Commonly encountered feline behavior problems.
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Biomedical subjects
Publications and source records attributed to S Heath.
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Resistance to complement-mediated lysis in Trypanosoma cruzi is due to the expression of complement-regulatory factors by the virulent developmental forms of this protozoan parasite. An 87- to 93-kDa molecule, which we have termed T-DAF (trypomastigote decay-accelerating factor), is present on the surface of the parasite and inhibits complement activation in a manner functionally similar to the mammalian complement regulatory component, decay-accelerating factor. In this report, we characterized monospecific polyclonal and monoclonal antibodies which were obtained from mice and rabbits immunized with fast protein liquid chromatography-purified T-DAF. These polyclonal antibodies were shown to inhibit T-DAF activity and were capable of inducing lysis of the parasites. Both the polyclonal and monoclonal antibodies were used to screen a cDNA expression library prepared from T. cruzi trypomastigote mRNA. From this library, we obtained a partial lambda gt11 cDNA clone which showed genetic and functional similarity to the human C3 convertase inhibitor DAF (A. Nicholson-Weller, J. Burge, D. T. Fearon, P. F. Weller, and K. F. Austen, J. Immunol. 129:184-189, 1982).
The need for health care reform in South Africa is acknowledged by the government as well as by the non-governmental health sector. There is, however, no unanimity regarding the nature of the envisaged reform. A country-wide postal survey of 700 private sector general practitioners (GPs) from a commercial database of 5,000 was conducted to explore attitudes towards health care. A response rate of 67.4% was obtained. Respondents were mostly male (92%) and urban-based (64%). The median age was 42 years. Most respondents: (i) believed health care to be a right for all citizens; (ii) favoured private or a combination of private and public funding mechanisms with fee-for-service arrangements; (iii) opposed cost-containment measures imposed by funders, e.g. medical aids; and (iv) believed doctors should be responsible for primary care in under-served areas. After sex, age, location (urban versus rural) and GP postgraduate qualification had been controlled for by means of logistic regression techniques, the university at which a respondent's basic degree was obtained emerged as the only independent predictor of attitudes to the following: (i) comprehensive care as a right; (ii) integration of the public and private sectors; (iii) preferred funding source for a future health system; and (iv) preference for fee-for-service remuneration. Both university and gender independently predicted attitudes on GPs' income. Graduates of white, Afrikaans-medium universities were strongly in favour of a privately funded and fee-for-service orientated system. Those who qualified at black universities, on the other hand, favoured public funding with less emphasison fee-for-service.(ABSTRACT TRUNCATED AT 250 WORDS)
Complementary DNA clones representing transcripts selectively expressed in the non-dividing, infective (metacyclic) stage of Leishmania major promastigotes (MP) were identified by differential and subtractive screening. The majority of the selected clones hybridized on Northern blots to a set of transcripts highly expressed by MP, but to a much lower extent in proliferating and stationary-phase attenuated promastigotes. Stationary, but not log-phase cultures, of each of 5 L. major strains showing a potential for differentiation to metacyclics, expressed these transcripts (MAT-1; MP-associated transcripts). From sequence analysis of full-length cDNA clones corresponding to the predominating MAT-1 species, an open reading frame encoding a 139 aa polypeptide (15.4 kDa) was predicted and supported by immunoprecipitation by kala-azar sera of reticulocyte extract translation products using in vitro transcribed RNA. Although no significant primary sequence homology to database nucleic acid and protein sequences was found, the sequence displays similarities to the basic-zipper families of transcription regulatory proteins.
The proportion of women entering medical school has increased at some faculties but remains at around 20% at others. A postal survey of 2,626 women on the Medical Register of the South African Medical and Dental Council was conducted to investigate aspects related to their work. Fifty-five per cent responded, with a possible bias towards older doctors and graduates from Afrikaans-language faculties. Although a significant majority (86.5%) are in practice, about one-third (33.4%) are employed part-time and nearly one-third (29.4%) reported that they had experienced an interruption of their careers for periods of more than 5 years. Major factors relating to this wastage of medical resources identified by this study were the women's dual responsibility at home and at work, the one-time joint taxation system and discrimination in the workplace, in particular with regard to housing loans. Few women find their way into specialist practice (10.8%) [corrected], although 68.2% indicated that they would have liked to specialise. Home responsibilities (48.2%) and the structure of the curriculum (31.5%) were the commonly reported difficulties experienced with further study. In addition, the lack of part-time training and the geographical location of such facilities also played a role.
Stable resistance to the anthelmintic hycanthone can be produced in the human blood fluke Schistosoma mansoni by exposing immature parasites in mice to the drug. Within a single generation, genomic rearrangements, detected as rRNA-encoding DNA restriction fragment length polymorphisms (RFLPs), accompany the appearance of resistance in this model. One of these RFLPs, an approximately 3.6-kilobase BamHI fragment, was shown previously to associate consistently with resistance in independent generations of the JHU strain of S. mansoni. To characterize the genetic changes responsible for this RFLP, the fragment was cloned and sequenced. A comparison of the cloned fragment with a normal 18S rRNA gene demonstrated that the drug resistance-associated RFLP fragment arises through the addition of 732 base pairs into an 18S rRNA gene, 134 base pairs downstream of the junction of the intergenic spacer and the mature 18S rRNA gene. The mutation is nonrandom, targets one, or a few only, of the 100 or so copies of the ribosomal genes, and may represent the incomplete duplication of the gene since the inserted element is identical in sequence to the region contiguous to it. The sequence spanning the junction of the insertion and the original 18S rRNA gene was used as a specific primer for the BamHI RFLP in PCR experiments. The analysis conclusively demonstrated that the mutation is induced rather than selected by the drug since the junctional sequence was not detectable in the drug-sensitive parent population of schistosomes. In addition, analysis of four, independently derived, resistant lines indicated that the same region of the gene was mutated each time. Together, these data demonstrate that reproducible changes are induced during the acquisition of resistance in schistosomes and suggest that the resistant phenotype is induced rather than selected from preexisting forms.
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Osteoporosis in RA is mediated by numerous inflammatory substances. This study was undertaken to see if SAARD could modify the rate of metacarpal bone loss in RA. Combined cortical thickness (CCT) measured at the midshaft of the right second metacarpal was used to calculate bone mass (CA%) using a digitizer. Eighty-one subjects were studied, all of whom had at least three sets of hand X-rays, the last of which was approximately 18 months following initiation of SAARD therapy. There were 12 males and 69 females. The mean age at time of starting therapy was 51 (SD 12) years while the mean duration of disease at the time was 7.6 (SD 8) years. The mean time to referral for SAARD from the general clinic was 2.5 (SD 3) years. The percentage fall in bone mass prior to therapy was 2.51%/day compared to a gain of 0.6%/day after therapy (P less than 0.05). Forty-nine patients were aged over 50 years while 32 were 50 years or younger at the time of study. Comparison showed that in the pretreatment period, the rate of change in CCT and CA% was not significantly dependent age (P less than 0.1). During that therapy, the rate of change in CCT and CA% significantly different in the two age groups. Patients aged over 50 years continued to lose bone, but at a slower rate (P less than 0.05). Patients aged 50 years or less either stopped losing or gained metacarpal bone mass during the study period (P less than 0.005). The time to referral for SAARD and disease duration (comparable in the two age groups) did not have a significant effect on changes in CA% during therapy. Change in bone mass could be predicted by change in disease activity. We conclude that SAARD have a significant sparing effect on metacarpal osteoporosis in RA. This positive effect is masked by the overwhelming influence of age (and menopause) and could be missed. Metacarpal osteoporosis seems a pathophysiologically more useful measure of radiological change in RA than erosions or joint space narrowing.
By using a subtractive hybridization strategy, we have identified a gene (TC26) that is expressed in metacyclic and tissue culture derived trypomastigotes of Trypanosoma cruzi but not log stage epimastigotes and is induced during the differentiation of metacyclic stages in vitro. In contrast, the TC26 transcript is absent from stationary phase epimastigotes of a strain that fails to undergo metacyclogenesis under the same culture conditions. Transcription of TC26 can be induced in epimastigotes by incubation with cyclic AMP and cyclic AMP analogues but it is inhibited by activators of cAMP dependent phosphodiesterases. Cyclic AMP fails to enhance tubulin gene expression in the same parasites. While present in the genome in multiple copies, the TC26 gene is expressed as a single mRNA species of approximately 5 kb. Computer analysis of the sequence of a 650-bp cDNA clone revealed no significant homologies at either the nucleotide or amino acid levels with other known proteins. Possible roles for the TC26 gene product in metacyclogenesis are discussed.
This study describes the characterisation of externally oriented surface peptides of both morphological forms of Leishmania donovani, the causative agent of visceral leishmaniasis (kala-azar). Using 125I surface labelling techniques and peptide extraction in the detergents Triton X-100 and Triton X-114, a major iodinable promastigote peptide at 63 kDa or 65 kDa (depending on detergent used) was identified. This peptide was demonstrated to be the immunodominant membrane peptide of L. donovani and was strongly recognised by human sera from parasitologically confirmed cases of kala-azar. This peptide was not demonstrated on the surface of tissue amastigotes, although in vitro translations of poly(A+) RNA from both promastigotes and amastigotes demonstrated that both forms possessed mRNA that directs the synthesis of a 63 kDa peptide. It is suggested therefore that in amastigotes this peptide may be a processed antigen. We also report the isolation of a recombinant cDNA clone in the bacteriophage vector lambda gt10 which encodes a 63 kDa polypeptide that is recognised by human kala-azar sera. It is proposed that this surface peptide could be used in a specific immunodiagnostic test for leishmaniasis.
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This study compared splenic and hepatic uptake of free and liposome-entrapped sodium antimony gluconate after i.v. administration to mice infected with Leishmania donovani. It was demonstrated that entrapment within liposomes greatly altered the kinetics of uptake of the drug. We were also able to show that liposomes composed of sphingomyelin, stearylamine and cholesterol were marginally better than any other preparation in delivering entrapped drug to liver and spleen. X-ray microanalytical studies on the uptake of liposomes by Kupffer cells infected with L. donovani have indicated that internalised liposomes probably fuse with parasitophorous vacuoles, transferring their contents into the immediate locality of the leishmanial parasites. It is proposed that this is the way in which liposome entrapped antileishmanial agents have an enhanced therapeutic effect over free drug therapy.
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A highly specific medium was developed for the enumeration of lactate-utilizing bacteria in the rumen of sheep. This medium, which contained 2.0% lactate, 2.0% Trypticase, 0.2% yeast extract, and volatile fatty acids, hemin, and trace elements in place of rumen fluid, enabled high counts (42 x 10 to 190 x 10/g of ingesta) of lactate-utilizing bacteria to be made with a high degree of specificity (96%). The medium also supported the growth of all species of predominant lactate-utilizing bacteria reported to occur in the rumen and thus is of importance for ecological studies where the incidence and influence of the different species on lactate metabolism under changing conditions in the rumen cannot be predicted. The survival rate of isolates was increased from 60 to 96% by addition to the modified maintenance medium of 40% rumen fluid in place of the volatile fatty acids, hemin, and trace elements used in the counting medium. These results, together with the slow growth of colonies in roll bottles, showed that, although highly selective, the counting medium was not optimal for the types selected.
Intranasal betamethasone valerate aerosol, given for 28 days, was compared with an oral antihistamine compound in a couble-blind, double-dummy, cross-over trial involving thirty patients with perennial rhinitis. The steroid aerosol was more effective in reducing symptoms and was preferred by the patients (P less than 0-01). Nasal blockage index, calculated from oral and nasal peak expiratory flow measurements, did not provide useful or additional information. There were no side effects from the steroid and Candida albicans was not cultured from nasal swabs. It is concluded that beta-methasone valerate aerosol is a suitable short-term alternative for patients whose perennial rhinitis fails to respond to conventional therapy.
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Histidinol dehydrogenase from three differing revertants of ICR-191A-induced frameshift hisD3018 has been purified and examined for amino acid replacements. The enzyme from one spontaneously arising revertant, R7, contains an extra proline residue, whereas that from another, R5, contains an extensive frameshifted sequence, four amino acid residues of which have been identified to date. The amino acid replacement data are in agreement with the in vitro code word assignments and allow the characterization of the hisD3018 frameshift as an addition of one nucleotide pair, most likely guanine plus cytosine. Enzymatic data for those ICR-191A-induced revertants of hisD3018 arising within the hisD gene indicate that the enzyme is wild type and, therefore, that ICR-191A can cause deletions as well as additions of single base pairs. The wild-type amino acid sequence is restored in enzyme from an N-methyl-N'-nitro-N-nitrosoguanidine (NG)-induced revertant, R29, suggesting that NG is a base-deleting as well as a base-substituting mutagen. The unusual response of hisD3018 to external suppressors is considered in terms of reinitiation of protein synthesis out of phase, coupled with suppression of a nonpermissive missense codon so generated, and of an alternative hypothesis invoking a true frameshift suppressor transfer ribonucleic acid with an extended or deleted anticodon.