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Biomedical subjects

C Meyer

Publications and source records attributed to C Meyer.

At least 145 records · Page 8Linked to original sources
PubMed2000

mu1A-adaptin-deficient mice: lethality, loss of AP-1 binding and rerouting of mannose 6-phosphate receptors.

The heterotetrameric AP-1 complex is involved in the formation of clathrin-coated vesicles at the trans-Golgi network (TGN) and interacts with sorting signals in the cytoplasmic tails of cargo molecules. Targeted disruption of the mouse mu1A-adaptin gene causes embryonic lethality at day 13.5. In cells deficient in micro1A-adaptin the remaining AP-1 adaptins do not bind to the TGN. Polarized epithelial cells are the only cells of micro1A-adaptin-deficient embryos that show gamma-adaptin binding to membranes, indicating the formation of an epithelial specific AP-1B complex and demonstrating the absence of additional mu1A homologs. Mannose 6-phosphate receptors are cargo molecules that exit the TGN via AP-1-clathrin-coated vesicles. The steady-state distribution of the mannose 6-phosphate receptors MPR46 and MPR300 in mu1A-deficient cells is shifted to endosomes at the expense of the TGN. MPR46 fails to recycle back from the endosome to the TGN, indicating that AP-1 is required for retrograde endosome to TGN transport of the receptor.

Adaptor Protein Complex 1↗
PubMed2000

Subliminal activation of abandonment- and eating-related schemata: relationship with eating disordered attitudes in a nonclinical population.

OBJECTIVE: Previous research has demonstrated that subliminal abandonment cues can facilitate eating behavior. It is believed that such eating is a response to the activation of specific core schemata. However, the precise nature of those schemata has not been established. This study examined whether the presentation of subliminal abandonment and food/shape cues results in the activation of abandonment-related or food-related schemata. METHOD: Eighty-two women were exposed to one of three subliminal cues- an abandonment cue ("lonely"), an appetitive cue ("hungry"), and a neutral cue ("gallery"). They subsequently completed Stroop tasks to measure activation of relevant schemata. RESULTS: Subliminal presentation of abandonment cues led to the activation of food- and shape-related schemata. In contrast, subliminal appetitive cues resulted in an activation of abandonment-related schemata. CONCLUSIONS: The results show preliminary support for a multilevel cognitive model, involving indirect links between subliminal cue type and the activation of eating-related cognitions.

Adult↗
PubMed2000

Cognitive avoidance and bulimic psychopathology: the relevance of temporal factors in a nonclinical population.

OBJECTIVE: Previous research has provided evidence of both an attentional bias towards, and a cognitive avoidance of threat cues, by individuals with unhealthy eating attitudes and disorders. It has been suggested that an initial attentional bias might be followed by a later avoidance process. The present study assessed the speed of processing of self-directed ego threat words following different interstimulus intervals (500, 1,000, 1,500, and 2,000 ms). METHOD: Fifty female students completed a computer-driven threat processing task and the Eating Disorders Inventory. RESULTS: Women were significantly slower to process ego-self threat cues following the 2, 000-ms interval than following the other intervals (500, 1,000, and 1,500 ms). Those women with increased levels of bulimic attitudes were slower to process threats following the 1,500-ms interval, but not after the longer or shorter intervals. CONCLUSIONS: The results stress the importance of temporal factors in the processing of threat by individuals with high levels of eating psychopathology. The findings are discussed in terms of an appropriate cognitive model.

Adult↗
PubMed2000

Cognitive content among bulimic women: the role of core beliefs.

OBJECTIVE: Most cognitive analyses of bulimic disorders have stressed the role of negative automatic thoughts or dysfunctional assumptions regarding weight, shape, and food. This study considered the role of more general core beliefs in the cognitive content of bulimic disorders. METHODS: Fifty bulimic and 50 comparison women completed the Schema Questionnaire (YSQ) and a diary measure of bulimic behaviors. RESULTS: The groups could be differentiated using just three of the beliefs: perceived Defectiveness/Shame, Insufficient Self-Control, and Failure to Achieve. This discrimination included differences between bulimic subgroups. At the symptomatic level, the bulimic women's Emotional Inhibition beliefs predicted their severity of binging, whereas their Defectiveness/Shame beliefs predicted severity of vomiting. CONCLUSIONS: The findings support a model of bulimic psychopathology where the central cognitions encompass more than beliefs about food, shape, and weight. Clinical implications are considered.

Adult↗
PubMed2000

Multiple regulation of constitutive and induced interleukin 8 secretion in human myelomonocytic cell lines.

Secretion of interleukin 8 (IL-8) and its regulation was investigated in myelomonocytic leukaemia cell lines. Quantification by ELISA revealed a constitutive production in the cell lines HL-60, ML-2, MONO-MAC-6 and MUTZ-3 ranging between 1500 and ca. 5000 pg/ml IL-8 per million cells. No measurable IL-8 was detected in the culture medium of MONO-MAC-1 and THP-1. Stimulation with lipopolysaccharide (LPS) or tetradecanoyl phorbol acetate (TPA) significantly increased the IL-8 level secreted by all cell lines; the best producers were TPA-treated MONO-MAC-6 and MUTZ-3 cultures, generating more than 50 000 pg/ml IL-8. Also the calcium ionophore A-23187, IL-13, macrophage colony-stimulating factor (M-CSF), thapsigargin, an inhibitor of the Ca(2+)-ATPase, and tumour necrosis factor-alpha (TNF-alpha) strongly enhanced the IL-8 production in MONO-MAC-6 cells. The glucocorticoid dexamethasone and the protein kinase inhibitor staurosporine distinctively inhibited the IL-8 production of MONO-MAC-6 cells. Thus, our results demonstrate a strong constitutive IL-8 secretion in human myelomonocytic leukaemia cell lines; the variety of different modulators affecting IL-8 production leads to the suggestion of a multiple regulation of IL-8 expression and secretion.

Humans↗
PubMed2000

Induction and secretion of the chemokines interleukin-8 and monocyte chemotactic protein-1 in human immature leukemia cell lines.

We investigated expression and secretion of the chemokines interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) in human myeloid cell lines. Quantitative determination by ELISA revealed a significant constitutive production of both chemokines in the cell lines HL-60 and NB-4 (>1000 pg/ml IL-8 and >400 pg/ml MCP-1 per million cells), while in the cell lines EOL-1, KASUMI-1 and KG-1 only 10-100 pg/ml IL-8 and MCP-1 were detected. Tetradecanoyl phorbol acetate (TPA) strongly increased the IL-8 and MCP-1 amounts in the culture supernatants of all five cell lines. The TPA-induced NB-4 produced the largest amounts of both chemokines (>40,000 pg/ml). The strongest induction was seen in EOL-1 (>100-fold increase). Besides TPA, tumor necrosis factor-alpha (TNF alpha) also distinctively enhanced IL-8 and MCP-1 production. The calcium ionophore A-23187 and thapsigargin, an inhibitor of the Ca(2+)-ATPase, differentially induced IL-8 and MCP-1 secretion in the cell lines investigated, suggesting that, at least in some cell lines, intracellular free Ca(2+) might be important for chemokine secretion. Dexamethasone significantly prevented the IL-8 and MCP-1 production of stimulated cells, emphasizing the potent anti-inflammatory property of glucocorticoids. Similarly, the protein kinase inhibitor staurosporine clearly decreased the TPA-induced chemokine secretion in NB-4 cells, indicating the involvement of protein kinases in the signal transduction pathway which leads to enhanced chemokine secretion.

Calcimycin↗
PubMed2000

Differentiation of polymorphonuclear neutrophils in patients with systemic infections and chronic inflammatory diseases: evidence of prolonged life span and de novo synthesis of fibronectin.

Polymorphonuclear neutrophils (PMN) are considered to be short-lived, terminally differentiated cells undergoing spontaneous apoptosis if not appropriately stimulated. In patients with systemic infections and inflammatory disease, however, PMN have an extended life span and acquire new surface receptors and functions. Expression of CD64, the high-affinity receptor for immunoglobulin, has been found, and functionally active elastase and surface-associated fibronectin as well. The latter is of particular interest since fibronectin is known as a multifunctional, multimodal extracellular matrix protein, participating in cell adherence, cell signaling, and cell cycle control. To study the surface-associated fibronectin further, PMN of healthy donors were cultivated to induce de novo synthesis of fibronectin. PMN produced fibronectin, which remained associated with the cell surface, where it was partially cleaved. PMN derived fibronectin exhibited a rare splice pattern: predominantly fibronectin containing the extradomain B (EDB) was generated, but evidently no IIICS domain; the latter is known as a receptor for beta1 integrins. How the presence of EDB affects the properties of fibronectin is not yet understood. Studies with recombinant EDB have failed to show a membrane-binding site or a direct participation of EDB in the adhesion process. The function of PMN-associated fibronectin is still under investigation. The rapid cleavage by surface-associated proteases suggests that fibronectin acts as a tightly regulated adhesion protein, and probably also as a precursor molecule for fibronectin-derived biologically active mediators.

Alternative Splicing↗
PubMed2000

[Lifetime prevalence of mental disorders in general adult population. Results of TACOS study].

The present paper reports lifetime prevalence rates of mental disorders in the 18- to 64-year-old general population of a northern German region. A representative random sample from registration office files of 4,075 individuals was examined in personal interviews using the fully standardized and computerised "Munich Composite International Diagnostic Interview" (M-CIDI). The response rate was 70.2%. Individuals were classified according to the DSM-IV. Substance use disorders were most frequent with 25.8% followed by anxiety (15.1%), somatoform (12.9%), affective (12.3%), and eating disorders (0.7%). Disorders other than substance use were more frequent in women and less frequent in men. A trend toward less psychiatric morbidity exists in individuals with higher educational level, higher income, and those who are married or reside in rural communities. Of all individuals affected by mental disorders, 42% fulfilled the criteria for at least one additional disorder. The results are discussed against the background of selected previous studies.

Adult↗
PubMed2000

Prevalence of alcohol consumption, abuse and dependence in a country with high per capita consumption: findings from the German TACOS study. Transitions in Alcohol Consumption and Smoking.

BACKGROUND: The aim of the Transitions in Alcohol Consumption and Smoking (TACOS) project is to investigate substance use and use disorders in the adult general population in a region of the under-researched north of Germany, focussing on smoking and alcohol consumption. In this study, the design and quality assurance provisions of the baseline cross-section of the longitudinal project are described. Prevalence rates of alcohol use disorders, consumption pattern, and the nature of their association are also analysed with regard to preventive strategies. METHOD: A random sample of 4075 participants, aged 18 to 64 and drawn from residents registration office files, was interviewed with a DSM-IV adapted version of WHO CIDI. Fieldwork resulted in a response rate of 70.2% and an unbiased database with regard to demographic characteristics. RESULTS: Low lifetime prevalence of alcohol use disorders (4.5% abuse, 3.8% dependence) and hazardous consumption (13.2% lifetime; 6.0% 12-month) was found compared to southern regions of Germany and US American data. In contrast, we found a comparatively high percentage of moderate alcohol uses. Male subjects are more affected by lifetime alcohol use disorders (abuse OR 8.3, 95% CI 5.3-13.2; dependence OR 4.3, 95% CI 2.8-6.4). The association between alcohol use disorders and alcohol consumption pattern revealed a weaker relation for alcohol abuse compared to dependence. CONCLUSION: National and regional drinking habits and norms have to be considered as a significant source of variance, supporting the need for European epidemiological research on substance use in addition to US American activities, and emphasising the advantages of community-based preventive measures. An evaluation of public recommendations for safe limits of alcohol consumption and prevention targets referring to average consumption is indicated. There is also a need for a clear distinction between alcohol abuse and dependence.

Adult↗
PubMed2000

Prevalence, quality of life and psychosocial function in obsessive-compulsive disorder and subclinical obsessive-compulsive disorder in northern Germany.

BACKGROUND: Despite the worldwide relevance of obsessive-compulsive disorder (OCD) there are considerable differences in prevalence rates and gender ratios between the studies and a substantial lack of prevalence data on subclinical OCD. Moreover, data on quality of life and on psychosocial function of subjects with OCD and subclinical OCD in the general population are missing to date. METHODS: German versions of the DSM-IV adapted Composite International Diagnostic Interview were administered to a representative sample of 4075 persons aged 18-64 years living in a northern German region. Specific DSM-IV based criteria for subclinical OCD were used. RESULTS: The life-time prevalence rates for OCD and subclinical OCD were 0.5% and 2%, respectively. Twelve month prevalence rates were 0.39% and 1.6%, respectively. The gender female:male ratio was 5.7 in OCD and 1.2 in subclinical OCD. In various measures of psychosocial function and quality of life, OCD and subclinical OCD were significantly impaired. However, subclinical OCD subjects did not visit mental health professionals more often than controls. CONCLUSION: Due to different epidemiological characteristics subclinical OCD might represent a syndrome distinct from OCD which is also associated with significant impairments in personal and interpersonal functions and in quality of life.

Adolescent↗
PubMed2000

[Laparoscopic splenectomy for hematologic diseases. Study of 275 cases. French Society of Laparoscopic Surgery].

AIM OF THE STUDY: To evaluate the results of laparoscopic splenectomy for hematologic diseases by a multicenter retrospective study. PATIENTS AND METHODS: Between 1991 and 1998, 275 patients (mean age: 40.4 years [18-93]) underwent splenectomy for idiopathic thrombocytopenic purpura (ITP) (n = 209, 76%), for hemolytic anemia (HA) (n = 37) including hereditary spherocytosis (n = 13) and auto-immune anemia (n = 24), lymphoma (n = 12), tumor (n = 6) and uncommon hematologic syndromes (n = 11). Laparoscopic splenectomy was attempted in every patient. The lateral approach was most commonly used with an anterior approach to the splenic hilar vessels, which were cut after hemostasis using a stapling gun; other techniques were also employed. RESULTS: The mean operating time was 165 minutes (45-360); it was shorter in the case of conversion (144 minutes) and became shorter with the operator's experience. Conversion was necessary in 55 patients (20%), due to hemorrhage in 2/3 of cases, related to splenic vessels (20 cases), short gastric vessels (9 cases), or injury of the spleen (8 cases). In ten cases (2%), conversion was necessary for extraction of the spleen. Conversion rate varied from 5.3 to 46.7%, depending on the surgical team. Univariate analysis of factors predisposing to conversion identified four causes: obesity; technique used to achieve hemostasis of the splenic hilar vessels; operator's experience; and presence of splenomegaly. An accessory spleen was found in 44 patients (16%). The weight of the spleen was more than 350 g in 43 patients (15.6%). There were no deaths. There were no significant complications in 236 patients (85.8%) and the mean hospital stay was 6.4 days. In comparison with patients who had a conversion, bowel function returned significantly earlier, use of analgesia was reduced and hospital stay was shorter. The overall morbidity rate was 13.8% (n = 38); morbidity rate was only 10.4% (n = 22) for laparoscopic splenectomy. In these 22 patients, the complications were: subphrenic collections (n = 5, 2.2%), abdominal wall infections (n = 5), thromboembolic events (n = 2), anemia (n = 2), pneumonia (n = 1), peptic ulcer (n = 1), bowel obstruction (n = 1), splenic vein thrombosis (n = 1). Re-operations were required in 4 patients (1.8%) because of hemorrhage, pancreatitis and bowel obstruction. Morbidity rate was significantly increased in the case of conversion (27%), obesity (20%), malignant disease (30%) and splenomegaly (21.8%). Forty-four patients (16%) received perioperative or postoperative blood transfusion and 23 (8.3%) received platelet transfusion. Mean time to return to normal activity was 21 days and was shorter in the absence of conversion (18.5 days versus 35 days). In patients with ITP, the mean platelet count was 240,000 after 3 months, and the failure rate was 8.3%. CONCLUSION: Laparoscopic splenectomy is a real alternative to conventional splenectomy for some hematologic diseases, particularly ITP and HA. The advantages are an uneventful postoperative course, a lower morbidity rate, a shorter hospital stay and an earlier return to normal activity. The limits of this technique are related to the operator's experience, the size of the spleen, the nature of the underlying disorders and patient characteristics, mainly obesity.

Adolescent↗
PubMed2000

[Laparoscopic treatment of perforated duodenal ulcers. Results of a retrospective multicentric study. French Society of Laparoscopic Surgery].

STUDY AIM: The aim of this multicentric retrospective study was to report procedures, mortality and morbidity rate in a series of patients operated on for perforated duodenal ulcer with a laparoscopic approach. PATIENTS AND METHODS: Four-hundred and nineteen patients from 18 centers were included. The duration of the study was ten years (1990 to 1999). There were 299 men and 120 women aged from 19 to 98 years (mean: 48 years). The ASA scores were as follows: I (48.7%), II (31.3%), III (17.5%), IV (2.5%). The mean duration between the onset of perforation and the time of operation was 13.4 hours (range: 1-70). The surgical procedures were suture (76.7%), epiploplasty (9.9%), only irrigation of the abdominal cavity (2.7%). RESULTS: Conversion into laparotomy was performed in 10.6% of the patients. Mean operative time was 85 minutes. The morbidity and mortality rates were 13.4 and 1.4% respectively. Seventeen patients were reoperated because of fistula (n = 5), intra-abdominal abscess (n = 5), small bowel obstruction (n = 4), bleeding ulcer (n = 1), iatrogenic perforation of the gallbladder (n = 1) and small bowel (n = 1). Mean hospital stay was 8.5 days. All patients were discharged with a medical treatment of the peptic ulcer disease and in most of the cases, with antibiotics for Helicobacter pylori eradication. Six patients out of 96 with a medical history of chronic peptic ulcer underwent a vagotomy. CONCLUSION: Laparoscopic repair of perforated duodenal ulcer is a safe option providing low rates of morbidity, reoperation and mortality, and can be considered the treatment of choice.

Adult↗
PubMed2000

Urine free light chains in SLE: clonal markers of B-cell activity and potential link to in vivo secreted Ig.

As a marker of in vivo B-cell activity, urine levels of free light chain (FLC) were measured twice weekly by radioimmunoassay (RIA) and correlated with disease activity over periods of 5-10 months in seven patients with systemic lupus erythematosus (SLE). In addition, RIA-measured urine albumin was used to track glomerular injury, and alpha1-microglobulin (alpha1-M) levels, 28- to 32-kDa protein, provided control measurements on excretion of low-molecular-weight proteins. As controls, urine FLC levels were obtained from healthy normals and in subjects with acute pharyngitis, sickle-cell anemia, and acute sepsis or pneumonia. The control results showed that with acute sepsis/pneumonia had marked increases in urine FLC, while pharyngitis and sickle-cell controls had normal FLC levels. In SLE, active patients receiving intravenous cyclophosphamide and high-dose steroids exhibited highly increased urine FLC that fluctuated widely during therapy and fell to normal range levels with disease remission. During active SLE, urine albumin often was increased, while alpha1-M levels remained in normal range. In contrast to the increased FLC of active disease, inactive patients on low-dose maintenance therapy had predominantly normal FLC levels throughout the collection period. These results support our hypothesis that longitudinal levels of urine FLC can be used to track disease-related B-cell activity in SLE. Furthermore, we suggest that the urine FLC of active SLE would share LC idiotype with the clonal associated in vivo secreted Ig, and thus permit the identification of these antibodies that are targeted to the culprit immunogen(s) responsible for the pathogenesis of SLE.

Adult↗
PubMed2000

Studies on natural recovery from alcohol dependence: sample selection bias by media solicitation?

AIMS: To assess the selection bias of recruiting participants in studies on natural recovery from alcohol dependence through media solicitation. DESIGN: Two samples with different recruitment strategies are compared. SETTING: Media solicitation and general population. PARTICIPANTS: Sample 1 consists of 176 alcohol-dependent individuals remitted without formal help and recruited through media solicitation, sample 2 consists of 32 natural remitters derived from a representative general population study with a sample size of 4075 respondents and a response rate of 70.2%. MEASUREMENTS: Several triggering mechanisms and maintenance factors of remission were assessed in a personal interview using standardized questionnaires. FINDINGS: Results of logistic regression analyses show that media-solicited subjects were more often abstinent in the last 12 months, were more severely dependent, were less satisfied with eight life domains prior to remission and showed higher scores in a coping behaviour measure. Besides these major differences from the multivariate analysis, media subjects revealed more health problems prior to remission, experienced more social pressure to change drinking behaviour, and showed differences in reasons for not seeking help. CONCLUSIONS: Media solicitation leads to a sample selection bias in research on natural recovery from alcohol dependence. When measures to foster self-change are derived from such studies, findings from representative samples have to be considered.

Female↗
PubMed2000

Mandibular pseudocarcinomatous hyperplasia.

AIMS: Three unusual cases of pseudocarcinomatous (pseudoepitheliomatous) hyperplasia (PH) affecting chronic osteomyelitic mandibular sequestra are reported to highlight the differences with the various squamous neoplasms which occur in that site. METHODS AND RESULTS: In two patients carrying a mandibular graft following the excision of an ameloblastoma, mucosal ulcers resulted in chronic osteomyelitis. In a third patient, an apical dental infection was associated with fistulated osteomyelitis. Histology of the three sequestra showed an intraosseous squamous proliferation. It was characterized by a peripheral involvement of medullary spaces, the more mature epithelial layer covering the bone trabeculae without intervening stroma, and the basal type epithelial layer surrounding a central fibrovascular core. There were no histological or cytological signs of malignancy. CONCLUSION: PH shows an inverted pattern when compared with the centro-medullary tumoural islands seen in the various oral or odontogenic squamous neoplasms which occur in the jaws. The lack of signs of malignancy distinguish PH from common squamous cell carcinomas. A short clinical course is an important feature in the distinction of PH from the well differentiated squamous cell carcinomas which may develop in fistulated chronic osteomyelitis.

Adolescent↗
PubMed2000

Characterization of a nif-regulated flavoprotein (FprA) from Rhodobacter capsulatus. Redox properties and molecular interaction with a [2Fe-2S] ferredoxin.

A flavoprotein from Rhodobacter capsulatus was purified as a recombinant (His)6-tag fusion from an Escherichia coli clone over-expressing the fprA structural gene. The FprA protein is a homodimer containing one molecule of FMN per 48-kDa monomer. Reduction of the flavoprotein by dithionite showed biphasic kinetics, starting with a fast step of semiquinone (SQ) formation, and followed by a slow reduction of the SQ. This SQ was in the anionic form as shown by EPR and optical spectroscopies. Spectrophotometric titration gave a midpoint redox potential for the oxidized/SQ couple of Em1 = +20 mV (pH 8.0), whereas the SQ/hydroquinone couple could not be titrated due to the thermodynamic instability of SQ associated with its slow reduction process. The inability to detect the intermediate form, SQ, upon oxidative titration confirmed this instability and led to an estimate of Em2 - Em1 of > 80 mV. The reduction of SQ by dithionite was significantly accelerated when the [2Fe-2S] ferredoxin FdIV was used as redox mediator. The midpoint redox potential of this ferredoxin was determined to be -275 +/- 2 mV at pH 7.5, consistent with FdIV serving as electron donor to FprA in vivo. FdIV and FprA were found to cross-react when incubated together with the 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, giving a covalent complex with an Mr of approximately 60 000. Formation of this complex was unaffected by the redox states of the two proteins. Other [2Fe-2S] ferredoxins, including FdV and FdVI from R. capsulatus, were ineffective as electron carriers to FprA, and cross-reacted poorly with the flavoprotein. The possible function of FprA with regard to nitrogen fixation was investigated using an fprA-deleted mutant. Although nitrogenase activity was significantly reduced in the mutant compared with the wild-type strain, nitrogen fixation was apparently unaffected by the fprA deletion even under iron limitation or microaerobic conditions.

Amino Acid Sequence↗
PubMed2000

Microsatellite instability and allelic imbalance in primary and secondary colorectal cancer.

BACKGROUND: Several studies of colorectal cancer have shown an association between the number and type of genomic defects and the stage of disease. A subset of colorectal tumours are due to inactivation of DNA mismatch repair genes and these tumours exhibit microsatellite instability. The aim of the present study was to compare and contrast the genomic defects present in both the primary and metastatic stages of the disease using microsatellite probes. METHODS: Modifications of the allelic profiles of 25 microsatellite regions were studied in a total of 85 colorectal tumours using fluorescent polymerase chain reaction (PCR) technology and subsequent direct analysis on an automatic sequencer. This approach was used because it allows the study of microsatellite instability and allelic imbalance. Stepwise logistic regression analysis was used to develop a model to predict whether the tumour was primary or secondary from the percentage of allelic imbalance. Subsequently, a group of 17 patients with primary colorectal tumours was analysed prospectively to test the proposed model. RESULTS: Six of 39 primary tumours showed microsatellite instability compared to 0 of 29 liver metastases (P = 0.03). Primary tumours showed significantly less allelic imbalance than liver metastases (P < 0.001). Three probes (d18s53, d9s158 and d10s191) were selected for use in a model to classify a tumour as primary or secondary on the basis of the degree of allelic imbalance. When tested prospectively this model had a specificity of 82%. CONCLUSIONS: The present study demonstrates the potential importance of using microsatellite probes both as a diagnostic tool and as a research technique to investigate the mechanisms of tumour progression. An important clinical finding is that none of the colorectal liver metastases showed microsatellite instability (0 of 29). This analysis also confirmed other work that has shown a direct relationship between the degree of allelic imbalance and the stage of disease.

Alleles↗