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Biomedical subjects

J Perry

Publications and source records attributed to J Perry.

At least 55 records · Page 3Linked to original sources

Strategic planning and progress under the All Wales Strategy: reflecting the perceptions of stakeholders.

Nominated representatives from the various stakeholder interests, i.e. social services, health, education, voluntary organizations, parent groups and self-advocacy groups, involved in the implementation of the All Wales Strategy for the development of services for people with intellectual disability were interviewed 2 years after the end of the initial 10-year phase. Interviewees were asked to reflect on the strengths and weaknesses of policy implementation, including: changing priorities, planning arrangements, agency roles, central guidance and financial mechanisms, consumer participation, and the impact of more recent policy or structural developments. Despite recognition of the leadership of the Welsh Office, the shift in thinking achieved, the developments made in joint agency collaboration and in consumer participation in planning, and an increasing competence to plan effectively over time, the overriding perception was that more could have been made of the opportunity afforded by the clearest and best resourced central government policy within the UK in this area. At the heart of this judgement lay concerns about pragmatic rather than strategic planning, a failure to link annual service developments to a final comprehensive end point and a related failure to integrate planning to meet community needs with hospital resettlement Factors which may have contributed to these weaknesses are discussed, as are lessons for subsequent community care policy.

Community Health Planning↗

Safety in the OR.

Explore the source record for details and available documents.

Accidents, Occupational↗

Phase 2 clinical trial of attenuated Salmonella enterica serovar typhi oral live vector vaccine CVD 908-htrA in U.S. volunteers.

Salmonella enterica serovar Typhi strain CVD 908-htrA is a live attenuated strain which may be useful as an improved oral typhoid vaccine and as a vector for cloned genes of other pathogens. We conducted a phase 2 trial in which 80 healthy adults received one of two dosage levels of CVD 908-htrA in a double-blind, placebo-controlled, crossover study. There were no differences in the rates of side effects among volunteers who received high-dose vaccine (4.5 x 10(8) CFU), lower-dose vaccine (5 x 10(7) CFU), or placebo in the 21 days after vaccination, although recipients of high-dose vaccine (8%) had more frequent diarrhea than placebo recipients (0%) in the first 7 days. Seventy-seven percent and 46% of recipients of high- and lower-dose vaccines, respectively, briefly excreted vaccine organisms in their stools. All blood cultures were negative. Antibody-secreting cells producing antilipopolysaccharide (LPS) immunoglobulin A (IgA) were detected in 100 and 92% of recipients of high- and lower-dose vaccines, respectively. Almost half the volunteers developed serum anti-LPS IgG. Lymphocyte proliferation and gamma interferon production against serovar Typhi antigens occurred in a significant proportion of vaccinees. This phase 2 study supports the further development of CVD 908-htrA as a single-dose vaccine against typhoid fever and as a possible live vector for oral delivery of other vaccine antigens.

Administration, Oral↗

Adverse drug reactions: a review of relevant factors.

We examined some of the factors that contribute to the development of adverse drug reactions (ADRs) and analyzed postmarketing ADR reports for 22 drugs. The role of metabolic-based drug-drug interaction in the development of ADRs can not be overstated. Assessment of the postmarketing ADR data for 22 drugs revealed that drugs with high potential for eliciting clinically significant ADRs are usually detected and either withdrawn from the market or placed on restricted use within the first year or two of marketing. Postmarketing data could be a useful tool for understanding the ADR profile of drugs if reporting can be adequately monitored and verified. It is hoped that early evaluation of the clinically meaningful factors such as metabolism, pharmacogenetics, and effect of physiologic and pathophysiologic states on the clinical effect of a drug during drug development would significantly reduce the incidence and severity of post-marketing ADRs.

Adverse Drug Reaction Reporting Systems↗

Legislating sharps safety.

Various state laws, passed and pending, stress the need for federal legislation on needle-stick prevention.

Accidents, Occupational↗

FXY2/MID2, a gene related to the X-linked Opitz syndrome gene FXY/MID1, maps to Xq22 and encodes a FNIII domain-containing protein that associates with microtubules.

Opitz G/BBB syndrome (OS) is a genetically heterogeneous disorder with an X-linked locus and an autosomal locus linked to 22q11.2. OS affects multiple organ systems with often variable severity even between siblings. The clinical features, which include hypertelorism, cleft lip and palate, defects of cardiac septation, hypospadias, and anorectal anomalies, indicate an underlying disturbance of the developing ventral midline of the embryo. The gene responsible for X-linked OS, FXY/MID1, is located on the short arm of the human X chromosome within Xp22.3 and encodes a protein with both an RBCC (RING finger, B-box, coiled coil) and a B30.2 domain. The Fxy gene in mice is also located on the X chromosome but spans the pseudoautosomal boundary in this species. Here we describe a gene closely related to FXY/MID1, called FXY2, which also maps to the X chromosome within Xq22. The mouse Fxy2 gene is located on the distal part of the mouse X chromosome within a region syntenic to Xq22. Analysis of genes flanking both FXY/MID1 and FXY2 (as well as their counterparts in mouse) suggests that these regions may have arisen as a result of an intrachromosomal duplication on an ancestral X chromosome. We have also identified in both FXY2 and FXY/MID1 proteins a conserved fibronectin type III domain located between the RBCC and B30.2 domains that has implications for understanding protein function. The FXY/MID1 protein has previously been shown to colocalize with microtubules, and here we show that the FXY2 protein similarly associates with microtubules in a manner that is dependent on the carboxy-terminal B30.2 domain.

Abnormalities, Multiple↗

Evolutionary rate of a gene affected by chromosomal position.

Genes evolve at different rates depending on the strength of selective pressure to maintain their function. Chromosomal position can also have an influence [1] [2]. The pseudoautosomal region (PAR) of mammalian sex chromosomes is a small region of sequence identity that is the site of an obligatory pairing and recombination event between the X and Y chromosomes during male meiosis [3] [4] [5] [6]. During female meiosis, X chromosomes can pair and recombine along their entire length. Recombination in the PAR is therefore approximately 10 times greater in male meiosis compared with female meiosis [4] [5] [6]. The gene Fxy (also known as MID1 [7]) spans the pseudoautosomal boundary (PAB) in the laboratory mouse (Mus musculus domesticus, C57BL/6) such that the 5' three exons of the gene are located on the X chromosome but the seven exons encoding the carboxy-terminal two-thirds of the protein are located within the PAR and are therefore present on both the X and Y chromosomes [8]. In humans [7] [9], the rat, and the wild mouse species Mus spretus, the gene is entirely X-unique. Here, we report that the rate of sequence divergence of the 3' end of the Fxy gene is much higher (estimated at 170-fold higher for synonymous sites) when pseudoautosomal (present on both the X and Y chromosomes) than when X-unique. Thus, chromosomal position can directly affect the rate of evolution of a gene. This finding also provides support for the suggestion that regions of the genome with a high recombination frequency, such as the PAR, may have an intrinsically elevated rate of sequence divergence.

Animals↗

An iterative structure-assisted approach to sequence alignment and comparative modeling.

Correct alignment of the sequence of a target protein with those of homologues of known three-dimensional structure is a key step in comparative modeling. Usually an iterative approach that takes account of the local and overall structural features is required. We describe such an approach that exploits databases of structural alignments of homologous proteins (HOMSTRAD, http:/(/)www-cryst.bioc.cam.ac.uk/ approximately homstrad) and protein superfamilies (CAMPASS, http:/(/)www-cryst.bioc.cam.ac.uk/ approximately campass), in which structure-based alignments are analyzed and formatted with the program JOY (http:/(/)www-cryst.bioc.cam.ac.uk/ approximately joy) to reveal conserved local structural features. The databases facilitate the recognition of a family or superfamily, they assist in the selection of useful parent structures, they are helpful in alignment of the target sequences with the parent set, and are useful for deriving relationships that can be used in validating models. In the iterative approach, a model is constructed on the basis of the proposed sequence alignment and this is then reexpressed in the JOY format and realigned with the parent set. This is repeated until the model and sequence alignment is optimized. We examine the case for comparison and use of multiple structures of family members, rather than a single parent structure. We use the targets attempted by our group in CASP3 to assess the value of such procedures.

Algorithms↗

RESEARCH: Comparison of Temporal Trends in Ambient and Compliance Trace Element and PCB Data in Pool 2 of the Mississippi River, USA, 1985-1995.

/ The Intergovernmental Task Force on Monitoring has suggested studies on ambient (in-stream) and compliance (wastewater) data to determine if monitoring can be reduced locally or nationally. The similarity in temporal trends between retrospective ambient and compliance water-quality data collected from Pool 2 of the Mississippi River, USA, was determined for 1985-1995. Constituents studied included the following trace elements: arsenic (As), cadmium (Cd), chromium (Cr), hexavalent chromium (Cr(6+)), copper (Cu), lead (Pb), mercury (Hg), nickel (Ni), selenium (Se), zinc (Zn), and polychlorinated biphenyls (PCBs). Water-column, bed-sediment, and fish-tissue (fillets) data collected by five government agencies comprised the ambient data set; effluent data from five registered facilities comprised the compliance data set. The nonparametric Mann-Kendall trend test indicated that 33% of temporal trends in all data were statistically significant (P < 0.05). Possible reasons for this were low sample sizes, and a high percentage of samples below the analytical detection limit. Trends in compliance data were more distinct; most trace elements decreased significantly, probably due to improvements in wastewater treatment. Seven trace elements (Cr, Cd, Cu, Pb, Hg, Ni, and Zn) had statistically significant decreases in wastewater and portions of either or both ambient water and bed sediment. No trends were found in fish tissue. Inconsistency in trends between ambient and compliance data were often found for individual constituents, making overall similarity between the data sets difficult to determine. Logistical differences in monitoring programs, such as varying field and laboratory methods among agencies, made it difficult to assess ambient temporal trends.KEY WORDS: Mann-Kendall trend test; Ambient data; Compliance data; Trace elements; PCBs, Mississippi Riverhttp://link.springer-ny.com/link/service/journals/00267/bibs/24n4p497.html</HEA

Journal Article↗