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Biomedical subjects

G R Martin

Publications and source records attributed to G R Martin.

At least 289 records · Page 16Linked to original sources

Isolation and characterization of a factor from calf serum that promotes the pigmentation of embryonic and transformed melanocytes.

A protein (Mr = 63,000) from calf serum that promotes the pigmentation of cultured chick neural crest and mouse melanoma cells has been partially isolated and characterized in this study. The stimulation of melanin synthesis in cultured cells was used to follow its activity during purification. The pigment-promoting factor was isolated by sequential column chromatography on dye-agarose matrices followed by hydroxyapatite and high pressure molecular sieve chromatography. The factor was found to stimulate melanin biosynthesis at 2-4 micrograms/ml and was specific for melanin-producing cells and their precursors. Antibodies raised in rabbits against the factor inhibited its pigment-promoting activity as well as that of whole calf serum. Enzyme-linked immunoadsorbent assays demonstrated that calf and bovine sera contain molecules that cross-react with the pigment-promoting factor. Horse, human, rat, and chicken sera, which lack the biological activity, also lacked immunological cross-reactivity. Extracts of certain tissues, particularly the submaxillary gland, were observed to be rich sources of pigment-promoting activity.

Animals↗

Application of the operational model of agonism to establish conditions when functional antagonism may be used to estimate agonist dissociation constants.

The operational model of agonism (Black & Leff, 1983) has been used to analyse comparatively functional antagonism and irreversible antagonism as methods for estimating agonist dissociation constants (KAs). A general condition is established in terms of the model parameters which defines the type of experimental interventions at the receptor and the post-receptor level that allow valid KA estimation. It is shown that functional antagonism and other post-receptor interventions may produce changes in agonist-concentration effect curves which are qualitatively indistinguishable but quantitatively distinct, from those produced by irreversible antagonism. Experimental data obtained with the guinea-pig tracheal strip preparation are in keeping with the theoretical predictions and show how studies using functional antagonism may overestimate agonist affinity. In general, functional antagonism, unlike irreversible antagonism, is in principle an unreliable method for quantifying agonism.

Animals↗

Defective actin organization in cultured skin fibroblasts from individuals with inherited colon adenocarcinoma is not restored by addition of fibronectin.

Cultured skin fibroblasts from patients with hereditary adenomatosis of the colon and rectum (ACR) have a disorganized cytoskeleton. Since fibronectin has been found to restore normal cytoskeletal and cellular morphology to transformed cells, we investigated the fibronectin pattern in ACR cells. We found that although both fibronectin synthesis and binding to the cell surface were apparently normal, addition of fibronectin did not restore a normal distribution of actin cables to ACR cells. The data suggest that coupling of cell surface-bound fibronectin to the cytoskeleton might be constitutively defective in ACR cells.

Actins↗

Stimulation of granulation tissue formation by platelet-derived growth factor in normal and diabetic rats.

Subcutaneous implantation of Hunt-Schilling wound chambers in rats induces a wound repair response causing the chamber first to fill with fluid and subsequently with connective tissue. The presence of a type I collagen gel encouraged a more rapid dispersion of cells throughout the chamber but had no effect on the rate of new collagen deposition. Addition of platelet-derived growth factor (PDGF; 50 ng/chamber) to the collagen-filled chambers caused an earlier influx of connective tissue cells, a marked increase in DNA synthesis, and a greater collagen deposition in the chamber during the first 2 wk after implantation. After 3 wk, however, the levels of collagen were similar in PDGF-supplemented and control chambers. Diabetic animals exhibited a decreased rate of repair which was restored to normal by addition of PDGF to the wound chamber. Combinations of PDGF and insulin caused an even more rapid increase in collagen deposition. These results suggest that the levels of various growth factors, particularly PDGF, may be limiting at wound sites and that supplementation of wounds with these factors can accelerate the rate of new tissue formation.

Animals↗

Pharmacokinetics of dibekacin in children with cystic fibrosis.

Dosages and pharmacokinetics of dibekacin were studied in a group of 15 children with cystic fibrosis (CF) and a control group of 9 children. The mean dosage regimens of dibekacin were respectively equal to 2.19 mg/kg and 2.16 mg/kg in the CF and non-CF patients. The mean peak serum values for the CF and non-CF groups were respectively equal to 5.3 micrograms/ml. Comparison of pharmacokinetic parameters (i.e. half-life, distribution volume, total body clearance and area under the curve) showed no significant difference between the two groups (p greater than 0.05).

Aspartate Aminotransferases↗

The eye of the humboldt penguin, Spheniscus humboldti: visual fields and schematic optics.

Construction of a schematic eye indicates that the eye of Spheniscus humboldti is aquatic in design. The lens has a power of 100 dioptres (D) while (in air) the cornea has a power of 29 D. In air, the eye is myopic (approximately 28 D) but in water it is emmetropic. Minimum pupil size would seem insufficient to allow the pupil to function as a stenopaic aperture and increase depth of focus sufficiently to overcome the eye's aerial myopia. Entry into water reduces maximum image brightness by approximately three times. In air, the maximum width of the retinal binocular field is 45 degrees and this occurs approximately 10 degrees above the line of the bill. The bill intrudes into the retinal field and binocular field width in the plane containing the bill and the optic axes is 28 degrees. The vertical extent of the binocular field is 125 degrees. In the plane containing the optic axes the cyclopean field equals 282 degrees and the optic axes diverge by 116 degrees. In this plane the mean uniocular field is 155 degrees with the temporal hemifield approximately 11 degrees larger than the nasal hemifield. Entry into water reduces the widths of the visual fields such that maximum binocular field width is only 17 degrees and the vertical extent is reduced to about 80 degrees. Binocular vision is lost in the plane of the bill, and the uniocular retinal field is reduced by 32 degrees and the cyclopean field by 36 degrees.

Air↗

Isolation and characterization of a cDNA clone for the amino-terminal portion of the pro-alpha 1(II) chain of cartilage collagen.

We have isolated a cDNA clone (pRcol 2) which is complementary to the 5'-terminal portion of the rat pro-alpha 1(II) chain mRNA. A synthetic oligonucleotide was used both as a primer for cDNA synthesis and as a probe for screening a cDNA library. The probe was a mixture of sixteen 14-mers deduced from an amino acid sequence present in the amino-terminal telopeptide of the rat cartilage alpha 1(II) chain. This primer was chosen so that the resulting cDNA would contain the sequence of the 5' end of the mRNA. The nucleotide sequences of the cDNA were determined and compared with that of three other interstitial procollagen chain mRNAs (pro-alpha 1(I), pro-alpha 2(I), and pro-alpha 1(III) chain mRNA). pRcol 2 contains a 521-base pair (bp) insert, including 153 bp of the 5' untranslated region plus 368 bp coding for the signal peptide, the amino-terminal propeptide, and a part of the telopeptide. The signal peptide of the type II collagen chain is composed of about 20 amino acids. There is little homology between the amino acid sequence of the signal peptide in the pro-alpha 1(II) chain and that of three other interstitial procollagen chains. The NH2-terminal propeptide is deduced to contain short nonhelical sequences at its amino and carboxyl ends and an internal helical collagenous domain comprising 25 repeats of Gly-X-Y with one interruption. There is a strong conservation of the amino acid sequence of the carboxyl-terminal part of the NH2-terminal propeptide in the pro-alpha 1(II), pro-alpha 1(I), and pro-alpha 2(I) chains. Type II collagen mRNA does not contain a sequence corresponding to a uniquely conserved nucleotide sequence around the translation initiation site which occurs in mRNA for other procollagen chains.

Amino Acid Sequence↗

Modulation of the metastatic activity of melanoma cells by laminin and fibronectin.

Metastatic mouse melanoma cells have a high affinity for the basement membrane and the ability to degrade it; these properties may allow tumor cells to invade the membrane and disseminate. In this study it was found that the metastatic potential of mouse melanoma cells varied when the cells were exposed in culture to fibronectin or laminin. After removal of fibronectin or exposure to laminin, the cells had an increased affinity for basement membrane collagen, were more invasive of basement membranes in vitro, and produced more lung colonies in vivo. These changes are correlated with and may be due to an increase in the laminin-binding capacity of the tumor cell surface.

Amnion↗

The regulation of basement membrane formation and cell-matrix interactions by defined supramolecular complexes.

Several constituents of basement membranes, including type IV collagen, laminin, heparan sulphate proteoglycan and nidogen, form a defined supramolecular complex that is an obligatory intermediate in the formation of this matrix. We have named this defined supramolecular complex the 'basement membrane matrisome'. Matrisome structures composed of other collagens, proteoglycans and glycoproteins may participate in the formation of other extracellular matrices. Cells show specific interactions with components of the extracellular matrix. We discuss studies that indicate that melanoma cells can express receptors for both laminin and fibronectin. However, these receptors are expressed in a reciprocal fashion, depending on the exposure of the cell to these proteins. Binding of either fibronectin or laminin to the cells elicits a distinct phenotype. This represents a mechanism in which cellular activity can be regulated by extracellular matrix factors during development and in repair.

Animals↗

Fine structure of the glomerular basement membrane and immunolocalization of five basement membrane components to the lamina densa (basal lamina) and its extensions in both glomeruli and tubules of the rat kidney.

Electron microscopic immunostaining was used to examine the localization of type IV collagen, laminin, entactin , heparan sulfate proteoglycan, and fibronectin within the basement membranes of the rat kidney. In preliminary experiments, various methods of processing formaldehyde-fixed kidney were compared using antilaminin antiserum and the indirect immunoperoxidase method. Little or no laminin immunostaining of the glomerular basement membrane was present in sections unless they had been frozen-thawed; and even in this case, the immunostaining was light in comparison to that of basement membranes in adjacent tubules. However, when frozen-thawed sections were treated with 0.5% sodium borohydride, immunostaining was then as strong in glomerular as in tubular basement membranes. Accordingly, this treatment was applied to frozen-thawed sections before immunostaining for any of the substances under study. Immunostaining of the glomerular basement membrane for each of the five substances was fairly uniform throughout the lamina densa (also called basal lamina), but uneven in the lamina lucida interna and externa (also called lamina rara interna and externa) in which stained bands extended from the lamina densa. Similarly in the basement membranes of tubules, immunostaining for the five substances was localized to the lamina densa and bands extending into the lamina lucida. When the ultrastructure of the glomerular basement membrane was examined, three structures were found: (1) a network of 4-nm-thick "cords," which seems to be the main component; the cords are closely packed in the lamina densa and more loosely arranged in the lamina lucida interna and externa; (2) straight, hollow 7-10-nm-thick structures referred to as " basotubules "; and (3) 3.5-nm elements composed of minute paired rods, referred to as "double pegs." The distribution of the cords, but not that of the other two structures, was related to the immunostaining pattern. It is concluded that (1) to fully reveal the antigenicity of the glomerular basement membrane, frozen-thawed sections must be treated with sodium borohydride prior to immunostaining, possibly because this basement membrane is more compact than the others; and (2) in both glomerular and tubular basement membranes, type IV collagen, laminin, entactin , heparan sulfate proteoglycan and fibronectin are colocalized in the lamina densa and its extensions to the laminae lucidae . Since the distribution of the cords corresponds to that of immunostaining, it is likely that the five substances are present within the cords.

Animals↗

An alpha globin pseudogene is located within the mouse t complex.

Restriction fragment length polymorphisms have been identified in the alpha-globin pseudogene carried on chromosome 17. Different inbred strains of mice carry one of two forms of the sequence, whereas all complete t haplotypes carry a third form. With the use of partial t haplotypes, the alpha-psi 4 sequence has been mapped to the distal end of the t complex. This sequence appears to be closely linked to the tufted locus in the t complex.

Animals↗

Studies of the temporal relationship between the cytogenetic and biochemical manifestations of X-chromosome inactivation during the differentiation of LT-1 teratocarcinoma stem cells.

Previous biochemical studies have suggested that both X chromosomes produce gene products when cells of the LT-1 teratocarcinoma stem cell line are maintained in the undifferentiated state, and that dosage compensation, the biochemical manifestation of X inactivation, occurs when the cells are induced to differentiate in vitro (Martin et al., 1978). In this study the differentiation of LT-1 cells in vitro is described in detail, and data from cytogenetic studies of the time of X-chromosome replication in LT-1 cells are presented. They show that as long as the cells are maintained in the undifferentiated state both X chromosomes in each cell show the isocyclic replication pattern typical of a genetically active chromosome. However, when the LT-1 cells are induced to differentiate under appropriate conditions, one of the two X chromosomes in each cell of a large proportion of the population displays the allocyclic (either early or late) replication pattern typical of an inactive X chromosome. These data thus confirm that undifferentiated LT-1 cells contain two active X chromosomes and that X inactivation occurs in differentiating cultures of LT-1 cells. It is further demonstrated that there is a close temporal correlation between the biochemical and cytogenetic manifestations of the X-inactivation process. In addition, we observed that although X inactivation does not occur in the absence of morphological differentiation, it does not always occur when the cells differentiate in vitro.

Animals↗

The visual fields of the tawny owl, Strix aluco L.

The uniocular retinal field of Strix aluco is highly asymmetrical. The maximum width of 124 degrees is less than that recorded in any other vertebrate. Maximum retinal binocular field width equals 48 degrees and the optic axes diverge by 55 degrees. Maximum binocularity occurs above the bill whose tip lies outside of the visual field. The cyclopean retinal field has a maximum width of 201 degrees. Limited data on the visual fields of the pigeon are also presented. All of these data are compared with visual field widths in other species and the significance of the owl eye's tubular shape, its nasad asymmetry, and the possible factors influencing binocular field width are discussed.

Animals↗

Optics of retinal oil droplets: a model of light collection and polarization detection in the avian retina.

A wave optical model was used to analyse the scattering properties of avian retinal oil droplets. Computations for the near field region showed that oil droplets perform significant light collection in cone photoreceptors and so enhance outer segment photon capture rates. Scattering by the oil droplet of the principal cone of a double cone pair, combined with accessory cone dichroic absorption under conditions of transverse illumination, may mediate avian polarization sensitivity.

Animals↗

Regulation of type I collagen fibril assembly by link protein and proteoglycans.

Link protein, a glycoprotein, that is present both in cartilaginous and non-cartilaginous tissues, has previously been shown to bind to collagen and to proteoglycan. Here, we have examined the effects of link protein and proteoglycans, both alone and in combination, on the assembly of type I collagen fibrils in vitro. Link protein alone had no effect on the kinetics of fibril formation or on the size of the fibrils. Link protein, however, modulated the effects of various proteoglycans including those from bone, cartilage, cornea and sclera. Link protein had the most significant effect on fibril assembly in the presence of the low molecular weight bone proteoglycan. Although the bone proteoglycan alone had no effect on fibril formation, the fibrils were wider in the presence of link protein and proteoglycan. Cartilage proteoglycan alone increased the extent of fibril formation and the resultant fibrils were wider in diameter with a complement of incompletely assembled fibrils. In the presence of both link protein and cartilage proteoglycan, the fibrils were fully formed with the characteristic banding pattern. Further, corneal and scleral proteoglycans alone decreased the extent of fibril formation and the width of the fibrils was either unaltered or slightly decreased in the presence of the link protein. Our results indicate that both link protein and tissue-specific proteoglycans may regulate the organization of collagen fibrils in tissues.

Animals↗

Enzymic development of the small intestine: are glucocorticoids necessary?

The aim of this study was to determine the extent to which the postnatal maturation of intestinal hydrolases in the rat is dependent on the developmental rise of circulating corticosterone that occurs at the end of the 2nd wk of life. Pups were adrenalectomized (adX) on day 9 (i.e., before the developmental surge of corticosterone begins) and were killed on days 17, 20, 23, and 26. Serum corticosterone was measured to eliminate any incompletely adX animals. The rates of the developmental increases of sucrase and maltase activities and the developmental decreases of lactase and acid beta-galactosidase activities were depressed in adX pups aged 23 days and younger as compared with sham-operated controls. Administration of corticosterone (10 micrograms X g body wt-1 X day-1) to adX pups restored the developmental changes of these enzyme activities to rates equal to or greater than those in the sham-operated pups. By 26 days of age, all four enzyme activities of adX pups had reached their normal ontogenic plateau. We conclude that adrenal corticosteroids are potent determinants of the rate of developmental changes of intestinal hydrolases but that these hormones are not necessary for enzymes to eventually reach adult activities.

Adrenalectomy↗

Presence of alveolar macrophages as a criterion for determining the suitability of sputum specimens for bacterial culture.

The microscopic and bacteriological findings in paired saliva and sputum specimens from 66 patients with chronic bronchitis were compared in order to determine whether the presence of alveolar macrophages is a valid criterion for determining the suitability of a sputum specimen for bacterial culture. Alveolar macrophages were mainly present in sputum specimens, the culture results of which differed from the culture results of the matching saliva specimen (p less than 0.001). Sputum specimens containing alveolar macrophages appeared to be contaminated less with oropharyngeal flora than specimens which did not contain alveolar macrophages. Potential pathogens such as Streptococcus pneumoniae and Haemophilus influenzae were isolated only from sputum specimens containing alveolar macrophages. It is concluded that the presence of alveolar macrophages indicates that sputum originates from the lower respiratory tract. The results also showed that the presence of leukocytes in sputum may be considered significant if alveolar macrophages are also present.

Bacteria↗

Amikacin assay: correlation between rapid bioassay, enzyme immuno-assay (EMIT) and fluoro-immuno-assay (FIA).

Three methods (rapid bioassay, enzyme immunoassay and fluoroimmunoassay) for the determination of amikacin level in serum are compared. The statistical analysis of the results show correlation coefficients equal to 0.967 (EMIT versus FIA), 0.970 (bioassay versus FIA) and 0.983 (bioassay versus EMIT). The three methods are acceptable for routine clinical use. The enzyme immunoassay adapted on a centrifugal analyzer appears to be a method of choice for laboratories with a large workload. However, the rapid bioassay described in this paper remains adequate for laboratories testing 5 to 10 sera per day.

Amikacin↗