Antineutrophil cytoplasmic antibodies (ANCA) and the systemic necrotizing vasculitides.
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Antibodies, Antineutrophil Cytoplasmic↗
Biomedical subjects
A J Robinson
Publications and source records attributed to A J Robinson.
Conservation of gene structure and arrangement between vaccinia virus and orf virus.
A 3.3-kb BamHI fragment from the center of the orf virus (OV) NZ2 genome has been sequenced, revealing three major open reading frames (ORFs) with homology to vaccinia virus (VAC) genes. These ORFs have been designated F2L, F3R, and F4R and the proteins they encode were found to be homologous to VAC genes H4L (RNA polymerase-associated protein RAP94), H5R (35-kDa virion envelope antigen) and H6R (topoisomerase), respectively. The OV ORFs are arranged on the genome in an almost identical manner to their VAC counterparts revealing the common evolutionary origin of the two viruses despite the extreme difference in their G+C content. Like its VAC counterpart, F3R was shown to be transcribed early and late during infection. S1 and primer extension analysis located the 5' ends of F3R early transcripts to a position 15-16 nt and 5-10 nt, respectively, downstream from an AT-rich sequence resembling a VAC early promoter. The 5' ends of F3R late transcripts were located to an A within the sequence 5'-TAAAG, 41 nt downstream from the early promoter and 17 nt upstream from the initiation codon. S1 analysis of F2L, which is transcribed only late in infection, revealed transcripts initiating from within the sequence 5'-TAAATG. No transcriptional start point could be detected for F4R but the VAC late transcriptional initiation sequence TAAAT was found close to the predicted translational start point. Another late promoter-like sequence, 5'-TAAATG, was found at the 3' end of F2L. This preceded a short ORF tentatively designated as F1L and predicted to be the beginning of a homologue of VAC H3L.
Amino Acid Sequence↗
Comparison of azithromycin and doxycycline in the treatment of non-gonococcal urethritis in men.
Azithromycin has activity in vitro against Chlamydia trachomatis, and its novel pharmacokinetics suggest that even single doses may be effective in the treatment of non-gonococcal urethritis (NGU). This study compared the efficacy and safety of a single 1 g oral dose of azithromycin versus doxycycline 100 mg bid for seven days in the treatment of NGU. Men with symptoms and/or signs of NGU, and with > or = 5 polymorphonuclear leucocytes/high-power field in a Gram's-stained urethral smear, were recruited. Investigations included endourethral swabs for C. trachomatis cell culture. Patients were randomized to receive azithromycin or doxycycline, and were re-assessed on day 7-10 and on day 14-21. Of the 143 men recruited, C. trachomatis was isolated from 51 (40%) of the 128 evaluable patients. Both treatments were well tolerated and had comparable cure rates. Azithromycin 1 g appears to be an effective and safe alternative to doxycycline for the treatment of chlamydial and non-chlamydial urethritis, and its single-dose administration is an advantage in terms of patient compliance.
Administration, Oral↗
In vitro recognition of an orf virus early promoter in a vaccinia virus extract.
DNA fragments containing varying lengths of the 5' end of an orf virus early gene (ORF3) and its associated promoter were introduced into sodium deoxycholate-solubilized vaccinia virus extracts capable of initiating transcription in vitro from vaccinia virus early promoters. After separation of the radiolabelled products of the reactions on a 5% polyacrylamide/7 M urea gel, discrete transcripts were detected the sizes of which were consistent with initiation of transcription from the orf virus early promoter. This is the first demonstration in a functional assay of the conservation of early transcriptional promoters between an orthopoxvirus and a parapoxvirus.
Base Sequence↗
In vivo recognition of orf virus early transcriptional promoters in a vaccinia virus recombinant.
The 4.4-kb BamHI-E fragment of the orf virus (OV) genome contains three discrete open reading frames designated ORF-pp, ORF-1, and ORF-3, all of which are flanked by vaccinia virus-like early transcriptional control sequences. To determine whether the vaccinia transcriptional machinery would recognize these promoters and faithfully transcribe OV genes in vivo the BamHI-E fragment was inserted into the thymidine kinase (TK) locus of vaccinia virus and the recombinant used in transcription studies. Northern blotting analysis of early RNA isolated from 143B-TK- cells infected with the recombinant virus showed that OV genes were transcribed and that the three transcripts of 0.70-(ORF-pp), 0.48- (ORF1), and 0.75-kb (ORF-3) were the same size as their counterparts in OV-infected cells. Analysis of the 5' end of transcripts by S1 nuclease and primer extension showed that the transcriptional start points (tsp) of ORF-pp, ORF-1, and ORF-3 in the recombinant were identical or within four nucleotides of the tsps of the same ORFs in OV. However, there were quantitative differences. ORF-1 was transcribed more efficiently in recombinant virus-infected cells than in those infected with OV and analysis of the putative promoter, 5'-AAAATTGTAAATGTA, showed that it was similar to the 7.5-kDa early promoter of vaccinia virus. This demonstrates that the transcriptional control sequences of OV genes are recognized by vaccinia virus transcriptional factors but that quantitative differences exist suggesting that the generically different transcriptional factors have different promoter sequence requirements for maximal transcription.
Animals↗
Effects of phenothiazine and thiabendazole on bovine dorsal pedal vein contractility induced by ergonovine and serotonin; potential for alleviation of fescue toxicity.
Phenothiazine and thiabendazole were studied for their ability to antagonize venoconstriction induced by ergonovine, and the biogenic amine serotonin, in the isolated dorsal pedal vein of cattle. The two compounds are commercially available, approved for usage in cattle and have been reported to reverse some of the toxic effects associated with the intake of Acremonium coenophialum-infested fescue forage by cattle. Neither compound had any antagonistic activity against venoconstriction induced by ergonovine. However, thiabendazole did have some activity against venoconstriction induced by serotonin. Ergot alkaloids are known to cause venoconstriction through effects on biogenic amine receptors, including serotonergic receptors, and since thiabendazole has anti-serotonin activity, part of the reported beneficial effects of thiabendazole in alleviating fescue toxicity may be due to the anti-serotonin activity of the drug. Further work is needed to determine if phenothiazine and thiabendazole have any effect on other types of alkaloids that are present in A. coenophialum-infested fescue.
Acremonium↗
Chemical design of peripherally acting compounds.
1. Some guanidines, related in structure to mianserin and to 2-methyl-1,2,9,13b-tetrahydro-3H-dibenz[c,f]imadazo[1,5a] azepin-3-imine hydrobromide (WAL 801), have been synthesized and shown to be peripherally acting 5-HT2 antagonists. Structurally related compounds but not bearing a charged ionic group have been shown to have central activity. 2. Computer-aided molecular modelling has been used to establish a 5-HT2 pharmacophore. 3. The principle of exclusion from the CNS by incorporating a highly polar group to a biologically active molecule has been extended to the design and synthesis of a peripherally acting analgesic.
Computer Simulation↗
Seventh IUVDT Regional Conference on Sexually Transmitted Diseases, Kuala Lumpur, 5-7 September 1991.
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Acquired Immunodeficiency Syndrome↗
Two-step PCR in the retrospective diagnosis of enteroviral viraemia.
Enteroviral infections are potentially serious in man causing a variety of syndromes and a viraemic phase is probable in most patients. However, virological diagnosis is usually indirect by isolation of the agent from throat or stools when possible, and/or slow due to the need to titrate antibodies in paired sera. Because of its high sensitivity the polymerase chain reaction (PCR) offers the possibility of rapid detection of even low-grade viraemia. We have developed a 2-step PCR procedure adapted for enteroviruses and applied it to stored sera from patients with enteroviral meningitis. The acute sera from 7/12 patients were positive but the 4 convalescence sera tested, 2 of which had been positive at the acute phase, were negative. The assay should now be tested prospectively on serum and cerebrospinal fluid and could be developed for routine diagnosis.
Adolescent↗
Severity of cystic fibrosis.
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Cystic Fibrosis↗
Vaccinia virus-like early transcriptional control sequences flank an early gene in orf virus.
The purpose of this study was to map the initiation (tsp) and termination points of transcripts arising from an open reading frame (ORF3) found in the inverted terminal repeat of the orf virus genome and also, to identify probable transcriptional control sequences. Early transcripts of approx. 0.76 kb were mapped to ORF3 and found to be transcribed toward the ends of the genome. Using the S1 nuclease and primer-extension methods, the bulk of the tsp were mapped to a position 12-13 nucleotides (nt) downstream from a sequence which resembles A + T-rich vaccinia virus early promoters. The 5' ends were 81-82 nt upstream from the first ATG in ORF3. Most of 3' ends of the transcripts mapped to a region 24-32 nt downstream from a T5NT sequence found near the ORF3 stop codon. A second transcription termination point was found 25 nt downstream from another T5NT sequence located downstream and separated by 85 nt from the first. These results infer that the A + T-rich, early transcriptional control sequences found in other poxvirus genomes have been conserved in the G + C-rich genome of orf virus.
Amino Acid Sequence↗
Detection of white blood cell populations in the ejaculates of fertile men.
Using a now established, reliable technique for detecting white blood cells in human semen, we have examined the ejaculates of a fertile group of men. We have also highlighted the need for strict recruitment criteria to be established to enable accurate comparisons to be drawn between different patient groups and results from different laboratories.
Antibodies, Monoclonal↗
An orf virus sequence showing homology to the 14K 'fusion' protein of vaccinia virus.
The nucleotide sequence of a region of DNA 30 kb from the right end of the orf virus genome has been determined. Examination of the sequences revealed an open reading frame encoding a 10K peptide with significant amino acid homology to the 14K 'fusion' protein reported in vaccinia virus. The orf virus sequence has a 31% identity with the vaccinia virus protein, but a higher level of homology of core predicted residues. The secondary structure of both proteins is also similar. The occurrence of the TAAAT sequence upstream from the initiation codon indicates that the sequence is likely to be transcribed late in infection.
Amino Acid Sequence↗
Repeat sequences from complex ds DNA viruses can be used as minisatellite probes for DNA fingerprinting.
In a search for new fingerprinting probes for use with sheep, repeat sequences derived from five poxviruses, an iridovirus and a baculovirus were screened against DNA from sheep pedigrees. Probes constructed from portions of the parapox viruses, orf virus and papular stomatitis virus and the baculovirus from the alfalfa looper, Autographa californica, nuclear polyhedrosis virus all gave fingerprint patterns. Probes from three other poxviruses and an iridovirus did not give useful banding patterns.
Animals↗
Characterization of the 5-HT receptor subtypes involved in the motor behaviours produced by intrathecal administration of 5-HT agonists in rats.
1. The motor behavioural effects of intrathecal injections of 5-hydroxytryptamine (5-HT) and a variety of 5-HT receptor agonists were examined in adult Wistar rats to establish; (a) which 5-HT receptor subtype/s elicit each behaviour and (b) whether these receptors are located within the spinal cord. 2. Intrathecal injection of 5-methoxy-N,N'-dimethyltryptamine (5-MeODMT), (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) or 2,5-dimethoxy-alpha,4-dimethylbenzene ethamine hydrochloride (DOM) produced dose-related back muscle contractions (BMC) and wet dog shakes (WDS) which were both markedly attenuated by intraperitoneal pretreatment with either ritanserin (1 mg kg-1), ketanserin (0.16 mg kg-1) or mianserin (0.6 mg kg-1) indicating the involvement of 5-HT2 receptors in both these motor behaviours. Both fluoxetine (1-20 mg kg-1, i.p.) and high doses of 5-HT (50 micrograms) following fluoxetine (5 mg kg-1, i.p.) also elicited BMC, further confirming the involvement of 5-HT in this behaviour. 3. Intrathecal 5-carboxamidotryptamine (5-CT) evoked a marked wet-dog shake response without producing any BMC. Intrathecal pretreatment with 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT) enhanced, while in contrast 2-methyl-5-HT pretreatment attenuated, 5-HT agonist-induced BMC without affecting WDS. These data suggest that the spinal 5-HT2 receptors mediating BMC are positively modulated by 5-HT1A but negatively influenced by 5-HT3 receptor activation and may be of a different subtype to the supra-spinal 5-HT2 receptors which elicit WDS. 4. A contrast, reciprocal forepaw treading, lateral head weaving, flat body posture and Straub-tail were evoked by 5-MeODMT, 8-OH-DPAT or 5-CT but not by DOI or DOM indicating that these behaviours were not produced by 5-HT2 receptor activation alone. Ritanserin (1 mg kg- 1, i.p.) or ketanserin (0.16mgkg-1, i.p.) pretreatment reduced the reciprocal forepaw treading induced by high intrathecal doses of either 5-MeODMT (25.pg) or 5-CT (50,ug) suggesting that this behaviour may be facilitated by 5-HT2 receptor activation. 5. Intrathecal injection of 5-HT (0.05-50pg, after systemic fluoxetine, 5mg kg 1, i.p.), or 1-(3-chlorophenyl) piperazine (mCPP) produced dose-related forepaw-licking and grooming, neither of which were attenuated by ketanserin (0.16 mgkg-1, i.p.) pretreatment suggesting these behaviours may be mediated by 5-HT1c receptors. In contrast, 2-methyl-5-HT (50 and 100pg) produced sideward tail-flicks, not evoked by any other 5-HT agonist and could therefore be mediated by spinal 5-HT3 receptor activation. 6. These data provide behavioural evidence for the existence of spinal 5-HT2 receptors which produce a novel motor behaviour, BMC. Ligand binding studies and dose-response studies with a range of selective 5-HT antagonists are required to establish whether BMC and WDS are mediated by different subtypes of 5-HT2 receptors.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
Implications of inflammatory changes on cervical cytology.
OBJECTIVE: To assess premenopausal women with inflammatory changes on cervical cytology for genital infections and cervical abnormalities. DESIGN: Prospective study of women attending general practice and family planning clinics who had a recent cervical cytology result with inflammatory changes. SETTING: Department of genitourinary medicine. PATIENTS: 102 Premenopausal women with recent cytology result showing inflammatory changes and with no history of antibiotic or antifungal treatment since their smear. INVESTIGATIONS: Genital examination and microbiological screening for genital infections; colposcopic examination about six weeks later. MAIN OUTCOME MEASURES: Detection of genital infections, particularly those sexually acquired, and abnormalities on colposcopy. RESULTS: Genital infections were isolated in 77 patients, and one or more sexually acquired infections were found in 22. Prevalence of sexually acquired infections was significantly correlated with younger age (particularly being under 25), being single, separated, or divorced; using non-barrier contraception; and recent change of sexual partner. An abnormality on colposcopy was found in 36 women. There was a strong correlation of a sexually acquired infection with an abnormality at colposcopy; hence younger women were more likely to have a colposcopic abnormality. CONCLUSIONS: Inflammatory changes on cytology are often associated with the presence of a sexually acquired infection and premalignant disease of the cervix, particularly in younger, single women using non-barrier contraception.
Adolescent↗
Sequence analysis of the inverted terminal repetition in the genome of the parapoxvirus, orf virus.
Two BamHI fragments from the right-hand terminal region of the orf virus genome have been sequenced. The bulk of the inverted terminal repetition (ITR) sequence is contained within these fragments and makes up 3388 bp of the 4425-bp sequence reported. The overall base composition of the larger sequence is 59.4% G + C and of the ITR, 60.2% G + C. An extremely G/C-rich (83.2%) block of sequence was found spanning the ITR/unique sequence junction. The bulk of the ITR could be divided into three blocks of directly repeated sequences. One block begins about 250 nucleotides from the terminus and is a direct repeat 15 bp long, repeated 14 times. The other blocks contain seven sequence sets ranging from 16 to 36 nucleotides which are repeated 2 to 4 times, interspersed with one another, interrelated in sequence, and sometimes separated by unique sequence. Eight open reading frames (ORFs), each with the potential to code for polypeptides of 50 residues or more, were identified. Three were found within the ITR, four spanned the ITR/unique sequence junction and one was found outside the ITR. A search for putative poxvirus transcriptional control signals indicated that three of the eight ORFs are likely to be transcribed early, all in the same direction toward the right end of the genome. Sequences of the type T(A)3-5T were found only twice in the sequence and only one preceded an ORF.
Amino Acid Sequence↗
Acute epididymitis: why patient and consort must be investigated.
In this prospective study of 49 patients under 35 years of age with clinically diagnosed epididymitis, detailed microbiological investigation identified an infective cause in 67%. Chlamydia trachomatis was the commonest agent, present in 25 patients, but in 12 of these detection was based solely on raised antibody titres; 20 of the 28 female consorts screened were partners of men with chlamydial epididymitis and 80% of them were also positive for this infection. Isolating the micro-organism from 14 of 16 consorts indicated active infection despite the negative swabs from the men. If this important infection is to be adequately treated we recommend that all patients in this age group with epididymitis and their partners should be referred to a specialist unit with access to full chlamydia laboratory facilities.
Acute Disease↗