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Biomedical subjects

R Wall

Publications and source records attributed to R Wall.

At least 127 records · Page 7Linked to original sources
PubMed1992

The second century of the antibody. Molecular perspectives in regulation, pathophysiology, and therapeutic applications.

The modern age of immunology began in 1890 with the discovery of antibodies as a major component of protective immunity. The 2nd century of the antibody begins with a focus on the molecular physiology and pathophysiology of immunoglobulin production. Numerous human variable-region antibody genes have been identified through advances in molecular cloning and anti-variable-region monoclonal antibodies. Some of these variable-region genes are now known to be involved in specific stages of B-lymphocyte differentiation and immune development. This connection has yielded new insights into the pathogenesis of immune dyscrasias and lymphoid neoplasia; common variable immunodeficiency and cryoglobulinemia are highlighted here. The molecular regulation of immunoglobulin expression suggests new targets for pathogenesis and clinical intervention. Finally, genetically engineered antibodies offer novel opportunities for diagnostic and therapeutic applications.

Agammaglobulinemia↗
PubMed1991

Computer Rx: more harm than good?

Clinical information systems (CIS) are health care technologies that can assist clinicians and clinical managers to improve the performance of health care organizations. However, failure to consider scientific evidence of efficacy, effectiveness, and efficiency when selecting CISs is one factor explaining the adoption of systems that do not improve either the quality or efficiency of patient care. This paper discusses a technology assessment framework that can assist decision-makers to evaluate alternative CISs. Existing methodologies developed to evaluate diagnostic and therapeutic technologies can be used by researchers to provide evidence needed by decision-makers at each step of the framework. The rigorous evaluation of CISs prior to their implementation can help decision-makers to avoid adopting "white elephants."

Clinical Medicine↗
PubMed1991

Meningococcal infection: evidence for school transmission.

Intimate contacts of a patient with meningococcal disease are at greater risk of disease than the general population and are offered chemoprophylaxis in order to prevent secondary cases. School contact is not considered a risk factor unless a further case develops. Bacteriological sampling of contacts to identify potential sources of infection is not considered warranted. We have questioned these approaches and investigated the contacts of a 9-year-old child with meningitis caused by sulphonamide-sensitive Neisseria meningitidis group C. Household carriers were not identified but 7/34 classmates were carrying the index strain suggesting that transmission was occurring within this population. The current recommendations for prophylaxis are based on information gathered in socioepidemiological settings, and involving strains which differ from those now prevalent. Such extrapolations may not be justified and further microbiological studies seem warranted to re-examine meningococcal transmission and prophylaxis usage in school children.

Carrier State↗
PubMed1991

Interleukin-6 signals activating junB and TIS11 gene transcription in a B-cell hybridoma.

The events in interleukin-6 (IL-6) signal transduction leading to primary response gene activation were analyzed in murine B-cell hybridoma and plasmacytoma cells which require IL-6 for growth. IL-6 stimulation of IL-6-deprived cells resulted in the rapid and transient tyrosine phosphorylation of a 160-kDa cellular protein (p160). This was followed by the highly selective induction of two primary response genes, junB/AP-1 transcription factor and TIS11. junB and TIS11 inductions were unaffected by cycloheximide, suggesting that posttranslational modifications accounted for their activation. Activation of junB and TIS11 transcription required rapid tyrosine kinase activity as well as a different protein kinase activity sensitive to the potent kinase inhibitor, H7, and activated following p160 tyrosine phosphorylation. This H7-sensitive kinase appears to be distinct from any well-characterized protein kinase-second messenger system. On the basis of these findings, we propose that IL-6-induced signal transduction proceeds through a novel protein kinase cascade which activates junB and TIS11 gene transcription.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

Eye movement patterns in REM sleep.

Eye movements in 6 healthy men and women were studied for recurrent patterns during REM sleep. The REM periods of nocturnal polysomnograms, on 2 consecutive nights, were analyzed in each subject. A discrete scale from 1 to 8 was used to record each eye position. The total number of recorded eye positions for the 2 nights of testing varied from 1314 to 3006. The distributions of eye movement were similar for males and females, for both nights of testing for each subject, among individual REM periods, and between subjects. This was in spite of marked differences in the number and length of REM periods, and in the number of eye movements per minute of REM sleep. In 5 of 6 subjects there was a marked tendency for the eyes to move between the 2 opposite lateral positions. Regardless of the eye position, the opposite movement was generally most likely, with an underlying tendency to return to the most opposite of the two lateral positions. In the remaining subject the opposite movement was also favored, but in this subject eye movements were more likely to be vertical rather than horizontal. Our data suggest that eye movements in REM sleep are organized in complex recurring patterns, with marked similarities between subjects. The significance of these patterns and the significance of deviations from these patterns require further study.

Adult↗
PubMed1990

The chemical control of livestock parasites: problems and alternatives.

Over 200 classes of chemical compounds are currently in use for the treatment of livestock parasites. Here Les Strong and Richard Wall review some of the problems arising from the total reliance on chemical control and consider some of the alternative methods that might be given more thought and application.

Journal Article↗
PubMed1990

Lipopolysaccharide-unresponsive mutant pre-B-cell lines blocked in NF-kappa B activation.

NF-kappa B activation is a crucial late step in the induction of immunoglobulin kappa light-chain gene expression in pre-B cells by lipopolysaccharide (LPS). We have analyzed NF-kappa B activation in three independent mutant lines of 70Z/3 pre-B cells which are unresponsive to LPS. All three variant cell lines failed to activate NF-kappa B when induced with LPS or the phorbol ester 12-O-tetradecanoylphorbol 13-acetate. However, all three cell lines contained functional NF-kappa B, as revealed by detergent treatment of cytoplasmic extracts. Moreover, cycloheximide induced limited activation of NF-kappa B comparable to that in wild-type 70Z/3 pre-B cells in two of the three variant lines. These results indicate that the mutations blocking kappa gene induction in these variant 70Z/3 pre-B-cell lines affect NF-kappa B activation.

Animals↗
PubMed1990

Hemolytic potential of guaifenesin in cattle.

The hemolytic effect on bovine red blood cells of 5%, 10%, and 15% guaifenesin solutions in 5% dextrose, 0.9% saline (NaCl), or distilled water was determined in vitro at 2 plasma concentrations (250 micrograms/ml, 500 micrograms/ml). A solution of 5% guaifenesin in a 5% dextrose solution or 5% guaifenesin in 0.9% saline produced minimal hemolysis in vitro. The amount of hemolysis of bovine red blood cells in vitro was related to the concentration of guaifenesin, diluent (5% dextrose, 0.9% NaCl, distilled water) and the plasma concentration of guaifenesin. In addition, plasma hemoglobin was determined in 4 adult dairy cows following the IV administration of 5% and 10% guaifenesin. These studies suggest that a solution of 5% guaifenesin in 5% dextrose is the most suitable solution for clinical use in cattle.

Animals↗
PubMed1989

Immunoglobulin enhancer and promoter motifs 5' of the B29 B-cell-specific gene.

B29 is a B-cell-specific member of the immunoglobulin gene superfamily that is expressed throughout B-cell development beginning with the earliest precursor B cells undergoing immunoglobulin heavy-chain gene segment rearrangements. We have analyzed the region upstream of the B29 gene to identify DNA sequences involved in transcriptional regulation of this gene. The B29 gene lacks a TATA box and transcription is initiated at multiple sites. The B29 gene sequence 5' of these transcription start sites contains six promoter and enhancer motifs known to control immunoglobulin gene transcription. The most notable is a perfect octamer (5'-ATTTGCAT-3'), which binds the Oct-2 B-cell-specific transcription factor and thereby can account for the tissue-specific expression of this gene.

Animals↗
PubMed1989

The roles of vision and olfaction in mate location by males of the tsetse fly Glossina morsitans morsitans.

The roles of visual and/or olfactory stimuli in eliciting mating responses from male Glossina morsitans morsitans Westwood were examined, using a system for automatically recording the number and duration of mating strikes made towards decoys, under controlled conditions. The results confirm that there is no olfactory component of the female sex recognition pheromone sensed by the male antennae, and the attraction of males to females appears to be visual. The absence of male-male mating strikes was the result of the absence of female sex-pheromone, rather than the presence of a repellent mating deterrent in the male cuticle. Experiments with coloured, artificial, sex-pheromone-dosed, cotton decoys showed that colour had only weak effects on attractiveness and number of encounters with decoys, and that no colour caused significant enhancement of mating responses over those shown to decoy females.

Animals↗
PubMed1989

Increases in plasma concentrations of a prostaglandin metabolite in acute airway obstruction.

Plasma concentrations of a stable prostaglandin F2 alpha metabolite were measured by radioimmunoassay during and after recovery from acute airway obstruction in 15 infants. Mean (SEM) metabolite concentrations (ng/l) in plasma obtained both before (1033 (418)) and after (1470 (413)) initial treatment for airway obstruction were significantly higher than those obtained from the same subjects after resolution of the obstruction--25.5 (6.6)--and those obtained from two comparison groups. Infants positive for respiratory syncytial virus (mean 1122 (227)) had significantly higher concentrations than those who were negative (207.6 (46)). Additionally, seven subjects with a history of recurrent wheezing after resolution of airway obstruction had a significantly higher mean level (3500 (1400)) during attacks of airway obstruction than those without (600 (100)). These data suggest that prostaglandin F2 alpha mediates respiratory inflammation in airway obstruction and that trials of specific anti-inflammatory agents for the treatment of airway obstruction may be warranted.

Airway Obstruction↗
PubMed1988

Induction of kappa transcription by interferon-gamma without activation of NF-kappa B.

The induction of immunoglobulin kappa light chain expression in 70Z/3 pre-B cells treated with bacterial lipopolysaccharide (LPS) requires the activation of the B cell-specific factor NF-kappa B, which binds to the kappa enhancer motif, GGGACTTTCC. This sequence alone can function as a tissue-specific enhancer for LPS-induced gene expression. A potent inhibitor of B lymphopoiesis [transforming growth factor-beta (TGF-beta)] was used to explore the mechanisms in the activation of kappa transcription by LPS and by interferon-gamma (IFN-gamma). TGF-beta inhibited LPS-induced kappa transcription but not the activation and in vitro binding of NF-kappa B. This indicates that NF-kappa B activation, while necessary, is not sufficient for LPS-induced kappa transcription. TGF-beta had no effect on IFN-gamma-induced kappa transcription, and NF-kappa B was not activated by IFN-gamma. These results reveal that LPS and IFN-gamma activate transcription through different mechanisms.

B-Lymphocytes↗
PubMed1988

Retinoic acid induces the differentiation of B cell hybridomas from patients with common variable immunodeficiency.

Human-human B cell hybridomas constructed from B lymphocytes of common variable immunodeficiency (CVI) patients and the nonsecreting cell line WIL2/729 HF consistently secrete low levels of Ig and appear to retain a defect characteristic of the CVI patient's B cells. We assessed the differentiative capacity of retinoic acid (RA) on these hybridomas, as well as on hybridomas constructed from normal B cells and from patients with selective IgA deficiency. RA at concentrations varying between 10(-5) and 10(-9) M augmented IgM secretion 4-20-fold from four of four CVI hybridomas tested, but did not affect Ig secretion from normal or IgA-deficiency hybridomas. In support of this elevated Ig secretion, RA enhanced the de novo synthesis of biosynthetically labeled light (kappa) and heavy (mu) Ig (up to 4- and 15-fold, respectively) in the CVI hybridoma line JK32.1. The increase in IgM synthesis/secretion could not be accounted for by RA-induced alteration in the cell cycle. In inducing this increase in IgM production, RA was found to affect two aspects of Ig gene expression: (a) the steady-state levels of heavy and light chain mRNAs were enhanced, and (b) the processing of mu heavy chain transcripts to the secreted mRNA form became favored over the membrane mRNA form. We also show that expression of Leu-17 (CD38), a surface marker that is re-expressed in the late pre-plasma stage of B cell development, was increased by RA from less than 20% to greater than 90% of the total cell population, with a concomitant 4-10-fold augmentation in the mean fluorescence intensity. Changes in both Leu-17 expression and de novo Ig synthesis were prominent by 24 h, but could be observed as early as 8 h after induction. Taken together, our study demonstrates that RA affects a marked alteration in the differentiated state of the CVI hybridoma clones. This finding suggests that retinoids can enhance the functional capabilities of B cells with defects in maturation and support further studies to evaluate their clinical potential in CVI.

B-Lymphocytes↗
PubMed1988

Sequence-dependent variability of DNA structure. Influence of flanking sequences and fragment length on digestion by conformationally sensitive nucleases.

DNase I and 1,10-phenanthroline-copper are two nucleolytic activities which are sequence-dependent in their scission reaction yet are not nucleotide-specific at their site of cutting. When these two nucleases are used to digest identical sequences in 18-base pair oligonucleotides and in restriction fragments 10-fold longer, the digestion patterns are similar at sequence positions in the interior of the fragment. Changes in reactivity to 1,10-phenanthroline-copper associated with mutational changes in the lac promoter in biochemically functional restriction fragments are duplicated in 18-base pair oligonucleotides. The structural variability of a given DNA sequence detected by these conformationally sensitive nucleolytic activities is therefore encoded in local sequence and not sensitive to fragment length. Digestion patterns of a repeated 7-base pair sequence within a longer sequence have the same characteristic except for the two nucleotides at the 5' periphery of the direct repeat. This conclusion is based on the digestion pattern of a restriction fragment which contains the polyadenylation site of the mouse immunoglobulin mu heavy chain gene. Two pairs of different 7-base pair sequences repeated in this fragment retain their distinctive digestion patterns. DNA sequences which comprise the binding sites of regulatory proteins, retain a characteristic structure only influenced at their peripheries by two to three bases of the flanking sequence.

DNA↗