PubMed Health⌕ Search

Biomedical subjects

R A Harper

Publications and source records attributed to R A Harper.

At least 19 recordsLinked to original sources
PubMed1989

Keloid fibroblasts in culture: abnormal growth behaviour and altered response to the epidermal growth factor.

Keloid fibroblasts were propagated in culture and their proliferative behaviour and response to the Epidermal Growth Factor (EGF) were studied. Keloid fibroblasts grew at a rate which was approximately one-half that of normal age, sex and race matched control fibroblasts. Keloid fibroblasts were stimulated to grow in the presence of EGF (10 ng/ml), but to a lesser degree than the normal control fibroblasts. Scatchard analysis of the binding data obtained using 125I-labeled EGF revealed no difference in binding affinity or receptor numbers between keloid and normal fibroblasts.

Adult↗
PubMed1989

Glare and contrast sensitivity in contact lens corrected aphakia, epikeratophakia and pseudophakia.

The effects of glare on contrast sensitivity and high contrast Snellen acuity were investigated in a group of unilaterally aphakic patients with normal fellow eyes. In spite of relatively good visual acuity and apparently satisfactory surgical results, there was a marked reduction in contrast sensitivity in epikeratophakia and contact lens corrected aphakic eyes, relative to fellow normal eyes, especially in the presence of glare (P less than 0.05). Although the results from the pseudophakic patients were more variable, there is some evidence to suggest that epikeratophakia provides inferior visual function to contact lens correction or intraocular lens implantation. The results also suggest that the measurement of visual acuity in the presence of glare fails to identify many patients with a functional visual impairment secondary to glare.

Adolescent↗
PubMed1988

Specificity in the synergism between retinoic acid and EGF on the growth of adult human skin fibroblasts.

Vitamin A (retinol) and five retinoids were tested for their ability to enhance epidermal growth factor (EGF) stimulation of adult human skin fibroblast growth in vitro. The retinoids utilized in this study were RO-1-5488 (all-trans-retinoic acid), RO-4-3780 (13-cis-retinoic acid), RO-10-9359, RO-10-1670, and RO-21-6583. Retinol and each retinoid were capable of stimulating fibroblast growth alone (0-86%), while 13-cis and all-trans-retinoic acid were the most potent in potentiating the EGF promotion of fibroblast growth. Other growth factors tested in addition to EGF were nerve growth factor (NGF), fibroblast growth factor (FGF), and thrombin. While EGF and FGF stimulated fibroblast growth to the same degree (2.3-fold), only growth stimulated by EGF was potentiated by retinoic acid. Since retinoic acid might enhance the EGF stimulation of cell growth by increasing either EGF receptor number or binding affinity, the binding of 125I-labeled EGF was carried out in the presence of retinoic acid and the data were subjected to a Scatchard-type analysis. No change in EGF receptor number or affinity was seen in the presence of retinoic acid. The data indicate a specific interaction between retinoid acid and EGF which results in the potentiation of the EGF-stimulated cell growth. Furthermore, the mechanism of this interaction does not seem to involve the initial binding of EGF to its plasma membrane receptor or the available number of EGF receptors located on the cell surface.

Adult↗
PubMed1988

Colour discrimination in pseudophakia.

A study was undertaken to examine the colour discrimination of fifty pseudophakic patients and to compare results with fifty age matched normal observers. Using the Farnsworth-Munsell 100-Hue test and Desaturated panel D15, performance does not differ significantly from the age matched normals, although a theoretically superior colour discriminative ability might be expected in pseudophakia. A slight trend for increasing error scores with advancing age in pseudophakia lends some support to the importance of neural factors in the ageing of colour discrimination. Several other factors influencing colour vision in pseudophakia are discussed.

Aged↗
PubMed1988

Characterization of a renal tubular epithelial cell line which secretes the autologous target antigen of autoimmune experimental interstitial nephritis.

Proximal tubular epithelial cells from mice which develop autoimmune interstitial nephritis were found to express the nephritogenic target antigen, 3M-1. Anti-3M-1 mAbs (alpha 3M-1-Ab) were used to positively select for 3M-1-secreting tubular epithelium and, after stabilization in culture, this new cell line (MCT) was examined for the production of several moieties important to either immune interactions or to the development of extracellular matrix. Alkaline phosphatase-staining MCT cells also express epithelial growth factor receptors with a Kd of 0.87 nM and an epithelial growth factor receptor constant (Ro) of 2.1 X 10(4) receptors/cell. MCT culture supernatants contain greater amounts of laminin, and types IV and V procollagens compared to types I and III procollagens, and growing MCT cells on type I collagen matrix causes them to preferentially secrete even more type IV and V procollagen. The 30,000-Mr 3M-1 antigen could be immunoprecipitated from biosynthetically labeled MCT cell supernatants with alpha 3M-1-Ab. An identical-sized moiety was isolated by immunoaffinity chromatography from collagenase-solubilized mouse kidney tubular basement membranes. The 3M-1 antigen can be found on the MCT cell surface by radioimmunoassay, or deposited in a linear array in the extracellular matrix surrounding the MCT cells in culture by immunofluorescence. Mature messenger RNA species for both class I and class II major histocompatibility complex (MHC) molecules were detected by Northern hybridization, and their corresponding cell surface gene products were detected by cytofluorography of MCT cells stained with haplotype-specific antibodies. Both the cell surface 3M-1 and the small amounts of detected class II MHC molecules appear to be biologically functional, as MCT cells can support the proliferation of 3M-1-specific, class II MHC-restricted helper T cells in culture. These findings suggest that MCT cells provide all the necessary biological parameters for interfacing both as the target of a nephritogenic immune response, and as a potential source for new extracellular matrix which develops as a fibrogenic response to interstitial nephritis.

Animals↗
PubMed1985

125I-EGF binding to responsive and nonresponsive cells in culture: loss of cell-associated radioactivity relates to growth induction.

A comparison of the binding and overall processing of epidermal growth factor (EGF) was made in ten mammalian fibroblast-like and three epithelial-like cell lines. EGF stimulated the growth of five fibroblastic cell lines (132 to 224%) after 10 days in the constant presence of EGF and were termed "responsive". Eight of the lines did not respond or were growth inhibited by EGF (-64 to + 21%) and were listed as "nonresponsive". Both "responsive" and "nonresponsive" cell lines possessed specific saturable membrane receptors for EGF, but no consistent differences were found between the number of apparent receptors per cell or the concentrations of 125I-EGF required for half maximal binding. However, a consistent difference between the "responsive" and "nonresponsive" cell lines was observed when the amount of cell associated 125I-labeled EGF was measured as a function of incubation time at 37 degrees C in the constant presence of the hormone. In every cell line we classified as responsive, the binding of 125I-EGF reached a maximum after 30 minutes incubation at 37 degrees C and the cell associated radiolabel subsequently decreased by 42-68% within 4 hours. In contrast, the "nonresponsive" cell lines required 1-2 h to reach maximal binding and showed a minimal decrease of 1-10% during the 4-h period. These data indicate that a variety of different cell lines can possess receptors with similar binding properties but process EGF in a dissimilar manner. This difference in processing may reflect the specific events which are necessary for the induction of cell growth.

Animals↗
PubMed1985

Blockade of the pressor response to angiotensins I and II in the bullfrog, Rana catesbeiana.

We examined the effects of three angiotensin II (AII) analogs, [Sar1,Ala8] AII, [Sar1,Ile8] AII, and [Sar1,Thr8] AII, phenoxybenzamine and captopril on the pressor response to angiotensins I (AI) and II (AII) and norepinephrine (NE) in the bullfrog, Rana catesbeiana. Injection of AI and AII at 0.25, 0.5, and 1.0 micrograms/kg, or NE at 3 micrograms/kg elicited dose-dependent rises in blood pressure. [Sar1,Ile8] AII (10 micrograms/kg/min) significantly blocked the pressor effects of all AI and AII doses. [Sar1,Ala8] AII blocked only the highest dose, and [Sar1,Thr8] AII produced no blockade. Captopril (0.1 mg/kg bolus + 0.5 mg/kg/hr) significantly reduced the response to AI, but not AII or NE. Phenoxybenzamine (5-10 mg bolus + 1 mg/kg/hr) blocked NE, and partially inhibited (36-49%) the pressor effects of AI and AII. These results demonstrate that (1) [Sar1,Ile8] AII is a potent angiotensin antagonist in the bullfrog, while [Sar1,Ala8] AII is partially effective and [Sar1,Thr8] AII is largely ineffectual; (2) captopril is an effective converting enzyme inhibitor; and (3) a portion of the angiotensin response can be inhibited by alpha-receptor blockade and is apparently due to catecholamine release.

Angiotensin I↗
PubMed1983

Monoclonal antibody to human epidermal growth factor.

A monoclonal antibody directed to a species-specific determinant of human epidermal growth factor (h-EGF) was obtained by fusing murine myeloma cells with BALB/c mouse splenocytes sensitized to h-EGF. This antibody, referred to as 863.D4, did not react with either rat or mouse epidermal growth factor or with 11 other polypeptide hormones tested as shown by solid-phase radioimmunoassay (SPRIA), and immunoprecipitation followed by sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE). Scatchard analysis of the antibody binding to purified h-EGF revealed an apparent equilibrium dissociation constant of 1 X 10(-8) M. The antibody blocked both the binding of h-EGF and h-EGF stimulation of 3H-thymidine incorporation into DNA by greater than 90% in confluent cultures of human foreskin fibroblasts.

Animals↗
PubMed1982

Fluid flow in bone in vitro.

Recent dielectric measurements suggest that the electromechanical effect in wet (fluid saturated) bone is not due to a piezoelectric effect. This would imply that the electromechanical effect observed in wet bone is due to a streaming potential and is therefore dependent on fluid flow in stressed bone. A model for fluid flow in bone in vitro is presented. This model predicts a rapid decay (of the order of a millisecond or less) for the fluid flow in Haversian systems. The implications of this result for the interpretation of the electromechanical effect in wet bone are discussed.

Biomechanical Phenomena↗
PubMed1981

Relative resistance to methotrexate by proliferating normal rabbit epidermal cells in vitro.

Primary cell cultures of normal rabbit epidermal cells (keratinocytes) were established without the use of enzymatic techniques. Six experiments were carried out on cells from six different rabbits. When these cells were exposed to methotrexate (MTX) for 24 h at 1 micrograms/ml, proliferation, as measured by cells entering mitosis, was significantly inhibited (P less than 0.05) in only one experiment. When the dose of MTX was elevated to 100 micrograms/ml, only two experiments showed significant inhibition of mitosis. This minimal inhibition of mitosis by MTX was contrasted by the dramatic inhibitory effect of this antimetabolite on DNA synthesis. At 1 micrograms/ml MTX for 24 h, DNA synthesis, as measured by [3H]deoxyuridine uptake, was inhibited greater than 95%. We can conclude that under certain conditions, the rabbit keratinocyte may represent a normal cell type that is inherently resistant to the anti-proliferative effects of methotrexate.

Animals↗
PubMed1981

Micromechanical oscillators and techniques for determining the dynamic moduli of microsamples of human cortical bone at microstrains.

Two micromechanical oscillators are described along with methods and techniques which have been successfully used to determine the elastic, dynamic, shear and Young's moduli at microstrain levels, and which with proper design modifications might, under restricted experimental conditions, also be employed to determine viscous moduli. Although these systems can be used with any microsamples, they were designed originally for dynamic studies of the unit microstructural element of human cortical bone, the secondary osteon (Haversian system).

Biomechanical Phenomena↗
PubMed1981

Scanning electron microscopy studies of collagen, mineral and ground substance in human cortical bone.

This paper presents scanning electron microscopy (SEM) observations made on the collagen, mineral and ground substance components comprising human cortical bone, which to a very large extent have been made possible by a sample preparation technique which takes advantage of the fracture propagation behavior inherent to the mature, highly heterogeneous, lamellar cortical bone tissue. By varying the extent to which bone samples are decalcified, it is possible to study certain morphological aspects of all these three main components of bone. Collagen features observable at fairly low magnification (approximately 1000x) include collagen bundle orientations with respect to the long axis of bone or of the osteon samples and collagen bundle morphological interrelationships. Much higher magnifications (approximately 20,000x) reveal spherical structures attached to the collagen fibrils which comprise the fiber bundle. Ground substance, yet to be identified biochemically, was noted in so-called interlamellar regions of osteons and of periosteal and endosteal tissue as well as in resting lines, cement lines and hypercalcified rings. It was observed to contain sulfur and to be trypsin soluble, providing evidence for the presence of a noncollagenous protein and of chondroitin sulfate which may be biochemically related in a protein polysaccharide complex. Such conclusion does not, however, preclude the presence of other ground substance components in this observed material. Large concentrations of mineral were noted in the interlamellar region of osteons and of periosteal and endosteal bone. This mineral does not seem to be directly associated with collagen. This study involves the use of scanning electron microscopy in both the secondary and back-scattered electron detection modes and energy dispersive x-ray microanalysis (XMA).

Bone Matrix↗
PubMed1980

Ion migration energies and color center absorption in hydroxyapatite.

By modelling a hydroxyapatite crystal lattice as a finite cluster of atoms surrounded by an array of point ions, molecular orbital MS-Xalpha calculations point to differences in fluoride and hydroxyl migration energies. Despite the fluoride ion being more tightly bound to the lattice, it is in fact more mobile. Color center optical absorption is predicted to be in the infrared region of the spectrum for hydroxyapatite, whereas for fluorapatite the absorption peak of a vacancy is predicted to within 2% of the observed peak in the optical region. This result is discussed in terms of experimental studies of bonding between the calcified and organic phases of bone.

Absorption↗
PubMed1980

Vitamin A potentiates the mitogenic effect of epidermal growth factor in cultures of normal adult human skin fibroblasts.

The polypeptide hormone, epidermal growth factor (EGF) and Vitamin A (retinoic acid) were added to log phase cultures of adult human skin fibroblasts and the effect on cell growth observed. At the end of seven days EGF alone stimulated cell growth 68%, while trans-retinoic acid alone had no significant effect. However, when EGF was added in combination with trans-retinoic acid, cell growth was increased 159 to 214%. Cis-retinoic acid gave similar results. These results indicate that, under certain conditions, a presumed inhibitor of fibroblast growth (retinoic acid) can potentiate the mitogenic action of a hormone, namely, epidermal growth factor.

Adult↗