Antiproliferative activity of a humanized anti-CD74 monoclonal antibody, hLL1, on B-cell malignancies

The humanized anti-CD74 monoclonal antibody (mAb) hLL1 is under evaluation as a therapeutic agent. The effects of hLL1-at times in comparison with the CD20 mAb rituximab-were assessed on non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) cell lines and in tumor-bearing SCID mice. In vitro, hLL1 caused growth inhibition and induction of apoptosis in B-cell lines when cross-linked with an antihuman immunoglobulin G (IgG) second antibody. The sensitivity profile of the cell lines was different for hLL1 and rituximab, and antiproliferative activity was augmented when the 2 mAbs were combined. Unlike rituximab, hLL1 did not induce antibody-dependent cellular cytotoxicity or complement-mediated cytotoxicity. In xenograft models of NHL and MM, treatment with hLL1 yielded significant survival benefits without cross-linking agents. Efficacy was greater in the MM model, in which median survival time was increased more than 4.5-fold. Thus, hLL1 has therapeutic potential as a naked mAb for B-cell malignancies because of high antigen expression on malignant cells, specifically MM, with limited expression on normal tissue, and because of its antiproliferative activity. Further, hLL1 may be a therapeutic candidate for rituximab-resistant disease because the 2 antibodies apparently act through distinct mechanisms and exhibit different expression and sensitivity profiles, and activity can be augmented when the mAbs are combined.     

Regulatory effect of sense line diet on cholesterol and body weight in mice fed a high-fat diet

BACKGROUND/AIMS: Sense line diet (SLD) is a newly developed dietary functional food that is composed of a lot of herbs. The function of SLD is to help control weight. Although it is reported that each herb has effects on lipid metabolism and obesity, these effects are not the same as SLD. The aim of this study was therefore to investigate whether SLD combined with high fat (HF) diet can influence body weight and fat accumulation. METHODS: An experiment was conducted with 40 C57BL/6J mice with an initial body weight of about 16 g. Body weight was recorded every week, plasma levels of triglyceride, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol were analyzed at the end of the study. RESULTS: Weight increases in the 10 or 20% SLD group were significantly less than in the HF diet group (p < 0.05). Plasma triglyceride and LDL cholesterol levels were decreased by 52.1 and 34.2% in the 10% SLD group and 15.4 and 15.4% in the 20% SLD group, respectively, compared to the high-fat diet group. HDL cholesterol level was increased by 7.8% in the 10% SLD and by 54.9% in the 20% SLD group. CONCLUSIONS: Our findings indicate that SLD may be beneficial in the regulation of high-fat-diet-induced blood circulatory disorders as well as overweight.     

Prevalence,Trends, and Outcomes of Higher-Risk Percutaneous Coronary Interventions Among Patients Without Acute Coronary Syndromes

Background/purpose

Patients and lesions at a higher procedural risk for percutaneous coronary intervention (PCI) are an understudied population. We examined the frequency, clinical characteristics, and outcomes of higher risk and non-higher risk PCIs at a large tertiary center.

降钙素原和C-反应蛋白在导尿管相关尿路感染早期诊断中的临床意义

目的:研究降钙素原(PCT)和C反应蛋白(CRP)在导尿管相关尿路感染(CAUTIs)早期诊断中的意义。方法:前瞻性观测疑诊CAUTIs患者88例,评价PCT和CRP对诊断CAUTIs的敏感性、特异性及相关性。结果:88例疑诊为CAUTIs患者中,根据中段尿细菌培养阳性结果分为2组,病例组65例,对照组23例,2组PCT和CRP水平差异有统计学意义(P0.05);PCT和CRP水平在CAUTIs诊断中ROC曲线下面积分别为0.898和0.743;对诊断CAUTIs的敏感度分别为83.1%、56.9%,特异度分别为82.6%、87.0%;PCT和CPR的相关系数为0.562(P0.01)。结论:PCT与CRP间具有正相关性,结合二者综合分析对于CAUTIs的早期诊断具有更好的临床价值。     

Endocardial cushion and myocardial defects after cardiac myocyte-specific conditional deletion of the bone morphogenetic protein receptor ALK3

Receptors for bone morphogenetic proteins (BMPs), members of the transforming growth factor-beta (TGFbeta) superfamily, are persistently expressed during cardiac development, yet mice lacking type II or type IA BMP receptors die at gastrulation and cannot be used to assess potential later roles in creation of the heart. Here, we used a Cre/lox system for cardiac myocyte-specific deletion of the type IA BMP receptor, ALK3. ALK3 was specifically required at mid-gestation for normal development of the trabeculae, compact myocardium, interventricular septum, and endocardial cushion. Cardiac muscle lacking ALK3 was specifically deficient in expressing TGFbeta2, an established paracrine mediator of cushion morphogenesis. Hence, ALK3 is essential, beyond just the egg cylinder stage, for myocyte-dependent functions and signals in cardiac organogenesis.     

Virtual combinatorial libraries: Dynamic generation of molecular and supramolecular diversity by self-assembly

Molecular and supramolecular diversity may be generated, respectively, by reversible, covalent or noncovalent self-assembly of basic components whose various potential combinations in number and nature represent a virtual combinatorial library. This concept is applied to the induction of inhibitors of carbonic anhydrase (CA) by reversible recombination of aldehyde and amine components. It is found that the presence of CA favors the formation of those condensation compounds that may be expected to present the strongest binding to the CA active site. The virtual combinatorial library approach may represent a powerful methodology for the discovery of substrates, inhibitors, receptors, catalysts, and carriers for a variety of processes.     

Autoimmune hemolytic anemia in patients with de novo acute myelocytic leukemia

Autoantibody against erythrocytes has occasionally been observed in patients with de novo acute myelocytic leukemia (AML). However, it is not clear whether this autoantibody in AML patients induces frank hemolysis (autoimmune hemolytic anemia, AIHA), as seen in lymphoid neoplasms. We present two de novo AML patients who showed hemolysis due to antiglobulin test-positive and test-negative AIHA, respectively. AIHA should be considered as one cause of anemia in de novo AML patients, and blood transfusions should be given carefully in such cases to avoid harmful hemolysis.     

Osteopontin, a key component of the hematopoietic stem cell niche and regulator of primitive hematopoietic progenitor cells

Although recent data suggests that osteoblasts play a key role within the hematopoietic stem cell (HSC) niche, the mechanisms underpinning this remain to be fully defined. The studies described herein examine the role in hematopoiesis of Osteopontin (Opn), a multidomain, phosphorylated glycoprotein, synthesized by osteoblasts, with well-described roles in cell adhesion, inflammatory responses, angiogenesis, and tumor metastasis. We demonstrate a previously unrecognized critical role for Opn in regulation of the physical location and proliferation of HSCs. Within marrow, Opn expression is restricted to the endosteal bone surface and contributes to HSC transmarrow migration toward the endosteal region, as demonstrated by the markedly aberrant distribution of HSCs in Opn-/- mice after transplantation. Primitive hematopoietic cells demonstrate specific adhesion to Opn in vitro via beta1 integrin. Furthermore, exogenous Opn potently suppresses the proliferation of primitive HPCs in vitro, the physiologic relevance of which is demonstrated by the markedly enhanced cycling of HSC in Opn-/- mice. These data therefore provide strong evidence that Opn is an important component of the HSC niche which participates in HSC location and as a physiologic-negative regulator of HSC proliferation.