Effect of gastric dysrhythmias on postcibal motor activity of the stomach

The effect of electrical dysrhythmias on the mechanical activity of the fed stomach was investigated in 5 conscious dogs implanted with Ag-AgCl electrodes and strain gauge force transducers. Each dog was fed 1 can of ALPO^® and electromechanical activities of the stomach were recorded for the next 120 min. The results show that intraarterial boluses of met-enkephalin (75 g/kg), PGE₂ (36 g/kg), and epinephrine (36 g/kg) induced episodes of antral dysrhythmias whereas saline (1 cc) did not. The postcibal antrat motility index for the test period was not altered following saline injection, but it was reduced by 61%, 70%, and 81% following the administration of met-enkephalin, epinephrine, and PGE₂, respectively (p<0.01 vs. baseline period). During periods of normal electrical rhythm, PGE₂ and epinephrine significantly reduced the antral motility index (2.07±0.93 and 3.24±0.79, respectively) vs. saline (7.92±0.44) (p<0.05 for both drugs) whereas met-enkephalin (4.98±0.56) did not. In contrast, during episodes of dysrhythmia, met-enkephalin significantly depressed antral motility (1.70±0.74) (p<0.05 vs. periods with normal electrical rhythm) whereas neither epinephrine nor PGE₂ caused a further reduction in antral motility from what was seen during periods of normal electrical rhythm (1.84±0.72 and 1.34±0.37, respectively). We thus conclude that intraarterial administration of met-enkephalin, PGE₂, or epinephrine induce gastric dysrhythmias postcibally and depress antral contractile activity. The relaxatory effect of met-enkephalin on antral contractions is primarily due to its dysrhythmic effect whereas PGE₂ and epinephrine inhibit antral motility even when the electrical rhythm is undisturbed.This work was supported in part by the USPHS, NIH grants AM26428, AM07198, and AM34988 and the Mayo Foundation.     

Flavonoids ofElscholtzia cristata

Apigenin, apigenin-7-O-glucoside, luteolin-7-O-glucoside and linarin were isolated fromElscholtzia cristata (Labiatae).     

Dual action of 2,3-butanedione monoxime (BDM) on K+ current in human T lymphocytes.

Originally developed as antidotes to organophosphorus nerve poisons, the oximes have attracted renewed interest in studies of cellular regulation. In particular, 2,3-butanedione monoxime (BDM) has gained attention as a useful membrane-permeant "chemical phosphatase" for studying roles of protein phosphorylation. It has been proposed that effects of BDM on cardiac muscle tension, action potentials, neuromuscular transmission and ion currents are related to dephosphorylation of substrates as diverse as myofibrils and ion channels. In the present study, voltage-dependent K+ currents in human T lymphocytes were studied using the whole cell patch clamp technique. Preincubating intact cells briefly in 5 mM BDM before recording reduced the K+ current in an irreversible manner, consistent with chemical (phosphatase?) modification of the channels. In contrast, acute BDM treatment produced a rapid, reversible block of K+ current with half block at about 5 mM. Moreover, including adenosine-O-5'-(3-thiotriphosphate) (500 microM) in the patch pipette did not prevent the rapid, reversible block by BDM. Under these conditions, the most likely mechanism was a direct block of channels from the outside. Because similar K+ currents are present in many tissue and cell types, a direct channel block suggests caution in interpreting the effects of oximes as resulting from protein dephosphorylation.     

Test of genetic heterogeneity of cleft lip with or without cleft palate as related to race and severity

The question of possible heterogeneity among population groups and phenotypic groups on the role of major gene in the etiology of cleft lip with or without cleft palate [CL(P)] was examined using the uniformly collected data in Hawaii. Complex segregation analysis was used to analyze patterns of family resemblance under the mixed model incorporating the effects of major gene and multifactorial inheritance. Analysis of the entire data showed superior fit of the mixed model including the effects of both major gene and multifactorial inheritance over the model of major gene alone or multifactorial inheritance alone. No significant heterogeneity could be detected between the high-incidence group (Oriental or Japanese) and the low-incidence group (non-Oriental) in the underlying general model, although higher heritability was observed in general. When families were classified into "severe" and "mild" phenotypes based on cleft lip vs. cleft lip and palate or unilateral vs. bilateral cleft in the proband, no significant differences could be detected between the two types in the underlying genetic model.     

Genetic basis of tobacco smoking: strong association of a specific major histocompatibility complex haplotype on chromosome 6 with smoking behavior

The genetic basis for addiction to tobacco smoking--particularly that of the perception of olfactory stimuli that may be important in reinforcing smoking addiction--is largely unknown. A cluster of genes for olfactory receptors is in close proximity to the MHC region on chromosome 6. Polymorphisms of MHC class III genes (RCCX modules, TNFA promoter polymorphisms) were determined in 101 healthy subjects and 232 coronary artery disease (CAD) patients from Hungary with defined tobacco smoking habits. A highly significant association between ever smoking (past + current smokers) and a specific MHC haplotype was observed (odds ratios = 2.14-4.13; P-values = 0.012 to <0.001). This haplotype is characterized by the presence of C4A null alleles and a solitary short C4B gene linked to the TNF2 allele of the promoter for TNFA gene. This haplotype occurred more frequently in the ever smokers than in the never smokers [odds ratio: 4.97 (1.96-12.62); P = 0.001], and such associations were stronger in women (odds ratio = 13.6) than in men (odds ratio = 2.79). An independent study of complement C4 protein polymorphism and smoking habits in Icelandic subjects (n = 351) yielded similar and confirmative results. Considering the documented link between olfactory stimuli and smoking in females, and the presence of a cluster of odorant receptor genes close to the MHC class I region, our findings implicate a potential role of the MHC-linked olfactory receptor genes in the initiation of smoking.     

Immunocytochemical localization of zinc transporter 3 in the ependyma of the mouse spinal cord

We report, for the first time, the light microscopical and ultrastructural appearance of ZnT3-immunoreactivities in the ependymal cells of the central canal of the mouse spinal cord. Light microscopy revealed the presence of ZnT3-immunoreactive (Ir) ependymal cells in 1 microm thick epon sections stained by the ABC method. The ZnT3-Ir cells were observed at all levels of the spinal cord, but were a little more numerous in lumbosacral segments than in cervicothoracic segments. The ZnT3-Ir cells had large, ovoid nuclei with abundant cytoplasm, and protruded into the lumen of the central canal. Our ultrastructural findings suggest that the ZnT3-Ir ependymal cells possess secretory activity directed towards the central canal. We propose that they may play a role in the trans-ependymal mechanism responsible for zinc homeostasis between cerebrospinal fluid and the central area of the gray matter.     

Combined effects of inhaled nitric oxide and a recruitment maneuver in patients with acute respiratory distress syndrome

Nitric oxide (NO) inhalation therapy has been employed in the management of acute respiratory distress syndrome (ARDS), in order to improve oxygenation. Several factors have been implicated as being responsible for the action of inhaled NO. Alveolar recruitment methods, such as prone positioning and a sufficient positive end expiratory pressure (PEEP), have been identified as having a positive impact on the NO response. A Recruitment maneuver (RM) was introduced for the treatment of ARDS, along with a lung protective strategy. Here, we hypothesized that a RM may further augment the oxygenation of patients treated with NO inhalation. Therefore, the effects of the inhalation of NO, either in combination with a RM, or separately, were evaluated on patients with ARDS for their enhancing action. 23 patients with ARDS were enrolled, and divided into three groups. The patients in group 1 (n=11) were treated with 5 ppm NO via inhalation, followed by a RM, applying a sustained inflation pressure of 30 - 35 cmH2O for 30 seconds. Group 2 (n=6) received a RM alone, while group 3 (n=3) was treated with NO inhalation alone. The oxygenation and hemodynamic parameters were obtained prior to, and 2, 12, and 24 h after, the respective treatment procedures. For group 1, the PaO2/FiO2 increased from its initial value of 171.8 +/- 67.8 to 203.2 +/- 90.0 2 h after NO inhalation. Further improvement was noted with the continual application of the RM reaching, 215.5 +/- 74.6 (p=0.05) and 254.2 +/- 109.5 (p < 0.05), after 12 and 24 h, respectively. Initially 7 of the subjects did not respond to NO inhalation, but 3 of these non-responders changed into responders 12 h after the RM. The changes in the PaO2/FiO2 from baseline at each time period were greater in group 1 than in the other groups, but with no statistical significance. The hemodynamics of the patients was not significantly altered during the entire study period. We conclude that the combined application of NO inhalation and a RM could be beneficial and safe for patients with ARDS, showing an enhancing effect in improvement of oxygenation.     

Role of predicted transmembrane domains for type III translocation, pore formation, and signaling by the Yersinia pseudotuberculosis YopB protein

YopB is a 401-amino-acid protein that is secreted by a plasmid-encoded type III secretion system in pathogenic Yersinia species. YopB is required for Yersinia spp. to translocate across the host plasma membrane a set of secreted effector proteins that function to counteract immune signaling responses and to induce apoptosis. YopB contains two predicted transmembrane helices (residues 166 to 188 and 228 to 250) that are thought to insert into the host plasma membrane during translocation. YopB is also required for pore formation and host-cell-signaling responses to the type III machinery, and these functions of YopB may also require membrane insertion. To elucidate the importance of membrane insertion for YopB function, YopB proteins containing helix-disrupting double consecutive proline substitutions in the center of each transmembrane domain were constructed. Yersinia pseudotuberculosis strains expressing the mutant YopB proteins were used to infect macrophages or epithelial cells. Effector translocation, pore formation, and host-cell-signaling responses were studied. Introduction of helix-disrupting substitutions into the second transmembrane domain of YopB resulted in a nonfunctional protein that was not secreted by the type III machinery. Introduction of helix-disrupting substitutions into the first transmembrane domain of YopB resulted in a protein that was fully functional for secretion and for interaction with YopD, another component of the translocation machinery. However, the YopB protein with helix-disrupting substitutions in the first transmembrane domain was partially defective for translocation, pore formation, and signaling, suggesting that all three functions of YopB involve insertion into host membrane.     

Leukocyte apoptosis and its significance in sepsis and shock

Sepsis and multiple organ failure continue to be significant problems among trauma, burn, and the critically ill patient population. Thus, a number of laboratories have focused on understanding the role of altered apoptotic cell death in contributing to immune and organ dysfunction seen in sepsis and shock. Immune cells that undergo altered apoptotic changes include neutrophils, macrophages, dendritic cells, as well as various lymphocyte populations. Evidence of epithelial as well as endothelial cell apoptotic changes has also been reported. Although mediators such as steroids, tumor necrosis factor, nitric oxide, C5a, and Fas ligand (FasL) appear to contribute to the apoptotic changes, their effects are tissue- and cell population-selective. As inhibiting Fas-FasL signaling (e.g., gene deficiency, Fas fusion protein, or Fas short interfering RNA administration), caspase inhibition (caspase mimetic peptides), and/or the overexpression of downstream antiapoptotic molecules (e.g., Bcl-2, Akt) improve survival of septic mice, it not only demonstrates the pathological significance of this process but points to novel targets for the treatment of sepsis.