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Biomedical subjects

M J Ball

Publications and source records attributed to M J Ball.

At least 55 records · Page 3Linked to original sources

The abundant latency-associated transcripts of herpes simplex virus type 1 are bound to polyribosomes in cultured neuronal cells and during latent infection in mouse trigeminal ganglia.

During herpes simplex virus type 1 (HSV-1) latency, limited viral transcription takes place. This transcription has been linked to the ability of the HSV-1 genome to reactivate and consists of abundant 2.0- and 1.5-kb collinear latency-associated transcripts (LATs), spanned by minor hybridizing RNA (mLAT). The 1.5-kb LAT is derived from the 2.0-kb LAT by splicing, and both transcripts contain two large overlapping open reading frames. The molecular action mechanisms of the latency-associated gene expression are unknown, and no HSV-1 latency-encoded proteins have been convincingly demonstrated. We have cloned the entire latency-associated transcriptionally active HSV-1 DNA fragment (10.4 kb) under control of a constitutive promoter and generated a neuronal cell line (NA4) stably transfected with the viral LAT's region. NA4 cells produced the 2.0- and the 1.5-kb LATs. Northern blotting and reverse transcription-PCR analysis of RNA from NA4 cells and from trigeminal ganglia of mice latently infected with HSV-1 revealed that the two abundant LAT species were present in the polyribosomal RNA fractions. After addition of EDTA, which causes dissociation of mRNA-ribosome complexes, both LATs could be detected only in subpolyribosomal, but not in polyribosomal fractions. These results show that (i) HSV-1 LATs are bound to polyribosomes during latency in vivo, as well as in neuronal cells in vitro, and therefore might be translated, and that (ii) the NA4 cell line is a suitable tool with which to look for HSV-1 latency-encoded gene products.

Animals↗

Metabolic effects of alterations in meal frequency in type 2 diabetes.

OBJECTIVE: The effects of altering meal frequency on measures of glucose and lipid metabolism in type 2 diabetes were examined by comparing isocaloric dietary regimens in which daily food intake was provided by three or nine meals each day. RESEARCH DESIGN AND METHODS: A total of 13 free-living men and women with type 2 diabetes or persistently impaired glucose tolerance participated in a randomized crossover study in which three- and nine-meal regimes were followed for 4-week periods. Fasting plasma lipid and lipoprotein, glucose and insulin concentrations were measured at weekly intervals and glucose, insulin, and triglyceride responses following a 75-g glucose load at weeks 2 and 4 of each diet period. Dietary intake was also recorded during these weeks. RESULTS: Nutrient intakes and all measures of carbohydrate and lipid metabolism were similar on the three- and nine-meal regimes. CONCLUSIONS: This longer-term study could not confirm the potential benefits of increased meal frequency suggested by comparable 4-week studies in type 2 diabetic individuals and acute experiments in individuals with diabetes. However, as there were no adverse effects of consuming nine meals per day, it would seem appropriate that meal frequency in those with type 2 diabetes should be left to personal choice, provided that energy balance is maintained.

Aged↗

New challenges for nursing informatics.

Long a leader in health informatics, nursing faces new challenges. The full and effective use of technology requires an understanding of cognitive processes and organizational behavior. Nursing can play a key role in addressing aims supportive of a new vision of health informatics. The evolving paradigm for knowledge transfer will give rise to new educational models and new institutional entities which will nurture learning and relearning.

Education, Nursing↗

Philosophy into practice: a health informatics course proposal.

International health informaticians acknowledge the critical importance of education and training to the successful implementation of information technology in the health-care setting. As access to the Internet grows, so does the richness of resources the Internet can supply. With the changes in health care brought by communication, telematics will become the successor to informatics. The authors present the philosophy of telematics training and propose a short training course designed to help health professionals in developing nations take advantage of telematics, providing conceptual understanding and hands-on training.

Developing Countries↗

Water-soluble Abeta (N-40, N-42) oligomers in normal and Alzheimer disease brains.

Ultracentrifugation and graded molecular sieving, as well as a sensitive sandwich enzyme-linked immunosorbent assay were used to isolate and quantitate the amounts of water-soluble oligomers of beta amyloid (Abeta) peptides N-40 and N-42 in cerebral cortex of normal and Alzheimer disease (AD) brains. AD brains contained 6-fold more water-soluble Abeta (wsAbeta) than control brains. The majority of water-soluble peptides in most AD cases was A beta N-42, representing 12 times the amount found in control brains. The wsAbeta was present in the form of monomers and oligomers ranging from less than 10 kDa to greater than 100 kDa. The amount of wsAbeta N-42 in AD brains is about 50 times greater than the level of soluble Abeta N-42 found in the CSF of AD patients. This disparity may be due to the rapid association of wsAbeta N-42 into fibrillar deposits and/or to the integrity of the anatomical barriers which separate the two extracellular spaces. In this paper, we consider soluble any form of Abeta which has not yet polymerized into its insoluble, filamentous form. This includes both the newly synthesized forms of Abeta and those peptides which may be loosely attached to insoluble filaments but which can, nevertheless, still be considered soluble. It has been previously shown that, once it has aggregated into its filamentous form, the Abeta peptides are resistant to disaggregation and degradation by a number of denaturing agents and aqueous buffers containing proteolytic enzymes. Therefore, it is likely that the water-soluble Abeta peptides we quantified are precursors to its insoluble, filamentous form. Consequently, reducing the levels of soluble Abeta in AD brains could have profound effects on AD pathophysiology.

Adult↗

Fat and calcium intake in women dieters.

Low-fat diets are widely recommended to treat hyperlipidemia and obesity and to reduce the risk of coronary heart disease, but concern has been expressed that they may not provide adequate calcium. This study assessed the calcium intake of 247 women from Otago, New Zealand aged 50-65 y consuming a variety of diets. Calcium intake was not reduced in women consuming a lipid-lowering or weight-reducing diet compared with nondieters. Intake was also similar in women consuming < 25 - 30%, or > 33% of energy from fat, indicating that calcium intake is not specifically compromised in a low-fat diet. The mean calcium intake of 754 mg/d was, however, below that recommended, with 80% of women receiving < 1000 mg Ca/d and one-third < 600 mg. Thus, most women need to increase their calcium intake irrespective of dietary energy and fat intakes.

Aged↗

Response of plasma lathosterol concentration to change in the quality of dietary fat in men and women.

OBJECTIVE: The aim of the study was to determine the effect of replacing saturated fatty acids (SAFA) with polyunsaturated fatty acids (PUFA) in the diet on plasma lathosterol concentration, an index of cholesterol synthesis, in mildly hypercholesterolaemic subjects. DESIGN: The study was a randomised, cross-over trial. SUBJECTS: Seventy-six subjects were recruited and one dropped out. Twenty-nine men and 46 women with baseline plasma cholesterol levels in the range 5.5-7.9 mmol/l were entered into the trial. INTERVENTIONS: Subjects were placed on two isocaloric diets, one rich in SAFA and the other high in PUFA, for 6 weeks each. Plasma lathosterol and lipid and lipoprotein concentrations were measured. RESULTS: When PUFA replaced SAFA in the diet, there was a significant (P = 0.01) fall in plasma lathosterol concentration in all subjects combined [-1.37 (-0.36 to -2.38) mumol/l] which was largely due to a significant (P = 0.03) decrease in men [-2.35 (-0.42 to -4.28) mumol/l] but not in women. The concomitant decreases in plasma cholesterol, low density lipoprotein (LDL) cholesterol and high density lipoprotein (HDL) cholesterol were similar in men and women. Plasma lathosterol concentration and the ratio lathosterol/cholesterol were significantly higher in men at baseline and during diets rich in SAFA but were not significantly different between the sexes during diets rich in PUFA. CONCLUSIONS: These data suggest that replacing SAFA with PUFA in the diet may reduce cholesterol synthesis in mildly hypercholesterolaemic men and markedly reduce the gender-related difference in cholesterol synthesis commonly observed.

Adult↗

Enterprise systems.

Looking to the next generation of hospital information systems (HIS), the paper first provides an overview of enterprise systems, including the concept, current developments, hospital perspectives, critical issues and requirements, and future value-added enhancements. The paper then focuses on efforts drawing upon existing expertise in these critical areas, including infrastructure, workstations, standards, computerized patient records, and security. It concludes by stressing the importance of collaborative efforts in the creating of the next generation of HIS, health information systems or HIS.

Computer Security↗

The library of the future: an informatics institution.

As technology transforms how information is accessed, stored and disseminated, the concept of the library changes as well. In its plans for a new building to house both library and computing services, the University of Maryland at Baltimore (UMAB) will give physical form and organizational dimensions to this new concept of the library. UMAB's library of the future will be an 'informatics institution,' designed to accommodate new technologies that support problem-based learning in the health sciences curricula. This new library will embody the concept and the discipline of health informatics.

Baltimore↗

Oxidation of low density lipoproteins from patients with renal failure or renal transplants.

Peroxidation of low density lipoproteins (LDL) may be involved in the development of atherosclerosis which is prevalent in patients with chronic renal failure and renal transplant recipients. We determined the copper ion catalyzed oxidation in vitro, vitamin E content, and chemical and fatty acid composition of LDL isolated from 38 patients with renal disease and 15 healthy subjects. Also the acute effect of hemodialysis treatment on LDL oxidation variables was tested. The lag time in conjugated diene formation during oxidation was significantly (P = 0.011) shorter in LDL from renal transplant recipients (66 min, N = 18) mainly due to significantly (P < 0.05) shorter times in women (47 min, N = 7), compared with healthy subjects (83 min, N = 15), patients on hemodialysis (91 min, N = 13) and patients treated by continuous ambulatory peritoneal dialysis (CAPD) (82 min, N = 7). The maximum rate and the extent of LDL oxidation were significantly (P < 0.01) lower in all patients with renal disease compared with healthy subjects. The triglyceride content of LDL was significantly (P < 0.001) higher in women with kidney grafts (7.3%) compared with levels in the corresponding men (5.3%) and healthy women (5.0%), and was correlated significantly with the lag time in LDL oxidation in renal transplant recipients (Spearmans r = -0.502, P = 0.034). The percentage oleic acid in LDL was significantly higher (P = 0.002) and the percentage linoleic acid was significantly lower (P = 0.046) in patients with renal disease, and may largely account for their lower rates and extent of LDL oxidation. Levels of the LDL oxidation variables and organic lipid peroxide content of LDL were not significantly different before and after hemodialysis and 24 hours later. These results suggest that LDL from women with renal transplants may be abnormally susceptible to oxidation possibly due to increased triglyceride content.

Adult↗

Cholesterol precursor concentration in plasma from patients with chronic renal failure or kidney grafts.

Plasma lathosterol concentration which is an index of cholesterol synthesis rate was measured in 36 patients with chronic renal failure (CRF) including 13 who were dialysis independent, 12 receiving hemodialysis and 11 on continuous ambulatory peritoneal dialysis (CAPD), 17 renal transplant recipients and 27 healthy control subjects. Concentrations of plasma lathosterol were significantly (ANOVA p = 0.03) lower in all categories of renal patients excepting those treated by CAPD, compared with control values. In normolipidemic subjects (cholesterol < or = 6.50 mmol/l and triglycerides < or = 2.0 mmol/l) plasma lathosterol levels in hemodialysis patients and renal transplant recipients were still significantly (ANOVA p = 0.02) lower than control values. In transplant recipients, the plasma lathosterol/cholesterol ratio was significantly (p = 0.02) lower than those treated with azathioprine and prednisone compared with those treated with these drugs and cyclosporin. Significant (p < 0.001) positive correlations were recorded between plasma lathosterol concentration and plasma levels of apolipoprotein B (apoB) and very low density lipoprotein (VLDL) lipids in the renal patients. These data suggest that the rate of cholesterol synthesis may be low in undialysed and hemodialysed patients with CRF and in renal transplant recipients, particularly those treated with double therapy, and may be linked to the metabolism of apoB and VLDL.

Adolescent↗

Cell cholesterol transport to plasma in blood from patients with renal failure or a kidney transplant.

Accumulation and distribution of cell cholesterol in plasma lipoproteins of incubated blood was examined in 36 patients with chronic renal failure including 13 who were dialysis-independent, 12 on haemodialysis, and 11 on continuous ambulatory peritoneal dialysis (CAPD), 17 renal transplant recipients, and 8 healthy controls. In addition, transport of cholesterol between red blood cells and high-density lipoprotein subfraction 3 (HDL3) isolated from a subgroup of patients with chronic renal failure was determined. Significantly less cell cholesterol appeared in plasma (P < 0.002) and HDL (P = 0.03), the main recipient of cell cholesterol, in patients with chronic renal failure compared with healthy subjects. Corresponding values in blood from renal transplant recipients were similar to controls. In patients with chronic renal failure, plasma HDL3 cholesterol levels (P < 0.02), HDL3 phospholipid content (P < 0.001) and net transport of red cell cholesterol to isolated HDL3 (P < 0.001) were significantly lower compared with controls. The data suggest that in patients with chronic renal failure, low levels of plasma HDL3 of abnormal composition may restrict the incorporation of cell cholesterol into the antiatherogenic HDL fraction potentially leading to inefficient transport of cholesterol from peripheral tissues and the development of atherosclerosis. These abnormalities appear to be reversed by renal transplantation.

Adolescent↗

Health information networks.

Health information networks could link health care providers throughout the community. Development activities in the United States are varied and numerous. Collaboration is key to the ultimate "network of networks" and is actively fostered.

Community Networks↗

Proteolysis of A beta peptide from Alzheimer disease brain by gelatinase A.

It has been recently reported that the 72 kDa proteolytic enzyme gelatinase A/type IV collagenase/matrix metalloproteinase 2 (MMP2) hydrolyzed the Lys 16-Leu 17 peptide bond of a synthetic decapeptide (YEVHHQKLVFF) representing the soluble A beta sequence of amino acid residues 10-20. Our aim was to test if this enzyme could also degrade the insoluble 40-42 residues long A beta peptides purified from Alzheimer Disease brain. Our results indicate that MMP2 hydrolyzes A beta 1-40 and A beta 1-42 peptides at Lys 16-Leu 17, at Leu 34-Met 35, and Met 35-Val 36 peptide bonds. These results suggest that MMP2 has the ability of degrading A beta of AD in vitro. If this hydrolysis also occurs in the brain's extracellular matrix, the enzymatic action of gelatinase a could prevent the generation of amyloidogenic A beta 1-40(42).

Alzheimer Disease↗

Brain N-acetyl-L-aspartic acid in Alzheimer's disease: a proton magnetic resonance spectroscopy study.

This study was performed in order to measure changes in brain N-acetyl-L-aspartic acid (NAA) in post-mortem brain tissue in Alzheimer's disease (AD) in comparison to normal control subjects using the technique of magnetic resonance spectroscopy. Brain tissue was obtained at autopsy and frozen until use, from seven patients diagnosed according to current research criteria for AD and 7 control subjects. Detailed clinical evaluations were available for all the dementia cases. Representative brain samples were obtained from three neocortical regions and a limbic region (parahippocampal gyrus) in white and grey matter. NAA was quantified on perchloric acid extracts using proton nuclear magnetic resonance (NMR) spectroscopy. Regional NAA did not vary significantly with age. In AD, reductions were present in the grey matter of the neocortex but not in the white matter. Within the parahippocampal gyrus there were reductions in both tissue types; only cortical levels correlated with clinical scales of dementia severity. A pattern of increasing correlation was observed between dementia severity as measured by the mini mental state examination during life and NAA levels from brain areas of increasing pathological predilection in AD. These post-mortem studies show reductions in brain NAA in AD which correlate with dementia severity during life and which support the use of future in vivo NAA spectroscopic images in the evaluation of AD patients.

Aged↗

Chemical characterization of A beta 17-42 peptide, a component of diffuse amyloid deposits of Alzheimer disease.

A peptide corresponding to the amino acid sequence of A beta 17-42 (LVFFAEDVGSNKGAIIGLMVGGVVIA) was isolated from Alzheimer Disease patient brains containing large deposits of diffuse-type amyloid. Brain homogenates were lysed in SDS and submitted to high speed centrifugations. A beta peptides were purified by size exclusion chromatography on Superose 12 and TSK 3000 SW columns. An A beta peptide with M(r) of 3,000 was recovered that on automatic gas-phase Edman degradation yielded the amino acid sequence of A beta starting at residue 17 (Leu). The 3-kDa peptide was subsequently hydrolyzed with trypsin and reacted with CNBr, and the resulting peptides were separated by reverse phase high pressure liquid chromatography and characterized by amino acid analyses, peptide microsequencing, and mass spectrometry. Hydrolysis of beta-amyloid precursor protein 695 at Lys612-Leu613 or at Lys16-Leu17 of its A beta 1-42 derivative prevents the generation of neurotoxic A beta filaments, thus leading to the formation of A beta 17-42 localized in the diffuse amyloid deposits. An outstanding feature in the pathology of Alzheimer Disease is that the predominant A beta peptides have their C termini at position 42, whether in the cores of the neuritic plaques, in the vascular walls, or in the diffuse deposits. Based on these observations, we postulate that the accumulation of insoluble A beta N-42 in Alzheimer Disease is due to the anomalous processing of the C-terminal region.

Alzheimer Disease↗

The professional workstation as enabler: conference recommendations. International Medical Informatics Association.

This paper reports on the Working Conference on Healthcare Professional Workstation sponsored by the International Medical Informatics Association (IMIA) and held in Washington DC, 14-16 June 1993. It sets forth the vision of a health care infostructure in which the workstation acts as enabler, giving professionals access to information when, where, and how it is needed. The paper explains upon the conference methodology and provides the conference cochairs' summary recommendations, both short- and long-term. These recommendations are based upon the work of five breakout groups, which addressed Functional Requirements, User Interfaces, Data and Knowledge Management, Processing, and Sharing and Communications. Presented in detailed and display formats, these summary recommendations address issues in the areas of architecture, linkages, evaluation, security, standards, education, and training. The paper also sets forth immediate next steps for the workstation initiative, including the formation of a formal IMIA Working Group on Workstations.

Computer Communication Networks↗