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Biomedical subjects

R Wall

Publications and source records attributed to R Wall.

At least 19 recordsLinked to original sources
PubMed1992

Membrane mu poly(A) signal and 3' flanking sequences function as a transcription terminator for immunoglobulin-encoding genes.

Developmentally regulated mechanisms involving alternative RNA splicing and/or polyadenylation, as well as transcription termination, are implicated in controlling the levels of secreted mu (mu s), membrane mu (mu m) and delta immunoglobulin (Ig) heavy chain mRNAs during B cell differentiation (mu gene encodes the mu heavy chain). Using expression vectors constructed with genomic DNA segments composed of the mu m polyadenylation signal region, we analyzed poly(A) site utilization and termination of transcription in stably transfected myeloma cells and in murine fibroblast L cells. We found that the gene segment containing the mu m poly(A) signals, along with 536 bp of downstream flanking sequence, acted as a transcription terminator in both myeloma cells and L cell fibroblasts. Neither a 141-bp DNA fragment (which directed efficient polyadenylation at the mu m site), nor the 536-bp flanking nucleotide sequence alone, were sufficient to obtain a similar regulation. This shows that the mu m poly(A) region plays a central role in controlling developmentally regulated transcription termination by blocking downstream delta gene expression. Because this gene segment exhibited the same RNA processing and termination activities in fibroblasts, it appears that these processes are not tissue-specific.

Alternative Splicing↗
PubMed1992

Prevalence, regional distribution and control of blowfly strike in England and Wales.

The prevalence and control of blowfly strike in England and Wales was investigated by a postal survey of 2451 sheep farmers, divided into five regions, who were asked about the blowfly seasons of 1988 and 1989. These were important years for the control of blowfly strike because the number of compulsory dips for the control of sheep scab was reduced from two to one in 1989. The response rate was 74.2 per cent. A larger proportion of farmers in the south west and south east reported strike (90 per cent), than in the north of England (60 per cent). The proportion of sheep with strike showed a similar regional variation (0.7 per cent in the north of England to 2.8 per cent in the south west). Dipping was the most common method of blowfly control, followed by tail amputation, dagging, spraying and cyromazine. Twenty per cent of farmers reported reducing the frequency of dipping in 1989, and of those 20 per cent increased the frequency of spraying and 20 per cent used cyromazine.

Administration, Topical↗
PubMed1992

The IRG-47 gene is IFN-gamma induced in B cells and encodes a protein with GTP-binding motifs.

The murine pre-B cell line 70Z/3 has been studied extensively as a model system for B cell differentiation induced by cytokines and mitogens. IFN-gamma treatment of 70Z/3 pre-B cells activates Ig kappa L chain gene expression, resulting in the appearance of surface IgM characteristic of B cells. We have isolated and characterized a new cDNA clone, called IRG-47, whose mRNA is transiently elevated up to 30-fold at 4 to 6 h after IFN-gamma induction of 70Z/3 pre-B cells. The IFN-gamma induction of IRG-47 mRNA occurs in all pre-B and in most B lineage cell lines examined but is only induced in three cell lines tested from other lineages. Activation of IRG-47 gene transcription appears to account for the rapid increase in IRG-47 mRNA after induction. Transcription of the IRG-47 gene is down-regulated 10 h postinduction at a time when the level of IRG-47 mRNA is also declining. The complete sequence of the IRG-47 cDNA clone is predicted to encode a 47-KDa protein which, although unique in its sequence, bears resemblance to a number of nucleotide-binding proteins. The IRG-47 coding sequence contains all three highly conserved peptide motifs in the appropriate spacing characteristic of guanine nucleotide-binding proteins.

Amino Acid Sequence↗
PubMed1992

B29 gene products complex with immunoglobulins on B lymphocytes.

B29 is a B-lineage-specific gene predicted from sequence information to be a transmembrane member of the immunoglobulin (Ig) superfamily, with a single extracellular Ig-like domain. Its presumptive cytoplasmic region contains a peptide motif present in CD3 and other molecules involved in lymphocyte activation. Affinity-purified goat antibodies were prepared to a TrpE fusion protein of B29 and used to study B29 expression on lymphoid cells. The antiserum precipitated surface-labeled heterodimers from B lymphoma cells. One was 65-88 kDa (unreduced) or 36-47 plus 32-34 kDa (reduced) by SDS/PAGE analysis, regardless of detergent. A smaller heterodimer was detected only with Triton detergent extraction. IgM molecules were coprecipitated by the B29 antiserum when the weak detergent digitonin was used. In addition, cocapping experiments revealed that most B29 molecules codistribute with Ig on the cell surface. Although early B-lineage cells and plasma cells contain B29 mRNA, surface expression was detectable only on B cells that had significant amounts of surface Ig. The surface expression was B-lineage-specific and included cells from mutant xid mice and B-cell lines representing mu, delta, gamma, and alpha heavy-chain isotypes and both kappa and lambda light-chain types. The density of surface B29 protein correlated directly with surface mu heavy-chain density on subclones of a B-cell lymphoma and lipopolysaccharide-stimulated pre-B cells. These findings show that B29 is covalently linked in a heterodimer and are consistent with a recently proposed model of surface Ig complexes.

Animals↗
PubMed1992

Pulsatile activation of the hypothalamic-pituitary-adrenal axis during major surgery.

To examine the response of the hypothalamic-pituitary-adrenal (HPA) axis to severe surgical stress, we measured the immunoreactive plasma levels of corticotropin-releasing hormone (CRH), corticotropin, cortisol, arginine-vasopressin (AVP), atrial natriuretic factor (ANF), neuropeptide Y (NPY), interleukin-1 (IL-1), IL-6, interferon gamma (INF), and tumor necrosis factor-alpha (TNF-alpha) in eight patients with Zollinger-Ellison syndrome (ZES) or mediastinal parathyroid carcinoma, all undergoing major surgery with a standardized anesthetic technique. Blood samples were drawn the morning before surgery, every 10 to 30 minutes throughout surgery (average, 308.7 +/- 15 minutes), and every morning for the next 4 postoperative days (POD). During surgery, plasma CRH concentrations were slightly but not significantly elevated compared with those before surgery and with those of the next 4 POD. However, the values were within the normal range (less than 2.2 pmol/L) and showed 8.9 +/- 0.6 pulses (one pulse every 34.7 +/- 1.6 minutes). Plasma corticotropin, on the other hand, was quite elevated, but was also released in a pulsatile fashion during the surgical procedure (one pulse every 36.7 +/- 1.6 minutes). Most of these secretory episodes of corticotropin were temporally related to those of CRH. Corticotropin returned to basal levels on the first POD and remained so for all 4 POD. Plasma cortisol concentrations increased steadily during surgery and remained elevated the first POD. Cortisol showed 6.2 +/- 1.1 pulses during the operative sampling period (one pulse every 71.8 +/- 13 minutes). Plasma AVP concentrations were also markedly elevated during surgery, but individual secretory pulses were not detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytokines↗
PubMed1992

Development of an attractive target for the sheep blowfly Lucilia sericata.

Coloured, odour-baited, sticky targets, designed to catch the sheep blowfly Lucilia sericata Meigen are described and the results of field trials are presented. The number of L. sericata caught by the targets was positively related to target surface area and was dependent on target colour. The performance of the coloured targets is described by a model in which catch is related negatively to reflectivity in the 300-450 nm (ultra-violet/blue) band of the spectrum and positively to the reflectivity in the 450-580 nm (blue-green-yellow) band. Of the Lucilia blowflies caught by the targets, 13-16% were L.sericata and 72-75% of the L.sericata were female. The number of L.sericata caught appeared to be positively related to the availability of sheep over a relatively localized area and showed a marked decline following insecticidal dipping of sheep. The further development of targets and the implications of the results for L.sericata control are discussed.

Animals↗
PubMed1992

Lipopolysaccharide-induced NF-kappa B activation in mouse 70Z/3 pre-B lymphocytes is inhibited by mevinolin and 5'-methylthioadenosine: roles of protein isoprenylation and carboxyl methylation reactions.

We show that both the lipopolysaccharide (LPS)-induced activation of NF-kappa DNA binding and kappa gene expression are blocked by treating murine pre-B lymphocyte 70Z/3 cells with 5'-methylthioadenosine (MTA), an inhibitor of several S-adenosylmethionine-dependent methylation reactions. We further show that the LPS-induced incorporation of radioactivity from [methyl-3H]methionine into methyl ester-like linkages on a group of membrane polypeptides is also inhibited by MTA treatment, suggesting the involvement of protein methylation reactions in the LPS signal transduction pathway. We also find that NF-kappa B and kappa gene activation in LPS-treated 70Z/3 cells is blocked by mevinolin, an inhibitor that prevents protein isoprenylation. Interestingly, mevinolin-treated cells also exhibited a marked reduction in the methylation of membrane proteins. Neither MTA nor mevinolin significantly inhibited NF-kappa B activation by phorbol myristate acetate, suggesting that these agents act early in signal transduction. These results provide the first evidence that carboxyl methylated and/or isoprenylated proteins play an essential role in the LPS-signaling pathway.

Adenosine↗
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

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↗