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Biomedical subjects

J Rogers

Publications and source records attributed to J Rogers.

At least 73 records · Page 4Linked to original sources
PubMed2001

A quantitative trait locus influencing activin-to-estrogen ratio in pedigreed baboons maps to a region homologous to human chromosome 19.

Activin is a multifunctional hormone playing a major role in the regulation of reproduction and growth and development. We performed a genomewide scan using multipoint linkage analysis implemented in a general pedigree-based variance component approach to identify genes with measurable effects on variation in the activin-to-estrogen ratio in baboons. A microsatellite polymorphism, D19S714, which maps to human chromosome 19p13.2, showed marginal evidence of linkage with a lod (log10 of the odds in favor of genetic linkage) score of 1.95 (0.014). This region contains several potential candidate genes including PKA (protein kinase, cAMP-dependent, catalytic alpha) and the gene pair JUN-B and JUN-D. This is the first evidence of a quantitative trait locus with a significant effect on the activin-to-estrogen ratio.

Activins↗
PubMed2001

GALEN ten years on: tasks and supporting tools.

The GALEN technology has matured over more than a decade of use. We describe a set of software tools and associated methodologies that together are supporting ontological engineering in a production, rather than a research setting.

Artificial Intelligence↗
PubMed2001

Assessment of the GALEN methodology on holistic classifications for professions allied to medicine.

In the field of health care terminology it has proven to be difficult, but not impossible, to build a formal Reference Model (knowledge-model) for medical terminology. The intuition is that it is even more difficult to build such a reference model for the so called â holistic' classification schemes as used by Nursing and Allied Health Care Professionals. There is a growing perceived need for formal reference models for specific professional groups. These reference models are used in many different ways, such as for building, maintaining and manipulating classification schemes. This paper focuses on the usability of the GALEN methodology for the formalisation of the Dutch Classification of Pain (NCP) as an example of such a â holistic classification'. The first results of this exploration show that the GALEN methodology is very useful for analysing and understanding a' holistic classification'. A high number of necessary concepts from the NCP already exist within the OpenGalen Common Reference Model-2 (OCRM2). A substantial number of concepts from the NCP do not yet exist in the OCRM2 or are underspecified. Additional modelling of the OCRM2 has to be performed, to enrich the expressivity of the model.

Allied Health Occupations↗
PubMed2001

Improving systems related to clinical practice: an interdisciplinary team approach.

An interdisciplinary forum to examine systems related to clinical practice strengthens collaboration and capitalizes on the collective knowledge base of all members. The success of the clinical practice committee is dependent primarily on the ability of the group to negotiate complex systems, as well as authorize changes in clinical practice. The nurse leader plays a critical role as facilitator and mentor in this process. This report describes the evolution of the clinical practice committees at Children's Hospital Boston, provides practical strategies for group development, includes methods to maximize the effectiveness of a diverse group, and presents examples of system improvements and outcomes that have emerged from this interdisciplinary team.

Boston↗
PubMed2001

Cadaveric renal transplantation in African-Americans in South Carolina.

The renal transplant program at the MUSC was established in 1968 and is the only transplant center in South Carolina. It serves a large population of African American patients who constitute nearly two-thirds of the waiting list and more than half of all renal transplants. Between 1968-2000, 969 transplants were performed in 906 AA patients. Most received organs from cadaveric donors, while only 99 (10%) of AA patients received living donor transplants. The acceptance of living unrelated donors and the use of laparoscopic nephrectomy have had a negligible impact on living donations in this racial group. Primary disease had little effect on outcome except in diabetics whose mortality was higher. The one-year graft survival rates improved dramatically with the aggressive use of CsA without the use of antibody induction. The overall one- and 5-year graft survival rates improved from 53% and 32%, respectively, in the 1978-1983 era to 87% and 59%, respectively, in the 1993-2001 era. At MUSC, the emphasis has been on reducing mortality due to sepsis by limiting the number of rejections treated particularly in recipients of cadaveric organs. While this has resulted in reduced overall early mortality, it has not adversely affected graft survival. Our experience suggests that while short-term graft survival has improved significantly over the years for AA patients, the long-term outcome still remains relatively unchanged.

Black or African American↗
PubMed2001

Necessity, private defence and the killing of Mary.

This article examines the reasons used by the Court of Appeal in Re A (Children) to authorise and justify an operation which would inevitably kill the weaker of a pair of conjoined twins in order to offer the stronger twin a good chance of a long and happy life. The crux of the judgment was that a utilitarian theory of necessity could justify this operation. This article seeks to define the criminal law defences at issue in the case and to argue that utilitarian necessity is such a dangerous doctrine that it should never be employed if there is any other defence which can be made to serve the same purpose--as there was in the present case.

Criminal Law↗
PubMed2000

Neural tract tracing using Di-I: a review and a new method to make fast Di-I faster in human brain.

The use of Di-I in tract-tracing is briefly reviewed and a novel delayed-fixation approach to neural tract-tracing in the postmortem human adult brain is reported. Using the new approach, fast Di-I, a highly lipophilic fluorescent dye was injected into a particular region or nucleus and labelled tracts were followed for distances of some 20-40 mm. The procedure required approximately 36 h, yielding dye penetration rates of 1.0 mm/h or more. This contrasts with previous Di-I, silver impregnation, and horseradish peroxidase protocols, where the tracer penetration rate is typically 0.003 mm/h or less, and the distance traversed amounts to only a few mm even after months of incubation. The new method hinges on the simple consideration that aldehyde fixation, which is normally employed prior to administration of the marker, crosslinks membrane proteins and impedes dye diffusion. The short postmortem samples used in our protocol permit delaying fixation until after the dye has had time to penetrate, dramatically increasing the length and scope of neural circuits that can be traced. Using these methods, for example, we have confirmed the presence of an ipsilateral olivocerebellar climbing fiber projection in the human.

Animals↗
PubMed2000

Mucopolysaccharidosis type IIIB: characterisation and expression of wild-type and mutant recombinant alpha-N-acetylglucosaminidase and relationship with sanfilippo phenotype in an attenuated patient.

Mucopolysaccharidosis type IIIB (MPS-IIB) is a lysosomal storage disorder characterised by the defective degradation of heparan sulfate due to a deficiency of alpha-N-acetylglucosaminidase (NAG). The clinical severity of MPS-IIIB ranges from an attenuated to severely affected Sanfilippo phenotype. This paper describes the expression and characterisation of wild-type recombinant NAG and the molecular characterisation of a previously identified R297X/F48L compound heterozygous MPS-IIIB patient with attenuated Sanfilippo syndrome. We have previously shown R297X to be the most common mutation in a cohort of Dutch and Australian patients, occurring at a frequency of approximately 12.5%. To date F48L has only been described in the proband. To determine the contribution of each mutation to the overall clinical phenotype of the patient, both mutant alleles were engineered into the wild-type NAG cDNA and expressed in Chinese hamster ovary cells. The wild-type NAG and F48L mutant alleles were also retrovirally expressed in MPS-IIIB skin fibroblasts. Residual NAG activity and the stability and maturation of immunoprecipitated NAG were determined for wild-type NAG and mutant NAG. The combined biochemical phenotypes of the two NAG mutant alleles demonstrated a good correspondence with the observed attenuated Sanfilippo phenotype of the patient.

Acetylglucosaminidase↗
PubMed2000

Deficiency of complement defense protein CD59 may contribute to neurodegeneration in Alzheimer's disease.

Complement defense 59 (CD59) is a cell surface glycophosphoinositol (GPI)-anchored protein that prevents complement membrane attack complex (MAC) assembly. Here, we present evidence from ELISA assays that CD59 protein levels are significantly decreased in the frontal cortex and hippocampus of Alzheimer's disease (AD) compared with nondemented elderly (ND) patients, whereas complement component 9, a final component to form MAC, is significantly increased. To further confirm the CD59 deficit, PI-specific phospholipase C (PIPLC) was used to cleave the CD59 GPI anchor at the cell surface in intact slices from AD and ND cortex. CD59 released by PIPLC cleavage was significantly reduced in AD compared with ND samples. By the use of a ribonuclease protection technique, amyloid beta-peptide was found to downregulate CD59 expression at the mRNA level, suggesting a partial explanation of CD59 deficits in the AD brain. To evaluate the pathophysiological significance of CD59 alterations in neurons, we exposed cultured NT2 cells, which normally underexpress CD59, and NT2 cells transfected to overexpress CD59 to homologous human serum. Lactic acid dehydrogenase assays revealed significant complement-induced cell lysis in CD59-underexpressing NT2 cells and significant protection from such lysis in CD59-overexpressing NT2 cells. Moreover, cells expressing normal levels of CD59 showed no evidence of MAC assembly or damage after exposure to homologous serum, whereas pretreatment of these cells with a CD59-neutralizing antibody resulted in MAC assembly at the cell surface and morphological damage. Taken together, these data suggest that CD59 deficits may play a role in the neuritic losses characteristic of AD.

Aged↗
PubMed2000

Detection of complement alternative pathway mRNA and proteins in the Alzheimer's disease brain.

Previous research on complement activation in the Alzheimer's disease (AD) brain has focused almost exclusively on the classical complement pathway. The alternative pathway represents another important arm for complement activation, converging with the classical cascade at the C5 cleavage step. Here, we show that mRNA for a critical alternative pathway component, factor B, is present in AD frontal cortex and that the factor D cleaved split products of factor B, Bb and Ba, are significantly increased, indicating alternative pathway activation. By contrast, the two major inhibitors of alternative pathway activation, factor H and factor I, are present at the level of mRNA and protein but are not significantly upregulated. Immunohistochemical analysis reveals significant positive staining in AD sections for all three components. Taken together with previous reports demonstrating alternative pathway activation by amyloid beta peptide, these findings suggest that conditions conducive to chronic alternative pathway activation may exist in the AD brain.

Aged↗
PubMed2000

An SNP map of human chromosome 22.

The human genome sequence will provide a reference for measuring DNA sequence variation in human populations. Sequence variants are responsible for the genetic component of individuality, including complex characteristics such as disease susceptibility and drug response. Most sequence variants are single nucleotide polymorphisms (SNPs), where two alternate bases occur at one position. Comparison of any two genomes reveals around 1 SNP per kilobase. A sufficiently dense map of SNPs would allow the detection of sequence variants responsible for particular characteristics on the basis that they are associated with a specific SNP allele. Here we have evaluated large-scale sequencing approaches to obtaining SNPs, and have constructed a map of 2,730 SNPs on human chromosome 22. Most of the SNPs are within 25 kilobases of a transcribed exon, and are valuable for association studies. We have scaled up the process, detecting over 65,000 SNPs in the genome as part of The SNP Consortium programme, which is on target to build a map of 1 SNP every 5 kilobases that is integrated with the human genome sequence and that is freely available in the public domain.

Cell Line↗
PubMed2000

Genomic sequence and transcriptional profile of the boundary between pericentromeric satellites and genes on human chromosome arm 10q.

The organization of centromeric heterochromatin has been established in a number of eucaryotes but remains poorly defined in human. Here we present 1025 kb of contiguous human genomic sequence which links pericentromeric satellites to the RET proto-oncogene in 10q11.2 and is presumed to span the transition from centric heterochromatin to euchromatin on this chromosome arm. Two distinct domains can be defined within the sequence. The proximal approximately 240 kb consists of arrays of satellites and other tandem repeats separated by tracts of complex sequence which have evolved by pericentromeric-directed duplication. Analysis of 32 human paralogues of these sequences indicates that most terminate at or within repeat arrays, implicating these repeats in the interchromosomal duplication process. Corroborative PCR-based analyses establish a genome-wide correlation between the distribution of these paralogues and the distribution of satellite families present in 10q11. In contrast, the distal approximately 780 kb contains few tandem repeats and is largely chromosome specific. However, a minimum of three independent intrachromosomal duplication events have resulted in >370 kb of this sequence sharing >90% identity with sequences on 10p. Using computer-based analyses and RT-PCR we confirm the presence of three genes within the sequence, ZNF11/33B, KIAA0187 and RET, in addition to five transcripts of unknown structure. All of these transcribed sequences map distal to the satellite arrays. The boundary between satellite-rich interchromosomally duplicated DNA and chromosome-specific DNA therefore appears to define a transition from pericentromeric heterochromatin to euchromatin on the long arm of this chromosome.

Centromere↗
PubMed2000

A genetic linkage map of the baboon (Papio hamadryas) genome based on human microsatellite polymorphisms.

A first-generation genetic linkage map of the baboon (Papio hamadryas) genome was developed for use in biomedical and evolutionary genetics. Pedigreed baboons (n = 694) were selected from the breeding colony maintained by the Southwest Foundation for Biomedical Research. To facilitate comparison with the human genome, the baboon linkage map consists primarily of human microsatellite loci amplified using published human PCR primers. Genotypes for 325 human microsatellites and 6 novel baboon microsatellites were used in linkage analyses performed with the MultiMap expert system. The resulting sex-averaged meiotic recombination map covers all 20 baboon autosomes, with average spacing among loci of 7.2 cM. Direct comparison among homologous (orthologous) loci reveals that, for 7 human autosomes, locus order is conserved between humans and baboons. For the other 15 autosomes, one or more rearrangements distinguish the two genomes. The total centimorgan distances among homologous markers are 28.0% longer in the human genome than in the baboon, suggesting that rates of recombination may be higher in humans. This baboon linkage map is the first reported for any nonhuman primate species and creates opportunities for mapping quantitative trait loci in baboons, as well as for comparative evolutionary analyses of genome structure.

Animals↗
PubMed2000

Human herpesvirus-6 in liver transplant recipients: role in pathogenesis of fungal infections, neurologic complications, and outcome.

BACKGROUND: The clinical impact and relevance of human herpesvirus-6 (HHV-6) infection in liver transplant recipients, has not been fully discerned. METHODS: A prospective study of 80 consecutive liver transplant recipients was performed using surveillance cultures for HHV-6 at weeks 2, 3, 4, and 6 after transplantation. Viral isolation was used for the detection of HHV-6. RESULTS: HHV-6 infection occurred in 39% (31 of 80) of the patients. Patients with HHV-6 infection were more likely to have hepatocellular carcinoma as underlying liver disease (P=.09). Mental status changes of unidentifiable etiology were significantly more likely to occur in patients with HHV-6 compared with those without (26%, 9 of 31 vs. 6%, 3 of 49, P=.008). HHV-6 infection was an independent predictor of invasive fungal infections (odds ratio 8.3, 95% confidence interval, 1.2-58.0, P=.03). A significant association between HHV-6 infection and CMV infection after transplantation, CMV recipient and donor serostatus, rejection, or fever of unknown origin, could not be documented. Mortality at last follow-up in patients with HHV-6 infection (29%, 9 of 31) was significantly greater than those without HHV-6 (6%, 3 of 49, P=.008). CONCLUSIONS: Central nervous system complications of unknown etiology after liver transplantation may be related to HHV-6 infection. HHV-6 viremia was an independently significant predictor of invasive fungal infections and was associated with late mortality in liver transplantation recipients.

Adult↗