Morphogen gradients, positional information, and Xenopus: interplay of theory and experiment.

The idea of morphogen gradients has long been an important one in developmental biology. Studies with amphibians and with Xenopus in particular have made significant contributions to demonstrating the existence, identity, and mechanisms of action of morphogens. Mesoderm induction and patterning by activin, nodals, bone morphogenetic proteins, and fibroblast growth factors have been analyzed thoroughly and reveal recurrent and combinatorial roles for these protein growth factor morphogens and their antagonists. The dynamics of nodal-type signaling and the intersection of VegT and beta-catenin intracellular gradients reveal detailed steps in early long-range patterning. Interpretation of gradients requires sophisticated mechanisms for sharpening thresholds, and the activin-Xbra-Gsc system provides an example of this. The understanding of growth factor signal transduction has elucidated growth factor morphogen action and provided tools for dissecting their direct long-range action and distribution. The physical mechanisms of morphogen gradient establishment are the focus of new interest at both the experimental and theoretical level. General themes and emerging trends in morphogen gradient studies are discussed.     

Bionomics of Anopheles maculatus complex and their role in malaria transmission in Thailand

The bionomics of Anopheles maculatus complex and its role in malaria transmission were conducted in Pakchong and Sadao districts, Nakhon Ratchasima and Songkhla provinces, respectively, from January 1984 to July 1985. In Pakchong, An. maculatus species A was the most dominant species, followed by species B form F and species C which was rare. The densities of species A and species B form F were high between July and November, with their peaks in October. Biting activities of both species occurred through out the night, with a major peak during the first quarter of the night on all seasons. In Sadao, only An. maculatus species B form E was detected with peak densities between February and June. Biting activities of this species varied according to seasons. The prevalence of mosquitoes was influenced by monthly rainfall, relative humidity and air-temperature. All species of female An. maculatus complex studied prefered to feed on animal rather than on human, and tended to bit human more outdoors than indoors, and thus exhibiting a zoophilic and exophagic behaviour. Life expectancies of An. maculatus species A ranged from 1.6 to 6.6 days, species B form F from 1.1 to 8.1 days, and species B form E from 0.7 to 21.2 days. The natural malaria infection rate was very low. Out of 4,430 guts dissected, only 0.23% were found infected with oocysts. There were no sporozoites detected in the 4,472 dissected salivary glands.     

Divergent pediatric elbow dislocation. A case report

A six-year-old boy with divergent elbow dislocation is reported, emphasizing the rarity of this condition. A literature review revealed only three roentgenographically documented divergent elbow dislocations in the pediatric age group. Reduction is usually accomplished with ease; however, a full range of elbow motion and forearm rotation must be obtained to ensure complete reduction of the radiohumeral joint.     

An oral selective M3 cholinergic receptor antagonist in COPD.

Cholinergic antagonists have been used since the early 1900s as bronchodilators for chronic obstructive pulmonary disease (COPD). The present study investigated whether an oral muscarinic M3-selective anticholinergic agent (OrM3) would provide an improved therapeutic advantage compared with an inhaled anticholinergic agent in patients with COPD. A 6-week, multicentre, randomised, placebo- and active-controlled, parallel-group study was performed at 56 sites in the USA. In total, 412 male and female patients (aged 35-86 yrs) with a clinical history consistent with COPD were randomised to receive OrM3 0.5, 2, 3 or 4 mg orally once daily, ipratropium bromide 36 mug by inhalation four times daily or placebo. OrM3 demonstrated a significant dose-related improvement in serial forced expiratory volume in one second and a trend for dose-related improvement in patient-reported symptoms compared with placebo. However, at a dose that provided efficacy less than that of ipratropium, the incidence of dose-related, mechanism-based side-effects for OrM3 exceeded those observed for ipratropium. In patients with chronic obstructive pulmonary disease, the oral M3-selective agent did not offer a therapeutic advantage over inhaled ipratropium. These results do not support the hypothesis that high selectivity for muscarinic M3 receptors over airway neuronal M2 receptors will represent a more effective therapy than current inhaled anticholinergics in obstructive airway disease.     

Evaluation of a rapid peptide-based anti-human immunodeficiency virus-1 antibody immunoassay.

A qualitative, visually interpreted, rapid, and synthetic peptide-based anti-human immunodeficiency virus-1 (HIV) antibody immunoassay has been developed that may be of value in situations in which rapid determination of HIV-1 status is important. Because questions have been raised about the accuracy of rapid anti-HIV-1 assays, the sensitivity, specificity, interobserver and intraobserver variability of the Genie HIV-1 assay (Genetics Systems, Seattle, WA) were determined. Sera from 56 patients with HIV-1 infections documented by enzyme immunoassay and western blot tested positive by this assay. Enzyme immunoassay- and western blot-negative sera from 30 visceral organ transplant donors were negative using the Genie assay. Specificity was examined further by testing sera from 29 patients hospitalized with a variety of medical disorders, including acute bacterial pneumonia, acute myocardial infarction, monoclonal gammopathy, and high titer antinuclear or antimitochondrial antibodies. Two of these patients were reactive with the enzyme immunoassay, both of which tested negative by western blot. All 29 tested negative using the Genie assay. In addition, sera from five patients with repeatedly reactive enzyme immunoassays and negative western blots tested negative by the Genie system. There was 100% agreement in interobserver and intraobserver studies. With the western blot as the reference method, the Genie assay exhibited 100% sensitivity and specificity and there was no observer variability.     

Cinefluoroscopic evaluation of periprosthetic cardiac valve regurgitation

The results of cinefluoroscopic evaluation in 509 patients in whom there was no evidence of prosthetic mitral or aortic valve regurgitation were compared with those in 41 patients who had perivalvular aortic or mitral regurgitation. Rotational motion of the base ring of each prosthesis (base-ring tilt) was measured in at least two views. A base-ring tilt of 7 degrees or more for aortic prostheses or 11 degrees or more for mitral prostheses was associated with an increased incidence of significant perivalvular regurgitation. Likewise, in patients who had multiple studies, a change between studies in base-ring tilt of 4 degrees or more for aortic prostheses or 5 degrees or more for mitral prostheses was associated with significant perivalvular regurgitation. These data suggest that the presence of either an abnormal base-ring tilt or an abnormal increase in base-ring tilt is strong, supportive evidence of partial prosthetic valve dehiscence.     

Synthesis, chemical, and biological properties of vinylogous hydroxamic acids: dual inhibitors of 5-lipoxygenase and IL-1 biosynthesis.

Vinylogous hydroxamic acids (3-(N-hydroxy-N-alkylamino)-2-propen-1-ones, VHA) were prepared as antiinflammatory agents. The synthesis, chemical properties, and in vitro biological activities of these relatively unexplored compounds are described. The VHAs were prepared by condensation of the appropriate N-substituted hydroxylamine with any of the three reagents: a 1,3-dicarbonyl compound (method A); a vinylogous amide (method B); or an alkynone (method C). The VHAs exist as one or more tautomers in solution with the relative proportions of each being dependent upon the structure of the VHA, solvent, and pH. VHAs undergo some of the typical reactions of hydroxamic acids as well as those of vinylogous amides. VHAs are active as inhibitors of 5-lipoxygenase and of IL-1 biosynthesis in vitro, which do not inhibit other enzymes of the arachidonic acid cascade. They have been shown by ESR studies to bring about inhibition of soybean type 1 15-lipoxygenase by reduction of the active site iron.     

Effects of amoxapine and imipramine on evoked potentials in the Continuous Performance Test in patients with affective disorder

Twenty patients with major depressive disorder were studied with evoked potential (EP) topographic mapping after receiving placebo, imipramine, or amoxapine for 2 days in a random-assignment, double-blind design. Patients performed the Continuous Performance Test (CPT), a visual vigilance test. The stimuli were the digits 0-9, with 0 a target to be responded to with a button press. EPs were recorded from 32 channels and were averaged separately for detected and undetected targets and for false positives and correctly identified nontargets (no button press). Twenty-one normal controls were also tested. Amoxapine enhanced N120 amplitude in midline parietal and right parietal cortex where selective attention effects have been found to be greatest in studies of normal controls. Both amoxapine and imipramine enhanced differences in P200 between target and nontarget stimuli in comparison to placebo, with amoxapine differences again being greatest over midline parietal locations. CPT performance was significantly better on amoxapine than placebo.