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The counterclockwise coiling of the intestines is initiated by a leftward tilt of the primitive gut tube, imparted by left-right asymmetries in the architecture of the dorsal mesentery. In silico analysis suggests that this is achieved by synergistic changes in its epithelium and mesenchyme. Within the mesenchymal compartment, cells are more densely packed on the left than on the right. In silico results indicate that this property can result from asymmetries in both extracellular matrix (ECM) and cell:cell adhesion. We find that the dorsal mesentery ECM is indeed left-right asymmetric and moreover that the adhesion molecule N-cadherin is expressed exclusively on the left side. These asymmetries are regulated by the asymmetrically expressed transcription factors Pitx2 and Isl1. Functional studies demonstrate that N-cadherin acts upstream of the changes in the ECM and is both necessary and sufficient to explain the asymmetric packing of the mesenchymal cells. left-right asymmetry | N-cadherin | dorsal mesentery | hyaluronic acid | in silico modeling

Mathematical models have predicted the existence of P[o.sub.2] gradients between erythrocytes in capillaries in the usual case where plasma contributes substantial resistance to oxygen diffusion. According to theoretical predictions, these gradients could be detected as rapid P[o.sub.2] fluctuations (erythrocyte-associated transients, EATs) along the capillary. However, verification of a model and correct choice of its parameters can be made only on the basis of direct experimental measurements. We used phosphorescence quenching microscopy to measure P[o.sub.2] in 52 capillaries of rat mesentery to obtain plasma P[o.sub.2] values 100 times/s at a given point along a capillary. A 532-nm laser generated 10-[micro]s pulses of light, concentrated by a x 100 objective, onto a spot 0.9 [micro]m in diameter. The presence of erythrocytes in the excitation region was detected on the basis of phosphorescence amplitude (PA), proportional to the amount of plasma encountered by the laser beam, and on the basis of the intensity of transmitted laser light (LT), detected by a photodiode placed under the capillary. The data revealed correlated waveforms in PA, LT, and P[o.sub.2] in capillaries. The magnitude of the P[o.sub.2] gradients between erythrocytes and plasma was correlated with average capillary P[o.sub.2]. EATs in P[o.sub.2] were more readily detected in capillaries with relatively low oxygenation. The correlation coefficients between PA and P[o.sub.2] for the half of the capillaries (n = 26) below the median P[o.sub.2] (mean P[o.sub.2] = 17 mmHg; R = -0.72) was higher than that for the other half (mean P[o.sub.2] = 39 mmHg; R = -0.38). These results support the theoretical predictions of EATs and plasma P[o.sub.2] gradients in capillaries. microcirculation; red blood cells; oxygen transport; oxygen tension gradients; phosphorescence quenching microscopy

Rats were used in an experiment to identify the signal transduction pathways that are activated by angiotensin II (ANG II) and thromboxane A2 (TxA2) in the mesenteric circulation and to determine their impact for each agonist. Results showed that the major mediators of the vasoconstrictor effect of ANG II in mesenteric circulation are the increase in intracellular Ca2+ and the activation of protein kinase C. However, these mediators play a small role for the effects of TxA2.

One of the most important functions of the blood circulation is [O.sub.2] delivery to the tissue. This process occurs primarily in microvessels that also regulate blood flow and are the site of many metabolic processes that require [O.sub.2]. We measured the intraluminal and perivascular p[O.sub.2] in rat mesenteric arterioles in vivo by using noninvasive phosphorescence quenching microscopy. From these measurements, we calculated the rate at which [O.sub.2] diffuses out of microvessels from the blood. The rate of [O.sub.2] efflux and the [O.sub.2] gradients found in the immediate vicinity of arterioles indicate the presence of a large [O.sub.2] sink at the interface between blood and tissue, a region that includes smooth muscle and endothelium. Mass balance analyses show that the loss of [O.sub.2] from the arterioles in this vascular bed primarily is caused by [O.sub.2] consumption in the microvascular wall. The high metabolic rate of the vessel wall relative to parenchymal tissue in the rat mesentery suggests that in addition to serving as a conduit for the delivery of [O.sub.2] the microvasculature has other functions that require a significant amount of [O.sub.2].

A physiological model has been established to define flow elevation in rat mesenteric vasculature. Research indicates that endothelial cell hyperplasia and smooth muscle are involved in the flow induction process. Experiments using male Wistar rat ileal arteries with arterial ligations and medial wall hypertrophy are described. The flow model is illustrated.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the human digestive tract, but their molecular etiology and cellular origin are unknown. Sequencing of c-kit complementary DNA, which encodes a proto-oncogenic receptor tyrosine kinase (KIT), from five GISTs revealed mutations in the region between the transmembrane and tyrosine kinase domains. All of the corresponding mutant KIT proteins were constitutely activated without the KIT ligand, stem cell factor (SCF). Stable transfection of the mutant c-kit complementary DNAs induced malignant transformation of Ba/F3 murine lymphoid cells, suggesting that the mutations contribute to tumor development. GISTs may originate from the interstitial cells of Cajal (ICCs) because the development of ICCs is dependent on the SCF-KIT interaction and because, like GISTs, these cells express both KIT and CD34., The c-kit proto-oncogene encodes a type III receptor tyrosine kinase (KIT) (1), the ligand of which is SCF (2), SCF-KIT interaction is essential for development of melanocytes, erythrocytes, germ cells, [...]

Research was conducted to study the mode of action of mesentericin Y105, a bacteriocin bactericidal agent against Listeria monocytogenes using a genetic approach. A recombinant plasmid was utilized to transform Escherichia coli DH5-alpha while a new chromosomal mutant was determined by plasmid insertion in rpoN. Results showed that transposon insertions leading to mesentericin resistance interrupt gene encoding putative proteins involved in different metabolic pathways.

The role of the chondroitin-dermatan sulfate-containing proteoglycans in the contractile and elastic properties of small resistance arteries from rat mesentery was examined. Functional and mechanical tests on resistance-sized mesenteric arteries were carried out. Results of the experiments revealed that significant alterations in myogenic behavior are associated with changes in passive mechanics. These alterations are caused by stress transfers between cells and collagen fibrils.

Experiment was conducted to examine the relationship between intestinal ischemia-reperfusion and cytokine release in rat models of hemorrhagic or endotoxic shock. An assessment of the plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6, lactate and endotoxin and macrophage TNF-alpha and IL-6 mRNA expression was made at the end of shock and resuscitation. Results indicate that intestinal ischemia-reperfusion upon hemorrhage and resuscitation may be a major trigger for cytokine gene expression in the absence of endotoxin.

Experimental studies indicate that variations in calcium concentration or aging do not influence the contractile response of the human mesenteric artery to physiological vasoconstrictors. The reduction of extracellular ionized calcium does not inhibit contraction to U46619, a thromboxane analogue, while the contraction to noradrenaline is only slightly affected.