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Biomedical subjects

A L Jones

Publications and source records attributed to A L Jones.

At least 73 records · Page 4Linked to original sources
PubMed1998

De novo methylation and co-suppression induced by a cytoplasmically replicating plant RNA virus.

The relationship between co-suppression and DNA methylation was explored in transgenic plants showing inducible co-suppression following infection with a cytoplasmically replicating RNA virus. Induction resulted in a loss of transgene mRNA and resistance to further infection, factors typical of post-transcriptional gene silencing. In infected plants, de novo methylation of the transgene appeared to precede the onset of resistance and only occurred in plants where the outcome was co-suppression. The methylation was limited to sequences homologous to the viral RNA and occurred at both symmetric and non-symmetric sites on the DNA. Although methylation is predicted to occur in mitotic cells, the virus was found not to access the meristem. A diffusible sequence-specific signal may account for the epigenetic changes in those tissues.

DNA Methylation↗
PubMed1998

Carcinoid tumour.

Carcinoid tumours are often indolent asymptomatic tumours. However, a small but significant proportion are malignant and difficult to manage. Multiple endocrine neoplasia type 1 (MEN-1) may be associated with carcinoid tumours and should therefore be considered in the investigation of these patients. This review puts into context the use of newer imaging modalities, including octreotide scintigraphy. The therapeutic treatment options are discussed, including the use of octreotide, the role of receptor-targeted therapy, hepatic-artery embolisation, and the arguments against chemotherapy. We review the need for careful patient selection when considering curative and palliative surgery, including liver transplantation. We conclude that there are now better diagnostic tools and therapeutic options available for those patients with malignant carcinoid tumours, and that these patients are best managed by a multidisciplinary approach. Earlier detection and treatment of these tumours should lead to improved quality of life and survival, which, ideally, should be assessed in formal trials.

Carcinoid Tumor↗
PubMed1998

Cholesterol 7alpha-hydroxylase (CYP7A): patterns of messenger RNA expression during rat liver development.

Cholesterol 7-hydroxylase is a rate-limiting enzyme in bile acid synthesis, a major pathway for cholesterol catabolism. It plays a crucial role in postnatal development and survival. In an adult liver, its activity and messenger RNA (mRNA) are heterogeneously distributed with concentration in the pericentral area. We defined how the pattern of cholesterol 7-hydroxylase mRNA evolves during rat liver development, correlated this with its total liver mRNA levels, and determined when its heterogeneous pattern of expression is established. Cholesterol 7-hydroxylase mRNA was undetectable in 18-day-old fetal livers by Northern blot. It was increased markedly in newborns with a homogeneous liver lobular distribution as determined by in situ hybridization. At postnatal day four, mRNA levels were markedly decreased with concomitant appearance of a lobular gradient: mRNA was detected only in a few hepatocytes located around efferent venules. At 22 days, the time of highest mRNA expression, a marked extension of the gradient towards the periportal area was observed, indicating that the increase in total liver cholesterol 7-hydroxylase mRNA level was a result of recruitment of hepatocytes upstream from the central vein area. By 28 days, the adult pattern was observed. Thus, expression of cholesterol 7-hydroxylase mRNA is tightly regulated during rat liver development, both temporally and spatially supporting its critical role in normal postnatal development.

Aging↗
PubMed1998

Huntingtin protein colocalizes with lesions of neurodegenerative diseases: An investigation in Huntington's, Alzheimer's, and Pick's diseases.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease associated with a CAG trinucleotide repeat expansion in a large gene on chromosome 4. The gene encodes the protein huntingtin with a polyglutamine tract encoded by the CAG repeat at the N-terminus. The number of CAG repeats in HD are significantly increased (36 to 120+) compared with the normal population (8-39). The pathological mechanism associated with the expanded CAG repeat in HD is not clear but there is evidence that polyglutamine is directly neurotoxic. We have immunolocalized huntingtin with an in-house, well-characterised, polyclonal antibody in HD, Alzheimer's disease (AD), and Picks disease (PiD) brains. Control brain tissue sections were from head injured and cerebral ischaemia cases. In HD, huntingtin was immunopositive in the surviving but damaged neurons and reactive astrocytes of the caudate and putamen. However, in AD and PiD the immunostaining was largely restricted to the characteristic intracellular inclusion bodies associated with the disease process in each case. In AD, huntingtin was localized only in the intracellular neurofibrillary tangles and dystrophic neurites within the neuritic amyloid plaques but not with the amyloid. In PiD, strongly positive huntingtin immunostaining was present within cytoplasmic Pick bodies. Our findings suggest huntingtin selectively accumulates in association with abnormal intracytoplasmic and cytoskeletal filaments of neurons and glia in neurodegenerative diseases such as HD, AD, and PiD. Cells in the CNS appear sensitive to damage by the aggregated, toxic levels of huntingtin and evidence of its interaction with neurofilaments could provide information about its potential role in the aetiology of HD.

Adult↗
PubMed1998

Detection of carboxypeptidases as taxonomic markers for gram-negative bacteria.

The use of seven benzoyl-L-amino acids for the detection of carboxypeptidase activities in strains of Gram-negative aerobic and facultatively anaerobic bacteria is reported. A simple overnight assay was designed using ninhydrin for the demonstration of the amino acid released by hydrolysis. Detection of carboxypeptidase activity was shown to have some taxonomic relevance within the Enterobacteriaceae; it was also useful for differentiation within the genus Acinetobacter and for distinction between Pseudomonas aeruginosa and Pseudomonas fluorescens.

Amino Acids↗
PubMed1998

Huntingtin interacts with cystathionine beta-synthase.

We have screened a rat brain library to identify proteins which interact with the 5'-end of huntingtin (amino acids 1-171), including the polyglutamine tract, in the yeast two-hybrid system. We detected an interaction with cystathionine beta-synthase (CBS) [L-serine hydrolyase (adding homocysteine), EC 4.2.1.22], which was confirmed in vitro using His-tagged CBS expressed in Escherichia coli , which was able to specifically bind both rat and human full-length huntingtin. Neither normal nor expanded polyglutamine repeat alone interacted with CBS in the yeast two-hybrid system and nor did constructs containing SBMA or DRPLA with normal or expanded polyglutamine tracts. CBS therefore appears to bind specifically to huntingtin. CBS deficiency is associated with homocystinuria, which is known to affect various physiological systems, including the central nervous system. Homocysteine, one of the substrates of CBS, is known to accumulate in homocystinuria and is metabolized to homocysteate and homocysteine sulphinate, both known to be powerful excitotoxic amino acids. It has been suggested that Huntington's disease involves the action of excitotoxic amino acids and this interaction with CBS may suggest a mechanism for such excitotoxic damage.

Animals↗
PubMed1998

Haemodynamic parameters predicting variceal haemorrhage and survival in alcoholic cirrhosis.

The relationship between the various haemodynamic abnormalities observed in cirrhosis and their prognostic value remains unclear. We report haemodynamic measurements on 96 patients with alcoholic cirrhosis (mean Childs-Pugh Score, CPS, 9.0 +/- 0.2, mean age 55.6 +/- 1.0 years) and assess their value in predicting variceal bleeding and death during a mean follow-up of 19.3 +/- 1.5 months. Baseline CPS correlated with hepatic venous pressure gradient (HVPG) (p = 0.001), azygos blood flow (p < 0.05), cardiac index (p < 0.05), and inversely with mean arterial pressure (p < 0.01) and systemic vascular resistance index (p < 0.05). Renal blood flow was not related to any haemodynamic parameter or CPS. Thirty-eight patients died during follow-up, and 16 had a variceal bleed. Death (p = 0.001) and variceal bleeding (p < 0.05) were more likely in patients with HVPG > 16 mmHg than in those with HVPG < 16 mmHg, and variceal bleeding was more likely in patients with HVPG > 12 mmHg (vs. HVPG < 12 mmHg, p < 0.05). HVPG also predicted death and variceal haemorrhage on univariate and multivariate analyses. No other haemodynamic parameter predicted death or bleeding. In alcoholic cirrhosis, severity of liver disease is related to HVPG, collateral blood flow and degree of systemic circulatory abnormalities. HVPG is a useful predictor of survival and variceal bleeding in these patients.

Adult↗
PubMed1998

Drug abusers and poisoned patients: a potential source of organs for transplantation?

One of the major constraints to transplantation of solid organs is lack of availability of grafts and any attempt to use all available donors is to be welcomed. We address the possibility of expanding the transplant donor pool by inclusion of more patients who have suffered intoxication with drugs premortem. Particularly important in this context is the exclusion of organ-specific damage, and also infective risk to the potential recipient due to viral causes in the donor.

Brain Death↗
PubMed1998

Percutaneous fixation of the columns of the acetabulum: a new technique.

A technique for percutaneous placement of cannulated screws in the acetabulum is presented. Surgical technique is described, and fluoroscopic imaging techniques used to guide screw placement are also illustrated. The technique was used to limit soft tissue dissection in three patients. Results and examples are presented.

Acetabulum↗
PubMed1998

Specificity of resistance to pea seed-borne mosaic potyvirus in transgenic peas expressing the viral replicase (Nlb) gene.

Transgenic pea lines carrying the replicase (NIb) gene of pea seed-borne mosaic potyvirus (PSbMV) were generated and used in experiments to determine the effectiveness of induced resistance upon heterologous isolates. Three pea lines showed inducible resistance in which an initial infection by the homologous isolate (PSbMV-DPD1) was followed by a highly resistant state. Resistance was observed in plants in either the homozygous or hemizygous condition and resulted in no overall yield loss despite the initial infection. Resistance was associated with a loss of both viral and transgene RNA, which is indicative of a mechanism based upon post-transcriptional gene silencing. There was no correlation between the steady-state levels of transgene RNA and ability of the plants to show resistance. To test the specificity of the resistance, plants were also inoculated with the most distantly related sequenced PSbMV isolate, NY. PSbMV-NY varied between experiments in its ability to induce resistance, suggesting that the sequence identity in the NIb gene is borderline for the specificity required for triggering gene silencing. Upon challenge inoculation of virus-free recovered leaves, the specificity of the induced resistance varied between the two isolates and indicated that the virus and transgene additively determined the resistant state. These results suggest that the sequence requirements for triggering gene silencing may differ from those involved in the degradation process.

Cell Transformation, Viral↗
PubMed1998

Effect of recombinant human bone morphogenetic protein-2 on fracture healing in a goat tibial fracture model.

Bone morphogenetic proteins (BMPs) are considered to have important regulatory roles in skeletal embryogenesis and bone healing. Recombinant human BMPs (rhBMPs) have been shown to heal critical size defects and promote spinal fusion. We studied the effects of rhBMP-2 in an absorbable collagen sponge (ACS) on bone healing in a large animal tibial fracture model. Bilateral closed tibial fractures were created in 16 skeletally mature goats and reduced and stabilized using external fixation. In each animal, one tibia received the study device (0.86 mg of rhBMP-2/ACS or buffer/ACS), and the contralateral fracture served as control. The device was implanted as a folded onlay or wrapped circumferentially around the fracture. Six weeks following fracture, the animals were sacrificed and the tibiae harvested for torsional testing and histomorphologic evaluation. Radiographs indicated increased callus at 3 weeks in the rhBMP-2/ACS treated tibiae. At 6 weeks, the rhBMP-2/ACS wrapped fractures had superior radiographic healing scores compared with buffer groups and controls. The rhBMP-2/ACS produced a significant increase in torsional toughness (p = 0.02), and trends of increased torsional strength and stiffness (p = 0.09) compared with fracture controls. The device placed in a wrapped fashion around the fracture produced significantly tougher callus (p = 0.02) compared with the onlay application. Total callus new bone volume was significantly increased (p = 0.02) in the rhBMP-2/ACS fractures compared with buffer groups and controls regardless of the method of device application. The rhBMP-2/ACS did not alter the timing of onset of periosteal/endosteal callus formation compared with controls. Neither the mineral apposition rates nor bone formation rates were affected by rhBMP-2/ACS treatment. The increased callus volume associated with rhBMP-2 treatment produced only moderate increases in strength and stiffness.

Animals↗