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Biomedical subjects

G R Martin

Publications and source records attributed to G R Martin.

At least 199 records · Page 11Linked to original sources
PubMed1989

A seven year survey of antibiotic susceptibility and its relationship with usage.

Bacterial susceptibilities to 14 antibiotics of 7385 clinical isolates, belonging to six species of Gram-negative bacilli, were analysed during seven years (1980-86). The recovery of Serratia marcescens, Acinetobacter calcoaceticus and Pseudomonas aeruginosa increased while their sensitivity to antibiotics decreased significantly, especially to aminoglycosides and tetracycline. There were significant correlations between increase in antibiotic use and decrease in susceptibility. There was a striking relationship between third-generation cephalosporin use and increasing number of isolates of the species mentioned above.

Anti-Bacterial Agents↗
PubMed1989

Cardiac determinants of cerebral blood flow during extracorporeal membrane oxygenation.

Doppler recordings of the pericallosal artery (PCA) and echocardiographic examinations were performed on nine infants before, and at 24-, 72-, and 96-hour intervals during extracorporeal membrane oxygenation (ECMO). Systolic indices of left ventricular (LV) function, as well as mean blood flow velocity and pulsatility in the PCA, were measured. Arterial blood gases and blood pressure were monitored. LV cardiac output and LV stroke volume decreased during early ECMO and returned toward baseline as ECMO flow rates decreased. In the PCA, changes in pulsatility paralleled changes in ventricular performance. Pulsatility decreased during early ECMO and returned toward baseline with time. There was an inverse relationship between mean blood flow velocity in the PCA and ventricular function during early ECMO. Mean blood flow velocity increased during early ECMO and returned toward baseline as ECMO flow rates decreased. Early changes in mean blood flow velocity were associated with an initial increase in arterial pO2, pCO2, and mean blood pressure. Total aortic flow (ECMO flow + LV cardiac output in cc/kg), arterial blood gases, and mean blood pressure remained unchanged during prolonged ECMO. These data suggest that the pulsatility of cerebral blood flow is related to cardiac function during partial bypass and that the regulation of cerebral blood flow during prolonged bypass may be dependent on the presence of pulsatile flow.

Aorta, Thoracic↗
PubMed1989

Contrasting patterns of myc and N-myc expression during gastrulation of the mouse embryo.

myc and N-myc are related genes whose similar protein products may be used for different purposes in vertebrate organisms. We have explored this possibility by using hybridization in situ to examine the expression of myc and N-myc during gastrulation of mouse embryos. Throughout gastrulation, myc RNA was most abundant in extraembryonic cells; by contrast, N-myc RNA was found at highest levels in the expanding primitive streak and other portions of the embryonic mesoderm. Differentiation of mesoderm to epithelioid cells was accompanied by diminished expression of N-myc. Expression of myc was not an inevitable correlate of cellular proliferation. Instead, the gene appeared to be regulated in concert with changes that affect a diversity of cellular properties, including proliferation, invasiveness, and differentiation.

Animals↗
PubMed1989

Developmentally regulated use of alternative promoters creates a novel platelet-derived growth factor receptor transcript in mouse teratocarcinoma and embryonic stem cells.

Embryonal carcinoma and embryonic stem cells expressed a novel form of platelet-derived growth factor receptor mRNA which was approximately 1,100 base pairs shorter than the 5.3-kilobase (kb) transcript expressed in fibroblasts and other cell types. The 4.2-kb stem cell transcript was initiated within the genomic region immediately upstream of exon 6 of the 5.3-kb transcript and therefore lacked the first five exons, which encode much of the extracellular domain of the receptor expressed in fibroblasts. In stem cells, the short form was predominant, although both forms were present at low levels. Following differentiation in vitro, expression levels of the long form increased dramatically. These findings suggest that during early embryogenesis, a stem cell-specific promoter is used in a stage- and cell type-specific manner to express a form of the platelet-derived growth factor receptor that lacks much of the extracellular domain and may function independently of ligand.

Animals↗
PubMed1989

Increased calcium levels alter cellular and molecular events in wound healing.

Surgical morbidity is dictated directly by wound healing. We have studied the effects of elevated calcium levels using cultured keratinocytes in vitro on two of the rate-limiting steps of wound healing, chemotaxis (directed migration) and adhesion. We found that the increased calcium (10 mmol/L) significantly inhibited both keratinocyte chemotaxis and adhesion (p less than 0.05). The calcium effect on adhesion could be partially reversed by pretreatment with the calcium channel blocker verapamil. Based on these data, an animal model was formulated in which topical calcium (5 mmol/L/day) was added to linear incision wounds. This resulted in significantly (p less than 0.05) delayed wound contraction characteristic of a chronic or impaired wound. Wound contraction depends on the presence of fibroblasts that synthesize collagen. The chronic wound was characterized by increased collagenase activity (p less than 0.05) but little alteration in collagen I synthesis. The addition of verapamil to these chronic wounds resulted in improved wound closure. These studies define the molecular and cellular events occurring as a result of the addition of elevated levels of calcium both in vitro and in vivo. Calcium may play a key role in the pathogenesis of chronic wounds.

Animals↗
PubMed1989

Increased prevalence of ventricular septal defect: epidemic or improved diagnosis.

The Baltimore-Washington Infant Study is an ongoing case-control study of congenital cardiovascular malformations in infants in whom the clinical diagnoses have been confirmed by echocardiography, catheterization, surgery, or autopsy. An increase in the prevalence of ventricular septal defects was detected in 1,494 infants with congenital cardiovascular malformations between 1981 and 1984. The prevalence of congenital cardiovascular malformations increased from 3.6 to 4.5 per 1,000 live births (P less than .025) and the prevalence of ventricular septal defect increased from 1.0 to 1.6 per 1,000 live births (P less than .001). The increase in ventricular septal defects accounted for the total increase in congenital cardiovascular malformations. The prevalence of isolated ventricular septal defect increased from 0.67 to 1.17 per 1,000 live births (P less than .001). The prevalence of ventricular septal defect with associated coarctation of the aorta, patent ductus arteriosus, atrial septal defect, and pulmonic stenosis did not change. The prevalence of ventricular septal defect diagnosed by catheterization, surgery, and autopsy did not change; however, defects diagnosed by echocardiography increased from 0.30 to 0.70 per 1,000 live births (P less than .001). It is concluded that the reported increase in prevalence of ventricular septal defect is due to improved detection of small, isolated ventricular septal defects and that there is no evidence of an "epidemic."

Cardiac Catheterization↗
PubMed1988

Differential regulation of growth and invasiveness of MCF-7 breast cancer cells by antiestrogens.

Estrogen increases the ability of the estrogen-dependent MCF-7 human breast cancer cell line to both proliferate and invade through an artificial basement membrane. In studying the response of MCF-7 cells to various antiestrogens, we found that 4-hydroxytamoxifen and tamoxifen inhibited cell proliferation but increased their invasiveness. In contrast, the structurally unrelated benzothiophene antiestrogens, LY117018 and LY156758, were potent antiproliferative agents which did not stimulate invasiveness. The differential effects of these antiestrogenic agents on invasion correlated with changes in production of collagenase IV, while no significant change was seen in the chemotactic activity of the cells. Invasiveness was increased by 17 beta-estradiol or 4-hydroxytamoxifen after a few hours of treatment and was rapidly lost when 17 beta-estradiol was withdrawn. Stimulation of invasiveness with 17 beta-estradiol was blocked by the antiestrogen, LY117018. Cells from the MDA-MB-231 line which lacks estrogen receptors were not affected by estrogen or antiestrogen in terms of proliferation or invasion. These studies indicate that the invasiveness of MCF-7 cells is regulated by antiestrogens through the estrogen receptor and may be mediated by collagenase IV activity. Antiestrogens which reduce both the proliferation and invasiveness of these cells may be interesting new candidates for clinical application.

Breast Neoplasms↗
PubMed1988

Doppler echocardiographic evaluation of cardiac performance in infants on prolonged extracorporeal membrane oxygenation.

Cardiac performance was evaluated by Doppler echocardiography in 19 infants with persistent pulmonary hypertension before, during and after prolonged extracorporeal membrane oxygenation (ECMO). Systemic arterial pressure was normal before ECMO (67 +/- 12 mm Hg), increased during ECMO (78 +/- 13 mm Hg) and decreased to baseline after ECMO (p less than or equal to 0.01). Heart rate was normal before ECMO and did not change during or after ECMO. The left ventricular shortening fraction was normal before ECMO (37 +/- 11%), decreased after beginning ECMO (25 +/- 11%) and returned to baseline 72 hours after beginning ECMO (p less than or equal to 0.01). Pulmonary arterial and aortic blood flow velocities were normal before ECMO, decreased 30 to 50% during ECMO and increased to baseline 72 hours after beginning ECMO (p less than or equal to 0.01). Stroke volume had an identical trend (p less than or equal to 0.01). Left ventricular velocity of circumferential shortening--an index of contractility--decreased after beginning ECMO (p less than or equal to 0.05). Left ventricular systolic wall stress--an index of systemic afterload--increased after beginning ECMO (p less than or equal to 0.01). A patent ductus arteriosus was present in 13 of 19 infants before ECMO, 16 of 19 infants during ECMO and in none of 19 infants after ECMO. Pulmonary arterial systolic pressure was high before ECMO (72 +/- 25 mm Hg), began to decrease after 48 hours on ECMO (59 +/- 24 mm Hg) and was normal after ECMO (38 +/- 18 mm Hg), p less than or equal to 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Flow Velocity↗
PubMed1988

Characterization of the promoter for the alpha 1 (IV) collagen gene. DNA sequences within the first intron enhance transcription.

Two overlapping clones spanning 19 kilobase pairs (kb) of the 5' end of the alpha 1 (IV) collagen gene were isolated and found to contain a single exon which encoded the 5'-untranslated sequence and 84 base pairs of the signal peptide. The 5' end of this exon was determined to be the 5' end of the transcript by S1 nuclease protection and primer extension. The nucleotide sequence of 1 kb of the 5'-flanking DNA was extremely G + C-rich (greater than 70%) and contained two GC boxes and a putative cAMP regulatory sequence. The transcriptional regulation of the alpha 1 (IV) gene was studied with chimeric gene constructs utilizing 2.5 kb of the 5'-flanking sequence coupled to the gene for chloramphenicol acetyltransferase. Transfection of this construct into differentiating F9 cells resulted in low chloramphenicol acetyltransferase activity compared to beta-actin or Rous sarcoma virus long terminal repeat promoters, although these cells produce large amounts of collagen IV. Inclusion of a 2.7-kb sequence 2.3 kb downstream from the first exon in either orientation increased the transcription of the chloramphenicol acetyltransferase construct approximately 10-fold in F9 cells, but was not active in NIH 3T3 cells, which synthesize little collagen IV. These results indicate the presence of an enhancer within the first intron, which increases the expression of this gene.

Acetyltransferases↗
PubMed1988

Novobiocin inhibits the SV40 enhancer activity.

Using a transient expression assay, we have analysed the effect of novobiocin, DNA topoisomerase II inhibitor, on simian virus 40(SV40) enhancer activities. We used the recombinant clones containing type I or II collagen promoters placed upstream of the bacterial chloramphenicol acetyltransferase (CAT) gene with or without SV40 enhancer. We observed the expected increase in CAT activities due to the presence of the SV40 enhancer. Interestingly, CAT gene expression of the enhancer-containing constructs were inhibited more sensitively by novobiocin than that of the enhancer-less construct. This findings lead us propose that DNA superhelicity mediated by topoisomeraseII is one of the important factor for the manifestation of SV40 enhancer activity.

Acetyltransferases↗
PubMed1988

Effects of inhibitors of plasminogen activator, serine proteinases, and collagenase IV on the invasion of basement membranes by metastatic cells.

Using both human and murine cell lines, we show that malignant cells are able to invade through basement membrane and also secrete elevated amounts of collagenase IV, an enzyme implicated in the degradation of basement membranes. Using serine proteinase inhibitors and antibodies to plasminogen activators as well as a newly described collagenase inhibitor we demonstrate that a protease cascade leads to the activation of an enzyme(s) that cleaves collagen IV. Inhibition at each step reduces the invasion of the tumor cells through reconstituted basement membrane in vitro. Treatment with a collagenase inhibitor reduced the incidence of lung lesions in mice given i.v. injections of malignant melanoma cells.

Animals↗
PubMed1988

The structure of anchorin CII, a collagen binding protein isolated from chondrocyte membrane.

cDNA clones for anchorin CII (Mr = 34,000), a collagen-binding protein, were isolated from a lambda gt 11 cDNA library prepared from chick cartilage mRNA. Several overlapping clones were characterized which gave rise to an open reading frame coding for 329 residues and a 3'-untranslated segment of 500 base pairs. The clones were identified as coding for anchorin by hybrid select translation analysis and by comparing the deduced amino acid sequence with the sequence of 10 tryptic peptides of the protein. A hydrophobic domain of 25 residues interrupted with 3 polar residues was identified with the carboxyl-terminal portion. There was no evidence for an aminoterminal signal peptide. Northern analysis revealed that the 5' probe hybridizes to a single 1.7-kilobases (kb) mRNA species, whereas the 3' probe hybridizes to two mRNA species of 1.7 kb and 5 kb, which are present in many cells including chondrocytes, crop cells, and fibroblasts. The level of anchorin mRNA in chick embryo fibroblasts was increased by infection with Rous sarcoma virus.

Amino Acid Sequence↗
PubMed1988

Inhibitors of collagenase IV and cell adhesion reduce the invasive activity of malignant tumour cells.

The invasive activities of some malignant cells appear to be activated by contact with laminin. This protein occurs solely in basement membranes and the binding of malignant cells to the surface of this extracellular matrix initiates the invasion process. Passage of the cells across basement membrane requires degradative activity and laminin induces the production of collagenase IV which lyses the collagen IV network. The motility of the cells is enhanced by chemo-attractants and by matrix molecules. Peptides that inhibit the binding of tumour cells to laminin, inhibitors of collagenase IV, and inhibitors of specific pathways of arachidonic acid metabolism prevent invasion as well as the metastasis of malignant cells and could be employed to stop the spread of cancer.

Animals↗
PubMed1988

Four classes of mRNA are expressed from the mouse int-2 gene, a member of the FGF gene family.

Mouse embryos at 7.5 days of gestation and endodermal cells derived from embryonal carcinoma cells each express four int-2 mRNAs of similar size and relative abundance. To determine their structure and coding potential, we prepared a cDNA library from endoderm mRNA and isolated several int-2 cDNAs. Structural analysis of these cDNAs combined with Northern blot hybridization and primer extension analyses of int-2 mRNA revealed that the differences between the mRNAs are generated through the use of two alternate transcriptional start sites and two alternate polyadenylation sites. All four mRNAs share a common core sequence that encodes a protein with amino acid similarity to fibroblast growth factor.

Amino Acid Sequence↗
PubMed1988

Invasive activity and chemotactic response to growth factors by Kaposi's sarcoma cells.

Kaposi's sarcoma (KS) is a relatively low grade neoplasm, classically occurring in the skin of elderly men. A more virulent and invasive form of Kaposi's sarcoma has been described in patients with acquired immune deficiency syndrome (AIDS). The origin and identification of the tumor cells in these lesions is controversial. Here we have studied the behavior of cells derived from KS lesions in an in vitro assay which measures the ability of cells to invade through a reconstituted basement membrane. In agreement with previous work, KS cells obtained under selective culture conditions were invasive showing activity comparable to that of malignant tumor cells. Normal fibroblasts, smooth muscle cells, and endothelial cells did not demonstrate invasive behavior under the same experimental conditions. To characterize further the nature of the KS cells we tested the chemotactic response of cells from the most invasive line to a variety of growth factors and compared their response to those of fibroblasts, smooth muscle, and endothelial cells. These studies suggest that normal cells respond to a unique repertoire of chemotactic factors. The chemotactic response of the KS cells most closely resembled that of smooth muscle cells and was quite distinct from endothelial cells. These results indicate that the KS-derived cultures contain invasive cells with a smooth muscle cell-like phenotype.

Biopsy↗
PubMed1988

Synthetic pentapeptide from the B1 chain of laminin promotes B16F10 melanoma cell migration.

Laminin is a basement membrane-specific glycoprotein that promotes cell adhesion, proliferation, differentiation, and tumor cell migration. Synthetic peptides from the amino acid sequence deduced from a cDNA clone of the B1 chain of laminin were tested for their ability to promote the migration of B16F10 melanoma cells. A peptide, CDPGYIGSR, that is able to mediate epithelial cell attachment to laminin was found to promote migration, and the constituent pentapeptide YIGSR was also active but to a lesser degree. This nine-amino acid peptide blocked migration of melanoma cells to laminin but had no effect on migration to fibronectin. These data suggest that the cell-binding site and migration site on laminin share a common sequence that is unique to laminin.

Animals↗
PubMed1988

Factors regulating basement membrane invasion by tumor cells.

Basement membranes serve as significant barriers to the passage of tumor cells but ones which metastatic cells can pass. This involves the production of a cascade of proteases leading to the activation of a specific collagenase that degrades the unique collagen network in basement membrane. Breast cancer cells, when estrogen dependent, show a requirement for estrogen for invasive activity. However, when these cells progress to an estrogen independent state and increased malignancy, they express an invasive phenotype constitutively. Studies with various anti-estrogens suggest that these responses are mediated via the estrogen receptor. Anti-estrogens lacking agonist activity suppress invasiveness as well as growth of the breast cancer cells.

Basement Membrane↗