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G R Martin

Publications and source records attributed to G R Martin.

At least 325 records · Page 18Linked to original sources
PubMed1982

Platelet-derived growth factor is a chemoattractant for vascular smooth muscle cells.

In previous experiments (Grotendorst et al, 1981), we showed that platelet-derived growth factor promotes the migration of smooth muscle cells in vitro. Using a "checkerboard" analysis, we now establish that platelet-derived growth factor (PDGF) acts as a true chemoattractant for cultured aortic smooth muscle cells. Other growth factors such as epidermal growth factor, fibroblast growth factor, and insulin are not chemoattractants. The chemotactic response occurs before the initiation of DNA synthesis and is not affected by inhibition of DNA synthesis. Chemotaxis occurs at levels of PDGF lower than required for mitogenesis. RNA and protein synthesis are required for the chemotactic response. As found previously in bacteria and leucocytes, we find that methylation reactions are required for the chemotactic response. The possibility is discussed that PDGF acts in vivo at sites of vascular injury to attract smooth muscle cells from the medial layer to the luminal surface, and is involved in the early stages of the formation of atherosclerotic plaques.

Animals↗
PubMed1982

Laminin.

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Animals↗
PubMed1982

Modulation of type I and type III collagen production in normal and mutant human skin fibroblasts by cell density, prostaglandin E2 and epidermal growth factor.

Previously, we found that, at high cell density, human skin fibroblasts produce a higher proportion of type III to type I collagen. Treatment of sparse cultures with prostaglandin E2 also increases this ratio, while treatment of dense cultures with epidermal growth factor reduces it. Similar changes were observed using some strains of fibroblasts from patients with the Ehlers-Danlos syndrome type IV and osteogenesis imperfecta. Studies on the extent of intracellular degradation suggest that the changes observed could be caused in part by changes in the breakdown of collagen inside the cell with preferential loss of type I collagen and/or changes in synthesis of the two proteins.

Cell Adhesion↗
PubMed1982

Platelet-derived growth factor in chemotactic for fibroblasts.

Chemotaxis assays in modified Boyden chambers were used to detect fibroblast chemoattractants in materials released from early-stage inflammatory cells, namely, mast cells, platelets, and neutrophils. Strong attractant activity was found in substances released from platelets. This activity was accounted for mainly by the platelet-derived growth factor (PDGF), which is released from the platelets and which was active as a chemoattractant at 0.5-1.0 mitogenic units/ml. The mitogenic activity of purified PDGF, measured by [3H]thymidine incorporation, occurs at a similar concentration range. By varying the gradient of PDGF, we demonstrated that PDGF stimulates chemotaxis rather than random motility. Preincubation of suspensions of fibroblasts in the presence of PDGF decreased the subsequent migration of cells to a gradient of PDGF as well as to a gradient of fibronectin, which is also in attractant for fibroblasts. The chemotactic response of fibroblasts to PDGF was not inhibited by hydroxyurea or azidocytidine but was inhibited by actinomycin D and cycloheximide, suggesting that synthesis of RNA and proteins but not of DNA is required for the chemotactic response to occur. Fibroblast growth factor, epidermal growth factor, nerve growth factor, and insulin were not chemotactic for human skin fibroblasts, suggesting that the chemoattractant activity of PDGF for fibroblasts is not a general property of growth factors and mitogens. These results suggest that PDGF could have two functions in wound healing: to attract fibroblasts to migrate into the clot and then to induce their proliferation.

Blood Platelets↗
PubMed1982

Codistribution of heparan sulfate proteoglycan, laminin, and fibronectin in the extracellular matrix of normal rat kidney cells and their coordinate absence in transformed cells.

We used antibodies raised against both a heparan sulfate proteoglycan purified from a mouse sarcoma and a chondroitin sulfate proteoglycan purified from a rat yolk sac carcinoma to study the appearance and distribution of proteoglycans in cultured cells. Normal rat kidney cells displayed a fibrillar network of immunoreactive material at the cell surface when stained with antibodies to heparan sulfate proteoglycan, while virally transformed rat kidney cells lacked such a surface network. Antibodies to chondroitin sulfate proteoglycan revealed a punctate pattern on the surface of both cell types. The distribution of these two proteoglycans was compared to that of fibronectin by double-labeling immunofluorescent staining. The heparan sulfate proteoglycan was found to codistribute with fibronectin, and fibronectin and laminin gave coincidental stainings. The distribution of chondroitin sulfate proteoglycan was not coincidental with that of fibronectin. Distinct fibers containing fibronectin but lacking chondroitin sulfate proteoglycan were observed. When the transformed cells were cultured in the presence of sodium butyrate, their morphology changed, and fibronectin, laminin, and heparan sulfate proteoglycan appeared at the cell surface in a pattern resembling that of normal cells. These results suggest that fibronectin, laminin, and heparan sulfate proteoglycan may be complexed at the cell surface. The proteoglycan may play a central role in assembly of such complexes since heparan sulfate has been shown to interact with both fibronectin and laminin.

Animals↗
PubMed1982

Localization of type IV collagen, laminin, heparan sulfate proteoglycan, and fibronectin to the basal lamina of basement membranes.

Electron microscopic immunostaining of rat duodenum and incisor tooth was used to examine the location of four known components of the basement-membrane region: type IV collagen, laminin, heparan sulfate proteoglycan, and fibronectin. Antibodies or antisera against these substances were localized by direct or indirect peroxidase methods on 60-microns thick slices of formaldehyde-fixed tissues. In the basement-membrane region of the duodenal epithelium, enamel-organ epithelium, and blood-vessel endothelium, immunostaining for all four components was observed in the basal lamina (also called lamina densa). The bulk of the lamina lucida (rara) was unstained, but it was traversed by narrow projections of the basal lamina that were immunostained for all four components. In the subbasement-membrane fibrous elements or reticular lamina, immunostaining was confined to occasional "bridges" extending from the epithelial basal-lamina to that of adjacent capillaries. The joint presence of type IV collagen, laminin, heparan sulfate proteoglycan, and fibronectin in the basal lamina indicates that these substances do not occur in separate layers but are integrated into a common structure.

Animals↗
PubMed1982

Laminin and bullous pemphigoid antigen are distinct basement membrane proteins synthesized by epidermal cells.

We sought to determine if laminin, a high molecular weight glycoprotein of basement membrane, is synthesized by epidermal cells and whether it is distinct from bullous pemphigoid (BP) antigen, another high molecular weight-protein of basement membrane. By indirect immunofluorescence we detected laminin in cultures of Pam cells ( a mouse keratinocyte cell line) and normal human epidermal cells. To directly demonstrate its biosynthesis, we labeled the cells with radioactive amino acids and then extracted the cell layers with nonionic detergent. Using immunoprecipitation followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and fluorography to identify radiolabeled laminin, we could precipitate the 2 chains of laminin from cell culture medium and extracts of the cell layers. BP antigen, immunoprecipitated from the cells, did not comigrate with laminin on SDS-PAGE. In addition, BP antigen could be immunoprecipitated from the cell extracts depleted of laminin, and conversely, laminin could be immunoprecipitated from cell extracts depleted of BP antigen. We conclude that laminin is synthesized by epidermal cells (specifically, keratinocytes) and is distinct from BP antigen.

Animals↗
PubMed1982

Structure and function of basement membrane.

Progress has been made in identifying and characterizing basement membrane macromolecules, including type IV collagen, laminin, a heparan sulfate proteoglycan and bullous pemphigoid antigen. Basement membrane contains a unique collagen, type IV collagen, which is formed of pro alpha 1(IV) (Mr = 185,000) and pro alpha 2(IV) (Mr = 170,000) chains. As opposed to the fibrillar pattern seen with other collagens, the type IV collagen molecules are thought to be arranged in a honey-comb or reticular pattern which provides the major structural element of the basement membrane. Consistent with this model, type IV collagen has been localized to the basement membrane lamina densa, a nonfibrillar structure. Laminin is a large (Mr = 1,000,000) noncollagenous glycoprotein with chains of 200,000 and 400,000 daltons. It has been localized to the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. A heparan sulfate proteoglycan has also been identified in the basement membrane. Its biological function may be to restrict the penetration of anionic macromolecules through the basement membrane. In contrast to the above-mentioned components which are found in all tissue basement membranes, bullous pemphigoid antigen is only found in certain basement membranes, mostly those of stratified squamous epithelia. Bullous pemphigoid antigen is a protein, synthesized by keratinocytes in culture, with disulfide-linked chains (Mr = 220,000). By immunoelectron microscopy, it is localized in the lamina lucida of epidermal basement membrane and is closely associated with the basal cell surface. Its biological function is not known, but could involve epidermal basal cell-substrate interactions which occur when basal cells re-epithelialize wounds.

Animals↗
PubMed1982

A microcomputer system for clinical bacteriology: experience of 12 months' trial.

A data processing system using microcomputers was developed in a hospital bacteriology laboratory processing more than 60 000 specimens yearly. The purchase price of the hardware was frs 200 000 (17 500 pounds) and the software was written by the authors. The system has been running since May 1980 without general breakdown. The present configuration allows the processing of specimens, enquiries, scientific and administrative tasks but multiprogramming and cumulative reports are not possible.

Bacteriology↗
PubMed1982

Quantitative bacteriological analysis of amniotic fluid.

Quantitative bacteriological analysis of amniotic fluid (AF) was performed on 60 fluid samples collected by catheter from 50 selected labor patients regarded as liable to infection. AF cultures were positive in 52 cases. The bacterial colony counts ranged from less than 10(2) colony-forming units (CFU) per milliliter to 10(9) CFU/ml. Pathogenic bacteria in neonates such as group B Streptococcus, Escherichia coli, and Listeria monocytogenes were encountered with numerations equal to or greater than 10(7) CFU/ml in groups with clinical findings. An excellent correlation was noted between bacterial counts in AF and clinical data (p less than 0.00006). The results confirm that the quantitative bacteria analysis of the AF is a useful tool for evaluation of an infection risk for neonates.

Amniotic Fluid↗
PubMed1982

Intracellular localization of basement membrane precursors in the endodermal cells of the rat parietal yolk sac. II. Immunostaining for type IV collagen and its precursors.

Antibodies to type IV collagen were linked with peroxidase and used for direct immunostaining of Reichert's membrane and the associated cells of the rat parietal yolk sac. Immunostaining was observed throughout the thickness of Reichert's membrane and within the endodermal cells arranged as a single layer on its inner side. The immunostaining of endodermal cells was mainly present in the cisternae of rough endoplasmic reticulum (rER) and in the Golgi apparatus, where it could occur in any saccule, but predominated in the GERL elements and associated prosecretory granule-like structures. Moreover, the secretory granule-like structures present in the ectoplasm next to Reichert's membrane were also immunostained. Finally, immunostaining was observed in multivesicular bodies and occasionally in secondary lysosomes. The antigenicity detected by immunostaining in Reichert's membrane is attributed to type IV collagen itself, whereas the antigenicity of endodermal cells is assigned to precursors of this collagen. It is proposed that initial precursors arise in rER cisternae, migrate to Golgi saccules, and pass to the GERL element, where they accumulate into prosecretory granules, which, perhaps by fusion with one another, become secretory granules. The secretory granules in turn migrate to the cell surface where they release their content, which becomes the type IV collagen of Reichert's membrane. Some diversion from this pathway may account for the immunostaining of multivesicular bodies and lysosomes.

Animals↗
PubMed1982

Intracellular localization of basement membrane precursors in the endodermal cells of the rat parietal yolk sac. III. Immunostaining for laminin and its precursors.

Reichert's membrane and the endodermal cells of the parietal yolk sac were examined for the presence of laminin antigenicity using anti-laminin antibodies and the peroxidase-antiperoxidase sequence. Immunostaining was observed through the full width of Reichert's membrane and within endodermal cells. In these cells immunostaining was observed in rough endoplasmic reticulum (rER) cisternae and Golgi apparatus. The Golgi staining could occur in any saccule, but predominated in components interpreted as the last saccule of the stack, the GERL element, and associated prosecretory granules. The secretory granules found in the ectoplasm were also immunostained. Finally, multivesicular bodies showed some staining. The immunostaining of Reichert's membrane indicates the presence of laminin itself, while that of rER cisternae and the Golgi apparatus is attributed to laminin precursors. Presumably the biosynthesis of laminin occurs along the usual protein pathway, that is, from rER through Golgi saccules and the GERL element to secretory granules, which release their content into Reichert's membrane. The laminin immunostaining of Reichert's membrane and endodermal cells is similar to that of type IV collagen. It is, therefore, likely that the two substances are processed and secreted simultaneously.

Animals↗
PubMed1982

Relative importance of corticosterone and thyroxine in the postnatal development of sucrase and maltase in rat small intestine.

Both corticosterone and T4 have been previously implicated as causal factors in the ontogenic increases in jejunal sucrase and maltase activities during the third week of life in the rat. Furthermore, it is known that the administration of exogenous T4 during the developmental period causes significant increases in serum corticosterone concentrations. To determine whether the effects of T4 on sucrase and maltase are secondary to the corticosterone rise, we examined the effect of T4 administration in adrenalectomized (adX) pups. Serum corticosterone was measured in all operated animals. Some of the adX pups had substantial concentrations of circulating corticosterone. In adX pups with serum corticosterone levels below 0.1 microgram/dl, there was no effect of T4 on either maltase or sucrase activity. We also studied the effect of propylthiouracil-induced hypothyroidism on sucrase and maltase. At 21 days of age, both enzyme activities were significantly reduced in hypothyroid pups. Injections of either T4 or cortisone acetate were equally effective in restoring activities to normal. For sucrase, there was no further increase in activity when both hormones were administered. For maltase, the combined treatment gave activities that were significantly higher than those with either hormone alone. We conclude that for both sucrase and maltase, the effects of changes in thyroid status are primarily due to the accompanying changes in serum corticosterone. The normal rate of development of both enzymes appears to be principally under glucocorticoid control, although for maltase, T4 may have a facilitory action.

Adrenalectomy↗
PubMed1982

Alterations in the basement membrane (heparan sulfate) proteoglycan in diabetic mice.

We have grown the EHS (Engelbreth-Holm, Swarm) tumor in normal and genetically diabetic mice (db/db) and measured some components of basement membrane produced in the tumor. These studies showed similar amounts of total protein in control and diabetic tissue and similar patterns of proteins on SDS gel electrophoresis of extracts of the tissue. Laminin, a basement membrane specific glycoprotein utilized as an attachment factor by epithelial cells, was present in increased amounts in diabetic tissue. In contrast, the amount of BM-1 (heparan sulfate) proteoglycan was reduced. Less 35S-sulfate was incorporated into this proteoglycan, and the proteoglycan, but not its component glycosaminoglycans, was heterogeneous in size. The data indicate that either the synthesis of proteoglycan was decreased or its degradation was increased in diabetic tissue. Since the heparan sulfate proteoglycan serves to block the passage of anionic macromolecules through the basement membrane, decreased levels could account for the increased porosity of diabetic basement membrane. Compensatory synthesis of the basement membrane components to restore normal permeability could account for the thickened basement membranes observed in diabetes.

Animals↗