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Biomedical subjects

J Richardson

Publications and source records attributed to J Richardson.

At least 127 records · Page 7Linked to original sources
PubMed1998

Delayed infection after immunization with a peptide from the transmembrane glycoprotein of the feline immunodeficiency virus.

Recent advances in the quantitative assessment of viral burden, by permitting the extension of criteria applied to assess the efficacy of vaccines from all-or-none protection to diminution of the viral burden, may allow the identification of original immunogens of value in combined vaccines. Peptides corresponding to three domains of the envelope glycoproteins of feline immunodeficiency virus that are recognized during natural infection were used to immunize cats. After challenge with a primary isolate of feline immunodeficiency virus, the development of acute infection was monitored by quantitative assessment of the viral burden in plasma and tissues by competitive reverse transcription-PCR, by measurement of the humoral response developed to viral components, and by lymphocyte subset analysis. Whereas immunization with two peptides derived from the surface glycoprotein had no effect on the early course of infection, immunization with a peptide derived from the transmembrane glycoprotein delayed infection, as reflected by a diminished viral burden in the early phase of primary infection and delayed seroconversion. This peptide, located in the membrane-proximal region of the extracellular domain, has homology to an epitope of human immunodeficiency virus type 1 recognized by a broadly neutralizing monoclonal antibody. These results suggest that lentivirus transmembrane glycoproteins share a determinant in the juxtamembrane ectodomain which could be of importance in the design of vaccines against AIDS.

Acute Disease↗
PubMed1998

Lens-specific gene recruitment of zeta-crystallin through Pax6, Nrl-Maf, and brain suppressor sites.

Zeta-Crystallin is a taxon-specific crystallin, an enzyme which has undergone direct gene recruitment as a structural component of the guinea pig lens through a Pax6-dependent mechanism. Tissue specificity arises through a combination of effects involving three sites in the lens promoter. The Pax6 site (ZPE) itself shows specificity for an isoform of Pax6 preferentially expressed in lens cells. High-level expression of the promoter requires a second site, identical to an alphaCE2 site or half Maf response element (MARE), adjacent to the Pax6 site. A promoter fragment containing Pax6 and MARE sites gives lens-preferred induction of a heterologous promoter. Complexes binding the MARE in lens nuclear extracts are antigenically related to Nrl, and cotransfection with Nrl elevates zeta-crystallin promoter activity in lens cells. A truncated zeta promoter containing Nrl-MARE and Pax6 sites has a high level of expression in lens cells in transgenic mice but is also active in the brain. Suppression of the promoter in the brain requires sequences between -498 and -385, and a site in this region forms specific complexes in brain extract. A three-level model for lens-specific Pax6-dependent expression and gene recruitment is suggested: (i) binding of a specific isoform of Pax6; (ii) augmentation of expression through binding of Nrl or a related factor; and (iii) suppression of promoter activity in the central nervous system by an upstream negative element in the brain but not in the lens.

Animals↗
PubMed1998

Trigeminal nerve hypertrophy in chronic inflammatory demyelinating polyradiculoneuropathy.

An unusual clinical manifestation of nerve hypertrophy in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is described. A patient with a 13-year history of CIDP developed diplopia and proptosis. Imaging of the neuraxis showed marked bilateral trigeminal nerve hypertrophy and lumbosacral nerve root hypertrophy. Biopsy of the right infraorbital nerve revealed inflammatory infiltrates and extensive onion bulb formation, consistent with CIDP.

Adult↗
PubMed1998

Overlapping functions of the myogenic bHLH genes MRF4 and MyoD revealed in double mutant mice.

The myogenic basic helix-loop-helix (bHLH) genes - MyoD, Myf5, myogenin and MRF4 - exhibit distinct, but overlapping expression patterns during development of the skeletal muscle lineage and loss-of-function mutations in these genes result in different effects on muscle development. MyoD and Myf5 have been shown to act early in the myogenic lineage to establish myoblast identity, whereas myogenin acts later to control myoblast differentiation. In mice lacking myogenin, there is a severe deficiency of skeletal muscle, but some residual muscle fibers are present in mutant mice at birth. Mice lacking MRF4 are viable and have skeletal muscle, but they upregulate myogenin expression, which could potentially compensate for the absence of MRF4. Previous studies in which Myf5 and MRF4 null mutations were combined suggested that these genes do not share overlapping myogenic functions in vivo. To determine whether the functions of MRF4 might overlap with those of myogenin or MyoD, we generated double mutant mice lacking MRF4 and either myogenin or MyoD. MRF4/myogenin double mutant mice contained a comparable number of residual muscle fibers to mice lacking myogenin alone and myoblasts from those double mutant mice formed differentiated multinucleated myotubes in vitro as efficiently as wild-type myoblasts, indicating that neither myogenin nor MRF4 is absolutely essential for myoblast differentiation. Whereas mice lacking either MRF4 or MyoD were viable and did not show defects in muscle development, MRF4/MyoD double mutants displayed a severe muscle deficiency similar to that in myogenin mutants. Myogenin was expressed in MRF4/MyoD double mutants, indicating that myogenin is insufficient to support normal myogenesis in vivo. These results reveal unanticipated compensatory roles for MRF4 and MyoD in the muscle differentiation pathway and suggest that a threshold level of myogenic bHLH factors is required to activate muscle structural genes, with this level normally being achieved by combinations of multiple myogenic bHLH factors.

Animals↗
PubMed1998

The management of postsurgical pain in the elderly population.

It is likely that the trend towards ever more aggressive surgery in elderly and possibly frail patients will continue, with the lifting of traditional age limits. Recent evidence has show that surgical trauma induces processes of nervous system sensitisation that contributes to and enhances postoperative pain and leads to chronic pain. This knowledge provides a rational basis for pro-active, pre-operative and post-operative analgesic strategies which can reduce the neuronal barrage associated with tissue damage. As well as a reduction or elimination of post-operative pain, an improvement in physiological variables, such as neuroendocrine stress responses and post-operative pulmonary function can be expected. Complete pain control cannot be achieved with a single agent or technique without significant serious adverse effects, a problem which is compounded in the elderly patient due to a combination of slower drug metabolism, decreased organ function and physiological changes in cardiovascular and respiratory reserves. A balanced analgesic regimen that includes an effective afferent block (regional analgesia) is more appropriate. By preventing postoperative pain and its associated neuroendocrine sequelae, major surgical procedures in traditionally unsuitable patients can be seriously considered.

Aged↗
PubMed1998

Lung volume reduction surgery for emphysema. A review.

Lung volume reduction surgery is emerging as a promising treatment option for selected patients with severe, debilitating end-stage emphysema refractory to medical management. Lung volume reduction surgery involves the removal of space occupying severely diseased, slowly ventilating and hyperexpanded lung, thus allowing the better conserved adjoining lung parenchyma to expand into the vacated space and function effectively. The operation can be accomplished by unilateral or bilateral thoracoscopy, thoracotomy or median sternotomy. The most emphysematous areas are excised using stapling or laser techniques or both. This review summarises the results of lung volume reduction surgery performed by various operative techniques. Results indicate that in the majority of patients improvement occurs in subjective dyspnoea and objective pulmonary function while oxygen and steroid dependence are reduced or eliminated at the cost of acceptable mortality and morbidity. Even though bilateral procedures produced much greater improvement, it is emphasized that it is the lung resection and not the operative approach that is critical to the success of the operation. Regardless of the technique used, the surgical treatment of emphysema is palliative in nature.

Endoscopy↗
PubMed1997

Molecular characterization of two mammalian bHLH-PAS domain proteins selectively expressed in the central nervous system.

Here we describe two mammalian transcription factors selectively expressed in the central nervous system. Both proteins, neuronal PAS domain protein (NPAS) 1 and NPAS2, are members of the basic helix-loop-helix-PAS family of transcription factors. cDNAs encoding mouse and human forms of NPAS1 and NPAS2 have been isolated and sequenced. RNA blotting assays demonstrated the selective presence of NPAS1 and NPAS2 mRNAs in brain and spinal cord tissues of adult mice. NPAS1 mRNA was first detected at embryonic day 15 of mouse development, shortly after early organogenesis of the brain. NPAS2 mRNA was first detected during early postnatal development of the mouse brain. In situ hybridization assays using brain tissue of postnatal mice revealed an exclusively neuronal pattern of expression for NPAS1 and NPAS2 mRNAs. The human NPAS1 gene was mapped to chromosome 19q13.2-q13.3, and the mouse Npas1 gene to chromosome 7 at 2 centimorgans. Similarly, the human NPAS2 gene was assigned to chromosome 2p11.2-2q13, and the mouse Npas2 gene to chromosome 1 at 21-22 centimorgans. The chromosomal regions to which human NPAS1 and NPAS2 map are syntenic with those containing the mouse Npas1 and Npas2 genes, indicating that the mouse and human genes are true homologs.

Amino Acid Sequence↗
PubMed1997

Protective immune responses to Theileria annulata of relevance to vaccine development.

A series of projects on Theileria annulata funded by the European Union (STD1/STD2/STD3) have provided convincing evidence that macrophage and natural killer (NK) cell-dependent immune mechanisms may directly control the proliferation of different stages of T. annulata in cattle. The evidence for this conclusion and the implications for vaccine development are discussed in the following paper.

Animals↗
PubMed1997

Anticipatory postural adjustments in stance and grip.

The reactive forces and torques associated with moving a hand-held object between two points are potentially destabilising, both for the object's position in the hand and for body posture. Previous work has demonstrated that there are increases in grip force ahead of arm motion that contribute to object stability in the hand. Other studies have shown that early postural adjustments in the legs and trunk minimise the potential perturbing effects on body posture of rapid voluntary arm movement. This paper documents the concurrent evolution of grip force and postural adjustments in anticipation of dynamic and static loads. Subjects held a manipulandum in precision grasp between thumb and index finger and pulled or pushed either a dynamic or a fixed load horizontally towards or away from the body (the grasp axis was orthogonal to the line of the load force). A force plate measured ground reaction torques, and force transducers in the manipulandum measured the load (tangential) and grip (normal) forces acting on the thumb and finger. In all conditions, increases in grip force and ground reaction torque preceded any detectable rise in load force. Rates of change of grip force and ground reaction torque were correlated, even after partialling out a common dependence on load force rate. Moreover, grip force and ground reaction torque rates at the onset of load force were correlated. These results imply the operation of motor planning processes that include anticipation of the dynamic consequences of voluntary action.

Adult↗
PubMed1997

Prevalence of asthma and wheezing in public schoolchildren: association with maternal smoking during pregnancy.

BACKGROUND: Asthma is the most common chronic disease in childhood. The prevalence of asthma is especially high in inner city children. The occurrence of asthma may be associated with many environmental factors, including involuntary exposure to maternal smoking. OBJECTIVES: This study reports prevalence of asthma and wheezing in a sample of public school students in Chicago and examines the association between maternal smoking during pregnancy and childhood asthma. METHODS: A total of 705 fifth grade students from 13 public schools participated in the study. A slightly modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was administered in classrooms to assess students' wheezing and asthma prevalence. RESULTS: Overall, 34.5% of children reported ever wheezing, 28.9% reported wheezing in the past year, 21.1% reported exercise-related wheezing in the past year, 23.6% reported physician-diagnosed asthma, 16.1% reported taking asthma or wheezing medication in the past 2 weeks, and 15.2% reported visiting emergency rooms for treatment of asthma in the past year. After adjusting for confounding variables in a logistic model, maternal smoking during pregnancy was significantly associated with children's asthma (adjusted odds ratio = 1.9; 95% confidence interval: 1.1 to 3.5). CONCLUSIONS: This study reports high prevalence of asthma and wheezing among the students and suggests that maternal smoking during pregnancy may increase the risk of asthma in children.

Asthma↗
PubMed1997

Monochromatic energy-subtraction radiography using a rotating anode source and a bent Laue monochromator.

A system for area-beam energy-subtraction monochromatic radiography was developed and tested. It utilizes a bent Laue crystal monochromator developed at the National Synchrotron Light Source (NSLS), and a compact rotating anode X-ray source developed at the Science Research Laboratory (SRL). The K(alpha) characteristic lines (both K(alpha 1) and K(alpha 2) of the cerium and barium targets were diffracted by the monochromator and used for the above- and below-K-edge imaging, respectively, of phantoms with iodine contrast agents. Digital subtraction of the images produced an iodine image.

Angiography, Digital Subtraction↗
PubMed1997

Amitriptyline accumulation and elimination in Calliphora vicina larvae.

Calliphora vicina larvae reared on artificial foodstuffs spiked with human equivalent therapeutic (100 ng/g), toxic (300 ng/g), lethal (500 ng/g), and 10 x lethal (5,000 ng/g) concentrations of amitriptyline and nortriptyline, alone and in various combinations, were harvested at various stages of development and analysed for drug content by high-pressure liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). Mean (range) larval amitriptyline concentrations (ng/g) in larvae reared on foodstuffs containing 100 ng/g, 500 ng/g, and 5,000 ng/g amitriptyline were 3.21 (<1-5.72), 21.3 (14.2-27.4), and 50.1 (38.8-64.3), respectively, on day 5; 6.62 (5.98-7.72), 22.5 (16.4-32.4), and 38 (22.8-50.9) on day 8; and 4.45 (3.45-5.93), 25.2 (18.6-38.4), and 26.2 (22.7-29.7) on day 11. Nortriptyline concentrations (ng/g) in larvae reared on foodstuffs containing 100 ng/g, 500 ng/g, and 5,000 ng/g nortriptyline were 6.86 (4.48-8.96), 14.1 (11.9-17.8), and 18.5 (16.7-20.6), respectively, on day 5; 8.32 (4.9-11.7), 12.9 (11.5-14.2), and 18.8 (11.5-23) on day 8; and 5.06 (3.27-7.25), 19.4 (17.8-22.4), and 26.6 (11.7-44.7) on day 11. Among 45 separate larval rearings fed on the same foodstuff, mean larval weight ranged from 24-96 mg and larval amitriptyline concentration from <1-148 ng/g. Biological variability in larval drug concentrations were greatest in larvae reared on high drug concentrations. Such variability makes quantitative extrapolation back to the drug concentration in foodstuff unreliable. Larval drug accumulation became unpredictable when larvae encounter more than one drug or different concentrations of a single drug. Drug concentrations measured were partly due to surface contamination with drug-rich putrefactive residue and they also depend partly on the analytical method used. Fly larvae are unreliable samples for quantitative toxicological analysis.

Administration, Oral↗
PubMed1997

A small region of the ecotropic murine leukemia virus (MuLV) gag gene profoundly influences the types of polytropic MuLVs generated in mice.

The vast majority of recombinant polytropic murine leukemia viruses (MuLVs) generated in mice after infection by ecotropic MuLVs can be classified into two major antigenic groups based on their reactivities to two monoclonal antibodies (MAbs) termed Hy 7 and 516. These groups very likely correspond to viruses formed by recombination of the ecotropic MuLV with two distinct sets of polytropic env genes present in the genomes of inbred mouse strains. We have found that nearly all polytropic MuLVs identified in mice infected with a substrain of Friend MuLV (F-MuLV57) are reactive with Hy 7, whereas mice infected with Moloney MuLV (Mo-MuLV) generate major populations of both Hy 7- and 516-reactive polytropic MuLVs. We examined polytropic MuLVs generated in NFS/N mice after inoculation with Mo-MuLV-F-MuLV57 chimeras to determine which regions of the viral genome influence this difference between the two ecotropic MuLVs. These studies identified a region of the MuLV genome which encodes the nucleocapsid protein and a portion of the viral protease as the only region that influenced the difference in polytropic-MuLV generation by Mo-MuLV and F-MuLV57.

Animals↗
PubMed1997

Enhancement of feline immunodeficiency virus (FIV) infection after DNA vaccination with the FIV envelope.

Despite intensive experimentation to develop effective and safe vaccines against the human immunodeficiency viruses and other pathogenic lentiviruses, it remains unclear whether an immune response that does not afford protection may, on the contrary, produce adverse effects. In the present study, the effect of genetic immunization with the env gene was examined in a natural animal model of lentivirus pathogenesis, infection of cats by the feline immunodeficiency virus (FIV). Three groups of seven cats were immunized by intramuscular transfer of plasmid DNAs expressing either the wild-type envelope or two envelopes bearing mutations in the principal immunodominant domain of the transmembrane glycoprotein. Upon homologous challenge, determination of plasma virus load showed that the acute phase of viral infection occurred earlier in the three groups of cats immunized with FIV envelopes than in the control cats. Genetic immunization, however, elicited low or undetectable levels of antibodies directed against envelope glycoproteins. These results suggest that immunization with the FIV env gene may result in enhancement of infection and that mechanisms unrelated to enhancing antibodies underlay the observed acceleration.

Amino Acid Sequence↗
PubMed1997

An epidemiological study of asthma prevalence and related factors among young adults.

Asthma and related factors were assessed by mailed questionnaires among 2041 young adult participants in a smoking prevention project in California in 1993. Hispanics had lower prevalence of physician-reported asthma when compared to blacks and whites. Blacks were significantly more likely to be hospitalized or visit emergency rooms because of asthma or wheezing. After adjusting for sex, race, and educational level, family history of asthma was strongly associated with subjects' asthma (odds ratio = 3.1, 95% CI: 2.4-4.3 for physician-reported asthma; OR = 3.3, 95% CI: 2.4-4.5 for current asthma). Exposure to parental smoking (both parents smoked more than half a pack of cigarettes a day) during childhood (reported when participants were in grade 7) was significantly associated with physician-reported asthma (OR = 2.9, 95% CI: 1.6-5.6) and current asthma (OR = 3.3, 95% CI: 1.7-6.4). The study also found that self-reported mold growth at home was significantly associated with asthma (OR = 2.0, 95% CI: 1.2-3.2). After adjusting for cigarette smoking and demographic variables, use of crack cocaine was marginally significantly associated with current asthma (OR = 2.3, 95% CI: 1.0-5.2), but not with physician-reported asthma (OR = 1.5, 95% CI: 0.7-3.3).

Adult↗