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Biomedical subjects

R Michaels

Publications and source records attributed to R Michaels.

At least 37 records · Page 2Linked to original sources

Characterization of two evolutionarily conserved, alternatively spliced nuclear phosphoproteins, NFAR-1 and -2, that function in mRNA processing and interact with the double-stranded RNA-dependent protein kinase, PKR.

We report here the isolation and characterization of two proteins, NFAR-1 and -2, which were isolated through their ability to interact with the dsRNA-dependent protein kinase, PKR. The NFAR proteins, of 90 and 110 kDa, are derived from a single gene through alternative splicing and are evolutionarily conserved nuclear phosphoproteins that interact with double-stranded RNA. Both NFAR-1 and -2 are phosphorylated by PKR, reciprocally co-immunoprecipitate with PKR, and colocalize with the kinase in a diffuse nuclear pattern within the cell. Transfection studies indicate that the NFARs regulate gene expression at the level of transcription, probably during the processing of pre-mRNAs, an activity that was increased in fibroblasts lacking PKR. Subsequent functional analyses indicated that amino acids important for NFAR's activity were localized to the C terminus of the protein, a region that was found to specifically interact with FUS and SMN, proteins also known as regulators of RNA processing. Accordingly, both NFARs were found to associate with both pre-mRNAs and spliced mRNAs in post-transcriptional studies, similar to the known splicing factor ASF/SF-2. Collectively, our data indicate that the NFARs may facilitate double-stranded RNA-regulated gene expression at the level of post-transcription and possibly contribute to host defense-related mechanisms in the cell.

Alternative Splicing↗

Dynamics of the 16O(e, e'p) reaction at high missing energies.

We measured the cross section and response functions for the quasielastic 16O(e,e'p) reaction for missing energies 25< or =E(m)< or =120 MeV at missing momenta P(m)< or =340 MeV/c. For 25<E(m)<50 MeV and P(m) approximately 60 MeV/c, the reaction is dominated by a single 1s(1/2) proton knockout. At larger P(m), the single-particle aspects are increasingly masked by more complicated processes. Calculations which include pion exchange currents, isobar currents, and short-range correlations account for the shape and the transversity, but for only half of the magnitude of the measured cross section.

Journal Article↗

Polarization measurements in high-energy deuteron photodisintegration.

We present measurements of the recoil proton polarization for the d(gamma-->,p-->)n reaction at straight theta(c.m.) = 90 degrees for photon energies up to 2.4 GeV. These are the first data in this reaction for polarization transfer with circularly polarized photons. The induced polarization p(y) vanishes above 1 GeV, contrary to meson-baryon model expectations, in which resonances lead to large polarizations. However, the polarization transfer Cx does not vanish above 1 GeV, inconsistent with hadron helicity conservation. Thus, we show that the scaling behavior observed in the d(gamma,p)n cross sections is not a result of perturbative QCD. These data should provide important tests of new nonperturbative calculations in the intermediate energy regime.

Journal Article↗

Characteristics of odorant elicited calcium changes in cultured human olfactory neurons.

An important step in establishing and utilizing a cell culture system for the in vitro study of olfaction is assessing whether the cultured cells possess physiological properties similar to those of mature olfactory neurons. Various investigators have successfully established proliferating cell lines from olfactory tissue, but few have demonstrated the characteristics of odor sensitivity of these cells. We successfully established cultured cell lines from adult human olfactory tissue obtained using an olfactory biopsy procedure and measured their ability to respond to odor stimulation using calcium imaging techniques. A subset of the human olfactory cells in culture displayed a distinct morphology and specifically expressed immunocytochemical markers characteristic of mature human olfactory neurons such as OMP, G(olf), NCAM and NST. Under defined growth conditions, these cultured cells responded to odorant mixes that have been previously shown to elicit intracellular calcium changes in acutely-isolated human olfactory neurons. These odorant-elicited calcium responses displayed characteristics similar to those found in mature human olfactory neurons. First, cultured cells responded with either increases or decreases in intracellular calcium. Second, increases in calcium were abolished by removal of extracellular calcium. Third, inhibitors of the olfactory signal transduction cascades reversibly blocked these odorant-elicited intracellular calcium changes. Our results demonstrate that cultures of adult human olfactory cells established from olfactory biopsies retain some of the in vivo odorant response characteristics of acutely isolated cells from the adult olfactory epithelium. This work has important ramifications for investigation of olfactory function and dysfunction using biopsy procedures and in vitro assays of odor sensitivity.

Biopsy↗

Negative-pressure pulmonary edema: a complication of shoulder arthroscopy.

Negative-pressure pulmonary edema has been increasingly reported in surgical literature since 1977, yet there are no references to this condition in current orthopedic textbooks. We report a case of negative-pressure pulmonary edema occurring during arthroscopic surgery of the shoulder. The patient required reintubation for 5 days and hospitalization for 1 week. Because arthroscopic surgery is widely believed to be without complications, we want to make orthopedic surgeons aware of the possibility of negative-pressure pulmonary edema.

Adult↗

Activation of mechanical responses in leukocytes.

Different kinds of leukocytes undergo cytoskeleton-dependent mechanical responses associated with their specific physiological functions. We have investigated cellular stiffening of several types of leukocytes using a method which measures the force resisting cellular indentation. We have found that lymphocytes stiffen in response to crosslinking cell surface antigens in a process associated with the much studied capping and patching processes. Further studies of myosin-deficient mutants of the ameba Dictyostelium discoideum suggest that this stiffening process results from a myosin dependent contractile process. Rat basophilic leukemia cells and pancreatic islet cells stiffen when triggered to secrete. The function of these cytoskeleton dependent processes is now unknown, but, at least in the islet cells, may be related to a regulation of the rate of secretion. Primary neutrophils stiffen in response to the chemotactic agent, fMet-Leu-Phe. This stiffening may be responsible for retention of these cells in the pulmonary microcirculation during response to inflammation. These observations pose the challenge of determining the structural basis, mechanism, and physiological function of each of these cellular responses.

Animals↗

Selective defect in the antibody response to Haemophilus influenzae type b in children with recurrent infections and normal serum IgG subclass levels.

We studied 15 children with recurrent infections and normal serum IgG, IgM, IgA, and IgG-subclass levels. After immunization, the geometric mean serum IgG antibody concentration to Haemophilus influenzae type b (Hib) was eightfold lower than that of age-matched control subjects (p = 0.002). The patients also had a lower geometric mean concentration of serum IgM and IgA directed to Hib, although these differences did not reach significance. However, the groups did not differ in their response to diphtheria toxoid and pneumococcal polysaccharides. To confirm these findings, an additional 11 patients were identified and immunized. The geometric mean serum IgG anti-Hib concentration for this group of patients was also significantly lower than of normal subjects (p = 0.004). We propose that the defect in the antibody response to Hib may be a marker for a poor antibody response to a variety of bacterial and viral antigens that results in an increased propensity to recurrent infections. The defect was not associated with IgG-subclass deficiency. The identification of children with selective antibody deficiency and recurrent infections is important for diagnostic and therapeutic reasons.

Adolescent↗

Electrophysiological measures of regional neural interactive coupling. Linear and non-linear dependence relationships among multiple channel electroencephalographic recordings.

Linear spectral coherence (Sklar et al., 1973) measures have been used in the neurosciences to test hypotheses which address the question of whether multiple EEG recording sites are independent or whether they are activated by common sources of neurophysiological activity. This measure is appropriate when regional neural sources interact and thereby electrically activate several recording sites through linear transmission pathways which may or may not be different in their linear transformation properties. However, if the transmission media are non-linear, then interactive dependency is not necessarily revealed by a linear coherence test. Therefore, if common sources are activating EEG recording sites through nonlinear media, evaluating the resulting relationships among the signals recorded from these sites requires a test which reveals the presence of such nonlinear relationships. In neurophysiological applications, a polycoherence cross-spectral measure provides such a test for nonlinear dependency (similar to the linear coherence test) among EEG recording sites. The data requirements and statistical properties of these linear and non-linear measures are described and results of a linear coherence analysis are presented in the context of an EEG pilot study of learning-disabled children.

Biometry↗

Efficacy of topical antibiotic therapy in acute conjunctivitis in children.

We studied 102 children aged 1 month to 18 years in a randomized, double-blind trial designed to determine both the natural history of bacterial conjunctivitis and whether topical antibiotic therapy is beneficial. Affected eyes were treated four times a day for 7 days with drug (polymyxin-bacitracin ophthalmic ointment) or placebo. Eighty-four patients had proved bacterial conjunctivitis (Haemophilus influenzae 61, Streptococcus pneumoniae 22, both one); 66 of these received only topical therapy. By 3 to 5 days, 21 of 34 (62%) patients receiving topical antibiotic were clinically cured, whereas only nine of 32 (28%) patients given placebo were cured (P less than 0.02). By 8 to 10 days, 31 (91%) of the patients given antibiotic and 23 (72%) of the placebo group were cured (P = NS). The bacterial pathogen was eradicated by day 3 to 5 in 71% and by day 8 to 10 in 79% of patients given antibiotic, compared to 19% and 31% of the placebo group (P less than 0.001). Acute bacterial conjunctivitis is a self-limited disease, but topical antibiotic therapy with polymyxin-bacitracin shortens the duration of clinical disease and enhances eradication of the causative organism from the conjunctiva.

Acute Disease↗

Epidemiologic features of Reye syndrome seen in southwestern Pennsylvania 1970-80.

In 11 years of surveillance in southwestern Pennsylvania there were 97 cases of Reye syndrome. Peak incidence was in February and March, corresponding to periods of influenza A and B activity. Mean age of cases was 7.9 years; 57 per cent were female. Case fatality declined from 55 per cent in 1970-75 to 16 per cent in 1976-80 (p less than .001). Influenza was associated with 45 per cent of cases, varicella 19 per cent; the remaining 36 per cent of cases did not occur during periods of influenza activity. Reye syndrome occurred significantly more frequently in suburban and rural areas than in central city (p less than .01), more frequently among White persons than Blacks (p less than .01), and more frequently in counties where the total population under 17 years was less than 25,000 (p less than .01).

Adolescent↗

Elastic recoil of the lung in cigarette smokers: the effect of nebulized bronchodilator and cessation of smoking.

The mechanical properties of the lung, forced vital capacity, flow-volume relationships, lung volume, and single-breath N2 curve were determined in 16 nonsmokers and 19 smokers. Pulmonary elastic recoil, Pst (1), was significantly lower at all lung volumes, as were flow parameters, whereas lung volumes were higher in smokers of both sexes. The variables derived from forced vital capacity and single-breath N2 were significantly different from nonsmokers in male smokers but not in female smokers. The inhalation of nebulized bronchodilator was attended by a significant decrease in Pst (1) and in upstream flow resistance in smokers. After cessation of smoking Pst (1) decreased to values similar to those seen after bronchodilator administration, whereas resumption of smoking led to reversal of the pressure-volume curve. The data suggest that the elastic properties of the lungs are altered in cigarette smokers, but the extent of the disturbance is masked by constriction of the alveolar ducts or peripheral airways while smoking, and that these are unmasked by the administration of nebulized bronchodilator or by cessation of smoking.

Adult↗