Delayed synaptic dysfunction of association cortices in carbon monoxide intoxication.
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Alzheimer Disease↗
Biomedical subjects
T Lee
Publications and source records attributed to T Lee.
Epidemic of adenovirus-induced respiratory illness among US military recruits: epidemiologic and immunologic risk factors in healthy, young adults.
Adenovirus (Ad)-induced acute respiratory illnesses resurged among civilian adults and selected military training populations in the United States during the late 1990s. We examined the epidemiologic and immunologic correlates of Ad-induced respiratory illnesses during a large outbreak at an Army basic training installation in southeast United States during a 9-day period in November 1997. A total of 79 recruits hospitalized with acute respiratory illnesses were evaluated during the outbreak period; confirmation of Ad infection by isolation of Ad-like cytopathic agents from throat cultures was detected in 71 (90%) of these patients. Serotyping of 19 (27%) of these 71 isolates identified the etiologic agent to be Ad type 4 (Ad4). In addition, 30 (81%) of 37 patients in whom paired sera were collected demonstrated significant increases (i.e., 4-fold or higher) in serum anti-Ad4 neutralizing antibodies. Anti-Ad4 immunity in new recruits was found to be very low (15 to 22%). A case-control study involving 66 of the 79 hospitalized cases and 189 non-ill controls from the same units was conducted. A lower risk of hospitalization for acute respiratory illnesses was documented for female recruits (odds ratio[OR] = 0.47, P <.05) whereas, a higher risk was noted for smokers (OR = 1.89, P <.05). Unit (training company) attack rates as high as 8 to 10% per week were documented and the outbreak quickly subsided after live, oral Ad types 4 and 7 vaccination was resumed in November 1997. Re-establishment of a military Ad vaccination program is critical for control of Ad-induced acute respiratory illnesses.
Acute Disease↗
Altered nociceptive response in mice deficient in the alpha(1B) subunit of the voltage-dependent calcium channel.
Calcium influx through N-type calcium channels mediates synaptic transmission at numerous central synapses and transduces nociceptive information in the spinal dorsal horn. However, the precise role of N-type calcium channels in pain perception is not fully elucidated. To address this issue, we generated and analyzed knockout mice for alpha(1B,) the pore-forming subunit of the N-type calcium channel. Homozygous mutants are viable, fertile, and show normal motor coordination. In small-diameter dorsal root ganglion neurons from mutants the density of calcium channel currents is significantly reduced, which can be accounted for by the abolition of N-type currents. We performed several pain-related behavioral tests using the mutant mice. alpha(1B)-Deficient mice show reduced response to mechanical stimuli in the von Frey test and increased tail flick latency in response to radiant heat, indicating altered spinal reflexes. However, pain response in the hot plate test is normal. In the formalin paw test, the mutant mice exhibit significantly attenuated response in Phase 2, but normal pain behaviors in Phase 1. The response to visceral inflammatory pain caused by acetic acid is also reduced in alpha(1B) knockout mice. These results suggest that the alpha(1B) subunit of N-type calcium channel plays a major role in pain perception by acting at the spinal level, but not at the supraspinal level.
Animals↗
Secretory leukocyte protease inhibitor, but not alpha-1 protease inhibitor, blocks tryptase-induced bronchoconstriction.
Alpha-1-protease inhibitor (alpha(1)-PI) and secretory leukocyte protease inhibitor (SLPI) are two natural airway serine protease inhibitors. While inhibition of neutrophil elastase is a function common to both alpha(1)-PI and SLPI, we showed previously that they exhibit different patterns of protection against antigen-induced changes in airway function in allergic sheep. Specifically, the protective effect seen with SLPI was similar to the profile of action of synthetic tryptase inhibitors in the model. Based on these data, and the fact that tryptase is a serine protease, we hypothesized that SLPI, but not alpha(1)-PI, would block tryptase-induced bronchoconstriction. To test this, we compared the responses to inhaled tryptase in five sheep without treatment or after treatment with either aerosol alpha(1)-PI (10 mg) or aerosol SLPI (50 mg). The doses of alpha(1)-PI and SLPI selected had been shown to be effective in previous antigen-provocation studies. Treatments were given 30 min before aerosol challenge with tryptase (500 ng). Tryptase alone increased (mean+/-SEM) pulmonary resistance (R(L)) 142 +/- 24% over baseline. Pretreatment with alpha(1)-PI had no effect on the tryptase response (R(L)increased 122 +/- 20%). Pretreatment with SLPI, however, blocked the tryptase-induced response (R(L) increased only 40 +/- 4% P<0.05 vs. tryptase). These are the first studies comparing the inhibitory activity of SLPI and alpha(1)-PI on inhaled tryptase-induced bronchoconstriction. We conclude that, in vivo, SLPI, but not alpha(1)-PI, can block tryptase-induced bronchoconstriction and that this activity may explain the differential effects of these two serine protease inhibitors on antigen-induced airway responses in allergic sheep.
Administration, Inhalation↗
Chips and Qi: microcomponent-based analysis in traditional Chinese medicine.
Over the last 50 years or so Traditional Chinese medicine (TCM) has been subject to intensive basic and clinical research. Although the effectiveness and remarkable safety of TCM have been documented after controlled clinical studies, there are several herbal and animal parts that are toxic or difficult to identify. DNA polymorphism-based assays have recently been developed for the identification of herbal medicines. In this approach, small amounts of DNA are amplified by the polymerase chain reaction and the reactions products are analyzed by gel electrophoresis, sequencing, or hybridization with species-specific probes. With the DNA based identification of TCM materials as an example, chip-based analytical micro devices were developed with the goal of fabricating an integrated device that will enable sample preparation, amplification, and analysis on a single microchip-based device ("lab-on-a-chip"). The application of a silicon-based polymerase chain reaction microreactor and a DNA microarray for the DNA sequence-based identification of toxic medicinal plants is reported here.
DNA, Plant↗
Polyketide synthase genes in insect- and nematode-associated fungi.
Production of polyketides is accomplished through complex enzymes known as polyketide synthases (PKS); these enzymes have highly conserved domains that might be useful in screens for PKSs in diverse groups of organisms. A degenerate PCR-based approach was used to amplify PKS fragments of the ketosynthase domain from genomic DNA of a group of insect- and nematode-associated fungi. Of 157 isolates (representing 73 genera and 144 species) screened, 92 isolates generated PCR products of predicted size (approximately 300 bp). The ability to detect PKS domains was a function of the number of different primer pairs employed in the screen. Cloning and sequencing revealed that 66 isolates had at least one unique PKS sequence; ten members of this set contained multiple PKS fragments, for a total of 76 unique PKS fragments. Since PKS genes appear to be widespread among fungi, a PCR-based screening system appears to be an efficient, directed means to identify organisms having the potential to produce polyketides.
Amino Acid Sequence↗
Etiology and epidemiology of preterm premature rupture of the membranes.
Preterm premature rupture of membranes continues to be a common complication of pregnancy with significant implications for perinatal outcome. Unfortunately, given the multiple risk factors that have been presented, which are reportedly associated with PPROM, attempts to reduce the incidence of this clinical event may seem daunting to the clinician. Despite this, one should attempt to address the potential risk factors that avail themselves to change. Unfortunately, although many risk factors have been identified, there are few randomized intervention trials for PPROM prevention. Examples of interventions documented to be beneficial include smoking cessation and screening for and treatment of chlamydial infections. These seem to be reasonable and logical interventions to consider in general, and may potentially have an effect on various causal agents of PPROM.
Female↗
Mosaic analysis with a repressible cell marker (MARCM) for Drosophila neural development.
We have modified an FLP/FRT-based genetic mosaic system to label either neurons derived from a common progenitor or isolated single neurons, in the Drosophila CNS. These uniquely labeled neurons can also be made homozygous for a mutation of interest within an otherwise phenotypically wild-type brain. Using this new mosaic system, not only can normal brain development be described with unprecedented single cell resolution, but also the underlying molecular mechanisms can be investigated by identifying genes that are required for these developmental processes.
Animals↗
Pneumococcal immunizations at flu clinics: the impact of community-wide outreach.
This study examined the effectiveness of a community-wide outreach campaign to promote the use of pneumococcal vaccine at public flu immunization clinics, and assessed whether this intervention was more effective than simply making pneumococcal vaccination available at such clinics. In 1997, a community-wide outreach campaign promoting pneumococcal and influenza immunizations was launched in a 17 zip code area of Dutchess County, NY. The campaign was aimed at 7,961 Medicare beneficiaries urging them to obtain pneumococcal immunization from local flu clinics. Medicare reimbursement data were used to assess the countywide pneumococcal vaccination rate, and to analyze differences between rates for beneficiaries in the target area and elsewhere in the county. Between 1996 and 1997 there was a 94% increase in pneumococcal vaccination billed to Medicare beneficiaries in Dutchess County. The 1997 annual rate of pneumococcal immunization in the target area reached 16.3% versus 12.2% elsewhere in the county (p < 0.001), with an increase over the previous year of 8.7% and 5.6%, respectively. Nearly all of the increase is accounted for by pneumococcal vaccination delivered at flu clinics. It is possible to significantly increase the use of pneumococcal immunization by linking its delivery to community-based flu clinics and by developing local outreach strategies. The outreach campaign has a significant additive effect over simply making PPV available at flu shot clinics. Additional community-wide outreach can further improve pneumococcal immunization utilization rates.
Aged↗
Molecular basis of the Dombrock null phenotype.
BACKGROUND: The Dombrock blood group system consists of two antithetical antigens, Do(a) and Do(b), and three high-incidence antigens, Gregory (Gy(a)), Holley (Hy), and Joseph (Jo(a)). The null phenotype of the Dombrock blood group system (Do(null)) was identified when it was found that Gy(a-) RBCs also lack Do(a), Do(b), Hy, and Jo(a). STUDY DESIGN AND METHODS: DNA from three Gy(a-) persons was analyzed. PCR products for each of the three DO exons and their flanking intronic regions were sequenced in both directions. The cDNA from two of the people was subjected to PCR using primers in exon 1 and exon 3, and the products were sequenced. RESULTS: The Do(null) phenotype is associated with a single nucleotide mutation in the acceptor splice site of DO (IVS1-2a>g), which results in outsplicing of exon 2. CONCLUSION: Outsplicing of exon 2 is predicted to cause a -1 frameshift and a premature stop codon. Any product of such a transcript would lack the glycosyl-phosphatidylinositol-anchor motif, and RBCs would be devoid of the Do glycoprotein.
Amino Acid Sequence↗
Giant aneurysm treated by bilateral cervical carotid artery to proximal middle cerebral artery bypass and balloon embolisation: a case report.
The authors describe a case of a 59 year-old Chinese lady with a history of spontaneous left caroticocavernous fistula in 1988 treated by left internal carotid artery clipping and muscle embolisation. She subsequently presented with a subarachnoid haemorrhage in November 1997 secondary to rupture of an unclippable giant right internal carotid artery aneurysm. This was treated satisfactorily with bilateral cervical carotid artery to proximal middle cerebral artery bypass followed by balloon occlusion. Postoperatively, the patient has no neurological deficit and CT angiogram shows good patency of both grafts 6 months after surgery.
Balloon Occlusion↗
Inhibition of mast cell tryptase by inhaled APC 366 attenuates allergen-induced late-phase airway obstruction in asthma.
BACKGROUND: APC 366, a selective inhibitor of mast cell tryptase, has been shown to inhibit antigen-induced early asthmatic response (EAR), late asthmatic response (LAR), and bronchial hyperresponsiveness (BHR) in a sheep model of allergic asthma. OBJECTIVE: The purpose of this study was to investigate the effects of APC 366 on antigen-induced EAR, LAR, and BHR in mild atopic asthmatics not on any anti-inflammatory therapy. METHODS: Sixteen mild atopic asthmatics, each with a demonstrable antigen-induced EAR, LAR, and BHR to histamine, were recruited into this randomized, double-blinded, crossover study. APC 366 (5 mg)/placebo was administered by aerosol inhalation 3 times per day on treatment days 1 through 4. Allergen challenge was carried out on day 4. Histamine challenge was performed the following morning, 1 hour after final dosing. RESULTS: Subjects were shown to have a significantly smaller overall mean area under the curve for the LAR (P =.012) and mean maximum fall in FEV(1) for the LAR (P =.007) after pretreatment with APC 366 in comparison with placebo. No significant effects on BHR were demonstrable. Although the EAR was reduced by 18% after treatment with APC 366 in comparison with placebo, this was not statistically significant. CONCLUSION: Short-term repeated administration of APC 366 significantly reduced the magnitude of antigen-induced LAR in atopic asthmatics, which supports the role of mast cell tryptase in the pathophysiology of the LAR.
Administration, Inhalation↗
Intra-abdominal actinomycosis with hepatic pseudotumor and xanthogranulomatous pyelonephritis in a 6-y-old boy.
We report the case of a 6-y-old boy with actinomycosis, presenting as xanthogranulomatous pyelonephritis (XGP), hepatic pseudotumor and abdominal abscess. Symptoms included intermittent fever, abdominal pain and significant weight loss. Hepatic and renal tumor masses were suspected on sonography and computerized tomography. XGP and actinomycosis were proven by pathology. The patient recovered well with antibiotic alone.
Abdominal Abscess↗
The importance of posture in the early stages of stroke: its influence on cerebral perfusion.
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Brain↗
Randomized structured triglycerides increase lymphatic absorption of tocopherol and retinol compared with the equivalent physical mixture in a rat model of fat malabsorption.
Previously we demonstrated that the digestion, absorption and lymphatic transport of lipid and key essential fatty acids (EFA) from randomly interesterified fish oil/medium-chain structured triglycerides (STG) were significantly higher than an equivalent physical mixture (PM) in a normal lymph fistula rat model and in a rat model of lipid malabsorption caused by ischemia/reperfusion (I/R) injury. The goals of this study were to further explore the potential absorptive benefits of STG by comparing the intestinal absorption and lymphatic transport of tocopherol and retinol when delivered gastrically with either STG or PM under normal conditions and after I/R injury to the small bowel. Food-deprived male Sprague-Dawley rats were randomly assigned to two treatments (sham controls or I/R). Under halothane anesthesia, the superior mesenteric artery (SMA) was occluded for 20 min and then reperfused in I/R rats. The SMA was isolated but not occluded in control rats. In both groups, the mesenteric lymph duct was cannulated and a gastric tube was inserted. Each treatment group received 1 mL of the fish oil/MCT STG or PM (7 rats/group) along with (14)C-alpha-tocopherol and (3)H-retinol through the gastric tube followed by an infusion of PBS at 3 mL/h for 8 h. Lymph was collected hourly for 8 h. Under steady-state conditions, the amount of (14)C-alpha-tocopherol and (3)H-retinol transported into lymph was significantly higher in the STG-fed rats compared with those fed PM in both control and I/R groups. In addition, control and I/R rats given STG had earlier steady-state outputs of (14)C-alpha-tocopherol and (3)H-retinol and maintained approximately 30% higher outputs in lymph throughout the 8-h lymph collection period compared with rats given the PM. We conclude that STG provides the opportunity to potentiate improved absorption of fat-soluble vitamins under normal and malabsorptive states.
Animals↗
Systemic lupus erythematosus and antiphospholipid syndrome in children and adolescents.
Systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) can be associated with significant morbidity in children and adolescents. Renal involvement in SLE appears to be more severe and more frequent in the pediatric age group, with the major predictors for poor outcome being the severity of histopathologic lesions, severity of renal impairment at diagnosis, and hypertension. In addition to currently recognized cardiovascular and pulmonary involvement, accelerated atherosclerosis is of increasing concern in young individuals with SLE, because of both disease effects and medication usage. Neuropsychiatric SLE seen in childhood ranges from subtle cognitive dysfunction to severe central nervous system involvement; however, there is controversy over the value of different diagnostic studies. APS in children may be associated with SLE, idiopathic, or associated with viral infections. Systemic anticoagulation is recommended for patients with thrombotic events, but long-term management has not been well studied in children.
Adolescent↗
Simultaneous determination of plasma prednisolone, prednisone, and cortisol levels by high-performance liquid chromatography.
Recipients of organ transplants remain particularly dependent on prednisolone as part of their maintenance immunosuppression. Despite this, the pharmacokinetics of prednisolone have never been fully characterized in these patients, and consequently dosing remains empirical. Accurate monitoring of prednisolone, its primary metabolite prednisone, and endogenous cortisol suppression in such patients may provide a means of improving the clinical outcome by adjusting for variability in prednisolone pharmacokinetics and pharmacodynamics. Measurement of endogenous cortisol may provide an independent marker of prednisolone pharmacodynamics. A simple isocratic reverse-phase high-performance liquid chromatography procedure, using betamethasone as an internal standard, was developed to quantify plasma prednisolone, prednisone, and cortisol simultaneously. The steroids were extracted from 0.5 mL plasma with 3 mL (1:1 v/v) ethyl acetate/tert-methyl butyl ether and 0.1 mL phosphoric acid, washed in 0.1 mol/L NaOH before a final drying step and reconstitution in mobile phase for injection. Separation was achieved using a Supelcosil LC-18-DB, 150 x 4.6-mm, 5-microm particle size, reverse-phase column attached to a Newguard 15 x 3-mm, RP8 guard column maintained at 25 degreesC, with ultraviolet detector set at 254 nm. The mobile phase consisted of 16% isopropanol in water containing 0.1% trifluoroacetic acid, set at a flow rate of 1.2 mL/min. The assay was linear up to 1,002 microg/L for prednisolone, 982 microg/L for prednisone, and 545 microg/L for cortisol. Mean intra-assay and interassay imprecision levels were 6.0% and 7.2%, respectively, for prednisolone, 5.8% and 7.2% for prednisone, and 5.6% and 7.9% for cortisol. Intra-assay inaccuracy was <7% of nominal values for prednisolone, prednisone, and cortisol. The lower limit of quantification was 7 microg/L for prednisolone and prednisone and 10 microg/L for cortisol. Corticosteroid recoveries were 73%, 74%, and 90% for prednisolone, prednisone, and cortisol, respectively. The authors describe a robust, inexpensive, and simple method suitable for therapeutic drug monitoring or pharmacokinetic studies of prednisolone; it may also be used to measure the suppression of endogenous cortisol production.
Anti-Inflammatory Agents↗
Damping properties of lead metaniobate.
Mechanical damping, tan delta, of lead metaniobate was determined experimentally over a wide range of frequency. Damping at audio and sub-audio frequency was lower than at ultrasonic frequency. The experiments were conducted in torsion and bending using an instrument capable of determining viscoelastic properties over more than 10 decades of time and frequency. Mechanical damping was higher in bending than torsion at all frequencies. Damping observed in this study at the highest frequencies approach the high value 0.09 previously observed at ultrasonic frequency.
Journal Article↗