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Biomedical subjects

G A Meijer

Publications and source records attributed to G A Meijer.

At least 19 recordsLinked to original sources
PubMed2001

[Possibilities for further research of chronic wasting in dairy cows].

In this study, we reviewed the research that has been conducted in relationship with the problem of 'chronic wasting' in dairy cows in the Netherlands as was experienced during 1998 and 1999. Emphasis was drawn towards three aspects of this 'chronic wasting'; the definition, the magnitude, and the possible cause or causes. It appeared that a clear, objective definition of 'chronic wasting' in cows, and of farms with a problem of 'chronic wasting' cows is still lacking. Furthermore, the incidence (of the problem) was restricted to approximately 150 dairy farms at most. Currently, no farms with 'chronic wasting' cows are known. Combined with the uncertainty in the definition, this will hamper future research. Many of the studies were related to the hypothesis that the vaccination with the BHV1 marker vaccine had caused 'chronic wasting' in the cows. None of the results, however, substantiated this hypothesis. Other possible causes have hardly been investigated and further research would be needed to evaluate the role of nutrition, infectious agents, and genetics. However, due to the waning of the phenomenon, the availability of data and controls will be limiting.

Animal Nutritional Physiological Phenomena↗
PubMed2001

Comparative genomic hybridization of microdissected familial ovarian carcinoma: two deleted regions on chromosome 15q not previously identified in sporadic ovarian carcinoma.

The vast majority of familial ovarian cancers harbor a germline mutation in either the breast cancer gene BRCA1 or BRCA2 tumor suppressor genes. However, mutations of these genes in sporadic ovarian cancer are rare. This suggests that in contrast to hereditary disease, BRCA1 and BRCA2 are not commonly involved in sporadic ovarian cancer and may indicate that there are two distinct pathways for the development of ovarian cancer. To characterize further differences between hereditary and sporadic cancers, the comparative genomic hybridization technique was employed to analyze changes in copy number of genetic material in a panel of 36 microdissected hereditary ovarian cancers. Gains at 8q23-qter (18 of 36, 5 cases with high-level amplifications), 3q26.3-qter (18 of 36, 2 cases with high-level amplifications), 11q22 (11 of 36) and 2q31-32 (8 of 36) were most frequent. Losses most frequently occurred (in decreasing order of frequency) on 8p21-pter (23 of 36), 16q22-pter (19 of 36), 22q13 (19 of 36), 9q31-33 (16 of 36), 12q24 (16 of 36), 15q11-15 (16 of 36), 17p12-13 (14 of 36), Xp21-22 (14 of 36), 20q13 (13 of 36), 15q24-25 (12 of 36), and 18q21 (12 of 36). Comparison with the literature revealed that the majority of these genetic alterations are also common in sporadic ovarian cancer. Deletions of 15q11-15, 15q24-25, 8p21-ter, 22q13, 12q24 and gains at 11q22, 13q22, and 17q23-25, however, appear to be specific to hereditary ovarian cancer. Aberrations at 15q11-15 and 15q24-25 have not yet been described in familial ovarian cancer. In these regions, important tumor suppressor genes, including the hRAD51 gene, are located. These and other yet unknown suppressor genes may be involved in a specific carcinogenic pathway for familial ovarian cancer and may explain the distinct clinical presentation and behavior of familial ovarian cancer.

BRCA2 Protein↗
PubMed2001

Distinct chromosomal aberrations in Epstein-Barr virus-carrying gastric carcinomas tested by comparative genomic hybridization.

BACKGROUND & AIMS: Approximately 10% of gastric adenocarcinomas carry the human pathogenic Epstein-Barr virus (EBV). The role of EBV in the pathogenesis of these carcinomas remains to be established. METHODS: To obtain a comprehensive overview of chromosomal aberrations in EBV-carrying and EBV-negative gastric carcinomas we performed comparative genomic hybridization (CGH) on 44 gastric carcinomas, 10 EBV-positive, and 34 EBV-negative. Additionally, DNA flow cytometry was done. RESULTS: Loss of chromosome 4p (P < 0.001) and of 11p (P < 0.02) was exclusively restricted to EBV-carrying gastric carcinomas. In addition, loss of 18q (P < 0.02) was significantly more frequent in EBV-carrying gastric carcinomas. The latter involves loci, which have already been linked to gastric carcinogenesis such as the DCC and SMAD4 gene. In contrast, the losses on chromosome 4 and 11 do not yet harbor a gene related to gastric carcinogenesis. No significant correlation was found between DNA-ploidy and the EBV-status. A number of chromosomal aberrations were found at comparable frequencies in both groups, i.e., losses of chromosome 17, 12q, and loss of 1p. Interestingly, gains of 13q (10/34) and 3q (5/34) and loss of 1q (5/34) were solely observed in EBV-negative gastric carcinomas. CONCLUSIONS: These data indicate that EBV-carrying and EBV-negative gastric carcinomas have different pathogenetic pathways in which EBV might play a crucial role.

Adenocarcinoma↗
PubMed2001

Quantitative assessment of gastric corpus atrophy in subjects using omeprazole: a randomized follow-up study.

OBJECTIVES: Atrophy of the gastric mucosa most frequently results from chronic Helicobacter pylori infection and is a risk factor for the development of gastric cancer. Profound acid suppression has been suggested to accelerate the onset of gastric mucosal atrophy. The aim of the present study was to evaluate the effects of H. pylori eradication and acid inhibition by omeprazole on gastric atrophy by means of quantitative analysis of tissue morphology. METHODS: Corpus biopsy specimens were obtained during endoscopy in 71 gastroesophageal reflux disease (GERD) patients at baseline and after 3 and 12 months. A total of 48 subjects were H. pylori positive and 23 were H. pylori negative. All subjects received omeprazole 40 mg once daily after the first endoscopy for 12 months. After randomization, 27 of the 48 H. pylori-positive patients also received eradication therapy. In hematoxylin and eosin-stained slides the volume percentages of glands (VPGL), volume percentages of stroma (VPS), and volume percentages of infiltrate (VPI) were measured in the glandular zone of the mucosa. The results were evaluated by computerized morphometric analysis. RESULTS: In the eradication group, the mean VPGL increased from 63.0% to 67.7% and 71.5% after 3 and 12 months (p < 0.001), respectively. The mean VPS and VPI decreased from 33.1% and 4.0% to 29.3% and 3.0% and to 26.4% and 2.1% (p < 0.001 and p = 0.04), respectively. Patients with the lowest VPGL at baseline showed the largest increases of VPGL after eradication treatment as compared to patients with high a VPGL at baseline. In the H. pylori-persistent group the VPI showed a significant increase (p = 0.01), and in the H. pylori-negative group VPGL increased significantly from 71.9% to 75.2% (p = 0.03) after 12 months. CONCLUSIONS: Eradication of H. pylori leads to restitution of the volume percentage of glandular epithelium to normal levels, even during treatment with proton pump inhibitors. Whether this effect can also be seen in patients with marked atrophy needs further investigation.

Adult↗
PubMed2001

Rapid quantitative assessment of gastric corpus atrophy in tissue sections.

BACKGROUND/AIMS: Grading of Helicobacter pylori induced atrophic gastritis using the updated Sydney system is severely limited by high interobserver variability. The aim of this study was to set up a quantitative test of gastric corpus mucosal atrophy in tissue sections and test its reproducibility and correlation with the Sydney scores of atrophy. METHOD: Mucosal atrophy was assessed in 124 haematoxylin and eosin stained corpus biopsy specimens by two experienced gastrointestinal pathologists (EB, JL) according to the updated Sydney system as none (n = 33), mild (n = 33), moderate (n = 33), or pronounced (n = 25). In each specimen, the proportions of glands, stroma, infiltrate, and intestinal metaplasia in the glandular zone were measured as volume percentages using a point counting method. The optimal point sample size, intra-observer and interobserver reproducibility, discriminative power for degrees of atrophy, and correlations with H pylori status were evaluated. RESULTS: Counting 400 points in 200 fields of vision provided the smallest sample size that still had excellent intra-observer and interobserver reproducibility (r > or = 0.96). Overall, the volume percentage of glands (VPGL), infiltrate (VPI), and stroma (VPS) correlated well with the Sydney scores for atrophy (p < or = 0.003). However, no differences were found between non-atrophic mucosa and mild atrophy. No correlation was found between age and either the Sydney grade of atrophy or the VPGL or VPS. In non-atrophic mucosa and mild atrophy, H pylori positive cases showed a significantly higher VPI than did H pylori negative cases. A lower VPGL was seen in H pylori positive cases than in H pylori negative cases in the mild atrophy group. VPS did not correlate with H pylori status within each grade of atrophy. CONCLUSION: Point counting is a powerful and reproducible tool for the quantitative analysis of mucosal corpus atrophy in tissue sections. These data favour the combination of "none" and "mild" atrophy into one category, resulting in a three class grading system for corpus atrophy, when using the updated Sydney system.

Adult↗
PubMed2001

Rapid stereology based quantitative immunohistochemistry of dendritic cells in lymph nodes: a methodological study.

This study was done to arrive at a fast and reliable protocol for assessment of fractional volumes of immunohistochemically stained dendritic cells in lymph nodes. Twenty axillary lymph nodes of patients with locally advanced breast cancer were immuno-histochemically stained with an S100 antibody. Fractional volumes of dendritic cells were assessed by stereology based quantitative immunohistochemistry using an interactive video overlay system including an automated microscope. The gold standard percentage of dendritic cells was the fractional volume of S100 stained cells in 500 fields systematically spread over the whole lymph node. Then, in a computer simulation, different sample sizes (1-200 fields of vision) were tested and the coefficient of variation (CV) for each sample size was calculated. The CV dropped with increasing sample size. A sample size of 100 fields of vision appeared to be optimal. Intra- and interobserver reproducibility appeared to be good (correlation coefficients of 0.95 and 0.86, respectively) when re-analyzing the cases with the established protocol. In conclusion, a fast and reliable assessment of the fractional volume of dendritic cells in lymph nodes is possible with semi-automated quantitative immuno-histochemistry. This method will form the base for further clinical studies into the immunological response in lymph nodes of patients with locally advanced breast cancer.

Breast Neoplasms↗
PubMed2000

Helicobacter pylori-related and -non-related gastric cancers do not differ with respect to chromosomal aberrations.

Gastric carcinogenesis is strongly associated with Helicobacter pylori infection, but the underlying genetic mechanisms are largely unknown. The aim of this study was to correlate chromosomal aberrations in gastric cancer to H. pylori status and its different strains, as well as to histological type and other clinico-pathological variables. DNA from 46 gastric cancers (male/female 35/11, age 27-85 years) was extracted from formaldehyde-fixed, paraffin-embedded material and tested for chromosomal gains and losses by comparative genomic hybridization (CGH). Chromosomal aberrations with frequencies of 20% or higher were considered to be non-random changes associated with gastric cancer. The mean number of chromosomal events per tumour was 9.7 (range 0-27), with a mean of 3.2 gains (range 0-16) and 6.5 losses (range 0-15). Gains were most frequently found at chromosomes 8q and 13q (24% and 26%, respectively). Losses were predominantly found on chromosome arms 2q, 9p, 12q, 14q, 15q, 16p, 16q, 17p, 17q, 19p, 19q, and 22q (22%, 30%, 43%, 22%, 33%, 50%, 28%, 50%, 39%, 33%, 39%, and 37%, respectively). Common regions of overlap narrowed down to 2q11-14, 8q23, 9p21, 12q24, 13q21-22, 14q24 and 15q11-15. The mean number of gains was higher in tumours with metastases than in localized tumours (4.1 vs. 1.9, p=0.04). Tumours with a loss at 17p showed a higher number of losses than tumours without a 17p loss (9. 5 vs. 4.7 on average, p<0.001). Neither H. pylori status (+, n=25; -, n=21) nor H. pylori strain was correlated to the total number of events or to any specific chromosomal aberration, nor were there differences between intestinal (n=30) and diffuse (n=15) cancers or any other clinico-pathological variable tested. In conclusion, a complex of chromosomal aberrations is involved in gastric cancer, but their pattern does not depend on H. pylori status or strain, nor on the histological type of the tumour. The exact biological meaning of these aberrations in carcinogenesis needs further clarification.

Adult↗
PubMed2000

Helicobacter pylori gastritis in Africa.

* Helicobacter pylori gastritis progresses to gland loss and intestinal metaplasia in a considerable proportion of colonized subjects. * The progression to atrophic gastritis is a slow process, occurring with an incidence of 1-2% per year. * The progression of chronic H. pylori gastritis is the same in Africa as in Europe and South America. * This supports the concept of H. pylori as a causative factor of pre-neoplastic conditions of the gastric mucosa; other factors must play a modulating role in the progression to cancer. H. pylori gastritis may progress to atrophic gastritis and lead to the development of intestinal metaplasia, dysplasia and eventually gastric cancer in a minority of subjects. The available data on the kinetics of H. pylori gastritis are limited, but nevertheless very consistent. They suggest that the progression to gland loss or atrophic gastritis among H. pylori-positive subjects occurs at a rate of 1-2% per year. As H. pylori gastritis usually persists for life, a considerable proportion of H. pylori-positive subjects thus eventually show signs of gastric gland loss. The majority of these subjects progress to intestinal metaplasia. Despite these consistent findings in different areas of the world, the incidence of gastric cancer is only moderately related to the prevalence of H. pylori. An example is the so-called African enigma, referring to a low incidence of gastric cancer in certain countries of Africa, despite a high prevalence of H. pylori in all age groups. This is not due to differences in progression to atrophic gastritis; other yet unidentified factors therefore must play a role.

Adult↗
PubMed2000

Microarray techniques in pathology: tool or toy?

Microarray technology allows the simultaneous analysis of up to thousands of different genes in histological or cytological specimens. Although microarray technology has so far mainly been applied in the research setting, its clinical application in pathology is expected in the foreseeable future. This paper presents an overview of the technical "ins and outs" of microarray technology, and discusses several putative applications in diagnostic pathology, which include tumour classification, the prediction of responses to certain chemotherapeutical or hormonal agents, the biological staging of tumours, the risk assessment of premalignant lesions, and the detection of microorganisms.

DNA Mutational Analysis↗
PubMed2000

Intratumor heterogeneity of k-ras and p53 mutations among human colorectal adenomas containing early cancer.

The molecular pathways and the timing of genetic events during human colorectal carcinogenesis are still not fully understood. We have addressed the intratumor heterogeneity of the mutational status of the k-ras oncogene and of the p53 oncosuppressor gene during the adenoma-carcinoma sequence by investigating 26 human colorectal adenomas containing early cancer. An intratumor comparative analysis was obtained among the adenomatous and carcinomatous component pairs. Additionally, we have analyzed 17 adenomas having cancer in the near vicinity. The adenomatous components of the adenomas containing early cancer and the adenomas having cancer in the near vicinity had comparable frequencies for k-ras mutations (28 and 47%) but different for p53 mutations (52 and 7%, p-value = 0.01). Interestingly, the adenomatous and carcinomatous components of the adenomas containing early cancer were rarely heterogeneous for the k-ras mutational status (only in 13% of the cases) but were characterized by heterogeneity of the p53 status in 59% of the cases (p-value < 0.01). In addition, the mutations of p53 for the adenomatous components of the adenomas containing early cancer were statistically significantly associated with severe dysplasia (p-value = 0.01). Intratumor homogeneity of k-ras status during the human colorectal adenoma-carcinoma sequence suggests that the role of k-ras is more related to tumor initiation than to tumor progression. On the contrary, intratumor heterogeneity of p53 mutations indicates that the type of the p53 mutations may also be relevant for selection and expansion of new subclones leading to tumor progression.

Adenoma↗
PubMed2000

Experience with a dynamic inexpensive video-conferencing system for frozen section telepathology.

AIM: To evaluate the feasibility of an inexpensive, generally applicable video-conferencing system for frozen section telepathology (TP). METHODS: A commercially widely available PC-based dynamic video-conferencing system (Picture-Tel LIVE, model PCS 100) has been evaluated, using two, four and six ISDN channels (128-384 kilobits per second (kbs)) bandwidths. 129 frozen sections have been analyzed which were classified by TP as benign, uncertain (the remark probably benign, or probably malignant was allowed), malignant, or not acceptable image quality. The TP results were compared with the original frozen section diagnosis and final paraffin diagnosis. RESULTS: Only 384 kbs (3 ISDN-2 lines) resulted in acceptable speed and quality of microscope images, and synchronous image/speech transfer. In one of the frozen section cases (0.7%), TP image quality was classified as not acceptable, leaving 128 frozen sections for the analysis. Five of these cases were uncertain by TP, and also deferred by frozen section procedure (FS). One more benign and three malignant FS cases were classified as uncertain by TP. Three additional cases were uncertain by FS, but benign according to TP (in agreement with the final diagnosis). In one case, FS diagnosis was uncertain but TP was malignant (in agreement with the final diagnosis). Thus, test efficiency (i.e., cases with complete agreement) was 120/128 (93.8%, Kappa = 0.88) between FS and TP. Sensitivity was 93.5%, specificity 98.6%, positive and negative predictive values were 97.7% and 96.0%. Between TP and final diagnosis agreement was even higher. More importantly, there was not a single discrepancy as to benign-malignant. Moreover, there was a clear learning effect: 5 of the 8 FS/TP discrepancies occurred in the first 42 cases (5/42 = 11.9%), the remaining 3 in the following 86 cases (3/86 = 3.5%). DISCUSSION: The results are encouraging. However, TP evaluation is time-consuming (5-15 min for one case instead of 2-4 min although speed went up with more experience) and is more tiring. The system has the following technical drawbacks: no possibility to point at objects or areas of interest in the life image at the other end, resolution (rarely) may become suboptimal (blocky), storage of images evaluated (which is essential for legal reasons) is not easy and no direct control of a remote motorized microscope. Yet, all users were positive about the system both for telepathology and personal contact by video-conferencing. CONCLUSION: With a relatively simple videoconferencing system, accurate dynamic telepathology frozen section diagnosis can be obtained without false positive or negative results, although a limited number of uncertain cases will have to be accepted.

Costs and Cost Analysis↗
PubMed1999

Analysis by comparative genomic hybridization of epithelial and spindle cell components in sarcomatoid carcinoma and carcinosarcoma: histogenetic aspects.

Sarcomatoid carcinomas and carcinosarcomas are histologically malignant biphasic neoplasms with an epithelial and a spindle cell component. Both a polyclonal and a monoclonal origin have been postulated for these tumours, but the latter has been favoured. For carcinosarcoma, the stem cell from which the epithelial and mesenchymal components are derived is expected to be more immature than the epithelial stem cell from which different components of sarcomatoid carcinoma originate, since in the latter, immunohistochemical or ultrastructural epithelial characteristics are still detectable. In the present study, comparative genomic hybridization was used to test the hypothesis that both tumour components in sarcomatoid carcinoma have more chromosomal aberrations in common than those in carcinosarcoma. From three sarcomatoid carcinomas originating from the urinary bladder and two carcinosarcomas from the pharynx, the epithelial and spindle cell components were microdissected and analysed for their respective chromosomal aberrations, using comparative genomic hybridization. High-level homology was seen in chromosomal aberrations between the different components in each tumour. This level of homology was even higher in the carcinosarcomas (65 and 91 per cent) than in both sarcomatoid carcinomas (21-51 per cent). The different phenotypic components of both sarcomatoid carcinoma and carcinosarcoma show a large overlap of chromosomal aberrations, strongly suggesting a monoclonal origin for all of these tumours. These findings do not support the hypothesis that the divergence between epithelial and spindle cell components occurs at an earlier stage in carcinosarcomas than in sarcomatoid carcinoma.

Carcinoma↗
PubMed1999

p21(Waf1/Cip1) expression and the p53/MDM2 feedback loop in gastric carcinogenesis.

Data are non-existent regarding coincidental alterations in the expression of p53 and its downstream target genes MDM2 and p21(Waf1/Cip1) in gastric carcinogenesis. An immunohistochemical study was therefore performed to examine the interrelationships of p53, MDM2, and p21(Waf1/Cip1) expression in a series of Caucasian early gastric carcinomas and precursor lesions. In normal gastric mucosa, chronic gastritis, and intestinal metaplasia, the surface cells expressed p21(Waf1/Cip1) in the absence of detectable nuclear p53 and MDM2 protein. Nuclear p53 protein accumulation was found in 60 per cent of the carcinomas, with significant differences in staining characteristics between the Lauren types in the absence of detectable MDM2 protein ( p< 0.005). Nearly 80 per cent of the carcinomas expressed p21(Waf1/Cip1), irrespective of Lauren type. Stratification of the carcinomas according to histological grade and growth pattern did not result in significant differences in p53 and p21(Waf1/Cip1) expression. Finally, no significant correlation was found between overall p53 and p21(Waf1/Cip1) expression in early gastric carcinomas. It is concluded that p21(Waf1/Cip1) expression in the non-neoplastic mucosa most likely relates to cell senescence and/or terminal differentiation, perhaps even in a p53-independent manner. In view of p53/MDM2 homeostasis, the differences in p53 staining characteristics between intestinal and diffuse-type carcinomas probably result, at least in part, from a difference in the prevalence of p53 gene mutations. Moreover, p53-independent induction of p21(Waf1/Cip1) expression apparently occurs in a considerable proportion of early carcinomas. Finally, in contrast to other carcinomas, p21(Waf1/Cip1) expression is not significantly correlated with histological grade in gastric carcinomas, suggesting possible defects downstream of p21(Waf1/Cip1) as an underlying cause for this apparent discrepancy.

Carcinoma↗
PubMed1999

Immunohistochemical differentiation between primary adenocarcinomas of the ovary and ovarian metastases of colonic and breast origin. Comparison between a statistical and an intuitive approach.

AIM: To discriminate between adenocarcinomas that are primary to the ovary and metastatic to the ovary, especially of colonic and breast origin, by immunohistochemistry, using stepwise discriminant analysis or a decision tree. METHODS: 312 routinely processed, formalin fixed tissue specimens were used. The tumours were divided into a learning set (n = 159), composed of primary tumours of ovary, breast, and colon, and a test set, comprising 134 metastases from these sites and an additional 19 primary ovarian carcinomas. The immunohistochemical panel was composed of antibodies against cytokeratin 7 (CK7) and 20 (CK20), CA125, vimentin, carcinoembryonic antigen (CEA), gross cystic disease fluid protein-15 (GCDFP-15), and the oestrogen receptor (ER). The staining results of the tumours were expressed as the product of the staining intensity and the percentage of positive tumour cells. Analyses were first performed on the learning set and then evaluated on the test set. RESULTS: Although the immunostaining patterns showed a considerable overlap between the three types of adenocarcinoma, the breast carcinomas were typically positive for GCDFP-15 and often for ER, and negative for vimentin. Ovarian carcinomas were always positive for CK7 and to a lesser extent for CA125. Colonic carcinomas showed prominent positivity for CEA and CK20, while no staining was seen for ER and vimentin. In discriminant analysis, six antibodies (alpha CK7, alpha CK20, alpha CA125, alpha CEA, alpha ER, and alpha GCDFP-15) appeared to be necessary for optimal classification: 89% of the learning set and 82% of the test set were classified correctly. In the decision tree, only four antibodies (alpha CK7, alpha CEA, alpha ER, and alpha GCDFP-15) were used to obtain a correct classification score of 89% for the learning set and 84% for the test set. CONCLUSIONS: Using a semiquantitative assessment of the immunostaining results by a restricted panel of six antibodies with stepwise discriminant analysis, 80-90% of the adenocarcinomas of colon, breast, and ovary can be correctly classified. Discriminant analysis is computer aided and therefore an easy method and for each case a probability value of the classification result is obtained. The intuitive decision tree method provides a slightly better result, requires only four antibodies, and offers a more practical method for the surgical pathologist.

Adenocarcinoma↗
PubMed1999

Increased expression of multidrug resistance related proteins Pgp, MRP1, and LRP/MVP occurs early in colorectal carcinogenesis.

AIM: To analyse the expression of multidrug resistance (MDR) related proteins at different steps in colorectal carcinogenesis. METHODS: The presence of three MDR related proteins (Pgp, MRP1, and LRP/MVP) was studied by means of immunohistochemistry in normal, adenomatous, and malignant colorectal epithelium. Formaldehyde fixed, paraffin embedded tissue sections of 17 samples of colorectal tissue were used (normal mucosa, n = 4; adjacent mucosa, n = 5; adenoma, n = 5; carcinoma, n = 3). RESULTS: For all three proteins, expression was found in the surface epithelium and the upper parts of the crypts in normal colon. In the adenomas, staining was seen along the complete length of the crypts. In the carcinomas analysed, all epithelium showed positive staining. Mucosa adjacent to either carcinoma or adenoma showed staining patterns mostly resembling those of normal mucosa, but sometimes some extension of staining was seen along the crypt. CONCLUSIONS: These proteins already show increased expression in the adenoma stage. In the absence of adequate mucin production in adenomas, MDR related proteins could be an important factor in protecting the epithelium against further environmentally induced genetic damage. This could be one of the reasons why only about 5% of colorectal adenomas will actually progress to carcinomas.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Comparative genomic hybridisation.

Comparative genomic hybridisation (CGH) is a technique that permits the detection of chromosomal copy number changes without the need for cell culturing. It provides a global overview of chromosomal gains and losses throughout the whole genome of a tumour. Tumour DNA is labelled with a green fluorochrome, which is subsequently mixed (1:1) with red labelled normal DNA and hybridised to normal human metaphase preparations. The green and red labelled DNA fragments compete for hybridisation to their locus of origin on the chromosomes. The green to red fluorescence ratio measured along the chromosomal axis represents loss or gain of genetic material in the tumour at that specific locus. In addition to a fluorescence microscope, the technique requires a computer with dedicated image analysis software to perform the analysis. This review aims to provide a detailed discussion of the CGH technique, and to provide a protocol with an emphasis on crucial steps.

Chromosome Aberrations↗
PubMed1999

Hepatic fatty acid composition in periparturient dairy cows with fatty liver induced by intake of a high energy diet in the dry period.

The present study compared the hepatic fatty acid composition of cows that were fed a high energy diet during the dry period to induce fatty liver after parturition with that of control cows. Treated cows had higher concentrations of plasma nonesterified fatty acids as a result of greater lipolysis after parturition than did control cows; consequently, the treated cows accumulated greater amounts of triacylglycerols in the liver. Before parturition, treated cows had lower percentages of oleic acid and higher percentages of linoleic acid than did control cows, but percentages of other fatty acids were similar for both groups. After parturition, percentages of each fatty acid were changed substantially, particularly the four major fatty acids (palmitic, stearic, oleic, and linoleic acids). For treated cows, the percentages of palmitic and oleic acids were higher at 0.5 wk after parturition than at 1 wk before parturition; percentages of stearic and linoleic acids decreased. Unlike treated cows, the percentages of both oleic and linoleic acids in the control cows did not change during that time. Moreover, we found that when lipolysis decreased, as indicated by lower plasma nonesterified fatty acid concentrations, the percentages of each fatty acid gradually rebounded toward the concentrations measured before parturition; this observation indicates that the shift in hepatic fatty acid composition is influenced by lipolysis. The increased lipolysis after parturition led to a vast increase in the hepatic triacyglycerol concentration and to a shift in hepatic fatty acid composition.

3-Hydroxybutyric Acid↗