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K Rask

Publications and source records attributed to K Rask.

8 recordsLinked to original sources
PubMed2003

Wnt-signalling pathway in ovarian epithelial tumours: increased expression of beta-catenin and GSK3beta.

Beta-catenin is involved in both cell-cell adhesion and in transcriptional regulation by the Wingless/Wnt signalling pathway. Alterations of components of this pathway have been suggested to play a central role in tumorigenesis. The present study investigated, by immunohistochemistry and immunoblotting, the protein expression and localisation of beta-catenin, adenomatous polyposis coli (APC), glycogen synthase kinase 3beta (GSK3beta) and lymphocyte enhancer factor-1 (Lef-1) in normal human ovaries and in epithelial ovarian tumours in vivo and in vitro. Immortalised human ovarian surface epithelium and ovarian cancer cell cells (OVCAR-3) expressed beta-catenin, APC, GSK3beta and Lef-1. Nuclear staining of beta-catenin and Lef-1 were demonstrated only in OVCAR-3 cells. There were significant increases of beta-catenin and GSK3beta, while APC was reduced in ovarian cancer compared to the normal ovary. Beta-catenin and Lef-1 were coimmunoprecipitated in ovarian tumours, but not in the normal ovary. Nuclear localisation of beta-catenin or Lef-1 could not be demonstrated in the normal ovary or in the ovarian tumours. The absence of nuclear localisation of beta-catenin could be due to an increased binding to the cadherin-alpha-catenin cell adhesion complex. In fact, we have earlier reported an increased expression of E-cadherin in ovarian adenocarcinomas. In summary, this study demonstrates an increase in the expression of components of the Wingless/Wnt pathway in malignant ovarian tumours. The increase suggests a role for this signalling pathway in cell transformation and in tumour progression. However, it remains to be demonstrated whether it is an increased participation of beta-catenin in transcriptional regulation, or in the stabilisation of cellular integrity, or both, that is the crucial event in ovarian tumorigenesis.

Adenocarcinoma↗
PubMed2001

The future of capitation: the physician role in managing change in practice.

Capitation-based reimbursement significantly influences the practice of medicine. As physicians, we need to assure that payment models do not jeopardize the care we provide when we accept higher levels of personal financial risk. In this paper, we review the literature relevant to capitation, consider the interaction of financial incentives with physician and medical risk, and conclude that primary care physicians need to work to assure that capitated systems incorporate checks and balances which protect both patients and providers. We offer the following proposals for individuals and groups considering capitated contracts: (1) reimbursement for primary care physicians should recognize both individual patient encounters and the administrative work of patient care management; (2) reimbursement for subspecialists should recognize both access to subspecialty knowledge and expertise as well as patient care encounters, but in some situations, subspecialists may provide the majority of care to individual patients and will be reimbursed as primary care providers; (3) groups of physicians should accept financial risk for patient care only if they have the tools and resources to manage the care; (4) physicians sharing risk for patient care should meet regularly to discuss care and resource management; and (5) physicians must disclose the financial relationships they have with health plans and medical care organizations, and engage patients and communities in discussions about resource allocation. As a payment model, capitation offers opportunities for primary care physicians to influence the future of health care by improving the management of resources at a local level.

Capitation Fee↗
PubMed2000

Increased expression of the transcription factors CCAAT-enhancer binding protein-beta (C/EBBeta) and C/EBzeta (CHOP) correlate with invasiveness of human colorectal cancer.

Regulation of cell differentiation is most often impaired in malignant tumors and may represent a key mechanism for the progression of the disease. CCAAT-enhancer binding protein (C/EBP) is a family of transcription factors involved in the regulation of embryonic gut development in rodents, which has also been detected in various malignancies, e.g., liposarcomas and breast and ovarian epithelial tumors. We studied the relationship between C/EBP and tumor histology (Duke's invasive stage and pathological grade) in colorectal cancer. Immunoblotting techniques were used on microdissected fresh frozen tumor specimens, and expression of C/EBPalpha, C/EBPbeta and C/EBPzeta (CHOP) was analyzed in addition to that of the cell-cycle regulator p53 and the proliferation marker PCNA. Expression of C/EBPbeta (LAP isoforms) was markedly increased in all tumors compared with normal colon mucosa. Although the inter-patient variability was large, we found that LIP, the isoform of C/EBPbeta known to inhibit transcription, was expressed at higher levels in Duke's stage B tumors compared with Duke's stage A, whereas Duke's C tumors had the lowest LIP expression. A similar relationship was seen for CHOP. The cell-cycle regulator gene p53 was the only factor that clearly correlated with pathological grade: a decrease in p53 expression was demonstrated. Our data suggest that genetic and cellular events involving C/EBPbeta and CHOP are important for tumor invasion and that these events do not appear to be related to the pathological grade of the tumor.

Aged↗
PubMed2000

Growth hormone induces CCAAT/enhancer binding protein alpha (C/EBPalpha) in cultured rat hepatocytes.

BACKGROUND/AIMS: The transcription factor CCAAT/enhancer binding protein alpha (C/EBPalpha) is a transactivator of several genes in the liver, which are regulated by growth hormone. METHODS: Growth hormone (100 ng/ml) was added to primary rat hepatocytes cultured on a laminin-rich matrix. C/EBP mRNA and protein levels were measured by RNase protection assay and Western blotting, respectively. DNA binding activity was measured by electrophoretic mobility shift assay (EMSA). RESULTS: Growth hormone treatment for 6 h to 3 days increased C/EBPalpha mRNA levels. Addition of growth hormone for 24 h and 4 days also enhanced the levels of the 42 and 30 kDa isoforms of immunoreactive C/EBPalpha. EMSA showed that addition of growth hormone for 24 h enhanced the abundance of a protein complex binding to a consensus C/EBP binding DNA oligonucleotide. This protein complex was supershifted by antibodies directed against C/EBPalpha but not against C/EBPbeta. There were no consistent effects on C/EBPbeta mRNA or protein at any timepoint. The growth hormone effect on C/EBPalpha expression was not affected by simultaneous incubation with insulin or glucocorticoids, two hormones that previously have been reported to affect C/EBPs. CONCLUSIONS: Growth hormone enhances the levels of C/EBPalpha mRNA and protein as well as the DNA binding activity of C/EBPalpha in cultured rat hepatocytes.

Animals↗
PubMed1984

Evolution of a geriatric evaluation clinic.

Multidisciplinary geriatric evaluation units are being established in hospitals and, to a lesser extent, as outpatient clinics. This paper presents results of a chart audit of 332 patients seen from 1978 to 1982 at a university based geriatric outpatient evaluation unit. The relationships of clinic staffing to types of referrals and other aspects of clinic operation are investigated. During the time under study, the proportion of patients whose problems were medical rather than psychiatric or social increased. Presenting problems varied by referral source. Family and self referrals were most likely to identify a medical presenting problem, while physician and community agency referrals were most likely to identify a psychiatric problem. Patients frequently received diagnoses in areas of function other than those identified as the presenting problems. For example, medical clinicians made at least one psychiatric diagnoses for 86 per cent of patients they evaluated. Important questions about the potential contribution of such geriatrics clinics to health care of the elderly remain to be answered.

Aged↗
PubMedDate not supplied

Higher levels of soluble E-cadherin in cyst fluid from malignant ovarian tumours than in benign cysts.

A major diagnostic dilemma in the clinical gynaecological oncology setting is to preoperatively determine whether a complex ovarian mass is benign or malignant. The cell-cell adhesion molecule E-cadherin has previously been localised in biopsies from both benign and malignant epithelial ovarian tumours. In this study, soluble E-cadherin levels was measured with ELISA-technique in peripheral blood, ascites and cystic fluids from patients (n = 33) undergoing surgery for ovarian cystic masses. The levels of soluble E-cadherin were significantly higher in cystic fluid from cystadenocarcinomas (p < 0.001) and borderline tumours (p < 0.05) as compared to cystic fluid from cystadenomas. In ascites fluid and peripheral blood no significant differences were seen. However, ratios of cystic fluid/peripheral blood levels were significantly higher in cystadenocarcinoma (p < 0.001) and borderline tumours (p < 0.05) as compared to benign tumours. In conclusion, measurements of soluble E-cadherin in cystic fluid from patients presenting with complex ovarian masses may be beneficial in increasing the accuracy of preoperative diagnosis.

Adenocarcinoma↗
PubMedDate not supplied

Phenobarbital, drug metabolism, and human cancer.

To investigate the possible influence of anticonvulsant treatment on cancer risk, a nested case-control study of 104 lung cancers, 18 bladder cancers, and 322 cancer-free controls was conducted. The background for the study was previous observations among 8004 epileptics in Denmark with a significantly high risk for lung cancer and a significantly low risk for bladder cancer. Cigarette smoking appears to explain the lung cancer excess but not the low risk for bladder cancer, another tobacco-related disease. Information was abstracted on 94 and 95% of the cases and controls, respectively. Lung cancer was not associated with any anticonvulsant drug, but bladder cancer was inversely related to use of phenobarbital (PB). The apparent protective effect of PB was further evaluated in a study of rats given 4-aminobiphenyl (ABP), a bladder carcinogen. The levels of 4-aminobiphenyl adducts in hemoglobin and in bladder and liver DNA were significantly lower in rats given PB prior to 4-aminobiphenyl, compared to controls. These studies suggest that PB may induce drug-metabolizing enzymes of the liver that deactivate bladder carcinogens found in cigarette smoke and provide clues to the role of activation and detoxification of carcinogens in humans.

Animals↗