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K Kayser

Publications and source records attributed to K Kayser.

At least 19 recordsLinked to original sources
PubMed2006

Digitized pathology: theory and experiences in automated tissue-based virtual diagnosis.

AIMS: To describe the theory and develop an automated virtual slide screening system. Theoretical considerations. Tissue-based diagnosis separates into (a) sampling procedure to allocate the slide area containing diagnostic information, and (b) evaluation of diagnosis from the selected area. Nyquist's theorem broadly applied in acoustics, serves to presetting the sampling accuracy. Tissue-based diagnosis relies on two different information systems: (a) texture, and (b) object information. Texture information can be derived by recursive formulas without image segmentation. Object information requires image segmentation and feature extraction. Both algorithms complete another to a "self-learning" classification system. METHODS: Non-overlapping compartments of the original virtual slide (image) are chosen at random with predefined error-rate (Nyquist's theorem). The standardized image compartments are subject for texture and object analysis. The recursive formula of texture analysis computes median gray values and local noise distribution. Object analysis includes automated measurements of immunohistochemically stained slides. The computations performed at different magnifications (x 2, x 4.5, x 10, x 20, x 40) are subject to multivariate statistically analysis and diagnosis classification. RESULTS: A total of 808 lung cancer cases of diagnoses groups: cohort (1) normal lung (318 cases) - cancer (490 cases); cancer subdivided: cohort (2) small cell lung cancer (10 cases) - non-small cell lung cancer (480 cases); non-small cell lung cancer subdivided: cohort (3) squamous cell carcinoma (318 cases) - adenocarcinoma (194 cases) - large cell carcinoma (70 cases) was analyzed. Cohorts (1) and (2) were classified correctly in 100%, cohort (3) in more than 95%. The selected area can be limited to 10% of the original image without increased error rate. A second approach included 233 breast tissue cases (105 normal, 128 breast carcinomas) and 88 lung tissue cases (58 normal, 38 cancer). Texture analysis revealed a correct classification with only 10 training set cases in >92% for both, breast and lung tissue. CONCLUSIONS: The developed system is a fast and reliable procedure to fulfill all requirements for an automated "pre-screening" of virtual slides in tissue-based diagnosis.

Algorithms↗
PubMed2005

Bronchioloalveolar carcinoma: a new cancer in Peutz-Jeghers syndrome.

Besides gastrointestinal hamartomatous polyposis and melanin spots in the skin and mucosa, patients with the Peutz-Jeghers syndrome (PJS) have repeatedly been observed with a variety of tumours, including lung cancer. Available data indicate an increased cancer risk among PJS patients, which suggests that the gene involved in PJS, STK11 on chromosome 19p13.3, may be a tumour suppressor gene. Herein, bronchioloalveolar carcinoma (BAC) of mucinous type is reported in a 22-year old male PJS patient with a novel germline frameshift insertion in exon 2 at codon 118 of the STK11 gene. Molecular studies of his BAC indicated loss of heterozygosity (LOH) in the region of STK11 on chromosome 19p13.3. This observation supports the hypothesis that STK11 is a tumour suppressor gene which is involved in the development of lung adenocarcinoma.

AMP-Activated Protein Kinase Kinases↗
PubMed2005

Processes in vertical-flow reed beds: nitrification, oxygen transfer and soil clogging.

Vertical-flow reed beds (VF) with intermittent feeding are extremely reliable regarding aerobic processes. For a save operation with high nitrification rates and without soil clogging it is essential to preserve aerobic conditions in the filter. The challenge is to keep aerobic conditions in the filter without oversizing the system (economical aspects). It is very difficult to determine the current oxygen content in the filters because it ultimately results from complex interactions of a large number of different influencing parameters such as loading rate, degree of clogging, temperature, and hydraulic behaviour of the reed bed. To gain better knowledge of this complex system, different tests and examinations were carried out over several years. Focusing on the questions of identification and the description of conversion and transport processes (water/gas), a full-scale treatment plant under clogged and non-clogged conditions was investigated in detail. Additionally soil column test were carried out. The results make it possible to describe some of the processes and their interactions in the filter body. Recommendations for a safe and controlled operation can be derived.

Bacteria, Aerobic↗
PubMed2005

Phenotype and genotype associations of lung carcinoma with atypical adenomatoid hyperplasia, squamous cell dysplasia, and chromosome alterations in non-neoplastic bronchial mucosa.

The frequency of preneoplastic lesions of the lung and bronchial mucosa as well as potential genotype alterations in spatial relationship to pulmonary malignancies still need intensive investigations in order to understand the occurrence and manifestation of lung cancer in detail. To investigate the contemporary manifestation of lung cancer precursor lesions, peripheral (non-neoplastic) lung parenchyma and bronchial mucosa of operated lung carcinomas were analyzed at distinct distances (1, 2, 3, and 4 cm) from the tumor boundary for pre-neoplastic lesions--atypical adenomatoid hyperplasia (AAH) and squamous cell dysplasia (SCD), in 150 surgical specimens. Short-term tissue cultures of additional 55 primary and secondary lung tumors and their surrounding non-neoplastic bronchial mucosa were performed at the same distances in order to search for chromosome alterations, i.e. genotype aberrations. In phenotype observations, atypical adenomatoid hyperplasia was noted in 19/150 (13%) cases, and squamous cell dysplasia in 46/150 (31%) cases. The degree of cellular atypia decreased with increasing distance from the tumor boundary in both AAH and SCM. AAH was observed more frequently in adenocarcinomas, SCQ more frequently in squamous cell carcinomas. In genotype observations, the average number of abnormal metaphases measured 4.5/10 high power fields (HPF) in primary lung carcinomas, and only 2/10 in metastases. Data indicate that the so-called preneoplastic lesions in the lung are not completely tumor-precursor lesions, but, in addition, induced by the tumor itself.

Bronchi↗
PubMed2003

Combined analysis of tumor growth pattern and expression of endogenous lectins as a prognostic tool in primary testicular cancer and its lung metastases.

The aim of this study was to glyco- and immunohistochemically analyze expression of distinct growth/adhesion-related markers of primary testicular carcinomas and their lung metastases in relation to the risk of developing lung metastases and survival of patients, and to correlate immunohistochemical staining profile and syntactic structure analysis in order to delineate new prognostic parameters for this tumor type. Clinical features of 50 patients with primary testicular carcinomas and their corresponding lung metastases were evaluated and compared to those of a control cohort of 25 cases. The set of eight probes including labeled galectins-1 and -3, specific non-cross-reactive antibodies against galectins-1, -3, and -8 as well as anti-Ki-67, anti-bcl-2, and anti-p53 was applied to formalin-fixed, paraffin-embedded tumor sections of both primary and metastatic lesions. Syntactic structure analysis computed staining intensities and structural features of the tumor cells. These parameters were set into relation separately and in combination to clinical data including tumor stages, smoking habits, applied cytostatic therapy, disease-free interval, and survival. The risk of testis cancer patients to develop lung metastases depends in descending order on the tumor cell type (non-seminoma versus seminoma), tumor cell heterogeneity (mixed versus monomorphous cell type), age of patients, and pT stage. The extent of differential expression of galectin-related features between primary and secondary lesions was pronounced. Prognostic correlations for distinct galectin-related features were delineated in combination with data from syntactic structure analysis, for example cluster radius of galectin-3-positive tumor cells and post-surgical and total survival. Lengths of disease-free interval and total survival of patients were also correlated to characteristics obtained by syntactic structure analysis and their combination with galectin data in the first place, then to smoking habits, percentage of proliferating cells in the primary and secondary tumors, and finally to expression of certain galectins and of p53. Patients with non-seminoma testicular cancer should be thoroughly controlled for lung metastases. Regarding marker selection, our study underscores that further investigation of the growth-regulatory network of galectins is clearly warranted.

Adult↗
PubMed2003

Nutrient removal from piggery effluent using vertical flow constructed wetlands in southern Brazil.

Santa Catarina State, southern Brazil, has the greatest swine breeding activities of Latin America. Generally, the piggery wastewater is treated in pond systems that are able to remove organic material according to local environmental legislation. However, these systems do not remove nitrogen and phosphorus efficiently. This work deals with a post-treatment system, using vertical flow constructed wetlands. The experiment was conducted in a swine production farm which has 45,000 animals. Although the pond system was able to partially remove the content of nutrients, their concentration in the effluent was high for environmental disposal. A four-bed vertical flow constructed wetland pilot plant, using Typha spp., was built. The pilot plant operated for 280 days for beds 2-4 (sand 2). However, the experiments with beds 1-3 (sand 1) were stopped after 111 days of operation, when a reduction in the wastewater drainage was observed. The beds with sand 2 showed a 33% COD removal, and about 49% of nitrification was observed from 111 days until the end of the operation. PO(4)-P removal was 45% with a loading rate of around 1.36 g m(-2) d(-1).

Animals↗
PubMed2003

Controlling a combined lagoon/reed bed system using the oxidation-reduction potential (ORP).

Lagoon systems achieve good and stable effluent data in regard to organic pollutants, but they charge the receiving waters with relatively high ammonium loads. Therefore an existing lagoon-plant was extended by a vertical flow reed-bed for the special purpose of nitrification. This paper presents the efficiency of the combination plant as well as the possibility to monitor and control the reed-bed operation by the oxidation-reduction potential (ORP). The results show that the combination plant achieved excellent purification results, the average efficiency degrees were 97% for COD, 77% for N(total) and 94% for the TKN elimination. The ORP in the effluent of the reed bed showed a clear dependence in its characteristic course and its absolute values on the current nitrification performance, the oxygen supply and the hydraulic behaviour of the reed bed. Therefore the ORP is a very good indicator for the state of the reed bed, which ultimately results from the accumulation of a large number of different influencing parameters. As the preservation of aerobic conditions in the reed bed is the crucial prerequisite for a high nitrification performance and for the avoidance of clogging, the ORP thus offers the possibility of immediate operation control.

Ecosystem↗
PubMed2002

Comparison of multiple DNA adduct types in tumor adjacent human lung tissue: effect of cigarette smoking.

Cigarette smokers inhale a broad range of carcinogens derived from tobacco and its pyrolysis products, including free radicals, which induce oxidative stress and subsequent lipid peroxidation (LPO). Miscoding carcinogen-DNA adducts are formed by cigarette smoke constituents and are thought to initiate lung carcinogenesis. The presence of various types of DNA damage was therefore analyzed in tumor adjacent uninvolved lung tissues of 13 smoking and 11 non-smoking operated lung cancer patients. O(4)-ethylthymidine (O(4)etT), 1,N(6)-ethenodeoxyadenosine ( epsilon dA) and 3,N(4)-ethenodeoxycytidine ( epsilon dC) were determined by immuno-enriched (32)P-postlabeling. Polycyclic aromatic hydrocarbon (PAH)-DNA adducts were measured as diagonal radioactive zones after nuclease P1 enriched (32)P-postlabeling. Mean O(4)etT and PAH-DNA adduct levels were higher in lung DNA of smokers than of non-smokers (O(4)etT/10(8) thymidine: 3.8 versus 1.6, P < 0.01; PAH-DNA adducts/10(8) nucleotides: 11.2 versus 2.2, P < 0.01). Pulmonary etheno-DNA adduct levels did not differ between smokers and non-smokers, but large inter-individual variations were observed (80- and 250-fold differences for epsilon dA and epsilon dC, respectively). As all smokers (except one) refrained from smoking at least for 1 week before surgery, our results demonstrate the persistence of O(4)etT and PAH-DNA adducts in human lung. A positive correlation obtained between O(4)etT and PAH-DNA adducts (R = 0.65, P < 0.01) suggests that both adducts are formed from cigarette smoke as the main exposure source. We conclude that in addition to the DNA adducts derived from PAH and tobacco-specific nitrosamines, miscoding O(4)etT lesions are formed by cigarette smoke that contribute to the increased genomic instability and increased lung cancer risk in smokers.

Aged↗
PubMed2002

Nitrification in reed beds--capacity and potential control methods.

Vertical-flow reed beds (VFBs) are known to be very effective regarding nitrification. However, a generally accepted design formula for dimensioning reed beds for a controlled nitrification process has still not been found. Especially for the purpose of nitrification a vertical-flow reed bed (VFB) has been installed following an existing unaerated pond-system. The paper presents the results concerning the limits of the VFB's performance as well as the main factors influencing the nitrification process gained by balancing the conversion rates under different loads. Even under high loads the VFB provides an excellent nitrification performance, which is mainly influenced by the wastewater temperature. The ammonia oxidation rate is about 90% at temperatures over 10 degrees C; at temperatures below 5 degrees C the average nitrification rate is still approximately 50%. The hydraulic load and the TKN load have almost no impact on this efficiency (the maximum load has been: 180 mm/d, 7.1 g TKN/(m2 x d)). The redox potenial, which is continuously measured in the effluent of the reed bed, proved to be dependent on the current nitrification performance and the oxygen supply of the VFB, and therefore appears to be a suitable control parameter for the operation of VFBs.

Ecosystem↗
PubMed2001

Small pulmonary lesions--a challenge for thoracic surgery?

We analyzed the diagnosis, the potentially associated external and clinical features, and the surgical procedures of small pulmonary lesions, especially hamartomas (in relation to peripheral T1 lung carcinomas and lymphoid hyperplasia) in 103 patients who experienced enucleation or resection of pulmonary hamartomas between March 1, 1995 and December 31, 2000. The causes of surgical intervention, presurgical diagnoses, surgical procedures, location, size, and histological compartments were analyzed, as well as clinical features potentially associated with the tumors (alcohol, asbestos, smoking, and chronic lung diseases). Follow up of patients lasted for 5.5 years at maximum. For comparison, 36 patients with peripheral T1 lung carcinomas are included as well as 50 patients with lymphoid hyperplasia. The sex and age distribution of the patients with hamartomas was comparable to that of patients with lymphoid hyperplasia. About 75% of men and 55% of women were heavy smokers, with an average history of 30 and 17 pack years, respectively. In 84% of patients, the lesions were incidentally detected in chest radiographs, whereas 12% of patients underwent thoracic surgery suspicious for intrapulmonary metastases of known extrapulmonary malignancies. Enucleation was performed in 21%, and wedge resection in 77% of patients. At average, hamartomas were smaller than T1 lung carcinomas, but considerably larger in comparison to lymphoid hyperplasia. No recurrent tumors or additionally detected hamartomas were noted during the follow up, and both surgical procedures (enucleation or wedge resection) were identical in curative treatment. All patients with peripherally localized T1 tumors underwent lobectomy. The 3/5 year survival rate was calculated to 69/52%. Lymphoid hyperplasia is of clinical importance for the estimation of prognosis in patients with metastatic disease, as the number of radiologically suggestive metastatic nodules can often be significantly changed due to this entity. Pulmonary hamartomas are benign lesions that display certain clinical associations with malignant lung carcinomas in respect to external risk factors, and to lymphoid hyperplasia. Both surgical procedures (enucleation or wedge resection) can be performed, giving identical results in respect to treatment.

Adolescent↗
PubMed2001

Cathepsin S in tumours, regional lymph nodes and sera of patients with lung cancer: relation to prognosis.

Cysteine proteinase cathepsin S (Cat S) is expressed mainly in lymphatic tissues and has been characterised as a key enzyme in major histocompatibility complex class II (MHC-II) mediated antigen presentation. Cat S has been measured in tissue cytosols of lung parenchyma, lung tumours and lymph nodes and in sera of patients with lung tumours and of healthy controls, by specific enzyme-linked immunosorbent assay (ELISA). A difference in Cat S level was found between tumour and adjacent control tissue cytosols of 60 lung cancer patients (median 4.3 vs. 2.8 ng mg(-1) protein). In lymph nodes obtained from 24 patients of the same group, the level of Cat S was significantly higher than in tumours or lung parenchyma (P< 0.001). Additionally, significantly higher levels were found in non-infiltrated than in infiltrated lymph nodes (median 16.6 vs 7.5 ng mg(-1) protein). Patients with low levels of Cat S in tumours and lung parenchyma exhibited a significantly higher risk of death than those with high levels of Cat S (P = 0.025 - tumours; P = 0.02 - parenchyma). Immunohistochemical analysis (IHA) of lung parenchyma revealed a staining reaction in alveolar type II cells, macrophages and bronchial epithelial cells. In regional lymph node tissue, strong staining of Cat S was found in lymphocytes and histiocytes. Nevertheless, Cat S was detected also in tumour cells, independently of their origin. Our results provide evidence that Cat S may be involved in malignant progression. Its role, however, differs from that of the related Cats B and L and could be associated with the immune response rather than with remodelling of extracellular matrix.

Antibody Specificity↗
PubMed2001

Glyco- and immunohistochemical refinement of the differential diagnosis between mesothelioma and metastatic carcinoma and survival analysis of patients.

The aim of this study was to analyse the diagnostic value of selected glyco- and immunohistochemical probes for discrimination between mesotheliomas and metastatic carcinomas within the pleura, and to evaluate prognostic indicators in the tested panel. A panel of nine markers (five antibodies, two neoglycoproteins, and labelled hyaluronic acid) was applied to a total of 264 specimens with mesotheliomas (118 cases) and metastatic carcinomas in the pleura (146 cases); the material consisted exclusively of surgical specimens. The diagnosis obtained by standard procedures was further substantiated through a detailed follow-up and clear-cut descriptions of primary sites. The metastatic tumours originated from the lung (82 cases), breast (47 cases), colon (three cases), and kidney (two cases); in 12 cases, however, the tumour origin could not be ascertained. In detail, the probes tested included antibodies against carcinoembryonic antigen (CEA), vimentin, calretinin, mesothelial cells (HBME-1), calcyclin and keratin-5; and also biotinylated neoglycoproteins with ganglioside GM1 and N-acetyl-D-glucosamine (GlcNAc) as the ligand part, and hyaluronic acid. Carrier-immobilized ganglioside GM1 and hyaluronic acid displayed the highest specificity and sensitivity for mesotheliomas, followed by calretinin and HBME-1, whereas keratin-5 and vimentin were of low specificity (43% and 52%, respectively). Metastatic carcinomas could be discerned by CEA detection and application of GlcNAc-bearing neoglycoprotein with similar sensitivity (76% and 72%, respectively) and specificity (91% and 86%, respectively). In cases of breast carcinoma, the maximum specificity (59%) and sensitivity (67%) were low for all markers. Patients with mesothelioma survived longer than those with metastatic carcinoma, especially those with detectable binding sites for hyaluronic acid. No association of tumour type and binding properties of the other applied probes with survival of the patients could be found at a statistically significant level. It is concluded that in routine practice, the application of carrier-immobilized GM1, hyaluronic acid, and antibodies against calretinin and HBME-1 is useful for confirmation of mesothelioma, whereas the detection of CEA and GlcNAc-specific binding sites is useful for distinguishing metastatic carcinoma from mesothelioma. Despite the rather infrequent occurrence of mesotheliomas in women, particular attention should be given to exclude or confirm metastatic breast carcinoma in cases of unknown history or long metastatic interval.

Acetylglucosamine↗
PubMed2001

[Benign, pulmonary metastatic leiomyoma of the uterus].

Pulmonary nodules resected in 10 patients were histologically classified as benign metastatic leiomyoma of the uterus. Hysterectomy because of myoma had been performed between 0 and 24 years earlier (median 14.9 years). Between 1 and 27 nodules were found in one or both lungs. Patients presenting with a single nodule had it resected with diagnostic intent and were followed up. Multiple nodules were resected if the loss of parenchyma was tolerable; otherwise, one lesion was resected for diagnosis. In some cases antihormonal therapy was performed postoperatively. The median duration of follow-up was 4.7 years. In this time, no local complication occurred, and no patient died of this disease. Apparently, benign metastatic leiomyoma of the uterus biologically shows benign behaviour. New manifestation or progressing growth of non-resected lesions does occur, however. Consequently, regular follow-up is required. Local complications indicate surgical intervention.

Adult↗
PubMed2001

[Proliferation rate of small cell lung carcinoma. A cytomorphometric parameter with prognostic significance].

AIM: Evaluation of prognosis-associated parameters in patients with small cell lung carcinoma. MATERIAL AND METHODS: Biopsies of 46 patients suffering from a non-treated small cell lung carcinoma were stained with Feulgen and immunohistochemically with Ki-67 antibody. The integrated optical density (IOD) and proliferation rate was measured by syntactic structure analysis and correlated with survival. RESULTS: About 85% of patients had a smoking history (46 pack years on average). The median survival time was 13.5 months, the proliferation rate (Ki-67 positive tumor cell nuclei) 68.2% and S-phase percentage 9.2%. Ot average, 25 proliferating tumor cell nuclei formed clusters (mean diameter 95 microns). The prognosis was associated with the proliferation rate (p < 0.04), tumor stage (stage I versus lib, p < 0.05), at threshold limits with S-phase rate (p < 0.07) and serum levels of LDH and NSE (p < 0.06 and p < 0.07 respectively). CONCLUSIONS: Immune histochemical determination of the Ki-67 protein is a useful method to estimate the prognosis of patients with small cell lung carcinoma.

Antigens, Neoplasm↗
PubMed2001

Endobronchial juvenile hemangioma--a case report of a neonate including immunohistochemical monitoring and nuclear, cellular, and vascular morphometry.

A 3-month-old female child suffered from tachypnea and dyspnea with abnormal blood gas values. Chest X-rays revealed an increased transparency of the left lung and a mediastinal shift to the right side. High resolution computed tomography (CT) documented a narrowing of the left upper stem bronchus. Ensuing endoscopy detected an occlusive endobronchial tumor mass that did not infiltrate the bronchial cartilage as confirmed with endobronchial ultrasonic monitoring. Based on gross histological examination of the surgical specimen obtained using sleeve resection, the highly vascularized tumor exhibited an adenomatoid growth pattern with a rather homogeneous population of nuclei. The light microscopical presentation was consistent with a juvenile (infantile) hemangioma, which was confirmed using immunohistochemical examinations despite the display of neuroendocrine features. Although endobronchial juvenile hemangiomas are an extremely rare event in early childhood, this case underscores the necessity to not neglect its occurrence in differential diagnosis.

Biomarkers, Tumor↗
PubMed2001

Survival, disease-free interval, and associated tumor features in patients with colon/rectal carcinomas and their resected intra-pulmonary metastases.

OBJECTIVE: Colon/rectum cancer often presents with intrapulmonary metastases. Surgical resection can be performed in a selected group of patients. In this study, the search for possible prognostic factors of patients with primary colon/rectum cancer and lung metastases was performed. METHODS: Medical records of 110 patients operated on pulmonary metastases of primary colon/rectum cancer were reviewed. The clinical parameters include age, sex, pTNM/UICC stage, grading, localization, surgical and adjuvant therapy of the primary cancer. The number, maximum diameter and total intra-thoracic resected tumor-mass ('load'), the pre-thoracotomy serum carcinoembryonic antigen (CEA) levels, localization of the metastases (uni- vs. bilateral), the presence of hilar/mediastinal tumor-infiltrated lymph nodes, the surgical procedure and performed therapy schemes of lung metastases were recorded. RESULTS: The cumulated 5- and 10-year total survival after diagnosis of the primary carcinomas was estimated to 71 and 33.7%, respectively. After resection of the pulmonary metastases, the 3- and 5-year post-thoracotomy survival measured 57 and 32.6%, respectively. The median time interval between diagnosis of the primary cancer and thoracotomy (disease free interval (DFI)) was found to be 35 months. A non-negligible percentage of patients (15.4%) displayed limited tumor stages of the primary cancer (pT1/2, pN0). The median diameter of the largest metastasis measured 28 mm, and the median resected intrathoracic tumor-load was calculated to 11.4 cm(3). In only 8 patients hilar or mediastinal tumor-involved lymph nodes were found. A potentially curative resection of lung metastases was recorded in 96 patients. The overall survival was significantly correlated with the DFI and the number of intrapulmonary metastases. The DFI correlated significantly with the tumor load and the number of metastases; the post-thoracotomy survival with the number of metastases, tumor-load and pre-thoracotomy serum CEA level. Treatment, stage and grade of the primary cancer, occurrence of liver metastases and local recurrences, mode of treatment of metastases and postoperative residual stage had no significant correlation with either total nor post-thoracotomy survival. CONCLUSIONS: Pulmonary metastases occur even in patients with limited tumor-stages of primary colon/rectum cancer. DFI is the major parameter to estimate the total survival of patients with lung metastases. The survival after thoracotomy depends on the number of metastases, the intrapulmonary tumor load and the presence of elevated serum CEA level prior to thoracotomy.

Adult↗
PubMed2001

Reduced T-cell receptor CD3zeta-chain protein and sustained CD3epsilon expression at the site of mycobacterial infection.

Control of mycobacterial infection by the cellular immune system relies both on antigen-presenting cells and on T lymphocytes. The quality of an effective cellular immune response is dependent on functional signal transduction residing in the cytoplasmic tails of the T-cell receptor CD3 components. In order to investigate potential effects of mycobacteria on T-cell receptor signalling, we examined the protein expression of T-cell signal transduction molecules (CD3zeta, ZAP-70, p59fyn, p56lck). In Western blots of peripheral blood mononuclear cells of Mycobacterium tuberculosis infected patients, only the CD3zeta-chain showed a marked reduction in protein expression. To investigate the situation in situ, immunoenzymatic and immunofluorescence stainings for CD3epsilon and CD3zeta expression were performed on sections of normal lymphoid tissue, M. leprae infected and sarcoid tissue. CD3epsilon and CD3zeta expression were similar with respect to intensity, localization and the number of cells stained in normal lymphoid tissue and in sarcoid granulomas. In contrast, the granulomas of M. leprae infected tissues showed a significantly reduced expression of CD3zeta compared to CD3epsilon. Using double immunofluorescence analysis, virtually no CD3zeta expression could be detected in comparison to the CD3epsilon expression in the lesions. Apparently, mycobacteria are capable of significantly reducing CD3zeta-chain expression, which may be restored by cytokines. IL-2-enhanced zeta-chain expression and T-cell effector functions, defined by interferon-gamma release, in M. tuberculosis-specific and human leucocyte antigen-DR restricted CD4+ T cells isolated from granuloma lesions from patients with pulmonary tuberculosis. Because CD3zeta is essential for CD3 signalling and for eliciting T-cell effector functions, reduced CD3zeta protein expression could result in altered signal transduction and inefficient T-cell effector functions. Alternatively, reduced CD3zeta-chain expression may protect T cells from repetitive TCR stimulation associated with anergy or apoptosis.

CD3 Complex↗