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Biomedical subjects

S M Smith

Publications and source records attributed to S M Smith.

At least 199 records · Page 11Linked to original sources

Horseback riding injuries among children and young adults.

BACKGROUND: Horseback riding injuries are responsible for an estimated 2300 hospital admissions annually among persons younger than 25 years of age in the United States, but injury rates, patterns of injury, and risk factors for this population have not been well studied. METHODS: Study participants were selected from a list provided by a national mail-order company that sells riding equipment. A total of 557 persons younger than 25 years of age who rode horses at least six times a year completed survey questionnaires. RESULTS: Among the study participants, 34 (6.1%) had been hospitalized at least once because of a riding injury and 153 (27.5%) had been treated by a physician within the previous 2 years for such an injury. The overall injury rate was 0.6 per 1000 riding hours. Among those injured, sprains or strains (41.8%), lacerations or bruises (40.0%), and fractures or dislocations (33.3%) were the most common types of injury. A total of 27.5% of those injured sustained concussions or other head injuries. Riding 15 to 24 hours per month (odds ratio [OR] = 2.04), being female (OR = 1.81), and riding English style (OR = 1.77) were the characteristics most strongly correlated with injury. CONCLUSIONS: Horseback riding injuries among participants in this study tended to be serious. Family physicians should inform their patients who ride horses about the risks associated with equestrian activities and should emphasize helmet use.

Adolescent↗

Sensitivity of multiple-cause mortality data for surveillance of deaths associated with head or neck injuries.

PROBLEM/CONDITION: Multiple-cause mortality data was assessed as a source of information for surveillance of deaths associated with head or neck injuries. REPORTING PERIOD COVERED: 1985-1986 DESCRIPTION OF SYSTEM: Data on causes of death were abstracted from death certificates in New Mexico and coded according to criteria of the International Classification of Diseases, Ninth Revision (ICD-9). Deaths with an external cause-of-death (E) code as the underlying cause of death and one or more head or neck injury nature-of-condition (N) codes as contributing causes of death were considered head or neck injury deaths. These data were compared with data for head or neck injury deaths obtained from computerized records from the New Mexico Office of the Medical Investigator (OMI). Data for alcohol or drug use were abstracted from both systems. RESULTS: Of the 699 head or neck injury deaths coded by the New Mexico OMI system in 1985-1986, 536 were identified as head or neck injury deaths in multiple-cause mortality data (sensitivity = 76.7%). Firearms were the leading cause of head or neck injury deaths, followed by motor vehicles. Multiple-cause mortality data contained alcohol codes for only 3.7% of OMI records with blood alcohol concentrations > or = 0.10 mg/dL and contained drug codes for none of the OMI records with positive toxicology tests for drugs. INTERPRETATION: The sensitivity of multiple-cause mortality data was relatively high for surveillance of head and neck injury deaths.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidental Falls↗

Inhibitory role for calcineurin in stimulus-secretion coupling revealed by FK506 and cyclosporin A in pituitary corticotrope tumor cells.

The properties of the calcium/calmodulin-dependent protein phosphatase calcineurin and its potential role in stimulus-secretion coupling were examined in AtT20 mouse pituitary corticotrope tumor cells. Protein phosphatase activity was assayed by measuring the liberation of 32P from 32P-casein, adrenocorticotropin secretion was measured by radioimmunoassay. About 60% of the total phosphatase activity was inhibited by 500 nM okadaic acid, suggesting the presence of protein phosphatases 1 and/or 2A. A further 25-30% reduction of phosphatase activity was achieved by chelating free calcium. Addition of the EF-hand protein blocker trifluoperazine or a calcineurin autoinhibitory peptide fragment markedly reduced okadaic acid resistant and calcium-dependent protein phosphatase activity indicating that calcium-dependent 32P release is largely due to calcineurin (protein phosphatase 2B). The remaining 10-15% of total activity was Mg2+ dependent and blocked by NaF, hence possibly due to protein phosphatase 2C. Calcineurin activity was inhibited by the immunosuppressants FK506 and cyclosporin A, either when added to the cell lysates or after preincubation of intact cells with the drugs for 30 min at 37 degrees C. When added to lysates, cyclosporin A inhibited calcium/calmodulin-dependent phosphatase more effectively than FK506. However, when tested on intact cells, FK506 proved 10-fold more potent than cyclosporin A. Both immunosuppressive agents enhanced the calcium-dependent release of adrenocorticotropic hormone into the medium, once more, FK506 was 10-fold more potent than cyclosporin A. Taken together, these data suggest that calcineurin is an inhibitory element in the signal transduction pathway controlling exocytotic secretion in pituitary cells that express voltage-operated calcium channels. This is in direct contrast with leukocytes where voltage-operated calcium channels are not found, and calcineurin is an important element for agonist-induced activation.

Adrenocorticotropic Hormone↗

Identification of potent mixed leukocyte reaction-stimulatory cells in human bone marrow. Putative differentiation stage of human blood dendritic cells.

Dendritic cells (DC) have been isolated from blood, lymphoid tissue, and other tissues, as potential members of a hemopoietic lineage of specialist APC for naive T lymphocyte activation. To define human bone marrow (BM) DC we have attempted to identify allostimulatory cells with DC-like characteristics among human BM mononuclear cells (BMMC) by FACS cell sorting and immunophenotyping, monitoring the APC function of different cell lineages in the human primary MLR. We show that fresh human BM stimulates allogeneic T lymphocytes with an activity equal to or greater than that of peripheral blood. As with DC from other tissue sources, the most potent stimulatory activity was found in the low density BMMC, and these cells, like peripheral blood, stimulated a maximal allogeneic MLR response at days 5 to 6. FACS purification of the allostimulatory population in fresh human BMMC was undertaken by using a wide range of mAb directed against lineage-associated molecules of mature and immature lymphoid, erythroid, and myeloid cells. The most potent constitutive BMMC stimulatory activity was located in the CD3-, CD11b-, CD14-, CD15-, CD16-, CD19-, CD57-, and glycophorin A- population. A mixture of antibodies to these Ag was used to isolate a "mix-negative" BMMC population, which contained the most highly potent MLR-stimulatory cells. Further cytologic and immunophenotypic analysis of this population revealed an enriched population of HLA-DP+, HLA-DQ+, HLA-DR+, and CD45+ cells, with morphologic similarities to the human tonsil and blood DC. These cells were CD4- and CD1a- and were weakly CD33+ (but CD15-), suggesting a possible early myeloid origin distinct from both the committed granulocytic and monocytic lineages. In addition, they lacked both CD10 and CD20, making a lymphoid origin unlikely. Further identification of these putative DC precursors will allow analysis of the early phases of DC hemopoiesis, whereas the characterization of the MLR-stimulatory cells in human BM will be of major importance in the understanding of BM transplant failure and graft-vs-host disease.

Animals↗

Disproportionating enzyme (4-alpha-glucanotransferase; EC 2.4.1.25) of potato. Purification, molecular cloning, and potential role in starch metabolism.

Disproportionating enzyme (D-enzyme, 4-alpha-glucanotransferase; EC 2.4.1.25) has been purified to homogeneity from potato tubers and its activity characterized. The enzyme catalyzes the transfer of maltooligosaccharides from one 1,4-alpha-D-glucan molecule to another, or to glucose. Maltooligosaccharides are effective donor molecules, but short chain amylose and amylopectin may also function as donors. Enzyme activity is not affected by inorganic phosphate, 3-phosphoglycerate, or hexose phosphates. A cDNA clone encoding the enzyme was isolated using oligonucleotide probes derived from partial peptide sequences of the purified enzyme. The identity of the cDNA clone was confirmed by expression in Escherichia coli resulting in D-enzyme activity. The amino acid sequence deduced from the cDNA shows significant homology with a 4-alpha-glucanotransferase from Streptococcus. The deduced sequence indicates the presence of an amino-terminal plastid transit peptide of 52 amino acid residues and a mature polypeptide of 524 residues. D-enzyme mRNA is present in leaves, stems, roots, and stolons but is most abundant in developing and mature tubers. The amount of mRNA in leaves increases in response to light and to sucrose added to the medium. These results are discussed in terms of the function of D-enzyme in potato starch metabolism.

Amino Acid Sequence↗

Scanning electrochemical microscopy of metallic biomaterials: reaction rate and ion release imaging modes.

The Scanning Electrochemical Microscope (SECM) is a nonoptical scanning microscopic instrument capable of imaging highly localized electrical currents associated with charge transfer reactions on metallic biomaterials surfaces. The SECM operates as an aqueous electrochemical cell under bipotentiostatic control with a microelectrode and sample independently biased as working electrodes. Microelectrode current and position is recorded as it is scanned very near a metallurgically polished planar sample surface. To date, the SECM has imaged metallic biomaterials surfaces in oxygen reaction rate imaging (ORRI) and ion release and deposition imaging (IRDI) modes. In ORRI, sample and microelectrode are biased at sufficiently negative potentials to reduce absorbed oxygen. As the microelectrode scans areas of active oxygen reduction, localized diffusion fields with decreased oxygen solution concentrations are encountered and resultant decrements in microelectrode current are observed. In IRDI mode the sample is positively biased and the microelectrode is negatively biased. The microelectrode detects anodic dissolution products with highest currents being observed over the most active areas. Performance of the SECM has been evaluated on Ni minigrids, gamma-1 Hg-Ag dental amalgam crystals, and sintered beads of Co-Cr-Mo alloy which represent significantly different geometries and corrosion processes to help demonstrate the potential of this instrument. The SECM is a valuable tool for imaging microelectrochemical processes on the surfaces of metallurgically polished metallic biomaterials samples and a wide variety of other surfaces of biological interest where charge transfer reactions occur. The SECM allows selective biasing of metallic biomaterials surfaces and Faradaic reactions can be selectively imaged while the surface is in the active, passive, or transpassive state.

Biocompatible Materials↗

In vitro hepatic thyroid hormone deiodination in iron-deficient rats: effect of dietary fat.

The effects of different dietary fats on thyroid indices were studied in weanling iron-deficient rats. Rats were fed one of five different diets (safflower oil with a casein protein source, safflower oil with defatted beef as the protein source, prime rib, beef tallow with casein and stearate with casein). Both dietary fat and iron status (adequate, CN; deficient, ID; or iron-deficient replete, ID-replete) had significant effects on body weight and hemoglobin concentrations. The tallow-fed animals weighed the least relative to animals fed the other fats; ID rats were smaller than CN rats. The tallow- and stearate-fed animals had the highest hemoglobin concentrations. Type of dietary fat affected plasma thyroxine (T4), but not plasma triiodothyronine (T3) or rate of deiodination of reverse T3 (rT3). Iron deficiency decreased plasma concentrations of T3 and T4 and increased in vitro hepatic rT3 deiodination, suggesting that the ID animals tend to metabolize thyroid hormones via deactivating pathways. The alterations in thyroid hormone metabolism associated with iron deficiency are reversible with iron repletion.

Animals↗

Mesangial proliferative glomerulonephritis in southwestern American Indians.

A series of 166 American Indian renal biopsy specimens from 1971 to 1989 showed a very high proportion with mesangial proliferative glomerulonephritis with mesangial immunoglobulin deposition (Ig-pos mesGN). This disease comprised 68.7% of all the biopsies and 83.8% of all primary GN, proportions much greater than those (23.5% and 37.7%, respectively) of a local contemporaneous biopsy series from non-Indians (P < 0.001). These proportions and the extrapolated population-based incidence rates of mesGN are the highest yet described in any population. Males and females were equally represented in the Indian Ig-pos mesGN series. Biopsy was most commonly performed in early adulthood, but duration of suspected disease prior to biopsy was often many years. Mesangial glomerulonephritis often occurred in family clusters. It was occasionally associated with rashes, arthralgias, and/or a history of alcohol abuse. Due to different surveillance and biopsy practices, the spectrum of severity was different in Zunis and Navajos, allowing examination of clinicopathologic correlations over a broad range of disease. Early disease was manifest by microscopic hematuria alone, but rates of severe disease, with hypertension, heavy proteinuria, and renal insufficiency, were very high. Clinical severity increased with age, with extension of pathology beyond the mesangium, and with scarring and vascular change. Changing patterns of deposition of mesangial immunoglobulin and of electron-dense deposits in sequential biopsy specimens, recurrence of disease in kidney transplants, and biopsy diagnosis of disease in asymptomatic relatives of afflicted subjects were all observed. Five-year renal failure rates were estimated at 41%, much higher than in most other series. This disease constituted most biopsied cases of GN-end stage renal disease in Navajos, and largely determined the young age of Navajo GN-end stage renal disease subjects compared with their US-wide counterparts. To reconcile the diversity of clinical and morphologic findings in such homogeneous ethnic groups, and in individual families within such groups, we propose a unifying hypothesis for a broader spectrum of mesGN than traditionally defined by immunoglobulin subtype deposition. We also argue against a major role for IgA aggregates or immune complexes in initiating or propagating the mesangial inflammatory process, and propose that mesangial pathology of another, independent cause might be primary. Hyperinsulinemia, or insulin resistance, which is common in these populations and in other transitional populations with similar GN and ESRD patterns, might be one such mesangiopathic factor.

Adolescent↗

Aortic aneurysm leak after streptokinase treatment for myocardial infarction.

A leak from an abdominal aortic aneurysm following the administration of streptokinase treatment for myocardial infarction is reported. It is important to assess candidates for cardiac thrombolytic therapy for aortic pathology and give such treatment with extreme caution in those patients with abdominal aortic aneurysms.

Aortic Aneurysm, Abdominal↗

Characterisation and distribution of inositol polyphosphate and Ryanodine receptors in the rat brain.

The regional distribution of inositol 1,4,5-trisphosphate (InsP3), inositol 1,3,4,5-tetrakisphosphate (InsP4), and ryanodine binding sites has been characterised and compared in the rat brain using radioligand binding assays. Cortical [3H]InsP3 binding indicated similar positional and stereospecificity as observed in other tissues, with 100-fold selectivity for InsP3 over InsP4. Similarly, high-affinity [32P]InsP4 binding also showed a high degree of positional specificity, with a 1,000-fold selectivity for InsP4 over InsP3. Initial characterisation of [3H]ryanodine binding to cortical membranes demonstrated that specific binding was highly dependent on high salt and micromolar Ca2+ concentrations and inhibited by Ca2+ levels of > 1 mM. [3H]-Ryanodine binding was also enhanced by beta, gamma-methylene-adenosine 5'-trisphosphate and caffeine and inhibited by magnesium and ruthenium red (Ki = 0.81 microM). However, dantrolene (300 microM) was ineffective on the binding. Therefore, although the results indicate a greater similarity to the binding properties of the Ca(2+)-induced Ca2+ release channel isoform present in skeletal, rather than cardiac, muscle, it does not appear to be identical. Detailed binding analysis of ryanodine and polyphosphate sites, with the exception of ruthenium red, indicated no interaction between binding sites. Ruthenium red markedly enhanced the binding of both [3H]InsP3 and [32P]InsP4, an effect most probably due to nonspecific complex formation. Regional binding of InP3, InsP4, and ryanodine in the rat brain was of similar affinity for each ligand in each area, but the density profile for each ligand was clearly different. The highest density of InsP3 sites was in the cerebellum, whereas the highest density of ryanodine sites was in the hippocampus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Increased natural killer cell activity in a model of immunoglobulin A nephropathy secondary to chronic alcohol consumption.

We investigated natural killer (NK) cell activity in an animal model of ethanol-induced immunoglobulin A (IgA) nephropathy. Two groups, of 10 rats each, received a continuous intragastric infusion of liquid diet through a permanent cannula for 6 weeks. The alcoholic group was infused additionally with intragastric ethanol, representing from 32% to 40% of the caloric requirement. The group of control rats received an isocaloric diet supplemented with glucose instead of alcohol. IgA nephropathy was observed in all the alcoholic rats but in none of the controls. NK cell activity was investigated in the two groups by measuring the cytotoxicity of spleen cells using the chromium release method. NK cell activity was found to be significantly increased in the alcoholic rats. In view of the known modulation of IgA synthesis by NK cells, we suggest that increased NK cell activity may be a contributing factor to the high levels of circulating IgA seen in IgA nephropathy secondary to chronic alcohol consumption.

Alcoholism↗

Is the left main angulated, stenosed, or "bent" by the guiding catheter?

Exact angiographic and identification of significant stenosis of the left main coronary artery is imperative prior to performing elective percutaneous transluminal coronary angioplasty. A patient is presented with an apparent angiographically significant, but physiologically insignificant, left main stenosis. Both angiographic and physiological methods of detecting "false positive and negative" left main stenoses are discussed.

Aged↗

Heparin inhibits the immediate response to antigen in the skin and lungs of allergic subjects.

Although heparin is used as an anticoagulant, its biologic function remains unclear. Substantial evidence exists that suggests it may modulate many aspects of immune function and inflammation. We demonstrated, in a double-blind, placebo-controlled, crossover study involving 10 allergic subjects, that a small dose of heparin (25 U/kg) administered intravenously 10 min before challenge reduced the acute cutaneous reaction to 10 allergens and histamine from a group-average sum of mean (+/- SD) wheal diameters at a baseline of 29.9 +/- 10 mm and after normal saline placebo (29.5 +/- 10.7 mm) to after heparin (14.4 +/- 10.4 mm) (p < 0.02, Wilcoxon's signed rank test). In 15 subjects with asthma and dust mite allergy, nebulized heparin 20,000 units administered in a double-blind, placebo-controlled, crossover fashion 10 min before challenge inhibited the bronchospasm induced by inhaled dust mite extract. Log2 of the provocative dose of mite extract causing a 20% fall in FEV1 at baseline was 4.1 +/- 1.5 protein nitrogen units (PNU); after normal saline it was 4.5 +/- 2.0 PNU, and after heparin it was 5.1 +/- 2.5 PNU (p = 0.04). These data suggest heparin may have an inhibitory role in acute mast-cell-mediated allergic inflammation.

Adult↗

Constraining effects of examples in a creative generation task.

In three experiments we tested the conformity hypothesis--that subjects' ideas would conform to examples they had been shown--by using a creative generation paradigm in which subjects imagined and sketched new exemplars of experimenter-defined categories. Designs made by subjects who had first seen three examples of ideas were compared with those of control subjects, who received no examples. In all three experiments, the designs of subjects who had seen the examples were more likely to contain features of the examples. This conformity effect did not significantly decrease in Experiment 2, when a 23-min task was interpolated between viewing the examples and generating related ideas. The hypothesis that the observed conformity effects may have been caused by subjects' assumptions that they should try to generate ideas similar to the examples was refuted in Experiment 3; explicitly instructing subjects to create ideas that were very different from the examples did not decrease conformity to the examples, and instructing them to conform to the examples significantly increased conformity. The results show that recent experience can lead to unintentional conformity, constraining the generation of creative ideas.

Adolescent↗