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PubMed1995

Dendritic cell presentation of PPD and 19 kDa protein of Mycobacterium tuberculosis and emergent T helper cell phenotype.

Protection against infection with Mycobacterium tuberculosis is preferentially associated with the development of the T helper 1 subset, IFN-gamma production and a cell-mediated response, rather than with T helper 2 cells, 4 (IL-4) and antibody production. The type of APC interacting with T cells responsive to mycobacterial peptides may influence which of these responses predominates. This investigation focuses on the role of dendritic cells (DC) because they are the most potent APC in both primary and recall immune responses. Our results show that splenic DC-enriched suspensions prepared from C57BL/6 mice and pulsed with either purified protein derivative (PPD) or the immunodominant 19 kDa protein from M. tuberculosis, can activate antigen-primed T cells in vitro, whereas spleen cell suspensions depleted of DC cannot. DC pulsed with PPD or 19 kDa antigen are able to prime naive T cells in vivo. Supernatants collected from cultures containing T cells from mice injected with PPD-pulsed DC and then challenged in vitro with PPD-pulsed DC were found to contain more IL-2 and IFN-gamma than those from control mice which received either DC or PPD alone. No such antigen-specific IFN-gamma response occurred if DC pulsed with 19 kDa were used in place of PPD-pulsed DC. IL-4 was not detected in any of the culture supernatants. We conclude that DC can induce production of cytokines associated with a protective immune response when presenting peptides derived from heterogeneous mycobacterial antigens but not when exposed to the single 19 kDa immunodominant protein.

Animals↗
PubMed2004

Clinical manifestation of pulmonary melioidosis in adults.

Between 1996 and 2002, 162 cases of pulmonary melioidosis were reported from Srinagarind Hospital, Khon Kaen, northeast Thailand, 90 acute vs 72 subacute/chronic. Patients averaged 50 years of age and half worked as farmers. The male to female ratio was between 2 and 3 to 1 depending on the subgrouping. Burkholderia pseudomallei was confirmed by a culture or a four-fold rise in titer in the majority of cases, while the others were presumptive diagnoses based on response to treatment. Pulmonary melioidosis presented as either acute fulminant pneumonia or as an indolent disease. The common concurrent medical illness was diabetes mellitus. Mean incubation of the acute vs the sub-acute/chronic form was 8.7 vs 54.4 days, respectively. Leukocytosis was detected in 70% of cases. Sputum Gram's stain was not sensitive for diagnosis. Sputum culture and blood culture were diagnostic for 31.1 vs 22.2 and 40 vs 37.5% of the acute vs subacute/chronic forms, respectively. The common radiographic patterns for acute pneumonia were localized patchy alveolar infiltrate or hematogenous pattern. A bilateral diffuse patchy alveolar infiltration or multiple nodular lesions characterized the latter. Upper-lobe involvement with early cavitation and rapid progression were common. In the subacute/chronic forms, the radiographic pattern sometimes mimicked tuberculosis, with upper lobe involvement, patchy alveolar infiltrate with cavities or fibroreticular lesions. In approximately 30% of cases, liver and/or splenic abscess were common sites of extrapulmonary infection. Respiratory failure and septic shock from acute pulmonary melioidosis was 20% fatal. Early empirical antibiotic therapy should be given for severe pneumonia.

Adolescent↗
PubMed1980

[Tuberculous stenosis of the transverse colon].

A 14 year old Turkish girl presented with unspecific abdominal symptoms and barium enema showed an almost complete obstruction in the region of the splenic flexure. The picture was that of a neoplasm and a left hemicolectomy was performed. Histological examination revealed ulcerating hypertrophic tuberculosis of the colon. The incidence, pathology and symptomatology of colonic tuberculosis are discussed.

Adolescent↗
PubMed2006

CD27 contributes to the early systemic immune response to Mycobacterium tuberculosis infection but does not affect outcome.

The development of a strong Th1-mediated adaptive immune response is considered of main importance for host defense against the intracellular pathogen Mycobacterium tuberculosis. The induction of a cellular immune response is not only dependent on the engagement of the TCR but also requires co-stimulation. In order to study the role of the co-stimulatory molecule of the tumor necrosis factor receptor family member CD27 during murine M. tuberculosis infection, we intranasally infected wild-type (WT) and CD27 knockout (KO) mice with 10(5) colony-forming units M. tuberculosis. Whereas there were no differences in bacterial growth, inflammation and IFNgamma production by CD4+ and CD8+ lymphocytes in the lungs early after infection, the number of splenic CD8+ T cells producing the key Th1 cytokine IFNgamma was lower in CD27 KO mice than in WT mice. After 6 weeks, CD27 KO mice had 3.6-fold higher mycobacterial counts in their lungs and displayed more pulmonary inflammation and increased numbers of infiltrated leukocytes. Despite these differences early in infection, an equal number of WT and CD27 KO mice died during a 43-week observation period and lung bacterial loads and inflammation were comparable in the surviving animals. Our data suggest that CD27 does not contribute to the local IFNgamma-mediated response and long-term protection against M. tuberculosis.

Animals↗
PubMed1992

Detection of mycobacterial rRNA in sarcoidosis with liquid-phase hybridisation.

Because sarcoidosis resembles tuberculosis clinically and histologically, it has been suggested that mycobacteria might have a role in the pathogenesis of the disorder. Mycobacteria have not been found in sarcoid tissues by conventional culture techniques, so we have used a liquid-phase hybridisation method to see whether we could detect mycobacterial rRNA in such tissues. RNA was extracted from five sarcoid and five normal spleens. Extracts were assayed by liquid-phase DNA/RNA hybridisation with a DNA probe specific for the rRNA of the Mycobacterium tuberculosis complex. Hybridisation obtained with the sarcoid spleens, from which mycobacteria were neither seen on microscopy nor cultured with standard methods, was 4.8 times higher than that with normal spleens (p less than 0.001). Our demonstration of mycobacterial nucleic-acid components in sarcoid splenic tissues supports the notion that mycobacteria play a part in the cause of sarcoidosis.

DNA Probes↗
PubMed1999

Imaging-guided percutaneous biopsy of focal splenic lesions: update on safety and effectiveness.

OBJECTIVE: The purpose of this study is to determine the safety and effectiveness of percutaneous imaging-guided biopsy in the diagnosis of focal splenic lesions. MATERIALS AND METHODS: From May 1995 to November 1997, 20 imaging-guided biopsies of focal splenic lesions were performed in 18 patients, including seven patients with a prior diagnosis of extrasplenic malignancy (breast cancer, n = 3; lymphoma, n = 2; ovarian cancer, n = 1; and osteogenic sarcoma, n = 1), three immunosuppressed patients (cause of immunosuppression: AIDS, n = 1; liver transplantation, n = 1; and bone marrow transplantation, n = 1), two patients with anemia, one patient with a recent history of IV drug abuse, and five patients with incidentally discovered splenic lesions. Biopsies were performed with an 18-gauge (n = 1), a 20-gauge (n = 8), or a 22-gauge (n = 14) self-aspirating needle or an 18-gauge cutting needle (n = 1). Biopsies were considered successful if a specific diagnosis of benign or malignant disease was made. RESULTS: A specific diagnosis was made in 16 (88.9%) of 18 patients, and no complications occurred. Malignancy was diagnosed in six patients including three patients with lymphoma. Benign conditions were diagnosed in 10 patients: a cyst in two patients; hamartoma in one; lipogranuloma in one; infarct in one; and infection in four, including one case each of Candida albicans, Pneumocystis carinii, Mycobacterium tuberculosis, and mixed flora. The tenth benign diagnosis was a pseudotumor of the spleen related to a bulbous tail of the pancreas that was inseparable from the splenic hilum. Biopsy did not establish a diagnosis in one patient with lymphoma and in one patient with presumed splenic candidiasis. A mean of 1.5 needle passes was made per biopsy. CONCLUSION: Imaging-guided splenic biopsy is a safe technique that provides a specific diagnosis in most patients with focal splenic lesions.

Adult↗
PubMed1996

Increase of tuberculous infection in the organs of B cell-deficient mice.

Protective immunity against infection with Mycobacterium tuberculosis is imparted by T cells rather than antibodies, but B cells can play a role as antigen-presenting cells and in granuloma formation. We re-evaluated the role of B cells in the course of tuberculous infection in mu-chain knock-out (Ig-) mice. Surprisingly, the organs of M. tuberculosis-infected Ig- mice were found to have three- to eight-fold elevated counts of viable bacilli compared with normal littermates at 3-6 weeks post-infection. Splenic interferon-gamma responses to whole antigen were unimpaired, whilst proliferation to certain mycobacterial peptides was found to be diminished. However, bacille Calmette-Guérin (BCG) vaccination significantly reduced the infection in Ig- mice. The mechanisms by which B cells can influence primary tuberculous infection need further study.

Animals↗
PubMed2006

[Pseudo-tumoral hepatic tuberculosis developing into a multinodular form despite treatment].

Localized macronodular tuberculosis of the liver is rare. In this location antituberculosis therapy results in a favorable clinical evolution in 100% of cases. We report a pseudo-tumoral form of this condition with no specific clinical, biological or radiological data. After ultrasound guided needle aspiration cytology suggesting metastasis, the correct diagnosis was obtained on liver biopsy after laparotomy. After what was probably inadequate therapy, the enlargement of several hepatic and splenic macronodules was observed. After two years and eight months, the clinical condition of the patient was good but radiological features remained. The risk of diagnostic errors and the therapeutic difficulties in the zones where the incidence of tuberculosis is low should be noted.

Antitubercular Agents↗
PubMed1986

Disseminated atypical mycobacterial infection in patients with hairy cell leukemia.

Disseminated atypical mycobacterial infections developed in nine of 186 patients with hairy cell leukemia who were seen over 10 years at the University of Chicago Hospital. Clinically, these patients had symptoms of fever and chills; an infiltrate was usually present on chest radiography. Invasive diagnostic studies, including thoracotomy and laparotomy, were necessary for confirmation of the diagnosis of atypical mycobacteria infection. Confirmatory culture specimens were obtained from lymph nodes, liver, and splenic tissue. Six patients had infections with Mycobacterium kansasii; two with M. avium-intracellulare; and one with M. chelonei. Treatment with multiple anti-tuberculosis drugs was initiated either empirically (six patients); after obtaining pathologic evidence of granuloma or acid-fast bacilli (two patients); or after obtaining a positive culture result (one patient). Five of the nine patients survived the infection and continued taking anti-tuberculosis drugs for total periods of nine months to two years. Awareness of the association between hairy cell leukemia and atypical mycobacteria infection, with early consideration of invasive diagnostic studies, as well as empiric anti-tuberculosis therapy, may prolong the survival time for many patients with hairy cell leukemia.

Adult↗
PubMed2002

[Multifocal tuberculosis: fatal outcome due to toxic drug reactions].

We report a case of multifocal tuberculosis with the following features: - skin involvement with multiple gommes disseminated on the left upper limb, the left flank, the right hypocondrium, and the right leg; - nodal involvement including the left supraclavicular, left axillary, right laterotracheal, pre and subcarineal, ceoeliomesenteric, and liver hilus nodes; splenic involvement; right pleural involvement; - spondylodiscitis of T11-T12 and of the head of the right fibula; - peritoneal involvement leading to ascitis; - multi-organ involvement. This 43-year-old woman had not particular history: no diabetes, no renal failure, no long-term corticosteroid treatment, no immunosuppressor treatment, negative HIV-1 and HIV-2 serology. Treatment with anti-tuberculosis agents led to severe drug reactions causing death due to hepatic encephalitis.

Adult↗
PubMed2003

Endoscopic ultrasound-guided biopsy for the diagnosis of focal lesions of the spleen.

OBJECTIVES: Needle biopsy of splenic lesions using computed tomography (CT) or ultrasound (US) is difficult if the size of the lesion is small. It may be dangerous if the lesion is adjacent to the splenic hilum or located peripherally. We used endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) to elucidate the tissue diagnosis of splenic abnormalities. METHODS: EUS-FNA was performed in 12 patients when US- or CT-guided biopsy was inconclusive (n = 5), was not attempted because of small tumor size (0.9-1.4 cm; N = 4), or was considered dangerous (n = 3). A linear echo-endoscope and 22-gauge needles were used for cytology and bacteriology. RESULTS: The age of the patients was 19-68 yr (median 32 yr). Seven patients were male and five female. The size of the lesions was 0.8-4.2 cm (median 1.4 cm). Cytology was inadequate in one patient. Bacteriology was positive for Staphylococcus aureus and Serratia in one patient each, and cultures were positive for Mycobacterium tuberculosis in two patients. A positive diagnosis was made in 10 of 12 patients (83%). Final diagnoses were tuberculosis in two patients, Hodgkin's disease in two, sarcoidosis in two, abscesses in two, metastatic colon cancer in one, and infarction in one. Suspected recurrence of non-Hodgkin's lymphoma was not confirmed in one case. One patient experienced pain after puncture, but no hematoma was demonstrated on subsequent US examination. CONCLUSIONS: EUS-FNA cytodiagnosis in patients with unknown splenic lesions seems feasible, even in very small foci, when CT- or US-guided biopsy fails. Additional material for bacteriology may show benign treatable diseases such as abscesses or tuberculosis.

Adult↗
PubMed1999

Immunogenicity of DNA vaccines expressing tuberculosis proteins fused to tissue plasminogen activator signal sequences.

Novel tuberculosis DNA vaccines encoding native ESAT-6, MPT-64, KatG, or HBHA mycobacterial proteins or the same proteins fused to tissue plasminogen activator (TPA) signal sequences were evaluated for their capacity to elicit humoral, cell-mediated, and protective immune responses in vaccinated mice. While all eight plasmids induced specific humoral responses, the constructs expressing the TPA fusions generally evoked higher antibody responses in vaccinated hosts. Although most of the DNA vaccines tested induced a substantial gamma interferon response in the spleen, the antigen-specific lung responses were 2- to 10-fold lower than the splenic responses at the time of challenge. DNA vaccines encoding the ESAT-6, MPT-64, and KatG antigens fused to TPA signal sequences evoked significant protective responses in mice aerogenically challenged with low doses of Mycobacterium tuberculosis Erdman 17 to 21 days after the final immunization. However, the protective response induced by live Mycobacterium bovis BCG vaccine was greater than the response induced by any of the DNA vaccines tested. These results suggest that the tuberculosis DNA vaccines were able to elicit substantial immune responses in suitably vaccinated mice, but further refinements to the constructs or the use of alternative immunization strategies will be needed to improve the efficacy of these vaccine candidates.

Animals↗
PubMed1999

T-cell epitope mapping of the three most abundant extracellular proteins of Mycobacterium tuberculosis in outbred guinea pigs.

The three most abundant extracellular proteins of Mycobacterium tuberculosis, the 30-, 32-, and 16-kDa major extracellular proteins, are particularly promising vaccine candidates. We have mapped T-cell epitopes of these three proteins in outbred guinea pigs by immunizing the animals with each protein and assaying splenic lymphocyte proliferation against a series of overlapping synthetic peptides covering the entire length of the mature proteins. The 30-kDa protein contained nine immunodominant epitopes, the 32-kDa protein contained two immunodominant epitopes, and the 16-kDa protein contained a highly immunodominant region at its N terminus. The immunodominant epitopes of the 30- and 32-kDa proteins in outbred guinea pigs were frequently identified in healthy purified-protein-derivative-positive or BCG-vaccinated individuals in previous studies. The immunodominant epitopes of these major extracellular proteins have potential utility in an epitope-based vaccine against tuberculosis.

Amino Acid Sequence↗
PubMed1994

Disseminated Mycobacterium genavense infection in two patients with AIDS.

Mycobacterium genavense is a recently defined fastidious organism that has been identified as a cause of disseminated infection in patients with AIDS. We report the cases of two patients who had advanced AIDS and a clinical syndrome of fever, anorexia, abdominal pain, diarrhea, and weight loss. In addition, splenomegaly and lymphadenopathy were prominent in both cases, and in one patient's case radiographic findings were suggestive of splenic abscesses. Mycobacteria isolated from specimens of blood and bone marrow grew in liquid media but not on solid media. The results of DNA probe tests for Mycobacterium tuberculosis and Mycobacterium avium complex were false-positive for both patients. After treatment of the broth cultures to lyse red blood cells, the results of DNA probe tests were negative for these pathogens. Amplification and sequencing of 16S rRNA with use of the polymerase chain reaction indicated that the mycobacterial isolates from both patients had sequences identical to those previously reported for M. genavense. One patient survived 5 months after diagnosis, the other 2 months after diagnosis; only one patient responded (transiently) to antimycobacterial chemotherapy.

AIDS-Related Opportunistic Infections↗
PubMed1995

[A case of chronic pancreatitis with eosinophilic pleural effusion].

A 48-year-old man was admitted for the evaluation of a massive left pleural effusion. Thoracenthesis yielded a bloody excudate with a high percentage of eosinophils (27%) and high values of pancreatic enzymes (amylase 16,000 Somogyi, Elastase 35,000 ng/dl, Lipase 12,800 U/l, Trypsin 77,000 ng/ml). The amylase isozyme of the exudate was 100% pancreatic-type fraction. The blood showed no eosinophilia (4%). A computed tomographic scan and magnetic resonance image of the abdomen revealed a pancreatic pseudocyst in contact with the diaphragm, and thrombi in the inferior vena cava and the splenic vein. After pancreatic cystectomy and splenectomy, the pleural effusion resolved rapidly. Eosinophilic pleural effusion has been reported as a complication of several disorders: pneumonia, lung carcinoma, pulmonary tuberculosis, and pulmonary infarction. However, we know of no previous report of eosinophilic pleural effusion with pancreatitis. In this case, it is interesting that the massive eosinophilic pleural effusion associated with chronic pancreatitis resolved immediately after the operation, and the patient was discharged.

Chronic Disease↗
PubMed1999

Expansion of neonatal tolerance to self in adult life: I. The role of a bacterial adjuvant in tolerance spread.

T cell neonatal tolerance to self evolves perturbation of the Th1/Th2 balance towards Th2-type self-specific T cells. In the current study we have demonstrated that a tolerant state could be extended to another encephalitogenic determinant only if the neonatally tolerizing determinant was co-administered in adult life with an emulsion of Mycobacterium tuberculosis (i.e. complete Freund's adjuvant). The mechanisms underlying tolerance elicitation and expansion were then explored by an in vitro system in which indirect suppression could be measured. Addition of a tolerizing epitope to splenic T cells from neonatally tolerized animals induced a marked suppression of the anti-MT response. This response could be restored by neutralizing antibodies to IL-4. In contrast, the neutralizing antibodies to IL-4 had no affect on the response of these cells to the tolerizing determinant. These findings are highly significant not only because they explore the important role of microbial antigens in neonatal tolerance, but also because they distinguish, for the first time, between tolerizing and tolerized T cells.

Aging↗