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Biomedical subjects

W A Smith

Publications and source records attributed to W A Smith.

At least 55 records · Page 3Linked to original sources
PubMed1992

Molecular polymorphisms of house dust mite allergens.

Previous studies from this laboratory have described the primary amino acid sequences of the group I and group II allergens from Dermatophagoides pteronyssinus and D. farinae. This report concentrates on polymorphisms of allergens within a species. Firstly, four cDNA clones of Der fII produced by polymerase chain reaction have been sequenced and are compared to the sequences published previously by ourselves and others. Although the sequences come from different sources, Australia and Japan, the overriding conclusion is one of similarity, with only two possible non-conservative changes in the six sequences. The nucleotides were also very conserved including the 3' untranslated regions, although some non-coding differences could be found which may provide a genetic marker. Experiments are reported to help define the group III D. pteronyssinus allergens. Previous studies have characterised the group III of D. farinae as a Mr 29-kDa molecule which can be defined by monoclonal antibodies. A Mr 17-kDa molecule of D. pteronyssinus has been reported with an almost identical N-terminal sequence. Here it is described that Der fIII isolated from different preparations of spent mite media by affinity chromatography have predominantly Mr 32-, 28- and 21-kDa forms which vary in degree from batch to batch. 83% of adults and 38% of children react with the preparation by radioimmune dot-blot. The difference between the children and adults is statistically significant and reactivity can be to at least the 32- and 28-kDa form. Antisera produced in mice against the Der fIII react to D. pteronyssinus mite extract by Western blotting primarily to a 32-kDa moiety, but also 28- and 21-kDa forms in some extracts.

Allergens↗
PubMed1992

Tolerance to imidazolinone herbicides in wheat.

An imidazolinone-tolerant wheat (Triticum aestivum L. em Thell) mutant in the winter wheat cultivar Fidel has been identified and characterized. The mutant was isolated from a population derived through seed mutagenesis of the variety with an aqueous solution containing sodium azide. Imidazolinone-tolerant wheat seedlings were selected from the M(2) generation of the population in the presence of imazethapyr herbicide and identified as herbicide-insensitive individuals. The trait is inherited as a single semidominant gene and confers high levels of tolerance to imazethapyr. Acetohydroxyacid synthase activity in extracts from imidazolinonetolerant plants was less inhibited by imazethapyr than the enzyme from the wild type. The herbicide-tolerant plants have a completely normal phenotype and display no negative effects on growth and yield in either the absence or presence of imazethapyr.

Journal Article↗
PubMed1992

Chemical hepatitis associated with occupational exposure to halothane in a research laboratory.

We report a case of clinical hepatitis associated with occupational exposure to halothane in a research laboratory. A biochemist who for 3 y repeatedly used halothane for sedation and euthanization of rats suffered recurrent episodes of epigastric discomfort, culminating in an episode of malaise, anorexia, jaundice and elevated liver associated enzymes that promptly resolved after removal from exposure to halothane. Serologic testing for viral sources and risk factors for non-infectious hepatitis were negative. Halothane-induced hepatitis has been documented as an idiosyncratic reaction among anesthetized patients and has been reported once in operating room personnel. The mechanism for halothane-induced hepatitis is proposed to be a hypersensitivity reaction to liver neo-antigens produced by the halothane metabolite 2-chloro-1, 1, 1-trifluoroethane.

Adult↗
PubMed1991

Effect of incubation temperature on zearalenone production by strains of Fusarium crookwellense.

After 6 weeks incubation on rice 2 strains of Fusarium crookwellense produced more zearalenone (6060-5010 mg/kg dry wt of culture) at ambient temperature (16-29 degrees C) in daylight than at ambient temperature (18-23 degrees C) in darkness or at controlled temperatures of 11 degrees C, 20 degrees C or 25 degrees C in darkness. Yields at 25 degrees C were low. Incubation at 11 degrees C during the second 3 weeks incubation increased yields only when preliminary incubation had been at 25 degrees C. After 6 weeks incubation at controlled temperatures in darkness, 4 strains produced most zearalenone at 20 degrees C (2460-21 360 mg/kg), 1 strain at 11 degrees C (6570 mg/kg). Yields at a temperature oscillating daily from 10-20 degrees C were less than at 15 degrees C. One of the 5 strains produced appreciable amounts of a-zearlaenol (1645 mg/kg at 20 degrees C) and 2 of nivalenol (340 and 499 mg/kg at 20 degrees C).

Fusarium↗
PubMed1990

Involvement of translation and transcription in insect steroidogenesis.

The involvement of protein and RNA synthesis in insect steroidogenesis was investigated using the prothoracic glands of the tobacco hornworm Manduca sexta. Ecdysone secretion stimulated by prothoracicotropic hormone (PTTH) and by cAMP analogs such as dibutyryl cAMP (dbcAMP), was suppressed by the translation inhibitors cycloheximide and puromycin, and by the transcription inhibitor actinomycin D. Inhibition of protein synthesis did not prevent the activation of glandular kinases, as indicated by continued protein phosphorylation in the presence of cycloheximide. Incorporation of radiolabeled amino acids and uridine increased within 60 min of glandular activation, suggesting that ecdysteroid secretion was accompanied by enhanced protein and RNA synthesis. One-dimensional gel electrophoresis revealed an increase in the translation of glandular proteins within 20 min of activation. The results suggest that the translation of protein from short-lived mRNA is necessary for optimal synthesis of ecdysteroids, and that the requisite proteins act beyond the activation of cAMP-dependent protein kinase.

Animals↗
PubMed1990

An epidemic of Oroya fever in the Peruvian Andes.

Between February and October 1987, a febrile illness killed 14 persons and seriously affected at least 14 others in Shumpillan, a remote Peruvian mountain village of 353 people. The illness was characterized by fever, headache, chills, and pallor. The fatality rate of untreated cases was 88%. The patients, 71% of whom were male, were 1-75 years of age. Fatal illnesses progressed from lethargy to coma to death in 3-60 days. Patients treated empirically with chloramphenicol survived. Bartonella bacilliformis was isolated from the whole blood of 3 patients. A serologic study revealed a high prevalence of antibodies to B. bacilliformis in the villagers. It is concluded that the villagers suffered from an epidemic of Oroya fever.

Adolescent↗
PubMed1989

Early events in peptide-stimulated ecdysteroid secretion by the prothoracic glands of Manduca sexta.

The prothoracic glands of the tobacco hornworm, Manduca sexta, have been an advantageous model for investigating the cellular mechanisms underlying hormone-stimulated ecdysteroid secretion in insects. The cerebral neuropeptide prothoracicotropic hormone (PTTH) is currently thought to activate the prothoracic glands via a calcium-dependent increase in cAMP synthesis, activation of cAMP-dependent protein kinase, and protein phosphorylation (Gilbert et al.: Bioessays, 8:153-158, '88). The present paper discusses current research regarding early changes in cell function elicited by PTTH, with emphasis on the regulation of cAMP synthesis and degradation and the involvement of translational events in PTTH action.

Animals↗
PubMed1989

Developmental changes in phosphodiesterase activity and hormonal response in the prothoracic glands of Manduca sexta.

Prothoracicotropic hormone (PTTH) stimulates ecdysteroid secretion by the prothoracic glands of Manduca sexta in a cAMP-dependent manner. However, larval and pupal glands differ markedly in the degree to which PTTH stimulates cAMP accumulation, suggesting a stage-specific difference in phosphodiesterase activity. The present study was designed to determine if and when such a difference arose during development, and its effect on PTTH-stimulated ecdysteroid secretion. The results reveal that soluble phosphodiesterase activity in the prothoracic glands changes significantly during the course of the fifth (last) larval instar, with a marked increase in activity occurring at the onset of prepupal development. Phosphodiesterase activity, particularly in the soluble cell fraction, is inversely correlated with PTTH-stimulated cAMP accumulation. Hormone-stimulated ecdysteroid secretion does not require cAMP accumulation, but does appear to require detectable cAMP synthesis as measured in the presence of phosphodiesterase inhibitors. The amount of ecdysteroid secreted, however, is not proportional to the amount of cAMP synthesized but rather is more closely correlated with developmental changes in glandular protein content.

Animals↗
PubMed1989

High-pressure portable pneumatic drive unit.

The left ventricular assist device (LVAD) of the Cleveland Clinic Foundation (CCF) is a single-chamber assist pump, driven by a high-pressure pneumatic cylinder. A low-cost, portable driver that will allow cardiac care patients, with a high-pressure pneumatic ventricle assist, more freedom of movement has been developed. The compact and light-weight configuration can provide periods of 2 h of freedom from a fixed position driver and does not use exotic technology.

Costs and Cost Analysis↗
PubMed1989

Estimates of wave front distortion from measurements of scattering by model random media and calf liver.

An expression based on a perturbation method is employed to estimate the correlation of path length difference in a plane normal to the direction of wave propagation from measurements of ultrasonic scattering by model random media and calf liver. The expression gives the correlation function of path length difference in terms of an integral of the correlation function of the medium variations or an equivalent integral of the power spectrum of medium variations, both for a scattering angle of zero degrees. Power spectra derived from measurements of average differential scattering cross section over a spatial-frequency window are used to fit analytic functions that extend over all spatial frequencies. The results for the windowed and unwindowed data yield correlation functions and corresponding power spectra that are used to estimate the correlation function of path length difference. The results suggest that the correlation length in calf liver is less than 100 microns and that a root-mean-square path length variation of about 20 microns results from propagation through a 100-mm calf liver path.

Animals↗
PubMed1989

Radionuclide assessment of the natural heart ejection fraction before and after LVAD implantation.

Complete pressure unloading of the ventricles can preserve ischemically damaged myocardium. Most clinical left heart assist device (LVAD) systems used after ischemic injury of the heart apply atrial cannulation which does not ensure pressure unloading. In order to assess the effect of the implantation of an intracorporeal LVAD on the function of the natural heart, we determined the ejection fraction (EF) in four male Holstein calves (90-105 kg) before and after insertion of a Cleveland Clinic pneumatic LVAD. A gated blood pool scan was obtained with a gamma camera after injection of 40 mCi Tc-labelled albumin. The animals were restrained in a sling to avoid movement artifacts. All animals showed a drop of 65 +/- 12% to 42 +/- 14% EF in the first postoperative (p.o.) week. Left ventricular output did not maintain sufficient blood pressure as assessed by pump-off tests. Systolic blood pressure dropped from 122 +/- 6.5 mm Hg to 81 +/- 6 mm Hg without pump support on the morning of the first p.o. day. Apical coring and possible restrained heart movement by the implanted LVAD may lead to impaired myocardial function that renders the individual LVAD dependent until adaptative corrections take place.

Animals↗
PubMed1988

A calmodulin-sensitive adenylate cyclase in the prothoracic glands of the tobacco hornworm, Manduca sexta.

The Ca2+/calmodulin (CaM) dependence of adenylate cyclase activity in Manduca sexta prothoracic glands was investigated. Membrane fractions from two developmental stages were used, day 3 of the last larval instar and day 0 of the pupal stage, both of which respond to the neuropeptide prothoracicotropic hormone (PTTH) with increased cAMP production dependent on extracellular Ca2+. The data revealed that both larval and pupal prothoracic gland membrane fractions have a Ca2+/CaM-dependent adenylate cyclase which is inhibited by CaM antagonists and EGTA. The larval adenylate cyclase shows a multiphasic response to Ca2+/CaM, with a 2-fold stimulation between 0.02 and 0.01 microM, a further increase in adenylate cyclase activity at concentrations greater than 2 microM and a potentiation of NaF-stimulated activity at doses greater than 0.1 microM Ca2+/CaM. Pupal prothoracic gland membrane fractions exhibit only the second phase of stimulation. Stimulation by the GTP analogs GTP-gamma-S and Gpp(NH)p is dependent on CaM in larval, but not in pupal membrane fractions, suggesting a role for CaM in Gs protein-mediated regulation of adenylate cyclase. However, adenylate cyclase activity in glands from both stages is dependent on CaM, supporting our initial premise that Ca2+ is required for cAMP synthesis in the prothoracic glands.

Adenylyl Cyclases↗
PubMed1988

The E4T electric powered total artificial heart (TAH).

The E4T is a totally implantable total artificial heart (TAH) resulting from many years of research work at the Cleveland Clinic Foundation (CCF) and Nimbus, Inc. It consists of four implanted subsystems: the pumping unit, the variable volume device, the transcutaneous transformer, and the internal battery. The pumping unit consists of two CCF biolized pusher plate pumps, and a Nimbus electrohydraulic energy converter. The control logic is based on a left master, alternating beating scheme. The timing difference between end right eject and end left fill determines the actuator speed adjustment. The pumps free fill, so left-right flow differences are easily accommodated. A prototype system has been built and begun testing to validate and refine the design details.

Electric Power Supplies↗
PubMed1987

Intrathecally administered natural human fibroblast interferon reduces exacerbations of multiple sclerosis. Results of a multicenter, double-blind study.

A randomized, double-blinded, placebo-controlled, two-year multicenter study demonstrated that natural human fibroblast interferon (interferon beta) administered intrathecally (IT) is effective in reducing the exacerbations of exacerbating-remitting multiple sclerosis (MS). The mean reduction in exacerbation rate of 34 patients with MS who received interferon beta administered IT was significantly greater during the study than that of 35 control patients who received placebo. The prestudy exacerbation rates were comparable for both patients who received interferon beta and control patients, but the exacerbation rate of patients receiving interferon beta at the end of the study was significantly lower than that of the control patients. Interferon beta was administered by nine or ten lumbar punctures for the first six months of the study, and observations were continued for two years. In 95% of the recipients, interferon beta therapy was well tolerated, and the side effects experienced were clearly acceptable for the benefits achieved. Low doses of indomethacin dramatically reduced the toxicity of interferon beta therapy and played an important role in successful double blinding. This study confirms a preliminary report on 20 patients that initially suggested that interferon beta administered IT was of benefit in patients with MS. The number of treatments was fewer and the dosage of interferon beta administered was less in the present study than in the preliminary one. It is possible that even fewer treatments with lower doses of interferon beta administered might provide a similar degree of prophylaxis against exacerbations.

Adult↗
PubMed1986

Involvement of cyclic AMP-dependent protein kinase in prothoracicotropic hormone-stimulated ecdysone synthesis.

Prothoracicotropic hormone (PTTH) is a brain neuropeptide that stimulates the prothoracic glands to synthesize ecdysone, an event that leads to insect molting. Both cyclic AMP (cAMP) and calcium have been implicated in PTTH action, with current evidence favoring cAMP as the messenger directly regulating ecdysone synthesis. To further define the role of cAMP in PTTH action, the activity of cAMP-dependent protein kinase (cAMP-PK) was examined in prothoracic glands from two developmental stages of the tobacco hornworm, Manduca sexta (day 3 fifth instar larvae and day 0 pupae). Prothoracic glands at each of these stages of development possess two forms of cAMP-PK which resemble the vertebrate type I and type II isozymes, with the latter being the predominant form (greater than 90%). Marked developmental differences exist in the degree of activation of soluble cAMP-PK following in vitro exposure of the prothoracic glands to PTTH. In larval glands, soluble cAMP-PK is activated within 3-10 min of initial exposure to doses of PTTH that stimulate ecdysone synthesis. By contrast, activation of soluble cAMP-PK in pupal glands occurs only when PTTH is administered in the presence of a phosphodiesterase inhibitor. Developmental differences in the activation of cAMP-PK by PTTH were qualitatively identical to previously observed differences in PTTH-stimulated accumulation of intracellular cAMP. The results suggest an involvement of soluble cAMP-PK in the response of day 3 fifth instar larval prothoracic glands to PTTH, but indicate a difference in the nature, intracellular location, or time course of activation, of hormone-sensitive protein kinase in day 0 pupal glands.

Animals↗
PubMed1986

Cellular changes in the prothoracic glands of diapausing pupae of Manduca sexta.

Prothoracic glands from diapausing pupae of the tobacco hornworm, Manduca sexta, synthesize markedly less ecdysone in vitro in response to prothoracicotropic hormone (PTTH) than do glands from non-diapausing pupae. Impaired steroidogenesis is also observed in glands from diapausing animals exposed to agents that enhance ecdysone synthesis in non-diapausing pupal glands by increasing intracellular levels of cAMP (1-methyl-3-isobutylxanthine, dibutyryl cAMP, and the calcium ionophore A23187). In contrast, prothoracic glands from diapausing pupae synthesize significantly more cAMP in response to PTTH and A23187 than do those from non-diapausing pupae. These observations indicate that the PTTH-refractoriness characteristic of prothoracic glands during diapause results from a lesion in the steroidogenic pathway occurring beyond the level of the PTTH receptor-adenylate cyclase system. The diapause condition of the prothoracic glands (reduced ecdysone synthesis accompanied by enhanced cAMP formation) can be mimicked by extirpation of the brain of a non-diapausing pupa. Thus, cellular changes in the prothoracic glands associated with diapause may arise as a result of the absence of some factor produced by the pupal brain (e.g. PTTH).

1-Methyl-3-isobutylxanthine↗