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Biomedical subjects

S Smith

Publications and source records attributed to S Smith.

At least 235 records · Page 13Linked to original sources
PubMed1999

Dibromopropanone cross-linking of the phosphopantetheine and active-site cysteine thiols of the animal fatty acid synthase can occur both inter- and intrasubunit. Reevaluation of the side-by-side, antiparallel subunit model.

The objective of this study was to test a new model for the homodimeric animal FAS which implies that the condensation reaction can be catalyzed by the amino-terminal beta-ketoacyl synthase domain in cooperation with the penultimate carboxyl-terminal acyl carrier protein domain of either subunit. Treatment of animal fatty acid synthase dimers with dibromopropanone generates three new molecular species with decreased electrophoretic mobilities; none of these species are formed by fatty acid synthase mutant dimers lacking either the active-site cysteine of the beta-ketoacyl synthase domain (C161A) or the phosphopantetheine thiol of the acyl carrier protein domain (S2151A). A double affinity-labeling strategy was used to isolate dimers that carried one or both mutations on one or both subunits; the heterodimers were treated with dibromopropanone and analyzed by a combination of sodium dodecyl sulfate/polyacrylamide gel electrophoresis, Western blotting, gel filtration, and matrix-assisted laser desorption mass spectrometry. Thus the two slowest moving of these species, which accounted for 45 and 15% of the total, were identified as doubly and singly cross-linked dimers, respectively, whereas the fastest moving species, which accounted for 35% of the total, was identified as originating from internally cross-linked subunits. These results show that the two polypeptides of the fatty acid synthase are oriented such that head-to-tail contacts are formed both between and within subunits, and provide the first structural evidence in support of the new model.

Acetone↗
PubMed1999

Conserved function of mSpry-2, a murine homolog of Drosophila sprouty, which negatively modulates respiratory organogenesis.

In Drosophila embryos, the loss of sprouty gene function enhances branching of the respiratory system. Three human sprouty homologues (h-Spry1-3) have been cloned recently, but their function is as yet unknown [1]. Here, we show that a murine sprouty gene (mSpry-2), the product of which shares 97% homology with the respective human protein, is expressed in the embryonic murine lung. We used an antisense oligonucleotide strategy to reduce expression of mSpry-2 by 96%, as measured by competitive reverse transcriptase PCR, in E11. 5 murine embryonic lungs cultured for 4 days [2]. Morphologically, the decrease in mSpry-2 expression resulted in a 72% increase in embryonic murine lung branching morphogenesis as well as a significant increase in expression of the lung epithelial marker genes SP-C, SP-B and SP-A. These results support a striking conservation of function between the Drosophila and mammalian sprouty gene families to negatively modulate respiratory organogenesis.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Sequence scanning chicken cosmids: a methodology for genome screening.

The chicken genome is relatively poorly studied at the molecular level. The karyotype 2n=78 is divided into three main chromosomal sub-groups: the macrochromosomes (six pairs), the intermediate microchromosomes (four pairs) and the microchromosomes (29 pairs). Whilst the microchromosome group comprise only 25% of the DNA, increasing evidence is proving that this is disproportionate to their gene content. This paper demonstrates the utility of cosmid sequence scanning as a potential method for analysing the chicken genome, providing an economical method for the production of a molecular map. The GC content, gene density and repeat distribution are analysed relative to chromosomal origin. Results indicate that gene density is higher on the microchromosomes. During the scanning process an example of conserved linkage between chicken and human (12q34.2) has been demonstrated.

Animals↗
PubMed1999

Dynamic holographic imaging of the beating human heart

Background--Currently, the reporting and archiving of echocardiographic data suffer from the difficulty of representing heart motion on printable 2-dimensional (2D) media. Methods and Results--We studied the capability of holography to integrate motion into 2D echocardiographic prints. Images of normal human hearts and of a variety of mitral valve function abnormalities (mitral valve prolapse, systolic anterior motion of the mitral leaflets, and obstruction of the mitral valve by a myxoma) were acquired digitally on standard echocardiographic machines. Images were processed into a data format suitable for holographic printing. Angularly multiplexed holograms were then printed on a prototype holographic "laser" printer, with integration of time in vertical parallax, so that heart motion became visible when the hologram was tilted up and down. The resulting holograms displayed the anatomy with the same resolution as the original acquisition and allowed detailed study of valve motion with side-by-side comparison of normal and abnormal findings. Comparison of standard echocardiographic measurements in original echo frames and corresponding hologram views showed an excellent correlation of both methods (P<0.0001, r2=0.979, mean bias=2.76 mm). In this feasibility study, both 2D and 3D holographic images were produced. The equipment needed to view these holograms consists of only a simple point-light source. Conclusions--Holographic representation of myocardial and valve motion from echocardiographic data is feasible and allows the printing on a 2D medium of the complete heart cycle. Combined with the recent development of online holographic printing, this novel technique has the potential to improve reporting, visualization, and archiving of echocardiographic imaging.

Journal Article↗
PubMed1999

Hepatitis B maternal screening, infant vaccination, and infant prophylaxis practices in North Carolina.

OBJECTIVES: To determine if the Advisory Committee on Immunization Practices hepatitis B screening, vaccination, and prophylaxis recommendations were being followed in North Carolina, and to establish a baseline hepatitis B seroprevalence rate. DESIGN: A survey of mother and infant birthing facility medical records. SETTING: Four birthing facilities selected from each of the 7 districts in North Carolina (a total of 28 facilities). PARTICIPANTS: A probability proportional to size survey design was used to select 4763 mother-infant record pairs. All records came from the 1996 birth cohort. MAIN OUTCOME MEASURES: Maternal hepatitis B screening status, infant vaccination status, infants prophylaxis status, hepatitis B seroprevalence rate, demographic and clinical predictors for maternal infection, failure to receive prenatal care or for whom status was unknown, failure to screen, and failure to vaccinate. RESULTS: Ninety-two percent of pregnant women were screened for hepatitis B surface antigen. Eighty-six percent of infants received dose 1 of the hepatitis B vaccine. Four of the 9 infants with mothers who were hepatitis B surface antigen-positive did not receive both vaccine and hepatitis B immune globulin. The hepatitis B seroprevalence rate was 0.2%. Mothers who were not screened for infection were 3.4 times more likely to have infants who were not vaccinated. White mothers were twice as likely not to have their child vaccinated as mothers of other races. CONCLUSIONS: Not all infants with hepatitis B-infected mothers were receiving vaccine and hepatitis B immune globulin as recommended. Seroprevalence of hepatitis B infection may be lower in North Carolina than in other states. Hepatitis B laboratory test results should be included in every mother's medical record.

Birthing Centers↗
PubMed1999

Phosphotyrosine signalling as a regulator of neural crest cell adhesion and motility.

We demonstrate that neural crest cell-cell adhesion, cell-substrate adhesion, and ultimately cell motility, are highly dependent on the balanced action of tyrosine kinases and tyrosine phosphatases. Neural crest cell migration on fibronectin is diminished in the presence of the tyrosine phosphatase inhibitor vanadate or tyrosine kinase inhibitor herbimycin A, while cadherin-rich cell-cell adhesions are significantly increased. In contrast, cells treated with the kinase inhibitor genistein have decreased motility, rearrange rapidly and reversibly into a pavement-like monolayer, but have no increase in cadherin interactions. Genistein-sensitive tyrosine kinases may therefore abrogate a latent sensitivity of neural crest cells to contact-mediated inhibition of movement. Furthermore, we show that the activity of herbimycin A-sensitive kinases is necessary for focal adhesion formation in these cells. Moreover, the size and distribution of these adhesions are acutely sensitive to the actions of tyrosine phosphatases and genistein-sensitive kinases. We propose that in migrating neural crest cells there is a balance in phosphotyrosine signalling which minimises both cell-cell adhesion and contact inhibition of movement, while enhancing dynamic cell-substrate interactions and thus the conditions for motility.

Animals↗
PubMed1999

A prospective analysis of cognitive function and anticardiolipin antibodies in systemic lupus erythematosus.

OBJECTIVE: To prospectively analyze the association between changes in cognitive function and circulating anticardiolipin antibodies (aCL) over a period of 5 years in patients with systemic lupus erythematosus (SLE). METHODS: Cognitive function was assessed in 51 unselected female SLE patients at baseline and after a mean followup of 64.5 months (range 52-71 months), using standardized tests of cognitive function, i.e., the Wechsler Adult Intelligence Scale-Revised, the Wechsler Memory Scale-Revised, and the California Verbal Learning Test. Circulating IgG, IgA, and IgM aCL and anti-double-stranded DNA (anti-dsDNA) antibody levels were determined by enzyme-linked immunosorbent assay on 4-7 occasions over the same time period. Persistent antibody reactivity was defined as levels more than 2 standard deviations (moderately positive) and more than 5 standard deviations (highly positive) above the mean for normal controls over the duration of the study. Changes in overall cognitive performance and in raw scores on individual cognitive tests were compared in patients who were persistently positive or negative for aCL. RESULTS: At baseline 11 patients (22%) were cognitively impaired, compared with 7 (14%) at followup. Between 16% and 37% of patients had persistently elevated aCL levels of different isotypes. There was no significant difference in the prevalence of overall cognitive impairment in patients who were persistently positive for aCL compared with those who were not. In contrast, over the period of study, patients who had persistent IgG aCL positivity had a reduction in psychomotor speed, and patients who had persistent IgA aCL positivity had a reduction in conceptual reasoning and executive ability. Similar associations with anti-dsDNA antibodies were not found. CONCLUSION: These results suggest that IgG and IgA aCL may be responsible for long-term subtle deterioration in cognitive function in patients with SLE.

Adult↗
PubMed1999

Large repulsion, but not attraction, tilt illusions occur when stimulus parameters selectively favour either transient (M-like) or sustained (P-like) mechanisms.

A vertical test grating appears tilted away from a surrounding inducing grating which is 15 degrees from vertical (repulsion effect) but towards an inducer 75 degrees from vertical (attraction effect). This is the tilt illusion (TI) and similar effects occur when inducing and test stimuli are presented successively (tilt after-effect or TAE). When it was reported [Wolfe, J. (1984). Vision Research, 24, 1959-1964] that large repulsion TAEs occurred with short test flashes, Wolfe postulated that either there are distinct mechanisms which process brief and longer duration stimuli; or that there are distinct mechanisms which are not primarily concerned with duration but are differentially responsive to temporal parameters, amongst several others. Other evidence that TI attraction effects are not modulated by test flash duration resulted in an hypothesis that repulsion and attraction effects are mediated by transient and sustained mechanisms, respectively [Wenderoth, P., van der Zwan, R., & Johnstone, S. (1989). Perception, 18, 715-728]. We demonstrate that large repulsion TIs can be induced when parameters other than duration are manipulated, including contrast and spatial frequency but that these parameters fail to modulate attraction TIs. These results are consistent with some previous hypotheses regarding the origin of repulsion and attraction effects and with Wolfe's latter hypothesis but do not support the view that the two effects are processed, respectively, by transient and sustained mechanisms.

Contrast Sensitivity↗
PubMed1999

Comparison of restimulation methods to elicit SIV specific cytotoxic T-lymphocytes (CTL) in vitro: Staphylococcal enterotoxin B (SEB) provides a novel method for the quantification of SIV specific CTL precursors.

Most investigators believe that an effective HIV-1 vaccine will have to induce high levels of HIV-1 specific cytotoxic T-cells (CTL). The macaque SIV challenge/protection model system has been used to test candidate vaccines, but quantitative immunogenicity measurements are difficult due to technical limitations of the assays available. The quantification of SIV specific CTLp is crucial to understanding correlates of immunity for these vaccines, but are difficult to measure. We have compared various methods to quantify SIV specific CTLp, and describe a novel method of SIV specific CTL in vitro stimulation using the superantigen Staphylococcal enterotoxin B (SEB). SEB can stimulate high levels of CTLp in vitro, and provides an alternative method to induce SIV specific CTL.

Animals↗
PubMed1999

The natural history of tibial radiolucent lines in a proximally cemented stemmed total knee arthroplasty.

A total of 207 tibial components in total knee arthroplasty (TKA) have been reviewed at a maximum of 10 years after replacement. Twelve knees developed aseptic femoral loosening and were reviewed separately from the remaining 195. All tibial components were fixed with cement confined to the proximal surface of the implant combined with an uncemented stem. In the 195 TKAs with well-fixed femoral components and (presumably) low wear, 15% of tibiae developed early-onset, nonprogressive partial radiolucent lines (RLLs), typically in relation to preoperative sclerosis. Tibial component vertical migration was measured in 36 components: no migration was detected over the course of 5 years whether or not an RLL was present. There was no case of tibial osteolysis, no tibial component was revised for aseptic loosening, and no implant was radiologically loose. In 12 knees, the femoral component loosened with subsidence exposing peripheral bone that caused severe HDP wear. Tibial RLLs were present in 9, and osteolysis was present in 11 (although the tibial component was actually loose in only 1). This material has been used to study 1) the natural history of RLLs in cemented TKA and 2) the outcome of using cement confined to the proximal part of the tibial interface. We conclude that in low-wear prostheses RLLs are due to a failure to inject cement into sclerotic bone. Such lines are nonprogressive and do not affect fixation. In the presence of severe wear, however, they may provide a portal for the entry of debris into the interface causing progression of the RLL and lysis. Proximal cement plus an uncemented stem furnishes adequate tibial fixation, provided that the HDP wear rate is low.

Adult↗