Virulent HIV strains, chimpanzees, and trial vaccines.
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AIDS Vaccines↗
Biomedical subjects
J Allan
Publications and source records attributed to J Allan.
AIDS vaccine development.
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AIDS Vaccines↗
The HIV type 1 replication block in nonhuman primates is not explained by differences in cyclophilin A primary structure.
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Animals↗
Loin pain haematuria syndrome: distress resolved by pain relief.
Loin pain haematuria syndrome (LPHS) is a syndrome of severe chronic pain of unknown aetiology. This study assessed pain, mood variables and psychiatric status in patients (n=26) with LPHS. Patients were assessed before and after treatment with capsaicin. Assessment inventories used were the McGill Pain Questionnaire, the Pain Discomfort Scale, the General Health Questionnaire and the Hospital Anxiety and Depression Scale. Pain relief was achieved in 65% of patients. In this group pain (P < 0.001) and psychiatric (P < 0.01) scores were significantly reduced. By comparison, in those patients who did not gain pain relief, scores remained steady (P > 0.05). In addition, most pain-free patients completely stopped their opiate analgesia without addictive symptoms. These results suggest an organic pathology to LPHS and militate against suggestions of primary psychological cause or drug addiction. The results also show that the psychiatric disturbances associated with this chronic pain disappear if the pain disappears.
Adult↗
Identification of a novel multifunctional structural domain in the herpes simplex virus type 1 genome: implications for virus latency.
A domain, previously termed RE1, exists within the herpes simplex virus type 1 genome potentially influencing expression of immediate early genes and the latency associated transcripts. This domain consists of 10 tandem copies of a CT-rich sequence. We demonstrate that this domain binds multiple host-cell factors that may allow RE1 to act either as a transcriptional regulator and/or to affect nucleosomal and DNA structure in the latent genome.
Animals↗
CpG methylation remodels chromatin structure in vitro.
One of the mechanisms proposed to explain how CpG methylation effects gene repression invokes a DNA methylation-determined chromatin structure. Previous work implied that this DNA modification does not influence nucleosome formation in vitro, thus current models propose that certain non-histone proteins or a preferential affinity by linker histones for methylated DNA may mediate changes in chromatin structure. We have reinvestigated whether CpG methylation alters the chromatin structure of reconstitutes comprising only core histones and DNA. We find that DNA methylation prevents the histone octamer from interacting with an otherwise high affinity positioning sequence in the promoter region of the chicken adult beta-globin gene. This exclusion is attributed to methylation-determined changes in DNA structure within a triplet of CpG dinucleotides. In the affected nucleosome, this sequence motif is located 1.5 helical turns from the dyad axis and is oriented towards the histone core. These findings establish that DNA methylation does have the capacity to modulate chromatin structure directly, at its most fundamental level. Furthermore, our observations strongly suggest that a very limited number of nucleotides can make a decisive contribution to the translational positioning of nucleosomes.
Animals↗
Simian T-lymphotropic virus type 1 (STLV-1) infection in wild yellow baboons (Papio hamadryas cynocephalus) from Mikumi National Park, Tanzania.
Serum and peripheral blood leukocytes from wild yellow baboons (Papio hamadryas cynocephalus) were tested for the presence of STLV-1-specific antibodies and proviral DNA. Fourteen of 30 sera tested positive by radioimmunoprecipitation assay (RIPA) with HTLV-1. Among 36 DNA samples tested by PCR 15 were positive by double nested PCR for a fragment of the STLV-1 env gene, the most sensitive assay among PCR tests employed. Of 30 animals that were tested both serologically and by PCR in only 1 case were the results discordant (PCR-positive, antibody-negative). The DNA sequences from env (378 bp), pol (212 bp), and LTR (705 bp) were determined for 5, 5, and 2 Mikumi STLV-1 isolates, respectively. The DNA sequences of Mikumi STLV-1 isolates were virtually identical and phylogenetic analysis revealed that they were clearly distinct from previously published baboon STLV-1 sequences, including those STLV-1 isolates presumed to be from yellow baboons. The results of this study suggest that reliable placement of individual STLV-1 within the PTLV-1 phylogeny requires genomic sequences of STLV-1 isolates from wild animals whose taxonomic identity and geographical origin are firmly established and that the LTR is the genomic region of STLV-1 which is the most informative for cladistic analysis of these viruses.
Animals↗
Development and evaluation of a health education intervention against Taenia solium in a rural community in Mexico.
A comprehensive study was undertaken in a rural community in the state of Morelos, Mexico to evaluate health education as an intervention measure against Taenia solium. An educational program was developed to promote recognition and knowledge of the transmission of the parasite and to improve hygienic behavior and sanitary conditions that foster transmission. The effects of educational intervention were evaluated by measuring changes in knowledge and practices and prevalence of human taeniasis and swine cysticercosis before and after the campaign. The health education strategy was implemented with the active participation of the population based on the information obtained from a sociologic study. A questionnaire was designed and used before, immediately after the intervention, and six months later. Statistically significant improvements occurred in knowledge of the parasite, its life cycle, and how it is acquired by humans; however, changes in behavior related to transmission were less dramatic and persistent. The prevalences of cysticercosis in pigs at the start of the education intervention were 2.6% and 5.2% by lingual examination and antibody detection (immunoblot assay), respectively, and approximately one year after the intervention they were 0% and 1.2% (P < 0.05). These changes were accompanied by significant reductions in the reported access of pigs to sources of infection and freedom to roam. We conclude that health education, developed along with community involvement, reduced opportunities for transmission of T. solium in the human-pig cycle.
Animals↗
Identification and partial characterization of a myosin-like protein from cysticerci and adults of Taenia solium using a monoclonal antibody.
The host-parasite relationship in taeniosis due to Taenia solium is practically unknown. Monoclonal antibodies were prepared against whole extracts of adult T. solium parasites and evaluated with tapeworms recovered from experimentally infected hamsters and with cysticerci from naturally infected pigs. With one antibody, mAb 4B3, it was possible to identify, purify and partially characterize a T. solium myosin. Some findings indicate that it corresponds to conventional myosin or myosin type II such as: purification with KCl, high molecular weight, size, structure (dimeric protein with globular and long tail portions), reaction with commercial anti-myosin antibodies, distribution in muscle fibres of parasites and cross-reactivity with antibodies against paramyosin from T. solium cysticerci. The reaction of the mAb was only with taeniids and not with other parasites. Also myosin was detected in faeces of infected animals and in supernatants of parasite cultures. Its presence in biological fluids may be useful for diagnosis of infected hosts.
Animals↗
Getting through ethics committees: partnerships between researchers and clinicians working with mentally ill clients.
This paper discusses principles of ethics in nursing research with people suffering from mental illness. It offers a set of protocols which have been successful in obtaining approval from ethics committees to conduct research in the area of mental illness-'getting through'. The paper argues that nurse researchers and clinicians can achieve successful outcomes in mental health nursing research by working in partnership. An important aspect of this partnership is a commitment to uphold the rights of consumers of mental health care.
Ethics Committees↗
Periodicity of strong nucleosome positioning sites around the chicken adult beta-globin gene may encode regularly spaced chromatin.
Positioned nucleosomes contribute to both the structure and the function of the chromatin fiber and can play a decisive role in controlling gene expression. We have mapped, at high resolution, the translational positions adopted by limiting amounts of core histone octamers reconstituted onto 4.4 kb of DNA comprising the entire chicken adult beta-globin gene, its enhancer, and flanking sequences. The octamer displays extensive variation in its affinity for different positioning sites, the range exhibited being about 2 orders of magnitude greater than that of the initial binding of the octamer. Strong positioning sites are located 5' and 3' of the globin gene and in the second intron but are absent from the coding regions. These sites exhibit a periodicity (approximately 200 bp) similar to the average spacing of nucleosomes on the inactive beta-globin gene in vivo, which could indicate their involvement in packaging the gene into higher-order chromatin structure. Overlapping, alternative octamer positioning sites commonly exhibit spacings of 20 and 40 bp, but not of 10 bp. These short-range periodicities could reflect features of the core particle structure contributing to the pronounced sequence-dependent manner in which the core histone octamer interacts with DNA.
Animals↗
Nucleosome positioning on chicken and human globin gene promoters in vitro. Novel mapping techniques.
We have developed two new techniques to assess the positions adopted by core histone octamers when reconstituted onto DNA. These, together with a previously described technique, were applied to mapping binding sites on plasmid DNAs containing either the human zeta-globin or chicken beta-globin gene promoters. Each of the approaches enabled the sites occupied by histone octamers to be measured at high resolution and, in qualitative terms, revealed the same pattern of multiple, overlapping sites. Monomer extension, one of the novel techniques, can be used to reveal binding sites over extensive stretches of a single reconstitute (approximately 1000 bp). We found the distribution of histone octamer binding sites to be largely independent of the conditions employed for reconstitution, the topology of the DNA substrate and prolonged incubation under various post-reconstitution conditions. These properties, and features of the binding site maps that we derived, suggest that histone octamer positioning on these DNAs is predominantly a characteristic of the DNA sequence itself and, by implication, that nucleosome-nucleosome interactions and the formation of nucleosome arrays are of minor influence. Some of the techniques provide quantitative information concerning the relative binding strengths of the core histone octamer for different positioning sequences. In this context, it is notable that the majority of potential binding sites compete very poorly for the histone octamer, demonstrating that under the conditions pertinent to our analysis, the range of binding strengths exhibited by the octamer for particular DNA sequences is extensive, and greater than that observed when competitive binding has been studied by methods that do not reflect precise positioning.
Animals↗
Self-association of the globular domain of histone H5.
The capacity of the globular domain of the chicken erythrocyte linker histone H5 (GH5) to self-associate in solution has been demonstrated by chemical cross-linking with dimethyl 3,3'-dithiobis-(propionimidate) (DTBP), dithiobis(succinimidyl propionate) (DSP), and 3,3'-dithiobis(sulfosuccinimidyl propionate) (DTSSP). Several observations suggest that the GH5-GH5 interactions that mediate self-association are specific: (a) Incubation with each of the above reagents produces a discrete and characteristic pattern of cross-linked products; (b) GH1, the related peptide from chicken erythrocyte H1, is not cross-linked under the same conditions; (c) GH5 is not cross-linked with disuccinimidyl tartrate (DST), which has a shorter cross-linking span (6.4 A) than the other reagents (12 A); and (d) analysis of cross-linking as a function of peptide concentration provides an equilibrium constant for GH5 self-association of (4.8 +/- 1.3) x 10(3) M-1. The ability of GH5 to specifically self-associate is compatible with the proposal [Thoma, F., Koller, T., & Klug, A. (1979) J. Cell Biol. 83, 403-427] that linker histone globular domains occupy an axial position within the higher order chromatin fiber; the spatial juxtaposition of the GH5 domains at this location would be expected to promote their association and exert a stabilizing effect upon higher order chromatin structure.
Animals↗
Neurological symptoms in occult neurocysticercosis after single taeniacidal dose of praziquantel.
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Brain Diseases↗
An audit of hospital discharge letters in patients admitted with acute asthma. Tayside Asthma Audit Group.
The management of patients following discharge with acute asthma is dependent on effective communication with general practitioners. A retrospective audit was therefore performed on copies kept of 81 typed discharge letters with a diagnosis of acute asthma between March and October 1991. A subset of 42 interim (handwritten) letters were also audited where case notes could be retrieved. Details on clinic follow up were also obtained from the case notes (n = 42). In the typed letter documentation of severity and treatment of the acute attack was accurate in most cases. Information concerning a precipitating factor was provided in 54% of cases and a smoking history in 57%. Deficiencies were found in specifying inhaler delivery devices (40% recorded), and whether inhaler technique had been formally assessed whilst in hospital (17%). Drug prescribing on discharge was as follows: oral steroid (69%), inhaled steroids (77%), inhaled B2-agonists (92%), theophylline slow release (38%), salbutamol controlled release (20%), and antibiotics (30%). The implementation of a self-management plan and domiciliary peak flow was mentioned in 66% of the letters. The interim letter was generally poor in particular for mention if discharge peak flow (2%), clinic follow-up (64%) and prednisolone regime (61%). Mean +/- s.d. time for clinic follow-up (n = 42) was 4.7 +/- 1.7 weeks (range 1-13 weeks) with 24% non-attendance. Thus, improvements in discharge letters are clearly required for optimum continuity of care in the community.
Acute Disease↗
Site-directed mutagenesis studies on the binding of the globular domain of linker histone H5 to the nucleosome.
The globular domain of the linker histone H5 has been expressed in Escherichia coli. The purified peptide is functional as it permits chromatosome protection during micrococcal nuclease digestion of chromatin reconstituted with the peptide, indicating that it binds correctly at the dyad axis of the nucleosomal core particle. The globular domain residue lysine 64 is highly conserved within the linker histone family, and site-directed mutagenesis has been used to assess the importance of this residue in the binding of the globular domain of linker histone H5 to the nucleosome. Recombinant peptides mutated at lysine 64 are unable to elicit chromatosome protection to the same degree as the wild-type peptide, and since they appear to be fully folded, these observations confirm a major role for this residue in determining the effective interaction between the globular domain of histone H5 and the nucleosome.
Amino Acid Sequence↗
Salivary and serum antibodies in experimental canine taeniasis.
Specific IgG and IgA antibodies against adult Taenia pisiformis excretory/secretory antigen were detected in sera and saliva by enzyme-linked immunosorbent assay (ELISA) in experimentally infected dogs. IgG titres in serum and IgA in saliva corresponded with infection status, while serum IgA levels closely reflected faecal egg counts. The salivary IgA response was particularly raised and could have significant immunodiagnostic use for taeniasis in dogs.
Animals↗