Prevention of leukocyte migration to inflamed skin with a novel fluorosugar modifier of cutaneous lymphocyte-associated antigen

E-selectin and P-selectin on dermal postcapillary venules play critical roles in the migration of effector T cells into inflamed skin. P-selectin glycoprotein ligand-1 (PSGL-1) modified by alpha1,3-fucosyltransferase is the principal selectin ligand on skin-homing T cells and is required for effector T cell entry into inflamed skin. We have previously shown that a fluorinated analog of N-acetylglucosamine peracetylated-4-fluorinated-d-glucosamine (4-F-GlcNAc), inhibits selectin ligand expression on human T cell PSGL-1. To analyze 4-F-GlcNAc efficacy in dampening effector T cell migration to inflamed skin, we elicited allergic contact hypersensitivity (CHS) reactions in mice treated with 4-F-GlcNAc. We also investigated 4-F-GlcNAc efficacy on lymphocyte E-selectin ligand expression in LNs draining antigen-sensitized skin and on other immunological processes requisite for CHS responses. Our results showed that 4-F-GlcNAc treatment attenuated lymphocyte E-selectin ligand expression in skin-draining LNs and prevented CHS reactions. Significant reductions in inflammatory lymphocytic infiltrate were observed, while pathways related to antigenic processing and presentation and naive T cell recognition within skin-draining LNs were unaffected. These data indicate that 4-F-GlcNAc prevents CHS by inhibiting selectin ligand activity and the capacity of effector T cells to enter antigen-challenged skin without affecting the afferent phase of CHS.     

von Willebrand disease "Vicenza" with larger-than-normal (supranormal) von Willebrand factor multimers

When normal volunteers or patients with type I von Willebrand disease (VWD) are given desmopressin (DDAVP), a set of larger-than-normal (supranormal) von Willebrand factor (VWF) multimers, similar to those present in VWF-containing cells such as platelets megakaryocytes and endothelial cells, appear transiently in postinfusion plasma. In two kindreds with mild lifelong bleeding symptoms transmitted as an autosomal dominant trait, all ten symptomatic members (but none of the five asymptomatic members) had a supranormal multimeric structure for plasma VWF, apparently identical to that seen for postdesmopressin normal plasma. Plasma factor VIII coagulant activity (VIII:C), VWF antigen (VWF:Ag), ristocetin-induced platelet agglutination, and ristocetin cofactor (RiCof) activity were low. Platelet VWF:Ag and RiCof levels (tested for three patients only) were normal. Bleeding times were normal or slightly prolonged. The patients' platelet multimeric structure was the same as that for normal platelets. After desmopressin infusion the plasma VWF multimeric structure remained supranormal as for preinfusion plasma, with VIII:C VWF:Ag and RiCof increasing markedly over baseline values and disappearing at a normal rate. Examination of the VWF subunit composition from three of these patients indicated that proteolytic processing of their VWF did not differ from normal. This study describes the first variant of VWD with a supranormal multimeric structure.     

Differential induction of intercellular adhesion molecule-1 in human skin by recombinant cytokines

We examine the effects of the recombinant epidermal cytokines interleukin 1α (IL-1α), interleukin 1β (IL-1β), interleukin 3 (IL-3), interleukin 6 (IL-6), granulocyte-macrophage colony stimulating factor (GM-CSF), macrophage colony stimulating factor (M-CSF), tumor necrosis factor alpha (TNF), and the effect of the lymphokine gamma interferon (γ-IFN) on the expression of ICAM-1 in short term organ cultures of newborn human foreskins. In normal skin, ICAM-1 was detected immunohistochemically exclusively on endothelial cells. In addition to enhanced ICAM-1 expression by endothelial cells (at 1 h) and keratinocytes (by 6 h) exposed to γ-IFN, increased endothelial cell expression also resulted at 24 h after exposure to IL-6 and GM-CSF and at 48 h to M-CSF. Dermal dendritic cell reactivity for ICAM-1 was observed at 24 h after supplementation with IL-1α, IL-1β and IL-6, and at 48 h with GM-CSF and M-CSF. Incubation with culture medium alone or with IL-3 resulted in no change in baseline ICAM-1 expression on any cell type, and incubation with TNF resulted in enhanced ICAM-1 expression only by endothelial cells. Thus, in skin explains (as opposed to isolated cell in culture), ICAM-1 is induced on various cell types by a wide range of epidermal cytokines, including IL-6, GM-CSF, M-CSF, IL-1α and IL-1β Endogenous production and release of these cytokines which may stimulate adhesion molecule expression directly or indirectly may govern lymphoid adhesion to specific dermal as well as epidermal types of skin cells under physiologic and pathologic conditions.     

NEONATAL OUTCOME IN MECONIUM STAINED DELIVERIES — A PROSPECTIVE STUDY

This prospective study analyzes the neonatal outcome in deliveries complicated by meconium stained amniotic fluid. In a study of 1000 live born deliveries, meconium staining of amniotic fluid was seen in 50 (5%) deliveries. Out of these, 20 newborns (40%) developed classical signs of meconium aspiration syndrome and were managed according to a predetermined protocol. Multiparity, term deliveries, use of sedatives in mother, intrauterine growth retardation and prolonged labour were some of the risk factors for development of meconium aspiration syndrome in newborns. This study highlights the need for review of management protocol in newborns after meconium staining of the amniotic fluid, including the use of prophylactic antibiotics.KEY WORDS: Amniotic fluid, Delivery, Meconium aspiration, Respiratory distress syndrome     

Sample size requirements for interval estimation of the odds ratio

Sample sizes are calculated for unmatched case-control (or cohort) studies where the goal is interval estimation of the odds ratio. The procedure used gives the smallest sample size for which a 100(1-alpha)% confidence interval for the log odds ratio will not exceed a specified width with specified probability (1-gamma). Tables of sample sizes for various choices of parameter values are presented. Considerable disagreement is found with a published method which has as its basis expected cell counts.     

用电化学检测器的高效液相色谱法测定血清及尿中速尿的含量

本文报告了用电化学检测器的高效液相色谱法测定血清及尿中速尿含量的方法。样品予处理方法:血清用乙腈除蛋白,尿用蒸馏水稀释50倍。采用作者合成的FD-Val-OH作为内标物。色谱条件为:反相柱,以含35%乙醇的5mmol/L四丁基铵水溶液为流动相(pH7.50),流速1.0ml/min;用电化学检测器,检测电压0.90V:速尿及内标物的保留时间分别为10和15min。通过计算速尿对内标物的峰高比求得速尿含量。血清及尿中的最低检测浓度分别为16和9ng/ml。标准曲线在0.25～5ng/μl(血清)、0.5～10ng/μl(尿)的浓度范围内呈线性关系。血清及尿中回收率分别为100.5%和100.6%。变异系数在4.6%以下。     

The metabolism of N-nitrosobis(2-oxopropyl)amine by microsomes and hepatocytes from Fischer 344 rats

The metabolism of N-nitrosobis(2-oxopropyi)amine (BOP) was examinedin microsomes from uninduced F-344 rats. Even when the conditionswere varied, no metabolism of this compound was detected. Onthe other hand, freshly isolated hepatocytes from F-344 ratsmetabolized BOP efficiently to CO₂. The kinetics of conversionshowed there were at least two components. The high affinitycomponent had a K_m of 0.13 mM while the lower had a K_m of 1.3mM. As products of the metabolism, N-nitroso{2-hydroxypropyl)(2-oxopropyl)-amine(HPOP) and N-iutrosobis(2-hydroxypropyl)amine (BHP) were foundwhereas little acetol and no N-nitroso-methyl-2-oxopropylamine(MOP) were detected.