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Biomedical subjects

P Nørgaard

Publications and source records attributed to P Nørgaard.

10 recordsLinked to original sources
PubMed1992

Tetrahymena gene encodes a protein that is homologous with the liver-specific F-antigen and associated with membranes of the Golgi apparatus and transport vesicles.

The F-antigen is a prominent liver protein which has been extensively used in studies on natural and induced immunological tolerance. However, its intracellular localization and biological function have remained elusive. It has generally been assumed that the F-antigen is confined phylogenetically to vertebrates. Now we have cloned and characterized a gene from the ciliated protozoan Tetrahymena thermophila encoding a protein which clearly is homologous with the rat F-antigen. The coding region of the Tetrahymena F-antigen (TF-ag) gene specifies a 46,051 M(r) protein and is interrupted by three introns. In accordance with the predicted molecular mass of the TF-ag protein, antibodies raised against a cro-lacZ'-TF-ag fusion protein specifically recognized a 45,000 M(r) protein in Western blots of total T. thermophila protein. Immunoelectron microscopy demonstrated that the TF-ag is associated with membranes of the Golgi apparatus and transport vesicles pointing to a role of TF-ag in membrane trafficking. Transcription of the TF-ag gene, as determined by run-on analyses, was only detectable in growing cells, and following transfer to starvation condition pre-existing TF-ag mRNA was rapidly degraded. The abundance of the TF-ag protein, however, declined only moderately during prolonged periods of starvation demonstrating that extensive release of the TF-ag did not take place. In combination these results suggest that the TF-ag protein is a recycled constituent of the intracellular membrane network in T. thermophila.

Amino Acid Sequence↗
PubMed1992

Chromatin structure and conserved sequence elements in genes encoding ribosomal proteins in Tetrahymena thermophila.

The chromatin structure of the macronuclear genes encoding ribosomal proteins S25 and L1 in the ciliated protozoan Tetrahymena thermophila was analyzed. Using the indirect end-labelling technique, DNase-I-hypersensitive regions were located in the promoter regions as well as in the 3' regions of the genes. The DNase-I-hypersensitive regions were present in chromatin of exponentially growing cells, where the rate of ribosomal-protein gene transcription is high, and in chromatin from starved cells, where transcription of ribosomal-protein genes is severely depressed. Micrococcalnuclease-digestion experiments revealed that the promoter regions of the S25 gene and the L1 gene are devoid of nucleosomes in exponentially growing cells. In starved cells, no nucleosomal organisation of the promoter region of the L1 gene could be detected, whereas nucleosomal structures were discernible in the promoter region of the S25 gene. A conspicuous polypurine sequence motif, AARGGGAAA, is present within or adjacent to the DNase-I-hypersensitive regions in the promoter of the S25 and the L1 gene, and interestingly, the same motif is found also in the promoter regions of the genes encoding ribosomal proteins L21 and L37.

Animals↗
PubMed1992

[Transforming growth factor beta. A potent multifunctional growth factor for normal and malignant cells].

The polypeptide growth factor transforming growth factor-beta (TGF-beta) is a multifunctional regulator of basic cellular functions: proliferation, differentiation, cell adhesion and interactions with the extracellular matrix. TGF-beta is part of a regulatory network of which our knowledge is still incomplete, together with other substances such as steroid hormones, oncogene products and integrins. Five isoforms for TGF-beta and five different TGF-beta receptors have been described. TGF-beta exhibits an antiproliferative effect in vitro and in vivo on many cells of epthelial, myeloid, lymphoid and mesenchymal origin together with a growth-stimulating effect on various cells like endothelial cells and epidermal keratinocytes. Production of TGF-beta and receptors for TGF-beta has been found in many cell types, both normal and malignant. Nevertheless the amount of in vivo data is too limited to identify possibilities for therapeutic intervention in the physiological and patophysiological functions of TGF-beta.

Breast Neoplasms↗
PubMed1991

Mechanical properties of trabecular bone. Dependency on strain rate.

The effect of strain rate (epsilon) and apparent density (rho) on stiffness (E), strength (sigma u), and ultimate strain (epsilon u) was studied in 60 human trabecular bone specimens from the proximal tibia. Testing was performed by uniaxial compression to 5% specimen strain. Six different strain rates were used: 0.0001, 0.001, 0.01, 0.1, 1, and 10 s-1. Apparent density ranged between 0.23 and 0.59 g cm-3. Linear and non-linear regression analyses using strength, stiffness and ultimate strain as dependent variables (Y) and strain rate and apparent density as independent variables were performed using the following models: Y = a rho b epsilon c, Y = rho b(a + c epsilon; Y = (a + b rho)epsilon c, Y = a rho 2 epsilon c, E = a rho 3 epsilon c. The variations of strength and stiffness were explained equally well by the linear and the power function relationship to strain rate. The exponent was 0.07 in the power function relationship between strength and strain rate and 0.05 between stiffness and strain rate. The variation of ultimate strain was explained best using a power function relationship to strain rate (exponent = 0.03). The variation of strength and stiffness was explained equally well by the linear, power function and quadratic relationship to apparent density. The cubic relationship between stiffness and apparent density showed a less good fit. Ultimate strain varied independently of apparent density.

Aged↗
PubMed1991

Glucocorticoid receptors in human malignancies: a review.

The present knowledge of the human glucocorticoid receptor (hGCR) in primary malignancies is reviewed. It is concluded that hGCR is present in a large number of these tissues; in all tissue specimens of lymphoid malignancies and in varying fractions of the different solid tumors. The hGCR functions as a hormone dependent, specific enhancer interacting protein in mediating the considerable effects of glucocorticoids on growth regulation, both through stimulation and inhibition of expression of the target genes, including other transcription regulation systems. The processes of receptor activation and regulation, as well as the effects of glucocorticoids, are tissue-specific. Subjects for future research are proposed: Establishment of more cell lines and animal models to extend investigation beyond the present concentration on only a few cell lines, especially CEM-C7, application of 'dynamic' assays to cells obtained from patients, in an attempt to predict development of glucocorticoid resistance, and further investigation of the relationships among GCR and growth factors and oncogenes.

Animals↗
PubMed1989

Malignancy in ulcerative colitis.

All patients with ulcerative colitis referred to Rigshospitalet, Copenhagen, from 1 April 1964 to 1 January 1983 (18 years and 9 months) were studied from time of referral until death, proctocolectomy, or end of the study (1983). There were 759 patients, 423 females (56%) and 336 males (44%). None was lost to follow-up study. Median time from onset of disease until death, proctocolectomy, or end of the study was 11 years (range, 0-54 years). Median age at onset was 28 years (range, 0-83) among the males and 28 years (range, 4-83) among the females. Pancolitis was present in 312 patients (41%), left-sided colitis in 212 (28%), and haemorrhagic proctitis in 235 (31%). Surgical treatment was performed in 299 patients (39%): proctocolectomy in 197 (26%), colectomy with occluded rectal stump in 72 (9%), and colectomy with ileorectal anastomosis in 30 (4%). Altogether, 49 patients developed cancer, 20 being intestinal and 29 extraintestinal cancer. Compared with the general population matched for age, sex, and calendar time, there was an excessive number with intestinal cancer in both sexes (p less than 0.05). In females the number with extraintestinal cancer was higher than in the general population (p less than 0.01), a finding that has not been reported elsewhere. We found a similar, significantly increased incidence of extraintestinal cancer in females with Crohn's disease in a previous report. We found no increased risk of colorectal cancer in patients with early onset of ulcerative colitis. For all age classes we found that the age of appearance of colorectal cancer followed the equation: age at colorectal cancer = 14 + age at onset of ulcerative colitis. We found no higher potential for development of colorectal cancer in patients with pancolitis. In our series the incidence of colorectal cancer in pancolitis and left-sided colitis was equal. The incidence in patients with haemorrhagic proctitis was zero.

Adolescent↗
PubMed1986

Malignancy in Crohn's disease.

The incidence of cancer in Crohn's disease has been evaluated in 473 patients admitted to Rigshospitalet during the period 1 April 1964 to 1 January 1983. The patients' condition at the end of the survey, their survival, and the number and location of cancers were registered. During the survey period 23 cancers (4.9%) were found. Five were intestinal (1.1%) and were split evenly among the two sexes, whereas among 18 patients with extraintestinal cancers there was only 1 man. There was no increased risk of developing cancer inside the gastrointestinal tract compared with a background population matched for age, sex, and calendar time. Extraintestinal cancer in women was, however, significantly in excess.

Adolescent↗