Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Matrix”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,351 records · Page 75Linked to original sources
PubMed2003

Immobilization of mercury and zinc in an alkali-activated slag matrix.

The behavior of heavy metals mercury and zinc immobilized in an alkali-activated slag (AAS) matrix has been evaluated using physical property tests, pore structure analysis and XRD, TG-DTG, FTIR and TCLP analysis. Low concentrations (0.5%) of mercury and zinc ions had only a slight affect on compressive strength, pore structure and hydration of AAS matrixes. The addition of 2% Hg ions to the AAS matrix resulted in a reduction in early compressive strength but no negative effects were noticed after 28 days of hydration. Meanwhile, 2% Hg ions can be effectively immobilized in the AAS matrix with the leachate meeting the USEPA TCLP mercury limit. For a 2% Zn-doped AAS matrix, the hydration of the AAS paste was greatly retarded and the zinc concentration in the leachate from this matrix was higher than 5mg/l even at 28 days. Based on these results, we conclude that the physical encapsulation and chemical fixation mechanisms were likely to be responsible for the immobilization of Hg ions in the AAS matrix while only chemical fixation mechanisms were responsible for the immobilization of Zn ions in the AAS matrix.

Compressive Strength↗
PubMed2002

The influence of particles of a minor component on the matrix strength of sodium chloride.

This paper deals with the matrix strength of sodium chloride particles in pure sodium chloride tablets and in tablets compressed from binary mixtures of sodium chloride with low concentrations of pregelatinised starch. Because this study concerns the strength of the sodium chloride matrix, the tablet strength is reflected as a function of the sodium chloride volume fraction in the tablet. Starch particles in the mixture tablets decrease the sodium chloride volume fraction-tensile strength relationship compared with that of pure sodium chloride tablets. To determine the contribution of the sodium chloride matrix to the tablet strength, the starch particles were removed from the mixture tablets by heat treatment. Determination of the strengths of these heat-treated tablets reveals that the sodium chloride matrix strength determines the tablet strength of mixture tablets containing a single matrix of sodium chloride particles. The decrease of the sodium chloride matrix density in the three different tablets (pure sodium chloride tablets, mixture tablets and heat-treated tablets) is reflected by an increase of the median pore size. The matrix in sodium chloride tablets shows a higher tensile strength to median pore size relation than the matrices in the mixture and heat-treated tablets. Based on calculations according to the theory of elastic-brittle fracture, it is suggested that the initial presence of starch particles during tablet compaction causes the pores in the matrices of the mixtures and heat-treated tablets to be relatively more flat and longer. These pores weaken the sodium chloride matrix in the mixture and heat-treated tablets to a larger extent than the shorter, more spherical pores formed during compaction of pure sodium chloride.

Drug Compounding↗
PubMed1994

Quantification of fetal heart rate variation using a probability distribution matrix.

Analysis of FHR variability attempts to be able to distinguish which FHR changes are physiological and which are pathological. From the results of such studies, it is hoped that clinicians will be provided with the means to identify accurately which fetuses are healthy, which are at risk and which are actually in distress at any gestational age. The probability distribution matrix presented has the outstanding advantage of enabling one to condense any amount of FHR data into one uniform description for analysis en bloc. Not even one FHR is sacrificed; each one contributes to the FHR vs. DFHR distribution pattern. Where the probability distribution matrix is made from many FHR samples taken from healthy fetuses under natural day-to-day maternal circumferences, as we have done, this matrix can be considered as a physiologically unbiased reference. The subtraction matrix is characterized by the difference in FHR vs. DFHR distribution patterns between two probability distribution matrices compared, representing the equal residue of net absolute value. The larger the difference in FHR vs. DFHR distribution between two probability distribution matrices, the larger these kinds of residue values, and if two probability distribution matrices are identical, all the elements in the subtraction matrix indicate the residue values of zero. Our probability distribution matrix approach confirms the results of previously reported studies which utilized other analytical strategies. Therefore, we can evaluate quantitatively age-related FHR changes used as variables, such as the subtraction matrix and difference rate. By varying intervals between paired FHRs (e.g. selecting the original FHR--skip--select the following FHR--skip 2 FHR--select the next FHR, etc.), the probability distribution matrix could be adopted as a general tool for analysis of sequential changes in large numbers of FHR for further studies.

Bias↗
PubMed2000

Chitin is only a minor component of the peritrophic matrix from larvae of Lucilia cuprina.

The gut of most insects is lined with a peritrophic matrix that facilitates the digestive process and protects insects from invasion by micro-organisms and parasites. It is widely accepted that the matrix is composed of chitin, proteins and proteoglycans. Here we critically re-examine the chitin content of the typical type 2 peritrophic matrix from the larvae of the fly Lucilia cuprina using a range of techniques. Many of the histochemical and biochemical techniques indicate the presence of chitin, although they are often adversely influenced by the presence of highly glycosylated proteins, a principal component of the matrix. The alkali-stable fraction, which is used as an indicator of the maximum chitin content in a biological sample, is only 7.2% of the weight of the matrix. Larvae fed on the potent chitin synthase inhibitor polyoxin D or the chitin-binding agent Calcofluor White, showed strong concentration-dependent inhibition of larval weight and survival but no discernible effects on the matrix structure. A bacterial endochitinase fed to larvae had no effect on larval growth and no observable effect in vitro on the structure of isolated peritrophic matrix. RT-PCR did not detect a chitin synthase mRNA in cardia, the tissue from which PM originates. It is concluded that chitin is a minor structural component of the type 2 peritrophic matrix of this insect.

Animals↗
PubMed1986

Preribosomal ribonucleoprotein particles are a major component of a nucleolar matrix fraction.

Biochemical and morphological studies were performed on Novikoff hepatoma ascites cell nucleolar matrix fractions prepared by deoxyribonuclease I digestion and high-molarity salt extractions essentially according to a published method [Berezney, R., & Buchholz, L. A. (1981) Exp. Cell Res. 20, 4995-5002]. The nucleolar matrix fraction was enriched in polypeptides of molecular mass of 28, 37.5, 40, 70, 72, 110 (protein C23), and 160 kDa, compared to the nuclear fraction in which polypeptides of molecular mass of 31, 33.5, 43.5, 46, 50, 56, and 59 kDa were predominant. About one-fourth of the protein, half of the RNA, and less than 4% of the DNA originally present in the nucleoli remained in the matrix fraction. Addition of single agents such as ethylenediaminetetraacetic acid, ribonuclease A, or mercaptoethanol during preparation had no significant effect on the polypeptide composition of the nucleolar matrix fraction. However, the combination of mercaptoethanol and ribonuclease A caused most of the RNA and protein to be removed, including protein C23 and the 160-kDa polypeptide, with polypeptides in the range of Mr 30 000-50 000 remaining. Electron microscopy of nucleolar matrix fractions revealed the presence of particles similar in size to the granular elements of nucleoli. However, when ribonuclease A and mercaptoethanol were included in the procedure, only amorphous material remained. Many proteins of nucleolar preribosomal RNP particles were also associated with the nucleolar matrix fraction. RNA from the nucleolar matrix fraction was enriched in sequences from 18S and 28S ribosomal RNA. These results indicate that preribosomal RNP particles are major constituents of a nucleolar matrix fraction prepared by the deoxyribonuclease I-high-molarity salt method.

Animals↗
PubMed1990

NMR structural refinement of an extrahelical adenosine tridecamer d(CGCAGAATTCGCG)2 via a hybrid relaxation matrix procedure.

Until very recently interproton distances from NOESY experiments have been derived solely from the two-spin approximation method. Unfortunately, even at short mixing times, there is a significant error in many of these distances. A complete relaxation matrix approach employing a matrix eigenvalue/eigenvector solution to the Bloch equations avoids the approximation of the two-spin method. We have calculated the structure of an extrahelical adenosine tridecamer oligodeoxyribonucleotide duplex, d(CGCAGAATTCGCG)2, by an iterative refinement approach using a hybrid relaxation matrix method combined with restrained molecular dynamics calculations. Distances from the 2D NOESY spectra have been calculated from the relaxation rate matrix which has been evaluated from a hybrid NOESY volume matrix comprising elements from the experiment and those calculated from an initial structure. The hybrid matrix derived distances have then been used in a restrained molecular dynamics procedure to obtain a new structure that better approximates the NOESY spectra. The resulting partially refined structure is then used to calculate an improved theoretical NOESY volume matrix which is once again merged with the experimental matrix until refinement is complete. Although the crystal structure of the tridecamer clearly shows the extrahelical adenosine looped out way from the duplex, the NOESY distance restrained hybrid matrix/molecular dynamics structural refinement establishes that the extrahelical adenosine stacks into the duplex.

Adenosine↗
PubMed2006

Development of N,O-(carboxymethyl)chitosan/collagen matrixes as a wound dressing.

In an attempt to accelerate wound healing by stimulating the recruitment of fibroblasts and improve the mechanical properties of collagen matrixes, N,O-(carboxymethyl)chitosan (NOCC) was incorporated into the backbone of a collagen (COL) matrix without or with chondroitin sulfate (CS) or an acellular dermal matrix (ADM). The result of a cell migration study demonstrated that the migration of fibroblasts was significantly enhanced by NOCC in a concentration-dependent manner. In the analysis with a dynamic mechanical analyzer, NOCC/CS/COL matrixes presented higher tensile strengths than did NOCC/ADM/COL matrixes. Skin fibroblasts cultured on the matrixes containing NOCC showed increased proliferation and secretion of three kinds of cytokines compared with the control. Results of the in vivo wound healing study showed that matrixes incorporating NOCC showed markedly enhanced wound healing compared with the control. Therefore, the above results clearly suggest that NOCC/COL matrixes containing CS or ADM can be potential wound dressings for clinical applications.

Animals↗
PubMed2001

Calculation of nail plate and nail matrix parameters by 20 MHz ultrasound in healthy volunteers and patients with skin disease.

BACKGROUND/AIMS: The objective, but noninvasive, assessment of the nail plate and nail matrix is of interest in dermatology, and cosmetics as well. These cutaneous structures were investigated with 20 MHz ultrasound. This study was performed to obtain data on normal nails in adults of different age groups, with a left-right comparison, and to investigate nail changes in selected dermatologic diseases. METHODS: Healthy controls (n = 34) and patients with dermatologic complaints and nail disease (n = 37) were included after informed consent. In the control group, 18 woman and 16 men with a mean age of 37.2 years (range 15 to 82 years) were investigated for age- and gender-related differences. Patients with one of the following disorders were investigated: systemic lupus erythematosus (SLE; n = 11), systemic sclerosis (PSS; n = 8), psoriasis (n = 9), chronic hand eczema (n = 5), and others (n = 4). Measurements of length and width of the nail plate and the lunulae were performed with a micrometer device. Sonography was performed with a 20 MHz probe in B-scan mode. RESULTS: The mean nail thickness of healthy controls varied between 0.481 mm (right thumb) and 0.397 mm (left fifth finger). The nail volume and the matrix volume disclosed a positive, but mostly nonsignificant, correlation for all controls. Age-specific differences were investigated for both genders. In men and women, the matrix volume increased significantly with age. The nail and matrix volume was higher in men than in women, independent of age. The left-right comparison disclosed a trend to higher nail and matrix volumes on the right hand. In patients with SLE there was an increase in nail thickness and in matrix volume. Patients with PSS showed a significant decrease in nail thickness and matrix volume. In other diseases the measurements disclosed no confident differences to healthy controls. CONCLUSION: The 20 MHz ultrasound offers a noninvasive method to calculate nail thickness, nail volume and matrix volume in healthy volunteers and in nail disease. Skin diseases show characteristic quantitative changes in these parameters.

Adolescent↗
PubMed2002

Turnover of matrix proteins in mammalian mitochondria.

In cultured hepatocytes the turnover of several mitochondrial matrix proteins (e.g. acetyl-CoA acetyltransferase) appears to be initiated by CoA-mediated, sequential transformation into CoA-modified forms. This modification favours the notion that intramitochondrial degradation by a matrix-resident ATP-dependent protease may be preceded by a specific modification by CoA. In a mitochondrial matrix fraction the MgATP-dependent decrease in anti-CoA immunoreactivity coincided with both a decrease in the anti-protein immunoreactivity of acetyl-CoA acetyltransferase and/or of 3-ketoacyl-CoA thiolase, and with the appearance of proteolytic fragments. A closer analysis of the degradation pattern revealed, however, a breakdown of the unmodified acetyl-CoA acetyltransferase and of its CoA-modified form, A1, whereas the form that is more highly modified by CoA, A2, proved to be inaccessible towards an ATP-dependent protease. In mammalian mitochondrial matrix, proteins can be degraded selectively by a matrix-resident ATP-dependent protease. The process of CoA modification results finally in the protection of matrix proteins from degradation. In cultured hepatocytes, leupeptin, an inhibitor of lysosomal proteases, did not affect the steady-state level of the mitochondrial matrix protein acetyl-CoA acetyltransferase. However, leupeptin mediated a specific accumulation of mitochondrial matrix proteins in the cytosolic fractions of hepatocytes cultured over a 24 h period. The levels of acetyl-CoA acetyltransferase, 3-ketoacyl-CoA thiolase and glutamate dehydrogenase proteins increased 1.9-, 2.0- and 2.2-fold respectively. Their status as mature, oligomeric, but enzymically inactive enzymes strongly suggests that they originate from a leakage of autophagosomes, a constituent of the non-selective autophagic/lysosomal pathway for degradation of whole mitochondria.

Acetyl-CoA C-Acetyltransferase↗
PubMed1978

Codistribution of pericellular matrix proteins in cultured fibroblasts and loss in transformation: fibronectin and procollagen.

Antibodies to fibronectin and to distinct types of procollagens and collagens were used in immunofluorescent staining to localize these proteins in cell cultures. Normal human skin or lung fibroblasts produced a fibrillar pericellular matrix in which fibronectin and procollagen (types I and III) showed extensive codistribution. Fibronectin and procollagen were synthesized by the same cells as judged by double-stain immunofluorescence. Pericellular procollagen was specifically digested with collagenase without an effect on the fibrillar distribution of matrix fibronectin. Brief treatment with trypsin removed both matrix proteins. The human tumor cell lines HT-1080 (fibrosarcoma) and RD (rhabdomyosarcoma) produced little or no matrix fibronectin or procollagen. At sites of cell contact, simian virus 40-transformed lung fibroblasts (VA13) produced small amounts of pericellular fibrillar matrix fibronectin that codistributed with procollagen type I. Intracellular fibronectin and procollagen were visualized in all of these human sarcoma cell lines. When chicken embryo fibroblasts infected with a T class mutant (NY68) of Rous sarcoma virus temperature-sensitive for transformation were maintained at the nonpermissive temperature (41 degrees ) the cells had normal phenotype and a fibrillar matrix containing fibronectin and procollagen was present. At the permissive temperature (35 degrees ), the cells showed transformed phenotype and the matrix was lost. The failure to produce a pericellular fibronectin/collagen matrix may account for several phenotypic characteristics of transformed cultured fibroblasts.

Cell Line↗
PubMed1995

Sorting of cytochrome b2 to the intermembrane space of mitochondria. Kinetic analysis of intermediates demonstrates passage through the matrix.

Precytochrome b2 is targeted to the mitochondrial intermembrane space by a dual targeting sequence comprising 80 amino acids. A kinetic analysis of intramitochondrial sorting was performed. The intermediate-size form accumulated transiently in the matrix. When import was performed in the presence of metal chelators to prevent the first processing by the matrix processing peptidase, > 40% of the imported precursor was localized in the matrix. A deletion of 13 amino acids in the intermembrane space sorting sequence caused partial inhibition of the first processing, and a transient accumulation of the precursor form in the matrix was also observed. The decrease in this matrix-localized precursor form paralleled an increase in the mature-size form in the intermembrane space. A point mutation in the mitochondrial targeting sequence (N-terminal to the sorting sequence) resulted in missorting to the matrix space. Furthermore, a chimeric protein consisting of the initial 85 residues of cytochrome b2 fused to dihydrofolate reductase was partially targeted to the matrix at 15 degrees C, but not at 25 degrees C. Together, the results presented here indicate that cytochrome b2 passes through the matrix on its sorting pathway to the intermembrane space.

Amino Acid Sequence↗
PubMed2002

Superoxide activates mitochondrial uncoupling protein 2 from the matrix side. Studies using targeted antioxidants.

Superoxide activates nucleotide-sensitive mitochondrial proton transport through the uncoupling proteins UCP1, UCP2, and UCP3 (Echtay, K. S., et al. (2002) Nature 415, 1482-1486). Two possible mechanisms were proposed: direct activation of the UCP proton transport mechanism by superoxide or its products and a cycle of hydroperoxyl radical entry coupled to UCP-catalyzed superoxide anion export. Here we provide evidence for the first mechanism and show that superoxide activates UCP2 in rat kidney mitochondria from the matrix side of the mitochondrial inner membrane: (i) Exogenous superoxide inhibited matrix aconitase, showing that external superoxide entered the matrix. (ii) Superoxide-induced uncoupling was abolished by low concentrations of the mitochondrially targeted antioxidants 10-(6'-ubiquinonyl)decyltriphenylphosphonium (mitoQ) or 2-[2-(triphenylphosphonio)ethyl]-3,4-dihydro-2,5,7,8-tetramethyl-2H-1-benzopyran-6-ol bromide (mitoVit E), which are ubiquinone (Q) or tocopherol derivatives targeted to the matrix by covalent attachment to triphenylphosphonium cation. However, superoxide-induced uncoupling was not affected by similar concentrations of the nontargeted antioxidants Q(o), Q(1), decylubiquinone, vitamin E, or 6-hydroxy-2,5,7,8-tetramethylchroman 2-carboxylic acid (TROLOX) or of the mitochondrially targeted but redox-inactive analogs decyltriphenylphosphonium or 4-chlorobutyltriphenylphosphonium. Thus matrix superoxide appears to be necessary for activation of UCP2 by exogenous superoxide. (iii) When the reduced to oxidized ratio of mitoQ accumulated by mitochondria was increased by inhibiting cytochrome oxidase, it induced nucleotide-sensitive uncoupling that was not inhibited by external superoxide dismutase. Under these conditions quinols are known to produce superoxide, and because mitoQ is localized within the mitochondrial matrix this suggests that production of superoxide in the matrix was sufficient to activate UCP2. Furthermore, the superoxide did not need to be exported or to cycle across the inner membrane to cause uncoupling. We conclude that superoxide (or its products) exerts its uncoupling effect by activating the proton transport mechanism of uncoupling proteins at the matrix side of the mitochondrial inner membrane.

Aconitate Hydratase↗
PubMed2000

Estradiol pharmacokinetics after transdermal application of patches to postmenopausal women: matrix versus reservoir patches.

OBJECTIVE: A new matrix 17 beta-estradiol transdermal patch incorporating lauric acid to improve estradiol skin absorption has been designed for hormone replacement therapy. Estradiol pharmacokinetics obtained with the prototype, its industrial counterpart, a matrix-type, System 50, and a reservoir-type, Estraderm TTS 50, transdermal patch have been compared. Each device delivers 50 micrograms estradiol daily. METHODS: Twenty postmenopausal women received each of the four formulations for 3 days in a Latin-square design and with a minimum 4-day wash-out period between treatments. Estradiol plasma concentrations were measured by radioimmunoassay at 6, 12, 24, 48 and 72 h after application. RESULTS: The prototype patch and its industrial counterpart showed no significant difference in estradiol delivery, with 72-h systemic exposure to estradiol similar to that of the reservoir patch but greater than that of the reference matrix formulation, with average baseline-corrected concentrations (SEM) of 35 (4), 32 (3), 32 (2) and 19 (1.8) pg/ml, respectively. In addition, they ensured more stable delivery, with coefficients of variation of plasma estradiol concentrations (12-72 h) of 29, 41, 63 and 84%, respectively. All matrix patches demonstrated the same patients to be poor estradiol absorbers, different from those encountered with the reservoir patch type, despite an improved estradiol bioavailability with the lauric acid-containing matrix patch. CONCLUSION: Matrix patches incorporating lauric acid led to estradiol plasma levels more stable than with the reference matrix and reservoir patches, and greater than those with the reference matrix patch.

Administration, Cutaneous↗
PubMed1977

Reversibly contractile nuclear matrix. Its isolation, structure, and composition.

From Tetrahymena macronuclei we have isolated a reversibly contractile nucleo-skeleton, i.e., an "expanded" nuclear matrix which reversibly contracts when the total concentration of the bivalent cations, Ca and Mg (3:2), is decreased to 5 mM or increased to 125 mM. During contraction the average diameter of the expanded matrix becomes reduced by about 24%; this corresponds to a volume contraction of about 55%. The reversible contraction of the nuclear matrix does not depend on ATP and cannot be inhibited by salygran. The expanded matrix is obtained by removing carefully from the macronuclei 89.7% of the phospholipid, 99.6% of the DNA, 98.5% of the RNA, and 74.8% of the protein by treatment with Triton X-100 and digestion with DNase and RNase followed by an extraction with 2 M NaCl. Electron microscopy reveals, within the expanded matrix, residual equivalents to the structures characteristic for macronuclei: (a) a residual nuclear envelope with nuclear pore complexes; (b) residual nucleoli at the periphery; (c) a fibrillar internal network. The expanded matrix is essentially composed of proteins (96.2%) and traces of DNA (0.8%), RNA (0.5%), phospholipid (1.6%), and carbohydrates (0.9%). The last, which have been determined by gas chromatography, contain glucose, mannose, and an unidentified sugar in the ratio 1:5.4:5.7. The ratio of acidic to basic amino acids of the expanded matrix is 1.55. Sodium dodecyl sulfate (SDS) gel electrophoresis reveals a predominant protein with a mol wt of 18,000 which is apparently involved in the reversible contractile process. The mechanism of this reversible contraction of the expanded matrix remains to be elucidated, but it differs both from actin-myosin contraction systems and from the contractile spasmoneme system in vorticellids.

Calcium↗
PubMed2004

Effects of matrix heterogeneity on animal dispersal: from individual behavior to metapopulation-level parameters.

Mounting theoretical and empirical evidence shows that matrix heterogeneity may have contrasting effects on metapopulation dynamics by contributing to patch isolation in nontrivial ways. We analyze the movement properties during interpatch dispersal in a metapopulation of Iberian lynx (Lynx pardinus). On a daily temporal scale, lynx habitat selection defines two types of matrix habitats where individuals may move: open and dispersal habitats (avoided and used as available, respectively). There was a strong and complex impact of matrix heterogeneity on movement properties at several temporal scales (hourly and daily radiolocations and the entire dispersal event). We use the movement properties on the hourly temporal scale to build a simulation model to reconstruct individual dispersal events. The two most important parameters affecting model predictions at both the individual (daily) and metapopulation scales were related to the movement capacity (number of movement steps per day and autocorrelation in dispersal habitat) followed by the parameters representing the habitat selection in the matrix. The model adequately reproduced field estimates of population-level parameters (e.g., interpatch connectivity, maximum and final dispersal distances), and its performance was clearly improved when including the effect of matrix heterogeneity on movement properties. To assume there is a homogeneous matrix results in large errors in the estimate of interpatch connectivity, especially for close patches separated by open habitat or corridors of dispersal habitat, showing how important it is to consider matrix heterogeneity when it is present. Movement properties affect the interaction of dispersing individuals with the landscape and can be used as a mechanistic representation of dispersal at the metapopulation level. This is so when the effect of matrix heterogeneity on movement properties is evaluated under biologically meaningful spatial and temporal scales.

Animal Migration↗
PubMed1995

Inhibition of angiogenesis and murine hemangioma growth by batimastat, a synthetic inhibitor of matrix metalloproteinases.

BACKGROUND: The importance of matrix metalloproteinases in angiogenesis, tumor growth, and metastasis is well known. However, little is known about the role of matrix metalloproteinases in the formation of hemangiomas and about the possible therapeutic use of matrix metalloproteinase inhibitors in aggressive vascular tumors. PURPOSE: To study the role of matrix metalloproteinase in vascular tumors, we tested the antineoplastic activity of a synthetic inhibitor of matrix metalloproteinases, batimastat, on an experimental model of hemangioma, formed by murine endothelioma cells transformed by polyoma middle-T oncogene (eEnd.1). METHODS: The effect of batimastat was studied in vivo on the formation of hemorrhaging, cavernous hemangiomas by eEnd.1 endothelioma cells injected subcutaneously in nude mice and on the angiogenic response induced by an endothelioma cell supernatant embedded in a pellet of reconstituted basement membrane (Matrigel). The effect of batimastat was investigated in vitro on endothelial cell proliferation, motility, and invasion of a layer of Matrigel. RESULTS: Daily treatment with batimastat (30, 3, and 0.3 mg/kg at the site of eEnd.1 cell injection) inhibited tumor growth, with increased doubling time. The carboxamide derivative of batimastat, BB-374, a poor inhibitor of matrix metalloproteinase activity, was less active in reducing hemangioma growth. Histologic analysis of treated tumors indicated a reduction in the size of blood-filled spaces and in hemorrhage. Batimastat also inhibited the angiogenic response induced by cultured eEnd.1 endothelioma cell supernatant embedded in a pellet of Matrigel. Batimastat significantly inhibited endothelial cell invasion in vitro through a layer of Matrigel, but it showed no direct cytotoxic activity. CONCLUSIONS: Batimastat reduces in vivo growth of experimental hemangiomas, most probably by blocking endothelial cell recruitment by the transformed cells or by interfering with cell organization in vascular structures. IMPLICATIONS: These results confirm the importance of matrix metalloproteinase in endothelial cell recruitment that occurs in angiogenesis and in the formation of vascular tumors and suggest a therapeutic potential for synthetic matrix metalloproteinase inhibitors.

Animals↗
PubMed1983

The association of transcriptionally active genes with the nuclear matrix of the chicken oviduct.

Eucaryotic DNA is organized into a series of supercoiled loops that are anchored to the nuclear matrix. When these DNA loops are cleaved by endonucleases, the DNA sequences which remain associated with the nuclear matrix can be recovered and analyzed for their content of specific genes. Using restriction endonucleases to cleave the loops, we demonstrate that ovalbumin and conalbumin gene sequences are preferentially associated with the nuclear matrix of hen oviduct cells but not with the nuclear matrix of hen brain cells. Furthermore, we determined that several regions of the ovalbumin gene were independently attached to the nuclear matrix of hen oviduct cells. This included sequences located 3.8 kb downstream from the 3' end of the ovalbumin gene transcription unit. To determine whether the nuclear matrix association of the ovalbumin gene was regulated by hormones, we examined the oviduct cells of chicks that underwent primary estrogen stimulation, estrogen withdrawal and secondary estrogen stimulation. Ovalbumin gene sequences selectively dissociated from the chick oviduct nuclear matrix during estrogen withdrawal and reassociated with the nuclear matrix following restimulation.

Animals↗
PubMed1983

Organization of DNA replication in Physarum polycephalum. Attachment of origins of replicons and replication forks to the nuclear matrix.

We have investigated the attachment of the DNA to the nuclear matrix during the division cycle of the plasmodial slime mold Physarum polycephalum. The DNA of plasmodia was pulse labelled at different times during the S phase and the label distribution was studied by graded DNase digestion of the matrix-DNA complexes prepared from nuclei isolated by extraction with 2 M NaCl. Pulse labelled DNA was preferentially recovered from the matrix bound residual DNA at any time of the S phase. Label incorporated at the onset of the S phase remained preferentially associated with the matrix during the G2 phase and the subsequent S phase. The occurrence of the pulse label in the matrix associated DNA regions was transiently elevated at the onset of the subsequent S phase. Label incorporated at the end of the S phase was located at DNA regions which, in the G2 phase, were preferentially released from the matrix by DNase treatment. From the results and previously reported data on the distribution of attachment sites it can be concluded that origins of replicons or DNA sites very close to them are attached to the matrix during the entire nuclear cycle. The data further indicate that initiations of DNA replication occur at the same origins in successive S phases. Replicating DNA is bound to the matrix, in addition, by the replication fork or a region close to it. This binding is loosened after completion of the replication.

Cell Cycle↗