Glucans as immunological adjuvants.
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Biomedical subjects
Publications and source records attributed to A Judd.
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To study the functional mechanism of the hepatitis B virus (HBV) X (hbx) gene product, we have expressed the hbx protein in E. coli and purified it by HPLC. The purified hbx protein was shown to be active in transactivating transcription directed by the LTR sequence of HIV-1. The hbx protein was found to have an intrinsic serine/threonine protein kinase activity. The hbx protein was detected in hepatitis B virions, and tryptic phosphopeptide maps of the hbx protein phosphorylated in the virion and of the in vitro phosphorylated bacterially expressed hbx protein were similar. Inactivation of the hbx protein by heat, protein-denaturing agents, or an ATP affinity analog, p-fluorosulfonylbenzoyl 5'-adenosine, resulted in loss of both protein kinase activity and trans-activation activity. These results suggest that the HBV-encoded trans-activator hbx is a novel protein kinase.
A nonvirulent Salmonella dublin flagellin-negative, aromatic-dependent live vaccine strain has been used to express hepatitis B virus surface antigen epitopes in an immunogenic form. The envelope proteins of the virion are encoded by the S gene, which contains the pre-S1, pre-S2, and S coding regions. Synthetic oligonucleotides corresponding to amino acid residues S-(122-137) and pre-S2-(120-145) were inserted in-frame into the hypervariable region of a cloned Salmonella flagellin gene, and the recombinant plasmids were introduced into a flagellin-negative aroA mutant live vaccine strain of S. dublin, SL5928. The flagellin gene was expressed in bacteria carrying the plasmids as detected by immunoblotting with anti-flagellin (H1-d) serum. Both the S and pre-S2 epitopes were detected in bacteria carrying the relevant plasmid by immunoblotting with anti-HBs (antibody to hepatitis B virus surface antigen) and anti-peptide antisera. Animals immunized intramuscularly or orally with the live recombinant bacteria developed antibodies specific to these hepatitis B virus epitopes as detected by ELISA.
Fifty patients were interviewed, on discharge from hospital, about their medications. Nine (18%) patients did not know, and a further four (8%) had inappropriate beliefs about why they were taking at least one of their discharge medications. Very few patients knew of significant side-effects which they might expect, or precautions which they should take, and over half did not know how long they were to continue taking their medicines. A small proportion was unable to read the bottle or open the container. Thus, even patients who, by virtue of an in-patient stay, have had a prolonged opportunity for education regarding their medicines have very little knowledge of their medicines upon discharge from hospital.
A panel of 16 monoclonal antibodies recognizing M protein (M1) of influenza virus was generated. Competition analyses resulted in localization of 14 monoclonal antibodies to three antigenic sites. Three monoclonal antibodies localized to site 1B recognized a peptide synthesized to M1 (residues 220 to 236) with enzyme-linked immunosorbent assay titers equivalent to or greater than that seen with purified M1; therefore, site 1B is located near the C terminus of M1. Sites 2 and 3 localize to the N-terminal half of M1. Antigenic variation of M proteins was seen when the monoclonal antibodies were tested against 14 strains of type A influenza viruses. Several monoclonal antibodies showed specific recognition of A/PR/8/34 and A/USSR/90/77 M proteins and little or no reactivity for all other strains tested. Immunofluorescence analysis with the monoclonal antibodies showed migration of M protein to the nucleus during the replicative cycle and demonstrated association of M protein with actin filaments in the cytoplasm. Use of a vaccinia virus recombinant containing the M-protein gene demonstrated migration of M protein to the nucleus in the absence of synthesis of gene products from other influenza virus RNA segments.
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Fifty patients were randomised in a double blind placebo controlled study to examine the influence of lorazepam (4 mg orally) before bone marrow aspiration and trephine biopsy. Assessment was made by a visual analogue linear pain scale compiled after the procedure and again 24 hours later. There was no difference in the pain recalled immediately after the procedure between the two groups, but the next day the patients who had received lorazepam showed amnesia with a 60% (p less than 0.01) reduction in the pain scale; 36% of the patients in this group had no recall of the procedure at all. There was no amnesic effect in the group taking placebo. Side effects were few, and it is concluded that lorazepam is a useful premedication agent before bone marrow biopsy.
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The first portion of this paper is devoted to an overview of the normal function of the hypothalamo-pituitary-thyroid axis. This section emphasizes areas of current research interest and it identifies several sites and mechanisms that are potentially important interfaces with toxins or toxic mechanisms. We then describe an in vitro technique for the continuous superfusion of enzymatically dispersed pituitary cells; this approach is particularly valuable in studying the dynamics of the TSH responses to the factors known (or suspected) to regulate TSH secretion in vivo. Using this technique, we have found that 10(-5)M prostaglandin (PG)I2 stimulates TSH secretion without altering the response to TRH (10(-8)M), and that this stimulation is not due to its rapid conversion to 6-keto PGF1 alpha. In contrast PGs of the E series (PGE1 and PGE2, 10(-5)M) increase responsiveness to TRH but have no effect alone. We found no effects of any of the other prostanoids tested (PGs A2, B2, F1 alpha, F2 alpha, thromboxanes A2 and B2, and the endoperoxide analog, U-44069. Somatostain (10(-9)M inhibits TRH-induced TSH secretion, but does not alter the responsiveness to PGI2. These findings suggest that somatostatin blocks TSH secretion at a point that is functionally prior to the involvement of the PGs, and perhaps does so by blocking synthesis or limiting availability of selected PGs.
1. The administration of 15 mg/kg tranylcypromine sulphate (Tc) to rats which have been given lithium chloride (LiCl) in the diet (30 mmol/kg dry food) for 14 days produces hyperactivity within 4 hrs, and this lasts for at least 4 further hours. 2. If LiCl is replaced by rubidium chloride (RbCl) at the same dose, the hyperactivity following Tc is increased and it appears within 2 hrs. 3. 5-Hydroxytryptamine (5HT) accumulation after a monoamine oxidase inhibitor (Tc) is increased 46% and 85% respectively above control values by LiCl and RbCl administration. 4. The hyperactivity produced by the above combinations is inhibited by alpha-methyl-p-tyrosine (alphampt). The inhibition is more effective following LiCl than RbCl treatment. 5. After sodium chloride (NaCl) and LiCl treatment, but not after RbCl treatment, the combination of alphampt and Tc produced rat brain concentrations of dopamine (DA) significantly below control values. 6. The smaller increase of brain noradrenaline (NA) after Tc and RbCl suggests that a lower percentage of NA is being metabolised by MAO. The greater decrease of NA after giving alphampt to RbCl and LiCl treated rats suggests an increased "turnover" rate of Na. 7. The hyperactivity syndrome seen in rats after the administration of LiCl or RbCl and Tc is dependent upon both 5HT and dopamine mechanisms.
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1 The tissue solubilizer Soluene-100 provides an efficient and easy means of preparing small amounts of rat tissue for cation analysis. 2 Administration of lithium ions to rats for two days to 42 days by the addition of lithium chloride to the diet at a concentration of 30 mmol/kg dry weight results in (a) the uniform distribution of lithium throughout the brain at a concentration comparable to that found in plasma; (b) decrease in the brain sodium concentration: (c) a decrease in brain magnesium concentration and an increase in plasma magnesium concentration; (d)no change in brain water content. 3 The inclusion of LiCl in the diet at a concentration of 30 mmol/kg dry food gives consistent and predictable plasma and brain levels of lithium in the rat without the occurrence of serious side effects over periods of up to 42 days.
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Data are presented from a screening study of ambulant attendees at two London Accident and Emergency (A&E) departments. Among young people (aged 16-24 years), 37.2% were drinking harmfully [an Alcohol-Use Disorders Identification Test (AUDIT) score of 8 or more]; 17.3% admitted to drinking alcohol in the 6 h prior to attendance; and 14.6% considered that their attendance was alcohol related. Young women were as likely as men to score 8 or over. This age group had nearly twice the odds of scoring highly on the AUDIT, compared to those over 25 years old, and were more likely to report that their attendance was alcohol related. Screening in A&E departments would identify considerable numbers of young people who might benefit from brief intervention, but the problems of doing so are acknowledged.