G. Caramori, Kazuhiro Ito, E. Jazrawi, P. Casolari, K. Chung, P. Barnes, I. Adcock, A. Papi
{"title":"Recent Thymic Emigrants Do Not Account for the Increased Number of TCells Seen in the Lungs of Stable Chronic Obstructive Pulmonary Disease","authors":"G. Caramori, Kazuhiro Ito, E. Jazrawi, P. Casolari, K. Chung, P. Barnes, I. Adcock, A. Papi","doi":"10.2174/1874375700802010102","DOIUrl":"https://doi.org/10.2174/1874375700802010102","url":null,"abstract":"Chronic obstructive pulmonary disease (COPD) patients have an increased number of T cells within their lungs. It is unknown whether these T cells, remain there forever or if there is a continuous turnover from the blood. In the adult, there is a significant T lymphocytopoiesis from the thymus producing cells known as recent thymic emigrants (RTEs). T cell receptor excision circles (TREC) are a marker of RTEs. We investigated the number of TREC in blood from patients with untreated stable, mild to moderate COPD (n=6) compared with age-matched smokers with normal lung function (n=6) and nonsmokers (n=8). The results showed variable expression of TREC in each subject group and no sig- nificant difference between TREC expressions in any group of subjects. Changes in T-cell numbers in the lung of stable COPD patients may reflect prolonged survival or proliferation of these cells within the lung rather than continuous re- cruitment from the blood.","PeriodicalId":89507,"journal":{"name":"The open pathology journal","volume":"33 1","pages":"102-105"},"PeriodicalIF":0.0,"publicationDate":"2008-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87443721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correlation Between mRNA Detected by Microarrays and qRT-PCR and Protein Detected by Immunohistochemistry of Cyclins in Tumour Tissue from Colonic Adenocarcinomas","authors":"K. Jonsdottir, R. Størkson, A. Krog, I. Bukholm","doi":"10.2174/1874375700802010096","DOIUrl":"https://doi.org/10.2174/1874375700802010096","url":null,"abstract":"There are several studies evaluating the prognostic value of overexpression of cyclin proteins, detected by im- munohistochemistry. Overexpression detected by microarray and real-time PCR techniques is now applied in analyzing the prognostic value of different genes on patient outcome. In this study we wanted to evaluate the correlation between these three methods for detection of cyclins (A2, B1, D1, D3, E and H) overexpression, as well as correlation between overexpression and gene amplification of the cyclin genes. We used both normal mucosa and tumour tissue obtained from 22 patients at the time of surgery. None of the cyclins were defined to be amplified at the gene level. qRT-PCR and cDNA microarray results are comparable, but no correlation between gene expression and protein expression, measured by im- munohistochemistry was observed. This may indicate that immunohistochemistry detects some other parameters than gene expression analysis measured by cDNA microarray and qRT-PCR. It is of interest to evaluate which of the three methods may give the most important information about patient prognosis.","PeriodicalId":89507,"journal":{"name":"The open pathology journal","volume":"8 1","pages":"96-101"},"PeriodicalIF":0.0,"publicationDate":"2008-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79601719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Miklossy, R. Martins, N. Darbinian, K. Khalili, P. Mcgeer
{"title":"Type 2 Diabetes: Local Inflammation and Direct Effect of Bacterial Toxic Components","authors":"J. Miklossy, R. Martins, N. Darbinian, K. Khalili, P. Mcgeer","doi":"10.2174/1874375700802010086","DOIUrl":"https://doi.org/10.2174/1874375700802010086","url":null,"abstract":"Objectives: It has been known for almost a century that amyloidosis is frequently associated with chronic bacte- rial infection. Islet amyloid deposit is characteristic of type 2 diabetes. Periodontal disease, which is predominantly caused by several Gram negative bacteria, is a risk factor for type 2 diabetes. The goal of the study was to explore whether bacte- ria or their toxic components may play a role in type 2 diabetes. Material & Methods: The pancreas in 22 autopsy cases was analyzed for the presence of lipopolysaccharide (LPS), bacte- rial peptidoglycan (BPG) and local inflammatory processes. Ten of the cases had clinically diagnosed type 2 diabetes, and 12 were age matched controls. Results: The results of an immunohistochemical analysis showed the presence of LPS and BPG in association with islet amyloid deposits in all the 10 diabetic cases as well as in 3 controls with clinically silent amyloid deposits. Chlamydia pneumoniae and Helicobacter pylori specific antigens were detected in the affected islets in a subset of diabetic patients. Clumps of HLA-DR positive activated macrophages, abundant immunoreactivity to the activated complement compo- nents C3d, C4d and C5b-9, the terminal attack complex, and a moderate numbers of T4 and particularly of T8 lympho- cytes were present in the pancreas of all diabetic cases. Conclusions: These results suggest that bacteria or their slowly degradable remnants may initiate and sustain chronic in- flammation in the pancreas and therefore play a role in the pathogenesis of type 2 diabetes. They also indicate that local immune responses, including activation of the classical complement pathway are important in the pathogenesis of type 2 diabetes. There may also be some involvement of the adaptive immune system. Further investigations are essential since a parallel use of antibacterial and anti-inflammatory drugs may prevent or slow down the disease progression.","PeriodicalId":89507,"journal":{"name":"The open pathology journal","volume":"18 1","pages":"86-95"},"PeriodicalIF":0.0,"publicationDate":"2008-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81299340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H. Nishino, April A. Ewton, A. Euton, Y. Zu, A.Ponce de León, K. Baker, G. Carrum, S. Chakraborty, L. Rice, C. Chang
{"title":"Quantitative Flow Cytometry Immunophenotypic Data in Myelodysplastic Syndromes (MDS)","authors":"H. Nishino, April A. Ewton, A. Euton, Y. Zu, A.Ponce de León, K. Baker, G. Carrum, S. Chakraborty, L. Rice, C. Chang","doi":"10.2174/1874375700802010078","DOIUrl":"https://doi.org/10.2174/1874375700802010078","url":null,"abstract":"Background: Recent studies using qualitative analysis of flow cytometry data have demonstrated various im- munophenotypic abnormalities associated with myelodysplastic syndromes (MDS). However, there are limited reports as- sessing the ability of quantitative immunophenotypic analysis to discriminate MDS from other cytopenic conditions. Design: Using flow cytometry, we studied 37 bone marrow specimens from 23 patients with MDS and 14 cytopenic pa- tients with non-clonal hematologic disorders. Samples were analyzed quantitatively for percentages of T-cells, B-cells, NK cells, granulocytes, monocytes, blasts, erythroid precursors, and plasma cells; CD4:CD8 ratio; % granulocyte subsets; % CD56+ monocytes; and % erythroid precursor subsets. Results: Quantitative analysis of immunophenotypic data in MDS patients compared to controls showed decreases in total granulocytes (p=0.037) and more mature subsets of CD11b + CD16 bright granulocytes (p=0.0046) and CD10 + granulocytes (p=0.022). MDS patients also showed a trending increase in subset percentage of CD56+monocytes (p=0.056). Using re- ceiver operating characteristic (ROC) analysis, cut-off values for these parameters favoring a diagnosis of MDS were identified as follows: total granulocytes 10%. Subsequently, a scoring system was proposed whereby a score of one was assigned for the presence of each quantitative abnormality. Using this system on the original study population, the pres- ence of at least two abnormalities (score 2) revealed optimal sensitivity (69.6%) and specificity (71.4%) for a diagnosis of MDS. Conclusion: These findings suggest that quantitative analysis of immunophenotypic data can be complementary to quali- tative interpretation. These data may be useful for distinguishing MDS from non-clonal cytopenic disorders and warrant prospective study in additional MDS patients.","PeriodicalId":89507,"journal":{"name":"The open pathology journal","volume":"14 1","pages":"78-85"},"PeriodicalIF":0.0,"publicationDate":"2008-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77102913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Aller, Luis Ortega, F. Sánchez-Patán, R. Anchuelo, Arturo Cruz, M. Losada, J. Arias
{"title":"Microsurgical Extrahepatic Cholestasis in the Rat: A Histopathological Liver Study","authors":"M. Aller, Luis Ortega, F. Sánchez-Patán, R. Anchuelo, Arturo Cruz, M. Losada, J. Arias","doi":"10.2174/1874375700802010071","DOIUrl":"https://doi.org/10.2174/1874375700802010071","url":null,"abstract":"Fibrosis, bile duct proliferation and mast cell hyperplasia characterize extrahepatic cholestasis. We studied these liver alterations in a new microsurgical model of extrahepatic cholestasis in the rat. Male Wistar rats: Sham-operated (n=9) and Microsurgical Cholestasis (n=10). After 4 weeks, a liver morphometric study was carried out using an image analysis system to assess bile proliferation and the fibrosis. The liver expression of alpha-smooth muscle actin was assayed by an immunohistochemical technique and mast cells were also counted. Cholestatic-rats presented portal hypertension, portosystemic circulation, and increased (p=0.0001) plasma bilirubin, alkaline phosphatase, Aspartateaminotransferase, Alanine-aminotransferase, and Lactate-dehydrogenase. Plasma levels of Albumin decreased (p=0.001). Cholestatic-rats showed intense biliary duct proliferation (p=0.0001) and fibrosis (p=0.0001). Mast cells accumulate (p=0.0001) around proliferating bile ducts and fibrous septa. The microsurgical cholestasis in the rat induces fibrosis and hyperplasia of bile ducts and mast cells. Mast cell liver infiltration could be an etiopathogenic remodeling factor in experimental cholestasis.","PeriodicalId":89507,"journal":{"name":"The open pathology journal","volume":"28 1","pages":"71-77"},"PeriodicalIF":0.0,"publicationDate":"2008-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73897921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Role of Systems Biology in Predictive Health and Personalized Medicine","authors":"E. Voit, K. Brigham","doi":"10.2174/1874375700802010068","DOIUrl":"https://doi.org/10.2174/1874375700802010068","url":null,"abstract":"Increasing health care costs mandate a shift in our thinking about health and disease from treatment to preven- tion. Effective prevention requires that we improve our abilities to predict and personalize health and disease risks. The article proposes that systems biology will play an essential role in personalized health assessments.","PeriodicalId":89507,"journal":{"name":"The open pathology journal","volume":"31 1","pages":"68-70"},"PeriodicalIF":0.0,"publicationDate":"2008-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76891274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P. Zauber, M. Sabbath‐Solitare, S. Marotta, W. Foulkes, T. Bishop
{"title":"The Gene Variant MLH1*D132H is Not Associated with an Increased Risk for Colorectal Adenomas in a Suburban United States Jewish Population","authors":"P. Zauber, M. Sabbath‐Solitare, S. Marotta, W. Foulkes, T. Bishop","doi":"10.2174/1874375700802010063","DOIUrl":"https://doi.org/10.2174/1874375700802010063","url":null,"abstract":"Background: MLH*D132H, a variant of the mismatch repair gene MLH1, was reported linked to an increased risk for colorectal carcinoma in Israeli patients. We evaluated U.S. Jewish patients with adenomas for this gene variant and compared the results to that of three other minor variants. Methods: DNA was screened for the MLH1*D132H variant using standard PCR followed by melting point analysis or by single-stranded conformation polymorphism. Results: Of the 632 patients screened there were three carriers among patients with adenomas and one carrier among those patients with no lesions for an incidence of 0.63% and a relative risk of 0.81 (C.I.=0.08-7.85, p=1.00). Conclusion: We did not detect a significant risk for colorectal adenoma in association with the MLH1*D132H variant. The personal, family history and germ line features of the carriers illustrate the complexity of minor genetic determinants.","PeriodicalId":89507,"journal":{"name":"The open pathology journal","volume":"96 1","pages":"63-67"},"PeriodicalIF":0.0,"publicationDate":"2008-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86522428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Senescence as a Target for Cancer Therapy","authors":"H. Kondoh, T. Maruyama, M. Lleonart","doi":"10.2174/1874375700802010057","DOIUrl":"https://doi.org/10.2174/1874375700802010057","url":null,"abstract":"Primary mammalian cells reach replicative exhaustion after several passages in vitro, a process called replica- tive senescence. During such a state of permanent growth arrest, senescent cells are refractory to physiological prolifera- tion stimuli with altered cell morphology and gene expression patterns, although they remain viable with preserved meta- bolic activity. Interestingly, senescent cells have also been detected in vivo in human tumors, particularly in benign le- sions. Tumor suppressor genes are closely involved in senescence, as their knockdown and ectopic expression confer im- mortality and senescence induction, respectively. By using high throughput genetic screenings to search for genes in- volved in senescence, several candidate oncogenes and putative tumour suppressor genes have been isolated recently, in- cluding subtypes of miRNAs. Senescence is thus an anti-tumorigenic mechanism for avoidance of indefinite cell prolif- eration when an oncogenic alteration has occurred. In this review, we remark how these findings offer new perspectives in the modulation of senescence and open new approaches for cancer therapy.","PeriodicalId":89507,"journal":{"name":"The open pathology journal","volume":"56 1","pages":"57-62"},"PeriodicalIF":0.0,"publicationDate":"2008-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86765866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Godel, P. Peyron, Marie-Pierre Puissegur, Puissegur Botanch, B. Payre, S. Khatibi, P. Massip, B. Marchou, F. Altare
{"title":"TST-Negative Individuals Do Not Lack Anti-Mycobacterial Responsiveness","authors":"A. Godel, P. Peyron, Marie-Pierre Puissegur, Puissegur Botanch, B. Payre, S. Khatibi, P. Massip, B. Marchou, F. Altare","doi":"10.2174/1874375700802010053","DOIUrl":"https://doi.org/10.2174/1874375700802010053","url":null,"abstract":"Tuberculin-skin-test (TST) is widely used for the diagnosis of Tuberculosis. Negative TSTs are occasionally found in individuals vaccinated or infected by Mycobacterium tuberculosis. We show that false negative results are due to a lack of the Tuberculin-specific immune response as replacing tuberculin by unselected M. tuberculosis antigens im- proved the efficiency of the assay.","PeriodicalId":89507,"journal":{"name":"The open pathology journal","volume":"69 1","pages":"53-56"},"PeriodicalIF":0.0,"publicationDate":"2008-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79025679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. Becker, H. Mack, C. Schott, S. Hipp, A. Rappl, G. Piontek, H. Höfler
{"title":"Extraction of Phosphorylated Proteins from Formalin-Fixed Cancer Cells and Tissues","authors":"K. Becker, H. Mack, C. Schott, S. Hipp, A. Rappl, G. Piontek, H. Höfler","doi":"10.2174/1874375700802010046","DOIUrl":"https://doi.org/10.2174/1874375700802010046","url":null,"abstract":"Deregulated signal pathways are promising targets for cancer therapy as they can drive tumour growth, sur- vival, invasion, and metastasis. In most hospitals around the world, histopathological cancer diagnosis is based upon for- malin-fixed and paraffin-embedded (FFPE) tissues. In this study, we evaluated whether phosphorylated signaling proteins can be extracted from cells and tissues after formalin fixation. Three epidermal growth factor (EGF) receptor-positive cell lines were stimulated with EGF for various time points and then either fixed with formalin or left unfixed before protein extraction. Using Western blot, we were able to detect all phosphorylated proteins analyzed, including activated (phos- phorylated) extracellular signal-regulated kinase (ERK) 1 and 2. There were no differences between formalin-fixed and unfixed cells. Because ERK1/2 kinases are involved in HER2-mediated signal transduction, we applied our methodology to study ERK1/2 and phospho-ERK1/2 in 20 primary breast cancers using protein lysate microarray technology. We found a statistically significant correlation between HER2 status and ERK1/2 expression; however, activation (phosphory- lation) of ERK1/2 was independent of HER2 expression. Our study demonstrates the successful extraction of phosphory- lated proteins from FFPE tissue samples. Monitoring phosphorylated signaling proteins in FFPE tissues, as applied here, may allow us in the near future to infer the activity levels of proteins in particular pathways as starting point for the design of individual combination therapy regimens without changing the routine clinical workflow for tissue analysis.","PeriodicalId":89507,"journal":{"name":"The open pathology journal","volume":"37 1","pages":"46-52"},"PeriodicalIF":0.0,"publicationDate":"2008-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81526959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}