Biomedical subjects
Publications and source records attributed to R French.
The Physical Educators' Perceptions of Inclusion Inventory was administered to 80 paraprofessionals in special education. A Mann-Whitney U analysis indicated a significant difference in scores on knowledge related to inclusion by years of experience working. There was a significant difference between knowledge scores for length of time working but none for scores on perception.
Based on visual inspection of data, reinforcement procedures, namely, use of verbal praise and verbal praise plus token exchange, were at least mildly influential in improving performance of 5 youth with moderate mental retardation compared to their initial performance without reinforcers. These findings suggest specific reinforcement may improve the time for aerobic activity by adolescents with moderate mental retardation.
These data establish that cytokines, such as IL-1, can act on specific receptors within the brain to induce many symptoms of sickness. A number of inflammatory stimuli in the periphery can activate both the transcription and translation of IL-1 within the central nervous system. It will now be important to determine if similar central IL-1 pathways are activated during SLE and whether these central inflammatory cytokines are involved in the neurologic complications that often accompany this disease.
Cyclosporin A (CsA) can be regiospecifically alkylated at the NH of Val-5 with reactive bromides in the presence of phosphazene-base P4-t-Bu to yield derivatives 2-5. These are devoid of immunosuppressive activity in vitro but they have binding affinity for cyclophilin A (CypA) similar to that of CsA and thus represent a new class of cyclosporin antagonists. 1H NMR (DMSO-d6) studies have shown that the compounds exist in a single, all trans conformation. A comparison of this NMR data with X-ray crystallographic analysis of a CypA/CsA derivative complex demonstrates that the solution structure does not correspond to the bioactive conformation.
OBJECTIVES: To evaluate the extent to which larger genitourinary medicine (GUM) clinics in England have established local clinic policies for HIV Partner Notification (PN) and to describe the process of HIV PN within this setting. DESIGN: A cross-sectional survey of HIV PN policies and practices within GUM clinics. SUBJECTS AND SETTING: Senior consultants in 59 GUM clinics in England. MAIN OUTCOME MEASURES: The presence of clinic policies for HIV PN, indicators of HIV PN activity (that is, its initiation, documentation, performance and evaluation) and factors hindering the acceptance of HIV PN into clinical practice. RESULTS: Only 18% (10/57) of respondents stated that their clinics had developed their own local policies for HIV PN. Fifteen percent (9/58) of clinics had audited HIV PN activity, 15% had provided specific HIV PN training for doctors and 47% (27/58) for health advisers. Within GUM clinics, health advisers play a key role in the HIV PN process, being responsible for initiating the discussion of partners, patient follow-up and documenting HIV PN activity in patients' notes. Notifying partners was primarily seen as the responsibility of the newly diagnosed HIV positive patient. Although 77% (43/56) of responding consultants believed that HIV PN had become an accepted part of their clinics' practice, the perceived unacceptability of HIV PN to patients and health care workers were seen as important limiting factors. CONCLUSION: In many GUM clinics, local policies on HIV PN have yet to be established and appropriate training for the health personnel provided. Nevertheless, there appears to be wide-spread acceptance of HIV PN in clinical practice with an acknowledgement of its limiting factors. Further research into the acceptability of HIV PN to health care workers and patients in this setting should be undertaken.
Complementary DNAs encompassing the coat protein coding and adjacent regions of Agropyron mosaic virus (AgMV) and Hordeum mosaic virus (HoMV) were cloned and sequenced. Comparison with other sequenced potyviruses indicated that each clone contained the 3'-non-coding region (3'NCR), the coat protein (CP) gene and part of the nuclear inclusion protein (NIb) gene. Nucleotide and amino acid sequence comparisons of the 3'-terminal regions of these and other rymoviruses indicate that distinct groups exist. Ryegrass mosaic virus (RGMV) strains share sequence similarity with AgMV and HoMV. Wheat streak mosaic virus (WSMV) and brome streak mosaic virus (BrSMV) form a separate group, sharing limited sequence similarity with the other rymoviruses. It is proposed that subgroups occur within the Rymovirus genus, depending on the vector species involved in transmission and on sequences.
A Montana barley yellow dwarf virus (BYDV) isolate, BYDV-RMV-MT, is serologically identical to the New York RMV type isolate (RMV-NY) but differs in aphid transmission phenotype. A purification procedure for BYDV-RMV-MT was developed and cDNAs encompassing the entire coat protein gene and a portion of the putative polymerase gene of both RMV-MT and RMV-NY were cloned and sequenced. Diameters of RMV-MT virions averaged 24.7 nm. Average virus yield was 4.2 mg/kg plant tissue. There was 81% sequence identity between the clones of MT and NY RMV isolates at the nucleotide level. At the amino acid level the polymerase genes were 91% identical to each other and 74% homologous with that of beet western yellow virus. The coat protein amino acid sequences of the two RMV isolates were only 81% identical and, compared to other sequenced luteoviruses, both were most similar to cucurbit aphid-borne yellows virus.
The 2094 nucleotides at the 3'-terminus of a South African isolate of ryegrass mosaic virus (RGMV) was cloned and sequenced. Two putative polyprotein cleavage sites were found: Q/L and E/A, both of which are novel in the Potyviridae. The RGMV-SA cDNA was cloned into an expression vector, pUEX, and a fusion protein of 185 kDa was obtained which reacted strongly to anti-RGMV-SA antiserum. Alignment of the predicted amino acid sequence of RGMV-SA with those of other Potyviridae members showed limited identity, indicating that RGMV-SA is a definite and distinct virus.
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OBJECTIVE: To examine ethnic differences in the socio-epidemiological and clinical characteristics of a cohort of women with HIV infection in Britain and Ireland. DESIGN AND METHODS: Analysis of baseline data (ethnic group, sexual history, likely route of HIV infection, reasons for HIV testing and first AIDS-defining disease) from 400 women with HIV infection recruited into a cohort study from 15 genitourinary medicine/HIV clinics in Britain and Ireland. RESULTS: Sixty-five per cent of women were white and 29% black African. Their median number of lifetime sexual partners was seven and three, respectively (P < 0.001). Ninety-three per cent of black African and 43% of white women were probably infected through sexual intercourse. Injecting drug use was the most likely route of infection in 55% of white women, but none of the black African women. Perceived risk (33%) or investigation of symptoms (26%) were the most common reasons for HIV testing. Seven per cent of white women and 16% of black African women (P < 0.001) had AIDS when HIV infection was diagnosed. The distribution of first AIDS-defining diagnoses differed (P = 0.001) by ethnic group. For white women, the most common disease was Pneumocystis carinii pneumonia; for black African women it was pulmonary tuberculosis. CONCLUSION: There are important differences between black African and white women in sexual history and route of transmission, disease stage at diagnosis and pattern of AIDS-defining diseases.
A PCR diagnostic procedure for wheat streak mosaic virus (WSMV) was developed using a primer derived from 3'-terminal sequences of five WSMV isolates and an oligo d(T)-based primer. Cereal extracts prepared by digestion with proteinase K and boiling permitted PCR-based detection of both WSMV and BYDV in field samples. This procedure saves time, eliminates multiple liquid transfer steps, and reduces the chances of cross contamination. Sensitivity of such assays is still very good; BYDV could be readily detected in plant sap diluted over 1000-fold. Further, parallel detection of WSMV and barley yellow dwarf virus (BYDV) in the same samples is possible with this method.
A partial nucleotide sequence spanning the coat protein (CP) gene of a Nebraskan isolate of tobacco necrosis virus (TNV-NE) has been determined. The sequence contains at least four open reading frames (ORFs). The 5'-terminal ORF encodes a protein that has 86% and 38% homology with the polymerases of strains A (TNV-A) and D (TNV-D), respectively. The second and third ORFs probably encode 10.7 kDa and 6.2 kDa proteins (p 10.7 and p 6.2). These are respectively 90% and 96% amino acid homologous encoded by similar ORFs in TNV-A but only 26% and 20% homologous with those in TNV-D. The fourth 3'-proximal ORF encodes the 30.3 kDa CP. The amino acid sequence of TNV-NE CP is only 51% and 44% homologous to those of TNV-A and TNV-D, respectively. Thus, the CP genes of TNV-NE, TNV-A, and TNV-D are quite different. Like the sequences to the 5' side of the CP gene, that of TNV-NE is more closely related to TNV-A than to TNV-D.
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GR63178A (NSC D611615) is the second pentacyclic pyrolloquinone to be evaluated clinically as an anticancer drug. Its mechanism of action is unknown but may be related either to its quinone group or planar ring system. In this report we have investigated the ability of GR63178A to bind non-covalently to DNA, inhibit topoisomerase II and undergo reduction to reactive free radical species. Using two DNA duplexes, a 12-mer oligonucleotide which is a preferred sequence for minor groove binders and a hexamer which is a preferred sequence for intercalators, no evidence of significant binding with GR63178A was found. Neither GR63178A nor GR54374X (its 9-hydroxy metabolite) inhibited purified human topoisomerase II in a decatenation assay. Free radical chemistry was studied by both pulse radiolysis and ESR spectroscopy as well as by in vitro drug incubations with NADPH-fortified rat liver microsomes and purified cytochrome P450 reductase. The one-electron reduction potential of GR63178A was -207 mV +/- 10 which is much more positive than other quinone-containing anticancer drugs such as doxorubicin, mitomycin C and mitozantrone. GR63178A underwent enzyme-catalysed quinone reduction more readily than doxorubicin but produced significantly fewer reactive oxygen species. No evidence was detected of drug-induced, radical-mediated DNA damage in vitro using pBR322 plasmid DNA. Disproportionation of the GR63178A semi-quinone free radical proceeded with a rate constant of 1 x 10(9) M-1 sec-1 under anaerobic conditions, one order of magnitude faster than doxorubicin. The preferential disproportionation of the semi-quinone may explain our inability to detect a free radical signal by ESR. The hydroquinone of GR63178A was stable and exhibited strong visible absorption with a bathochromic shift of 120 nm over the parent drug. These unusual properties may be due to the hydroquinone undergoing a form of keto-enol tautomerization. Thus, GR63178A free radical formation does not appear to result in significant drug activation. In conclusion, GR63178A is unlikely to mediate its antitumour activity by DNA binding, topoisomerase II inhibition or free radical formation in direct contrast to similar anthracycline- and anthraquinone-based anticancer drugs.
The genus Rymovirus of the family Potyviridae is comprised of seven rod-shaped viruses with the shared characteristic of being transmitted by mites. Aside from this distinguishing feature, rymoviruses are similar to aphid-transmitted potyviruses in that they share a similar particle morphology, some similar antigenic determinants, similar physico-chemical properties, the ability to induce the formation of cytoplasmic cylindrical inclusions, and the ability to infect only graminaceous hosts. In vitro translation studies with wheat streak mosaic virus (WSMV) suggest that this rymovirus uses a potyviral proteolytic processing strategy to express the 3' terminal capsid protein. At the molecular level, limited nucleotide sequence data for WSMV show similarities with aphid-transmitted potyviruses in the potyviral capsid protein, large nuclear inclusion and cylindrical inclusion regions. Thus, given the similarities between the rymoviruses and the potyviruses, it is appropriate to include this genus within the family Potyviridae.