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Biomedical subjects

M Popovic

Publications and source records attributed to M Popovic.

At least 37 records · Page 2Linked to original sources
PubMed2000

So-called malignant and extra-ventricular neurocytomas: reality or wrong diagnosis? A critical review about two overdiagnosed cases.

Central neurocytoma (CN) is described as a rare intra-ventricular benign neuronal tumor of the brain. Two primary tumors first diagnosed as malignant and extra-ventricular neurocytomas are reported here. Histologically, the tumor of the first patient, a forty-one-year-old man, consisted of monotonous cells with round nuclei, but no fibrillar background. The second tumor, in a nineteen-year-old girl, showed areas of moderately pleomorphic round cells, with numerous rosettes and ganglion cell differentiation, in an abundant fibrillary network. Both presented calcifications. Mitoses were more frequent in recurrences and spinal locations than in the primaries. All tumors stained strongly for synaptophysin, and GFAP was partly positive in the first case only. Patients received post-surgical radiotherapy and were still alive eight and six years, respectively, after initial surgery. The interpretation of atypical cases, such as ours is not easy: the diagnoses finally retained were oligodendroglioma in the first case and ganglioneuroblastoma in the second case. Furthermore, neurocytomas atypical either by their unusual topographical or histological presentation or by their poor prognosis, have been frequently entitled in this way on synaptophysin positivity. So, we were prompted to reassess the entity of CN, seventeen years after the first description, to re-appreciate the reality of anatomo-clinical variants and to discuss the value of synaptophysin positivity in these tumors. In conclusion, it seems preferable to individualize true classical CN, which has a favorable outcome, from so-called extra-ventricular, atypical and anaplastic, clinically malignant neurocytomas for which complementary treatment is required.

Adolescent↗
PubMed2000

Hereditary motor and sensory neuropathy associated with auditory neuropathy in a Gypsy family.

In a Slovene Gypsy family of 19 subjects from four generations three patients with clinical characteristics compatible with hereditary motor and sensory neuropathy - Lom (HMSNL). were found They had severe distal and milder proximal muscle atrophy and weakness with areflexia of myotatic jerks. Two had facial weakness at the time when already wheelchair bound. All sensory modalities were affected distally in the limbs. Sluggish pupillary responses to light and convergence were found. They had skeletal abnormalities. One patient had polydactily on the hand. Nerve conduction studies were compatible with demyelinative polyneuropathy. Nerve biopsy showed mainly axonal loss without hypertrophic changes. Auditory neuropathy was diagnosed in all of them. None of the patients had duplication of 17p1.2-12 or point mutations in the Protein zero. Peripheral myelin protein and Connexin32 genes. Similar disorder that mapped to 8q24 was previously described in some Bulgarian and Italian Gypsy families. Members of our family may suffer from the same hereditary disease and may carry the same ancestor mutation, which was in the past spread in European Gypsy populations.

Adolescent↗
PubMed1999

Hereditary auditory, vestibular, motor, and sensory neuropathy in a Slovenian Roma (Gypsy) kindred.

Members of a Roma (Gypsy) family with hereditary motor and sensory peripheral neuropathy (HMSN) and concomitant auditory and vestibular cranial neuropathies were identified in Kocevje, Slovenia. The illness begins in childhood with a severe and progressive motor disability and the deafness is delayed until the second decade. There are no symptoms of vestibular dysfunction. The family structure is consistent with an autosomal recessive pattern of inheritance and the genetic locus for the disorder is linked to the same region of chromosome 8q24 as other Roma families with HMSN and deafness from Lom, Bulgaria (HMSN-Lom). The present study shows that the deafness is caused by a neuropathy of the auditory nerve with preserved measures of cochlear outer hair cell function (otoacoustic emissions and cochlear microphonics) but absent neural components of auditory brainstem potentials. The hearing loss affects speech comprehension out of proportion to the pure tone loss. Vestibular testing showed absence of caloric responses. Physiological and neuropathological studies of peripheral nerves were compatible with the nerve disorder contemporaneously affecting Schwann cells and axons resulting in both slowed nerve conduction and axonal loss. Genetic linkage studies suggest a refinement of the 8q24 critical region containing the HMSN-Lom locus that affects peripheral motor and sensory nerves as well as the cranial auditory and vestibular nerves.

Acoustic Stimulation↗
PubMed1999

Estrus cycle and gastric lesions in individual- and group-stressed female rats.

The aim of the present study was to analyze the influence of the estrus cycle on the development of cold restraint-induced gastric lesions in single- and group-stressed female rats. Therefore, adult female Wistar rats, in different phases of the estrus cycle (proestrus, estrus, metestrus and diestrus), were restrained individually or in groups (two, three, six or nine rats) and exposed to a temperature of 4 degrees C for 2 h. The comparison between stressed female rats in different phases of the estrus cycle indicated that gastric pathology was significantly higher in estrus phase as compared to the other phases of the estrus cycle. The intensity of stress-induced gastric pathology was either not changed (estrus), moderately decreased (proestrus and metestrus) or highly decreased (diestrus) by increasing the number of concomitantly exposed rats to cold restraint. The vulnerability to cold restraint-induced stress ulcer rose as followed: proestrus < metestrus < diestrus < estrus. It could be concluded that female rats are more vulnerable to cold restraint-induced stress ulcer in estrus period and that in this phase, social interaction did not made any significant influence on the stress induced gastric lesions.

Animals↗
PubMed1999

Classification of tetraplegics through automatic movement evaluation.

The general problem of classification of functional movements in humans with spinal cord injuries requires the following questions to be answered: what are the essential kinematic parameters that we have to observe during the movement? Is it possible to estimate preserved motor skills based on kinematics? Which computational method for identification is suited to geometric feature analysis? To answer these questions we have developed the methodology which has two phases: (1) recordings of a series of specified arm movements; and (2) custom made software for graphical presentation of arm movements and the design of wavelet and neural networks for movement classification. The proposed protocol is automated and both graphical presentation and neural networks allow easy interpretation of the instrumented assessment to accomplish automatic classification of arm movements in tetraplegics. The protocol was evaluated on 16 spinal cord injury (SCI) patients and seven healthy control subjects for three different arm movements. The classification rate yielded results in the range 46-100% for movement trials that were tested. The application of neural networks for classification of arm movements is completed with results using different neural networks: backpropagation, radial basis, recurrent (Elman), self-organizing and Learning Vector Quantization (LVQ).

Adolescent↗
PubMed1999

Immune Responses in Nucleus Basalis Magnocellularis-Lesioned Rats Exposed to Chronic Isolation Stress.

The present study was designed to establish the influence of chronic social isolation stress on humoral and cellular immunity in nucleus basalis magnocellularis (NBM)-lesioned rats. Therefore, ten days after bilateral electrolytic lesions of NBM, adult male Wistar rats were immunized with bovine serum albumin in complete Freund's adjuvant (BSA-CFA) and placed individually or in groups of five rats during 21 days. On days 10 and 21 after immunization, the Arthus and delayed hypersensitivity skin reactions to BSA as well as anti-BSA antibody production were determined. On day 10, the diameter and intensity of delayed hypersensitivity skin reaction to BSA were significantly higher in social-isolated rats in comparison with the group-reared ones. On day 21, the diameter and intensity of the Arthus skin reaction were significantly higher in social-isolated rats compared to group-reared rats. Between days 10 and 21, the diameter and intensity of the Arthus skin reaction significantly increased in social-isolated rats, while the diameter of delayed hypersensitivity skin reaction significantly decreased. In contrast to social-isolated rats, there were no significant differences in Arthus and delayed hypersensitivity skin reactions in group-reared rats, between days 10 and 21. Also there were no significant differences in the production of anti-BSA antibody between social-isolated and group-reared rats. The relative spleen weight was significantly lower in social-isolated rats. These data suggest that chronic isolation stress modify humoral and cellular immunity in NBM-lesioned rats.

Journal Article↗
PubMed1998

The leukotriene B4 receptor functions as a novel type of coreceptor mediating entry of primary HIV-1 isolates into CD4-positive cells.

The recently cloned human chemoattractant receptor-like (CMKRL)1, which is expressed in vivo in CD4-positive immune cells, has structural homology with the two chemokine receptors C-C chemokine receptor (CCR)5 and C-X-C chemokine receptor (CXCR)4, which serve as the major coreceptors necessary for fusion of the HIV-1 envelope with target cells. In view of the structural similarity, CMKRL1 was tested for its possible function as another HIV-1 coreceptor after stable expression in murine fibroblasts bearing the human CD4 receptor. The cells were infected with 10 primary clinical isolates of HIV-1, and entry was monitored by semiquantitative PCR of viral DNA. The efficiency of the entry was compared with the entry taking place in CD4-positive cells expressing either CCR5 or CXCR4. Seven of the isolates used CMKRL1 for viral entry; they were mainly of the syncytium-inducing phenotype and also used CXCR4. Entry efficiency was higher with CMKRL1 than with CXCR4 for more than half of these isolates. Three of the ten isolates did not use CMKRL1; instead, entry was mediated by both CCR5 and CXCR4. The experiments thus indicate that CMKRL1 functions as a coreceptor for the entry of HIV-1 into CD4-positive cells. In the course of this study, leukotriene B4 was shown to be the natural ligand for this receptor (now designated BLTR), which therefore represents a novel type of HIV-1 coreceptor along with the previously identified chemokine receptors. BLTR belongs to the same general chemoattractant receptor family as the chemokine receptors but is structurally more distant from them than are any of the previously described HIV-1 coreceptors.

3T3 Cells↗
PubMed1996

Sensitivity to inhibition by beta-chemokines correlates with biological phenotypes of primary HIV-1 isolates.

Primary HIV-1 isolates were evaluated for their sensitivity to inhibition by beta-chemokines RANTES (regulated upon activation, normal T-cell expressed and secreted), macrophage inflammatory protein 1 alpha (MIP-1 alpha), and MIP-1 beta. Virus isolates of both nonsyncytium-inducing (NSI) and syncytium-inducing (SI) biological phenotypes recovered from patients at various stages of HIV-1 infection were assessed, and the results indicated that only the isolates with the NSI phenotype were substantially inhibited by the beta-chemokines. More important to note, these data demonstrate that resistance to inhibition by beta-chemokines RANTES, MIP-1 alpha, and MIP-1 beta is not restricted to T cell line-adapted SI isolates but is also a consistent property among primary SI isolates. Analysis of isolates obtained sequentially from infected individuals in whom viruses shifted from NSI to SI phenotype during clinical progression exhibited a parallel loss of sensitivity to beta-chemokines. Loss of virus sensitivity to inhibition by beta-chemokines RANTES, MIP-1 alpha, and MIP-1 beta was furthermore associated with changes in the third variable (V3) region amino acid residues previously described to correlate with a shift of virus phenotype from NSI to SI. Of interest, an intermediate V3 genotype correlated with a partial inhibition by the beta-chemokines. In addition, we also identified viruses sensitive to RANTES, MIP-1 alpha, and MIP-1 beta of NSI phenotype that were isolated from individuals with AIDS manifestations, indicating that loss of sensitivity to beta-chemokine inhibition and shift in viral phenotype are not necessarily prerequisites for the pathogenesis of HIV-1 infection.

Acquired Immunodeficiency Syndrome↗
PubMed1996

SIV infection of monkey spleen cells including follicular dendritic cells in different stages of disease.

Immunoaffinity enriched spleen follicular dendritic cells (FDCs), lymphocytes, and macrophages from SIVsm-inoculated cynomolgus monkeys (Macaca fascicularis) at different stages of disease were compared for latent and productive SIV infection. Analysis of FDCs by in situ hybridization, electron microscopy, and coculture assays indicated that comparatively high levels of virus were associated with the FDC fraction. Polymerase chain reaction (PCR) and RT-PCR results revealed that the levels for SIVpol DNA did not correlate with the level of env mRNA in the various cell subsets, suggesting differences in latency. Limiting dilution assays for spliced env mRNA showed a 10-100-fold higher amount of env mRNA in FDCs than in other spleen cell subsets early during SIV infection. At late stages of disease, the number of productively infected FDCs significantly decreased in parallel with a marked reduction of the FDC network and follicular involution. Our findings indicate that destruction of FDCs probably reflects a cytopathic effect of SIV and/or the activity of specific antiviral cytotoxic T lymphocytes.

Animals↗
PubMed1995

Safety and effectiveness of leflunomide in the treatment of patients with active rheumatoid arthritis. Results of a randomized, placebo-controlled, phase II study.

OBJECTIVE: To assess the safety and effectiveness of leflunomide versus placebo in patients with active rheumatoid arthritis (RA) treated for 6 months. METHODS: Four hundred two patients were randomly assigned to receive placebo or leflunomide at 5 mg, 10 mg, or 25 mg daily. A washout period of 6-12 weeks from prior second-line therapy was required. RESULTS: Statistically significant improvement in primary and secondary outcome measures, as well as by responder analyses, occurred in the 10-mg and 25-mg dosage groups compared to placebo. Twenty-one patients (7.0%) in the active treatment groups withdrew due to adverse events (AEs). The incidence of AEs was higher with leflunomide than with placebo. Gastrointestinal symptoms, weight loss, allergic reactions, skin rash, and reversible alopecia were more common in the 10-mg and 25-mg dosage groups. The incidence of infections was similar between the treatment and placebo groups; no opportunistic infections were seen. Transient elevations in liver function studies were noted in a small number of patients. CONCLUSION: Leflunomide is effective in daily doses of 10 mg and 25 mg in patients with active RA. Improved efficacy at the 25-mg dose was associated with a higher incidence of AEs. Randomized, placebo-controlled trials using daily doses of 10 mg and 20 mg are under way in the US and Europe to confirm these positive results.

Adult↗
PubMed1995

Small nerve fibre dysfunction in a patient with Sjögren's syndrome. Neurophysiological and morphological confirmation.

An morphological confirmation of neurophysiologically assessed small nerve fibre dysfunction in a patient with Sjögren's syndrome was sought. Conventional motor and sensory nerve conduction studies were normal, while examination of the thermal specific and thermal pain sensitivity and an autonomic nervous system evaluation showed striking abnormalities. Sural nerve electron microscopy showed almost normally large nerve fibres and abnormalities in unmyelinated nerve fibres or Schwann cells, and verified morphologically the neurophysiologically supposed small nerve fibre involvement.

Female↗
PubMed1995

Interaction of avian sarcoma/leukemia viruses with heterologous hosts: inference for host-range and some pathogenic properties of human immunodeficiency viruses.

Although there are substantial differences between retroviruses originating from avian and primate species, a comparison of these two different biological systems reveals that interaction of these retroviruses with heterologous hosts involves similar biological principles. Retroviral isolates with high replicative capacity in natural targets (e.g. CD4+ lymphocytes and macrophages for human immunodeficiency viruses (HIVs) can infect other cell types [e.g. CD- astrocytes, follicular dendritic cells (FDC) in vivo and/or CD4+ neoplastic T cells in vitro] as well. These viral isolates may have a potential of infecting heterologous cells in vitro and can enlarge their host-range by establishing infection in other species, distantly related. Strains of avian sarcoma/leukemia viruses (ASLV) originating from their natural hosts, chickens, and infectious for other avian species, ducks, can frequently infect mammals (rodents). Similarly, HIV-1 strains infectious for chimpanzees possess capacity of establishing chronic infection in pig-tailed macaques. The broad host-range of retroviral isolates in both viral systems is accompanied by presence of additional structures in viral envelope. These novel or additional envelope structures may recognize alternate viral receptor(s). Moreover, the enlarged host range of primary HIV-1 isolates is evaluated by infection of neoplastic CD4+ permanent cell line, MT2, and serves as a predictive marker of progression of the viral infection toward AIDS.

Alpharetrovirus↗