Molecular pathology : MP最新文献

{"title":"Molecular Analysis of Cancer","authors":"J. Crocker","doi":"10.1136/MP.55.5.336","DOIUrl":"https://doi.org/10.1136/MP.55.5.336","url":null,"abstract":"As always with this sort of book, it is not certain who would purchase it and I would suspect that it would be more an institutional copy than a personal one. This is because the contents range from general chapters, such as those on spectral karyotyping and on comparative genomic hybridisation analysis …","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"55 1","pages":"336 - 336"},"PeriodicalIF":0.0,"publicationDate":"2002-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/MP.55.5.336","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64433061","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":"Alterations of the MDV oncogenic regions in an MDV transformed lymphoblastoid cell line","authors":"E. le Rouzic, P. Thoraval, M. Afanassieff, Y. Chérel, G. Dambrine, B. Perbal","doi":"10.1136/mp.55.4.262","DOIUrl":"https://doi.org/10.1136/mp.55.4.262","url":null,"abstract":"Aims: Lymphoblastoid cell lines derived from Marek’s disease virus (MDV) induced tumours have served as models of MDV latency and transformation. They are stable and can be cultured with no detectable MDV genomic alterations upon repeated passaging. An MDV transformed lymphoblastoid T cell line (T9 cell line) has been reported to contain a disrupted MDV BamHI-H fragment and a Rous associated virus insertional activation of the c-myb protooncogene. In an attempt to define the respective participation of c-myb and MDV in the transformed phenotype of T9 cells, an analysis of MDV oncogenic sequences (BamHI-H, BamHI-A, and EcoQ fragments) was performed in these cells. Methods: Using two different passages of the T9 cell line (late and early passages), the organisation of the MDV oncogenic regions and their expression in these cells were analysed. In vivo assessment of the oncogenicity of the virus contained within these cells was assessed by injecting them into 1 day old chickens. Results: In T9 cells maintained in culture for up to six months (late T9), the MDV ICP4 gene was disrupted, whereas the meq gene was actively transcribed. The alterations of the MDV genome in these cells correlated with the inability of the virus to induce the classic signs of Marek’s disease in 1 day old chickens. However, early T9 cells submitted to a limited number of passages induced classic MDV pathogenicity, as efficiently as the MDV control cell line (T5), and did not show gross structural changes in the oncogenic MDV sequences. Conclusions: Although the expression pattern of the MDV oncogenes in early T9 cells was identical to the one reported for other MDV transformed cells, longterm culture of an MDV transformed cell line containing a RAV insertional activation of the c-myb protooncogene led to the disruption of the MDV BamHI-H and BamHI-A oncogenic regions. In the late T9 cells MEQ was the only detected MDV oncoprotein. These results suggest that in the late T9 cells the truncated MYB protein compensates for the loss of MDV oncoproteins and reinforce the possibility that MEQ and MYB cooperate in the maintenance of the transformed state and the tumorigenic potential of these cells.","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"55 1","pages":"262 - 272"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.55.4.262","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64432474","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":"Chaperonins in disease: mechanisms, models, and treatments","authors":"J. C. Ranford, B. Henderson","doi":"10.1136/mp.55.4.209","DOIUrl":"https://doi.org/10.1136/mp.55.4.209","url":null,"abstract":"Chaperonins are oligomeric proteins that assist in the folding of nascent or denatured proteins. Bacterial chaperonins are strongly immunogenic and can cause tissue pathology. They have been implicated in infection, autoimmune disease, and idiopathic or multifactorial diseases, such as arthritis and atherosclerosis. Chaperonin 60 proteins are also involved in prion diseases. In the past few years, much progress has been made in unravelling the involvement of various bacterial and mammalian chaperonin 60 (Cpn 60 or hsp 60) proteins in such diseases, and in proposing mechanisms for their biological actions, although we are still some way from a full understanding of chaperonin action that might lead to immunotherapeutic approaches. This review focuses on the current knowledge of the roles of Cpn 60 in the pathology of infectious and immune diseases, and discusses models for the actions of this molecule. Some potential therapeutic strategies will also be reviewed.","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"55 1","pages":"209 - 213"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.55.4.209","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64431990","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":"Epidermal expression of serine protease, neuropsin (KLK8) in normal and pathological skin samples","authors":"K. Kuwae, K. Matsumoto-Miyai, S. Yoshida, T. Sadayama, K. Yoshikawa, K. Hosokawa, Sadao Shiosaka","doi":"10.1136/mp.55.4.235","DOIUrl":"https://doi.org/10.1136/mp.55.4.235","url":null,"abstract":"Aim: The expression of human neuropsin (KLK8) mRNA in normal and pathological skin samples was analysed and the results compared with those for tissue plasminogen activator (tPA) mRNA. Methods: Northern blot and in situ hybridisation analyses of KLK8 mRNA in normal and lesional skin of patients with cutaneous diseases were performed. Results: A weak signal for KLK8 mRNA and no signal for tPA mRNA was seen in normal skin on northern blot analysis. Weak signals for KLK8 were localised to the superficial cells beneath the cornified layer in normal skin on in situ hybridisation. Psoriasis vulgaris, seborrheic keratosis, lichen planus, and squamous cell carcinoma skin samples, which show severe hyperkeratosis, displayed a high density of KLK8 mRNA on northern and in situ hybridisation analyses. The signals were localised in granular and spinous layers of lesional skin in all hyperkeratic samples, including the area surrounding the horn pearls of squamous cell carcinoma. To examine the relation between mRNA expression and terminal differentiation, the expression of KLK8 mRNA was analysed in cell cultures. When keratinisation proceeded in high calcium medium, a correlative increase in the expression of KLK8 mRNA was observed. Conclusion: The results are consistent with a role for this protease in the terminal differentiation of keratinocytes.","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"55 1","pages":"235 - 241"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.55.4.235","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64432620","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":"Picornavirus uncoating","authors":"M. Smyth, J. Martin","doi":"10.1136/mp.55.4.214","DOIUrl":"https://doi.org/10.1136/mp.55.4.214","url":null,"abstract":"Recently, much has been learned about the molecular mechanisms involved in the pathogenesis of picornaviruses. This has been accelerated by the solving of the crystal structures of many members of this virus family. However, one stage of the virus life cycle remains poorly understood: uncoating. How do these simple but efficient pathogens protect their RNA genomes with a stable protein shell and yet manage to uncoat this genome at precisely the right time during infection? The purpose of this article is to review the current state of knowledge and the most recent theories that attempt to answer this question. The review is based extensively on structural data but also makes reference to the wealth of biochemical information on the topic.","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"55 1","pages":"214 - 219"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.55.4.214","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64432041","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":"Gut reaction","authors":"","doi":"10.1136/mp.55.4.226","DOIUrl":"https://doi.org/10.1136/mp.55.4.226","url":null,"abstract":"","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"55 1","pages":"226 - 226"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.55.4.226","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64432235","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":"Synthetic inhibitors of CDKs induce different responses in androgen sensitive and androgen insensitive prostatic cancer cell lines.","authors":"J Mad'arová, M Lukesová, A Hlobilková, M Strnad, B Vojtesek, R Lenobel, M Hajdúch, P G Murray, S Perera, Z Kolár","doi":"10.1136/mp.55.4.227","DOIUrl":"10.1136/mp.55.4.227","url":null,"abstract":"<p><strong>Aims: </strong>Because of the high prevalence of prostatic cancer and the limitations of its treatment, enormous effort has been put into the development of new therapeutic modalities. One potential tool is the use of cyclin dependent kinase (CDK) inhibitors, which are based on the trisubstituted derivatives of purine. The aim of this study was to analyse alterations of the regulatory pathways in both androgen sensitive and androgen insensitive prostatic cancer cell lines (LNCaP and DU-145, respectively) after blockage of the cell cycle by the synthetic CDK inhibitors, olomoucine and bohemine.</p><p><strong>Methods: </strong>The effects of olomoucine and bohemine were studied on the following parameters: (1) cell proliferation, by measurement of DNA content; (2) viability, by the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) and/or XTT (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide) test; and (3) the expression of p53, pRB, Bcl-2, Bax, p16, p21, p27, cyclins A, B, D1, E, p34(cdc2), and the androgen receptor (AR), by western blot analysis.</p><p><strong>Results: </strong>Both olomoucine and bohemine were potent inhibitors of growth and viability; however, bohemine was two to three times more effective than olomoucine. The sensitivity of LNCaP cells to both agents was significantly higher. After treatment, both cell lines revealed quite different spectra of protein expression.</p><p><strong>Conclusions: </strong>These results indicate the existence of specific cell cycle regulating pathways in both cell lines, which may be associated with both p53 and AR status. CDK inhibitors exhibited valuable secondary effects on the expression of numerous regulators and thus may modulate the responsiveness of tumour cells to treatment, including treatment with hormone antagonists.</p>","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"55 1","pages":"227-34"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1187184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64432423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A role for CCN3 (NOV) in calcium signalling","authors":"C. Li, V. Martinez, B. He, A. Lombet, Bernard Perbal","doi":"10.1136/mp.55.4.250","DOIUrl":"https://doi.org/10.1136/mp.55.4.250","url":null,"abstract":"Aims: In animals and humans increased expression of CCN3 (NOV) is detected in tissues where calcium is a key regulator, such as the adrenal gland, central nervous system, bone and cartilage, heart muscle, and kidney. Because the multimodular structure of the CCN proteins strongly suggests that these cell growth regulators are metalloproteins, this study investigated the possible role of CCN3 in ion flux and transport during development, control of cell proliferation, differentiation, and pathobiology. Methods: The isolation of CCN3 partners was performed by means of the two hybrid system. Yeasts were cotransfected with an HL60 cDNA library fused to the transactivation domain of the GAL4 transcription factor, and with a plasmid expressing CCN3 fused to the DNA binding domain of GAL4. Screening of the recombinant clones selected on the basis of leucine, histidine, and tryptophan prototrophy was performed with a β-galactosidase assay. After the interaction between CCN3 and its putative partners was checked with a GST (glutathione S-transferase) pull down assay, the positive clones were identified by cloning. To establish whether the CCN3 protein affected calcium ion flux, a dynamic imaging microscopy system was used, which allowed the fluorometric measurement of the intracellular calcium concentration. The proteins used in the assays were GST fused with either CCN3 or CCN2 (CTGF) and GST alone as a control. Results: The two hybrid system identified the S100A4 (mts1) calcium binding protein as a partner of CCN3 and the use of the GST fusion proteins showed that the addition of CCN3 and CCN2 to G59 glioblastoma and SK-N-SH neuroblastoma cells caused a pronounced but transient increase of intracellular calcium, originating from both the entry of extracellular calcium and the mobilisation of intracellular stores. Conclusions: The interaction of CCN3 with S100A4 may account, in part, for the association of CCN3 with carcinogenesis and its pattern of expression in normal conditions. The increased intracellular calcium concentrations induced by CCN3 and CCN2 both involve different processes, among which voltage independent calcium channels might be of considerable importance in regulating the calcium flux associated with cell growth control, motility, and spreading. These observations assign for the first time a biological function to the CCN3 protein and point out a broader role for the CCN proteins in calcium ion signalling.","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"55 1","pages":"250 - 261"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.55.4.250","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64432841","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":"Inactivation of phosphoglycerate mutase and creatine kinase isoenzymes in human serum","authors":"N. Durany, J. Carreras, M. Valenti, Jordi Càmara","doi":"10.1136/mp.55.4.242","DOIUrl":"https://doi.org/10.1136/mp.55.4.242","url":null,"abstract":"Aims/Background: Total phosphoglycerate mutase (PGM) activity in serum has been shown to be increased in acute myocardial infarction with the same time course as creatine kinase (CK) activity. However, the increase in the muscle (MM) and in the cardiac (MB) PGM isoenzymes was not as high as expected. The present study was undertaken to characterise PGM inactivation by serum and to compare it with serum CK inactivation. Methods: The PGM and the CK activities of extracts of human heart, skeletal muscle, and brain were determined spectrophotometrically after incubation with different media, namely: plasma, whole serum, dialysed serum, heated serum, serum ultrafiltrate, urate solution, and buffer solution. Results: Type MM PGM was inactivated by plasma, whole serum, heated serum, dialysed serum, and serum ultrafiltrate. Inactivation in dialysed serum was reduced by EDTA and largely reversed by thiol agents. Inactivation in serum ultrafiltrate was not prevented by EDTA and only partially reversed by dithiothreitol. The muscle and type BB CK isoenzymes were inactivated in all the tested media. The incubation of human and rabbit skeletal muscle PGM and CK in urate solution showed that urate does not affect mutase activity under conditions that inactivate CK. Conclusions: These results confirm the mechanisms of CK inactivation proposed by others and show that the type M PGM subunit is inactivated by two different mechanisms, which appear to involve the thiol groups of the enzyme. One mechanism is caused by either a protein component or a protein bound serum component and involves calcium ions and/or another chelatable metal ion. The other mechanism is caused by a lower molecular weight serum component and is metal ion independent.","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"55 1","pages":"242 - 249"},"PeriodicalIF":0.0,"publicationDate":"2002-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.55.4.242","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64432679","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":"Temporal and spatial expression of connective tissue growth factor (CCN2; CTGF) and transforming growth factor β type 1 (TGF-β1) at the utero–placental interface during early pregnancy in the pig","authors":"E. Moussad, M. Rageh, A. K. Wilson, R. Geisert, D. Brigstock","doi":"10.1136/mp.55.3.186","DOIUrl":"https://doi.org/10.1136/mp.55.3.186","url":null,"abstract":"Aims: To determine the localisation and distribution of connective tissue growth factor (CCN2; CTGF) and transforming growth factor β type 1 (TGF-β1) in uterine tissues from cycling and early pregnant pigs. Methods: In situ hybridisation and immunohistochemistry were used to localise CCN2 (CTGF) or TGF-β1 in uteri obtained from gilts on days 0, 5, 10, 12, 15, and 18 of the oestrous cycle or days 10, 12, 14, 16, 17, and 21 of gestation. Results: In cycling animals, CCN2 (CTGF) mRNA and protein were abundant in luminal epithelial cells (LECs) and glandular epithelial cells (GECs), with lesser amounts in stromal fibroblasts and little or none in endothelial cells. A similar pattern of staining was seen up to day 10 of pregnancy, except that overall staining intensities for CCN2 (CTGF) mRNA or protein were higher and that stromal and endothelial cells were CCN2 (CTGF) positive. However, on days 12–17 there was a striking decrease in the amount of CCN2 (CTGF) in LECs at the utero–conceptus interface, which was associated with maternal stromal matrix reorganisation and the onset of subepithelial neovascularisation. This differential distribution of CCN2 (CTGF) was localised to those LECs that were in close proximity to or in apposition with trophoblast cells. This decrease in CCN2 (CTGF) staining was transient in nature and high amounts of CCN2 (CTGF) were again apparent in LECs on days 17–21, when endometrial neovascularisation and matrix remodelling were complete. The expression of uterine TGF-β1 was comparable to that of CCN2 (CTGF) at most stages of the oestrous cycle or early pregnancy. Pre-elongation blastocysts recovered on day 10 were positive for both CCN2 (CTGF) and TGF-β1 in the extra-embryonic trophectoderm, endoderm, and inner cell mass. On day 12, trophectoderm expressed low amounts of TGF-β1 mRNA and non-detectable amounts of TGF-β1 protein or CCN2 (CTGF) mRNA or protein. By days 17–21, the expression of both growth factors in the extra-embyronic/placental membranes increased and frequently exceeded that seen in LECs. Conclusions: The pattern of CCN2 (CTGF) production during the initial attachment phase supports a role for this factor in stromal remodelling and neovascularisation, although alternative functions at later stages such as epithelial–epithelial interactions are also possible. In most major cell types in the uterus or utero–placental unit, CCN2 (CTGF) expression was highly correlated with that of TGF-β1, indicating that CCN2 (CTGF) may mediate some of the functions of TGF-β in the reproductive tract during the oestrous cycle and pregnancy. The data further highlight epithelium as an important source of CCN2 (CTGF) in the regulation of uterine function.","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"730 1","pages":"186 - 192"},"PeriodicalIF":0.0,"publicationDate":"2002-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.55.3.186","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64431867","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}