Interaction of monocytes with tumor cells coated with complement with or without antibody

Raji, a human B lymphoblastoid cell line has the ability to activate the complement cascade by alternate pathway mechanisms with subsequent fixation of C3 to receptors on the Raji cell membrane. Using this property, we examined the role that complement plays in mediating a cytolytic event between human peripheral blood monocytes and Raji cells coated with C3b, antibody, or both. Presence of C3 was confirmed by immune adherence. IgG bound to the Raji membrane was quantitated using I¹²⁵ Staphylococcal protein A assay. The presence of alternate pathway-activated C3 on Raji cells failed to produce monocyte-mediated cytotoxicity. These same target cells subsequently coated with antibody concentration ranging from 200 to >600,000 SPA molecules per Raji cell produced neither enhancement nor inhibition of antibody-dependent, cell-mediated cytotoxicity (ADCC). ADCC was enhanced by complement when complement activation and binding of C3 to the cell surface occurred by classical pathway mechanisms. ADCC of 32% ± 3.2 occurred with undiluted antiserum (625,000 SPA molecules bound/Raji cell) with enhancement to 52% ± 1.1 in the presence of C3. IgG inhibition of ADCC was unaffected by the presence of membrane-bound C3.     

疏血通联合氟伐他汀治疗糖尿病肾病的临床观察

目的:观察疏血通和氟伐他汀对糖尿病肾病(DN)患者的保护作用.方法:52例糖尿病肾痛患者,均为临床肾病期,随机分为两组,治疗组、对照组各26例,两组患者均予以糖尿病饮食、控制血糖和降血压等常规治疗.对照组疏血通注射液6ml/d静滴,1疗程为3周;治疗组在对照组的基础上加用氟伐他汀40mg每晚1次口服,治疗2月.于治疗前后分别检测血清肌酐(Scr)、24小时尿蛋白(24hUP)、低密度脂蛋白(LDL-C)、血浆脂蛋白-a[LP(a)]、C反应蛋白(CRP)等指标,并进行比较.结果:治疗后和治疗前比较,对照组24hUP、Scr明显降低(P<0.05),治疗组24hUP、Scr、LDL-C、LP(a)、CRP下降(P<0.01或0.05);治疗后3w及2months后,治疗组24hUP、Scr、LDL-C、LP(a)、CRP较对照组下降(P<0.05).结论:疏血通联合氟伐他汀治疗糖尿病肾病减轻尿蛋白、延缓 肾功能减退方面更加安全有效.     

Staining with Fluorescein Diacetate Correlates with Hepatocyte Function

To establish the importance of fluorescein diacetate (FDA) as a viability stain for cultured hepatocytes. we hypothesized that FDA staining would correlate positively with hepatocyte viability and function. Mixtures of live and dead cells were stained with FDA and scanned by flow cytometry. A close correlation was observed between the live cell fraction and percent viability as determined by FDA staining (R² = 0.962). Hepatocytes were also sorted into low fluorescence and high fluorescence groups. Both albumin production and lidocaine metabolism (P-450 activity) were significantly increased in the high fluorescence group compared to the low fluorescence group. An automated, fluorescence-activated assay was useful for rapid assessment of hepatocyte viability. In addition. the intensity of green fluorescence following staining with FDA correlated well with two specific measures of hepatocyte function.     

Effect of Pretreatment with Carbimazole in Patients with Thyrotoxicosis Subsequently Treated with Radioactive Iodine

Preliminary treatment with carbimazole in a series of 181 patients with thyrotoxicosis selected for treatment with radioactive iodine did not make any significant difference to the subsequent response to ¹³¹I therapy.     

Chronic pretreatment with methylphenidate induces cross-sensitization with amphetamine

Consequence of the long-term use of psychostimulants as treatment for attention deficit/hyperactivity disorder (ADHD) is unknown, particularly whether treatment with psychostimulants at an early age increases an individual's potential for cross-sensitization to other stimulants exposed at a later age. Cross-sensitization occurs when pretreatment with one stimulant leads to greater sensitivity to another stimulant. The aims of this study were to investigate whether chronic treatment with methylphenidate (MPD; Ritalin) in both juvenile and adult rats induced cross-sensitization to amphetamine at a later time and whether this cross-sensitization to amphetamine was age-dependent. Male Sprague-Dawley rats were randomly divided into four treatment groups: (1) group treated intraperitoneally (i.p.) with saline as juveniles and adults, (2) group treated with 0.6 mg/kg amphetamine, i.p., as juveniles and adults, (3) group treated with 2.5 mg/kg MPD, i.p., as juveniles and adults, and (4) group treated with saline, i.p., as juveniles and 2.5 mg/kg MPD, i.p., as adults. All of the animals received an amphetamine (0.6 mg/kg, i.p.) challenge on the last experimental day. We examined the effects of chronic MPD treatment in juvenile and adult rats on their locomotor response to an acute amphetamine exposure. Three different locomotor indices were studied using an automated activity monitoring system. Changes in the locomotor responses to amphetamine of these animals were compared to those of control rats that were pretreated with saline as juveniles and as adults. It was found that prior chronic treatment with MPD produced cross-sensitization to the locomotor response to amphetamine as observed in the horizontal activity and total distance traveled. It also appears that this cross-sensitization to amphetamine may not be dependent on the age of the subjects, i.e., whether subjects were juvenile or adult rats when they received drugs, but rather it depended on the behavioral index examined.     

Immunologic correction with immunoglobulin of toxemia with exicosis in infants with acute intestinal infections]

The clinical course of acute intestinal infections complicated by toxicosis and exicosis was studied in 150 infants undergoing multimodality therapy, including natural human immunoglobulin for intravenous injections. The use of the new complex in the treatment of intestinal toxicoses was accompanied by increasing host immunological reactivity within short periods and decreasing of the treatment duration by 5.0 +/- 1.3 days; there were no persisting and chronic forms of the diseases and fatal outcomes. It was concluded that the use of the immunoglobulin for intravenous injections in the multimodality therapy of intestinal toxicoses in infants made it possible to prevent death in complicated intestinal infections and at the same time to accelerate their recovery.     

Interactions of retinol with binding proteins: studies with retinol-binding protein and with transthyretin.

The interactions within the molecular complex in which retinol circulates in blood were studied. To monitor binding between retinol-binding protein (RBP) and transthyretin (TTR), TTR was labeled with a long-lived fluorescence probe (pyrene). Changes in the rotational volume of TTR following its association with RBP were monitored by fluorescence anisotropy of the probe. Titration of TTR with holo-RBP revealed the presence of 1.5 binding sites characterized by a dissociation constant Kd = 0.07 microM. At 0.15 M NaCl, binding of RBP to TTR showed an absolute requirement for the native ligand, retinol. At higher ionic strength (0.5 M NaCl), RBP complexed with retinal also bound to TTR with high affinity (Kd = 0.134 microM). RBP containing retinoic acid did not bind to TTR even at the high salt concentration. The data suggest that the TTR binding site on RBP is in close proximity to the retinoid binding site and that the head group of retinoic acid, when bound to RBP, presents steric hindrance for the interactions with TTR. The implications of the data for selectivity in retinoid transport in the circulation are discussed. The kinetics of the steps leading to complete dissociation of the retinol-RBP-TTR complex was also studied. The first step of this process was dissociation of retinol, which had a rate constant of 0.06/min. Following loss of retinol, the two proteins dissociate. The rate of dissociation is slow (k = 0.055/h), however, indicating that the complex apo-RBP-TTR will be an important factor in regulating serum levels of retinol.