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Biomedical subjects

K Elgjo

Publications and source records attributed to K Elgjo.

At least 55 records · Page 3Linked to original sources

Synthetic epidermal pentapeptide and related growth regulatory peptides inhibit proliferation and enhance differentiation in primary and regenerating cultures of human epidermal keratinocytes.

A pentapeptide that inhibits proliferation of mouse epidermal keratinocytes in vivo and in vitro has been purified from mouse skin extracts. In the present study the effect of a synthetic analog of the epidermal pentapeptide on proliferation and differentiation of cultured human epidermal keratinocytes was investigated. In young, rapidly growing primary cultures the pentapeptide caused a dramatic decrease in mitotic activity and also induced pronounced changes in the balance between kinetically defined subpopulations of proliferating cells. A dipeptide derived from the pentapeptide was found to be at least as potent. A serine derivative of a hemoregulatory peptide also seemed to be active. When tested in epidermal cultures regenerating after removal of the suprabasal cell layers, both the pentapeptide and the dipeptide were shown to cause a delay in the proliferative response. Both peptides were also able to stimulate early (increase in cell size) and late (cornified envelope formation) events in the differentiation pathway of the keratinocyte. The apparent stimulatory effect on differentiation was most clearly seen in regenerating cultures, whereas the effect on primary cultures varied with the experimental set-up. It is suggested that homologous epidermal peptide(s) may play a major role in the regulation of human epidermal homeostasis.

Autoradiography↗

Hepatic lesions in adult coeliac disease.

In the period 1970 to 1987, 171 patients with small-intestinal mucosal atrophy have been hospitalized in our department. Of these, 132 patients fulfilled the diagnostic criteria of coeliac disease on the basis of histologic findings and clinical improvement on a gluten-free diet. Aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), and alkaline phosphatase (ALP) were chosen as markers of hepatic involvement. Elevation above the normal range in one or more of these tests was seen in 62 patients (47.0%, group I). In 70 patients (53.0%, group II) of similar age the levels of these variables were normal. In group I, 14 (10.6%) patients had an elevation of ALP only, leaving 48 (36.4%) patients with pathologic values for one or both transaminases. In group I, 32 patients had their ASAT, ALAT, and ALP reexamined after at least 6 months of gluten-free diet. Among the patients with increased values of one or both transaminases 18 patients were tested before and at least 6 months after start of gluten-free diet. The variables were significantly reduced in all patients. Liver biopsies were performed in 37 patients, and findings were normal in 5. In 25 patients the changes were classified as non-specific. Chronic active hepatitis was demonstrated in five patients. In one of these patients primary sclerosing cholangitis and ulcerative colitis were also diagnosed. Concomitant malignant disease was found in 22 patients, of whom 16 had malignant lymphoma. Malignant disease was seen more often in group I than group II (p less than 0.01). In conclusion, liver lesions were found in a great proportion of the patients with coeliac disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The significance of anti-hepatitis C virus antibodies measured in chronic liver disease.

The frequency of hepatitic C virus (HCV) antibodies was determined in two different laboratories in stored sera from 128 consecutive patients with chronic liver disease and from 41 healthy blood donors. Repeated measurements were performed in most patients. At the first determination the frequency of HCV antibodies was 7% in primary sclerosing cholangitis, 42% in primary biliary cirrhosis, 40% in autoimmune chronic active hepatitis, and 27% in alcoholic liver disease. The reproducibility of the determinations was rather poor, with a within-assay variation of 9.9%, whereas the between-assay variation was 34% and 47% in the two laboratories. There was a significant difference in the results obtained in the controls, depending on the handling of the sera. Freezing and thawing and, possibly, protracted storing of sera had a major impact on the assay and may have invalidated the results obtained in many studies. A significant association between IgG levels and titers of HCV antibodies was found in the total group of patients (p less than 0.005), in autoimmune chronic active hepatitis (p less than 0.005), and in primary biliary cirrhosis (p less than 0.01). It may be questioned whether the assay really is specific for anti-HCV antibodies in these patients. Whether HCV has anything to do with the etiology and pathogenesis of chronic liver disease apart from NANB-hepatitis is still undetermined.

Adolescent↗

Factors of prognostic importance in primary biliary cirrhosis.

To determine survival and the risk factors of death in primary biliary cirrhosis, data from 52 symptomatic and 13 asymptomatic patients were analyzed. The mean follow-up time was 6.3 years (range, 0.4-23 years). The average length of survival was 18 years for the symptomatic and 8.4 years for the asymptomatic patients. By a univariate analysis, ascites, presence of esophageal varices, gastrointestinal bleeding, jaundice, hepatomegaly and the logarithms of albumin and bilirubin were all associated with a poor prognosis. A multivariate analysis of the clinical features showed that the presence of bleeding from esophageal varices and the logarithm of bilirubin were the only predictors for poor prognosis. The survival of the symptomatic patients is longer than reported previously, while the life expectancy for the asymptomatic patients seems no better than for the symptomatic group.

Chronic Disease↗

Pentapeptide inhibitor of epidermal mitosis: production and responsiveness in cultures of normal, transformed and neoplastic human keratinocytes.

A pentapeptide, pyroGlu-Glu-Asp-Ser-GlyOH, was previously isolated from mouse skin and shown to inhibit reversibly proliferation of murine keratinocytes, both in intact skin and in culture. In the present report we have shown that proliferation of normal human keratinocytes in culture is also inhibited by the pentapeptide, whether the cells are grown under standard conditions or prevented from stratifying in medium containing a low concentration of calcium ions. An SV40-transformed line of human keratinocytes, SVK14, was completely insensitive to the pentapeptide and a line derived from a squamous cell carcinoma of the oral cavity, SCC-9, was less sensitive than the normal cells. The effect of the pentapeptide on terminal differentiation was determined by measuring the proportion of cells expressing involucrin after a single dose or repeated doses of the pentapeptide: no consistent change in the number of terminally differentiating cells was observed. Cell extracts and conditioned medium from all three cell types contained the epidermal pentapeptide, suggesting a role for the peptide in both autocrine (normal keratinocytes) and paracine (SVK14, SCC-9) growth control. A proportion of the pentapeptide isolated from conditioned medium was phosphorylated; since it was as active as the non-phosphorylated form, when assayed on mouse epidermis, the role of phosphorylation remains to be determined.

Amino Acid Sequence↗

Enhancement of methylnitrosourea-induced skin tumorigenesis and carcinogenesis in hairless mice by pretreatment with a mitosis-inhibiting epidermal pentapeptide.

Two groups of 48 hr/hr mice (24 males, 24 females) were pretreated i.p. with 0.03 nmol of a synthetic epidermal mitosis-inhibiting pentapeptide (EPP), pGlu-Glu-Asp-Ser-GlyOH, dissolved in bovine serum albumin solution (BSA) at -6, -3 and 0 h before a topical skin application of 1 mg N-methyl-N-nitrosourea (MNU) in 100 microliters reagent-grade acetone. A control group was pretreated with three solvent injections only -6, -3 and 0 h before application. The results were also compared with a large, historical control group of 333 animals treated once with 1 mg MNU and without any pretreatment. The production of benign and malignant skin tumours was recorded and the results were assessed statistically. There was no statistically significant difference between the large control group without pretreatment and the actual control group pretreated with BSA. Pretreatment with EPP led to significant enhancement of the number of tumour-bearing animals with time and to a very significant increase in the total number of tumours. The group pretreated with EPP also developed more malignant skin tumours. The results are in agreement with earlier findings after i.p. pretreatment with crude skin extracts, hydroxyurea, or when MNU was applied in relation to diurnal rhythms in epidermal cell proliferation. They are also consistent with the assumption that EPP is one of the active growth-inhibitory substances in the epidermal extracts, and support the hypothesis that epidermal basal cells may be more sensitive to MNU-induced carcinogenesis when the rate of cell proliferation is low, because then more cells are in late G1 or early S phase where MNU binding to DNA may be relatively strong.

Animals↗

Bacteria of the gastric antrum and their relation to chronic gastritis.

Biopsy samples from the gastric antrum were taken from 61 patients. On bacteriological culture, Campylobacter pylori was isolated in 27 subjects. Thirty-four patients had chronic gastritis, as seen in routine-stained histological sections. By means of the May-Grünwald-Giemsa (MGG) staining technique, bacteria were demonstrated in sections from 26 subjects. Of these, 22 had gastritis histologically. In 13 subjects, structures similar to Campylobacter pylori were found in MGG-stained sections, 11 of these having chronic active gastritis histologically. Scanning electron microscopy demonstrated bacteria with the typical appearance of Campylobacter pylori, but other types of bacteria were also found, both on electron microscopy and on bacteriological culture. The study confirms that there is an increased frequency of histological gastritis when Campylobacter pylori is present in the samples (p = 0.009). However, a causative role of the bacteria could not be demonstrated in this study, and bacterial penetration into the epithelium was not observed.

Adult↗

Local immune defence in relation to gastritis in Billroth-II-resected stomachs.

Biopsy specimens from Billroth-II-resected stomachs obtained endoscopically 28-32 years after the operation were subjected to an immunohistochemical study by two-colour immunofluorescence staining. The epithelial distribution of immunoglobulin A (IgA), secretory component (SC), lysozyme (Ly), and lactoferrin (Lf) was evaluated, and IgA-, IgM-, and IgG-producing cells were quantified in the lamina propria. Gastric body mucosa excised from resected stomachs obtained from patients with duodenal ulcer was used as control and showed considerably less extensive gastritis than the stump mucosa. Both specimen categories showed enhanced expression of epithelial IgA, SC, Ly, and Lf associated with severe gastritis, except for areas with intestinal metaplasia, which lacked Ly and Lf. The number of IgA-, IgM-, and IgG-producing cells was significantly increased with increasing degree of gastritis, particularly so for IgG cells on a relative basis. After partial gastrectomy, therefore, the stump mucosa generally responds with activation of local immune mechanisms; this response is principally similar to that seen in simple gastritis of comparable severity.

Adult↗

Isolation and structure of an epidermal mitosis inhibiting pentapeptide.

A mitosis inhibiting peptide pyroGlu-Glu-Asp-Ser-GlyOH has been isolated from mouse skin extracts. Both the biological and a synthetic peptide with the same structure reversibly inhibit epidermal mitoses in a curvilinear fashion after intraperitoneal injection. The two compounds are chromatographically identical.

Animals↗

Circulating secretory immunoglobulins of the A and M isotypes in chronic liver disease.

Serum levels of secretory IgA (SIgA) and secretory IgM (SIgM) were quantified by an enzyme-linked immunosorbent assay in 97 patients with various chronic liver diseases and 17 patients with uncomplicated ulcerative colitis. The values obtained were compared with 89 matched controls and related to other serum variables. All types of liver disease had elevated median levels of serum SIg. Patients with primary biliary cirrhosis (PBC) had the highest SIg levels, particularly SIgM, but increased total serum IgM was slightly more specific for PBC. Thus, the SIg levels did not add more discriminative information than several other variables. Elevated levels of circulating SIgA correlated mainly with variables that indicate reduced liver function. The difference observed between patients with PBC and primary sclerosing cholangitis (PSC) in the alkaline phosphatase (ALP)-to-SIg ratio is discussed.

Alkaline Phosphatase↗

Heterogeneous epithelial expression of class II (HLA-DR) determinants and secretory component related to dysplasia in ulcerative colitis.

The intensity and degree of heterogeneous epithelial marker expression were evaluated immunohistochemically in 29 mucosal biopsy specimens from 7 ulcerative colitis (UC) patients with dysplasia. Biopsy specimens from UC patients with mild (n = 7) or severe (n = 6) inflammation and from histologically normal samples (n = 7) served as controls. HLA-DR showed heterogeneous epithelial expression in all lesions with high grade dysplasia and in 6 of 8 with low grade dysplasia. SC was heterogeneous stained in 17 of 21 lesions with high grade dysplasia and in all but two lesions with low grade dysplasia. In histologically normal mucosa, SC was homogeneously expressed and epithelial DR was virtually absent. In mildly inflamed UC lesions, SC exhibited patchy distribution in only one sample and DR in two, whereas both SC and DR showed a slight degree of heterogeneous expression in all lesions with severe inflammation. Moreover, the overall intensity of SC staining tended to decrease with increasing degree of inflammation, whereas the opposite was seen for DR. Decreased SC and increased DR expression thus seemed to be related to intensified inflammatory activity, whereas heterogeneous expression of these markers was significantly more related to dysplasia.

Adolescent↗

Local immunoglobulin production is different in gastritis associated with dermatitis herpetiformis and simple gastritis.

The degree of inflammation and atrophy in gastric body mucosal specimens (n = 38) from 28 patients with dermatitis herpetiformis (DH) was graded histologically. Immunoglobulin (Ig) producing cells were enumerated by paired immunofluorescence staining in a 500 microns wide section area from the muscularis mucosae to the lumen (mucosal 'tissue unit'). The number of immunocytes of the three main classes (IgA, IgM, and IgG) was significantly raised with increasing degree of gastritis. All three classes were increased in specimens showing atrophy compared with those without atrophy. IgA cells predominated as in simple gastritis, but a striking difference was a marked increase of IgM cells in specimens with the most pronounced DH-associated gastritis. Relative class distribution of immunocytes within different mucosal zones showed that the percentage of IgA cells was significantly higher in the luminal than in the basal zone, whereas the contrary was true for IgG cells. IgM cells did not show any zonal preference. No relation was seen between small bowel and gastric lesions. The disproportionate increase of gastric IgM producing cells in DH might nevertheless reflect seeding of precursor cells of the secretory immune system generated in the proximal small intestine where the local IgM response is relatively pronounced.

Adolescent↗

Primary sclerosing cholangitis: a long-term follow-up study.

During the 10-year period from 1 January 1975 to 31 December 1984, primary sclerosing cholangitis (PSC) was diagnosed in 45 patients. Twelve of the patients have died (26.7%), 10 of them of causes related to PSC. Inflammatory bowel disease was found in all patients; ulcerative colitis was found in 37, Crohn's disease in 6, and unclassified colitis in 2 patients. Of the patients alive, 27 were submitted to a follow-up study in 1985. At the follow-up examination no general progression of the liver disease, as measured on the basis of clinical examination and levels of transaminases, alkaline phosphatases, and bilirubin, was found. Cholangiographic evaluation in 24 patients showed that the stage of ductal changes progressed from mild to moderate in 3 patients; in the other patients the stage was not altered. Morphologic examination of liver biopsy specimens in patients with a benign clinical course usually showed portal inflammation, fibrosis, and minor signs of piecemeal necrosis, whereas widespread piecemeal necrosis was found in patients who deteriorated and died. The 50% survival since diagnosis of liver disease was calculated to be 17 years in patients with PSC and 50 years in a comparable group among the general population. The estimated survival curve in PSC was displaced to the left, indicating a reduced life expectancy of about 30 years.

Adolescent↗

Altered growth kinetics precede calcium-induced differentiation in mouse epidermal cells.

Primary cultures of newborn mouse epidermal cells proliferate rapidly and with a high growth fraction for several months when grown in medium with low calcium (0.02 to 0.1 mM). Addition of calcium to levels generally used in culture medium (1.2 mM) was followed by rapid changes in the pattern of proliferation. By using a combination of technics (a stathmokinetic method, autoradiography, [3H]thymidine incorporation into DNA, DNA flow cytometry) it was found that cell flux was blocked for 5 to 6 h, followed by a short rise in the mitotic rate at 10 h, and a gradual fall in all growth parameters until about 32 h after the calcium switch. There was no accumulation of cells in any particular cell cycle phase. The results indicate that the calcium switch is followed by a strong reduction in cell flux from G1 whereas the majority of the cells that had left G1 at the time of the switch completed one cell division before cessation of all proliferative activity. Both before and after the switch the primary epidermal cultures consisted of one diploid and one tetraploid G1 DNA stemline that seemed to react in the same way to calcium.

Animals↗

Purified epidermal pentapeptide inhibits proliferation and enhances terminal differentiation in cultured mouse epidermal cells.

Skin extracts contain an epidermal mitosis inhibitor that recently has been purified and identified as a pentapeptide. To develop an in vitro assay system for further biologic characterization, primary mouse epidermal cells and an established mouse epidermal cell line (line 308) were used for testing of the purified pentapeptide. In primary cell cultures the mitotic activity, as estimated by means of vinblastine, was reversibly inhibited by 44% at a peptide concentration of 10(-8) M in high-calcium (1.2 mM Ca++), and by 27-38% at peptide concentrations of 10(-10) and 10(-8) M in low-calcium (0.02 mM Ca++) medium. The 308 cells were inhibited by 46% at a peptide concentration of 10(-6) M but only after the cells had reached near-confluence and had a moderate rate of proliferation. A low concentration of adrenaline (0.18 micrograms/ml) in the medium rendered the primary cultures more sensitive to the peptide. After repeated peptide treatments over 24 h, the number of cornified envelopes (a marker of terminal differentiation) was increased both in primary cultures and in the 308 cells. The epidermal pentapeptide thus seems to influence both proliferation and terminal differentiation in cultured mouse epidermal cells.

Animals↗

Quantitative distribution of immunoglobulin-producing cells in gastric mucosa: relation to chronic gastritis and glandular atrophy.

Immunoglobulin (Ig)-producing immunocytes were quantified by paired immunofluorescence staining in specimens of gastric antral (n = 52) and body (n = 117) mucosa obtained from 45 patients with various gastrointestinal disorders. Enumerations were carried out in a 500 micron wide zone from the muscularis mucosae to the lumen ('tissue unit'). The specimens were divided into three categories according to the degree of inflammation, and each specimen received a grade for atrophy (0-2). The total number of IgA-, IgM- and IgG-producing cells per tissue unit increased strikingly with increasing degree of inflammation, both in antral and body mucosa. IgA immunocytes predominated (61-91%) in all specimens, but the IgG isotype showed the largest relative increase (four to 17-fold), particularly in the basal part of the mucosa. In this layer of the gastric body the proportion of IgG cells was also significantly raised in association with atrophy, irrespective of degree of inflammation. Locally produced IgG may be of protective significance in terms of internal (or 'second line') defence but may at the same time maintain immunopathological mechanisms contributing to the chronicity of gastritis.

Adolescent↗