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Biomedical subjects

J S Gordon

Publications and source records attributed to J S Gordon.

At least 37 records · Page 2Linked to original sources
PubMed1993

Regulation of collagen synthesis in human dermal fibroblasts in contracted collagen gels by ascorbic acid, growth factors, and inhibitors of lipid peroxidation.

Ascorbic acid has been shown to stimulate collagen synthesis in monolayer cultures of human dermal fibroblasts. In the present studies, we examined whether the presence of a collagen matrix influences this response of dermal fibroblasts to ascorbic acid. Fibroblasts and collagen were mixed and allowed to gel and contract for 6 days to form a matrix prior to determining the concentration and time dependence for ascorbic acid to affect collagen synthesis by fibroblasts within the matrix. Collagen synthesis was stimulated at levels at or above 10 microM ascorbic acid and was maximal after 2 days of treatment. This concentration and time dependence is similar to that of cells grown in monolayer cultures. The effects of transforming growth factor-beta (TGF-beta) and fibroblast growth factor (FGF) were also examined in this model. TGF-beta increased and FGF inhibited collagen synthesis in the gels, as has been shown for cells in monolayer cultures. The effects of potential inhibitors of lipid peroxidation induced by ascorbic acid were also examined in these matrices and compared to previous results obtained in monolayer cultures. Propyl gallate, cobalt chloride, alpha,alpha-dipyridyl, and alpha-tocopherol inhibited the ascorbic acid-mediated stimulation of collagen synthesis while mannitol had no effect. Natural retinoids inhibited total protein synthesis without the specific effect on collagen synthesis that was seen in monolayer cultures. These results indicate that ascorbic acid stimulates collagen synthesis in fibroblasts grown in a collagen matrix in a manner similar to that found in monolayer cultures. In contracting collagen gels, however, the magnitude of the effect is less and retinoids do not specifically inhibit collagen synthesis.

2,2'-Dipyridyl↗
PubMed1993

Regulation of collagen synthesis in human dermal fibroblasts by the sodium and magnesium salts of ascorbyl-2-phosphate.

Ascorbic acid has been shown to stimulate collagen synthesis in dermal fibroblasts by increasing the rate of transcription of collagen genes. Experiments involving the use of ascorbic acid require daily supplementation due to the instability of the molecule in aqueous solutions. In order to provide a more stable alternative to ascorbic acid, two salts of ascorbyl-2-phosphate, having a greater chemical stability than ascorbic acid, were tested for their ability to stimulate collagen synthesis in monolayer fibroblast cultures. The concentration and time dependence of their activities were compared with ascorbic acid. The magnesium salt of ascorbyl-2-phosphate was found to be equivalent to ascorbic acid in stimulating collagen synthesis in these assays, while the sodium salt required at least a tenfold greater concentration to produce the same effect as ascorbic acid. Solutions of either ascorbic acid or the ascorbyl-2-phosphate analogs (at 10 mM) in phosphate-buffered saline (PBS) were relatively stable as shown by their decay rates and their ability to stimulate collagen synthesis even after nine days in solution prior to testing their effects on cultured cells. Ascorbic acid was unstable at neutral pH compared to solutions of either sodium or magnesium ascorbyl-2-phosphate. These data support the use of magnesium ascorbyl-2-phosphate in experiments where stability of ascorbic acid is a concern, e.g. in long-term cultures or in in vivo studies.

Ascorbic Acid↗
PubMed1991

Modulation of collagen synthesis by growth factors: the role of ascorbate-stimulated lipid peroxidation.

Ascorbic acid has been shown to stimulate collagen synthesis through induction of lipid peroxidation leading to increased transcription of the collagen genes. The mechanism by which lipid peroxidation stimulates collagen transcription is unknown; however, an alteration of cell membranes may affect the activity of serum growth factors leading to a change in gene expression. To test this hypothesis, we treated dermal fibroblasts with transforming growth factor-beta (TGF-beta), epidermal growth factor (EGF), interleukin-1 (IL-1), platelet-derived growth factor (PDGF), or fibroblast growth factor (FGF) in the presence of lipid peroxidation stimulating (200 microM) and nonstimulating (1 microM) concentrations of ascorbic acid. EGF and IL-1 had no effect on collagen synthesis at either concentration of ascorbic acid. FGF affected collagen synthesis only in the presence of 200 microM ascorbic acid, producing both a stimulation (0.4-2 ng/ml) and an inhibition (greater than 50 ng/ml). PDGF and TGF-beta stimulated collagen synthesis in the presence of both concentrations of ascorbic acid, with TGF-beta producing an 11-fold increase in collagen synthesis in the presence of ascorbate. This synergism produced by the combination of ascorbic acid and TGF-beta was inhibitable by the lipid peroxidation inhibitor, propyl gallate. These results indicate that regulation of collagen synthesis by ascorbic acid does not occur through altering the response to EGF or Il-1. Ascorbate has no effect on PDGF but the effects of TGF-beta and FGF on collagen synthesis appear to be sensitive to lipid peroxidation.

Ascorbic Acid↗
PubMed1991

Regulation of collagen synthesis by ascorbic acid: characterization of the role of ascorbate-stimulated lipid peroxidation.

Recently, we have described the ability of traditional lipid peroxidation inhibitors to inhibit ascorbate-stimulated collagen synthesis. In order to characterize further this effect, we have tested the ability of known and potential inhibitors of lipid peroxidation for their effects on ascorbate-stimulated collagen synthesis and lipid peroxidation. In our experiments, mannitol, a water soluble antioxidant, had no effect on ascorbate-induced collagen synthesis nor on lipid peroxidation. However, alpha-tocopherol, which is a lipophilic antioxidant, inhibited both effects of ascorbate. Superoxide dismutase, catalase, and their polyethylene glycol conjugate forms did not inhibit the ascorbate-stimulated collagen synthesis or lipid peroxidation. In addition, no effect was seen with the oxygen radical scavengers isopropanol, ethanol, or dimethyl sulfoxide. Two iron chelators, o-phenanthroline and alpha,alpha-dipyridyl, both inhibited ascorbate-induced lipid peroxidation and collagen synthesis, consistent with the previously described iron-dependence of lipid peroxidation by ascorbate. These results support a correlation between collagen synthesis and lipid peroxidation and provide a theory for the mechanism of ascorbic acid regulation of collagen synthesis.

Antioxidants↗
PubMed1991

Knowing that you know: an essay on mechanistic metaknowledge.

Humans are adept at providing accurate statements of confidence in their perceptual identification and recall memory responses. In spite of this, mechanical pattern-recognition systems and other artificial intelligence devices seldom express response certainty. The purpose of this paper is to show how useful confidence ratings can be in integrating the results of a variety of pattern-recognition systems to produce a single, optimal decision concerning the target to be recognized. We outline several ways neural network pattern-recognition systems could be modified to issue confidence ratings with each classification response. In sketching a mechanical system of confidence ratings we find we have also provided a preliminary framework for understanding human confidence judgments and human metacognition.

Artificial Intelligence↗
PubMed1990

Retinoids affect collagen synthesis through inhibition of ascorbate-induced lipid peroxidation in cultured human dermal fibroblasts.

Ascorbate has been shown to stimulate collagen synthesis in cultured human dermal fibroblasts by increasing transcription of the collagen genes. In the present studies, ascorbate stimulates lipid peroxidation at concentrations similar to those necessary to affect collagen synthesis. Molecules which inhibit lipid peroxidation, such as propyl gallate, cobalt chloride, and alpha-naphthol, also inhibit collagen synthesis, suggesting a correlation between the two phenomena. Retinoic acid and some synthetic retinoids have previously been shown to inhibit collagen synthesis in cultured human dermal fibroblasts. In our studies two different retinoids, at similar concentrations, inhibit both ascorbate-stimulated lipid peroxidation and collagen synthesis. Since high concentrations of retinoids were required, the ability of retinoids to inhibit the oxidant effect of ascorbate, and not their receptor-mediated activity, may be responsible for their effect on collagen synthesis.

Antioxidants↗
PubMed1990

Holistic medicine and mental health practice: toward a new synthesis.

Holistic medicine offers insights and techniques which can significantly enlarge and enrich mental health practice. This approach, which recognizes the uniqueness of each patient, the centrality of the therapeutic partnership, and the primacy of self-care, regards the spiritual dimension as a vital enlargement of the biopsychosocial model. After outlining the holistic approach and its congruence with psychological thinking, this paper explores the ways in which holism may shape the future of mental health practice.

Holistic Health↗
PubMed1990

Effects of aging and xerosis on the amino acid composition of human skin.

Amino acid compositions of skin samples from young and old subjects and from age-matched donors with dry skin syndrome (xerosis) were examined. The amino acid contents of the free amino acid (FAA) fraction, soluble hydrolysate (SH) fraction, and whole cell hydrolysate (WCH) were determined. The greatest differences were observed between the FAA compositions of the young and old normal subjects. Xerosis did not appear to affect the amino acid compositions of samples from young subjects as much as old subjects. Overall, the effect of aging on the amino acid contents was more pronounced than the effect of xerosis. The amino acid composition of the FAA showed a high degree of similarity to filaggrin, whereas the WCH showed a similarity to keratin.

Aging↗
PubMed1985

Changes in the H-1 histone complement during myogenesis. I. Establishment by differential coupling of H-1 species synthesis to DNA replication.

Proportions of the four major chicken H-1 histones (referred to as H-1's a-d) change during in vitro skeletal myogenesis. As myoblasts fuse and differentiate into myotubes, the relative amount of H-1c increases dramatically. The change occurs primarily because synthesis of the H-1 species is coupled to DNA synthesis to different extents. H-1c synthesis is least tightly coupled to DNA replication in precursor myoblasts and in differentiated myotubes. Thus H-1c synthesis predominates after dividing myoblasts fuse into postmitotic myotubes. This results in the replacement of pre-existing H-1 and therefore increases the relative amount of H-1c. Differences in the stability of the H-1's are also involved in changing H-1 proportions. The results show that changes in H-1 proportions during myogenesis are a consequence of withdrawal from the cell cycle. The data provides a general mechanistic explanation of how tissue-specific H-1 proportions are established.

Animals↗
PubMed1985

Changes in the H-1 histone complement during myogenesis. II. Regulation by differential coupling of H-1 variant mRNA accumulation to DNA replication.

We have shown that changes in proportions of the four chicken H-1's during in vitro myogenesis are primarily the result of differential coupling of their synthesis to DNA replication (see the previous paper). We show here that the four major chicken H-1's are encoded by distinct mRNAs which specify primary amino acid sequence variants. Accumulation of the H-1-variant mRNAs is coupled to DNA replication to different extents. The level of mRNA encoding H-1c (the H-1 variant that increases relative to the other H-1's in nondividing muscle cells) is completely uncoupled. In contrast, the level of mRNAs encoding H-1's a, b, and d (which have levels that decrease in nondividing muscle cells) are more tightly coupled. Polyadenylation is not involved in uncoupling H-1c mRNA accumulation from DNA replication.

Amino Acid Sequence↗
PubMed1982

Holistic medicine: advances and shortcomings.

Holistic medicine is an attitudinal approach to health care rather than a particular set of techniques. It addresses the psychological, familial, societal, ethical and spiritual as well as biological dimensions of health and illness. The holistic approach emphasizes the uniqueness of each patient, the mutuality of the doctor-patient relationship, each person's responsibility for his or her own health care and society's responsibility for the promotion of health. As holism has become an increasingly popular concept, it has been distorted by both proponents and critics. Tendencies to equate holism with particular therapeutic modalities, to neglect public health for a one-sided emphasis on individual responsibility and to reject rather than elaborate on the scientific method have hampered the movement's progress. In the future orthodox and alternative approaches and techniques must all be seen as complementary parts of a larger synthesis that will genuinely deserve the name of holism.

Holistic Health↗
PubMed1981

Heterogeneous binding of high mobility group chromosomal proteins to nuclei.

A dramatic difference is observed in the intracellular distribution of the high mobility group (HMG) proteins when chicken embryo fibroblasts are fractionated into nucleus and cytoplasm by either mass enucleation of cytochalasin-B-treated cells or by differential centrifugation of mechanically disrupted cells. Nuclei (karyoplasts) obtained by cytochalasin B treatment of cells contain more than 90 percent of the HMG 1, while enucleated cytoplasts contain the remainder. A similar distribution between karyoplasts and cytoplasts is observed for the H1 histones and the nucleosomal core histones as anticipated. The presence of these proteins, in low amounts, in the cytoplast preparation can be accounted for by the small percentage of unenucleated cells present. In contrast, the nuclei isolated from mechanically disrupted cells contain only 30-40 percent of the total HMGs 1 and 2, the remainder being recovered in the cytosol fraction. No histone is observed in the cytosol fraction. Unike the higher molecular weight HMGs, most of the HMGs 14 and 17 sediment with the nuclei after cell lysis by mechanical disruption. The distribution of HMGs is unaffected by incubating cells with cytochalasin B and mechanically fractionating rather than enucleating them. Therefore, the dramatic difference in HMG 1 distribution observed using the two fractionation techniques cannot be explained by a cytochalasin-B-induced redistribution. On reextraction and sedimentation of isolated nuclei obtained by mechanical cell disruption, only 8 percent of the HMG 1 is released to the supernate. Thus, the majority of the HMG 1 originally isolated with these nuclei, representing 35 percent of the total HMG 1, is stably bound, as is all the HMGs 14 and 17. The remaining 65 percent of the HMGs 1 and 2 is unstably bound and leaks to the cytosol fraction under the conditions of mechanical disruption. It is suggested that the unstably bound HMGs form a protein pool capable of equilibrating between cytoplasm and stably bound HMGs.

Animals↗
PubMed1981

Holistic medicine: toward a new medical model.

The holistic approach to medicine and health care emphasizes the integrity of each person's physical, mental, and spiritual being, the psychosocial context of health and illness, the importance of health promotion, a respectful partnership between physician and patient, and the actual or potential utility of techniques derived from a variety of healing traditions. It represents a recent attempt to enlarge and humanize the perspective and practice of modern biomedicine. After a discussion of the historical forces which have shaped the development of holistic medicine, this paper describes the salient characteristics of its paradigm, some of the evidence on which it is based, and some of its implications for medical practice.

Attitude of Health Personnel↗
PubMed1980

Evidence for a quantitative tissue-specific distribution of high mobility group chromosomal proteins.

The quantitative tissue specificity of the high mobility group (HMG) chromosomal proteins was investigated. Perchloric acid (PCA) extracts of four different chicken tissues and erythrocytes contained three proteins which comigrated on NaDodSO4-polyacrylamide gels with the HMG's 1,2, and E from erythrocyte nuclei. These three HMG's from embryonic skeletal muscle and erythrocytes also comigrated on two-dimensional gels, employing an acid-urea system in the first dimension and an NaDodSO4 system in the second. Interpretation of the two-dimensional gels suggested that the two low molecular weight proteins of this triplet arose from the HMG 2 band of the acid-urea gels. These have been designated HMG 2A and HMG 2B. Three proteins of similar molecular weights were also found in the PCA extracts of calf thymus. They were arranged in a similar but not identical pattern on two-dimensional gels. Thus, these three HMG's appear to be neither tissue nor species specific. In addition, the 2.0% PCA extracts of all chicken tissues examined contain a 38 000-dalton (38K) nuclear protein which coisolates with the HMG's. These four proteins are found in different relative amounts in each of the four chicken tissues and erythrocytes. They are found in the same relative amounts, however, in embryonic skeletal muscles from different chicken strains with widely different highly repetitive sequence content, suggesting that none of these individual proteins is selectively localized to constitutive heterochromatin. The quantitative tissue specificity of the HMG's and the 38K protein, however, suggests that they may participate in regulating cell-specific gene expression.

Animals↗