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Biomedical subjects

M D Smith

Publications and source records attributed to M D Smith.

At least 163 records · Page 9Linked to original sources
PubMed1998

Bcl-2 transcription from the proximal P2 promoter is activated in neuronal cells by the Brn-3a POU family transcription factor.

The BCL-2 protein is able to protect neuronal and other cell types from apoptotic programmed cell death and plays a key role in regulating the rate of apoptosis during development of the nervous system. We have previously demonstrated that the Brn-3a POU domain transcription factor protects sensory neurons from apoptotic programmed cell death induced by nerve growth factor withdrawal. We report here that Bcl-2 transcription is predominantly initiated from the Bcl-2 P2 promoter in both the ND7 neuronal cell line and primary dorsal root ganglion neurons, in contrast to the predominant use of the Bcl-2 P1 promoter in other cell types. Moreover, Bcl-2 transcription initiated from the P2 region increases in ND7 cells stably overexpressing Brn-3a, resulting in enhanced BCL-2 protein levels. Similarly, the Bcl-2 P2 promoter is directly activated by Brn-3a in co-transfection assays in both ND7 cells and dorsal root ganglion neurons. Analysis of the Bcl-2 regulatory sequence revealed a binding site for Brn-3a that is required for maximal activation by Brn-3a both in transfected cells and during differentiation of ND7 cells. Together these data identify Brn-3a as the first transcription factor regulating Bcl-2 activity specifically in neuronal cells and indicate that the anti-apoptotic effect of Brn-3a is likely to be mediated, at least in part, via the up-regulation of Bcl-2 expression.

Base Sequence↗
PubMed1998

The Brn-3c transcription factor contains a neuronal-specific activation domain.

Brn-3a, Brn-3b and Brn-3c are closely related POU family transcription factors which are expressed predominantly in neuronal cells. Previously Brn-3a has been shown to activate a number of gene promoters in co-transfections carried out in different cell types, while Brn-3b inhibits the basal activity of these promoters. We show here that Brn-3c activates the same promoters as Brn-3a but only in co-transfections into neuronal cells and not in other cell types. This effect is dependent upon an N-terminal region of Brn-3c which acts as a neuronal cell specific activation domain when linked to a heterologous DNA binding domain. To our knowledge this is the first report of an activation domain with apparently neuronal specific activity.

Animals↗
PubMed1998

The structure of the upper atmosphere of mars: In situ accelerometer measurements from mars global surveyor

The Mars Global Surveyor (MGS) z-axis accelerometer has obtained over 200 vertical structures of thermospheric density, temperature, and pressure, ranging from 110 to 170 kilometers, compared to only three previous such vertical structures. In November 1997, a regional dust storm in the Southern Hemisphere triggered an unexpectedly large thermospheric response at mid-northern latitudes, increasing the altitude of thermospheric pressure surfaces there by as much as 8 kilometers and indicating a strong global thermospheric response to a regional dust storm. Throughout the MGS mission, thermospheric density bulges have been detected on opposite sides of the planet near 90 degreesE and 90 degreesW, in the vicinity of maximum terrain heights. This wave 2 pattern may be caused by topographically-forced planetary waves propagating up from the lower atmosphere.

Journal Article↗
PubMed1998

Results from the Mars Global Surveyor Thermal Emission Spectrometer.

The Thermal Emission Spectrometer spectra of low albedo surface materials suggests that a four to one mixture of pyroxene to plagioclase, together with about a 35 percent dust component provides the best fit to the spectrum. Qualitative upper limits can be placed on the concentration of carbonates (<10 percent), olivine (<10 percent), clay minerals (<20 percent), and quartz (<5 percent) in the limited regions observed. Limb observations in the northern hemisphere reveal low-lying dust hazes and detached water-ice clouds at altitudes up to 55 kilometers. At an aerocentric longitude of 224 degrees a major dust storm developed in the Noachis Terra region. The south polar cap retreat was similar to that observed by Viking.

Atmosphere↗
PubMed1998

Pathogenic mechanisms in the rheumatoid nodule: comparison of proinflammatory cytokine production and cell adhesion molecule expression in rheumatoid nodules and synovial membranes from the same patient.

OBJECTIVE: To investigate the production of proinflammatory cytokines and expression of cell adhesion molecules in the rheumatoid nodule. METHODS: Cytokine content (tumor necrosis factor alpha [TNFalpha], interleukin-1beta [IL-1beta], and IL-1 receptor antagonist [IL-1Ra]), at the messenger RNA (mRNA) and protein levels, and cell adhesion molecule expression were studied in 16 rheumatoid nodules and 6 synovial membranes. RESULTS: Macrophages in the rheumatoid nodules contained TNFalpha, IL-1beta, and IL-1Ra mRNA and protein, particularly in perivascular cells of the stroma and in the palisading layer. All cell adhesion molecules studied were expressed in both the rheumatoid nodules and synovial membranes, with increased expression of E-selectin in the rheumatoid nodule compared with the synovial membrane, and with the absence of vascular cell adhesion molecule 1 expression on cells of the palisading layer in the rheumatoid nodule. CONCLUSION: The presence of similar proinflammatory cytokines and cell adhesion molecules in the rheumatoid nodule and synovial membrane suggests that similar pathogenic processes result in the chronic inflammation and tissue destruction in these lesions.

Adult↗
PubMed1998

Invasive pneumococcal infection in South and West England.

Variation in the incidence of invasive pneumococcal disease across South and West England, in 1995, was measured through a survey of microbiology laboratories. A 100% response rate was achieved. The incidence by laboratory varied between 5.2 and 20.4 per 100,000 catchment population (P < 0.001). Adjusting for pneumococcal vaccine uptake rate in over 65 year olds, hospital admission rates, blood culture system used and for the age and sex structure of the population, did not account for this variation. When blood culture sampling rates were included in a logistic regression model, the variation between laboratories was much less and of lower statistical significance (P = 0.019). Higher rates of blood culture sampling were associated with a higher incidence of invasive pneumococcal disease. Consistently high sampling should be encouraged because a higher diagnostic rate should result in more selective prescribing of antibiotics, and secondly because improved ascertainment of severe pneumococcal infections is a prerequisite for the evaluation of new pneumococcal conjugate vaccines.

Adolescent↗
PubMed1998

Left atrial function in congestive heart failure: assessment by transmitral and pulmonary vein Doppler.

The relation of transmitral flow patterns and pulmonary venous velocities was analyzed from 50 heart failure patients (28 men, 22 women; mean [+/- SD] age 61 +/- 9 years) with a left ventricular ejection fraction < 40%. Doppler echocardiography was performed in all patients. Transmitral flow measurements included early (E) and atrial (A) velocities and deceleration time of E wave (DT). Patients were assigned to two groups according to E/A ratio, DT, or both: 20 patients in the restrictive group, and 30 patients in the nonrestrictive group. Pulmonary venous flow was obtained by the transthoracic approach. Systolic (S), diastolic (D) and atrial reversal (Ar) velocities were measured. Of the study population, 13 patients had simultaneously determined pulmonary capillary wedge pressure (PCWP). The results showed a lower S (28 +/- 11 vs. 51 +/- 10 cm/sec, p < 0.01), a higher D (66 +/- 13 vs. 44 +/- 10 cm/sec, p < 0.01) and a smaller Ar (12 +/- 10 vs. 24 +/- 9 cm/sec, p < 0.01) in the restrictive group compared with those in nonrestrictive group. In the subgroup of patients undergoing invasive hemodynamic studies, there was no relationship between PCWP and atrial reversal velocity. However, a significant correlation was observed for pulmonary systolic (r = -0.70, p < 0.01) and diastolic (r = 0.76, p < 0.01) velocities to PCWP. These findings suggest a reduction in left atrial compliance and atrial systolic function and both play important roles in heart failure patients with the restrictive transmitral flow pattern.

Aged↗
PubMed1998

South Australian Scleroderma Register: analysis of deceased patients.

The demographic, clinical, pathological and serological features of 123 decreased patients with systemic sclerosis have been analysed. These patients consisted of all identified patients dying with this disease in South Australia between 1983 and 1996 inclusive. There were 85 females and 38 males, with the ratio of limited:diffuse:overlap disease subset being 9:5:1. Disease characteristics revealed that patients with the limited disease tended to be female with high frequencies of the centromere autoantibody, while patients with the diffuse disease had equal gender representation with the frequent presence of nucleolar, speckled or homogeneous antinuclear antibody. Mean duration of disease and mean age of death for the limited:diffuse:overlap subsets differed significantly between groups (p < 0.05) and were 16.5, 9.3 and 10.9 years and 71.9, 57.8 and 52.8 years respectively. Cumulative survival curves for the subsets differed highly significantly, with patients with the limited diseases dying more commonly from right heart failure (documented terminally in 25% of the centromere positive limited subset), cardiovascular disease or cancer, while patients with the diffuse subset died from respiratory failure, renal failure or cardiovascular disease. In conclusion, this retrospective analysis has revealed that scleroderma is a relatively common but clinically heterogeneous disorder. There are important clinical and prognostic implications in defining limited versus diffuse versus overlap disease.

Adult↗
PubMed1998

Synovial mast cell responses during clinical improvement in early rheumatoid arthritis.

OBJECTIVES: To determine the synovial mast cell response in early rheumatoid arthritis (RA) during clinical improvement, and to examine for relations with clinical and histological parameters of disease activity. METHODS: Twenty two synovial samples were obtained from six patients with RA using needle arthroscopy. The mean disease duration at baseline was eight months, and two to three further samples were obtained over a mean follow up period of 15 months during which treatment initiated clinical improvement occurred. Sections were immunostained to detect MCT and MCTC mast cells and correlations were sought between clinical and histological data. RESULTS: The overall mean synovial mast cell density was 40.3 cells/mm2, with regional densities of 60.6 and 34.2 mast cells/mm2 in the superficial and deeper synovial layers respectively. The MCT subset predominated, outnumbering MCTC by 3:1. There was a significant correlation between the histological inflammation index and the MCT density, (r = 0.4, p < 0.05) but not the MCTC subset. The regional distribution and predominant subset of mast cells varied in individual patient's synovia over time, with a trend towards restriction of the mast cell response to the superficial synovium during clinical improvement. CONCLUSIONS: The mast cell response in early RA is characterised by substantial expansion of predominantly MCT mast cells that correlates with histological indices of inflammation. During clinical improvement, this expansion tended to become more superficial. Taken together with previous studies of long duration RA, which implicate MCTC cells in synovial damage and disease progression, these results suggest that MCT and MCTC mast cells may possess distinct functions in the spectrum of inflammatory events occurring during RA.

Arthritis, Rheumatoid↗
PubMed1998

Differential chromosome sensitivity to 5-azacytidine in Alzheimer's disease.

BACKGROUND: The methylation process in the DNA has been considered a control mechanism of gene activity, connected with genetic imprinting. 5-Azacytidine (5-AZC) is known to be a demethylation agent. OBJECTIVE: We studied the cytogenetic effect of 5-AZC in Alzheimer's disease patients and in two control groups. METHODS: Peripheral lymphocyte cultures derived from 8 patients with Alzheimer's disease and 8 elderly and 8 healthy young individuals, all female, were studied. The parameters investigated were: the undercondensation of constitutive heterochromatin of chromosomes 1, 9, and 16: the number of lesions in fragile sites 1q42 and 19q13; heterochromatin association, and the total number of induced lesions. RESULTS: Our results showed a significantly increased frequency of undercondensation of chromosomes 1, 9, and 16 in Alzheimer's disease patients when compared with elderly and young healthy groups. CONCLUSION: These results suggest that the demethylating action of 5-AZC could reveal differential gene activity in the Alzheimer group at the level of cellular division.

Adult↗