MAdCAM-1 dependent colonization of developing lymph nodes involves a unique subset of CD4+CD3- hematolymphoid cells

During fetal lymph node organogenesis in mice, lymph node postcapillary high endothelial venules briefly express the Peyer's patch addressin MAdCAM-1. This allows initial seeding by two unusual lymphocyte populations selectively expressing the Peyer's patch homing receptor integrin alpha4beta 7: CD4+CD3- oligolineage progenitors and TCR gammadelta+ T cells. It was found that the CD4+CD3- cells are lineage-restricted progenitors that express surface lymphotoxin-beta (LTbeta) and the chemokine receptor BLR1. They can differentiate into natural killer cells, dendritic antigen-presenting cells, and follicular cells of unknown outcome, but these cells do not become T or B lymphocytes. In addition to LN, CD4+CD3- cells can also be found in fetal spleen starting at 13.5 dpc, while absent from fetal liver. In view of the necessity of lymphotoxin in lymphoid organ development, it is thought that the novel subset of CD4+CD3- LTbeta+ fetal cells is instrumental in the development of lymphoid tissue architecture.     

Ergosteroids III. Syntheses and biological activity of seco-steroids related to dehydroepiandrosterone

The unusual activity of some D-ring-seco estrogens led us to prepare several seco steroids related to dehydroepiandrosterone (DHEA) and to test for their ability to mimic thyroid hormone and 7-oxo-DHEA (1) as inducers of thermogenic enzymes in rats' livers. Only one, 3 beta-acetoxy-17a-oxa-androst-5-ene-7,17-dione (17), was capable of inducing both mitochondrial glycerophosphate dehydrogenase and malic enzyme. The closely related 3 beta-hydroxy-17a-oxa-androsta-5,15-diene-7,17-diones (both 14 alpha and 14 beta, 14 and 15) induce the formation of malic enzyme but not of glycerophosphate dehydrogenase. The 3 beta-propionyl ester of the above 14 alpha steroid was not active, presumably because it was not deacylated in vivo. The 16,17 dicarboxylic acid (9) produced by opening the D-ring also induced the formation of malic enzyme but not of glycerophosphate dehydrogenase. 3 beta-Acetoxyandrost-5-ene-7,16,17-trione, an intermediate in the synthesis of D-ring seco compounds enhanced the formation of both enzymes. Twelve other D-ring seco compounds were not active. Seco androstanes oxygenated at position 7 and with expanded A or B rings were not active.     

Role of the active-site carboxylate in dihydrofolate reductase: kinetic and spectroscopic studies of the aspartate 26-->asparagine mutant of the Lactobacillus casei enzyme

A mutant of Lactobacillus casei dihydrofolate reductase, D26N, in which the active site aspartic acid residue has been replaced by asparagine by oligonucleotide-directed mutagenesis has been studied by NMR and optical spectroscopy and its kinetic behavior characterized in detail. On the basis of comparisons of a large number of chemical shifts and NOEs, it is clear that there are only very slight structural differences between the methotrexate complexes of the wild-type and mutant enzymes and that these are restricted to the immediate environment of the substitution. The data suggest a slight difference in orientation of the pteridine ring in the binding site in the mutant enzyme. Both NMR and UV spectroscopy show that methotrexate is protonated on N1 when bound to the wild-type enzyme but not when bound to the mutant. Binding constant measurements by fluorescence quenching and steady-state kinetic measurements of dihydrofolate (FH2) and folate reduction show that the substitution has little or no effect on substrate, coenzyme, and inhibitor binding (< 7-fold increase in Kd) and only a modest effect on kcat (up to a factor of 9 for FH2 and 25 for folate) and kcat/KM (up to a factor of 13 for FH2 and 14 for folate). Measurements of deuterium isotope effects and direct measurements of hydride ion transfer and product release by stopped-flow methods revealed that for the mutant enzyme hydride ion transfer is rate-limiting across the pH range 5-8. This allowed a direct comparison of the rate of hydride ion transfer in the wild-type and mutant enzymes; the asparagine substitution was found to decrease this rate by 62-fold at pH 5.5 and 9-fold at pH 7.5. This effect is much smaller than that seen for the corresponding mutant of Escherichia coli dihydrofolate reductase [Howell, E. E., Villafranca, J. E., Warren, M. S., Oatley, S. J., & Kraut, J. (1986) Science 231, 1123-1128], estimated as a 1000-fold decrease in the rate of hydride ion transfer. The change in pH dependence of kcat resulting from the substitution is consistent with, but does not prove, the idea that the group of pK 6.0 which must be protonated for hydride ion transfer to occur is Asp26. For folate reduction, the pH dependence of kcat is determined by two pKs, one of which, pK 5, disappears in the mutant enzyme, suggesting that it may correspond to ionization of Asp26.(ABSTRACT TRUNCATED AT 400 WORDS)     

一个为GIS提供分布定位数据的CORBA结构

CORBA规范为应用提供了可互操作性和分布功能。利用CORBA技术 ,结合GPS无线设备 ,设计并实现了一个为GIS提供全球实时定位数据的面向对象的分布式CORBA结构     

The effect of a lyophilized extract of the mucosa of the proximal small intestine on kidney water- and salt-excretory functions in rats

Experiments on Wistar rats injected intragastrically deionized water (1 % of the body weight) and intra-abdominally 0.1 mg/kg of the lyophilized water extract (LWE) from the thin intestine have shown that under these conditions diuresis and excretion of K+ with the urine increase and retention of Na+ excretion decreases. After intragastric injection of isotonic NaCl solution, the LWE has exerted only the K-excretion effect. An increase in the LWE doses from 1 to 10 mg/kg has weakened all these reactions. It has been found in experiments in vitro that the LWE has exerted an activatory dose-dependent effect on Na, K-ATPase from the kidney cortex cells.     

Effect of non-random missing data mechanisms in clinical trials

A simple form of non-ignorable missing data mechanisms based on two parameters is used to characterize the amount of missing data and the severity of non-randomness in clinical trials. Based on the formulation, the effect of non-randomly missing data on simple analyses which ignore the missing data is studied for binary and normally distributed response variables. In general, the effect of the non-randomly missing data on the bias and the power increases with the severity of non-randomness. The bias can be positive or negative and the power can be less than or greater than when the data are missing at random. The results of the analysis, ignoring the missing data, can be seriously flawed if the non-randomness is severe, even when only a small proportion of the sample is missing. The problem is more pronounced in the case of normally distributed response variables with unequal variances.     

Guiding occlusal development with functional appliances

In 24 patients with bacterial pneumonia, reliability of the samples routinely taken for etiologic diagnosis (sputum, throat swab, bronchial brushing, bronchoalveolar lavage fluid--BALF, blood, pleural fluid) was determined. Organisms detected in blood, pleural fluid, transbronchial biopsy (TBB) or percutaneous transthoracic needle aspiration biopsy (PTNAB) samples were considered as truly causative, whereas those isolated in at least two various samples from a single patient were considered as presumably causative. Most sensitive diagnostic samples were BALF, TBB and PTNAB (100% each). However, the specificity of BALF was very low (17%). Bronchial aspirate was highly sensitive (95%) but not specific (14%). Bronchial brushing was sensitive (86%) but its specificity low (14%). Sputum was hardly sensitive (40%) and had no specificity. Throat swab had virtually no diagnostic value because of its low sensitivity (10.5%) and specificity (50%).     

Solution nonideality related to solute molecular characteristics of amino acids

By measuring the freezing-point depression for dilute, aqueous solutions of all water-soluble amino acids, we test the hypothesis that nonideality in aqueous solutions is due to solute-induced water structuring near hydrophobic surfaces and solute-induced water destructuring in the dipolar electric fields generated by the solute. Nonideality is expressed with a single solute/solvent interaction parameter I, calculated from experimental measure of delta T. A related parameter, I(n), gives a method of directly relating solute characteristics to solute-induced water structuring or destructuring. I(n)-values correlate directly with hydrophobic surface area and inversely with dipolar strength. By comparing the nonideality of amino acids with progressively larger hydrophobic side chains, structuring is shown to increase with hydrophobic surface area at a rate of one perturbed water molecule per 8.8 square angstroms, implying monolayer coverage. Destructuring is attributed to dielectric realignment as described by the Debye-Hückel theory, but with a constant separation of charges in the amino-carboxyl dipole. By using dimers and trimers of glycine and alanine, this destructuring is shown to increase with increasing dipole strength using increased separation of fixed dipolar charges. The capacity to predict nonideal solution behavior on the basis of amino acid characteristics will permit prediction of free energy of transfer to water, which may help predict the energetics of folding and unfolding of proteins based on the characteristics of constituent amino acids.     

The dynamics of cardiac vagal sinus arrhythmia in cats under the action of met-enkephalin

When stimulating the peripheral and of the right n. vagus in anesthetised cats, the sinus arrhythmia occurred in case the vagal bursts were beyond the limits of the controlled bradycardia range. I. v. administration of met-enkephaline suppressed the arrhythmia immediately but the latter reappeared within 15-20 minutes. The data obtained suggests a biphasic effect of met-enkephaline upon the vagal sinus arrhythmia.