Detection of Mycobacterium tuberculosis in peripheral blood.
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DNA, Bacterial↗
Biomedical subjects
C Richter
Publications and source records attributed to C Richter.
Phenylarsine oxide stimulates pyridine nucleotide-linked Ca2+ release from rat liver mitochondria.
Rat liver mitochondria contain a specific Ca2+ release pathway which operates when oxidized mitochondrial pyridine nucleotides are hydrolysed to ADPribose and nicotinamide. Here we report that the hydrophobic bifunctional thiol reagent phenylarsine oxide (PhAsO) at low concentrations stimulates this pathway by promoting a Ca(2+)-dependent hydrolysis of oxidized mitochondrial pyridine nucleotides. Ca2+ release is inhibited by cyclosporine A or m-iodobenzylguanidine, compounds known to prevent intramitochondrial pyridine nucleotide hydrolysis or protein mono(ADPribosyl)ation, respectively. At higher concentrations, PhAsO causes non-specific leakiness of mitochondria.
3-Iodobenzylguanidine↗
Wavelength-dependent power-law Josephson photoresponse of a Tl2Ba2CaCu2O8 thin film.
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Journal Article↗
Influence of HIV status on pathological changes in tuberculous pleuritis.
SETTING: The AIDS epidemic has been associated with an increase in the incidence of tuberculosis, pulmonary or extrapulmonary. OBJECTIVE: To compare morphological changes in tuberculous pleurisy, and response to therapy in HIV-positive and-negative patients. DESIGN: 57 consecutive patients admitted between January and August 1991 with tuberculous pleurisy who were biopsy proven were studied. 36 were HIV-positive and 21 were HIV-negative. RESULTS: 3 types of morphological changes were observed: reactive, hyporeactive and non-reactive. Hypo- and non-reactive patterns were found in 14 of 36 HIV-positive patients but in only 2 of 21 HIV-negative patients (P < 0.02). In the HIV-positive group, 10 of the 14 with hypo- or non-reactive patterns had other HIV-related complications, compared to 6 of 22 with reactive patterns (P < 0.01). When HIV-positive patients' response to therapy was investigated, 2 of 5 patients with hypo- and non-reactive patterns improved compared to all 13 with reactive patterns (P < 0.05). CONCLUSION: A hypo- or non-reactive tissue reaction in HIV-positive patients with tuberculous pleuritis seems to indicate a less favourable prognosis.
AIDS-Related Opportunistic Infections↗
Enlarged cervical lymph nodes at helical CT.
PURPOSE: To evaluate criteria for differentiating malignant versus reactive lymph nodes in the head and neck on the basis of findings at helical computed tomography (CT). MATERIALS AND METHODS: Helical CT scans were evaluated of 70 consecutive patients (46 men and 24 women, aged 20-78 years [mean, 51 years]) with known head and neck tumors and cervical lymph node enlargement. The ratio of the maximal longitudinal to the maximal axial diameter (L/T) was calculated for nodes larger than 8 mm in diameter based on measurements obtained from coronal, paraxial, and sagittal reconstructions. RESULTS: At histologic examination, 96 of 164 nodes were malignant. Of these, 94 of 96 nodes had an L/T of less than 2 (sensitivity, 97%; specificity, 97%; accuracy, 97% for malignancy). Minimal diameter was more than 8 mm in 83 of 96 nodes (sensitivity, 87%; specificity, 89%; accuracy, 88% for malignancy). Low-attenuation centers and rim enhancement were seen in 75 of 96 nodes (sensitivity, 78%; specificity, 100%; accuracy, 86% for malignancy). CONCLUSION: The L/T at helical CT provide an accurate assessment of reactive versus malignant nodes in the head and neck.
Adult↗
Clinical features of HIV-seropositive and HIV-seronegative patients with tuberculous pleural effusion in Dar es Salaam, Tanzania.
In a prospective study, we investigated whether human immunodeficiency virus (HIV) infection alters the clinical presentation in patients with tuberculous pleuritis. One hundred twelve of 118 patients who presented with pleural effusion suffered from tuberculosis (TB); 65 patients (58%) were HIV seropositive. Evidence of disseminated TB was found more often in HIV-positive than in HIV-negative patients (30.8% vs 10.6%, p < 0.02). Dyspnea, fever, night sweat, fatigue, and diarrhea, severe tachypnea, hepatomegaly, splenomegaly, and lymphadenopathy were significantly more common in HIV-infected than in HIV-negative patients with TB. The same applied to a negative Mantoux reaction, lower hemoglobin, higher beta 2-microglobulin values, and in pleural fluid, lower albumin and higher gamma-globulin levels. Among HIV-infected patients, PPD skin test anergy was significantly associated with relative low albumin and gamma-globulin levels of pleural fluid. However, the radiographic features did not differ with respect to HIV status; they were predominantly those of primary pleuritis (78% in each group). We conclude that coexisting HIV infection affects clinical and laboratory features, but not the radiographic presentation of patients with TB pleuritis in Tanzania.
AIDS-Related Opportunistic Infections↗
Chest radiography and beta-2-microglobulin levels in HIV-seronegative and HIV-seropositive African patients with pulmonary tuberculosis.
To examine the relationship between radiographic features, serum beta-2-microglobulin (beta-2-M) levels, results of sputum-smear microscopy and outcome, we performed a retrospective study of 99 HIV-seropositive and 162 HIV-seronegative patients with pulmonary tuberculosis (TB) in Dar es Salaam, Tanzania. Radiographic features of primary TB were more common and features of postprimary TB less common in HIV-seropositive compared to seronegative patients (50% vs 31%, p < 0.002; and 40% vs 63%, p < 0.001), respectively). HIV infection had a strong independent effect on the beta-2-M levels. Among HIV-infected patients radiographic findings of primary TB were significantly more often associated with beta-2-M levels of > 4 mg/l than features of postprimary TB (71.1% vs 44.4%, p < 0.02). In patients with features of postprimary TB, acid-fast bacilli were more often detected in sputum smears than in patients with primary TB (65% vs 47%, p > 0.05, in HIV-seropositive patients; and 63% vs 31%, p < 0.001) in seronegative patients). The observed mortality was too low to identify radiographic predictors of survival. We conclude that HIV-infected patients with features of primary pulmonary TB are likely in an advanced stage of HIV infection and deserve close supervision during anti-tuberculous therapy.
AIDS-Related Opportunistic Infections↗
Diagnosis of tuberculous lymphadenitis in an area of HIV infection and limited diagnostic facilities.
In order to evaluate procedures leading to the diagnosis of tuberculous lymphadenitis, a prospective clinical study was carried out of patients with lymphadenopathy admitted to the medical wards of a referral hospital in Tanzania. The yield of diagnostic procedures (direct auramine/Ziehl-Neelsen (ZN) stained smears, Löwenstein-Jensen (LJ) cultures, cytology and histological examinations of fine needle aspirations (FNA) and biopsy material of lymph nodes, respectively, was compared. We also tried to identify clinical diagnostic markers. One hundred and twenty-eight (99 HIV-seropositive) patients were included. In 89 (67 HIV-positive) patients TB lymphadenitis could be proven. Histology and LJ culture of a lymph node biopsy had the highest diagnostic yield, 85% and 88% respectively, followed by detection of acid-fast bacilli (AFB) in biopsy smear (53%) and in fine-needle aspirations (35%). The diagnostic yield of the several procedures was not affected by associated HIV infection. Macroscopic caseation was 100% predictive for TB with a sensitivity of 69%. Firm and matted lymph nodes, ESR > 100 mm/hr, a positive PPD skin test and pleural opacity on a chest x-ray proved to be independent predictors for TB. Retrospective testing of a stepwise diagnostic approach based on direct smears of FNA, macroscopic visible caseation and direct smear of biopsy tissue, suggests that in 93% of the patients a definite diagnosis of TB lymphadenitis could have been made. Our data suggest that in HIV/TB epidemic areas most of the cases of TB lymphadenitis can be diagnosed correctly by simple and cheap methods which are generally available at district hospitals. Our findings need further prospective validation, however.
Adolescent↗
Diagnosis of tuberculosis in patients with pleural effusion in an area of HIV infection and limited diagnostic facilities.
In a prospective study of 118 patients with pleural effusion, tuberculosis (TB) was diagnosed in 112. In 84 patients the diagnosis of TB was made by detection of acid-fast bacilli by stain (auramine, Ziehl-Neelsen) or by culture of mycobacteria (Löwenstein-Jensen medium) in pleural fluid or pleural tissue (obtained by closed biopsy) or by the presence of caseating granulomas in histological sections. In 28 patients the diagnosis of TB was considered probable, based on good response to anti-tuberculous therapy. The highest diagnostic yield was obtained by histology (85%), followed by culture of pleural biopsy (37%) and pleural fluid culture (36%). Pulmonary tuberculosis was found in 8 patients and dissemination of TB to other sites in 25 patients of whom 20 were HIV positive. By logistic regression analysis we identified 2 independent diagnostic markers for TB pleuritis: pleural fluid protein > 50 g/l (Odds ratio 12.1, 95% confidence interval (CI): 1.1-128.3) and adenosine deaminase of > 10 U/l (Odds ratio 11.08, 95% CI: 1.3-96.4). We conclude that conventional facilities of a referral hospital are sufficient to diagnose tuberculous pleuritis as well as disseminated tuberculosis irrespective of HIV infection. However, for regions with overstretched health services and high prevalences of tuberculous pleurisy in patients with pleural effusion we suggest a simplified diagnostic approach based on exclusion of other causes of pleural effusion by simple means and use of these diagnostic markers.
Adult↗
[Magnetic resonance tomography and computerized tomography of Wegener's granulomatosis of the orbits].
Of a total of 121 patients with histological proven Wegener's Granulomatosis, orbital involvement occurred in 12 cases. Eight of them underwent magnetic resonance imaging (MRI) of the head and brain, in 2 cases computed tomography (CT) was additionally performed. With MRI orbital granulomas had a low signal intensity in T1- and T2-weighted spin-echo sequences. After i.v. contrast medium administration an inhomogeneous enhancement was found. Because of the multiple imaging planes and high soft tissue contrast, orbital granulomas were better delineate with regard to the intraorbital muscles and the optic nerve using MRI than with CT. Osseous destruction and sclerosis of the orbital walls were demonstrated more effectively using CT. MRI and CT are thus complementary for diagnosing and staging, of orbital granulomas and periorbital involvement in Wegener's Granulomatosis.
Adult↗
Cyclosporine A protects mitochondria in an in vitro model of hypoxia/reperfusion injury.
Hypoxia/reperfusion injury is a major clinical problem. One of its hallmarks is an increased cytosolic Ca2+ content and an increased generation of reactive oxygen species in the cytosol and in mitochondria. In the present study of an in vitro model of hypoxia/reperfusion injury, mitochondria are exposed to Ca2+ in combination with extra- and intramitochondrially acting prooxidants. In this model mitochondria are damaged in a Ca(2+)-dependent manner. The extent and the site(s) of damage depend on both the kind of respiratory substrate and prooxidant used. The major damage occurs specifically at site I of the respiratory chain, and is due to hydrolysis of oxidized pyridine nucleotides and Ca2+ release followed by Ca2+ re-uptake (Ca2+ 'cycling'). Cyclosporine A completely protects against this damage. The protection is due to inhibition of pyridine nucleotide hydrolysis, an obligatory step in the sequence of events that links prooxidants to Ca2+ release from intact mitochondria.
Adenosine Diphosphate↗
Senile cataractic lenses do not accumulate galactitol in either lactose tolerant or intolerant subjects.
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Aged↗
Pro-oxidants and mitochondrial Ca2+: their relationship to apoptosis and oncogenesis.
Apoptosis is a physiological process for active cell removal. One of its hallmarks is an increased cytosolic Ca2+ content. Several genes involved in apoptosis control have been identified, but their mode of action is not understood in detail. Apoptosis may relate to oncogenesis, in that some malignant tumors may grow because genes engaged in apoptosis control are altered. L929 cells overexpressing the proto-oncogene bcl-2 have an increased mitochondrial membrane potential (delta psi), as have many carcinoma cells. bcl-2 protects L929 cells against apoptosis caused by pro-oxidant-induced mitochondrial Ca2+ 'cycling' and increased cytosolic Ca2+ levels. Nerve growth factor, which induces catalase, and inhibitors of mitochondrial Ca2+ release also prevent apoptosis. It is suggested that a pro-oxidant-induced Ca2+ release from mitochondria, followed by Ca2+ cycling and ATP depletion, is a common basic event during apoptosis. Accordingly, maintenance of delta psi stabilizes mitochondria, thereby prevents apoptosis, and may confer increased growth potential to cells.
Animals↗
Expression of BCL-2 protein enhances the survival of mouse fibrosarcoid cells in tumor necrosis factor-mediated cytotoxicity.
Tumor necrosis factor (TNF) kills some types of tumor cells in vitro and participates in tumor elimination in vivo. TNF has been shown to kill cells by altering their mitochondria structurally and functionally. The oncogene BCL-2 codes for a protein located in the inner membrane of mitochondria which is able to inhibit the commitment to cell death in various cell types. We have therefore investigated whether TNF-mediated killing of the cell line L929 could be modulated by expression of the protein BCL-2. We report here that L929 cells transfected with a BCL-2 expression vector have an increased survival compared to wild type cells after TNF challenge. The protective effect is greatest at moderate TNF concentrations and is still significant at concentrations that killed 100% of wild type cells. The action of BCL-2 is selective inasmuch as cells are not protected against other cytotoxic agents blocking various mitochondrial functions. We show that cells expressing BCL-2 have a higher mitochondrial membrane potential (delta psi) than wild type cells. The increase in delta psi could be linked with the enhanced survival of cells after TNF challenge. Indeed, we found that treatment of wild type L929 cells with the ionophore nigericin, which increases delta psi, protects them even at high TNF concentrations.
Animals↗
Sensitivity of mitochondrial peptidyl-prolyl cis-trans isomerase, pyridine nucleotide hydrolysis and Ca2+ release to cyclosporine A and related compounds.
Prooxidants activate a specific Ca2+ release pathway from mitochondria. Here we investigate the inhibitory potency of cyclosporine A and six related compounds with respect to peptidyl-prolyl cis-trans isomerase (PPIase), pyridine nucleotide hydrolysis and Ca2+ release. Whereas the absolute inhibitory potency of the compounds varies by about three orders of magnitude, a given compound is always most effective on PPIase, followed by pyridine nucleotide hydrolysis, and least effective in Ca2+ release inhibition. The data show that pyridine nucleotide hydrolysis is a prerequisite but not a consequence of Ca2+ release. They also strongly suggest that PPIase participates in the Ca2+ release mechanism from intact mitochondria by regulating the intramitochondrial NAD+ glycohydrolase, and thereby ascribe a physiological function to the protein. Furthermore, a complete lack of correlation between the inhibitory potencies described here and the reported immunosuppressive activities of the drugs is evident.
Amino Acid Isomerases↗
Tumour necrosis factor-alpha induces superoxide anion generation in mitochondria of L929 cells.
Within a few minutes after addition to L929 cells, tumour necrosis factor-alpha (TNF alpha) induced an increase in lucigenin-enhanced chemiluminescence that could be inhibited by superoxide dismutase. The generation of superoxide anion (O2.-) was sensitive to treatment with rotenone, antimycin A and cyanide, indicating that the signal originated from mitochondria. The mechanism of production of O2.- was shown to be independent of ATP synthesis, as uncoupling of this event from mitochondrial electron transport did not alter the generation of O2.- induced by TNF alpha. Chemiluminescence was further dependent on the presence of extracellular calcium, suggesting a role for this cation as a second messenger. This hypothesis was supported by the finding that inhibition of mitochondrial calcium uptake by Ruthenium Red exerted a protective effect on TNF alpha-treated L929 cells. Increased O2.- generation was followed by a marked decrease in mitochondrial dehydrogenase activity and cellular ATP levels, while cell membrane permeability was moderately increased. A role for mitochondrial O2.- generation in TNF alpha cytotoxicity was further supported by the finding that resistant L929 cells had decreased ability to produce O2.- in response to TNF alpha. In addition, we detected a decreased activity of the mitochondrial enzyme succinate dehydrogenase in these cells, suggesting that this component of the respiratory chain might be an important contributor to the TNF alpha-induced generation of O2.-.
Adenosine Triphosphate↗
Treatment of Wegener's granulomatosis with intravenous immunoglobulin.
We report about the treatment of eight patients with Wegener's granulomatosis and one patient with systemic pANCA-associated vasculitis with a single course of high-dose intravenous immunoglobulin (IVIG). In 5 of 9 patients (55%) this resulted in significant clinical improvement, in two patients a decrease of the ANCA-titre was seen.
Adult↗
Mitochondrial calcium release induced by prooxidants.
Hydrogen peroxide, a physiological metabolite, and a variety of other potentially toxic prooxidants, cause oxidation of the pyridine nucleotides NAD(P)H to NAD(P)+ in mitochondria. In Ca(2+)-loaded mitochondria NAD+ thus formed is hydrolyzed to ADP-ribose and nicotinamide. Subsequent to NAD+ hydrolysis, Ca2+ is released from the organelles via a specific pathway which is sensitive to several inhibitors, among them cyclosporine A and some of its derivatives. The release is probably regulated by peptidyl-prolyl cis-trans isomerase. Prolonged stimulation of the release pathway by certain prooxidants followed by re-uptake and release of Ca2+ (Ca2+ 'cycling') leads to collapse of the mitochondrial membrane potential, and is detrimental to the organelles. Excessive Ca2+ 'cycling' is likely to be a basis for the cell toxicity of some prooxidants. On the other hand, the toxicity of inhibitors of the prooxidant-induced Ca2+ release pathway may be due to long-term Ca2+ overloading of mitochondria.
Animals↗