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1.
Unfallchirurg ; 117(7): 624-32, 2014 Jul.
Article in German | MEDLINE | ID: mdl-23754552

ABSTRACT

STUDY AIM: The aim of the study was an estimation of the incidence and clinical aspects of emergency room (ER) parameters of penetrating abdominal injury patients with bowel evisceration. STUDY DESIGN AND METHODS: The study involved a retrospective cohort analysis of ER data from the Chris Hani Baragwanath Academic Hospitals, Soweto, Johannesburg, South Africa between September 2000 to May 2005. RESULTS: Out of 9,010 ER patients, 4,390 suffered penetrating injuries with 8 out of 71 eviscerations due to a single gunshot wound, 60 out of 71 eviscerations due to single stab wounds and 3 further patients suffered multiple injuries. The ER mortality was 1 out of 71(1.6 %) with an average ER mortality of 4.2 %. The only death seen was a single abdominal gunshot wound with vascular injury. The causative mortality due to abdominal stab wounds with evisceration of the bowels was therefore zero. The heart rate in patients with abdominal stab wounds with and without bowel evisceration showed no significant difference, thus mesentery tearing or vagal overstimulation could not be seen, neither with bradycardia nor hypotension. CONCLUSION: Evisceration itself is not a cause for increased mortality or cardiovascular instability seen in the ER. There is ample time for diagnostic procedures before laparotomy is performed.


Subject(s)
Abdominal Injuries/mortality , Emergency Medical Services/statistics & numerical data , Emergency Service, Hospital/statistics & numerical data , Hernia/mortality , Intestines/injuries , Wounds, Gunshot/mortality , Wounds, Stab/mortality , Adolescent , Adult , Age Distribution , Comorbidity , Emergency Service, Hospital/organization & administration , Female , Humans , Incidence , Male , Middle Aged , Risk Factors , Sex Distribution , South Africa/epidemiology , Survival Rate , Young Adult
2.
Scand J Immunol ; 65(5): 467-78, 2007 May.
Article in English | MEDLINE | ID: mdl-17444958

ABSTRACT

Novel diagnostic tools are needed to diagnose latent infection and to provide biologically meaningful surrogate markers to define cellular immune responses against Mycobacterium tuberculosis (MTB). Interferon gamma-based assays have recently been developed in addition to the more than 100-year-old tuberculin skin test (TST) for the immune diagnosis of MTB in blood. The advent of soluble MHC/peptide tetramer molecules allows to objectively enumerate antigen-specific T cells. We identified novel MHC class II-restricted MTB epitopes and used HLA-DR4 tetrameric complexes to visualize ex vivo CD4(+) T cells directed against the antigens Ag85B and the 19-kDa lipoprotein, shared between MTB and other Mycobacterium species, and CD4(+) T cells which recognize the MTB-associated ESAT-6 antigen. MTB-reactive CD4(+) T cells reside predominantly in the CD45RA(+) CD28(+) and CD45(-) CD28(+) T-cell subset and recognize naturally processed and presented MTB epitopes. HLA-DR4-restricted, Ag85B or ESAT-6-specific CD4(+) T cells show similar dynamics over time in peripheral blood mononuclear cells (PBMC) when compared with CD8(+) T cells directed against the corresponding HLA-A2-presented MTB epitopes in patients with pulmonary MTB infection and subsequent successful therapy. This was not found to be true for T-cell responses directed against the 19-kDa lipoprotein. The dissection of the cellular immune response in M. tuberculosis infection will enable novel strategies for monitoring MTB vaccine candidates and to gauge CD4(+) T cells directed against MTB.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/microbiology , Epitopes, T-Lymphocyte/blood , Histocompatibility Antigens Class II/blood , Mycobacterium tuberculosis/immunology , Tuberculosis, Pulmonary/immunology , Amino Acid Sequence , Antigen Presentation , Antigens, Bacterial/immunology , Antigens, Bacterial/metabolism , CD4-Positive T-Lymphocytes/metabolism , Histocompatibility Antigens Class II/chemistry , Humans , Molecular Sequence Data , Tuberculosis, Pulmonary/blood , Tuberculosis, Pulmonary/microbiology , Tuberculosis, Pulmonary/pathology
3.
Rom J Morphol Embryol ; 47(1): 21-8, 2006.
Article in English | MEDLINE | ID: mdl-16838053

ABSTRACT

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.


Subject(s)
Diagnostic Techniques and Procedures , Image Cytometry , Image Processing, Computer-Assisted , Pathology/methods , Algorithms , Breast Neoplasms/diagnosis , Breast Neoplasms/pathology , Female , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/pathology
4.
Rom J Morphol Embryol ; 46(1): 5-10, 2005.
Article in English | MEDLINE | ID: mdl-16286978

ABSTRACT

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.


Subject(s)
Bronchi/pathology , Carcinoma, Squamous Cell/genetics , Chromosome Aberrations , Lung Neoplasms/genetics , Respiratory Mucosa/pathology , Carcinoma, Squamous Cell/pathology , Cell Nucleus/genetics , Cell Nucleus/pathology , Cell Size , Genotype , Humans , Hyperplasia , Lung Neoplasms/pathology , Mitosis , Phenotype
5.
Water Sci Technol ; 51(9): 177-84, 2005.
Article in English | MEDLINE | ID: mdl-16042257

ABSTRACT

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.


Subject(s)
Ecosystem , Waste Disposal, Fluid/methods , Bacteria, Aerobic , Biodegradation, Environmental , Filtration , Nitrogen/metabolism , Oxygen/metabolism , Soil , Water Movements
6.
Lung Cancer ; 47(2): 283-8, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15639728

ABSTRACT

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.


Subject(s)
Adenocarcinoma, Bronchiolo-Alveolar/etiology , Adenocarcinoma, Bronchiolo-Alveolar/genetics , Chromosomes, Human, Pair 19 , Lung Neoplasms/etiology , Lung Neoplasms/genetics , Peutz-Jeghers Syndrome/complications , Peutz-Jeghers Syndrome/genetics , Protein Serine-Threonine Kinases/genetics , AMP-Activated Protein Kinase Kinases , Adult , Base Sequence , Genes, Tumor Suppressor , Humans , Loss of Heterozygosity , Male , Molecular Sequence Data , Polymerase Chain Reaction
7.
Water Sci Technol ; 48(5): 167-74, 2003.
Article in English | MEDLINE | ID: mdl-14621161

ABSTRACT

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.


Subject(s)
Ecosystem , Waste Disposal, Fluid/methods , Water Purification/methods , Nitrogen/metabolism , Organic Chemicals/isolation & purification , Oxidation-Reduction , Water Movements , Water Pollutants/isolation & purification
8.
Water Sci Technol ; 48(2): 129-35, 2003.
Article in English | MEDLINE | ID: mdl-14510203

ABSTRACT

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).


Subject(s)
Nitrogen/isolation & purification , Phosphorus/isolation & purification , Waste Disposal, Fluid/methods , Water Purification/methods , Animals , Biodegradation, Environmental , Brazil , Ecosystem , Swine , Typhaceae , Water Movements
9.
Histol Histopathol ; 18(3): 771-9, 2003 07.
Article in English | MEDLINE | ID: mdl-12792889

ABSTRACT

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.


Subject(s)
Lectins/metabolism , Lung Neoplasms/pathology , Prognosis , Testicular Neoplasms/metabolism , Testicular Neoplasms/pathology , Adult , Carcinoma/metabolism , Carcinoma/pathology , Cell Division , Cohort Studies , Disease-Free Survival , Humans , Immunohistochemistry , Lung Neoplasms/secondary , Male , Neoplasm Metastasis , Neoplasms/pathology , Time Factors
11.
Water Sci Technol ; 46(6-7): 363-70, 2002.
Article in English | MEDLINE | ID: mdl-12381013

ABSTRACT

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.


Subject(s)
Nitrogen/metabolism , Waste Disposal, Fluid/methods , Water Purification/methods , Ecosystem , Oxidation-Reduction , Temperature , Water Movements
12.
Appl Microbiol Biotechnol ; 59(6): 737-45, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12226734

ABSTRACT

An organism, identified as Mycobacterium phlei GTIS10, was isolated based on its ability to use dibenzothiophene (DBT) as a sole source of sulfur for growth at 30-52 degrees C. Similar to other biodesulfurization-competent organisms, M. phlei GTIS10 converts DBT to 2-hydroxybiphenyl (2-HBP), as detected by HPLC. The specific desulfurization activity of the 50 degrees C M. phlei GTIS10 culture was determined to be 1.1+/-0.07 micromol 2-HBP min(-1) (g dry cell)(-1). M. phlei GTIS10 can also utilize benzothiophene and thiophene as sulfur sources for growth. The dszABC operon of M. phlei GTIS10 was cloned and sequenced and was found to be identical to that of Rhodococcus erythropolis IGTS8. The presence of the R. erythropolis IGTS8 120-kb plasmid pSOX, which encodes the dszABC operon, has been demonstrated in M. phlei GTIS10. Even though identical dsz genes are contained in both cultures, the temperature at which resting cells of R. erythropolisIGTS8 reach the highest rate of DBT metabolism is near 30 degrees C whereas the temperature that shows the highest activity in resting cell cultures of M. phlei GTIS10 is near 50 degrees C, and activity is detectable at temperatures as high as 57 degrees C. In M. phlei GTIS10, the rate-limiting step in vivo appears to be the conversion of DBT to dibenzothiophene sulfone catalyzed by the product of the dszC gene, DBT monooxygenase. The thermostability of individual desulfurization enzymes was determined and 2-hydroxybiphenyl-2-sulfinate sulfinolyase, encoded by dszB, was found to be the most thermolabile. These results demonstrate that the thermostability of individual enzymes determined in vitro is not necessarily a good predictor of the functional temperature range of enzymes in vivo.


Subject(s)
DNA, Bacterial/genetics , Mycobacterium/isolation & purification , Thiophenes/metabolism , DNA, Bacterial/chemistry , Hot Temperature , Mycobacterium/genetics , Mycobacterium/metabolism , Oxidoreductases/chemistry , Oxidoreductases/genetics , Oxygenases/chemistry , Oxygenases/genetics , Polymerase Chain Reaction , Sequence Analysis, DNA
13.
Carcinogenesis ; 23(12): 2081-6, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12507931

ABSTRACT

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.


Subject(s)
DNA Adducts , Deoxycytidine/analogs & derivatives , Lung Neoplasms/pathology , Smoking/adverse effects , Thymidine/analogs & derivatives , Aged , DNA Damage , Deoxyadenosines/analysis , Deoxycytidine/analysis , Female , Humans , Hydrocarbons , Male , Middle Aged , Thymidine/analysis , Time Factors
14.
Pneumonol Alergol Pol ; 69(5-6): 247-56, 2001.
Article in Polish | MEDLINE | ID: mdl-11732286

ABSTRACT

The authors assessed the diagnostic accuracy of the static telepathology (sTP) for practical consultations in the controversial pulmonary oncology cases. The short characteristics of the diagnostic cases is included. We reported the results of 6 difficult clinico-pathological cases submitted to Dept Quantitative Pathology [DQP] for consultations (5F and 1M, age: 26-68 yrs). Digital images of histological or cytological samples were captured at DQP and transmitted to telepathologist (TPat) in Thoraxklinik, Heidelberg or AFIP, Washington DC. Simultaneously, the same slides (or with a paraffin block) were mailed to TPats for re-evaluation with the conventional microscope (dgn-zwPat). The controversial cases presented 2 types of diagnostic problems: 1/rare entities, 2/common difficulties in the routine work of pathologist, but with indefinitely proved diagnosis. The first group encounters TPat diagnoses as follows: * case A: pulmonary plasma cell granuloma with lymphoidal interstitial infiltrates [LIP]--preleukemia; * case B: microfoci of early metastases of benign uterine leiomyoma; * case D: small cell carcinoma spreading along pleura. The second group included: * case C: invasive epidermoidal carcinoma in bronchus; *case E: probably metastatic adenocarcinoma of colon; *case F: synchronous or metastasising 2 lung tumours sharing NE morphology or NE immunohistochemical features. There was very high concordance between referring pathologist (ref-Pat) diagnoses and TPat diagnoses as well as a consensus in zw-TPat diagnoses. In 2 cases the conceptual problem was solved by TPat. Telepathology offered a support or improved the quality of the final diagnosis. The implementation of sTP remarkably reduced the time of consultations and allowed to present the diagnostic problems to the international group of experts.


Subject(s)
Lung Neoplasms/pathology , Telepathology/standards , Adenocarcinoma/pathology , Adenocarcinoma/secondary , Adult , Aged , Carcinoma, Small Cell/pathology , Carcinoma, Small Cell/secondary , Colonic Neoplasms/pathology , Diagnosis, Differential , Female , Granuloma, Plasma Cell/pathology , Humans , Leiomyoma/pathology , Lung Neoplasms/secondary , Male , Middle Aged , Reproducibility of Results , Uterine Neoplasms/pathology
15.
Pharmacogenetics ; 11(9): 757-64, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11740339

ABSTRACT

Polymorphic glutathione-S-transferase (GST) genes causing variations in enzyme activity may influence individual susceptibility to lung cancer. In this case-control study (consisting of 389 Caucasian lung cancer patients, including 151 adenocarcinomas (ACs) and 172 squamous cell carcinomas (SCCs), and 353 hospital control subjects without malignant disease, genotype frequencies for GSTM1, GSTM3, GSTP1 and GSTT1 were determined by polymerase chain reaction (PCR)/ restriction fragment length polymorphism (RFLP)-based methods. While adjusted odds ratios (ORs) indicated no significantly increased risk for lung cancer overall due to any single GST genotype, the risk alleles for GSTM1, GSTM3 and GSTP1 conferring reduced enzyme activity were present at higher frequency in SCC than in AC patients. This is consistent with a reduced detoxification of carcinogenic polycyclic aromatic hydrocarbons (PAHs) from cigarette smoke that are more important for the development of SCC than for AC. An explorative data analysis also identified statistically significantly increased ORs for the combinations GSTT1 non-null and GSTP1 GG or AG for lung cancer overall (OR 2.23, CI 1.11-4.45), and for SCC (OR 2.69, CI 1.03-6.99). For lung cancer overall, and especially among SCC patients, the GSTT1 null genotype was underrepresented (SCC 11.2% v. control subjects 19%, P = 0.026, OR 0.57, CI 0.30-1.06). Additionally, in 28 patients with hamartomas, the GSTT1 null genotype was also protective (P = 0.013), while GSTP1 variant allele carriers were overrepresented (OR 2.48, CI 1.06-6.51). In conclusion, GST genotypes may act differently, either by detoxifying harmful tobacco carcinogens and/or by eliminating lung cancer chemopreventive agents. The latter role for GSTT1 would explain the observed lower risk of SCC and hamartoma associated with GSTT1 null. Further confirmatory studies are required.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Genetic Predisposition to Disease , Glutathione Transferase/genetics , Hamartoma/genetics , Lung Diseases/genetics , Lung Neoplasms/genetics , Adenocarcinoma/enzymology , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/enzymology , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Squamous Cell/enzymology , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Case-Control Studies , Female , Gene Frequency , Genotype , Glutathione S-Transferase pi , Hamartoma/enzymology , Hamartoma/pathology , Humans , Isoenzymes/genetics , Lung Diseases/enzymology , Lung Diseases/pathology , Lung Neoplasms/enzymology , Lung Neoplasms/pathology , Male , Middle Aged , Polymerase Chain Reaction , Polymorphism, Genetic
16.
Immunology ; 104(3): 269-77, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11722641

ABSTRACT

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.


Subject(s)
CD3 Complex , Membrane Proteins/metabolism , Mycobacterium Infections/immunology , Receptors, Antigen, T-Cell/metabolism , Fluorescent Antibody Technique , Granuloma/immunology , Humans , Immunoenzyme Techniques , Interleukin-2/immunology , Leprosy, Lepromatous/immunology , Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/blood , Palatine Tonsil/immunology , Protein-Tyrosine Kinases/blood , Proto-Oncogene Proteins/blood , Proto-Oncogene Proteins c-fyn , Sarcoidosis, Pulmonary/immunology , Signal Transduction/immunology , Tuberculosis, Pulmonary/immunology , ZAP-70 Protein-Tyrosine Kinase
17.
Br J Cancer ; 85(8): 1193-200, 2001 Oct 19.
Article in English | MEDLINE | ID: mdl-11710834

ABSTRACT

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.


Subject(s)
Cathepsins/metabolism , Lung Neoplasms/enzymology , Lymph Nodes/enzymology , Antibody Specificity , Cytosol/enzymology , Enzyme-Linked Immunosorbent Assay , Humans , Immunohistochemistry , Lung Neoplasms/mortality , Prognosis
18.
J Appl Behav Anal ; 34(3): 289-312, 2001.
Article in English | MEDLINE | ID: mdl-11678525

ABSTRACT

Three experiments were conducted in an outpatient setting with young children who had been referred for treatment of noncompliant behavior and who had coexisting receptive language or receptive vocabulary difficulties. Experiment 1 studied differential responding of the participants to a brief hierarchical directive analysis (least-to-most complex stimulus prompts) to identify directives that functioned as discriminative stimuli for accurate responding. Experiment 1 identified distinct patterns of accurate responding relative to manipulation of directive stimulus characteristics. Experiment 2 demonstrated that directives identified as effective or ineffective in obtaining stimulus control of accurate responding during Experiment 1 continued to control accurate responding across play activities and academic tasks. Experiment 3 probed effects of the interaction between the type of directive (effective vs. ineffective) and the reinforcement contingency (differential reinforcement for attempts vs. differential reinforcement for accurate responses) on accurate task completion and disruptive behavior. Results suggested that behavioral escalation from inaccurate responding to disruptive behavior occurred only when ineffective directives were combined with differential reinforcement for accurate task completion. The overall results are discussed in terms of developing a methodology for identifying stimulus characteristics of directives that affect accurate responding.


Subject(s)
Cognition , Language Disorders/diagnosis , Child , Child Behavior Disorders/complications , Child Behavior Disorders/therapy , Child, Preschool , Dyslexia/complications , Dyslexia/diagnosis , Educational Measurement , Female , Humans , Language Disorders/complications , Male , Play and Playthings , Reinforcement, Psychology , Severity of Illness Index , Vocabulary
19.
Pathologe ; 22(5): 326-32, 2001 Sep.
Article in German | MEDLINE | ID: mdl-11572113

ABSTRACT

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.


Subject(s)
Carcinoma, Small Cell/pathology , Lung Neoplasms/pathology , Antigens, Neoplasm/analysis , Biopsy , Carcinoembryonic Antigen/analysis , Carcinoma, Small Cell/mortality , Female , Follow-Up Studies , Histocytochemistry , Humans , Immunohistochemistry , Keratin-19 , Keratins , Ki-67 Antigen/analysis , L-Lactate Dehydrogenase/analysis , Lung Neoplasms/mortality , Male , Middle Aged , Neoplasm Staging , Predictive Value of Tests , Prognosis , Retrospective Studies , Smoking , Survival Rate , Time Factors
20.
Anticancer Res ; 21(2B): 1439-44, 2001.
Article in English | MEDLINE | ID: mdl-11396228

ABSTRACT

Squamous cell carcinomas of the esophagus, a disease with poor prognosis, are especially frequent in China and South Africa. To initiate the study of endogenous lectins in this tumor class we employed synthetic neoglycoconjugates and focused on galectins as markers. Histological sections of 43 cases of esophageal carcinomas were analyzed with labeled galectins-1 and -3 and their specific antibodies, neoglycoconjugates exposing chemically prepared histo-blood group A-, B- and H-trisaccharides and the antibody MIB-1 (Ki-67). Features of structural and numerical staining intensities determined quantitatively were correlated to clinical data sets of pTN stages, sex and age of patients. Low tumor stages (pT1/T2) were seen in 10/43 cases (23%) and 65% of the carcinomas surgically treated lacked notable lymph node involvement (pN0). The women were younger than the men (47 years versus 54 years). The proliferation activity of the tumor cells was high and amounted to 75% at average. The presence of galectin-1 and the structural entropy of distribution of staining with carrier-immobilized A-trisaccharide were associated with pN stages. These initial data indicate that distinct glycohistochemical features appear to have prognostic significance in this tumor class, adding to the emerging significance of this marker class in lung cancer.


Subject(s)
Antigens, Differentiation/analysis , Carcinoma, Squamous Cell/chemistry , Esophageal Neoplasms/chemistry , Hemagglutinins/analysis , Nuclear Proteins/analysis , ABO Blood-Group System/metabolism , Antigens, Nuclear , Biomarkers, Tumor , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Epitopes, B-Lymphocyte/metabolism , Esophageal Neoplasms/pathology , Esophageal Neoplasms/surgery , Female , Galectin 1 , Galectin 3 , Humans , Ki-67 Antigen , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Staging
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