Biomedical subjects

M B Lazarevic

Publications and source records attributed to M B Lazarevic.

8 recordsLinked to original sources

PubMed1995

Reduction of cortisol levels after single intra-articular and intramuscular steroid injection.

BACKGROUND: This study was undertaken to determine the influence of single intra-articular or intra muscular injections of methylprednisolone acetate on the hypothalamic-pituitary-adrenal axis. PATIENTS AND METHODS: Twenty-one patients with rheumatic disease who had never been treated with systemic glucocorticoids and had not received local injections of these agents for the preceding 2 months, were given 40 mg of methylprednisolone acetate. Group I (11 patients) received one intra-articular injection into the knee, and Group II (10 patients) received the same dose intramuscularly. RESULTS: In Group I, serum cortisol levels were significantly decreased 24 hours after injection (228.2 +/- 8.7 nmol/L versus 193 +/- 16.3 nmol/L; P < 0.05). Serum cortisol levels were decreased in 9 of the 11 patients, by an average of 21.5%. Two patients' levels were below 138 nmol/L, which is considered to be the lower limit of normal range. Serum cortisol levels were below normal range in 3 patients 72 hours after intra-articular steroid injection. In Group II, serum cortisol levels were significantly decreased at 72 hours after injection (239.6 +/- 10.3 nmol/L versus 175.6 +/- 21.4 nmol/L; P < 0.01). Three patients' levels were below normal. By 72 hours postinjection, serum cortisol concentrations in 9 of 10 patients were decreased by an average of 31% compared to preinjection values. CONCLUSION: The present study suggests that decreased adrenocortical secretion, as reflected in depressed cortisol levels, can result from a single, low-dose, intra-articular or intramuscular injection of depot corticosteroids.

Adult↗

PubMed1994

Synthetic peptides as probes for G protein function. Carboxyl-terminal G alpha s peptides mimic Gs and evoke high affinity agonist binding to beta-adrenergic receptors.

The molecular interfaces between Gs and the beta-adrenergic receptor were investigated using synthetic peptides corresponding to various regions of its alpha subunit, alpha s. These experiments were carried out on saponin-permeable C6 glioma cells in which the beta-adrenergic receptor appears tightly coupled to Gs. Synthetic site-specific peptides from alpha s (corresponding to amino acids 15-29, 354-372, and 384-394) and alpha i (8-22, 315-324, and 345-455) were tested for their ability to interfere with coupling between the beta-adrenergic receptor and Gs. The two carboxyl-terminal peptides from alpha s blocked beta-adrenergic stimulation of adenylyl cyclase in permeable cells. However, only alpha s-354-372 had this effect in C6 membranes. It is suggested that the partial uncoupling of Gs, which occurs subsequent to cell disruption, may be related to a change in the interaction of the alpha s carboxyl terminus with the beta-adrenoreceptor. Two carboxyl-terminal peptides, 354-372 and 384-394, could also mimic the effect of Gs to increase agonist affinity for the beta-adrenergic receptor. In combination, alpha s-354-372 and alpha s-384-394 increased the ability of isoproterenol to compete with 125I-pindolol binding in a partially additive manner. Synthetic peptides from alpha i and amino-terminal peptides from alpha s had no effect on beta-agonist binding, suggesting a high specificity of peptide effects. Two findings suggest that these peptides bind directly to the beta-adrenergic receptor and stabilize its high agonist affinity conformation. First, GTP and hydrolysis-resistant GTP analogs did not alter the high affinity binding in the presence of high concentrations of the peptides. Second, in S49 lymphoma cyc- cells, which lack Gs, these peptides evoked the high affinity agonist binding state of the beta-receptor. Neither peptide had an effect on antagonist binding affinity, as measured by propranolol displacement of 125I-pindolol. These data suggest that at least two regions on the alpha subunit of Gs participate in high affinity Gs binding to the beta-adrenergic receptor. The fact that these small peptides could mimic the holo-Gs effect on the receptor is rather surprising, and the specificity of the effect suggests that the primary and secondary structure of small regions of alpha s contain much of the information for specific interaction with beta-adrenergic receptors.

Adenylyl Cyclases↗

PubMed1993

Cholesterol crystals in synovial and bursal fluid.

Cholesterol crystals were found in two patients with classic rheumatoid arthritis (RA). In one patient, cholesterol crystals were found in synovial fluid from both shoulder joints, and in the second they were in an olecranon bursa. To examine the possible systemic etiology of cholesterol crystals in synovial and bursal fluid, lipid concentrations and the presence of serum antilipoprotein antibodies were measured. Antilipoprotein antibodies were not found. The concentration of lipid and lipoproteins, as well as the normal pattern of lipoprotein on agarose gel, eliminates the possibility of hyperlipoproteinemia. Results seemed to exclude a systemic etiology for the formation of cholesterol crystals in synovial and bursal fluid in the RA patients. It appears that several local factors such as defective drainage, local destruction, increased permeability of synovial membrane, and intraarticular (bursal) bleeding are possible etiologies.

Arthritis, Rheumatoid↗

PubMed1993

Antilipoprotein antibodies in rheumatoid arthritis.

Antibodies against very low-density lipoproteins and low-density lipoproteins (aLA) were found in 26 of 69 (38%) patients with active rheumatoid arthritis (RA) but not in any control subjects (ie, 40 patients with psoriatic arthritis, 21 patients with osteoarthritis, and 65 healthy blood donors). In 21 RA patients (30%), lipoproteins were found in the dissociated components of circulating immune complexes. RA patients with aLA had significantly decreased cholesterol levels in all lipoprotein fractions and total serum lipids, while serum triglycerides were significantly increased compared with RA patients without aLA. Anticardiolipin antibodies as measured by the Venereal Disease Research Laboratory test were not found in any subject in this study. These findings suggest a possible autoimmune origin of dyslipoproteinemia in some patients with active RA.

Antibodies↗

PubMed1993

Systemic lupus erythematosus and Hodgkin's lymphoma.

OBJECTIVE: Systemic lupus erythematosus (SLE) is associated with lymphoproliferative diseases such as Hodgkin's lymphoma. Since there is considerable overlap between the features of SLE and Hodgkin's lymphoma (SLE/HL) there can be a great difficulty in diagnosing Hodgkin's lymphoma in the presence of SLE. Our objective was to determine the features that can suggest coexistent SLE/HL: METHODS: We describe 3 cases of Hodgkin's lymphoma that occurred in the setting of SLE and review the features of 11 reported cases in which the diseases occurred simultaneously. We compare the features of these cases with those of Hodgkin's lymphoma and SLE occurring alone. RESULTS: Mediastinal adenopathy was seen in 58% and retroperitoneal adenopathy in 17% of patients with SLE/HL, while it was seen only rarely in these sites in cases with SLE. Severe generalized pruritus, which occurs in only 2.8% of cases of SLE, was seen in 63% of cases with SLE/HL: Features such as fever, weight loss, peripheral lymphadenopathy, splenomegaly and hepatomegaly are common to both Hodgkin's lymphoma and SLE. Renal disease is seen in half of the cases of SLE. It is rare in Hodgkin's lymphoma where, unlike SLE, it is only of minimal change or membranous type. Arthritis and positive antinuclear antibodies are rare in Hodgkin's lymphoma. CONCLUSIONS: Persistent lymphadenopathy, especially mediastinal and/or retroperitoneal lymphadenopathy, eosinophilia and generalized pruritus in a patient with SLE not responding to treatment may be indicative of coexistent Hodgkin's lymphoma.

Adult↗

PubMed1993

Myasthenia gravis and scleroderma.

Myasthenia gravis is an autoimmune disease that is associated with antibodies to acetylcholine receptors. It is associated with other autoimmune diseases such as thyroiditis (10%), systemic lupus erythematosus (2-8%), rheumatoid arthritis (4-7%), Sjögren's syndrome and polymyositis. It is not commonly found with scleroderma. We describe a case of scleroderma developing in a patient 6 years after the onset of myasthenia gravis. HLA-B8/DR3 may play a role in the association of the 2 conditions.

Adult↗

PubMed1992

Effect of gold compounds on the activity of adenylyl cyclase in human lymphocyte membranes.

OBJECTIVE: To determine the effects of aurothioglucose, aurothiomalate, and auranofin on basal and forskolin-activated adenylyl cyclase activity in human total lymphocyte membranes, and in membranes of T and B lymphocyte subsets. METHODS: Membranes were isolated from human total lymphocytes and T and B cell subsets. The effects of gold compounds on basal and forskolin-stimulated activity of adenylyl cyclase were measured by radioassay. RESULTS: The gold compounds inhibited adenylyl cyclase activity. This inhibitory effect required the presence of both the sulfhydryl ligands and aurous cation. CONCLUSION: Regulation of lymphocyte adenylyl cyclase by gold compounds represents a potential mode of action of these drugs in rheumatic diseases.

Adenylyl Cyclases↗

PubMed1992

Dyslipoproteinemia in the course of active rheumatoid arthritis.

Concentrations of serum lipids and serum very low-density lipoproteins and low-density lipoproteins (VLDL+LDL, originally called beta lipoproteins) were measured and agarose gel electrophoresis of serum lipoproteins was performed in 69 patients with active rheumatoid arthritis (RA), 40 patients with psoriatic arthritis (PA), 21 patients with osteoarthritis (OA), and 65 healthy blood donors. These lipid parameters were also compared in 21 RA and 40 PA patients during periods of severe disease activity (SA) versus minimal disease activity (MA). RA patients had significantly decreased concentrations of total serum lipids, total serum cholesterol, cholesterol in LDL, and cholesterol in high-density lipoproteins (HDL) compared with healthy blood donors. RA patients with SA had significantly decreased cholesterol in LDL and HDL compared with patients with MA. As the disease activity decreased, RA patients had normalization of almost all serum lipid concentrations. Electrophoresis of serum lipoproteins showed heterogeneous patterns in RA patients. Patients with PA also had some evidence of dyslipoproteinemia. Serum lipids changed with disease activity in PA patients in a manner similar to that in RA patients. These data show that patients with RA and PA have a dyslipoproteinemia that is related to disease activity.

Arthritis, Psoriatic↗