosting HIVA vaccines for their immunogenic synergy. We found that both BCG.HIVA(401) and BCG.HIVA(222) primed HIV-1-specific CD8(+) T-cell-mediated responses. The strongest boosts were delivered by human adenovirus-vectored HAdV5.HIVA and sheep atadenovirus-vectored OAdV7.HIVA vaccines, followed by poxvirus MVA.HIVA; the weakest was plasmid pTH.HIVA DNA. The prime-boost regimens induced T cells capable of efficient in vivo killing of sensitized target cells. We also observed that the BCG.HIVA(401) and BCG.HIVA(222) vaccines have broadly similar immunologic properties, but display a number of differences mainly detected through distinct profiles of soluble intercellular signaling molecules produced by immune splenocytes in response to both HIV-1- and BCG-specific stimuli. These results encourage further development of the rBCG prime-boost regimen. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

BCG Vaccination at Birth and Rate of Hospitalization for Infection Until 15 Months of Age in Danish Children

DEFF Research Database (Denmark)

Stensballe, Lone Graff; Ravn, Henrik; Birk, Nina Marie

2018-01-01

Background: The bacillus Calmette-Guérin (BCG) vaccine against tuberculosis might reduce the non-tuberculosis-related child mortality rate in low-income settings. We tested the hypothesis that BCG vaccination at birth would reduce early childhood hospitalization for infection in Denmark, a high...... analysis, we observed 588 hospitalizations for infection (mean, 0.28 hospitalization per child) among the 2129 children allocated to receive the BCG vaccine and 595 hospitalizations for infection (mean, 0.28 hospitalization per child) among the 2133 children allocated to the control group (hazard ratio [HR...... months in Danish children. In future studies, the role of maternal BCG-vaccination, premature birth, and cesarean delivery needs further exploration....

Activity in mice of recombinant BCG-EgG1Y162 vaccine for Echinococcus granulosus infection.

Science.gov (United States)

Ma, Xiumin; Zhao, Hui; Zhang, Fengbo; Zhu, Yuejie; Peng, Shanshan; Ma, Haimei; Cao, Chunbao; Xin, Yan; Yimiti, Delixiati; Wen, Hao; Ding, Jianbing

2016-01-01

Cystic hydatid disease is a zoonotic parasitic disease caused by Echinococcus granulosus which is distributed worldwide. The disease is difficult to treat with surgery removal is the only cure treatment. In the high endemic areas, vaccination of humans is believed a way to protect communities from the disease. In this study we vaccinated BALB/c mice with rBCG-EgG1Y162, and then detected the level of IgG and IgE specifically against the recombinant protein by ELISA, rBCG-EgG1Y162 induced strong and specific cellular and humoral immune responses. In vitro study showed that rBCG-EgG1Y162 vaccine not only promote splenocytes proliferation but also active T cell. In addition, the rBCG-EgG1Y162 induced a protection in the mice against secondary infection of Echinococcus granulosus.

Toxicogenomic response of Mycobacterium bovis BCG to peracetic acid and a comparative analysis of the M. bovis BCG response to three oxidative disinfectants.

Science.gov (United States)

Nde, Chantal W; Toghrol, Freshteh; Jang, Hyeung-Jin; Bentley, William E

2011-04-01

Tuberculosis is a leading cause of death worldwide and infects thousands of Americans annually. Mycobacterium bovis causes tuberculosis in humans and several animal species. Peracetic acid is an approved tuberculocide in hospital and domestic environments. This study presents for the first time the transcriptomic changes in M. bovis BCG after treatment with 0.1 mM peracetic acid for 10 and 20 min. This study also presents for the first time a comparison among the transcriptomic responses of M. bovis BCG to three oxidative disinfectants: peracetic acid, sodium hypochlorite, and hydrogen peroxide after 10 min of treatment. Results indicate that arginine biosynthesis, virulence, and oxidative stress response genes were upregulated after both peracetic acid treatment times. Three DNA repair genes were downregulated after 10 and 20 min and cell wall component genes were upregulated after 20 min. The devR-devS signal transduction system was upregulated after 10 min, suggesting a role in the protection against peracetic acid treatment. Results also suggest that peracetic acid and sodium hypochlorite both induce the expression of the ctpF gene which is upregulated in hypoxic environments. Further, this study reveals that in M. bovis BCG, hydrogen peroxide and peracetic acid both induce the expression of katG involved in oxidative stress response and the mbtD and mbtI genes involved in iron regulation/virulence.

Non-clinical efficacy and safety of HyVac4:IC31 vaccine administered in a BCG prime-boost regimen.

Science.gov (United States)

Skeiky, Yasir A W; Dietrich, Jes; Lasco, Todd M; Stagliano, Katherine; Dheenadhayalan, Veerabadran; Goetz, Margaret Ann; Cantarero, Luis; Basaraba, Randall J; Bang, Peter; Kromann, Ingrid; McMclain, J Bruce; Sadoff, Jerald C; Andersen, Peter

2010-01-22

Despite the extensive success with the introduction of M. bovis Bacille Calmette-Guérin (BCG), tuberculosis (TB) remains a major global epidemic infecting between 8 and 9 million people annually with an estimated 1.7 million deaths each year. However, because of its demonstrated effectiveness against some of the most severe forms of childhood TB, it is now realized that BCG vaccination of newborns is unlikely to be replaced. Therefore, BCG or an improved BCG will continue to be used as a prime TB vaccine and there is a need to develop effective boost vaccines that would enhance and prolong the protective immunity induced by BCG prime immunization. We report on a heterologous booster approach using two highly immunogenic TB antigens comprising Ag85B and TB10.4 (HyVac4) delivered as a fusion molecule and formulated in the proprietary adjuvant IC31. This vaccine was found to be immunogenic and demonstrated greater protection in the more stringent guinea pig model of pulmonary tuberculosis than BCG alone when used in a prime/boost regimen. Significant difference in lung involvement was observed for all animals in the HyVac4 boosted group compared to BCG alone regardless of time to death or sacrifice. A vaccine toxicology study of the HyVac4:IC31 regimen was performed and it was judged safe to advance the vaccine into clinical trials. Therefore, all non-clinical data supports the suitability of HyVac4 as a safe, immunogenic, and effective vaccination in a prime-boost regimen with BCG.

Genomic expression catalogue of a global collection of BCG vaccine strains show evidence for highly diverged metabolic and cell-wall adaptations

KAUST Repository

Abdallah, Abdallah

2015-10-21

Although Bacillus Calmette-Guérin (BCG) vaccines against tuberculosis have been available for more than 90 years, their effectiveness has been hindered by variable protective efficacy and a lack of lasting memory responses. One factor contributing to this variability may be the diversity of the BCG strains that are used around the world, in part from genomic changes accumulated during vaccine production and their resulting differences in gene expression. We have compared the genomes and transcriptomes of a global collection of fourteen of the most widely used BCG strains at single base-pair resolution. We have also used quantitative proteomics to identify key differences in expression of proteins across five representative BCG strains of the four tandem duplication (DU) groups. We provide a comprehensive map of single nucleotide polymorphisms (SNPs), copy number variation and insertions and deletions (indels) across fourteen BCG strains. Genome-wide SNP characterization allowed the construction of a new and robust phylogenic genealogy of BCG strains. Transcriptional and proteomic profiling revealed a metabolic remodeling in BCG strains that may be reflected by altered immunogenicity and possibly vaccine efficacy. Together, these integrated-omic data represent the most comprehensive catalogue of genetic variation across a global collection of BCG strains.

Genomic expression catalogue of a global collection of BCG vaccine strains show evidence for highly diverged metabolic and cell-wall adaptations

KAUST Repository

Abdallah, Abdallah; Hill-Cawthorne, Grant A.; Otto, Thomas D.; Coll, Francesc; Guerra-Assunç ã o, José Afonso; Gao, Ge; Naeem, Raeece; Ansari, Hifzur Rahman; Malas, Tareq Majed Yasin; Adroub, Sabir; Verboom, Theo; Ummels, Roy; Zhang, Huoming; Panigrahi, Aswini Kumar; McNerney, Ruth; Brosch, Roland; Clark, Taane G.; Behr, Marcel A.; Bitter, Wilbert; Pain, Arnab

2015-01-01

Although Bacillus Calmette-Guérin (BCG) vaccines against tuberculosis have been available for more than 90 years, their effectiveness has been hindered by variable protective efficacy and a lack of lasting memory responses. One factor contributing to this variability may be the diversity of the BCG strains that are used around the world, in part from genomic changes accumulated during vaccine production and their resulting differences in gene expression. We have compared the genomes and transcriptomes of a global collection of fourteen of the most widely used BCG strains at single base-pair resolution. We have also used quantitative proteomics to identify key differences in expression of proteins across five representative BCG strains of the four tandem duplication (DU) groups. We provide a comprehensive map of single nucleotide polymorphisms (SNPs), copy number variation and insertions and deletions (indels) across fourteen BCG strains. Genome-wide SNP characterization allowed the construction of a new and robust phylogenic genealogy of BCG strains. Transcriptional and proteomic profiling revealed a metabolic remodeling in BCG strains that may be reflected by altered immunogenicity and possibly vaccine efficacy. Together, these integrated-omic data represent the most comprehensive catalogue of genetic variation across a global collection of BCG strains.

A diatom-based biological condition gradient (BCG) approach for assessing impairment and developing nutrient criteria for streams.

Science.gov (United States)

Hausmann, Sonja; Charles, Donald F; Gerritsen, Jeroen; Belton, Thomas J

2016-08-15

Over-enrichment leading to excess algal growth is a major problem in rivers and streams. Regulations to protect streams typically incorporate nutrient criteria, concentrations of phosphorus and nitrogen that should not be exceeded in order to protect biological communities. A major challenge has been to develop an approach for both categorizing streams based on their biological conditions and determining scientifically defensible nutrient criteria to protect the biotic integrity of streams in those categories. To address this challenge, we applied the Biological Condition Gradient (BCG) approach to stream diatom assemblages to develop a system for categorizing sites by level of impairment, and then examined the related nutrient concentrations to identify potential nutrient criteria. The six levels of the BCG represent a range of ecological conditions from natural (1) to highly disturbed (6). A group of diatom experts developed a set of rules and a model to assign sites to these levels based on their diatom assemblages. To identify potential numeric nutrient criteria, we explored the relation of assigned BCG levels to nutrient concentrations, other anthropogenic stressors, and possible confounding variables using data for stream sites in New Jersey (n=42) and in surrounding Mid-Atlantic states, USA (n=1443). In both data sets, BCG levels correlated most strongly with total phosphorus and the percentage of forest in the watershed, but were independent of pH. We applied Threshold Indicator Taxa Analysis (TITAN) to determine change-points in the diatom assemblages along the BCG gradient. In both data sets, statistically significant diatom changes occurred between BCG levels 3 and 4. Sites with BCG levels 1 to 3 were dominated by species that grow attached to surfaces, while sites with BCG scores of 4 and above were characterized by motile diatoms. The diatom change-point corresponded with a total phosphorus concentration of about 50μg/L. Copyright © 2016 Elsevier B

Análise da positivação do teste tuberculínico, após administração da vacina BCG, pela via oral, a crianças sadias

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Yvone Khairallah de Oliveira e Silva

1974-10-01

Full Text Available Efetuaram os autores teste tuberculínico, com PPD (RT 23, 10 UT, em 3.6S4 crianças sadias, que receberam, pela via oral, em três oportunidades separadas por intervalos de um mês, vacina BCG líquida ou liofilizada e placebo representado por preparação sem bacilos. Dois grupos foram basicamente estabelecidos, tendo os limites etários correspondido a noventa dias em um deles e a essa idade e quinze anos no outro. Considerando os módulos com tamanhos superiores a cinco milímetros, observaram taxas de positividades de 37,6% e 21% relativamente aos indviduos separados da maneira citada e em avaliações levadas a efeito no máximo nove meses depois, mas as cifras pertinentes ao produto isento de bacilos álcool-ácido-resistentes e ao submetido à liofilização mostraram-se expressivamente menores. Valorizada somente a alergização, as percentagens indicadas e não desprezíveis atestaram a ocorrência de destacada absorção, sobretudo ao ser levado em conta o sucedido quanto às pessoas de menores idades.Oral BCG vaccine, either liquid or liophyllized, or a placebo was administered in three monthly doses to 3,684 healthy children. The study population was divided in two great groups, one to ninety days of age and the other from nine y days to jifteen years of age. A tuberculin test, with PPD (RT 23, 10 TU, was performed up to nine months later on each child, corsidering a nodule layer than five millimeters as a positive test. A positive incidence of 37.6% and 21% was found for the younger and the older age groups, respectively, who reccived liquid BCG. The children who took liophyllized BCG or placebo showed significantly smaller incidences. If allerginization moy be valued, then it can be seen that there is significant absortion, especially in the younger subjects

The Effect of Oral Vaccination with Mycobacterium bovis BCG on the Development of Tuberculosis in Captive European Badgers (Meles meles).

Science.gov (United States)

Chambers, Mark A; Aldwell, Frank; Williams, Gareth A; Palmer, Si; Gowtage, Sonya; Ashford, Roland; Dalley, Deanna J; Davé, Dipesh; Weyer, Ute; Salguero, Francisco J; Nunez, Alejandro; Nadian, Allan K; Crawshaw, Timothy; Corner, Leigh A L; Lesellier, Sandrine

2017-01-01

The European badger ( Meles meles ) is a reservoir host of Mycobacterium bovis and responsible for a proportion of the tuberculosis (TB) cases seen in cattle in the United Kingdom and Republic of Ireland. An injectable preparation of the bacillus Calmette-Guérin (BCG) vaccine is licensed for use in badgers in the UK and its use forms part of the bovine TB eradication plans of England and Wales. However, there are practical limitations to the widespread application of an injectable vaccine for badgers and a research priority is the development of an oral vaccine deliverable to badgers in bait. Previous studies reported the successful vaccination of badgers with oral preparations of 10 8 colony forming units (CFU) of both Pasteur and Danish strains of BCG contained within a lipid matrix composed of triglycerides of fatty acids. Protection against TB in these studies was expressed as a reduction in the number and apparent progression of visible lesions, and reductions in the bacterial load and dissemination of infection. To reduce the cost of an oral vaccine and reduce the potential for environmental contamination with BCG, it is necessary to define the minimal efficacious dose of oral BCG for badgers. The objectives of the two studies reported here were to compare the efficacy of BCG Danish strain in a lipid matrix with unformulated BCG given orally, and to evaluate the efficacy of BCG Danish in a lipid matrix at a 10-fold lower dose than previously evaluated in badgers. In the first study, both BCG unformulated and in a lipid matrix reduced the number and apparent progression of visible lesions and the dissemination of infection from the lung. In the second study, vaccination with BCG in the lipid matrix at a 10-fold lower dose produced a similar outcome, but with greater intra-group variability than seen with the higher dose in the first study. Further research is needed before we are able to recommend a final dose of BCG for oral vaccination of badgers against TB

Influence of isoniazid on naturally acquired tuberculin allergy and on induction of allergy by BCG vaccination*

Science.gov (United States)

Narain, Raj; Bagga, A. S.; Naganna, K.; Mayurnath, S.

1970-01-01

Previous studies on the influence of isoniazid on the size of the tuberculin reaction have given conflicting results. A controlled study in an area with high prevalence of low-grade allergy has been carried out by the administration of isoniazid or placebo tablets. For those not vaccinated with BCG, isoniazid in a single daily dose of 5 mg/kg body-weight tended to reduce somewhat the size of the tuberculin reaction among those with reactions of 12 mm or more at the initial tuberculin test. In people who were vaccinated with BCG, isoniazid given simultaneously resulted in significantly less increase in the size of post-vaccination tuberculin reactions as compared with controls; the difference was still significant, in tests conducted 4½ months after the discontinuation of isoniazid. However, in spite of isoniazid, the post-vaccination allergy induced by BCG was quite considerable. This considerable increase in post-vaccination allergy suggests that the vaccination was successful in spite of the administration of isoniazid and makes it clear that primary chemoprophylaxis could be combined with BCG vaccination. Administration of isoniazid for 2 months is estimated to have killed about 90% of the bacilli in the BCG vaccine injected intracutaneously. PMID:5312322

Original Article Failure of Bacillus Calmette Guerin (BCG) Therapy ...

African Journals Online (AJOL)

Administrator

urinary bladder at the Urology Department, Al-Azhar University, Cairo, Egypt. Patients and Methods: A ... option in high and intermediate risk patients with superficial TCC. Failure of BCG treatment is .... Urge incontinence. 135. 77. 45. 41. 12.

Effect of revaccination with BCG in early childhood on mortality: randomised trial in Guinea-Bissau

DEFF Research Database (Denmark)

Roth, A.E.; Benn, Christine Stabell; Ravn, H.

2010-01-01

-up. Compared with controls, the BCG revaccinated children had a hazard ratio of 1.20 (95% confidence interval 0.77 to 1.89). Two hundred and fifty children were admitted to hospital for the first time between enrolment and the end of the study, with an incidence rate ratio for BCG revaccinated children versus...

Protection against bovine tuberculosis induced by oral vaccination of cattle with Mycobacterium bovis BCG is not enhanced by co-administration of mycobacterial protein vaccines.

Science.gov (United States)

Wedlock, D Neil; Aldwell, Frank E; Vordermeier, H Martin; Hewinson, R Glyn; Buddle, Bryce M

2011-12-15

Mycobacterium bovis bacille Calmette-Guérin (BCG) delivered to calves by the oral route in a formulated lipid matrix has been previously shown to induce protection against bovine tuberculosis. A study was conducted in cattle to determine if a combination of a low dose of oral BCG and a protein vaccine could induce protective immunity to tuberculosis while not sensitising animals to tuberculin. Groups of calves (10 per group) were vaccinated by administering 2 × 10(7)colony forming units (CFU) of BCG orally or a combination of 2 × 10(7)CFU oral BCG and a protein vaccine comprised of M. bovis culture filtrate proteins (CFP) formulated with the adjuvants Chitin and Gel 01 and delivered by the intranasal route, or CFP formulated with Emulsigen and the TLR2 agonist Pam(3)CSK(4) and administered by the subcutaneous (s.c.) route. Two further groups were vaccinated with the CFP/Chitin/Gel 01 or CFP/Emulsigen/Pam(3)CSK(4) vaccines alone. Positive control groups were given 10(8)CFU oral BCG or 10(6)CFU s.c. BCG while a negative control group was non-vaccinated. All animals were challenged with M. bovis 15 weeks after vaccination and euthanized and necropsied at 16 weeks following challenge. Groups of cattle vaccinated with s.c. BCG, 10(8)CFU or 2 × 10(7)CFU oral BCG showed significant reductions in seven, three and four pathological or microbiological disease parameters, respectively, compared to the results for the non-vaccinated group. There was no evidence of protection in calves vaccinated with the combination of oral BCG and CFP/Emulsigen/Pam(3)CSK(4) or oral BCG and CFP/Chitin/Gel 01 or vaccinated with the protein vaccines alone. Positive responses in the comparative cervical skin test at 12 weeks after vaccination were only observed in animals vaccinated with s.c. BCG, 10(8)CFU oral BCG or a combination of 2 × 10(7)CFU oral BCG and CFP/Chitin/Gel 01. In conclusion, co-administration of a protein vaccine, administered by either systemic or mucosal routes with oral

A NOVEL BCG SENSOR-ARRAY FOR UNOBTRUSIVE CARDIAC MONITORING

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Anna Böhm

2013-12-01

Full Text Available Unobtrusive heart rate monitoring is a popular research topic in biomedical engineering. The reason is that convential methods, e.g. the clinical gold standard electrocardiography, require conductive contact to the human body. Other methods such as ballistocardiography try to record these vital signs without electrodes that are attached to the body. So far, these systems cannot replace routine procedures. Most systems have some drawbacks that cannot be compensated, such as aging of the sensor materials or movement artifacts. In addition, the signal form differs greatly from an ECG, which is an electrical signal. The ballistocardiogram has a mechanical source, which makes it harder to evaluate. We have developed a new sensor array made of near-IR-LEDs to record BCGs. IR-sensors do not age in relevant time scales. Analog filtering was neccesary, because the signal amplitude was very small. The digitized data was then processed by various algorithms to extract beat-to-beat or breath-to-breath intervals. The redundancy of multiple BCG channels was used to provide a robust estimation of beat-to-beat intervals and heart rate. We installed the system beneath a mattress topper of a hospital bed, but any other bed would have been sufficient. The validation of this measurement system shows that it is well suited for BCG recordings. The use of multiple channels has proven to be superior to relying on a single BCG channel.

Surgical management of BCG vaccine-induced regional axillary ...

African Journals Online (AJOL)

The age of the patient and mode of presentation, imaging findings, and results of tuberculin skin testing (Mantoux test) ... Primary surgical treatment (incisional drainage or biopsy) is therefore not considered an ideal form of management in BCG lymphadenitis because of the high fistulisation and poor wound healing, ...

A Modified Bacillus Calmette-Guérin (BCG Vaccine with Reduced Activity of Antioxidants and Glutamine Synthetase Exhibits Enhanced Protection of Mice despite Diminished in Vivo Persistence

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Douglas S. Kernodle

2013-01-01

Full Text Available Early attempts to improve BCG have focused on increasing the expression of prominent antigens and adding recombinant toxins or cytokines to influence antigen presentation. One such modified BCG vaccine candidate has been withdrawn from human clinical trials due to adverse effects. BCG was derived from virulent Mycobacterium bovis and retains much of its capacity for suppressing host immune responses. Accordingly, we have used a different strategy for improving BCG based on reducing its immune suppressive capacity. We made four modifications to BCG Tice to produce 4dBCG and compared it to the parent vaccine in C57Bl/6 mice. The modifications included elimination of the oxidative stress sigma factor SigH, elimination of the SecA2 secretion channel, and reductions in the activity of iron co-factored superoxide dismutase and glutamine synthetase. After IV inoculation of 4dBCG, 95% of vaccine bacilli were eradicated from the spleens of mice within 60 days whereas the titer of BCG Tice was not significantly reduced. Subcutaneous vaccination with 4dBCG produced greater protection than vaccination with BCG against dissemination of an aerosolized challenge of M. tuberculosis to the spleen at 8 weeks post-challenge. At this time, 4dBCG-vaccinated mice also exhibited altered lung histopathology compared to BCG-vaccinated mice and control mice with less well-developed lymphohistiocytic nodules in the lung parenchyma. At 26 weeks post-challenge, 4dBCG-vaccinated mice but not BCG-vaccinated mice had significantly fewer challenge bacilli in the lungs than control mice. In conclusion, despite reduced persistence in mice a modified BCG vaccine with diminished antioxidants and glutamine synthetase is superior to the parent vaccine in conferring protection against M. tuberculosis. The targeting of multiple immune suppressive factors produced by BCG is a promising strategy for simultaneously improving vaccine safety and effectiveness.

A genetic map of mouse chromosome 1 near the Lsh-Ity-Bcg disease resistance locus.

Science.gov (United States)

Mock, B; Krall, M; Blackwell, J; O'Brien, A; Schurr, E; Gros, P; Skamene, E; Potter, M

1990-05-01

Isozyme and restriction fragment length polymorphism (RFLP) analyses of backcross progeny, recombinant inbred strains, and congenic strains of mice positioned eight genetic markers with respect to the Lsh-Ity-Bcg disease resistance locus. Allelic isoforms of Idh-1 and Pep-3 and RFLPs detected by Southern hybridization for Myl-1, Cryg, Vil, Achrg, bcl-2, and Ren-1,2, between BALB/cAnPt and DBA/2NPt mice, were utilized to examine the cosegregation of these markers with the Lsh-Ity-Bcg resistance phenotype in 103 backcross progeny. An additional 47 backcross progeny from a cross between C57BL/10ScSn and B10.L-Lshr/s mice were examined for the cosegregation of Myl-1 and Vil RFLPs with Lsh phenotypic differences. Similarly, BXD recombinant inbred strains were typed for RFLPs upon hybridization with Vil and Achrg. Recombination frequencies generated in the different test systems were statistically similar, and villin (Vil) was identified as the molecular marker closest (1.7 +/- 0.8 cM) to the Lsh-Ity-Bcg locus. Two other DNA sequences, nebulin (Neb) and an anonymous DNA fragment (D2S3), which map to a region of human chromosome 2q that is homologous to proximal mouse chromosome 1, were not closely linked to the Lsh-Ity-Bcg locus. This multipoint linkage analysis of chromosome 1 surrounding the Lsh-Ity-Bcg locus provides a basis for the eventual isolation of the disease gene.

Immunogenic Properties of a BCG Adjuvanted Chitosan Nanoparticle-Based Dengue Vaccine in Human Dendritic Cells.

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Taweewun Hunsawong

2015-09-01

Full Text Available Dengue viruses (DENVs are among the most rapidly and efficiently spreading arboviruses. WHO recently estimated that about half of the world's population is now at risk for DENV infection. There is no specific treatment or vaccine available to treat or prevent DENV infections. Here, we report the development of a novel dengue nanovaccine (DNV composed of UV-inactivated DENV-2 (UVI-DENV and Mycobacterium bovis Bacillus Calmette-Guerin cell wall components (BCG-CWCs loaded into chitosan nanoparticles (CS-NPs. CS-NPs were prepared by an emulsion polymerization method prior to loading of the BCG-CWCs and UVI-DENV components. Using a scanning electron microscope and a zetasizer, DNV was determined to be of spherical shape with a diameter of 372.0 ± 11.2 nm in average and cationic surface properties. The loading efficacies of BCG-CWCs and UVI-DENV into the CS-NPs and BCG-CS-NPs were up to 97.2 and 98.4%, respectively. THP-1 cellular uptake of UVI-DENV present in the DNV was higher than soluble UVI-DENV alone. DNV stimulation of immature dendritic cells (iDCs resulted in a significantly higher expression of DCs maturation markers (CD80, CD86 and HLA-DR and induction of various cytokine and chemokine productions than in UVI-DENV-treated iDCs, suggesting a potential use of BCG- CS-NPs as adjuvant and delivery system for dengue vaccines.

Variation of growth in the production of the BCG vaccine and the association with the immune response. An observational study within a randomised trial

DEFF Research Database (Denmark)

Biering-Sørensen, Sofie; Jensen, Kristoffer Jarlov; Aamand, Susanne Havn

2015-01-01

INTRODUCTION: Bacille Calmette-Guérin (BCG) vaccine has beneficial non-specific effects on overall survival. After BCG vaccination, positive PPD response and scar formation are associated with increased survival. During a trial randomising low-birth-weight neonates to BCG at birth or the usual...... randomised to BCG at birth and examined for scar at 12 months; a subgroup was tested for PPD response at 2 and 6 months. The BCG batches from the Slow growth period were compared with the precedent and subsequent Normal growth batches with regard to prevalence and size of BCG scar and PPD response. We also...... batches were associated with larger scar size (5.0mm) than precedent (4.4mm, pPPD responses, and among PPD positive children, a larger PPD...

Difference in TB10.4 T-cell epitope recognition following immunization with recombinant TB10.4, BCG or infection with Mycobacterium tuberculosis

DEFF Research Database (Denmark)

Billeskov, Rolf; Grandal, Michael V; Poulsen, Christian

2010-01-01

vaccine Ag, TB10.4, in a recombinant form, or when expressed by the pathogen Mycobacterium tuberculosis (M.tb), or by the current anti-tuberculosis vaccine, Mycobacterium bovis BCG. We showed that BCG and M.tb induced a similar CD4(+) T-cell specific TB10.4 epitope-pattern, which differed completely from...... that induced by recombinant TB10.4. This difference was not due to post-translational modifications of TB10.4 or because TB10.4 is secreted from BCG and M.tb as a complex with Rv0287. In addition, BCG and TB10.4/CAF01 were both taken up by DC and macrophages in vivo, and in vitro uptake experiments revealed...... that both TB10.4 and BCG were transported to Lamp(+)-compartments. BCG and TB10.4 however, were directed to different types of Lamp(+)-compartments in the same APC, which may lead to different epitope recognition patterns. In conclusion, we show that different vectors can induce completely different...

Uptake of newly introduced universal BCG vaccination in newborns.

LENUS (Irish Health Repository)

Braima, O

2012-01-31

Universal neonatal BCG vaccination was discontinued in Cork in 1972. Following an outbreak of TB in 2 creches in the HSE South, a universal BCG vaccination program was re-introduced in October 2008. The aim of this study was to determine the vaccination process (in-hospital and community) and the in-hospital uptake of the vaccine. Following informed parental consent, babies of birth weight > 2.5 Kg were eligible for in-hospital vaccination if they were not: febrile, jaundiced on phototherapy, on antibiotics and if not born to HIV- positive mothers. Parents of babies not vaccinated in-hospital were asked to book an appointment in either of the 2 Cork community clinics. The immunisation nurse collected data on BCG vaccination, prospectively. This study examined vaccination uptakes in-hospital and community over a 6 month period (October 2008 to March 2009). There were 4018 deliveries during the study period. In-hospital consent was declined in only 16 babies (<1%) while the in-hospital vaccination uptake was 80% of total liv births. Although 635 newborns were admitted to the NICU, only 46 (8%) were vaccinated while in the NICU. At least 48% of planned community vaccination has been achieved to date. In conclusion, in-hospital consent was almost universal and vaccination uptake was satisfactory. NICU exclusion criteria accounted for a significant proportion of non-vaccination in-hospital. These criteria need to be readdressed considering that all premature babies are given other routine newborn vaccines at 2 months of age, regardless of weight.

Uptake of newly introduced universal BCG vaccination in newborns.

LENUS (Irish Health Repository)

Braima, O

2010-06-01

Universal neonatal BCG vaccination was discontinued in Cork in 1972. Following an outbreak of TB in 2 creches in the HSE South, a universal BCG vaccination program was re-introduced in October 2008. The aim of this study was to determine the vaccination process (in-hospital and community) and the in-hospital uptake of the vaccine. Following informed parental consent, babies of birth weight > 2.5 Kg were eligible for in-hospital vaccination if they were not: febrile, jaundiced on phototherapy, on antibiotics and if not born to HIV- positive mothers. Parents of babies not vaccinated in-hospital were asked to book an appointment in either of the 2 Cork community clinics. The immunisation nurse collected data on BCG vaccination, prospectively. This study examined vaccination uptakes in-hospital and community over a 6 month period (October 2008 to March 2009). There were 4018 deliveries during the study period. In-hospital consent was declined in only 16 babies (<1%) while the in-hospital vaccination uptake was 80% of total liv births. Although 635 newborns were admitted to the NICU, only 46 (8%) were vaccinated while in the NICU. At least 48% of planned community vaccination has been achieved to date. In conclusion, in-hospital consent was almost universal and vaccination uptake was satisfactory. NICU exclusion criteria accounted for a significant proportion of non-vaccination in-hospital. These criteria need to be readdressed considering that all premature babies are given other routine newborn vaccines at 2 months of age, regardless of weight.

A booster vaccine expressing a latency-associated antigen augments BCG induced immunity and confers enhanced protection against tuberculosis.

Directory of Open Access Journals (Sweden)

Bappaditya Dey

Full Text Available BACKGROUND: In spite of a consistent protection against tuberculosis (TB in children, Mycobacterium bovis Bacille Calmette-Guerin (BCG fails to provide adequate protection against the disease in adults as well as against reactivation of latent infections or exogenous reinfections. It has been speculated that failure to generate adequate memory T cell response, elicitation of inadequate immune response against latency-associated antigens and inability to impart long-term immunity against M. tuberculosis infections are some of the key factors responsible for the limited efficiency of BCG in controlling TB. METHODS/PRINCIPAL FINDINGS: In this study, we evaluated the ability of a DNA vaccine expressing α-crystallin--a key latency antigen of M. tuberculosis to boost the BCG induced immunity. 'BCG prime-DNA boost' regimen (B/D confers robust protection in guinea pigs along with a reduced pathology in comparison to BCG vaccination (1.37 log(10 and 1.96 log(10 fewer bacilli in lungs and spleen, respectively; p<0.01. In addition, B/D regimen also confers enhanced protection in mice. Further, we show that B/D immunization in mice results in a heightened frequency of PPD and antigen specific multi-functional CD4 T cells (3(+ simultaneously producing interferon (IFNγ, tumor necrosis factor (TNFα and interleukin (IL2. CONCLUSIONS/SIGNIFICANCE: These results clearly indicate the superiority of α-crystallin based B/D regimen over BCG. Our study, also demonstrates that protection against TB is predictable by an increased frequency of 3(+ Th1 cells with superior effector functions. We anticipate that this study would significantly contribute towards the development of superior booster vaccines for BCG vaccinated individuals. In addition, this regimen can also be expected to reduce the risk of developing active TB due to reactivation of latent infection.

Cosmological Constraints From SDSS MaxBCG Cluster Abundances

International Nuclear Information System (INIS)

Rozo, Eduardo; Wechsler, Risa H.; KICP, Chicago; Koester, Benjamin P.; McKay, Timothy A.; Evrard, August E.; Johnston, David; Sheldon, Erin S.; Annis, James; Frieman, Joshua A.

2007-01-01

We perform a maximum likelihood analysis of the cluster abundance measured in the SDSS using the maxBCG cluster finding algorithm. Our analysis is aimed at constraining the power spectrum normalization σ 8 , and assumes flat cosmologies with a scale invariant spectrum, massless neutrinos, and CMB and supernova priors (Omega) m h 2 = 0.128 ± 0.01 and h = 0.72 ± 0.05 respectively. Following the method described in the companion paper Rozo et al. (2007), we derive σ 8 = 0.92 ± 0.10 (1σ) after marginalizing over all major systematic uncertainties. We place strong lower limits on the normalization, σ 8 > 0.76 (95% CL) (> 0.68 at 99% CL). We also find that our analysis favors relatively low values for the slope of the Halo Occupation Distribution (HOD), α = 0.83 ± 0.06. The uncertainties of these determinations will substantially improve upon completion of an ongoing campaign to estimate dynamical, weak lensing, and X-ray cluster masses in the SDSS maxBCG cluster sample

BCG: A throwback from the stone age of vaccines opened the path for bladder cancer immunotherapy.

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Morales, Alvaro

2017-06-01

It is 40 years since the initial documentation of the efficacy of bacille Calmette-Guérin (BCG) in the management of non-muscle invasive bladder cancer (NMIBC) and probably an opportune a time as any to retrace the origins of this development and to reflect on the progress that has occurred on the use of immune modifiers in the treatment of NMIBC. A PubMed search for publications on the history of BCG was conducted, and those related to the development of the vaccine for protection against tuberculosis as well as those published in the last 40 years related to its use for treatment for NMIBC were selected for review. A manual search was also carried out for recent articles on immunotherapy for NMIBC failing to respond to BCG. Publications were selected for their usefulness in exemplifying the development of BCG as an antineoplastic agent, elucidating its mechanisms of action of BCG or introducing significant modifications in treatment regimens resulting in enhancement of its efficacy. Alternative innovative immunotherapeutic approaches were chosen to illustrate current trends in the management of this disease. Well thought-out modifications of the original protocol resulted in enhanced efficacy of the vaccine, which currently ranks as the best-known and most-used and investigated agent for high risk NMIBC. Despite its efficacy, a considerable number (30%-40%) of these tumors fail to respond to BCG. In addition, as a live bacterium it carries the potential for serious adverse effects and some patients are unable to tolerate it. These shortcomings have created the need for new agents. These range from other mycobacteria and viruses to monoclonal antibodies alone or in combination with other agents currently at various stages of development. After 4 decades of use, BCG remains the most effective agent against high risk NMIBC, but it still holds substantial drawbacks. The enduring use of immunotherapy for NMIBC has created a propitious environment to search for better

Differential Adverse Event Profiles Associated with BCG as a Preventive Tuberculosis Vaccine or Therapeutic Bladder Cancer Vaccine Identified by Comparative Ontology-Based VAERS and Literature Meta-Analysis.

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Jiangan Xie

Full Text Available M. bovis strain Bacillus Calmette-Guérin (BCG has been the only licensed live attenuated vaccine against tuberculosis (TB for nearly one century and has also been approved as a therapeutic vaccine for bladder cancer treatment since 1990. During its long time usage, different adverse events (AEs have been reported. However, the AEs associated with the BCG preventive TB vaccine and therapeutic cancer vaccine have not been systematically compared. In this study, we systematically collected various BCG AE data mined from the US VAERS database and PubMed literature reports, identified statistically significant BCG-associated AEs, and ontologically classified and compared these AEs related to these two types of BCG vaccine. From 397 VAERS BCG AE case reports, we identified 64 AEs statistically significantly associated with the BCG TB vaccine and 14 AEs with the BCG cancer vaccine. Our meta-analysis of 41 peer-reviewed journal reports identified 48 AEs associated with the BCG TB vaccine and 43 AEs associated with the BCG cancer vaccine. Among all identified AEs from VAERS and literature reports, 25 AEs belong to serious AEs. The Ontology of Adverse Events (OAE-based ontological hierarchical analysis indicated that the AEs associated with the BCG TB vaccine were enriched in immune system (e.g., lymphadenopathy and lymphadenitis, skin (e.g., skin ulceration and cyanosis, and respiratory system (e.g., cough and pneumonia; in contrast, the AEs associated with the BCG cancer vaccine mainly occurred in the urinary system (e.g., dysuria, pollakiuria, and hematuria. With these distinct AE profiles detected, this study also discovered three AEs (i.e., chills, pneumonia, and C-reactive protein increased shared by the BCG TB vaccine and bladder cancer vaccine. Furthermore, our deep investigation of 24 BCG-associated death cases from VAERS identified the important effects of age, vaccine co-administration, and immunosuppressive status on the final BCG

Nano-BCG: A Promising Delivery System for Treatment of Human Bladder Cancer.

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Buss, Julieti Huch; Begnini, Karine Rech; Bender, Camila Bonemann; Pohlmann, Adriana R; Guterres, Silvia S; Collares, Tiago; Seixas, Fabiana Kömmling

2017-01-01

Mycobacterium bovis bacillus Calmette-Guerin (BCG) remains at the forefront of immunotherapy for treating bladder cancer patients. However, the incidence of recurrence and progression to invasive cancer is commonly observed. There are no established effective intravesical therapies available for patients, whose tumors recur following BCG treatment, representing an important unmet clinical need. In addition, there are very limited options for patients who do not respond to or tolerate chemotherapy due to toxicities, resulting in poor overall treatment outcomes. Within this context, nanotechnology is an emergent and promising tool for: (1) controlling drug release for extended time frames, (2) combination therapies due to the ability to encapsulate multiple drugs simultaneously, (3) reducing systemic side effects, (4) increasing bioavailability, (5) and increasing the viability of various routes of administration. Moreover, bladder cancer is often characterized by high mutation rates and over expression of tumor antigens on the tumor cell surface. Therapeutic targeting of these biomolecules may be improved by nanotechnology strategies. In this mini-review, we discuss how nanotechnology can help overcome current obstacles in bladder cancer treatment, and how nanotechnology can facilitate combination chemotherapeutic and BCG immunotherapies for the treatment of non-muscle invasive urothelial bladder cancer.

Nano-BCG: A Promising Delivery System for Treatment of Human Bladder Cancer

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Julieti Huch Buss

2018-01-01

Full Text Available Mycobacterium bovis bacillus Calmette–Guerin (BCG remains at the forefront of immunotherapy for treating bladder cancer patients. However, the incidence of recurrence and progression to invasive cancer is commonly observed. There are no established effective intravesical therapies available for patients, whose tumors recur following BCG treatment, representing an important unmet clinical need. In addition, there are very limited options for patients who do not respond to or tolerate chemotherapy due to toxicities, resulting in poor overall treatment outcomes. Within this context, nanotechnology is an emergent and promising tool for: (1 controlling drug release for extended time frames, (2 combination therapies due to the ability to encapsulate multiple drugs simultaneously, (3 reducing systemic side effects, (4 increasing bioavailability, (5 and increasing the viability of various routes of administration. Moreover, bladder cancer is often characterized by high mutation rates and over expression of tumor antigens on the tumor cell surface. Therapeutic targeting of these biomolecules may be improved by nanotechnology strategies. In this mini-review, we discuss how nanotechnology can help overcome current obstacles in bladder cancer treatment, and how nanotechnology can facilitate combination chemotherapeutic and BCG immunotherapies for the treatment of non-muscle invasive urothelial bladder cancer.

Vacuna contra la tuberculosis BCG: Eficacia y efectos adversos

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Quezada-Andrade, Steven

2015-12-01

Full Text Available TB is the second leading cause of death from an infectious agent, disease caused by Mycobacterium tuberculosis. It allowed the creation of a vaccine officially launched in 1924 and known as Bacillus Calmette-Guerin (BCG used since then. However, there has been extensive research on its effectiveness and other related factors have shown an imbalance. Several countries recommend the use of this vaccine in infants, but in the case of Ecuador has failed to suggest its application, although there are no data regarding the efficacy of the vaccine in that country. Other studies show that the knowledge of people about the disease is destitute, thus allowing this could spread more quickly because the infected person does not know the type of symptoms that generates Tuberculosis. This article aims to identify the current status of the efficiency and safety of BCG through review and analysis of collected items related to the use of the vaccine and its effectiveness in the research population.

IMPROVEMENT OF THE RICHNESS ESTIMATES OF maxBCG CLUSTERS

International Nuclear Information System (INIS)

Rozo, Eduardo; Rykoff, Eli S.; Koester, Benjamin P.; Hansen, Sarah; Becker, Matthew; Bleem, Lindsey; McKay, Timothy; Hao Jiangang; Evrard, August; Wechsler, Risa H.; Sheldon, Erin; Johnston, David; Annis, James; Scranton, Ryan

2009-01-01

Minimizing the scatter between cluster mass and accessible observables is an important goal for cluster cosmology. In this work, we introduce a new matched filter richness estimator, and test its performance using the maxBCG cluster catalog. Our new estimator significantly reduces the variance in the L X -richness relation, from σ lnLx 2 = (0.86±0.02) 2 to σ lnLx 2 = (0.69±0.02) 2 . Relative to the maxBCG richness estimate, it also removes the strong redshift dependence of the L X -richness scaling relations, and is significantly more robust to photometric and redshift errors. These improvements are largely due to the better treatment of galaxy color data. We also demonstrate the scatter in the L X -richness relation depends on the aperture used to estimate cluster richness, and introduce a novel approach for optimizing said aperture which can easily be generalized to other mass tracers.

Tuberculin skin reactivity after neonatal BCG vaccination in preterm infants in Minas Gerais, Brazil, 2001-2002 Reactividad cutánea a la tuberculina tras la vacunación con BCG de neonatos prematuros en Minas Gerais, Brasil, 2001-2002

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Paulo Camargos

2006-06-01

Full Text Available OBJECTIVES: The efficacy of BCG vaccination in preterm babies is unknown, and available data on conversion rates to tuberculin in this age group are scarce and controversial. This study assessed the tuberculin response in preterm infants after BCG vaccination. METHODS: This randomized cohort study was carried out at the Neonatal Department, University Hospital, Federal University of Minas Gerais in Brazil during 2001 and 2002. The BCG vaccine was administered at birth to 65 full-term (control and 40 preterm newborns. All of them were tested with 5 tuberculin units of purified protein derivative-S approximately 3 months after vaccination. RESULTS: A typical BCG scar was verified in 96.9% of the control group and in 90.0% of the preterm infants (P = 0.19. Indurations > 5 mm in diameter were recorded in 87.7% of the full-term and 67.5% of the preterm infants (P = 0.02. Indurations > 10 mm were recorded in 70.8% of the full-term and 42.5% of the preterm infants (P = 0.007. For indurations > 5 mm the upper and the lower limits of the 95% confidence interval for the difference between proportions were 8.5% to 31.8%, and for indurations > 10 mm these limits were 18.0% to 38.4%. No adverse reactions were observed in the study population. CONCLUSION: BCG vaccination could be recommended for preterm infants upon discharge from the neonatal unit to reduce morbidity and mortality in infants at risk for tuberculous infection, and to increase BCG vaccination coverage rates, especially in countries with high prevalence rates of tuberculosis.OBJETIVOS: Se desconoce la eficacia de la vacunación con Bacilo de Calmette-Guérin (BCG en neonatos prematuros, y los datos que existen acerca de la proporción de casos de conversión tuberculínica en este grupo de edad son pocos y cuestionables. En este estudio se evaluó la respuesta a la prueba de tuberculina de neonatos prematuros tras la vacunación con BCG. MÉTODOS: Este estudio de cohorte aleatorizado se llev

BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity

NARCIS (Netherlands)

Arts, Rob J W; Moorlag, Simone J C F M; Novakovic, Boris; Li, Yang; Wang, Shuang-Yin; Oosting, Marije; Kumar, Vinod; Xavier, Ramnik J; Wijmenga, Cisca; Joosten, Leo A B; Reusken, Chantal B E M; Benn, Christine S; Aaby, Peter; Koopmans, Marion P; Stunnenberg, Hendrik G; van Crevel, Reinout; Netea, Mihai G

2018-01-01

The tuberculosis vaccine bacillus Calmette-Guérin (BCG) has heterologous beneficial effects against non-related infections. The basis of these effects has been poorly explored in humans. In a randomized placebo-controlled human challenge study, we found that BCG vaccination induced genome-wide

BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity

DEFF Research Database (Denmark)

Arts, Rob J W; Moorlag, Simone J C F M; Novakovic, Boris

2018-01-01

The tuberculosis vaccine bacillus Calmette-Guérin (BCG) has heterologous beneficial effects against non-related infections. The basis of these effects has been poorly explored in humans. In a randomized placebo-controlled human challenge study, we found that BCG vaccination induced genome-wide ep...

Effect of milk fermentation by kefir grains and selected single strains of lactic acid bacteria on the survival of Mycobacterium bovis BCG.

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Macuamule, C L S; Wiid, I J; van Helden, P D; Tanner, M; Witthuhn, R C

2016-01-18

Mycobacterium bovis that causes Bovine tuberculosis (BTB) can be transmitted to humans thought consumption of raw and raw fermented milk products from diseased animals. Lactic acid bacteria (LAB) used in popular traditional milk products in Africa produce anti-microbial compounds that inhibit some pathogenic and spoilage bacteria. M. bovis BCG is an attenuated non-pathogenic vaccine strain of M. bovis and the aim of the study was to determine the effect of the fermentation process on the survival of M. bovis BCG in milk. M. bovis BCG at concentrations of 6 log CFU/ml was added to products of kefir fermentation. The survival of M. bovis BCG was monitored at 12-h intervals for 72 h by enumerating viable cells on Middlebrook 7H10 agar plates enriched with 2% BD BACTEC PANTA™. M. bovis BCG was increasingly reduced in sterile kefir that was fermented for a period of 24h and longer. In the milk fermented with kefir grains, Lactobacillus paracasei subsp. paracasei or Lactobacillus casei, the viability of M. bovis BCG was reduced by 0.4 logs after 24h and by 2 logs after 48 h of fermentation. No viable M. bovis BCG was detected after 60 h of fermentation. Results from this study show that long term fermentation under certain conditions may have the potential to inactivate M. bovis BCG present in the milk. However, to ensure safety of fermented milk in Africa, fermentation should be combined with other hurdle technologies such as boiling and milk pasteurisation. Copyright © 2015 Elsevier B.V. All rights reserved.

Comparative Tuberculosis (TB) Prevention Effectiveness in Children of Bacillus Calmette-Guérin (BCG) Vaccines from Different Sources, Kazakhstan

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Favorov, Michael; Ali, Mohammad; Tursunbayeva, Aigul; Aitmagambetova, Indira; Kilgore, Paul; Ismailov, Shakhimurat; Chorba, Terence

2012-01-01

Background Except during a 1-year period when BCG vaccine was not routinely administered, annual coverage of infants with Bacillus Calmette-Guérin (BCG) in Kazakhstan since 2002 has exceeded 95%. BCG preparations from different sources (Japan, Serbia, and Russia) or none were used exclusively in comparable 7-month time-frames, September through March, in 4 successive years beginning in 2002. Our objective was to assess relative effectiveness of BCG immunization. Methods/Findings We compared outcomes of birth cohorts from the 4 time-frames retrospectively. Three cohorts received vaccine from one of three manufacturers exclusively, and one cohort was not vaccinated. Cohorts were followed for 3 years for notifications of clinical TB and of culture-confirmed TB, and for 21 months for TB meningitis notifications. Prevention effectiveness based on relative risk of TB incidence was calculated for each vaccinated cohort compared to the non-vaccinated cohort. Although there were differences in prevention effectiveness observed among the three BCG vaccines, all were protective. The Japanese vaccine (currently used in Kazakhstan), the Serbian vaccine, and the Russian vaccine respectively were 69%, 43%, and 22% effective with respect to clinical TB notifications, and 92%, 82%, and 51% effective with respect to culture confirmed TB. All three vaccines were >70% effective with respect to TB meningitis. Limitations Potential limitations included considerations that 1) the methodology used was retrospective, 2) multiple risk factors could have varied between cohorts and affected prevention effectiveness measures, 3) most cases were clinically diagnosed, and TB culture-positive case numbers and TB meningitis case numbers were sparse, and 4) small variations in reported population TB burden could have affected relative risk of exposure for cohorts. Conclusions/Significance All three BCG vaccines evaluated were protective against TB, and prevention effectiveness varied by

Comparative tuberculosis (TB prevention effectiveness in children of Bacillus Calmette-Guérin (BCG vaccines from different sources, Kazakhstan.

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Michael Favorov

Full Text Available BACKGROUND: Except during a 1-year period when BCG vaccine was not routinely administered, annual coverage of infants with Bacillus Calmette-Guérin (BCG in Kazakhstan since 2002 has exceeded 95%. BCG preparations from different sources (Japan, Serbia, and Russia or none were used exclusively in comparable 7-month time-frames, September through March, in 4 successive years beginning in 2002. Our objective was to assess relative effectiveness of BCG immunization. METHODS/FINDINGS: We compared outcomes of birth cohorts from the 4 time-frames retrospectively. Three cohorts received vaccine from one of three manufacturers exclusively, and one cohort was not vaccinated. Cohorts were followed for 3 years for notifications of clinical TB and of culture-confirmed TB, and for 21 months for TB meningitis notifications. Prevention effectiveness based on relative risk of TB incidence was calculated for each vaccinated cohort compared to the non-vaccinated cohort. Although there were differences in prevention effectiveness observed among the three BCG vaccines, all were protective. The Japanese vaccine (currently used in Kazakhstan, the Serbian vaccine, and the Russian vaccine respectively were 69%, 43%, and 22% effective with respect to clinical TB notifications, and 92%, 82%, and 51% effective with respect to culture confirmed TB. All three vaccines were >70% effective with respect to TB meningitis. LIMITATIONS: Potential limitations included considerations that 1 the methodology used was retrospective, 2 multiple risk factors could have varied between cohorts and affected prevention effectiveness measures, 3 most cases were clinically diagnosed, and TB culture-positive case numbers and TB meningitis case numbers were sparse, and 4 small variations in reported population TB burden could have affected relative risk of exposure for cohorts. CONCLUSIONS/SIGNIFICANCE: All three BCG vaccines evaluated were protective against TB, and prevention effectiveness

Comparative tuberculosis (TB) prevention effectiveness in children of Bacillus Calmette-Guérin (BCG) vaccines from different sources, Kazakhstan.

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Favorov, Michael; Ali, Mohammad; Tursunbayeva, Aigul; Aitmagambetova, Indira; Kilgore, Paul; Ismailov, Shakhimurat; Chorba, Terence

2012-01-01

Except during a 1-year period when BCG vaccine was not routinely administered, annual coverage of infants with Bacillus Calmette-Guérin (BCG) in Kazakhstan since 2002 has exceeded 95%. BCG preparations from different sources (Japan, Serbia, and Russia) or none were used exclusively in comparable 7-month time-frames, September through March, in 4 successive years beginning in 2002. Our objective was to assess relative effectiveness of BCG immunization. We compared outcomes of birth cohorts from the 4 time-frames retrospectively. Three cohorts received vaccine from one of three manufacturers exclusively, and one cohort was not vaccinated. Cohorts were followed for 3 years for notifications of clinical TB and of culture-confirmed TB, and for 21 months for TB meningitis notifications. Prevention effectiveness based on relative risk of TB incidence was calculated for each vaccinated cohort compared to the non-vaccinated cohort. Although there were differences in prevention effectiveness observed among the three BCG vaccines, all were protective. The Japanese vaccine (currently used in Kazakhstan), the Serbian vaccine, and the Russian vaccine respectively were 69%, 43%, and 22% effective with respect to clinical TB notifications, and 92%, 82%, and 51% effective with respect to culture confirmed TB. All three vaccines were >70% effective with respect to TB meningitis. Potential limitations included considerations that 1) the methodology used was retrospective, 2) multiple risk factors could have varied between cohorts and affected prevention effectiveness measures, 3) most cases were clinically diagnosed, and TB culture-positive case numbers and TB meningitis case numbers were sparse, and 4) small variations in reported population TB burden could have affected relative risk of exposure for cohorts. All three BCG vaccines evaluated were protective against TB, and prevention effectiveness varied by manufacturer. When setting national immunization policy, consideration

Contemporary management of patients with high-risk non-muscle-invasive bladder cancer who fail intravesical BCG therapy.

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Yates, D R; Rouprêt, M

2011-08-01

It is advocated that patients with high-risk non-muscle-invasive bladder cancer (NMIBC) receive an adjuvant course of intravesical Bacille Calmette-Guerin (BCG) as first-line treatment. However, a substantial proportion of patients will 'fail' BCG, either early with persistent (refractory) disease or recur late after a long disease-free interval (relapsing). Guideline recommendation in the 'refractory' setting is radical cystectomy, but there are situations when extirpative surgery is not feasible due to competing co-morbidity, a patient's desire for bladder preservation or reluctance to undergo surgery. In this review, we discuss the contemporary management of NMIBC in patients who have failed prior BCG and are not suitable for radical surgery and highlight the potential options available. These options can be categorised as immunotherapy, chemotherapy, device-assisted therapy and combination therapy. However, the current data are still inadequate to formulate definitive recommendations, and data from ongoing trials and maturing studies will give us an insight into whether there is a realistic efficacious second-line treatment for patients who fail intravesical BCG but are not candidates for definitive surgery.

Immune response profiles of calves following vaccination with live BCG and inactivated Mycobacterium bovis vaccine candidates.

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E M D L van der Heijden

Full Text Available Conventional control and eradication strategies for bovine tuberculosis (BTB face tremendous difficulties in developing countries; countries with wildlife reservoirs, a complex wildlife-livestock-human interface or a lack of veterinary and veterinary public health surveillance. Vaccination of cattle and other species might in some cases provide the only suitable control strategy for BTB, while in others it may supplement existing test-and-slaughter schemes. However, the use of live BCG has several limitations and the global rise of HIV/AIDS infections has furthermore warranted the exploration of inactivated vaccine preparations. The aim of this study was to compare the immune response profiles in response to parenteral vaccination with live BCG and two inactivated vaccine candidates in cattle. Twenty-four mixed breed calves (Bos taurus aged 4-6 months, were allocated to one of four groups and vaccinated sub-cutaneously with live M. bovis BCG (Danish 1331, formalin-inactivated M. bovis BCG, heat-killed M. bovis or PBS/Montanide™ (control. Interferon-γ responsiveness and antibody production were measured prior to vaccination and at weekly intervals thereafter for twelve weeks. At nine weeks post-priming, animals were skin tested using tuberculins and MTBC specific protein cocktails and subsequently challenged through intranodular injection of live M. bovis BCG. The animals in the heat-killed M. bovis group demonstrated strong and sustained cell-mediated and humoral immune responses, significantly higher than the control group in response to vaccination, which may indicate a protective immune profile. Animals in this group showed reactivity to the skin test reagents, confirming good vaccine take. Lastly, although not statistically significant, recovery of BCG after challenge was lowest in the heat-killed M. bovis group. In conclusion, the parenteral heat-killed M. bovis vaccine proved to be clearly immunogenic in cattle in the present study

The HyVac4 subunit vaccine efficiently boosts BCG-primed anti-mycobacterial protective immunity.

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Rolf Billeskov

Full Text Available BACKGROUND: The current vaccine against tuberculosis (TB, BCG, has failed to control TB worldwide and the protective efficacy is moreover limited to 10-15 years. A vaccine that could efficiently boost a BCG-induced immune response and thus prolong protective immunity would therefore have a significant impact on the global TB-burden. METHODS/FINDINGS: In the present study we show that the fusion protein HyVac4 (H4, consisting of the mycobacterial antigens Ag85B and TB10.4, given in the adjuvant IC31® or DDA/MPL effectively boosted and prolonged immunity induced by BCG, leading to improved protection against infection with virulent M. tuberculosis (M.tb. Increased protection correlated with an increased percentage of TB10.4 specific IFNγ/TNFα/IL-2 or TNFα/IL-2 producing CD4 T cells at the site of infection. Moreover, this vaccine strategy did not compromise the use of ESAT-6 as an accurate correlate of disease development/vaccine efficacy. Indeed both CD4 and CD8 ESAT-6 specific T cells showed significant correlation with bacterial levels. CONCLUSIONS/SIGNIFICANCE: H4-IC31® can efficiently boost BCG-primed immunity leading to an increased protective anti-M.tb immune response dominated by IFNγ/TNFα/IL-2 or TNFα/IL2 producing CD4 T cells. H4 in the CD4 T cell inducing adjuvant IC31® is presently in clinical trials.

Limitations of the BCG vaccine and new prophylaxis strategies against human tuberculosis

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Arioldo Carvalho Vasconcelos-Junior

2009-09-01

Full Text Available BCG (Bacille Calmette Guérin, an attenuated vaccine derived from Mycobacterium bovis, is the current vaccine against tuberculosis. Notwithstanding its protection of children, BCG has failed to protect adults against active pulmonary tuberculosis, especially in countries where the disease is endemic. Any new tuberculosis vaccine should protect several categories of people, including children, adults, the elderly and immunodeppressed patients. An important feature is immunization safety for all of these classes. The aim of this review is to describe new vaccination strategies, such as subunit vaccines, DNA vaccines, vaccines with live microorganisms and vectors, and to discuss the application of these new strategies for the control and eradication of tuberculosis.

Failure of bacillus calmette guerin (bcg) therapy for the treatment of ...

African Journals Online (AJOL)

BCG) instillation following complete transurethral resection of superficial transitional cell carcinoma (TCC) of the urinary bladder at the Urology Department, Al-Azhar University, Cairo, Egypt. Patients and Methods: A prospective analysis of 160 ...

BCG vaccination status of children with tuberculous meningitis and ...

African Journals Online (AJOL)

From 1985 to 1992, 193 children with tuberculous meningitis (TBM) with a median age of 26 months were admitted to the Department of Paediatrics and Child Health, Tygerberg Hospital. Of these children 143 (74%) were documented to have received BCG, either by reference to 'Road to Health' cards or by contact with ...

BCG vaccination status of children with tuberculous meningitis and ...

African Journals Online (AJOL)

From 1985 to 1992, 193 children with tuberculous meningitis (TBM) with a median age of 26 months were admitted to the Department of Paediatrics and Child. Health, Tygerberg Hospital. Of these children 143 (74%) were documented to have received BCG, either by reference to 'Road to Health' cards or by contact with.

How do parents make their decision about letting their child get a BCG vaccination?

DEFF Research Database (Denmark)

Thybo Pihl, Gitte; Ammentorp, Jette; Schmidt Jensen, Jane

Introduction: In a large prospective randomised clinical trial in Denmark we are testing the hypothesis that compared to non-BCG-vaccinated infants, infants who are BCG vaccinated at birth experience less hospitalisations, use less antibiotics, and develop less atopic disease in early childhood. My...... of illness and atopic diseases in their personal network and family to evaluate risk for their child to develop atopic diseases or get hospitalised. This lay epidemiologi forms the basis for their decision. Davison C, Frankel S, Davey Smith G. Inheriting heart trouble: the relevance of common-sense ideas...

Immunological Links to Nonspecific Effects of DTwP and BCG Vaccines on Infant Mortality

DEFF Research Database (Denmark)

Claesson, Mogens Helweg

2011-01-01

females and males may have their lives saved each year by the nonspecific immunological benefits of Bacillus Calmette-Guerin (BCG) vaccination. From an immunological point of view, we hypothesise that the adverse effects of DTwP vaccine may occur because of the Th2-polarising effect of the aluminium...... phosphate adjuvant in the vaccine and because intramuscular administration of the vaccine may cause chronic inflammation at the site of injection. However, the Th1-polarising effect of BCG is likely to be beneficial. Sexual dimorphism affecting immune functions and vitamin A supplementation may influence...

The mycobacterial DNA-binding protein 1 (MDP1 from Mycobacterium bovis BCG influences various growth characteristics

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Maurischat Sven

2008-06-01

Full Text Available Abstract Background Pathogenic mycobacteria such as M. tuberculosis, M. bovis or M. leprae are characterised by their extremely slow growth rate which plays an important role in mycobacterial virulence and eradication of the bacteria. Various limiting factors influence the generation time of mycobacteria, and the mycobacterial DNA-binding protein 1 (MDP1 has also been implicated in growth regulation. Our strategy to investigate the role of MDP1 in mycobacterial growth consisted in the generation and characterisation of a M. bovis BCG derivative expressing a MDP1-antisense gene. Results The expression rate of the MDP1 protein in the recombinant M. bovis BCG containing the MDP1-antisense plasmid was reduced by about 50% compared to the reference strain M. bovis BCG containing the empty vector. In comparison to this reference strain, the recombinant M. bovis BCG grew faster in broth culture and reached higher cell masses in stationary phase. Likewise its intracellular growth in mouse and human macrophages was ameliorated. Bacterial clumping in broth culture was reduced by the antisense plasmid. The antisense plasmid increased the susceptibility of the bacteria towards Ampicillin. 2-D protein gels of bacteria maintained under oxygen-poor conditions demonstrated a reduction in the number and the intensity of many protein spots in the antisense strain compared to the reference strain. Conclusion The MDP1 protein has a major impact on various growth characteristics of M. bovis BCG. It plays an important role in virulence-related traits such as aggregate formation and intracellular multiplication. Its impact on the protein expression in a low-oxygen atmosphere indicates a role in the adaptation to the hypoxic conditions present in the granuloma.

Naive helper T cells from BCG-vaccinated volunteers produce IFN-gamma and IL-5 to mycobacterial antigen-pulsed dendritic cells.

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JoĂŤl Pestel

2008-06-01

Full Text Available Mycobacterium bovis bacillus Calmette-GuĂŠrin (BCG is a live vaccine that has been used in routine vaccination against tuberculosis for nearly 80 years. However, its efficacy is controversial. The failure of BCG vaccination may be at least partially explained by the induction of poor or inappropriate host responses. Dendritic cells (DCs are likely to play a key role in the induction of immune response to mycobacteria by polarizing the reactivity of T lymphocytes toward a Th1 profile, contributing to the generation of protective cellular immunity against mycobacteria. In this study we aimed to investigate the production of Th1 and Th2 cytokines by naive CD4+ T cells to mycobacterial antigen-pulsed DCs in the group of young, healthy BCG vaccinated volunteers. The response of naive helper T cells was compared with the response of total blood lymphocytes. Our present results clearly showed that circulating naive CD45RA+CD4+ lymphocytes from BCG-vaccinated subjects can become effector helper cells producing IFN-gamma and IL-5 under the stimulation by autologous dendritic cells presenting mycobacterial protein antigen-PPD or infected with live M. bovis BCG bacilli.

Naive helper T cells from BCG-vaccinated volunteers produce IFN-gamma and IL-5 to mycobacterial antigen-pulsed dendritic cells.

Science.gov (United States)

Kowalewicz-Kulbat, Magdalena; Kaźmierczak, Dominik; Donevski, Stefan; Biet, Franck; Pestel, Joël; Rudnicka, Wiesława

2008-01-01

Mycobacterium bovis bacillus Calmette-Guérin (BCG) is a live vaccine that has been used in routine vaccination against tuberculosis for nearly 80 years. However, its efficacy is controversial. The failure of BCG vaccination may be at least partially explained by the induction of poor or inappropriate host responses. Dendritic cells (DCs) are likely to play a key role in the induction of immune response to mycobacteria by polarizing the reactivity of T lymphocytes toward a Th1 profile, contributing to the generation of protective cellular immunity against mycobacteria. In this study we aimed to investigate the production of Th1 and Th2 cytokines by naive CD4+ T cells to mycobacterial antigen-pulsed DCs in the group of young, healthy BCG vaccinated volunteers. The response of naive helper T cells was compared with the response of total blood lymphocytes. Our present results clearly showed that circulating naive CD45RA+CD4+ lymphocytes from BCG-vaccinated subjects can become effector helper cells producing IFN-gamma and IL-5 under the stimulation by autologous dendritic cells presenting mycobacterial protein antigen-PPD or infected with live M. bovis BCG bacilli.

Is tuberculin testing before BCG vaccination necessary for children over three months of age?

LENUS (Irish Health Repository)

Hennessy, B

2008-03-01

In July 2007 Irish national policy changed such that children aged 3 months to 6 years no longer routinely require tuberculin (Mantoux) skin testing prior to BCG vaccination. Previous to that a tuberculin test was required in all children in this age group pre vaccination. While the previous policy was in place this study was conducted to assess the value of this test. The observation that children are frightened by the test (an injection into the skin) prompted the study. The author conducted a retrospective study of the results of 1,854 tuberculin tests performed as a prerequisite to BCG vaccination and found that only 0.7% of children had a positive test result (induration > 5mm). None of 107 children < 6 years of age tested positive. Those > 12 years were more likely to test positive than younger children (1.09% vs 0.4% respectively, p < 0.05). This study suggests that testing young children before BCG vaccination has a low yield of positive results and adds little to the detection of latent or active TB.

Lack of a Negative Effect of BCG-Vaccination on Child Psychomotor Development

DEFF Research Database (Denmark)

Kjærgaard, Jesper; Stensballe, Lone Graff; Birk, Nina Marie

2016-01-01

MEASURES: Psychomotor development measured using Ages and Stages Questionnaire (ASQ) completed by the parents at 12 months. Additionally, parents of premature children (gestational age Developmental assessment was available for 3453/4262 (81%). RESULTS......OBJECTIVES: To assess the non-specific effect of Bacillus Calmette-Guérin (BCG) vaccination at birth on psychomotor development. DESIGN: This is a pre-specified secondary outcome from a randomised, clinical trial. SETTING: Maternity units and paediatric wards at three university hospitals...... was -7.8 points (-20.6 to 5.0, p = 0.23), d = -0.23 (-0.62 to 0.15). CONCLUSIONS: A negative non-specific effect of BCG vaccination at birth on psychomotor development was excluded in term children. TRIAL REGISTRATION: ClinicalTrials.gov NCT01694108....

TLR9 played a more important role than TLR2 in the combination of maltose-binding protein and BCG-induced Th1 activation.

Science.gov (United States)

Ni, Weihua; Wang, Fang; Liu, Guomu; Zhang, Nannan; Yuan, Hongyan; Jie, Jing; Tai, Guixiang

2016-11-01

Our previous study demonstrated that maltose-binding protein (MBP) combined with BCG induced synergistic mouse Th1 activation in vivo. Here, to explore the mechanism of MBP combined with BCG on Th1 activation, mouse purified CD4 + T cells were stimulated with MBP and BCG in vitro. The results showed that MBP combined with BCG synergistically increased IFN-γ production, accompanied with the upregulation of TLR2/9 expressions, suggesting that TLR2/9 were involved in the combination-induced Th1 activation. Next, TLR2 antibodies and TLR9 inhibitor were used to further analyze the effects of TLRs in Th1 activation. Results showed TLR2 antibody partly decreased MBP combined with BCG-induced IFN-γ production, MyD88 expression and IκB phosphorylation, indicating that TLR2-mediated MyD88-dependent pathway was involved in the MBP combined with BCG-induced Th1 activation. Moreover, MBP combined with BCG-induced Th1 activation was completely abrogated by TLR9 inhibitor, suggesting that TLR9-mediated MyD88-dependent pathway played a more important role than TLR2 in the combination-induced Th1 activation. Further study showed that TLR9 inhibitor downregulated TLR2 expression, suggesting that TLR9 signaling regulated TLR2 activation to favor Th1 resonse induced by MBP combined with BCG. Collectively, we demonstrated for the first time that the cross-talk of TLR2 and TLR9 triggered Th1 activation collaboratively and our findings provided valuable information about designing more effective adjuvant for cancer therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

BCG vaccination drives accumulation and effector function of innate lymphoid cells in murine lungs.

Science.gov (United States)

Steigler, Pia; Daniels, Naomi J; McCulloch, Tim R; Ryder, Brin M; Sandford, Sarah K; Kirman, Joanna R

2018-04-01

The tuberculosis (TB) vaccine bacille Calmette-Guérin (BCG) prevents disseminated childhood TB; however, it fails to protect against the more prevalent pulmonary TB. Limited understanding of the immune response to Mycobacterium tuberculosis, the causative agent of TB, has hindered development of improved vaccines. Although memory CD4 T cells are considered the main mediators of protection against TB, recent studies suggest there are other key subsets that contribute to antimycobacterial immunity. To that end, innate cells may be involved in the protective response. In this study, we investigated the primary response of innate lymphoid cells (ILCs) to BCG exposure. Using a murine model, we showed that ILCs increased in number in the lungs and lymph nodes in response to BCG vaccination. Additionally, there was significant production of the antimycobacterial cytokine IFN-γ by ILCs. As ILCs are located at mucosal sites, it was investigated whether mucosal vaccination (intranasal) stimulated an enhanced response compared to the traditional vaccination approach (intradermal or subcutaneous). Indeed, in response to intranasal vaccination, the number of ILCs, and IFN-γ production in NK cells and ILC1s in the lungs and lymph nodes, were higher than that provoked through intradermal or subcutaneous vaccination. This work provides the first evidence that BCG vaccination activates ILCs, paving the way for future research to elucidate the protective potential of ILCs against mycobacterial infection. Additionally, the finding that lung ILCs respond rigorously to mucosal vaccination may have implications for the delivery of novel TB vaccines. © 2018 Australasian Society for Immunology Inc.

Ojo de buey en tomografía hepática.

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Jorge Alberto Cortés

2004-03-01

Full Text Available Las infecciones micóticas invasoras se presentan con mayor frecuencia en pacientes con neutropenia posterior al uso de quimioterapia para el tratamiento del cáncer. Se presenta una paciente de 4 años con diagnóstico de leucemia linfoide aguda, quien, luego de la quimioterapia, desarrolló neutropenia febril y diarrea. Recibió tratamiento antibiótico y antimicótico de amplio espectro. Se aisló Candida albicans y se observaron trofozoítos de Entamoeba histolytica en la materia fecal. La paciente desarrolló candidiosis crónica diseminada que fue tratada con anfotericina B y, posteriormente, con fluconazol. Se ilustra la imagen tomográfica conocida como 'ojo de buey' y su correspondiente estudio histopatológico. Candida spp. es la levadura más común en pacientes inmunosuprimidos con tumores hematológicos que reciben quimioterapia. La candidiosis diseminada que se presenta en estos pacientes persiste y se hace evidente clínicamente una vez se resuelve la neutropenia; se denomina candidiosis crónica diseminada. En la paciente se presentaron varios factores de riesgo, como el tratamiento previo con antibióticos de amplio espectro, la colonización del tracto gastrointestinal por Candida y la neutropenia prolongada. El diagnóstico por imagen se hace principalmente por ecografía, tomografía axial computarizada y resonancia magnética. Se han descrito cuatro patrones tanto ecográficos como tomográficos, de los cuales se destacan el tipo 1 ('ruedas entre ruedas' y el tipo 2 ('ojo de buey', que son característicos de

Molecular Characterization of Heterologous HIV-1gp120 Gene Expression Disruption in Mycobacterium bovis BCG Host Strain: A Critical Issue for Engineering Mycobacterial Based-Vaccine Vectors

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Joseph, Joan; Fernández-Lloris, Raquel; Pezzat, Elías; Saubi, Narcís; Cardona, Pere-Joan; Mothe, Beatriz; Gatell, Josep Maria

2010-01-01

Mycobacterium bovis Bacillus Calmette-Guérin (BCG) as a live vector of recombinant bacterial vaccine is a promising system to be used. In this study, we evaluate the disrupted expression of heterologous HIV-1gp120 gene in BCG Pasteur host strain using replicative vectors pMV261 and pJH222. pJH222 carries a lysine complementing gene in BCG lysine auxotrophs. The HIV-1 gp120 gene expression was regulated by BCG hsp60 promoter (in plasmid pMV261) and Mycobacteria spp. α-antigen promoter (in plasmid pJH222). Among 14 rBCG:HIV-1gp120 (pMV261) colonies screened, 12 showed a partial deletion and two showed a complete deletion. However, deletion was not observed in all 10 rBCG:HIV-1gp120 (pJH222) colonies screened. In this study, we demonstrated that E. coli/Mycobacterial expression vectors bearing a weak promoter and lysine complementing gene in a recombinant lysine auxotroph of BCG could prevent genetic rearrangements and disruption of HIV 1gp120 gene expression, a key issue for engineering Mycobacterial based vaccine vectors. PMID:20617151

Molecular Characterization of Heterologous HIV-1gp120 Gene Expression Disruption in Mycobacterium bovis BCG Host Strain: A Critical Issue for Engineering Mycobacterial Based-Vaccine Vectors

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Joan Joseph

2010-01-01

Full Text Available Mycobacterium bovis Bacillus Calmette-Guérin (BCG as a live vector of recombinant bacterial vaccine is a promising system to be used. In this study, we evaluate the disrupted expression of heterologous HIV-1gp120 gene in BCG Pasteur host strain using replicative vectors pMV261 and pJH222. pJH222 carries a lysine complementing gene in BCG lysine auxotrophs. The HIV-1 gp120 gene expression was regulated by BCG hsp60 promoter (in plasmid pMV261 and Mycobacteria spp. α-antigen promoter (in plasmid pJH222. Among 14 rBCG:HIV-1gp120 (pMV261 colonies screened, 12 showed a partial deletion and two showed a complete deletion. However, deletion was not observed in all 10 rBCG:HIV-1gp120 (pJH222 colonies screened. In this study, we demonstrated that E. coli/Mycobacterial expression vectors bearing a weak promoter and lysine complementing gene in a recombinant lysine auxotroph of BCG could prevent genetic rearrangements and disruption of HIV 1gp120 gene expression, a key issue for engineering Mycobacterial based vaccine vectors.

Intratumoral Th2 predisposition combines with an increased Th1 functional phenotype in clinical response to intravesical BCG in bladder cancer.

Science.gov (United States)

Pichler, Renate; Gruenbacher, Georg; Culig, Zoran; Brunner, Andrea; Fuchs, Dietmar; Fritz, Josef; Gander, Hubert; Rahm, Andrea; Thurnher, Martin

2017-04-01

Th1-type immunity is considered to be required for efficient response to BCG in bladder cancer, although Th2 predisposition of BCG responders has recently been reported. The aim was to evaluate the relationship of Th1 and Th2 components in 23 patients undergoing BCG treatment. Peripheral blood, serum and urine samples were prospectively collected at baseline, during and after BCG. Th1 (neopterin, tryptophan, kynurenine, kynurenine-to-tryptophan ratio (KTR), IL-12, IFN-γ, soluble TNF-R75 and IL-2Rα) and Th2 (IL-4, IL-10) biomarkers as well as CD4 expression in T helper (Th), effector and regulatory T cells were determined. Local immune cell subsets were measured on formalin-fixed, paraffin-embedded cancer tissue by immunohistochemistry to examine expression of transcription factors that control Th1 (T-bet) and Th2-type (GATA3) immunity. We confirmed a Th2 predisposition with a mean GATA3/T-bet ratio of 5.51. BCG responders showed significantly higher levels of urinary (p = 0.003) and serum neopterin (p = 0.012), kynurenine (p = 0.015), KTR (p = 0.005), IFN-γ (p = 0.005) and IL-12 (p = 0.003) during therapy, whereas levels of IL-10 decreased significantly (p Th1-type immune responses and thus contribute to the BCG success.

BCG-unresponsive non-muscle-invasive bladder cancer: recommendations from the IBCG

NARCIS (Netherlands)

Kamat, A.M.; Colombel, M.; Sundi, D.; Lamm, D.; Boehle, A.; Brausi, M.; Buckley, R.; Persad, R.; Palou, J.; Soloway, M.; Witjes, J.A.

2017-01-01

Intravesical immunotherapy with live attenuated BCG remains the standard of care for patients with high-risk and intermediate-risk non-muscle-invasive bladder cancer (NMIBC). Most patients initially respond, but recurrence is frequent and progression to invasive cancer is a concern. No established

Cosmological Constraints from the SDSS maxBCG Cluster Catalog

Energy Technology Data Exchange (ETDEWEB)

Rozo, Eduardo; /CCAPP; Wechsler, Risa H.; /KIPAC, Menlo Park /SLAC; Rykoff, Eli S.; /UC, Santa Barbara; Annis, James T.; /Fermilab; Becker, Matthew R.; /Chicago U. /KICP, Chicago; Evrard, August E.; /Michigan U. /Michigan U., MCTP; Frieman, Joshua A.; /Fermilab /KICP, Chicago /Chicago U.; Hansen, Sarah M.; /UC, Santa Cruz; Hao, Jia; /Michigan U.; Johnston, David E.; /Northwestern U.; Koester, Benjamin P.; /KICP, Chicago /Chicago U.; McKay, Timothy A.; /Michigan U. /Michigan U., MCTP; Sheldon, Erin S.; /Brookhaven; Weinberg, David H.; /CCAPP /Ohio State U.

2009-08-03

We use the abundance and weak lensing mass measurements of the SDSS maxBCG cluster catalog to simultaneously constrain cosmology and the richness-mass relation of the clusters. Assuming a flat {Lambda}CDM cosmology, we find {sigma}{sub 8}({Omega}{sub m}/0.25){sup 0.41} = 0.832 {+-} 0.033 after marginalization over all systematics. In common with previous studies, our error budget is dominated by systematic uncertainties, the primary two being the absolute mass scale of the weak lensing masses of the maxBCG clusters, and uncertainty in the scatter of the richness-mass relation. Our constraints are fully consistent with the WMAP five-year data, and in a joint analysis we find {sigma}{sub 8} = 0.807 {+-} 0.020 and {Omega}{sub m} = 0.265 {+-} 0.016, an improvement of nearly a factor of two relative to WMAP5 alone. Our results are also in excellent agreement with and comparable in precision to the latest cosmological constraints from X-ray cluster abundances. The remarkable consistency among these results demonstrates that cluster abundance constraints are not only tight but also robust, and highlight the power of optically-selected cluster samples to produce precision constraints on cosmological parameters.

Biochemical characterization of the maltokinase from Mycobacterium bovis BCG

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Lamosa Pedro

2010-05-01

Full Text Available Abstract Background Maltose-1-phosphate was detected in Mycobacterium bovis BCG extracts in the 1960's but a maltose-1-phosphate synthetase (maltokinase, Mak was only much later purified from Actinoplanes missouriensis, allowing the identification of the mak gene. Recently, this metabolite was proposed to be the intermediate in a pathway linking trehalose with the synthesis of glycogen in M. smegmatis. Although the M. tuberculosis H37Rv mak gene (Rv0127 was considered essential for growth, no mycobacterial Mak has, to date, been characterized. Results The sequence of the Mak from M. bovis BCG was identical to that from M. tuberculosis strains (99-100% amino acid identity. The enzyme was dependent on maltose and ATP, although GTP and UTP could be used to produce maltose-1-phosphate, which we identified by TLC and characterized by NMR. The Km for maltose was 2.52 ± 0.40 mM and 0.74 ± 0.12 mM for ATP; the Vmax was 21.05 ± 0.89 μmol/min.mg-1. Divalent cations were required for activity and Mg2+ was the best activator. The enzyme was a monomer in solution, had maximal activity at 60°C, between pH 7 and 9 (at 37°C and was unstable on ice and upon freeze/thawing. The addition of 50 mM NaCl markedly enhanced Mak stability. Conclusions The unknown role of maltokinases in mycobacterial metabolism and the lack of biochemical data led us to express the mak gene from M. bovis BCG for biochemical characterization. This is the first mycobacterial Mak to be characterized and its properties represent essential knowledge towards deeper understanding of mycobacterial physiology. Since Mak may be a potential drug target in M. tuberculosis, its high-level production and purification in bioactive form provide important tools for further functional and structural studies.

Sex-differential effects on mortality of BCG and diphtheria-tetanus-pertussis vaccines in a rural area with high vaccination coverage

DEFF Research Database (Denmark)

Aaby, Peter; Nielsen, Jens; Benn, Christine S

2016-01-01

and inactivated polio vaccine (DTP-IPV) with BCG. Subsequent doses of DTP-IPV were administered alone. We analysed mortality according to sex and number of doses of DTP-IPV vaccine. RESULTS: BCG and DTP-IPV1 simultaneously reduced mortality from 60/1000 person-years in unvaccinated girls to 35/1000 person...

Serological monitoring of previously treated lepromatous patients during a course of multiple immunotherapy treatments with heat-killed Mycobacterium leprae and BCG

NARCIS (Netherlands)

Douglas, J. T.; Hirsch, D. S.; Fajardo, T. T.; Guido, L. S.; Klatser, P. R.

1990-01-01

Two-hundred and seventy lepromatous patients who had completed treatment received multiple treatments with heat-killed M. leprae and BCG and were monitored for changes in humoral responses to M. leprae-specific antigens. These patients were divided into four treatment groups: placebo (n = 69); BCG

Application of RAD-BCG calculator to Hanford's 300 area shoreline characterization dataset

Energy Technology Data Exchange (ETDEWEB)

Antonio, Ernest J.; Poston, Ted M.; Tiller, Brett L.; Patton, Gene W.

2003-07-01

Abstract. In 2001, a multi-agency study was conducted to characterize potential environmental effects from radiological and chemical contaminants on the near-shore environment of the Columbia River at the 300 Area of the U.S. Department of Energy’s Hanford Site. Historically, the 300 Area was the location of nuclear fuel fabrication and was the main location for research and development activities from the 1940s until the late 1980s. During past waste handling practices uranium, copper, and other heavy metals were routed to liquid waste streams and ponds near the Columbia River shoreline. The Washington State Department of Health and the Pacific Northwest National Laboratory’s Surface Environmental Surveillance Project sampled various environmental components including river water, riverbank spring water, sediment, fishes, crustaceans, bivalve mollusks, aquatic insects, riparian vegetation, small mammals, and terrestrial invertebrates for analyses of radiological and chemical constituents. The radiological analysis results for water and sediment were used as initial input into the RAD-BCG Calculator. The RAD-BCG Calculator, a computer program that uses an Excel® spreadsheet and Visual Basic® software, showed that maximum radionuclide concentrations measured in water and sediment were lower than the initial screening criteria for concentrations to produce dose rates at existing or proposed limits. Radionuclide concentrations measured in biota samples were used to calculate site-specific bioaccumulation coefficients (Biv) to test the utility of the RAD-BCG-Calculator’s site-specific screening phase. To further evaluate site-specific effects, the default Relative Biological Effect (RBE) for internal alpha particle emissions was reduced by half and the program’s kinetic/allometric calculation approach was initiated. The subsequent calculations showed the initial RAD-BCG Calculator results to be conservative, which is appropriate for screening purposes.

Recombinant M. bovis BCG expressing the PLD protein promotes survival in mice challenged with a C. pseudotuberculosis virulent strain.

Science.gov (United States)

Leal, Karen Silva; de Oliveira Silva, Mara Thais; de Fátima Silva Rezende, Andréa; Bezerra, Francisco Silvestre Brilhante; Begnini, Karine; Seixas, Fabiana; Collares, Tiago; Dellagostin, Odir; Portela, Ricardo Wagner; de Carvalho Azevedo, Vasco Ariston; Borsuk, Sibele

2018-06-14

The aim of this study was to evaluate the survival of mice inoculated with M. bovis BCG Pasteur recombinant expressing the PLD protein and challenged with a C. pseudotuberculosis virulent strain. Four groups were immunized with a sterile 0.9% saline solution (G1), 10 6  CFU of M. bovis BCG Pasteur (G2), 10 6  CFU of M. bovis BCG/pld (G3) or 10 6  CFU of M. bovis BCG/pld with a booster with rPLD (G4) and challenged with 10 4 CFU of C. pseudotuberculosis MIC-6 strain. The highest survival rate of 88% was observed in G4, followed by 77% in G3 and 66% in G2. A significant statistical difference was observed in the levels of cytokines IFN-γ and IL-10 in vaccinated groups (G3 and G4) when compared with the control group (G1) (p < 0.05). The results seem promising as the recombinant vaccine elicited a cellular immune response and provided significant survival after a high virulent challenge. Copyright © 2018 Elsevier Ltd. All rights reserved.

Long-Lasting Effects of BCG Vaccination on Both Heterologous Th1/Th17 Responses and Innate Trained Immunity

DEFF Research Database (Denmark)

Kleinnijenhuis, Johanneke; Quintin, Jessica; Preijers, Frank

2013-01-01

'. In the present study we assessed whether BCG was able to induce long-lasting effects on both trained immunity and heterologous T helper 1 (Th1) and Th17 immune responses 1 year after vaccination. The production of TNFα and IL-1β to mycobacteria or unrelated pathogens was higher after 2 weeks and 3 months...... in proinflammatory cytokine production after stimulation with the TLR4 ligand lipopolysaccharide. The heterologous production of Th1 (IFN-γ) and Th17 (IL-17 and IL-22) immune responses to nonmycobacterial stimulation remained strongly elevated even 1 year after BCG vaccination. In conclusion, BCG induces sustained...... changes in the immune system associated with a nonspecific response to infections both at the level of innate trained immunity and at the level of heterologous Th1/Th17 responses. © 2013 S. Karger AG, Basel....

Systemic BCG immunization induces persistent lung mucosal multifunctional CD4 T(EM cells which expand following virulent mycobacterial challenge.

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Daryan A Kaveh

Full Text Available To more closely understand the mechanisms of how BCG vaccination confers immunity would help to rationally design improved tuberculosis vaccines that are urgently required. Given the established central role of CD4 T cells in BCG induced immunity, we sought to characterise the generation of memory CD4 T cell responses to BCG vaccination and M. bovis infection in a murine challenge model. We demonstrate that a single systemic BCG vaccination induces distinct systemic and mucosal populations of T effector memory (T(EM cells in vaccinated mice. These CD4+CD44(hiCD62L(loCD27⁻ T cells concomitantly produce IFN-γ and TNF-α, or IFN-γ, IL-2 and TNF-α and have a higher cytokine median fluorescence intensity MFI or 'quality of response' than single cytokine producing cells. These cells are maintained for long periods (>16 months in BCG protected mice, maintaining a vaccine-specific functionality. Following virulent mycobacterial challenge, these cells underwent significant expansion in the lungs and are, therefore, strongly associated with protection against M. bovis challenge. Our data demonstrate that a persistent mucosal population of T(EM cells can be induced by parenteral immunization, a feature only previously associated with mucosal immunization routes; and that these multifunctional T(EM cells are strongly associated with protection. We propose that these cells mediate protective immunity, and that vaccines designed to increase the number of relevant antigen-specific T(EM in the lung may represent a new generation of TB vaccines.

Different effects of BCG strains - A natural experiment evaluating the impact of the Danish and the Russian BCG strains on morbidity and scar formation in Guinea-Bissau

DEFF Research Database (Denmark)

Frankel, H; Byberg, S; Andersen, Morten Bjerregaard

2016-01-01

's urban study area received the Danish or Russian BCG in a natural experiment. Health center consultations were registered at point of care and scar status and size at age 4½ months. We assessed the effect of strain on consultation rates between vaccination and age 45days in Cox proportional hazards...

Interruption of persistent exposure to leprosy combined or not with recent BCG vaccination enhances the response to Mycobacterium leprae specific antigens.

Science.gov (United States)

de Carvalho, Fernanda Marques; Rodrigues, Luciana Silva; Duppre, Nádia Cristina; Alvim, Iris Maria Peixoto; Ribeiro-Alves, Marcelo; Pinheiro, Roberta Olmo; Sarno, Euzenir Nunes; Pessolani, Maria Cristina Vidal; Pereira, Geraldo Moura Batista

2017-05-01

Household contacts of multibacillary leprosy patients (HCMB) constitute the group of individuals at the highest risk of developing leprosy. Early diagnosis and treatment of their index cases combined with Bacille Calmette-Guerin (BCG) immunization remain important strategies adopted in Brazil to prevent HCMB from evolving into active disease. In the present study, we assessed the impact of these measures on the immune response to Mycobacterium leprae in HCMB. Peripheral blood mononuclear cells (PBMC) from HCMB (n = 16) were obtained at the beginning of leprosy index case treatment (T0). At this time point, contacts were vaccinated (n = 13) or not (n = 3) in accordance with their infancy history of BCG vaccination and PBMCs were recollected at least 6 months later (T1). As expected, a significant increase in memory CD4 and CD8 T cell frequencies responsive to M. leprae whole-cell sonicate was observed in most contacts. Of note, higher frequencies of CD4+ T cells that recognize M. leprae specific epitopes were also detected. Moreover, increased production of the inflammatory mediators IL1-β, IL-6, IL-17, TNF, IFN-γ, MIP1-β, and MCP-1 was found at T1. Interestingly, the increment in these parameters was observed even in those contacts that were not BCG vaccinated at T0. This result reinforces the hypothesis that the continuous exposure of HCMB to live M. leprae down regulates the specific cellular immune response against the pathogen. Moreover, our data suggest that BCG vaccination of HCMB induces activation of T cell clones, likely through "trained immunity", that recognize M. leprae specific antigens not shared with BCG as an additional protective mechanism besides the expected boost in cell-mediated immunity by BCG homologues of M. leprae antigens.

Comparison of the immunogenicity and protection against bovine tuberculosis following immunization by BCG-priming and boosting with adenovirus or protein based vaccines.

Science.gov (United States)

Dean, G; Whelan, A; Clifford, D; Salguero, F J; Xing, Z; Gilbert, S; McShane, H; Hewinson, R G; Vordermeier, M; Villarreal-Ramos, B

2014-03-05

There is a requirement for vaccines or vaccination strategies that confer better protection against TB than the current live attenuated Mycobacterium bovis Bacillus Calmette-Guerin (BCG) vaccine for use in cattle. Boosting with recombinant viral vectors expressing mycobacterial proteins, such as Ag85A, has shown a degree of promise as a strategy for improving on the protection afforded by BCG. Experiments in small animal models have indicated that broadening the immune response to include mycobacterial antigens other than Ag85A, such as Rv0288, induced by boosting with Ad5 constructs has a direct effect on the protection afforded against TB. Here, we compared the immunogenicity and protection against challenge with M. bovis afforded by boosting BCG-vaccinated cattle with a human type 5 (Ad5)-based vaccine expressing the mycobacterial antigens Ag85A (Ad5-85A); or Ag85A, Rv0251, Rv0287 and Rv0288 (Ad5-TBF); or with protein TBF emulsified in adjuvant (Adj-TBF). Boosting with TBF broaden the immune response. The kinetics of Ad5-TBF and Adj-TBF were shown to be different, with effector T cell responses from the latter developing more slowly but being more durable than those induced by Ad5-TBF. No increase in protection compared to BCG alone was afforded by Ad5-TBF or Adj-TBF by gross pathology or bacteriology. Using histopathology, as a novel parameter of protection, we show that boosting BCG vaccinated cattle with Ad5-85A induced significantly better protection than BCG alone. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Hemostasia normal y coagulación intravascular diseminada en obstetricia Normal hemostasis and disseminated intravascular clotting in Obstetrics

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Danilo Nápoles Méndez

2012-03-01

Full Text Available En el período gravido - puerperal, la coagulación sanguínea sufre cambios que se impone conocer para interpretar correctamente esos trastornos cuando se presentan en esta etapa, teniendo en cuenta las posibles complicaciones y el peligro para la vida que pueden presentarse. El objetivo del presente artículo es proporcionar a los obstetras una revisión bibliográfica que les permita actualizarse acerca del tema y facilite su modo de actuación ante pacientes con coagulación intravascular diseminada. Se concluye que es preciso diagnosticar tempranamente el proceso en la fase bioquímica de bajo grado y aplicar en las féminas el tratamiento expedito de la enfermedad de base para eliminar las complicaciones o disminuir su ocurrenciaIn the period from pregnancy to puerperium, blood clotting suffers changes which are important to be known in order to interpret correctly those dysfunctions when they appear in this stage, keeping in mind the possible complications and the danger for life which can take place. The objective of the present work is to provide the obstetricians a literature review that allows them to be updated about the topic and facilitate their performance in case of patients with disseminated intravascular clotting. It is concluded that it is necessary to have an early diagnosis on the process during the low grade biochemical phase and to apply in these women the expedite treatment of the base disease to eliminate complications or to decrease their occurrence.

The effect of BCG vaccine from protection of type 1 diabetes mellitus

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Mehmet Karaci

2012-03-01

As a result, we concluded that if BCG is vaccine is applied at least twice and , the first dose is gives in the newborn period may exert a protective effect for the development of type I DM in children . [J Contemp Med 2012; 2(1.000: 1-8

Efficacy of oral BCG vaccination in protecting free-ranging cattle from natural infection by Mycobacterium bovis.

Science.gov (United States)

Nugent, Graham; Yockney, Ivor J; Whitford, Jackie; Aldwell, Frank E; Buddle, Bryce M

2017-09-01

Vaccination of cattle against bovine tuberculosis could be a valuable control strategy, particularly in countries faced with intractable ongoing infection from a disease reservoir in wildlife. A field vaccination trial was undertaken in New Zealand. The trial included 1286 effectively free-ranging cattle stocked at low densities in a remote 7600ha area, with 55% of them vaccinated using Mycobacterium bovis BCG (Danish strain 1311). Vaccine was administered orally in all but 34 cases (where it was injected). After inclusion, cattle were exposed to natural sources of M. bovis infection in cattle and wildlife, most notably the brushtail possum (Trichosurus vulpecula). Cattle were slaughtered at 3-5 years of age and were inspected for tuberculous lesions, with mycobacteriological culture of key tissues from almost all animals. The prevalence of M. bovis infection was 4.8% among oral BCG vaccinates, significantly lower than the 11.9% in non-vaccinates. Vaccination appeared to both reduce the incidence of detectable infection, and to slow disease progression. Based on apparent annual incidence, the protective efficacy of oral BCG vaccine was 67.4% for preventing infection, and was higher in cattle slaughtered soon after vaccination. Skin-test reactivity to tuberculin was high in vaccinates re-tested 70days after vaccination but not in non-vaccinates, although reactor animals had minimal response in gamma-interferon blood tests. In re- tests conducted more than 12 months after vaccination, skin-test reactivity among vaccinates was much lower. These results indicate that oral BCG vaccination could be an effective tool for greatly reducing detectable infection in cattle. Copyright © 2017 Elsevier B.V. All rights reserved.

Avaliação da resposta inflamatória hematológica em cascavéis (Crotalus durissus Linnaeus, 1758 inoculadas com BCG Assessment of blood inflammatory response in BCG stimulated rattlesnakes (Crotalus durissus Linnaeus, 1758

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Wellington Bandeira da Silva

2009-12-01

Full Text Available A criação de serpentes peçonhentas em cativeiro para produção de soros antipeçonhas possui crescente importância para a saúde pública devido ao aumento do número de notificações de acidentes ofídicos a cada ano no Brasil. Iniciado no século XX, ainda hoje essa atividade apresenta alguns desafios como a instalação de doenças no plantel. O hemograma é um exame de triagem clínica que auxilia no diagnóstico de diversas moléstias que acometem diferentes espécies de animais, no entanto ainda pouco estudado em serpentes. A caracterização das alterações hematológicas em cascavéis inoculadas experimentalmente com BCG pode servir de base na utilização deste exame no auxílio ao diagnóstico de infecções bacterianas na espécie. Dessa forma, foram realizados exames hematológicos em 10 serpentes da espécie Crotalus durissus pertencentes ao plantel da Divisão de Herpetologia do Instituto Vital Brazil. Os animais foram divididos em dois grupos (Grupos 1 e 2, homogêneos entre si em relação ao peso e proporção sexual. Os dois grupos foram inoculados com BCG e submetidos à coleta de sangue antes da inoculação e em três momentos pós-inoculação (3º, 5º, e 7º dias para o Grupo 1 e 11º, 17º e 21º dias para o Grupo 2. O hemograma foi realizado por método semidireto pela utilização de líquido de Natt e Herrick e as lâminas foram coradas pelo Giemsa. Observou-se anemia discreta, com redução dos valores de concentração de hemoglobina corpuscular média e da hemoglobina globular média no Grupo 1 que foi relacionada à doença inflamatória. A trombocitopenia observada no Grupo 2 sugeriu a atuação deste tipo celular em processos inflamatórios. Um único animal do Grupo 1 apresentou granulocitose e alguns animais apresentaram discreta azurofilia. Observaram-se alterações morfológicas nos leucócitos. Os granulócitos apresentaram granulações grosseiras e os azurófilos apresentaram aumento de tamanho e

Newborn Mice Vaccination with BCG.HIVA222 + MVA.HIVA Enhances HIV-1-Specific Immune Responses: Influence of Age and Immunization Routes

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Narcís Saubi

2011-01-01

Full Text Available We have evaluated the influence of age and immunization routes for induction of HIV-1- and M. tuberculosis-specific immune responses after neonatal (7 days old and adult (7 weeks old BALB/c mice immunization with BCG.HIVA222 prime and MVA.HIVA boost. The specific HIV-1 cellular immune responses were analyzed in spleen cells. The body weight of the newborn mice was weekly recorded. The frequencies of HIV-specific CD8+ T cells producing IFN-γ were higher in adult mice vaccinated intradermally and lower in adult and newborn mice vaccinated subcutaneously. In all cases the IFN-γ production was significantly higher when mice were primed with BCG.HIVA222 compared with BCGwt. When the HIV-specific CTL activity was assessed, the frequencies of specific killing were higher in newborn mice than in adults. The prime-boost vaccination regimen which includes BCG.HIVA222 and MVA.HIVA was safe when inoculated to newborn mice. The administration of BCG.HIVA222 to newborn mice is safe and immunogenic and increased the HIV-specific responses induced by MVA.HIVA vaccine. It might be a good model for infant HIV and Tuberculosis bivalent vaccine.

Newborn Mice Vaccination with BCG.HIVA222 + MVA.HIVA Enhances HIV-1-Specific Immune Responses: Influence of Age and Immunization Routes

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Saubi, Narcís; Im, Eung-Jun; Fernández-Lloris, Raquel; Gil, Olga; Cardona, Pere-Joan; Gatell, Josep Maria; Hanke, Tomáš; Joseph, Joan

2011-01-01

We have evaluated the influence of age and immunization routes for induction of HIV-1- and M. tuberculosis-specific immune responses after neonatal (7 days old) and adult (7 weeks old) BALB/c mice immunization with BCG.HIVA222 prime and MVA.HIVA boost. The specific HIV-1 cellular immune responses were analyzed in spleen cells. The body weight of the newborn mice was weekly recorded. The frequencies of HIV-specific CD8+ T cells producing IFN-γ were higher in adult mice vaccinated intradermally and lower in adult and newborn mice vaccinated subcutaneously. In all cases the IFN-γ production was significantly higher when mice were primed with BCG.HIVA222 compared with BCGwt. When the HIV-specific CTL activity was assessed, the frequencies of specific killing were higher in newborn mice than in adults. The prime-boost vaccination regimen which includes BCG.HIVA222 and MVA.HIVA was safe when inoculated to newborn mice. The administration of BCG.HIVA222 to newborn mice is safe and immunogenic and increased the HIV-specific responses induced by MVA.HIVA vaccine. It might be a good model for infant HIV and Tuberculosis bivalent vaccine. PMID:21603216

The Type of Growth Medium Affects the Presence of a Mycobacterial Capsule and Is Associated With Differences in Protective Efficacy of BCG Vaccination Against Mycobacterium tuberculosis.

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Prados-Rosales, Rafael; Carreño, Leandro J; Weinrick, Brian; Batista-Gonzalez, Ana; Glatman-Freedman, Aarona; Xu, Jiayong; Chan, John; Jacobs, William R; Porcelli, Steven A; Casadevall, Arturo

2016-08-01

Bacillus Calmette-Guerin (BCG) vaccine is widely used for the prevention of tuberculosis, despite limited efficacy. Most immunological studies of BCG or Mycobacterium tuberculosis strains grow bacteria in the presence of detergent, which also strips the mycobacterial capsule. The impact of the capsule on vaccine efficacy has not been explored. We tested the influence of detergent in cultures of BCG and M. tuberculosis strains on the outcome of vaccination experiments on mice and transcriptional responses on M. tuberculosis  Vaccination of mice with encapsulated BCG promoted a more potent immune response relative to vaccination with unencapsulated BCG, including higher polysaccharide-specific capsule antibody titers, higher interferon γ and interleukin 17 splenic responses, and more multifunctional CD4(+) T cells. These differences correlated with variability in the bacterial burden in lung and spleen of mice infected with encapsulated or unencapsulated M. tuberculosis The combination of vaccination and challenge with encapsulated strains resulted in the greatest protection efficacy. The transcriptome of encapsulated M. tuberculosis was similar to that of starvation, hypoxia, stationary phase, or nonreplicating persistence. The presence of detergent in growth media and a capsule on BCG were associated with differences in the outcome of vaccination, implying that these are important variables in immunological studies. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Evaluation of two different dendritic cell preparations with BCG reactivity

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Fol Marek

2016-01-01

Full Text Available Dendritic cells (DCs play a key-role in the immune response against intracellular bacterial pathogens, including mycobacteria. Monocyte-derived dendritic cells (MoDCs are considered to behave as inflammatory cell populations. Different immunomagnetic methods (positive and negative can be used to purify monocytes before their in vitro differentiation and their culture behavior can be expected to be different. In this study we evaluated the reactivity of two dendritic cell populations towards the Bacillus Calmette-Guérin (BCG antigen. Monocytes were obtained from the blood of healthy donors, using positive and negative immunomagnetic separation methods. The expression of DC-SIGN, CD86, CD80, HLA-DR and CD40 on MoDCs was estimated by flow cytometry. The level of IL-12p70, IL-10 and TNF-α was measured by ELISA. Neither of the tested methods affected the surface marker expression of DCs. No significant alteration in immunological response, measured by cytokine production, was noted either. After BCG stimulation, the absence of IL-12, but the IL-23 production was observed in both cell preparations. Positive and negative magnetic separation methods are effective techniques to optimize the preparation of monocytes as the source of MoDCs for potential clinical application.

Lactococcus lactis carrying a DNA vaccine coding for the ESAT-6 antigen increases IL-17 cytokine secretion and boosts the BCG vaccine immune response.

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Pereira, V B; da Cunha, V P; Preisser, T M; Souza, B M; Turk, M Z; De Castro, C P; Azevedo, M S P; Miyoshi, A

2017-06-01

A regimen utilizing Bacille Calmette-Guerin (BCG) and another vaccine system as a booster may represent a promising strategy for the development of an efficient tuberculosis vaccine for adults. In a previous work, we confirmed the ability of Lactococcus lactis fibronectin-binding protein A (FnBPA+) (pValac:ESAT-6), a live mucosal DNA vaccine, to produce a specific immune response in mice after oral immunization. In this study, we examined the immunogenicity of this strain as a booster for the BCG vaccine in mice. After immunization, cytokine and immunoglobulin profiles were measured. The BCG prime L. lactis FnBPA+ (pValac:ESAT-6) boost group was the most responsive group, with a significant increase in splenic pro-inflammatory cytokines IL-17, IFN-γ, IL-6 and TNF-α compared with the negative control. Based on the results obtained here, we demonstrated that L. lactis FnBPA+ (pValac:ESAT-6) was able to increase the BCG vaccine general immune response. This work is of great scientific and social importance because it represents the first step towards the development of a booster to the BCG vaccine using L. lactis as a DNA delivery system. © 2017 The Society for Applied Microbiology.

Code system BCG for gamma-ray skyshine calculation

International Nuclear Information System (INIS)

Ryufuku, Hiroshi; Numakunai, Takao; Miyasaka, Shun-ichi; Minami, Kazuyoshi.

1979-03-01

A code system BCG has been developed for calculating conveniently and efficiently gamma-ray skyshine doses using the transport calculation codes ANISN and DOT and the point-kernel calculation codes G-33 and SPAN. To simplify the input forms to the system, the forms for these codes are unified, twelve geometric patterns are introduced to give material regions, and standard data are available as a library. To treat complex arrangements of source and shield, it is further possible to use successively the code such that the results from one code may be used as input data to the same or other code. (author)

A TetR family transcriptional factor directly regulates the expression of a 3-methyladenine DNA glycosylase and physically interacts with the enzyme to stimulate its base excision activity in Mycobacterium bovis BCG.

Science.gov (United States)

Liu, Lei; Huang, Cheng; He, Zheng-Guo

2014-03-28

3-Methyladenine DNA glycosylase recognizes and excises a wide range of damaged bases and thus plays a critical role in base excision repair. However, knowledge on the regulation of DNA glycosylase in prokaryotes and eukaryotes is limited. In this study, we successfully characterized a TetR family transcriptional factor from Mycobacterium bovis bacillus Calmette-Guerin (BCG), namely BCG0878c, which directly regulates the expression of 3-methyladenine DNA glycosylase (designated as MbAAG) and influences the base excision activity of this glycosylase at the post-translational level. Using electrophoretic mobility shift assay and DNase I footprinting experiments, we identified two conserved motifs within the upstream region of mbaag specifically recognized by BCG0878c. Significant down-regulation of mbaag was observed in BCG0878c-overexpressed M. bovis BCG strains. By contrast, about 12-fold up-regulation of mbaag expression was found in bcg0878c-deleted mutant M. bovis BCG strains. β-Galactosidase activity assays also confirmed these results. Thus, BCG0878c can function as a negative regulator of mbaag expression. In addition, the regulator was shown to physically interact with MbAAG to enhance the ability of the glycosylase to bind damaged DNA. Interaction between the two proteins was further found to facilitate AAG-catalyzed removal of hypoxanthine from DNA. These results indicate that a TetR family protein can dually regulate the function of 3-methyladenine DNA glycosylase in M. bovis BCG both at the transcriptional and post-translational levels. These findings enhance our understanding of the expression and regulation of AAG in mycobacteria.

Distribution of 35S-labelled BCG after application to the camera oculi anterior of BCG vaccinated and non-vaccinated rabbits

International Nuclear Information System (INIS)

Luelf, U.

1976-01-01

After application of 35 S-labelled BCG to the camera oculi anterior of the rabbit, the escape pathways of germs and their quantitative and qualitative distribution in eyes and blood has been studied in BCG-vaccinated and non-vaccinated animals while varying the amount of germs applied. As criteria, 35 S concentration and the amount of 35 S in ocular sections and in the blood which can be identified by means of distributing germs under the chosen conditions, have been detected. After only 10 minutes, elimination of germs is to be seen, continuing for a period longer than the 2 hours of post-injection period observed. Relatively high 35 S concentrations indicate a long-term storage in the iris and in the ciliary body. The flow continues regularly but restrained via choroid and sclera into the blood. Flow velocity depends only within specific limits on the amount of germs injected into the anterior chamber. Under study conditions the flow mode via N.opticus and via lymphs is rather unimportant. The rest of the germs are distributed in the organism via blood vessels. A comparison of 35 S concentration in sections of both eyes shows germ enrichment in tissues with sufficient blood supply, particularly in the choroid. Differences in germ distribution in vaccinated and non-vaccinated animals are not to be seen in the 35 S distribution pattern. Neither higher nor lower germ doses indicate a stronger retention in the ocular sections of vaccinated animals. The necessity to complete this study by applying germ doses smaller than 1 mg (humidity weight) is stated pointing out technical difficulties involved while applying a test model. (orig.) [de

Estudo sobre a evolução do risco de infecção tuberculosa em área com elevada cobertura por BCG The trend in the risk of tuberculous infection in an area with wide coverage with BCG vaccination

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Gilberto Ribeiro Arantes

1985-04-01

Full Text Available A partir da prevalência de infecção tuberculosa em escolares com 7 anos de idade, calculou-se a taxa de redução do risco anual de infecção na cidade de São Paulo (Brasil, entre 1974 e 1982. Nesse período o declínio médio foi de 5% ao ano. Nas 59 escolas municipais pesquisadas não houve correlação entre a cobertura de vacinação BCG e a prevalência de infecção natural em não-vacinados, à idade estudada. A alergia tuberculínica no grupo de crianças vacinadas, que recebeu a vacina em alguma idade anterior entre o 1° e o 6° ano de vida, revelou-se 2,5 vezes mais intensa do que a alergia no grupo de mesma idade (7 anos, não vacinado previamente. Foram feitos comentários quanto à impropriedade do material utilizado com vistas ao cálculo do verdadeiro valor do risco de infecção tuberculosa na área em questão.The estimation of the risk of tuberculous infection from prevalence data obtained at school-age, in 1974 and in 1982, permitted the determination of the relevant trend in the city of S. Paulo, Brazil, between those years. The risk of infection decreased, on average, by 5% annually during the period. There was no evidence of any association between the proportions of vaccinated children and that of infected children among those unvaccinated, in the 59 schools studied. Tuberculin sensitivity in 7 years old school-children, vaccinated with BCG at any age between the 1st and the 6th year of life was 2.5 times more intense than that in unvaccinaetd children of the same age. With regard to the calculation of the true value of the risk of tuberculous infection, commentaries about the unrealiability of the available data were made.

Bacillus Calmette-Guérin (BCG) vaccine: A global assessment of demand and supply balance.

Science.gov (United States)

Cernuschi, Tania; Malvolti, Stefano; Nickels, Emily; Friede, Martin

2018-01-25

Over the past decade, several countries across all regions, income groups and procurement methods have been unable to secure sufficient BCG vaccine supply. While the frequency of stock-outs has remained rather stable, duration increased in 2014-2015 due to manufacturing issues and attracted the attention of national, regional and global immunization stakeholders. This prompted an in-depth analysis of supply and demand dynamics aiming to characterize supply risks. This analysis is unique as it provides a global picture, where previous analyses have focused on a portion of the market procuring through UN entities. Through literature review, supplier interviews, appraisal of shortages, stock-outs and historical procurement data, and through demand forecasting, this analysis shows an important increase in global capacity in 2017: supply is sufficient to meet forecasted BCG vaccine demand and possibly buffer market shocks. Nevertheless, risks remain mainly due to supply concentration and limited investment in production process improvements, as well as inflexibility in demand. Identification of these market risks will allow implementation of risk-mitigating interventions in three areas: (1) enhancing information sharing between major global health actors, countries and suppliers, (2) identifying interests and incentives to expand product registration and investment in the BCG manufacturing process, and (3) working with countries for tighter vaccine management. Copyright © 2017. Published by Elsevier Ltd.

Coley's toxin and BCG vaccine in prevention and treatment of malignant melanoma in humans

Czech Academy of Sciences Publication Activity Database

Kučerová, Petra; Vlasáková, Jitka; Červinková, Monika

2017-01-01

Roč. 28, č. 3 (2017), s. 124-128 ISSN 0954-139X R&D Projects: GA MŠk(CZ) LO1609 Institutional support: RVO:67985904 Keywords : BCG vaccine * Coley´s toxin * cytokines Subject RIV: EC - Immunology OBOR OECD: Immunology

NKG2D is a key receptor for recognition of bladder cancer cells by IL-2-activated NK cells and BCG promotes NK cell activation

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Eva María García-Cuesta

2015-06-01

Full Text Available Intravesical instillation of Bacillus Calmette-Guérin (BCG is used to treat superficial bladder cancer, either papillary tumors (after trans-urethral resection or high-grade flat carcinomas (carcinoma in situ, reducing recurrence in about 70% of patients. Initially, BCG was proposed to work through an inflammatory response, mediated by phagocytic uptake of mycobacterial antigens and cytokine release. More recently, other immune effectors such as monocytes, Natural Killer (NK and NKT cells have been suggested to play a role in this immune response. Here, we provide a comprehensive study of multiple bladder cancer cell lines as putative targets for immune cells and evaluated their recognition by NK cells in the presence and absence of BCG. We describe that different bladder cancer cells can express multiple activating and inhibitory ligands for NK cells. Recognition of bladder cancer cells depended mainly on NKG2D, with a contribution from NKp46. Surprisingly, exposure to BCG did not affect the immune phenotype of bladder cells nor increased NK cell recognition of purified IL-2-activated cell lines. However, NK cells were activated efficiently when BCG was included in mixed lymphocyte cultures, suggesting that NK activation after mycobacteria treatment requires the collaboration of various immune cells. We also analyzed the percentage of NK cells in peripheral blood of a cohort of bladder cancer patients treated with BCG. The total numbers of NK cells did not vary during treatment, indicating that a more detailed study of NK cell activation in the tumor site will be required to evaluate the response in each patient.

Targeted BCG Vaccination Against Severe Tuberculosis in Low-prevalence Settings Epidemiologic and Economic Assessment

NARCIS (Netherlands)

Altes, Hester Korthals; Dijkstra, Frederika; Lugnèr, Anna; Cobelens, Frank; Wallinga, Jacco

2009-01-01

Background: BCG vaccine protects against the severe forms of tuberculosis (TB) in children. Several low-prevalence countries are reviewing their policy, usually shifting from universal vaccination to vaccination of infants in high-risk groups only. We combined an epidemiologic analysis with a

Field evaluation of the efficacy of Mycobacterium bovis BCG vaccine against tuberculosis in goats.

Science.gov (United States)

Vidal, Enric; Arrieta-Villegas, Claudia; Grasa, Miriam; Mercader, Irene; Domingo, Mariano; Pérez de Val, Bernat

2017-08-17

Control of animal tuberculosis (TB) through vaccination has emerged as a long-term strategy to complement test and slaughter control strategy. A pilot trial under field conditions was conducted in a goat herd with high TB prevalence to assess the efficacy of the Mycobacterium bovis BCG vaccine. Twenty-three goat kids vaccinated with BCG and other 22 unvaccinated control kids were euthanized at 18 months post-vaccination. Gross pathological and histopathological examination of target tissues was performed for detection of tuberculous lesions and assessment of vaccine efficacy. Mycobacterial culture and DNA detection were used to confirm Mycobacterium caprae infection. Vaccination significantly reduced the number of animals with TB lesions compared to unvaccinated controls (35% and 77%, respectively; P goats can significantly reduce the TB lesion rates in high disease exposure conditions, indicating that vaccination could contribute to the control of TB in domestic goats.

A single dose of a DNA vaccine encoding apa coencapsulated with 6,6'-trehalose dimycolate in microspheres confers long-term protection against tuberculosis in Mycobacterium bovis BCG-primed mice.

Science.gov (United States)

Carlétti, Dyego; Morais da Fonseca, Denise; Gembre, Ana Flávia; Masson, Ana Paula; Weijenborg Campos, Lívia; Leite, Luciana C C; Rodrigues Pires, Andréa; Lannes-Vieira, Joseli; Lopes Silva, Célio; Bonato, Vânia Luiza Deperon; Horn, Cynthia

2013-08-01

Mycobacterium bovis BCG prime DNA (Mycobacterium tuberculosis genes)-booster vaccinations have been shown to induce greater protection against tuberculosis (TB) than BCG alone. This heterologous prime-boost strategy is perhaps the most realistic vaccination for the future of TB infection control, especially in countries where TB is endemic. Moreover, a prime-boost regimen using biodegradable microspheres seems to be a promising immunization to stimulate a long-lasting immune response. The alanine proline antigen (Apa) is a highly immunogenic glycoprotein secreted by M. tuberculosis. This study investigated the immune protection of Apa DNA vaccine against intratracheal M. tuberculosis challenge in mice on the basis of a heterologous prime-boost regimen. BALB/c mice were subcutaneously primed with BCG and intramuscularly boosted with a single dose of plasmid carrying apa and 6,6'-trehalose dimycolate (TDM) adjuvant, coencapsulated in microspheres (BCG-APA), and were evaluated 30 and 70 days after challenge. This prime-boost strategy (BCG-APA) resulted in a significant reduction in the bacterial load in the lungs, thus leading to better preservation of the lung parenchyma, 70 days postinfection compared to BCG vaccinated mice. The profound effect of this heterologous prime-boost regimen in the experimental model supports its development as a feasible strategy for prevention of TB.

BCG stimulated dendritic cells induce an interleukin-10 producing T-cell population with no T helper 1 or T helper 2 bias in vitro

DEFF Research Database (Denmark)

Madura Larsen, Jeppe; Benn, Christine Stabell; Fillie, Yvonne

2007-01-01

. Monocyte-derived DCs were matured in the presence or absence of BCG. The DC phenotype was assessed by CD83 expression, interleukin-12 (IL-12) and IL-10 production, as well as for the ability to polarize T-cell responses. Following stimulation with CD40 ligand, DCs matured in the presence of BCG showed...

BCG-vaccination of newborns – a descriptive study about shared decision making and decisional conflicts

DEFF Research Database (Denmark)

Thybo Pihl, Gitte

BCG-vaccination of newborns – a descriptive study about shared decision making and decisional conflicts Objective: To evaluate the use of shared decision making to support the parent in a low-evidence decision about a vaccine when using telephone consultations. The present study was conducted........ The principles included promoting trust through transparency and creating “shared minds” regarding uncertainties about the evidence. O’Connor’s Decisional Conflict Scale was used to identify decisional conflicts after the process of shared decision making. Findings: A decisional conflict score was obtained...... on the phone based on their need and wishes, this uncertainty about the best choice might reflect the principle of letting parents make an autonomous decision in combination with low evidence for the benefits of BCG. The process of sharing responsibility and the impact of the health care providers’ attitude...

The toxicity of rifampicin polylactic acid nanoparticles against Mycobacterium bovis BCG and human macrophage THP-1 cell line

International Nuclear Information System (INIS)

Erokhina, M; Rybalkina, E; Lepekha, L; Barsegyan, G; Onishchenko, G

2015-01-01

Tuberculosis is rapidly becoming a major health problem. The rise in tuberculosis incidence stimulates efforts to develop more effective delivery systems for the existing antituberculous drugs while decreasing the side effects. The nanotechnology may provide novel drug delivery tools allowing controlled drug release. Rifampicin is one of the main antituberculous drugs, characterized by high toxicity, and Poly (L-lactic acid) (PLLA) is a biodegradable polymer used for the preparation of encapsulated drugs. The aim of our work was to evaluate the toxicity of rifampicin-PLLA nanoparticles against Mycobacterium bovis BCG using human macrophage THP-1 cell line. Our data demonstrate that rifampicin-PLLA is effective against M. bovis BCG in the infected macrophages. The drug is inducing the dysfunction of mitochondria and apoptosis in the macrophages and is acting as a potential substrate of Pgp thereby modulating cell chemosensitivity. The severity of the toxic effects of the rifampicin-PLLA nanoparticles is increasing in a dose-dependent manner. We suggest that free rifampicin induces death of M. bovis BCG after PLLA degradation and diffusion from phago-lysosomes to cytoplasm causing mitochondria dysfunction and affecting the Pgp activity. (paper)

Tuberculin Skin Test and Quantiferon in BCG Vaccinated, Immunosuppressed Patients with Moderate-to-Severe Inflammatory Bowel Disease.

Science.gov (United States)

Kurti, Zsuzsanna; Lovasz, Barbara Dorottya; Gecse, Krisztina Barbara; Balint, Anita; Farkas, Klaudia; Morocza-Szabo, Agnes; Gyurcsanyi, Andras; Kristof, Katalin; Vegh, Zsuzsanna; Gonczi, Lorant; Kiss, Lajos Sandor; Golovics, Petra Anna; Lakatos, Laszlo; Molnar, Tamas; Lakatos, Peter Laszlo

2015-12-01

There are few data available on the effect of immunomodulator/biological therapy on the accuracy of the tuberculin skin test (TST) and interferon-gamma release assay (IGRA) in BCG-vaccinated immunosuppressed patients with inflammatory bowel disease (IBD). Our aim was to define the accuracy, predictors and agreement of TST and IGRA in a BCG-vaccinated immunosuppressed referral IBD cohort. 166 consecutive moderate-to-severe IBD patients (122 Crohn's disease, CD and 44 ulcerative colitis, UC) were enrolled in a prospective study from three centers. Patients were treated with immunosuppressives and/or biologicals. IGRA and TST were performed on the same day. Both in- and outpatient records were collected and comprehensively reviewed. TST positivity rate was 23.5%, 21.1%,14.5% and 13.9% when cut-off values of 5, 10, 15 and 20mm were used. IGRA positivity rate was 8.4% with indeterminate result in 0.6%. Chest X-ray was suggestive of latent tuberculosis in 2 patients. Correlation between TST and IGRA was moderate (kappa: 0.39-0.41, p15mm) should be considered to identify patients at risk for latent TB. Accuracy is satisfactory in BCG-vaccinated, immunosuppressed IBD patients. Smoking is a risk factor for TST positivity.

Immunological Links to Nonspecific Effects of DTwP and BCG Vaccines on Infant Mortality

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Mogens Helweg Claesson

2011-01-01

Full Text Available A number of mainly observational studies suggest that many African females below the age of one year die each year from the nonspecific effects of vaccination with diphtheria-tetanus toxoids and killed (whole-cell Bordetella pertussis (DTwP. In contrast, similar studies suggest that many African females and males may have their lives saved each year by the nonspecific immunological benefits of Bacillus Calmette-Guerin (BCG vaccination. From an immunological point of view, we hypothesise that the adverse effects of DTwP vaccine may occur because of the Th2-polarising effect of the aluminium phosphate adjuvant in the vaccine and because intramuscular administration of the vaccine may cause chronic inflammation at the site of injection. However, the Th1-polarising effect of BCG is likely to be beneficial. Sexual dimorphism affecting immune functions and vitamin A supplementation may influence both the deleterious and beneficial nonspecific effects of immunisation.

Informática: La nueva geografía de Internet.

OpenAIRE

Pisani, Francis

2002-01-01

Se ha dicho que las tecnologías de la información y de la comunicación provocan la muerte de la distancia, de los Estados-Nación y, por consiguiente, de la geografía. La imagen en este caso, diseminada en números medios, es la de una nube. Todo indica que no es en absoluto el caso, y los trabajos efectuados por varios estudiosos del caso llevan a preguntarse si no somos nosotros quienes estamos en las nubes al hacer afirmaciones de esta índole.

Prime-boost BCG vaccination with DNA vaccines based in β-defensin-2 and mycobacterial antigens ESAT6 or Ag85B improve protection in a tuberculosis experimental model.

Science.gov (United States)

Cervantes-Villagrana, Alberto R; Hernández-Pando, Rogelio; Biragyn, Arya; Castañeda-Delgado, Julio; Bodogai, Monica; Martínez-Fierro, Margarita; Sada, Eduardo; Trujillo, Valentin; Enciso-Moreno, Antonio; Rivas-Santiago, Bruno

2013-01-11

The World Health Organization (WHO) has estimated that there are about 8 million new cases annually of active Tuberculosis (TB). Despite its irregular effectiveness (0-89%), the Bacillus Calmette-Guérin) BCG is the only vaccine available worldwide for prevention of TB; thus, the design is important of novel and more efficient vaccination strategies. Considering that β-defensin-2 is an antimicrobial peptide that induces dendritic cell maturation through the TLR-4 receptor and that both ESAT-6 and Ag85B are immunodominant mycobacterial antigens and efficient activators of the protective immune response, we constructed two DNA vaccines by the fusion of the gene encoding β-defensin-2 and antigens ESAT6 (pDE) and 85B (pDA). After confirming efficient local antigen expression that induced high and stable Interferon gamma (IFN-γ) production in intramuscular (i.m.) vaccinated Balb/c mice, groups of mice were vaccinated with DNA vaccines in a prime-boost regimen with BCG and with BCG alone, and 2 months later were challenged with the mild virulence reference strain H37Rv and the highly virulent clinical isolate LAM 5186. The level of protection was evaluated by survival, lung bacilli burdens, and extension of tissue damage (pneumonia). Vaccination with both DNA vaccines showed similar protection to that of BCG. After the challenge with the highly virulent Mycobacterium tuberculosis strain, animals that were prime-boosted with BCG and then boosted with both DNA vaccines showed significant higher survival and less tissue damage than mice vaccinated only with BCG. These results suggest that improvement of BCG vaccination, such as the prime-boost DNA vaccine, represents a more efficient vaccination scheme against TB. Copyright © 2012 Elsevier Ltd. All rights reserved.

BCG vaccination reduces risk of tuberculosis infection in vaccinated badgers and unvaccinated badger cubs.

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Stephen P Carter

Full Text Available Wildlife is a global source of endemic and emerging infectious diseases. The control of tuberculosis (TB in cattle in Britain and Ireland is hindered by persistent infection in wild badgers (Meles meles. Vaccination with Bacillus Calmette-Guérin (BCG has been shown to reduce the severity and progression of experimentally induced TB in captive badgers. Analysis of data from a four-year clinical field study, conducted at the social group level, suggested a similar, direct protective effect of BCG in a wild badger population. Here we present new evidence from the same study identifying both a direct beneficial effect of vaccination in individual badgers and an indirect protective effect in unvaccinated cubs. We show that intramuscular injection of BCG reduced by 76% (Odds ratio = 0.24, 95% confidence interval (CI 0.11-0.52 the risk of free-living vaccinated individuals testing positive to a diagnostic test combination to detect progressive infection. A more sensitive panel of tests for the detection of infection per se identified a reduction of 54% (Odds ratio = 0.46, 95% CI 0.26-0.88 in the risk of a positive result following vaccination. In addition, we show the risk of unvaccinated badger cubs, but not adults, testing positive to an even more sensitive panel of diagnostic tests decreased significantly as the proportion of vaccinated individuals in their social group increased (Odds ratio = 0.08, 95% CI 0.01-0.76; P = 0.03. When more than a third of their social group had been vaccinated, the risk to unvaccinated cubs was reduced by 79% (Odds ratio = 0.21, 95% CI 0.05-0.81; P = 0.02.

Effects of low birth weight on time to BCG vaccination in an urban poor settlement in Nairobi, Kenya: an observational cohort study.

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Mutua, Martin Kavao; Ochako, Rhoune; Ettarh, Remare; Ravn, Henrik; Echoka, Elizabeth; Mwaniki, Peter

2015-04-18

The World Health Organization recommends Bacillus Calmette-Guérin (BCG) vaccination against tuberculosis be given at birth. However, in many developing countries, pre-term and low birth weight infants get vaccinated only after they gain the desired weight. In Kenya, the ministry of health recommends pre-term and low birth weight infants to be immunized at the time of discharge from hospital irrespective of their weight. This paper seeks to understand the effects of birth weight on timing of BCG vaccine. The study was conducted in two Nairobi urban informal settlements, Korogocho and Viwandani which hosts the Nairobi Urban Health and Demographic Surveillance system. All infants born in the study area since September 2006 were included in the study. Data on immunization history and birth weight of the infant were recorded from child's clinic card. Follow up visits were done every four months to update immunization status of the child. A total of 3,602 infants were included in this analysis. Log normal accelerated failure time parametric model was used to assess the association between low birth weight infants and time to BCG immunization. In total, 229 (6.4%) infants were low birth weight. About 16.6% of the low birth weight infants weighed less than 2000 grams and 83.4% weighed between 2000 and 2490 grams. Results showed that, 60% of the low birth weight infants received BCG vaccine after more than five weeks of life. Private health facilities were less likely to administer a BCG vaccine on time compared to public health facilities. The effects of low birth weight on females was 0.60 and 0.97-times that of males for infants weighing 2000-2499 grams and for infants weighing <2000 grams respectively. The effect of low birth weight among infants born in public health facilities was 1.52 and 3.94-times that of infants delivered in private health facilities for infants weighing 2000-2499 grams and those weighing < 2000 grams respectively. Low birth weight infants

Natural killer cell cytokine response to M. bovis BCG Is associated with inhibited proliferation, increased apoptosis and ultimate depletion of NKp44(+CD56(bright cells.

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Damien Portevin

Full Text Available Mycobacterium bovis BCG, a live attenuated strain of M. bovis initially developed as a vaccine against tuberculosis, is also used as an adjuvant for immunotherapy of cancers and for treatment of parasitic infections. The underlying mechanisms are thought to rely on its immunomodulatory properties including the recruitment of natural killer (NK cells. In that context, we aimed to study the impact of M. bovis BCG on NK cell functions. We looked at cytotoxicity, cytokine production, proliferation and cell survival of purified human NK cells following exposure to single live particles of mycobacteria. We found that M. bovis BCG mediates apoptosis of NK cells only in the context of IL-2 stimulation during which CD56(bright NK cells are releasing IFN-γ in response to mycobacteria. We found that the presence of mycobacteria prevented the IL-2 induced proliferation and surface expression of NKp44 receptor by the CD56(bright population. In summary, we observed that M. bovis BCG is modulating the functions of CD56(bright NK cells to drive this subset to produce IFN-γ before subsequent programmed cell death. Therefore, IFN-γ production by CD56(bright cells constitutes the main effector mechanism of NK cells that would contribute to the benefits observed for M. bovis BCG as an immunotherapeutic agent.

The Type of Growth Medium Affects the Presence of a Mycobacterial Capsule and Is Associated With Differences in Protective Efficacy of BCG Vaccination Against Mycobacterium tuberculosis

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Prados-Rosales, Rafael; Carreño, Leandro J.; Weinrick, Brian; Batista-Gonzalez, Ana; Glatman-Freedman, Aarona; Xu, Jiayong; Chan, John; Jacobs, William R.; Porcelli, Steven A.; Casadevall, Arturo

2016-01-01

Background. Bacillus Calmette-Guerin (BCG) vaccine is widely used for the prevention of tuberculosis, despite limited efficacy. Most immunological studies of BCG or Mycobacterium tuberculosis strains grow bacteria in the presence of detergent, which also strips the mycobacterial capsule. The impact of the capsule on vaccine efficacy has not been explored.

Altered Liver Proteoglycan/Glycosaminoglycan Structure as a Manifestation of Extracellular Matrix Remodeling upon BCG-induced Granulomatosis in Mice.

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Kim, L B; Shkurupy, V A; Putyatina, A N

2017-01-01

Experimental BCG-induced granulomatosis in mice was used to study changes in the dynamics of individual liver proteoglycan components reflecting phasic extracellular matrix remodeling, determined by the host-parasite interaction and associated with granuloma development. In the early BCG-granulomatosis period, the increase in individual proteoglycan components promotes granuloma formation, providing conditions for mycobacteria adhesion to host cells, migration of phagocytic cells from circulation, and cell-cell interaction leading to granuloma development and fibrosis. Later, reduced reserve capacity of the extracellular matrix, development of interstitial fibrosis and granuloma fibrosis can lead to trophic shortage for cells within the granulomas, migration of macrophages out of them, and development of spontaneous necrosis and apoptosis typical of tuberculosis.

Low dose chronic Schistosoma mansoni infection increases susceptibility to Mycobacterium bovis BCG infection in mice

DEFF Research Database (Denmark)

Elias, D; Akuffo, H; Thors, C

2005-01-01

The incidence of mycobacterial diseases is high and the efficacy of Bacillus Calmette Guerin (BCG) is low in most areas of the world where chronic worm infections are common. However, if and how concurrent worm infections could affect immunity to mycobacterial infections has not been elucidated. ...

[BCG vaccination in low risk tuberculosis; first experiences after the suspension of BCG vaccination of newborns in Czechoslovakia].

Science.gov (United States)

Trnka, L; Danková, D

1989-01-01

With the steadily declining risk of tuberculosis infection in CSR the question arose whether vaccination of infants remains worthwhile considering not only resources spent but also complications to vaccination vis-a-vis benefits derived. A prospective study has been designed in which BCG vaccination of newborns is discontinued in an area with 30,000 newborns yearly. In the period from April 1, 1986 to January 31, 1988 there were not vaccinated 43,428 children (84.8% of the newborns). The collaboration of mothers was good. The one year old non-vaccinated children were tested with 2 TU PPD RT 23 with Tween 80. The distribution of positive tuberculin reactions appears unimodal, relatively large reactions being absent. 8 children had reactions with 6 or more mm induration. That corresponds to a risk of infection of 0.04%. The project continues in the research area and might be extended to another area.

Characterization of immune response to killed leishmania major promastigotes plus BCG vaccine in Sudanese volunteers: a double-blind placebo controlled study

International Nuclear Information System (INIS)

Sati, Iman Nasr Eldin

1996-12-01

This work was examined whether intradermal immunization of healthy adult Sudanese volunteers with killed leishmania major (KLM) promastigotes plus BCG would induce antigen-specific T cell responses. Only healthy Sudanese volunteers with negative reactivity to leishmania skin test and with ≤20 mm induration of reactivity to purified protein derivative (PPD) were included in the trial. Group (A) (n=3): received a single dose (0.1ml) at a concentration of 10 mg protein of a whole cell component of KLM promastigotes/ml BCG, group (B) (n=12): received as a single dose of viable attenuated BCG alone (0.1 ml) at a concentration of 1 mg protein/ml diluent, group (C) (n=11): received the vaccine diluent only (Placebo) (o.1 ml). Study subjects were tested for their immunological and clinical responses before intervention, . Following vaccination 65% of group (A) subjects converted in their reactivity to leishmanin skin testing,non of the BCG vaccinated subjects converted in leishmanin skin test and only one subject of group (C) became leishmanin positive. Levels of Interferon-gamma (IFN-γ), interleukin-5 (IL-5) and interleukin-10 (IL-10) were measured by a double sandwich enzyme-linked immunosorbent assay (ELISA). A vaccine was considered as a positive responder in terms of cytokine production when the level of the produced cytokine was equal to the 80th percentile of the levels produced by the volunteers in the placebo group. 92% of the group vaccinated with KLM=BCG had circulating T cells. No significant of IL-5 or Il-10 was reported in any of the volunteers in the three group. Levels of anti l eishmania specific IgG were measured by ELISA in optical densities. Volunteers with mean antibody titre above the cut-off point (mean=3X standard deviation) were considered to have positive scores. Accordingly after vaccination 7.69% one volunteers in group (A) had a positive antibody response corresponding to 0% in the other two groups. No serious side effects were reported

Cell wall lipids from Mycobacterium bovis BCG are inflammatory when inoculated within a gel matrix: characterization of a new model of the granulomatous response to mycobacterial components.

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Rhoades, Elizabeth R; Geisel, Rachel E; Butcher, Barbara A; McDonough, Sean; Russell, David G

2005-05-01

The chronic inflammatory response to Mycobacterium generates complex granulomatous lesions that balance containment with destruction of infected tissues. To study the contributing factors from host and pathogen, we developed a model wherein defined mycobacterial components and leukocytes are delivered in a gel, eliciting a localized response that can be retrieved and analysed. We validated the model by comparing responses to the cell wall lipids from Mycobacterium bovis bacillus Calmette-Guerin (BCG) to reported activities in other models. BCG lipid-coated beads and bone marrow-derived macrophages (input macrophages) were injected intraperitoneally into BALB/c mice. Input macrophages and recruited peritoneal exudate cells took up fluorescently tagged BCG lipids, and matrix-associated macrophages and neutrophils produced tumor necrosis factor, interleukin-1alpha, and interleukin-6. Leukocyte numbers and cytokine levels were greater in BCG lipid-bearing matrices than matrices containing non-coated or phosphatidylglycerol-coated beads. Leukocytes arrived in successive waves of neutrophils, macrophages and eosinophils, followed by NK and T cells (CD4(+), CD8(+), or gammadelta) at 7 days and B cells within 12 days. BCG lipids also predisposed matrices for adherence and vascularization, enhancing cellular recruitment. We submit that the matrix model presents pertinent features of the murine granulomatous response that will prove to be an adaptable method for study of this complex response.

COSMOLOGICAL CONSTRAINTS FROM THE SLOAN DIGITAL SKY SURVEY MaxBCG CLUSTER CATALOG

International Nuclear Information System (INIS)

Rozo, Eduardo; Weinberg, David H.; Wechsler, Risa H.; Rykoff, Eli S.; Annis, James T.; Frieman, Joshua A.; Becker, Matthew R.; Evrard, August E.; Hao Jiangang; McKay, Timothy A.; Hansen, Sarah M.; Johnston, David E.; Koester, Benjamin P.; Sheldon, Erin S.

2010-01-01

We use the abundance and weak-lensing mass measurements of the Sloan Digital Sky Survey maxBCG cluster catalog to simultaneously constrain cosmology and the richness-mass relation of the clusters. Assuming a flat ΛCDM cosmology, we find σ 8 (Ω m /0.25) 0.41 = 0.832 ± 0.033 after marginalization over all systematics. In common with previous studies, our error budget is dominated by systematic uncertainties, the primary two being the absolute mass scale of the weak-lensing masses of the maxBCG clusters, and uncertainty in the scatter of the richness-mass relation. Our constraints are fully consistent with the WMAP five-year data, and in a joint analysis we find σ 8 = 0.807 ± 0.020 and Ω m = 0.265 ± 0.016, an improvement of nearly a factor of 2 relative to WMAP5 alone. Our results are also in excellent agreement with and comparable in precision to the latest cosmological constraints from X-ray cluster abundances. The remarkable consistency among these results demonstrates that cluster abundance constraints are not only tight but also robust, and highlight the power of optically selected cluster samples to produce precision constraints on cosmological parameters.

Assessment of different formulations of oral Mycobacterium bovis Bacille Calmette-Guérin (BCG) vaccine in rodent models for immunogenicity and protection against aerosol challenge with M. bovis.

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Clark, Simon; Cross, Martin L; Smith, Alan; Court, Pinar; Vipond, Julia; Nadian, Allan; Hewinson, R Glyn; Batchelor, Hannah K; Perrie, Yvonne; Williams, Ann; Aldwell, Frank E; Chambers, Mark A

2008-10-29

Bovine tuberculosis (bTB) caused by infection with Mycobacterium bovis is causing considerable economic loss to farmers and Government in the United Kingdom as its incidence is increasing. Efforts to control bTB in the UK are hampered by the infection in Eurasian badgers (Meles meles) that represent a wildlife reservoir and source of recurrent M. bovis exposure to cattle. Vaccination of badgers with the human TB vaccine, M. bovis Bacille Calmette-Guérin (BCG), in oral bait represents a possible disease control tool and holds the best prospect for reaching badger populations over a wide geographical area. Using mouse and guinea pig models, we evaluated the immunogenicity and protective efficacy, respectively, of candidate badger oral vaccines based on formulation of BCG in lipid matrix, alginate beads, or a novel microcapsular hybrid of both lipid and alginate. Two different oral doses of BCG were evaluated in each formulation for their protective efficacy in guinea pigs, while a single dose was evaluated in mice. In mice, significant immune responses (based on lymphocyte proliferation and expression of IFN-gamma) were only seen with the lipid matrix and the lipid in alginate microcapsular formulation, corresponding to the isolation of viable BCG from alimentary tract lymph nodes. In guinea pigs, only BCG formulated in lipid matrix conferred protection to the spleen and lungs following aerosol route challenge with M. bovis. Protection was seen with delivery doses in the range 10(6)-10(7) CFU, although this was more consistent in the spleen at the higher dose. No protection in terms of organ CFU was seen with BCG administered in alginate beads or in lipid in alginate microcapsules, although 10(7) in the latter formulation conferred protection in terms of increasing body weight after challenge and a smaller lung to body weight ratio at necropsy. These results highlight the potential for lipid, rather than alginate, -based vaccine formulations as suitable delivery

HIV-1 Subtype C Mosaic Gag Expressed by BCG and MVA Elicits Persistent Effector T Cell Responses in a Prime-Boost Regimen in Mice.

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Tsungai Ivai Jongwe

Full Text Available Over 90% of HIV/AIDS positive individuals in sub-Saharan Africa are infected with highly heterogeneous HIV-1 subtype C (HIV-1C viruses. One of the best ways to reduce the burden of this disease is the development of an affordable and effective prophylactic vaccine. Mosaic immunogens are computationally designed to overcome the hurdle of HIV diversity by maximizing the expression of potential T cell epitopes. Mycobacterium bovis BCG ΔpanCD auxotroph and modified vaccinia Ankara (MVA vaccines expressing HIV-1C mosaic Gag (GagM were tested in a prime-boost regimen to demonstrate immunogenicity in a mouse study. The BCG-GagM vaccine was stable and persisted 11.5 weeks post vaccination in BALB/c mice. Priming with BCG-GagM and boosting with MVA-GagM elicited higher Gag-specific IFN-γ ELISPOT responses than the BCG-GagM only and MVA-GagM only homologous vaccination regimens. The heterologous vaccination also generated a more balanced and persistent CD4+ and CD8+ T cell Gag-specific IFN-γ ELISPOT response with a predominant effector memory phenotype. A Th1 bias was induced by the vaccines as determined by the predominant secretion of IFN-γ, TNF-α, and IL-2. This study shows that a low dose of MVA (104 pfu can effectively boost a BCG prime expressing the same mosaic immunogen, generating strong, cellular immune responses against Gag in mice. Our data warrants further evaluation in non-human primates. A low dose vaccine would be an advantage in the resource limited countries of sub-Saharan Africa and India (where the predominating virus is HIV-1 subtype C.

Enhanced effect of BCG vaccine against pulmonary Mycobacterium tuberculosis infection in mice with lung Th17 response to mycobacterial heparin-binding hemagglutinin adhesin antigen.

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Fukui, Masayuki; Shinjo, Kikuko; Umemura, Masayuki; Shigeno, Satoko; Harakuni, Tetsuya; Arakawa, Takeshi; Matsuzaki, Goro

2015-12-01

Although the BCG vaccine can prevent tuberculosis (TB) in infants, its ability to prevent adult pulmonary TB is reportedly limited. Therefore, development of a novel effective vaccine against pulmonary TB has become an international research priority. We have previously reported that intranasal vaccination of mice with a mycobacterial heparin-binding hemagglutinin adhesin (HBHA) plus mucosal adjuvant cholera toxin (CT) enhances production of IFN-γ and anti-HBHA antibody and suppresses extrapulmonary bacterial dissemination after intranasal infection with BCG. In the present study, the effects of intranasal HBHA + CT vaccine on murine pulmonary Mycobacterium tuberculosis (Mtb) infection were examined. Intranasal HBHA + CT vaccination alone failed to reduce the bacterial burden in the infected lung. However, a combination vaccine consisting of s.c. BCG priming and an intranasal HBHA + CT booster significantly enhanced protective immunity against pulmonary Mtb infection on day 14 compared with BCG vaccine alone. Further, it was found that intranasal HBHA + CT vaccine enhanced not only IFN-γ but also IL-17A production by HBHA-specific T cells in the lung after pulmonary Mtb infection. Therefore, this combination vaccine may be a good candidate for a new vaccine strategy against pulmonary TB. © 2015 The Societies and Wiley Publishing Asia Pty Ltd.

Effect of revaccination with BCG in early childhood on mortality: randomised trial in Guinea-Bissau

DEFF Research Database (Denmark)

Roth, A.E.; Benn, Christine Stabell; Ravn, H.

2010-01-01

Objective To determine whether BCG revaccination at 19 months of age reduces overall child mortality. Design Randomised trial, with follow-up to age 5. Setting A health project in Bissau, Guinea-Bissau, which maintains a health and demographic surveillance system in an urban area with 90 000 inha...

Infecciones micobacterianas en pacientes infectados por el virus de la inmunodeficiencia humana en Cali, Colombia

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Crespo María del Pilar

1999-01-01

Full Text Available Se determinó la prevalencia de las infecciones por micobacterias en una muestra de 155 individuos infectados por el virus de la inmunodeficiencia humana (VIH tratados en el Instituto de los Seguros Sociales (ISS de Cali, Colombia. Se les realizó la prueba de la tuberculina (PPD 2UT RT23 y se investigó activamente la presencia de micobacterias mediante microscopia directa y cultivo de sangre, orina, heces y aspirado gástrico; cuando así lo indicó el cuadro clínico, también se examinaron y cultivaron muestras de líquido cefalorraquídeo, médula ósea y esputo. La ausencia de reactividad a la tuberculina fue significativamente más frecuente en los pacientes que en los controles (91,3%, frente a 57,4%. ji² = 33; P = 0. La prevalencia de la tuberculosis fue de 6,5%, en comparación con 0,04% en los afiliados al ISS VIH-negativos (intervalo de confianza binomial exacto de 95%: 0,0313 a 0,1154%. Las micobacterias no tuberculosas (MNT, presentes en 43 pacientes, fueron significativamente más frecuentes que Mycobacterium tuberculosis (27,7% frente a 6,5%. ji² = 24,78; P = 0,000 001, pero solo fueron causa de enfermedad en algunos casos. Las especies más frecuentes fueron las del complejo M. avium-intracellulare. M. avium-intracellulare y M. fortuitum tuvieron una prevalencia total de 7,1% y fueron las MNT de mayor prevalencia como causantes de enfermedad en estos pacientes (4,5%; además fueron responsables de tres casos de infección diseminada. La enfermedad clínica por M. tuberculosis o MNT y la anergia completa a la tuberculina se asociaron al estadio IV de la infección por VIH y a los recuentos de linfocitos CD4 <= 400/µL. No obstante, la falta de respuesta inmunocelular, manifestada por una escasa reactividad a la tuberculina, se detectó desde el estadio de portador asintomático del VIH. El progresivo deterioro del sistema inmunitario de los pacientes VIH-positivos es el factor determinante de la alta morbilidad y mortalidad de

Infecciones micobacterianas en pacientes infectados por el virus de la inmunodeficiencia humana en Cali, Colombia

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María del Pilar Crespo

1999-10-01

Full Text Available Se determinó la prevalencia de las infecciones por micobacterias en una muestra de 155 individuos infectados por el virus de la inmunodeficiencia humana (VIH tratados en el Instituto de los Seguros Sociales (ISS de Cali, Colombia. Se les realizó la prueba de la tuberculina (PPD 2UT RT23 y se investigó activamente la presencia de micobacterias mediante microscopia directa y cultivo de sangre, orina, heces y aspirado gástrico; cuando así lo indicó el cuadro clínico, también se examinaron y cultivaron muestras de líquido cefalorraquídeo, médula ósea y esputo. La ausencia de reactividad a la tuberculina fue significativamente más frecuente en los pacientes que en los controles (91,3%, frente a 57,4%. ji² = 33; P = 0. La prevalencia de la tuberculosis fue de 6,5%, en comparación con 0,04% en los afiliados al ISS VIH-negativos (intervalo de confianza binomial exacto de 95%: 0,0313 a 0,1154%. Las micobacterias no tuberculosas (MNT, presentes en 43 pacientes, fueron significativamente más frecuentes que Mycobacterium tuberculosis (27,7% frente a 6,5%. ji² = 24,78; P = 0,000 001, pero solo fueron causa de enfermedad en algunos casos. Las especies más frecuentes fueron las del complejo M. avium-intracellulare. M. avium-intracellulare y M. fortuitum tuvieron una prevalencia total de 7,1% y fueron las MNT de mayor prevalencia como causantes de enfermedad en estos pacientes (4,5%; además fueron responsables de tres casos de infección diseminada. La enfermedad clínica por M. tuberculosis o MNT y la anergia completa a la tuberculina se asociaron al estadio IV de la infección por VIH y a los recuentos de linfocitos CD4 <= 400/µL. No obstante, la falta de respuesta inmunocelular, manifestada por una escasa reactividad a la tuberculina, se detectó desde el estadio de portador asintomático del VIH. El progresivo deterioro del sistema inmunitario de los pacientes VIH-positivos es el factor determinante de la alta morbilidad y mortalidad de

The Mean and Scatter of the Velocity Dispersion-Optical Richness Relation for MaxBCG Galaxy Clusters

Energy Technology Data Exchange (ETDEWEB)

Becker, M.R.; McKay, T.A.; /Michigan U.; Koester, B.; /Chicago U., Astron. Astrophys. Ctr.; Wechsler, R.H.; /KIPAC, Menlo Park /SLAC /Stanford U., Phys. Dept.; Rozo, E.; /Ohio State U.; Evrard, A.; /Michigan U. /Michigan U., MCTP; Johnston, D.; /Caltech, JPL; Sheldon, E.; /New York U.; Annis, J.; /Fermilab; Lau, E.; /Chicago U., Astron. Astrophys. Ctr.; Nichol, R.; /Portsmouth U., ICG; Miller, C.; /Michigan U.

2007-06-05

The distribution of galaxies in position and velocity around the centers of galaxy clusters encodes important information about cluster mass and structure. Using the maxBCG galaxy cluster catalog identified from imaging data obtained in the Sloan Digital Sky Survey, we study the BCG--galaxy velocity correlation function. By modeling its non-Gaussianity, we measure the mean and scatter in velocity dispersion at fixed richness. The mean velocity dispersion increases from 202 {+-} 10 km s{sup -1} for small groups to more than 854 {+-} 102 km s{sup -1} for large clusters. We show the scatter to be at most 40.5{+-}3.5%, declining to 14.9{+-}9.4% in the richest bins. We test our methods in the C4 cluster catalog, a spectroscopic cluster catalog produced from the Sloan Digital Sky Survey DR2 spectroscopic sample, and in mock galaxy catalogs constructed from N-body simulations. Our methods are robust, measuring the scatter to well within one-sigma of the true value, and the mean to within 10%, in the mock catalogs. By convolving the scatter in velocity dispersion at fixed richness with the observed richness space density function, we measure the velocity dispersion function of the maxBCG galaxy clusters. Although velocity dispersion and richness do not form a true mass--observable relation, the relationship between velocity dispersion and mass is theoretically well characterized and has low scatter. Thus our results provide a key link between theory and observations up to the velocity bias between dark matter and galaxies.

Effect of 50 000 IU vitamin A given with BCG vaccine on mortality in infants in Guinea-Bissau: randomised placebo controlled trial

DEFF Research Database (Denmark)

Diness, B.R.; Roth, A.; Nante, E.

2008-01-01

Objective To investigate the effect of high dose vitamin A supplementation given with BCG vaccine at birth in an African setting with high infant mortality. Design Randomised placebo controlled trial. Setting Bandim Health Project's demographic surveillance system in Guinea-Bissau, covering.......84 (0.55 to 1.27) compared with 1.39 (0.90 to 2.14) in girls (P for interaction=0.10). An explorative analysis revealed a strong interaction between vitamin A and season of administration. Conclusions Vitamin A supplementation given with BCG vaccine at birth had no significant benefit in this African...

Alteraciones cerebrales en enfermedad hipertensiva asociada a embarazo

OpenAIRE

Tena Suck, Martha Lilia; Fabíán San Miguel, María Guadalupe; Molina Cárdenas, Hugo Roberto; Parraguirre Martínez, Sara

2004-01-01

La mortalidad por eclampsia varía entre el rango de 0 al 20% según las diferentes series a nivel mundial. La muerte de las pacientes con eclampsia puede presentarse como resultado de la asociación de factores clinicopatológicos y terapéuticos. Una frecuencia alta de muerte por eclampsia se atribuye a complicaciones cerebrales y sobre todo a la hemorragia cerebral, factores que se asocian a daño renal y hepático, así como a la coagulación intravascular diseminada, situación que se presenta en ...

Comparison of the effect of the viral paramunity-inducers BCG and levamisole on the growth of a radiation-induced transplanted osteosarcoma in mice

International Nuclear Information System (INIS)

Mueller-Brunecker, G.

1983-02-01

Treatment with paramunity inducers Pind avi and Pind orf resulted in general in a smaller number of tumor takes as compared to BCG, Levamisol or untreated controls. Tumor growth curves were independent of treatment. Each experiment was replicated three times. A comparison of pooled results showed significant differences between Pind avi treatment and untreated controls for each level of tumor cells. When pooling levels of tumor cells and testing each replication separately there was a highly significant difference between Pind avi and controls and Pind orf and controls. BCG and Levamisole showed no significant difference to controls. Pind avi and Pind orf considerably raised the number of tumor cells needed to results in 50% takes. For BCG on the other hand less cells were needed. The TD 50 with Levamisole was somewhat higher than the TD 50 of controls. The formation of metastases was infrequent (0,65%), and only seen in lung tissue. (orig./MG) [de

Goma o absceso tuberculoso metastásico como diagnóstico inicial de tuberculosis en un paciente inmunocompetente: una presentación inusual

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A. Marco

2014-10-01

Full Text Available Fundamento y Objetivo: Los abscesos fríos tuberculosos o gomas son inusuales y producto de la diseminación hematógena de micobacterias latentes, formando abscesos en extremidades o tronco, generalmente sin compromiso de tejidos profundos.Se presenta un caso de goma como diagnóstico inicial de tuberculosis diseminada. Métodos: Caso estudiado en 2012 por los servicios médicos del centro penitenciario de Hombres de Barcelona y el Servicio de Medicina Interna del Hospital Consorci Sanitari de Terrassa. Se recogen los datos de la historia clínica, de los informes hospitalarios y de las pruebas complementarias practicadas. Resultados: Preso, 35 años, de Cabo Verde, residente en España desde los 4 años. IDR Mantoux positiva. Inmunocompetente. Por síndrome constitucional se programó estudio hospitalario. Exploración anodina, excepto palpación de masa en región lumbar. La punción aspirativa fue positiva para M. tuberculosis mediante PCR y cultivo Lowenstein. La TC mostró nódulos pulmonares, apical D cavitado y en LSD. Tras aislamiento respiratorio, tratamiento antituberculoso y excelente evolución fue dado de alta con diagnóstico de tuberculosis diseminada. Discusión: Se recomienda vigilar lesiones que, aunque infrecuentes, pueden ser secundarias a infección por M tuberculosis, especialmente en población inmunocomprometida y en inmigrantes procedentes de zonas hiperendémicas de tuberculosis.

Impact of PGL-I seropositivity on the protective effect of BCG vaccination among leprosy contacts: a cohort study.

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Nádia C Düppre

Full Text Available BACKGROUND: Contacts of leprosy patients are at increased risk of developing leprosy and need to be targeted for early diagnosis. Seropositivity to the phenolic glycolipid I (PGL-I antigen of Mycobacterium leprae has been used to identify contacts who have an increased risk of developing leprosy. In the present study, we studied the effect of seropositivity in patient contacts, on the risk of developing leprosy, stratified by Bacille Calmette Guerin (BCG vaccination after index case diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: Leprosy contacts were examined as part of the surveillance programme of the Oswaldo Cruz Institute Leprosy Outpatient Clinic in Rio de Janeiro. Demographic, social, epidemiological and clinical data were collected. The presence of IgM antibodies to PGL-I in sera and BCG vaccination status at the time of index case diagnosis were evaluated in 2,135 contacts. During follow-up, 60 (2.8%; 60/2,135 leprosy cases were diagnosed: 41 among the 1,793 PGL-I-negative contacts and 19 among the 342 PGL-I-positive contacts. Among PGL-I-positive contacts, BCG vaccination after index case diagnosis increased the adjusted rate of developing clinical manifestations of leprosy (Adjusted Rate Ratio (aRR = 4.1; 95% CI: 1.8-8.2 compared with the PGL-I-positive unvaccinated contacts (aRR = 3.2; 95% CI: 1.2-8.1. The incidence density was highest during the first year of follow-up for the PGL-I-positive vaccinated contacts. However, all of those contacts developed PB leprosy, whereas most MB cases (4/6 occurred in PGL-I-positive unvaccinated contacts. CONCLUSION: Contact examination combined with PGL-I testing and BCG vaccination remain important strategies for leprosy control. The finding that rates of leprosy cases were highest among seropositive contacts justifies targeting this specific group for close monitoring. Furthermore, it is recommended that PGL-I-positive contacts and contacts with a high familial bacteriological index

Socio-demographic determinants of timely adherence to BCG, Penta3, measles, and complete vaccination schedule in Burkina Faso.

Science.gov (United States)

Schoeps, A; Ouédraogo, N; Kagoné, M; Sié, A; Müller, O; Becher, H

2013-12-17

To identify the determinants of timely vaccination among young children in the North-West of Burkina Faso. This study included 1665 children between 12 and 23 months of age from the Nouna Health and Demographic Surveillance System, born between September 2006 and December 2008. The effect of socio-demographic variables on timely adherence to the complete vaccination schedule was studied in multivariable ordinal logistic regression with 3 distinct endpoints: (i) complete timely adherence, (ii) failure, and (iii) missing vaccination. Three secondary endpoints were timely vaccination with BCG, Penta3, and measles, which were studied with standard multivariable logistic regression. Mothers' education, socio-economic status, season of birth, and area of residence were significantly associated with failure of timely adherence to the complete vaccination schedule. Year of birth, ethnicity, and the number of siblings was significantly related to timely vaccination with Penta3 but not with BCG or measles vaccination. Children living in rural areas were more likely to fail timely vaccination with BCG than urban children (OR=1.79, 95%CI=1.24-2.58 (proximity to health facility), OR=3.02, 95%CI=2.18-4.19 (long distance to health facility)). In contrast, when looking at Penta3 and measles vaccination, children living in rural areas were far less likely to have failed timely vaccinations than urban children. Mother's education positively influenced timely adherence to the vaccination schedule (OR=1.42, 95%CI 1.06-1.89). There was no effect of household size or the age of the mother. Additional health facilities and encouragement of women to give birth in these facilities could improve timely vaccination with BCG. Rural children had an advantage over the urban children in timely vaccination, which is probably attributable to outreach vaccination teams amongst other factors. As urban children rely on their mothers' own initiative to get vaccinated, urban mothers should be

Impact of PGL-I Seropositivity on the Protective Effect of BCG Vaccination among Leprosy Contacts: A Cohort Study

Science.gov (United States)

Düppre, Nádia C.; Camacho, Luiz Antonio B.; Sales, Anna M.; Illarramendi, Ximena; Nery, José Augusto C.; Sampaio, Elizabeth P.; Sarno, Euzenir N.; Bührer-Sékula, Samira

2012-01-01

Background Contacts of leprosy patients are at increased risk of developing leprosy and need to be targeted for early diagnosis. Seropositivity to the phenolic glycolipid I (PGL-I) antigen of Mycobacterium leprae has been used to identify contacts who have an increased risk of developing leprosy. In the present study, we studied the effect of seropositivity in patient contacts, on the risk of developing leprosy, stratified by Bacille Calmette Guerin (BCG) vaccination after index case diagnosis. Methodology/Principal Findings Leprosy contacts were examined as part of the surveillance programme of the Oswaldo Cruz Institute Leprosy Outpatient Clinic in Rio de Janeiro. Demographic, social, epidemiological and clinical data were collected. The presence of IgM antibodies to PGL-I in sera and BCG vaccination status at the time of index case diagnosis were evaluated in 2,135 contacts. During follow-up, 60 (2.8%; 60/2,135) leprosy cases were diagnosed: 41 among the 1,793 PGL-I-negative contacts and 19 among the 342 PGL-I-positive contacts. Among PGL-I-positive contacts, BCG vaccination after index case diagnosis increased the adjusted rate of developing clinical manifestations of leprosy (Adjusted Rate Ratio (aRR) = 4.1; 95% CI: 1.8–8.2) compared with the PGL-I-positive unvaccinated contacts (aRR = 3.2; 95% CI: 1.2–8.1). The incidence density was highest during the first year of follow-up for the PGL-I-positive vaccinated contacts. However, all of those contacts developed PB leprosy, whereas most MB cases (4/6) occurred in PGL-I-positive unvaccinated contacts. Conclusion Contact examination combined with PGL-I testing and BCG vaccination remain important strategies for leprosy control. The finding that rates of leprosy cases were highest among seropositive contacts justifies targeting this specific group for close monitoring. Furthermore, it is recommended that PGL-I-positive contacts and contacts with a high familial bacteriological index, regardless of

Effect of deworming on human T cell responses to mycobacterial antigens in helminth-exposed individuals before and after bacille Calmette-Guérin (BCG) vaccination

DEFF Research Database (Denmark)

Elias, D; Wolday, D; Akuffo, H

2001-01-01

The protective efficacy of BCG vaccination against pulmonary tuberculosis (TB) is highly variable in different populations. The reason remains to be elucidated. This study aims to investigate the possible effect of intestinal helminths on the immune response to PPD in naturally immunized or BCG......-vaccinated humans. The study population was assessed for helminthic infection and those found to be positive were randomly assigned to either an albendazole treatment group or a control group who received a placebo. The immune response to PPD was compared between the two groups. In addition, subjects who were...... tuberculin skin test-negative in both groups were BCG vaccinated and later on tested for PPD-specific responses. Albendazole induced elimination/or reduction in intestinal worms resulting in a significant improvement in T cell proliferation and in interferon-gamma production by peripheral blood mononuclear...

The BCG (Boston Consulting Group) matrix for management of periodic publications

OpenAIRE

Serrano Gallardo, Mª del Pilar; Arroyo Gordo, Mª Pilar; Giménez Maroto, Ana Mª

2005-01-01

El marketing documental se ha de encargar de satisfacer las necesidades informativas de los usuarios de forma rentable para ellos y para el centro; para ello se ha de partir de un conjunto de herramientas técnicas que se conocen como el Marketing - Mix, y que abarcan el Producto, el Precio, la Distribución y la Comunicación. Dentro de las herramientas destinadas al producto se encuentra la matriz BCG (Boston Consulting Group), que está orientada a gestión, sobre la base de la situación del pr...

Developing the Biological Condition Gradient (BCG), as a Tool for Describing the Condition of US Coral Reefs

Science.gov (United States)

Understanding effects of human activity on coral reefs requires knowing what characteristics constitute a high quality coral reef and identifying measurable criteria. The BCG is a conceptual model that describes how biological attributes of coral reefs change along a gradient of ...

Oral vaccination of white-tailed deer (Odocoileus virginianus with Mycobacterium bovis Bacillus Calmette-Guerin (BCG.

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Mitchell V Palmer

Full Text Available Wildlife reservoirs of Mycobacterium bovis represent serious obstacles to the eradication of tuberculosis from livestock, particularly cattle. In Michigan, USA tuberculous white-tailed deer transmit M. bovis to other deer and cattle. One approach in dealing with this wildlife reservoir is to vaccinate deer, thus interfering with the intraspecies and interspecies transmission cycles. Thirty-three white-tailed deer were assigned to one of two groups; oral vaccination with 1 × 10(8 colony-forming units of M. bovis BCG Danish (n = 17; and non-vaccinated (n = 16. One hundred eleven days after vaccination deer were infected intratonsilarly with 300 colony-forming units of virulent M. bovis. At examination, 150 days after challenge, BCG vaccinated deer had fewer gross and microscopic lesions, fewer tissues from which M. bovis could be isolated, and fewer late stage granulomas with extensive liquefactive necrosis. Fewer lesions, especially those of a highly necrotic nature should decrease the potential for dissemination of M. bovis within the host and transmission to other susceptible hosts.

Production of BCG alginate-PLL microcapsules by emulsification/internal gelation.

Science.gov (United States)

Esquisabel, A; Hernández, R M; Igartua, M; Gascón, A R; Calvo, B; Pedraz, J L

1997-01-01

A biocompatible emulsification method for microencapsulation of live cells and enzymes within a calcium alginate matrix applied to Bacillus Calmette-Guérin (BCG) has been developed. Small-diameter alginate beads (microcapsules) were formed via internal gelation of an alginate solution emulsified within vegetable oil. Five different oils (sesame, sweet almond, perhydrosqualene, camomile and jojoba) were used. The rheological analysis of the oils showed a Newtonian behaviour, with viscosities = 30.0, 37.7, 51.2, 59.3 and 67.1 mPa.s for perhydrosqualene, jojoba, camomile, sesame and sweet almond oil respectively. The particle size of the microcapsules obtained ranged from 30.3 microns for the microcapsules prepared with sweet almond oil to 57.0 microns for those made with perhydrosqualene. The mean particle diameter obtained was found to be dependent on the viscosity of the oil employed, according to the equation: phi (micron) = 76.6-0.628 eta (mPa.s) (r2 = 0.943). The encapsulated BCG was identified by the Difco TB stain set K, followed by observation under optical microscopy. Freeze-drying of the microcapsules was carried out to ensure their stability during storage. Two batches of microcapsules (those prepared with sesame and jojoba oil) and four types of cryoprotectors (glucose, trehalose, mannitol and sorbitol), at three concentration levels (5, 10 and 20% w/v) were studied. The parameters evaluated were particle size, physical appearance, reconstitution of lyophilizates and microscopical evaluation. For both batches of microcapsules the best results were obtained with trehalose 5%, showing particle sizes of 42.1 microns in the case of the microcapsules prepared with sesame oil, and of 45.3 microns for those prepared with jojoba.

Ureteric angioplasty balloon placement to increase localised dosage of BCG for renal pelvis TCC.

LENUS (Irish Health Repository)

Forde, J C

2012-03-01

Endoscopic percutaneous resection of a renal pelvis transitional cell carcinoma (TCC) is a viable treatment option in those who would be rendered dialysis dependent following a nephroureterectomy. We report endoscopic percutaneous resection of an upper tract TCC recurrence in a single functioning kidney followed by antegrade renal pelvis BCG instillation with novel placement of inflated angioplasty balloon in the ureter to help localise its effect.

The expression of ferritin, lactoferrin, transferrin receptor and solute carrier family 11A1 in the host response to BCG-vaccination and Mycobacterium tuberculosis challenge.

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Thom, R E; Elmore, M J; Williams, A; Andrews, S C; Drobniewski, F; Marsh, P D; Tree, J A

2012-05-02

Iron is an essential cofactor for both mycobacterial growth during infection and for a successful protective immune response by the host. The immune response partly depends on the regulation of iron by the host, including the tight control of expression of the iron-storage protein, ferritin. BCG vaccination can protect against disease following Mycobacterium tuberculosis infection, but the mechanisms of protection remain unclear. To further explore these mechanisms, splenocytes from BCG-vaccinated guinea pigs were stimulated ex vivo with purified protein derivative from M. tuberculosis and a significant down-regulation of ferritin light- and heavy-chain was measured by reverse-transcription quantitative-PCR (P≤0.05 and ≤0.01, respectively). The mechanisms of this down-regulation were shown to involve TNFα and nitric oxide. A more in depth analysis of the mRNA expression profiles, including genes involved in iron metabolism, was performed using a guinea pig specific immunological microarray following ex vivo infection with M. tuberculosis of splenocytes from BCG-vaccinated and naïve guinea pigs. M. tuberculosis infection induced a pro-inflammatory response in splenocytes from both groups, resulting in down-regulation of ferritin (P≤0.05). In addition, lactoferrin (P≤0.002), transferrin receptor (P≤0.05) and solute carrier family 11A1 (P≤0.05), were only significantly down-regulated after infection of the splenocytes from BCG-vaccinated animals. The results show that expression of iron-metabolism genes is tightly regulated as part of the host response to M. tuberculosis infection and that BCG-vaccination enhances the ability of the host to mount an iron-restriction response which may in turn help to combat invasion by mycobacteria. Copyright © 2012 Elsevier Ltd. All rights reserved.

CONSTRAINING THE SCATTER IN THE MASS-RICHNESS RELATION OF maxBCG CLUSTERS WITH WEAK LENSING AND X-RAY DATA

International Nuclear Information System (INIS)

Rozo, Eduardo; Rykoff, Eli S.; Evrard, August; McKay, Timothy; Hao Jiangang; Becker, Matthew; Wechsler, Risa H.; Koester, Benjamin P.; Hansen, Sarah; Frieman, Joshua; Sheldon, Erin; Johnston, David; Annis, James

2009-01-01

We measure the logarithmic scatter in mass at fixed richness for clusters in the maxBCG cluster catalog, an optically selected cluster sample drawn from Sloan Digital Sky Survey imaging data. Our measurement is achieved by demanding consistency between available weak-lensing and X-ray measurements of the maxBCG clusters, and the X-ray luminosity-mass relation inferred from the 400 days X-ray cluster survey, a flux-limited X-ray cluster survey. We find σ lnM|N 200 =0.45 -0.18 +0.20 (95% CL) at N 200 ∼ 40, where N 200 is the number of red sequence galaxies in a cluster. As a byproduct of our analysis, we also obtain a constraint on the correlation coefficient between ln L X and ln M at fixed richness, which is best expressed as a lower limit, r L,M|N ≥ 0.85(95% CL). This is the first observational constraint placed on a correlation coefficient involving two different cluster mass tracers. We use our results to produce a state-of-the-art estimate of the halo mass function at z = 0.23-the median redshift of the maxBCG cluster sample-and find that it is consistent with the WMAP5 cosmology. Both the mass function data and its covariance matrix are presented.

Constraining the Scatter in the Mass-Richness Relation of maxBCG Clusters With Weak Lensing and X-ray Data

Energy Technology Data Exchange (ETDEWEB)

Rozo, Eduardo; /Ohio State U.; Rykoff, Eli S.; /UC, Santa Barbara; Evrard, August; /Michigan U.; Becker, Matthew R.; /Chicago U.; McKay, Timothy; /Michigan U.; Wechsler, Risa H.; /SLAC; Koester, Benjamin P.; /Chicago U. /KICP, Chicago; Hao, Jiangang; /Michigan U.; Hansen, Sarah; /Chicago U. /KICP, Chicago; Sheldon, Erin; /New York U.; Johnston, David; /Houston U.; Annis, James T.; /Fermilab; Frieman, Joshua A.; /Chicago U. /KICP, Chicago /Fermilab

2009-08-03

We measure the logarithmic scatter in mass at fixed richness for clusters in the maxBCG cluster catalog, an optically selected cluster sample drawn from SDSS imaging data. Our measurement is achieved by demanding consistency between available weak lensing and X-ray measurements of the maxBCG clusters, and the X-ray luminosity-mass relation inferred from the 400d X-ray cluster survey, a flux limited X-ray cluster survey. We find {sigma}{sub lnM|N{sub 200}} = 0.45{sub -0.18}{sup +0.20} (95%CL) at N{sub 200} {approx} 40, where N{sub 200} is the number of red sequence galaxies in a cluster. As a byproduct of our analysis, we also obtain a constraint on the correlation coefficient between lnL{sub X} and lnM at fixed richness, which is best expressed as a lower limit, r{sub L,M|N} {ge} 0.85 (95% CL). This is the first observational constraint placed on a correlation coefficient involving two different cluster mass tracers. We use our results to produce a state of the art estimate of the halo mass function at z = 0.23 - the median redshift of the maxBCG cluster sample - and find that it is consistent with the WMAP5 cosmology. Both the mass function data and its covariance matrix are presented.

Comparison of BCG, MPL and cationic liposome adjuvant systems in leishmanial antigen vaccine formulations against murine visceral leishmaniasis

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Bhowmick Sudipta

2010-06-01

Full Text Available Abstract Background The development of an effective vaccine against visceral leishmaniasis (VL caused by Leishmania donovani is an essential aim for controlling the disease. Use of the right adjuvant is of fundamental importance in vaccine formulations for generation of effective cell-mediated immune response. Earlier we reported the protective efficacy of cationic liposome-associated L. donovani promastigote antigens (LAg against experimental VL. The aim of the present study was to compare the effectiveness of two very promising adjuvants, Bacille Calmette-Guerin (BCG and Monophosphoryl lipid A (MPL plus trehalose dicorynomycolate (TDM with cationic liposomes, in combination with LAg, to confer protection against murine VL. Results All the three formulations afforded significant protection against L. donovani in both the visceral organs, liver and spleen. Although comparable level of protection was observed in BCG+LAg and MPL-TDM+LAg immunized mice, highest level of protection was exhibited by the liposomal LAg immunized group. Significant increase in anti-LAg IgG levels were detected in both MPL-TDM+LAg and liposomal LAg immunized animals with higher levels of IgG2a than IgG1. But BCG+LAg failed to induce any antibody response. As an index of cell-mediated immunity DTH responses were measured and significant response was observed in mice vaccinated with all the three different formulations. However, highest responses were observed with liposomal vaccine immunization. Comparative evaluation of IFN-γ and IL-4 responses in immunized mice revealed that MPL-TDM+LAg group produced the highest level of IFN-γ but lowest IL-4 level, while BCG+LAg demonstrated generation of suboptimum levels of both IFN-γ and IL-4 response. Elicitation of moderate levels of prechallenge IFN-γ along with optimum IL-4 corresponds with successful vaccination with liposomal LAg. Conclusion This comparative study reveals greater effectiveness of the liposomal vaccine for

Role of interleukin-8 in onset of the immune response in intravesical BCG therapy for superficial bladder cancer

NARCIS (Netherlands)

de Boer, E. C.; Somogyi, L.; de Ruiter, G. J.; de Reijke, T. M.; Kurth, K. H.; Schamhart, D. H.

1997-01-01

In intravesical therapy for superficial bladder carcinoma urothelial cells may, through the production of cytokines, contribute to the bacillus Calmette-Guerin (BCG)-induced local immunological reaction and associated antitumor efficacy. The aim of this study was to investigate such a role for the

Effect of 50,000 IU vitamin A given with BCG vaccine on mortality in infants in Guinea-Bissau

DEFF Research Database (Denmark)

Benn, Christine Stabell; Diness, Birgitte Rode; Roth, Adam

2008-01-01

OBJECTIVE: To investigate the effect of high dose vitamin A supplementation given with BCG vaccine at birth in an African setting with high infant mortality. DESIGN: Randomised placebo controlled trial. Setting Bandim Health Project's demographic surveillance system in Guinea-Bissau, covering...... approximately 90,000 inhabitants. Participants 4345 infants due to receive BCG. INTERVENTION: Infants were randomised to 50,000 IU vitamin A or placebo and followed until age 12 months. MAIN OUTCOME MEASURE: Mortality rate ratios. RESULTS: 174 children died during follow-up (mortality=47/1000 person......-years). Vitamin A supplementation was not significantly associated with mortality; the mortality rate ratio was 1.07 (95% confidence interval 0.79 to 1.44). The effect was 1.00 (0.65 to 1.56) during the first four months and 1.13 (0.75 to 1.68) from 4 to 12 months of age. The mortality rate ratio in boys was 0...

The effect of neonatal BCG vaccination on atopy and asthma at age 7 to 14 years: an historical cohort study in a community with a very low prevalence of tuberculosis infection and a high prevalence of atopic disease.

Science.gov (United States)

Marks, Guy B; Ng, Kitty; Zhou, Jie; Toelle, Brett G; Xuan, Wei; Belousova, Elena G; Britton, Warwick J

2003-03-01

There are conflicting reports on the effect of BCG vaccination on the subsequent development of atopy and asthma. There are no data on the effects of neonatal BCG vaccination on cytokine responses of lymphocytes that are exposed in vitro to allergens. We sought to test the hypothesis that neonatal BCG vaccination or, alternatively, evidence of an immunologic memory of this vaccination is associated with a reduced prevalence of allergic sensitization, asthma, eczema, and hay fever during childhood. An historical cohort study was conducted among 7- to 14-year-old children who were born in 2 districts in Sydney, Australia, and whose mothers were born in southeast Asia. One district had routinely administered BCG vaccination to infants born to overseas-born mothers and the other had not. Eligible subjects were identified from birth registers. Consenting subjects completed questionnaires, performed spirometric and airway hyperresponsiveness testing, and had allergen skin prick testing and tuberculin skin testing. Blood was collected to measure total serum IgE levels and for in vitro lymphocyte culture in the presence of an extract of house dust mite, the dominant allergen in this region, and purified protein derivative of Mycobacterium tuberculosis (tuberculin). IL-4, IL-5, IL-10, and IFN-gamma were measured in the culture supernatant. The cohort included 309 BCG-vaccinated subjects and 442 non-BCG-vaccinated subjects. BCG-vaccinated subjects did not have a lower rate of allergic sensitization than nonvaccinated subjects. However, among the subgroup of subjects with a family history of rhinitis or eczema, BCG vaccination was associated with a lower prevalence of current asthma (defined as recent wheezing plus airway hyperresponsiveness; relative risk, 0.46; 95% CI, 0.22-0.95). BCG vaccination was also associated with lower levels of allergen-stimulated IL-10 production in vitro. Among the BCG-vaccinated subjects, the 44 (14.3%) who had tuberculin skin test reaction

Analysis of Service Quality Management in the Materials Industry using the BCG Matrix Method

OpenAIRE

Adrian Ioana; Vasile Mirea; Cezar Balescu

2009-01-01

For each product or service, the area of the circle represents the value of its sales. The BCG (Boston Consulting Group) matrix thus offers a very useful map of the organization's service strengths and weaknesses, at least in terms of current profitability, as well as the likely cash flows. The criteria function concept consists of transforming the criteria function (CF) in a qualityeconomical matrix MQE. The levels of prescribing the criteria function were obtained by using a composition alg...

Structural features of lipoarabinomannan from Mycobacterium bovis BCG. Determination of molecular mass by laser desorption mass spectrometry.

Science.gov (United States)

Venisse, A; Berjeaud, J M; Chaurand, P; Gilleron, M; Puzo, G

1993-06-15

It was recently shown that mycobacterial lipoarabinomannan (LAM) can be classified into two types (Chatterjee, D., Lowell, K., Rivoire B., McNeil M. R., and Brennan, P. J. (1992) J. Biol. Chem. 267, 6234-6239) according to the presence or absence of mannosyl residues (Manp) located at the nonreducing end of the oligoarabinosyl side chains. These two types of LAM were found in a pathogenic Mycobacterium tuberculosis strain and in an avirulent M. tuberculosis strain, respectively, suggesting that LAM with Manp characterizes virulent and "disease-inducing strains." We now report the structure of the LAM from Mycobacterium bovis Bacille Calmette-Guérin (BCG) strain Pasteur, largely used throughout the world as vaccine against tuberculosis. Using an up-to-date analytical approach, we found that the LAM of M. bovis BCG belongs to the class of LAMs capped with Manp. By means of two-dimensional homonuclear and heteronuclear scalar coupling NMR analysis and methylation data, the sugar spin system assignments were partially established, revealing that the LAM contained two types of terminal Manp and 2-O-linked Manp. From the following four-step process: (i) partial hydrolysis of deacylated LAM (dLAM), (ii) oligosaccharide derivatization with aminobenzoic ethyl ester, (iii) HPLC purification, (iv) FAB/MS-MS analysis; it was shown that the dimannosyl unit alpha-D-Manp-(1-->2)-alpha-D-Manp is the major residue capping the termini of the arabinan of the LAM. In this report, LAM molecular mass determination was established using matrix-assisted UV-laser desorption/ionization mass spectrometry which reveals that the LAM molecular mass is around 17.4 kDa. The similarity of the LAM structures between M. bovis BCG and M. tuberculosis H37Rv is discussed in regard to their function in the immunopathology of mycobacterial infection.

Ultrastructural characteristics of type A epithelioid cells during BCG-granulomatosis and treatment with lysosomotropic isoniazid.

Science.gov (United States)

Shkurupii, V A; Kozyaev, M A; Nadeev, A P

2006-04-01

We studied BCG-granulomas, their cellular composition, and ultrastructure of type A epithelioid cells in the liver of male BALB/c mice with spontaneous granulomatous inflammation. The animals received free isoniazid or isoniazid conjugated with lysosomotropic intracellularly prolonged matrix (dialdehyde dextran, molecular weight 65-75 kDa). Lysosomotropic isoniazid was accumulated in the vacuolar apparatus of epithelioid cells and produced a stimulatory effect on plastic processes in these cells.

Exploring Relations Between BCG & Cluster Properties in the SPectroscopic IDentification of eROSITA Sources Survey from 0.05 < z < 0.3

Science.gov (United States)

Furnell, Kate E.; Collins, Chris A.; Kelvin, Lee S.; Clerc, Nicolas; Baldry, Ivan K.; Finoguenov, Alexis; Erfanianfar, Ghazaleh; Comparat, Johan; Schneider, Donald P.

2018-04-01

We present a sample of 329 low to intermediate redshift (0.05 data from ROSAT, maximum likelihood outputs from an optical cluster-finder algorithm and visual inspection. Using SDSS imaging data, we fit Sérsic profiles to our BCGs in three bands (g, r, i) with SIGMA, a GALFIT-based software wrapper. We examine the reliability of our fits by running our pipeline on ˜104 psf-convolved model profiles injected into 8 random cluster fields; we then use the results of this analysis to create a robust subsample of 198 BCGs. We outline three cluster properties of interest: overall cluster X-ray luminosity (LX), cluster richness as estimated by REDMAPPER (λ) and cluster halo mass (M200), which is estimated via velocity dispersion. In general, there are significant correlations with BCG stellar mass between all three environmental properties, but no significant trends arise with either Sérsic index or effective radius. There is no major environmental dependence on the strength of the relation between effective radius and BCG stellar mass. Stellar mass therefore arises as the most important factor governing BCG morphology. Our results indicate that our sample consists of a large number of relaxed, mature clusters containing broadly homogeneous BCGs up to z ˜ 0.3, suggesting that there is little evidence for much ongoing structural evolution for BCGs in these systems.

Ag85A-specific CD4+ T cell lines derived after boosting BCG-vaccinated cattle with Ad5-85A possess both mycobacterial growth inhibition and anti-inflammatory properties.

Science.gov (United States)

Metcalfe, Hannah J; Biffar, Lucia; Steinbach, Sabine; Guzman, Efrain; Connelley, Tim; Morrison, Ivan; Vordermeier, H Martin; Villarreal-Ramos, Bernardo

2018-05-11

There is a need to improve the efficacy of the BCG vaccine against human and bovine tuberculosis. Previous data showed that boosting bacilli Calmette-Guerin (BCG)-vaccinated cattle with a recombinant attenuated human type 5 adenovirally vectored subunit vaccine (Ad5-85A) increased BCG protection and was associated with increased frequency of Ag85A-specific CD4 + T cells post-boosting. Here, the capacity of Ag85A-specific CD4 + T cell lines - derived before and after viral boosting - to interact with BCG-infected macrophages was evaluated. No difference before and after boosting was found in the capacity of these Ag85A-specific CD4 + T cell lines to restrict mycobacterial growth, but the secretion of IL-10 in vitro post-boost increased significantly. Furthermore, cell lines derived post-boost had no statistically significant difference in the secretion of pro-inflammatory cytokines (IL-1β, IL-12, IFNγ or TNFα) compared to pre-boost lines. In conclusion, the protection associated with the increased number of Ag85A-specific CD4 + T cells restricting mycobacterial growth may be associated with anti-inflammatory properties to limit immune-pathology. Copyright © 2018 Department for Environment Food and Rural Affairs. Published by Elsevier Ltd.. All rights reserved.

Endogenous and Exogenous KdpF Peptide Increases Susceptibility of Mycobacterium bovis BCG to Nitrosative Stress and Reduces Intramacrophage Replication

Science.gov (United States)

Rosas Olvera, Mariana; Vivès, Eric; Molle, Virginie; Blanc-Potard, Anne-Béatrice; Gannoun-Zaki, Laila

2017-01-01

Emerging antibiotic resistance in pathogenic bacteria like Mycobacterium sp., poses a threat to human health and therefore calls for the development of novel antibacterial strategies. We have recently discovered that bacterial membrane peptides, such as KdpF, possess anti-virulence properties when overproduced in pathogenic bacterial species. Overproduction of the KdpF peptide in Mycobacterium bovis BCG decreased bacterial replication within macrophages, without presenting antibacterial activity. We propose that KdpF functions as a regulatory molecule and interferes with bacterial virulence, potentially through interaction with the PDIM transporter MmpL7. We demonstrate here that KdpF overproduction in M. bovis BCG, increased bacterial susceptibility to nitrosative stress and thereby was responsible for lower replication rate within macrophages. Moreover, in a bacterial two-hybrid system, KdpF was able to interact not only with MmpL7 but also with two membrane proteins involved in nitrosative stress detoxification (NarI and NarK2), and a membrane protein of unknown function that is highly induced upon nitrosative stress (Rv2617c). Interestingly, we showed that the exogenous addition of KdpF synthetic peptide could affect the stability of proteins that interact with this peptide. Finally, the exogenous KdpF peptide presented similar biological effects as the endogenously expressed peptide including nitrosative stress susceptibility and reduced intramacrophage replication rate for M. bovis BCG. Taken together, our results establish a link between high levels of KdpF and nitrosative stress susceptibility to further highlight KdpF as a potent molecule with anti-virulence properties. PMID:28428950

Análise da positivação do teste tuberculínico, após administração da vacina BCG, pela via oral, a crianças sadias

Directory of Open Access Journals (Sweden)

Yvone Khairallah de Oliveira e Silva

1974-10-01

Full Text Available Efetuaram os autores teste tuberculínico, com PPD (RT 23, 10 UT, em 3.6S4 crianças sadias, que receberam, pela via oral, em três oportunidades separadas por intervalos de um mês, vacina BCG líquida ou liofilizada e placebo representado por preparação sem bacilos. Dois grupos foram basicamente estabelecidos, tendo os limites etários correspondido a noventa dias em um deles e a essa idade e quinze anos no outro. Considerando os módulos com tamanhos superiores a cinco milímetros, observaram taxas de positividades de 37,6% e 21% relativamente aos indviduos separados da maneira citada e em avaliações levadas a efeito no máximo nove meses depois, mas as cifras pertinentes ao produto isento de bacilos álcool-ácido-resistentes e ao submetido à liofilização mostraram-se expressivamente menores. Valorizada somente a alergização, as percentagens indicadas e não desprezíveis atestaram a ocorrência de destacada absorção, sobretudo ao ser levado em conta o sucedido quanto às pessoas de menores idades.

Stimulation of alveolar macrophages by BCG vaccine enhances the process of lung fibrosis induced by bleomycin.

Science.gov (United States)

Chyczewska, E; Chyczewski, L; Bańkowski, E; Sułkowski, S; Nikliński, J

1993-01-01

It was found that the BCG vaccine injected subcutaneously to the rats enhances the process of lung fibrosis induced by bleomycin. Pretreatment of rats with this vaccine results in accumulation of activated macrophages in lung interstitium and in the bronchoalveolar spaces. It may be suggested that the activated macrophages release various cytokines which may stimulate the proliferation of fibroblasts and biosynthesis of extracellular matrix components.

Presencia de Inmunocomplejos circulantes y alteraciones del sistema complemento en pacientes con leucemia promielocítica y coagulación intravascular diseminada Presence of circulating immune complexes and alterations of the complement system in patients with promyelocytic leukaemia and disseminates intravascular coagulation

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Rinaldo Villaescusa Blanco

1999-04-01

Full Text Available Se efectuó la determinación de inmunocomplejos circulantes (ICC así como la medición del sistema complemento por la vía clásica, vía alterna, actividad del factor B y la cuantificación del tercer (C3 y cuarto (C4 componentes de complemento en 30 pacientes con leucemia promielocítica (LPM al diagnóstico, 22 de los cuales presentaron coagulación intravascular diseminada (CID. Se demostró la existencia de niveles elevados de ICC en los enfermos con CID y una disminución significativa de la actividad de la vía clásica, los componentes C3 y C4 en los enfermos con CID, al compararlos con el grupo de pacientes que no presentaba el trastorno de la hemostasia y los controles normales, lo que sugiere la posible participación de estos parámetros en el fenómeno de la CID en estos enfermosThe determination of the circulating immunecomplexes (CIC as well as the measurement of the complement system were carried out by the classical pathway, alternate pathway, factor B activity and the quantitation of the third (C3 and fourth (C4 components of the complement in 30 patients with promyelocytic leukaemia (PML on diagnosis, 22 of whom presented disseminated intravascular coagulation (DIC. It was proved the existance of elevated levels of CIC in patients with DIC and a marked reduction of the ativity of the classical pathway and of the C3 and C4 components in patients with DIC, on comparing them with the group of patients that did not have hemostasis disorder and with the normal controls, which suggest the possible participation of these parameters in the phenomenon of DIC in these patients

Effect of 50,000 IU vitamin A given with BCG vaccine on mortality in infants in Guinea-Bissau: randomised placebo controlled trial.

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Benn, Christine Stabell; Diness, Birgitte Rode; Roth, Adam; Nante, Ernesto; Fisker, Ane Baerent; Lisse, Ida Maria; Yazdanbakhsh, Maria; Whittle, Hilton; Rodrigues, Amabelia; Aaby, Peter

2008-06-21

To investigate the effect of high dose vitamin A supplementation given with BCG vaccine at birth in an African setting with high infant mortality. Randomised placebo controlled trial. Setting Bandim Health Project's demographic surveillance system in Guinea-Bissau, covering approximately 90,000 inhabitants. Participants 4345 infants due to receive BCG. Infants were randomised to 50,000 IU vitamin A or placebo and followed until age 12 months. Mortality rate ratios. 174 children died during follow-up (mortality=47/1000 person-years). Vitamin A supplementation was not significantly associated with mortality; the mortality rate ratio was 1.07 (95% confidence interval 0.79 to 1.44). The effect was 1.00 (0.65 to 1.56) during the first four months and 1.13 (0.75 to 1.68) from 4 to 12 months of age. The mortality rate ratio in boys was 0.84 (0.55 to 1.27) compared with 1.39 (0.90 to 2.14) in girls (P for interaction=0.10). An explorative analysis revealed a strong interaction between vitamin A and season of administration. Vitamin A supplementation given with BCG vaccine at birth had no significant benefit in this African setting. Although little doubt exists that vitamin A supplementation reduces mortality in older children, a global recommendation of supplementation for all newborn infants may not contribute to better survival. Clinical trials NCT00168597.

Strategic analysis of PKM Duda SA. on Polish meat market with the application of BCG growth-share matrix

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Anna Zielińska-Chmielewska

2012-01-01

Full Text Available The main goal of this paper was to examine the market position of one leading meat processing enterprise PKM Duda SA. on the domestic meat market. The assessment of the activity portfolio on its three strategic units was undertaken with the usage of BCG matrix. The PKM Duda SA. was chosen for the study because: a processes more than 20 tons of slaughter per week, b is located in the country of origin, c exists on Warsaw Stock Exchange Market, d preserves continuity of its database in Monitor Polski „B”. The analysis proved that all three examined strategic units have different market shares and operate on markets of a different acceleration. The highest income rate brings the meat processing unit (B, the lowest slaughter unit (A. The market position of PKM Duda SA. can be improved when a retail trade unit (B moves away from question marks into stars. Although BCG matrix draws a fast and a complex strategic situation, is not free from disadvantages. That is the reason why further, also portfolio, analysis should be im-plemented.

An oral Mycobacterium bovis BCG vaccine for wildlife produced in the absence of animal-derived reagents.

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Cross, Martin L; Lambeth, Matthew R; Aldwell, Frank E

2009-09-01

Cultures of Mycobacterium bovis BCG, comprising predominantly single-cell bacilli, were prepared in broth without animal-derived reagents. When formulated into a vegetable-derived lipid matrix, the vaccine was stable in vitro and was immunogenic in vivo upon feeding it to mice. This formulation could be useful for oral vaccination of wildlife against tuberculosis, where concern over transmissible prions may preclude the field use of vaccines containing animal products.

The lack of therapeutic effects in mice of the combined gamma-irradiated Mycobacterium leprae and viable BCG against Mycobacterium leprae infection

International Nuclear Information System (INIS)

Saito, Hajime; Tomioka, Haruaki; Kitagawa, Toshiyuki

1985-01-01

Gamma-irradiated M. leprae in combination with BCG given once biweekly to mice from 2 weeks for up to 187 days after infection with M. leprae caused no significant growth inhibition of M. leprae, at the site of the infection. (author)

Efectos del consumo de panes integrales elaborados con harina de Amaranthus dubius Mart. ex Thell. y harina de trigo en ratas con sídrome metabólico

OpenAIRE

Montero Quiroga, Keyla Carolina

2014-01-01

El género Amaranthus se caracteriza por su alto contenido de nutrientes comparables a los alimentos de origen animal. Sin embargo, la especie Amaranthus dubius, la cual está diseminada en Venezuela, se considera un arvense de cultivos de subsistencia, como el maíz, sorgo y leguminosas; esto impulso la investigación sobre la posible aplicación del amaranto venezolano para la alimentación humana. El estudio se inició con la evaluación de la composición proximal, el contenid...

Presentación sistémica de Aspergillus spp con semiología neurológica en un Pastor Alemán: informe de un caso clínico

OpenAIRE

Hernández Tapia, Ana Laura; Santoscoy Mejía, Eduardo Carlos; Ramírez Lezama, José; Cervantes Olivares, Roberto A.; Quiroz Mercado, Joaquín Arturo

2010-01-01

La infección del sistema nervioso en el perro es poco común; posibles causas son Aspergillus spp, Cryptococcus neoformans, Blastomyces dermatidis y Coccidioides immitis. La infección por Aspergillus spp afecta al aparato respiratorio y en pocas ocasiones se presenta de manera diseminada. Sin embargo, en el Pastor Alemán hay mayor incidencia de éste, pues dicha infección se asocia con una deficiencia inmunológica. Se describe el caso de una perra de raza Pastor Alemán, de 1.5 años de edad, ref...

Evaluación del desempeño de pruebas diagnósticas de tuberculosis en pacientes VIH positivo en dos hospitales públicos de Bogotá

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Gómez Cruz, Andrea Paola; Sanchez Rodriguez, Liliana Carolina

2016-01-01

La tuberculosis TB es una de las principales causas de muerte en el mundo en individuos con infección por VIH. En Colombia esta coinfección soporta una carga importante en la población general convirtiéndose en un problema de salud pública. En estos pacientes las pruebas diagnósticas tienen sensibilidad inferior y la enfermedad evoluciona con mayor frecuencia hacia formas diseminadas y rápidamente progresivas y su diagnóstico oportuno representa un reto en Salud. El objetivo de este proyecto ...

Hongos Fitopatógenos asociados a semillas de palto (Persea Americana mill.)

OpenAIRE

Leon Ttacca, Betsabe; Mattos Calderon, Leonor

2016-01-01

Una serie de enfermedades severas de origen fungoso son diseminadas por semillas de palto, y pueden causar una disminución de la producción en aproximadamente el 14 % y una reducción de calidad en un 10 %. El presente trabajo consistió en aislar e identificar hongos fitopatógenos presentes en las semillas de palto (Persea americana Mill.) raza mexicana utilizadas para patrón. A partir del embrión y cotiledón de 200 semillas de palto, se aislo los hongos fotopatogenos en medio de cultivo Papa ...

The effect of high-dose vitamin A supplementation administered with BCG vaccine at birth may be modified by subsequent DTP vaccination

DEFF Research Database (Denmark)

Benn, Christine Stabell; Rodrigues, Amabelia; Yazdanbakhsh, Maria

2009-01-01

Unexpectedly, we found no overall beneficial effect on mortality in a randomised trial of vitamin A supplementation (VAS) or placebo administered with BCG vaccine at birth in Guinea-Bissau. We conducted an explorative analysis to examine whether subsequent diphtheria-tetanus-pertussis (DTP) vacci...

Sonic hedgehog-dependent induction of microRNA 31 and microRNA 150 regulates Mycobacterium bovis BCG-driven toll-like receptor 2 signaling.

Science.gov (United States)

Ghorpade, Devram Sampat; Holla, Sahana; Kaveri, Srini V; Bayry, Jagadeesh; Patil, Shripad A; Balaji, Kithiganahalli Narayanaswamy

2013-02-01

Hedgehog (HH) signaling is a significant regulator of cell fate decisions during embryogenesis, development, and perpetuation of various disease conditions. Testing whether pathogen-specific HH signaling promotes unique innate recognition of intracellular bacteria, we demonstrate that among diverse Gram-positive or Gram-negative microbes, Mycobacterium bovis BCG, a vaccine strain, elicits a robust activation of Sonic HH (SHH) signaling in macrophages. Interestingly, sustained tumor necrosis factor alpha (TNF-α) secretion by macrophages was essential for robust SHH activation, as TNF-α(-/-) macrophages exhibited compromised ability to activate SHH signaling. Neutralization of TNF-α or blockade of TNF-α receptor signaling significantly reduced the infection-induced SHH signaling activation both in vitro and in vivo. Intriguingly, activated SHH signaling downregulated M. bovis BCG-mediated Toll-like receptor 2 (TLR2) signaling events to regulate a battery of genes associated with divergent functions of M1/M2 macrophages. Genome-wide expression profiling as well as conventional gain-of-function or loss-of-function analysis showed that SHH signaling-responsive microRNA 31 (miR-31) and miR-150 target MyD88, an adaptor protein of TLR2 signaling, thus leading to suppression of TLR2 responses. SHH signaling signatures could be detected in vivo in tuberculosis patients and M. bovis BCG-challenged mice. Collectively, these investigations identify SHH signaling to be what we believe is one of the significant regulators of host-pathogen interactions.

Immunoregulation of antitumor response; differential secretion of arachidonic acid metabolites by macrophages during stimulation ''in vitro'' with BCG and ''Corynebacterium parvum''

International Nuclear Information System (INIS)

Tomecki, Jaroslaw; Sukiennik, Jadwiga; Kordowiak, Anna

1993-01-01

The level of arachidonic acid (AA) metabolites in the supernatants of cultures peritoneal exudate cells (PEC) were studied under various conditions using BCG and ''Corynebacterium parvum'' as stimulators. The metabolite levels were analyzed by thin layer chromatography (TLC). The degree of macrophage cytotoxic/cytostatic activity was dependent on the dose and character of stimulators used and the source of macrophages. The application of micro cytotoxicity assay for the evaluation of tumor cell lysis (lung sarcoma SaL-1) ''in vitro'' revealed that peritoneal macrophages from healthy and tumor bearing BALB/c mice may affect the degree of antitumor response. In the supernatants of cultured PEC from tumor bearing mice AA level increased (by 10-fold) in comparison with PEC from healthy mice. Stimulation with BCG induced over a double level of AA in PEC isolated from tumor bearing mice non-stimulated or stimulated with ''C.parvum''. A lower level of prostaglandins (PGs) was found in the supernatants of cultured PEC isolated from healthy mice (stimulated and non-stimulated), but the highest level of PGs was observed in the supernatants of cultured PEC isolated from tumor bearing mice stimulated with BCG. The unique metabolite of AA was found only in the supernatants form non-stimulated PEC from tumor bearing mice. PEC from tumor bearing mice produced metabolites of AA which were not detected in control group. These results suggest that macrophages also play a regulatory role by secretion of AA. This process can be modified by bacterial antigens. (author). 21 refs, 7 figs

"Lay epidemiology": an important factor in Danish parents' decision of whether to allow their child to receive a BCG vaccination. A qualitative exploration of parental perspective.

Science.gov (United States)

Pihl, Gitte Thybo; Johannessen, Helle; Ammentorp, Jette; Jensen, Jane Schmidt; Kofoed, Poul-Erik

2017-11-21

Vaccination is used worldwide to prevent infectious diseases. However, vaccination programmes in western countries face challenges in sustaining high coverage rates. The aim of this study was to explore how parents in Denmark make a decision about whether to allow their child to receive a Bacille Calmette Guerin vaccine at birth for the purpose of achieving non-specific effects on the immune system. A total of five focus groups were conducted with expectant mothers and fathers. Written information about the vaccine and information about the hypothesis of non-specific effects of the vaccine were delivered in order to discuss considerations and determinants of parents' decisions. Heritable factors and the possibility of stimulating the immune system of the child to achieve less atopic diseases and fewer infections were identified as arguments in favour of receiving the BCG vaccine. Arguments against receiving BCG mainly focused on concerns about its described and non-described side effects. Both arguments for and arguments against the vaccine were seen as parents attempt to make an individual risk evaluation for their child. Attitudes and beliefs in the local network were identified as important for parents' decisions. It is discussed how "lay epidemiology" characterizes parents' risk evaluation as an individual addition to the population-based risk declaration. It is furthermore discussed how health professionals should engage with both the empirical element and the value element of "Lay epidemiology". "Lay epidemiology" forms the basis for the parental decision of whether to allow their child to receive a BCG vaccination. Attitudes and beliefs about the causes and distribution of illnesses in the family or local network influence parents' risk evaluations. It would be ideal for parents if health professionals focused their communication about the BCG vaccine on individual risk evaluations.

Asociación de encefalomielitis diseminada aguda y síndrome de Guillain-Barré en un adulto Association between acute disseminated encephalomyelitis and Guillain Barré syndrome in an adult

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Miguel A. Pagano

2011-06-01

Full Text Available La encefalomielitis diseminada aguda (EMDA y el síndrome de Guillain-Barré (SGB son reconocidas como entidades distintas, que afectan diferentes sectores del sistema nervioso, pero que comparten varias características tales como la patogenia autoinmune, el impacto sobre la mielina y el antecedente de infección viral o vacunación una a cuatro semanas previas al cuadro clínico. Se presenta un paciente varón de 41 años de edad que consultó por presentar fiebre, debilidad en miembros inferiores y somnolencia dos semanas posteriores a episodio agudo de gastroenteritis. Al ingreso se constató deterioro del sensorio (obnubilación hiperreflexia patelar, Babinski bilateral y vejiga neurogénica. Veinticuatro horas después desarrolló paraplejía flácida y arreflexia generalizada, requiriendo asistencia respiratoria mecánica por insuficiencia respiratoria. El líquido cefalorraquídeo mostró pleocitosis mononuclear e hiperproteinorraquia. El estudio electrofisiológico evidenció importante disminución de las velocidades de conducción en ambos nervios ciáticos poplíteos externos, compatible con polineuropatía desmielinizante. La resonancia magnética nuclear mostró imágenes compatibles con desmielinización en cerebro, protuberancia y segmentos medulares dorsales. Se realizó diagnóstico de ASEMDA-SGB e inició tratamiento con metilprednisolona e inmunoglobulina intravenosa. Evolucionó favorablemente, recuperando las funciones motoras, vesical y la sensibilidad, siendo capaz de deambular luego de seis meses. La asociación de EMDA y SGB (ASEMDA-SGB es una condición infrecuente, generalmente señalada como de mal pronóstico, en la cual un diagnóstico precoz y un rápido y enérgico tratamiento pueden mejorar substancialmente la evolución.Acute disseminated encephalomyelitis (ADEM and Guillain-Barré Syndrome (GBS are commonly recognized as separated entities involving different parts of the nervous system. However, they share

Predictive Value of NRAMP1 and HGPX1 Gene Polymorphism for Maintenance BCG Response in Non-muscle-invasive Bladder Cancer.

Science.gov (United States)

Lenormand, Claire; Couteau, Jérôme; Nouhaud, François-Xavier; Maillet, Géraldine; Bou, Jacqueline; Gobet, Françoise; Pfister, Christian

2016-04-01

To assess the potential predictive value of natural resistance-associated macrophage protein 1 (NRAMP1) and human glutathione peroxidase 1 (hGPX1) polymorphism in non-muscle-invasive bladder cancer treated with bacillus Calmette-Guerin (BCG) instillation, we conducted an original ancillary multicenter study. We evaluated patients included in the multicenter URO-BCG 4 trial, who received three weekly instillations of one-third dose BCG every 6 months (group I) or two weekly instillations every 3 months (group II) for 3 years. For clinical evaluation we also evaluated tumor recurrence and muscle progression. NRAMP1 and hGPX1 polymorphism analyses were performed on blood DNA. NRAMP1 exon 15 and hGPX1 exon 1c were amplified using Type-it Microsatellite PCR Kit® for multiplex polymerase chain reaction. From June 2004 to April 2010, 146 randomized patients were included in this retrospective study. Blood samples were obtained from 107 patients. With 36 months of follow-up, 13.6% of patients had a tumor recurrence and muscle-invasive progression was observed in 4.3% of patients. Concerning NRAMP1 D543N polymorphism, patients with allele A had no tumor recurrence or muscle-invasive progression. No significant difference was observed in gene polymorphism distribution between groups I and II. Moreover, we did not observe any significant association of gene polymorphisms, tumor recurrence or muscle-invasive progression, event time and disease-free survival. Our results suggest that no significant difference was found for NRAMP1 and hGPX1 gene polymorphisms associated with recurrence time, muscle invasion frequency and disease-free survival, nevertheless, we observed that the NRAMP1 D543N GG genotype group had a shorter time to tumor recurrence. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Subcutaneous immunization against Leishmania major - infection in mice: efficacy of formalin-killed promastigotes combined with adjuvants Imunização subcutânea na infecção do camundongo pela Leishmania major: eficácia dos promastigotos mortos pela formalina combinada com adjuvantes

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Joshua M. Mutiso

2010-04-01

Full Text Available Formalin-killed promastigotes (FKP of Leishmania major, in combination with Montanide ISA 720 (MISA, BCG or alum were used in vaccination of an inbred murine model against cutaneous leishmaniasis (CL. Significant and specific increases in anti-FKP IgG responses were detected for both alum-FKP and BCG-FKP compared to MISA-FKP (p Promastigotos mortos pela formalina (FKP de Leishmania major combinados com Montanide ISA 720 (MISA, BCG ou alumen foram usados na vacinação de modelo murino cutâneo de leishmaniose (CL. Aumento significante e específico de resposta IgG anti FKP foram detectados tanto no FKP com alumen como naquele com BCG comparados ao MISA-FKP (p < 0,001. Aumento significante da proliferação esplênica de linfócitos de memória foi obtida nos camundongos vacinados com MISA-FKP quando comparados aos grupos vacinados com alumen-FKP ou BCG-FKP (p < 0,01. As maiores respostas por interferon-gama foram observadas no grupo BCG-FKP seguido pelo MISA-FKP enquanto que o alumen-FKP deu a menor resposta. No grupo MISA-FKP foram obtidas reduções significantes do tamanho das lesões quando comparado aos grupos vacinados com BCG/adjuvante de alumen-FKP. Embora o grupo BCG-FKP tenha mostrado a maior resposta por interferon-gama, não houve controle das lesões cutâneas. Redução significante no número de parasitas foi observada tanto no grupo vacinado com MISA-FKP como no BCG-FKP (p < 0,001. Houve boa correlação entre a carga parasitária e o nível de interferon-gama indicando que a resposta do interferon-gama é parâmetro sensível do estado imunológico. Em conclusão, MISA-FKP é a forma mais eficaz de vacina contra a leishmaniose cutânea murina.

The combination of maltose-binding protein and BCG-induced Th1 activation is involved in TLR2/9-mediated upregulation of MyD88-TRAF6 and TLR4-mediated downregulation of TRIF-TRAF3.

Science.gov (United States)

Liu, Guomu; Zhai, Xiaoyu; Zhou, Hongyue; Yang, Xiaoyu; Zhang, Nannan; Tai, Guixiang; Ni, Weihua

2018-03-01

Our previous study demonstrated that maltose-binding protein (MBP) activated Th1 through the TLR2-mediated MyD88-dependent pathway and the TLR4-mediated TRIF-dependent pathway. The combination of MBP and BCG synergistically induced Th1 activation, and the TLR2/9-mediated MyD88-dependent pathway is involved in this process. To further explore this mechanism, we stimulated purified mouse CD4 + T cells with MBP and BCG in vitro. The results demonstrated that MBP combined with BCG synergistically increased IFN-γ production and TLR2/4/9 expression, suggesting the involvement of TLR2/4/9 in the combination-induced Th1 activation. Next, TLRs 2/4/9 were blocked to analyze the effects of TLRs on Th1 activation. The results demonstrated that MBP induced a low level of Th1 activation by upregulating TLR2-mediated MyD88-TRAF6 and TLR4-mediated TRIF-TRAF3 expression, whereas MBP combined with BCG induced synergistic Th1 activation, which was not only triggered by strong upregulation of TLR2/9-mediated MyD88-TRAF6 expression but also by shifting TLR4-mediated TRIF-TRAF3 into the TRIF-TRAF6 pathway. Moreover, we observed that a TLR4 antibody upregulated MyD88 expression and a TLR9 inhibitor downregulated TRIF expression, indicating that there was cross-talk between TLRs 2/4/9 in MBP combined with BCG-induced Th1 activation. Our findings may expand the knowledge regarding TLR cross-talk involved in regulating the Th1 response. Copyright © 2018 Elsevier Inc. All rights reserved.

Listeria-vectored vaccine expressing the Mycobacterium tuberculosis 30 kDa major secretory protein via the constitutively active prfA* regulon boosts BCG efficacy against tuberculosis.

Science.gov (United States)

Jia, Qingmei; Dillon, Barbara Jane; Masleša-Galić, Saša; Horwitz, Marcus A

2017-06-19

A potent vaccine against tuberculosis, one of the world's deadliest diseases, is needed to enhance the immunity of people worldwide, most of whom have been vaccinated with the partially effective BCG vaccine. Here we investigate novel live attenuated recombinant Listeria monocytogenes (rLm) vaccines expressing the Mycobacterium tuberculosis (Mtb) 30 kDa major secretory protein (r30/Ag85B) (rLm30) as heterologous booster vaccines in animals primed with BCG. Using three attenuated Lm vectors, rLm Δ actA (LmI), rLm Δ actA Δ inlB (LmII), and rLm Δ actA Δ inlB prfA * (LmIII), we constructed five rLm30 vaccine candidates expressing the r30 linked in-frame to the Lm Listeriolycin O signal sequence and driven by the hly promoter (h30) or linked in-frame to the ActA N-terminus and driven by the actA promoter (a30). All five rLm30 vaccines secreted r30 in broth and macrophages; while rLm expressing r30 via a constitutively active prfA * regulon (rLmIII/a30) expressed the greatest amount of r30 in broth culture, all five rLm vaccines expressed equivalent amounts of r30 in infected macrophages. In comparative studies, boosting BCG-immunized mice with rLmIII/a30 induced the strongest antigen-specific T-cell responses, including splenic and lung polyfunctional CD4+ T-cells expressing the three cytokines of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and interleukin-2 (IL-2) ( P vaccines were generally more potent booster vaccines than r30 in adjuvant and a recombinant adenovirus vaccine expressing r30. In a setting in which BCG alone was highly immunoprotective, boosting mice with rLmIII/a30, the most potent of the vaccines, significantly enhanced protection against aerosolized Mtb ( P <0.01). Copyright © 2017 American Society for Microbiology.

Inflamación crónica granulomatosa en el pez teleósteo Piaractus mesopotamicus: modelo de estudio histopatológico

OpenAIRE

G Manrique, Wilson; AP Figueiredo, Mayra; Belo, Marco AA; Martins, Maurício L; Moraes, Flávio R

2017-01-01

Objetivo. Este estudio evaluó la cinética celular y la formación de granuloma durante la inflamación crónica inducida por el Bacilo Calmette-Guérin (BCG) en el músculo esquelético de Piaractus mesopotamicus, como modelo histopatológico para estudiar la inmunidad innata. Materiales y métodos. Sesenta peces fueron divididos en dos grupos: peces inoculados con BCG y no inoculados y la respuesta inflamatoria analizada en 3, 7, 14, 21 y 33 días post-inóculo (DPI) por medio del análisis histopatoló...

Lipid-formulated bcg as an oral-bait vaccine for tuberculosis: vaccine stability, efficacy, and palatability to brushtail possums (Trichosurus vulpecula) in New Zealand.

Science.gov (United States)

Cross, Martin L; Henderson, Ray J; Lambeth, Matthew R; Buddle, Bryce M; Aldwell, Frank E

2009-07-01

Bovine tuberculosis (Tb), due to infection with virulent Mycobacterium bovis, represents a threat to New Zealand agriculture due to vectorial transmission from wildlife reservoir species, principally the introduced Australian brushtail possum (Trichosurus vulpecula). An oral-delivery wildlife vaccine has been developed to immunize possums against Tb, based on formulation of the human Tb vaccine (M. bovis BCG) in edible lipid matrices. Here BCG bacilli were shown to be stable in lipid matrix formulation for over 8 mo in freezer storage, for 7 wk under room temperature conditions, and for 3-5 wk under field conditions in a forest/pasture margin habitat (when maintained in weatherproof bait-delivery sachets). Samples of the lipid matrix were flavored and offered to captive possums in a bait-preference study: a combination of 10% chocolate powder with anise oil was identified as the most effective attractant/palatability combination. In a replicated field study, 85-100% of wild possums were shown to access chocolate-flavored lipid pellets, when baits were applied to areas holding approximately 600-800 possums/km(2). Finally, in a controlled vaccination/challenge study, chocolate-flavored lipid vaccine samples containing 10(8) BCG bacilli were fed to captive possums, which were subsequently challenged via aerosol exposure to virulent M. bovis: vaccine immunogenicity was confirmed, and protection was identified by significantly reduced postchallenge weight loss in vaccinated animals compared to nonvaccinated controls. These studies indicate that, appropriately flavored, lipid delivery matrices may form effective bait vaccines for the control of Tb in wildlife.

BCG: a code for calculating pointwise neutron spectra and criticality in fast reactor cells

International Nuclear Information System (INIS)

Leite, S.B.; Caldeira, A.D.; Garcia, R.D.M.

1988-02-01

The BCG code for determining the space and energy neutron flux distribution and criticality of fast reactor cylindrical cells is presented. The code solves the unidimensional neutron transport equation together with interface current relations at each energy in an unionized grid prepared for the cell and at an arbitrary number of spatial zones. While the spatial resolution is user specified, the energy dependence of the flux distribution is resolved according to the degree of variation in the reconstructed total microscopic cross sections of the atomic species in the cell. Results for a defined sample problem illustrate the high resolution and accuracy that can be obtained with the code. (author) [pt

Interpretación de la prueba de tuberculina en niños y vacunados con BCG

OpenAIRE

Piñeiro Pérez, Roi

2012-01-01

Revisados 20 años de literatura médica, el debate sobre la conveniencia de la vacunación con Bacilo de Calmette-Guérin (BCG) continúa abierto. La OMS se muestra a favor de su utilización en países con endemia elevada de Tuberculosis (TB), pero no se ha esclarecido el beneficio ni las indicaciones de la inmunización en poblaciones con endemia intermedia o baja, y existen numerosos expertos que se muestran contrarios a su administración en cualquier caso. Existen muchas publicaciones sobre el ...

La fiebre amarilla y su control.

Directory of Open Access Journals (Sweden)

Martha Patricia Velandia

2004-03-01

Full Text Available la candidiosis crónica diseminada. El tercer patrón (imágenes hipoecoicas, aunque no es específico de la candidiosis crónica diseminada, es el más comúnmente hallado en ambas técnicas. En la paciente se observaron los patrones 2 y 3, y el diagnóstico se confirmó con el estudio histopatológico.

Un exponente de gestión económica de la «fidalguía» gallega y de producción de hierro en la montaña lucense. La herrería de Quinta durante el Antiguo Régimen

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Vítor Manuel MIGUÉS

2009-11-01

Full Text Available Tradicionalmente vinculadas a la percepción de rentas agrarias, las economías señoriales en Galicia fueron frecuentemente observadas desde tal atalaya. Es por eso por lo que estrategias diferentes de comportamiento económico son tan desconocidas como casi inabordadas. Esto, si cabe, se acentúa aún más en el caso de la producción de hierro, actividad desarrollada a lo largo de los siglos en pequeñas y diseminadas unidades de producción conocidas comúnmente en Galicia como «ferrarías», y tradicionalmente desconocidas no sólo como integrantes de economías señoriales de más amplio fuste, sino como representantes del débil sector industrial del Antiguo Régimen.

Increased TNF-alpha/IFN-gamma/IL-2 and decreased TNF-alpha/IFN-gamma production by central memory T cells are associated with protective responses against bovine tuberculosis following BCG vaccination

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Mayara Fernanda Maggioli

2016-10-01

Full Text Available Central memory T cells (Tcm and polyfunctional CD4 T cell responses contribute to vaccine-elicited protection with both human and bovine tuberculosis (TB; however, their combined role in protective immunity to TB is unclear. To address this question, we evaluated polyfunctional cytokine responses by CD4 T cell effector / memory populations from bacille Calmette Guerin (BCG vaccinated and non-vaccinated calves prior to and after aerosol challenge with virulent Mycobacterium bovis. Polyfunctional cytokine expression patterns in the response by Tcm, effector memory, and effector T cell subsets were similar between BCG-vaccinated and M. bovis-infected calves; only differing in magnitude (i.e., infected > vaccinated. BCG vaccination, however, did alter the kinetics of the ensuing response to virulent M. bovis infection. Early after challenge (three weeks post-infection, non-vaccinates had greater antigen-specific IFN-γ/TNF-α and lesser IFN-γ/TNF-α/IL-2 responses by Tcm cells than did vaccinated animals. Importantly, these differences were also associated with mycobacterial burden upon necropsy. Polyfunctional responses to ESAT-6:CFP10 (antigens not synthesized by BCG strains were detected in memory subsets, as well as in effector cells, as early as three weeks after challenge. These findings suggest that cell fate divergence may occur early after antigen priming in the response to bovine TB and that memory and effector T cells may expand concurrently during the initial phase of the immune response. In summary, robust IFN-γ/TNF-α response by Tcm cells is associated with greater mycobacterial burden while IFN-γ/TNF-α/IL-2 response by Tcm cells are indicative of a protective response to bovine TB.

Duas epidemias de tuberculose em crianças menores de três anos de idade, vacinadas com BCG oral, numa creche do município de São Paulo, Brasil Two epidemics of tuberculosis in children under three years of age vaccinated with oral BCG in a day-nursery in S. Paulo county, Brazil

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Roberto Brólio

1974-09-01

Full Text Available São descritas duas epidemias de tuberculose em crianças menores de 3 anos de idade vacinadas com BCG oral, ocorridas numa creche para crianças menores de 5 anos de idade, no município de São Paulo, nos anos de 1967 e 1969. Em 1967 havia no estabelecimento 96 crianças, inicialmente não reatoras ao teste tuberculínico padronizado (PPD, Rt-23, 2 UT. Foram encontrados 19 reatores, sendo 12 reatores fortes (63,2% e 7 reatores fracos (36,8% e imagens radiológicas indicativas de anormalidade pulmonar em 15 crianças ou 78,9% dos reatores. Em 1969 havia no estabelecimento mais 62 crianças não reatoras, que foram acompanhadas separadamente em relação ao grupo de 1967, embora convivessem no mesmo ambiente. Foram encontrados 36 reatores à tuberculina, sendo 29 reatores fortes (80,5% e 7 reatores fracos (19,5% e imagens radiológicas indicativas de anormalidade pulmonar em 11 crianças, ou 30,5% dos reatores. Nesse mesmo ano houve viragem tuberculínica em mais 7 crianças pertencentes ao grupo de não reatores de 1967, sendo 5 reatores fortes e 2 reatores fracos. Nas duas epidemias, as viragens tuberculínicas e as alterações radiológicas pulmonares foram constatadas apenas nas crianças menores de 3 anos de idade, em sua maioria vacinadas previamente com 3 doses de BCG oral, com intervalo de uma semana entre uma dose e outra. A fonte de infecção foi um operário que trabalhou no estabelecimento durante aproximadamente dois meses em 1967 e um mês em 1969, nos locais onde eram mantidas as crianças menores de 3 anos de idade. A vacina administrada por esse método não parece ter influenciado nas conversões tuberculínicas e no desenvolvimento de imunidade específica.Two epidemics of tuberculosis in children under three years of age vaccinated with oral BCG, in the year of 1967 and 1969, in a day-nursery in S. Paulo borough, are here described. In 1967 there were 96 children in the place, at first non-reactors, to the standard

Infección diseminada por Penicillium marneffei en un paciente HIV-positivo: Primera observación en la República Argentina Disseminated infection due to Penicillium marneffei related to HIV infection: First observation in Argentina

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GABRIELA SANTISO

2011-12-01

Full Text Available Se presenta el primer caso humano de peniciliosis por Penicillium marneffei observado en la República Argentina. El paciente era un joven de 16 años, HIV-positivo, procedente de un área rural del sur de China. El paciente fue internado en el Hospital "F. J. Muñiz" por padecer una neumonía grave con insufciencia respiratoria aguda. El agente causal fue aislado de un lavado broncoalveolar y se lo observó en un citodiagnóstico de piel. La identifcación de P. marneffei fue confrmada por las características fenotípicas del aislamiento y la amplifcación del ADNr. El enfermo padecía una infección muy avanzada por HIV que condujo a la aparición simultánea de infecciones por citomegalovirus, Pneumocystis jirovecii y procesos bacterianos nosocomiales. Este complejo cuadro derivó en una evolución fatal.The frst case observed in Argentina of AIDS-related human penicillosis is herein presented. The patient was a six- teen year-old young man coming from a rural area of southern China. He was admitted at the F. J. Muñiz Hospital of Buenos Aires city with severe pneumonia and adult respiratory distress. Penicillium marneffei was isolated from bronchoalveolar lavage fuid and was microscopically observed in a skin cytodiagnosis. P. marneffei identifcation was confrmed by rRNA amplifcation and its phenotypic characteristics. The patient suffered an advanced HIV infection and also presented several AIDS-related diseases due to CMV, nosocomial bacterial infections and Pneumocystis jirovecii which led to a fatal outcome.

Mycobacterium tuberculosis PPD-induced immune biomarkers measurable in vitro following BCG vaccination of UK adolescents by multiplex bead array and intracellular cytokine staining

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Worth Andrew

2010-07-01

Full Text Available Abstract Background The vaccine efficacy reported following Mycobacterium bovis Bacillus Calmette Guerin (BCG administration to UK adolescents is 77% and defining the cellular immune response in this group can inform us as to the nature of effective immunity against tuberculosis. The aim of this study was to identify which cytokines and lymphocyte populations characterise the peripheral blood cellular immune response following BCG vaccination. Results Diluted blood from before and after vaccination was stimulated with Mycobacterium tuberculosis purified protein derivative for 6 days, after which soluble biomarkers in supernatants were assayed by multiplex bead array. Ten out of twenty biomarkers measured were significantly increased (p Mycobacterium tuberculosis purified protein derivative stimulation of PBMC samples from the 12 month group revealed that IFNγ expression was detectable in CD4 and CD8 T-cells and natural killer cells. Polyfunctional flow cytometry analysis demonstrated that cells expressing IFNγ alone formed the majority in each subpopulation of cells. Only in CD4 T-cells and NK cells were there a notable proportion of responding cells of a different phenotype and these were single positive, TNFα producers. No significant expression of the cytokines IL-2, IL-17 or IL-10 was seen in any population of cells. Conclusions The broad array of biomarker responses detected by multiplex bead array suggests that BCG vaccination is capable, in this setting, of inducing a complex immune phenotype. Although polyfunctional T-cells have been proposed to play a role in protective immunity, they were not present in vaccinated adolescents who, based on earlier epidemiological studies, should have developed protection against pulmonary tuberculosis. This may be due to the later sampling time point available for testing or on the kinetics of the assays used.

Strategy to better select HIV-infected individuals for latent TB treatment in BCG-vaccinated population.

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Chin-Hui Yang

Full Text Available OBJECTIVE: To evaluate the T-SPOT.TB interferon-γ releasing assay and the tuberculin skin test (TST, for the diagnosis of latent tuberculosis infection(LTBI and the development of subsequent active tuberculosis, in BCG-vaccinated HIV-infected individuals. METHODS: HIV-infected individuals without clinical suspicion of active TB or a past history of TB were enrolled from 1 January 2008 to 30 November 2010. Both T-SPOT.TB test and TST were offered to the participants whom were followed up prospectively until April 30, 2012 for development of TB. RESULTS: Among the 909 participants, 25% had positive TST reactions with cut-off point of 5 mm and 15% had positive T-SPOT.TB results. After a median follow-up of 2.97 years, there were 5 cases developed culture-confirmed active TB (all had dual positive TST and T-SPOT.TB results, and the incidence was 0.17 per 100 person-years. The relative risks (RRs for subsequent active TB in HIV-infected individuals with positive TST results, positive T-SPOT.TB results and dual positive results compared with the risk for individuals with negative results were 40.6 (95% CI 2.1-767.9, 73.9 (95% CI 3.9-1397.7 and 226.5 (95% CI 12.0-4284, respectively. The number needed to treat to prevent one subsequent TB case among patients with a positive TST, a positive T-SPOT.TB and dual positive results was 35, 22 and 8 respectively. CONCLUSIONS: Adopting positive results of the TST and T-SPOT.TB to screen LTBI among BCG-vaccinated HIV-infected individuals might be feasible. Number needed to treat for isoniazid preventive therapy could be reduced significantly by using dual positive strategy.

Efeitos do reiki na evolução do granuloma induzido através da inoculação do BCG em hamsters e do tumor ascítico de Ehrlich induzido em camundongos

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Ricardo Rodrigues Garé

2008-01-01

Estudaram-se os efeitos da influência do Reiki na evolução do granuloma induzido experimentalmente pela inoculação do BCG no coxim plantar de hamsters, assim como os efeitos da mesma terapia em camundongos portadores do tumor ascítico de Ehrlich in vivo e in vitro. No modelo de inflamação granulomatosa crônica, utilizou-se 40 hamsters machos, os quais após serem inoculados com BCG no dia 0 no coxim da pata posterior direita, foram separados em dois grupos contendo 20 animais em cada. Um grupo...

Interleukin-17-positive mast cells influence outcomes from BCG for patients with CIS: Data from a comprehensive characterisation of the immune microenvironment of urothelial bladder cancer.

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Alexander C Dowell

Full Text Available The tumour immune microenvironment is considered to influence cancer behaviour and outcome. Using a panel of markers for innate and adaptive immune cells we set out to characterise and understand the bladder tumour microenvironment of 114 patients from a prospective multicentre cohort of newly-diagnosed bladder cancer patients, followed-up for 4.33±1.71 years. We found IL-17-positive cells were significantly increased in primary and concomitant carcinoma in situ (CIS, p<0.0001, a highly malignant lesion which is the most significant single risk factor for disease progression. Further characterisation of the tumour immunophenotype identified IL-17+ cells as predominantly mast cells rather than T-cells, in contrast to most other tumour types. Expression of the IL-17-receptor in bladder tumours, and functional effects and gene expression changes induced by IL-17 in bladder tumour cells in vitro suggest a role in tumour behaviour. Finally, we assessed the effects of IL-17 in the context of patient outcome, following intravesical BCG immunotherapy which is the standard of care; higher numbers of IL-17+ cells were associated with improved event-free survival (p = 0.0449, HR 0.2918, 95% CI 0.08762-0.9721 in patients with primary and concomitant CIS (n = 41, we propose a model of IL-17+ Mast cells mechanism of action. Thus, in the context of bladder CIS, IL-17+ mast cells predict favourable outcome following BCG immunotherapy indicative of a novel mechanism of BCG immunotherapy in UBC and could form the basis of a stratified approach to treatment.

BCG: a computer code for calculating neutron spectra and criticality in cells of fast reactors

International Nuclear Information System (INIS)

Leite, S.B.; Caldeira, A.D.; Garcia, R.D.M.

1988-01-01

The BCG code for determining the space and energy neutron flux distribution and criticality of fast reactor cylindrical cells is discussed. The code solves the unidimensional neutron transport equation together with interface current relations at each energy point in an unionized energy grid prepared for the cell and at an arbitrary number of spatial zones. While the spatial resolution is user specified, the energy dependence of the flux distribution is resolved according to the degree of variation in the reconstruced total microscopic cross sections of the atomic species in the cell. Results for a simplified fuel cell illustrate the high resolution and accuracy that can be obtained with the code. (author) [pt

A Unique Sample of Extreme-BCG Clusters at 0.2 < z < 0.5

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Garmire, Gordon

2017-09-01

The recently-discovered Phoenix cluster harbors the most extreme BCG in the known universe. Despite the cluster's high mass and X-ray luminosity, it was consistently identified by surveys as an isolated AGN, due to the bright central point source and the compact cool core. Armed with hindsight, we have undertaken an all-sky survey based on archival X-ray, OIR, and radio data to identify other similarly-extreme systems that were likewise missed. A pilot study demonstrated that this strategy works, leading to the discovery of a new, massive cluster at z 0.2 which was missed by previous X-ray surveys due to the presence of a bright central QSO. We propose here to observe 6 new clusters from our complete northern-sky survey, which harbor some of the most extreme central galaxies known.

The results of treatments and complications of immunotherapy (BCG and alpha-interferon in superficial TCC of bladder

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Jabalameli P

1994-04-01

Full Text Available The treatment of choice for bladder tumors is TUR, but because of high incidence of recurrence in these tumors, various treatments are suggested. In one study, 32 patients involved with superficial T.C.C. of bladder selected and divided in two equal groups. In the first group, after T.U.R, 10 million IU of a alpha-interferon was injected into the bladder through a catheter and in the other group, after TUR, they treated with injection of BCG into bladders. The results of these two drugs in prevention of recurrence and their side effects were studied and compaired

Úlcera de lengua como presentación del Histoplasma capsulatum Tongue ulceration as a presentation of Histoplasma capsulatum infection

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E J Carbó Amoroso

2008-06-01

Full Text Available La histoplasmosis diseminada progresiva es una enfermedad que se manifiesta como reactivación de una infección latente en pacientes inmunodeprimidos, especialmente en personas con déficit en la inmunidad celular. Existen formas agudas, subagudas y crónicas. Las lesiones focales, en especial úlceras mucocutáneas, predominan en la forma diseminada crónica. Reportamos el caso de una paciente con artritis reumatoidea, que controlaba su patología con fármacos antirreumáticos modificadores de la enfermedad (DMARD, la que consultó por úlcera de lengua como única manifestación de una histoplasmosis diseminada crónica. La histopatología fue compatible y el cultivo positivo para Histoplasma capsulatum. La serología para el HIV fue negativa. Existen pocos casos publicados de pacientes con esta localización atípica en forma aislada, en particular aquellos HIV negativos. El itraconazol y la anfotericina B son las dos drogas más utilizadas para tratar esta enfermedad. Los datos clínicos sobre los nuevos azoles, voriconazol y posaconazol son limitados.The progressive disseminated histoplasmosis is a disease produced by reactivation of latent infection in immunocompromised host, specially in persons with defective cell-mediated immunity. There are acute, subacute and chronic forms in the progressive illness. Focal lesions, specially mucocutaneous ulcers, are most frequent in the chronic disseminated forms. We reported a patient with rheumatoid arthritis treated with disease modifying antirheumatic drug (DMARD, with an ulcer of the tongue as only clinical manifestation of a chronic disseminated histoplasmosis. The histopathology was compatible, and the culture was positive for Histoplasma capsulatum. The serology for the HIV was negative. There are few published cases of this isolated form, particularly in patients with HIV negative serological test. Itraconazole and amphotericin B are the most frequently drugs used for the treatment in this

A randomised controlled trial of the effects of albendazole in pregnancy on maternal responses to mycobacterial antigens and infant responses to bacille Calmette-Guérin (BCG immunisation [ISRCTN32849447

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Nampijja Margaret

2005-12-01

Full Text Available Abstract Background Maternal schistosomiasis and filariasis have been shown to influence infant responses to neonatal bacille Calmette-Guérin (BCG immunisation but the effects of maternal hookworm, and of de-worming in pregnancy, are unknown. Methods In Entebbe, Uganda, we conducted a randomised, double-blind, placebo-controlled trial of a single dose of 400 mg of albendazole in the second trimester of pregnancy. Neonates received BCG. Interferon-gamma (IFN-γ and interleukin (IL-5 responses to a mycobacterial antigen (crude culture filtrate proteins (CFP of Mycobacterium tuberculosis were measured in a whole blood assay. We analysed results for binary variables using χ2 tests and logistic regression. We analysed continuous variables using Wilcoxon's tests. Results Maternal hookworm was associated with reduced maternal IFN-γ responses to CFP (adjusted odds ratio for IFN-γ > median response: 0.14 (95% confidence interval 0.02–0.83, p = 0.021. Conversely, maternal hookworm was associated with subsequent increased IFN-γ responses in their one-year-old infants (adjusted OR 17.65 (1.20–258.66; p = 0.013. Maternal albendazole tended to reduce these effects. Conclusion Untreated hookworm infection in pregnancy was associated with reduced maternal IFN-γ responses to mycobacterial antigens, but increased responses in their infants one year after BCG immunisation. The mechanisms of these effects, and their implications for protective immunity remain, to be determined.

Comparison of Tuberculin Skin Test result and interferon gamma response to human PPD in BCG scar positive and negative children.

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Sayyahfar, Shirin; Karimi, Abdollah; Fahimzad, Alireza; Shamshiri, Ahmad Reza

2014-03-01

The aim of this study is to compare Tuberculin Skin Test (TST) result and interferon gamma response to human PPD (purified protein derivative), in scar positive and scar negative BCG-vaccinated children. Between August 2007 and May 2008 a total of 236 children aged 1-168 months (mean 21 months) admitted to Mofid Children's Hospital, Tehran, Iran, were enrolled in a cross-sectional study. Each patient was examined for BCG vaccine scar and tested with TST and human PPD-based Interferon Gamma Release Assay (IGRA). Two hundred and twenty one cases out of 236 (44% female, 1-168 months, mean age 21 months) were scar positive of whom 95% TST result was negative. Human PPD-based IGRA was positive in 110 (49.8%), negative in 85 (38.4 %) and indeterminate in 26 (11.8%) of scar positive patients. Fifteen children (40% female, 1-156 months; mean age 42 months) were scar negative. All the scar negative cases were TST negative. Human PPD-based IGRA was positive in 10 (66.7%), negative in 4 (26.7%) and indeterminate in 1 (6.7%) of scar negative patients. Immune responsiveness to human PPD antigens in scar positive and negative children may not correspond with results of the Tuberculin Skin Test. Copyright © 2013 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

Cell-mediated immunity in operable bronchial carcinoma: the effect of injecting irradiated autologous tumour cells and BCG

International Nuclear Information System (INIS)

Stack, B.H.R.; McSwan, N.; Stirling, J.M.

1979-01-01

In 52 patients undergoing tests of cell-mediated immunity before surgical resection of bronchial carcinoma a positive tuberculin test result was found in 71% compared with 68% of age - and sex-matched controls. Sensitization to DNCB occurred in 52% of 37 patients but in 78% controls. There was depression of lymphocyte transformation by PPD in 19 patients compared with controls (p=0.001), but there was no difference in lymphocyte transformation by PHA pr pokeweed mitogen between 34 patients and controls. In a pilot study patients were randomly allocated to autograft (eight) or non-autograft (seven) groups. The autograft group were given an intradermal injection of a suspension of irradiated autologous tumour-cells mixed with intradermal BCG on the day of operation. Tests of cell-mediated immunity were repeated two weeks after operation. Five patients in each group received a course of radiotherapy to the mediastinum three weeks after operation. There was a rise in a cutaneous tuberculin reactivity (p=0.08) and total leucocyte count (p=0.09) in the autograft group postoperatively with a fall in total lymphocyte and T lymphocyte counts in the non-autograft group (p<0.05). These differences, however, were not followed by any difference in the frequency of tumour recurrence or the survival rate two years after operation. The results show that the immunological surveillance mechanism is impaired even in patients with early bronchial carcinoma and that it is possible to overcome postoperative immunological depression with specific immunotherapy combined with BCG. This treatment did not produce any clinical advantage in this small number of patients and the skin lesions caused the patients considerable discomfort. (author)

Tuberculin-purified protein derivative-, MPT-64-, and ESAT-6-stimulated gamma interferon responses in medical students before and after Mycobacterium bovis BCG vaccination and in patients with tuberculosis

DEFF Research Database (Denmark)

Johnson, P D; Stuart, R L; Grayson, M L

1999-01-01

QuantiFERON-TB (QIFN) (CSL Limited) is a whole-blood assay for the recognition of infection with Mycobacterium tuberculosis. QIFN measures gamma interferon (IFN-gamma) production when purified protein derivatives (PPDs) of mycobacteria are incubated with venous blood samples. The specificity...... of QIFN in medical students before and after BCG immunization was assessed, and sensitivity in patients with tuberculosis was assessed. Antigens were PPD derived from M. tuberculosis and two M. tuberculosis-specific proteins, ESAT-6 and MPT-64. Of 60 medical students, all of whom had 0-mm tuberculin skin...... tests (TSTs) at study entry, 58 (97%) were initially classified as negative for M. tuberculosis infection by PPD QIFN. Five months after BCG immunization, 7 of 54 students (13%) had a TST result of >/=10 mm and 11 of 54 students (20%) tested positive by PPD QIFN. ESAT-6- and MPT-64-stimulated IFN...

The effect of oral vaccination with Mycobacterium bovis BCG on the development of tuberculosis in captive European badgers (Meles meles)

OpenAIRE

Chambers, MA; Aldwell, F; Williams, GA; Palmer, S; Gowtage, S; Ashford, R; Dalley, D; Davé, D; Weyer, U; Salguero Bodes, FJ; Nunez, A; Nadian, A; Crawshaw, T; Corner, LAL; Lesellier, S

2017-01-01

The European badger (Meles meles) is a reservoir host of Mycobacterium bovis and responsible for a proportion of the tuberculosis (TB) cases seen in cattle in the United Kingdom and Republic of Ireland. An injectable preparation of the bacillus Calmette-Guérin (BCG) vaccine is licensed for use in badgers in the UK and its use forms part of the bovine TB eradication plans of England and Wales. However, there are practical limitations to the widespread application of an injectable vaccine for b...

Joint effect of MCP-1 genotype GG and MMP-1 genotype 2G/2G increases the likelihood of developing pulmonary tuberculosis in BCG-vaccinated individuals.

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Malathesha Ganachari

2010-01-01

Full Text Available We previously reported that the -2518 MCP-1 genotype GG increases the likelihood of developing tuberculosis (TB in non-BCG-vaccinated Mexicans and Koreans. Here, we tested the hypothesis that this genotype, alone or together with the -1607 MMP-1 functional polymorphism, increases the likelihood of developing TB in BCG-vaccinated individuals. We conducted population-based case-control studies of BCG-vaccinated individuals in Mexico and Peru that included 193 TB cases and 243 healthy tuberculin-positive controls from Mexico and 701 TB cases and 796 controls from Peru. We also performed immunohistochemistry (IHC analysis of lymph nodes from carriers of relevant two-locus genotypes and in vitro studies to determine how these variants may operate to increase the risk of developing active disease. We report that a joint effect between the -2518 MCP-1 genotype GG and the -1607 MMP-1 genotype 2G/2G consistently increases the odds of developing TB 3.59-fold in Mexicans and 3.9-fold in Peruvians. IHC analysis of lymph nodes indicated that carriers of the two-locus genotype MCP-1 GG MMP-1 2G/2G express the highest levels of both MCP-1 and MMP-1. Carriers of these susceptibility genotypes might be at increased risk of developing TB because they produce high levels of MCP-1, which enhances the induction of MMP-1 production by M. tuberculosis-sonicate antigens to higher levels than in carriers of the other two-locus MCP-1 MMP-1 genotypes studied. This notion was supported by in vitro experiments and luciferase based promoter activity assay. MMP-1 may destabilize granuloma formation and promote tissue damage and disease progression early in the infection. Our findings may foster the development of new and personalized therapeutic approaches targeting MCP-1 and/or MMP-1.

Joint effect of MCP-1 genotype GG and MMP-1 genotype 2G/2G increases the likelihood of developing pulmonary tuberculosis in BCG-vaccinated individuals.

Science.gov (United States)

Ganachari, Malathesha; Ruiz-Morales, Jorge A; Gomez de la Torre Pretell, Juan C; Dinh, Jeffrey; Granados, Julio; Flores-Villanueva, Pedro O

2010-01-25

We previously reported that the -2518 MCP-1 genotype GG increases the likelihood of developing tuberculosis (TB) in non-BCG-vaccinated Mexicans and Koreans. Here, we tested the hypothesis that this genotype, alone or together with the -1607 MMP-1 functional polymorphism, increases the likelihood of developing TB in BCG-vaccinated individuals. We conducted population-based case-control studies of BCG-vaccinated individuals in Mexico and Peru that included 193 TB cases and 243 healthy tuberculin-positive controls from Mexico and 701 TB cases and 796 controls from Peru. We also performed immunohistochemistry (IHC) analysis of lymph nodes from carriers of relevant two-locus genotypes and in vitro studies to determine how these variants may operate to increase the risk of developing active disease. We report that a joint effect between the -2518 MCP-1 genotype GG and the -1607 MMP-1 genotype 2G/2G consistently increases the odds of developing TB 3.59-fold in Mexicans and 3.9-fold in Peruvians. IHC analysis of lymph nodes indicated that carriers of the two-locus genotype MCP-1 GG MMP-1 2G/2G express the highest levels of both MCP-1 and MMP-1. Carriers of these susceptibility genotypes might be at increased risk of developing TB because they produce high levels of MCP-1, which enhances the induction of MMP-1 production by M. tuberculosis-sonicate antigens to higher levels than in carriers of the other two-locus MCP-1 MMP-1 genotypes studied. This notion was supported by in vitro experiments and luciferase based promoter activity assay. MMP-1 may destabilize granuloma formation and promote tissue damage and disease progression early in the infection. Our findings may foster the development of new and personalized therapeutic approaches targeting MCP-1 and/or MMP-1.

Retrospective study of various conservative treatment options with bacille Calmette-Guérin in bladder urothelial carcinoma T1G3: Maintenance therapy.

Science.gov (United States)

Palou-Redorta, J; Solsona, E; Angulo, J; Fernández, J M; Madero, R; Unda, M; Martínez-Piñeiro, J A; Portillo, J; Chantada, V; Moyano, J L

2016-01-01

To compare various conservative treatment options for high-grade T1 nonmuscle-invasive bladder cancer (NMIBC). Bacille Calmette-Guérin (BCG) is the preferred intravesical treatment for high-grade T1 tumours; however, a number of experts still question the need for maintenance BCG. We retrospectively analysed data from 1039 patients with primary and recurrent T1G3 NMIBC. All patients underwent complete transurethral resection of the bladder tumour (TURBT), with muscle in the sample and multiple bladder biopsies. The patients were treated with the following: only one initial TURBT (n=108), re-TURBT (n=153), induction with 27mg of BCG (Connaught strain) (n=87), induction with 81mg of BCG (n=489) or induction with 81mg of BCG+maintenance (n=202). The time to first recurrence, progression (to T2 or greater or to metastatic disease) and specific mortality of the disease was assessed using the Kaplan-Meier survival function and were compared using the log-rank test and the Cox multivariate regression model of proportional risks. The mean follow-up was 62±39 months. The risk of recurrence was significantly lower for the patients treated with maintenance therapy of 81mg of BCG than in the other treatment groups (P<.001). The risk of tumour progression was also significantly lower for the patients treated with maintenance BCG than for the patients treated only with one TURBT, re-TURBT and with induction therapy with 27mg of BCG (P=.0003). The specific disease mortality was significantly lower with BCG maintenance (9.4%) than with only one TURBT (27.8%; P=.003). In the case of T1G3 NMIBC, a complete dose of BCG with maintenance is associated with better recurrence results than are other conservative treatment modalities. The results of progression and survival specific to the disease were also better with induction BCG, with or without maintenance. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Prevalencia de la infección tuberculosa y por el VIH en los usuarios de un programa de reducción de riesgos para usuarios de drogas por vía parenteral (UDVP

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Álvarez Rodríguez Miguel

1999-01-01

Full Text Available FUNDAMENTO: Determinar la prevalencia de la infección tuberculosa y por el VIH, así como los factores asociados, en la población de usuarios del programa de reducción de riesgos de la ciudad de Lleida. MÉTODOS: La muestra la formaron los nuevos usuarios del programa en el período abril-junio de 1996, entre los los cuales se realizó un cuestionario para la recogida de datos de las variables: edad, sexo, resultado de la prueba de la tuberculina, vacunación BCG, conocimiento de la serología frente al VIH, ingreso en prisión y años de consumo de heroína. Se calculó la prevalencia de la infección tuberculosa y por el VIH, con el intervalo de confianza (IC del 95%. La asociación de ambas variables con el resto de variables del estudio se determinó mediante la odds ratio (OR y su IC del 95% . RESULTADOS: Acudieron 150 pacientes diferentes, de los cuales 45 eran nuevos usuarios. De ellos, el 80,0% eran varones, con una edad media de 31,1 años. La prevalencia de la coinfección fue del 8,9% (IC 95% 2,8-22,1. La prevalencia de la infección tuberculosa fue de 27,3% (IC 95% 12,4-43,0, siendo superior en los que tenían antecedentes de ingreso en prisión (OR=3,4; IC 95% 0,5-27,4. La prevalencia de la infección por el VIH fue del 36,1% (IC 95% 21,3-53,8, siendo superior en los que tenían una antigüedad, en el consumo de heroína, superior a los 11 años ( OR = 7,3; IC 95% 1,0-65,9. CONCLUSIONES: El antecedente de ingreso en prisión es el principal factor de riesgo de la infección tuberculosa. Los años de consumo se asocian con la infección por el VIH, especialmente a partir de los 11 años. Los programas de reducción de riesgos de nuestro país deberían realizar actividades de control de la infección tuberculosa y por VIH.

EFISIENSI PERSAINGAN BANK UMUM SYARIAH: PENDEKATAN DATA ENVELOPMENT ANALYSIS (DEA DAN BOSTON CONSULTING GROUP (BCG

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Rizqon Halal Syah Aji

2015-10-01

Full Text Available Islamic Banking industry in Indonesia has begun dynamic. Product availability and standardization of Islamic banking products, the level of understanding by the public of products of Islamic banks and human resources. Market share of Islamic Banking in Indonesia to lock everything. Recent data Directorate of Islamic Banking in 2011 reached Rp 127,19 T, assets of BPRS amounting to Rp 3.35 T, can be calculated total Islamic banking assets as of October 2011 reached Rp 130,5 T. Financing very important factor, Data Envelopment Analisys (DEA is a measuring instrument of financing. Map of the Bank's performance in the competition between banks can be analyzed by matrix BCG (Boston Consulting Group. This matrix is used to describe the difference between the position of the relative market share of the Bank.DOI: 10.15408/sjie.v3i1.2059

Histologic responses in sixty multibacillary leprosy patients inoculated with autoclaved Mycobacterium leprae and live BCG.

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Meyers, W M; McDougall, A C; Fleury, R N; Neves, R; Reyes, O; Binford, C H

1988-06-01

Sixty lepromatous or borderline lepromatous patients were submitted to immunotherapy with a mixture of autoclaved Mycobacterium leprae and BCG. The histopathologic findings in skin biopsy specimens taken before and after immunotherapy were evaluated independently by six histopathologists in a workshop setting. Their pooled observations on diagnosis and classification were analyzed to assess the histopathologic changes following various periods of immunotherapy. Expressing the results as the average value of five to six independent observations, there were changes in classification of reversal or upgrading toward the tuberculoid end of the leprosy spectrum in 90.5% of the patients initially classified as lepromatous (LL), and in 83.3% of those initially classified as borderline lepromatous (BL). The histopathologic findings amply support the clinical, bacteriologic and immunological changes following immunotherapy from LL or BL, to BL, mid-borderline (BB) or even borderline tuberculoid (BT) leprosy.

Detection of BCG bacteria using a magnetoresistive biosensor: A step towards a fully electronic platform for tuberculosis point-of-care detection.

Science.gov (United States)

Barroso, Teresa G; Martins, Rui C; Fernandes, Elisabete; Cardoso, Susana; Rivas, José; Freitas, Paulo P

2018-02-15

Tuberculosis is one of the major public health concerns. This highly contagious disease affects more than 10.4 million people, being a leading cause of morbidity by infection. Tuberculosis is diagnosed at the point-of-care by the Ziehl-Neelsen sputum smear microscopy test. Ziehl-Neelsen is laborious, prone to human error and infection risk, with a limit of detection of 10 4 cells/mL. In resource-poor nations, a more practical test, with lower detection limit, is paramount. This work uses a magnetoresistive biosensor to detect BCG bacteria for tuberculosis diagnosis. Herein we report: i) nanoparticle assembly method and specificity for tuberculosis detection; ii) demonstration of proportionality between BCG cell concentration and magnetoresistive voltage signal; iii) application of multiplicative signal correction for systematic effects removal; iv) investigation of calibration effectiveness using chemometrics methods; and v) comparison with state-of-the-art point-of-care tuberculosis biosensors. Results present a clear correspondence between voltage signal and cell concentration. Multiplicative signal correction removes baseline shifts within and between biochip sensors, allowing accurate and precise voltage signal between different biochips. The corrected signal was used for multivariate regression models, which significantly decreased the calibration standard error from 0.50 to 0.03log 10 (cells/mL). Results show that Ziehl-Neelsen detection limits and below are achievable with the magnetoresistive biochip, when pre-processing and chemometrics are used. Copyright © 2017 Elsevier B.V. All rights reserved.

Distribution of radioactively labelled myobacterium tuberculosis (65Zn, 35S-BCG) after injection into the anterior chamber. Studies in rabbits with and without anterior chamber sensitisation

International Nuclear Information System (INIS)

Tabillion, M.

1985-01-01

The rabbit model was used to study the behaviour of antigens in the eye as well as their spread to extraocular regions. Prior to the investigations, a test dose of 35 S-labelled and 65 Zn-labelled BCG (Bacille Calmette Guerin) had been injected into the anterior chamber of the eyes of sensitised and non-sensitised rabbits. The percentage of BCG escaping from the aqueous humor and iris was mostly not dependent of the test dose given, nor did the rate of its spread show any relation to the occurrence of an antigen-antibody reaction. On the 32nd day p.i., there were still acid-resisting rods in the uvea, which could be proven by histological examination. As shown by the levels of activity in the iris and ciliary body, the bacteria appear to migrate mostly to these organs and, in the second place, to the choroid membrane. The spread of bacteria in previously sensitised rabbits was not different from the observed in non-sensitised animals. Theories claiming that more antigens are formed in sensitised tissue as compared to non-sensitised tissue cannot be confirmed by the findings revealed here. (TRV) [de

Tuberculous meningitis in children: a review of clinical, laboratory, epidemiological, and therapeutic aspects and of the usefulness of BCG vaccination Meningitis tuberculosa en niños: una revisión de aspectos clínicos, de laboratorio, epidemiológicos y terapéuticos y de la utilidad de la vacunación con BCG

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José William Cornejo Ochoa

2010-08-01

Full Text Available

Tuberculous meningitis is the most frequent extrapulmonary form of tuberculosis in underdeveloped countries, among them Colombia. It is associated with high rates of morbidity and mortality. In this article a review is presented of the following aspects of the disease: clinical, epidemiological, therapeutic, prophylactic by means of BCG vaccination, laboratory diagnosis, and tomographic findings.

La tuberculosis meníngea (MTB es la enfermedad tuberculosa extrapulmonar más frecuente en los países del tercer mundo, incluida Colombia, y tiene tasas altas de morbilidad y mortalidad. En este artículo se presenta una revisión de la literatura sobre los siguientes aspectos de la enfermedad: clínicos, epidemiológicos, de laboratorio, tomográficos, terapéuticos y de prevención con la vacuna BCG.

Influence of initial L-asparagine and glycerol concentrations on the batch growth kinetics of Mycobacterium bovis BCG Influência das concentrações iniciais de asparagina e glicerol sobre a cinética de crescimento submerso de Mycobacterium bovis

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Maria Betania Batista Leal

2004-12-01

Full Text Available The influences of the L-asparagine and glycerol initial concentrations in Sauton medium on the productivities of biomass and colony forming units were studied. The submerged batch cultivations of Mycobacterium bovis were carried out in a 20 L bioreactor. The L-asparagine and glycerol initial concentrations of 4.54 g/L and 25 mL/L, respectively, corresponded to the best biomass productivity, namely 2.5 g/L.day. On the other hand, the concentrations of 2.27 g/L and 25 mL/L, respectively, led to the highest productivity in terms of colony forming units, namely 2.7·10(6 colonies/mg.day. In addition, by means of the relative consumption analysis of L-asparagine and glycerol (50 and 26% respectively, it was concluded that the concentrations of such components could be reduced, with respect to the original Sauton medium composition, aiming the obtainment of an optimal BCG vaccine production in the bioreactor.Estudou-se a influência das concentrações iniciais, no meio de Sauton, de asparagina e glicerol sobre as produtividades, expressas em unidades formadoras de colônias e biomassa microbiana, referentes aos cultivos submersos do Mycobacterium bovis, em biorreator de 20 mL. As concentrações iniciais de 2,27 e 25 mL/L de asparagina e glicerol, respectivamente, conduziram à maior produtividade, em unidades formadoras de colônias, a saber 2,7.10(6 colônias/mg.dia. Por outro lado, as concentrações de 4,54 e 25 mL/L dos mesmos componentes, corresponderam à melhor produtividade em biomassa, a saber: 2,5 g/dia. Através das análises dos consumos relativos de asparagina e glicerol (50 e 26% respectivamente, verificou-se também que as concentrações destes componentes podem ser reduzidas na composição original do meio de Sauton, com o objetivo de obter uma produção otimizada de vacina BCG em bioreator.

High-sensitive and rapid detection of Mycobacterium tuberculosis infection by IFN-γ release assay among HIV-infected individuals in BCG-vaccinated area

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Jiang Weimin

2009-05-01

Full Text Available Abstract Background An accurate test for Mycobacterium tuberculosis infection is urgently needed in immunosuppressed populations. The aim of this study was to investigate the diagnostic power of enzyme-linked immunospot (ELISPOT-based IFN-γ release assay in detecting active and latent tuberculosis in HIV-infected population in bacillus Calmette-Guerin (BCG-vaccinated area. A total of 100 HIV-infected individuals including 32 active tuberculosis patients were recruited. An ELISPOT-based IFN-γ release assay, T-SPOT.TB, was used to evaluate the M. tuberculosis ESAT-6 and CFP-10 specific IFN-γ response. Tuberculin skin test (TST was performed for all recruited subjects. Results The subjects were divided into group HIV+ATB (HIV-infected individuals with active tuberculosis, n = 32, group HIV+LTB (HIV-infected individuals with positive results of T-SPOT.TB assay, n = 46 and group HIV only (HIV-infected individuals with negative results of T-SPOT.TB assay and without evidence of tuberculosis infection, n = 22. In group HIV+ATB and HIV+LTB, T-SPOT.TB positive rate in subjects with TST P 85% in patients with TB treatment for less than 1 month and CD4+ T cells ≥200/μl, while for patients treated for more than 3 months and CD4+ T cells Conclusion ELISPOT-based IFN-γ release assay is more sensitive and rapid for the diagnosis of TB infection in Chinese HIV-infected individuals with history of BCG vaccination, and could be an effective tool for guiding preventive treatment with isoniazid in latently infected people and for TB control in China.

Packaging BCG: standardizing an anti-tuberculosis vaccine in interwar Europe.

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Bonah, Christian

2008-06-01

Using the example of the anti-tuberculosis vaccine BCG during the 1920s and 1930s, this article asks how a labile laboratory-modified bacteria was transformed into a genuine standard vaccine packaged and commercialized as a pharmaceutical product. At the center of the analysis lies the notion of standardization inquiring why and how a local laboratory process with standard operating procedures (SOPs) reached its limits and was transformed when the product faced international distribution. Moving from Paul Ehrlich's initial technological notion of Wertbestimmung referring to a practice physiologically testing the effects of ill-defined antitoxins, the concept of standardization is extended to pharmaceutical and economical meanings implying quality control for biological therapeutic agents produced by a variety of industrial entrepreneurs. Following the request for product uniformity, two ways to maintain levels of compatibility and commonality are depicted opposing SOPs and end-product control. Furthermore, standardization is understood as a spiral, never ending process where progressive transformation of the vaccine in its production and medical uses periodically recreated the necessity of standardization. Developments analyzed are thus understood as a stabilization process aligning laboratory settings, products, and practices with medical theories and practices through technical, bureaucratic, and organizational systems. A paradox of the analysis is that standardization as a historical phenomenon and moment in the history of drug development was initially linked to a problem of under-determination of what was to be standardized and to a knowledge gap before it could become a central concept for quality control.

MicroRNA expression profiling of PPD-B stimulated PBMC from M. bovis-challenged unvaccinated and BCG vaccinated cattle.

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Golby, P; Villarreal-Ramos, B; Dean, G; Jones, G J; Vordermeier, M

2014-10-07

There is an urgent need to identify additional diagnostic biomarkers for bovine TB to complement existing read-out systems such as interferon-gamma and for predictive markers of vaccine efficacy to accelerate vaccine development. To evaluate the potential of miRNAs as such biomarkers, we have analysed their expression in bovine PPD stimulated PBMC isolated from unvaccinated and BCG vaccinated cattle before and following Mycobacterium bovis (M. bovis) infection. Using a bovine microRNA microarray, miR-155 was found to show a significant up-regulation in expression in early (week 2) and late (week 11) M. bovis post-infection samples from unvaccinated cattle, while in BCG vaccinated cattle up-regulation was observed only in late post-infection samples. No differential expression of miR-155 was observed in pre-infection samples from unvaccinated and vaccinated cattle. These observations suggest that miR-155 could be exploited as a marker distinguishing vaccinated from infected animals (DIVA). Analysis by TaqMan RT-PCR, verified the up-regulation of miR-155 in unvaccinated cattle post-infection. Significant correlation was found between the degree of pathology and miR-155 induction in the experimentally infected cattle, suggesting miR-155 is a biomarker of disease development and/or severity. Induction of miR155 expression in cattle sourced from farms with confirmed bTB that tested positive in the tuberculin skin or interferon-gamma blood test was found to be significantly higher in cattle presenting with more advanced pathology (defined by the presence of visible TB lesions) compared to infected cattle without visible pathology and thus likely to be of lower infectivity than those with more advanced disease. In conclusion, our data indicate that miR-155 has potential both as a diagnostic and prognostic biomarker that could be used to identify animals with advanced pathology and as a DIVA test read-out. Its role in the immune biology of bovine TB will also be discussed

Analisis Matriks Boston Consulting Group (BCG untuk Memenangkan Strategi Organisasi (Studi Kasus Perguruan Tinggi Di Kopertis Wilayah III – DKI Jakarta

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Haryadi Sarjono

2013-05-01

Full Text Available This research intends to know position of market growth in higher education, especially Sekolah Tinggi, based on market share, using BCG metrics. Unit analysis is all private higher educations in Kopertis III – DKI Jakarta, consisting of University, Sekolah Tinggi, Institute, and Academics. The object of analysis is the numberof new student admission. Method of data collection in this paper is field research including observation and literature research method. The secondary data used in this study is data from Kopertis region III. Based on the results of the study, it is obtained Sekolah Tinggi for the academic year 2008 and 2009 is in quadrant III (Cash Cow.

Resposta de testes de hipersensibilidade tardia utilizando PPD e outros antígenos em crianças e adolescentes saudáveis e infectados pelo HIV-1 e vacinados com BCG

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Natalia Moriya Xavier da Costa

2011-10-01

Full Text Available INTRODUÇÃO: A contagem de células CD4+ representa marcador da resposta imune celular em pacientes infectados pelo HIV-1. Testes cutâneos de hipersensibilidade tardia (DTH podem ser empregados para avaliar in vivo respostas celulares a antígenos comuns. MÉTODOS: DTH para derivado proteico purificado de tuberculina (PPD, esporotriquina, tricofitina, candidina e estreptoquinase/estreptodornase foram realizados. Foram testados crianças/adolescentes infectados pelo HIV-1 (n=36 e indivíduos saudáveis (n=56, soronegativos para HIV-1/HIV-2 pareados por sexo-idade, todos com cicatriz vacinal por BCG. Teste exato de Fisher foi aplicado (p<0,05. RESULTADOS: Entre as crianças/adolescentes infectados pelo HIV-1, mediana de idade=8,1 anos; 20/36 eram do sexo masculino; 35 casos de transmissão vertical; 34 casos de AIDS sob terapia antirretroviral; mediana de carga viral = 3.04lc10 cópias/ml; mediana de contagem de células CD4+ = 701 células/μl. Entre os infectados e saudáveis a reatividade DTH a pelo menos um dos antígenos foi, respectivamente, 25% (9/36 e 87,5% (49/56 (p<0,001. Reatividade à candidina predominou nos infectados (8/36, 22% e ao PPD nos indivíduos saudáveis (40/56, 71,4%. A reatividade ao PPD entre infectados foi de 8,3% (p<0,01. A mediana da induração ao PPD foi 2,5mm (variação: 2-5mm entre infectados e 6,0mm (variação: 3-15mm entre os saudáveis. Não observamos correlação entre positividade ao PPD e idade. No grupo de infectados, não observamos correlação entre contagens de células CD4+ e reatividade ao DTH. CONCLUSÕES: Respostas DTH significativamente diminuídas, incluindo a reatividade ao PPD foram observadas em crianças/adolescentes infectados pelo HIV-1 comparadas com controles saudáveis, provavelmente refletindo doença avançada e supressão da imunidade mediada por células T.

The 3H-thymidine incorporation into the DNA of different tissues of the guinea pip after BCG-vaccination and the radiation insultus

International Nuclear Information System (INIS)

Langbein, U.

1976-01-01

The radioprotective effects of BCG vaccines have been examined. The 3 H-thymidine incorporation into the DNA of different tissues of the guinea-pig after solitary whole-body irradiation by the doses of 160, 400, and 700 R have been used as a parameter for radiation injuries and radioprotection. The specific activity of DNA has been detected by means of liquid scintillation counting and by indirect photomeric determination of the amount at 7 h p.r. It has been revealed that independent of the chosen irradiation dose, there was no significant difference in the rate of DNA synthesis in the duodenal, testicular, bone marrow, liver, and lymphatic ganglion tissues of animals vaccinated 30 days before irradiation insultus and the rate of DNA synthesis in normal animals. Based on medical evidence, effect principles which can be observed on other antigenous radioprotective substances can be excluded this time. The dose effect curve has qualitatively the same features as the curves of cell cultures and synchronized cell systems in mammals. Furthermore, the process of DNA synthesis was observed for 56 days. During this observation period there was no significant difference to be seen in the rate of duodenal, testicular, bone marrow, and liver tissues in vaccinated and in normal animals. Only in lymphatic tissues the synthesis rate of vaccinated animals has shown a significantly more decreasing tendency than that of normal animals. A relation concerning radioprotective substances containing SH-groups and 'short-term' protectors (endotoxines) could be excluded because of medical evidence. It is suggested to carry out further tests with parameters affecting the RES in order to comprehend radioprotection after BCG vaccination. (orig./MG) [de

Current clinical practice gaps in the treatment of intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC) with emphasis on the use of bacillus Calmette-Guerin (BCG): results of an international individual patient data survey (IPDS)

NARCIS (Netherlands)

Witjes, J.A.; Palou, J.; Soloway, M.; Lamm, D.; Kamat, A.M.; Brausi, M.; Persad, R.; Buckley, R.; Colombel, M.; Bohle, A.

2013-01-01

OBJECTIVES: To examine the management of intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC), particularly with regard to the use of bacillus Calmette-Guerin (BCG) therapy, in North America and Europe. To compare NMIBC management practices to European Association of Urology (EAU)

Portable exhausters POR-004 SKID B, POR-005 SKID C, POR-006 SKID D storage plan

International Nuclear Information System (INIS)

Nelson, O.D.; Keller, G.M.

1997-01-01

This document provides a storage plan for portable exhausters POR-004 SKID B, POR-005 SKID C, AND POR-006 SKID D. The exhausters will be stored until they are needed by the TWRS (Tank Waste Remediation Systems) Saltwell Pumping Program. The storage plan provides criteria for portable exhauster storage, periodic inspections during storage, and retrieval from storage

The effect of current Schistosoma mansoni infection on the immunogenicity of a candidate TB vaccine, MVA85A, in BCG-vaccinated adolescents: An open-label trial.

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Anne Wajja

2017-05-01

Full Text Available Helminth infection may affect vaccine immunogenicity and efficacy. Adolescents, a target population for tuberculosis booster vaccines, often have a high helminth burden. We investigated effects of Schistosoma mansoni (Sm on the immunogenicity and safety of MVA85A, a model candidate tuberculosis vaccine, in BCG-vaccinated Ugandan adolescents.In this phase II open label trial we enrolled 36 healthy, previously BCG-vaccinated adolescents, 18 with no helminth infection detected, 18 with Sm only. The primary outcome was immunogenicity measured by Ag85A-specific interferon gamma ELISpot assay. Tuberculosis and schistosome-specific responses were also assessed by whole-blood stimulation and multiplex cytokine assay, and by antibody ELISAs.Ag85A-specific cellular responses increased significantly following immunisation but with no differences between the two groups. Sm infection was associated with higher pre-immunisation Ag85A-specific IgG4 but with no change in antibody levels following immunisation. There were no serious adverse events. Most reactogenicity events were of mild or moderate severity and resolved quickly.The significant Ag85A-specific T cell responses and lack of difference between Sm-infected and uninfected participants is encouraging for tuberculosis vaccine development. The implications of pre-existing Ag85A-specific IgG4 antibodies for protective immunity against tuberculosis among those infected with Sm are not known. MVA85A was safe in this population.ClinicalTrials.gov NCT02178748.

Effect of vaccine dose on the safety and immunogenicity of a candidate TB vaccine, MVA85A, in BCG vaccinated UK adults.

Science.gov (United States)

Pathan, Ansar A; Minassian, Angela M; Sander, Clare R; Rowland, Rosalind; Porter, David W; Poulton, Ian D; Hill, Adrian V S; Fletcher, Helen A; McShane, Helen

2012-08-17

A non-randomised, open-label, Phase I safety and immunogenicity dose-finding study to assess the safety and immunogenicity of the candidate TB vaccine Modified Vaccinia virus Ankara expressing Antigen 85A (MVA85A) from Mycobacterium tuberculosis (MTB) in healthy adult volunteers previously vaccinated with BCG. Healthy BCG-vaccinated volunteers were vaccinated with either 1×10(7) or 1×10(8)PFU of MVA85A. All adverse events were documented and antigen specific T cell responses were measured using an ex vivo IFN-γ ELISPOT assay. Safety and immunogenicity were compared between the 2 dose groups and with a previous trial in which a dose of 5×10(7)PFU MVA85A had been administered. There were no serious adverse events recorded following administration of either 1×10(7) or 1×10(8)PFU of MVA85A. Systemic adverse events were more frequently reported following administration of 1×10(8)PFU of MVA85A when compared to either 5×10(7) or 1×10(7)PFU of MVA85A but were mild or moderate in severity and resolved completely within 7 days of immunisation. Antigen specific T cell responses as measured by the IFN-γ ELISPOT were significantly higher following immunisation in adults receiving 1×10(8)PFU compared to the 5×10(7) and 1×10(7) doses. Additionally, a broader range of Ag85A epitopes are detected following 1×10(8)PFU of MVA85A. A higher dose of 1×10(8)PFU of MVA85A is well-tolerated, increases the frequency of IFN-γ secreting T cells detected following immunisation and broadens the range of Ag85A epitopes detected. Copyright © 2012 Elsevier Ltd. All rights reserved.

A safe and efficient BCG vectored vaccine to prevent the disease caused by the human Respiratory Syncytial Virus.

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Rey-Jurado, Emma; Soto, Jorge; Gálvez, Nicolás; Kalergis, Alexis M

2017-09-02

The human Respiratory Syncytial Virus (hRSV) causes lower respiratory tract infections including pneumonia and bronchiolitis. Such infections also cause a large number of hospitalizations and affects mainly newborns, young children and the elderly worldwide. Symptoms associated with hRSV infection are due to an exacerbated immune response characterized by low levels of IFN-γ, recruitment of neutrophils and eosinophils to the site of infection and lung damage. Although hRSV is a major health problem, no vaccines are currently available. Different immunization approaches have been developed to achieve a vaccine that activates the immune system, without triggering an unbalanced inflammation. These approaches include live attenuated vaccine, DNA or proteins technologies, and the use of vectors to express proteins of the virus. In this review, we discuss the host immune response to hRSV and the immunological mechanisms underlying an effective and safe BCG vectored vaccine against hRSV.

Lack of a Negative Effect of BCG-Vaccination on Child Psychomotor Development: Results from the Danish Calmette Study - A Randomised Clinical Trial.

Science.gov (United States)

Kjærgaard, Jesper; Stensballe, Lone Graff; Birk, Nina Marie; Nissen, Thomas Nørrelykke; Foss, Kim Thestrup; Thøstesen, Lisbeth Marianne; Pihl, Gitte Thybo; Andersen, Andreas; Kofoed, Poul-Erik; Pryds, Ole; Greisen, Gorm

2016-01-01

To assess the non-specific effect of Bacillus Calmette-Guérin (BCG) vaccination at birth on psychomotor development. This is a pre-specified secondary outcome from a randomised, clinical trial. Maternity units and paediatric wards at three university hospitals in Denmark. Children born at gestational age (GA) 32 weeks and above. All women planning to give birth at the three sites were invited during the recruitment period. Out of 4262 randomised children, 144 were premature (GA Psychomotor development measured using Ages and Stages Questionnaire (ASQ) completed by the parents at 12 months. Additionally, parents of premature children (gestational age psychomotor development was excluded in term children. ClinicalTrials.gov NCT01694108.

Histoplasmosis en América Latina

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Ricardo Negroni

2011-03-01

Francisco, Paraná y de La Plata, así como la Serra do Mar, en Suramérica. Los factores de riesgo para la histoplasmosis pulmonar crónica son el sexo masculino, la edad mayor de 50 años, la raza blanca, el hábito de fumar y la enfermedad pulmonar obstructiva crónica. Las formas progresivas diseminadas se observan con mayor frecuencia en niños menores de dos años y en adultos del sexo masculino, de más de 54 años de edad. La histoplasmosis diseminada crónica puede presentarse en estos pacientes aun en ausencia de antecedentes claros de inmunodeficiencia. Las personas con diversos grados de compromiso de la inmunidad mediada por células, son propensas a presentar las formas graves de histoplasmosis diseminada, cuyo curso es tanto más agudo y grave cuanto más serio sea el deterioro de la inmunidad. La causa más común de histoplasmosis diseminada progresiva es la infección avanzada por virus de la inmunodeficiencia humana (VIH; le siguen las leucemias linfáticas tratadas con medicamentos antiblásticos, los linfomas, los pacientes que reciben corticosteroides en altas dosis durante lapsos prolongados, los receptores de trasplantes de órganos sólidos con rechazo crónico, los que presentan enfermedades autoinmunitarias, el síndrome de Sweet y los enfermos tratados con anticuerpos monoclonales contra el factor de necrosis tumoral. La incidencia real de la histoplasmosis es desconocida por tratarse de una enfermedad cuya notificación no es obligatoria; la mayor parte de los datos provienen de publicaciones o de la experiencia personal de expertos. En América Latina predominan las formas respiratorias agudas, que corresponden a infecciones primarias sintomáticas, y las formas diseminadas progresivas relacionadas con el sida. Las primeras se manifiestan habitualmente en brotes de un número variable de casos, desde seis hasta más de un centenar, y se vinculan a "focos epidémicos", en donde muchas veces se ha conseguido el aislamiento del agente causal del

PPD-induced monocyte mitochondrial damage is associated with a protective effect to develop tuberculosis in BCG vaccinated individuals: A cohort study.

Science.gov (United States)

Marín, Diana; Marín, Nancy; Del Corral, Helena; López, Lucelly; Ramirez-Agudelo, María Elena; Rojas, Carlos A; Arbeláez, María P; García, Luis F; Rojas, Mauricio

2017-01-01

The mechanisms of mononuclear phagocyte death have been associated with the permissiveness and resistance to mycobacterial replication, but it remains unknown whether or not they help predict the risk of developing TB. To describe the factors associated with the induction of monocyte mitochondrial and membrane damage in response to PPD as well as determine if this type of damage might predict the susceptibility of developing active tuberculosis in a cohort of household contacts (HHCs) from Medellin, Colombia from 2005 to 2008. The prospective cohort study contains 2060 HHCs patients with pulmonary tuberculosis who were meticulously followed for two years. A survey of the socio-demographic, clinical, epidemiological factors and blood samples were collected. Mononuclear cell cultures were stimulated with or without PPD and the type of monocyte death was determined by the flow of cytometry, an indicator was also used for its analysis. Logistic regression was adjusted by the Generalized Estimations Equations and the survival was estimated with the Kaplan-Meier and Cox regression. Confidence intervals were used for estimating the association. 1,859 out of 2,060 blood samples of the HHCs patients analyzed showed monocyte death. In response to PPD, 83.4% underwent mitochondrial damage while 50.9% had membrane damage. The membrane damage in response to PPD was higher in children under 4 years (OR: 1.57; (95% CI: 1.1 to 2.4) and the HHCs who slept regularly in the same household has an index case of (OR: 1.54; 95% CI: 1.0 to 2.3). After adjustment by age, comorbidities, nutritional status, proximity to index case and overcrowding, the risk of developing active TB among BCG vaccinated HHCs individuals with induction of mitochondrial damage was HR = 0.19 (95% CI: 0.1 to 0.5). The induction of monocytes mitochondrial damage by PPD stimulation correlates with protection of TB disease development in BCG-vaccinated HHCs. This represents a potential tool to predict susceptibility

Celulitis por citomegalovirus

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A. Ruiz Lascano

2002-12-01

Full Text Available Las lesiones cutáneas por citomegalovirus (CMV son infrecuentes y a menudo una manifestación tardía de una enfermedad sistémica, que generalmente anuncia un curso fatal. Comunicamos un caso de celulitis por CMV: una mujer de 70 años con trasplante renal efectuado 1 mes antes de la consulta, terapia inmunosupresora con ciclosporina A y metilprednisona. La paciente ingresó por fiebre, dolor e impotencia funcional en pierna derecha. Comprobamos la existencia de una placa de 8 por 4 cm eritematoedematosa. La tratamos con antibióticos sin mejoría, por lo que realizamos un estudio histopatológico de piel que mostró cambios citopáticos compatibles con infección por CMV. Los cultivos bacteriológicos y micológicos fueron negativos. La inmunohistoquímica específica para CMV y el estudio de reacción en cadena de la polimerasa (PCR de la biopsia de piel fueron positivas, al igual que la antigenemia. El tratamiento con ganciclovir produjo la mejoría del cuadro clínico. En la literatura revisada no hemos encontrado la celulitis como manifestación de enfermedad cutánea por CMV.

Serum, liver, and lung levels of the major extracellular matrix components at the early stage of BCG-induced granulomatosis depending on the infection route.

Science.gov (United States)

Kim, L B; Shkurupy, V A; Putyatina, A N

2015-01-01

Experiments on the model of mouse BCG-induced granulomatous showed that the content of glycosaminoglycans and proteoglycans in the extracellular matrix of the liver and lungs are changed at the early stages of inflammation (days 3 and 30 postinfection) before cell destruction in the organs begins. This is related to degradation of extracellular matrix structures. Their high content in the blood and interstitium probably contributes to the formation of granulomas, fibroblast proliferation and organ fibrosis. These processes depend on the infection route that determines different conditions for generalization of the inflammation process. Intravenous method of vaccine injection is preferable to use when designing the experiments simulating tuberculosis granulomatosis, especially for the analysis of its early stages.

Portable exhauster POR-007/Skid E and POR-008/Skid F storage plan

International Nuclear Information System (INIS)

Nelson, O.D.

1998-01-01

This document provides storage requirements for 1,000 CFM portable exhausters POR-O07/Skid E and POR-008/Skid F. These requirements are presented in three parts: preparation for storage, storage maintenance and testing, and retrieval from storage. The exhauster component identification numbers listed in this document contain the prefix POR-007 or POR-008 depending on which exhauster is being used

DESAJUSTE EDUCATIVO POR REGIONES EN COLOMBIA: ¿COMPETENCIA POR SALARIOS O POR PUESTOS DE TRABAJO?

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Maribel Castillo Caicedo

2007-06-01

Full Text Available Este trabajo aporta una perspectiva del fenómeno de la sobreeducación, entendida como un desajuste por exceso, entre el nivel educativo alcanzado por el individuo y el exigido por el puesto de trabajo en el cual se desempeña; esto se debe a que existe una demanda laboral estrecha de puestos de trabajo para personas calificadas en Colombia. Se analizan las contribuciones empíricas existentes y el debate sobre las mismas; se examinan las teorías que permiten explicar la existencia de un desajuste educativo y se realiza una revisión de la literatura internacional y nacional sobre el tema. Adicionalmente, se plantean una serie de hipótesis para desarrollar un esquema que permita determinar el comportamiento del individuo en el fenómeno de la sobreeducación.

Desajuste educativo por regiones en Colombia: ¿competencia por salarios o por puestos de trabajo?

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Castillo Caicedo Maribel

2007-08-01

Full Text Available Este trabajo aporta una perspectiva del fenómeno de la sobreeducación,
entendida como un desajuste por exceso, entre el nivel educativo alcanzado
por el individuo y el exigido por el puesto de trabajo en el cual se
desempeña; esto se debe a que existe una demanda laboral estrecha de
puestos de trabajo para personas calificadas en Colombia. Se analizan las
contribuciones empíricas existentes y el debate sobre las mismas; se
examinan las teorías que permiten explicar la existencia de un desajuste
educativo y se realiza una revisión de la literatura internacional y
nacional sobre el tema. Adicionalmente, se plantean una serie de hipótesis
para desarrollar un esquema que permita determinar el comportamiento
del individuo en el fenómeno de la sobreeducación.

Structural Insights into the PorK and PorN Components of the Porphyromonas gingivalis Type IX Secretion System.

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Dhana G Gorasia

2016-08-01

Full Text Available The type IX secretion system (T9SS has been recently discovered and is specific to Bacteroidetes species. Porphyromonas gingivalis, a keystone pathogen for periodontitis, utilizes the T9SS to transport many proteins including the gingipain virulence factors across the outer membrane and attach them to the cell surface via a sortase-like mechanism. At least 11 proteins have been identified as components of the T9SS including PorK, PorL, PorM, PorN and PorP, however the precise roles of most of these proteins have not been elucidated and the structural organization of these components is unknown. In this study, we purified PorK and PorN complexes from P. gingivalis and using electron microscopy we have shown that PorN and the PorK lipoprotein interact to form a 50 nm diameter ring-shaped structure containing approximately 32-36 subunits of each protein. The formation of these rings was dependent on both PorK and PorN, but was independent of PorL, PorM and PorP. PorL and PorM were found to form a separate stable complex. PorK and PorN were protected from proteinase K cleavage when present in undisrupted cells, but were rapidly degraded when the cells were lysed, which together with bioinformatic analyses suggests that these proteins are exposed in the periplasm and anchored to the outer membrane via the PorK lipid. Chemical cross-linking and mass spectrometry analyses confirmed the interaction between PorK and PorN and further revealed that they interact with the PG0189 outer membrane protein. Furthermore, we established that PorN was required for the stable expression of PorK, PorL and PorM. Collectively, these results suggest that the ring-shaped PorK/N complex may form part of the secretion channel of the T9SS. This is the first report showing the structural organization of any T9SS component.

Structural Insights into the PorK and PorN Components of the Porphyromonas gingivalis Type IX Secretion System.

Science.gov (United States)

Gorasia, Dhana G; Veith, Paul D; Hanssen, Eric G; Glew, Michelle D; Sato, Keiko; Yukitake, Hideharu; Nakayama, Koji; Reynolds, Eric C

2016-08-01

The type IX secretion system (T9SS) has been recently discovered and is specific to Bacteroidetes species. Porphyromonas gingivalis, a keystone pathogen for periodontitis, utilizes the T9SS to transport many proteins including the gingipain virulence factors across the outer membrane and attach them to the cell surface via a sortase-like mechanism. At least 11 proteins have been identified as components of the T9SS including PorK, PorL, PorM, PorN and PorP, however the precise roles of most of these proteins have not been elucidated and the structural organization of these components is unknown. In this study, we purified PorK and PorN complexes from P. gingivalis and using electron microscopy we have shown that PorN and the PorK lipoprotein interact to form a 50 nm diameter ring-shaped structure containing approximately 32-36 subunits of each protein. The formation of these rings was dependent on both PorK and PorN, but was independent of PorL, PorM and PorP. PorL and PorM were found to form a separate stable complex. PorK and PorN were protected from proteinase K cleavage when present in undisrupted cells, but were rapidly degraded when the cells were lysed, which together with bioinformatic analyses suggests that these proteins are exposed in the periplasm and anchored to the outer membrane via the PorK lipid. Chemical cross-linking and mass spectrometry analyses confirmed the interaction between PorK and PorN and further revealed that they interact with the PG0189 outer membrane protein. Furthermore, we established that PorN was required for the stable expression of PorK, PorL and PorM. Collectively, these results suggest that the ring-shaped PorK/N complex may form part of the secretion channel of the T9SS. This is the first report showing the structural organization of any T9SS component.

Modification of in vitro and in vivo BCG cell wall-induced immunosuppression by treatment with chemotherapeutic agents or indomethacin

International Nuclear Information System (INIS)

DeSilva, M.A.; Wepsic, H.T.; Mizushima, Y.; Nikcevich, D.A.; Larson, C.H.

1985-01-01

The in vitro inhibition of spleen cell blastogenesis response and the in vivo enhancement of tumor growth are phenomena associated with BCG cell wall (BCGcw) immunization. What effect treatment with chemotherapeutic agents and the prostaglandin inhibitor indomethacin would have on the in vitro and in vivo responses to BCGcw immunization was evaluated. In vitro blastogenesis studies showed that chemotherapy pretreatment prior to immunization with BCGcw resulted in a restoration of the spleen cell blastogenesis response. In blastogenesis addback studies, where BCGcw-induced irradiated splenic suppressor cells were admixed with normal cells, less inhibition of blastogenesis occurred when spleen cells were obtained from rats that had received the combined treatment of chemotherapy and BCGcw immunization versus only BCGcw immunization. The cocultivation of spleen cells from BCGcw-immunized rats with indomethacin resulted in a 30-40% restoration of the blastogenesis response. In vivo studies showed that BCGcw-mediated enhancement of intramuscular tumor growth of the 3924a ACI rat tumor could be abrogated by either pretreatment with busulfan or mitomycin or by the feeding of indomethacin

Disseminated toxoplasmosis in an immunocompetent patient from Peruvian Amazon Toxoplasmosis diseminada en un paciente inmunocompetente procedente de la Amazonía peruana

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Juan Nunura

2010-04-01

Full Text Available We report a case of severe toxoplasmosis in an immunocompetent patient, characterized by pneumonia, retinochoroiditis, hepatitis and myositis. Diagnosis was confirmed by serology, T. gondii in thick blood smear and presence of bradyzoites in muscle biopsy. Treatment with pyrimethamine plus sulfadoxine was successful but visual acuity and hip extension were partially recovered. This is the first case report of severe toxoplasmosis in an immunocompetent patient from Peru.Reportamos un caso de toxoplasmosis severa en un paciente inmunocompetente caracterizado por neumonía, retinocoroiditis, hepatitis y miositis. El diagnóstico fue confirmado por serología, el hallazgo de T. gondii en gota gruesa y la presencia de bradizoitos en biopsia muscular. El tratamiento con pirimetamina mas sulfadoxina fue exitoso pero solo hubo una parcial recuperación de la agudeza visual y de la capacidad de extensión de la cadera. Este es el primer reporte de un caso de toxoplasmosis severa en el Perú.

The PorX response regulator of the Porphyromonas gingivalis PorXY two-component system does not directly regulate the Type IX secretion genes but binds the PorL subunit.

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Maxence S Vincent

2016-08-01

Full Text Available The Type IX secretion system (T9SS is a versatile multi-protein complex restricted to bacteria of the Bacteriodetes phylum and responsible for the secretion of surface attachment of diverse proteins that participate to S-layer formation, gliding motility or pathogenesis. The T9SS is poorly characterized but a number of proteins involved in the assembly of the secretion apparatus in the oral pathogen Porphyromonas gingivalis have been identified based on genome substractive analyses. Among these proteins, PorY and PorX encode typical two-component system (TCS sensor and CheY-like response regulator respectively. Although the porX and porY genes do not localize at the same genetic locus, it has been proposed that PorXY form a bona fide TCS. Deletion of the porX in P. gingivalis causes a slight decrease of the expression of a number of other T9SS genes, including sov, porT, porP, porK, porL, porM, porN and porY. Here, we show that PorX and the soluble cytoplasmic domain of PorY interact. Using electrophoretic mobility shift, DNA-protein co-purification and heterologous host expression assays, we showed that PorX does not bind and does not directly regulate expression of the T9SS genes. Finally, we show that PorX interacts with the cytoplasmic domain of PorL, a component of the T9SS membrane core complex and propose that the CheY-like PorX protein might be involved in the dynamics of the T9SS.

The PorX Response Regulator of the Porphyromonas gingivalis PorXY Two-Component System Does Not Directly Regulate the Type IX Secretion Genes but Binds the PorL Subunit

Science.gov (United States)

Vincent, Maxence S.; Durand, Eric; Cascales, Eric

2016-01-01

The Type IX secretion system (T9SS) is a versatile multi-protein complex restricted to bacteria of the Bacteriodetes phylum and responsible for the secretion or cell surface exposition of diverse proteins that participate to S-layer formation, gliding motility or pathogenesis. The T9SS is poorly characterized but a number of proteins involved in the assembly of the secretion apparatus in the oral pathogen Porphyromonas gingivalis have been identified based on genome substractive analyses. Among these proteins, PorY, and PorX encode typical two-component system (TCS) sensor and CheY-like response regulator respectively. Although the porX and porY genes do not localize at the same genetic locus, it has been proposed that PorXY form a bona fide TCS. Deletion of porX in P. gingivalis causes a slight decrease of the expression of a number of other T9SS genes, including sov, porT, porP, porK, porL, porM, porN, and porY. Here, we show that PorX and the soluble cytoplasmic domain of PorY interact. Using electrophoretic mobility shift, DNA-protein co-purification and heterologous host expression assays, we demonstrate that PorX does not bind T9SS gene promoters and does not directly regulate expression of the T9SS genes. Finally, we show that PorX interacts with the cytoplasmic domain of PorL, a component of the T9SS membrane core complex and propose that the CheY-like PorX protein might be involved in the dynamics of the T9SS. PMID:27630829

Strategies to eradicate minimal residual disease in small cell lung cancer: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.

Science.gov (United States)

Krug, L M; Grant, S C; Miller, V A; Ng, K K; Kris, M G

1999-10-01

In the last 25 years, treatment for small cell lung cancer (SCLC) has improved with advances in chemotherapy and radiotherapy. Standard chemotherapy regimens can yield 80% to 90% response rates and some cures when combined with thoracic irradiation in limited-stage patients. Nonetheless, small cell lung cancer has a high relapse rate due to drug resistance; this has resulted in poor survival for most patients. Attacking this problem requires a unique approach to eliminate resistant disease remaining after induction therapy. This review will focus on three potential strategies: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.

Mycobacterial RNA isolation optimized for non-coding RNA: high fidelity isolation of 5S rRNA from Mycobacterium bovis BCG reveals novel post-transcriptional processing and a complete spectrum of modified ribonucleosides.

Science.gov (United States)

Hia, Fabian; Chionh, Yok Hian; Pang, Yan Ling Joy; DeMott, Michael S; McBee, Megan E; Dedon, Peter C

2015-03-11

A major challenge in the study of mycobacterial RNA biology is the lack of a comprehensive RNA isolation method that overcomes the unusual cell wall to faithfully yield the full spectrum of non-coding RNA (ncRNA) species. Here, we describe a simple and robust procedure optimized for the isolation of total ncRNA, including 5S, 16S and 23S ribosomal RNA (rRNA) and tRNA, from mycobacteria, using Mycobacterium bovis BCG to illustrate the method. Based on a combination of mechanical disruption and liquid and solid-phase technologies, the method produces all major species of ncRNA in high yield and with high integrity, enabling direct chemical and sequence analysis of the ncRNA species. The reproducibility of the method with BCG was evident in bioanalyzer electrophoretic analysis of isolated RNA, which revealed quantitatively significant differences in the ncRNA profiles of exponentially growing and non-replicating hypoxic bacilli. The method also overcame an historical inconsistency in 5S rRNA isolation, with direct sequencing revealing a novel post-transcriptional processing of 5S rRNA to its functional form and with chemical analysis revealing seven post-transcriptional ribonucleoside modifications in the 5S rRNA. This optimized RNA isolation procedure thus provides a means to more rigorously explore the biology of ncRNA species in mycobacteria. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Low in vitro response to PPD and PHA in lymphocytes from BCG-induced pleurisy in guinea pigs

International Nuclear Information System (INIS)

Widstroem, O.; Nilsson, B.S.

1982-01-01

In order to study any correlation between functional properties of lymphocytes in BCG-induced pleural exudation and the development of the pleurisy a previously described experimental model was used. This model with a duration of effusion of more than 17 days has characteristic stages. From the third day and onwards there are lymphocytes in sufficient amount for in vitro cultures. Proliferation of lymphocytes from the fluid was measured as uptake of 14 C-thymidine. The response of the lymphocytes to PPD tuberculin and to phytohemagglutinin (PHA) was studied, and their spontaneous activity was measured. Comparisons were made with lymphocytes from regional lymph nodes. Pleural lymphocytes sampled on the third post-induction day did not respond to PPD or PHA stimulation. In later stages, pleural lymphocytes were stimulated by PPD to approximately the same degree as the lymph node lymphocytes. The response to PHA was weak at all stages of pleurisy, though in later stages there were some cases with high values. Variations in activation ability, related to disease staging, were demonstrated. However, low activities, and variability of the responces, without concomitant variations in disease, speak against a connection between the course of disease and functional status of the lymphocytes as measured in this study. (authors)

Successful immunotherapy with micrococcus, BCG or related polysaccharides on L1210 leukaemia after BCNU chemotherapy.

Science.gov (United States)

Verloes, R.; Atassi, G.; Dumont, P.; Kanarek, L.

1981-01-01

The experiments aimed at evaluating the optimal parameters in the chemo-immunotherapeutic treatment of the L1210 lymphoid leukaemia grafted to [female BALB/c (H2d) X male DBA/2 (H2d)]F1 hybrid mice, hereafter referred to as CDF1 mice. In vitro irradiation of leukaemic ascites cells by X- or gamma-rays and subsequent inoculation in mice showed that optimum immunogenicity is radiation dose-dependent. Grafting mice with 10(7) leukaemic ascites cells irradiated at optimum dose (80 GyX- or gamma-rays) delays mortality of the animals when challenged later with untreated L1210 cells, but is unable to cure mice. By contrast, specific immunoprophylaxis induced by Micrococcus, complement-triggering polysaccharides or BCG and irradiated leukaemic cells was able to protect mice against grafts of 10(4) L1210 cells. The i.p. route was notably superior to the i.v. route. When mice bearing advanced L1210 tumour were treated by chemotherapy (12 mg/kg of BCNU) on Day 6.5 after grafting 10(4) L1210 cells and subsequently treated by immunotherapy, a very high percentage (up to 90%) of mice with 10(8) leukaemic cells could be cured by repeated 1mg injections of bacterium or polysaccharide, and challenge with irradiated leukaemic cells was unnecessary. Because of the high cure rate obtained, the very regular response pattern and the non-pathogenicity, the bacterium Micrococcus lysodeikticus would seem a promising new candidate for chemo-immunotherapeutic antitumour strategies. PMID:7470382

Virulencia de cepas de Listeria monocytogenes procedentes de cabras y sus derivados

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Guicela Ramírez Bernal

2014-01-01

Full Text Available Se evaluó la virulencia de cepas de Listeria monocytogenes todas de serotipo 4b procedentes de cabras y sus derivados. Se observaron niveles de virulencia variables cuando se comparó la virulencia relativa (porcentaje de letalidad en ratones BALB/c inoculados vía intravenosa o intragástrica y su capacidad para infectar macrófagos J774A.1, y células epiteliales Caco-2. Dos cepas obtenidas de alimento de cabras produjeron 100 % de letalidad por ambas vías de inoculación y no mostraron diferencia significativa con la cepa testigo (P>0.05 respecto al porcentaje de invasión y a los parámetros de la cinética de crecimiento cuadrática observada en ambas líneas celulares. Si bien todas las cepas lograron invadir las células Caco-2, solamente algunas consiguieron invadir el bazo después de la inoculación por vía intragástrica. Las dos cepas provenientes de alimento de cabras fueron las más virulentas, representando un riesgo para la salud humana y animal, ya que pueden ser diseminadas en el hato y de este a otras explotaciones o a las instalaciones donde se elaboran alimentos.

Encefalopatía por priones

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Carlos Colegial

1999-01-01

Full Text Available Las encefalopatías espongiformes por priones son enfermedades neurodegenerativas que pueden ser esporádicas o transmisibles, ya sea por mecanismos infecciosos o hereditarios. Su investigación ha planteado enormes retos y en el recorrido histórico en busca de su causa dos médicos han recibido el premio Nobel de Medicina: Carleton Gajdusek, por sus trabajos en Nueva Guinea donde describió la transmisión infecciosa por ritos canibalísticos, que llevó a estudios de transmisión experimental en chimpancés y a su teoría de los "virus lentos" (por el largo período de incubación de la enfermedad.

O impacto da fibrose cística no perfil imunológico de pacientes pediátricos

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Daniela M. Bernardi

2013-02-01

Full Text Available OBJETIVO: Comparar o estado imunológico de 44 pacientes pediátricos com fibrose cística (FCa umgrupo-controle formado por 16 indivíduos saudáveis. MÉTODOS: Foram selecionados para o estudo pacientes com FC com idade entre 3 e 12 anos, apresentando um escore clínico moderado e bom. Foram avaliados a glutationa eritrocitária, a produção de espécies reativas de oxigênio, citocinas (TNF-α, IFN-γ, IL-8, IL-6, IL-10 em culturas de células mononucleares do sangue periférico em condições espontâneas e estimuladas por BCG ou PHA, a concentração sérica de TGF-β2, IgA, IgG, IgM, IgE e IgA salivar. RESULTADOS :A produção espontânea de TNF-α, IL-6 e IL-10, a produção de IL-6 estimulada por PHA e TGF-β2, IgA e IgG séricas aumentaram em amostras de pacientes com FC. Indivíduos saudáveis tiveram uma produção mais elevada de TNF-α em resposta a BCG. CONCLUSÃO: Apesar de os pacientes com FC parecerem clinicamente estáveis, os resultados de seus exames de sangue periférico mostraram que houve um impacto sobre o sistema imunológico.

Casipoemas por Navidad : (1969-2010)

OpenAIRE

Sena Medina, Guillermo

2011-01-01

PRESENTACIÓN AL AIRE DE LA POESÍA RELIGIOSA Y NAVIDEÑA DE GUILLERMO SENA MEDINA Constituye un gran honor hacer la presentación de Guillermo Sena Medina por un doble motivo; por la larga y sincera amistad que nos une desde hace muchos años al socaire de nuestra común afición por la Historia, como cronistas oficiales de nuestros municipios; y, sobre todo y particularmente, por su rica y profunda personalidad como hombre de letras, nacida de su aún más rica y profunda personalidad humana. A...

Evolution of NADPH-cytochrome P450 oxidoreductases (POR) in Apiales - POR 1 is missing

DEFF Research Database (Denmark)

Andersen, Trine Bundgaard; Hansen, Niels Bjørn; Laursen, Tomas

2016-01-01

The NADPH-dependent cytochrome P450 oxidoreductase (POR) is the obligate electron donor to eukaryotic microsomal cytochromes P450 enzymes. The number of PORs within plant species is limited to one to four isoforms, with the most common being two PORs per plant. These enzymes provide electrons to ...... (available from the SRA at NCBI). All three genes were shown to be functional upon reconstitution into nanodiscs, confirming that none of the isoforms are pseudogenes....

Osteomalacia inducida por tumor: hemangiopericitoma rinosinusal

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Enriqueta M. Serafini

2013-02-01

Full Text Available La osteomalacia inducida por tumor es una rara enfermedad del metabolismo óseo caracterizada por el aumento en la excreción de fosfato a nivel renal seguido de hipofosfatemia. Es causada por agentes fosfatúricos producidos por determinados tumores. La resección total del tumor resulta en la completa reversión de las anormalidades bioquímicas, la desaparición de las manifestaciones clínicas y los hallazgos en los estudios por imágenes. Presentamos el caso de un varón de 61 años con cuadro clínico y laboratorio compatibles con osteomalacia oncogénica inducida por tumor mesenquimático de localización rinosinusal. En nuestro caso el diagnóstico histológico correspondió a una neoplasia de tipo vascular: hemangiopericitoma.

Intravesical Bacillus Calmette-Guérin therapy for murine bladder tumors: initiation of the response by fibronectin-mediated attachment of Bacillus Calmette-Guérin.

Science.gov (United States)

Ratliff, T L; Palmer, J O; McGarr, J A; Brown, E J

1987-04-01

Intravesical Bacillus Calmette-Guérin (BCG) is considered to be one of the most effective treatments for superficial bladder cancer. Although the mechanisms by which BCG inhibits tumor growth are not known, previous studies have shown that systemic immunization to BCG and the local expression of the immune response in the bladder are associated with a favorable response to BCG therapy. We have investigated the conditions required for the initiation of an immunological response after the intravesical instillation of BCG. Initial histological studies showed that BCG attached to the bladder wall only in areas where the urothelium was damaged by electrocautery and suggested that attachment was associated with the fibrin clot. Quantitative studies verified the histological observations. Minimal BCG attachment (mean less than 10(2) colony forming units) was observed in normal bladders in contrast with a mean of 1.42 X 10(4) colony forming units/bladder in bladders damaged by electrocautery (10 separate experiments). BCG attachment to the bladder wall was durable since organisms were observed in bladders 48 h after instillation. To investigate the proteins to which BCG attached, we tested the binding of BCG to extracellular matrix and inflammatory proteins which comprise a significant portion of the fibrin clot. BCG bound in vitro to coverslips coated in vivo with extracellular matrix proteins but did not bind to control albumin-coated coverslips. BCG also bound to coverslips coated with purified plasma fibronectin but not to coverslips coated with other purified extracellular matrix proteins including laminin, fibrinogen, and type IV collagen. BCG attachment to coverslips coated with either extracellular matrix proteins or purified fibronectin was inhibited by antibodies specific for fibronectin. Moreover, BCG attachment to cauterized bladders in vivo was inhibited by antifibronectin antibodies. These results demonstrate that fibronectin mediates the attachment of BCG

Diseminación de Klebsiella pneumoniae productoras de KPC-3 en hospitales de Bogotá durante un periodo de tres años

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Edna Catering Rodríguez

2014-04-01

Full Text Available Introducción. Uno de los principales problemas de salud pública a nivel mundial son las infecciones producidas por enterobacterias resistentes a los carbapenémicos, entre las cuales Klebsiella pneumoniae es uno de los patógenos que con mayor frecuencia causa infecciones en el ámbito hospitalario. Objetivo. El objetivo del estudio fue describir la diseminación de aislamientos clínicos de K. pneumoniae productores de la enzima KPC-3 recuperados en hospitales de Bogotá. Materiales y métodos. Se analizaron 82 aislamientos de K. pneumoniae resistentes a antibióticos carbapenémicos recuperados entre el 2008 y el 2010 en 10 hospitales, a los cuales se les realizaron pruebas de detección fenotípica de enzimas por difusión de disco y microdilución, y de detección genotípica por PCR. La determinación de perfiles de sensibilidad frente a 13 antimicrobianos se realizó por métodos automatizados y manuales. La relación genética de los aislamientos se obtuvo por la técnica de PFGE. Resultados. Este estudio presenta el panorama del comportamiento de las enterobacterias resistentes a los carbapenémicos diseminadas en el curso de tres años en 10 hospitales de la ciudad, con características de resistencia a múltiples familias de antibióticos y pertenecientes a varios grupos de clones, cada uno con diferentes subtipos. Conclusiones. La diseminación de aislamientos clínicos de K. pneumoniae productores de enzima KPC-3 en Bogotá plantea la necesidad de fortalecer las acciones de vigilancia epidemiológica frente a este tipo de microorganismos y el desarrollo prioritario de actividades específicas de prevención y control de infecciones.

Th1 Cytokine-Secreting Recombinant Mycobacterium bovis Bacillus Calmette-Guérin and Prospective Use in Immunotherapy of Bladder Cancer

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Yi Luo

2011-01-01

Full Text Available Intravesical instillation of Mycobacterium bovis bacillus Calmette-Guérin (BCG has been used for treating bladder cancer for 3 decades. However, BCG therapy is ineffective in approximately 30–40% of cases. Since evidence supports the T helper type 1 (Th1 response to be essential in BCG-induced tumor destruction, studies have focused on enhancing BCG induction of Th1 immune responses. Although BCG in combination with Th1 cytokines (e.g., interferon-α has demonstrated improved efficacy, combination therapy requires multiple applications and a large quantity of cytokines. On the other hand, genetic manipulation of BCG to secrete Th1 cytokines continues to be pursued with considerable interest. To date, a number of recombinant BCG (rBCG strains capable of secreting functional Th1 cytokines have been developed and demonstrated to be superior to BCG. This paper discusses current rBCG research, concerns, and future directions with an intention to inspire the development of this very promising immunotherapeutic modality for bladder cancer.

Porøse materialer

DEFF Research Database (Denmark)

Hansen, Ernst Jan de Place

2000-01-01

Dette undervisningsnotat er en samling af noter, der refererer til den indledende del af kurset Materialmekanik og Porøse materailer på Insitut for Bærende Konstruktiner og Materialer (BKM).......Dette undervisningsnotat er en samling af noter, der refererer til den indledende del af kurset Materialmekanik og Porøse materailer på Insitut for Bærende Konstruktiner og Materialer (BKM)....

Composition and immunoreactivity of the A60 complex and other cell fractions from Mycobacterium bovis BCG.

Science.gov (United States)

Cocito, C; Vanlinden, F

1995-02-01

Surface static cultures of Mycobacterium bovis BCG contained cells embedded in an extracellular matrix, whose mechanical removal yielded free cells that were pressure disrupted and fractionated into cytoplasm and walls. Cell envelopes were either mechanically disrupted or extracted with detergents. Intracellular and extracellular fractions were analysed for proteins, polysaccharides, and antigen 6O (A60), a major complex immunodominant in tuberculosis. A60 was present in extracellular matrix, cytoplasm and walls: it represented a substantial portion of the proteins and polysaccharides of these fractions. While the protein/polysaccharide ratio varied according to the origin of A60 preparations, the electrophoretic patterns of A60 proteins (which accounted for the immunogenicity of the complex) remained unchanged. Western blots pointed to the proteins present within the 29-45 kDa range as the A60 components endowed with the highest immunogenicity level. Since the most heavily stained protein bands in SDS-PAGE patterns were located outside the region best recognized by antisera, a striking discordance was found between concentration and immunogenicity patterns of A60 proteins. The electrophoretic patterns of A60- and non-A60-proteins from cytoplasm were also different. A60 complexes in dot blots and some electrophoresed A60 proteins reacted with monoclonal antibodies directed against lipoarabinomannan (LAM), a highly immunogenic polymer of cell envelope. This contaminating compound was removed from A60 with organic solvents and detergents. SDS-PAGE and Western blot patterns of proteins from delipidated A60 were similar to those of native A60 proteins.

Fatores de risco para morte por pneumonia em menores de um ano em uma região metropolitana do sudeste do Brasil: um estudo tipo caso-controle Risk factors for death by pneumonia among children under one year of age in a metropolitan area of Southeastern Brazil: a case-control study

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Flávia Maria Leal Niobey

1992-08-01

Full Text Available Através de um estudo tipo caso-controle, foi comparada uma amostra de óbitos pós-neonatais por pneumonia ocorridos na Região Metropolitana do Rio de Janeiro, Brasil (1986-1987 e controles sadios, moradores na vizinhança. Os fatores de risco investigados foram variáveis relacionadas à história gestacional da mãe e ao nascimento da criança, às condições sociais da família e à utilização de serviços de saúde. Na primeira etapa de análise, através de um modelo de regressão logística univariada, foram estimados os coeficientes de cada variável independente, o risco relativo e seus limites de confiança. O peso ao nascer e a idade do desmame mostraram-se das mais fortemente associadas com a variável dependente. Na segunda etapa, foi feito o ajuste pelo modelo de regressão logística múltipla e somente 4 variáveis permaneceram estatisticamente associadas com a mortalidade: idade do desmame, peso ao nascer, número de moradores da casa e aplicação da vacina BCG. Conclui-se que a mortalidade por pneumonia em menores de um ano está fortemente associada às condições sociais da família, em particular da mãe.In a case-control study, a sample of post-neonatal deaths from pneumonia occurring in the Metropolitan Area of Rio de Janeiro, Brazil (1986-1987 were compared with healthy controls who lived in the same neighborhood. Risk factors investigated were variables related to the mother's pregnancy history and the child's birth, to the family's social condition and to the use of health services. Using the univariate logistic regression model, the coefficients of each independent variable, the relative risk and its confidence limits were first estimated. Birth weight and age of weaning were strongly associated with the dependent variable. After adjustment by means of the multiple logistic regression model, only 4 variables remained statistically associated with mortality: age of weaning, birth weight, over crowding, and BCG

Verdad por definición

OpenAIRE

Garrido Garrido, Julián

1997-01-01

Not available.La verdad por definición es un tipo peculiar de verdad científica, distinguible de las verdades lógicas, matemáticas y empíricas. La definición, por su parte, designa diversos procedimientos de asignación de significado, cuyas diferencias exigen una adjetivación cuidadosa: definiciones ostensivas y operacionales, definiciones de diccionario y definiciones teóricas. Pero sólo las del último tipo son verdaderas por definición. En el presente artículo se precisa el concepto formal ...

Adverse reactions to the Bacillus Calmette-Guérin (BCG) vaccine in new-born infants-an evaluation of the Danish strain 1331 SSI in a randomized clinical trial

DEFF Research Database (Denmark)

Nissen, Thomas Nørrelykke; Birk, Nina Marie; Kjærgaard, Jesper

2016-01-01

or no intervention. Follow-up until 13 months of age. SETTING: Pediatric and maternity wards at three Danish university hospitals. PARTICIPANTS: All women planning to give birth at the three study sites (n=16,521) during the recruitment period were invited to participate in the study. Four thousand one hundred...... lymphadenitis were hospitalized and thus classified as serious adverse reactions related to BCG. The most severe adverse reactions were 10 cases of suppurative lymphadenitis. This was nearly a fivefold increase compared to what was expected based on the summary of product characteristics of the vaccine. All...... cases were treated conservatively and recovered. Six of 10 (60%) families of children experiencing suppurative lymphadenitis compared to 117/2071 (6%) of those with no lymphadenitis indicated that the vaccine had more adverse effects than expected (p-value

Electrocardiografo por computadora

OpenAIRE

Tinoco Hernandez, Rosanna; Paredes Bejarano, Margarita; Romero Chaglia, Norman; Yapur Auad, Miguel Eduardo

2009-01-01

El presente trabajo trata sobrees el diseño y la implementación de un graficador de señales cardiacas por computadora, para lo cual diseñamos un circuito electrónico capaz de recibir la senal analógica proveniente de la actividad electrica del corazón , amplificarla, y luego convertirla en una señal digital para ser procesada por software y finalmente ser graficada, siendo posible así observar la señal cardiaca en el monitor de un computador como un tren de pulsos. Cabe destacar que par...

Enhancement of vitamin A combined vitamin D supplementation on immune response to Bacille Calmette-Guérin vaccine revaccinated in Chinese infants

DEFF Research Database (Denmark)

Zheng, Y; Wang, Q.Z.; Ma, Aiguo

2014-01-01

The diameter of BCG scars was effectively correlated with PPD response, which indicates BCG scar formation may be an useful tool to evaluate the effect of tuberculosis prevention. VA combined VD supplementation may play an immuno-regulatory role in BCG revaccination. This may contribute to the pr......The diameter of BCG scars was effectively correlated with PPD response, which indicates BCG scar formation may be an useful tool to evaluate the effect of tuberculosis prevention. VA combined VD supplementation may play an immuno-regulatory role in BCG revaccination. This may contribute...

Impacto das ações de imunização pelo Programa Saúde da Família na mortalidade infantil por doenças evitáveis em Olinda, Pernambuco, Brasil Impact of immunization measures by the Family Health Program on infant mortality from preventable diseases in Olinda, Pernambuco State, Brazil

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Tânia Maria Rocha Guimarães

2009-04-01

Full Text Available Este artigo aborda o impacto do Programa Saúde da Família (PSF na saúde infantil no Município de Olinda, Pernambuco, Brasil, por meio da avaliação da vacinação e mortalidade infantil por causas evitáveis. Realizou-se um estudo de série temporal com os dados dos principais sistemas de informação em saúde, usando-se a análise dos indicadores ex-ante e ex-post da implantação do PSF, em 1995. A variável independente foi o ano de nascimento relacionado com grau de cobertura da população pelo PSF. Analisou-se três períodos: 1990/1994 (anterior, 1995/1996 (implantação: cobertura de 0% a 30%, 1997/2002 (intervenção: cobertura de 38,6% a 54%. A tendência dos indicadores foi analisada pela regressão linear simples, sendo testada a significância pelo teste t. No período de implantação houve aumento de todas as médias das coberturas vacinais (176% BCG, 223% pólio, 52% DPT, 61% sarampo e redução da mortalidade infantil por causas evitáveis (12,7 óbitos/ano, mesmo não havendo diminuição da pobreza absoluta no município ou aumento das coberturas das redes públicas de saúde nem de esgotamento. A melhoria nos indicadores demonstra a efetividade das ações do PSF no município.This article analyzes the impact of the Family Health Program (FHP on infant health in Olinda, Pernambuco State, Brazil, evaluating immunization and infant mortality from vaccine-preventable diseases. A time-series study was conducted with data from the principal health information systems, analyzing indicators before and after implementation of the FHP in 1995. The independent variable was year of birth, related to degree of population coverage by the FHP. Three periods were analyzed: 1990-1994 (prior, 1995-1996 (implementation phase: 0 to 30% coverage, and 1997-2002 (intervention: coverage of 38.6% to 54%. Trends in the indicators were analyzed by simple linear regression, testing significance with the t test. During the implementation period

Celulitis por citomegalovirus Cytomegalovirus cellulitis

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A. Ruiz Lascano

2002-12-01

Full Text Available Las lesiones cutáneas por citomegalovirus (CMV son infrecuentes y a menudo una manifestación tardía de una enfermedad sistémica, que generalmente anuncia un curso fatal. Comunicamos un caso de celulitis por CMV: una mujer de 70 años con trasplante renal efectuado 1 mes antes de la consulta, terapia inmunosupresora con ciclosporina A y metilprednisona. La paciente ingresó por fiebre, dolor e impotencia funcional en pierna derecha. Comprobamos la existencia de una placa de 8 por 4 cm eritematoedematosa. La tratamos con antibióticos sin mejoría, por lo que realizamos un estudio histopatológico de piel que mostró cambios citopáticos compatibles con infección por CMV. Los cultivos bacteriológicos y micológicos fueron negativos. La inmunohistoquímica específica para CMV y el estudio de reacción en cadena de la polimerasa (PCR de la biopsia de piel fueron positivas, al igual que la antigenemia. El tratamiento con ganciclovir produjo la mejoría del cuadro clínico. En la literatura revisada no hemos encontrado la celulitis como manifestación de enfermedad cutánea por CMV.Cutaneous lesions in CMV infection are rare, often a late manifestation of systemic infection, and usually herald a fatal course. A 70 year-old woman received a kidney transplantation one month before consulting and immunosuppressive therapy that included cyclosporine A and methylprednisone. She complained of fever, local pain in her right leg, and an erythematous and swelling plaque. She was treated with intravenous antibiotics without improvement. A skin biopsy was performed and the tissue obtained was sent for bacterial and fungal cultures as well as for histological examination. Cultures were negative. The biopsy showed CMV cytopathic changes. Immunoperoxidase staining was positive for CMV and polymerase chain reaction (PCR testing revealed CMV DNA. She was treated with ganciclovir with resolution of the lesion. CMV cellulitis is a rare cutaneous manifestation

Modulation of fibronectin-mediated Bacillus Calmette-Guérin attachment to murine bladder mucosa by drugs influencing the coagulation pathways.

Science.gov (United States)

Hudson, M A; Brown, E J; Ritchey, J K; Ratliff, T L

1991-07-15

Adjuvant intravesical Bacillus Calmette-Guérin (BCG) has proved to be an effective treatment for superficial bladder cancer. Intraluminal attachment of BCG organisms via binding to the extracellular matrix protein, fibronectin (FN), appears to be required for expression of the antitumor efficacy of BCG against a murine bladder tumor. Initial studies demonstrated that radiolabeled FN localized to the acutely injured urothelium but not to intact urothelium. These studies also demonstrated that exogenous administration of FN enhanced BCG attachment to the injured but not to the intact urothelium. Because FN has been shown to be an integral part of clot formation at sites of urothelial injury, drugs known to affect fibrin clot formation were tested for their effects on BCG attachment and antitumor efficacy in a murine bladder tumor model. A stabilizer of fibrin clot formation was shown to enhance both BCG attachment and antitumor efficacy in the same model. An increased number of BCG organisms were also retained in the lymph nodes and spleens of mice receiving fibrin clot stabilizers, suggesting indirectly that immunological mechanisms are involved in the antitumor efficacy of BCG. The data presented herein provide further support for the hypothesis that BCG attachment to the injured bladder is mediated by FN. Furthermore, modulation of BCG-FN attachment is demonstrated to be possible with drugs influencing the coagulation pathway. This attachment is shown to be required for the antitumor efficacy in a murine bladder tumor model, and thus modulation of BCG-FN attachment appears to have significant influence on the antitumor efficacy of BCG in the murine bladder tumor model.

Tendencia de la mortalidad por cáncer en Chile según diferencias por nivel educacional, 2000-2010

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Cristian A. Herrera Riquelme

2015-01-01

Full Text Available Objetivo. Caracterizar la tendencia de la mortalidad por cáncer en Chile según diferencias por nivel educacional en el período 2000-2010 en la población mayor de 20 años. Métodos. Cálculo de las tasas de mortalidad específica por cáncer ajustadas por edad para diferentes niveles educacionales (NE, para el período 2000-2010. Las tasas obtenidas se analizaron con un modelo de regresión de Poisson, calculando el índice de desigualdad relativa (IDR y el índice de desigualdad de la pendiente (IDP para cada año. Resultados. Se registraron 232 541 muertes por cáncer en el período 2000-2010. Los tipos de cáncer más frecuentes fueron de mama, estómago y vesícula biliar en mujeres; y estómago, próstata y pulmón en hombres. Las tasas de mortalidad por cáncer estandarizadas por edad fueron mayores en los NE más bajos, excepto para el de mama en mujer y el de pulmón en hombres. Las mayores diferencias se encontraron en el de vesícula biliar en mujeres y el de estómago en hombres, con mayores tasas de mortalidad específica de hasta 49 y 63 veces respectivamente, para NE bajo respecto al NE alto. Entre 2000 y 2010, las diferencias en mortalidad por NE se redujeron para todos los cánceres combinados en ambos géneros, mama en mujeres, y pulmón y estómago en hombres. Conclusiones. Durante el período estudiado, la mortalidad por cáncer en Chile estuvo fuertemente asociada al NE de la población. Esta información debe ser considerada al definir estrategias nacionales para reducir la mortalidad específica por cáncer en los grupos más desprotegidos.

Estudio de la expresión y función del receptor de IFN y ?en pacientes con manifestaciones atípicas en infecciones por gérmenes intracelulares

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Pablo Javier Patiño Grajales

2000-02-01

Full Text Available

La inmunidad protectora a microorganismos intracelulares, como por ejemplo micobacaterium, se conoce que es dependiente de la inmunidad mediada por células (IMC. El principal mecanismo efector de la IMC depende de la activación del macrófago infectado mediante las citoquinas tipo I, particularmente el interferón gamma (IFNγ. Esta citoquina es una glicoproteína homodimérica, producida por células T y células NK. La transcripción de su gen se inicia por activación antigénica y se incrementa por efecto de otras citoquinas como la IL-2 y la IL-12. Entre sus principales efectos está el de activar las células NK y los fagotitos mononucleares, aumentar la expresión de moléculas del Complejo Mayor de Histocompatibilidad clase I y II, promover la diferenciación funcional de las células CD4+ hacia el patrón funcional TH1 e inducir la maduración de los linfocitos CD8+ hacia células citotóxicas. En las células B promueve el cambio isotípico de inmunoglobulinas hacia IgG1 e IgG3.

Recientemente se identificaron los primeros casos de deficiencia del receptor de IFN gamma (IFNγR en humanos. Esta deficiencia es un desorden autosómico recesivo, que ha sido caracterizado en niños que presentan una infección diseminada por micobacterias. Aparece como consecuencia de mutaciones del gen IFNMuerte materna por malaria grave por Plasmodium vivax

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Nancy Arróspide

Full Text Available Se presenta el caso de una mujer de 19 años con 29 semanas de gestación, procedente de Llumpe (Ancash con antecedentes de viajes a las localidades de Chanchamayo (Junín y Rinconada (Ancash. Ingresó al Hospital de Chacas (Ancash por presentar mal estado general, deshidratación, dificultad respiratoria, ictericia, sensación de alza térmica y dolor abdominal, tuvo reporte de: hemoparásitos 60% en frotis sanguíneo. Fue transferida al Hospital Ramos Guardia (Huaraz donde presentó mayor dificultad respiratoria, coluria, hematuria, disminución del débito urinario y reporte de Plasmodium (+, luego fue transferida al Hospital Cayetano Heredia (Lima donde ingresó a la Unidad de Cuidados Intensivos (UCI, con evolución a falla multiorgánica, óbito fetal y muerte materna. Se confirmó infección por Plasmodium vivax. Destacamos la importancia de mejorar nuestras capacidades de diagnóstico y manejo para brindar un tratamiento adecuado y oportuno.

Desenvolvimento de um kit de irrigação por microtubos com moto-bomba propulsionada por energia solar

OpenAIRE

Luiz Ricardo Sobenko

2016-01-01

O bombeamento de água por meio da energia solar vem se mostrando uma alternativa para localidades onde outras fontes de energia não estão disponíveis ou são limitadas. Torna-se interessante aliar essa alternativa a um sistema de irrigação que opera com vazão e pressão relativamente baixas, como a irrigação localizada por microtubos, possibilitando assim a obtenção de alta eficiência. No presente trabalho teve-se por objetivo dimensionar e avaliar um kit de irrigação por microtubos, alimentado...

Tendencia de la mortalidad por cáncer en Chile según diferencias por nivel educacional, 2000-2010

OpenAIRE

Cristian A. Herrera Riquelme; Lucy Kuhn-Barrientos; Roberto Rosso Astorga; Jorge Jiménez de la Jara

2015-01-01

Objetivo. Caracterizar la tendencia de la mortalidad por cáncer en Chile según diferencias por nivel educacional en el período 2000-2010 en la población mayor de 20 años. Métodos. Cálculo de las tasas de mortalidad específica por cáncer ajustadas por edad para diferentes niveles educacionales (NE), para el período 2000-2010. Las tasas obtenidas se analizaron con un modelo de regresión de Poisson, calculando el índice de desigualdad relativa (IDR) y el índice de desigualdad de la pendiente (ID...

Polución por material particulado fino (PM 2,5) incrementa las hospitalizaciones por insuficiencia cardiaca

OpenAIRE

Castro, Pablo; Vera, Jeanette; Cifuentes, Luis; Wellenius, Gregory; Verdejo, Hugo; Sepúlveda, Luis; Vukasovic, José Luis; Llevaneras, Silvana

2010-01-01

Antecedentes: Estudios recientes han reportado una asociación entre la contaminación ambiental por material particulado (PM) y el riesgo de hospitalizaciones de pacientes con insuficiencia cardiaca (IC). La región metropolitana de nuestro país constituye un área geográfica en la cual la contaminación es especialmente relevante, asociándose a incrementos periódicos en la morbimortalidad por causa respiratoria. Sin embargo el efecto de la polución por PM en la morbilidad de pacientes con IC no ...

Delayed-type hypersensitivity skin test responses to PPD and other antigens among BCG-vaccinated HIV-1-infected and healthy children and adolescents.

Science.gov (United States)

Costa, Natalia Moriya Xavierda; Albuquerque, Maly de; Lins, Janaína Bacelar Acioli; Alvares-Junior, João Teixeira; Stefani, Mariane Martins de Araújo

2011-10-01

Among HIV-1-infected patients, CD4+ T cell counts are well-established markers of cell-mediated immunity. Delayed-type hypersensitivity (DTH) skin tests can be used to evaluate in vivo cell-mediated immunity to common antigens. DTH responses to tuberculin purified protein derivative (PPD), sporotrichin, trichophytin, candidin and streptokinase/streptodornase antigens were assessed. Thirty-six HIV-1-infected children/adolescents and 56 age- and sex-matched HIV-1/HIV-2-seronegative participants were tested. All participants had a BCG scar. Fisher's exact test was used to evaluate significant differences between groups (pPPD positivity prevailed among healthy participants (40/56, 71.4%). PPD reactivity in the HIV-1-positive group was 8.3% (pPPD induration was 2.5mm (range: 2-5mm) in the HIV-1 group and 6.0 mm among healthy participants (range: 3-15 mm). There was no correlation between PPD positivity and age. No correlation between CD4+ T cell counts and DTH reactivity was observed among HIV-1-infected patients. DTH skin test responses, including PPD reactivity, were significantly lower among HIV-1-infected participants compared to healthy controls, which likely reflects advanced disease and T cell depletion.

Síndrome de Munchausen por mandato

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Esteban, Miguel A.; Pérez, Miriam R.; Bracco, Anahí

2006-01-01

El Síndrome de Munchausen por mandato, "un trastorno ficticio, por el cual la enfermedad del niño es inducida, promovida o provocada por la persona más próxima a él, generalmente su madre", es todavía mal conocido y su génesis imperfectamente comprendida. Esta comunicación está destinada a esclarecer al pediatra esta patología, con elevada morbilidad y secuelas, como así también de altísima mo...

DESGASTE POR ABRASIÓN DEL ACERO API 5L X65 REVESTIDO CON NIOBIO POR ASPERSIÓN TÉRMICA A PLASMA Y CON INCONEL 625 POR SOLDADURA

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JOSE MATOS

2012-01-01

Full Text Available El objetivo de este trabajo fue evaluar y caracterizar el comportamiento mecánico en desgaste del acero API 5L X65, revestido con niobio en comparación al desempeño del revestimiento de la aleación de inconel 625 empleados en la industria de petróleo y gas. El revestimiento de niobio fue obtenido por el proceso de aspersión térmica a plasma de arco no transferido y el revestimiento inconel 625 por soldadura con electrodo revestido. La resistencia al desgaste por abrasión fue evaluada según la norma Petrobras N-2568, en un tribómetro CTER, la rugosidad y el volumen de material desgastado se determinó a través de perfilometría y la dureza de los revestimientos por microscopia Vickers. Los revestimientos obtenidos fueron caracterizados respecto a su morfología por microscopia electrónica de barrido (MEB y microscopía óptica (MO. La mayor dureza del revestimiento con niobio obtenido puede haber contribuido a reducir la tasa de desgaste en comparación con el revestimiento de inconel 625.

Profilaxis antimicrobiana previa a procedimientos dentales. Situación actual y nuevas perspectivas

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Luis Fernando Rodríguez-Campos

2017-08-01

Full Text Available La bacteremia secundaria a los procedimientos dentales puede dar origen a episodios de endocarditis infecciosa. La implementación de la profilaxis antimicrobiana tiene como finalidad aminorar la bacteremia transitoria reduciendo la posibilidad de desarrollar endocarditis infecciosa, por lo que es indispensable conocer qué antibióticos son de elección y en qué casos o situaciones administrarlos u omitirlos. Existen múltiples guías para aplicar profilaxis antimicrobiana, éstas difieren en sus recomendaciones, a tal grado que pueden confundir al facultativo al momento de determinar si el paciente requiere antibiótico profiláctico y a elegir el antimicrobiano adecuado.   OBJETIVO: comparar las diferentes guías de profilaxis antimicrobiana y recomendaciones para converger en una recopilación única con las aportaciones destacadas de cada guía revisada; de la misma manera, exponer el régimen utilizado en nuestra institución por el servicio de estomatología.   CONCLUSIÓN: el estomatólogo se puede basar principalmente en las guías de la American Heart Association (AHA y el Centro Nacional de Excelencia Tecnológica en Salud (CENETEC para condiciones cardiacas que ameriten profilaxis antimicrobiana, y para pacientes con enfermedades sistémicas sobre la guía de la American Academy of Pediatric Dentistry (AAPD y las recomendaciones de nuestra institución. La administración de profilaxis antimicrobiana se da por razones científicas consolidadas y por carácter de tipo médico-legal, en un futuro se espera establecer criterios para aumentar los métodos no antibióticos preventivos de endocarditis infecciosa y aminorar el uso de antimicrobianos, reduciendo el uso de antibiótico profiláctico, sin exponer al paciente a infecciones diseminadas y con mínimos efectos secundarios posibles.

CARACTERÍSTICAS DA VIOLÊNCIA SEXUAL SOFRIDA POR CRIANÇAS ASSISTIDAS POR UM PROGRAMA DE APOIO

OpenAIRE

KELLY LINHARES VASCONCELOS; ADRIANA GOMES NOGUEIRA FERREIRA; ELIANY NAZARÉ OLIVEIRA; DANIELLE D\\u2019ÁVILA SIQUEIRA; PATRÍCIA NEYVA DA COSTA PINHEIRO

2010-01-01

En Brasil, las estadísticas de la violencia sexual contra niños están lejos de reflejar la verdadera realidad actual debido a la baja notificación de los casos. La finalidad de este estudio fue caracterizar el abuso sexual sufrido por niños asistidos por el Programa Sentinela y el perfil del agresor, en Sobral-Ceará, en el periodo que va del 2002 al 2006. La muestra no probabilística intencional fue compuesta por 50 víctimas de abuso sexual y de las mismas, el 66% es del sexo femenino, con pr...

Abdome agudo por obstrução por ileobiliar

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Márcia Cristina de Alencastro

Full Text Available OBJETIVO: descrever a experiência na abordagem dos doentes com abdome agudo por obstrução por IB, desde o diagnóstico até o tratamento definitivo. MÉTODOS: estudo retrospectivo incluindo todos os casos de IB tratados em um período de 23 anos. De acordo com a abordagem cirúrgica realizada, os pacientes foram divididos em dois grupos (1 enterolitotomia com colecistectomia no segundo momento; e (2 enterolitotomia, colecistectomia e abordagem da fístula. RESULTADOS: Doze pacientes foram incluídos, sendo 11 mulheres (91,6%, com média de idade de 72,2 anos. Todos os pacientes apresentavam doenças associadas, principalmente hipertensão arterial sistêmica (75%. Dois pacientes não apresentavam sintomas significativos de obstrução intestinal. O diagnóstico de IB foi realizado em seis pacientes (50% antes da laparotomia. O grupo 1 foi constituído de oito pacientes e o grupo 2 de quatro, e a morbidade foi, respectivamente, 33,3% e 8,3%. A mortalidade foi 16,6% (um paciente de cada grupo. CONCLUSÃO: O manejo do IB deve ser individualizado. O tratamento da obstrução mediante remoção do cálculo biliar por enterotomia proximal é a escolha inicial para o tratamento do IB. A colecistectomia e a correção da fístula bilioentérica podem ser realizadas juntamente com a remoção do cálculo, no entanto, em pacientes com comorbidades significativas, esses procedimentos devem ser realizados posteriormente.

Improvement of ballistocardiogram processing by inclusion of respiration information

International Nuclear Information System (INIS)

Tavakolian, Kouhyar; Vaseghi, Ali; Kaminska, Bozena

2008-01-01

In this paper a novel methodology for processing of a ballistocardiogram (BCG) is proposed in which the respiration signal is utilized to improve the averaging of the BCG signal and ultimately the annotation and interpretation of the signal. Previous research works filtered out the respiration signal while the novelty of the current research is that, rather than removing the respiration effect from the signal, we utilize the respiration information to improve the averaging and thus analysis and interpretation of the BCG signal in diagnosis of cardiac malfunctions. This methodology is based on our investigation that BCG cycles corresponding to the inspiration and expiration phases of the respiration cycle are different in morphology. BCG cycles corresponding to the expiration phase of respiration have been proved to be more closely related to each other when compared to cycles corresponding to inspiration, and therefore expiration cycles are better candidates to be selected for the calculation of the averaged BCG signal. The new BCG average calculated based on this methodology is then considered as the representative and a template of the BCG signal for further processing. This template can be considered as the output of a clinical BCG instrument with higher reliability and accuracy compared to the previous processing methods

Uso das diretrizes para tratamento da úlcera por pressão por enfermeiros de um hospital geral

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Elaine Maria Leite Rangel

2009-03-01

Full Text Available Este estudo objetivou identificar a freqüência do uso das diretrizes para o tratamento da úlcera por pressão(UP por enfermeiros de um hospital geral no interior do estado de São Paulo. É transversal de caráterdescritivo com análise quantitativa de dados. Amostra de 25 enfermeiros. Para a coleta de dados utilizou-se uminstrumento, construído a partir das diretrizes para o tratamento da UP. As questões foram relacionadas aostipos de intervenções usadas pelos enfermeiros para o tratamento da UP em estágio I, II, com necrose e comtecido de granulação. Para UP em estágio I, 24 (96% enfermeiros sempre realizavam a mudança de decúbito.Nas úlceras em estágio II a utilização de óleos vegetais na ferida era realizada sempre por 10 (40%enfermeiros e o curativo de hidrocolóide nunca era utilizado por 12 (57,1% enfermeiros. Em UP com necrose alimpeza com povidine era realizada por 4 (17,4% enfermeiros às vezes. Para o desbridamento, 16 (64% àsvezes utilizavam papaína e 15 (71,4% às vezes utilizavam colagenase. Em úlceras com tecido de granulaçãosempre era utilizado o soro fisiológico por 25 (100% enfermeiros. Houve variação nas práticas para otratamento da UP e falta de adesão às diretrizes.

Mortalidad por causas externas en Medellín, 1999-2006

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Doris Cardona Arango

2008-01-01

Full Text Available Caracterizar el comportamiento de la mortalidad por causas externas en la ciudad de Medellín, Colombia, entre 1999-2006, según sexo, edad y causa básica de muerte fue el objetivo de este estudio descriptivo longitudinal, con fuente de información secundaria de 22 128 registros de defunción por causas externas. El análisis realizado es univariado y bivariado por sexo, grupos de edad y causa de muerte. Las causas externas registradas en el periodo fueron: 72.9 por ciento por homicidio; 15.3 por ciento, accidente de transporte; 7.3 por ciento, traumatismos; 4.2 por ciento, por suicidio, y por otras causas, 0.4 por ciento. La mayor tasa de mortalidad se presentó en el grupo de edad de 20 a 24 años (27.6 por cien mil habitantes, hecho que merece especial consideración por las implicaciones sociales, familiares y laborales que representa el fallecimiento de una persona en su etapa productiva.

Rational design of diagnostic and vaccination strategies for tuberculosis

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Sibele Borsuk

Full Text Available The development of diagnostic tests which can readily differentiate between vaccinated and tuberculosis-infected individuals is crucial for the wider utilization of bacillus Calmette-Guérin (BCG as vaccine in humans and animals. BCG_0092 is an antigen that elicits specific delayed type hypersensitivity reactions similar in size and morphological aspects to that elicited by purified protein derivative, in both animals and humans infected with the tubercle bacilli. We carried out bioinformatics analyses of the BCG_0092 and designed a diagnostic test by using the predicted MHC class I epitopes. In addition, we performed a knockout of this gene by homologous recombination in the BCG vaccine strain to allow differentiation of vaccinated from infected individuals. For that, the flanking sequences of the target gene (BCG_0092were cloned into a suicide vector. Spontaneous double crossovers, which result in wild type revertants or knockouts were selected using SacB. BCG_0092 is present only in members of the Mycobacterium tuberculosis complex. Eight predicted MHC class I epitopes with potential for immunological diagnosis were defined, allowing the design of a specific diagnostic test. The strategy used to delete the (BCG_0092 gene from BCG was successful. The knockout genotype was confirmed by PCR and by Southern blot. The mutant BCG strain has the potential of inducing protection against tuberculosis without interfering with the diagnostic test based on the use of selected epitopes from BCG_0092.

Apendicitis por Paracoccidioides brasiliensis

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Ana Beatriz MUÑOZ URRIBARRI

2006-01-01

Full Text Available La paracoccidioidomicosis es la micosis más prevalente en Sudamérica. La forma aguda afecta el sistema fagocítico mononuclear de niños y personas inmunocomprometidas. El compromiso gastrointestinal es frecuente y su patogenia implica diseminación hematógena y linfática. La linfadenomegalia abdominal causa obstrucción intestinal y abdomen agudo. En este artículo damos a conocer el caso de un niño con compromiso gastrointestinal por apendicitis. Este es el primer caso reportado de apendicitis por esta patología. (Rev Med Hered 2006;17:58-60.

A Case of Acquired Rifampin Resistance in Mycobacterium bovis Bacillus Calmette-Guérin-Induced Cystitis: Necessity for Treatment Guidelines

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Joyce N Wolfe

2006-01-01

Full Text Available A case of presumed bacillus Calmette-Guérin (BCG cystitis in an elderly female patient following direct intravesical BCG instillation treatment for papillary transitional cell carcinoma is reported. The organism cultured from urine samples was eventually identified as a rifampin-resistant Mycobacterium bovis BCG isolate. Because the patient had received rifampin monotherapy during the course of treatment for presumed BCG disease, the clinical picture favoured acquired rifampin resistance. Sequencing of the target gene for rifampin (rpoB confirmed a known mutation responsible for conferring high levels of resistance to both rifampin and rifabutin (Ser531Tyr. To the authors' knowledge, this is the first reported case of M bovis BCG disease in a non-HIV patient where the organism had acquired drug resistance to rifampin, and the second reported case of M bovis BCG that had acquired drug resistance. The present case demonstrates the necessity to re-evaluate appropriate guidelines for the effective treatment of BCG disease.

Overestimation of Albumin Measured by Bromocresol Green vs Bromocresol Purple Method: Influence of Acute-Phase Globulins.

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Garcia Moreira, Vanessa; Beridze Vaktangova, Nana; Martinez Gago, Maria Dolores; Laborda Gonzalez, Belen; Garcia Alonso, Sara; Fernandez Rodriguez, Eloy

2018-05-22

Usually serum albumin is measured with dye-binding assay as bromocresol green (BCG) and bromocresol purple (BCP) methods. The aim of this paper was to examine the differences in albumin measurements between the Advia2400 BCG method (AlbBCG), Dimension RxL BCP (AlbBCP) and capillary zone electrophoresis (CZE). Albumin concentrations from 165 serum samples were analysed using AlbBCG, AlbBCP and CZE. CZE was employed to estimate different serum protein fractions. Influence of globulins on albumin concentration discrepancies between methods was estimated as well as the impact of the albumin method on aCa concentrations. Medcalc was employed for statistical analysis, setting a value of P albumin concentrations. AlbBCG were positively biased versus CZE (3.54 g/L). There was good agreement between CZE and ALbBCP (Albumin results from the BCP and BCG methods may result in unacceptable differences and clinical confusion, especially at lower albumin concentrations. Serum acute phase proteins contribute to overestimating the albumin concentration using AlbBCG.

Tatuaje por amalgama. Reporte de un caso

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Luis Fang Mercado

2012-01-01

Full Text Available El tatuaje por amalgama se origina por el depósito en el tejido conectivo subepitelial de fragmentos de amalgama resultado de procedimientos iatrogénicos por parte del operador. La profundidad a la que se encuentren albergados los residuos de este material influye en la presentación clínica de las lesiones. Radiográficamente se pueden identificar los fragmentos mientras tengan diámetros razonables; histológicamente se pueden observar las partículas de amalgama como gránulos oscuros, sólidos e irregulares dispuesto entre los haces de colágeno y vasos sanguíneos. Este artículo refiere el caso clínico de un paciente que presentó pigmentación por amalgama en mucosa vestibular, originada por una porción de amalgama usada como material obturador en una apicectomía del 11 realizada con anterioridad. Teniendo en cuenta las consideraciones clínicas y radiográficas se optó por realizar una segunda apicectomía con obturación retrógrada con MTA del 11. Durante el procedimiento quirúrgico se cureteó y adelgazó la cara interna del colgajo mucoperióstico para tratar de disminuir el grado de pigmentación.

La pintura vista por un pintor joven

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Fuentes Pozo, Pedro

2000-01-01

Full Text Available Not available

El pintor se define a lo largo del tiempo como un artista en mutación influenciado por la sociedad de su momento y por su propio mundo interior Esto ha contribuido a la creación de distintos estilos pictóricos y a una evolución que conlleva la despreocupación por el aspecto formal en aras de una introspección al mundo interior En el cambio constante se refleja la búsqueda del artista que valida la intemporalidad del arte. Así, el verdadero artista sobrevive al aplauso o rechazo de la crítica, convirtiéndose en un verdadero hombre renancentista preocupado por el hallazgo del conocimiento universal.

Experiência inicial com terapia por pressão negativa por instilação em feridas complexas

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Dimas André Milcheski

Full Text Available RESUMO Objetivo: relatar a experiência inicial com a terapia por pressão negativa por instilação em feridas complexas infectadas ou contaminadas. Métodos: a terapia por pressão negativa por instilação utilizada foi o V.A.C. Ulta com instilação Veraflo (Kinetic Concepts, Inc. O modo de operação foi contínuo com pressão sub-atmosférica ajustada em 125 mmHg por duas horas e instilação entre as pausas. O tempo de instilação foi de 20 minutos (tempo de contato do agente tópico com a ferida e a substância instilada foi solução salina padrão a 0,9%. Após obtenção de preparo adequado da ferida, ela foi coberta com enxerto ou retalho. Resultados: foram operados dez pacientes com feridas complexas contaminadas ou infectadas. O número médio de trocas da TPNi foi 1,4, o número médio total de cirurgias foi de 2,4, o intervalo até a cobertura da ferida foi de 6,3 dias e o intervalo até a alta foi de 11,4 dias. Conclusão: a comparação da terapia por pressão negativa por instilação com dois estudos prévios (controle histórico evidenciou um tempo de internação menor, favorecendo a TPNi. Este estudo teve um caráter inicial, fazendo-se necessário conduzir um trabalho randomizado e controlado para confirmar a eficácia desta terapia e verificar a sua custo-efetividade.

Neuropatia experimental por DDT: análise de nervo por microdissecção de fibras

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Edison Matos Nóvak

1984-09-01

Full Text Available Estudou-se o nervo gênito-femural do rato albino submetido a intoxicação crônica por DDT, administrado por 180 dias na dose de 5 mg/kg de peso via oral. Os resultados mostraram proporção anormal de fibras tipo C, sendo sugerido ocorrer degeneração tipo axonal determinada pelo DDT.

Ptose palpebral causada por Paquidermoperiostose

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Patricia Regina de Pinho Tavares

2014-08-01

Full Text Available A paquidermoperiostose é uma síndrome caracterizada por acometimento cutâneo e ósseo, e em alguns casos ocorre comprometimento palpebral leve. É uma síndrome rara, idiopática ou hereditária, com provável herança autossômica dominante de penetrância variável. Descreve-se o caso de um paciente com ptose grave por paquidermoperiostose elucidando sua fisiopatologia e conduta cirúrgica aplicada.

Plan Nacional de Salud Pública 2007-2010

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Ricardo Galán Morera

2007-09-01

en la producción de vacunas y biológicos, que como en el caso de la vacuna antiamarílica, se exportaba a nivel mundial con niveles óptimos de calidad, así como el caso de la D.P.T., B.C.G., y otros, (suero antiofídico y antirrabíco. Además su fortaleza se sustentaba en la investigación básica y en la investigación aplicada, dignas de elogio por parte de la Comunidad Científica...

Suppression of cytochrome P450 reductase (POR) expression in hepatoma cells replicates the hepatic lipidosis observed in hepatic POR-null mice.

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Porter, Todd D; Banerjee, Subhashis; Stolarczyk, Elzbieta I; Zou, Ling

2011-06-01

Cytochrome P450 reductase (POR) is a microsomal electron transport protein essential to cytochrome P450-mediated drug metabolism and sterol and bile acid synthesis. The conditional deletion of hepatic POR gene expression in mice results in a marked decrease in plasma cholesterol levels counterbalanced by the accumulation of triglycerides in lipid droplets in hepatocytes. To evaluate the role of cholesterol and bile acid synthesis in this hepatic lipidosis, as well as the possible role of lipid transport from peripheral tissues, we developed a stable, small interfering RNA (siRNA)-mediated cell culture model for the suppression of POR. POR mRNA and protein expression were decreased by greater than 50% in McArdle-RH7777 rat hepatoma cells 10 days after transfection with a POR-siRNA expression plasmid, and POR expression was nearly completely extinguished by day 20. Immunofluorescent analysis revealed a marked accumulation of lipid droplets in cells by day 15, accompanied by a nearly 2-fold increase in cellular triglyceride content, replicating the lipidosis seen in hepatic POR-null mouse liver. In contrast, suppression of CYP51A1 (lanosterol demethylase) did not result in lipid accumulation, indicating that loss of cholesterol synthesis is not the basis for this lipidosis. Indeed, addition of cholesterol to the medium appeared to augment the lipidosis in POR-suppressed cells, whereas removal of lipids from the medium reversed the lipidosis. Oxysterols did not accumulate in POR-suppressed cells, discounting a role for liver X receptor in stimulating triglyceride synthesis, but addition of chenodeoxycholate significantly repressed lipid accumulation, suggesting that the absence of bile acids and loss of farnesoid X receptor stimulation lead to excessive triglyceride synthesis.

Consanguinidad por isonimia en Salta

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Albeza, María V.

2007-01-01

Full Text Available Se estimó el coeficiente de parentesco por isonimia para localidades de la Puna, Valle Calchaquí y Valle de Lerma, a fin de evaluar diferentes factores evolutivos que podrían estar afectando la composición genética de la población. A partir de los apellidos de las parejas consignadas en fuentes primarias de información, se estimó la isonimia conyugal o marital, el coeficiente total Ft y sus componentes Fr (inbreeding azaroso y Fn (inbreeding no azaroso. De las localidades estudiadas, en la Puna se ha detectado sólo una pareja isónima en una de ellas, en el Valle Calchaquí, tres y ninguna en el Valle de Lerma. Tanto en el Valle Calchaquí como en el de Lerma, se han estimado valores negativos de Ft, y en la Puna se registran los valores más elevados. En las localidades estudiadas no se cumple el supuesto de transmisión patrilineal de apellidos por lo que los valores de Fr y por ende de Ft podrían estar subestimados. Es por ello que sería necesario contar con información desde otras vertientes metodológicas para corroborar, complementar y manejar cuidadosamente el análisis de los datos y las conclusiones que se obtienen.

Nefrectomía simple por puerto único (LESS) asistida por robot (da Vinci)

OpenAIRE

CASTILLO C,OCTAVIO A; VIDAL M,IVAR; SEPÚLVEDA T,FRANCISCO

2011-01-01

Introducción: La cirugía mínimamente invasiva en urología avanza rápidamente y la cirugía laparo-endoscópica a través de puerto único (LESS) no es la excepción. Esta técnica por vía laparoscópica presenta mucha dificultad y requiere de un cirujano laparoscópico experimentado debido a la falta de triangulación y el cruce de los instrumentos. Los beneficios del sistema quirúrgico da Vinci® han sido introducidos recientemente en LESS. Presentamos dos casos de nefrectomía LESS asistida por robot....

Suppurative supraclavicular bacille calmette-guerine lymphadenitis - A case report, awareness and management options

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U S Udgaonkar

2015-01-01

Full Text Available Diagnosis of Bacille calmette-guerine (BCG adenitis is clinical. Conventional laboratory tests do not differentiate BCG adenitis from tuberculous adenitis. We report a case of a 3-month-old healthy baby presenting with suppurative BCG adenitis. FNAC revealed AFB on ZN-Staining, later confirmed to be Mycobacterium bovis by multiplex PCR. The treatment of suppurative BCG adenitis is needle aspiration. Anti-tubercular treatment is unwarranted.

Análisis de costos por ausentismo laboral atribuibles a licencias médicas por enfermedad. Hospital Nacional Arzobispo Loayza 2015

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Jave Escalante, Gladys Lizeth

2015-01-01

Determina el costo generado por el ausentismo laboral atribuible a licencias médicas por enfermedad en el Hospital Nacional Arzobispo Loayza 2015. METODOLOGÍA: Estudio no experimental. La muestra estuvo conformada por 118 médicos asistenciales y personal de enfermería. Para el análisis de los costos se utilizó el costo de tiempo perdido del paciente, ingresos dejados de percibir por el hospital y descuento económico al trabajador. Además se realizó un análisis económico y de sensibilidad. ...

Indice por Materias

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Montoya H Luz Marina

1982-09-01

Full Text Available Un índice es una lista de palabras o frases indicadores asociados que permite la ubicación de material al interior de un libro o una publicación, en este caso será por el nombre de la materia.

Commentary on "Optimal schedule of bacillus Calmette-Guérin for non-muscle-invasive bladder cancer: A meta-analysis of comparative studies." Zhu S, Tang Y, Li K, Shang Z, Jiang N, Nian X, Sun L, Niu Y, Department of Urology Tianjin Institute of Urology, 2nd Hospital of Tianjin Medical University, People's Republic of China.: BMC Cancer 2013; 13:332. doi:10.1186/1471-2407-13-332.

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See, William A

2014-11-01

To explore the necessity of maintenance, efficacy of low-dose and superiority of various combination therapies of Bacillus Calmette-Guérin (BCG) in treatment of superficial bladder cancer (BCa). Comprehensive searches of electronic databases (PubMed, Embase, and the Cochrane Library), were performed, then a systematic review and cumulative meta-analysis of 21 randomized, controlled trials (RCTs) and 9 retrospective comparative studies were carried out according to, predefined inclusion criteria. Significantly better recurrence-free survivals (RFS) were observed respectively in patients who received BCG maintenance, standard-dose and BCG plus epirubicin therapy comparing to those received induction, low-dose and BCG alone. BCG maintenance therapy was also associated with significantly better progression-free survival (PFS), but there were more incidences of adverse events. Pooled results showed no remarkable advantage of BCG combined with Mitomycin C or with interferon α-2b in improving oncologic outcomes. Sensitivity-analyses stratified by study-design and tumor stage led to very similar overall results and often to a decrease of the between-study heterogeneity. Our data confirmed that non-RCT only affected strength rather than direction of the overall results. All patients with superficial BCa should be encouraged to accept BCG maintenance therapy with standard-dose if well tolerated. Patients can benefit from BCG combined with epirubicin but not from BCG combined with Mitomycin C or interferon α-2b. Copyright © 2014 Elsevier Inc. All rights reserved.

Mortalidad intrahospitalaria por accidente cerebrovascular

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Federico Rodríguez Lucci; Virginia Pujol Lereis; Sebastián Ameriso; Guillermo Povedano; María F. Díaz; Alejandro Hlavnicka; Néstor A. Wainsztein; Sebastián F. Ameriso

2013-01-01

La mortalidad global por accidente cerebrovascular (ACV) ha disminuido en las últimas tres décadas, probablemente debido a un mejor control de los factores de riesgo vascular. La mortalidad hospitalaria por ACV ha sido tradicionalmente estimada entre 6 y 14% en la mayoría de las series comunicadas. Sin embargo, los datos de ensayos clínicos recientes sugieren que esta cifra sería sustancialmente menor. Se revisaron datos de pacientes internados con diagnóstico de ACV del Banco de Datos de Str...

Bladder Contracture – A Rare and Serious Side Effect of Intravesical Bacillus Calmette-Guérin Therapy

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Cindy Garcia

2016-01-01

Full Text Available Instillation of intravesical bacillus Calmette-Guérin (BCG is an effective treatment for non-muscle invasive bladder cancer (NMIBC. The high incidence of side effects may limit its tolerability in patients. Local side effects including cystitis and hematuria are common but generally self-limiting. Bladder contractures are a rare but serious consequence of BCG treatment. In this case, an 82 year-old male developed BCG reactivation and subsequent bladder contractures following transurethral resection of the prostate (TURP three years post-BCG. To our knowledge, this is the first reported case of BCG reactivation post-TURP leading to the rare but serious effect of bladder contractures.

CARACTERÍSTICAS DA VIOLÊNCIA SEXUAL SOFRIDA POR CRIANÇAS ASSISTIDAS POR UM PROGRAMA DE APOIO

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KELLY LINHARES VASCONCELOS

2010-01-01

Full Text Available En Brasil, las estadísticas de la violencia sexual contra niños están lejos de reflejar la verdadera realidad actual debido a la baja notificación de los casos. La finalidad de este estudio fue caracterizar el abuso sexual sufrido por niños asistidos por el Programa Sentinela y el perfil del agresor, en Sobral-Ceará, en el periodo que va del 2002 al 2006. La muestra no probabilística intencional fue compuesta por 50 víctimas de abuso sexual y de las mismas, el 66% es del sexo femenino, con predominio de rango de edad entre 8-12 años incompletos, (58%; en el 36% de los casos los padres están separados, siendo la madre la principal responsable por la familia (62%. La mayoría de los agresores es del sexo masculino (78%. En el ambiente fuera de la familia los agresores son conocidos o amigos de la familia (14%; dentro del seno familiar el padrastro es identificado como siendo el agresor más frecuente (18%. Los datos destacan características similares a las de otros estudios, definiendo una cierta igualdad en este tipo de violencia.

Oral Tolerance to Environmental Mycobacteria Interferes with Intradermal, but Not Pulmonary, Immunization against Tuberculosis.

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Dominique N Price

2016-05-01

Full Text Available Bacille Calmette-Guérin (BCG is currently the only approved vaccine against tuberculosis (TB and is administered in over 150 countries worldwide. Despite its widespread use, the vaccine has a variable protective efficacy of 0-80%, with the lowest efficacy rates in tropical regions where TB is most prevalent. This variability is partially due to ubiquitous environmental mycobacteria (EM found in soil and water sources, with high EM prevalence coinciding with areas of poor vaccine efficacy. In an effort to elucidate the mechanisms underlying EM interference with BCG vaccine efficacy, we exposed mice chronically to Mycobacterium avium (M. avium, a specific EM, by two different routes, the oral and intradermal route, to mimic human exposure. After intradermal BCG immunization in mice exposed to oral M. avium, we saw a significant decrease in the pro-inflammatory cytokine IFN-γ, and an increase in T regulatory cells and the immunosuppressive cytokine IL-10 compared to naïve BCG-vaccinated animals. To circumvent the immunosuppressive effect of oral M. avium exposure, we vaccinated mice by the pulmonary route with BCG. Inhaled BCG immunization rescued IFN-γ levels and increased CD4 and CD8 T cell recruitment into airways in M. avium-presensitized mice. In contrast, intradermal BCG vaccination was ineffective at T cell recruitment into the airway. Pulmonary BCG vaccination proved protective against Mtb infection regardless of previous oral M. avium exposure, compared to intradermal BCG immunization. In conclusion, our data indicate that vaccination against TB by the pulmonary route increases BCG vaccine efficacy by avoiding the immunosuppressive interference generated by chronic oral exposure to EM. This has implications in TB-burdened countries where drug resistance is on the rise and health care options are limited due to economic considerations. A successful vaccine against TB is necessary in these areas as it is both effective and economical.

Granulomatous prostatitis after intravesical bacillus Calmette-Guérin instillation therapy: A potential cause of incidental F-18 FDG uptke in the prostate gland on F-18 FDG PET/CT in patients with bladder cancer

International Nuclear Information System (INIS)

Kim, Choon Young; Lee, Sang Woo; Choi, Seock Hwan; Son, Seung Hyun; Jung, Ji Hoon; Lee, Chang Hee; Jeong, Shin Young; Ahn, Byeong Cheol; Lee, Jae Tae

2016-01-01

This study aimed to evaluate the possibility that Bacillus Calmette-Guérin (BCG)-induced granulomatous prostatitis can be a potential cause of benign F-18 FDG uptake. A total of 395 bladder cancer patients who underwent F-18 FDG PET/CT (PET/CT) were retrospectively evaluated. Patients were divided into two groups according to BCG therapy status. Elapsed time after BCG therapy, serum PSA level, results of prostate biopsy, and the SUV max and uptake pattern in the prostate gland were reviewed. For patients who underwent follow-up PET/CT, the changes in SUV max were calculated. While 35 % of patients showed prostate uptake in the BCG therapy group, only 1 % showed prostate uptake in the non-BCG therapy group (p < 0.001). Among 49 patients with FDG-avid prostate lesions, none had suspected malignancy during the follow-up period (median: 16 months). Five patients revealed granulomatous prostatitis on biopsy. The incidence of FDG-avid prostate lesions was significantly higher if the elapsed time after BCG therapy was less than 1 year compared to more than 1 year (p < 0.001). Serum PSA was normal in 88 % of patients. All patients with incidental F-18 FDG uptake in the prostate gland showed focal or multifocal prostate uptake, and median SUV max was 4.7. In 16 patients who underwent follow-up PET/CT, SUV max was decreased in 14 patients (88 %) without treatment, and no patients demonstrated further increased prostate uptake (p < 0.001). BCG-induced granulomatous prostatitis can be a potential cause of benign F-18 FDG uptake, especially in those with a history of bladder cancer treated with BCG. In BCG-induced granulomatous prostatitis, focal or multifocal prostate uptake is frequently seen within 1 year after BCG therapy, and the intensity of prostate uptake is decreased on the follow-up PET/CT without any treatment

Improving Mycobacterium bovis bacillus Calmette-Guèrin as a vaccine delivery vector for viral antigens by incorporation of glycolipid activators of NKT cells.

Science.gov (United States)

Venkataswamy, Manjunatha M; Ng, Tony W; Kharkwal, Shalu S; Carreño, Leandro J; Johnson, Alison J; Kunnath-Velayudhan, Shajo; Liu, Zheng; Bittman, Robert; Jervis, Peter J; Cox, Liam R; Besra, Gurdyal S; Wen, Xiangshu; Yuan, Weiming; Tsuji, Moriya; Li, Xiangming; Ho, David D; Chan, John; Lee, Sunhee; Frothingham, Richard; Haynes, Barton F; Panas, Michael W; Gillard, Geoffrey O; Sixsmith, Jaimie D; Korioth-Schmitz, Birgit; Schmitz, Joern E; Larsen, Michelle H; Jacobs, William R; Porcelli, Steven A

2014-01-01

Recombinant Mycobacterium bovis bacillus Calmette-Guèrin (rBCG) has been explored as a vector for vaccines against HIV because of its ability to induce long lasting humoral and cell mediated immune responses. To maximize the potential for rBCG vaccines to induce effective immunity against HIV, various strategies are being employed to improve its ability to prime CD8+ T cells, which play an important role in the control of HIV infections. In this study we adopted a previously described approach of incorporating glycolipids that activate CD1d-restricted natural killer T (NKT) cells to enhance priming of CD8+ T cells by rBCG strains expressing an SIV Gag antigen (rBCG-SIV gag). We found that the incorporation of the synthetic NKT activating glycolipid α-galactosylceramide (α-GC) into rBCG-SIV gag significantly enhanced CD8+ T cell responses against an immunodominant Gag epitope, compared to responses primed by unmodified rBCG-SIV gag. The abilities of structural analogues of α-GC to enhance CD8+ T cell responses to rBCG were compared in both wild type and partially humanized mice that express human CD1d molecules in place of mouse CD1d. These studies identified an α-GC analogue known as 7DW8-5, which has previously been used successfully as an adjuvant in non-human primates, as a promising compound for enhancing immunogenicity of antigens delivered by rBCG.vectors. Our findings support the incorporation of synthetic glycolipid activators of NKT cells as a novel approach to enhance the immunogenicity of rBCG-vectored antigens for induction of CD8+ T cell responses. The glycolipid adjuvant 7DW8-5 may be a promising candidate for advancing to non-human primate and human clinical studies for the development of HIV vaccines based on rBCG vectors.

Early secreted antigen ESAT-6 of Mycobacterium tuberculosis promotes protective T helper 17 cell responses in a toll-like receptor-2-dependent manner.

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Samit Chatterjee

2011-11-01

Full Text Available Despite its relatively poor efficacy, Bacillus Calmette-Guérin (BCG has been used as a tuberculosis (TB vaccine since its development in 1921. BCG induces robust T helper 1 (Th1 immune responses but, for many individuals, this is not sufficient for host resistance against Mycobacterium tuberculosis (M. tb infection. Here we provide evidence that early secreted antigenic target protein 6 (ESAT-6, expressed by the virulent M. tb strain H37Rv but not by BCG, promotes vaccine-enhancing Th17 cell responses. These activities of ESAT-6 were dependent on TLR-2/MyD88 signalling and involved IL-6 and TGF-β production by dendritic cells. Thus, animals that were previously infected with H37Rv or recombinant BCG containing the RD1 region (BCG::RD1 exhibited improved protection upon re-challenge with virulent H37Rv compared with mice previously infected with BCG or RD1-deficient H37Rv (H37RvΔRD1. However, TLR-2 knockout (TLR-2⁻/⁻ animals neither showed Th17 responses nor exhibited improved protection in response to immunization with H37Rv. Furthermore, H37Rv and BCG::RD1 infection had little effect on the expression of the anti-inflammatory microRNA-146a (miR146a in dendritic cells (DCs, whereas BCG and H37RvΔRD1 profoundly induced its expression in DCs. Consistent with these findings, ESAT-6 had no effect on miR146a expression in uninfected DCs, but dramatically inhibited its upregulation in BCG-infected or LPS-treated DCs. Collectively, our findings indicate that, in addition to Th1 immunity induced by BCG, RD1/ESAT-6-induced Th17 immune responses are essential for optimal vaccine efficacy.

Improving Mycobacterium bovis bacillus Calmette-Guèrin as a vaccine delivery vector for viral antigens by incorporation of glycolipid activators of NKT cells.

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Manjunatha M Venkataswamy

Full Text Available Recombinant Mycobacterium bovis bacillus Calmette-Guèrin (rBCG has been explored as a vector for vaccines against HIV because of its ability to induce long lasting humoral and cell mediated immune responses. To maximize the potential for rBCG vaccines to induce effective immunity against HIV, various strategies are being employed to improve its ability to prime CD8+ T cells, which play an important role in the control of HIV infections. In this study we adopted a previously described approach of incorporating glycolipids that activate CD1d-restricted natural killer T (NKT cells to enhance priming of CD8+ T cells by rBCG strains expressing an SIV Gag antigen (rBCG-SIV gag. We found that the incorporation of the synthetic NKT activating glycolipid α-galactosylceramide (α-GC into rBCG-SIV gag significantly enhanced CD8+ T cell responses against an immunodominant Gag epitope, compared to responses primed by unmodified rBCG-SIV gag. The abilities of structural analogues of α-GC to enhance CD8+ T cell responses to rBCG were compared in both wild type and partially humanized mice that express human CD1d molecules in place of mouse CD1d. These studies identified an α-GC analogue known as 7DW8-5, which has previously been used successfully as an adjuvant in non-human primates, as a promising compound for enhancing immunogenicity of antigens delivered by rBCG.vectors. Our findings support the incorporation of synthetic glycolipid activators of NKT cells as a novel approach to enhance the immunogenicity of rBCG-vectored antigens for induction of CD8+ T cell responses. The glycolipid adjuvant 7DW8-5 may be a promising candidate for advancing to non-human primate and human clinical studies for the development of HIV vaccines based on rBCG vectors.

Urinary fibronectin levels in patients treated with intravesical bacillus Calmette-Guérin for superficial bladder cancer.

Science.gov (United States)

Danişman, A; Bulut, K; Kukul, E; Ozen, I; Sevük, M

2000-01-01

Intravesical bacillus Calmette-Guérin (BCG) has been shown to be an effective treatment for superficial transitional cell carcinoma (TCC) of the bladder, but the precise mechanism of action of BCG remains poorly understood. Fibronectin (FN), an important component of the extracellular matrix, has been found to play a role in BCG therapy. Some studies have shown that the soluble form of FN can compete efficiently with the matrix form of binding to the specific receptors on the bacteria and could consequently diminish the effect of BCG treatment. To evaluate a possible correlation between the urinary levels of FN and the efficacy of BCG therapy, we determined prospectively the urinary FN levels in 38 patients with TCC of the bladder and in 25 control subjects without malignancy matched for age and sex. All TCC patients were treated with transurethral tumor resection plus 6 weekly intravesical BCG instillations. After an average follow-up of 30 months, 8 patients (21.1%) had recurrent tumors, while 30 (78.9%) were free of tumor after intravesical BCG therapy. Urinary levels of FN in cancer patients have been shown to be significantly higher than controls (p 0. 05). It was also found that the mean urinary FN levels were not statistically significant between patients with recurrence and complete remission. The data suggest that BCG-bladder tumor cell binding is not influenced by soluble fibronectin and urinary FN may not be a ideal marker for selecting patients to BCG therapy. Copyright 2000 S. Karger AG, Basel

Vivencias psicosociales reveladas por niños que reciben tratamiento con quimioterapia por cáncer

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BLANCA CECILIA VANEGAS DE AHOGADO

2009-12-01

Full Text Available Se realizó un estudio cualitativo con el propósito de descubrir las vivencias psicosociales de niños y niñas de 9 a 12 años que recibían tratamiento con quimioterapia por cáncer. La recolección de la información se hizo mediante encuentros lúdicos con el apoyo de algunas preguntas básicas que facilitaron las revelaciones narrativas. Tres aspectos se destacan en los hallazgos del estudio: vivencias desfavorables, vivencias relacionadas con la autoestima y vivencias favorables; las dos primeras, de diversa manera, afectan en estos niños su vida personal, familiar, escolar y, en general, todo su entorno. Es de resaltar que, como consecuencia de la caída del cabello, con frecuencia han sido objeto de burla y de rechazo por sus compañeros de estudio, lo que produce el más notorio efecto sobre su autoimagen; por otra parte, el ausentismo escolar conlleva dificultades académicas y sentimientos de tristeza en estos niños, situación que empeora cuando, por motivos de tratamiento, su lugar de residencia está alejado de la ciudad, viéndose sometidos a largos periodos de separación, no solo de su familia sino de sus pares. Se concluye que la mayor parte de las revelaciones son impactantes por su gran contenido de sufrimiento y dolor para estos niños, lo que demuestra la urgencia de retomar los hallazgos del estudio para orientar el cuidado de enfermería de manera más integral y apoyar para que se haga lo propio en el hogar y en las instituciones educativas.

Nosocomial Mycobacterium bovis-bacille Calmette-Guérin infections due to contamination of chemotherapeutics: case finding and route of transmission

NARCIS (Netherlands)

Vos, Margreet C.; de Haas, Petra E. W.; Verbrugh, Henri A.; Renders, Nicole H. M.; Hartwig, Nico G.; de Man, Peter; Kolk, Arend H. J.; van Deutekom, Henk; Yntema, J. L.; Vulto, Arnold G.; Messemaker, Marja; van Soolingen, Dick

2003-01-01

We studied nosocomial infections due to Mycobacterium bovis bacille Calmette-Guérin (BCG) Onco-TICE bacteria, transmitted by contamination of medication prepared in BCG Onco-TICE-contaminated hoods in the pharmacy, in 5 immunocompromised patients at 3 hospitals. The BCG strains cultured from the

Pedro Teixeira y su viaje por Mesopotamia

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Fuente del Pilar, José Javier

2005-04-01

Full Text Available Pedro Teixeira es un integrante notable de la ilustre nómina de los viajeros portugueses que, a finales del s, XVI y principios del XVII, ensancharon para Occidente las fronteras del mundo. Su conocimiento en España se debe a la publicación en 1994 de su obra «Relaciones del Origen, Descendencia y Sucesión de los Reyes de Persia, y de Harmuz, y de un viaje hecho por el autor dende la India hasta Italia por tierra», en edición realizada por el profesor Eduardo Barajas Sala, lamentablemente fallecido en 1997. En este artículo se ofrece una reseña biográfica de Pedro Teixeira, y un análisis del viaje narrado por el autor en la última parte de sus «Relaciones »: el que desde Ormuz le conducirá, a través de Mesopotamia, hasta la costa del Mediterráneo.…

Violência e mortes por causas externas

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Graciete Oliveira Vieira

2003-02-01

Full Text Available Através de um estudo ecológico caracterizou-se a violência e as mortes por causas externas em Salvador e Bahia utilizando-se dados da Fundação Nacional de Saúde-Ministério da Saúde, dos registros de mortalidade e das estimativas populacionais do IBGE. O risco de morrer por homicídio no Brasil é 3 vezes o do Estados Unidos, chegando a ser 40 vezes superior ao do Japão. Homicídio foi a primeira causa de anos potenciais de vidas perdidos (13,4% no Brasil (1997, seguido por acidentes de trânsito (10,6%. Causas externas foi a segunda causa de morte em Salvador e Bahia (1996. A violência tem raízes sócio-culturais e político-ideológicas e pode ser prevenida por ações intersetoriais e multidisciplinares.

Associação entre violência por parceiro íntimo contra a mulher e infecção por HIV

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Claudia Barros

2011-04-01

Full Text Available OBJETIVO: Analisar a associação entre a violência por parceiro íntimo contra mulheres e a infecção ou suspeita de infecção pelo vírus da imunodeficiência humana (HIV. MÉTODOS: Estudo transversal com base em dados de questionários aplicados face-a-face e de prontuários médicos de 2.780 mulheres de 15 a 49 anos, atendidas em unidades do sistema único de saúde da Grande São Paulo, SP, em 2001-2002. As mulheres foram categorizadas em: usuárias em tratamento por serem "soropositivas para o HIV", com "suspeita de HIV" e aquelas que procuraram os serviços por outros motivos. A violência por parceiro íntimo contra mulheres na vida foi categorizada por gravidade e recorrência dos episódios de violência. A associação com o desfecho foi testada pelo modelo de Poisson com variância robusta e ajustada por variáveis sociodemográficas, sexuais e reprodutivas. RESULTADOS: A prevalência de violência foi de 59,8%. Sofrer violência reiterada e grave apresentou maior associação de infecção confirmada pelo HIV (RP = 1,91. A violência independente da gravidade e da recorrência dos episódios apresentou maior associação para a suspeita de infecção por HIV (RP = 1,29. CONCLUSÕES: A violência por parceiro íntimo contra mulheres tem papel relevante nas situações de suspeita e confirmação da infecção pelo HIV, sendo essencial incluir sua detecção, controle e prevenção como parte da atenção integral à saúde das mulheres.

Predominant porB1A and porB1B genotypes and correlation of gene mutations with drug resistance in Neisseria gonorrhoeae isolates in Eastern China

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Tang Renxian

2010-11-01

Full Text Available Abstract Background Variations of porB1A and porB1B genes and their serotypes exist in Neisseria gonorrhoeae isolates from different geographical areas, and some site mutations in the porB1B gene correlate with drug resistance. Methods The β-lactamase production of N. gonorrhoeae isolates was determined by paper acidometric test and nitrocefin discs. The porB1A and porB1B genes of 315 non-penicillinase-producting N. gonorrhoeae (non-PPNG strains were amplified by PCR for sequencing to determine serotypes and site mutations. A duplex PCR was designed to simultaneously detect both porB1A and porB1B genes. Penicillin and tetracycline resistance was assessed by an in vitro drug sensitivity test. Results Of the N. gonorrhoeae isolates, 31.1% tested positive for porB1A and 68.9% for porB1B genes. All the 98 porB1A+ isolates belonging to IA6 serotype with either no mutation at the 120 and 121 sites (88.8% or a D120G (11.2% mutation and were no resistance to both penicillin and tetracycline. Among the 217 porB1B+ isolates, 26.7%, 22.6% and 11.5% belonged to IB3, IB3/6 and IB4 serotypes, respectively. Particularly, two novel chimeric serotypes, IB3/6-IB2 and IB2-IB4-IB2, were found in 77 and 8 porB1B+ isolates. Two hundred and twelve (97.7% of the porB1B+ isolates were presented G120 and/or A121 mutations with 163 (76.9% at both sites. Interestingly, within the 77 porB1B+ isolates belonging to IB3/6-IB2 serotype, 15 were discovered to possess novel deletions at both A121 and N122 sites. All the replacement mutations at these sites in PorB1B were correlated with resistance and the deletion mutation showed the highest resistance. Conclusion N. gonorrhoeae isolates circulating in Eastern China include a sole PorB1A serotype (IA6 and five PorB1B serotypes. Multiple mutations in porB1B genes, including novel A121 and N122 deletions, are correlated with high levels of penicillin and tetracycline resistance.

Conservación por calor

OpenAIRE

Cobos García, Angel; Díaz Rubio, Olga

2011-01-01

Esta unidade didáctica denominada Conservación por calor forma parte da materia «Tecnoloxía do procesado de alimentos» que se impartirá no primeiro semestre do 2º curso do Grao en Nutrición Humana e Dietética. A materia estrutúrase en diferentes unidades didácticas, tratando cada unha delas as diferentes tecnoloxías de procesado dos alimentos, tanto de conservación coma de transformación. A presente unidade didáctica aborda a conservación dos alimentos por calor. Este método permite destruír ...

Las cosas por su nombre

OpenAIRE

Storani, Emilia

2017-01-01

El artículo propone indagar sobre los modos y diferentes formatos que se utilizan tanto en la escritura como en la lectura, para articular con las luchas por la identidad de género. La Ley de Identidad de Género ha sido un puntapié clave para pensarnos a nosotros mismos culturalmente y para pensar a los demás. Pero, ¿cómo mencionamos, escribimos y leemos las diferentes identidades? La escritura, también es un mundo transformador para quienes bregan por una sociedad más libre y sin prejuicios....

Diverticulitis yeyunal perforada por enterolito.

OpenAIRE

Marenco De la Cuadra, Beatriz; Gomez-Rosado, Juan-Carlos; Capitan-Morales, Luis-Cristobal; Valdés Hernández, Javier; Reyes-lopera, N.J. De los

2012-01-01

La diverticulosis yeyunal es una enfermedad adquirida rara. Casi el 60-70% keeps asymptomátic or Con síntomas crónicos inespecíficos, aunque puede presentarse como un abdomen agudo. La perforación debida a enterolitos es una causa extremadamente rara do complicación, y puede producirse por la impactación de ésta contra la pared intestinal. Presentamos caso de un varón de 82 años que acude a urgencias por un dolor súbito abdominal, difuso, con irritación peritoneal, leucocitosis con neutro...

Por y para en los manuales de ELE

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Sidoti, Rossana

2008-12-01

Full Text Available La oposición por / para es una de las cuestiones gramaticales que comportan mayor dificultad a la hora de acercarse al estudio del español como L2 sobre todo cuando remiten a conceptos lingüísticos difíciles de entender por no tener ésta referente alguno en el mundo extralingüístico. Si, por un lado, nos resulta fácil entender lo que tiene un referente en el mundo concreto; por otro, no podemos advertir el referente extralingüístico de preposiciones como por / para, si este no existe. Si las preposiciones son elementos abstractos, difíciles de aferrar de por sí, podemos sólo examinar los elementos que éstas ponen en relación y en qué contextos esta relación se determina. Para poder utilizar con precisión las dos preposiciones, es importante no reducirlas a una sola preposición como ocurre en otros idiomas, y sobre todo no relacionarlas sólo a los conceptos de causa y finalidad. Este trabajo se propone individualizar los manuales de español como lengua extranjera más utilizados en las universidades italianas para luego comparar las distintas fuentes de información sobre por / para y exponer comentarios, reflexiones y sugerencias sobre el tema con el fin de precisar en qué medida se puede mejorar lo que los manuales reducen o generalizan, puesto que para los estudiantes de ELE estos representan una herramienta valiosa a la que acudir.

Robust ballistocardiogram acquisition for home monitoring

International Nuclear Information System (INIS)

Inan, O T; Etemadi, M; Giovangrandi, L; Kovacs, G T A; Wiard, R M

2009-01-01

The ballistocardiogram (BCG) measures the reaction of the body to cardiac ejection forces, and is an effective, non-invasive means of evaluating cardiovascular function. A simple, robust method is presented for acquiring high-quality, repeatable BCG signals from a modified, commercially available scale. The measured BCG waveforms for all subjects qualitatively matched values in the existing literature and physiologic expectations in terms of timing and IJ amplitude. Additionally, the BCG IJ amplitude was shown to be correlated with diastolic filling time for a subject with premature atrial contractions, demonstrating the sensitivity of the apparatus to beat-by-beat hemodynamic changes. The signal-to-noise ratio (SNR) of the BCG was estimated using two methods, and the average SNR over all subjects was greater than 12 for both estimates. The BCG measurement was shown to be repeatable over 50 recordings taken from the same subject over a three week period. This approach could allow patients at home to monitor trends in cardiovascular health

Targeting estrogen/estrogen receptor alpha enhances Bacillus Calmette-Guérin efficacy in bladder cancer.

Science.gov (United States)

Shang, Zhiqun; Li, Yanjun; Hsu, Iawen; Zhang, Minghao; Tian, Jing; Wen, Simeng; Han, Ruifa; Messing, Edward M; Chang, Chawnshang; Niu, Yuanjie; Yeh, Shuyuan

2016-05-10

Recent studies showed the potential linkage of estrogen/estrogen receptor signaling with bladder tumorigenesis, yet detailed mechanisms remain elusive. Here we found a new potential therapy with the combination of Bacillus Calmette-Guerin (BCG) and the anti-estrogen ICI 182,780 led to better suppression of bladder cancer (BCa) than BCG alone. Mechanism dissection found ICI 182,780 could promote BCG attachment/internalization to the BCa cells through increased integrin-α5β1 expression and IL-6 release, which may enhance BCG-induced suppression of BCa cell growth via recruiting more monocytes/macrophages to BCa cells and increased TNF-α release. Consistently, in vivo studies found ICI 182,780 could potentiate the anti-BCa effects of BCG in the carcinogen-induced mouse BCa models. Together, these in vitro and in vivo results suggest that combining BCG with anti-estrogen may become a new therapeutic approach with better efficacy to suppress BCa progression and recurrence.

A review of the literature on the economics of vaccination against TB

NARCIS (Netherlands)

Tu, H.A.; Vu, H.D.; Rozenbaum, M.H.; Woerdenbag, H.J.; Postma, M.J.

The BCG vaccine was introduced in 1921 and remains the only licensed vaccine for the prevention of TB worldwide. Despite its extensive use, the BCG vaccine lacks the ability to fully control the TB-endemic and -pandemic situations. The BCG vaccine is most effective in preventing pediatric TB, in

Pronóstico de la diarrea por rotavirus

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Mota-Hernández Felipe

2001-01-01

Full Text Available Objetivo. Comparar la gravedad de la diarrea por rotavirus (RV y por no rotavirus. Material y métodos. Estudio transversal en 520 lactantes con diarrea aguda, efectuado entre octubre de 1994 y marzo de 1995 en siete centros del primer nivel de atención en cinco estados de México. El diagnóstico de RV se realizó con ensayo inmunoenzimático o por electroforesis. El análisis se hizo a través de medidas de tendencia central. Los resultados se presentan como promedio y desviación estándar o mediana o variación. Resultados. Se aisló RV en 264 lactantes (50.7% con predominio en varones de 6 meses a un año. Las manifestaciones clínicas fueron significativamente diferentes entre el grupo rotavirus positivo y el grupo rotavirus negativo en mediana de evacuaciones por 24 horas, frecuencia de vómitos, temperatura > 38° C, deshidratación y calificación de gravedad, respectivamente. Conclusiones. Estos resultados mostraron peor pronóstico por mayor gravedad de la diarrea por RV en lactantes, con relación a otra etiología. El texto completo en inglés de este artículo está disponible en: http://www.insp.mx/salud/index.html

A review of the literature on the economics of vaccination against TB.

Science.gov (United States)

Tu, Hong-Anh T; Vu, Hoa D; Rozenbaum, Mark H; Woerdenbag, Herman J; Postma, Maarten J

2012-03-01

The BCG vaccine was introduced in 1921 and remains the only licensed vaccine for the prevention of TB worldwide. Despite its extensive use, the BCG vaccine lacks the ability to fully control the TB-endemic and -pandemic situations. The BCG vaccine is most effective in preventing pediatric TB, in particular, miliary TB and tuberculous meningitis. However, it has a limited effect in preventing pulmonary TB, which occurs more frequently in adults. BCG vaccination has now been implemented in more than 157 countries worldwide. For various countries, the benefits of vaccination are only limited and potentially not cost effective. The International Union Against Tuberculosis and Lung Diseases had set the criteria for discontinuation of BCG vaccination in 1994. This decision, however, was not based on economic considerations. Many developed countries have met the criteria set by the International Union Against Tuberculosis and Lung Disease and stopped universal BCG vaccination. For developing countries, the BCG vaccine is still an effective intervention in protecting young children from TB infection. A lot of effort has been spent on R&D of new TB vaccines, the first of which are expected to be available within 5-7 years from now. Novel TB vaccines are expected to be better and more effective than the current BCG vaccine and should provide a viable strategy in controlling TB morbidity and mortality. In this review, the aim is to explore economic evaluations that have been carried out for vaccination against TB worldwide. In addition to epidemiological evidence, economic evidence can play a crucial role in supporting the governments of countries in making proper public health decisions on BCG vaccination policies, in particular, to implement, continue, or discontinue.

Miasis cutanea por cordylobia anthropophaga

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Alkorta Gurrutxaga Miriam

2001-01-01

Full Text Available El incremento progresivo en el número de personas que viajan a países tropicales ha hecho que las enfermedades importadas adquieran una relevancia cada vez mayor. Las miasis (o infestaciones por larvas de moscas cutáneas se encuentran entre este tipo de enfermedades siendo especialmente frecuentes en países tropicales. A propósito de la observación de un caso de miasis cutánea masiva por Cordylobia antropophaga, que ocurrió en una mujer de 34 años de edad al volver de un viaje a Senegal, se ha efectuado una revisión de los casos de miasis cutáneas forunculoides importadas publicados en España, así como de la biología, patología, tratamiento y prevención de la miasis humana por Cordylobia anthropophaga. El caso referido, se caracterizó por la infestación con un número inusualmente elevado de larvas, no sospechándose su etiología hasta la fase final de la enfermedad. La emergencia continuada de larvas (se recogieron 91 generó en la paciente un estado de ansiedad importante. Finalmente, la eliminación de las larvas provocó una rápida mejoría de la paciente. Aunque los casos de miasis cutánea no tienen la gravedad de otras enfermedades importadas, su conocimiento es necesario desde el punto de vista preventivo, diagnóstico y terapeútico. Es importante proceder a la identificación morfológica de las larvas diferenciándolas de otro tipo de miasis con implicaciones terapéuticas diferentes.

Associação entre violência por parceiro íntimo contra a mulher e infecção por HIV Asociación entre violencia contra la mujer por pareja íntima e infección por VIH Association between intimate partner violence against women and HIV infection

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Claudia Barros

2011-04-01

Full Text Available OBJETIVO: Analisar a associação entre a violência por parceiro íntimo contra mulheres e a infecção ou suspeita de infecção pelo vírus da imunodeficiência humana (HIV. MÉTODOS: Estudo transversal com base em dados de questionários aplicados face-a-face e de prontuários médicos de 2.780 mulheres de 15 a 49 anos, atendidas em unidades do sistema único de saúde da Grande São Paulo, SP, em 2001-2002. As mulheres foram categorizadas em: usuárias em tratamento por serem "soropositivas para o HIV", com "suspeita de HIV" e aquelas que procuraram os serviços por outros motivos. A violência por parceiro íntimo contra mulheres na vida foi categorizada por gravidade e recorrência dos episódios de violência. A associação com o desfecho foi testada pelo modelo de Poisson com variância robusta e ajustada por variáveis sociodemográficas, sexuais e reprodutivas. RESULTADOS: A prevalência de violência foi de 59,8%. Sofrer violência reiterada e grave apresentou maior associação de infecção confirmada pelo HIV (RP = 1,91. A violência independente da gravidade e da recorrência dos episódios apresentou maior associação para a suspeita de infecção por HIV (RP = 1,29. CONCLUSÕES: A violência por parceiro íntimo contra mulheres tem papel relevante nas situações de suspeita e confirmação da infecção pelo HIV, sendo essencial incluir sua detecção, controle e prevenção como parte da atenção integral à saúde das mulheres.OBJETIVO: Analizar la asociación entre la violencia contra mujeres por pareja íntima y la infección o sospecha de infección por el virus de inmunodeficiencia humana (VIH. MÉTODOS: Estudio transversal con base en datos de cuestionarios aplicados cara-a cara y de prontuarios médicos de 2.780 mujeres de 15 a 49 años, atendidas en unidades del sistema único de salud de la Gran Sao Paulo, Sureste de Brasil, en 2001-2002. Las mujeres fueron categorizadas en: usuarias en tratamiento por ser

Zigomicosis

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Gerson Arias León

2010-12-01

Full Text Available Las zigomicosis son infecciones fúngicas graves e inusuales, causadas por hongos ubicuos pertenecientes a la clase Zigomicetos, los cuales están subdivididos en dos órdenes: Mucorales y Entomoftorales. Las infecciones causadas por los Mucorales se caracterizan por su rápida evolución, con destrucción tisular e invasión de vasos sanguíneos. Se presentan en hospederos con factores de riesgo definidos, entre los que se incluyen alteraciones funcionales o cuantitativas de los neutrófilos, acidosis metabólica o aumento en los niveles séricos de hierro. Sus manifestaciones clínicas se dividen en rinocerebral, pulmonar, cutánea, gastrointestinal y diseminada. El principal mecanismo de infección es la vía inhalatoria, seguida por la mecánica por lesiones dérmicas. Tienen un curso clínico agresivo y a su vez inespecífico que usualmente pone en peligro la vida del paciente, por lo que se debe tener un alto índice de sospecha en aquellas personas con cuadro clínico sugestivo y factores de riesgo, para iniciar tratamiento agresivo temprano con antifúngicos y cirugía.Zygomycosis are severe and uncommon fungal infections caused by ubiquitous fungi members of the class zygomicetes, which are subdivided into two orders: Mucorales and Entomophtorales. Infections due to Mucorales are characterized by a rapid evolution along with a wide tissue destruction and direct invasion of blood vessels. These diseases are seen in individuals with clearly defined risk factors such as quantitative or qualitative neutrophil defects, metabolic acidosis, or elevated iron serum levels. The clinical forms of these diseases are divided into new categories: Rhinocerebral, pulmonary, cutaneous, gastrointestinal, and disseminated infections. The main mechanism of infection is by inhalation, but it is also possible to acquire the infection by direct inoculation into the dermis. The clinical course is aggressive but unspecified and usually threatens patients

EFECTOS DE LA POLÍTICA DE COLONIZACIÓN EN EL REGADÍO DE EXTREMADURA: BALANCE Y PERSPECTIVA

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Cipriano Juárez Sánchez\\u2013Rubio

1996-01-01

Full Text Available La puesta en funcionamiento de las directrices emanadas de la política de coloniza- ción de 1939–1977 tiene en Extremadura a una de las regiones más favorecidas por la cantidad de superficie transformada y su paralela organización del espacio agrario, la cuantía de familias instaladas, la creación de nuevos poblados y por el número de viviendas construidas, agrupadas y diseminadas. Una gran obra, que pretendía la crea- ción de auténticas empresas agrarias, de orientación marcadamente agrícola, capaces de conseguir un nivel de productividad que posibilitara la retención de la mano de obra familiar y obreros agrícolas en el campo, pero que no lo ha conseguido, aunque el impacto producido tiene aspectos positivos. La nueva morfología agraria no ha creado una industria agroalimentaria potente ni desarrollado los servicios, los sectores productivos más generadores de empleo y dispo- nibilidad de renta. Las inversiones realizadas para mejorar el aprovechamiento de los recursos naturales y provocar el despegue socioeconómico de la región no han tenido la eficacia consiguiente. Por ello, la situación heredada obliga a la Administración Autonó- mica a intervenir para que el potencial existente en Extremadura, vinculado al proceso de transformación y colonización, pueda ser ampliado selectivamente en superficie de rega- dío, más integrado con el territorio y respetuoso y racional con el medio ambiente. Una forma más práctica y conveniente para impulsar el definitivo y deseado desarrollo socioeconómico de la región.

Resultados post mórtem e infecciones oportunistas en pacientes VIH-positivos de un hospital público del Perú

Directory of Open Access Journals (Sweden)

Dominique Eza

2006-10-01

Full Text Available Existen pocos estudios que reporten datos acerca de autopsias de pacientes con VIH en Sudamérica y ninguno que documente los resultados post mórtem en los pacientes con VIH/SIDA en el Perú. Objetivos: Determinar el espectro de las infecciones oportunistas y las causas de mortalidad en pacientes VIH-positivos en un hospital público en Lima. Asimismo, se revisa la información clínico-epidemiológica con respecto a la infección con VIH en el Perú. Materiales y métodos: Se incluyeron en este análisis retrospectivo, 16 autopsias relacionadas con VIH del Hospital Dos de Mayo, realizadas entre 1999-2004. Resultados: La causa primaria de la muerte fue establecida en 12 pacientes: uno murió de neoplasia y 11 de enfermedades infecciosas, incluyendo tres con infección pulmonar, siete con infección diseminada, y dos con infección del sistema nervioso central (un caso presentó patología dual. Las infecciones oportunistas fueron identificadas en 14 casos, incluyendo citomegalovirus, histoplasmosis, criptococcosis, toxoplasmosis, neumonía por Pneumocistis, aspergilosis, tuberculosis, virus de la varicela-zoster y criptosporidiosis. Catorce pacientes tenían por lo menos una enfermedad relacionada con el SIDA que no había sido sospechada clínicamente ni diagnosticada antes de la muerte. Por otra parte, 82% de los diagnósticos considerados de significancia clínica importante, no habían sido sospechados antes de la muerte. Conclusiones: El espectro y la frecuencia de ciertas infecciones oportunistas reportadas en el presente estudio lo diferencia de otros estudios de autopsias realizados en Sudamérica; destacando la importancia de realizar necropsias en VIH/SIDA en países de recursos limitados, con el fin de observar los patrones locales específicos de la enfermedad.

Itinerarios Didácticos por la isla de Lanzarote

OpenAIRE

Becerra-Ramírez, Rafael; González Cárdenas, Elena; Gosálvez, Rafael U.; Escobar Lahoz, Estela; Dóniz-Páez, Javier

2013-01-01

Con la confección de esta guía de itinerarios didácticos por la isla de Lanzarote pretendemos contribuir a un mayor conocimiento de las características geográficas de este espacio dominado por las formas volcánicas que caracterizan un paisaje modificado por la mano del hombre que convive con los volcanes y los usa, tradicionalmente como soporte de sus cultivos, y modernamente como base de la industria turística. Los itinerarios didácticos por la isla de Lanzarote son la adaptación de los t...

Signos Vitales de los CDC-Muertes por intoxicación por alcohol (Alcohol Poisoning Deaths)

Centers for Disease Control (CDC) Podcasts

2015-01-06

Este podcast se basa en la edición de enero del 2015 del informe Signos Vitales de los CDC. En los Estados Unidos, mueren en promedio seis personas cada día debido a la intoxicación por alcohol. Infórmese sobre lo que puede hacer para prevenir los atracones de alcohol y las intoxicaciones por alcohol.  Created: 1/6/2015 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 1/6/2015.

Topoplastia de Cvintal assistida por laser de femtossegundo

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Alexandre Takayoshi Ishizaki

2013-06-01

Full Text Available Apresentamos um relato de astigmatismo tardio progressivo pós-transplante de córnea para ceratocone, associado à afinamento periférico na junção doador-receptor, o que presumidamente pode ser considerado como recorrência da ectasia. O caso foi tratado por meio de Topoplastia de Cvintal assistida por laser de femtossegundo para a confecção da incisão com geometria "top hat", seguido de sutura com ajuste per-operatório guiado por ceratoscopia.

Micetoma por Nocardia brasiliensis: reporte de caso

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Miriam Guevara R

2003-07-01

Full Text Available Se presenta el caso de un paciente peruano, agricultor, con una infección cutánea de origen traumático causada por Nocardia brasiliensis, que evolucionó hacia la amputación del miembro inferior afectado. El diagnóstico se realizó por examen directo y cultivo del espécimen.

Mortalidad por envenenamiento en niños

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Híjar Martha

1998-01-01

Full Text Available Objetivo. Conocer el panorama de las muertes por envenenamiento en niños de 0-14 años ocurridas en la República mexicana, entre 1979 y 1994. Material y métodos. Se utilizaron fuentes secundarias. Las variables analizadas fueron: edad, sexo, año, causa externa de traumatismos y envenenamientos, de la IX Clasificación Internacional de Enfermedades: E850-E858, E860-E869 y E905. Mediante un modelo de regresión Poisson se analizaron tendencias por causa específica y se obtuvieron riesgos relativos según edad, sexo y entidad federativa. Resultados. Hubo un total de 11 272 defunciones en menores de 15 años; las principales causas fueron el envenenamiento y las reacciones tóxicas causadas por plantas y animales venenosos (E905, el envenenamiento accidental por gas de uso doméstico y por monóxido de carbono (E868 y el envenenamiento accidental por otras drogas (E858. El grupo de edad que presentó los mayores riesgos, para las causas mencionadas, fue el de menores de un año con un riesgo relativo (RR de 29.6, IC95% 29.2-33.4; RR 3.47, IC95% 2.86-4.22, y RR 31.86, IC95% 24.8-40.9. El riesgo fue similar en ambos sexos, salvo para la causa E905. El estado de Aguascalientes se situó sistemáticamente entre los de mayor riesgo para todas las causas analizadas, mientras que Nuevo León siempre se ubicó entre los de riesgo más bajo. Conclusiones. El envenenamiento constituye una importante causa de muerte en los niños; el riesgo se incrementa al disminuir la edad. Considerando que esas muertes son potencialmente evitables y que la mayor parte de los envenenamientos ocurren en el hogar, para prevenirlos, se recomienda a los familiares vigilar y mantener fuera de peligro al niño. Por otra parte, la multicausalidad del fenómeno requiere que su prevención se realice desde una perspectiva multidisciplinaria que genere una cultura y un ambiente de seguridad en la sociedad.

The immunological effect of revaccination with Bacille Calmette-Guérin vaccine at 19 months of age.

Science.gov (United States)

Andersen, Andreas; Roth, Adam; Jensen, Kristoffer Jarlov; Erikstrup, Christian; Lisse, Ida Marie; Whittle, Hilton; Sartono, Erliyani; Yazdanbakhsh, Maria; Aaby, Peter; Benn, Christine Stabell

2013-04-19

Bacille Calmette-Guérin (BCG) vaccination has important non-specific immune effects. In a randomized trial in Guinea-Bissau, BCG revaccination was associated with significantly increased survival in children who received diphtheria-tetanus-pertussis (DTP)-booster vaccine before enrolment and in children who did not receive micronutrient supplementation (MN). Within the trial we assessed the immunological effects of BCG revaccination. Children were randomized to BCG or nothing. Blood was sampled 6-11 weeks after randomization (early sample group) or 5-9 months later (late sample group). In vitro cytokine responses (interferon (IFN)-γ, interleukin (IL)-13, tumor-necrosis-factor (TNF)-α, and IL-10) were assessed in whole blood cultures stimulated with lipopolysaccharide (LPS), purified protein derivative (PPD) or phytohaemagglutinin (PHA). Effect-modification by sex, DTP-booster vaccination and MN was studied. Cytokines were measured in 345 infants. BCG was associated with significantly increased IFN-γ (geometric mean ratio (GMR)=4.54 (95% confidence interval: 3.13-6.58)) and IL-13 (GMR=1.43 (1.00-2.05)) PPD responses, the effect being strongest in the early sample group. Across all three conditions BCG tended to increase IL-10 (LPS, PHA, PPD: GMR=1.20, 1.12, 1.20), most pronounced in the late sample group. BCG reduced the TNF-α/IL-10 ratio in boys with DTP-booster at bleeding and increased it in those without (interaction test: p=0.03). In children without MN, BCG was associated with reduced TNF-α response in the early sample group (p=0.006), and increased IL-10 in the late sample group (p=0.03). BCG revaccination resulted in a strong IFN-γ response to PPD, which waned slightly over time. BCG also affected the pro-/anti-inflammatory balance, with reduced TNF-α and increased IL-10 responses to LPS, PHA and PPD. This effect depended on sex, DTP-booster vaccination and micronutrient supplementation, being most pronounced in children who had received DTP

Compromiso vascular en la encefalitis herpética

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Carlos Alberto Cañas

1997-01-01

Full Text Available Describimos el caso de un paciente de 30 años de edad que desarrolla una encefalitis fatal par Herpes simple, en cuyos hallazgos de necropsia se destaca un compromiso vascular cerebral secundario. Se discute In posibilidad de que en la encefalitis herpética pueden presentarse dos tipos de compromiso vascular: uno reconocido desde hace tres décadas, la vasculomielinopatía diseminada, y otro, una forma de vasculitis séptica.

Desarrollo de una Sonda de ADN de Origen Plasmídico para la identificación y detección de Neisseria gonorrhoeae.

OpenAIRE

Torres Sánchez, María José

2016-01-01

Neisseria gonorrhoeae, es el agente causal de la gonococia, enfermedad de transmisión sexual reconocida como una de las causas principales de morbilidad en muchas zonas del mundo (Donegan, 1985). La gonococia es a menudo recurrente y ocasionalmente produce complicaciones, como la enfermedad inflamatoria pélvica –causa de embarazos ectópicos e infertilidad--, la infección gonocócica diseminada y la epididimitis, entre otras. Ya que el diagnós...

Modulating the internalization of bacille Calmette-Guérin by cathelicidin in bladder cancer cells.

Science.gov (United States)

Choi, Se Young; Kim, Soon-Ja; Chi, Byung Hoon; Kwon, Jong Kyou; Chang, In Ho

2015-04-01

To confirm the role of cathelicidin (LL-37) in the internalization of bacille Calmette-Guérin (BCG) into bladder cancer cells. Enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction analysis evaluated the changes in protein and messenger ribonucleic acid (RNA) expression with BCG incubation after LL-37 pretreatment in 5637 and T24 human bladder cancer cells. The internalization rate was evaluated by a double immunofluorescence assay, and confocal microscopy confirmed the function of LL-37 in BCG internalization. We also investigated the difference in internalization rates and cell viability between LL-37, anti-LL-37 antibody, and LL-37 plus anti-LL-37 antibody. The levels of LL-37 increased after BCG exposure in bladder cancer cells in dose- and time-dependent manners. Increasing LL-37 levels using recombinant LL-37 protein further dose dependently decreased BCG internalization in both cell lines. The internalization rates of BCG after LL-37 instillation were lower compared with the controls, and the internalization rate of BCG after anti-LL-37 antibody instillation was significantly higher compared with the controls in both cell lines (P internalization. Blocking the action of cathelicidin may increase the internalization and effectiveness of BCG in reducing bladder cancer cell proliferation. Copyright © 2015 Elsevier Inc. All rights reserved.

Sensitivity Improvement of Ammonia Gas Sensor Based on Poly(3,4-ethylenedioxy thiophene):Poly(styrenesulfonate) by Employing Doping of Bromo cresol Green

International Nuclear Information System (INIS)

Aba, L.; Yusuf, Y.; Triyana, K.; Aba, L.; Siswanta, D.

2014-01-01

The aim of this research is to improve the sensitivity of ammonia gas sensor (hereafter referred to as sensor) based on poly(3,4-ethylenedioxy thiophene):poly(styrenesulfonate) (PEDOT:PSS) by employing the doping dye of bromo cresol green (BCG). The doping process was carried out by mixing the BCG and the PEDOT:PSS in a solution with an optimum ratio of 1:1 in volume. The sensor was fabricated by using spin-coating technique followed by annealing process. For comparison, the BCG thin film and the PEDOT:PSS thin film were also deposited with the same method on glass substrates. For optical characterization, a red-light laser diode with a 650 nm wavelength was used as light source. Under illumination with the laser diode, the bare glass substrate and BCG film showed no absorption. The sensor exhibited linear response to ammonia gas for the range of 200 ppm to 800 ppm. It increased the sensitivity of sensor based on PEDOT:PSS with BCG doping being about twofold higher compared to that of without BCG doping. Furthermore, the response time and the recovery time of the sensor were found very fast. It suggests that the optical sensor based on BCG-doped PEDOT:PSS is promising for application as ammonia gas sensor.

Granulomatous prostatitis after intravesical bacillus Calmette-Guérin instillation therapy: A potential cause of incidental F-18 FDG uptke in the prostate gland on F-18 FDG PET/CT in patients with bladder cancer

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