Biomedical subjects

M Jones

Publications and source records attributed to M Jones.

At least 433 records · Page 24Linked to original sources

PubMed1995

Diet modification in lowering plasma cholesterol levels. A randomised trial of three types of intervention.

OBJECTIVE: To compare the efficacy of three types of diet and lifestyle interventions for lowering plasma lipid levels. DESIGN: Randomised parallel-group trial. SUBJECTS AND SETTING: Adults with plasma cholesterol levels of 5.5-8.0 mmol/L attending two Sydney community health screening clinics were asked to participate: 179 agreed and 131 completed the study. INTERVENTIONS: A pamphlet with brief advice; group dietary counselling; or individual counselling. Counselling included three sessions with a dietitian/nutritionist over six months. MAIN OUTCOME MEASURES: Plasma total cholesterol levels measured by Reflotron analyser; fasting serum lipid levels measured by standard laboratory methods; and calculated low-density lipoprotein cholesterol levels. RESULTS: Significantly lower plasma total cholesterol levels (Reflotron) were observed at two months and at six months with each of the three interventions. Additionally, both types of dietitian-based counselling resulted in small but significant decreases in plasma low-density lipoprotein cholesterol levels at six months in a subset of subjects. CONCLUSION: Although there were no statistically significant differences in efficacy between the three types of intervention, dietitians have a role to play in setting up such counselling programs.

Adult↗

PubMed1995

The DNA sequence of human herpesvirus-6: structure, coding content, and genome evolution.

The complete DNA sequence was determined for strain U1102 of human herpesvirus-6, a CD4+ T-lymphotropic virus with disease associations in immunodeficient settings and a possible complicating factor in AIDS. The genome is 159,321 bp in size, has a base composition of 43% G + C, and contains 119 open reading frames. The overall structure is 143 kb bounded by 8 kb of direct repeats, DRL (left) and DRR (right), containing 0.35 kb of terminal and junctional arrays of human telomere-like simple repeats. Since eight open reading frames are duplicated in the repeats, six span repetitive elements and three are spliced, the genome is considered to contain 102 separate genes likely to encode protein. The genes are arranged colinearly with those in the genome of the previously sequenced betaherpesvirus, human cytomegalovirus, and has a distinct arrangement of conserved genes relative to the sequenced gammaherpesviruses, herpesvirus saimiri and Epstein-Barr virus, and the alphaherpesviruses, equine herpesvirus-1, varicella-zoster virus, and herpes simplex virus. Comparisons of predicted amino acid sequences allowed the functions of many human herpesvirus-6 encoded proteins to be assigned and showed the closest relationship in overall number and similarity to human cytomegalovirus products, with approximately 67% homologous proteins as compared to the 21% identified in all herpesviruses. The features of the conserved genes and their relative order suggested a general scheme for divergence among these herpesvirus lineages. In addition to the "core" conserved genes, the genome contains four distinct gene families which may be involved in immune evasion and persistence in immune cells: two have similarity to the "chemokine" chemotactic/proinflammatory family of cytokines, one to their peptide G-protein-coupled receptors, and a fourth to the immunoglobulin superfamily.

AIDS-Related Opportunistic Infections↗

PubMed1995

Neurological examination of the preterm and full-term infant at risk for developmental disabilities using the Dubowitz Neurological Assessment.

The Dubowitz Neurological Assessment of the Preterm and Full-term Infant was used to evaluate infants at risk for developmental disabilities. Criteria for categorising the results of the Dubowitz Neurological Assessment were developed by documenting the findings on a group of relatively low risk infants managed in a NICU. The criteria, expressed as a number of deviant responses on items in the assessment, were used to test the concurrent and predictive validity. The Dubowitz Neurological Assessment was found to correlate with a perinatal risk rating and the findings on brain ultrasonography, indicating concurrent validity. Predictive validity was demonstrated by correlation with neurodevelopmental outcome and neurological status at 1 year corrected age. The sensitivity and specificity of the assessment were also used to develop a management protocol for graduates of the NICU.

Apgar Score↗

PubMed1995

Expression of a B-cell marker, CD24, on nasopharyngeal carcinoma cells.

Random sequencing of clones from a lambda gt10 cDNA library, made from mRNA expressed in an Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) has revealed the gene transcript of human CD24. The CD24 antigen, a glycosylphosphatidylinositol-anchored cell surface molecule, has been identified as a B-cell marker that is lost during cell maturation. We show here that it is expressed on 3 NPC xenografts, previously defined as consisting of poorly differentiated epithelial cells, and on an NPC biopsy. In the case of the former, the level of expression of CD24 corresponds to the EBV load. A B-lymphoblastoid cell line carrying the same EBV genome as one of the tumours, C15, and an EBV-negative Burkitt's lymphoma cell line do not display the antigen, but epithelial-like cells of a laryngeal tumour cell line (Hep2) do express it. Our data suggest that CD24 may be a marker of cell differentiation not only for B cells but also for epithelial cells and may have an indirect association with EBV gene expression.

Animals↗

PubMed1995

Expression of TAL-1 proteins in human tissues.

Rearrangement of the tal-1 gene (also known as SCL or TCL-5) occurs in at least 25% of T-cell acute lymphoblastic leukemias (T-ALLs) and results in the aberrant expression of tal-1 mRNA in the neoplastic cells. Also, tal-1 mRNA is constitutively expressed in erythroid precursors and megakaryocytes. This report describes a direct immunocytochemical study of the distribution and localization of TAL-1 protein in normal human tissues and cell lines using four monoclonal antibodies raised against recombinant TAL-1 proteins. One of these reagents recognizes a protein of 41 kD molecular weight in in vitro-translated TAL-1 proteins, two others recognize proteins of 39 and 41 kD molecular weight, and the fourth antibody also recognizes a TAL-1 protein of 22 kD in addition to the 39- and 41-kD proteins. These anti-TAL-1 antibodies label the nuclei of erythroid precursor cells and megakaryocytes in fetal liver and adult bone marrow. The punctate pattern of nuclear labeling suggests that TAL-1 may comprise part of a novel nuclear structure, similar to that recently found for the PML protein. The nuclei of T cell lines known to express mRNA encoding the full-length TAL-1 protein (eg, CCRF-CEM, RPMI 8402, and Jurkat) are also labeled. A study of normal human tissues (including thymus) showed labeling of smooth muscle, some tissue macrophages, and endothelial cells. TAL-1 protein is undetectable in other cell types. These reagents may play an important role in the diagnosis of T-ALL and could also be used in the context of lymphoma diagnosis on routinely fixed material.

Antibodies↗

PubMed1995

IL-7 drives donor T cell proliferation and can costimulate cytokine secretion after MHC-matched allogeneic bone marrow transplantation.

Transplantation of MHC-matched, allogeneic B10.D2 bone marrow plus T cells into BALB/c recipients ultimately results in chronic graft-vs-host disease (GVHD) and mortality 8 to 12 wk post-transplant. We have identified IL-7-specific mRNA in the spleens of BALB/c bone marrow transplantation (BMT) recipients during the first week post-transplant. The response by T cells from B10.D2-->BALB/c BMT recipients to stimulation with IL-7 in vitro during the early period after transplant was then examined. The findings indicated that within the first week post-transplant, spleen cells removed from recipients injected with allogeneic, but not syngeneic, T cells proliferated vigorously to rIL-7. Both IL-2-dependent and -independent components were identified. Depletion of responding cells before culture with anti-Thy-1.2 Ab virtually eliminated this response. We conclude that transplant of allogeneic T cells is required for the observed IL-7 response, and moreover, such cells proliferate after exposure to this cytokine in vitro. To determine whether IL-7 could have a functional effect on donor T cells, the production of IFN-gamma by T cells from allogeneic BMT recipients stimulated with anti-T cell receptor (i.e., anti-V beta) Ab was examined. IL-7 was demonstrated to enhance IFN-gamma production by donor T cells postallogeneic BMT. These results suggest that a cytokine presumably produced in the host for the physiologic function of hematologic reconstitution is playing an additional role during the early events after allogeneic BMT mediated via the expansion and augmented cytokine production by donor T cells.

Animals↗

PubMed1995

Prospective randomised trial of chemotherapy given before radiotherapy in childhood medulloblastoma. International Society of Paediatric Oncology (SIOP) and the (German) Society of Paediatric Oncology (GPO): SIOP II.

In a multicentre randomised clinical trial 364 children with biopsy proven medulloblastoma were randomly assigned to receive or not pre-radiotherapy chemotherapy. Children with total or subtotal removal of the tumour, no evidence of invasive brain stem involvement, and no evidence of metastatic disease either within or without the cranium were designated "low risk", those with gross residual tumour, evidence of invasive brain stem involvement or metastases in the central nervous system were designated "high risk". All children were prescribed 55 Gy to the tumour bearing area. "Low risk" children could be randomised to "standard" radiotherapy 35 Gy to the craniospinal axis or "reduced" dose 25 Gy to the craniospinal axis. Chemotherapy consisted of vincristine, procarbazine, and methotrexate given in a 6-week module before radio-therapy, and for "high risk" children, vincristine and CCNU given after radiotherapy. No benefit for the receipt of pre-radiotherapy chemotherapy could be demonstrated for any group. In addition, a negative interaction was observed between the receipt of the chemotherapy and reduced dose radio-therapy with a particularly poor outcome being observed in this group of children.

Adolescent↗

PubMed1995

Use of human somatotrophin in the treatment of a patient with methylmalonic aciduria.

Growth hormone (GH) insufficiency was demonstrated in a patient with methylmalonic aciduria. GH administration at 14-21 U/m2 per week accelerated linear growth, stimulated lipolysis, and produced clinical improvement and reduced urinary methylmalonate excretion. The clinical and metabolic benefits were lost as the dose of GH was increased to 28 U/m2 per week. CONCLUSION. The use of GH in other patients with methylmalonic aciduria (and other disorders of intermediary metabolism demonstrating similar clinical and metabolic features) warrants further study.

Amino Acid Metabolism, Inborn Errors↗

PubMed1995

Relation of left atrial V-wave/left ventricular systolic pressure ratio to mitral regurgitant volume.

Evaluation of mitral regurgitation is difficult whether invasive or noninvasive methods are used. The determination of the regurgitant volume itself cannot be done in clinical practice with reasonable accuracy. In six sheep with chronic mitral regurgitation, left ventricular and left atrial pressures were recorded with high-fidelity catheters. The regurgitant volume was measured directly with electromagnetic flow probes positioned at the mitral annulus and around the ascending aorta, balanced against each other. A total of 24 hemodynamic states were obtained varying preload and afterload by fluid expansion and angiotensin infusion. On the basis of these studies, the pressure ratio of the V wave divided by the left ventricular systolic pressure is proposed as an index of regurgitant volume. A good correlation was found between this ratio and the regurgitant volume (r = 0.75). The ratio is easily recorded during routine heart catheterization.

Animals↗

PubMed1995

Color flow Doppler determination of transmitral flow and orifice area in mitral stenosis: experimental evaluation of the proximal flow-convergence method.

To evaluate the in vivo accuracy of color Doppler flow-convergence methods for determining transmitral flow volumes and effective orifice areas in mitral stenosis, we studied two models for flow-convergence surface geometry, a hemispheric (HS) model and an oblate hemispheroid (OH) model in a chronic animal model with quantifiable mitral flows. Color Doppler flow mapping of the proximal flow-convergence region has been reported to be useful for evaluation of intracardiac flows. Flow-convergence methods in patients with mitral stenosis that use HS assumption for the isovelocity surface have resulted in underestimation of actual flows. Chronic mitral stenosis was created surgically in six sheep with annuloplasty rings (group 1) and 11 sheep with bioprosthetic porcine valves (group 2). Hemodynamic and echocardiographic/Doppler studies (n = 18 in group 1; n = 21 in group 2) were performed 20 to 34 weeks later. Left ventricular inflow obstruction was of varied severity, with mean transmitral valve gradients in group 1 ranging from 1.3 to 18 mm Hg and in group 2 ranging from 6.3 to 25.6 mm Hg. Although transmitral flows derived by both geometric flow convergence models showed significant correlations with reference cardiac outputs, the correlations for the OH model were better than those for the HS model (group 1, r = 0.86 for the OH model vs r = 0.72 for the HS model; group 2; r = 0.84 for the OH model vs r = 0.62 for the HS model). The OH model was also superior to the HS model in determining effective orifice areas compared to reference orifice areas determined by postmortem planimetry of anatomic orifices (group 1 only, r = 0.64 for OH vs 0.58 for HS), by the Gorlin and Gorlin formula (group 1, r = 0.63 for OH vs 0.72 for HS; group 2, r = 0.82 for OH vs 0.76 for HS), and by the Doppler pressure half-time method (group 1, r = 0.76 for OH vs 0.69 for HS; group 2, r = 0.84 for OH vs 0.62 for HS).(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of Variance↗

PubMed1995

SCL/Tal-1 expression in T-acute lymphoblastic leukemia: an immunohistochemical and genotypic study.

A comparative study of the immunohistochemical (Stem cell leukemia/T-cell acute leukemia [SCL/TAL-1] protein expression) and genotypic (deletions in the SCL/tal-1 gene) findings in T-acute lymphoblastic leukemia (T-ALL) is presented. Formalin-fixed tissue from 50 cases of T-ALL were stained with a novel monoclonal antibody, 2TL 242, which recognizes SCL/TAL-1 protein. Twenty-four cases showed nuclear immunolabeling of leukemic cells. Nuclear positivity was not evident in any other type of leukemia or lymphoma tested with the antibody. Genotypic analysis of 25 cases of T-ALL showed a deletion involving the SCL/tal-1 gene in nine cases. These results suggest that protein expression is not dependent on derangement of the SCL/tal-1 gene, because immunohistochemical detection of the protein was noted in the presence and absence of a tal-d1 deletion.

Base Sequence↗

PubMed1995

Doppler evaluation of severity of mitral regurgitation: relation to pulmonary venous blood flow patterns in an animal study.

OBJECTIVES: This study examined the influence of regurgitant volume on pulmonary venous blood flow patterns in an animal model with quantifiable mitral regurgitation. BACKGROUND: Systolic pulmonary venous blood flow is influenced by atrial filling and compliance and ventricular output and by the presence of mitral regurgitation. The quantitative severity of the regurgitant volume itself is difficult to judge in clinical examinations. METHODS: Six sheep with chronic mitral regurgitation produced by previous operation to create chordal damage were examined. At reoperation the heart was exposed and epicardial echocardiography performed. Pulmonary venous blood flow waveforms were recorded by pulsed Doppler under color flow Doppler guidance using a Vingmed 750 scanner. The pulmonary venous systolic inflow to the left atrium was expressed as a fraction of the total inflow velocity time integral. Flows across the aortic and mitral valves were recorded by electromagnetic flowmeters balanced against each other. Pressures in the left ventricle and left atrium were measured directly with high fidelity manometer-tipped catheters. Preload and afterload were systematically manipulated, resulting in 24 stable hemodynamic states. RESULTS: Simple logarithmic correlation between the regurgitant volume and size of a positive or negative pulmonary venous inflow velocity time integral during systole was good (r = -0.841). By stepwise linear regression analysis with pulmonary venous negative systolic velocity time integral as a dependent variable compared with the regurgitant volume, fractional shortening, left atrial v wave size, systemic vascular resistance and left ventricular systolic pressure, only contributions from v wave size and regurgitant volume (r = 0.80) reached statistical significance in determining pulmonary venous negative systolic flow. CONCLUSIONS: Evaluation of systolic pulmonary venous blood flow velocity time integral can give valuable information helpful for estimating the regurgitant volume secondary to mitral regurgitation.

Animals↗

PubMed1995

Dynamic change in mitral regurgitant orifice area: comparison of color Doppler echocardiographic and electromagnetic flowmeter-based methods in a chronic animal model.

OBJECTIVES: The aim of the present study was to investigate dynamic changes in the mitral regurgitant orifice using electromagnetic flow probes and flowmeters and the color Doppler flow convergence method. BACKGROUND: Methods for determining mitral regurgitant orifice areas have been described using flow convergence imaging with a hemispheric isovelocity surface assumption. However, the shape of flow convergence isovelocity surfaces depends on many factors that change during regurgitation. METHODS: In seven sheep with surgically created mitral regurgitation, 18 hemodynamic states were studied. The aliasing distances of flow convergence were measured at 10 sequential points using two ranges of aliasing velocities (0.20 to 0.32 and 0.56 to 0.72 m/s), and instantaneous flow rates were calculated using the hemispheric assumption. Instantaneous regurgitant areas were determined from the regurgitant flow rates obtained from both electromagnetic flowmeters and flow convergence divided by the corresponding continuous wave velocities. RESULTS: The regurgitant orifice sizes obtained using the electromagnetic flow method usually increased to maximal size in early to midsystole and then decreased in late systole. Patterns of dynamic changes in orifice area obtained by flow convergence were not the same as those delineated by the electromagnetic flow method. Time-averaged regurgitant orifice areas obtained by flow convergence using lower aliasing velocities overestimated the areas obtained by the electromagnetic flow method ([mean +/- SD] 0.27 +/- 0.14 vs. 0.12 +/- 0.06 cm2, p < 0.001), whereas flow convergence, using higher aliasing velocities, estimated the reference areas more reliably (0.15 +/- 0.06 cm2). CONCLUSIONS: The electromagnetic flow method studies uniformly demonstrated dynamic change in mitral regurgitant orifice area and suggested limitations of the flow convergence method.

Animals↗

PubMed1995

Use of the "triple test" for palpable breast lesions yields high diagnostic accuracy and cost savings.

BACKGROUND: The "triple test" for palpable breast lesions consists of physical examination, mammography, and fine-needle aspiration. METHODS: Forty-six lesions in 43 patients were subjected to all three components of the triple test, followed by confirmatory open biopsy. RESULTS: In all 21 cases where the triple test was concordant (elements had either all malignant or all benign results), pathologic analysis of open biopsy samples was confirmatory (predictive value and sensitivity 100%). Fine-needle aspiration was the most reliable element of the triple test in cases where the elements of the test were nonconcordant (negative predictive value and sensitivity of 95% and 96%, respectively). CONCLUSIONS: The triple test was 100% accurate in the diagnosis of palpable breast lesions when all three elements were concordant. Cost analysis revealed that elimination of confirmatory open biopsy in such cases and also in cases in which the fine-needle aspiration and one other element of the test had a suspicious or malignant result, could yield an average per-case cost savings of up to $1,412 compared to triple test followed by routine confirmatory open biopsy.

Adult↗

PubMed1995

A comparison of failure modes of glutaraldehyde-treated versus antibiotic-preserved mitral valve allografts implanted in sheep.

Morphologic studies and calcium analyses were made on mitral valve allografts from 12 juvenile sheep surviving 12 to 24 weeks after mitral valve replacement. Before implantation, the allografts were treated with 0.625% glutaraldehyde (group I, n = 4) or with cold antibiotic solution (group II, n = 8). Three group I animals died 12 to 19 weeks after implantation because of dysfunction of calcified valves; the surviving animal also had extensive allograft calcification. One group II animal died of mitral regurgitation; the valves of the other seven (including five with regurgitation shown by Doppler and ventriculographic studies) were explanted at 19 to 24 weeks. Chordal rupture related to calcific deposits was found in all group I valves. Leaflet perforations (n = 4) and ruptured chordae (n = 4), each caused by connective tissue deterioration, were found in group II valves. Inflammatory reaction was absent or minimal in group I valves but moderate or severe in group II valves. Fibrous sheaths were thicker in group II than in group I valves. Calcium levels were much higher in group I than in group II valves. Calcification in group I valves was diffuse and involved collagen, elastic fibers, and connective tissue cells and matrix; in group II valves, it was localized in connective tissue cells. Thus glutaraldehyde-treated allografts failed because of extensive calcification, whereas antibiotic-preserved allografts underwent deterioration of connective tissue and infiltration by inflammatory cells.

Animals↗

PubMed1995

Expression of p53 in urothelial cell cultures from tumour-bearing and tumour-free patients.

An explant culture technique was used to culture normal urothelium from patients with muscle-invasive bladder cancer (transitional cell carcinoma, TCC) (n = 11) and from non-tumour-bearing patients (n = 60). Cell cultures were examined for expression of p53 using the monoclonal antibody p53-240. There was a statistically significant increase in p53 expression in normal urothelial cell cultures from patients with TCC (P < 0.0005). Normal urothelial cultures from patients with TCC also showed more rapid proliferation in vitro when compared with non-tumour-bearing patients (P < 0.0005). A subgroup of non-tumour-bearing patients (n = 14) showed > 5% of cells expressing p53. p53 expression in this subgroup was found to correlate with cell proliferation in vitro (r2 = 0.766). None of these urothelial specimens was observed to express p53 when paraffin-embedded preparations were stained with p53-D07 antibody prior to culture. The rate of cellular proliferation in this subgroup did not differ from that of normal urothelium from TCC patients. Twenty-two paraffin-embedded, muscle-invasive TCC specimens were also evaluated for p53 expression using p53-D07. The expression of p53 in these tumours did not differ from that observed in normal urothelial cell cultures from patients with TCC (P = 0.26). This study identifies an overexpression of p53 in normal urothelial cells from patients with TCC and in proliferating cultures from a significant subgroup of patients without malignant disease. Increased p53 expression in normal cultured urothelial cells from patients with bladder cancer implies a global change in the mechanisms controlling urothelial cell division. This may represent an early step in the pathway to carcinogenesis.

Carcinoma, Transitional Cell↗

PubMed1995

Clinical reasoning and pain.

Clinical reasoning is reviewed with respect to the historical and continuing need for critical inquiry skills, the hypothetico-deductive basis of sound reasoning, factors influencing therapists' reasoning, and ways of promoting critical yet creative reasoning. The importance of clinicians' organisation of biomedical and clinical knowledge and the inclusion of the patient in the problem solving and decision making processes are emphasised.

Journal Article↗

PubMed1995

Mutations in the p53 gene are not limited to classic 'hot spots' and are not predictive of p53 protein expression in high-grade non-Hodgkin's lymphoma.

We have investigated the relationship between the p53 genotype and phenotype in a series of 22 high-grade non-Hodgkin's lymphomas (NHLs) in which we sequenced the p53 gene open reading frame (exons 2-11). Immunostaining for p53 was already available for these cases. Mutations were found in 10/22 cases (45%) and 3/10 were in exons 4 or 10 outside the classic 'hot spot' regions (exons 5-8). Comparison with immunostaining indicated that, besides cases with the 'expected' patterns (in which gene mutation and protein detection were either both present or both absent) there were also cases in which p53 protein was detected in the absence of any mutation and those with a mutant gene in which the protein was undetectable. These data show that: (1) in high-grade NHLs mutations frequently occur outside the classic hot spot regions and (2) staining for p53 is not predictive of the status of the gene, i.e. whether or not a mutation is present. Therefore in order to document p53 involvement in lymphoid tumours it is necessary both to sequence at least the whole translated open reading frame of the gene and to show evidence of protein expression by immunostaining.

Amino Acid Sequence↗