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Germinal matrix microvascular maturation correlates inversely with the risk period for neonatal intraventricular hemorrhage.

The risk period for intraventricular hemorrhage (IVH) of the preterm neonate is the first 3-4 postnatal days. For infants of < 34 weeks' gestation, this risk period is independent of gestational age. We hypothesized that this risk period is attributable to the perinatal induction of maturation of the germinal matrix microvasculature and tested this hypothesis by examining changes in the classical ultrastructural features of the blood-brain barrier over the first ten postnatal days in the newborn beagle model for neonatal IVH. Newborn beagle pups (n = 6) were anesthetized and systemically perfused and the brains were removed and prepared for electron microscopic examination. Examination of electron micrographs from the germinal matrix of animals on the first, fourth and tenth postnatal days demonstrated no difference in perimeter lengths and capillary and endothelial cell areas; in contrast, luminal areas significantly decreased across postnatal age (P = 0.04). Significant increases were found in basement membrane area between days 1 and 4 (P = 0.01) and tight junction length (day 1 vs. day 10, P = 0.02). In addition, on day 1, 19% of germinal matrix capillary perimeter was determined not to be covered by supporting cell processes, while by day 10, only 5% was bare. In contrast, the microvessels of the white matter exhibited no changes in these parameters during these three time points. These studies are consistent with the concept that basal lamina deposition and organization precede increases in endothelial cell tight junction formation and coverage by supporting cells.

Animals↗

Correlated random band matrices: localization-delocalization transitions

We study the statistics of eigenvectors in correlated random band matrix models. These models are characterized by two parameters, the bandwidth B(N) of a Hermitian NxN matrix and the correlation parameter C(N) describing correlations of matrix elements along diagonal lines. The correlated band matrices show a much richer phenomenology than models without correlation as soon as the correlation parameter scales sufficiently fast with matrix size. In particular, for B(N) approximately sqrt[N] and C(N) approximately sqrt[N], the model shows a localization-delocalization transition of the quantum Hall type.

Journal Article↗

Clinicopathological study of the expression of syndecan-1 in invasive breast carcinomas. correlation with extracellular matrix components.

Syndecan-1, a cell surface proteoglycan found predominantly on epithelia of mature tissues, binds both extracellular matrix (ECM) components and basic fibroblast growth factor (bFGF) and is implicated in the restriction of growth and invasiveness of neoplastic cells, as it induces the adhesion capacity of neoplastic cells with the stroma. In this study we investigated breast carcinomas for the immunohistochemical expression of syndecan-1 protein and these results were assessed in relation to clinicopathological parameters, in order to clarify its prognostic value. The possible relationship with hormone receptors content, p53, cell proliferation markers, and extracellular matrix components was also estimated. Tissue sections from 102 breast carcinomas were used and immunostainings were performed on formalin-fixed, paraffin-embedded tissue sections by the labelled streptavidin avidin biotin (LSAB) method. High expression levels were observed, as 75/102 (73.5%) cases expressed immunoreactivity in more than 80% of neoplastic cells, while 67/102 (65.7%) exhibited high staining intensity. The survival analysis showed an increased mortality risk associated with high syndecan-1 staining intensity with borderline significance (p=0.041). In addition, there was a strong negative correlation between syndecan-1 protein expression and ECM, specifically collagen IV (p=0.026) and tenascin (p=0.0067). The results of the present study show the implication of this protein in the remodeling of breast cancer tissue, through the interaction with other extracellular matrix components, probably influences the tumour progression.

Avidin↗

The effect of polyion complex formation on in vitro/in vivo correlation of hydrophilic matrix tablets.

The aim of this study was to investigate the effects of polyion complex formation on in vivo performance of hydrophilic matrix tablets. Three kinds of controlled release theophylline tablets were prepared by direct compression using carboxymethyldextran (CMD), a mixture of CMD and [2-(diethylamino)ethyl]dextran (EA), and a mixture of dextran sulfate (DS) and EA. According to a conventional dissolution test, in vitro drug release profiles of these tablets were similar to each other. In vivo absorption profiles of theophylline after oral administration to beagle dogs, however, were quite different and were not consistent with in vitro release profiles. Thus, we applied a modified in vitro release test considering destructive forces. An excellent in vitro/in vivo correlation was obtained in the cases of CMD/EA- and DS/EA-tablets. The results suggested that the drug was released constantly in the overall gastrointestinal tract, and even in the colon. Then, hydrophilic matrices were characterized by swelling rate, matrix density and strength in a wet state. DS/EA-tablets showed limited swelling, higher density and a larger value of wet strength than the others. These findings indicated that polyion complex formation in gel layer contributes to prevent over-swelling and strengthen the wetted matrices.

Administration, Oral↗

Degradation of endothelial cell matrix collagen is correlated with induction of stromelysin by an activated ras oncogene.

A conditional expression system was established whereby the human K-ras, v-src, and v-mos genes were cloned into a conditional expression vector downstream of the dexamethasone-inducible mouse mammary tumor virus long terminal repeat. Rat-1 fibroblasts were transfected with these constructs and selected in medium containing G418. Cloned transfectants were isolated and characterized for absolute dependence on dexamethasone for expression of oncogene products and anchorage-independent growth in soft agar. Expression of activated p21K-ras(val12) enabled the fibroblasts to degrade extracellular matrix collagen secreted by murine microvessel endothelial cells. Concurrent with p21K-ras(val12) induction a proteinase with the characteristic size and substrate specificity of transin, the murine homologue of the human matrix metalloproteinase stromelysin, was expressed and secreted. Induction of v-mos and v-src oncogenes resulted in little or no detectable transin expression respectively coinciding with a relative or absolute failure to increase degradation of extracellular matrix collagen. This study suggests that in this system the expression of the ras oncogene can contribute to the in vitro invasive behavior of tumor cells by upregulating the production of a metalloproteinase capable of degrading collagen synthesized by vascular endothelial cells.

Animals↗

Bronchoalveolar lavage procollagen-III-peptide in recent onset hypersensitivity pneumonitis: correlation with extracellular matrix components.

Hypersensitivity pneumonitis (HP) is characterized by the accumulation of inflammatory cells in the lung parenchyma, and may progress to fibrosis. The content of the fibroblast derived collagen metabolite procollagen-III-peptide (PCP-III) in bronchoalveolar lavage (BAL) fluid of HP patients has been found to be increased. Previous studies have shown elevation of the fibroblast adhesion molecules, vitronectin and fibronectin in the BAL fluid of recent onset HP. In view of these observations, it was hypothesized that increases in PCP-III would be associated with increases in vitronectin and fibronectin in the BAL fluid of subjects with untreated recent onset HP. BAL was performed in 14 patients with HP and nine normal controls. The aminoterminal domain of PCP-III was measured by radioimmunoassay, and vitronectin and fibronectin by enzyme-linked immunosorbent assay. Detectable amounts of BAL PCP-III were seen in all HP patients but not in the normal controls (mean +/- SEM 5.1 +/- 1.2 versus < 0.2 ng.ml-1; i.e. below the limit of detection of the PCP-III assay). The BAL fluid concentration of PCP-III correlated well with the amount of vitronectin (r = 0.638) and fibronectin (r = 0.710). Except for PCP-III and mast cells, no significant correlations were found between PCP-III, vitronectin, fibronectin and the cellular parameters. The findings suggest that an increased turnover of collagens and proteoglycans is present in the lower respiratory tract of patients with recent onset HP, possibly reflecting remodelling of the extracellular matrix.

Adult↗

Serum levels of cartilage oligomeric matrix protein (COMP) correlate with radiographic progression of knee osteoarthritis.

OBJECTIVE: To evaluate the prognostic utility of serum COMP level measured with a new sandwich ELISA, by correlating COMP level with outcome measures of osteoarthritis (OA) progression. DESIGN: Patients (N=48) had symptomatic primary knee OA of Kellgren-Lawrence (K-L) grade I-III and met ACR criteria. These patients were evaluated prospectively as part of a double-blind drug trial of 3 years' duration and represented the placebo arm of the study. Serum COMP levels were measured by sandwich ELISA with monoclonal antibodies 16-F12 and 17-C10 at baseline and at study end and levels were correlated with changes in (1) joint space width (JSW), (2) K-L grade, (3) Lequesne, and (4) WOMAC indices, over 3 years. RESULTS: The change in JSW over 3 years, summed for both knees, correlated positively with serum COMP level at baseline as well as at study end. Patients were sorted by level of progression based upon a change in K-L grade summed for both knees over 3 years; patients who progressed by two K-L grades were shown to have had significantly higher COMP levels at baseline as well as at study end. Baseline and study end COMP levels did not correlate with the change of Lequesne or WOMAC indices. Baseline COMP levels correlated strongly with end serum COMP levels. CONCLUSION: Serum COMP has the potential to be a prognostic marker of disease progression. High COMP levels, persisting over the 3-year study period in the patients with radiographic progression, indicated differences in disease activity detectable throughout the entire follow-up interval.

Aged↗

Expression of interstitial collagenase (matrix metalloproteinase-1) is related to the activity of human endometriotic lesions.

OBJECTIVE: To determine whether interstitial collagenase (matrix metalloproteinase-1), known to play a pivotal role in the initiation of menstruation, contributes to the pathogenesis of endometriosis. DESIGN: Serial sections of peritoneal red and black endometriotic lesions, ovarian endometriotic cysts, and rectovaginal adenomyotic nodules were analyzed by in situ hybridization for the expression of matrix metalloproteinase-1 by silver staining for the integrity of the fibrillar extracellular matrix and by immunolabeling for the abundance of sex steroid receptors. SETTING: Academic hospital and research laboratory. PATIENT(S): Premenopausal women undergoing laparoscopy for endometriosis. INTERVENTION(S): Biopsy of endometriotic lesions, combined with endometrium whenever possible. MAIN OUTCOME MEASURE(S): Expression of matrix metalloproteinase-1 messenger RNA (mRNA). RESULT(S): Matrix metalloproteinase-1 mRNA was expressed focally in red peritoneal and ovarian endometriosis irrespective of the phase of the menstrual cycle but was not detectable in black peritoneal and rectovaginal lesions. Foci of matrix metalloproteinase-1 expression closely correlated with matrix breakdown and with the absence of P receptors in adjacent epithelial cells. CONCLUSION(S): Correlation of matrix metalloproteinase-1 expression with activity of endometriotic tissue suggests its involvement in tissue remodeling and bleeding, and possibly in the secondary shedding and reimplantation of endometriotic lesions.

Adult↗

Increased expression of matrix metalloproteinase 9 correlates with poor prognostic variables in renal cell carcinoma.

BACKGROUND: MMP2 and MMP9 are two gelatinolytic enzymes, which are key regulators of tumor invasion and metastasis. This study aimed to clarify the prognostic significance of MMP2 and MMP9 with particular regard to their transcript levels, enzymatic activities in renal cell carcinomas (RCCs). MATERIALS AND METHODS: Through cDNA array, the differential expression of the MMP superfamily was evaluated in RCC. Various properties of MMP2 and MMP9 were quantified, in 178 patients with RCC, based on the Heidelberg classification. Of these, 145 cases including 16 fresh-frozen cases were available for MMP2 and MMP9 transcript level evaluation. In addition, gelatinolytic activity was assessed by zymography in 16 other fresh-frozen samples from new RCC cases. RESULTS: MMP2, 9, 11, 14, and 16 were upregulated in the conventional RCC in comparison with the chromophobe RCC, whereas MMP1, 11 and 16 were pronounced in papillary RCC. MMP9 transcript levels were strongly associated with the MMP9 enzymatic activity (p=0.001), and therefore, with disease-free survival (p=0.001) and metastasis (p=0.011). Gelatinolytic activity of MMP9 by zymography was strongly associated with MMP9 mRNA expression, which was more intense in 'conventional' RCC than in 'chromophobe' RCC (p=0.001), irrespective of tumor grade or stage. MMP9 was proven to be a significant prognostic predictor by multi-variate survival analysis (p=0.0054). MMP2 enzymatic activity disappeared in spite of its constant transcript expression in RCC. CONCLUSIONS: MMP9 appears to be regulated at the transcript level, whereas MMP2 is regulated at the posttranscriptional level. Poor survival with a high frequency of metastases in 'conventional' RCC is associated with MMP9, which exhibits a high transcriptional level, and a high gelatinolytic activity. As a result, MMP9 may be a candidate of predictors of disease-free survival in RCC.

Carcinoma, Renal Cell↗

Correlation of extracellular matrix components with the cytoarchitecture of mouse Peyer's patches.

The distribution patterns of extracellular matrix elements were determined to ascertain whether they play a role in the localization of lymphocytes in discrete T-cell, B-cell and dome antigen-processing domains within Peyer's patches. Antibodies against collagen types I, III and IV, laminin and fibronectin were applied to cryosections of mouse Peyer's patches and localized by direct or indirect immunoperoxidase methods. T-cell domains were identified with a monoclonal antibody against Thy-1.2. Labeled reticular fibers in distinctive patterns were more numerous in parafollicular and dome areas than within follicles. Germinal centers contained few such fibers. In parafollicular areas, fibers were oriented predominantly toward follicle domes; their distribution corresponded to T-cell zones and lymphocyte traffic areas, with their orientation being parallel to the migration pathways of lymphocytes from high endothelial venules to the antigen-processing domes. Subepithelial and subendothelial basal laminae were immunopositive for type-IV collagen, laminin and fibronectin. The dome subepithelial basal lamina had pore-like discontinuities through which lymphocytes migrated to and from the epithelium. The correspondence of the distribution patterns of extracellular matrix to specific functional domains of Peyer's patches suggests that this matrix provides a structural framework for lymphocyte migration and localization.

Animals↗

Adsorption of 5'-AMP and catalytic synthesis of 5'-ADP onto phosphate surfaces: correlation to solid matrix structures.

A non-enzymatic formation of 5'-ADP starting from phosphorylation of 5'-AMP in the presence of either calcium phosphate or calcium pyrophosphate precipitates is reported. This reaction is taken as a model for the study of heterogeneous catalysis of transphosphorylation in prebiotic conditions. Experiments were performed in completely aqueous media and in media containing dimethyl sulfoxide (Me2SO), to simulate periods of dehydration in primitive aquatic environments. It has been observed that the nucleotide is adsorbed onto both calcium phosphate and calcium pyrophosphate in accordance with Langmuir isotherms. Adsorptive capacity and affinity of the precipitates for nucleotide are changed by the presence of Me2SO, suggesting that the interaction between biomonomers and surfaces can be modulated by the degree of hydration of the anionic components of these compounds. In completely aqueous environments, formation of 5'-ADP from 5'-AMP adsorbed on precipitates of calcium phosphate and calcium pyrophosphate is very small. However, in the presence of 60% Me2SO this synthesis increases by factors of 3 and 6 for surfaces of calcium phosphate and calcium pyrophosphate, respectively, and follows first-order kinetics. Determinations of free energy changes show that phosphorylation of 5'-AMP adsorbed to these precipitates is thermodynamically favorable. Depending on the precipitation time of the samples and the composition of the medium, structural analysis of these precipitates by electron and X-ray diffraction shows changes in their cristallinity grade. It is proposed that these changes are responsible for the modulation of the quantity of adsorbed nucleotides to the surface of solid matrices as well as the catalytic activity of the precipitates.

Adenosine Diphosphate↗

Lipoproteins, atherogenicity, age and risk of myocardial infarction.

OBJECTIVE: To perform basic statistical analysis of laboratory lipoprotein data, i.e. the measures of very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL), to assist in their interpretation. In particular, to find any difference in male and female data that might explain the known difference in atherogenic susceptibility between the sexes. METHOD: The study subjects were patients of doctors in city and country New South Wales. Statistical methodology to find the inter-relations of the lipoproteins was the construction of the matrix of correlation, then by matrix algebra to display the independent trends in the data. RESULTS AND CONCLUSIONS: The findings have been an atherogenicity function involving LDL and HDL and a risk function of myocardial infarction (MI) involving LDL, HDL and age, confirmed by reference to the age and sex incidence of MI in the Australian population. The principal conclusion is a simple mathematical model of the incidence of MI. IMPLICATIONS: The means given for identification of at-risk individuals before symptoms appear, also the means given of lowering whole population risk of MI by health education and lifestyle change with increased longevity for all. These concepts call for a prospective trial.

Adult↗

[Reconstruction of genetic distance matrix].

A method for reconstruction of genetic distances' matrix, based on linear combination of physical distances' matrices among populations and mean sizes of the population matrices is proposed. The analogue of genetic distances' matrix obtained correlates with the matrix at the level 0.59. The reconstruction may be used for the populations of about 2-3 neighbour districts. An index xi is introduced, as a constant describing some big regions. Comparison of reconstructed matrix of genetic distances with some well-known matrices of genetic distances is performed.

Alleles↗

Determination of cellular shape by the extracellular matrix and its correlation with the control of cellular growth.

Although the problem of cellular proliferation may seem at first glance to be tremendously complex, the mechanisms which control it may be extremely simple. One of the primary factors which regulates the mitogenic response of a given cell type to a given class of mitogenic agents seems to be the cellular shape. We have found that corneal epithelial cells, for example, adopt a flattened configuration when maintained in vitro on plastic and are very sensitive to fibroblast growth factor, but not to epidermal growth factor. When maintained on collagen, on the other hand, they become tall and columnar and respond primarily to epidermal growth factor. The cellular shape is dictated in vivo by the extracellular material upon which the cells rest and in vitro by the substrate upon which the cells are maintained. The substrate itself may, in turn, induce the cells to manufacture their extracellular material and specific cell surface proteins which control the cellular shape.

Animals↗

Correlated expression of matrix metalloproteinases and ets family transcription factor E1A-F in invasive oral squamous-cell-carcinoma-derived cell lines.

Matrix metalloproteinases (MMPs) have been implicated in invasion and metastasis of tumor cells. Transcription regulatory regions of MMP genes often contain binding sites for ets transcription factors. We recently isolated a cDNA encoding human E1A-F, a member of the ets oncogene family, and showed that E1A-F can upregulate MMP genes by CAT assay. We attempted to investigate the relationship between E1A-F mRNA expression and MMP protein expression in four different types of oral squamous-cell-carcinoma-derived cell lines (HSC 3, SAS, KB, and Ca 9.22). HSC 3 and SAS are highly invasive cell lines when they are injected in the tongue of nude mice. Raft culture of HSC 3 and SAS revealed the same characteristics as seen in tumors implanted in vivo. Both type I collagenase (MMP-1) and 92-kd type IV collagenase (MMP-9) were detected in cultured HSC 3 and SAS cells. E1A-F mRNA was demonstrated to be highly expressed in HSC 3 and SAS by Northern blotting, and in situ hybridization confirmed E1A-F mRNA expression at the invasion front of tumor cells seeded on collagen gel. On the other hand, KB and Ca 9.22 have little potential for invasion, and MMP-1 and MMP-9 protein and E1A-F mRNA could not be detected. These results suggest that the ets-related E1A-F participates in the regulation of invasion-associated MMP genes and is involved in presenting invasive activity in tumor cells of oral squamous cell carcinoma.

Blotting, Northern↗

Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinase in uterine endometrial carcinoma and a correlation between expression of matrix metalloproteinase-7 and prognosis.

Matrix metalloproteinases (MMPs) are associated with invasion and metastasis of several human malignant tumors, in particular MMP-7, which is mainly produced by the cancer cell itself. We examined the expression of MMP-2, 7 and 9, and tissue inhibitors of metalloproteinase (TIMP)-1 and 2 in uterine endometrial carcinoma, and compared the expression with clinicopathological characteristics in uterine endometrial carcinoma (UEC). A group of 256 patients with UEC received surgery at the Osaka City University Medical School Hospital, and 196 tumor samples were immunohistochemically stained to examine the expression of MMP-2, 7 and 9, and TIMP-1 and 2. Additionally, the invasion ability of cell stain established from UEC was examined using an in vitro invasion assay. The expression of MMP-2, 7 and 9, and TIMP-1 and 2 was observed in the cytoplasm, and the expression of MMP-2 and 7, and TIMP-1 and 2 was observed in stromal cells around the tumor cells. The expression of MMP-7 was significantly stronger in higher-grade than lower-grade tumors (P<0.05). The invasion assay showed that the invasion of cells derived from UECs was significantly inhibited by TIMP-1 and 2. The disease-free interval was significantly shorter when MMP-7 expression was intense. This increased expression of MMP-7 in high grade UECs may be associated with tumor invasion and metastasis, and MMP-7 could serve as a prognostic maker in UEC.

Adult↗