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Biomedical subjects

R Walder

Publications and source records attributed to R Walder.

At least 19 recordsLinked to original sources
PubMed2001

Bovine immunodeficiency virus in experimentally infected rabbit: tropism for lymphoid and nonlymphoid tissues.

The bovine immunodeficiency virus (BIV)/New Zealand (Oryctolagus cuniculus) rabbit model was used to study events that underlie the early and chronic stages of viral replication, routes and time course of viral dissemination and the distribution of the virus in the lymphoid. nonlymphoid and mucosa associated tissues. The results indicated that BIV, a lentivirus with genetic relatedness to the HIV, induced changes of clinical (anorexia, weight loss, muscular wasting, diarrhea, hypoalgesia, torticollis), immunological (recurrent T- and B-cell dysfunctions) and histopathological (lymphadenopathy, splenomegaly) nature that closely parallels those described for cat (Fly), monkey (SIV) and human (HIV) lentiviral diseases. These findings showing that BIV induces both splenomegaly and lymphadenopathy syndromes with associated fatal immune dysfunctions and the ability of the virus to replicate productively at the mucosal surfaces in rabbits, emphasize the importance of the BIV/rabbit system as a good small-animal model for the study of retrovirus-induced AIDS and offers the opportunity to evaluate prophylactic and therapeutic anti-retroviral agents of relevance to HIV-1 as well as the opportunity to study mechanisms of drug resistance phenomena.

Animals↗
PubMed2001

Genetic diversity and relationships among Venezuelan equine encephalitis virus field isolates from Colombia and Venezuela.

During field studies of enzootic Venezuelan equine encephalitis (VEE) viruses associated with epizootic emergence, a large number of virus isolates were made in sylvatic foci of Venezuela and Colombia. To rapidly characterize these isolates, antigenic subtypes were determined by means of immunofluorescence and by single-strand conformational polymorphism (SSCP) analysis by use of an 856-bp fragment from the P62 gene, which we used to distinguish genetic variants. Representative isolates were sequenced to assess the sensitivity of SSCP to detect genetic differences. The SSCP analysis distinguished isolates differing by as little as 1 nucleotide; overall, differences of > or = 1 nucleotide were recognized 89% of the time, and the sensitivity to distinguish strains that differed by only 1 or 4 nucleotides was 17 and 57%, respectively. Phylogenetic analyses of representative sequences showed that all recent isolates from the Catatumbo region of western Venezuela and the middle Magdalena Valley of Colombia were closely related to epizootic subtype IAB and IC strains; strains from Yaracuy and Miranda States were more distantly related. Cocirculation of the same virus genotype in both Colombian and Venezuelan foci indicated that these viruses are readily transported between enzootic regions separated by > 300 km. The SSCP analysis appears to be a simple, fast, and relatively efficient method of screening VEE virus isolates to identify meaningful genetic variants.

Aedes↗
PubMed2000

Detection of genetic diversity among bovine immunodeficiency virus population by single-strand conformation polymorphism analysis.

Serial virus specimens rescued from rabbits, experimentally infected with bovine immunodeficiency (BIV) strain R29, were monitored for changes in quasispecies population, using the single-strand conformation polymorphism (SSCP) analysis. The generation of characteristic SSCP patterns enables the rapid differentiation of BIV variants derived from the conserved part on the env region of the BIV genome, reducing the need for expensive and time-consuming direct sequencing analyses. Our results showed genetic polymorphism among a number of sampled BIV population in experimentally infected rabbits. At least three SSCP patterns (BIV quasispecies) were detected. The SSCP analysis allows for an easy, sensitive, and rapid screening of genetic variants of the virus and the assessment of variation at a number of tissue target sites. These variations may relate to cell-type targets and/or disease progression, and could be significant to our understanding of lentiviral pathogenesis.

Animals↗
PubMed1998

Selective in vitro protection of SIVagm-induced cytolysis by ajoene, [(E)-(Z)-4,5,9-trithiadodeca-1,6,11-triene-9 oxide].

We studied the effect of synthetic ajoene on simian immunodeficiency virus (SIVagm)-mediated cell fusion and subsequent virus-induced cytolysis. Our data indicate that this compound is a strong antifusion agent with a 50% syncytium inhibitory concentration (SIC50%) value of about 2.9 microM. We suggest that ajoene interacts with the cell-specific integrin molecules and sterically hinders the association between fusion (or other co-receptors) and the CD4-gp120 complex at the cell surface of SIV-infected cells. Although ajoene was maximally effective in suppressing syncytium formation during the early period (ie, up to 6 h) of the fusion process, when the compound was recurrently added to the co-cultures, the inhibitory effect was regained and further cell death was markedly delayed. This indicates that ajoene was also effective after the initial cell-to-cell contact stage. These data suggest that ajoene may be a promising approach for the treatment of SIV/human immunodeficiency virus (HIV) infections.

Antiviral Agents↗
PubMed1998

Infection of rabbits with R29 strain of bovine immunodeficiency virus: virulence, immunosuppression, and progressive mesenteric lymphadenopathy.

To assess the value of bovine immunodeficiency virus (BIV) infection as a model for human immunodeficiency virus (HIV) infection in man, we studied the impairment of certain immunologic functions in New Zealand white rabbits experimentally infected with an uncloned virulent isolate of the virus, BIV R29. Serum samples were tested by Western blot for the presence and persistence of antibody production. The T- and B-lymphocyte function was studied by evaluation of the blastogenic responsiveness to concanavalin A (Con A) and to dextran sulfate (DxS). All infected rabbits seroconverted to BIV antigens within 2 to 4 weeks postinfection (p.i.) The BIV was isolated from the peripheral blood lymphocytes (PBLs) of 13 of 17 rabbits (77%) early in the infection and also from 5 of 17 hyperplastic mesenteric lymph nodes (29%) and 10 of 17 spleens (59%) during the chronic stage of infection. Seven of 17 BIV-infected rabbits (41%) developed marked immunodepression 2 to 5 months p.i., and later, 5 exhibited a rapidly progressive disease with anorexia, weight loss, neurologic impairment, splenomegaly, and mesenteric lymphadenopathy. These data underline the value of the BIV model for studying HIV pathogenesis in vivo and the development of interventional strategies for AIDS.

Animals↗
PubMed1998

Genome scan and congenic strains for blood pressure QTL using Dahl salt-sensitive rats.

An F2 population (n = 151) derived from Dahl salt-sensitive (S) and Lewis rats was raised on a 8% NaCl diet for 9 weeks and analyzed for blood pressure quantitative trait loci (QTL) by use of a whole genome scan. Chromosomes 5 and 10 yielded lod scores for linkage to blood pressure that were significant; chromosomes 1, 2, 3, 8, 16, 17, and 18 gave lod scores suggestive for linkage. Chromosome 7 gave a significant signal for heart weight with a lesser effect on blood pressure. Congenic strains were constructed by introgressing Lewis low-blood-pressure QTL alleles for chromosomes 1, 5, 10, and 17 into the S genetic background. Congenic strains for chromosomes 1, 5, and 10 had significantly lower blood pressure than S, proving the existence of QTL on these chromosomes, but the chromosome 17 congenic strain failed to trap a contrasting QTL allele. The QTL allele increasing blood pressure originated from S rats for all QTL except those on chromosomes 2 and 7 in which the Lewis allele increased blood pressure. Interactions between each QTL and every other locus in the genome scan yielded significant interactions between chromosomes 10 and 4, and between chromosomes 2 and 3.

Animals↗
PubMed1997

Blood pressure and survival of a chromosome 7 congenic strain bred from Dahl rats.

11 beta-hydroxylase (Cyp11b1) mutations were previously linked to altered steroid biosynthesis and blood pressure in Dahl salt-resistant (R) and Dahl salt-sensitive (S) rats. In the present work, interval mapping identified a putative blood pressure quantitative trait locus (QTL) near Cyp11b1 in an F1(SxR)xS population (LOD = 2.0). Congenic rats (Designated S.R-Cyp11b) were constructed by introgressing the R-rat Cyp11b1 allele into the S strain. S.R-Cyp11b rats had significantly lower blood pressure and heart weight compared with S rats, proving the existence of a blood pressure QTL on Chromosome (Chr) 7 despite the fact that QTL linkage analysis of blood pressure never achieved stringent statistical criteria for significance. To test the effects of the introgressed region on blood pressure and survival, S.R.-Cyp11b and S rats were maintained on a 4% NaCl diet until they died or became moribund. Analysis of variance (ANOVA) indicated significant strain differences in blood pressure and days survived (P < 0.0001 for both) as well as gender differences in days survived (P = 0.0003). Kaplan-Meier survival analysis also found significant strain (P < 0.0001) and gender (P = 0.007) differences in days survived. However, when the effects of blood pressure were removed, significant strain differences in survival essentially disappeared. This suggests that the increased survival of S.R-Cyp11b rats was largely due to their decreased blood pressure and thus strongly corroborates the existence of a blood pressure QTL on Chr 7 near or at Cyp11b1.

Adrenal Hyperplasia, Congenital↗
PubMed1997

Anti-HIV activity of extracts from Calendula officinalis flowers.

Extracts of dried flowers from Calendula officinalis were examined for their ability to inhibit the human immunodeficiency virus type 1 (HIV-1) replication. Both organic and aqueous extracts were relatively nontoxic to human lymphocytic Molt-4 cells, but only the organic one exhibited potent anti-HIV activity in an in vitro MTT/tetrazolium-based assay. In addition, in the presence of the organic extract (500 micrograms/mL), the uninfected Molt-4 cells were completely protected for up to 24 h from fusion and subsequent death, caused by cocultivation with persistently infected U-937/HIV-1 cells. It was also found that the organic extract from Calendula officinalis flowers caused a significant dose- and time-dependent reduction of HIV-1 reverse transcription (RT) activity. An 85% RT inhibition was achieved after a 30 min treatment of partially purified enzyme in a cell-free system. These results suggested that organic extract of flowers from Calendula officinalis possesses anti-HIV properties of therapeutic interest.

Anti-HIV Agents↗
PubMed1997

In vitro suppression of HIV-1 replication by ajoene [(e)-(z)-4,5,9-trithiadodeca-1,6,11-triene-9 oxide].

Studies were performed to establish whether synthetic ajoene exhibited differential inhibitory activity against human immunodeficiency virus (HIV)-1 (IIIB) and to clarify the mechanism of its antiviral effects. Our results demonstrate that ajoene protected acutely infected Molt-4 cells against HIV-1 and blocked further destruction of CD4 T-cells in vitro. Ajoene showed dose-dependent inhibition, with 50% cytotoxic concentration (CTC50%) and 50% effective inhibitory concentration (EIC50%) values of 1.88 microM and about 0.35 microM, respectively, when the test compound was added before or after HIV-1 infection and incubation carried out at 37 degrees C for 4 days. Ajoene proved relatively more active than dextran sulfate in blocking HIV-1 virus-cell attachment. The mode of anti-HIV action of ajoene can be ascribed to the inhibition of early events of viral replication, particularly virus adsorption.

Adsorption↗
PubMed1997

Different effects of phorbol ester derivates on human immunodeficiency virus 1 replication in lymphocytic and monocytic human cells.

The mode of action of the phorbol 12,13-dibutyrate (PDBu) and phorbol 12-myristate 13-acetate (PMA) on the human immunodeficiency virus 1 (HIV-1) replication in human lymphocytes and monocytes was studied. PDBu and PMA appear to have similar effects on the regulation of HIV-1 replication in acutely infected cells. Here we show a significantly increased replication of HIV-1 induced by PDBu and PMA in Molt-4 and Jurkat cells, but a reduced replication in THP-1 and U-937 cells. Moreover, quantitatively different activity of the two derivatives in relation to HIV-1 replication was observed. PDBu proved to be a stronger stimulator or suppressor of HIV-1 replication as compared to PMA. Although the precise mechanism of the activation of HIV-1 replication by phorbol ester derivatives is not clear, it can be assumed that the hydrophilycity of PDBu may cause its stronger effect.

HIV-1↗
PubMed1995

Acquired immune dysfunction in rabbits experimentally infected with an infectious molecular clone of the bovine immunodeficiency virus (BIV127).

To investigate the effect of bovine immunodeficiency virus (BIV) infection on the rabbit immune system, we studied the proliferative responses of peripheral blood lymphocytes (PBLs) of rabbits experimentally inoculated with BIV. All BIV127-inoculated rabbits seroconverted after 6 weeks and remained seropositive over a prolonged period of time. Assays for specific lymphocyte reactivity to concanavalin A (Con A) were performed monthly for over 1 year. One-hundred percent of infected rabbits developed abnormally low T cell responses, as measured by Con A stimulation. By 3 months postinoculation, the PBL response to Con A was diminished and remained depressed for 6 months. All animals were clinically asymptomatic within 14 months of BIV inoculation. By 15 and 16 months postinoculation, two of three infected rabbits exhibited recurrent lowering of the T cell responsiveness including a decrease in absolute PBL counts. One of these animals died unexpectedly. Our results further confirmed that a functional impairment of lymphocytes was induced early in the course of BIV infection, prior to clinical disease. These findings suggested that BIV infection may mimic asymptomatic infection of human immunodeficiency virus (HIV) and provided further evidence of the importance of BIV-induced disease in rabbits as a relevant model for the study of AIDS.

Animals↗
PubMed1995

[Natural products from the tropical rain forest of Venezuela as inhibitors of HIV-1 replication].

More than 100 plant extracts from the Amazonian rain forest of Venezuela were evaluated for their cytotoxicity and inhibitory activity against the human immunodeficiency virus type-1 (HIV-1). Aqueous extracts from Fomitella supina (S # 0389-4), Phellinus rhabarbarinus (S # 0389-7), Trichaptum perrottetti (S # 0389-8) and Trametes cubensis (S # 0389-13), Polyporaceae exhibited strong anti-HIV-1 activity, without toxicity for Molt-4 lymphocytic cells. Our results demonstrated, that the compound(s) acted by mechanism of direct virion inactivation and by inhibition of syncytium formation in an in vitro culture system. These results support the suggestion that the test extracts specifically act at the level of CD4-gp120 binding. The active components of these extracts is at present unknown, but anti-AIDS agents, such as those found in this study, individually or in combination, may be of therapeutic relevance.

Antiviral Agents↗
PubMed1990

Cerebral serotonin in viral encephalitis.

In order to evaluate central serotonergic function during viral encephalitis biochemical, behavioural and immunohistofluorescence studies were carried out. Mice were inoculated with the moderate virulent strain of venezuelan equine encephalomyelitis virus, Pixuna. Signs of encephalitis were observed in 50-60% of infected animals. Levels of serotonin and 5-hydroxyindolacetic acid, and the ratio of the indolamine and its metabolite in raphe and cortex did not change with respect to sham-inoculated mice. A differential decrease in turnover rate by pharmacological methods, such as pargyline, p-chlorophenylalanine and probenecid administration, was observed in raphe and cortex. The ratio serotonin turnover rate/steady state concentration of serotonin was only decreased in the raphe of sick animals. The response to 5-methoxy-N,N-dimethyltryptamine was greater in infected animals. The duration of immobility in the swim test was shorter in the infected group. A greater number of viral antigen particles was localized in raphe and periraphe areas than in cortex, brain stem or striatum. The results suggest a serotonin presynaptic deficit, a postsynaptic hyperreactivity of serotonin system, and a region-selective distribution of the virus.

Animals↗
PubMed1988

Eosinophils from granulomas in murine schistosomiasis mansoni produce substance P.

Granulomas are chronic, usually focal, tissue-destructive inflammatory reactions that usually form around slowly degradable, poorly soluble substances. They are dynamic lesions, regulated by complex immune mechanisms. Tachykinins are a family of neuropeptides characterized by the common C-terminal amino acid sequence -Phe-X-Gly-Leu-Met-NH2. One such tachykinin, substance P, has been reported to modulate immunologic responses. In this investigation, granulomas were examined for substance P. Granulomas were isolated from the livers of mice infected with murine schistosomiasis, and substance P was extracted. Immunoreactive substance P was detected by RIA. The authenticity of the molecule was confirmed by elution profile on HPLC. Immunoreactive substance P, identified by immunostaining, localized to eosinophils derived from collagenase-dispersed granulomas. Granulomas were then probed for expression of the gene for substance P (preprotachykinin). Preprotachykinin mRNA was localized to granuloma eosinophils by in situ oligonucleotide hybridization. It is concluded that substance P is present within the granuloma as a result of preprotachykinin production by eosinophils.

Animals↗
PubMed1988

Behavioural effects produced in mice infected with venezuelan equine encephalomyelitis virus.

Pixuna, a strain of intermediate virulence of venezuelan equine encephalomyelitis virus, was inoculated intracranially to 24-day-old mice. Signs of encephalitis were present in 60% of the animals between 6 and 9 days with a maximum at 7 days postinoculation. The rest of the infected mice did not show clinical signs of encephalitis. In order to study the functional state of serotonergic systems a series of tests susceptible to modifications by serotonin activity were carried out. Locomotor activity was measured in an open field test. Virus-inoculated animals presented a variety of changes in their locomotor behavior at various days postinoculation with respect to the sham-inoculated group, however, they were not significant. Central serotonergic function was examined by the production of the serotonergic syndrome with the receptor agonist, 5-methoxy-N,N-dimethyltryptamine and the precursor, 5-hydroxytryptophan, both administered 4 days after the inoculation. The dose of the agonists was established by a prior drug-response analysis. Intensity of the syndrome was significantly higher in infected mice than in the sham-inoculated group only in 5-methoxy-N,N-dimethyltryptamine-treated animals. The behaviour in the swim test was also measured. Duration of immobility was much shorter in infected than in control mice. The decrease in central serotonin turnover previously reported might be responsible for the modification in locomotor behaviour and for the supersensitivity of serotonin receptors observed in infected mice.

Animals↗