Biomedical subjects

Veli-Matti Kosma

Publications and source records attributed to Veli-Matti Kosma.

45 records · Page 3Linked to original sources

PubMed2002

Gonadotrophins inhibit the expression of insulin-like growth factor binding protein-related protein-2 mRNA in cultured human granulosa-luteal cells.

Insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) have been shown to be involved in ovarian follicular growth/development and steroidogenesis. Recently, a number of low-affinity IGFBP-related proteins (IGFBP-rP) have been characterized. In this study, we investigated the expression of the gene for IGFBP-rP2 (also known as connective tissue growth factor, CTGF) in human granulosa cells in vitro and in vivo. Northern blot analysis demonstrated that IGFBP-rP2 mRNA is expressed in cultured human granulosa-luteal cells obtained from women undergoing an IVF programme. Accumulation of IGFBP-rP2 mRNA was dose-dependently down-regulated by FSH and LH after 24 h treatment (both P < 0.05) in cultured granulosa-luteal cells. The inhibitory effects of gonadotrophins were mimicked by treatment with the protein kinase A activator, (Bu)(2)cAMP. Protein kinase C inhibitor staurosporine reduced, whereas protein kinase C activator TPA (12-O-tetradecanoyl phorbol 13-acetate) increased, IGFBP-rP2 mRNA accumulation. These results suggest that the inhibitory effects of gonadotrophins on IGFBP-rP2 gene expression may involve signal transduction via both protein kinase A and C pathways. Immunohistochemical analysis revealed positive staining for IGFBP-rP2 in the granulosa and theca cells of normal human ovarian follicles. Corpus luteum and ovarian surface epithelial cells were also positively stained. Modulation of IGFBP-rP2 expression by gonadotrophic hormones may have a role in ovarian follicular development and in the ovulatory process.

Cells, Cultured↗

PubMed2002

Inducible nitric oxide synthase expression in pharyngeal squamous cell carcinoma: relation to p53 expression, clinicopathological data, and survival.

OBJECTIVE: To investigate the expression of inducible nitric oxide synthase (iNOS) in oropharyngeal and hypopharyngeal squamous cell carcinoma (SCC) and its relation to p53 expression, histologic differentiation, clinical data, and prognosis. STUDY DESIGN: A retrospective survey. METHODS: Primary tumors for analyses were obtained from 118 patients diagnosed with SCC of the oropharynx or hypopharynx between 1975 and 1998 in eastern Finland. Immunohistochemical analysis was used to evaluate the expression of iNOS and p53. The expression pattern of iNOS was related to p53 expression, clinical data, and survival. RESULTS: High iNOS score was associated significantly with high nuclear p53 expression index (P = .006) and positive cytoplasmic p53 expression (P = .025). The score for iNOS expression was significantly lower in the largest (T4) tumors (P = .043). No association was seen between iNOS score and N or M class, tumor stage, or histologic differentiation. The score for iNOS expression was not related to overall survival. CONCLUSIONS: The expressions of iNOS and p53 seem to be inter-related in pharyngeal SCC, although the causality remains to be clarified. The expression of iNOS shows no prognostic value in pharyngeal SCC.

Adult↗

PubMed2002

Combined COMT and GST genotypes and hormone replacement therapy associated breast cancer risk.

Our previous studies suggested that both COMT and GST genotypes might modify individual breast cancer risk. Here, we extended the studies to examine the potential combined effect of these genotypes in susceptibility to breast cancer. Our study population consisted of 483 Finnish breast cancer cases and 482 population control subjects. The odds ratios (ORs) and (95%) confidence intervals (CIs) were calculated by unconditional logistic regression adjusting for known or suspected confounding factors. No significant increase in the overall breast cancer risk was seen for any combinations of the studied genotypes. However, a substantially increased risk of breast cancer was seen for women who had used hormone replacement therapy (HRT) and simultaneously carried the COMT-L allele containing genotypes and either the GSTP1 Ile/Ile genotype (OR 4.10, 95% CI 1.24-13.6) or the GSTT1 null genotype (OR 4.19, 95% CI 1.30-13.5). These associations appeared to be mainly attributable to long-term users of HRT; the respective ORs were 7.00 (95% CI 1.21-40.6) and 8.36 (95% CI 1.44-49.0) among the users of HRT of more than 30 months. In addition, the combination of COMT-L allele containing genotypes with the GSTM1 null genotype posed a remarkably increased risk (OR 9.10, 95% CI 1.84-45.0) of breast cancer in this study group. These results suggest that the use of HRT could substantially increase the risk of breast cancer among women with specific combinations of the at-risk genotypes of COMT and GST genes.

Adult↗

PubMed2002

Mycobacterium terrae isolated from indoor air of a moisture-damaged building induces sustained biphasic inflammatory response in mouse lungs.

Occupants in moisture-damaged buildings suffer frequently from respiratory symptoms. This may be partly due to the presence of abnormal microbial growth or the altered microbial flora in the damaged buildings. However, the specific effects of the microbes on respiratory health and the way they provoke clinical manifestations are poorly understood. In the present study, we exposed mice via intratracheal instillation to a single dose of Mycobacterium terrae isolated from the indoor air of a moisture-damaged building (1 X 10(7), 5 X 10(7), or 1 X 10(8) microbes). Inflammation and toxicity in lungs were evaluated 2 hr later. The time course of the effects was assessed with the dose of 1 X 10(8) bacterial cells for up to 28 days. M. terrae caused a sustained biphasic inflammation in mouse lungs. The characteristic features for the first phase, which lasted from 6 hr to 3 days, were elevated proinflammatory cytokine [i.e., tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6)] levels in the bronchoalveolar lavage fluid (BALF). TNF-alpha was produced in the lungs more intensively than was IL-6. Neutrophils were the most abundant cells in the airways during the first phase, although their numbers in BALF remained elevated up to 21 days. The characteristics of the second phase, which lasted from 7 to 28 days, were elevated TNF-alpha levels in BALF, expression of inducible nitric oxide synthase in BAL cells, and recruitment of mononuclear cells such as lymphocytes and macrophages into the airways. Moreover, total protein, albumin, and lactate dehydrogenase concentrations were elevated in both phases in BALF. The bacteria were detected in lungs up to 28 days. In summary, these observations indicate that M. terrae is capable of provoking a sustained, biphasic inflammation in mouse lungs and can cause a moderate degree of cytotoxicity. Thus, M. terrae can be considered a species with potential to adversely affect the health of the occupants of moisture-damaged buildings.

Air Pollution, Indoor↗

PubMed2002

Reduced nuclear expression of transcription factor AP-2 associates with aggressive breast cancer.

PURPOSE: We proposed to investigate the expression and prognostic significance of activator protein 2 (AP-2) in breast cancer. EXPERIMENTAL DESIGN: AP-2 was immunohistochemically analyzed in a prospective, consecutive series of 420 breast cancer patients diagnosed and treated between 1990 and 1995 at Kuopio University Hospital, Kuopio, Finland. AP-2 expression was further compared with clinicopathological parameters and patients' survival. RESULTS: Nuclear AP-2 expression was lower in carcinomas compared with normal ductal breast epithelium (P < 0.001). Nuclear expression was more often seen in lobular than in ductal or other carcinomas (P = 0.048). Cytoplasmic staining was present in 47% of the carcinomas. Low nuclear AP-2 expression level in carcinomas was associated with advanced stage (P = 0.002), axillary lymph node positivity (P = 0.012), poor differentiation (P = 0.001), and recurrences (P = 0.003). In univariate survival analyses, low nuclear AP-2 expression (P = 0.0028), advanced stage (P < 0.0001), lymph node metastases (P < 0.0001), and poor differentiation (P = 0.0498) predicted shorter recurrence-free survival (RFS). Low nuclear AP-2 staining and/or shift to cytoplasmic expression predicted shorter RFS (P = 0.0050) and breast cancer-related survival (BCRS; P = 0.0314) in univariate analyses. Cytoplasmic expression alone did not have prognostic value. In multivariate analysis, low nuclear AP-2 expression (P = 0.0292) and advanced stage (P = 0.0001) were independent predictors of shorter RFS; and stage (P < 0.0001) and ER-status (P = 0.0321) independently predicted BCRS. In the lymph-node positive patients, RFS was independently predicted by stage (P = 0.0110) and nuclear AP-2 status (P = 0.0151). CONCLUSIONS: AP-2 seems to have a protective role in breast cancer. Low nuclear AP-2 expression was associated with disease progression and increased metastatic capability of the tumor. In addition, reduced nuclear AP-2 expression independently predicted elevated risk of recurrent disease in breast cancer.

Adult↗

PubMedDate not supplied

Obstetric prognosis after placental abruption.

OBJECTIVE: To assess obstetric outcome in women with a history of placental abruption. METHODS: We utilised the population-based birth registry data of Kuopio University Hospital to investigate pregnancy outcome in 59 women with prior placental abruption. The general obstetric population was used as a reference group in logistic regression analysis. RESULTS: Recurrent placental abruption and associated adverse neonatal outcome occurred in 11.9% (7:59) of the women. If the disease did not recur, a history of placental abruption had no significant effects on birth weight, fetal distress or prematurity rate, whereas the incidence of pre-eclampsia was found to be increased. CONCLUSIONS: Women in whom placental abruption does not recur have a good outcome in their subsequent delivery, almost comparable to that in the general obstetric population. However, the recurrence rate of 11.9% is high (OR: 16.9, 95% CI: 8.2-34.9) when compared with the background incidence of placental abruption (0.7%).

Abruptio Placentae↗

PubMedDate not supplied

Expression of p53 and p21 Ki-ras proteins in rat thyroid gland tumors induced by 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX).

BACKGROUND: 3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), a disinfection by-product in chlorinated drinking water, induces follicular tumors in thyroid glands in Wistar rats. The mechanisms of the MX-induced thyroid gland tumorigenesis are not known. MATERIALS AND METHODS: The expressions of p53 (primary antibody CM5) and p21 Ki-ras (primary antibody F234) proteins were evaluated by immunohistochemisty in MX-induced tumors in Wistar rats. p53 expression was studied in 3 follicular adenomas, 29 follicular carcinomas and two C-cell carcinomas of thyroid glands. p21 Ki-ras expression was studied in 13 follicular carcinomas and one C-cell carcinoma. RESULTS: A weak expression of p53 protein (1-5% of tumor cells) observed in six follicular carcinomas (21%) and one C-cell carcinoma was not considered to be p53-positive. No expression of p21 Ki-ras was observed in any of the samples. CONCLUSION: These data indicate that p53 and Ki-ras proteins are not overexpressed in the MX-induced thyroid tumors in rats.

Animals↗

PubMedDate not supplied

alpha-, beta- and chi-catenin expression in human pancreatic cancer.

BACKGROUND: Previous studies have revealed that cadherin-catenin-complex have an impact on adhesive function between the cells and that the expression of these complexes are associated with tumour invasion and metastatic potential. In this study we investigated the expression of catenins (alpha, beta, chi) and their relationship to clinicopathological factors and prognosis in human pancreatic adenocarcinoma. PATIENTS AND METHODS: The expression of catenins was analysed immunohistochemically in 36 patients with pancreatic ductal adenocarcinoma, diagnosed and treated between 1994 and 1999 at Kuopio University Hospital, Finland. The staining results were compared with clinicopathological characteristics and survival. RESULTS: Immunohistochemical findings demonstrated that alternation of alpha- and beta-catenin expression correlated significantly with tumour grade. A clear trend between low catenin expression and poor survival was demonstrated among all catenin groups. In multivariate analysis, lymph node status and beta-catenin expression showed prognostic value. CONCLUSION: Abnormal catenin expression seemed to be related to poor survival in pancreatic cancer patients, and especially beta-catenin expression may have prognostic value.

Aged↗

PubMedDate not supplied

The expression and prognostic value of alpha-, beta- and gamma-catenins in renal cell carcinoma.

BACKGROUND: Catenins have prognostic value in several human tumours. The aim of the study was to analyse the prognostic value of catenin expression in a prospectively followed series of renal cell carcinoma. PATIENTS AND METHODS: One hundred and twenty-four renal cell carcinomas were prospectively followed-up for a mean of 3.5 years and the survival data of patients were related to standard prognostic factors and to the results of alpha-, beta- and gamma-catenin immunohistochemistry. The data of catenin immunohistochemistry were also related to the clinical and histopathological characteristics of the tumours. RESULTS: Low cytoplasmic alpha-catenin expression was related to lymphatic tumour growth (p=0.02) and to tumour necrosis (p=0.02). The weak expression intensity of beta-catenin on cell membranes was related to venous growth inside the tumour (p=0.02), extratumoural venous growth (p=0.03) and to perineural growth (p<0.001). Nuclear gamma-catenin expression was strongly associated with clear cell type (p=0.0001) and high WHO grade (p=0.038). Short recurrence-free survival was predicted by weak membranous alpha-catenin (p=0.015) and beta-catenin (p=0.006) expression intensity, while their cytoplasmic expression was of lower significance (p=0.07 and 0.045, respectively). All the conventional prognostic factors predicted short recurrence-free survival: Fuhrman classification (p=0.02), WHO grade (p=0.026), perineural growth (p=0.013), venous invasion (p=0.0024), tumour size (p=0.004) and T-category (p=0.0001). Independent predictors of short recurrence-free survival were weak membranous expression intensity of beta-catenin (RR=0.15, p=0.004), high T-category (RR=2.70, p=0.0001) and high WHO grade (RR=2.24, p=0.025). CONCLUSION: The results show that immunohistochemical analysis of beta-catenin expression may be used as an indicator of aggressiveness in renal cell carcinoma.

Adult↗