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Biomedical subjects

K Elgjo

Publications and source records attributed to K Elgjo.

At least 73 records · Page 4Linked to original sources

DNA synthesis rate changes during the S phase in mouse epidermis.

The in vivo DNA synthesis rate throughout the S phase of mouse epidermal cells was investigated. Epidermal basal cells were isolated at various times of the day from normal animals injected with [3H]TdR 30 min before sacrifice, and from pulse-labelled animals with regenerating and growth-inhibited epidermis. The cells were analysed by DNA flow cytometry combined with cell sorting. Cells from successive fractions of the S phase were sorted on glass slides and subjected to quantitative [3H]TdR autoradiography. The results confirmed the presence of unlabelled (slowly replicating) cells in the S phase, the proportion of which was circadian stage-dependent with minimum values at midnight and in the early morning. The DNA synthesis rate throughout the S phase showed a general trend with high values in the mid-fractions, a pattern which was similar in normal and in growth perturbed epidermis. In the early morning the DNA synthesis rate pattern was bimodal with maxima both in the first and second half of the S phase, with a corresponding trough in mid-S. At this time of day the cell progression rate through S is at its maximum, indicating a relationship between the overall DNA synthesis rate and the rate distribution pattern through S.

Animals↗

Lactate dehydrogenase isoenzymes in mucosal biopsy specimens from patients with ulcerative colitis.

Biopsy specimens from long-standing ulcerative colitis were frozen shortly after resection and homogenized before measurement of lactate dehydrogenase (LD) isoenzymes by agar electrophoresis. Results were related to histological changes in inflammation or dysplasia. The percentage of total LD M monomers was significantly higher in homogenates of specimens with dysplastic changes than in homogenates of specimens with only inflammatory changes. A positive correlation was found between total LD M monomers and LD5 monomers (isoenzyme) for the whole material, for each of the histological subgroups of ulcerative colitis, and for the control specimens of adenomas, carcinomas, and normal mucosa. A positive correlation between total LD activity and total percentage of LD5 monomers was only seen for dysplastic, adenomatous, and malignant tissues. The results support the use of dysplasia as a marker for premalignant changes in mucosal specimens and indicate a possible role for LD isoenzyme measurements in specimens from patients with long-standing ulcerative colitis.

Adenoma↗

Crohn's disease. Diagnostic procedures and problems.

Two hundred and fourteen patients with Crohn's disease (CD) were investigated by radiological methods, endoscopy, and histological examinations of multiple biopsy and surgical specimens. Radiological lesions suggestive of CD were found in all patients with small-bowel disease but in less than half of those with large-bowel CD. Endoscopic findings were conclusive in 36% of patients with small-bowel disease, in 91% of those with small- and large-bowel disease, and in 86% of those with CD of the large bowel. Histological examinations of biopsy specimens were conclusive in less than one third of the patients. Histological examination of operative specimens, however, was conclusive in 90-100% of all patients. In 43 patients initially diagnosed as having ulcerative colitis, abdominal pain was less frequent, but diarrhea and visible blood were more frequent as initial symptoms. Of these patients, 21 had combined small- and large-bowel disease at the end of the observation time. In intestinal CD, multiple biopsy specimens may disclose Crohn-specific lesions even in endoscopically normal mucosa at a distance from visible lesions.

Colitis, Ulcerative↗

Crohn's disease. Clinical manifestations.

Two hundred and fourteen patients with Crohn's disease (CD) consecutively admitted during a 5-year period were observed for a mean of 9 years (range, 0-35 years). Sixty-five per cent had their initial symptoms between 10 and 30 years of age and 9.2% after the age of 50 years. The CD diagnosis was delayed for more than 10 years in 8% (mean, 4.5; range, 0-31 years). Large-bowel involvement was seen in 82.5% and was the only localization of the disease in a fourth of the patients. Recurrent abdominal pain occurred in two-thirds of patients with ileal or ileocolic disease. Acute abdominal pain was the cause of laparotomy in 14% of the patients with ileocolic CD. Diarrhea and rectal bleeding occurred significantly more often in colonic CD, whereas fistula complicated ileocolic disease more often than isolated involvement of small or large bowel. Associated extraintestinal diseases were seen in 117 patients (55%), most frequently related to colonic involvement (joint disease, 21%; eye, 12%, skin, 8%). Of 26 patients (12%) with liver pathology, 10 patients had amyloid deposits. Amyloidosis was diagnosed in altogether 12 patients (6%).

Adolescent↗

Enzyme activity and protein patterns as premalignant markers in mucosal biopsy specimens from the large intestine.

Total enzyme activity of glucose-6-phosphate dehydrogenase (G6PD) and lactate dehydrogenase (LD) was measured in homogenates of resected biopsy specimens and in endoscopic biopsy specimens. LD isoenzyme patterns were scanned by a laser technique after agarose gel electrophoresis. Examinations were performed in homogenates of premalignant lesions such as ulcerative colitis and adenomas of the colon, with normal mucosa and carcinomas as control material. Additionally, two-dimensional electrophoretic protein patterns were compared for normal mucosa, adenomas, and carcinomas of the large intestine. The mean activity of both G6PD and LD was highest in the presence of dysplasia; however, only G6PD activity seemed independent of inflammatory changes. The percentage of LD isoenzyme M monomers was significantly higher in homogenates of specimens with dysplastic changes than in specimens with only inflammatory changes. A positive correlation was found between total LD isoenzyme M monomers and LD 5 monomers for the whole material and for each of the histological subgroups of ulcerative colitis. A positive correlation between total LD activity and the percentage of LD 5 monomers was seen only for dysplastic, adenomatous, and malignant tissues. The several hundred protein spots seen on two-dimensional protein maps showed that most of the spots were common for normal mucosa, adenomas, and carcinomas, but differences were also seen. Polyps and carcinomas had strikingly similar protein patterns, different from that of normal mucosa. The results of the two-dimensional protein electrophoresis lend further support to the hypothesis that polyps are precursors of carcinomas of the large intestine.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗

Follow-up and prospective studies of the classification of liver disease.

Two hundred patients with different liver diseases were observed during a period of 6-8 years. The diagnosis at the first hospitalization was based on morphological criteria (and, in some cases, additional clinical information). In 162 of the cases an initial 'specific' diagnosis could be made. By the time of the follow-up study the diagnosis was confirmed in 73% of them. In 22 of 38 patients who were initially unclassifiable, the diagnosis was made definite by the follow-up study. Eighty-five patients were hospitalized for re-examination 6-8 years after the initial study. Several of the liver diseases initially had quite typical patterns of clinical chemical data. Allocation by discriminant analysis was therefore in good agreement with the morphological classification. The follow-up study showed that several patients with initially atypical patterns of clinical chemical results had their diagnosis changed. In 35 patients with the final diagnosis of chronic active hepatitis (CAH) or primary biliary cirrhosis (PBC), laboratory data from the last hospitalization were used for discriminant analysis with teaching data from the initial study. Ninety-seven per cent were correctly allocated, and we conclude that these patients retain recognizable patterns of laboratory results for several years, even when given immunosuppressive treatment. The potential clinical usefulness of discriminant analysis of laboratory data for differential diagnosis was evaluated by a prospective study of 65 patients with the morphological diagnosis of CAH or PBC. Correspondence with the morphological classification system was found in almost 90% of the cases.

Chronic Disease↗

Chronic active hepatitis. Experience from a Norwegian reference hospital during a decade.

During the decade from 1 January 1971 to 31 December 1980. 90 hospitalized patients fulfilled the diagnostic criteria of chronic active hepatitis (CAH). An aetiological agent was identified in 13 of the patients: hepatitis B virus infection in 6 and a drug in 7. The other 77 cases were assumed to be idiopathic. The mean age at presentation was 32 years, and 66 (73%) of the patients were female. The patients have been followed up until death or until 31 December 1981. The mean observation period was 114 months. Twenty-five (28%) patients died. 19 of them of liver disease. Complications or signs of portal hypertension were observed in 62%. Of the 18 patients with upper gastrointestinal bleeding 15 had a portal-systemic shunt performed. Associated diseases in other organ systems were observed in 16 (18%) of the patients. Pronounced biochemical activity was found in 80 (89%) of the patients. Immunosuppressive therapy was started in 84 (93%), either as corticosteroids alone (40 patients) or in combination with azathioprine (44 patients). Azathioprine was later withdrawn in 29 (66%), in 6 because of side effects and in 20 because of clinical and biochemical improvement. Corticosteroids were withdrawn in 22 (26%), in 2 because of side effects and in 18 because of improvement. In 35 of the 45 patients in whom discontinuation was attempted, the treatment had to be reinstituted. Eight of the patients on combined therapy could discontinue both immunosuppressive drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Dimethyl nitrosamine-induced proliferative and neoplastic lesions in the mouse liver characterized by histopathology and flow cytometric DNA measurements.

Thirty-one liver tumours induced in NMRI mice by treatment of the newborn animals with the carcinogen demethyl nitrosamine were examined histopathologically and by flow cytometric determination of nuclear DNA content. The tumours were classified as nodules of hyperplasia, adenomas or hepato-cellular carcinomas. Single cell suspensions from each tumour were analyzed by flow cytometry. The lesions consisted of cells with stemlines of low ploidy (2c and 4c) as compared to the high ploidy of the surrounding parenchymal cells (4c, 8c and 16c). The hyperplastic nodules contained stemlines of both diploid and tetraploid DNA content, whereas the adenomas and most of the carcinomas were diploid. The possible occurrence of aneuploid cells in the lesions is discussed.

Adenoma↗

Incorporation of precursors into sterols and proteins in liver biopsies from patients with liver disorders.

Incorporation of 14C-acetate into 3-beta-OH sterols and of 3H-leucine into proteins was examined in liver biopsies from patients with liver disorders. Biopsies obtained from patients in whom no liver disease was found served as controls. Reduced 14C-acetate incorporation into sterols was found in biopsies from patients with chronic active hepatitis and primary biliary cirrhosis. Stimulated incorporation of 3H-leucine into proteins was demonstrated in patients with alcoholic liver cirrhosis and in patients with ulcerative colitis associated with liver disease. No correlation could be established between serum proteins and lipids, respectively, on the one hand, and between incorporation of precursors into proteins and sterols, on the other. 'Incorporation parameters' were also inferior to conventional liver tests when used in the differential diagnosis between different liver disorders by discriminant analysis. Our findings may suggest, however, that hepatic sterol synthesis is frequently decreased in patients with chronic active hepatitis and primary biliary cirrhosis.

Adult↗

Specific and nonspecific humoral defense factors in the epithelium of normal and inflamed gastric mucosa. Immunohistochemical localization of immunoglobulins, secretory component, lysozyme, and lactoferrin.

Epithelial distributions of immunoglobulin A, secretory component, lysozyme, and lactoferrin were studied by paired immunofluorescence staining in ethanol-fixed biopsy specimens from gastric antral and body mucosa. Fluorescence scores were assigned semiquantitatively for the epithelium in three mucosal zones (foveolar, isthmus, and glandular). In each case, degree of inflammation was graded blindly after conventional histologic staining of serial sections. The results showed that the overall epithelial expression of local defense factors was significantly enhanced in association with gastritis, both with regard to nonspecific antimicrobial substances (lysozyme and lactoferrin) and the external transfer of immunoglobulin A (mediated by secretory component) as a potential carrier of protective antibodies. The antral isthmus and glandular zones were most active in both respects. Despite the expression of relatively large amounts of epithelial immunoglobulin A and secretory component in metaplastic glands, these elements lacked the nonspecific defense factors (except for lysozyme in Paneth cells)--even when they occurred in the antral mucosa--and may, therefore, represent particularly vulnerable areas.

Adult↗

Measurement of enzyme activity in colonic biopsies: a test for premalignancy in ulcerative colitis?

Enzyme activity was studied in relationship to histological changes in biopsy specimens removed after resection from patients with inflammatory bowel disease. Glucose-6-phosphate dehydrogenase (G6-PDH) and lactate dehydrogenase activities were measured in homogenates from 276 large-intestinal biopsy specimens, classified histologically in accordance with grade of inflammation and dysplasia. The mean activity of both enzymes was highest in the presence of dysplasia; however, only G6-PDH activity seemed independent of inflammatory changes. In the seven patients with dysplasia both enzyme activities were significantly raised in segments with dysplasia, compared with those without. The results support the use of dysplasia as a marker of premalignancy and may suggest a role for measurements of enzyme activity in the evaluation of patients with ulcerative colitis.

Biopsy↗

Distribution of dysplasia in ulcerative colitis.

Epithelial dysplasia was found in the large intestine of 8 of 15 patients with ulcerative colitis operated on between 1980 and 1982. In six of eight patients, dysplasia was found in the cecum and ascending colon, in one of eight in the descending or sigmoid colon, and in four of eight in the rectum. None of the five carcinomas in three patients were located in the sigmoid colon or rectum. The age of onset was much lower, 19 +/- 7 years, and the duration of colitis longer, 15 +/- 7 years, for the group with dysplasia compared with that without dysplasia, 37 +/- 18 and 4 +/- 3 years, respectively. Our study indicates that malignant transformation may frequently occur in the proximal colon and emphasizes the need for total colonoscopy with multiple biopsies in the evaluation of patients with long-standing ulcerative colitis.

Adolescent↗

Proliferation-dependent effect of skin extracts (chalone) on mouse epidermal cell flux at the G1-S, S-G2 and G2-M transitions.

Epidermal cell proliferation in mice was studied from 4 to 11 h following a single intraperitoneal (IP) injection of a crude skin extract. Cell cycle flux parameters were evaluated by a combination of several methods. The G1-S and S-G2 transit rates were estimated by means of a 3(H)TdR double labelling technique, and the mitotic rate by use of colcemid. The 3(H)TdR labelling index was also measured. To examine the possible influence of the circadian rhythm, all experiments were performed at two different times of the day with high or low rate, respectively, of epidermal cell proliferation. All flux parameters were altered for the whole 7-h period. The relative inhibitory effect of the skin extract was related to the proliferative state of the epidermal cell population. Cell flux at the G1-S transition showed only minor circadian variations, and treatment with skin extract was followed by a relative reduction of cell flux at this transition that was similar at the two times of the day investigated. In contrast, cell flux at the S-G2 transition showed pronounced circadian variations. The effect of the skin extract on cells at this transition was different at the two times in the 24-h period. In general, inhibition expressed as percent of the controls was stronger when the skin extract was given at times when the cell flux was low or decreasing, and vice versa. In spite of the changes in flux values following administration of a skin extract, the 3(H)TdR labelling indices were reduced only after a delay of 10 h, confirming previous results.

Animals↗

DNA synthesis in mouse epidermis: S phase cells that remain unlabeled after pulse labeling with DNA precursors progress slowly through S.

Epidermal basal cells from hairless mice were isolated after pulse labeling with tritiated DNA precursors and subjected to DNA flow cytometry combined with cell sorting. Cells were sorted from a window in the middle of the S phase, collected on glass slides, and subjected to autoradiography. Unlabeled cells in the middle of the S phase were found in normal mouse epidermis after optimal pulse labeling with tritiated thymidine [( 3H]dThd), in accordance with previous results. The proportion of unlabeled S phase cells was considerably increased among basal cells from mice treated with growth-inhibitory epidermal extracts. Reanalysis and re-sorting of cells previously sorted from mid S showed that unlabeled cells could not be accounted for by G1 contamination. Furthermore, labeling with precursors incorporated into DNA by "de novo" metabolic pathway [( 3H]Urd) did not reduce the proportion of unlabeled S phase cells, either when given alone or when given in combination with the precursor for DNA incorporated by the "salvage" pathway [( 3H]dThd). This strongly indicates that the unlabeled S phase cells do not synthesize DNA continuously, or are synthesizing DNA at a rate below the level of detection. A reduced proportion of unlabeled S phase cells was found in regenerating epidermis. This may be explained by a dilution effect caused by the 3-fold increase in the total number of cells within S phase at this condition. The observation that essentially all cells in mid S phase were labeled during 4 days of continuous labeling with [3H]dThd, indicates that cells in S phase that remain unlabeled after optimal pulse labeling are cycling, albeit slowly. Two-parameter sorting based on DNA and light scatter indicated that slowly cycling cells are larger than the average. These cells may represent a subpopulation of basal cells going through their last division cycle before differentiation.

Animals↗

Mouse epidermal cell proliferation after a single application of dimethyl sulphoxide (DMSO).

Hairless mouse epidermis was treated topically with a single application of undiluted DMSO. Epidermal cell proliferation during the following 72 hr was examined by means of DNA flow cytometry, [3H]TdR autoradiography, and a stathmokinetic method with colcemid. Topical application of DMSO was followed by perturbations in the epidermal cell proliferation that were in general similar to those observed in epidermal regeneration due to sudden cell loss. In contrast to such regenerative reactions, no hyperplasia could be detected after DMSO treatment, in spite of a consistently increased mitotic rate the first 3 days after DMSO treatment. The augmented epidermal cell production following exposure to DMSO therefore appears to be balanced by a correspondingly increased cell loss.

Animals↗

Epidermal proliferation characteristics are similar in the pilary canal of mouse hair follicles and in interfollicular epidermis.

Proliferation characteristics of basal cells in the pilary canal of resting hair follicles were investigated and compared with corresponding parameters in interfollicular epidermis of hairless mice. The mitotic rates had similar 24-h means at both locations. Distinct circadian rhythms which showed phasing and amplitudes similar to that in interfollicular epidermis, were demonstrated by the 3H-TdR labelling index, the mitotic rate and the mitotic index. Influx of cells to and efflux of cells from the S phase were measured in the early morning and in the evening by a 3H-TdR double labelling method. The influx values were similar at both times of both locations. The efflux values recorded in the morning were more than twice the values seen in the evening in both the pilary canal and in interfollicular epidermis. The epidermal motitic rate in the pilary canal was depressed by epidermal extracts, and increased after adhesive tape stripping in the same way as in interfollicular epidermis. The results indicate no heterogeneity in cell proliferation characteristics between the two locations, and suggest that similar mechanisms are responsible for maintainance of growth equilibrium at both sites.

Animals↗