可溶性细胞间粘附分子-1在妊娠期高血压疾病中的作用

目的:探讨可溶性细胞间粘附分子-1在妊娠期高血压疾病患者血浆中的变化,为临床诊治提供依据。方法:用ELISA法检测29例妊娠期高血压疾病患者血浆中可溶性细胞间粘附分子-1水平,并与正常妊娠组和正常对照组进行组间比较。结果:子痫前期组、妊娠期高血压组、正常妊娠组晚期及正常对照组的可溶性细胞间粘附分子-1水平分别为1129.82±399.16、794.35±255.57、661.51±301.79及549.23±139.98ng/ml。组间比较,子痫前期组与妊娠期高血压组之间P<0.05,与正常妊娠组晚期及正常对照组之间P<0.001;妊娠期高血压组与正常对照组之间P<0.001;妊娠期高血压组与正常妊娠组晚期相比P>0.05,正常妊娠组3个不同孕龄阶段P>0.05。结论:可溶性细胞间粘附分子-1在妊娠期高血压疾病时显著升高,并随病情的加重而增高,可作为该病诊断和监控的一项指标。     

Comparison of salivary calmodulin binding proteins in Sjögren''s syndrome and healthy individuals

Background: Reduction in salivary secretion is the hallmark of Sjögren's syndrome (SS). Calmodulin (CaM) and calmodulin binding proteins (CaMBPs) play a key role in the secretory process of saliva. Recent studies have suggested that SS‐B, an autoantibody associated with SS, is a CaMBP. This finding suggests that CaMBP may contribute to the loss of saliva in SS. To better understand the role(s) of these proteins in SS, the purpose of this study was to compare salivary CaMBPs in Sjögren's patients and controls. Methods: Saliva samples were collected from 20 patients and 20 age‐, race‐, and gender‐matched controls. CaM overlay was used to identify CaMBPs in saliva of patients and controls. Results: Higher number of salivary CaMBPs was observed among patients than controls. Conclusions: The increased number of salivary CaMBPs in SS may suggest a potential role for these proteins in the pathogenesis of the disease.     

胃癌病人NK细胞活性变化机理的初步研究

应用~(51)Cr释放试验和效靶结合试验,同时测定了正常人和胃癌病人外周血NK细胞活性与靶结合细胞数(TBC),研究了正常人及病人血浆对NK细胞功能的影响。发现正常人NK细胞活性与靶结合细胞数之间的关系呈直线正相关,但在NK活性降低的病人中靶结合细胞数却无明显改变,二者无相关性,而病人的血浆对正常人外周血NK活性则有明显的抑制作用(P<0.05),且抑制率与胃癌人NK细胞活性存有着负相关的关系,提示胃癌病人血浆具有抑制NK细胞活性的物质。     

Drug-Biomacromolecule Interaction XII: Comparative binding study of sulfaethidole to bovine serum albumin by equilibrium dialysis,fluorescence probe technique,uv difference spectrophotometry and circular dichroism

Binding of sulfaethidole to bovine serum albumin was studied by equilibrium dialysis, fluorescence probe technique, uv difference spectrophotometry and circular dichroism. Equilibrium dialysis method enabled us to estimate the total number of drug binding sites of albumin molecule. For sulfaethidole, albumin had 6 primary and 40 secondary binding sites. The primary and secondary binding constants were 0.9×10⁵ M⁻¹ and 0.2×10⁶ M⁻¹, respectively. 1-Anilino-8-naphthalenesulfonate (ANS) and 2-(4′-hydroxylbenzeneazo)-benzoic acid (HBAB) were used as the fluorescence probe and the uv spectrophotometric probe, respectively. In fluorescence probe technique, results indicated that the number of higher affinity drug binding site of albumin was 1 and the number of lower affinity drug binding sites of albumin was 3, and the primary and secondary drug binding constants for bovine serum albumin were 2.15×10⁵ M⁻¹ and 1.04×10⁵ M⁻¹, respectively. In uv difference spectrophotometry, binding sites were 3 and binding constant was 1.88×10⁵ M⁻¹. The above results suggest that several different methods should be used in ompensation for insufficient information about drug binding to albumin molecule given by only one method.     

Pharmacological properties of the norepinephrine-induced depolarization of astrocytes in primary culture: evidence for the involvement of an α1-adrenergic receptor

The membrane potentials of astrocytes in primary cultures prepared from neonatal rat cerebral cortices were depolarized by (−)-norepinephrine. The average first response to 10⁻⁵ M (−)-norepinephrine was 24 mV from an average resting potential of −68 mV, and the average for the second response was 14 mV. Thus this process showed marked desensitization. The response was attributed to an activation of an α₁-receptor since it was about 1000 times more sensitive to inhibition by prazosin than to yohimbine or idazoxan. In addition, depolarization was seen to the application of 10⁻⁵ M phenylephrine.     

Axonal transport of dopamine D1 receptors in the rat brain

Binding of a specific dopamine D₁ receptor antagonist,¹²⁵I-SCH 23982, was measured in rat brain sections by quantitative autoradiography at various time intervals, following a knife cut through the striatonigral pathway. Twenty-four hours after lesioning, accumulations of D₁ receptor binding sites were found in sagittal sections both rostral and caudal to the lesion site. No other regions studied (caudate-putamen, nucleus accumbens, olfactory tubercle, and substantia nigra pars reticulata) showed any change in D₁ receptor binding 24h after the lesion. In brain sections obtained 10 days after lesioning, only the substantia nigra pars reticulata had a significant decrease in D₁ receptors ipsilateral to the lesion. These findings suggest the possibility of a presence of bidirectional axonal transport of D₁ receptors in rat striatonigral pathway.     

Influence of continuous infusion of interleukin-1 alpha on the core protein and the core protein fragments of the small proteoglycan decorin in cartilage.

Decorin, a collagen-binding small proteoglycan, is considered to have a specific function in the organization or stability of the collagen network. Therefore, alteration of its molecular properties may be of pathophysiological relevance during the development of cartilage damage. It is shown here that normal cartilage from rabbit knee-joint contains glycosaminoglycan chain-bearing core protein fragments of 39, 23, and 18 kDa, each one amounting to approximately 5-6% of the intact decorin core protein. Continuous infusion of human recombinant interleukin-1 alpha for 14 days (200 ng/day) into a knee-joint led in condylar cartilage to a reduction in the amount of intact core protein from 2 micrograms/mg wet tissue to about 1.1 micrograms/mg. The increase in its quantity found after infusion of heat-inactivated interleukin-1 was not statistically significant. The concentration of all three core protein fragments became reduced to a similar extent as the intact core protein under the influence of the cytokine, and additional fragments were not found. Surprisingly, there was a much smaller response to interleukin-1-treatment in patellar cartilage.     

The effects of A 5-HT1A receptor agonist and antagonist on the 5-hydroxytryptamine release in the central nucleus of the amygdala: a microdialysis study with flesinoxan and WAY 100635

The modulation of extracellular 5-hydroxytryptamine (5-HT) in the central nucleus of the amygdala (CeA) by 5-HT_1A receptors was studied by intracerebral microdialysis in awake and freely moving rats. Local administration of 1 μM tetrodotoxin (TTX), 60 mM K⁺ and perfusion with Ca²⁺-free Ringer containing EGTA confirmed that the major part of dialysate 5-HT levels from the CeA is of neuronal origin. Administration of 300 nM of RU 24969, a 5-HT_1B receptor agonist, through the probe into the CeA decreased dialysate 5-HT levels to 67.2% of the baseline value. Systemic administration of the 5-HT_1A receptor agonists 8-OH-DPAT and flesinoxan dose-dependently decreased 5-HT levels in the CeA. The effect of 0.3 mg/kg of flesinoxan could be completely antagonized by systemic administration of 0.05 mg/kg WAY 100635, a 5-HT_1A receptor antagonist. WAY 100635 alone had only minimal effects at this dose. These data show that a major part of the extracellular 5-HT in the CeA stems from 5-HT neurons and that the amount of 5-HT released into this brain region can be modulated by 5-HT_1A receptors. Received: 11 September 1996 / Accepted: 25 November 1996     

Cytoprotective effect of epidermal growth factor on acid- and pepsininduced damage to rat gastric epithelial cells: Roles of Na+/H+ exchangers

We have previously established a cell damage model, with damage induced by either acid or pepsin treatment for 30 min, involving a rat gastric epithelial cell line (RGM1). In the present study, pretreatment of cells with epidermal growth factor (EGF; 0.1–10ng/mL) or sucralfate (0.1–3 mg/mL) for 4 h prevented such cell damage in a concentration-dependent manner. Protection of cells by these drugs was not affected by pretreatment with indomethacin (10⁻⁵ mol/L) for 4 h. Removal of Na⁻, but not Ca²⁺, from the acidified medium totally abolished the inhibitory effect of EGF, but not that of sucralfate. Genistein (a tyrosine kinase inhibitor) apparently reduced the inhibitory effect of EGF. DNA synthesis by RGM1 cells did not increase when cells were incubated with EGF for 4 h. We conclude that both EGF and sucralfate protect RGM1 cells from acid- and pepsin-induced damage and that the mechanism of protection by EGF against acid-induced damage seems to be via activation of Na⁺/H⁺ exchangers.     

Anti-inflammatory effect of β2-agonists: Inhibition of TNF-α release from human mast cells

β₂-Agonists inhibit the release of preformed mediators such as histamine and newly synthesized mediators such as prostaglandin D₂ from mast cells. However, although mast cells have been identified as an important source of several cytokines including tumor necrosis factor-α (TNF-α), there is no information about their regulation by β₂-agonists. Thus given the importance of TNF-α in inflammation and the widespread use of β₂-agonists, we investigated the effect of long-acting (salmeterol) and short-acting (salbutamol) β₂-agonists on the secretion of TNF-α from human skin mast cells. Treatment of mast cells with salmeterol or salbutamol (100 nmol/L) inhibited the IgE-dependent release of TNF-α (82% and 74%, respectively). Moreover, 2-hour treatment with salmeterol, isoproterenol, or salbutamol inhibited mast cell cytotoxicity against a TNF-α–sensitive cell line, WEHI-164, with an IC₅₀ of 71, 50, and 29 nmol/L, respectively. Specificity for β-adrenergic receptors was shown with propranolol. The inhibitory effect of β₂-agonists was observed after only 20 minutes of treatment but was lost by 24 hours after removal of salbutamol and isoproterenol (7% and 11% inhibition remaining, respectively). In contrast, the inhibition of TNF-α release was increased 1 hour after removal of salmeterol and remained significant 24 hours later. Furthermore, β₂-agonists did not show tachyphylaxis for the inhibition of TNF-α release. Thus selective β₂-agonists demonstrate anti-inflammatory activity by inhibiting the release of TNF-α from mast cells stimulated through their IgE receptor or by a tumor target cell. This inhibitory effect of β-agonists may be important in their mode of action in the treatment of allergic diseases. (J Allergy Clin Immunol 1997;100:825-31.)