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Biomedical subjects

Thomas M Smith

Publications and source records attributed to Thomas M Smith.

10 recordsLinked to original sources
PubMed2006

Characterization of an alternative splice variant of human nucleoside triphosphate diphosphohydrolase 3 (NTPDase3): a possible modulator of nucleotidase activity and purinergic signaling.

Nucleoside triphosphate diphosphohydrolase 3 (NTPDase3) is a cell surface, membrane-bound enzyme that hydrolyzes extracellular nucleotides, thereby modulating purinergic signaling. An alternatively spliced variant of NTPDase3 was obtained and analyzed. This alternatively spliced variant, termed "NTPDase3beta", is produced through the use of an alternative terminal exon (exon 11) in place of the terminal exon (exon 12) in the full-length NTPDase3, now termed "NTPDase3alpha". This results in an expressed protein lacking the C-terminal cytoplasmic sequence, the C-terminal transmembrane helix, and apyrase conserved region 5. The cDNA encoding this truncated splice variant was detected in a human lung library by PCR. Like the full-length NTPDase3alpha, the alternatively spliced NTPDase3beta was expressed in COS cells after transfection, but only the full-length NTPDase3alpha is enzymatically active and properly trafficked to the plasma membrane. However, when the truncated NTPDase3beta was co-transfected with full-length NTPDase3alpha, there was a significant reduction in the amount of NTPDase3alpha that was properly processed and trafficked to the plasma membrane as active enzyme, indicating that the truncated form interferes with normal biosynthetic processing of the full-length enzyme. This suggests a role for the NTPDase3beta variant in the regulation of NTPDase3 nucleotidase activity, and therefore the control of purinergic signaling, in those cells and tissues expressing both NTPDase3alpha and NTPDase3beta.

Adenosine Triphosphatases↗
PubMed2005

Democratic school climate and sense of community in school: a multilevel analysis.

This study examines individual- and school-level predictors of sense of community in school among adolescents. Hierarchical linear modeling was used to examine the relationships between individual (demographics, control and monitoring by parents, and perception of democratic school climate), class, and school characteristics (mean democratic school climate, demographics, activities, school size, public/private governance of the school, and facilities) and students' sense of community in the school. Data were analyzed using a three-level model based on 4,092 10- to 18-year-old students nested within 248 classes (across three grade levels: 6th, 8th, and 10th grade level, where the median age was 11, 13, and 15, respectively) in 134 schools in the Veneto region of northeast Italy. Individual and contextual measures of the perception of a democratic school climate, modeled at the individual, class, and school levels simultaneously, were each significant predictor of school sense of community. More parental monitoring and less parental control were also predictive at the individual level. School-level SES predicted between school variation in sense of community, controlling for individual student SES and other student and school-level predictors. School size, facilities (physical spaces resources), level of interaction of the school with the community, public, or private governance, and number of extracurricular activities offered were all nonsignificant. The study demonstrates significant variation in school sense of community at the student, class, and school levels and the important role played by democratic school practices, such as student participation in making rules and organizing events, freedom of expression, and the perceived fairness of rules and teachers, in determining this variable.

Adolescent↗
PubMed2005

Metal-on-metal total hip arthroplasty with large heads may prevent early dislocation.

UNLABELLED: Postoperative dislocation is one of the major causes of morbidity and failure of total hip arthroplasty. We reviewed 327 patients (377 hips) retrospectively with varying diagnoses and indications but all of whom received large-diameter metal-on-metal prostheses. Two surgical approaches were used: the anterolateral abductor splitting (342 procedures) and a mini-incision posterior approach (35 procedures). Average age at time of surgery was 55.9 years and average followup was 4.0 months. There were 346 (91.8%) primary procedures, 15 (4.0%) conversion procedures, and 16 (4.2%) revisions or reimplantations. The most common preoperative diagnoses included osteoarthritis (250 hips; 66.3%) and avascular necrosis (46 hips; 12.2%). There were 62 (16.4%) patients with high-risk diagnoses for dislocation. The status in terms of postoperative dislocation was known for all patients. During the short followup period, there were no dislocations. Use of large-diameter femoral heads and metal-on-metal articulations decreases the risk of dislocations, making their use a viable choice for primary and revision procedures. LEVEL OF EVIDENCE: Therapeutic study, Level IV-1 (case series). See the Guidelines for Authors for a complete description of levels of evidence.

Adult↗
PubMed2005

Isolated liner exchange using the anterolateral approach is associated with a low risk of dislocation.

UNLABELLED: Authors of reports on the outcome of isolated liner exchange for osteolysis and wear have reported high dislocation rates. Twenty-six patients (27 hips) with a minimum of 2 years of followup had isolated liner exchange for wear and osteolysis done using the abductor splitting anterolateral approach. The mean followup was 41 months. The average age at time of surgery was 51 years. Preoperative Harris hip scores averaged 70, and increased to 82 at the most recent followup. We observed improvements in pain and functional scores. The average operating time was 82 minutes, and the average blood loss was 255 mL. Only three (12%) patients required transfusion. No components were rerevised for aseptic loosening, and one patient (one hip) had a dislocation (3.7%). Isolated liner exchange for osteolysis and wear done using the anterolateral approach has a lower risk of dislocation than previously reported and provides substantial improvements in pain, function, and Harris hip score. LEVEL OF EVIDENCE: Therapeutic study, Level IV (case series). See the Guidelines for Authors for a complete description of levels of evidence.

Adult↗
PubMed2005

Acute hip arthroplasty for the treatment of intertrochanteric fractures in the elderly.

Arthroplasty for intertrochanteric fractures in elderly patients may allow early weightbearing and avoid fixation failure. Clinical results are reviewed in a consecutive group of acute arthroplasties (5 hemiarthroplasties and 29 total hip arthroplasties) performed via the anterolateral approach for intertrochanteric fractures. Age averaged 80.2 years. Follow-up averaged 35 months for living patients. Twenty-six patients died during follow-up. Time to death averaged 3.5 years. Five hips, all total hip arthroplasties, required subsequent surgeries: four for dislocation and one revised for sepsis. Acute intertrochanteric fractures are associated with high early mortality. In this series, a 15% complication rate and high mortality rate at 12 years was associated with acute arthroplasty. Dislocation is higher than in primary total hip arthroplasty utilizing the same surgical approach. The results do not support routine use of arthroplasty in treatment of intertrochanteric hip fractures in the elderly.

Aged↗
PubMed2004

Structure and protein design of a human platelet function inhibitor.

Hematophagous arthropods secrete a salivary apyrase that inhibits platelet activation by catabolizing ADP released from damaged tissues and blood cells. We report the X-ray crystal structures of a human enzyme of the soluble apyrase family in its apo state and bound to a substrate analog. The structures reveal a nucleotide binding domain comprising a five-blade beta propeller, binding determinants of the substrate and the active site, and an unusual calcium binding site with a potential regulatory function. Using a comparative structural biology approach, we were able to redesign the human apyrase so as to enhance its ADPase activity by more than 100-fold. The engineered enzyme is a potent inhibitor of platelet aggregation and may serve as the basis for the development of a new class of antithrombotic agents.

Amino Acid Sequence↗
PubMed2004

Mid-term results of a polyethylene-free metal-on-metal articulation.

Beginning in December 1995, 193 patients (195 hips) were enrolled into this prospective, randomized, controlled multicenter investigational device exemption study. Ninety-eight patients (99 hips) with 46 polyethylene liners and 53 metal liners had minimum 5-year follow-up (mean, 5.7 years). Average follow-up, Harris hip score improvement, and radiographic analysis were not statistically different between groups. No stress shielding or osteolysis was observed in either group. Three polyethylene liners and no metal liners had acetabular radiolucencies <1 mm in 1 or more zones. There have been no device-related complications, no acetabular revisions performed, and none pending in either group. Based on these mid-term results, the authors conclude that a metal-on-metal articulation represents a viable alternative in young, high-demand, active patients.

Arthroplasty, Replacement, Hip↗
PubMed2002

Cloning, expression, and characterization of a soluble calcium-activated nucleotidase, a human enzyme belonging to a new family of extracellular nucleotidases.

The salivary apyrases of blood-feeding arthropods are nucleotide-hydrolyzing enzymes implicated in the inhibition of host platelet aggregation through the hydrolysis of extracellular adenosine diphosphate. A human cDNA homologous to the apyrase cDNA of the blood-feeding bed bug was identified, revealing an open reading frame encoding a 371-amino acid protein. A cleavable signal peptide generates a secreted protein of 333 residues with a predicted core molecular mass of 37,193 Da. Expression in COS-1 cells produced a secreted apyrase in the cell media. The ADPase and ATPase activities were dependent upon calcium, with a pH optimum between pH 6.2 and 7.2. Interestingly, the preferred substrate was not ADP, as might be expected for an enzyme modulating platelet aggregation, but rather UDP, followed by GDP, UTP, GTP, ADP, and ATP. The nucleotidase did not hydrolyze nucleoside monophosphates. Size-exclusion chromatography and Western blot analysis revealed a molecular mass of approximately 34-37 kDa. Treatment of the enzyme with peptide N-glycosidase F indicated that the protein is glycosylated. Northern analysis identified the transcript in a range of human tissues, including testis, placenta, prostate, and lung. No traditional apyrase-conserved regions or nucleotide-binding domains were identified in this human enzyme, indicating membership in a new family of extracellular nucleotidases.

Adenosine Triphosphatases↗