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Biomedical subjects

D Walker

Publications and source records attributed to D Walker.

At least 253 records · Page 14Linked to original sources

Linkage studies of HLA and primary Sjögren's syndrome in multicase families.

OBJECTIVE: To define the role of HLA-DR phenotype in the expression of primary Sjögren's syndrome (SS). METHODS: A family study of Caucasian probands with definite primary SS was conducted. Relatives with features of primary SS were classified according to the Fox criteria. Several types of linkage analysis between primary SS and HLA haplotype (HLA-A, B, and DR) were performed. RESULTS: A trend toward haplotype sharing between affected siblings was evident for definite/probable primary SS when analyzed by the Green and Woodrow method. This reached statistical significance when data from other published family studies were included. LOD scores and analyses using the Penrose method showed little evidence of linkage. CONCLUSION: In view of the strong association with HLA-DR3, these results suggest that the HLA-DR3 allele is an important susceptibility factor for expression of primary SS in Caucasians. The apparent haplotype sharing may be a consequence of this association. The potential influence of other genetic factors (major histocompatibility complex [MHC] and non-MHC) is discussed.

Adolescent↗

Cartilage and bone formation in repairing Achilles tendons within diffusion chambers: evidence for tendon-cartilage and cartilage-bone conversion in vivo.

Rodent Achilles tendons were subjected to midpoint tenotomy and allowed to recover for various times in situ before the operated tissue was removed, placed into a Millipore diffusion chamber, and inserted intraperitoneally into syngeneic hosts. Diffusion chambers were then removed at weekly intervals, such that the total time after the operation (i.e., time allowed to recover in situ plus time within the diffusion chamber) was up to 8 weeks, and examined histologically. Ectopic cartilage was produced within the diffusion chamber after a total of 4 weeks but only if the first 2 weeks of recovery were in situ. With increasing time, calcified cartilage, osteoid, and bone were also observed. Overall, the evidence suggests that the cartilage forms via a direct conversion from tendon tissue and that the bone may form as a result of differentiative changes of hypertrophic chondrocytes.

Achilles Tendon↗

Thyroid disease and other autoimmune phenomena in a family study of primary Sjögren's syndrome.

Autoimmune diseases and autoantibodies have been documented in 42 index cases with definite primary Sjögren's syndrome (1 degree SS), 207 relatives and 39 spouses. The results were compared with control data from a local population survey. Thyroid disease, 1 degree SS and their associated autoantibodies were the commonest autoimmune abnormalities observed and found predominantly in older female relatives. The HLA-DR3 phenotype associated with 1 degree SS, antinuclear factor, hypothyroidism, and thyroid microsomal antibody. Rheumatoid arthritis and systemic lupus erythematosus were not found in excess in the families. Primary Sjögren's syndrome is frequently associated with thyroid disease and we suggest that there is a common genetic predisposition between these diseases which differs from 2 degrees SS associated with rheumatoid arthritis and systemic lupus erythematosus. This includes MHC and non-MHC genes.

Adolescent↗

Radium needle used to calibrate germanium gamma-ray detector.

A standard platinum-iridium needle that contains 374 MBq 226Ra was tested as a source for calibrating a portable germanium detector used with a gamma-ray spectrometer for environmental radioactivity measurements. The counting efficiencies of the 11 most intense gamma rays emitted by 226Ra and its short-lived radioactive progeny at energies between 186 and 2,448 keV were determined, at the full energy peaks, to construct a curve of counting efficiency vs. energy. The curve was compared to another curve between 43 and 1,596 keV obtained with a NIST mixed-radionuclide standard. It was also compared to the results of a Monte Carlo simulation. The 226Ra source results were consistent with the NIST standard between 248 and 1,596 keV. The Monte Carlo simulation gave a curve parallel to the curve for the combined radium and NIST standard data between 250 and 2,000 keV, but at higher efficiency.

Calibration↗

Loss of basic fibroblast growth factor in substantia nigra neurons in Parkinson's disease.

Basic fibroblast growth factor (bFGF) has a neurotrophic effect on mesencephalic dopaminergic neurons in vitro and in vivo. To explore whether an abnormality in bFGF expression occurs in Parkinson's disease (PD), we examined the substantia nigra (SN) of six PD and eight control cases immunohistochemically using a monoclonal antibody to bFGF. The mean number of melanin-positive neurons in sections of PD SN was 30.3% of the control mean, but the number of bFGF-immunopositive neurons was only 4.7% of the control mean. bFGF-immunoreactivity was present in only 8.2% of PD, but in 93.7% of control melanin-positive neurons. These results suggest a profound depletion of bFGF in surviving dopaminergic neurons of the SN in PD, and this depletion may be related to the disease process.

Adult↗

Key residues in the allosteric transition of Bacillus stearothermophilus pyruvate kinase identified by site-directed mutagenesis.

The structural gene for pyruvate kinase from Bacillus stearothermophilus has been cloned in Escherichia coli and sequenced. The open reading frame from the ATG start codon to the TAG stop codon is 1482 base-pairs and encodes a peptide of relative molecular mass 52,967. In the expression vector pKK223-3, containing the synthetic tac promoter, the gene is overexpressed in E. coli cells to an estimated level of 30% total soluble cell protein. A purification procedure for the overexpressed protein has been established. The construction and characterization of a pair of mutant proteins has given insight into the structural basis of allosteric regulation in the tetrameric enzyme. Substituting tryptophan for tyrosine at position 466 (mutant Trp466-->Tyr) resulted in an activated form of the enzyme, having a reduced K1/2 for the substrate phosphoenolpyruvate. We propose that the characteristics of this mutant might be the result of bulk removal releasing steric inhibition to the formation of an interdomain salt bridge between Asp356 and Arg444. The regulatory behaviour of the double mutant produced by making the additional substitution aspartate for glutamate at position 356 (Trp466-->Tyr/Asp356-->Glu) corroborates this. The position of the salt bridge is such that it might be pivotal to the conformation of a pocket that is proposed to open up when the active R-conformation is adopted. We suggest that the mechanism of activation of B. stearothermophilus pyruvate kinase by ribose-5-phosphate might hinge on an interaction with, or indirectly through, residue Trp466, removing it from the vicinity of the potential salt bridge between Asp356 and Arg444 and thus effecting a closing together of the protein structure concomitant with an opening up of the pocket region.

Allosteric Regulation↗

High molecular weight basic fibroblast growth factor-like protein is localized to a subpopulation of mesencephalic dopaminergic neurons in the rat brain.

A rabbit antiserum (R917) was raised to a purified fraction of bovine brain basic fibroblast growth factor (bFGF). On Western blots of rat midbrain extract, the antiserum did not recognize low molecular weight forms of bFGF. Instead, it recognized a single band of 27-28 kDa. Immunohistochemically, the antiserum preferentially stained a subpopulation of calbindin-negative mesencephalic dopaminergic neurons. The positive somata were mainly packed in a ventral portion of the tegmentum including the A10 region, the ventral tegmental area and the pars compacta of the medial substantia nigra, but were also scattered in both the pars compacta and reticulata portions of the lateral substantia nigra. Processes of dendrites and axons were clearly visible. Terminal fields were located in striosomes, the dorsolateral rim of the neostriatum, the anterodorsal aspect of the nucleus accumbens shell, the infralimbic cortex, and the medial prefrontal cortex. These results suggest that trophic specialization in subpopulations may occur in all three of these dopaminergic projection systems, i.e. the nigrostriatal, mesolimbic and mesocortical pathways.

Animals↗

Academic and environmental effects of small group arrangements in classrooms for students with autism and other developmental disabilities.

The use of small group instructional formats with children who have autism and developmental disabilities has received mixed results in the research literature (Reid & Favell, 1984). The purpose of the two studies reported herein was to address this controversy by comparing the performance of students in one-to-one instruction to those transitioned to small groups for a variety of teachers, students, settings, and under different training circumstances. In the first study, 41 students, ranging in age from 5 to 21 years old, from six classrooms, participated; and 25 students from six classrooms participated in the second study. Measures of environmental effects included academic gains via pre- and posttests, on-task and self-stimulatory behavior levels, correct responding, and frequencies of teacher behaviors during both one-to-one and small group formats. Results of both experiments indicated that students were able to successfully transition to small group formats across several curriculum areas including language, math, readiness, and shopping. Further, experienced teachers and administrators were able to train a second group of staff to use the small group procedures effectively. The successful application for this number of students and teachers within natural learning environments is unprecedented and provides important documentation for both the utility and practicality of small group instruction with students who have developmental disabilities.

Achievement↗

Pulmonary hemorrhage in premature infants after treatment with synthetic surfactant: an autopsy evaluation. The American Exosurf Neonatal Study Group I, and the Canadian Exosurf Neonatal Study Group.

In an across study analysis of five multicenter, placebo-controlled trials of the synthetic surfactant, Exosurf Neonatal in infants weighing at least 700 gm, the incidence of clinical pulmonary hemorrhage was 1.9% in treated infants and 1.0% in control infants. To investigate whether a similar increase was also present histologically at postmortem examination, a blinded retrospective review of all autopsy reports from infants dying during these five trials was conducted. Pulmonary hemorrhage was present in 55% of 159 infants undergoing autopsy; the incidence was not different in infants treated with surfactant or air placebo. Birth weight was inversely related to the incidence of pulmonary hemorrhage in both groups. Pulmonary pathologic findings significantly associated with pulmonary hemorrhage included pulmonary interstitial emphysema and necrotizing laryngotracheitis in both groups. In the surfactant group, patent ductus arteriosus, intraventricular hemorrhage, and pneumothorax were significantly more frequent among those who developed pulmonary hemorrhage. In contrast to clinical diagnosis, pathologic diagnosis of pulmonary hemorrhage at autopsy was not more common in infants treated with Exosurf Neonatal.

Autopsy↗

Out of the laboratory and into the community. 26 years of applied behavior analysis at the Juniper Gardens Children's Project.

Application of Skinner's principles to socially significant human behavior had been well articulated by 1968 (Baer, Wolf, & Risley, 1968). Applications of these principles by Baer, Wolf, Risley, Hall, Hart, Christophersen, and their colleagues were in evidence as early as 1964 in the homes, schools, and clinics of inner-city Kansas City, Kansas, at the Juniper Gardens Housing Project. The work continues relatively uninterrupted, having contributed extensively to the literature of applied behavior analysis and the lives of community residents. This article describes the project and illustrates how applied behavioral research was initiated and extended, how the work addressed general concerns in psychology, and how it continues to address contemporary concerns within the community.

Behavior Therapy↗

Some effects of feeding Tribulus terrestris, Ipomoea lonchophylla and the seed of Abelmoschus ficulneus on fetal development and the outcome of pregnancy in sheep.

Pregnant ewes and their fetuses were chronically catheterized using aseptic procedures under general anaesthesia, and the ewes were then fed either lucerne chaff alone, or lucerne mixed with dried plant material obtained from one of three forb species, Tribulus terrestris (caltrop), Abelmoschus ficulneus (native rosella) or Ipomoea lonchophylla (cowvine), from 103-112 days gestation until term. Ingestion of the forb material was not associated with changes in maternal blood gases, plasma glucose concentrations, or the length of gestation. However, ingestion of rosella seed was associated with a significantly greater fall of fetal arterial pO2 with advancing gestation, and ingestion of either rosella or cowvine was associated with significantly lower fetal mean arterial pressure at 127-131 days, compared with the Tribulus and lucerne groups. Also, the incidence of fetal breathing movements was significantly lower, and did not show a normal day-night variation, in each of the forb-fed groups compared with the lucerne-fed group. The results indicate that these forb plants may contain substances that affect the functional development of the fetal brain. Although ingestion of these plants did not appear to affect the outcome of pregnancy in this study, the possibility that these forbs have a greater impact in sheep populations with poor nutrition and in more extreme environmental conditions is discussed.

Animal Feed↗

Association of DR3 with susceptibility to and severity of primary Sjögren's syndrome in a family study.

A study of HLA and primary Sjögren's syndrome (1 degree SS) was performed in 40 index cases and 180 relatives all of whom were Caucasian. The association of DR3 and 1 degree SS was confirmed. In probands, DR3 associated with extraglandular manifestations of 1 degree SS and homozygosity for DR3 associated with younger onset of disease. Familial clustering of 1 degree SS was evident. Definite or probable 1 degree SS (Fox criteria) occurred with a prevalence of 4.4% in the relatives, exclusively in older female first degree relatives and was associated with DR3. The relative risk was greatest in those who expressed anti-nuclear factor, rheumatoid factor or Ro and DR3. We identified a group of young females expressing some criteria for 1 degree SS and the same immunogenetic markers. They may be at risk of full expression of 1 degree SS as they become older. Milder forms of 1 degree SS were common in older relatives but not DR3 associated. 1 degree SS in males was rare and mild irrespective of immunogenetic status. Symptoms of 1 degree SS in relatives were mild or absent. Such individuals will only be identified through a family study or a community survey.

Adolescent↗

Herpes simplex virus type I (HSV I)-induced multifocal central nervous system (CNS) demyelination in mice.

Multifocal central nervous system (CNS) demyelination develops in the brains of SJL/J, PL/J, and A/J mice following lip inoculation with a specific strain of herpes simplex virus I (HSV I). The lesions in all three inbred strains of mice share similar characteristics including demyelination, relative preservation of axons, and a mononuclear cell (MNC) infiltrate. The lesions, developing during the early phase of demyelination, also appear sequentially in the CNS (trigeminal root entry zone of the brainstem greater than cerebellum greater than cerebral hemispheres) of all three strains of mice but differ in the time of their initial appearance following infection as well as their morphology. In SJL/J mice, new areas of demyelination are observed for only 24 days following lip inoculation with virus. Late stage multifocal CNS demyelination persists throughout 28 weeks postinoculation (pi) in PL/J mice while in A/J mice the development of new areas of demyelination are restricted to 8 weeks pi. Although mononuclear inflammatory cells are present in the new areas of demyelination in either PL/J or A/J mice, viral antigens are not detected in the CNS beyond 12 days pi. In contrast, in situ hybridization studies using 35S-cDNA HSV probes and performed beyond day 12 pi identify probe-positive cells central to a number of the multifocal CNS demyelinating lesions in A/J mice. Results from studies with inbred and congenic strains of mice indicate that the major histocompatibility complex (H-2) does not determine the development of multifocal CNS demyelination following lip inoculation with HSV I but does influence the morphological appearance of the lesions that do develop.

Animals↗

Concerning a dual function of coupled cyclic electron transport in leaves.

Coupled cyclic electron transport is assigned a role in the protection of leaves against photoinhibition in addition to its role in ATP synthesis. In leaves, as in reconstituted thylakoid systems, cyclic electron transport requires "poising," i.e. availability of electrons at the reducing side of photosystem I (PSI) and the presence of some oxidized plastoquinone between photosystem II (PSII) and PSI. Under self-regulatory poising conditions that are established when carbon dioxide limits photosynthesis at high light intensities, and particularly when stomata are partially or fully closed as a result of water stress, coupled cyclic electron transport controls linear electron transport by helping to establish a proton gradient large enough to decrease PSII activity and electron flow to PSI. This brings electron donation by PSII, and electron consumption by available electron acceptors, into a balance in which PSI becomes more oxidized than it is during fast carbon assimilation. Avoidance of overreduction of the electron transport chain is a prerequisite for the efficient protection of the photosynthetic apparatus against photoinactivation.

Journal Article↗

Somatosensory evoked responses via electronic brain imaging (EBI).

This study of a series of 40 mildly head injured (concussed) patients suggests that different physiologic pathways underlying the tests done in a six-part resting EEG, and for the 11 evoked electrical potential shifts occurring in the cerebral terrain, are testable. Further work seems likely in order to ascertain which clinical signs and symptoms may be related to specific individual types of recorded electronic brain imaging (EBI) abnormality. Which of the 11 parameters studied, EEG, VER, AER, and SER, would be more or less likely to be abnormal in their individual patterns (as being deviant from normal controls) also remains to be defined. The relationship of these neurophysiologic abnormalities to certain postconcussive symptoms, i.e., headache, dizziness, blurred vision, etc., at this point in time remains to be evaluated more precisely. The authors suggest that further research is necessary in evaluating the clinical use of somatosensory evoked responses as an additional parameter in electronic brain imaging (EBI) technology.

Adolescent↗