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Y Collan

Publications and source records attributed to Y Collan.

At least 73 records · Page 4Linked to original sources
PubMed1994

Sources of variation in the assessment of cell proliferation using proliferating cell nuclear antigen immunohistochemistry.

The reproducibility in quantitation of proliferation activity, determined using the monoclonal antibody 19A2 to proliferating cell nuclear antigen (PCNA), was tested in visual and computer-assisted analyses of brain tumor material. The PCNA labeling index was scored using count (PCNA-LI, visual and computer analyses) and area (PCNA-LIa, computer analysis) estimates of immunopositivity. The quality of immunostaining was the most important reason for variation in the assessment results. Other significant variation sources in the assessment were experience in selecting microscopic fields and distinguishing immunopositive nuclei from immunonegative ones. Computer-assisted analysis improved the reproducibility of quantitation between different observers (visual rPCNA-LI = 0.624 versus computer assisted rPCNA-LI = 0.904). Also, the use of PCNA-LIa improved the intraobserver and interobserver reproducibility in different stainings (observer 1:rPCNA-LI = 0.857 versus rPCNA-LIa = 0.874; observers 1 and 2: rPCNA-LI = 0.904 versus rPCNA-LIa = 0.927; observers 3 and 4: rPCNA-LI = 0.848 versus rPCNA-LIa = 0.906). PCNA-LIa by computerized image analysis improves accuracy in the evaluation of the granularly expressed PCNA level. Furthermore, the effect of tumor heterogeneity on the assessment results can be diminished with the computerized method because large tissue areas can be analyzed faster.

Astrocytoma↗
PubMed1994

Evaluating the response to antioestrogen toremifene treatment in DMBA induced rat mammary carcinoma.

Evaluation of the treatment response to hormonal therapy in experimental mammary carcinoma models usually consists of recording the changes in tumour volume or in number of tumours. We performed quantitative histology on dimethylbenz[a]anthracene(DMBA) induced rat mammary carcinoma treated with the antioestrogen toremifene. The inhibition of growth of the treated regressing tumours was not only associated with inhibition of mitosis and reduction of the neoplastic epithelium, but toremifene seemed to reduce all main tissue components. The percentual area fractions of epithelium and stroma were equal in the untreated and the treated tumours. The estimated absolute volumes of epithelium, stroma and glandular luminae as well as the mitotic index were significantly reduced during toremifene treatment in those tumours which were responding by regression to the treatment. The findings indicate growth inhibiting effect on both epithelium and stroma or on interactions between epithelium and stroma. Adding quantitative histology to the gross response analysis in experimental animal models is feasible and may elucidate the mechanisms of action of a novel hormonal treatment.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1994

Cell loss in dimethylbenz(a)anthracene-induced rat mammary carcinoma treated with toremifene and ovariectomy.

The antiestrogen toremifene treatment results in regression or stabilization of dimethylbenz(a)anthracene(DMBA)-induced rat mammary tumors by reducing the mitotic activity and possibly by modifying the abundant spontaneous apoptosis seen in these tumors. A comparative study on the modes of cell loss was performed in untreated DMBA tumors and in tumors treated with toremifene and ovariectomy. Ovariectomy results in massive apoptotic cell death throughout the tumors with apoptotic cells exfoliating into the glandular lumina. Apoptosis accounts for most of the cell death also in the untreated tumors. The distinctly different morphology of the apoptotic cells in the untreated tumors (condensed apoptosis) and tumors treated with ovariectomy (blebbing apoptosis) may reflect the different type or schedule of the apoptotic process. Both morphologies of apoptotic cells were seen in the toremifene-treated tumors. Blebbing apoptosis is not easily examined in paraffin-embedded material but is best detectable in plastic sections and by electron microscopy.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1993

Mitotic activity, apoptosis and TRPM-2 mRNA expression in DMBA-induced rat mammary carcinoma treated with anti-estrogen toremifene.

Anti-estrogen toremifene inhibits growth of the 7,12-dimethylbenz(a)anthracene(DMBA)-induced rat mammary carcinoma. The changes in proliferation and cell death were studied in detail. Proliferation was measured by counting mitotic figures in histologic sections, expressed by volume-corrected mitotic index (M/V INDEX). Respective volume corrected apoptotic index (A/V INDEX) was measured by counting apoptotic nuclei in the same sections. The presence of apoptotic cells was confirmed by transmission electron microscopy. In the untreated tumors, both mitosis and apoptosis were frequent. In the toremifene-treated tumors, the mean M/V INDEX was about half of the mean M/V INDEX in the untreated control tumors. The mean A/V INDEX in the toremifene-treated tumors was about 3/4 of the mean A/V INDEX in the controls. In toremifene-treated tumors, A/V INDEX was strongly correlated with TRPM-2-gene expression, which was also enhanced when compared with the controls. TRPM-2 gene has been associated with programmed cell death induced by hormonal ablation in prostate- and breast-cancer cells. No such correlation was seen in control tumors. These findings suggest that, in the DMBA-tumor model, toremifene affects the cell turnover by inhibiting mitotic activity and modifying abundant spontaneous apoptosis. In this model, the inhibition of tumor growth results mostly from reduction of mitotic activity.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1992

Significance of variation in DNA flow cytometric analyses from paraffin-embedded breast cancers. Evaluation of the grading efficiency of ploidy determination, DNA index, and S-phase fraction.

116 paraffin-embedded breast cancer samples were analyzed by flow cytometry. From each sample 3 consecutive 50 microns sections were cut for the study. The presence of neoplastic tissue was verified from light microscope sections cut before and after the adjacent sections. One laboratory started with one section from each block and was allowed extra sections when needed for analysis. At the end the laboratory obtained results from all 116 cases. The rest of the samples were studied by 2 other laboratories. Samples with results from 2 or 3 laboratories then allowed variability analysis and the estimation of the grading efficiency in a 2-grade system. Inconsistency in diploidy/aneuploidy distinction was present in 36 of 111 (32.4%) cases studied by two or three laboratories. This inconsistency was less obvious in samples graded as multiploid by at least one of the laboratories. The grading efficiency as analyzed from the results of 3 laboratories was 0.89, and of 2 laboratories, 0.84. The DNA index showed a slightly higher grading efficiency. At the cutoff point of 1.3, 91% of cases could be expected to be correctly classified into low ploidy and high ploidy groups (grading efficiency 0.91). The S-phase fraction had a mean grading efficiency of 0.89, a performance comparable to that of diploidy/aneuploidy distinction. In the light of the available data the flow cytometric analysis can add to the consistency of grading, especially when compared with subjective histological grading. However, the data do not suggest that flow cytometric analysis of paraffin sections as a grading method would be more consistent than quantitative histopathology from sections.

Aneuploidy↗
PubMed1992

Quantitative analysis of quadriceps muscle biopsy in systemic sclerosis.

The lesser diameter of the fibers, separately of type 1 and type 2 fibers, and the capillary density evaluated as number of capillaries/area and number of capillaries/fiber were quantitatively estimated in muscle biopsies from 12 patients with systemic sclerosis. Nine patients with polymyositis or rheumatoid arthritis and six patients with muscle dystrophy and neurogenic atrophy served as controls. The results showed that patients with systemic sclerosis had low values of the lesser diameter of the fibers. This reduction was most obvious in type 2 fibers. The capillaries were also significantly reduced when compared with the control groups. When considering the capillaries/fiber ratio, seven out of eight patients with values lower than 0.7 belonged to the systemic sclerosis group. In systemic sclerosis the capillary density values were not significantly correlated with those of the lesser diameters of the fibers.

Adult↗
PubMed1992

Ultrastructural changes in human nasal cilia caused by the common cold and recovery of ciliated epithelium.

Changes in the ultrastructure of human respiratory cilia caused by the common cold were studied in 12 patients. The nasal mucosa was studied three times: on the first or second day after the beginning of symptoms, and 1 week and 3 weeks after the first biopsy. The damage was most severe at 1 week. The most remarkable finding was the loss of cilia and ciliated cells. However, the ultrastructure was usually normal, without any increase in tubular anomalies, as compared with the normal material of the previous reports. Three weeks after the beginning of the disease the number of cilia and ciliated cells had increased to nearly normal. However, as a sign of regeneration, immature short cilia (0.7 to 2.5 microns in length) were often seen. The ciliary orientation was uniform, dynein arms were normal, and there was no increase in the number of tubular anomalies. The results suggest that the impaired mucociliary function during viral infections is due to the loss of cilia and ciliated cells, rather than to ultrastructural anomalies in the cilia. The development of tubular anomalies and random ciliary orientation may require more extensive exposure to factors affecting ciliary function.

Biopsy↗
PubMed1991

Short nasal respiratory cilia and impaired mucociliary function.

A 48-year-old man was examined because of anosmia. He was otherwise healthy except for mild arterial hypertension. He had stopped smoking 20 years ago. Previously he had been exposed to sulfuric acid gases for 3 years in his work. Clinical examination revealed no findings to explain his anosmia. The patient was fertile, indicating normal sperm/cilia motility. Nasal mucociliary function was examined by radioactive tracer and found to be markedly and constantly impaired. Ciliary ultrastructure in cross-sections was normal. However, in longitudinal sections the length of the cilia varied from 0.6 microns to 3.9 microns. The mean length of the cilia from the cell membrane to the tip was 2.5 +/- 0.9 microns, in contrast to normal ciliary length of 5-7 microns. These findings represent a new structural defect among the various known ciliary abnormalities.

Cilia↗
PubMed1991

The role of nucleolar organiser regions as prognostic factors in breast cancer.

Nucleolar organiser regions (NORs) were stained in paraffin-embedded biopsy specimens of 80 female breast carcinomas by the silver (Ag) technique. The patients were prospectively followed up for a mean of 12.4 years (range 11.5-13.3). The number of different types of Ag-NORs was correlated with the histological grade, clinical stage, DNA ploidy, S-phase fraction (SPF) and clinical outcome. Grade III tumours showed higher Ag-NOR counts than low grade tumours. The total number of Ag-NORs (P = 0.0059) and the number of dispersed Ag-NOR (P = 0.0199) were significantly related to DNA ploidy aneuploid tumours showing higher Ag-NOR counts. The number of aggregated Ag-NORs was predictive (P = 0.0413) for the development of metastatic disease during follow-up. On the other hand, crude, cancer-related or recurrence-free survival could not be predicted significantly by the Ag-NORs. The results suggest that the number of Ag-NORs is clearly related to the proliferative activity in breast cancer, but the prognostic value of Ag-NOR counting is inferior to the previously recognised prognostic factors.

Breast Neoplasms↗
PubMed1991

Immunohistochemical staining of CA 50 antigen in human bladder cancer. Relation to histologic grade, clinical stage, and prognosis.

The immunohistochemical detection of tumor marker CA 50 was studied in bladder cancer of WHO grades I-III. The material consisted of tumors in 83 patients and the mean clinical follow-up time was thirteen years (range 9.6-22 years). The fraction of CA 50-positive cells (FPtot) in microscopic image was scored 0-100 percent. Also the maximally staining region was selected, and the fraction of CA 50-positive cells in this region was scored 0-100 percent (FPmax). The average staining intensity of CA 50-positive cells was scored from 0 to 3 in the whole section (ASItot) and in the maximally staining area (ASImax). The inverse relation between histologic grade, FPtot (p = 0.0001), and ASItot (p = 0.006) was statistically significant. FPtot (p = 0.039) and ASItot (p = 0.018) were also inversely related to clinical stage. Occurrence of metastasis during the follow-up was associated with low CA 50 positivity (FPtot, p = 0.003; ASItot, p = 0.002). The lower the staining intensity or the lower the fraction of CA 50-positive cells, the more aggressive was the tumor. In survival analysis, low FPtot (p = 0.002) and ASItot (p = 0.007) values were related to high risk of bladder cancer death. The results show that immunohistochemical staining of bladder tumor specimens with CA 50 can be used to predict bladder cancer aggressiveness and survival.

Aged↗
PubMed1991

Relationship between DNA ploidy and survival in patients with exocrine pancreatic cancer.

The DNA ploidy of pancreatic cancer tissue from paraffin blocks was measured by flow cytometry in 46 patients whose disease had been detected and treated with surgery. Lymph node involvement was observed at the time of diagnosis in 36% of patients with diploid tumors and in 79% of patients with aneuploid tumors (p = 0.017), but no clear relation to metastasis could be observed (p = 0.201). The S-phase fraction (SPF) was significantly higher in aneuploid than in diploid tumors (p = 0.007). All patients who underwent radical surgery had diploid DNA content and SPF below the median (11.5%). Seven patients with a diploid tumor (32%) and none of the aneuploid cases survived 1 year. Over the 1-year period, in order of importance, the type of treatment (p less than 0.001), DNA ploidy (p = 0.004), tumor size (p = 0.0046), and lymph node status (p = 0.027) predicted survival. Aneuploidy showed a significant association with decreased cumulative survival (p = 0.015), and a suggestive relationship with SPF was found. The results suggest that DNA ploidy of pancreatic cancer can be used in dividing the patients into different prognostic groups. The value of the detection of aneuploidy, however, is limited, because diploid pancreatic cancers are also generally rapidly fatal.

Adult↗
PubMed1991

Nephropathia epidemica: mild variant of hemorrhagic fever with renal syndrome.

The diagnosis of nephropathia epidemica (NE) is primarily not histological, but because biopsy samples sometimes reach the pathologist, knowledge of histology may be of diagnostic value, in addition to clarifying the pathogenesis. The authors collected 80 biopsies from 65 patients taken after the onset of NE from various hospital files in Finland. Light microscopic, morphometric, electron microscopic, and immunohistochemical methods were applied in studying these samples. There was slight tubular dilatation and interstitial edema best evidenced during the first month after the onset of the disease. There was limited electron microscopic evidence of endothelial cell damage or reaction, also in the glomeruli. Occasional tubular necrotic cells or mitoses were found. About half of the cases were positive for IgG or IgM, and C3 and fibrin in the tubular basement membrane. Samples of the recovery phase showed interstitial fibrosis. Medullary interstitial hemorrhages were seen in 60% of samples of the first two weeks after onset. Interstitial inflammatory changes were diffuse in the early phases and often focal thereafter. During the first two weeks there was congestion and mild hypercellularity of the glomeruli. There was also slight prominence of mesangium, and evidence of endothelial cell damage or reaction. Osmiophilic glomerular deposits were scanty. Focal immunoglobulin (usually IgG) and complement deposits were present in the glomeruli, but less intense than in classical glomerulonephritis. Without medullary hemorrhages in the biopsy, the suggestive diagnosis could rest on interstitial edema, diffuse but sparse inflammatory infiltrate, dilatation of occasional tubules, changes suggestive of tubular cell death, and congestion and slight hypercellularity of the glomeruli.

Adolescent↗
PubMed1991

Quantitative histopathology of soft tissue calcifications.

Quantitative evaluation of soft tissue calcifications in histological sections, e.g. in connection with nephrocalcinosis, can be based on numerous methods. Staining methods detecting the calcifications do not give a detailed idea about their chemical composition, which can be analysed through electron probe x-ray microanalysis or chemical analysis. When the idea is to compare two groups in terms of calcifications several approaches are possible. Subjective quantitation into several grades will detect larger differences. Morphometrical or stereological methods are to be recommended, however. These methods can be based on volume fraction estimation through point-counting procedures. The point-counting method can be adjusted to detect changes at a predefined accuracy level by varying the number of points used in the estimation. Stereological estimation can best be carried out by defining the volume of the organ studied and the volume occupied by the deposits. The volumes as absolute values or as volume fractions can be used to compare the groups studied. Counting of the deposits can be done from single sections or from consecutive sections. The stereological estimates can be based on the formula of Ebbeson and Tang and on the disector principle derived from it. In comparing different groups, parametric statistical methods can be used when absolute volumes of deposits are considered. Nonparametric methods should be used when volume fractions or subjective grades are compared.

Animals↗
PubMed1991

Tumour ploidy, morphometry, histological grading and clinical features in ovarian carcinoma: mutual relations.

The relationship between tumour ploidy and qualitative and quantitative histopathology was assessed in a series of 95 ovarian carcinomas. 67% of the tumours were non-diploid (DNA aneuploid). 56% of the early stage (I-II) tumours were non-diploid and 81% of the tumours in advanced (III-IV) stages were aneuploid. Histological grading failed to show a clear relationship between increasing malignancy grade and ploidy. There was a close association between DNA ploidy and nuclear perimeter, area and shortest and longest nuclear diameter: the nuclei of non-diploid tumours were generally larger. Also the number of mitotic figures per square millimeter of epithelium in the microscope image (volume-corrected mitotic index, M/V-index) differed significantly between near-diploid and non-diploid tumours. Discriminant analysis showed that 74% of the learning-set tumours (67% of the test set tumours) could be correctly classified in low-ploidy and high-ploidy categories with morphometric features (nuclear perimeter, M/V-index and volume percentage of epithelium). Characteristic features of non-diploid ovarian tumours--rapid proliferation and large nuclear size--could be assessed with morphometric methods which allowed a relatively large aneuploid tumour group to be distinguished.

Chromosomes↗
PubMed1990

Ciliary orientation in the "immotile cilia" syndrome.

Ciliary orientation was studied in 43 patients with the "immotile cilia" syndrome. Twenty-four of these patients had total situs inversus. One mucosal specimen was taken from uterine cervical epithelium, 2 were from bronchial mucosa and 40 from nasal mucosa. The orientation of the cilia was measured from micrographs using a semiautomatic image analyzer (IBAS I). The results from patients were compared with those of 10 control subjects. The mean standard deviation and its standard deviation of the angles of ciliary orientation was 39.7 degrees +/- 9.2 degrees in 43 patients and 27.4 degrees +/- 4.3 degrees in the control group. The difference between the groups is highly significant statistically (P less than or equal to 0.001). However, there were no statistically significant differences in the standard deviations of ciliary orientation between the fields sectioned near the cell membrane or near the ciliary tip. We were also unable to find any significant differences in the standard deviations of the ciliary angles in the specimens taken from brush biopsies and excisional biopsies. There were also no statistically significant differences between the standard deviations of the ciliary angles for the groups with or without situs inversus. If 35 degrees is considered to be the limit value for the mean standard deviation between normal and pathological specimens in our total material, this would give a specificity of 0.90 and a sensitivity of 0.72.

Biopsy↗
PubMed1990

Carcinoma of the breast in children.

Carcinoma of the breast in children is an extremely rare disease, only 44 patients have been reported in the world literature. We report on a case of breast cancer in a 9-year-old girl, who was admitted to the hospital because of a four-month history of a painless mass in the right breast. Clinical examination and mammography resulted in a strong suspicion of malignancy. The histology corresponded to juvenile secretory carcinoma, the histological type without the characteristics of prepubertal cancer cases. Electron microscopy demonstrated intracellular large vacuoles and acini filled with secretory material. The mitotic index was low, the highest measured value was 4 mitotic figures per 10 high power fields corresponding to 2.78 mitotic figures per mm2 of epithelium in the microscope field. Flow cytometry showed that the neoplastic cells were diploid and had a low S-phase fraction. A simple mastectomy including axillary evacuation was performed. No lymph node or distant metastases were found. Postoperative radiation treatment or chemotherapy were not administered. Our patient has been in follow-up for six years without recurrence. In this case simple mastectomy with axillary evacuation seems to have given a cancer-free development into adulthood. Earlier reports have also shown a favourable outcome in these tumours.

Breast↗