[Williams syndrome--developmental syndrome's common cardiovascular disorders].
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Biomedical subjects
Publications and source records attributed to A Westerlund.
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OBJECTIVE: Expression of the immunoreactive protein of matrix metalloproteinase 2 (MMP-2) was studied in cervical tumors representing various stages of cell atypia and differentiation. In this study, we evaluated whether the expression of MMP-2 is an early or late event in the process of dedifferentiation and cancer progression. METHODS: Paraffin tissue sections from 60 cervical neoplasias including 38 cervical intraepithelial neoplasias (CINs) and 22 early-stage (stage IB and IIA) squamous cervical carcinomas were studied with respect to the expression of MMP-2 protein by using immunoperoxidase staining. RESULTS: The staining pattern of MMP-2 in the CIN lesions usually differed from that in squamous carcinoma. Latent MMP-2 protein localized, in most of the cases, to the periphery of the CIN cells, but was diffuse in the cytoplasm of the carcinoma cells. No correlation was found between overexpression of MMP-2 protein and degree of dysplasia, nor was there any association between MMP-2 and human papillomavirus (HPV). High scores for MMP-2 were observed only in histologically higher-grade early-stage cervical carcinomas. The lymph node metastases derived from high-MMP-2-score primary tumors were also positive for MMP-2. No correlation between MMP-2 staining and clinical course or prognosis was found. CONCLUSIONS: MMP-2 expression is an early event during dedifferentiation and malignant transformation in cervical neoplasias. The pattern of staining is different in CIN than in squamous carcinoma cells, in which overexpression may correlate with the degree of anaplasia.
OBJECTIVE: Gelatinase A (MMP-2) is a member of the matrix metalloproteinase family and it degrades the major component of the basement membrane, type IV collagen. MMP-2 has been linked to invasion in different types of cancer. METHOD: We have studied the localization of MMP-2 in 18 benign, 3 borderline, and 33 malignant ovarian lesions by immunohistochemical stainings using a monoclonal antibody against MMP-2. RESULTS: MMP-2-immunoreactive protein was localized in epithelial cells and in fibroblasts. Two types of cytoplasmic staining were observed, a diffuse and a granular pattern. The diffuse staining model was found more often. In 19% of the cases, both staining patterns were present in epithelial cells. Granular staining was found in epithelial cells in cystadenomas and in ovarian cancer cells. The pattern of MMP-2 positivity in fibroblasts was diffuse. MMP-2 positivity in cancer cells was associated with recurrent disease (P < 0.05) in ovarian cancers. MMP-2 negativity in fibroblasts correlated to Grade 3 (P < 0.01), Stage III-IV (P < 0.001), recurrency (P < 0.05), and refractory disease (P < 0.05) in ovarian cancer. The relative survival rate was 32% in patients with an MMP-2-positive ovarian cancer, 57% in patients with an MMP-2-negative ovarian cancer, and 19% in patients with MMP-2 positivity in cancer cells and concomitant negativity in stromal fibroblasts. The disease-free 5-year survival rates were 25, 57, and 12.5%, respectively. CONCLUSIONS: These data suggest that MMP-2 may contribute to poor prognosis of ovarian cancer.
Young adults (n = 54 for Exp. 1, n = 50 for Exp. 2) and elderly adults (the same n = 40 in each experiment) participated in studies that required nonspeeded magnitude estimation scaling in response to words that varied in frequency and number of meanings. Across both experiments and across both groups, subject and item analyses indicated significant word frequency effects (low-frequency words were judged more difficult to process than high-frequency words) and significant word meaning effects (unambiguous words were judged to be more difficult to process than ambiguous words). Mean magnitude estimate values were significantly and positively correlated with mean lexical-decision task values obtained from the same subjects on the same stimuli based on data from a previous experiment. Results suggest that processes required for magnitude estimation are similar to those measured with the lexical decision task in word-recognition studies involving young and elderly adults.
OBJECTIVE: The host-tumor interactions and tumor stroma may participate in the regulation of invasive behavior of tumor cells. In order to better understand the human ovarian cancer invasion we explored the possibility that normal fibroblasts could participate in the control of the spread of human ovarian cancer. RESULTS: A 3.5-fold increase (from 2.83 +/- 0.97 to 10.2 +/- 3.43%) in human ovarian cancer cell (Ovcar-3) invasion through a reconstituted basement membrane was noted when normal fibroblasts (CRL 1295) were added to the invasion chambers in conjunction with tumor cells. Conditioned medium from either fibroblasts or Ovcar-3 also enhanced the in vitro invasion of Ovcar-3 by 2- to 2.5-fold (from 2.83 +/- 0.97 to 5.71 +/- 3.5 and to 7.15 +/- 1.2%, respectively) compared to nonstimulated control cells. Zymographic analysis and assays of mRNA for the 72-kDa matrix metalloproteinase (MMP-2) showed that Ovcar-3 cells alone produced very low levels of MMP-2; the expression of this gelatinase was detectable in zymography only with stimulation by incubation of these cells with conditioned media from either fibroblasts or ovarian cancer cells themselves. Interestingly, MMP-2 activity was increased also in fibroblasts when using either ovarian cancer cell-conditioned (to 178 +/- 67%) or fibroblast-conditioned medium (to 215 +/- 61%) and the gene expression for MMP-2 was similarly increased in both fibroblasts and Ovcar-3 cells when using either fibroblast-conditioned medium or ovarian cancer cell-conditioned medium from 1.00 +/- 0.25 to 2.20 +/- 0.50 and 1.86 +/- 0.10 in fibroblasts and from 1.00 +/- 0.26 to 1.60 +/- 0.34 and 2.15 +/- 0.30 in Ovcar-3 cells, respectively. CONCLUSIONS: These results show that interplay between tumor cells and normal cells in the control of invasion and secretion of proteolytic enzymes may involve not only paracrine but also autocrine elements. Thus, such interactions are possible and may play an important role in the spread of cancer.
Overproduction of matrix metalloproteinases (MMPs) and alterations in adhesive and migratory behavior are common characteristics of metastatic cancer cells. Ovarian cancer is a highly invasive type of malignancy. The effect of the antineoplastic drug paclitaxel on human ovarian cancer cell (Ovcar-3) invasion was studied using an in vitro invasion assay with reconstituted basement membrane. The effect of treatment with paclitaxel was also determined separately on certain invasion-associated events, such as the secretion of 72 kDa type IV collagenase (gelatinase A/MMP-2), the expression of the tissue inhibitor of metalloproteinase-2 (TIMP-2), cell attachment and migration. Ovcar-3 cell attachment, migration and in vitro invasion were significantly decreased after paclitaxel treatment (P = 0.02, P < 0.01 and P = 0.001, respectively) whereas no alteration in the secretion of latent MMP-2 was noted. However, the intracellular localization of the immunoreactive protein for MMP-2 was altered in response to paclitaxel treatment. Interestingly, paclitaxel increased the appearance of TIMP-2 protein in culture medium (P = 0.002) but did not change the expression of mRNA for TIMP-2 in Ovcar-3 cells. These data show that paclitaxel is an effective suppressor of Ovcar-3 cell invasion. It inhibits attachment and migratory activities of the cells but also causes a release of TIMP-2 protein into the tissue culture medium.
This study was conducted to identify the long term effects of traumatic brain injury (TBI) on the roles of caregivers. The subjects consisted of 155 caregivers of survivors with TBI who were randomly selected from 15 midwestern state brain injury association databases. A questionnaire was developed by the researchers to determine factors affecting role changes of caregivers. The Role Checklist, by Barris, Oakley and Kielhofner, was also included with the questionnaire. Both were mailed to each selected caregiver and used for data gathering. The data obtained were analysed to determine existing trends in the data. Graphs were utilized to depict the trends that was identified. The following trends and conclusions established by this research include: (a) behavioural effects of the survivor with a TBI are associated with the number of role changes experienced by caregivers; (b) participation in support systems is associated with the number of role changes experienced by caregivers; and (c) caregivers who care for a person with a TBI in the home will show a larger number of role changes than those who do not provide direct care for a person with a TBI.
OBJECTIVE: To examine the hormonal regulation of 72-kd type IV collagenase-gelatinase-matrix metalloproteinase-2 in human granulosa-lutein cells. DESIGN: The effect of E2 and GnRH agonist (GnRH-a) on matrix metalloproteinase-2 amount was examined on a long-term granulosa-lutein cell cultures. PATIENTS: The preovulatory follicles from women participating in our IVF program were aspirated through the vaginal wall. Follicular fluids were centrifuged and the granulosa cells were separated and pooled for culturing. MAIN OUTCOME MEASURES: Matrix metalloproteinase-2 enzyme activity was assayed with type IV collagen degradation assay and zymography. The matrix metalloproteinase-2 immunoreactive protein was studied by using specific antibodies. RESULTS: Matrix metalloproteinase-2 was the predominant form of gelatinase in cultured granulosa-lutein cells. The enzyme activity as well as the immunoreactive protein increased in the culture medium of the granulosa-lutein cells in the presence of E2. The effect of E2 was abolished by GnRH-a. CONCLUSIONS: Estradiol regulates the matrix metalloproteinase-2 enzyme amount in granulosa-lutein cells; the effect may be antagonized by GnRH-a.
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In an out-patient clinic for specialised medical care, 30 patients were questioned about their worries prior to the visit. The purpose of the study was to obtain basic knowledge about emotional experiences of patients visiting a doctor. The theoretical viewpoint was that of social interaction and social construction of reality. The statements of the patients were categorized as follows: before the encounter, the social interaction, the outcome of the encounter, and unspecific worries. A tool for measuring the degree and profile of the worries will be developed. Some of the worries described will be studied in depth. An education programme for all staff members is planned.
Previous investigations have suggested that hydrophilic beta-blockers, which appear at low concentrations in brain tissue, are less likely to produce CNS-related side-effects than are lipophilic beta-blockers, which occur at higher concentrations in the brain. The validity of this hypothesis was tested in a double-blind crossover study in which the hydrophilic beta-blocker atenolol was compared with the lipophilic agents metoprolol and propranolol, in 14 patients with a previous history of nightmares or hallucinations when treated with lipophilic beta-blockers. Nightmares or hallucinations were reported by all patients receiving lipophilic beta-blockers but by only three patients receiving atenolol. The total number of episodes was significantly lower (p less than 0.01) for patients receiving atenolol (8) than for those receiving lipophilic beta-blockers (54). It is concluded that atenolol is significantly less likely to provoke nightmares and hallucinations than are the lipophilic beta-blockers, metoprolol and propranolol. It seems likely that this finding is due to the differences in hydrophilicity amongst these drugs.
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Propranolol was given to 30 patients with essential hypertension following randomised, double-blind administration of either placebo or a new cardioselective beta-adrenergic receptor antagonist, atenolol (Tenormin, ICI 66 082). Both atenolol and propranolol caused statistically significant reduction of recumbent and erect blood pressure and heart rate. There were no important differences between these variables on comparison of atenolol and propranolol.