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Biomedical subjects

A L Smith

Publications and source records attributed to A L Smith.

At least 91 records · Page 5Linked to original sources
PubMed1999

Humoral immunity and protection of mice challenged with homotypic or heterotypic parvovirus.

BACKGROUND AND OBJECTIVES: Two serotypes of autonomously replicating parvoviruses infect laboratory mice. Genome regions coding for the nonstructural proteins of minute virus of mice [MVM] and mouse parvovirus [MPV] are almost identical, whereas capsid-coding sequences are divergent. We addressed these questions: Does humoral immunity confer protection from acute infection after challenge with homotypic or heterotypic parvovirus, and if it confers protection against acute MPV infection, does it also protect against persistent MPV infection? METHODS: Infant mice without maternal antibody or antibody to MVM or MPV and young adult mice given normal mouse serum or antibody to MVM or MPV were challenged with homotypic or heterotypic virus. In situ hybridization with target tissues was the indicator of infection. RESULTS: Humoral immunity failed to confer protection against acute heterotypic parvovirus infection. In passive transfer studies, MPV DNA was observed occasionally in lymph nodes, intestine, or the spleen of MPV-challenged mice given homotypic antibody and kept for 6 or 28 days. Variable proportions of mice given MPV antibody and homotypic challenge had viral DNA in lymphoid tissues 56 days after virus inoculation. CONCLUSION: A mouse or colony that has sustained infection with MVM or MPV is probably fully susceptible to infection with the heterotypic virus.

Animals↗
PubMed1999

Comparison of the pathogenicity in rats of rat coronaviruses of different neutralization groups.

BACKGROUND AND PURPOSE: Rat coronaviruses (RCVs) are common natural pathogens of rats that cause clinical illness, necrosis, and inflammation of respiratory, salivary, and lacrimal organs. The aim of the study was to determine whether antigenically different strains of RCV vary in their pathogenic potential in rats. METHODS: Neutralization groups were identified by use of RCV strain-specific antisera. Sprague Dawley rats were inoculated oronasally with RCV-SDA, RCV-BCMM, or RCV-W. Histologic examination, immunohistochemical analysis, and reverse transcriptase-polymerase chain reaction analysis were performed on tissues from infected rats. RESULTS: Clinical illness was not evident in any of the inoculated rats. The RCV-SDA strain caused mild lesions in the exorbital gland of one rat. The RCV-BCMM strain caused severe lesions in the Harderian and parotid glands and mild lesions in the exorbital glands, lungs, and nasal mucosa. The RCV-W strain caused severe lesions in the Harderian, exorbital, and parotid glands and mild lesions in the submandibular glands, lungs, and nasal mucosa. The RNA concentration was highest in the Harderian, parotid, and exorbital glands of RCV-BCMM- and RCV-W-infected rats at postinoculation day 7. CONCLUSIONS: Although RCV-SDA, RCV-BCMM, and RCV-W caused different degrees and patterns of lesions, neutralization groups are not useful for predicting the pathogenic potential of a new RCV isolate.

Animals↗
PubMed1998

The development of topography in the hamster geniculo-cortical projection.

Precise point-to-point connectivity is the basis of ordered maps of the visual field. The immaturity of the newborn hamster's visual system has allowed us to examine emerging topography in the geniculo-cortical projection well before thalamic axons have reached their cortical target, layer IV. Using anterograde transneuronal labeling with wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP), we visualized the ingrowth of the whole population of geniculate fibers in the neonatal hamster. Two days after birth (P2), the bulk of the fibers is in the deep cortical layers and the subplate. At the same age, injections of paired retrograde tracers (red and green fluorescent latex microspheres) into area 17 reveal an unordered projection from the dorsal lateral geniculate nucleus (dLGN) to cortex. Individual labeled cells are found throughout the dLGN, and quantitative analysis reveals no segregation of the red and the green populations. At P6, when the pattern of geniculate back label appears ordered and essentially adult-like, geniculate fibers have reached layer IV. The role of selective cell death in this process was investigated by making a tracer injection at P2 and allowing the animals to survive to P6 or P12, when the map is mature. The results show early labeled neurons that made inappropriate connections when the projection was scattered surviving through the period of geniculate cell death. We conclude that the geniculo-cortical map develops from an initially unordered projection to the subplate and the lower cortical layers. Selective cell death appears not to contribute significantly to this process.

Animals↗
PubMed1998

Mouse parvovirus infection potentiates allogeneic skin graft rejection and induces syngeneic graft rejection.

BACKGROUND: The recently identified autonomous mouse parvovirus designated mouse parvovirus-1 (MPV-1) persists in adult BALB/c mice for at least 9 weeks, infects lymphoid tissues, interferes with the ability of cloned T cells to proliferate, and exhibits immunomodulatory properties. As a consequence of these findings, the present studies were undertaken to characterize further the inmunomodulatory effects of MPV-1 on T cell-mediated immune responses in vivo and in vitro. METHODS: To evaluate the effect of MPV-1 infection on CD8+ T cell-mediated responses, BALB/c-H2dm2 mice were infected after transplantation of allogeneic BALB/c skin. RESULTS: MPV-1 potentiated the rejection of allogeneic skin grafts. This potentiation was not a result of virus infecting the cellular or vascular component of the graft as determined by in situ hybridization, but was mediated by T cells. However, the proliferative capacity of alloantigen-reactive lymphocytes from graft-sensitized infected mice was diminished. MPV-1 also induced the rejection of syngeneic skin grafts, and T cells from these infected graft-sensitized mice lysed syngeneic P815 target cells. CONCLUSIONS: These results suggest that MPV-1 infection of skin-grafted mice may disrupt normal mechanisms of peripheral tolerance and provide a unique model to study virus-induced autoimmunity.

Animals↗
PubMed1998

Development of laminar distributions of kainate receptors in the somatosensory cortex of mice.

Kainate receptors were present at birth in the murine somatosensory cortex as revealed by quantitative in vitro autoradiography. During the first five postnatal days [3H]kainate binding rapidly increased and the maximum density in layer IV was reached at P12. The adult laminar pattern of receptor binding distribution was established by the third postnatal week with the heaviest labeling of infragranular layers. The sharp increase of kainate receptor during the first postnatal week coincides with the critical period for cytoarchitectonic plasticity of the barrels and establishment of functional thalamo-cortical connections in the barrel field.

Animals↗
PubMed1998

Progress in the management of Alzheimer's disease.

As the population of the United States continues to age, age-related diseases such as Alzheimer's, the most common form of dementia, pose an increasing clinical challenge. The diagnosis of Alzheimer's disease hinges on the evaluation of cognitive function. Management options are expanding and include new cholinesterase inhibitors, cholinergic agonists, antioxidants, monoamine oxidase inhibitors, and estrogen.

Adult↗
PubMed1998

Genetic analysis of the essential components of the immunoprotective response to infection with Eimeria vermiformis.

The immune responses generated after infection with Eimeria spp. are complex, include both cellular and humoral components, and lead to protection against re-infection. To facilitate the rational development of the next generation of anticoccidial vaccines it is important that the nature of the immunoprotective response against infection with Eimeria spp. is determined. In this brief report we discuss results that were obtained using a combination of genetic and cellular approaches to dissect the essential immune effector components that operate against infection with Eimeria vermiformis. Mice rendered deficient of immune function by targeted gene disruption at a variety of immune loci represent an integral component of our studies and include those with targeted gene disruption at loci that encode the B- and T-cell receptors (BCR, TCR), antigen presentation molecules and immune-effector molecules. Our studies demonstrated that TCR-alpha-beta + T cells are essential for immunoprotection during both primary and secondary infection. Moreover, during primary infection the major effector cell type is a population of major histocompatibility complex class II-restricted, interferon-gamma-producing TCR-alpha-beta T cell consistent with a T helper 1 phenotype. In addition, there is a supplementary role for another class of cells (presumably T cells) that are restricted to either non-classical antigen presentation molecules or classical major histocompatibilty complex class I loaded via an atypical pathway. Mice with a deficiency in interleukin-6 were slightly more susceptible to primary infection than intact animals, consistent with the reported effects of interleukin-6 upon the generation of T helper 1-type responses in vivo. In terms of the host response to re-infection, TCR-alpha-beta T cells were essential for immunity, but the requirement for specific cell subsets and effector mechanisms was much less stringent. Mice deficient in gamma-delta T cells, classical major histocompatibility complex class I, non-classical antigen presentation pathways, the cytokines interferon-gamma, interleukin-4, interleukin-6 and the cytolytic effector molecules perforin or FasL were completely immune to secondary infection. Moreover, major histocompatibility complex class II-deficient I-A-beta-/- mice were capable of mounting a substantial response to secondary infection, manifest by a 95% reduction in oocyst output compared with primary infection. These data have important consequences for the development of immune intervention strategies and indicate that vaccine development may be targeted toward the generation of a wider range of effector mechanisms than those that operate during primary infection.

Animals↗
PubMed1998

Observational learning and the fearful child: influence of peer models on swimming skill performance and psychological responses.

This study examined the role of peer mastery and coping models on children's swimming skills, fear, and self-efficacy. Children (N = 24; M age = 6.2 years), who were identified as fearful of the water, were matched to control, peer-mastery, or peer-coping model conditions. Day 1 included a preintervention assessment. Days 2-4 included exposure to model conditions followed by a 20-min swimming lesson, Day 5 consisted of postintervention assessments, and a follow-up test was conducted 4 days later. Data were analyzed in a series of 3 x 3 (Model Type x Assessment Period) repeated measures analyses of variance on the dependent variables. Results revealed differences between modeling and control groups at postintervention and follow-up, but the small sample size and large within-group variability compromised many statistically significant findings. Calculation of effect sizes indicated moderate-to-large pre- to posintervention differences between control and modeling groups on skill, self-efficacy, and fear of swimming. These findings suggest that a modeling intervention combined with swimming lessons is a more effective behavior change agent for fearful children than swimming lessons alone.

Adaptation, Psychological↗
PubMed1998

Evolution of the major pilus gene cluster of Haemophilus influenzae.

Haemophilus influenzae is a ubiquitous colonizer of the human respiratory tract and causes diseases ranging from otitis media to meningitis. Many H. influenzae isolates express pili (fimbriae), which mediate adherence to epithelial cells and facilitate colonization. The pilus gene (hif) cluster of H. influenzae type b maps between purE and pepN and resembles a pathogenicity island: it is present in invasive strains, absent from the nonpathogenic Rd strain, and flanked by direct repeats of sequence at the insertion site. To investigate the evolution and role in pathogenesis of the hif cluster, we compared the purE-pepN regions of various H. influenzae laboratory strains and clinical isolates. Unlike Rd, most strains had an insert at this site, which usually was the only chromosomal locus of hif DNA. The inserts are diverse in length and organization: among 20 strains, nine different arrangements were found. Several nontypeable isolates lack hif genes but have two conserved open reading frames (hicA and hicB) upstream of purE; their inferred products are small proteins with no data bank homologs. Other isolates have hif genes but lack hic DNA or have combinations of hif and hic genes. By comparing these arrangements, we have reconstructed a hypothetical ancestral genotype, the extended hif cluster. The hif region of INT1, an invasive nontypeable isolate, resembles the hypothetical ancestor. We propose that a progenitor strain acquired the extended cluster by horizontal transfer and that other variants arose as deletions. The structure of the hif cluster may correlate with colonization site or pathogenicity.

Amino Acid Sequence↗
PubMed1998

Molecular evidence for distinct genotypes of monkey B virus (herpesvirus simiae) which are related to the macaque host species.

Although monkey B virus (herpesvirus simiae; BV) is common in all macaque species, fatal human infections appear to be associated with exposure to rhesus macaques (Macaca mulatta), suggesting that BV isolates from rhesus monkeys may be more lethal to nonmacaques than are BV strains indigenous to other macaque species. To determine if significant differences that would support this supposition exist among BV isolates, we compared multiple BV strains isolated from rhesus, cynomolgus, pigtail, and Japanese macaques. Antigenic analyses indicated that while the isolates were very closely related to one another, there are some antigenic determinants that are specific to BV isolates from different macaque species. Restriction enzyme digest patterns of viral DNA revealed marked similarities between rhesus and Japanese macaque isolates, while pigtail and cynomolgus macaque isolates had distinctive cleavage patterns. To further compare genetic diversity among BV isolates, DNA sequences from two regions of the viral genome containing genes that are conserved (UL27 and US6) and variable (US4 and US5) among primate alphaherpesviruses, as well as from two noncoding intergenic regions, were determined. From these sequence data and a phylogenetic analysis of them it was evident that while all isolates were closely related strains of BV, there were three distinct genotypes. The three BV genotypes were directly related to the macaque species of origin and were composed of (i) isolates from rhesus and Japanese macaques, (ii) cynomolgus monkey isolates, and (iii) isolates from pigtail macaques. This study demonstrates the existence of different BV genotypes which are related to the macaque host species and thus provides a molecular basis for the possible existence of BV isolates which vary in their levels of pathogenicity for nonmacaque species.

Animals↗
PubMed1998

Flare during drug withdrawal as a method to support efficacy in rheumatoid arthritis: amiprilose hydrochloride as an example in a double blind, randomized study.

OBJECTIVE: To evaluate the use of a randomized, double blind, drug withdrawal design as a means to test the efficacy of longterm therapy with antirheumatic drugs. METHODS: We evaluated 286 patients with rheumatoid arthritis (RA) treated with amiprilose hydrochloride for 1-3 years, with response, with or without other antirheumatic therapy, in a double blind, 12 week withdrawal study that compared patients randomized to continue amiprilose therapy vs patients randomized to placebo. The primary efficacy variable was preventing a predefined degree of clinical reactivation, or flare; the statistical tests of success were a difference in the proportion of flares and in the mean time to flare. RESULTS: Thirty percent of patients taking amiprilose and 43% of placebo patients experienced flare (p = 0.026). Patients taking amiprilose had a longer flare-free interval compared to placebo patients (p = 0.027), with the time to reactivation or flare becoming statistically different 73 days after withdrawal. CONCLUSION: Placebo controlled withdrawal designs are useful as evidence to support the longterm effectiveness of therapy in a proportion of patients with RA.

Adolescent↗
PubMed1998

Single-field total lymphoid irradiation in the treatment of refractory rejection after heart transplantation.

Nine heart transplant recipients were treated with single-field total lymphoid irradiation (TLI) for early (<1 year) or late (>1 year) rejection that was refractory to multiple regimens of immunosuppressive therapy. For patients with early rejection (n = 6), the rejection frequency (rejections/patient/month) decreased from pre-TLI of 1.63 to post-TLI of .02 (p < .001), and for patients with late rejection (n = 3), the rejection frequency decreased from pre-TLI of .23 to post-TLI of .05 (p < .02). The reduced rejection frequencies have been maintained for a mean follow-up of 28.6 (8 to 78) months, and adverse events during or late after TLI were uncommon. Single-field TLI is a safe and effective technique in the management of refractory rejection early or late after heart transplantation.

Adolescent↗