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Biomedical subjects

A Cerami

Publications and source records attributed to A Cerami.

At least 289 records · Page 16Linked to original sources
PubMed1981

Studies of endotoxin-induced decrease in lipoprotein lipase activity.

A variety of invasive stimuli have been shown to induce hyperlipidemia due to impaired removal of triglyceride from the circulation. The mechanism by which endotoxin induces a deficiency in the activity of the key enzyme of triglyceride metabolism, lipoprotein lipase (LPL), has been studied. In C3H/HeN (endotoxin-sensitive) mice, LPL activity in adipose tissue was markedly suppressed 16 h after endotoxin administration. In contrast, the endotoxin-resistant C3H/HeJ mice were less sensitive to the suppressive effect of endotoxin on LPL activity. After endotoxin administration, a transferable factor had been detected in the blood of C3H/HeN mice 2 h after the injection of endotoxin that causes a suppression of adipose tissue LPL activity in C3H/HeJ mice as well as in C3H/HeN mice. Conditioned medium from the cultures of peritoneal exudate cells of C3H/HeN mice incubated in endotoxin also suppresses adipose tissue LPL in C3H/HeJ mice. These studies demonstrate that exudate cells produce a humoral factor in response to endotoxin, which suppresses adipose tissue LPL.

Adipose Tissue↗
PubMed1981

Biochemical and rheological characterization of sputum mucins from a patient with cystic fibrosis.

The studies described herein entail the isolation and characterization of native mucin isolated in the absence of disulfide reducing agents. The rheological characteristics of mucin closely resemble those of whole sputum. The aggregation of mucin molecules is responsible for the high viscosity of concentrated mucin solutions such as sputum. Disulfide reducing agents reduce the viscosity of concentrated mucin solutions by dissociation of soluble mucin aggregates without affecting the insoluble aggregates. Detailed chemical analyses of the mucins have been carried out and indicate that the reduction of interchain disulfides is accompanied, not only by a reduction in mucin viscosity, but by the liberation of two small proteins from the large mucin molecule. Detailed analyses of the cysteine plus cystine content of native mucin indicate that none of the free cysteines are accessible to alkylation in the absence of denaturants. Approximately 80% of the cystine content of the molecule is accessible to disulfide reduction in the absence of denaturants. This finding accounts for the ability of disulfide reducing agents to reduce sputum viscosity under nondenaturing conditions.

Amino Acids↗
PubMed1981

Inhibition of glutathione synthesis as a chemotherapeutic strategy for trypanosomiasis.

With the expectation that trypanosomal glutathione (GSH) plays a major protective role against the endogenous oxidant stress that results form high intracellular levels of H2O2, we sought to deplete Trypanosoma brucei brucei of their GSH through inhibition of its biosynthesis. Administration of buthionine sulfoximine (BSO), a reversible inhibitor of gamma-glutamylcysteine synthetase, to parasitemic mice resulted in a progressive decrease in trypanosome GSH content, such that parasites isolated after 5 h or BSO treatment contained 50% of normal values. When BSO administration was continued for 18 h (intraperitoneal injection of 4 mmol/kg every 1.5 h), parasitemias temporarily cleared. When inhibitory plasma levels of BSO were maintained for about 27 h, two out of six infected mice were cured and the rest had significantly prolonged survival. These findings demonstrate the potential value of GSH depletion for the treatment of trypanosomiasis.

Animals↗
PubMed1981

Nonenzymatic browning in vivo: possible process for aging of long-lived proteins.

The incubation of lens proteins with reducing sugars leads to the formation of fluorescent yellow pigments and cross-like similar to those reported in aging and cataractous human lenses. Called nonenzymatic browning or the Maillard reaction, this aging process also occurs in stored foods. Reducing sugars condense with the free amino group of proteins, then rearrange and dehydrate to form unsaturated pigments and cross-linked products. Although most proteins in living systems turn over with sufficient rapidity to avoid nonenzymatic browning, some, such as lens crystallins and skin collagen, are exceptionally long-lived and may be vulnerable.

Aging↗
PubMed1981

Nonenzymatic glycosylation of peripheral nerve protein in diabetes mellitus.

A new affinity chromatography system that selectively retains glycosylated amino acids has been utilized to determine the amount of nonenzymatic glycosylation present in peripheral nerve from diabetic and control rats and dogs. The mean value for glycosylated amino acids in diabetic rats was 2.8 times greater than the mean value in normal rats (P less than 0.001). In diabetic dogs, mean values were 2.15 times greater than normal values (P less than 0.05). Amino acid analysis of reduced, glycosylated amino acids previously isolated by affinity chromatography showed that glycosylated lysine and its hydrolysis rearrangement products were the major borohydride-reducible adduct present. In addition, another glycosylated product was noted to be present in major proportions. This radioactive product did not chromatograph with any of the available glycosylated amino acid standards. The finding that diabetes results in a nearly 3-fold increase of peripheral nerve glycosylation is consistent with a number of previous investigations in which glycosylation was measured in hemoglobin, serum albumin, and urinary amino acids and peptides from diabetics and normals. The results reported here provide evidence that increased nonenzymatic glycosylation is occurring in a tissue where physiological, morphological, and clinical degeneration characteristically develop as a result of diabetes mellitus.

Animals↗
PubMed1981

Acetaldehyde adducts with hemoglobin.

Clinical studies on the minor hemoglobins (hemoglobin A1a-c) have suggested that a novel adduct may form in people abusing alcohol. Such patients were found to have an elevated concentration of minor hemoglobins, but normal or subnormal amounts of glycosylated hemoglobin (hemoglobin A1c) as determined by radioimmunoassay, Acetaldehyde, a reactive metabolite of ethanol, was postulated to form adducts with hemoglobin A that change its chromatographic properties. At physiological concentrations, acetaldehyde was found to form adducts with hemoglobin that were stable to extensive dialysis for several days. The amount of hemoglobin adducts formed were a function of the concentration and number of exposures to acetaldehyde. The reaction of acetaldehyde with hemoglobin A produced chromatographic variants, some of which migrated in the hemoglobin A1a-c region. Analysis of stable acetaldehyde-hemoglobin adducts demonstrated that valine, lysine, and tyrosine residues of globin were sites of reaction. The acetaldehyde-modified amino acid residues appear to exist in interconvertible conformations, only one of which is reducible by sodium borohydride. The amount of these adducts was found to be significantly elevated in hemoglobin from alcoholics as compared with normal volunteers.

Acetaldehyde↗
PubMed1980

DNA polymerases in parasitic protozoans differ from host enzymes.

Analysis of extracts of the bloodstream forms of Trypanosoma brucei showed that both DNA polymerase-alpha and DNA polymerase-beta activities were present. The detection of DNA polymerase-beta in T. brucei demonstrates the presence of this enzyme in unicellular organisms. DNA polymerase-beta is present also in Leishmania mexicana. The DNA polymerases in T. brucei are immunologically distinct from the host enzymes. The structural differences between the parasite and the host enzymes could be exploited for the development of agents to combat parasitic diseases.

Animals↗
PubMed1980

Low molecular weight iron-binding factor from mammalian tissue that potentiates bacterial growth.

A low molecular weight, iron-binding factor was isolated from horse liver. This host-associated iron transfer factor (HAITF) is capable of binding iron and stimulating bacterial growth by promoting iron uptake into bacteria. Also, when injected into infected animals, HAITF increases the virulence of bacterial infections. HAITF bioactivity is ubiquitous in animal tissues and present in serum. It is proposed that HAITF is a factor that inadvertently plays a role in the host-parasite competition for iron.

Animals↗
PubMed1980

Hypertriglyceridemia associated with Trypanosoma brucei brucei infection in rabbits: role of defective triglyceride removal.

Rabbits infected with Trypanosoma brucei brucei develop a hypertriglyceridemia characterized by an increase in very low density lipoprotein and, to a lesser extent, low density lipoprotein, with a decrease in high density lipoprotein. Triglyceride production studies showed that the triglyceride production rate was not significantly different in trypanosome-infected rabbits from controls. Studies of triglyceride degradation using very low density lipoprotein triglyceride endogenously labelled with [3H]palmitate demonstrated a marked slowing of triglyceride removal in the infected rabbits when compared to controls. Lipase activity in post-heparin plasma was found to be deficient in trypanosome-infected animals. Furthermore, the greater the decrease in lipolytic activity, the greater the increase in serum triglyceride level. We conclude that the hypertriglyceridemia associated with T. b. brucei infection in rabbits results predominantly from a defect in triglyceride degradation.

Animals↗
PubMed1980

Hemoglobin A Ic and diabetes mellitus.

Hemoglobin A Ic is produced when glucose reacts nonenzymatically with the NH2-termini of Hb A beta chains and then undergoes an Amadori rearrangement. The concentration of Hb A Ic measured at any given time reflects a patient's mean blood glucose level for the preceding weeks to months. Infrequent measurements of Hb A Ic can therefore be used to assess long-term carbohydrate control in outpatient diabetics. In addition, the synthesis of Hb A Ic may represent a model reaction to explain the pathogenesis of many of the sequelae of chronic diabetes. Nonenzymatic glycosylation reactions may also underlie some of the changes ascribed to normal aging.

Blood Glucose↗
PubMed1980

Measurement of glycosylated amino acids and peptides from urine of diabetic patients using affinity chromatography.

An affinity chromatography system has been developed that retains glycosylated amino acids and peptides. Using this system, synthetic 14C-glycosylated lysine (reduced with NaB3H4) was completely separated from a mixture of reduced 14C-glycosylated lysine and unmodified 3H-lysine. Amino acid analysis of the retained peak from hydrolyzed human diabetic hemoglobin previously reduced with NaB3H4 revealed an equimolar mixture of glycosylated valine and glycosylated lysine, in agreement with previously published data obtained using other methodologies. These data demonstrate that in alkaline solution, the NaB3H4-reducible breakdown products of nonenzymatically glycosylated proteins are adsorbed to m-aminophenyl boronic acid immobilized on Bio-Gel P-6, while nonglycosylated amino acids are not. This affinity chromatography system should facilitate the rapid evaluation of nonenzymatic glycosylation in a large number of diabetic tissues. Levels of retained compounds in urine from diabetic and normal patients were determined by measuring ninhydrin-positive material. Amino acid analysis of NaB3H4-reduced hydrolysates of these peaks showed that glycosylated lysine was the major borohydride-reducible adduct present (67%--86%). Linear regression analysis showed that the quantity of excreted compounds in normals correlated with body weight (r = 0.63). The mean level (mumol leucine-equivalent/24 h/kg body weight) in diabetics was over 1.5 times that found in urine from normal subjects (P < 0.005).

Carbon Radioisotopes↗
PubMed1980

Studies on the reduction of sputum viscosity in cystic fibrosis using an orally absorbed protected thiol.

The viscosity of cystic fibrosis fluids leads to clinical difficulties in adequate clearance of the respiratory and gastrointestinal tracts and in delivery of gases and nutrients to their respective sites. Various sulfhydryl agents are effective in reducing in vitro sputum viscosity. Present therapy for cystic fibrosis involves the aerosolization of N-acetylcysteine, presenting problems of toxicity and inadequate delivery to the small airways. We have been assessing various prodrugs which would liberate the free thiol in vivo and which would be orally absorbed. The free thiol of WR 2721, at a concentration of 1 mM, reduces sputum viscosity by 70% in 15 min. WR 2721 is hydrolyzed to the free thiol chemically at an acid pH and enzymatically by homogenates of the liver and gut. It is well absorbed (23%) after oral administration to rabbits. Clinical studies indicate that orally administered WR 2721 is without toxicity and reduces sputum viscosity in cystic fibrosis patients in 30 to 60 min after administration.

Adolescent↗