Search PubMed⌕ Search

Biomedical subjects

S Smith

Publications and source records attributed to S Smith.

At least 289 records · Page 16Linked to original sources
PubMed1998

Cat allergen levels in public places in New Zealand.

AIMS: Cat allergen (Fel d 1) is a known risk factor for asthma. Studies have demonstrated Fel d 1 in both public buildings and domestic dwellings where cats have never been. The aims of this study were to measure reservoir Fel d 1 levels in public buildings in New Zealand, to examine determinants of these levels and to compare them with previously measured domestic levels. METHODS: Dust was obtained in two centres (Wellington and Christchurch) from hotels, hospitals, rest homes, churches, primary schools, childcare centres, cinemas, bank head offices and aeroplanes; and from North Island ski lodges. Measurements of temperature and relative humidity were taken. Information was collected on building characteristics. Fel d 1 levels (microg/g of fine dust) for floors (n=203), beds (n=64) and seats (n=24) were expressed as geometric means (95% confidence intervals). RESULTS: Detectable Fel d 1 levels were found in 95% of floor samples, 91% of bed samples and 100% of seat samples. Fel d 1 levels [geometric mean (95% confidence intervals)] were significantly higher on cinema and domestic aircraft seats [36.8 (20.8-65.3) microg/g and 33.3 (28.0-39.7) microg/g respectively] than on floors [3.6 (2.5-5.1) microg/g and 2.4 (1.8-3.0) microg/g respectively]. Floor Fel d 1 levels in the public buildings sampled were lower than those of domestic dwellings without cats [0.9 (0.6-1.4) microg/g vs 1.7 (1.2-2.4)] microg/g in Wellington and [2.0 (1.6-2.6) microg/g vs 4.0 (2.7-6.0] microg/g in Christchurch. After controlling for potential confounders, floor Fel d 1 levels were higher with carpeted floors (p<0.001) and lower in banks and hospitals (p<0.001). CONCLUSION: Fel d 1 levels in public buildings are low in New Zealand public places except for cinema and domestic aircraft seats where all but one sample had Fel d 1 levels potentially high enough to precipitate asthma symptoms in sensitised individuals.

Air Pollution, Indoor↗
PubMed1998

ATP-dependent copper transport by the Menkes protein in membrane vesicles isolated from cultured Chinese hamster ovary cells.

The Menkes (MNK) protein is a vital component of copper homeostasis in mammalian cells. In this paper we provide the first biochemical evidence that the MNK protein functions as a copper-translocating P-type ATPase in mammalian cells. The enzyme activity in membrane vesicles prepared from Chinese hamster ovary cells overexpressing MNK was ATP-dependent, correlated with the amount of MNK and followed Michaelis-Menten kinetics with respect to copper. The copper transport was observed only under reducing conditions suggesting MNK transports Cu(I). This study opens the way to detailed structure-function studies and assessment of functional MNK derived from patients with Menkes disease.

Adenosine Triphosphatases↗
PubMed1998

Periapical cemental dysplasia: a case of misdiagnosis.

The correct diagnosis of pathological lesions of endodontic origin should allow for differentiation from those arising from other sources. A case of periapical cemental dysplasia (cementoma) is presented, whereby incorrect diagnosis resulted in not only inappropriate treatment, but an endodontic mishap and the superimposition of acute apical periodontitis in a previously disease-free site. This case report highlights the need for appropriate examination, simple special tests and diagnosis prior to management of lesions of questionable aetiology.

Adult↗
PubMed1998

Constitutive activation of TCR signaling molecules in IL-2-independent Herpesvirus saimiri-transformed T cells.

Both human T cell leukemia virus type I and simian Herpesvirus saimiri (HVS) transform human T cells in vitro. Although IL-2-independent growth in human T cell leukemia virus type I-transformed T cells is associated with constitutive phosphorylation of JAK/STAT kinases, we now demonstrate that different mechanisms may be responsible for the ability of HVS-transformed T cells to proliferate in the absence of exogenous cytokines. The IL-2 independence of an HVS-transformed cell line correlated with constitutive activation of protein tyrosine kinases known to be induced following TCR engagement. Thus, in these cells we observed increased phosphotransferase activity of Lck as well as constitutive tyrosine phosphorylation of the TCR-associated ZAP-70 kinase and expression of the related Syk protein tyrosine kinase. While Syk is generally not expressed in activated T cells, its introduction has been shown to enhance TCR responsiveness. These results suggest that distinct signal transduction cascades can participate in the transition of T cells to IL-2 independence.

Cell Division↗
PubMed1998

Differential affinity labeling of the two subunits of the homodimeric animal fatty acid synthase allows isolation of heterodimers consisting of subunits that have been independently modified.

To explore the domain interactions that are required for catalytic activity of the multifunctional, homodimeric fatty acid synthase (FAS), we have formulated a strategy that allows isolation of modified dimers containing independently mutated subunits. Either a hexahistidine or a FLAG octapeptide tag was incorporated into the FAS at either the amino terminus, within an internal noncatalytic domain, or at the carboxyl terminus. The presence of the tags had no effect on the activity of the wild-type FAS. His-tagged dimers were mixed with FLAG-tagged dimers, and the subunits were randomized to produce a mixture of His-tagged homodimers, FLAG-tagged homodimers, and doubly tagged heterodimers. The doubly tagged heterodimers could be purified to homogeneity by chromatography on an anti-FLAG immunoaffinity column followed by a metal ion chelating column. This procedure for isolation of FAS heterodimers was utilized to determine whether the two centers for fatty acid synthesis in the FAS dimer can function independently of each other. Doubly tagged heterodimers, consisting of one wild-type subunit and one subunit in which the thioesterase activity had been eliminated, either by mutation or by treatment with phenylmethanesulfonyl fluoride, have 50% of the wild-type thioesterase activity and, in the presence of substrates, accumulate a long chain fatty acyl moiety on the modified subunit, thus blocking further substrate turnover at this center. Nevertheless, the ability of the heterodimer to synthesize fatty acids is also 50% of the wild-type FAS, demonstrating that an individual center for fatty acid synthesis has the same activity when paired with either a functional or nonfunctional catalytic center.

Affinity Labels↗
PubMed1998

The malonyl/acetyltransferase and beta-ketoacyl synthase domains of the animal fatty acid synthase can cooperate with the acyl carrier protein domain of either subunit.

The active form of the animal fatty acid synthase (FAS) is a dimer of identical multifunctional polypeptides, each containing seven discrete functional domains, that cooperate to form two centers for palmitate synthesis. To assess the importance of domain cooperation across the subunit interface in the reaction mechanism, we have utilized a strategy based on complementation analysis in vitro of modified FASs carrying critical mutations in specific catalytic domains. Homodimeric FASs carrying the same mutation(s) in both subunits are unable to synthesize fatty acids. As predicted by the current head-to-tail model for the animal FAS, heterodimeric FASs formed between the acyl carrier protein (ACP) mutant and either the beta-ketoacyl synthase (KS) or malonyl/acetyltransferase (MAT) are active in palmitate synthesis, confirming that the KS and MAT domains can cooperate with the ACP domain of the opposite subunit. Contrary to this model however, heterodimeric FASs formed between the KS and MAT mutants, between a MAT, ACP double mutant, and a KS mutant, and between a KS, ACP double mutant, and a MAT mutant are also active in palmitate synthesis, indicating that the MAT and KS domains can also cooperate with the ACP domain of the same subunit. The results of this study reveal an unanticipated element of redundancy in the FAS reaction mechanism in that the amino-terminal KS and MAT domains can make functional contact with the penultimate carboxy-terminal ACP domain of either subunit. A revised model for the FAS is proposed in which the substrate loading and condensation reactions can be catalyzed either by one of the two subunits or by cooperation between domains across the subunit interface.

3-Oxoacyl-(Acyl-Carrier-Protein) Synthase↗
PubMed1998

Abrogation of Smad3 and Smad2 or of Smad4 gene expression positively regulates murine embryonic lung branching morphogenesis in culture.

Smad genes are recently identified intracellular effectors for receptor signaling in the BMP/activin/TGF-beta pathway. Since TGF-beta ligands are known to inhibit embryonic lung branching morphogenesis, we tested the hypothesis that Smad genes negatively regulate lung organogenesis. Antisense oligodeoxynucleotides were designed to attenuate Smad3 and Smad2 gene expression in embryonic (E11) mouse lungs over 4 days in culture. Endogenous Smad3 and Smad2 mRNA levels were suppressed by 97 and 91%, respectively, in cultured embryonic lungs when antisense oligodeoxynucleotide (40 microM) to Smad was added, compared to scrambled and sense sequence controls. The corresponding Smad3 and Smad2 protein amounts were also decreased respectively by 86 and 90% in lungs treated with Smad3 and Smad2 antisense oligodeoxynucleotide. Phenotypically, Smad antisense oligodeoxynucleotides resulted in a concentration-dependent increase in lung branching: embryonic lung branching was stimulated by up to 53% in culture with 40 microM antisense oligodeoxynucleotide, whereas both scrambled and sense controls showed no stimulatory effect. Thus, inhibition of endogenous Smad3 and Smad2 gene expression resulted in stimulation of embryonic lung branching similar to that caused by inhibition of TGF-beta type II receptor expression and signaling (J. Zhao et al., 1996, Dev. Biol. 180, 242-257). Abrogation of Smad4 (DPC4), the downstream mediator of Smad3 and Smad2 proteins, with antisense oligodeoxynucleotide, also resulted in increased branching morphogenesis. Furthermore, while TGF-beta alone inhibited lung branching morphogenesis in culture, addition of exogenous TGF-beta 1 could not overcome the stimulatory effect on lung branching of Smad antisense oligodeoxynucleotide treatment. By immunohistochemistry, Smad proteins were localized mainly to the epithelial cells lining the branching distal airways, indicating that Smad genes could regulate lung morphogenesis through mesoderm-endoderm interaction. Our results demonstrate, for the first time, that abrogation of Smad2 and Smad3 or of Smad4 gene expression stimulated early mouse embryonic lung branching morphogenesis in culture, possibly through reversing the negative influence of endogenous TGF-beta signaling upon lung branching morphogenesis.

Animals↗
PubMed1998

Large-scale temporal gene expression mapping of central nervous system development.

We used reverse transcription-coupled PCR to produce a high-resolution temporal map of fluctuations in mRNA expression of 112 genes during rat central nervous system development, focusing on the cervical spinal cord. The data provide a temporal gene expression "fingerprint" of spinal cord development based on major families of inter- and intracellular signaling genes. By using distance matrices for the pair-wise comparison of these 112 temporal gene expression patterns as the basis for a cluster analysis, we found five basic "waves" of expression that characterize distinct phases of development. The results suggest functional relationships among the genes fluctuating in parallel. We found that genes belonging to distinct functional classes and gene families clearly map to particular expression profiles. The concepts and data analysis discussed herein may be useful in objectively identifying coherent patterns and sequences of events in the complex genetic signaling network of development. Functional genomics approaches such as this may have applications in the elucidation of complex developmental and degenerative disorders.

Animals↗
PubMed1998

Quantitation of the extracellular domain of epidermal growth factor receptor in the plasma of dioxin-exposed individuals.

Animal models suggest that dioxins have a negative effect on the level of expression of the epidermal growth factor receptor in cells. In vivo the level of expression in tissue of the epidermal growth factor receptor can be monitored by assaying for the extracellular domain in blood using an enzyme linked immunosorbent assay. We have determined the levels of the extracellular domain of the epidermal growth factor receptor in the plasma of 30 individuals: 10 with high blood dioxin levels (TEQ range = 318-673 ppt), 10 with medium blood dioxin levels (TEQ range = 16-60 ppt), and 10 with low background blood dioxin levels (TEQ range = 3-10 ppt). The levels of the epidermal growth factor receptor extracellular domain were lower in the high blood dioxin group (mean +/- SD = 45 +/- 26 fmol/ml) and the medium blood dioxin group (mean +/- SD = 41 +/- 23 fmol/ml) compared with the low blood dioxin group (mean +/- SD = 73 +/- 43 fmol/ml). These results suggest that the extracellular domain of the epidermal growth factor receptor may be a marker of the biological effect of dioxin exposure.

Dioxins↗
PubMed1998

Lethal neonatal autosomal recessive axonal sensorimotor polyneuropathy.

Peripheral neuropathy is an uncommon cause of generalized hypotonia and weakness in infancy. It occurs as a part of the clinical syndrome in some neurodegenerative disorders of infancy, but seldom causes respiratory failure or swallowing difficulties. We report a lethal autosomal recessive axonal polyneuropathy with neonatal onset in a large kindred from Northern Mississippi. One patient was studied in detail at our medical center and the information on 12 other affected infants in this large family were gathered from medical records and by interviewing the family members. Patients were symptomatic for the polyneuropathy before birth and died in the first year of life from respiratory complications. Thirteen babies were affected by this clinical phenotype in four generations of this family with a high frequency of consanguinity. Affected babies were of both sexes and were born to healthy consanguineous parents. The clinical phenotype of polyneuropathy in our index patient and other affected babies in this family was similar, and represents a unique form of hereditary neonatal polyneuropathy.

Age of Onset↗
PubMed1998

A twin and family study of the association between immune system dysfunction and dyslexia using blood serum immunoassay and survey data.

We conducted a study of the association between developmental reading disability (DRD) and immune disorders (ID) using both survey and immunoassay data in two separate samples of families. One sample was made up of twins and their parents and was ascertained through a population-based sampling scheme. The other sample was a set of extended pedigrees selected for apparent autosomal dominant transmission of DRD. We failed to find an association between DRD and ID in either sample, regardless of the method used to assess immune system function. Even though our twin sample provided evidence that both DRD and immune conditions were significantly heritable, there was no evidence for a genetic correlation between ID and DRD nor was there any clear indication that a special subgroup of individuals may be comorbid for these conditions because of genetic reasons. How these negative findings can be reconciled with the developmental hypothesis of Geschwind, Behan, Galaburda, and colleagues, and how they may relate to the gene locus influencing DRD that has been recently located in the HLA region of the short arm of chromosome 6 is discussed.

Adolescent↗
PubMed1998

HLA typing in the United Kingdom multiple sclerosis genome screen.

The United Kingdom multiple sclerosis genome screen demonstrated a peak maximum lod score of 2.8 in the HLA region, together with statistically significant excess transmission of the 121-base pair (bp) allele of the tumour necrosis factor-a marker. In order to determine whether this association is independent of the established HLA association, or simply a consequence of the 121-bp allele being part of the same haplotype, we HLA-DR and -DQ typed the 227 sibling-pair families used in the original screen. The expected associations of multiple sclerosis with the DR15 (p=8.7E-18), DQ6 (p=2.0E-09) and DR51 (p=2.8E-16) phenotypes were confirmed, and excess transmission of the DRB1*1501 and DQB1*0602 alleles was demonstrated. Combining HLA typing with the original microsatellite data demonstrated extensive linkage disequilibrium between the 121-bp allele and the 1501-0602 haplotype. Outside this extended haplotype (121-1501-0602), none of the alleles demonstrated significant transmission distortion. Having established the importance of this extended haplotype, we reanalysed the entire genome screen data after excluding those sibling pairs sharing the extended haplotype (n=27). Conditioning the full genome screen data on the basis of identity by state sharing showed that some potential linkage regions identified in the original screen clustered in families, in which the extended haplotype was shared (1p, 2p and 17q), whereas others grouped with those in which it was not (5cen, 7p and Xq). This suggests complexity in the genetics of multiple sclerosis.

Genetic Markers↗
PubMed1998

Failure of intravenous ribavirin in the treatment of invasive adenovirus infection following allogeneic bone marrow transplantation: a case report.

We report a case of fatal adenovirus infection in a 37-year-old female who underwent allogeneic bone marrow transplantation (BMT) for acute myelogenous leukaemia (AML). Post BMT she developed acute grade II graft-vs.-host disease (aGVHD) requiring high-dose steroids and anti-thymocyte globulin. Additionally, her clinical course was complicated with adenovirus-associated haemorrhagic cystitis and viraemia. Intravenous ribavirin was obtained and administered for 5 days without success; the patient's mental status deteriorated rapidly and she died on day 69 post-transplant. Radiological imaging revealed diffuse cortical necrosis. At autopsy adenovirus was identified in her bladder, kidneys and lungs.

Adenovirus Infections, Human↗
PubMed1998

Abrogation of betaglycan attenuates TGF-beta-mediated inhibition of embryonic murine lung branching morphogenesis in culture.

Although betaglycan (TGF-beta type III receptor) is known to enhance TGF-beta ligand binding to its type II receptor in murine lung epithelial cell lines, the biological significance of this phenomenon in the process of lung organogenesis is not understood. Betaglycan gene expression was detected in embryonic murine lungs undergoing branching morphogenesis in ex vivo culture. Antisense betaglycan oligodeoxynucleotides (ODN) resulted in up to 56% stimulation of lung branching morphogenesis in culture, while betaglycan mRNA and protein expression levels were suppressed by 90 and 82%, respectively. Following abrogation of betaglycan expression with antisense oligodeoxynucleotide, embryonic lungs were relatively insensitive to TGF-beta: TGF-beta2 (0.5 ng/ml) and TGF-beta1 (20 ng/ml), respectively, down-regulated lung morphogenesis by 38 and 34% in control cultures, whereas TGF-beta-induced inhibition was attenuated to 13 and 26% respectively, in the presence of betaglycan antisense oligodeoxynucleotides. TGF-beta neutralizing antibodies also prevented TGF-beta-mediated inhibition of lung branching in culture, supporting the speculation that autocrine/paracrine TGF-beta signaling is minimal in the absence of betaglycan. Betaglycan was immunolocalized mainly to the epithelial cells in developing airways, a spatial distribution which overlaps with that of TGF-beta type II receptor. Furthermore, abrogation of endogenous betaglycan gene expression prevented the characteristic down-regulation of cyclin A and surfactant protein C (SP-C) mRNAs by exogenous TGF-beta ligands. These results show that betaglycan expression is essential for optimal TGF-beta signaling during embryonic lung development. We therefore conclude that the abrogation of endogenous betaglycan attenuates endogenous autocrine and/or paracrine TGF-beta-mediated negative regulation of lung organogenesis.

Animals↗
PubMed1998

Measurement of radiation dose delivered to breast tissue during mantle field irradiation for Hodgkin's disease.

The treatment of Hodgkin's disease involves mantle field irradiation. Patients with early stage (I-II) Hodgkin's are often in their 20's or 30's and can expect to live for many decades after the successful management of their disease; however, complications, including second cancers in the treatment area, occur in some survivors. Breast cancer is among the leading second solid cancers that develop in patients who have undergone mantle field irradiation. This paper attempts to determine the dose that may be delivered to breast tissue from mantle field irradiation to treat Hodgkin's disease. Utilizing an anthropomorphic phantom, thermoluminescent dosimeters (TLDs) were placed into a breast phantom constructed of Superflab and TX-150, and were irradiated with 6 MV photons. Readings from 170 TLDs in five layers of breast phantom were analyzed. The results show considerable doses reaching portions of breast tissue. In measured points under the blocks, 8-15% of the prescribed isocenter dose was delivered. For points in the primary beam, readings of up to 91% of the isocentric dose were obtained. Points in the breast near block or collimator edges also received substantial doses; upwards of 70% of the prescribed dose. Several points in the breast outside the treatment field were also measured and readings ranged from 2 to 29% of the prescribed dose. Similar patterns of dose distribution were found on computer plans; however, point-by-point comparisons were not performed. These results are compared with published reports.

Breast↗