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Biomedical subjects

M J Smith

Publications and source records attributed to M J Smith.

At least 91 records · Page 5Linked to original sources

Cardiovascular regulation during insulin infusion into the carotid or vertebral artery in dogs.

OBJECTIVE: To test the hypothesis that insulin increases heart rate and arterial pressure via direct effects on the central nervous system. METHODS AND DESIGN: Insulin was infused into the cerebral circulation of conscious dogs (n = 8) chronically instrumented for continuous infusions and measurement of arterial pressure, cardiac output, heart rate and other hemodynamic variables. In acute experiments, insulin was infused for 30 min into either a carotid or vertebral artery at several rates calculated to increase cerebral circulation insulin concentrations to levels in the physiological or pathophysiological range. It was infused with and without a simultaneous glucose infusion. During long-term experiments, insulin was infused into either a carotid or a vertebral artery for 4 days at 0.4 or 0.2 mU/kg per min, respectively. RESULTS: Insulin infusion alone into the cerebral circulation produced no changes in any measured cardiovascular variable. A simultaneous glucose infusion also produced no changes in cardiovascular dynamics, except at the highest rate of infusion into the carotid artery. The changes seen at the highest rate of infusion are unlikely to be insulin-induced, since similar changes occurred when either glucose or saline was infused in the absence of any insulin infusion. Long-term insulin infusion (4 days) into carotid or vertebral arteries also produced no changes in any measured cardiovascular or renal variable. CONCLUSIONS: These results provide no evidence that insulin, at physiological or pathophysiological concentrations, increases heart rate or arterial pressure by acting directly on the central nervous system, and suggest that sympathetic activation and tachycardia previously observed with systemic hyperinsulinemia may be secondary to peripheral actions of insulin.

Animals↗

Tau gene mutation G389R causes a tauopathy with abundant pick body-like inclusions and axonal deposits.

Exonic and intronic mutations in Tau cause familial neurodegenerative syndromes characterized by frontotemporal dementia and dysfunction of multiple cortical and subcortical circuits. Here we describe a G389R mutation in exon 13 of Tau. When 38 years old, the proband presented with progressive aphasia and memory disturbance, followed by apathy, indifference, and hyperphagia. Repeated magnetic resonance imaging showed the dramatic progression of cerebral atrophy. Positron emission tomography revealed marked glucose hypometabolism that was most severe in left frontal, temporal, and parietal cortical regions. Rigidity, pyramidal signs and profound dementia progressed until death at 43 years of age. A paternal uncle, who had died at 43 years of age, had presented with similar symptoms. The proband's brain showed numerous tau-immunoreactive Pick body-like inclusions in the neocortex and the fascia dentata of the hippocampus. In addition, large numbers of tau-positive filamentous inclusions were present in axons in the frontal, temporal, and parietal lobes. Immunoblot analysis of sarkosyl-insoluble tau showed 2 major bands of 60 and 64 kDa. Upon dephosphorylation, these bands resolved into 4 bands consisting of three- and four-repeat tau isoforms. Most isolated tau filaments were straight and resembled filaments found in Alzheimer disease and some frontotemporal dementias with tau mutations. A smaller number of twisted filaments was also observed. Biochemically, recombinant tau proteins with the G389R mutation showed a reduced ability to promote microtubule assembly, suggesting that this may be the primary effect of the mutation. Taken together, the present findings indicate that the G389R mutation in Tau can cause a dementing condition that closely resembles Pick's disease.

Adult↗

Middle range theory: spinning research and practice to create knowledge for the new millennium.

The foundation of middle range theory reported during the past decade was described and analyzed. A CINAHL search revealed 22 middle range theories that met selected criteria. This foundation is a firm base for new millennium theorizing. Recommendations for future theorizing include: clear articulation of theory names and approaches for generating theories; clarification of concept linkages with inclusion of diagrammed models; deliberate attention to research-practice connections of theories; creation of theories in concert with the disciplinary perspective; and, movement of middle range theories to the front lines of nursing research and practice for further analysis, critique, and development.

Humans↗

The Yersinia enterocolitica motility master regulatory operon, flhDC, is required for flagellin production, swimming motility, and swarming motility.

The ability to move over and colonize surface substrata has been linked to the formation of biofilms and to the virulence of some bacterial pathogens. Results from this study show that the gastrointestinal pathogen Yersinia enterocolitica can migrate over and colonize surfaces by swarming motility, a form of cooperative multicellular behavior. Immunoblot analysis and electron microscopy indicated that swarming motility is dependent on the same flagellum organelle that is required for swimming motility, which occurs in fluid environments. Furthermore, motility genes such as flgEF, flgMN, flhBA, and fliA, known to be required for the production of flagella, are essential for swarming motility. To begin to investigate how environmental signals are processed and integrated by Y. enterocolitica to stimulate the production of flagella and regulate these two forms of cell migration, the motility master regulatory operon, flhDC, was cloned. Mutations within flhDC completely abolished swimming motility, swarming motility, and flagellin production. DNA sequence analysis revealed that this locus is similar to motility master regulatory operons of other gram-negative bacteria. Genetic complementation and functional analysis of flhDC indicated that it is required for the production of flagella. When flhDC was expressed from an inducible ptac promoter, flagellin production was shown to be dependent on levels of flhDC expression. Phenotypically, induction of the ptac-flhDC fusion also corresponded to increased levels of both swimming and swarming motility.

Bacterial Proteins↗

Neuroendocrine influences and repercussions of the menopause.

In summary, the evidence that both the ovary and the brain are key pacemakers in the menopause is compelling. Our appreciation that estrogens are important neurotrophic and neuroprotective factors has grown rapidly. Future studies will allow us to better understand the ensemble of factors that interact to maintain regular reproductive cyclicity and how this precise dynamic balance changes with age. Furthermore, understanding how estrogen exerts trophic and protective actions should lead to its use as an important therapeutic agent in the maintenance of normal neural function during aging and after injury.

Aging↗

Fatal fulminant hepatitis associated with bromfenac use.

OBJECTIVE: To report a case of fulminant hepatic failure associated with the use of bromfenac, a new analog of the phenyl acetate class of nonsteroidal antiinflammatory drugs. CASE SUMMARY: A 60-year-old white woman with liver failure who had no known history of chronic liver disease was transferred to the liver transplant unit for evaluation. For three months preceding her illness, the patient was treated with bromfenac 25 mg po qid for arthritic pain. Prior to the initiation of bromfenac, her liver function test results were normal. Etiologic evaluation at presentation was unremarkable. The patient's condition continued to deteriorate, with the development of hepatic encephalopathy and worsening liver function test results while awaiting liver transplantation. Progressive hepatic and renal dysfunction along with respiratory decompensation ensued, and the patient died 48 days after initial presentation. CONCLUSIONS: Fulminant hepatic failure associated with the prolonged use of bromfenac appears to be an idiosyncratic response consistent with experience with other agents of its class. This case along with other cases of serious hepatotoxicity associated with the use of this agent ultimately resulted in bromfenac's removal from the market.

Anti-Inflammatory Agents, Non-Steroidal↗

Work organization, job stress, and work-related musculoskeletal disorders.

Recent studies indicate potential links among work organization, job stress, and work-related musculoskeletal disorders (WRMDs). In this paper we propose several pathways for a theoretical relationship between job stress and WRMDs. These pathways highlight the physiological, psychological, and behavioral reactions to stress that can affect WRMDs directly and indirectly. One model stipulates that psychosocial work factors (e.g., work pressure, lack of control), which can cause stress, might also influence or be related to ergonomic factors such as force, repetition, and posture that have been identified as risk factors for WRMDs. In order to fully understand the etiology of WRMDs, it is important to examine both physical ergonomic and psychosocial work factors simultaneously. Smith and Carayon-Sainfort (1989) have proposed a model of the work system for stress management that provides a useful framework for conceptualizing the work-related factors that contribute to WRMDs. Practical applications of this research include practitioners taking into account psychosocial work factors and job stress in their efforts to reduce and control WRMDs.

Arm↗

Occupational stress in human computer interaction.

There have been a variety of research approaches that have examined the stress issues related to human computer interaction including laboratory studies, cross-sectional surveys, longitudinal case studies and intervention studies. A critical review of these studies indicates that there are important physiological, biochemical, somatic and psychological indicators of stress that are related to work activities where human computer interaction occurs. Many of the stressors of human computer interaction at work are similar to those stressors that have historically been observed in other automated jobs. These include high workload, high work pressure, diminished job control, inadequate employee training to use new technology, monotonous tasks, por supervisory relations, and fear for job security. New stressors have emerged that can be tied primarily to human computer interaction. These include technology breakdowns, technology slowdowns, and electronic performance monitoring. The effects of the stress of human computer interaction in the workplace are increased physiological arousal; somatic complaints, especially of the musculoskeletal system; mood disturbances, particularly anxiety, fear and anger; and diminished quality of working life, such as reduced job satisfaction. Interventions to reduce the stress of computer technology have included improved technology implementation approaches and increased employee participation in implementation. Recommendations for ways to reduce the stress of human computer interaction at work are presented. These include proper ergonomic conditions, increased organizational support, improved job content, proper workload to decrease work pressure, and enhanced opportunities for social support. A model approach to the design of human computer interaction at work that focuses on the system "balance" is proposed.

Boredom↗

Heparin-induced skin necrosis and low molecular weight heparins.

Heparin-induced skin necrosis is a rare but potentially devastating side-effect of low molecular weight heparins. These agents are widely used in surgical practice and doctors prescribing them should be aware of the condition, as failure to recognise it may increase morbidity. An unusually severe case is presented with a review of the literature.

Aged↗

Attentively Embracing Story: a middle-range theory with practice and research implications.

This paper describes the middle-range theory of attentively embracing story. Attentively embracing story is connecting with self-in-relation through intentional dialogue to create ease. The theory emerged in the context of the neomodernist and simultaneity paradigms as the authors shared situations in practice and research and linked these encounters to the story literature. Practice implications with a client who has hypertension and research implications with a pregnant adolescent are presented. The proposed middle-range theory is offered for critical examination by the nursing community as a guide for practice and research aimed at the promotion of human growth and change.

Adaptation, Psychological↗

Tau proteins with FTDP-17 mutations have a reduced ability to promote microtubule assembly.

Recently exonic and intronic mutations in the gene for microtubule-associated protein tau have been discovered in cases of familial frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Intronic mutations have been shown to lead to an abnormal preponderance of four-repeat tau isoforms. The effects of the exonic mutations are unknown. We report here that the G272V, P301L, V337M and R406W mutations lead to a marked reduction in the ability of tau to promote microtubule assembly. This partial loss-of-function may be the primary effect of the known missense mutations in tau.

Amino Acid Substitution↗

Effects of fumonisin B1 on lipid peroxidation in membranes.

Electron spin resonance (ESR)1 spin-label oximetry and spin trapping techniques have been used to study the effect of fumonisin B1 (FB1), an amphipathic mycotoxin on lipid peroxidation in egg yolk phosphatidylcholine (EYPC) bilayers. In the study of the interaction between FB1 and lipid bilayers our results show that fumonisin disturbs the ordering of membranes, enhances oxygen transport in membranes, and also increases membrane permeability. In our model system, lipid peroxidations were initiated by extended incubation of the liposomes, or by inducing Fe2+ ions, UV illumination of H2O2 or ultrasound irradiation. As an indication of the rates of lipid oxidation in EYPC, the consumption of molecular oxygen was studied by monitoring the oxygen concentration in the aqueous phases of the liposomes. Lipid-derived free radicals generated during the oxidation process were measured by a spin trapping method. The incorporation of FB1 in the test samples made the membranes highly susceptible to oxidation. Our results provide the first evidence that the fumonisins appear to increase the rate of oxidation, promote the free radical intermediate production and accelerate the chain reactions associated with lipid peroxidation. The disruption of membrane structure, the enlargement of the relative oxygen diffusion-concentration products, as well as the enhancement effects on membrane permeability, thus provide additional insights into potential mechanisms by which the fumonisins could enhance oxidative stress and cell damage.

Carboxylic Acids↗

Memory impairment and schizophrenia: the role of processing speed.

A link between slowing of processing speed and cognitive disorders, including memory, has repeatedly been found in research on aging, and suggested in other cognitively impaired populations. We tested the hypothesis that a link between memory impairment and slowing of processing speed would also be observed in schizophrenia. Forty-four schizophrenic patients and 40 normal controls were administered a memory task involving free recall and recognition. Processing speed was assessed by the Digit Symbol Substitution Test. Working memory span was assessed as well. The measure of processing speed was consistently correlated with the various memory measures in patients, including efficiency of encoding. These correlations remained significant, or tended to be significant, when working memory span was partialled out. Memory deficits observed in schizophrenia may thus be partly accounted for by a slowing of processing speed. It is suggested that research on cognitive deficits in this and other mental diseases focus more on processing speed.

Adult↗

Functional characterization of L-selectin ligands on human neutrophils and leukemia cell lines: evidence for mucinlike ligand activity distinct from P-selectin glycoprotein ligand-1.

Recent reports have shown that leukocyte-leukocyte adhesion is dependent on L-selectin and that leukocyte recognition of L-selectin may be mediated by P-selectin glycoprotein ligand-1 (PSGL-1). We show that the specific attachment and rolling of human neutrophils and the leukemia cell lines HL-60 and U937 on immobilized, purified L-selectin under continuous shear stress is only partially inhibited by treatment with the PSGL-1 monoclonal antibody (MoAb), KPL1 (41% to 53% inhibition), suggesting that L-selectin ligand activity in addition to PSGL-1 may mediate myeloid cell rolling on L-selectin. K562 cells cotransfected with cDNAs encoding alpha (1,3)fucosyltransferase-VII (FucT-VII) and PSGL-1 rolled on L-selectin. Adhesion of FucT-VII-PSGL-1 transfectants to L-selectin was completely blocked by MoAb KPL1, indicating that both L-selectin and P-selectin bind similar sites on PSGL-1. In support of existence of a non-PSGL-1 L-selectin ligand activity on leukocytes, an HL-60 membrane preparation immunodepleted of PSGL-1 supported rolling of L-selectin, but not P-selectin transfectants. Treatment of HL-60 cells with O-sialoglycoprotein endopeptidase inhibited attachment and rolling on L-selectin and P-selectin. However, neuraminidase treatment completely blocked HL-60 rolling on L-selectin, but not P-selectin, suggesting L-selectin and P-selectin ligand activities have different contributions of sialic acid. These findings indicate that myeloid cells express sialylated, O-linked glycoprotein ligand activity independent of PSGL-1 that supports L-selectin-mediated rolling.

Antibodies, Monoclonal↗

An equation to QA check the total treatment time for single-catheter HDR brachytherapy.

PURPOSE: To develop a simple equation that can be used to quickly QA check the total treatment time needed for straight or moderately bending, single-catheter implants from the treatment length and dose-prescription depth. A method to quickly check the total treatment time is useful for high dose rate (HDR) treatments, but may be most useful for intravascular patients that are catheterized while planning the treatment. METHODS AND MATERIALS: Nucletron-Oldelft treatment planning software was used to plan treatments with treatment lengths from 50 to 200 mm, and dose-prescription depths from 2 to 14 mm. For each plan, dose points were defined at a fixed depth away from the catheter. Doses were calculated, normalized, and optimized using the dose points. From these plans, a single equation was developed for the total treatment time as a function of treatment length and dose-prescription depth. RESULTS: Total treatment time increases linearly with treatment length and supra-linearly with dose-prescription depth. A difference of 3% or more between the treatment time determined by the QA check equation and by the treatment planning software will alert the clinician and physicist to check for potential errors in dose prescription, prescription depth, source activity, treatment length, or inadvertent modifications to physics parameters used in the treatment planning software. CONCLUSION: The simple equation that is developed can be used to quickly and accurately QA check the total treatment time needed for straight or moderately bending, single-catheter implants.

Brachytherapy↗

Peptides that mimic the group B streptococcal type III capsular polysaccharide antigen.

Microbial polysaccharides are notably poor immunogens. We have developed an alternate route for the production of Abs to important carbohydrate epitopes. mAb S9, a protective mAb against the type III capsular polysaccharide of group B streptococci (GBS), was used to select epitope analogues from a peptide display phage library. Depending upon desorption conditions, two populations of phage were identified with displayed sequences of WENWMMGNA and FDTGAFDPDWPA. ELISA results demonstrated that these phage bound to S9 and no other Abs. Phage blocked the binding of S9 to type III GBS, but did not block binding by another anti-GBS mAb. Phage displaying the latter peptide sequence showed greater inhibition. Ab S9 and other monoclonal and polyclonal anti-GBS type III antisera bound the synthetic peptide FDTGAFDPDWPAC. The binding of S9 to GBS was inhibited by the free peptide with an IC50 of 30 microg/ml. The binding of polyclonal anti-GBS antibodies to peptide could be blocked by intact GBS as well as purified capsular polysaccharide. The peptide was conjugated to three different carriers and was used to immunize mice. All mice produced a significant antibody response to GBS and to the purified capsular polysaccharide following a single immunization. These data demonstrate that a peptide mimetic of the GBS capsular polysaccharide is both antigenic and immunogenic. The incorporation of such peptides into vaccine preparations may enhance the efficacy of vaccines in inducing Ab responses to important carbohydrate epitopes.

Amino Acid Sequence↗

Comparison of self-reported and expert-observed physical activities at work in a general population.

Concerns about exposure assessment quality have impeded research to identify risk factors for ergonomic disorders. We compared self-reported and expert-observed estimates of work-related physical factors for participants in a study of carpal tunnel syndrome (CTS). We analyzed data from 61 subjects, including 28 CTS cases and 33 controls randomly samples from a case-control study with 417 participants. For 11 posture and manual materials handling factors, the median difference in mean exposure between self-reported and expert-observed exposure at work was less than 1/2 hour a day. Measurements by the two methods in this study agreed more often than expected by chance (median kappa 0.31 in cases and 0.28 in controls). Kappa differed significantly by case-control status for two factors: bending at the waist (kappa 0.79 in cases versus 0.28 in controls, P = 0.01) and twisting of the forearm (kappa 0.45 in cases versus -0.02 in controls, P = 0.02). Although imperfect, exposure information collected from workers' self-reports is useful for many ergonomic epidemiology studies.

Adult↗