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Biomedical subjects

J Eriksen

Publications and source records attributed to J Eriksen.

At least 55 records · Page 3Linked to original sources
PubMed1996

Differential expression of urokinase-type plasminogen activator, its receptor, and inhibitors in mouse skin after exposure to a tumor-promoting phorbol ester.

The cellular distribution of mRNAS for urokinase-type plasminogen activator (uPA), its specific receptor (uPAR), and its inhibitors (PAI-1 and -2) in mouse skin was analyzed by in situ hybridization after topical application of the tumor promoter phorbol 12-myristate 13-acetate. In the epidermis, strong signals for uPA and PAI-1 mRNA were detected 24 h after treatment in the basal and suprabasal epidermal keratinocytes in areas with pronounced hyperproliferation and increased terminal differentiation, and in some hair follicle keratinocytes. After 48 h, both uPAR and PAI-2 mRNAs were expressed in the epidermal layers from the suprabasal keratinocytes up to the differentiating cells beneath the cornified layer and in hair follicle keratinocytes. Induction of PAI-2 mRNA was detected in epidermis as early as 3 h after treatment and remained stable for up to 7 days. In the dermis, 5 h after application of phorbol 12-myristate 13-acetate to the skin, uPA mRNA was detected in fibroblast-like cells below and around the skin muscle, and PAI-1 mRNA was detected in stromal cells located above the skin muscle. After longer exposure to phorbol 12-myristate 13-acetate, the PAI-1 mRNA-expressing stromal cells were located more superficially, apparently moving toward the epidermal layer. After 9 h, most of the PAI-1 mRNA-positive cells were identified as endothelial cells. Up to 24 h after the application of phorbol 12-myristate 13-acetate, the intensity of the signal for both uPA and PAI-1 increased, followed by a gradual decrease for up to 7 days. These results show that in mouse skin treated with a tumor-promoting phorbol ester, the various components of the plasminogen activation system are expressed by both epithelial and stromal cell types, which in dermis and subcutis are located in different places, depending on the time of exposure to the phorbol ester. Our results suggest that urokinase-mediated extracellular proteolysis has diverse functional roles during the early steps of tumor promotion.

Animals↗
PubMed1995

[Abuse--of hospital services too].

A 75 year-old man with a well known opioid abuse is described. Within the last 10 years the patient had 161 acute admissions to hospital--in total 942 in-hospital days. The diagnoses were either angina pectoris, low back pain or migraine. With time, the patient had become very skilled in mimicking these three diseases, knowing all subjective and objective signs even better than most of his doctors. In connection with all admissions he received the opioids he wanted. Nevertheless, he was astonished that it was so easy to fool the doctors. It is recommended that the patients' own doctor should be the coordinator and the only person responsible for prescription of opioids to these patients. In case of admissions to hospital, this should only be possible to a few selected departments who know the patient.

Aged↗
PubMed1995

Legal opioid consumption in Denmark 1981-1993.

According to the World Health Organisation, a country's morphine consumption is an important indicator of progress in cancer pain relief. Due to its very high opioid consumption, Denmark is often pointed out as a country worthy of imitation. The aim of the present study was to analyse Danish opioid consumption in order to elucidate the usage pattern and to identify the consumers. Total opioid consumption increased 353% from 1981 to 1993, exceeding 1.45 million defined daily doses per million inhabitants in 1993. Morphine accounted for 39%, methadone 22%, ketobemidone 21% and buprenorphine for 14% of the consumption use. The consumption of long acting opioids (sustained release morphine, methadone, buprenorphine) and short acting opioids (others) increased by 1427% and 105%, respectively. Analysis of a sample of 1854 prescriptions for opioids revealed that less than 10% of the prescriptions were issued for cancer pain conditions. It is concluded: that if other countries consider Denmark as worthy of imitation in opioid treatment for cancer pain, attention should be paid to the pattern of the Danish opioid consumption, which is outstanding with respect to quantity but the quality may be questionable.

Analgesia↗
PubMed1995

Neutrophils express tumor necrosis factor-alpha during mouse skin wound healing.

The expression pattern of tumor necrosis factor-alpha (TNF-alpha) mRNA and protein was examined in vivo in experimental mouse skin wounds by in situ hybridization and immunohistochemistry. TNF-alpha mRNA and protein is detected in a distinct layer of mainly neutrophils subadjacent to the would clot. The layer of TNF-alpha-positive cells extends from the margin of the advancing epithelial outgrowth to the opposing one. By in situ hybridization the TNF-alpha mRNA is detectable 12 h after wounding; the signal peaks after 72 h and remains visible up to at least 120 h after wounding. TNF-alpha mRNA could not be detected in the normal skin or in 5-hour-old wounds. Immunohistochemical staining for TNF-alpha and macrophages on adjacent sections confirms that the main part of TNF-alpha-positive cells are polymorphonuclear neutrophils and shows that most of the cells located just beneath the layer of TNF-alpha-positive neutrophils are macrophages with weak TNF-alpha immunoreactivity. The data reported here show that neutrophils serve as an important source of TNF-alpha during healing of mouse skin wounds. We suggest that this specific expression of TNF-alpha is related to the process of re-epithelialization.

Animals↗
PubMed1994

Expression of uPA and its receptor by both neoplastic and stromal cells during xenograft invasion.

Recent studies have shown that molecules involved in generation and regulation of extracellular proteolytic activity are often expressed by non-malignant stromal cells during human cancer invasion. We have studied the expression of the urokinase-type plasminogen activator and the urokinase-type plasminogen activator cell-surface receptor in xenografts of human MDA-MB-231 mammary carcinoma cells growing invasively in nude mice. Northern analysis showed the presence of both human and mouse urokinase-type plasminogen activator and urokinase-type plasminogen activator receptor mRNA in tumor extracts. By in situ hybridization, mRNA for human urokinase-type plasminogen activator and its receptor was detected in virtually all the cancer cells, while mouse urokinase-type plasminogen activator and urokinase-type plasminogen activator receptor mRNA was expressed by tumor-infiltrating fibroblast-like and macrophage-like cells. In invasive areas the cells expressing the 2 murine mRNAs were either the same or located immediately adjacent to each other. This model system has several advantages for studies of the mechanism by which cancer cells induce or recruit stromal cells to produce molecules involved in proteolysis.

Animals↗
PubMed1994

[Prevention of duodenal ulcer recurrence with penicillin].

The aim of this study was to test the hypothesis that infection with Helicobacter pylori is essential for recurrence of duodenal ulcer. We performed a randomized controlled trial of the relapse rate of duodenal ulcer during 12 weeks treatment with penicillin V or placebo in 170 out-patients from five centres. The relapse rate was 9% during treatment with penicillin and 50% with placebo, P < 0.0001. It is concluded that infection with penicillin-sensitive bacteria, i.e. H. pylori, plays an important role for recurrence of duodenal ulcer disease. Penicillin V suppresses this infection but does not eradicate it.

Adult↗
PubMed1994

[Opioid analgesics in the treatment of non-malignant chronic pain].

Opioid sensitivity, residual pain, development of tolerance, physical and psychological dependence are described and discussed in relation to long-term opioid therapy. Based on this, guidelines for long-term opioid administration are established for chronic pain conditions of non-cancer origin. The indication must be well-considered--a life-long treatment may be instituted. Prior to final initiation of the treatment, a testing of the selected drug and method of administration should be performed. Due to the compliance-reasons, only long acting opioids should be used (controlled release morphine preparations, methadone, buprenorphine) and the route of administration should always be oral. The treatment must be individualised, covering 24 hours a day. The single dosages should be identical and administered with identical time intervals, which are determined by the duration of action of the drug in use. P.r.n.-administration should not be allowed. Only one physician should be responsible for the treatment and for the prescription of the opioid analgesic drugs.

Analgesics, Opioid↗
PubMed1994

The prognosis of patients with alcoholic liver disease. An international randomized, placebo-controlled trial on the effect of malotilate on survival.

The aim of this study was to examine the effect of malotilate on survival in patients with alcoholic liver disease and to determine prognostic variables for survival. Four hundred and seven patients with alcoholic liver diseases, from seven European liver units, entered a randomized placebo-controlled, double-blind trial: 140 patients received malotilate 1500 mg/day, 133 patients received 750 mg/day, and 134 patients received placebo. The patients were included in the study over a period of 3 1/2 years, and the study was closed 1 year after the entry of the last patient. Eighty-four patients died (35, 19, 30 patients in groups 1500 mg/day, 750 mg/day, and placebo, respectively). Survival was slightly better in the 750 mg/day group than in the two other treatment groups, when tested by conventional log-rank tests (p = 0.06). However, a treatment effect was supported by a highly significant (p = 0.006) non-proportionality of the death intensity in patients receiving 750 mg/day against those receiving either 1500 mg/day or placebo. Prognostic variables for survival were evaluated using the multiple Cox regression analysis of clinical and laboratory variables and with or without liver histology variables, as determined at entry into the study. The analysis was stratified for the three treatment regimens. In the analysis including liver histology variables, independent significant prognostic variables were: years of high alcohol intake, prothrombin index, alkaline phosphatases, creatinine, immunoglobulin M, white blood cell count, and liver cell steatosis. In the analysis without liver histology variables, prognostic variables were: years of high alcohol intake, prothrombin index, alkaline phosphatases, creatinine, and immunoglobulin M.

Adult↗
PubMed1994

The receptor for urokinase-type plasminogen activator is expressed by keratinocytes at the leading edge during re-epithelialization of mouse skin wounds.

Expression of urokinase-type plasminogen activator receptor mRNA was examined in vivo in mouse skin wounds by in situ hybridization. Urokinase-type plasminogen activator receptor mRNA was found in keratinocytes at the front of the regenerative epithelial outgrowths at the edge of 12-, 48-, and 96-hour-old wounds. The signal was strongest in the keratinocytes just beginning to move 12 h after wounding. At later time-points the signal was weaker, but still confined to keratinocytes at the wound edges. Using in situ hybridization, no cells expressing urokinase-type plasminogen activator receptor mRNA could be detected in normal epidermis, in normal-looking epidermis adjacent to the wounds, in dermis, in subcutis, or in newly formed granulation tissue. The specificity of the results was supported by the use of antisense RNA from two different non-overlapping cDNA clones and the corresponding sense RNA probes, and by Northern analysis of tissue extracts. Together with previous findings on expression of urokinase-type plasminogen activator and its type 1 inhibitor, the localized and regulated expression of urokinase-type plasminogen activator receptor mRNA during skin wound healing indicates that focal extracellular proteolysis at the cell surface generated by receptor-bound urokinase-type plasminogen activator is implicated in the migration of re-epithelializing keratinocytes.

Animals↗
PubMed1993

An alternatively spliced variant of mRNA for the human receptor for urokinase plasminogen activator.

Using 3' RACE (rapid amplification of cDNA ends), we have isolated a cDNA variant for the receptor for human urokinase plasminogen activator (uPAR). The deduced protein includes the amino-terminal ligand binding domain in uPAR, but lacks the carboxy-terminal membrane attachment by a glycolipid anchor. Genomic DNA analysis showed that the uPAR mRNA variant is generated by alternative splicing. The new variant mRNA is expressed in various human cell lines and tissues and both variants are up-regulated by phorbol ester in A549 cells. We propose that the alternatively spliced uPAR mRNA encodes a soluble uPA binding protein, the possible function of which is discussed.

Amino Acid Sequence↗
PubMed1993

Prevention of duodenal ulcer recurrence with penicillin. A double-blind, placebo-controlled trial.

Eradication of Helicobacter pylori is associated with a reduced recurrence of duodenal ulcer (DU). The relationship between H. pylori and DU has been interpreted as causal, but the evidence has been criticized for methodologic reasons. To ascertain whether an antibiotic with no effect on epithelial-cell integrity prevents DU recurrence, we conducted a randomized double-blind trial of phenoxymethylpenicillin (PEN), 2.4 twice daily, and placebo (PLA). Patients with an active DU and positive H. pylori culture from antral biopsy specimens were treated with 40 mg omeprazole daily for 4 weeks, but at week 2 they were allocated at random to PEN (85 patients) or PLA (85 patients) for up to 14 weeks. Those without recurrence during this treatment were followed up for another 6 months. Endoscopy and H. pylori culture were performed at the end of the treatment period and at the end of follow-up, and in between if ulcer symptoms recurred. During the treatment period the ulcer relapse rate was 5 of 58 (9%) in the PEN group and 34 of 68 (50%) in the PLA group (P < 0.0001, log-rank test), with 53% and 14%, respectively, of the patients in the two groups being H. pylori-negative. The relapse rate in the PEN group did not differ between H. pylori-negative and H. pylori-positive patients. The recurrence rate in the PEN group remained low for another 5 months but then approached the rate in the PLA group. The prevalence of H. pylori-negative patients at the end of follow-up was 20% in the PEN group and 10% in the PLA group. These data provide strong evidence that DU has a bacterial cause, with H. pylori as the likely agent.

Double-Blind Method↗
PubMed1992

A soluble form of the glycolipid-anchored receptor for urokinase-type plasminogen activator is secreted from peripheral blood leukocytes from patients with paroxysmal nocturnal hemoglobinuria.

The cellular urokinase-type plasminogen-activator (uPA) receptor (uPAR) is a glycolipid-anchored membrane protein thought to be involved in pericellular proteolysis during cell migration and tumor invasion. In the present study, we have identified and characterized two soluble forms of uPAR which have retained their ligand-binding capability. One variant was generated in vitro by treatment of intact normal cells with either a phosphatidylinositol-specific phospholipase C (PLC) or endoproteinase Asp-N. The other soluble uPAR variant was secreted in vivo from peripheral blood leukocytes affected by the stem-cell disorder paroxysmal nocturnal hemoglobinuria (PNH), and was found in the plasma from these PNH patients as well as in the conditioned medium from cultured PNH leukocytes. Under normal conditions, we find no evidence for any shedding or secretion of a soluble uPA-binding counterpart to human uPAR in plasma. Unlike normal leukocytes, the PNH-affected cells do not express uPAR on the cell surface, although they do contain apparently normal levels of uPAR-specific mRNA. The secreted uPAR derived from PNH cells has a mobility in SDS/PAGE that is slightly higher than that of uPAR solubilized by PtdIns-specific PLC or detergent, but resembles that of a truncated, recombinant uPAR variant, which has its C-terminus close to the proposed glycolipid-attachment site, suggesting that the secreted protein has been proteolytically processed for glycolipid attachment. The presence in plasma from PNH patients of such a secreted, hydrophilic form of uPAR lends support to the hypothesis that the lesion underlying the PNH disorder resides either in glycolipid biosynthesis or in the function of an as-yet-unidentified transamidating enzyme assumed to cleave and assemble the truncated uPAR with the preformed glycolipid moiety.

Amino Acid Sequence↗
PubMed1992

Identification and characterization of the murine cell surface receptor for the urokinase-type plasminogen activator.

Cell-binding experiments have indicated that murine cells on their surface have specific binding sites for mouse urokinase-type plasminogen activator (u-PA). In contrast to the human system, chemical cross-linking studies with an iodinated ligand did not yield any covalent adducts in the murine system, but in ligand-blotting analysis, two mouse u-PA-binding proteins could be visualized. To confirm that these proteins are the murine counterpart of the human u-PA receptor (u-PAR), a peptide was derived from the murine cDNA clone assigned to represent the murine u-PAR due to cross-hybridization and pronounced sequence similarity with human u-PAR cDNA [Kristensen, P., Eriksen, J., Blasi, F. & Danø, K. (1991) J. Cell Biol. 115, 1763-1771]. A rabbit antiserum raised against this peptide specifically recognized two polypeptide bands with electrophoretic mobilities identical to those identified by ligand-blotting analysis. Binding of mouse u-PA to its receptor showed species specificity in ligand-blotting analysis, since mouse u-PA did not bind to human u-PAR and human u-PA did not bind to mouse u-PAR. The apparent M(r) of mouse u-PAR varied between different mouse cell lines and ranged over M(r) 45,000-60,000. In four of the cell lines, mouse u-PA bound to two mouse u-PAR variant proteins, whereas in the other two cell lines studied, there was only one mouse u-PA-binding protein. In the monocyte macrophage cell line P388D.1, trypsin-treatment of intact cells could remove only the large mouse u-PAR variant (M(r) 60,000) indicating that only this type was a cell-surface-exposed molecule. The smaller mouse u-PAR variant (M(r) 45,000), was deglycosylated by the enzyme endo-beta-N-acetylglucosaminidase H and is probably an intracellular precursor form carrying only high-mannose carbohydrate. Deglycosylation of this variant yielded a polypeptide with an apparent M(r) of about 30,000, which corresponds to the Mr calculated from the cDNA derived protein sequence of mouse u-PAR. Receptor-bound mouse u-PA could be released by phosphatidylinositol-specific phospholipase C treatment, indicating that mouse u-PAR is attached to the cell surface by glycosylphosphatidylinositol. Purification of the two mouse u-PAR variant proteins by diisopropylfluorophosphate-inactivated mouse u-PA-Sepharose affinity chromatography yielded two silver-stained bands when analysed by SDS/PAGE, corresponding in electrophoretic mobility to those seen by ligand-blotting analysis.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1991

[Severe prolonged hypotension after the first dose of enalapril in a patient with essential hypertension].

A case of severe and prolonged hypotension following intake of 10 mg enalapril in a patient with slight hyponatraemia is described. Despite administration of isotonic NaCl and treatment with dopamine infusion, it did not prove possible to maintain a stable blood pressure. Adrenaline and ephedrine were required intravenously on repeated occasions on account of symptom-producing hypotension with a systolic pressure as low as 60 mmHg. On account of the increasing use of ACE-inhibitors, it is recommended that the specific antidote, angiotension II, should be registered in Denmark and should be available in all hospitals.

Enalapril↗
PubMed1991

The plasminogen activation system in human colon cancer: messenger RNA for the inhibitor PAI-1 is located in endothelial cells in the tumor stroma.

Fourteen human colon adenocarcinomas were examined by in situ hybridization for the presence of mRNA for plasminogen activator inhibitor type 1 (PAI-1). All specimens contained PAI-1 mRNA in endothelial cells of some vessels in the stroma immediately surrounding the invasive tumor glands, in granulation tissue, and in some capillaries located under the free luminal surface of carcinomatous epithelium. In addition, a limited number of stromal cells in the cancerous areas located at the periphery of newly formed capillary networks, and presumably representing sprouting endothelial cells, contained PAI-1 mRNA. Cancer cells were devoid of detectable PAI-1 mRNA in all cases. PAI-1 mRNA was not seen in three biopsies of normal colon. Together with previous findings of urokinase-type plasminogen activator and its mRNA being located in fibroblast-like cells in the tumor stroma and mRNA for the urokinase receptor in the cancer cells at invasive foci, these results indicate a complex cooperativity among several cell types in regulation of plasminogen activation in colon cancer. A possible role of PAI-1 in protecting the extracellular matrix in the tumor tissue against degradation and a role in tumor-induced angiogenesis are discussed.

Adenocarcinoma↗