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Biomedical subjects

L Pickart

Publications and source records attributed to L Pickart.

At least 19 recordsLinked to original sources
PubMed1998

[Endoscopic surgical technique in appendectomy. Experiences and results of 950 laparoscopic appendectomies].

In a prospective study 950 appendectomies were done consecutively from May 1992 to September 1997. When indication for appendectomy was given all patients were operated on endoscopically. In 5.5% of cases had to be turned to open operation. 17 different surgeons are involved. Even the first appendectomy in adjucation of young residents was done endoscopically. 372 (39.15%) male and 578 (60.85%) female patients were operated. Average age was 25.3 years (4 to 84 years). In 11% of cases so-called chronic recurrent appenditicis as indication was accepted only after careful exclusion of other reasons for complaint. Mean duration of operation time was 44.5 min (15 to 170 min). Hospital stay was influenced subjectively 6.1 day (1 to 19 days). Examination of specimen by the pathologist shows following results: perforated appendicitis 7%; acute appendicitis 50%; chronic recurrent 33%; no pathologic changes 9%; carcinoide or oxyures 1%. The Postoperative complication rate was very small: only 2.7% (relaparotomy because of small bowel obstruction: 4, paracolic abscess after severe phlegmonic inflammation: 4, infected haematomas: 2, relaparotomy because of unobserved deverticula of Meckel with severe inflammation: 1, delayed woundhealing: 8, postoperative pain with duration long than: 24 hours: 7).

Adolescent↗
PubMed1990

Effects of glycyl-histidyl-lysyl chelated Cu(II) on ferritin dependent lipid peroxidation.

The copper binding tripeptide, glycyl-L-histidyl-L-lysine [GHK:Cu(II)] has a plethora of biological effects related to the wound healing process. The presence of iron complexes in damaged tissues is detrimental to wound healing, due to local inflammation, as well as microbial infection mediated by iron. To test if the wound healing properties of GHK:Cu(II) are due to an affect on iron metabolism, we examined the effects of GHK:Cu(II) on iron catalyzed lipid peroxidation. GHK:Cu(II) inhibited lipid peroxidation only if the iron source was ferritin. Whereas GHK:Cu(II) inhibited ferritin iron release it did not exhibit significant superoxide dismutase-like or ceruloplasmin-like activity. We propose that GHK:Cu(II) binds to the channels of ferritin involved in iron release and physically prevents the release of Fe(II). Thus, a biological effect of GHK:Cu(II), possibly related to wound healing, may be the inhibition of ferritin iron release in damaged tissues, preventing inflammation and microbial infections.

Animals↗
PubMed1989

ESR studies of the interaction of copper(II)GHK, histidine, and Ehrlich cells.

The tridentate complex CuGHK does not form ESR detectable adducts upon addition to either glutathione or Ehrlich ascites cells under our conditions. The absence of adducts is consistent with the poor uptake of CuGHK by cells. ESR spectra are used to characterize adduct formation between CuGHK and histidine. The CuGHK-histidine adduct is not stable in the presence of Ehrlich ascites tumor cells. It is argued that a Cu(His)2 complex is formed as a consequence of the interaction of GHK with cells.

Animals↗
PubMed1988

Stimulation of collagen synthesis in fibroblast cultures by the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+.

Glycyl-L-histidyl-L-lysine (GHK) is a tripeptide with affinity for copper(II) ions and was isolated from human plasma. This peptide appears to play a physiological role in wound healing. We report the stimulating effect of GHK-Cu on collagen synthesis by fibroblasts. The stimulation began between 10(-12) and 10(-11) M, maximized at 10(-9) M, and was independent of any change in cell number. The presence of a GHK triplet in the alpha 2(I) chain of type I collagen suggests that the tripeptide might be liberated by proteases at the site of a wound and exert in situ healing effects.

Cells, Cultured↗
PubMed1983

Increased ratio of plasma free fatty acids to albumin during normal aging and in patients with coronary heart disease.

The ratio of free fatty acids (FFA) to albumin, its carrier protein, was determined in 118 healthy men of ages 20 to 69 years and in 83 patients with coronary heart disease (CHD) of ages 33 to 69 years. During aging in normal men, this ratio increased progressively from an average value of 0.755 +/- 0.061 in the age 20-29 group to a value of 1.042 +/- 0.105 in the 60-69-year-old group. In patients with CHD this ratio was approximately 18% higher in each 10-year cohort than the corresponding control value, rising from a value of 1.029 +/- 0.081 in the 30-39-year-old group to a value of 1.212 +/- 0.106 in the 60-69-year-old group. The compositional spectrum of FFA among representative groups was similar, although linoleic acid was slightly reduced as a function of aging and the development of CHD. These results demonstrate that studies which measure only the absolute changes in FFA levels as a function of age or development of CHD tend to underestimate the magnitude of changes in FFA availability to tissues and for participation in biochemical reactions.

Adult↗
PubMed1982

Structure of the Glycyl-L-histidyl-L-lysine--copper(II) complex in solution.

Optical, electron paramagnetic resonance, and electron spin-echo envelope spectroscopies were used to examine the structure of the Cu(II) complex of glycyl-L-histidyl-L-lysine (GHL) in solution. At neutral pH, GHL forms a mononuclear 1:1 Cu(II) compound having an EPR spectrum resembling that of Cu(II) equatorially coordinated by two or three nitrogen atoms. Electron spin-echo studies demonstrate that one of these is located in the histidyl imidazole ring. A pH titration of Cu(II)-GHL shows three optical transitions with apparent pKs of 3.6, 9.2 and 11.4 and molecularities, with respect to protons, of 2, 2, and 1, respectively. At the lowest pK, GHL binds Cu(II), forming the species present at physiological pH. At elevated pH, spectroscopic experiments suggest that an alteration of the Cu(II) structure occurs, yet the bound imidazole is retained. These solution studies are consistent with nitrogen coordination of Cu(II) in Cu(II)-GHL, but the solid-state polymeric structure, with oxygen-bridged Cu(II) pairs as previously determined by X-ray crystallographic analysis [Pickart, L., Freedman, J. H., Loker, W. J., Peisach, J., Perkins, C. M., Steinkamp, R. E., & Weinstein, B. (1980) Nature (London) 288, 715-717; C. M. Perkins, N. J. Rose, R. E. Steinkamp, L. H. Jensen, B. Weinstein, and L. Pickart, unpublished results], does not exist in solution.

Copper↗
PubMed1981

Free fatty acidemia as an inducer of systemic hyperfibrinogenemia and fibrinolytic inhibition.

Many major inflammatory stimuli induce secondary conditions of blood hyperfibrinogenemia and fibrinolytic inhibition, changes which may be mediated by alterations in free fatty acid (FFA) metabolism. The effect of a free fatty acidemia induced by the intravenous infusion of a triglyceride into rabbits on the fibrinogen/fibrinolytic system was determined. A 3-h infusion of synthetic fat emulsion induced a rapid rise in FFA (0.4-2.1 microEq/ml in 3 h) followed by a more gradual rise in fibrinogen (2.6-4.3 mg/ml at 24 h), alpha 1-antitrypsin (1.1-1.9 mg/ml at 48 h), and serum fibrinolysis inhibitory activity (increased 202% at 48 h). Increases in protein concentration were due to increased synthesis. It is proposed that the changes in the fibrinogen/fibrinolytic system which follow major inflammatory stimuli are induced by a mediating free fatty acidemia. Possible pharmacological procedures to block these changes are discussed.

Animals↗
PubMed1981

The use of glycylhistidyllysine in culture systems.

Glycylhistidyllysine (GHL), a tripeptide isolated from plasma, has been shown to alter the growth rate of many cell types and organisms in culture systems. The tripeptide is optimally active at concentrations between 10 and 200 ng/ml. Some of the more interesting uses of GHL are highlighted in this paper. Present information suggests that GHL functions as a transporter of transition metals, in particular copper, to the cell surface for uptake into the cell.

Animals↗
PubMed1981

Fat metabolism, the fibrinogen/fibrinolytic system and blood flow: new potentials for the pharmacological treatment of coronary heart disease.

Recent studies have emphasized the role of blood fibrinogen as a major determinant of blood and plasma viscosity in the microcirculation, of red cell and platelet aggregation, and in the growth of atheromatous lesions. Blood fibrinogen levels are increased and the endogenous fibrinolytic activity decreased by conditions or factors which raise plasma free fatty acid levels. Conversely, a wide variety of hypolipidemic agents lower fibrinogen levels and increase endogenous fibrinolytic activity apparently by reducing hepatic synthesis of fibrinogen and antifibrinolysins. These observations may open a new avenue for the pharmacological development of agents capable of improving the patterns of blood flow in patients with circulatory impairments.

Arteriosclerosis↗
PubMed1981

Suppression of acute-phase synthesis of fibrinogen by a hypolipidemic drug (clofibrate).

The effect of pretreatment of rats with a hypolipidemic agent, clofibrate ethyl alpha-(p-chlorophenoxy)isobutyrate on the acute-phase induction of fibrinogen synthesis by thrombin injections was evaluated. Rats were pretreated with graded dosages of clofibrate (10-300 mg/kg day), then injected intraperitoneally with 1,000 U topical thrombin at 0 hours and at 24 hours to induce an acute-phase induction of fibrinogen synthesis. In control rats, thrombin injections rapidly diminished plasma fibrinogen levels and induced a marked rise in serum free fatty acids. However, by 48 hours after the initial injection, fibrinogen biosynthesis increased 5.6 fold and plasma levels were elevated twofold above normal. In contrast, clofibrate pretreatment of rats markedly attenuated both the thrombin-induced free fatty acid mobilization and the subsequent stimulation of fibrinogen synthesis. The optimal dosage of clofibrate which blocked the effect of thrombin of fibrinogen synthesis was 100 mg/kg day. These results suggest that the injection of acute-phase enhancements of fibrinogen synthesis is mediated by prior alterations in free fatty acid metabolism and that hypolipidemic drugs which block FFA mobilization will also suppress acute-phase fibrinogen hyperproduction.

Animals↗
PubMed1980

Growth-modulating plasma tripeptide may function by facilitating copper uptake into cells.

The plasma tripeptide glycyl-L-lysine (GHL), when added at nanomolar concentrations to a wide group of cultured systems, produces a disparate set of responses ranging from the stimulation of growth and differentiation to outright toxicity. Such diverse actions imply that this tripeptide mediates some basic biochemical function common to many types of cells and organisms. During the isolation of GHL we found the compound to co-isolate through a number of steps with approximately equimolar copper and about 1/5 molar iron. Maximal effects on hepatoma cells (HTC4) were seen when the peptide was added with copper and iron to the growth medium. Structure-function studies revealed that several tripeptides with a histidyl-lysyl linkage were nearly as active as GHL. The association of GHL with copper and a homology similarity between the tripeptide and the copper transport sites on albumin and alpha-fetoprotein, where the cupric atom is bound to a histidyl residue adjacent to a basic residue, suggested that GHL may act as a copper transport factor. We report here that the tripeptide readily forms complexes with copper(II) and enhances the uptake of the metal into cultured hepatoma cells.

Animals↗
PubMed1980

Responses of rat and chick chondrocytes and rate hepatoma cells to plasma fractions with insulin-like and growth-promoting activities.

Plasma protein Cohn fraction IV-1 was extracted and fractionated according to the method of Van Wyk et al.[1], with the omission of the Sephadex G-75 step. The fractionated polypeptides were investigated for insulin-like activity (lipid synthesis and lactate production) and growth-stimulatory activity (DNA synthesis) in three bioassay systems: rat hepatoma cells, and rat and chick chondrocyte suspensions. Binding of each fraction to insulin receptors in isolated plasma membranes was also determined. Three peptide subfractions, with molecular weights ranging from 400 to 20 000, stimulated lipid synthesis, lactate production and DNA synthesis in all three bioassay systems. There were distinct species- and cell-type-specific variations in the quantitative patterns produced by each subfraction. In contrast, authentic insulin (0.005-0.1 ng/ml) had no effect on DNA and lipid synthesis anad lactate production in hepatoma cells and chondrocytes. One of the three active subfractions and two relatively inactive fractions displaced insulin from its receptors. These observations indicate that acid-ethanol extracts of plasma contain a variety of peptide factors with insulin-like and growth-promoting effects whose expression in different cell types is modulated by inherent properties of each cell type which are determined genetically presumably. Surface receptors for authentic insulin do not appear to play an essential role in the insulin-like activities of the isolated plasma fractions.

Animals↗
PubMed1980

Growth-modulating tripeptide (glycylhistidyllysine): association with copper and iron in plasma, and stimulation of adhesiveness and growth of hepatoma cells in culture by tripeptide-metal ion complexes.

The tripeptide H-Gly-His-Lys-OH (GHL) is a human plasma constituent which has been previously shown to modulate the growth and viability of a variety of cell types and organisms. Experimental observations presented herein indicate that GHL is complexed with the transition metal ions Cu++ and Fe++ in vivo and may exert its biological effects as a peptide-metal chelate. At physiological pH in vitro, GHL associates with ionic copper, cobalt, iron, molybdenum, manganese, nickel, and zinc, but has no affinity for calcium, manganese, potassium, and sodium. GHL acts synergistically with copper, iron, cobalt, and zinc to alter patterns of cell growth in monolayer cultures of a tumorigenic hepatoma cell line (HTC4). These transition metals induce cellular flattening and adhesion to support surfaces, and inhibit DNA synthesis and lactic acid production when growth is limited by reduction of serum concentrations in medium. These inhibitory effects are neutralized, and intercellular adhesion and growth are stimulated by GHL in medium at nanomolar concentrations. Cu and Fe are the most active metals when combined with GHL. The results suggest that the inability of HTC4 cultures to replicate without adequate concentrations of serum in medium may reflect deficiency of GHL and transition metals, which appear to form complexes prior to interaction with cells. Chelation of transition metals with GHL and, potentially, with other growth-modulating peptide factors in plasma or medium, may provide a mechanism for expression and regulation of biological activities influenced by transition metals and polypeptide growth factors. The observed effects of GHL-metal complexes, including stimulation of cellular adhesiveness to substratum (flattening) and intercellular attachment (monolayer formation), appear to satisfy requirements for growth of hepatoma cells in monolayer culture.

Carcinoma, Hepatocellular↗