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Biomedical subjects

R M Smith

Publications and source records attributed to R M Smith.

At least 127 records · Page 7Linked to original sources
PubMed1998

Signs of depth and danger. 1962.

A large proportion of the serious complications that occur during pediatric anesthesia are caused by failure to recognize early signs of danger. The greatest dangers include excessive anesthetic depth, respiratory obstruction and depression, acid-base derangement, shock, myocardial depression, and extreme alterations in body temperature. Simple monitoring devices, including the anesthetic chart, stethoscope, blood pressure cuff, and thermometer, are essential in all major pediatric procedures. Use of the stethoscope should never be omitted in any case. Signs of cardiorespiratory and neuromuscular activity characteristic of infants and children should be familiar to all anesthetists who engage in pediatric work.

Anesthesia↗
PubMed1998

Modulation of insulin-like growth factor I mitogenic signaling in 3T3-L1 preadipocyte differentiation.

Insulin-like growth factor I (IGF-I) stimulates mitogenesis in proliferating 3T3-L1 preadipocytes. However, IGF-I functions to stimulate differentiation once growth arrest occurs at confluence. Epidermal growth factor (EGF) is also a potent mitogen in these cells, but inhibits differentiation of preadipocytes. We compared mitogenic signaling via the mitogen-activated protein kinase (MAPK) pathway in response to IGF-I or EGF in proliferating, growth-arrested, and differentiating 3T3-L1 cells. IGF-I stimulation of MAPK was rapid and maximal in proliferating 3T3-L1 preadipocytes, but decreased greatly in differentiating cells. EGF was more potent than IGF-I in stimulating MAPK activity in 3T3-L1 cells, and activation of MAPK was maintained in differentiating cells. These results suggest an uncoupling of MAPK activation specific to IGF-I-mediated 3T3-L1 preadipocyte differentiation. Studies of proximal signaling revealed Shc phosphorylation and Shc/Grb2 complex formation in IGF-I-treated proliferating, but not differentiating, cells. Insulin receptor substrate-1 phosphorylation after IGF-I treatment was present in proliferating, quiescent, and differentiating preadipocytes. Shc phosphorylation and Grb2 association after EGF treatment were present throughout all phases of growth. The change in IGF-I signaling via Shc phosphorylation and MAPK activity during 3T3-L1 differentiation indicates that loss of IGF-I mitogenic signaling via the MAPK pathway is part of the differentiation process.

3T3 Cells↗
PubMed1998

A medial linkage orthosis to assist ambulation after spinal cord injury.

A "proof of concept" prototype of a new device to link bilateral knee-ankle-foot orthoses, the Mooring Medial Linkage Orthosis (Moorong MLO), is presented. The device consists of an arcuate sliding link centred on the hip joints with rolling element bearings to minimise friction. A single repeated-measures case study is reported in which a woman with an incomplete C6 tetraplegia ambulated over different surfaces and gradients using both the Moorong MLO and the Walkabout orthosis. Results demonstrated a slight increase in gait velocity in the Moorong MLO (between 0.36-1.02 m/min faster) and a consistently lower oxygen cost across all conditions (between 18-61% reduction) compared to the Walkabout orthosis. The reduction was most noticeable on sloping surfaces. These preliminary results suggest an improved efficiency of ambulation in this new device.

Adult↗
PubMed1998

Flight controller alertness and performance during spaceflight shiftwork operations.

Decreased alertness and performance associated with fatigue, sleep loss, and circadian disruption are issues faced by a diverse range of shiftwork operations personnel. During Space Transportation System (STS) operations, Mission Operations Directorate (MOD) personnel provide 24-hr. coverage of critical tasks. A joint NASA Johnson Space Center and NASA Ames Research Center project was undertaken to examine these issues in flight controllers during MOD shiftwork operations. An initial operational test of procedures and measures was conducted during the STS-53 mission in December 1992. The study measures included a Background Questionnaire, a subjective daily logbook completed on a 24-hour basis (to report sleep patterns, work periods, etc.), and an 8 minute performance and mood test battery administered at the beginning, middle, and end of each shift period. Seventeen flight controllers representing the 3 Orbit shifts participated. The initial results clearly support the need for further data collection during other STS missions to document baseline levels of alertness and performance during MOD shiftwork operations. Countermeasure strategies specific to the MOD environment are being developed to minimize the adverse effects of fatigue, sleep loss, and circadian disruption engendered by shiftwork operations. These issues are especially pertinent for the night shift operations and the acute phase advance required for the transition of day shift personnel into the night for shuttle launch. Implementation and evaluation of the countermeasure strategies to maximize alertness and performance is planned. As STS missions extend to further EDO (extended duration orbiters), and timelines and planning for 24-hour Space Station operations continue, alertness and performance issues related to sleep and circadian disruption will remain highly relevant in the MOD environment.

Adult↗
PubMed1998

Using item mean squares to evaluate fit to the Rasch model.

Throughout the mid to late 1970's considerable research was conducted on the properties of Rasch fit mean squares. This work culminated in a variety of transformations to convert the mean squares into approximate t-statistics. This work was primarily motivated by the influence sample size has on the magnitude of the mean squares and the desire to have a single critical value that can generally be applied to most cases. In the late 1980's and the early 1990's the trend seems to have reversed, with numerous researchers using the untransformed fit mean squares as a means of testing fit to the Rasch measurement models. The principal motivation is cited as the influence sample size has on the sensitivity of the t-converted mean squares. The purpose of this paper is to present the historical development of these fit indices and the various transformations and to examine the impact of sample size on both the fit mean squares and the t-transformations of those mean squares. Because the sample size problem has little influence on the person mean square problem, due to the relatively short length (100 items or less), this paper focuses on the item fit mean squares, where it is common to find the statistics used with sample sizes ranging from 30 to 10,000.

Computer Simulation↗
PubMed1998

Corrected Rasch asymptotic standard errors for person ability estimates.

Most calibration programs designed for the family of Rasch psychometric models report the asymptotic standard errors for person and item measure estimates resulting from the calibration process. Although these estimates are theoretically correct, they may be influenced by any number of factors, e.g., restrictions due to the loss of degrees of freedom in estimation, targeting of the instrument, i.e., the degree of offset between mean item difficulty and mean person ability, and the presence of misfit in the data. The effect of these factors on the standard errors reported for the person has not been previously reported. The purpose of this study was to investigate the effects of these three factors on the asymptotic standard errors for person measures using simulated data. The results indicate that asymptotic errors systematically underestimate the observed standard deviation of ability in simulated data, though this underestimation is usually small for targeted instruments with reasonable sample size. However, the underestimation can easily be corrected with a simple linear function. These simulations use only dichotomous data and the results may not generalize to the rating scale and partial credit models.

Aptitude↗
PubMed1997

Purine nucleoside phosphorylase. 3. Reversal of purine base specificity by site-directed mutagenesis.

Human purine nucleoside phosphorylase (PNP) is highly specific for 6-oxopurine nucleosides with a catalytic efficiency (kcat/KM) for inosine 350000-fold greater than for adenosine. Crystallographic studies identified Asn243 and Glu201 as the residues largely responsible for the substrate specificity. Results from mutagenesis studies demonstrated that the side chains for both residues were also essential for efficient catalysis [Erion, M. D., et al. (1997a) Biochemistry 36, 11725-11734]. Additional mechanistic studies predicted that Asn243 participated in catalysis by stabilizing the transition state structure through hydrogen bond donation to N7 of the purine base [Erion, M. D., et al. (1997b) Biochemistry 36, 11735-11748]. In an effort to alter the substrate specificity of human PNP, mutants of Asn243 and Glu201 were designed to reverse hydrogen bond donor and acceptor interactions with the purine base. Replacement of Asn243 with Asp, but not with other amino acids, led to a 5000-fold increase in kcat for adenosine and a 4300-fold increase in overall catalytic efficiency. Furthermore, the Asn243Asp mutant showed a 2.4-fold preference for adenosine relative to inosine and a 800000-fold change in substrate specificity (kcat/KM) relative to wild-type PNP. The double mutant, Asn243Asp::Glu201Gln, exhibited a 190-fold increase in catalytic efficiency with adenosine relative to wild-type PNP, a 480-fold preference for adenosine relative to inosine, and a 1.7 x 10(8)-fold change in preference for adenosine over inosine relative to wild-type PNP. The Asn243Asp mutant was also shown to synthesize 2,6-diaminopurine riboside with a catalytic efficiency (1.4 x 10(6) M-1 s-1) on the same order of magnitude as wild-type PNP with its natural substrates hypoxanthine and guanine. The Asn243Asp mutants represent examples in which protein engineering significantly altered substrate specificity while maintaining high catalytic efficiency.

2-Aminopurine↗
PubMed1997

Prolongation of murine vascularized heart allograft survival by recipient-specific anti-major histocompatibility complex class II antibody.

BACKGROUND: Antibodies targeting recipient major histocompatibility complex (MHC) class II molecules have been demonstrated to be effective at prolonging allograft survival. However, antigen-presenting cell depletion would explain this effect and has not been definitively excluded as the mechanism of action of such antibodies. We have studied an anti-MHC class II antibody (OX6) proven to be noncytotoxic in the recipient strain used. METHODS: Antibody was administered the day before, 2 hr before, and the day after grafting. RESULTS: Antibody administration on the day before, 2 hr before, and the day after grafting significantly prolonged vascularized cardiac allograft survival. Importantly, treatment recognizing recipient MHC was effective, whereas a similar regimen recognizing donor MHC was not. CONCLUSIONS: Noncytotoxic recipient MHC class II-specific antibodies modify allograft rejection. Possible mechanisms for this therapeutic effect are discussed.

Animals↗
PubMed1997

Receptor-mediated cellular entry of nuclear localizing anti-DNA antibodies via myosin 1.

A unique subset of anti-DNA antibodies enters living cells, interacts with DNase 1, and inhibits endonuclease activity, before their nuclear localization and subsequent attenuation of apoptosis. We now report that endocytosis of these immunoglobulins is mediated by cell surface binding to brush border myosin (myosin 1). Cellular entry and internalization via this unique receptor provides initial contact for entry and sorting these immunoglobulins to translocate to the nuclear pore and enter the nucleus, interact with DNase 1 within the cytoplasm, or recycle back to the cell surface. This internalization pathway provides clues to the translocation of large proteins across cell membranes and the functional effects of intracellular antibodies on cytopathology. This is the first demonstration that brush border myosin functions as a specific cell surface receptor for internalization of large proteins.

Amino Acid Sequence↗
PubMed1997

Reamed against unreamed nailing of the femoral diaphysis: a retrospective study of healing time.

In order to assess the results of the AO unreamed femoral nail (URFN), and specifically its effects on healing, 147 consecutive patients treated were reviewed. These included 50 reamed femoral nails (RFN) and 97 unreamed femoral nails. Exclusion of pathological fractures, revisions and fractures outside the femoral diaphysis left 51 procedures in which the healing process could be studied. Twenty-four unreamed and 27 reamed femoral nails in patients with diaphyseal fractures AO (32) were followed up by clinical review and radiographically until union or death. There were two deaths from multiple injuries (one in each group) and two non-unions (at 52 weeks), one in each group. There were no cases of infection, angular deformity of leg length discrepancy; two cases required early rotational correction. There was a single broken distal locking screw in the URFN group but no other implant failures. The fractures in the URFN cases took longer to heal with a mean of 26.9 weeks as opposed to 20.5 weeks in the RFN group (P = 0.009). This did not cause a significant clinical problem. The URFN proved easy to use with a much shorter operation time.

Adolescent↗
PubMed1997

Heterotopic ossification: a comparison between reamed and unreamed femoral nailing.

Heterotopic ossification in the abductor region of the hip following reamed intramedullary femoral nailing has an incidence as high as 68 per cent. A definitive triggering factor for heterotopic ossification remains obscure, but it has been suggested that there may be both local and systemic influences. Previous work has only been able to show a statistical correlation with systemic factors. Sixty antegrade femoral nailings were performed in 58 patients, of which 32 were unreamed. There was no significant difference between the two groups for systemic risk factors known to have statistical correlation with the formation of heterotopic bone. The incidence of heterotopic ossification in the reamed nail group was 35.7 per cent and 9.4 per cent in the unreamed nail group (P = 0.01). The difference in the incidence of heterotopic bone formation seems to be due to local factors, in particular the generation of osteogenic reaming debris, which are important in the pathophysiology of heterotopic ossification seen in femoral intramedullary nailing.

Adolescent↗
PubMed1997

An audit of trauma documentation.

Research into aspects of the care of the injured depends on accurate and complete documentation. Inadequate records make audit almost impossible and are unacceptable medico-legally. An audit was made of the standard of trauma documentation in the Yorkshire region before the introduction of trauma charts in 1992. After it was established that a problem did exist, an audit was made of the standard of documentation before and after introduction of trauma charts in one city teaching hospital. Case notes were inspected for completeness of documentation of respiratory, circulatory and neurological status. Results from 1988-1989 showed that only 39.4 per cent of notes recorded the four parameters under investigation. In 1992-1994 the standard had improved. Without trauma charts documentation increased to 90 per cent, but with trauma charts in primary referrals the result improved to 97 per cent. Only 56 per cent of notes were complete for tertiary referrals when a trauma chart was not used. The standard of documentation in major injuries improved with the use of trauma charts. It is recommended that trauma charts are used routinely for all primary and tertiary referrals of injured patients. Tertiary referral patients should be reassessed fully after hospital transfer and a new trauma chart completed.

Blood Pressure↗
PubMed1997

Insulin internalization and other signaling pathways in the pleiotropic effects of insulin.

Insulin is the major anabolic hormone in humans and affects multiple cellular processes. Insulin rapidly regulates short-term effects on carbohydrate, lipid, and protein metabolism and is also a potent growth factor controlling cell proliferation and differentiation. The metabolic and growth-related effects require insulin binding to its receptor and receptor phosphorylation. Evidence suggests these events result in subsequent substrate phosphorylation and activation of multiple signaling pathways involving Src homology domain-containing proteins and the internalization of the insulin:receptor complex. The role of insulin internalization in insulin action is largely speculative. For more than two decades, extensive investigation has been carried out by numerous laboratories of the mechanisms by which insulin causes its pleiotropic responses and the cellular processing of insulin receptors. This chapter reviews our current knowledge of the phosphorylation signaling pathways activated by insulin and presents evidence that substrates other than insulin receptor substrate-1 are involved in insulin's regulation of immediate-early gene expression. We also review the mechanisms involved in insulin internalization and present evidence that internalization may play a key role in insulin action through both signal transduction processes and translocation of insulin to the cell cytoplasm and nucleus.

Animals↗