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PubMed1996

Adult human chondrocytes cultured in alginate form a matrix similar to native human articular cartilage.

The matrix formed by adult human chondrocytes in alginate beads is composed of two compartments: a thin rim of cell-associated matrix that corresponds to the pericellular and territorial matrix of articular cartilage and a more abundant further-removed matrix, the equivalent of the interterritorial matrix in the tissue. On day 30 of culture, the relative and absolute volumes occupied by the cells and each of the two matrix compartments in the beads were nearly identical to those in native articular cartilage. Furthermore, the concentration of aggrecan in the cell-associated matrix was similar to that in adult human articular cartilage and was approximately 40-fold higher than in the further removed matrix compartment. Fluorescence-activated cell sorting revealed that the cell-associated matrix was built on the cell membrane in part via interactions between hyaluronic acid and CD44-like receptors. Approximately 25% of the aggrecan molecules synthesized by the chondrocytes during a 4-h pulse in the presence of [35S]sulfate on day 9 of culture were retained in the cell-associated matrix where they turned over with a half-life (t1/2) = 29 days. Most [35S]aggrecan molecules reached the further removed matrix compartment where they turned over much more slowly (t1/2 > 100 days). These results add support to the contention that aggrecan molecules residing in the pericellular and territorial areas of the adult human articular cartilage matrix are more susceptible to degradation by proteolytic enzymes synthesized by the chondrocytes than those that inhabit the interterritorial areas further removed from the cells.

Adult↗

PubMed2003

Functional differences between growth plate apoptotic bodies and matrix vesicles.

UNLABELLED: Mineralization often occurs in areas of apoptotic changes. Our findings indicate that physiological mineralization is mediated by matrix vesicles. These matrix vesicles use mechanisms to induce mineralization that are different from the mechanisms used by apoptotic bodies released from apoptotic cells. Therefore, different therapeutic approaches must be chosen to inhibit pathological mineralization depending on the mechanism of mineralization (matrix vesicles versus apoptotic bodies). INTRODUCTION: Physiological mineralization in growth plate cartilage is restricted to regions of terminally differentiated and apoptotic chondrocytes. Pathological mineralization of tissues also often occurs in areas of apoptosis. We addressed the question of whether apoptotic changes control mineralization events or whether both events are regulated independently. METHODS: To induce mineralization, we treated growth plate chondrocytes with retinoic acid (RA); apoptosis in these cells was induced by treatment with staurosporine, anti-Fas, or TNFalpha. The degrees of mineralization and apoptosis were determined, and the structure and function of matrix vesicles and apoptotic bodies were compared. RESULTS: Release of matrix vesicles and mineralization in vivo in the growth plate occurs earlier than do apoptotic changes. To determine the functional relationship between apoptotic bodies and matrix vesicles, growth plate chondrocytes were treated with RA to induce matrix vesicle release and with staurosporine to induce release of apoptotic bodies. After 3 days, approximately 90% of staurosporine-treated chondrocytes were apoptotic, whereas only 2-4% of RA-treated cells showed apoptotic changes. RA- and staurosporine-treated chondrocyte cultures were mineralized after 3 days. Matrix vesicles isolated from RA-treated cultures and apoptotic bodies isolated from staurosporine-treated cultures were associated with calcium and phosphate. However, matrix vesicles were bigger than apoptotic bodies. Furthermore, matrix vesicles but not apoptotic bodies contained alkaline phosphatase and Ca2+ channel-forming annexins II, V, and VI. Consequently, matrix vesicles but not apoptotic bodies were able to take up Ca2+ and form the first mineral phase inside their lumen. Mineralization of RA-treated cultures was inhibited by antibodies specific for annexin V but not mineralization of staurosporine-treated cultures. CONCLUSION: Physiological mineralization of growth plate chondrocytes is initiated by specialized matrix vesicles and requires alkaline phosphatase and annexins. In contrast, mineral formation mediated by apoptotic bodies occurs by a default mechanism and does not require alkaline phosphatase and annexins.

Alkaline Phosphatase↗

PubMed1996

Differences in submicroscopic structure of the extracellular matrix of canine femoral and tibial condylar articular cartilages as revealed by polarization microscopical analysis.

The submicroscopic orientation patterns of sulfated glycosaminoglycan side chains of proteoglycan molecules and collagen fibrils were compared in different extracellular matrix areas of femoral and tibial articular cartilages of young adult beagle dogs using qualitative and quantitative polarization microscopic analytical methods. Paraffin sections were cut perpendicularly to the articular surfaces from the femoral and tibial condyles and stained. Picrosirius red F38 staining combined with an antecedent digestion with testicular hyaluronidase was used to enhance the optical anisotropy of collagen. Birefringence of sulfated glycosaminoglycan molecules was selectively amplified by a combination of carboxymethylation with CH3I and a subsequent staining with toluidine blue. The specimens were analysed in a polarization microscope equipped with compensator plates, and retardation values of birefringence were determined in territorial and interterritorial matrix areas of different zones using monochromatic plane polarized light. It was found that besides some similarities there were significant differences in the submicroscopic organization of extracellular matrix between femoral and tibial articular cartilages. Common structural features of the femoral and tibial cartilages were the sulfated glycosaminoglycans and collagen fibrils which were circularly oriented in the territorial matrix, and these components were longitudinally arranged within the trabeculae of the interterritorial matrix. Furthermore, the territorial matrix was a more densely packed structure than the interterritorial matrix. Our results revealed the following major differences between the two cartilages: The degree of orientation of sulfated glycosaminoglycans was higher in the femoral cartilage matrix areas as compared to the identical structures of the tibial cartilage; the collagen structure was more densely packed in the interterritorial matrix of the superficial and mineralization zones of the femoral cartilage than in the tibial cartilage, and except for the zone of mineralization, the degree of collagen orientation was higher in the territorial matrix of the femoral than the tibial cartilage. These findings suggest that the extracellular matrix of femoral condylar cartilage has a more densely packed molecular structure than the softer tibial cartilage matrix. This structural difference may have an influence on the pathogenesis of diseases involving articular cartilage.

Animals↗

PubMed1998

Matrix metalloproteinases and tissue inhibitors of metalloproteinases in loose artificial hip joints.

The role of extracellular matrix metalloproteinase enzymes and the tissue inhibitors of metalloproteinase in the periprostetic connective tissue matrix of loose artificial hip joints is reviewed. In the periprosthetic granulomatous interface connective tissues between bone and implants and inner cellular regenerating pseudocapsular tissues, matrix metalloproteinase 1, matrix metalloproteinase 2, matrix metalloproteinase 3, matrix metalloproteinase-9, and membrane type 1 matrix metalloproteinase enzymes can be shown in the light of immunohistochemistry, enzyme activity analysis, and messenger ribonucleic acid levels. Tissue inhibitors of metalloproteinase 1 and tissue inhibitors of metalloproteinase 2 also are found in the corresponding tissues. Analysis of matrix metalloproteinase and tissue inhibitors of metalloproteinase interaction shows imbalance between the enzymes and the endogenous inhibitors in favor of matrix metalloproteinase. This induces pathologic connective tissue remodeling in the interface and pseudocapsule. The data suggest that matrix metalloproteinase and tissue inhibitors of metalloproteinase system participate in the extracellular matrix degradation and tissue remodeling in artificial hip joints, and may contribute to the periprosthetic weakening, implant loosening, and osteolysis around implants. More evidence for their active involvement is sought by intervention studies with type specific matrix metalloproteinase inhibitors.

Animals↗

PubMed2002

Transforming growth factor beta induces fibroblast fibrillin-1 matrix formation.

OBJECTIVE: Fibrillin, an extracellular matrix protein implicated in dermal fibrosis, is increased in the reticular dermis of systemic sclerosis (SSc) skin. We undertook this study to investigate the hypothesis that transforming growth factor beta (TGFbeta) or other cytokines regulate fibrillin matrix formation by normal and SSc fibroblasts. We further investigated the mechanism of TGFbeta-induced fibrillin fibrillogenesis and its relationship to myofibroblasts. METHODS: Fibrillin and fibronectin matrix deposition and alpha-smooth muscle actin expression by fibroblast cultures from normal and SSc skin treated with TGFbeta or other cytokines were analyzed by immunofluorescence. Supernatant and extracellular matrix from normal and SSc fibroblasts treated with or without TGFbeta were evaluated by Western blot and Northern blot for fibrillin protein and messenger RNA (mRNA) expression, respectively. RESULTS: Immunofluorescence demonstrated increased fibrillin matrix formation by normal and scleroderma fibroblasts after TGFbeta treatment. Other cytokines, including tumor necrosis factor alpha, interleukin-1beta (IL-1beta), IL-4, granulocyte-macrophage colony-stimulating factor, and platelet-derived growth factor, did not affect fibrillin fibrillogenesis. Fibrillin matrix formed in proximity to myofibroblasts and independently of up-regulation of fibronectin matrix or cell number. Western blot analysis of extracellular matrix confirmed increased fibrillin after TGFbeta stimulation of normal or scleroderma fibroblasts. However, TGFbeta did not alter the expression of either soluble fibrillin protein or fibrillin mRNA. CONCLUSION: Our data show that TGFbeta induces fibrillin protein incorporation into the extracellular matrix without affecting fibrillin gene expression or protein synthesis, suggesting that fibrillin matrix assembly is regulated extracellularly. TGFbeta might increase fibrillin matrix by activating myofibroblasts. Such TGFbeta-mediated effects could account for the increased fibrillin matrix observed in SSc skin.

Cells, Cultured↗

PubMed2005

The intraclass covariance matrix.

Introduced by C.R. Rao in 1945, the intraclass covariance matrix has seen little use in behavioral genetic research, despite the fact that it was developed to deal with family data. Here, I reintroduce this matrix, and outline its estimation and basic properties for data sets on pairs of relatives. The intraclass covariance matrix is appropriate whenever the research design or mathematical model treats the ordering of the members of a pair as random. Because the matrix has only one estimate of a population variance and covariance, both the observed matrix and the residual matrix from a fitted model are easy to inspect visually; there is no need to mentally average homologous statistics. Fitting a model to the intraclass matrix also gives the same log likelihood, likelihood-ratio (LR) chi2, and parameter estimates as fitting that model to the raw data. A major advantage of the intraclass matrix is that only two factors influence the LR chi2--the sampling error in estimating population parameters and the discrepancy between the model and the observed statistics. The more frequently used interclass covariance matrix adds a third factor to the chi2--sampling error of homologous statistics. Because of this, the degrees of freedom for fitting models to an intraclass matrix differ from fitting that model to an interclass matrix. Future research is needed to establish differences in power-if any--between the interclass and the intraclass matrix.

Algorithms↗

PubMed2002

A three-layer guar gum matrix tablet for oral controlled delivery of highly soluble metoprolol tartrate.

The objective of the study is to design oral controlled drug delivery systems for highly water-soluble drugs using guar gum as a carrier in the form of a three-layer matrix tablet. Metoprolol tartrate was chosen as a model drug because of its high water solubility. Matrix tablets containing either 30 (M1), 40 (M2) or 50% (M3) of guar gum were prepared by wet granulation technique using starch paste as a binder. Three-layer matrix tablets of metoprolol tartrate were prepared by compressing on both sides of guar gum matrix tablet granules of metoprolol tartrate M1, M2 or M3 with either 50 (TL1M1, TL1M2 or TL1M3) or 75 mg (TL2M1, TL2M2 or TL2M3) of guar gum granules as release retardant layers. Both the matrix and three-layer matrix tablets were evaluated for hardness, thickness, drug content uniformity, and subjected to in vitro drug release studies. The amount of metoprolol tartrate released from the matrix and three-layer matrix tablets at different time intervals was estimated by using a HPLC method. Matrix tablets of metoprolol tartrate were unable to provide the required drug release rate. However, the three-layer guar gum matrix tablets (TL2M3) provided the required release rate on par with the theoretical release rate for metoprolol tartrate formulations meant for twice daily administration. The three-layer guar gum matrix tablet (TL2M3) showed no change either in physical appearance, drug content or in dissolution pattern after storage at 40 degrees C/75% RH for 6 months. The FT-IR study did not show any possibility of metoprolol tartrate/guar gum interaction with the formulation excipients used in the study. The results indicated that guar gum, in the form of three-layer matrix tablets, is a potential carrier in the design of oral controlled drug delivery systems for highly water-soluble drugs such as metoprolol tartrate.

Administration, Oral↗

PubMed2004

Sparsely cross-linked "nanogel" matrixes as fluid, mechanically stabilized polymer networks for high-throughput microchannel DNA sequencing.

We have developed sparsely cross-linked "nanogels", subcolloidal polymer structures composed of covalently linked, linear polyacrylamide chains, as novel replaceable DNA sequencing matrixes for capillary and microchip electrophoresis. Nanogels were synthesized via inverse emulsion (water-in-oil) copolymerization of acrylamide and a low percentage (approximately 10(-4) mol %) of N,N-methylene bisacrylamide (Bis). Nanogels and nanogel networks were characterized by multiangle laser light scattering and rheometry, respectively, and tested for DNA sequencing in both capillaries and chips with four-color LIF detection. Typical nanogels have an average radius of approximately 230 nm, with approximately 75% of chains incorporating a Bis cross-linker. The properties and performance of nanogel matrixes are compared here to those of a linear polyacrylamide (LPA) network, matched for both polymer weight-average molar mass (M(w)) and the extent of interchain entanglements (c/c). At sequencing concentrations, the two matrixes have similar flow characteristics, important for capillary and microchip loading. However, because of the physical network stability provided by the internally cross-linked structure of the nanogels, substantially longer average read lengths are obtained under standard conditions with the nanogel matrix at a 98.5% accuracy of base-calling (for CE: 680 bases, an 18.7% improvement over LPA, with the best reads as long as 726 bases, compared to 568 bases for the LPA matrix). We further investigated the use of the nanogel matrixes in a high-throughput microfabricated DNA sequencing device consists of 96 separation channels densely fabricated on a 6-in. glass wafer. Again, preliminary DNA sequencing results show that the nanogel matrixes are capable of delivering significantly longer average read length, compared to an LPA matrix of comparable properties. Moreover, nanogel matrixes require 30% less polymer per unit volume than LPA. The addition of a small amount of low molar mass LPA or ultrahigh molar mass LPA to the optimized nanogel sequencing matrix further improves read length as well as the reproducibility of read length (RSD < 1.6%). This is the first report of a replaceable DNA sequencing matrix that provides better performance than LPA, in a side-by-side comparison of polymer matrixes appropriately matched for molar mass and the extent of interchain entanglements. These results could have significant implications for the improvement of microchip-based DNA sequencing technology.

Acrylic Resins↗

PubMed1990

Matrix free Mg2+ changes with metabolic state in isolated heart mitochondria.

The concentration of free Mg2+ in the matrix of isolated heart mitochondria has been monitored by using the fluorescent probe furaptra (mag-fura-2). Beef heart mitochondria respiring in a KCl medium in the absence of external Mg2+ maintain free matrix Mg2+ near 0.50 mM. Addition of Pi under these conditions decreases free Mg2+ by 0.12-0.17 mM depending on the substrate. This decrease in free Mg2+ appears to reflect changing ligand availability in the matrix. The decrease is prevented when the Pi transporter is blocked by mersalyl. Addition of ADP to initiate state 3 respiration causes a marked increase in free matrix Mg2+ (0.1-0.2 mM) that persists as long as ATP formation is taking place; free Mg2+ then returns to the base level. This cyclic change is blocked by oligomycin and carboxyatractyloside and appears to reflect to a large extent the decrease in matrix Pi that accompanies oxidative phosphorylation. Exchange of external ADP for matrix ATP may also contribute to the increase in free matrix Mg2+. Addition of an uncoupler promotes anion efflux and increases free matrix Mg2+. Similar changes in free Mg2+ on addition of Pi, ADP, or uncoupler are seen when extramitochondrial Mg2+ is buffered from 0.5 to 2 mM, but the basal free matrix Mg2+ increases as external Mg2+ concentration increases in this range. Free matrix Mg2+ also increases when total mitochondrial Mg2+ is increased by respiration-dependent uptake in the presence of Pi. It is concluded that matrix free Mg2+ changes significantly with changing ligand availability and that such changes may contribute to the regulation of Mg2(+)-sensitive matrix enzymes and membrane transporters.

Animals↗

PubMed1999

Evaluation of the in vitro and in vivo performance of two sustained-release lithium carbonate matrix tablets. Effect of different diets on the bioavailability.

Two sustained-release (SR) lithium carbonate (Li) matrix tablets, which use a hydrophilic (HP) matrix of hydroxypropylmethylcellulose (Methocel 4K MP) and a lipid (L) matrix of hydrogenated castor oil (Cutina HR) as sustaining agents, have been studied. In vitro performance through dissolution tests in different media was established. The L and HP formulations were affected by the composition of the dissolution media, and liberation was complete in 8 hr using a variable-pH medium that simulates the gastrointestinal (Gl) pH. Liberation was better described by the diffusional model of the square root of time for the L matrix and by zero-order kinetics for the HP matrix. Absolute bioavailability (BA) and food-induced changes on BA of both formulations were studied. The in vivo study design was a 4 x 4 Latin square involving 12 subjects who received two tablets of a 300-mg dose of SR formulations while fasting or with a standardized normal, high-fat, or high-fat/high-protein meal. The results for both formulations showed no differences in the disposition parameters and mean residence time when the tablets were administered with any type of diet. Changes in rate of absorption were found when both types of tablets were administered with any class of diet. The analysis of the ratio Cmax/AUC (area under the curve) evidenced that changes in Cmax were attributable to a higher rate of absorption for the HP matrix and to a higher amount absorbed for the L matrix. In the last, high-fat and high-fat/high-protein diets produced higher AUCs than under fasting condition. The SR Li tablets formulated with hydrogenated castor oil were affected more by high-fat food, probably because of the increase of pancreatic and biliary secretions promoted by the meal, which would affect the matrix itself. The HP matrix was also affected, but to a lesser extent. The magnitude of the change in Cmax observed with this matrix probably is not important from a clinical point of view. Absolute BA was very low for the lipid matrix; in addition, since it is more seriously affected by food, probably it is not a good choice for a drug such as lithium. The in vivo behavior of the HP matrix makes it advisable to invest in efforts to achieve increased BA. Comparing in vitro and in vivo results, the focus should be achieving sustained, but complete, in vitro liberation in not more than 3 hr, with simulation of the transit time through the stomach and small bowel since lithium ion is only absorbed to this point.

Analysis of Variance↗

PubMed1977

Nuclear matrix. Isolation and characterization of a framework structure from rat liver nuclei.

A nuclear framework structure termed the nuclear matrix has been isolated and characterized. This matrix forms the major residual structure of isolated nuclei and consists largely of protein with smaller amounts of RNA, DNA, carbohydrate, and phospholipid. The nuclear matrix can be further resolved by combined treatment with DNase and RNase. The remaining nuclear protein structure, after extraction of 90 percent of the nuclear protein, 99.9 percent of the DNA, and 98 percent of the RNA and phospholipid, is termed the nuclear protein matrix. Electron microscopy of this final nuclear protein matrix reveals an interior framework structure composed of residual nucleolar structures associated with a granular and fibrous internal matrix structure. The internal matrix framework is derived from the interchromatinic structures of the nucleus, and is connected to a surrounding residual nuclear envelope layer containing residual nuclear pore complex structures. Sodium dodecyl sulfate-acrylamide gel electrophoresis of the nuclear matrix proteins demonstrates three major polypeptide fractions, P-1, P-2, and P-3, with average molecular weights of approximately 69,000, 66,000 and 62,000, as well as several minor polypeptides which migrate at approximately 50,000 and at higher molecular weights (>100,000). Polypeptides with molecular weights identical to those of P-1, P-2 and P-3 are also components of isolated nuclear envelopes and nucleoli, whereas isolated chromatin contains no detectable matrix polypeptides. This suggests that the major matrix polypeptides are localized in specific structural regions of the nucleus, i.e., nuclear envelope, nucleoli, and interchromatinic structures. The presence of cytochrome oxidase activity in the isolated nuclear matrix indicates that at least some integral proteins of the nuclear membrane are associated with the matrix.

Amino Acids↗

PubMed1991

Ionic control of the size of the vesicle matrix of beige mouse mast cells.

Isolated matrices of the giant secretory vesicles of mast cells of the beige mouse were reliably produced by the osmotic lysis of isolated vesicles. These matrices maintained their form, and their sizes were easily measured using Nomarski optics. The size of the matrix depended on the ionic composition of the bathing solution. The physiologically relevant ions, histamine and serotonin, contracted the matrix. Multivalent cations condensed the matrix relative to univalents. Ag+, acid pH (below 5), and basic pH (above 9) expanded the matrix. In the presence of 10 mM histamine, lowering the pH from 9 to 5 contracted the matrix more than can be attributed to the pH-dependent matrix contraction in zero histamine. The nontitratable organic cation, dimethonium, contracts the matrix with little effect of pH in the range of 5-9. These results suggest that histamine acts as a matrix contractor in the divalent form. The dose-response (contraction) relation for histamine was gradual from micromolar to 316 mM (millimolar) histamine. Experiments with mixtures of histamine and sodium show antagonistic effects on the matrix but are inconsistent with either a model where ions compete for identical sites or a parallel model where ions interact with separate independent sites. In vigorous histamine washoff experiments, the half time for vesicle expansion in 10(-4) M pH buffer was approximately 4 s; in isotonic NaCl solution, it was 0.5 s. When 1 M histamine was presented to closely apposed matrices, fusion resulted. The matrix material returned to its initial shape after being mechanically deformed with a glass probe. These results suggest that the matrix size is controlled by its ion exchange properties. The matrix expansion can quantitatively account for the vesicular size increase observed upon exocytosis (as a postfusional event) and the osmotic nonideality of intact vesicles. The mechanical expansion is probably significant in the widening of the exocytotic pore and the dispersal of the vesicular contents.

Animals↗

PubMed2002

An introduction to the Barell body region by nature of injury diagnosis matrix.

INTRODUCTION: The Barell body region by nature of injury diagnosis matrix standardizes data selection and reports, using a two dimensional array (matrix) that includes all International Classification of Diseases (ICD)-9-CM codes describing trauma. AIM: To provide a standard format for reports from trauma registries, hospital discharge data systems, emergency department data systems, or other sources of non-fatal injury data. This tool could also be used to characterize the patterns of injury using a manageable number of clinically meaningful diagnostic categories and to serve as a standard for casemix comparison across time and place. CONCEPT: The matrix displays 12 nature of injury columns and 36 body region rows placing each ICD-9-CM code in the range from 800 to 995 in a unique cell location in the matrix. Each cell includes the codes associated with a given injury. The matrix rows and columns can easily be collapsed to get broader groupings or expanded if more specific sites are required. The current matrix offers three standard levels of detail through predefined collapsing of body regions from 36 rows to nine rows to five rows. MATRIX DEVELOPMENT: This paper presents stages in the development and the major concepts and properties of the matrix, using data from the Israeli national trauma registry, and from the US National Hospital Discharge Survey. The matrix introduces new ideas such as the separation of traumatic brain injury (TBI), into three types. Injuries to the eye have been separated from other facial injuries. Other head injuries such as open wounds and burns were categorized separately. Injuries to the spinal cord and spinal column were also separated as are the abdomen and pelvis. Extremities have been divided into upper and lower with a further subdivision into more specific regions. Hip fractures were separated from other lower extremity fractures. FORTHCOMING DEVELOPMENTS: The matrix will be used for the development of standard methods for the analysis of multiple injuries and the creation of patient injury profiles. To meet the growing use of ICD-10 and to be applicable to a wider range of countries, the matrix will be translated to ICD-10 and eventually to ICD-10-CM. CONCLUSION: The Barell injury diagnosis matrix has the potential to serve as a basic tool in epidemiological and clinical analyses of injury data.

Data Collection↗

PubMed1986

Androgen binding in nuclear matrix of human genital skin fibroblasts from patients with androgen insensitivity syndrome.

Specific sex steroid-binding sites are associated with the salt-insoluble nuclear matrix from which lipids, histones, and chromatin have been extracted. In intact cultured normal human genital skin fibroblasts incubated for 1 h at 37 C with a saturating concentration (2 nM) of [3H]dihydrotestosterone [( 3H]DHT), approximately 50% of the total intracellular androgen receptor-steroid complexes were found in the nucleus. Within isolated nuclei from such cells, 28-49% of the specific androgen receptor binding was associated with the nuclear matrix. The antiandrogen cyproterone acetate inhibited DHT binding within the nuclear matrix. Cultured genital skin fibroblasts from two unrelated patients with receptor-positive complete androgen insensitivity (CAIS, AR+), had normal (approximately 50%) nuclear binding of DHT, and 35% and 45% of it was localized to the nuclear matrix. Genital skin fibroblasts from a patient with receptor-negative complete androgen insensitivity (CAIS, AR-) had no specific DHT binding in isolated nuclei or nuclear matrix. Scatchard analysis of specific DHT binding in the nuclear matrix isolated from cells of normal subjects after an in vitro exchange assay (0 C; 24 h) revealed the presence of saturable (maximum binding, approximately equal to 200 fmol/mg nuclear DNA), high affinity (Kd approximately equal to 1.0 nM) binding sites. By contrast, in the nuclear matrix isolated from cells of a patient with CAIS, AR+, the binding affinity for DHT was 3-fold lower (Kd approximately equal to 3.0 nM). When cytosolic androgen receptor-DHT complexes prepared from cells preincubated at 37 C for 1 h with [3H]DHT were incubated at 0 C for 1 h with isolated nuclei and nuclear matrix in the presence of 0.15 M KCl, 40-60% of specific nuclear binding was associated with the nuclear matrix. In these cell-free in vitro experiments, radiolabeled DHT-receptor complexes prepared from normal or mutant cells were mixed with isolated nuclei and nuclear matrix prepared from cells of normal subjects or patients with CAIS, AR+ or CAIS, AR-. Under these conditions, specific DHT binding in nuclei and nuclear matrix was quantitatively similar in the presence of a mutant (CAIS, AR+) receptor-steroid complex or in the presence of nuclei or nuclear matrix from the mutant cells (CAIS, AR- or AR+) when compared simultaneously with the same subcellular fractions prepared from the cells of normal subjects.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1993

[512 x 2048 matrix whole body scintigraphy with laser imaging system].

Although we could acquire a detailed 512 x 2048 matrix whole body scintigraphy, the 512 x 2048 matrix whole body scintigraphy was divided to the upper and lower half of the body, because a many of CRT system displayed only 1024 x 1024 matrix with non interlace mode. We made 12 dots of normal vertical image distance to 0 dot with laser imaging system (Li-10 Konica medical inc.), and we printed these divided whole body images in the four partition of the film. The lead bar phantom (interval from 6 mm to 3 mm) filled with 99mTcO4- was studied by both 512 x 2048 matrix whole body scanning mode and 256 x 1024 whole body scanning mode in the basic study. And the distance between the lead bar phantom and the gamma camera was changed from 10 mm to 100 mm. We studied 41 patients with metastatic bone tumor (14 breast cancer, 7 lung cancer, 7 prostate cancer, 5 others, 6 unknown origin) clinically. However the 512 x 2048 matrix whole body scan was better quality of images than 256 x 1024 matrix whole body scan at 100 mm distance in the basic study. The abnormal uptake of metastatic sites was shown equally in both 512 x 2048 and 256 x 1024 matrix whole body scintigraphy. The 512 x 2048 matrix whole body scan was better quality of images than 256 x 1024 matrix whole body scan in 26 out of 41 patients, equal in 10 out of 41 patients and worse in 3 out of 41 patients. The matrix size of 512 x 2048 matrix whole body scintigraphy (0.98 mm2) was smaller than that of 256 x 1024 matrix whole body scintigraphy (1.95 mm2).(ABSTRACT TRUNCATED AT 250 WORDS)

Bone and Bones↗

PubMed2003

Reciprocal modulation of matrix metalloproteinase-13 and type I collagen genes in rat hepatic stellate cells.

Collagen degradation by matrix metalloproteinases is the limiting step in reversing liver fibrosis. Although collagen production in cirrhotic livers is increased, the expression and/or activity of matrix metalloproteinases could be normal, increased in early fibrosis, or decreased during advanced liver cirrhosis. Hepatic stellate cells are the main producers of collagens and matrix metalloproteinases in the liver. Therefore, we sought to investigate whether they simultaneously produce alpha1(I) collagen and matrix metalloproteinase-13 mRNAs. In this communication we show that expression of matrix metalloproteinase-13 mRNA is reciprocally modulated by tumor necrosis factor-alpha and transforming growth factor-beta1. When hepatic stellate cells are co-cultured with hepatocytes, matrix metalloproteinase-13 mRNA is up-regulated and alpha1(I) collagen is down-regulated. Injuring hepatocytes with galactosamine further increased matrix metalloproteinase-13 mRNA production. Confocal microscopy and differential centrifugation of co-cultured cells revealed that matrix metalloproteinase-13 is localized mainly within hepatic stellate cells. Studies performed with various hepatic stellate cell lines revealed that they are heterogeneous regarding expression of matrix metalloproteinase-13. Those with myofibroblastic phenotypes produce more type I collagen whereas those resembling freshly isolated hepatic stellate cells express matrix metalloproteinase-13. Overall, these findings strongly support the notion that alpha1(I) collagen and matrix metalloproteinase-13 mRNAs are reciprocally modulated.

Animals↗

PubMed2002

Tissue levels of active matrix metalloproteinase-2 and -9 in colorectal cancer.

The bioactivity of matrix metalloproteinases was studied in tissues from colorectal cancer patients by means of both quantitative gelatin zymography and a fluorometric activity assay. Next to paired samples of tumour tissue and distant normal mucosa (n=73), transitional tissue was analysed from a limited (n=33) number of patients. Broad-spectrum matrix metalloproteinase activity and both the active and latent forms of the gelatinases matrix metalloproteinase-2 and -9 were higher in tumour than in normal mucosa. The ratio's between active and latent forms of matrix metalloproteinase-2 and -9 were highest in tumour tissue and normal mucosa, respectively. Matrix metalloproteinase-2 levels, both active and latent forms, correlated inversely with stage of disease, the tumours without synchronous distant metastases containing significantly (P=0.005) more active matrix metalloproteinase-2 than the others. At much lower levels of activity, the same trend was observed in distant normal mucosa. The level of latent form of matrix metalloproteinase-9 in tumour depended on tumour location. Neither the active form of matrix metalloproteinase-9 nor broad-spectrum matrix metalloproteinase activity in tumour tissue did correlate with any of the clinicopathological parameters investigated. The results demonstrate explicit differences between the activity of matrix metalloproteinase-2 and -9, indicating different roles for both gelatinases in tumour progression. Such data are necessary in order to develop rational anti-cancer therapies based on inhibition of specific matrix metalloproteinases.

Adenocarcinoma, Mucinous↗

PubMed2003

Monocyte adhesion to mesangial matrix modulates cytokine and metalloproteinase production.

BACKGROUND: Monocytes migrate into the glomerular mesangium during acute inflammatory renal disease, differentiate into macrophages, and may play a key role in the development and progression of glomerular scarring. Treatment strategies that inhibit monocyte infiltration ameliorate glomerular injury in animal models. Mesangial matrix contains several potential monocyte-binding domains that may contribute to monocyte entrapment and modulate cell activation. METHODS: Adhesion of peripheral blood-derived monocytes to matrix synthesized by human mesangial cells and to individual matrix proteins was assessed by colorimetry of nuclear staining with crystal violet. Monoclonal antibodies were used to identify the cell-surface integrins and matrix ligands involved. Monocyte proliferation was assessed by 3H-thymidine incorporation and cytokine production using enzyme-linked immunosorbent assay (ELISA). Secretion of metalloproteinases and their inhibitors was determined by zymography and ELISA, respectively. RESULTS: Monocytes bound to matrix synthesized by mesangial cells. Prestimulation of mesangial cells with tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta) enhanced matrix fibronectin content (P < 0.001) and monocyte binding (P < 0.001). Blocking antibodies to fibronectin, as well as to the integrins very late antigen-4 (VLA-4) and VLA-5, reduced monocyte adhesion to mesangial matrix by approximately 50%. Incubation of monocytes with matrix, fibronectin, laminin and collagen IV enhanced production of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), TNF-alpha and metalloproteinase-9 (MMP-9) when compared to cells incubated in plastic wells. However, there was no apparent difference in proliferation rate and no change in production of metalloproteinase inhibitors. CONCLUSION: Monocyte activation within the glomerulus may be mediated by binding to mesangial matrix components, particularly fibronectin. Matrix-mediated activation enhances production of inflammatory cytokines and matrix-degrading enzymes.

Cell Adhesion↗