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Biomedical subjects

K Elgjo

Publications and source records attributed to K Elgjo.

At least 37 records · Page 2Linked to original sources

Hepatobiliary disease in ulcerative colitis. An analysis of 18 patients with hepatobiliary lesions classified as small-duct primary sclerosing cholangitis.

BACKGROUND: The aim of the present study was to describe the characteristics of patients with ulcerative colitis (UC) and hepatobiliary disease that does not satisfy the diagnostic cholangiographic criteria of primary sclerosing cholangitis (PSC) and to compare this group with PSC patients. METHODS: Among 199 patients with UC admitted to our department during 1986-91, 64 patients had major hepatobiliary disease considered to be associated with the colitis. Biochemical tests, colonoscopy, endoscopic retrograde cholangiography (ERC), and liver biopsy were performed in these 64 patients and in 5 patients from our outpatient clinic. RESULTS: PSC was diagnosed in 51 patients (group I; 80%). The other 13 patients (20%) and the additional 5 patients (n = 18; group II) all had normal extrahepatic bile ducts. Five patients in group II also had normal intrahepatic ducts, whereas 13 patients had intrahepatic abnormalities. The male to female ratio in group II was 2.0:1. All of them had extensive colitis. The clinical symptoms and the biochemical and histologic findings were quite similar in groups I and II. CONCLUSIONS: The patients in group II of this study constitute a major group with hepatobiliary lesions associated with UC, amounting to one-fourth the number of PSC patients. They have several similarities with classical PSC of the large bile ducts, and we suggest that they be classified as having small-duct PSC.

Adult↗

Beta-receptor blockade by propranolol modifies the effect of the inhibitory, endogenous epidermal pentapeptide on epidermal cell flux at the G2-M transition but not at the G1-S transition.

The mitosis inhibitory pentapeptide, pGlu-Glu-Asp-Ser-GlyOH (EPP), which was isolated from mouse epidermis extracts, belongs to a group of growth inhibitory peptides that all have pyroglutamyl at the N-terminal end. Earlier experiments with crude or partially purified skin extracts have shown that the inhibitory effect could be enhanced by beta-receptor agonists and by dibutyryl cAMP, and that beta-receptor blockade could neutralise it. We now show that treatment with the beta receptor blocker propranolol before or after EPP treatment of hairless mice significantly modifies the effect of EPP on mouse epidermal cell proliferation, as estimated by using a metaphase-arrest technique (Colcemid) to estimate the G2-M cell flux. The interaction between propranolol and EPP is complex; only the EPP-induced inhibition of the G2-M cell flux was modified by beta-receptor blockade, while the late (18-21 h) inhibition of the mitotic rate was unaltered. Propranolol alone was followed by a dose-related and transient increase in the epidermal mitotic rate. The phosphodiesterase inhibitor caffeine had no effect on its own on epidermal cell proliferation but counter-acted the late (18-21 h) EPP-induced inhibition.

Amino Acid Sequence↗

Could development of malignant mesothelioma be induced by Yersinia enterocolitica infection?

Two out of 458 hospitalized patients with Yersinia enterocolitica infection developed malignant mesothelioma of pleura viz. pericard; both died after a few months. Malignant mesothelioma of the pleura is commonly related to asbestos exposure, whereas pericardiac mesothelioma is an extremely uncommon neoplasm. The possible promotion of malignant mesothelioma by the Yersinia enterocolitica infection should not be disregarded, as the infection may launch chronic immunological reactions resembling those observed among asbestos workers.

Adult↗

Moderate enhancement of the promotion phase of skin tumorigenesis in hairless mice by topical pretreatment with a mitosis-inhibiting epidermal pentapeptide.

The effect of the physiological epidermal proliferation inhibitory substance (EPP) pGlu-Glu-Asp-Ser-GlyOH on the promotion phase in two-stage carcinogenesis was investigated. EPP could be the active component in what has been called epidermal chalone. Hairless mice were given an initial application of 100 nmol 7,12-dimethylbenz[a]anthracene in 200 microliters acetone. One week later promotion was started with topical applications of 17 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) twice a week. Ninety minutes before each TPA application the control group received a topical application of 200 microliters reagent grade acetone and the two experimental groups were given either 0.005% or 0.01% EPP in 200 microliters acetone. The mice were observed for time of occurrence and time of regression of papillomas. The number of tumors produced by the group given the inhibitory substances before TPA increased, and so did the percentage of tumor-bearing animals. There was also a tendency towards a higher degree of papilloma regression in the animals treated with EPP before TPA. We have previously shown that EPP enhances methylnitrosourea (MNU) carcinogenesis. Since we regard TPA as a skin-irritating promoter with weak carcinogenic potency, very different from MNU, the fact that EPP has the same enhancing effect on promotion as it has on complete MNU carcinogenesis raises some very interesting questions, and may indicate a similarity between the mechanisms in promotion and complete carcinogenesis. Some possible explanations of the results are discussed, e.g. whether the transit zone late G1/S of the cell cycle is the most sensitive one for carcinogenic or tumorigenic effects.

9,10-Dimethyl-1,2-benzanthracene↗

[Natural products can be hazardous to health].

Side effects of herbal and health food products have been infrequently reported such as hepatic damage after use of such products. Four such patients were treated in our department in the course of two years. In all four patients, the use of herbal remedies was the probable cause of serious hepatic damage, but both etiology and pathogenesis were difficult to establish. Two major areas of concern are inaccurate formulation and contaminated preparations. As long as no therapeutic effect can be demonstrated from this type of medicine, serious side effects are unacceptable. A critical attitude should be adopted towards these medicines and the use of them.

Adult↗

The synthetic hepatic peptides pyroglutamylglutamylglycylserylasparagine and pyroglutamylglutamylglycylserylaspartic acid inhibit growth of MH1C1 rat hepatoma cells transplanted into Buffalo rats or athymic mice.

Repeated i.p. injections of the synthetic peptides pyroglutamylglutamylglycylserylasparagine and pyroglutamylglutamylglycylserylaspartic acid inhibited the long-term growth of MH1C1 rat hepatoma cells by 50-70% in three in vivo models: metastatic colony growth in the lungs of young Buffalo rats; s.c. tumor growth in young Buffalo rats; and s.c. tumor growth in athymic mice. The amide free peptide pyroglutamylglutamylglycylserylaspartic acid which inhibited the tumor growth in all the models showed a curvilinear dose-response relationship with a maximal effect at 1000 pmol/animal in mice and at 100 pmol/animal in rats. The amidated peptide pyroglutamylglutamylglycylserylasparagine, which was only tested in the lung model, showed growth inhibition with 2, 20, or 200 pmol/animal, but 200 pmol/animal was most effective. We have recently reported that these peptides show cochromatography with hepatic growth inhibitory peptides, isolated from mouse liver.

Animals↗

Modulation of KB and A431 cell adhesion by epidermal growth inhibitory pentapeptide.

A pentapaptide, pyroGlu-Glu-Asp-Ser-GlyOH (EPP), isolated from mouse epidermis, inhibits mitoses and enhances differentiation in primary cultures and in transformed mouse epidermal cells in vitro (Elgjo et al. 1986 b). The present work demonstrates that EPP also modulates the adhesiveness of two human tumour cell lines (KB and A431) of epidermal origin to uncoated plastic and to plastic coated with fibrinogen or collagen type 1. The adhesion modulatory effect of EPP was observed over a broad range of concentrations (10(-12)-10(-6) M), and depended on the substrate the cells were growing on. Thus, when cells were seeded on plastic or collagen, the attachment to the substrate was suppressed at the highest concentrations of EPP, and stimulated at the lowest ones. The opposite concentration-response pattern was observed when fibrinogen was used as substrate.

Amino Acid Sequence↗

Inhibitory epidermal pentapeptide modulates proliferation and differentiation of transformed mouse epidermal cells in vitro.

A transformed mouse epidermal cell line ("308 cells") and nontransformed rat tongue squamous epithelial cells ("RT10 cells") were treated 3 times weekly for a period of two weeks with relatively large doses (150 micrograms/ml) of a synthetic inhibitory epidermal pentapeptide; pyroGlu-Glu-Asp-Ser-GlyOH. The peptide was recently isolated from mouse skin extracts and inhibits normal epidermal cells in vivo and in vitro at a restricted and low dose level. Repeated treatments with the large dose was followed by a 30-40% reduction in the number of 308 cells per well, starting as early as day 1. The number of RT10 cells was reduced about 20% only at termination of the experiment on day 14. In contrast to this, the number of unattached cornified envelopes on day 10 in the RT10 cells was increased by 85%, while the number of cornified, unattached 308 cells was similar to that in the controls. The effects of the pentapeptide thus seem to affect differentiation stronger than proliferation in the nontransformed cell line. Bivariate BrdUrd/DNA flow cytometry analysis on day 10 indicated that the reduced number of 308 cells was mainly due to a slower rate of cell proliferation and not to a increased sloughing off of keratinized cells. This analysis also demonstrated that an inhibition of DNA synthesis in the RT10 cells could be detected prior to a reduction of the cell number per well.

Amino Acid Sequence↗

Liver steatosis in hypobetalipoproteinemia. A case report.

A case of hypobetalipoproteinemia is described; a 16-year-old girl had been suffering for nearly 2 years from diffuse abdominal pain. The only clinical features were liver steatosis, slightly increased amino transferases and an incipient polyneuropathy. No sign of malabsorption or gastrointestinal disease was found. She had extremely low levels of cholesterol and triacylglycerol in her serum, slightly decreased serum phospholipids and normal HDL-cholesterol levels. Apolipoprotein B-100 was approx. 8% of normal, whereas B-48 was present at essentially normal levels. Electron microscopy of lipoprotein particles showed normal morphology of LDL. Examination of close relatives showed no abnormalities. Southern blots revealed no major deletions or rearrangements at the genomic level. Although rare, a- and hypobetalipoproteinemia should be considered as possible etiologies in patients with unexplained steatosis in the liver.

Adolescent↗

Relationship of inflammatory bowel disease and primary sclerosing cholangitis.

There is a strong association between PSC and IBD. PSC is the most common hepatobiliary lesion seen in association with IBD. Whether there are two subsets of PSC, one associated with IBD and one unassociated, is controversial. A lower male to female ratio in patients without IBD supports this view. The demonstration of the haplotype DRw52a in 100% of patients with PSC, irrespective of the absence of IBD, speaks against this view. Patients with isolated PSC tend to present with jaundice, pruritus, and fatigue more frequently than those with combined PSC and IBD. There may also be a difference in bile duct involvement between patients with and without IBD combined with PSC. Apart from usually being a total colitis, either Crohn's colitis or UC, the IBD associated with PSC cannot be distinguished from IBD without PSC with respect to symptoms and clinical course. Patients with combined IBD and PSC may have somewhat worse prognosis than those with isolated PSC. The majority of patients developing BDC have concomitant IBD, suggesting that patients without IBD represent a different subgroup of PSC and run a different clinical course. Most studies have, however, found no differences in epidemiology, pathogenetic factors, clinical findings related to the hepatobiliary disease and prognosis between those who present with PSC alone and those who present with combined PSC and IBD. A major problem when discussing the relationship between IBD and PSC is that the bowel is inadequately examined in many of the studies relating to this question.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholangitis, Sclerosing↗

The peptide pyroGlu-Gln-Gly-Ser-Asn, isolated from mouse liver, inhibits growth of rat hepatoma cells in vitro.

The peptide pyroGlu-Gln-Gly-Ser-Asn, recently isolated from mouse liver, inhibited DNA synthesis and proliferation in vitro of MH1C1 cells, a rat clonal strain derived from a Morris transplantable hepatoma. Both the biological peptide isolated from mouse liver and the synthetic homolog showed bell-shaped dose-response curves. Maximal inhibition (approximately 50%) was observed at two separate dose ranges: one at 10(-7)-10(-10) M, and one at 10(-14)-10(-15) M.

Amino Acid Sequence↗

Eccrine angiomatous hamartoma of the finger leading to amputation.

A case of eccrine angiomatous naevus in a 34-year-old pregnant woman is described. The tumour was located on the dorsal aspect of the distal phalanx of the left little finger causing severe pain. Partial resection provided no improvement and finally amputation was necessary. Histological examination revealed the typical appearance of an eccrine angiomatous hamartoma with a large number of eccrine ducts combined with vascular structures.

Adult↗

The epidermal pentapeptide pyroGlu-Glu-Asp-Ser-GlyOH inhibits murine hair growth in vivo and in vitro.

Tissue growth may be controlled by negative feedback mechanisms. Recently, a pentapeptide, pyroGlu-Glu-Asp-Ser-GlyOH ('epidermal pentapeptide', EPP), which slows the growth of mouse epidermis in vivo and of mouse keratinocytes in vitro, was isolated from mouse epidermis. Since inhibitory molecules like EPP might be part of the feedback systems underlying hair growth control, we assessed the effect of synthesized EPP on the growth of hair follicles, using rodent in vivo and in vitro assays. We report for the first time that intraperitoneally injected EPP (30 nmol/animal/day over 6 days) significantly slows the growth of hair follicles in plucking-induced anagen skin of C57 B1-6 mice (as assessed by microscopic morphometry). Using an in vitro organ culture assay, EPP inhibits the incorporation of 3H-thymidine into mouse pelage anagen follicles. That this epidermal-derived peptide affects hair growth raises the possibility that hair growth may be regulated by an inhibition/disinhibition mechanism under participation of EPP-like molecules and that the epidermis may play a role in the control of hair growth.

Alopecia↗

[Chronic non-A non-B hepatitis treated with interferon].

Non-A non-B hepatitis remains a diagnostic and therapeutic problem. Recently published data indicate that interferon may represent a considerable step forward in the therapy of this disease. We have treated a patient with non-A non-B hepatitis with recombinant interferon alpha 2-B. Both biochemical and morphological liver parameters were normalized after nine months of treatment. Further studies are being performed to establish the efficacy and effective doses of interferon in the treatment of non-A non-B hepatitis.

Adult↗

[Primary sclerosing cholangitis and inflammatory bowel disease].

Primary sclerosing cholangitis (PSC) is a syndrome of unknown etiology, characterized by fibrosis and inflammation of the intra- and extrahepatic bile ducts. PSC is usually seen in association with inflammatory bowel disease, particularly in younger patients with extensive ulcerative colitis. Crohn's disease is seen in more than 10% of all patients with PSC. The bowel disease may produce no symptoms in some patients, and the clinical course is usually silent. The development and widespread use of endoscopic retrograde cholangiopancreaticography (ERCP) have enabled us to diagnose the disease far more often than was possible only a decade ago, and also to recognize that PSC has a much wider clinical and pathologic spectrum than previously realized. Most patients with concomitant ulcerative colitis and persistently abnormal liver function tests are likely to have PSC. Patients with PSC usually have a cholestatic biochemical profile, whereas the histologic features of the liver biopsy are variable and often nonspecific. Cholangiography displaying strictures and beading is diagnostic of the disease. The prognosis is variable, with a benign clinical course in many patients. However, an increased rate of cholangiocarcinoma is found in PSC, as is an increased rate of colonic cancer in patients with PSC and ulcerative colitis.

Adolescent↗

Mouse epidermal cell renewal after topical treatment with different concentrations of the epidermal peptide pyroGlu-Glu-Asp-Ser-GlyOH.

Earlier work has shown that epidermal cells contain a peptide, pyroGlu-Glu-Asp-Ser-GlyOH, that induces a moderate but long-lasting inhibition of epidermal cell proliferation when given at low (picomol) doses ip in vivo and in vitro. In the present study, the epidermal pentapeptide was applied topically to the back skin of hairless mice at different concentrations and in a water-miscible cream. A single topical application of either high (0.25% wt/wt) or low (0.004% or 0.02% wt/wt) doses of the pentapeptide was followed by oscillations in epidermal DNA synthesis and G2-M cell flux (mitotic rate). In general, epidermal cell proliferation was inhibited during the first 10-day period after treatment with the two lower doses, while the highest concentration of pentapeptide (0.25%) stimulated epidermal cell proliferation. In spite of the effects on epidermal cell proliferation the size of the epidermal cell population in the treated area (number of nucleated cells and epidermal thickness) showed no corresponding alterations. The results could imply that the epidermal pentapeptide modifies epidermal cell proliferation and terminal differentiation in such a way that the two are balance with each other.

Administration, Topical↗

Isolation of a growth and mitosis inhibitory peptide from mouse liver.

The isolation of a liver peptide that inhibits the growth, mitosis rate and thymidine incorporation in regenerating liver is described. The peptide has the structure Pyroglu-gln-gly-ser-asn, and the deamidated forms are also active. The peptide probably belongs to a class of growth inhibitors with a high degree of tissue specificity. Two such peptides have previously been isolated from the epidermis (Reichelt et al. 1987) and from colonic tissue (Skraastad et al. 1987).

Amino Acid Sequence↗

UVB-induced epidermal hyperproliferation is modified by a single, topical treatment with a mitosis inhibitory epidermal pentapeptide.

A single application of a water-miscible cream base containing the recently identified mitosis inhibitory epidermal pentapeptide pyroGlu-Glu-Asp-Ser-GlyOH (EPP) to hairless mouse skin is followed by a long-lasting period of reduced epidermal cell proliferation. To examine if a similar growth inhibition could be achieved in stimulated and rapidly proliferating epidermis, EPP was applied at two different concentrations, 0.005 or 0.02%, to hairless mouse skin immediately after exposure of the left flank to an erythemic dose of ultraviolet B light (UVB). This dose of UVB alone induces a sustained period of rapid epidermal cell proliferation, starting at about 18 h after the irradiation. Epidermal cell proliferation was followed from 18 to 54 h (0.005% cream) or from 18 to 30 h (0.02% cream) after the treatment by estimating the rate of G2-M cell flux (the mitotic rate) by means of Colcemid, and epidermal DNA synthesis by counting labeled cells after pulse-labeling with 3H-thymidine. The unirradiated side of the mice was used as reference. The results showed that topical treatment with a 0.02% EPP cream partially inhibited UVB-induced epidermal hyperproliferation, while the 0.005% EPP cream inhibited as well as stimulated the UVB-induced hyperproliferation. Thus, EPP is effective even in rapidly proliferating epidermal cell populations, but the outcome is obviously dose-dependent in this test system.

Animals↗