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Biomedical subjects

W Ebert

Publications and source records attributed to W Ebert.

At least 55 records · Page 3Linked to original sources

Karyotypic characterization of established cell lines derived from a squamous cell carcinoma and an adenocarcinoma of human lung cancers.

Two non-small cell carcinoma cell lines from the major histopathologic groups of human lung cancers have been karyotyped: HS-24 was established from a squamous cell carcinoma, and SB-3 was obtained from a metastasis of a poorly differentiated adenocarcinoma. Endoreduplication is characteristic for both cell lines. Subsequent loss of chromosomes led finally to hypotetraploid karyotypes with modal chromosome numbers of 66-68 and 70-72 for HS-24 and SB-3, respectively. The structural analysis was performed by G- and C-banding. Stable overrepresentation of chromosomes 7, 8, 12, and 16 was found. Both cell lines developed a characteristic set of disomic and stable markers. Chromosomes involved in markers were 1, 2, 5, 6, 10, 11, 16, and 17. Consistent numerical and structural normality for chromosomes 4, 18, and 21 was observed.

Adenocarcinoma↗

Beta-adrenergic receptors and adenylate cyclase activity in heart, muscle and adipose tissue of German Landrace pigs selectively bred for differences in backfat deposition.

The density of beta-adrenergic receptors was examined in heart, muscle (m. longissimus dorsi) and backfat tissue of German Landrace pigs using (-)-[3H]-dihydroalprenolol. The animals were selected for high (E(+)-line) or low (E(-)-line) activity of lipogenic enzymes in backfat and for low backfat thickness (U(-)-line) based on ultrasonic measurement. An unselected control (K0-line) also exists. The correlated selection response on stress susceptibility (measured by halothane reaction and by meat quality parameters) showed the following sequence of selection lines: U- greater than E- greater than E+ greater than K0. The strains used for examination descended from the 9th generation (heart and muscle tissue) and the 10th generation (heart, muscle and adipose tissue) of this selection experiment. No further selection took place between the 9th and 10th generation. Basal adenylate cyclase activity was determined as well as (-)-Isoproterenol + GTP or sodium fluoride (NaF) stimulated activity in heart and muscle of the 10th generation measuring [3H]-cAMP formation from [3H]-ATP. A good correlation (r greater than or equal to 0.59, n = 9) between beta-adrenergic receptor density and adenylate cyclase activity was found which pointed to an efficient receptor-effector system. The number of beta-adrenergic receptors and adenylate cyclase activity was higher in the U(-)-line in all investigated tissues compared to the other lines in the 9th and 10th generation. Most differences between these lines were also significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗

Significance of microbiological and biochemical analyses in empyema thoracis.

Following the indifferent results of a retrospective analysis, a prospective study was undertaken to analyse the causative organisms in 51 cases of empyema. Cultures were positive in 44/51 (= 86.3%) cases. 2 bacterial species were recovered for each empyema. The aerobic gram-positive cocci represented the largest group (57%), followed by aerobic gram-negative bacteria (18.6%), anaerobic bacteria (18.6%), and fungi (5.8%). Polymicrobial empyema accounted for 59.1% of the cases. Anaerobic bacteria were cultured from 36.4% of empyema. Anaerobic bacteria were more frequently isolated from pleural effusions than from other specimens. Swabs were found to be of minor value for anaerobics. Analyses of glucose and pH value in pleural effusions have been reported to be useful in differentiating complicated from uncomplicated effusions in cases where the aspirated fluid is not purulent and is negative on gram stain, but clinical as well as radiological findings point to an empyema. Our results have shown that pH-values less than 7.30 and Glucose less than 60 mg/dl were not absolutely specific for empyema. In contrast, PMN-elastase in pleural effusion and HI-30 in urine showed a statistically significant differentiation of empyema from exudates of other origin.

Anti-Bacterial Agents↗

Localization of cathepsin B in two human lung cancer cell lines.

We demonstrated the cysteine proteinase cathepsin B in two human lung tumor cell lines by cytochemical and immunocytochemical methods. The cell lines were derived from a squamous cell carcinoma of the lung (HS-24) and a metastasis to the adrenal gland from an adenocarcinoma of the lung (SB-3). For comparison and control, normal human lung fibroblasts cells (Wi-38) were also investigated. Intracellular cathepsin B activity was detected in all three cell lines. SB-3 and the normal fibroblast cells showed almost equal cathepsin B activity, which was considerably stronger than that in the HS-24 cells. Specific inhibitors for cathepsin B (E64, leupeptin, antipain) suppressed its activity completely. Stefin A, the physiological cathepsin B inhibitor, was less effective; this might depend on its limited penetrability into living cells. Localization of the cathepsin B was performed by conventional immunofluorescence microscopy and laser scanning microscopy. With specific anti-cathepsin B antibodies, the enzyme was localized in HS-24, SB-3, and Wi-38 fibroblast cells within perinuclear granules representing the lysosomal compartment. In the SB-3 cells, we additionally localized a minor fraction of the enzyme bound to the plasma membrane in a speckled distribution, accessible to the antibodies from the outside. This direct demonstration of cathepsin B distribution supports biochemical data about the dual localization of the enzyme in tumor cells. It also supports the possibility of a direct involvement of cathepsin B in the degradation of the extracellular matrix, and thus a contribution of the enzyme in invasion and metastasis.

Adenocarcinoma↗

Detection of cathepsin B, plasminogen activators and plasminogen activator inhibitor in human non-small lung cancer cell lines.

Human non-small lung cancer cell lines HS-24 (established from a primary squamous cell carcinoma) and SB-3 (established from a metastasis of a primary adenocarcinoma of the lung into the adrenal gland) were analysed for the proteinases tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator inhibitor (PAI-1). The proteinases were characterized by activity measurements, inhibition studies, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis. Cell-associated proteinases were determined in cell lysates, secreted proteinases in cell conditioned culture media. Both cell lines were found to secrete uPA and PAI-1, whereas tPA could be detected only in HS-24 conditioned media. No cathepsin B activity could be detected in media of both cell lines. However, activation experiments and western blot analysis showed, that at least HS-24 secrete an inactive precursor. Cell lysates of HS-24 and SB-3 show PA activity, but on a low level. Cathepsin B activity was also found to be low in HS-24 lysates. However, SB-3 lysates show high cathepsin B activity. Further characterization of the proteinases by their sensitivity against several inhibitors suggests that they are similar to the corresponding proteinases of normal, nonmalignant cells.

Adenocarcinoma↗

[Circular intrathoracic tracheal replacement by a devitalized artery in the dog].

Prepared artery (origin: human, calf, dog) with external or internal teflon-spiral-supporting was implanted in dogs (n = 10) as a circular intrathoracic tracheal substitute after cross-resection. Human arteries were rejected (n = 2). Calf arteries (n = 5) and dog arteries (n = 3) were incorporated fibrously. Central granulations appeared. The longest survival time was 36 days.

Animals↗

[Clinical aspects, results of diagnostic pulmonary function tests and biochemical parameters in children with homozygote alpha-1-antitrypsin deficiency].

The clinical course and pulmonary function tests of individuals with severe Alpha-1-Antitrypsin (Alpha-1-AT) deficiency reveal a marked interindividual variability. 4 patients with PI type ZZ and 2 patients with PI type SZ had been identified by neonatal cholestasis. None had pulmonary symptoms at a mean age of 13 (range 9-16) years. Lung function tests disclosed signs of incipient pulmonary emphysema in one girl. Bronchial hyperreactivity had led to the diagnosis of Alpha-1 AT-deficiency (PI type ZZ) in another girl at the age of 7 years. The biochemical analysis of the serum of three children (two PI ZZ and one PI SZ) revealed additional protease inhibitors that may be effective as compensatory mechanisms. The lack of those protective factors as well as the presence of environmental hazards may contribute to the increased risk of emphysema in individual patients.

Adolescent↗

[Trypsin and pancreatic elastase-inhibitory capacity of serum and bronchoalveolar lavage fluid of smokers, ex-smokers and nonsmokers].

Smoking habits have no differentiating effect on the functional activity of protease inhibitor (alpha 1PI) in the serum and bronchoalveolar lavage fluid (BALF). In the BALF, the trypsin-inhibitory capacity TIC/alpha 1PI ratio is significantly greater in patients with emphysema than in non-emphysematous subjects. PIC/alpha 1PI ratios that are greater than 1 demonstrate the existence of additional antiproteases in the lower respiratory tract.

Bronchoalveolar Lavage Fluid↗

[Clinical aspects, diagnostic lung function and biochemical parameters in children with homozygous alpha 1-antitrypsin deficiency].

Both the clinical course of the homozygous alpha 1-PI deficiency and also the pulmonary function and measured clinical parameters in these children revealed very marked inter-individual fluctuations. In one child, the lung function revealed certain signs of incipient pulmonary emphysema. The biochemical parameters of two children revealed TIC/alpha 1-PI- and PEIC/alpha 1-PI ratios greater than 1. This indicates that, in addition to alpha 1-PI, further inhibitors may develop a compensatory effect.

Child↗

Histopathologic evaluation of application of labeled neoglycoproteins in primary bronchus carcinoma.

Neoglycoproteins are readily available conjugates of a histochemically inert carrier protein and histochemically crucial carbohydrate moieties which are covalently attached to the carrier protein by chemical synthesis. Biotinylation renders these conjugates detectable in formalin-fixed, paraffin-embedded tissue sections of human lung cancer by standard staining protocols, thereby localizing endogenous receptors for carbohydrate moieties. Examination of 30 cases of main types of human lung cancer revealed the presence of alpha-fucosyl-, alpha-mannosyl-, and alpha-glucosyl-specific receptors in adenocarcinomas or epidermoid carcinomas with high positivity rates. The extent of the expression of receptors for alpha- and beta-galactosides appeared to be comparatively lower. Within the standard protocol, using a concentration of the biotinylated probes of 10 micrograms/mL, this panel of probes consistently failed to detect endogenous sugar receptors in ten cases of small cell anaplastic carcinoma of the lung. Whereas none of the sections from the tumor cases bound the sulfated fucan fucoidan, the accompanying inflammatory cells, especially the granulocytes, expressed receptors for the sulfated fucan. Pronounced labeling for macrophages was observed for the alpha-galactoside-specific probe, whereas no binding to inflammatory cells and pneumocytes was detectable for the beta-galactoside-specific probe. The results indicate that expression of endogenous receptors for neoglycoproteins may be useful in discriminating between small cell and non-small cell lung carcinoma and carcinomatous cells from accompanying inflammatory cells.

Carbohydrate Metabolism↗

[The pathogen spectrum in acute and chronic pleural empyema].

A retrospective analysis of the causative organisms was performed in 162 cases of empyema: 132/162 (= 81.5%) cases had positive cultures. Twenty-two different organisms were cultured from 235 isolates. The aerobic gram-positive bacteria were the largest group (61.7%), followed by aerobic gram-negative rods (21.7%), anaerobic bacteria (8.5%), and mycobacteria (5.1%). 1.8 bacterial species were recovered for each case of empyema. Polymicrobial empyema accounted for 48% of the cases. Therefore more than one antimicrobial agent should be administered to ensure adequate coverage.

Acute Disease↗

[Functional activity of the alpha1-proteinase inhibitor in serum and bronchoalveolar lavage fluid in congenital lung emphysema].

Pulmonary emphysema is thought to be due to an elastase-antielastase imbalance which leads to the destruction of alveolar walls. It is generally agreed that cigarette smoking is the major cause of acquired emphysema although many smokers fail to develop overt disease. Cigarette smoke inactivates alpha 1-proteinase inhibitor (alpha 1PI) which is believed to be the major antielastase in the lower respiratory tract. There is, however, controversy regarding the activity of alpha 1PI in smokers compared with nonsmokers. We, therefore, investigated the trypsin inhibitory capacity (TIC), the pancreatic elastase inhibitory capacity (PEIC), and the amount of immunoreactive alpha 1PI in serum and bronchoalveolar lavage fluid (BALF) of 24 individuals (15 smokers, 5 former smokers, 4 non-smokers) with clinical signs of emphysema and 32 persons (15 smokers, 6 former smokers, 11 non-smokers) without emphysema. Pancreatic elastase is known to be inhibited only by non-oxidised alpha 1PI whereas trypsin is inhibited by both native and oxidised alpha 1PI. Serum values of TIC/alpha 1PI and PEIC/alpha 1PI did not differ between the groups of subjects with emphysema (TIC/alpha 1PI: 0.71 +/- 0.12; PEIC/alpha 1PI: 0.44 +/- 0.06) and without emphysema (TIC/alpha 1PI: 0.68 +/- 0.13; PEIC/alpha 1PI: 0.41 +/- 0.07). Both serum-inhibitory capacities were found to be smaller than unit (= 1) indicating inactivation of alpha 1PI. BALF values of TIC/alpha 1PI showed a wide variation. TIC/alpha 1PI was greater than unity in 84% of subjects with emphysema (2.06 +/- 1.28) compared to 61% without emphysema (1.14 +/- 1.07) providing evidence for the presence of additional inhibitor(s) in those lavage fluids.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Proteins↗

Plasma glutamate concentration and lymphocyte activity.

Elevated glutamate concentrations are commonly observed in tumor patients, and glutamate was recently found to competitively inhibit the membrane transport of cystine. We therefore investigated the possibility that elevated plasma glutamate levels may damage the immune system. The experiments in this report demonstrate a link between the individual plasma glutamate level and the individual immunological reactivity as measured by mitogenic responses. This correlation has been analyzed in 39 colorectal carcinoma patients, 40 oat cell carcinoma patients, 24 large cell lung carcinoma patients, and 31 apparently healthy persons (blood donors). Blood cells from all three groups of tumor patients in comparison with cells from healthy persons produced markedly reduced mitogenic responses against PWM, and all three groups of tumor patients had on average significantly elevated plasma glutamic acid concentrations. Our analysis revealed a linear regression of the logarithm of the individual plasma glutamate levels (before therapeutic treatment) on the logarithm of the corresponding mitogenic reactivity against PWM for the entire population of 134 persons tested (correlation coefficient -0.80; level of significance P less than 0.00001). A statistically significant linear correlation with a similar regression equation was also observed in the group of the healthy blood donors (n = 31; correlation coefficient -0.56; P less than 0.01), indicating that this correlation is universal and not dependent on the presence of a tumor. Mitogenically stimulated murine lymphocyte cultures revealed an inverse correlation between glutamate concentration and cell proliferation in response to the mitogens PHA and PWM.

Adult↗

Expression of neuroendocrine markers (neuronspecific enolase, synaptophysin and bombesin) in carcinoma of the lung.

The value of immunoreactivity of antibodies against neuronspecific enolase (NSE), bombesin (GRP), and synaptophysin (SY 38) as markers for various human lung carcinoma has been assessed. One hundred-forty-two primary bronchus carcinomas (small cell anaplastic carcinoma, epidermoid carcinoma, adeno carcinoma, and large cell anaplastic carcinoma) were studied by the indirect immunoperoxidase method (PAP). SY 38 was found to react positively in 49/68 (79%) of the small cell anaplastic carcinoma (SCCL) and in 6/74 (8%) of the non-small cell carcinoma of the lung (NSCCL). Positive immunohistochemical data with antibody SY 38 showed in some cases an immunoreactive polypeptide of Mr = 40.000 obtained by immunoblotting similar in molecular weight as described for synaptophysin in other tumours. Reactivity of NSE was observed in 41/68 (61%) of the SCCL and in 8/74 (10%) of the NSCCL. Positive reactivity to GRP was similar to NSE in 42/68 (62%) of SCCL and in 7/74 (10%) of NSCCL. All cases of NSCCL reacting positively to SY 38 were found to react positively to NSE, and to GRP. Prognostic value of SY 38 was calculated vp = 0.71 for positive prediction and vn = 0.91 for negative prediction. The data indicate that SY 38 represents the broadest marker for neuroendocrine carcinoma of the lung since in addition to the majority of SCCL about 10% of NSCCL are recognized by the antibody SY 38.

Antibodies, Monoclonal↗

Secretion of antileucoprotease from a human lung tumor cell line.

Two human tumor cell lines were analyzed for the production of human antileucoprotease (ALP). One of them, a human squamous lung carcinoma cell line (HS-24) synthesized, as confirmed by Western blot analysis, high amounts of ALP in serum-free medium. The supernatant inhibited elastase, chymotrypsin and trypsin. Northern blot analysis with an 18-mer radiolabelled oligonucleotide, derived from an ALP specific cDNA clone, revealed a specific mRNA of about 700-800 nucleotides in HS-24 tumor cells. In contrast, a secondary human lung tumor cell line (SB-3), derived from the adrenal cortex, did not synthesize ALP when assayed under identical conditions. The supernatant inhibited only trypsin and chymotrypsin.

Carcinoma, Squamous Cell↗

Invasion of human lung carcinoma into cartilage of the bronchus.

In vivo invasion of human carcinoma of the lung into the cartilage of the bronchus was studied by light microscopy. Tumor spread into the cartilage was found in 26% (60/229). It occurred in 38/128 epidermoid carcinoma (30%) and in 14/55 adenocarcinoma (25%), but was observed in only 1/17 large cell anaplastic carcinoma (6%). Degradation of cartilage matrix was found to be limited. Destroyed area measured 9.9 +/- 1.8 mm2 on average. Tumors able to destroy bronchus cartilage were similar in size compared to tumors without detectable invasion into cartilage. Analysis of pTN stages revealed no differences between both groups. Tumor volume in extrapulmonary lymph nodes was significantly larger in case of cartilage degradation. Patients with tumors degrading bronchus cartilage showed poorer survival (median survival 360 vs. 780 days, p less than 0.10). Immunohistology differentiating inflammatory cells (B lymphocytes, T lymphocytes, monocytes, granulocytes, macrophages) revealed no participation of inflammatory cells in tumorous degradation of cartilage. The findings suggest that hyalin cartilage is highly resistant to invasion of human lung carcinoma although evidence exists for proteolytic activity of human lung carcinoma.

Adenocarcinoma↗

[Incidence and significance of bilharziasis in the Republic of Mozambique].

The bilharziosis, primarily a parasitosis of tropical countries sometimes plays a role also in the consulting hour of the physician in the GDR, especially of the urologist, therefore, it should be differential-diagnostically known to the physicians. The author reports on his activity at the Institute of Pathology of Maputo University, People's Republic Moçambique, and informs about bilharziosis on the basis of bioptic investigations especially of the urogenital tract. The high coincidence of the bilharziosis infection of the urinary bladder with the development of a in most cases planely growing squamous cell carcinoma. The frequency of the carcinoma of the urinary bladder in the People's Republic Moçambique is the greatest of the world. Pro year for 100,000 Africans in men there are 24 carcinomas, in women 19 ones. It is the second in frequency malignant tumour in the male following the primary liver carcinoma and the third in frequency of the female after the liver carcinoma and the uterine cervix carcinoma. The bilharziosis infection is also responsible for the great number of cervix carcinomas and tubal pregnancies.

Adult↗