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Biomedical subjects

R Ferlinz

Publications and source records attributed to R Ferlinz.

At least 19 recordsLinked to original sources

Modulation of IL-1 beta, IL-6, IL-8, TNF-alpha, and TGF-beta secretions by alveolar macrophages under NO2 exposure.

Activated alveolar macrophages (AMs) secrete interleukine (IL)-1 beta, IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta (TGF-beta), whose inflammatory and fibroblast-activating characteristics may play a role in the maintenance of pulmonary inflammatory processes and subsequent fibrosis. Human AMs were transferred to a gas cylinder and exposed to NO2 in concentrations ranging from 0.1 to 0.5 ppm in synthetic air for 30 min at 37 degree C. AMs were fixed on a polycarbonate membrane and placed on culture medium. A culture was established, with the exposed AM (nonstimulated or stimulated with 1 microgram/ml lipopolysaccharide [LPS]), and the remaining cells were used to determine the cytokines. IL-1 beta, IL-6, and IL-8 were quantified by commercial enzyme-linked immunosorbent assay kits (ELISA kits). TNF-alpha was determined with a "sandwich" ELISA, using the biotin-streptavidin system. NO2 exposure of nonstimulated AM did not result in changes in IL-1 beta, IL-6, TNF-alpha, and TGF-beta release, compared to the situation with control experiments. Exposure for 30 min to NO2 induced a significant decrease of LPS-stimulated IL-1 Beta, IL-6, IL-8, and TNF-alpha (p < .05). The release of TGF-beta was not significantly affected by NO2 exposure. Cytotoxicity of AM was checked by trypan blue exclusion, with values ranging from 1.3 to 3.0%. NO2 exposure of LPS-stimulated AM resulted in a functional impairment of AM after NO2 exposure regarding IL-1 beta, IL-6, IL-8, and TNF-alpha. Neither the spontaneous nor the stimulated release of TGF-beta were influenced by NO2.

Bronchoalveolar Lavage Fluid

Chemotactic response of human alveolar macrophages and blood monocytes elicited by exposure to sulfur dioxide.

An experimental study was undertaken to investigate the in vitro effect of sulfur dioxide on the chemotactic activity of alveolar macrophages (AM) and blood monocytes (BM). The cells were placed on a polycarbonate membrane and exposed to SO2 0.5, 1.5 and 2.5 ppm for 15 min. Control experiments were performed with exposure of the cells to synthetic air with 5% CO2. After gas exposure the cells were incubated with the chemotactic active agent C5a in 5% carbon dioxide (CO2) at 37 degrees C for 60 min. The numbers of AM and BM passing actively through the membrane were quantified using light microscopy. Our results show a dose-dependent reduction in the migration rate of cells under SO2 exposure. SO2 0.5 ppm induced a 29% and SO2 2.5 ppm a 53% decrease in migration of AM compared with the control exposure to synthetic air (P < 0.01). Identical experiments with BM resulted in a decrease in migration of up to 57% (P < 0.01). At SO2 concentrations of up to 2.5 ppm no significant cytotoxic effects were observed for AM or BM. The data demonstrate that exposure to SO2 may reduce the chemotactic activity of AM and BM. Our results further suggest that the decrease in cell migration induced by SO2 is due to changes in chemotactic mechanisms and not to cell death.

Aged

[Guidelines for environmental contact tracing in tuberculosis. German Central Committee for control of tuberculosis].

These guidelines were initiated by and worked out in cooperation with physicians of the public health service. Numerous publications and relevant legal regulations, particularly the Federal Law against Epidemics were taken into consideration. The responsibilities of the public health service in the fight against tuberculosis includes case finding, detection of the routes of infection and prevention of transmission. Within the scope of these duties contacts of index cases are traced after the notifications were received. The suspects of tuberculosis are examined considering their risk of infection and disease. While doing so the detection of the source of infection has priority. In general tuberculin tests, X-rays and bacteriology are available for public health services, in order to stick to the duties. The general procedures are explained and recommendations for intervals of investigations are given. Nevertheless there is leeway for decisions in isolated cases, but divergent steps should be documented with care. Specific features in the examination of contacts in institutions of communities and in companies are mentioned just as organizing and legal aspects. Requirements of coercive measures are described. Finally a short note is given on perspectives of molecular techniques on measures of the public health services.

Communicable Disease Control

[Therapy and prognosis of tuberculosis].

Treatment and prognosis of tuberculosis. Worldwide the so-called short-course chemotherapy has become the standard treatment for tuberculosis. The 6-month regimen consists of isoniazid, rifampin, and pyrazinamid given for 2 month followed by isoniazid and rifampin for 4 month. Ethambutol or streptomycin is added in the first 2 month in patients with advanced disease. This recommendation applies to both HIV-infected and uninfected persons. The major determinant of the outcome of treatment is patient adherence to the drug regimen. In susceptible strains the success rate with the 6-month regimen in sputum conversion is far beyond 90% within the first two month of therapy. The relapse rate after 3 to 5 years is about 0-3%. Multiple-drug-resistant tuberculosis (i.e., resistance to at least two drugs) presents difficult treatment problems. Treatment must be individualized and based on susceptibility studies. For patients with tuberculosis that is resistant to rifampin and isoniazid, even the best available treatment is often unsuccessful. The role of new agents such as the quinolone derivatives and amikacin in the treatment of multidrug-resistant disease is not known, although these drugs are commonly being used in such cases.

AIDS-Related Opportunistic Infections

[Clinical late manifestation of Ondine's syndrome with pronounced primary, especially sleep related alveolar hypoventilation].

We report on a very rare case of a primary, alveolar hypoventilation syndrome (Ondine's Curse syndrome) in a female patient who was first treated at the age of 26 years as a result of an influenza infection; however, the case history revealed a decreased performance in comparison to similar aged children from earliest childhood onwards as well as an intermittent zyanosis of the lips and distal extremities. Other diseases which could explain a global respiratory insufficiency and/or pulmonary arterial hypertension were excluded.

Adult

[Experimental determination of equivalent percentage changes in measurement parameters of dose-response relations with the inhaled methacholine provocation test].

For the experimental determination of equivalent changes of the measurement parameters in the non-specific inhalative provocation test with metacholine, 26 persons with exogenous allergic asthma bronchiale were examined during the symptom-free interval. The inhalative provocation test was performed as dose-response relationship. Linear regressions were calculated with the data obtained. The percentage change of the measurement parameters that occurred with a quantity of 400 micrograms of aerosolised methacholine was calculated on the basis of the regression equation. These changes correspond to equivalent changes of the individual measurement parameters compared with each other. Generally, a drop in FEV1 by 20% is demanded for a positive provocation test. If this value is defined as "gold standard", the measured data allow derivation of the equivalent changes. Our studies showed that an increase of Rt by 195% (triplication), a sGaw drop by 44%, a PEF drop by 20% and a drop of MEF75, MEF50 by 30% each, compared with the original value, is equivalent to a significant change in the sense of a positive inhalative provocation test.

Adolescent

[Lung function in chronic persistent pulmonary embolism].

Chronic thromboembolic pulmonary hypertension is characterized by widespread obstruction of the pulmonary arteries with organized thrombus. Typically, the afflicted patients present with complaints of progressive dyspnea and exercise intolerance. The typical functional picture of the 22 patients in this series revealed normal lung volumes. Only about 10% of the subjects had mild restrictive defects. The universal findings were mild to moderate hypoxemia, chronic respiratory alkalosis, high pulmonary vascular resistance and low cardiac output. Pathophysiological mechanisms responsible for dyspnea in chronic thromboembolic pulmonary hypertension are discussed.

Adolescent

[Equivalence of methacholine and carbachol in a nonspecific provocation test (dose-response relationship)].

Within the framework of unspecific inhalation provocation tests with pharmacological substances for the purpose of diagnosing bronchial hyperreactivity, the cholinergics methacholine and carbachol are often used besides histamine. We examined 21 patients with known bronchial hyperreactivity in the symptom-free interval using the methacholine inhalation provocation test and 15 hyperreactive patients using the carbachol inhalation provocation test with the purpose of determining the extent to which methacholine and carbachol differ from each other in respect of their effect. Standard reference values were the provocation doses PD100/0.5Rt and PD20FEV1. It was found that methacholine and carbachol exercise an equivalent effect in the inhalation provocation test. No statistically significant difference for the provocation doses PD100/0.5Rt and PD20FEB1 was seen in group comparisons.

Adolescent

[The chemotactic behavior of alveolar macrophages and blood monocytes after exposures to different NO2 concentrations].

The chemotaxis of alveolar macrophages (AM) and blood monocytes (BM) is important in the elimination of particles and microorganisms which have invaded the lung. The effect of nitrogen dioxide (NO2) on chemotaxis was tested on AM obtained by diagnostic bronchoscopy from five patients suspected of having bronchial carcinoma (four men, one woman; mean age 59 +/- 10 years). Blood monocytes were also studied with blood from seven healthy subjects (five men, two women; mean age 32 +/- 10 years). These cells were placed on polycarbonate membranes for 15 min each, exposed to NO2 concentrations between 1.0 and 5.0 parts per million (ppm), and then incubated with complement component C5a as chemotactically active agent. The number of AM or BM which actively migrated through the polycarbonate membrane under the influence of C5a was measured by means of a light microscope. The migration rate of AM (compared to air exposure) was reduced by 33% with 1.0 ppm NO2 and by 61% with 5.0 ppm. The migration rate of BM in similar conditions was reduced by as much as 55%. There was no significant cytotoxic effect of NO2 exposure at 1.0 and 3.0 ppm. With 5.0 ppm 13.0 +/- 3.0 cells were no longer viable. These results indicate that NO2 concentrations relevant to indoor conditions affect the chemotaxis of AM and BM after short-time NO2 exposures. The data further suggest that NO2 exposures of these cells depressed chemotactic mechanisms without relevant cytotoxicity.

Aged

In vitro study of human alveolar macrophage and peripheral blood mononuclear cell reactive oxygen-intermediates release induced by sulfur dioxide at different concentrations.

Sulfur dioxide (SO2) is a major air pollutant in urban areas. Alveolar macrophages (AM) located on the alveolar surface are in direct contact with this inhaled gas. We evaluated the dose-dependent effect of SO2 exposure on the oxidative metabolism of AM and peripheral blood mononuclear cells (PBMNC) by measuring the spontaneous and stimulated reactive oxygen intermediates (ROI) release. AM or PBMNC were placed on a polycarbonate membrane, which was in direct contact with the surface of a nutrient reservoir. For exposure of the cells to SO2 a special chamber was employed, in which humidified standard air with 5% CO2 at 37 degrees C was mixed with SO2 at the desired concentration. Periods of time between 30 and 120 minutes and concentrations between 0.3 and 1.5 ppm SO2 were chosen for exposure. Thirty minutes exposure of AM to SO2 (0.3-1.5 ppm) yielded a dose-dependent stimulation of ROI release; 2.0- to 3.6-fold of control (r = 0.965, p < 0.005). An exposure of 120 minutes to SO2 resulted in a similar ROI production of about 2.5-fold at all tested concentrations. These experiments provide evidence that AM and PBMNC become activated by SO2 producing large amounts of ROI.

Bronchoalveolar Lavage Fluid

Oncogene overexpression in non-small-cell lung cancer tissue: prevalence and clinicopathological significance.

In contrast to small-cell lung cancer, few data are available on the role of oncogene overexpression in non-small-cell lung cancers (NSCLC). To determine the prevalence and extent of the transcriptional activation of cancer genes in NSCLC we investigated the level of mRNA of the three important cellular oncogenes--erbB2, Ki-ras, and c-myc--in 39 surgically or endoscopically obtained tumor samples and 24 samples of normal bronchopulmonary tissue taken from the same patients. Tissue RNA was prepared and the specific mRNA analyzed by the highly sensitive nuclease S1 protection assay. Oncogene mRNA in the tumors was quantified by comparison with the homogeneously weak signals in normal lung tissue preparations with densitometry. The presence of two- to four-fold excess RNA was defined as moderate and a greater than fourfold RNA amount as strong gene overexpression. In contrast to normal tissue the oncogene mRNA amount varied considerably among tumors, showing increases up to 64-fold in erbB2, 13-fold in Ki-ras, and 57-fold in c-myc. Moderate and strong (in brackets) mRNA overexpression occurred with 33% (33%) in erbB2, 36% (18%) in Ki-ras, and 18% (23%) in c-myc. Simultaneous overexpression of two genes was observed with 41% and increased mRNA of all genes tested with 20% of the NSCLC samples. Augmented oncogene mRNA was observed most frequently in large-cell carcinoma. The c-myc overexpression was significantly more prevalent in large-cell cancer than in adenocarcinoma. Tumor differentiation was negatively correlated with c-myc mRNA amounts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

An experimental model for the exposure of human ciliated cells to sulfur dioxide at different concentrations.

Mucociliary transport is an important nonimmunological defense mechanism of the respiratory tract. The aim of this study was to investigate the effect of sulfur dioxide (SO2) at different concentrations on ciliary beat frequency (CBF). Ciliated cells were obtained from 12 volunteers by nose brush. CBF was quantified using video-interference microscopy. The cells were placed on a polycarbonate membrane in contact with the surface of a reservoir filled with RPMI 1640 (bicarbonate buffered) or Ringer's (electrolyte) solution, allowing the cells to be supplied by capillarity. In an exposure chamber the cells were exposed for 30 min to SO2 2.5-12.5 ppm at 37 degrees C and 100% air humidity. SO2 induced a dose-dependent decrease in CBF of the cells cultured in Ringer's solution. SO2 at 2.5 ppm caused a 42.8% decrease and at 12.5 ppm a 96.5% decrease (8.1 +/- 0.24 versus 0.28 +/- 0.20 Hz). CBF of cells cultured in RPMI 1640 was reduced only moderately after 12.5 ppm SO2 exposure (7.9 +/- 0.26 versus 6.70 +/- 0.30 Hz). In Ringer's solution a decrease in pH was observed after 30 min of SO2 exposure to 12.5 ppm to a minimum value of 3.6. By contrast, the pH of RPMI 1640 remained constant at 7.5 under identical conditions. After adding RPMI 1640 to Ringer's solution, CBF increased in parallel to the pH to control values (5.0 ppm: 4.64 +/- 0.45 to 8.51 +/- 0.60 Hz). These data suggest that the highly water-soluble SO2 reversibly eliminates CBF in correlation with a decrease in pH.

Adult

Effect of sulfur dioxide on mucociliary activity and ciliary beat frequency in guinea pig trachea.

The effects of 30 min exposure to sulfur dioxide on mucociliary activity (MCA) and ciliary beat frequency (CBF) were studied in 31 guinea pig tracheas. MCA was measured by recording the light reflected from ciliated mucous membranes using an infrared bar code reader. CBF of single ciliated cells obtained by brushing was measured with phase-contrast microscopy. Each tracheal sample was exposed to SO2 at concentrations ranging from 2.5 to 12.5 ppm, or to air for control purposes. MCA and CBF were measured before and immediately after gas exposure. A reduction in mean MCA of 63% (P = 0.0007) and statistically insignificant changes in CBF (P > 0.05) were recorded at concentrations of 2.5 ppm SO2. Higher SO2 concentrations caused a further impairment of MCA as well as a dose-dependent decrease in CBF (P = 0.002). A concentration of 12.5 ppm SO2 induced a decrease from baseline values of approximately 80% in mean MCA and of roughly 70% in mean CBF. This study demonstrates a dose-dependent SO2-induced decrease in MCA of guinea pig tracheas. The decrease in MCA was associated with an impairment of CBF only at SO2 concentrations higher than 5.0 ppm.

Animals