D1 and D2 dopamine receptor mediation of amphetamine-induced acetylcholine release in nucleus accumbens

To assess the interaction of dopamine and acetylcholine systems in the rat nucleus accumbens in response to direct D-amphetamine administration, in vivo microdialysis measures of acetylcholine were used during reverse dialysis of amphetamine alone and in combination with D1 and D2 receptor antagonists SCH 23390 and sulpiride, respectively. During a 15-min exposure to amphetamine (50 microM) in the nucleus accumbens, acetylcholine increased to 33% above pre-infusion levels, became maximal at 15 min post-infusion (+41%) and gradually returned to baseline levels by 60 min post-amphetamine. Conversely, amphetamine (1 mM) administration caused a biphasic change in acetylcholine release with a trend toward a decrease (-14%) during exposure followed by a significant increase (+36%) at 30 min post-amphetamine that returned to baseline levels by 60 min after infusion. The increases observed during amphetamine (50 microM) exposure and during recovery from amphetamine (1 mM) were both blocked by co-administration with the D1 antagonist, SCH 23390 (10 microM), but not with the D2 antagonist, sulpiride (10 microM). Co-infusion of sulpiride eliminated the trend toward reduced acetylcholine release observed during 1 mM amphetamine whereas co-administration of SCH 23390 potentiated this decrease. A possible tonic D1 facilitation of nucleus accumbens acetylcholine release was indicated by the consistent reductions in acetylcholine release observed during infusion of SCH 23390. These results suggest that amphetamine administration in the nucleus accumbens induces a bidirectional change in acetylcholine release that is dependent on dose and opposing effects of nucleus accumbens D1 and D2 activation. In general, relatively low doses of amphetamine administered into the nucleus accumbens caused an increase in acetylcholine release that was dependent on dopamine D1 receptors whereas higher doses of amphetamine resulted in a D2-mediated decrease.     

Fetal fast MR imaging: reproducibility, technical quality, and conspicuity of anatomy

PURPOSE: To evaluate the normal appearance of fetal anatomy, the conspicuity of fetal organs, the reproducibility of images, and the limitations to image quality with the use of half-Fourier, single-shot rapid acquisition with relaxation enhancement (RARE) magnetic resonance (MR) imaging. MATERIALS AND METHODS: Fifty-four fetuses of 49 pregnancies underwent MR imaging with the half-Fourier, single-shot RARE technique. Two reviewers attempted to identify 47 organs and anatomic regions in each fetus. Organ or region conspicuity, image quality, and the limitations of image quality were graded. RESULTS: Fetal anatomy was well depicted in fetuses over 20 weeks in gestational age. Fetal imaging was limited by gestational age of 20 weeks or less usually owing to the small size of the organ or region being evaluated and, less frequently, by motion. CONCLUSION: Half-Fourier, single-shot RARE MR imaging provided a detailed and reproducible evaluation of normal fetal anatomy, which can be used as a standard of reference in MR imaging of fetal anomalies.     

Sugar-induced molten-globule model

Proteins denature at low pH because of intramolecular electrostatic repulsions. The addition of salt partially overcomes this repulsion for some proteins, yielding a collapsed conformation called the A-state. A-states have characteristics expected for the molten globule, a notional kinetic protein folding intermediate. Here we show that the addition of neutral sugars to solutions of acid-denatured equine ferricytochrome c induces formation of the A-state in the absence of added salt. We characterized the structure and stability of the sugar-induced A-state with circular dichroism spectropolarimetry (CD) and NMR-monitored hydrogen-deuterium exchange experiments. We also examined the stability of the sugar-induced A-state as a function of sugar size and concentration. The results are interpreted using several models and we conclude that the stabilizing effect is consistent with increased steric repulsion between the protein and the sugar solutions.     

Somatic antigens of pseudomonads: structure of the O-specific polysaccharide of Pseudomonas fluorescens biovar B, strain IMV 247

The O-specific polysaccharide of Pseudomonas fluorescens biovar B, strain IMV 247, was studied by acid hydrolysis, GLC-MS and 1H and 13C NMR spectroscopy, including 1D and 2D NOE, 2D hybrid TOCSY and ROESY (TORO), and 2D H-detected heteronuclear multiple-bond correlation (HMBC) experiments. The polysaccharide was found to contain L-rhamnose, 3.6-dideoxy-3-[(S)-3-hydroxybutyramido]-D-glucose (D-Qui3NHb), 2-acetamido- 2,4,6-trideoxy-4-[(S)-3-hydroxybutyramido-D-glucose (D-QuiNAc4NHb) and 2-acetamido-2- deoxy-D-galacturonic acid (D-GalNAcA). Partial acid hydrolysis of the polysaccharide resulted in a non-reducing GalNAcA-->QuiNAc4NHb disaccharide with the 3-hydroxybutyryl group glycosylated intramolecularly by the QuiN4N residue. The following structure of the tetrasaccharide repeating unit of the polysaccharide was established:-->4) -alpha-D-GalpNAcA-(1-->3)- alpha-D-QuipNAc4NHb-(1-->2)-beta-D-Quip3NHb-(1-->2)-alpha-L- Rhap(1-->.     

Lizards as hosts for immature Ixodes scapularis (Acari: Ixodidae) in North Carolina

Previously archived museum specimens of lizards collected throughout North Carolina were examined for Ixodes scapularis (Say). Lizards (n = 1,349) collected in 80 of North Carolina's 100 counties were examined. Lizards with ticks were collected in 23 (29%) of the 80 counties from which lizards were examined. I. scapularis was detected on 8.7% (n = 117) of the lizards and was the sole species of tick obtained from lizards. Immature ticks were most frequently found on the southeastern five-lined skink, Eumeces inexpectatus, and the eastern glass lizard, Ophisaurus ventralis. Larvae were most frequently found on the six-lined racerunner, Cnemidophorus sexlineatus. One C. sexlineatus harbored 177 larvae and 2 nymphs. Nymphs were most frequently observed on E. inexpectatus. The majority of counties (chi 2, P < 0.01) where ticks were found on lizards were in the Coastal Plain.     

A patient with Wegener''s granulomatosis presenting with a subarachnoid hemorrhage: case report and review of CNS disease associated with Wegener''s granulomatosis

1. Travellers to high altitude often complain of paroxysmal cough, which has not been previously investigated. We recorded overnight cough frequency and cough-receptor sensitivity to inhaled citric acid in a group of climbers travelling to 5300 m or higher. 2. Cough frequency, monitored in ten subjects, increased from a median of 0 coughs at sea level (range 0-1) to 5 coughs at 5000 m (range 0-13) and to over 60 coughs in subjects ascending to 7000 m. Citric acid cough threshold, measured in 42 subjects, was unchanged on arrival at 5300 m compared with sea level (geometric mean difference 1.26, 95% confidence intervals 0.84-1.89, P = 0.25), but was significantly reduced after 6 days, or more, at altitude compared with sea level (geometric mean difference 2.2, 95% confidence intervals 1.54-3.15, P = 0.0002). Cough threshold was not related to symptoms of acute mountain sickness, oxygen saturation, carbon dioxide tension or lung function. 3. These results indicate an increase in cough and cough-receptor sensitivity after some days at altitude. This may be due to respiratory tract damage from breathing cold dry air at increased ventilatory rates. Other explanations, such as sub-clinical pulmonary oedema or an effect on the cough centre of acclimatization to altitude, cannot be excluded.     

Inhibition of sickle beta-chain (betaS)-dependent polymerization by nonhuman alpha-chains. A superinhibitory mouse-horse chimeric alpha-chain

Horse alpha-chain inhibits sickle beta-chain-dependent polymerization; however, its inhibitory potential is not as high as that of mouse alpha-chain. Horse alpha-(1-30) and alpha-(31-141) segments make, respectively, minor and major contributions to the inhibitory potential of horse alpha-chain. The sum of the inhibitory potential of the two segments does not account for the inhibitory potential of the full-length horse alpha-chain. Although the polymerization inhibitory potential of horse alpha-chain is lower than mouse alpha-chain, the inhibitory potential of horse alpha-(31-141) is comparable to that of mouse alpha-(31-141). When mouse alpha-(1-30) is stitched to horse alpha-(31-141), the product is a chimeric alpha-chain with an inhibitory potential greater than mouse alpha-chain. In contrast, the stitching of horse alpha-(1-30) with mouse alpha-(31-141) had no additional inhibitory potential. Molecular modeling studies of HbS containing the mouse-horse chimeric alpha-chain indicate altered side-chain interactions at the alpha1beta1 interface when compared with HbS. In addition, the AB/GH corner perturbations facilitate a different stereochemistry for the interaction of the epsilon-amino group of Lys-16(alpha) with the beta-carboxyl group of Asp-116(alpha), resulting in a decrease in the accessibility of the side chain of Lys-16(alpha) to the solvent. Based on molecular modeling, we speculate that these perturbations by themselves, or in synergy with the altered conformational aspects of the alpha1beta1 interactions, represent the molecular basis of the superinhibitory potential of the mouse-horse chimeric alpha-chains.     

Oesophageal intramural pseudodiverticulosis: a cause of dysphagia in a 10-year-old boy

We report a 10-year-old boy who presented with a piece of chicken stuck in his throat. He had similar episodes in the past that resolved spontaneously. The foreign body was removed and oesophagoscopy revealed no abnormality. Post-operative barium swallow showed oesophageal intramural pseudodiverticulosis.     

Activation of the mitogen-activated protein kinase pathway is involved in and sufficient for megakaryocytic differentiation of CMK cells

Activation of the mitogen-activated protein (MAP) kinase pathway has been associated with both cell proliferation and differentiation. Constitutively activated forms of Mek (MAP kinase/Erk kinase) and Erk (MAP kinase) have been previously shown capable of inducing differentiation or proliferation in nonhematopoietic cells. To specifically examine the role of Erk activation in megakaryocytic growth and development, we activated the MAP kinase pathway by the transfection of constitutively activated Mek or Erk cDNA into a human megakaryoblastic cell line, CMK, by electroporation. The CMK transfectant clones that expressed constitutively activated Mek or Erk showed morphologic changes of differentiation. Transfected cells also showed expression of mature megakaryocytic cell surface markers. The MAP kinase pathway was also activated by treatment of the hematopoietic cells with a cytokine that activates Erk. The treatment of CMK cells with stem cell factor (SCF ) caused MAP kinase activation and induced differentiation by the expression of mature megakaryocytic cell surface markers. The effects of the SCF treatment were inhibited by pretreatment with a specific inhibitor of the MAP kinase pathway, PD98059. In this report, we conclude that activation of the MAP kinase pathway was both necessary and sufficient to induce differentiation in this megakaryoblastic cell line.     

Ozone therapy of diffuse peritonitis in the early postoperative period

The functional status of the oxidative-antioxidative system was studied in 72 patients after vast cancer operations. Traditional surgical treatment and its combination with intraoperative irradiation were shown to lead to tense antioxidative defense and to suppressed T-cell immunity and to call for antioxidative and immunomodulating therapy. High intraoperative blood loss complicated by hemorrhagic shock injured the oxidative-antioxidative system greatly. The magnitude of this damage correlated with the rate of prehypoxia. Addition of the potent antioxidant Ceruloplasmin to the drug regimen normalized a recovery period, helped to correct posthypoxic multiorgan insufficiency, to recover oxidative-antioxidative balance, and to decrease the incidence of pyoinflammatory complications. Patients with endogenous intoxication showed activated lipid peroxidation, decreased functional activity of antioxidative defense components and of T-cell immunity in homeostasis. The use of Ceruloplasmin and Laprot had pronounced antiinflammatory and detoxifying effects on the patient's body and activated its antioxidative defense.