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Biomedical subjects

M Popovic

Publications and source records attributed to M Popovic.

At least 181 records · Page 10Linked to original sources
PubMedDate not supplied

The effect methoxsalene on hypnotic and subhypnotic doses of pentobarbital.

The effect of several doses of methoxsalen on hypnotic action of 40 mg/kg of pentobarbital in mice was studied. Methoxsalen was injected 30 minutes before the barbiturate. The highest methoxsalen dose of 22 mg/kg extended the duration of the hypnotic action of pentobarbital about 10 times compared to the control. The effect decreased with time, and 96 hours after this single dose of methoxsalen it was not significantly different from that observed with the control animals receiving only 40 mg/kg pentobarbital. The other methoxsalen doses (10, 5, and 2 mg/kg) exhibited an equal effect on the hypnotic action of pentobarbital, and only in the first measuring time. The effect could not be detected after 24 hours, and no dose dependence was observed. Small doses of methoxsalen of 2 and 1 mg/kg injected 30 minutes before a subhypnotic pentobarbital dose of 30 mg/kg produced sleep in 75% of animals of the both groups. In the control group, this dose produced no sleep in none of the animals.

Animals↗
PubMedDate not supplied

The effect of celery and parsley juices on pharmacodynamic activity of drugs involving cytochrome P450 in their metabolism.

Celery (Apium graveolens) and parsley (Petroselinum sativum), plants used worldwide in human nutrition, are the natural sources of methoxsalen. In this study we investigated the effect of mice pretreatment with juices of this plants on the hypnotic action of pentobarbital and analgesic action of paracetamol and aminopyrine, the drugs involving cytochrome P450 superfamily in their metabolism. In mice pretreated with celery and parsley juices a prolonged action of pentobarbital with respect to control was observed, statistical significance being attained only with parsley-pretreated animals. Both pretreatments increased and prolonged the analgesic action of aminopyrine and paracetamol, pretreatment with parsley being again more effective. Celery and parsley juices given to animals two hours before their decapitation caused a significant decrease of cytochrome P450 in the liver homogenate as compared to control.

Analgesics, Non-Narcotic↗
PubMedDate not supplied

Cell lines producing human T-cell lymphoma virus show altered HLA expression.

Human T-cell leukaemia/lymphoma virus (HTLV) can be identified in fresh and cultured T-lymphocytes from patients with adult T-cell malignancies. HLA typing of the peripheral blood lymphocytes and cultured cell lines from the patient from which the virus was originally isolated suggested the expression of additional HLA-A and -B locus antigens on the HTLV positive cultured T-cells that were not present on the EBV transformed B-cell line or on the peripheral blood lymphocytes. Peripheral blood lymphocytes (PBLs) and T-cell lines established from patients and cord blood lymphocytes, infected with virus by co-culture with T-cell lines, were typed for HLA antigens with alloantisera and in addition tested for reactivity with a monoclonal antibody (4D12) which recognizes a polymorphic HLA class-I antigen. In all HTLV positive cells, with demonstrable provirus replication, altered HLA alloantigen expression was observed. This may be explained by the observations reported in the accompanying paper which shows homology between the envelope gene region of HTLV and the region of an HLA-B locus gene which codes for the extracellular portion of a class I histocompatibility antigen.

Antigens, Surface↗
PubMedDate not supplied

Molecular cloning and characterization of the HTLV-III virus associated with AIDS.

We recently reported the isolation and characterization of a novel human T-lymphotropic retrovirus, HTLV-III, in patients with acquired immune deficiency syndrome (AIDS) and in those at risk for the disease. After extensive sero-epidemiological studies, together with numerous virus isolations from these patients, we concluded that HTLV-III is the causative agent of AIDS. Here we report the molecular cloning and characterization of two highly related but distinct forms of the HTLV-III genome. The viral genome is approximately 10 kilobases long and is detected in HTLV-III-infected cells but not in uninfected cells, including normal human tissue, indicating that this virus is exogenous to man. We also demonstrate distant nucleic acid sequence homology between the cloned genome of HTLV-III and those of HTLV-I and HTLV-II. The availability of the cloned HTLV-III genome will now allow an unambiguous comparison of this virus with other retroviruses that also have been associated with the pathogenesis of AIDS, and moreover, with facilitate the development of diagnostic and therapeutic measures in the treatment of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

Reactivity of HTLV-transformed human T-cell lines to MHC class II antigens.

T-cell lines established from individuals infected with human T-cell leukaemia virus (HTLV) or generated by co-cultivation of normal human T cells with HTLV-infected T-cells, express class II (HLA-D/DR or Ia) antigens of the major histocompatibility complex (MHC) and interleukin-2 (IL-2) receptors. Because the expression of these markers characterizes the differentiation of immunologically activated T cells, we have now explored the possibility that HTLV- infected T cells might be primed to autologous or allogeneic Ia antigens expressed by the infecting cells. Our studies on the capacity of HTLV-infected T cells to display responses on mixed lymphocyte culture indicate that such T cells as well as single-cell clones derived from them, react non-discriminatively to all known allelic variants of human HLA-D/DR antigens, including those expressed by the responding cells. This reaction is inhibited by antibody to human Ia and is not triggered by Ia-negative T-leukaemia cells. The structure recognized seems to be a common epitope determinant of human Ia antigens, as (HTLV-infected) T cells primed in vitro to one HLA-D/DR specificity display amplified responses to all other HLA-D/DR antigens. We therefore believe that autostimulation by a self-Ia determinant may trigger the clonal expansion of HTLV-infected T cells and potentiate autoimmune processes.

Antibodies, Monoclonal↗
PubMedDate not supplied

Gp120 sequence variation in brain and in T-lymphocyte human immunodeficiency virus type 1 primary isolates.

OBJECTIVE: We sought to identify genetic determinants within human immunodeficiency virus type 1 (HIV-1) gp120 that differentiate viral species in brain from those in lymphocytes. STUDY DESIGN/METHODS: Polymerase chain reaction (PCR) was used to amplify gp120 genes from paired brain and T-cell isolates from two infants and two adults with dementia. Amplimers were molecularly cloned and sequenced. RESULTS: The degrees of amino acid divergence between brain and T-cell clones for the two adults were 7.7% and 8.6% and, for the two infants, 2.4% and 2.7%. For one adult and one infant, divergence was greater among brain cell clones than T-cell clones. In the adults, a 3-amino acid insertion, located similarly within V4 and encoding asparagine residues, was identified in the T-cell clones. CONCLUSIONS: HIV-1 genetic variation within brain cells is not necessarily restricted compared with that in blood lymphocytes. The species in brain cells can be distinguished from those in lymphocytes by determinants within V4. These differences suggest that immune-mediated selection ongoing within lymphoid cell compartments may not occur within brain.

Adult↗
PubMedDate not supplied

Disease modifying and immunomodulatory effects of high dose 1 alpha (OH) D3 in rheumatoid arthritis patients.

OBJECTIVE: Vitamin D analogues such as 1 alpha (OH) D3 (alphacalcidiol) have a possible physiological paracrine effect on cell proliferation and differentiation. Experimentally established possibilities to prevent autoimmune diseases suggest that alphacalcidiol may have therapeutic value as an immunomodulatory agent in patients with rheumatoid arthritis. METHODS: We organized a 3-month open-label trial on 19 patients being treated with standard DMARD therapy for acute RA. They were divided into 2 subgroups, those with highly active RA and those with moderately active RA. Their regular drug regimen was maintained during the trial and oral alphacalcidiol 2 micrograms/day was added. Therapy results were evaluated by ESR, CRP, morning stiffness, the Richie index, and the Lee index. Immunomodulatory effects were investigated by measuring lymphocyte proliferation and apoptosis both in the patients and in vitro in 10 nM alphacalcidiol-supplemented culture medium. RESULTS: After 3 months, high dose oral alphacalcidiol therapy showed a positive effect on disease activity in 89% of the patients (45% or 9 pts. with complete remission and 44% or 8 pts. with a satisfactory effect). Only two patients (11%) showed no improvement, but no new symptoms occurred. No side effects were observed. CONCLUSION: These results suggest that alphacalcidiol is a powerful immunomodulatory agent with fairly low hypercalcemic activity. Clinical improvement was strongly correlated with the immunomodulating potential of this agent. We noticed dual effects on lymphocyte proliferation and apoptosis according to the prior cell activation state. Alphacalcidiol could therefore possibly be used as an adjunct therapy with DMARDs in patients with rheumatoid arthritis.

Adjuvants, Immunologic↗
PubMedDate not supplied

Coreceptor usage and RANTES sensitivity of non-syncytium-inducing HIV-1 isolates obtained from patients with AIDS.

OBJECTIVES: The biologic phenotype of HIV-1 primary isolates obtained from approximately 50% of patients who progress to AIDS switches from non-syncytium-inducing (NSI) to syncytium-inducing (SI). We evaluated possible associations between virus coreceptor usage, sensitivity to inhibition by beta-chemokines, and disease progression of patients who continue to yield NSI isolates after developing AIDS. STUDY DESIGN/METHODS: Sequential virus isolates were analyzed for biologic phenotype using the MT-2 cell assay, for sensitivity to beta-chemokines using RANTES inhibition, and for coreceptor usage using U87.CD4 and GHOST.CD4 cells expressing different chemokine/orphan receptors or donor peripheral blood mononuclear cells (PBMC) defective in CCR5 expression. In addition, the env V3 region was sequenced and the length of the V2 region determined. RESULTS: All NSI isolates, regardless of patient status at time of isolation, were dependent on CCR5 expression for cell entry. Furthermore, there was no indication of broadened coreceptor usage of NSI isolates obtained from persons with late-stage AIDS. A majority of NSI isolates remained RANTES sensitive; however, virus variants with reduced sensitivity were observed. The V2 lengths and the V3 sequences exhibited no or minor changes at analysis of sequential NSI isolates. CONCLUSIONS: Our data suggest that NSI isolates obtained from AIDS patients remain CCR5 dependent (ie, R5) and, in many cases, also remain sensitive to RANTES inhibition. However, virus variants with decreased sensitivity to RANTES inhibition may evolve during disease progression, not only as a result of a switch from NSI to SI but also in patients who develop AIDS while continuing to maintain R5 isolates.

Acquired Immunodeficiency Syndrome↗