Search PubMed⌕ Search

Biomedical subjects

J A Hamilton

Publications and source records attributed to J A Hamilton.

At least 307 records · Page 17Linked to original sources
PubMed1983

D-amphetamine in obsessive-compulsive disorder.

In a double-blind crossover study, single doses of d-amphetamine and placebo were administered to 12 patients with severe chronic obsessive-compulsive disorder (OCD). Improvement of obsessional symptoms was significant on clinical ratings and was correlated with improved performance on an attention task. Changes were also significant for self-rated measures of activation and altered reality. The behavior response to amphetamine was not statistically correlated with subsequent improvement during a 6-week clomipramine trial, although the direction of change was the same during both treatments for every patient studied.

Adolescent↗
PubMed1983

Suppression of the neutral protease activity of macrophages treated with asbestos in vitro.

Macrophages are often conspicuous in asbestos-induced inflammatory lesions. Chrysotile type B elicits macrophages into the peritoneal cavity of mice which produce high levels of the neutral protease, plasminogen activator; in vitro addition of these same fibers to mouse peritoneal macrophages stimulates enzyme production. It is reported here that, for endotoxin-elicited mouse peritoneal macrophages fed chrysotile type B in vitro, the increased plasminogen activator activity is suppressed by low concentrations of anti-inflammatory steroids. Other active drugs include colchicine and vinblastine. These studies are considered important, as they suggest an approach to controlling the levels of a potentially deleterious enzyme system (PA-plasmin) from macrophages treated with asbestos fibers.

Animals↗
PubMed1983

Asbestos fibers, plasma and inflammation.

Fibrin clots have been detected at sites of inflammation, and kinins have been implicated as mediators of the vascular phenomena of acute inflammation, systemic shock, and disseminated intravascular coagulation. It is now reported that both negatively and positively charged asbestos fibers shorten the partial thromboplastin time of human plasma, indicating coagulation of the plasma. A sample containing short (less than 5 micron in length) chrysotile fibers is ineffective. Only the negatively charged amphiboles (crocidolite and amosite) are able to activate factor XII (Hageman factor). This particular effect of the amphiboles is enhanced by high molecular weight kininogen and leads to kinin formation.

Asbestos↗
PubMed1983

Synovial cell activation. Studies on the mechanism of action of synovial activator activity.

Synovial activator (SA) from peripheral blood mononuclear cells stimulates the plasminogen activator (PA) levels of human synovial fibroblasts. Using the sensitive technique of transcriptional inhibition followed by a prolonged translation period, data suggested that the first synthesis of mRNA needed for the increase in PA activity began within 40-60 min; this increase in protease activity was reversible on removal of SA from the cultures and also declined after about 3 days even if SA was not withdrawn. The RNA dependent events necessary for the synovial cell activation were to a large extent completed by about 4-8 h while those dependent on protein synthesis lasted for about 12 h. The effectiveness of suboptimal concentrations of SA could be potentiated by all-trans retinoic acid. A similar potentiation was effected by phosphodiesterase inhibitors, 3-isobutyl-1-methylxanthine and theophylline, by 8-bromo-cAMP, and by prostaglandins of the E and F series; these last observations suggest cyclic nucleotide involvement in the SA-mediated elevation of synovial fibroblast PA activity.

Cycloheximide↗
PubMed1983

Hypothesis: in vitro evidence for the invasive and tumor-like properties of the rheumatoid pannus.

It is often considered that the inflammatory processes in the rheumatoid synovium are due to an immune response to an as yet unknown antigen; the resultant pannus has been referred to as "aggressive, invasive, proliferative and tumor-like." Data are presented which show that arthritogenic group A streptococcal cell walls stimulate human monocyte-macrophages to elevate the plasminogen activator (PA) activity of human synoviocytes. By analogy with other cellular systems, it is suggested that the monocyte-macrophage mediated elevation of synoviocyte PA activity can contribute to the tissue remodelling and cell migration found in the rheumatoid pannus. It is also proposed that the active moiety from the stimulated monocyte-macrophages is able to mimic, to some extent, the effects of transforming viruses and tumor promoters on cell function. This concept of a "tumor-like" synoviocyte transformation is suggested as being consistent with the descriptions of the rheumatoid pannus as "aggressive, invasive and tumor-like." Perhaps similar cellular interactions occur in other inflammatory diseases involving connective tissue turnover and cellular hyperplasia.

Animals↗
PubMed1982

Temperature-dependent molecular motions of cholesterol esters: a carbon-13 nuclear magnetic resonance study.

Carbon-13 NMR spectroscopy at 50.3 MHz has been used to study four long-chain cholesterol esters with a double bond in the omega-9 position: cholesteryl oleate, C18:1, omega-9; cholesteryl linoleate, C18:2, omega-6,9; cholesteryl erucate, C22:1, omega-9; cholesteryl nervonate, C24:1, omega-9. The linoleate and oleate esters exhibit two metastable liquid-crystalline phases (cholesteric and smectic), whereas the longer chain esters form a stable smectic phase but no cholesteric phase [Ginsburg, G. S., & Small, D. M. (1981) Biochim. Biophys. Acta 664, 98-107]. Line widths (nu 1/2), spin--lattice relaxation times (T1), and nuclear Overhauser enhancements (NOE) were measured for all well-resolved resonances from ring and fatty acyl (FA) carbons at different temperatures in the isotropic liquid of each ester. T1 and NOE values of FA resonances were constant between the FA-2 carbon and olefinic region of each acyl chain and increased markedly for carbons near the chain terminus. FA carbon motions are thus restricted and/or highly correlated in the region between the ring and the olefinic carbons, suggesting that strong interactions occur between cholesterol ester molecules in this region of the FA chain. These results also suggest that the FA chains are approximately extended in the isotropic liquid. Steroid ring methine C-6 and C-3 nu 1/2's increased differentially on cooling to the liquid leads to liquid crystal transition temperature (Tm) of each ester, indicative of increasingly anisotropic ring rotations. The rotational anisotropy was quantitated by using a prolate ellipsoid model for the cholesterol ester molecule for which two correlation times (corresponding to rotations about the long and short molecular axes) were calculated from the C-3 and C-6 nu 1/2 values. The C-3/C-6 nu 1/2 ratio was directly proportional to the anisotropy of the ring motions as measured by the ratio of the two correlation times. At any given temperature relative to Tm, the C-3 and C-6 nu 1/2's and the C-3/C-6 nu 1/2 ratios were larger for cholesterol esters which have a cholesteric phase than for esters which have no cholesteric phase, showing that steroid ring motions were more restricted and more anisotropic prior to the formation of a cholesteric phase. Cholesteryl erucate and cholesteryl nervonate have longer regions of FA chain interactions which result in greater chain cooperativity, apparently preventing the preordering of steroid rings to the degree necessary for formation of a cholesteric phase. Thus, these esters form the smectic phase directly from the isotropic liquid. These results are applied to the cholesterol ester transition in plasma low-density lipoproteins.

Carbon Isotopes↗
PubMed1982

Solubilization and localization of cholesteryl oleate in egg phosphatidylcholine vesicles. A carbon 13 NMR study.

Co-sonicated mixtures of egg phosphatidylcholine and small amounts (less than or equal to 4%, w/w) of [carbonyl-13C]cholesteryl oleate have been studied by 13C NMR spectroscopy at 50.3 MHz. The carbonyl chemical shift from cholesteryl oleate solubilized in vesicles was 1 ppm downfield from the carbonyl chemical shift of cholesteryl oleate present in a separate oil phase. The maximum solubility of the steroid in vesicles determined by chemical analysis of purified vesicles was 1.6 weight % (approximately 2 mol %), in close agreement with the maximum solubility estimated from NMR speak intensity measurements (1.4 weight %). The downfield shift indicates hydrogen bonding of solvent (H2O) molecules with the cholesteryl oleate carbonyl group, suggesting that vesicle-solubilized cholesteryl oleate molecules are located in the phospholipid bilayer with the carbonyl group close to the aqueous interface and the sterol ring and fatty acyl chain approximately parallel to the fatty acyl chains of the phospholipid. Such a folded conformation and localization of the carbonyl group at the aqueous interface may facilitate interactions of sterol esters with cholesterol ester transfer proteins and cholesterol esterases.

Cholesterol Esters↗
PubMed1982

Streptococcal cell walls and synovial cell activation. Stimulation of synovial fibroblast plasminogen activator activity by monocytes treated with group A streptococcal cell wall sonicates and muramyl dipeptide.

Group A streptococcal peptidoglycan has previously been shown to be arthritogenic in rats and has been implicated as a structure present in a class of possible etiologic agents for rheumatoid arthritis. The present study reports that conditioned medium from human monocytes, after interaction with cell wall sonicates of four group A streptococcal strains, stimulates the plasminogen activator (PA) activity of nonrheumatoid synovial fibroblasts. Low concentrations of N-acetylmuramyl-L-alanyl-D isoglutamine (muramyl dipeptide) can also generate this synovial activator (SA) activity from human monocytes. Preliminary biochemical data suggest that the SA activity is distinct from interferon-gamma, interleukin 1, and interleukin 2. These results indicate that agents that are arthritogenic in rats can modulate human synovial fibroblast functions via monocytes. The findings are proposed to have possible significance for an understanding of the cellular interactions involved in the formation and function of the rheumatoid pannus, because PA has been invoked as possibly being generally important for the processes of cell migration, tissue remodeling, and inflammation.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1982

Stimulation of the plasminogen activator activity of human synovial fibroblasts by retinoids.

Nonrheumatoid human synovial fibroblasts in culture, while having low basal plasminogen activator levels, were stimulated to produce much more of this protease activity by low concentrations of a series of retinoids. The most potent retinoid tested, all-trans retinoic acid, was active over the range 10(-11)-10(-6)M. The increased plasminogen activator activity in the presence of 10(-6)M retinoic acid was first observed within 40 minutes under appropriate experimental conditions, required RNA and protein synthesis, and was reversible after short incubation periods. This stimulation was suppressed by low concentrations of antiinflammatory glucocorticoids such as dexamethasone.

Dexamethasone↗
PubMed1982

Characteristics of bone marrow fibroblast colony-forming cells (CFU-F) and their progeny in patients with myeloproliferative disorders.

Chronic myeloproliferative disorders (MPD) are clonal diseases of the pluripotent hematopoietic stem cell frequently associated with myelofibrosis (MF). There is only indirect evidence indicating that the increased deposition of collagen in bone marrow matrix is a secondary phenomenon. A liquid culture system for cloning and growing bone marrow fibroblasts has permitted us to approach more directly the understanding of the pathogenesis of myelofibrosis by comparing the biophysical, growth, and functional characteristics of fibroblasts from normals, MPD patients without MF, and those with MF. In patients with MF, marrow fibroblast colony (CFU-F) formation could not be studied; fibroblasts were grown from marrow explants. CFU-E from normals and MPD patients exhibited similar cell density distribution and similar cell sedimentation rates. These similarities contrasted sharply with the differences seen when the erythroid and granulocyte-macrophage progenitors were studied by the same methods. There was a marked light density shift and a rapidly sedimenting shift of MPD hematopoietic colony-forming cells. Marrow fibroblasts from MPD patients with and without MF displayed the same in vitro growth characteristics as fibroblasts from normals. Both types of fibroblasts exhibited anchorage and serum dependence, and contact inhibition of growth. Marrow fibroblasts were also characterized for the presence and distribution of fibronectin and collagen types by immunofluorescent staining using monospecific antibodies. Extracellular matrix, membrane-, and cytoplasm-associated fibronectin, type I, type III, and type V collagen showed a similar staining pattern in both normal and myelofibrotic marrow fibroblasts. Plasminogen-dependent fibrinolytic activity elicited from normal and myelofibrotic marrow fibroblasts were equivalent. Chromosomal analysis of hematopoietic cells and marrow fibroblasts from Philadelphia chromosome positive chronic myelocytic leukemia patients with and without MF showed that the Philadelphia chromosome was present only in hematopoietic cells. The results of these studies taken together demonstrate that bone marrow collagen-producing cells from MPD patients with and without MF behave in vitro as do those from normals. These findings support the hypothesis that that the marrow fibrosis observed in patients with MPD results from a reactive process rather than from a primary disorder affecting the marrow collagen-producing cells.

Adult↗
PubMed1982

Physical studies of d less than 1.006 g/ml lymph lipoproteins from rats fed palmitate-rich diets.

At body temperature the stable form of triglycerides rich in saturated fatty acids is crystalline. We examined the physical state of triglyceride-rich lymph lipoproteins from rats fed saturated fat, as a function of temperature. When chylomicrons and very low density lipoproteins were collected, isolated, and examined at 37 degrees C, they were liquid as judged by differential scanning calorimetry, x-ray diffraction analysis and proton nuclear magnetic resonance spectroscopy, and they appeared spherical by electron microscopy. At 23-26 degrees C, triglyceride began to crystallize in the alpha form, which transformed to the stable beta form at lower temperatures. On cooling from 23 degrees C to 17 degrees C, considerable crystallization occurred and the particle density was increased significantly. When lipoproteins were held at 0-7 degrees C, about 75% of the triglyceride crystallized, distorting the lipoprotein shape. Reheating from 0 degrees C to 37 degrees C left 25% of the triglyceride unmelted. Heating to 58 degrees C was necessary to melt all the crystallized triglyceride and to restore the spherical lipoprotein shape. After complete melting of cooled lipoproteins, the liquid state was maintained on recooling to 37 degrees C, with formation of a metastable particle similar to the nascent lipoprotein. Isolation of lipoproteins containing highly saturated triglyceride at temperatures below 23-26 degrees C results in partial crystallization, alters their physical properties, and may affect their metabolism.

Animals↗
PubMed1982

Ionization behavior of aqueous short-chain carboxylic acids: a carbon-13 NMR study.

The 13C chemical shift of each carbon of aqueous acetic, propionic, and butyric acids has been measured as a function of pH or of added equivalents of base. A plot of chemical shifts for the carboxyl, alpha, and beta carbons as a function of pH is sigmoidal and yields pKa values that agree closely with values obtained by potentiometric titration. In contrast, a plot of chemical shift as a function of added equivalents of base is linear and has a sharp break at the equivalence point. Based on this result, we propose that the local (microscopic) ionization state of the carboxyl group can be determined directly by NMR without need for pH or pK determinations. In addition to titration curves, the effects of concentration, ionic strength, and temperature upon fatty acid chemical shifts are reported. For aqueous acids, changes in ionic strength and temperature have no effect on chemical shifts. However, changes in concentration do affect chemical shifts, probably as a result of changes in the relative degree of acid-acid and acid-water hydrogen bonding. Our results provide necessary background data for 13C NMR studies of higher fatty acids in lipid-lipid and lipid-protein systems.

Acetates↗
PubMed1981

Induction of macrophage DNA synthesis by phorbol esters.

Tumor-promoting phorbol esters, such as 12-0-tetradecanoylphorbol-13-acetate (TPA), stimulate mouse peritoneal exudate macrophages to undergo DNA synthesis without added macrophage growth factor (MGF). Resident peritoneal macrophages do not respond in this manner. Plasminogen activator (PA) levels of both exudate and resident peritoneal macrophages are elevated by TPA. Thus the phorbol esters appear to mimic the action(s) of MGF and may be useful in understanding the events involved in macrophage and precursor cell growth responsiveness.

Animals↗
PubMed1981

Solubilization and localization of triolein in phosphatidylcholine bilayers: a 13C NMR study.

Cosonicated mixtures of egg phosphatidylcholine and small amounts (less than 5% wt/wt) of triolein have been studied by 13C NMR spectroscopy. The 50.3-MHz 13C NMR spectrum of vesicles preparations containing 90% isotopically substituted [1-13C]triolein showed two carbonyl resonances at chemical shift values that indicate hydrogen bonding of H2O molecules with the carbonyl groups. The extent of hydration, estimated from the chemical shift values that indicate hydrogen bonding of H2O molecules with the chemical shift values (173.07 ppm and 172.39 is approximately 50%. The data suggest that the triolein is located in the bilayer with the three carbonyl groups at the aqueous interface. The acyl chains are extended toward the bilayer interior, with a conformation of the glyceryl region such that the primary (alpha) carbonyls are closer to the aqueous medium than is the secondary (beta) carbonyl. Thus, triolein is present in the bilayer in an orientation appropriate for enzymatic hydrolysis, with the second substrate (H2O) in close proximity to the hydrolytic site, and with a conformation that could explain, in part, enzymatic specificity for hydrolysis at the alpha position. Spectra of vesicles containing greater than or equal to 3% triolein showed two additional carbonyl peaks characteristic of pure (neat) triolein. This allowed a determination of the maximum solubility (approximately 2.8%) of surface-oriented triolein in the bilayer phase. Beyond this limit all excess triolein partitions into a separate oil phase.

Hydrogen Bonding↗
PubMed1981

Stimulation of human synovial fibroblast plasminogen activator production by mononuclear cell supernatants.

Conditioned medium from concanavalin A-stimulated human peripheral blood mononuclear cells (c-MCCM) stimulates the plasminogen activator (PA) production of nonrheumatoid human synovial fibroblasts obtained from explant cultures. The effect of this synovial fibroblast-stimulating activity is observed within 2 to 4 hr and requires RNA and protein synthesis. Reversible morphological changes in the synovial cells can be observed as a result of c-MCCM action. These enzymatic and morphologic changes are similar to some of the effects of transforming viruses and tumor promoters on target cells. The possible significance of these data for an understanding of the cellular interactions involved in the formation and function of the rheumatoid "pannus" is discussed.

Concanavalin A↗