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O P Kallioniemi

Publications and source records attributed to O P Kallioniemi.

At least 145 records · Page 8Linked to original sources
PubMed1990

Lipoprotein metabolism of human and rabbit arterial cells in primary culture.

The early atherosclerotic lesion, the fatty streak, consists of cholesteryl ester-containing foam cells originating mainly from monocyte-macrophages and to a lesser extent from smooth muscle cells. In this study, we describe lipoprotein uptake and cholesterol accumulation into enzyme-dispersed primary cell cultures from cholesterol-fed rabbit aortas and human aortic fatty streaks. Uptake of fluorescently labelled acetylated low density lipoprotein (acetyl-LDL) was demonstrable in macrophage-derived foam cells and in many smooth muscle cells in early primary cultures. The uptake of acetyl-LDL led to significantly enhanced cellular esterification of cholesterol. Fluorescent beta-migrating very low density lipoprotein (beta-VLDL) was internalized by a considerable number of lesion macrophages and also by smooth muscle cells. Also beta-VLDL uptake stimulated cholesterol esterification, although the effect was milder than that of acetyl-LDL. These findings lend support to the assumption that, during atherogenesis, arterial macrophages are capable of accumulating cholesteryl esters by receptor-mediated uptake of beta-VLDL and modified LDL. The internalization of modified LDL by smooth muscle cells represents a mechanism potentially contributing to the formation of foam cells in the atherosclerotic lesion.

Animals↗
PubMed1989

Immunohistochemical determination of estrogen and progesterone receptors in human breast carcinoma. Correlation with histopathology and DNA flow cytometry.

Human breast carcinomas (n = 232) were evaluated for estrogen and progesterone receptors (ER, PR) by immunohistochemical study and by cytosol steroid-binding assay (n = 185). The staining was scored (histoscore) by estimates of relative nuclear staining intensity and the percentage of positively stained carcinoma cells. Of the invasive ductal carcinomas 72% were ER-positive and 55% were PR-positive. The invasive lobular, intraductal, tubular, and mucinous carcinomas were the most frequent ER-positive tumor types, whereas comedo and medullary carcinomas only rarely contained ER. Progesterone receptor was most frequently present in intraductal, tubular, and mucinous carcinomas. Better differentiated tumors with lower histologic grade were significantly associated with high prevalence of immunohistochemically determined ER and PR (P less than 0.0001). Proliferative cell fraction, determined by DNA flow cytometric study (n = 63), was inversely related to ER (P = 0.03) and PR (P = 0.05) status. Aneuploidy was independent of ER or PR content.

Adult↗
PubMed1989

Different opinions on classification of DNA histograms produced from paraffin-embedded tissue.

Flow cytometric DNA ploidy determination has been regarded as an objective prognostic parameter in several types of human cancer. To test whether DNA histograms are similarly interpreted, a series of flow cytometric DNA histograms was posted to six investigators working in the field for independent classification. The histograms were produced from paraffin-embedded adrenal adenomas or non-neoplastic tissue and had several different patterns. Only 44% of the histograms were similarly classified by all investigators, and 85% by five of the six participants, when DNA ploidy was evaluated. Different criteria for tetraploidy existed, and also some uncertainty in classifying peridiploid and small aneuploid peaks. It is concluded that lack of consensus on histogram classification may result in widely varying percentages of DNA aneuploid tumors found even if the data are similar. Until general agreement is reached on the definition of DNA aneuploidy and its subclasses, classification of DNA histograms is variable and subjective.

Adenoma↗
PubMed1989

Flow cytometric DNA analysis of 199 histologically favourable or unfavourable non-Hodgkin lymphomas.

We have studied the nuclear DNA content of histologically favourable (n = 82) or unfavourable (n = 117) non-Hodgkin lymphomas (NHLs) diagnosed between 1957 and 1978 in the Tampere University Central Hospital. The DNA analysis was done by applying a trypsin digestion method to archival tumour samples. DNA aneuploidy was seen in 40 per cent of the unfavourable cases and in 10 per cent of the favourable cases, but varied considerably between different histological subtypes. The unfavourable cases showed high proliferative activity (S-phase fraction, SPF), while considerable variation in the SPF among the favourable NHLs was noted. Among the unfavourable NHLs, cases with DNA-aneuploid tumours had significantly (P less than 0.01) worse prognosis than stage and treatment matched cases with DNA-diploid tumours. In general, survival of the patients who had high SPF tumours was significantly lower compared with patients with low SPF tumours (P less than 0.01). However, SPF was not related to the prognosis in the unfavourable NHLs. We conclude that the flow cytometric DNA analysis revealed characteristic features in the favourable and unfavourable NHLs and may be useful in predicting the clinical outcome of patients.

Adult↗
PubMed1989

Analysis of DNA synthesis in herpes simplex virus infected cells by dual parameter flow cytometry.

The DNA incorporation of a thymidine analogue bromodeoxyuridine (BrdUrd) in herpes simplex virus type 2 (HSV-2) infected cervical cancer cell lines (CaSki and C-33 A) was studied by dual parameter flow cytometry. HSV-2 infection resulted in an exponential increase in DNA synthesis in the CaSki cells. In the less permissive C-33 A cells the proportion of DNA-synthesizing cells cycled during HSV-2 infection. The inhibition of viral DNA synthesis by phosphonoformate (PFA) was able to inhibit the virus induced changes in the CaSki but not in the C-33 A cells. In the C-33 A cells a part of the virus induced cellular DNA synthesis represents repair replication of cellular DNA.

Bromodeoxyuridine↗
PubMed1989

Primary invasive and in situ vaginal carcinoma. Flow cytometric analysis of DNA aneuploidy and cell proliferation from archival paraffin-embedded tissue.

Eleven invasive and five non-invasive primary vaginal carcinomas were studied by DNA flow cytometry using archival paraffin-embedded tissue as starting material. Overall frequency of DNA aneuploidy in the invasive carcinomas was 8/11 (73%). DNA aneuploidy occurred in all four advanced stage (III-IV) and in 4/7 (57%) of the early stage (I-II) carcinomas. Among the squamous cell carcinomas aneuploid DNA content was also associated with non-keratinizing tumor type. Invasive vaginal carcinomas showed a high median S-phase fraction (SPF) (18.4%, range 6.9-31.8%). High SPF values were associated with advanced stage and non-keratinizing tumors. Corrected 5-year survival rate in invasive vaginal cancer was 44%, with no significant relation to DNA ploidy or SPF. In situ carcinomas were almost as often DNA-aneuploid (3/5, 60%) as the invasive carcinomas and had comparable median SPF value (13.4%, range 5.5-24.6). One in situ carcinoma with a high DNA-index and SPF relapsed, but overall 5-year survival rate was 100%. In conclusion, both invasive and in situ vaginal carcinomas frequently contain DNA-aneuploid stemlines and show a high SPF. Although DNA aneuploidy and high SPF correlate with advanced stage and non-keratinizing tumor type, they do not have much prognostic relevance in vaginal neoplasia.

Aneuploidy↗
PubMed1989

Suppression of autologous mixed leukocyte reaction in type 1 diabetes mellitus by in vivo-activated T lymphocytes.

In vivo-activated interleukin 2 receptor-positive T lymphocytes (Tac cells) are demonstrable and the autologous mixed leukocyte reaction (AMLR) is impaired in several autoimmune diseases, including type 1 insulin-dependent diabetes mellitus (IDDM). We investigated AMLR in greater detail, together with possible relationships between AMLR and Tac lymphocytes in IDDM. Coculture experiments with HLA identical patient-healthy sibling pairs revealed that both responder and stimulator cells of diabetic patients function abnormally in AMLR. Suppressive Tac lymphocytes among responder T cells seemed to impair their proliferation. The removal of Tac cells by immunomagnetic beads led to a striking enhancement of proliferation, while the restoration of AMLR cultures with enriched Tac cells was accompanied by a diminished response. The reasons for the poor stimulatory capacity of patient cells are at present unknown but may be due to altered function and/or structure of HLA-DR molecules.

Cells, Cultured↗
PubMed1989

Serum CA 125 in acute pelvic inflammatory disease.

Serum levels of CA 125 and other selected tumour markers were measured in 31 patients with proven pelvic inflammatory disease (PID). Ten (32%) of the patients had elevated CA 125, one (4%) had elevated CEA, and none had elevated CA 15-3, AFP or beta 2-microglobulin. Compared to patients with normal CA 125, patients with elevated CA 125 were older, more often users of intrauterine contraceptive devices, had longer duration of symptoms, higher erythrocyte sedimentation rates, and more often had an adnexal mass on pelvic examination. There was a correlation between CA 125 levels and the severity of adnexal inflammation as defined by laparoscopy. Isolation of specific micro-organisms from the upper genital tract was not associated with elevated CA 125. In most women serum levels of CA 125 decreased during treatment. PID should be considered as a major cause of positive CA 125 findings among young women.

Adult↗
PubMed1989

Prognostic assessment in stage I ovarian cancer using a discriminant analysis with clinicopathological and DNA flow cytometric data.

We have previously defined three types of tumor DNA histograms, which are associated with favourable, intermediate and poor prognosis of patients with ovarian cancer. In the present study we evaluated the value of DNA histogram type combined with clinicopathological data in predicting long-term clinical outcome in stage I ovarian cancer. A stepwise discriminant analysis was done to find out the best combination of prognostic parameters in the distinction of two groups of stage I ovarian cancer patients; those with less than 5-year overall survival (22 cases) and those with longer than 5-year recurrence-free survival (47 cases). DNA histogram and histological type as well as FIGO stage in that order proved to be the most discriminating parameters and their combination allowed the correct prediction of clinical outcome in 78% of stage I ovarian cancer patients. In stage Ia the proportion of correctly classified cases based on DNA histogram and histological type was 82%. If DNA histogram was omitted from the discriminant analysis, the combination stage and histological type correctly classified a significantly lower percentage (68%) of patients. DNA flow cytometry thus improved the prognostic evaluation in stage I ovarian cancer, but even when combined with conventional clinicopathological factors failed to give correct prognostic assessment in about 20% of patients with stage I ovarian cancer.

Aged↗
PubMed1989

Cultured bovine aortic endothelial cells secrete factor(s) chemotactic for aortic smooth muscle cells.

Interactions of vascular endothelial cells (ECs) and smooth muscle cells (SMCs) were studied by testing the ability of cultured bovine aortic ECs to secrete factors influencing the migration of cultured aortic SMCs from the same species. Migration of SMCs was examined in blind-well chambers using gelatin-coated polycarbonate filters. Conditioned culture medium obtained by incubating confluent monolayers of ECs in serum-free RPMI-1640 medium for 48 hours caused a 2.4-fold increase in the migration of SMCs as compared with nonconditioned medium (p less than 0.001). The effect was dependent on the length of conditioning with the ECs and was chemotactic in nature as judged on the basis of checkerboard analysis. Preliminary characterization of the migration stimulating activity indicates that it is sensitive to trypsin, nondialyzable, and stable at 56 degrees C for 30 min. The activity was abolished by heating to 100 degrees C for 20 min but was not significantly inhibited by protamine sulphate, which suggests that most of the activity was not due to platelet-derived growth factor (PDGF)-like proteins. Our results thus show that ECs secrete polypeptide(s) chemotactic for vascular SMCs. Such interactions between ECs and SMCs in vivo might contribute to the migration of medial SMCs into the intima during atherogenesis.

Animals↗
PubMed1988

Improving the prognostic value of DNA flow cytometry in breast cancer by combining DNA index and S-phase fraction. A proposed classification of DNA histograms in breast cancer.

To optimize the prognostic value of DNA flow cytometry in breast cancer the authors calculated several parameters from the DNA histogram, including the DNA index, the size and number of aneuploid peaks as well as S-phase and G2/M-phase cell cycle fractions. Of these, DNA index and S-phase fraction (SPF) proved to be the most valuable prognostic indices. DNA aneuploidy was associated with a three-fold risk of death as compared to DNA diploidy (P less than 0.0001). The highest risk of death was associated with hypertetraploid (greater than 2.20) DNA index, whereas a tetraploid DNA index (1.80-2.20) was associated with a relatively low risk. The SPF had significant additional prognostic value in both DNA diploid (P = 0.0002) and DNA aneuploid (P = 0.02) tumors. By combining DNA index and SPF the authors defined three types of DNA histograms, which were associated with favorable, intermediate, and poor prognosis of the patients. DNA diploidy together with low (less than 7%) SPF (type I DNA histogram) was associated with very favorable prognosis, whereas DNA aneuploidy with high DNA index (greater than 2.20) or high (greater than 12%) SPF (type III DNA histogram) was related to the worst prognosis with approximately eight-fold relative risk of death. In a Cox multivariate regression analysis the type of DNA histogram was an independent and most powerful prognostic indicator in breast cancer. The other independent factors in the Cox analysis were primary tumor size, nodal status, and progesterone receptor status.

Aged↗
PubMed1988

DNA flow cytometric analysis indicates that many breast cancers detected in the first round of mammographic screening have a low malignant potential.

An organized mammographic screening program covered 8,690 women from selected birth cohorts (aged 50-59) in the Tampere University Central Hospital district. Forty-four breast cancer cases were detected in the first round of mammographic screening, which is 3.7 times the expected annual number of new cases in this population. To evaluate the proliferative kinetics and biological properties of these cancers, DNA flow cytometric analysis was carried out in 37 of the screen detected cancers (SDCs) using 60 clinically detected stage I-II cancers and 30 screen-detected benign lesions as reference. DNA aneuploidy was observed in 17/37 (46%) of the SDCs as compared to 41/60 (68%) in the clinical controls (p less than 0.05), while all the benign lesions were DNA-diploid. The median S-phase fraction (SPF) in the SDCs was significantly (p less than 0.001) lower (3.5%) than in the clinical controls (9.6%). Differences in SPF persisted in subgroups defined by DNA ploidy and histological type. In stage-I SDCs the median SPF value (2.5%) approached that of benign tumors (1.9%). Our epidemiological and biological data indicate that the first round of mammography predominantly detects prevalent preclinical lesions, some of which are of very low malignant potential. At present such patients may often receive too extensive treatment. DNA flow cytometry could help in the identification of cases which could be treated, for example, by breast-conserving methods.

Aneuploidy↗
PubMed1988

Prognostic significance of DNA index, multiploidy, and S-phase fraction in ovarian cancer.

Paraffin-embedded tumor samples from 157 ovarian cancer patients were analyzed by DNA flow cytometry. Tumor ploidy had prognostic significance in both early and advanced ovarian cancer. After adjusting for stage, residual tumor mass, histopathologic type, treatment, and age of patient in a Cox regression analysis, the relative risk of death was two-fold higher in single DNA-aneuploid and sixfold higher in DNA-multiploid tumors as compared to DNA-diploid tumors (P less than 0.0001). A tetraploid DNA index was associated with a relatively low risk ratio, whereas hypertetraploid tumors were highly malignant. S-phase fraction (SPF) had prognostic value especially in DNA-diploid tumors. The simultaneous evaluation of DNA index, the number of aneuploid cell clones, and SPF gave more prognostic information than the determination of tumor ploidy alone. On the basis of these parameters we have developed a classification of tumor DNA histograms for better prognostic assessment of ovarian cancer.

Aged↗
PubMed1988

Comparison of fresh and paraffin-embedded tissue as starting material for DNA flow cytometry and evaluation of intratumor heterogeneity.

Flow cytometric analysis of DNA ploidy and S-phase fraction (SPF) from paraffin-embedded tumors has become an important diagnostic and prognostic tool in clinical pathology and investigative oncology. The present study aimed at elucidating the reliability of the method. About 90% of the 1,400 paraffin-embedded tumors analyzed were evaluable for DNA index and about 70% for SPF, although considerable differences between various tumor types were detected. The within-assay coefficients of variation for determination of tumor DNA index and SPF were 2% and 6%, respectively. Intratumor variation in DNA index was observed in 24% of breast and in 21% of ovarian carcinomas and variation in SPF in 36% and 29% of the respective tumors. Intratumor variation in SPF was greatest in DNA-diploid tumors, which may indicate that SPF values in these tumors may be less reliable owing to variations in the proportions of tumor and nontumor cells. If the methodological variation and the intratumor variation were taken into account, there was a good correlation between DNA indices (r = 0.980) and between SPF values (r = 0.794) obtained from fresh and paraffin-embedded tumors. It is concluded that accurate determination of DNA index and SPF from paraffin-embedded tumors is possible in the majority of cases. Regardless of the type of starting material used for DNA flow cytometry it is advantageous to study several samples from each tumor to account for the intratumor heterogeneity.

Breast Neoplasms↗
PubMed1988

Elevated serum HMFG antigen levels in breast and ovarian cancer patients measured with a sandwich ELISA.

HMFG antigen is a tumour associated glycoprotein that has been immunohistochemically shown to be expressed by malignant cells in breast and ovarian and to a lesser degree in gastro-intestinal carcinomas. We have developed a non-isotopic sandwich ELISA for secretory HMFG antigen utilizing a polyclonal catcher and a tracer monoclonal antibody (MAb). 52/52 of healthy medical students (controls) had a serum value under 400 U/ml whereas 15/30 patients (50%) with evident ovarian cancer and 13/37 (35%) with advanced breast cancer had a value exceeding 400 U/ml. From other patients with malignant tumours 2/14 (14%) with endometrial carcinoma, 0/5 with cervical carcinoma, 0/5 with vulvar carcinoma, 1/33 with gastro-intestinal carcinoma, 0/4 with oesophageal carcinoma and 2/45 of patients with leukemia or lymphoma had an elevated serum HMFG value. Four cases of Crohn disease, 3 cases of ulcerative colitis and 2 cases of pelvic inflammatory disease all showed a serum value below 400 U/ml. Progression of ovarian cancer was accompanied by increasing serum HMFG antigen levels. The antigen detected by our assay is different from CA 125 but may be related with the tumour associated antigen CA 15-3.

Antigens↗