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Biomedical subjects

D B Wilson

Publications and source records attributed to D B Wilson.

At least 163 records · Page 9Linked to original sources
PubMed1991

Generation of T cells with lytic specificity for atypical antigens. I. A mitochondrial antigen in the rat.

F1 rats primed with normal parental strain lymphocyte populations and restimulated in culture with parental lymphoblasts generate potent cytotoxic T cell responses to unusual antigen systems. Here we describe in the Lewis (L)/DA anti-DA combination an antigen system most likely of mitochondrial origin with the following properties: it is transmitted maternally from DA strain females, inherited in an extra-chromosomal manner, restricted by class I RT1Aa major histocompatibility complex gene products, extinguished on target cells treated with chloramphenicol, and its pattern of expression in different rat strains correlates with restriction fragment-length polymorphisms of mitochondrial DNA. Sequence analysis of the rat ND1 gene indicates that the maternally transferred factor in the rat is not a homologue of the maternally transmitted factor responsible for the mitochondrial antigen in mice. In keeping with its inheritance from DA females, this antigen is present on target cells from (DA female x L male)F1 donors and all other F1 combinations derived from DA female parents, but absent from target cells from some F1 combinations (L/DA and Wistar-Furth [WF]/DA) derived from DA strain males. The presence of this antigen in other F1 combinations (Brown Norway [BN]/DA, August 2880 [AUG]/DA, and PVG/DA) indicates that this mitochondrial antigen system is shared by the DA, BN, and PVG strains, but not by the L and WF strains.

Amino Acid Sequence↗
PubMed1991

Generation of T cells with lytic specificity for atypical antigens. II. A novel antigen system in the rat dependent on homozygous expression of major histocompatibility complex genes of the class I-like RT1C region.

Lymphocytes from parental strain DA rats can induce potent killer cell responses to atypical antigen systems in F1 Lewis (L)/DA and DA/L recipients. Here, we describe an antigen system, H, present on homozygous parental target cells, but not on F1 cells. This antigen system is unusual in several respects: it does not involve class I RT1A gene products usually used by killer cell responses in the rat, it maps to the major histocompatibility complex (MHC) class I-like RT1C region, and it requires homozygous expression of RT1Cav1 alleles. This may be another example, this time involving the RT1C region, of an MHC gene product antigenically altered by an MHC-linked trans-activating modifier gene.

Animals↗
PubMed1991

Generation of T cells with lytic specificity for atypical antigens. III. Priming F1 animals with antigen-bearing cells also having reactivity for host alloantigens allows for potent lytic T cell responses.

Here, we explore the conditions required for generating two different highly potent F1 antiparental killer cell populations to unusual antigens in rats. The first, L/DA anti-DA, has lytic specificity for two antigen systems: MTA, a mitochondrial antigen expressed on DA and DA Lewis (L) target cells restricted by RT1A class I molecules; and H, an antigen that maps to the class I-like RT1C region and is present only on parental target cells from donors homozygous at the major histocompatibility complex. The second killer population is generated in the reciprocal DA/L anti-DA combination and has lytic specificity only for the H antigen system. We show that the killer cells are T cells, and that generation of these F1 cytotoxic T lymphocytes (CTL) requires an in vivo priming step in which it is essential that the inoculated parental cells bear the relevant target antigens and possess alloreactivity for F1 host antigens. The requirement for alloreactivity and antigen on the same priming cell population suggests that these potent lytic responses depend on a situation akin to a hapten-carrier effect that bypasses otherwise ineffective helper responses by the host to these unusual antigens. Restimulation of F1 lymphocytes in culture is also necessary, requiring the presence of antigen on irradiated lymphoblast stimulator cells, but alloreactivity to responder cell antigens is not necessary; normal, nonactivated lymph node cells are completely ineffective as stimulators. For effective lysis, the target cells need not possess the potential for alloreactivity to responder F1 CTL. We also demonstrate in a preliminary way additional antigen systems defined by killer populations raised with other F1 antiparental strain combinations.

Animals↗
PubMed1991

Human immunodeficiency virus infection of human-PBL-SCID mice.

Severe combined immunodeficient (SCID) mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID mice) have inducible human immune function and may be useful as a small animal model for acquired immunodeficiency syndrome (AIDS) research. Hu-PBL-SCID mice infected with human immunodeficiency virus-1 (HIV-1) contained virus that was recoverable by culture from the peritoneal cavity, spleen, peripheral blood, and lymph nodes for up to 16 weeks after infection; viral sequences were also detected by in situ hybridization and by amplification with the polymerase chain reaction (PCR). Mice could be infected with multiple strains of HIV-1, including LAV-1/Bru, IIIB, MN, SF2, and SF13. HIV-1 infection affected the concentration of human immunoglobulin and the number of CD4+ T cells in the mice. These results support the use of the hu-PBL-SCID mouse for studies of the pathogenesis and treatment of AIDS.

Animals↗
PubMed1991

Effect of tetrahydroaminoacridine on cognition, function and behaviour in Alzheimer's disease.

OBJECTIVE: To determine the efficacy of tetrahydroaminoacridine (THA) in Alzheimer's disease. DESIGN: Randomized, double-blind, multiple crossover trial with three treatment periods, each consisting of 3 weeks of active drug therapy and 3 weeks of placebo administration. SETTING: Referral-based geriatric practice in a community hospital. PATIENTS: Thirty-four patients with moderate to severe Alzheimer's disease. Subjects were included if they had stage 3 to 6 disease (as determined by the Reisberg scale) and had not been taking psychotropic drugs for at least 1 month and if informed consent had been obtained from the patients and their next of kin. INTERVENTIONS: Fifty to 100 mg of THA daily and matched placebo. RESULTS: Of the initial 34 patients 14 experienced liver toxicity and 3 gastrointestinal side effects during the study; however, all 22 who completed the study were able to tolerate at least the minimum dose. For the 22 patients there was no clinically or statistically significant effect of THA on cognition, functional status or behaviour. The results for individual patients showed no subgroup of THA-responsive patients. CONCLUSION: THA has no clinically important benefits in Alzheimer's disease and is associated with appreciable toxic effects.

Activities of Daily Living↗
PubMed1991

Ultrastructural analysis of the midaxial extracellular matrix in spinal dysraphism.

Ultrastructural aspects of the extracellular matrix (ECM) in the midaxial region of dysraphic embryos of the loop-tail (Lp) mutant mouse were analyzed by means of electron microscopy. In 17-23 somite embryos, ultrastructural differences in the ECM occurred with respect to the presence of a pair of long trailing basal laminar strands extending continuously from the ventral notochordal cells to the gut in abnormal (Lp/Lp) embryos, in contrast to short, ragged, discontinuous strands in normal (+/+; Lp/+) embryos. The ultrastructural localization and configuration of fibronectin (FN) and laminin (L) associated with these strands, however, were similar in normals and abnormals. In addition, FN occurred over interstitial bodies, fibrils, and sporadically along the basal laminae of the neural tube (or folds), notochord, gut, and vessels, whereas L was largely confined to the basal laminae. The results indicate that although the ultrastructural pattern of FN and L reactivity are similar in normal and abnormal embryos, a disturbance in the manner whereby the notochord detaches from the gut in dysraphic embryos may be of causal significance in the etiology of dysraphism in this mutant.

Animals↗
PubMed1991

DNA sequences of three beta-1,4-endoglucanase genes from Thermomonospora fusca.

The DNA sequences of the Thermomonospora fusca genes encoding cellulases E2 and E5 and the N-terminal end of E4 were determined. Each sequence contains an identical 14-bp inverted repeat upstream of the initiation codon. There were no significant homologies between the coding regions of the three genes. The E2 gene is 73% identical to the celA gene from Microbispora bispora, but this was the only homology found with other cellulase genes. E2 belongs to a family of cellulases that includes celA from M. bispora, cenA from Cellulomonas fimi, casA from an alkalophilic Streptomyces strain, and cellobiohydrolase II from Trichoderma reesei. E4 shows 44% identity to an avocado cellulase, while E5 belongs to the Bacillus cellulase family. There were strong similarities between the amino acid sequences of the E2 and E5 cellulose binding domains, and these regions also showed homology with C. fimi and Pseudomonas fluorescens cellulose binding domains.

Amino Acid Sequence↗
PubMed1991

A Bacteroides ruminicola 1,4-beta-D-endoglucanase is encoded in two reading frames.

Escherichia coli transformed with a plasmid containing a Bacteroides ruminicola endoglucanase (carboxymethyl cellulase [CMCase]) gene produced three immunologically cross-reacting CMCases which had molecular weights of 40,500, 84,000, and 88,000, while B. ruminicola produced CMCases with molecular weights of 82,000 and 88,000. The two B. ruminicola enzymes (purified from culture supernatants) had different N-terminal amino acid sequences, but each enzyme was encoded by the same gene (three independent clones had the same DNA sequence). The 88,000-molecular-weight CMCase (88K CMCase) gene appeared to contain two open reading frames which overlapped for 18 bp and were -1 out of frame, and each open reading frame contained several stop codons near the overlap region. The two 88K CMCase open reading frames had enough DNA to produce a protein of 106K, but the mobility of the enzyme in sodium dodecyl sulfate gels gave a value which was 20% lower. On the basis of the -1 frame shift and the large deviation in theoretical versus actual size, it appears that an unusual event (e.g., ribosomal hopping or RNA splicing) is involved in either the translation or the transcription of the 88K B. ruminicola CMCase gene. The 82K CMCase was completely encoded in the second reading frame, and its size was in agreement with the DNA sequence.

Amino Acid Sequence↗
PubMed1991

Low-intensity anticoagulation in mechanical cardiac prosthetic valves.

Retrospectively, we reviewed the charts of 101 patients at the University of Kansas Medical Center who received low-intensity anticoagulation for mechanical prosthetic valves implanted over a 17-yr period. The mean duration of follow-up was 4.6 yr, and the total duration of follow-up was 466.5 patient-yr. The patients' records were evaluated for evidence of hemorrhagic or thromboembolic complications. A prothrombin time ratio of 1.3 to 1.5 times control was considered to be low-intensity anticoagulation. There were three thromboembolic events or 2.9/100 patient-yr of follow-up at a prothrombin time ratio of less than 1.3, four thromboembolic events or 2.5/100 patient-yr of follow-up at 1.3 to 1.5 times control, four thromboembolic events or 2.2/100 patient-yr of follow-up at 1.6 to 2.0 times control, and no thromboembolic events at prothrombin time ratios greater than 2.0 times control. Hemorrhagic events occurred in three patients at a prothrombin time ratio of less than 1.3 times control or 2.8/100 patient-yr of follow-up, in six patients at 1.3 to 1.5 times control or 3.8/100 patient-yr of follow-up, in ten patients at 1.6 to 2.0 times control or 5.5/100 patient-yr of followup, and in two patients at 2.1 to 2.5 times control or 12.2/100 patient-yr of follow-up. The rate of hemorrhagic events at 2.5 times control was 470/100 patient-yr follow-up. While not providing definitive proof, we believe that our retrospective study provides supportive evidence for the use of low-intensity anticoagulation in patients with mechanical cardiac prostheses.

Adult↗
PubMed1991

Stroke rehabilitation: a model predicting return home.

We undertook this study to describe the changes in functional status for patients in a rehabilitation program for acute stroke and to identify the variables that best predict discharge home. Of 282 patients, 75% were discharged home. Increases in functional status were found for all 18 activities of the Functional Independence Measure from admission to discharge. Significant predictors of discharge disposition in a logistic regression model were the admission and discharge functional status scores, length of stay, and living arrangement before the stroke. The functional status at discharge was the most important predictor. Knowledge of these predictors can contribute to more appropriate treatment and discharge planning.

Adolescent↗
PubMed1990

Cytochemical analysis of the notochord in early rhesus monkey embryos.

Functional differentiation of the notochord in rhesus monkey embryos at stages 11-12 (25-28 days of gestation) was analyzed by means of ultrastructural cytochemistry. The notochordal cells exhibited well developed Golgi complexes, rough endoplasmic reticulum, mitochondria, and numerous coated vesicles. Large irregular intercellular spaces were common, and some contained fibrils and particulate matter similar to that observed in the perinotochordal space immediately surrounding the notochord. With the glycogen-specific thiocarbohydrazide-silver proteinate technique, solitary particles as well as large aggregates of glycogen were present within the notochordal cells. The center of some aggregates was electron lucent and contained collapsed membranous structures. The results indicate that as early as stage 11 the nonhuman primate notochord exhibits ultrastructural features suggestive of secretory activity and cytological complexity.

Animals↗
PubMed1990

Techniques for the determination of left ventricular mass by signal-averaged electrocardiography.

UNLABELLED: The standard ECG correlates poorly with LV mass. The SAECG precisely measures myocardial energy and may allow more exact noninvasive assessment of LV mass. A commercially available system (Corazonix Predictor I) was tested for its ability to reproduce and measure known input energy in square wave and QRS waveforms, using frequency bandwidths different from those used for late potential analysis. A test group of 15 patients was studied to determine optimum filter type and bandwidth for comparison of SAECG energy measurement versus LV mass as determined by echocardiography (Penn conversion) and LV hypertrophy via standard ECG criteria. The best means of energy measurement were maximum and total RMS voltage and the integral of the area under the QRS curve. Optimum correlation with echocardiography was seen with a bidirectional band-pass filter of 5 to 250 Hz applied either to the vector sum of the three orthogonal leads or to the Z lead alone (r values 0.61 to 0.73), which was equal to or superior to standard ECG LV hypertrophy determinants. A second group of 20 patients was studied prospectively to confirm these findings, which yielded similar results. CONCLUSION: (1) the SAECG when appropriately modified serves as a rapid noninvasive assessment of LV mass. (2) These modifications must examine the entire duration and energy spectrum of the surface ECG and not just the region of late potentials. (3) Very low frequencies (below 5 Hz) must be excluded to eliminate the energy present due to DC offset voltage.

Cardiomegaly↗
PubMed1990

Echocardiography. Basics for the primary care physician.

Echocardiography is commonly performed to assess aortic stenosis, mitral valve prolapse, pericardial effusion and cardiac tamponade, myocardial infarction, endocarditis, and valvular regurgitation. We have found that the more defined and appropriate a request for an echocardiogram is, the better the technician and interpreter can relate observations to the requesting physician. Thus, thorough understanding of the indications and limitations of echocardiography by the primary care physician will result in improved patient care.

Aortic Valve Stenosis↗
PubMed1990

Cyclosporine-induced autoimmunity in rats carrying thymus allografts.

An autoimmune syndrome occurs in cyclosporine-treated, lethally irradiated, and marrow-reconstituted rats after cyclosporine is discontinued. This syndrome, referred to as cyclosporine-induced autoimmunity, requires the presence of a thymus. In this report, we demonstrate that the disease will occur in animals transplanted with thymus tissue from an allogeneic donor, incompatible with the recipient at the major histocompatibility complex. T cells generated from these allogeneic thymic chimeras respond in vitro to thymic donor antigens, suggesting that cyclosporine inhibits self-tolerance induction in the thymus. Because disease is more frequent when the tolerizing antigens expressed in the thymus differ from those expressed in the periphery, the possibility that cyclosporine may mediate its effect via the downregulation of self-antigen presented in the thymus is discussed.

Animals↗
PubMed1990

Effects of temperature on Escherichia coli overproducing beta-lactamase or human epidermal growth factor.

The effects of temperature on strains of Escherichia coli which overproduce and excrete either beta-lactamase or human epidermal growth factor were investigated. E. coli RB791 cells containing plasmid pKN which has the tac promoter upstream of the gene for beta-lactamase were grown and induced with isopropyl-beta-D-thiogalactopyranoside in batch culture at 37, 30, 25, and 20 degrees C. The lower temperature greatly reduced the formation of periplasmic beta-lactamase inclusion bodies, increased significantly the total amount of beta-lactamase activity, and increased the purity of extracellular beta-lactamase from approximately 45 to 90%. Chemostat operation at 37 and 30 degrees C was difficult due to poor cell reproduction and beta-lactamase production. However, at 20 degrees C, continuous production and excretion of beta-lactamase were obtained for greater than 450 h (29 generations). When the same strain carried plasmid pCU encoding human epidermal growth factor, significant cell lysis was observed after induction at 31 and 37 degrees C, whereas little cell lysis was observed at 21 and 25 degrees C. Both total soluble and total human epidermal growth factor increased with decreasing temperature. These results indicate that some of the problems of instability of strains producing high levels of plasmid-encoded proteins can be mitigated by growth at lower temperatures. Further, lower temperatures can increase for at least some secreted proteins both total plasmid-encoded protein formed and the fraction that is soluble.

Amino Acid Sequence↗