Biomedical subjects

V M Kosma

Publications and source records attributed to V M Kosma.

At least 163 records · Page 9Linked to original sources

PubMed1985

Reproducibility of morphometric measurements of amyloid after various staining methods.

Four histologic staining methods used for detecting amyloid (Congo red, viewed in both normal and polarized light, Sirius red, Crystal violet and Thioflavine T) were applied to heart muscle autopsy samples from 19 patients who suffered from amyloidosis. The amount of amyloid present was evaluated with morphometry (point counting) by five pathologists, and the interobserver reproducibility and variation of point counting in these staining methods were analyzed. The Sirius red method showed the least variation and was the most suitable stain for demonstrating amyloid with respect to reproducibility. Thioflavine T showed the greatest variation and was the least suitable stain with respect to reproducibility. The range of variation was considerable in all staining methods. The results show that stains differ in their specificity and sensitivity in staining amyloid, observers differ in their interpretation of staining results and certain stains result in more uniform interpretations than do others.

Amyloid↗

PubMed1985

Reproducibility and variation of morphometric analysis of carcinoembryonic antigen staining in histopathology. The influence of standardized microscopic fields.

Using morphometric methods, five pathologists analyzed the positive staining for carcinoembryonic antigen (CEA) in sections from 17 ovarian tumors, with the intraclass correlation coefficient (ICC) and the mean values of the coefficients of variation (CV) used to assess reproducibility and variation. First, field and point scores for epithelium and mucin were estimated using 25 randomly selected square fields in sections from each of the tumors. The ICC range in the whole sample field was 0.53 to 0.81 (slight to substantial reproducibility) while the mean values of CV were 0.50 to 0.75. Second, the results of using random and standardized individual fields for the measurements were studied in three tumors. In random fields, the ICC was 0.57 to 0.71 (slight to moderate reproducibility) and the mean values of CV were 0.53 to 0.65. The corresponding values in standardized fields were 0.71 to 0.73 (moderate reproducibility) and 0.41 to 0.57, respectively. The results show that the variation is smaller and the degree of reproducibility higher in standardized fields. Considerable variation remains, however, revealing human factors as an important source of variation in practical morphometry.

Carcinoembryonic Antigen↗

PubMed1985

Regional lymph node reactions related to hormone receptor status in female breast carcinoma.

A series of 211 female breast carcinomas was studied with special reference to the relationships between estrogen (ER) and progesterone (PR) receptor status and the reactions of the axillary lymph nodes as manifestations of tumor-host reactivity. Carcinomas were classified according to their nuclear grade (NG), and the following nodal reactions were recorded: extent of cancer metastasis, paracortical activity (PCA), follicular hyperplasia (LFH), sinus histiocytosis (SH), and degenerative sinus histiocytosis (DSH). NG did not directly correlate with ER- or PR-positivity, albeit the highest frequency of both was found in well differentiated carcinomas. ER- and less significantly PR-values were higher in post- than in premenopausal females. ER- and PR-positivity as well as the absolute receptor values were lowest in the cases with extensive (Grade 4) nodal metastases, but did not show a direct relationship to the other grades (0 to 3). PCA did not show any relation to the receptor status, whereas LFH seemed to bear an inverse relationship with ER- (but not PR-) positivity. SH seemed to be associated with higher frequency of ER-positivity than did DSH-nodes, the differences being slight, however. It is concluded that hormone receptor assays connected with the morphological assessment of tumor-host reactivity provide some benefit in grouping the breast cancer patients according to the different expectancy of the outcome of their disease.

Aged↗

PubMed1984

Tumor-producing activity of dithranol (anthralin) and two of its 10-acyl analogs in the dorsal skin of female NMRI mice.

The tumor-producing activity of local applications of dithranol, 10-propionyl dithranol and butantrone was studied in 420 female white NMRI mice. An initiation with 20 micrograms of 7,12-dimethyl-benz(alpha)anthracene (DMBA) was followed 2 weeks later by three applications per week of the test compounds in 50 microliters of acetone for 50 weeks. Several control groups receiving only acetone or DMBA and test compounds without DMBA were included. Dithranol and 10-propionyl dithranol caused transient, although serious, skin irritation during the first 2 weeks of the treatment. Hyperplasia was a common finding in the same groups at the end of the treatment. Dithranol (3.5 mM) induced 11 papillomas in 8 mice (26.7%) without DMBA and 29 papillomas in 17 mice (56.7%) with DMBA. 10-Propionyl dithranol was tumorigenic as well: 3.5 mM caused 15 papillomas in 11 mice (36.6%) without DMBA and 28 papillomas in 17 mice (56.7%) with DMBA and 1.5 mM with DMBA caused 7 papillomas in 6 mice (20%). In the butantrone groups, there was only one single papilloma with the 1.5 mM concentration plus DMBA. It is concluded that, in contrast to dithranol and 10-propionyl dithranol, butantrone (3.5 mM) is not tumorigenic in the dorsal murine skin.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1982

Hormone receptor levels related to histological parameters of tumor-host relationships in female breast carcinoma.

A series of 115 female breast carcinomas was studied with special emphasis on the relationships between the hormone receptor (ER and PR) levels and the histological parameters reflecting tumor-host reactivity. Carcinomas were classified according to their nuclear grade (NC) and the stromal host reactions; perivenous lymphocyte infiltration (PVI), lymphocyte (LD), plasma cell (PCI), and mast cell infiltration (MI) were assessed. NG did correlate directly with the ER positivity, but not with the absolute ER values. LI and PCI, but not MI and PVI, showed an inverse relation to the ER values, but not to those of PR. ER and to lesser extent the PR values were higher in postmenopausal than in premenopausal women. The findings are discussed in the light of tumor-host relationships, and conclusion is drawn that the receptor determinations used in connection with the histological evaluation of these parameters (NG especially) are of definite benefit in dividing the breast cancer patients into groups of different expectancy of the future outcome of their disease.

Age Factors↗

PubMedDate not supplied

Stereospecificity of the sensory irritation receptor for nonreactive chemicals illustrated by pinene enantiomers.

To clarify the existence of a receptor protein for sensory irritants in trigeminal nerve endings, D- [i.e. (+)] and L- [i.e. (-)] enantiomers of alpha- and beta-pinene as models of nonreactive chemicals were evaluated for their potency in outbred OF1 and NIH/S mice using ASTM E981-84 bioassay. All pinenes possess sensory irritation properties and also induced sedation and signs of anaesthesia but had no pulmonary irritation effects. According to the ratio of RD50 (i.e. concentration which causes a 50% decrease in respiratory rate,f) and vapour pressure (Po), all pinenes are nonreactive chemicals. For nonreactive chemicals, Po and olive oil-gas partition (Loil) can be used to estimate their potency as sensory irritant. Thus, for enantiomers with identical physicochemical properties, the estimated RD50 values are the same. In addition, although alpha- and beta-pinene do not have identical Po and Loil values, their estimated potencies are quite close. However, the experimental results showed that D-enantiomers of pinenes were the most potent as sensory irritants and a difference in potency also exists between alpha- and beta-pinene. RD50 for D-enantiomers of alpha- and beta-pinene were almost equal, 1053 ppm and 1279 ppm in OF1 strain and 1107 ppm and 1419 ppm in NIH/S strain, respectively. Values differed by a factor of approximately 4 to 5 from L-beta-pinene for which the RD50 was 4663 ppm in OF1 and 5811 ppm in NIH/S mice. RD50 could not be determined for L-alpha-pinene; this pinene was almost inactive. D-alpha-pinene seems to best fit the receptor because its experimental RD50 was one-half of the estimated value while for D-beta-pinene those values were equal. On the contrary, L-beta-pinene was about 3 to 4 times less potent than estimated. L-alpha-pinene was only slightly active although it was estimated to be as potent as D-alpha-pinene. The remarkable difference in potency between L-enantiometers is most likely due to a structural difference between alpha- and beta-pinene: the more flexible beta-pinene can bend to fit into the receptor better than the rigid alpha-pinene. The results showed that the commonly used physicochemical descriptors cannot fully explain the potency of these chemicals; their three-dimensional structure should also be considered. Because of the stereospecificity of pinenes, a target site for nonreactive sensory irritants is most likely a receptor protein containing a chiral lipophilic pocket.

Animals↗

PubMedDate not supplied

Dopaminergic system and monoamine oxidase-B activity in Alzheimer's disease.

The possible involvement of dopaminergic neurons in dementia of Alzheimer type (AD/SDAT) was studied in autopsied brains from 20 patients with AD/SDAT. Dopamine (DA) concentrations were decreased significantly in the temporal cortex, hippocampal cortex and hippocampus in AD/SDAT patients. Levels of homovanillic acid (HVA) were not altered compared to controls. The HVA/DA ratio was significantly higher in the hippocampus of AD/SDAT patients, suggesting overactivity of the remaining DA neurons. Histological findings of substantia nigra suggesting coexistent pathology of Parkinson's disease (PD) found in 25% of cases were associated with lowered levels of DA in striatum and with reduced HVA in CSF. The activity of monoamine oxidase-B was significantly increased in the cortical areas and in the hippocampus, obviously reflecting the underlying cell loss and substantial gliosis in these areas of the brain. In general, DA neurons seemed to be only mildly involved in AD/SDAT. Coexistent PD pathology can explain the loss of DA in the striatum and the presence of clinical PD symptoms in some patients with AD/SDAT. Otherwise the clinical relevance of these dopaminergic alterations is unclear.

Aged↗

PubMedDate not supplied

Sensory irritating potency of some microbial volatile organic compounds (MVOCs) and a mixture of five MVOCs.

The authors investigated the ability/potencies of 3 microbial volatile organic compounds and a mixture of 5 microbial volatile organic compounds to cause eye and upper respiratory tract irritation (i.e., sensory irritation), with an animal bioassay. The authors estimated potencies by determining the concentration capable of decreasing the respiratory frequency of mice by 50% (i.e., the RD50 value). The RD50 values for 1-octen-3-ol, 3-octanol, and 3-octanone were 182 mg/m3 (35 ppm), 1359 mg/m3 (256 ppm), and 17586 mg/m3 (3360 ppm), respectively. Recommended indoor air levels calculated from the individual RD50 values for 1-octen-3-ol, 3-octanol, and 3-octanone were 100, 1000, and 13000 microg/m3, respectively-values considerably higher than the reported measured indoor air levels for these compounds. The RD50 value for a mixture of 5 microbial volatile organic compounds was also determined and found to be 3.6 times lower than estimated from the fractional concentrations and the respective RD50s of the individual components. The data support the conclusion that a variety of microbial volatile organic compounds may have some synergistic effects for the sensory irritation response, which constrains the interpretation and application of recommended indoor air levels of individual microbial volatile organic compounds. The results also showed that if a particular component of a mixture was much more potent than the other components, it may dominate the sensory irritation effect. With respect to irritation symptoms reported in moldy houses, the results of this study indicate that the contribution of microbial volatile organic compounds to these symptoms seems less than previously supposed.

Air Microbiology↗

PubMedDate not supplied

K-ras and p53 mutations and overexpressions as prognostic factors in female rectal carcinoma.

BACKGROUND: The present study was undertaken to determine the prognostic significance of K-ras, p53 and bcl-2 in female rectal carcinoma. MATERIALS AND METHODS: The mutations in K-ras and p53 genes were analysed using SSCP and direct sequencing. The expression of K-ras, bcl-2 and p53 proteins was determined immunohistochemically. RESULTS: Mutations of K-ras and p53 genes were detected in 12% and 38% of the tumours, respectively. The prevalence of K-ras overexpression was 67%. K-ras mutations were not associated with survival. However, more favourable survival was observed for patients with K-ras overexpression than with normal expression (adjusted hazard ratio from Cox model 0.4, 95% CI 0.2-0.8). Mutation or overexpression of p53 were not associated with survival. CONCLUSIONS: It may be possible, that the mutations and protein overexpression of K-ras and p53 in female rectal carcinoma have different clinical impact on patient survival as suggested in previous studies concerning colorectal carcinoma of both sexes.

Adenocarcinoma↗

PubMedDate not supplied

Receiver-operating characteristic (ROC) curve analysis of cathepsin D and pS2 in breast disease; results from a prospective study.

The cytosol values of estrogen-regulated proteins cathepsin D and pS2 were evaluated in 166 patients with breast diseases by a receiver-operating characteristic (ROC) curve analysis. Our aim was to compare their diagnostic accuracy and to define optimal cut-off levels for the cytosol values of these proteins in breast cancer (n = 133). The preoperative mean cytosol cathepsin D values in the breast cancer group were higher than in patients with benign breast disease (p < 0.001). The correlation coefficient (Pearson's r) between Cathepsin D and pS2 measurements was 0.286 (p < 0.001) in breast cancer patients. The ROC analysis indicated that the cathepsin D test was more sensitive than the pS2 test at all specificity levels, and the cathepsin D test reached considerably high sensitivity (86%) at the specificity level of 80%. According to present study, it would seem optimal to use the cut-off level of 33.0 pmol/mg for cathepsin D analysis and the level of 31.0 ng/mg for pS2 in breast cancer. In conclusion, the results of ROC curve analysis suggest that the cathepsin D test has advantage over pS2 because of its higher sensitivity in breast cancer.

Adolescent↗

PubMedDate not supplied

Preoperative high type I collagen degradation marker ICTP reflects advanced breast cancer.

Type I collagen synthesis (PINP, PICP) and degradation (ICTP) markers were analysed from preoperative serum samples of 138 women with breast cancer (BC), 94 women with benign breast disease (BBD) and 100 healthy controls to evaluate the levels of these markers and the stage of BC at the time of diagnosis. We also compared the clinical utility of these markers in detecting BC with CA15-3 and CEA. The mean value of ICTP was statistically significantly elevated in the BC group (p < 0.001), as compared with the control group, but the elevated values in BC group were due to stage IV disease. The sensitivity of ICTP in detecting BC was 0.23, which was equal with CA15-3(0.24) or CEA(0.23). The sensitivity of both PICP and PINP for diagnosing BC was poor, but a tendency to higher serum levels of PINP and low PICP/PINP ratio was detected in patients with advanced stage IV disease. These results indicate that high preoperative serum levels of ICTP are associated with advanced BC, but like CA15-3 and CEA, its clinical value in diagnosing purpose is poor.

Biomarkers, Tumor↗

PubMedDate not supplied

Inducible nitric oxide synthase (iNOS) expression and its prognostic value in prostate cancer.

OBJECTIVES: The expression of inducible nitric oxide synthase (iNOS) was evaluated in prostate cancer and the results were compared with other prognostic factors and patients outcome. MATERIALS AND METHODS: Clinical and histopathological data and follow-up information of 198 prostate cancer (PC) patients treated between the years 1973 and 1992 at Kuopio University Hospital, Finland were collected from patient files. Archival tumor specimens were used for immunohistochemical analysis of iNOS. The expression of iNOS was analysed by light microscopy and the expression was scored into 3 grades (negative weak or strong). RESULTS: iNOS was expressed in tumor cells and in inflammatory cells inside and around the tumor. Normal and hyperplastic prostate tissues adjacent to tumors were negative or weakly positive for iNOS. The strong iNOS expression in tumor cells was related to high T-classification (p=0.001), metastasis (p=0.06), high Gleason score (p=0.0004), DNA aneuploidy (p=0.0001) and perineural infiltration (p=0.0001). iNOS expression was not linked with the density of tumor infiltrating lymphocytes or the expression of p53. The mean values of Ki-67, mitotic index and S-phase fraction were higher in tumors strongly expressing iNOS. In univariate survival analysis the strong expression of iNOS was a significant predictor of poor survival in the entire cohort (p=0.0002) and in the MO patients (p=0.008), but was not an independent predictor of survival in Cox's multivariate analysis. CONCLUSION: iNOS has been related to stimulative and suppressive effects on cancer cell growth, but the prognostic value of iNOS has not been previously studied in PC. Here we could demonstrate an association between strong iNOS expression and rapid cancer cell proliferation rate, dedifferentiation and advanced stage cancer. The strong iNOS expression was a predictor of poor survival in univariate analysis, but was inferior to established prognostic factors in multivariate analysis.

Adenocarcinoma↗

PubMedDate not supplied

Surgical management of irradiation failures in T1-T2 squamous cell carcinoma of the glottic larynx.

BACKGROUND: The purpose of this study was to analyse the results of salvage surgery after failure of irradiation to control the primary T1-T2 glottic cancer. MATERIALS AND METHODS: Ninety-eight patients with T1 and T2 squamous cell cancer of the glottic larynx were treated with curative intent by radiotherapy. The tumour recurred in 22 of the 98 (22%) patients. Surgical management consisted of total and frontolateral laryngectomy. Survival rates were calculated from the date of the salvage operation. RESULTS: Two of the 22 patients refused to undergo salvage surgery and one patient had pulmonary metastasis. Of the 19 patients who underwent salvage surgery, 14 (74%) had total laryngectomy and 5 (26%) had frontolateral laryngectomy. The operations were curative in 15 (79%) of the 19 patients. The overall 5-year survival rate after surgery was 78%. CONCLUSION: Stringent follow-up of patients with irradiated T1 and T2 glottic laryngeal cancer is essential to permit a successful salvage.

Carcinoma, Squamous Cell↗

PubMedDate not supplied

Clinical, histological and quantitative prognostic factors in cutaneous malignant melanoma.

A retrospective study including 55 cutaneous melanoma patients with 9.5 years follow-up was carried out to assess the significance of various prognostic factors. The histological samples were evaluated according to Clark's and Breslow's classifications and six nuclear features were measured by interactive morphometry. Mitotic activity was assessed by two different methods: mitotic activity index (MAI) and volume corrected mitotic index (M/V index). The overall disease-related five-year survival of patients was 76.4%. TNM stage (p = 0.0001), sex (p = 0.0024), M/V index (p = 0.003), standard deviation of nuclear form factor (p = 0.023), MAI (p = 0.02), shortest nuclear axis (p = 0.023) and Breslow's classification (p = 0.044) predicted survival in univariate analysis. A multivariate analysis including clinical, histological and morphometric features pointed the Clark's classification as the most important predictor of survival (p = 0.002), while the other variables included had no independent prognostic value. The prognostic importance of mitotic indices and morphometric features is clearly a subject for further studies in superficial melanomas.

Female↗

PubMedDate not supplied

DNA ploidy, S-phase fraction and mitotic indices as prognostic predictors of female breast cancer.

DNA ploidy, S-phase fraction (SPF), mitotic index (MI), volume corrected mitotic index (M/V index) and standard prognostic factors were related to disease outcome in a series of 363 women with breast cancer followed-up for over 10 years in our clinic. DNA ploidy and SPF were significantly related to histological type, tumour grade and mitotic indices (p < 0.001). In univariate survival analysis, pN status (p < 0.0001), tumour diameter (p < 0.0001), MI (p = 0.001), M/V index (p = 0.0003) and SPF (p = 0.015) predicted survival. In pN(-) tumours. MI (p = 0.059) was related to survival. In pN(+) tumours, tumour diameter (p = 0.0004), M/V index (p = 0.023) and SPF (p = 0.045) predicted survival. In multivariate survival analysis, tumour diameter (p < 0.001). M/V index (p < 0.007), pN status (p = 0.014) and patient age (p = 0.09) were independently related to survival. In pN(-) tumours, tumour diameter independently predicted survival (p = 0.033). In pN(+) tumours, tumour diameter (p < 0.001), M/V index (p = 0.006) and the year of treatment (p = 0.08) were independent predictors. The results show that tumour diameter, pN status and proliferative activity of cancer cells are important prognostic factors in breast cancer. Of the proliferation indices, M/V index and SPF are equally powerful predictors, and the use of M/V index is advocated due to simplicity of the assessment.

Analysis of Variance↗

PubMedDate not supplied

Breast cancer in young women: clinical, histological and morphometric prognostic factors.

Clinical features, 8 histological features, 7 nuclear morphometric variables and 2 mitotic indices were entered in a univariate and in a multivariate survival analysis to assess their independent predictive value in 56 breast cancer patients under the age of 40 years who were followed up for over 10 years. The most important predictor of recurrence-free survival (RFS) in univariate analysis was the SD of nuclear perimetry (p = 0.003) followed by SD of nuclear area (p = 0.006), M/V index (p = 0.036), pN status (p = 0.046), nuclear area of 10 largest nuclei (p = 0.07), nuclear perimetry (p = 0.09) and nuclear area (p = 0.09) in that order. In pN(-) patients, SDPE (p = 0.04), SDNA (p = 0.07) and NA10 (p = 0.07) predicted RFS. In pN+ patients the most important predictor of RFS was the SDNA (p = 0.001) followed by NA 10 (p = 0.003), SDPE (p = 0.009), PE (p = 0.01), NA (p = 0.01) and Dmin (shortest diameter) (p = 0.04). In multivariate analysis the pN-status independently predicted RFS. Tumour size (p = 0.001), pN status (p = 0.002) and M/V-index (p = 0.079) were related to BS (breast cancer survival). In pN-patients, NA 10 (p = 0.097) predicted BS, whereas in pN+ tumours tumour size (p = 0.06) was the most important predictor of BS. In a multivariate analysis, tumour size (p = 0.02) and pN-status (p = 0.016) were independent predictors of BS.

Adult↗

PubMedDate not supplied

Sex steroid receptors, S-phase fraction and DNA ploidy as determinants of the risk of relapse and death of female breast cancer.

S phase fraction (SPF) and DNA ploidy were related to disease outcome by a separate analysis of sex steroid receptor positive and negative tumours in a series of 232 patients with breast carcinoma followed-up for over 8 years in our clinic. SPF was significantly higher in receptor-negative tumours than in receptor-positive ones (p = 0.037). SPF predicted recurrence only in ER+ or PR+ patients (p = 0.02-0.003). Recurrence-free survival (RFS) was significantly related to SPF only in ER+ (p = 0.001) and PR+ (p less than 0.001) tumours. In survival analysis, ER+ (p = 0.002) and PR+ (p less than 0.001) patients were efficiently divided into prognostic groups by SPF, whereas in ER- and in PR- tumours SPF had only suggestive predictive value. In N- tumours, SPF predicted recurrence-free survival and disease-related survival in ER+ (p = 0.003) (p = 0.039) and in PR+ (p = 0.003) (p = 0.012) tumours, respectively, whereas in ER-, PR-, tumours, SPF had no predictive value. In pN+ tumours, SPF also predicted survival in ER+ (p = 0.03) and in PR+ (p = 0.024) tumours. Thus the prognosis of ER+ or PR+ tumours with an SPF less than 9% is favourable with a risk of death of about 20%, in contrast to that of about 70% in tumours with an SPF greater than 9% during the follow-up period. To conclude, the proliferation rate as measured by S phase fraction by FCM is a highly significant prognostic factor in breast cancer. The prognostic value of S phase fraction is confined to steroid receptor-positive tumours, whereas in receptor-negative tumours SPF has no predictive value. The results thus suggest that all women with steroid receptor-negative breast tumours and those receptor-positive tumours with an SPF higher than 9% should be subjected to postoperative adjuvant chemotherapy immediately.

Biomarkers, Tumor↗

PubMedDate not supplied

The significance of nuclear morphometric variables as prognostic predictors in breast cancer.

The preoperative biopsies from primary breast carcinomas of 504 women were subjected to interactive morphometric analysis of a) the mean nuclear area (NA), b) standard deviation of nuclear area (SDNA), c) mean area of the 10 largest nuclei (NAl0), d) nuclear perimeter (PE), e) standard deviation of nuclear perimeter (SPDE), f) largest nuclear diameter (Dmax) and g) shortest nuclear diameter (Dmin), h) histological grade and i) classical prognostic variables. The above data were correlated with the disease outcome during the mean follow-up period of 11.2 years. Tumor size (p less than 0.0001), morphometric variables (p = 0.0001-0.005) and histological grade (p = 0.03) predicted axillary lymph node metastasis at the time of diagnosis. According to multivariate analysis, tumour size and NA predicted the axillary lymph node metastasis independently. Axillary lymph node status (p less than 0.0001) and histological grade (p = 0.01) predicted the tumour recurrence and recurrence-free survival, whereas the morphometric variables had no significant predictive value. Axillary lymph node status (p less than 0.0001), tumour size (p less than 0.0001), histological grade (p = 0.0012) and morphometric variables (p = 0.003-0.035) predicted the disease-related survival. Of the morphometric variables, NA and the Dmin were the two most important predictors of tumour-related survival in univariate analysis. Dmax had independent prognostic information in multivariate survival analysis. In the same analysis, tumour size and axillary lymph node status were more important predictors. In conclusion, the morphometric variables analysed have independent predictive value in female breast cancer. Their value is, however, inferior to that of the tumour size and axillary lymph node status, but equal to that of the histological grade.

Biopsy↗