Molecular pathology : MP最新文献_第4页

Molecular detection of the G(-248)A BAX promoter nucleotide change in B cell chronic lymphocytic leukaemia. B细胞慢性淋巴细胞白血病中G(-248)A BAX启动子核苷酸变化的分子检测

Molecular pathology : MP Pub Date : 2003-08-01 DOI: 10.1136/mp.56.4.205

O Moshynska, K Sankaran, A Saxena

{"title":"Molecular detection of the G(-248)A BAX promoter nucleotide change in B cell chronic lymphocytic leukaemia.","authors":"O Moshynska, K Sankaran, A Saxena","doi":"10.1136/mp.56.4.205","DOIUrl":"https://doi.org/10.1136/mp.56.4.205","url":null,"abstract":"Background: A novel single nucleotide polymorphism (SNP), G(-248)A, in the 5' untranslated region of the BAX promoter and its association with reduced protein expression, progression beyond Rai stage 0, and treatment resistance in chronic lymphocytic leukaemia (CLL) has been reported previously.Aim: To develop a restriction enzyme analysis (REA) based method for routine detection of BAX promoter SNP in a clinical laboratory.Methods: The BAX promoter was analysed in duplicate by REA and sequencing in 90 samples (from 45 patients with CLL, 43 controls, and two cell lines). The promoter region was amplified, digested with restriction endonucleases (Aci I and Tau I), and separated by gel electrophoresis.Results: After digestion, the normal GG genotype samples produced three distinct bands. The homozygous AA replacement abolished the cleavage site, resulting in a single band. Although the heterozygous samples produced three bands, the two smaller visible bands were reduced in intensity (> 50%). The test characteristics of Aci I REA were better than those of Tau I REA, in terms of sensitivity (100% v 77.8%), specificity (98.6% v 92.3%), positive predictive value (95.03% v 87.4%), and negative predictive value (100% v 85.83%).Conclusions: REA using Aci I is a highly sensitive and specific method for detecting the BAX G(-248)A SNP in CLL.","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"56 4","pages":"205-9"},"PeriodicalIF":0.0,"publicationDate":"2003-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.56.4.205","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22507886","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}

引用次数: 22

Potential viral pathogenic mechanism for new variant inflammatory bowel disease. 新型炎症性肠病的潜在病毒致病机制。

Molecular pathology : MP Pub Date : 2003-08-01 DOI: 10.1136/mp.56.4.248

J J O'Leary

引用次数: 5

Improved resolution by mounting of tissue sections for laser microdissection. 通过安装用于激光显微解剖的组织切片来提高分辨率。

Molecular pathology : MP Pub Date : 2003-08-01 DOI: 10.1136/mp.56.4.240

M C R F van Dijk, P D M Rombout, H B P M Dijkman, D J Ruiter, M R Bernsen

{"title":"Improved resolution by mounting of tissue sections for laser microdissection.","authors":"M C R F van Dijk, P D M Rombout, H B P M Dijkman, D J Ruiter, M R Bernsen","doi":"10.1136/mp.56.4.240","DOIUrl":"https://doi.org/10.1136/mp.56.4.240","url":null,"abstract":"Background: Laser microbeam microdissection has greatly facilitated the procurement of specific cell populations from tissue sections. However, the fact that a coverslip is not used means that the morphology of the tissue sections is often poor.Aims: To develop a mounting method that greatly improves the morphological quality of tissue sections for laser microbeam microdissection purposes so that the identification of target cells can be facilitated.Methods: Fresh frozen tissue and formalin fixed, paraffin wax embedded tissue specimens were used to test the morphological quality of mounted and unmounted tissue. The mounting solution consisted of an adhesive gum and blue ink diluted in water. Interference of the mounting solution with DNA quality was analysed by the polymerase chain reaction using 10-2000 cells isolated by microdissection from mounted and unmounted tissue.Results: The mounting solution greatly improved the morphology of tissue sections for laser microdissection purposes and had no detrimental effects on the isolation and efficiency of amplification of DNA. One disadvantage was that the mounting solution reduced the cutting efficiency of the ultraviolet laser. To minimise this effect, the mounting solution should be diluted as much as possible. Furthermore, the addition of blue ink to the mounting medium restores the cutting efficiency of the laser.Conclusions: The mounting solution is easy to prepare and apply and can be combined with various staining methods without compromising the quality of the DNA extracted.","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"56 4","pages":"240-3"},"PeriodicalIF":0.0,"publicationDate":"2003-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.56.4.240","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22508369","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}

引用次数: 18

Does leptin resistance contribute to infections in patients with diabetes? 瘦素抵抗会导致糖尿病患者感染吗？

Molecular pathology : MP Pub Date : 2003-08-01 DOI: 10.1136/mp.56.4.248-a

G N Malavige

引用次数: 0

Differential expression of E-cadherin and beta catenin in primary and metastatic Wilms's tumours. E-cadherin和β - catenin在原发性和转移性肾母细胞瘤中的差异表达。

Molecular pathology : MP Pub Date : 2003-08-01 DOI: 10.1136/mp.56.4.218

J Alami, B R Williams, H Yeger

{"title":"Differential expression of E-cadherin and beta catenin in primary and metastatic Wilms's tumours.","authors":"J Alami, B R Williams, H Yeger","doi":"10.1136/mp.56.4.218","DOIUrl":"https://doi.org/10.1136/mp.56.4.218","url":null,"abstract":"Background: The E-cadherin-catenin adhesion complex is crucial for intercellular adhesiveness and maintenance of tissue architecture. Its impairment is associated with poorly differentiated phenotype and increased invasiveness of carcinomas.Aims: To evaluate E-cadherin, beta catenin, gamma catenin, and ezrin expression and its relation to histopathological features of primary and metastatic Wilms's tumours.Methods: Immunohistochemistry was used to determine the expression and cellular distribution of E-cadherin, beta catenin, gamma catenin, and ezrin in primary and metastatic Wilms's tumours. Western blotting was used to determine polypeptide size and expression of E-cadherin and beta catenin in Wilms's tumours compared with normal kidney.Results: Moderate expression of E-cadherin was found mainly in cytoplasm and occasionally cell membranes of dysplastic tubules, whereas low expression was seen in cytoplasm of blastemal cells. Primary and metastatic tumours showed moderate to high beta catenin expression in blastemal and epithelial cells, with predominantly membranous and cytoplasmic staining. Occasional nuclear staining was noted in metastatic tumours. Low to high gamma catenin and ezrin expression was seen in cytoplasm of blastemal and epithelial cells of primary and metastatic tumours. Higher amounts of 92 kDa beta catenin were detected in tumours than in normal kidney. Low expression of 120 kDa E-cadherin was seen in moderately differentiated tumours, whereas expression was lacking in poorly differentiated tumours.Conclusions: Compared with primary tumours, metastatic tumours showed lower expression of E-cadherin and gamma catenin, with nuclear staining for beta catenin. Low E-cadherin was associated with poorly differentiated tumours. These results suggest that abnormal expression of adhesion proteins correlates with the invasive and metastatic phenotype in Wilms's tumours.","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"56 4","pages":"218-25"},"PeriodicalIF":0.0,"publicationDate":"2003-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.56.4.218","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22507888","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}

引用次数: 24

Efficiency and cost effectiveness: PAGE-SSCP versus MDE and Phast gels for the identification of unknown beta thalassaemia mutations. 效率和成本效益:PAGE-SSCP与MDE和Phast凝胶鉴别未知地中海贫血突变

Molecular pathology : MP Pub Date : 2003-08-01 DOI: 10.1136/mp.56.4.237

A Gupta, S Agarwal

{"title":"Efficiency and cost effectiveness: PAGE-SSCP versus MDE and Phast gels for the identification of unknown beta thalassaemia mutations.","authors":"A Gupta, S Agarwal","doi":"10.1136/mp.56.4.237","DOIUrl":"https://doi.org/10.1136/mp.56.4.237","url":null,"abstract":"Background: Prenatal diagnosis for β thalassaemia has proved to be very effective in preventing the birth of an affected child and hence in controlling the disease. The success of prenatal diagnosis depends on the delineation of the underlying mutations in the population at risk. Each population carries a limited number of frequent defects (89–91%) and a variable number of rare alleles (4–5%), whereas 2–3% of alleles remain uncharacterised. To offer prenatal diagnosis when the parental mutation is unknown, the application of a non-specific detection method (such as single stranded conformational polymorphism (SSCP)) to localise the mutation, followed by direct sequencing of the amplified gene sequence, is required. With this objective in mind, this study was designed to devise the best protocol and system of SSCP for the rapid screening of unknown mutations in the β globin gene. Methods: To detect mutations in this disease, three different systems—Phast gels, MDE gels, and polyacrylamide gels—were used under varying conditions. Results: Polyacrylamide gels were found to be the most efficient, both in terms of resolution and cost. Conclusion: Polyacrylamide gels are the most rapid, efficient, reliable, and cost effective means for DNA mutation analysis of the β globin gene.","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"56 4","pages":"237-9"},"PeriodicalIF":0.0,"publicationDate":"2003-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1136/mp.56.4.237","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22508368","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}

引用次数: 14

Concentrations of circulating matrix metalloproteinase 9 inversely correlate with autoimmune antibodies to double stranded DNA: implications for monitoring disease activity in systemic lupus erythematosus. 循环基质金属蛋白酶9的浓度与双链DNA自身免疫抗体成反比：对监测系统性红斑狼疮疾病活动的意义。

Molecular pathology : MP Pub Date : 2003-08-01 DOI: 10.1136/mp.56.4.244

G S Makowski, M L Ramsby

{"title":"Concentrations of circulating matrix metalloproteinase 9 inversely correlate with autoimmune antibodies to double stranded DNA: implications for monitoring disease activity in systemic lupus erythematosus.","authors":"G S Makowski, M L Ramsby","doi":"10.1136/mp.56.4.244","DOIUrl":"10.1136/mp.56.4.244","url":null,"abstract":"Aims: To compare circulating matrix metalloproteinase (MMP) concentrations with antibodies to single and double stranded DNA (ssDNA and dsDNA) to determine their relation in inflammatory arthritic diseases, such as systemic lupus erythematosus (SLE).Methods: Fibroblast MMP-2 and neutrophil MMP-9 were resolved by gelatin zymography and measured by densitometry. Anti-ssDNA and anti-dsDNA were determined by enzyme immunoassay and samples grouped on antibody content as follows: low anti-ssDNA/low anti-dsDNA antibodies (group 1); high anti-ssDNA/low anti-dsDNA antibodies (group 2); and high anti-ssDNA/high anti-dsDNA antibodies (group 3).Results: Group 3 samples contained significantly lower amounts of MMP-9 when compared with group 1 samples. Higher molecular weight MMP-9 forms (130 and 225 kDa) were virtually absent. Group 2 samples contained intermediate MMP-9 concentrations. Fibroblast MMP-2 was unchanged in all groups. Mean complement C3 and C4 concentrations showed a consistent, but variably significant, decrease with increasing anti-ssDNA and anti-dsDNA antibodies. The mean erythrocyte sedimentation rate was raised in all patient groups.Conclusions: Neutrophil MMP-9, an inflammatory marker, inversely correlates with anti-dsDNA antibodies, which are a specific marker for SLE, and may be important in monitoring disease activity during antibody deposition in tissues.","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"56 4","pages":"244-7"},"PeriodicalIF":0.0,"publicationDate":"2003-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1187330/pdf/mp56000244.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22508370","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}

引用次数: 0

Sonic hedgehog. 声波刺猬。

Molecular pathology : MP Pub Date : 2003-06-01 DOI: 10.1136/mp.56.3.129

H S Heussler, M Suri

{"title":"Sonic hedgehog.","authors":"H S Heussler, M Suri","doi":"10.1136/mp.56.3.129","DOIUrl":"https://doi.org/10.1136/mp.56.3.129","url":null,"abstract":"segment polarity genes that regulate segmental and imaginal disc patterning in the fruit fly, Drosophila melanogaster. Unlike drosophila and other invertebrates, which only have a single hh gene, vertebrates have a family of genes that are homologous to the hh gene. Mammals have three genes with homology to the hh gene. These comprise Sonic hedgehog (Shh), Indian hedgehog (Ihh), and Desert hedgehog (Dhh). All hedgehog genes encode signalling molecules that are involved in short and long range patterning processes during embryogenesis. Like all hedgehog proteins Shh protein also undergoes molecular processing in the endoplasmic reticulum. This involves cleavage of its signal peptide, followed by autocatalytic cleavage of the hedgehog protein precursor into a 19 kDa N-terminal domain (Shh-N) and a 25 kDa C-terminal domain (Shh-C). The signalling activity of hedgehog proteins resides in Shh-N. Shh-C has intramolecular cholesterol transferase activity and is responsible for covalently attaching a cholesterol molecule to the C-terminal end of Shh-N. The addition of cholesterol plays an important role in spatially restricting the zone of activity of Shh-N by anchoring it to the cell membrane and restricting its diffusion from the site of secretion. It is believed that inborn errors of cholesterol synthesis such as Smith–Lemli–Opitz syndrome (microcephaly, growth and mental retardation, facial dysmorphism, syndactyly of the second and third toes, congenital heart disease, hypotonia, and genital abnormalities in males) can interfere with SHH signalling by interfering with its molecular processing, in particular with the cholesterol modification of Shh-N.","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"56 3","pages":"129-31"},"PeriodicalIF":0.0,"publicationDate":"2003-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1187306/pdf/mp56000129.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22415156","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}

引用次数: 4

A prospective study of circulating mutant KRAS2 in the serum of patients with colorectal neoplasia: strong prognostic indicator in postoperative follow up 结肠直肠癌患者血清循环突变体KRAS2的前瞻性研究:术后随访中强有力的预后指标

Molecular pathology : MP Pub Date : 2003-06-01 DOI: 10.1136/mp.56.3.172

Barbara M. Ryan, F. Lefort, Ross McManus, J. Daly, Paul W.N. Keeling, Donald G. Weir, Dermot Kelleher

{"title":"A prospective study of circulating mutant KRAS2 in the serum of patients with colorectal neoplasia: strong prognostic indicator in postoperative follow up","authors":"Barbara M. Ryan, F. Lefort, Ross McManus, J. Daly, Paul W.N. Keeling, Donald G. Weir, Dermot Kelleher","doi":"10.1136/mp.56.3.172","DOIUrl":"https://doi.org/10.1136/mp.56.3.172","url":null,"abstract":"Background and aims: Mutant tumour derived DNA has been detected in the sera of colorectal cancer patients. We investigated if mutant serum KRAS2 was detectable preoperatively in a large group of patients with colorectal neoplasia. A prospective study of 94 patients who underwent putative curative resection for colorectal carcinoma (CRC) was performed to ascertain if serum mutant KRAS2 could be used postoperatively as a disease marker. Methods: Preoperative sera from 78 patients were analysed (group A). Sera from 94 patients were obtained three monthly for up to three years during the postoperative period (group B). Codon 12 and 13 KRAS2 mutations were analysed in matched tumour and serum samples. Results: In the preoperative group (group A), KRAS2 mutation was found in 41/78 (53%) tumours and in 32/78 (41%) preoperative sera. Of 41 tumour KRAS2 mutation positive cases, 31/41 (76%) had an identical serum mutation detectable. In group B, the postoperative follow up group, 60/94 cases were primary tumour KRAS2 mutation positive. Of these 60, 16/60 (27%) became persistently serum mutant KRAS2 positive postoperatively. Ten of 16 (63%) of these developed a recurrence compared with only 1/44 (2%) patients who remained serum mutant negative (odds ratio 71.7 (95% confidence interval 7.7–663.9; p=0.0000). None of 34 tumour mutation negative cases became serum mutant KRAS2 positive postoperatively, despite recurrence in 9/34 patients. The relative hazard of disease recurrence in postoperative serum mutant KRAS2 positive patients was 6.37 (2.26–18.0; p=0.000). Conclusions: Serum mutant KRAS2 can be detected preoperatively in all stages of colorectal neoplasia. Postoperatively, serum mutant KRAS2 is a strong predictor of disease recurrence, stronger even than Dukes’ stage of disease, and thus shows potential for use in clinical practice as a marker of preclinical disease recurrence.","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"56 1","pages":"172 - 179"},"PeriodicalIF":0.0,"publicationDate":"2003-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64433608","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}

引用次数: 73

Regions of allelic imbalance in the distal portion of chromosome 12q in gastric cancer. 胃癌中 12q 染色体远端等位基因失衡的区域。

Molecular pathology : MP Pub Date : 2003-06-01 DOI: 10.1136/mp.56.3.141

B G Schneider, S Y Rha, H C Chung, J C Bravo, R Mera, J C Torres, K T Plaisance, R Schlegel, C M McBride, X T Reveles, R J Leach

{"title":"Regions of allelic imbalance in the distal portion of chromosome 12q in gastric cancer.","authors":"B G Schneider, S Y Rha, H C Chung, J C Bravo, R Mera, J C Torres, K T Plaisance, R Schlegel, C M McBride, X T Reveles, R J Leach","doi":"10.1136/mp.56.3.141","DOIUrl":"10.1136/mp.56.3.141","url":null,"abstract":"Aims: To define regions of loss on the distal portion of chromosome 12q in gastric adenocarcinoma.Methods: Microsatellite analysis on chromosome 12 was performed on 19 human gastric cancer cell lines using 77 markers, 71 of which were within or distal to 12q21; some portions of this region showed extended regions of homozygosity (ERHs) in 10 of 19 gastric cancer cell lines. In addition, microdissected tumour cells from 76 primary gastric adenocarcinomas were examined using 13 markers of interest implicated by the cell line data; 70% of these showed allelic imbalance (AI) at one or more markers in or distal to 12q21.Results: Mapping ERHs in the cell lines and sites of AI in the tumours identified three regions that contain putative tumour suppressor genes: region A is located within 2.8 Mb between markers D12S1667 and D12S88; region B, within 1.9 Mb between markers D12S1607 and D12S78; and region C, in 0.74 Mb between markers D12S342 and D12S324. Fluorescence in situ hybridisation (FISH) analysis in two cell lines confirmed that two of the ERHs reflected deletions, not amplifications, of D12S81 in region A and D12S340 in region C. FISH analysis of marker D12S1075 within an ERH containing region B in one cell line showed neither amplification nor deletion. AI on 12q was not associated with prognosis, but was associated with ethnicity of the patient.Conclusions: These results identify regions on chromosome 12 that appear to contain tumour suppressor genes important in the development of gastric cancer.","PeriodicalId":79512,"journal":{"name":"Molecular pathology : MP","volume":"56 3","pages":"141-9"},"PeriodicalIF":0.0,"publicationDate":"2003-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1187309/pdf/mp56000141.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22416173","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}

引用次数: 0