Oxidized low density lipoprotein and innate immune receptors.

Purpose Of Review: Atherosclerosis is now recognized as a chronic inflammatory disease. This review discusses recent literature reporting that innate immune receptors bind oxidatively modified LDL and its many oxidized moieties and consequently modulate the atherogenic process. These innate pattern recognition receptors are known to play a central role in pro-inflammatory responses to bacteria by binding pathogen-associated molecular patterns.

Risperidone in acute and continuation treatment of mania.

In a prospective study, we examined the efficacy of risperidone added-on to mood stabilizers in the acute and continuation treatment of mania over a 12-week period. Patients (n=108) with a DSM-IV diagnosis of bipolar disorder, manic or mixed episode requiring treatment with an antipsychotic were recruited. All subjects were on one or two mood stabilizers at the time of initiation of risperidone (range 0.

Pneumococcal vaccination decreases atherosclerotic lesion formation: molecular mimicry between Streptococcus pneumoniae and oxidized LDL.

During the progression of atherosclerosis, autoantibodies are induced to epitopes of oxidized low-density lipoprotein (oxLDL) and active immunization of hypercholesterolemic mice with oxLDL ameliorates atherogenesis. We unexpectedly found that many autoantibodies to oxLDL derived from 'naive' atherosclerotic mice share complete genetic and structural identity with antibodies from the classic anti-phosphorylcholine B-cell clone, T15, which protect against common infectious pathogens, including pneumococci. To investigate whether in vivo exposure to pneumococci can affect atherogenesis, we immunized Ldlr(-/-) mice with Streptococcus pneumoniae.

Decreasing incidence of severe diabetic microangiopathy in type 1 diabetes.

Objective: Conflicting evidence of a decline in incidence of microvascular complications in type 1 diabetes during the last decades has been reported. To assess recent trends in the cumulative incidence of diabetic microangiopathy in type 1 diabetes, we analyzed data from long-term prospective observational studies lasting >/=20 years.

Research Design And Methods: A total of 600 Caucasian patients with onset of type 1 diabetes between 1965 and 1984 were followed until death or until the year 2000.

Helicobacter pylori in children and adolescents: increase of primary clarithromycin resistance, 1997-2000.

Background: The authors evaluate the prevalence of Helicobacter pylori resistance in 117 children and demonstrate the changes over a 4-year period.

Methods: In 117 children and adolescents, H. pylori-positive gastritis was revealed by diagnostic upper endoscopy.

Procalcitonin: a useful discriminator between febrile conditions of different origin in hemato-oncological patients?

Plasma concentrations of procalcitonin (PCT) have been shown to be elevated in bacterial and fungal infections. In contrast to C-reactive protein (CRP), PCT is not elevated in inflammations of noninfectious origin. Febrile inflammatory conditions are frequent in patients with hemato-oncological diseases.

Minimally modified LDL binds to CD14, induces macrophage spreading via TLR4/MD-2, and inhibits phagocytosis of apoptotic cells.

Minimally modified low density lipoprotein (mmLDL) is a pro-inflammatory and pro-atherogenic lipoprotein that, unlike profoundly oxidized LDL (OxLDL), is not recognized by scavenger receptors and thus does not have enhanced uptake by macrophages. However, here we demonstrate that mmLDL (as well as OxLDL) induces actin polymerization and spreading of macrophages, which results in such pro-atherogenic consequences as inhibition of phagocytosis of apoptotic cells but enhancement of OxLDL uptake. We also demonstrate for the first time that the lipopolysaccharide receptor, CD14, and toll-like receptor-4/MD-2 are involved in these mmLDL effects.

Hexadecylphosphocholine does not influence phospholipase D and sphingomyelinase activity in human leukemia cells.

Hexadecylphosphocholine (HePC) is the first representative of the alkylphosphocholines (APC), a new group of biologically active compounds. HePC has pronounced antiproliferative effects on neoplastic cells in vitro and in vivo. The molecular mechanism by which HePC exerts its biological effects is still under investigation.

Effects of hexadecylphosphocholine on phosphatidylcholine and phosphatidylserine metabolism in human lymphoma cells.

Hexadecylphosphocholine (HePC) belongs to a new group of antineoplastic agents, the alkylphosphocholines (APC). HePC shows a broad spectrum of biological effects in various cells in vitro and in vivo. It has pronounced antiproliferative effects on neoplastic cells.

A single dose, placebo controlled study of the fully human anti-tumor necrosis factor-alpha antibody adalimumab (D2E7) in patients with rheumatoid arthritis.

Objective: To assess the pharmacokinetics, safety profile, and efficacy of the fully human anti-tumor necrosis factor-alpha (anti-TNF-alpha) monoclonal antibody adalimumab (D2E7) in patients with long-standing, active rheumatoid arthritis (RA).

Methods: This was a randomized, double blind, placebo controlled study of single intravenous injections of ascending doses (0.5 to 10 mg/kg) of adalimumab in 5 cohorts of 24 patients each (18 adalimumab and 6 placebo in all cohorts except the 0.

C-reactive protein binds to both oxidized LDL and apoptotic cells through recognition of a common ligand: Phosphorylcholine of oxidized phospholipids.

C-reactive protein (CRP) is an acute-phase protein that binds specifically to phosphorylcholine (PC) as a component of microbial capsular polysaccharide and participates in the innate immune response against microorganisms. CRP elevation also is a major risk factor for cardiovascular disease. We previously demonstrated that EO6, an antioxidized LDL autoantibody, was a T15 clono-specific anti-PC antibody and specifically binds to PC on oxidized phosphatidylcholine (PtC) but not on native PtC.

Effects of risperidone on conduct and disruptive behavior disorders in children with subaverage IQs.

Objective: To determine whether risperidone is effective in reducing symptoms of disruptive behaviors (such as aggression, impulsivity, defiance of authority figures, and property destruction) associated with conduct disorder, oppositional defiant disorder, and disruptive behavior disorder-not otherwise specified in children with subaverage IQs.

Method: The trial consisted of a 1-week, single-blind, placebo run-in period and was followed by a 6-week, double-blind, placebo-controlled period. One hundred ten children (aged 5-12 years inclusive) with an IQ of 36-84 with a disruptive behavior disorder and a score of at least 24 on the Conduct Problem subscale of the Nisonger Child Behavior Rating Form (NCBRF) were enrolled.

Long-term safety and efficacy of risperidone for the treatment of disruptive behavior disorders in children with subaverage IQs.

Objective: The objective of this study was to investigate the long-term safety and efficacy of risperidone in disruptive behavior disorders in children with subaverage IQs. Disruptive behavior disorders were defined as oppositional defiant disorder, disruptive behavior disorder, and conduct disorder as per the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria.

Methods: This was a 48-week open-label (OL) extension study of risperidone in 77 children diagnosed with a disruptive behavior disorder, and either borderline intellectual function or mild or moderate mental retardation who had participated in a previous 6-week, double-blind (DB) study and completed at least 2 weeks of DB therapy.

Relaxin enhances in-vitro invasiveness of breast cancer cell lines by up-regulation of matrix metalloproteases.

Until recently, relaxin (RLX) has been known predominantly for its effects on the reproductive system, where it induces remodelling of the extracellular matrix and up-regulation of matrix metalloproteases (MMPs). In solid cancers, tissue remodelling and MMP activation are essential for invasion and metastasis. We therefore investigated the effect of RLX on invasiveness and MMP expression of human breast cancer cell lines.

Increased risk for therapy-associated hematologic malignancies in patients with carcinoma of the breast and combined homozygous gene deletions of glutathione transferases M1 and T1.

The most serious long-term complications of anti-tumor therapy are secondary malignancies. Parameters which might allow an estimation of the individual risk to develop a therapy-induced neoplasia are urgently needed. We examined whether the genotypes of the glutathione S-transferases (GST) M1 and T1, which metabolize various cytostatic drugs, as well as reactive oxygen species, influence the risk for secondary neoplasia.

mRNA expression of matrix metalloproteases and their inhibitors differs in subtypes of renal cell carcinomas.

Altered expression of matrix metalloproteases (MMPs) and their inhibitors, the tissue inhibitors of matrix metalloproteases (TIMPs), has been demonstrated in various tumour tissues. mRNA expression patterns of MMP-1, MMP-2, MMP-3, MMP-9, MMP-11, MMP-12, MMP-14 and TIMP-1, TIMP-2, TIMP-3 and TIMP-4 were evaluated by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in 30 renal cell carcinomas (RCC), as well as in the surrounding tissues. Expression of the MMPs was significantly stronger in the carcinomas than in non-malignant tissues.

Prospective, controlled, multi-center study on the effect of an amino-acid-based formula in infants with cow's milk allergy/intolerance and atopic dermatitis.

Cow's milk allergy/intolerance is treated by complete avoidance of cow's milk proteins. Because cow's milk is an important food for infants, its avoidance may lead to an increased risk of growth impairment. Whilst there is evidence for the beneficial effects of extensively hydrolyzed cow's milk formulate (eHF) in infants with cow's milk allergy/intolerance, little is known about the effects of amino-acid-based formulae (AA) in such infants.

Effects of hexadecylphosphocholine on thrombocytopoiesis.

Hexadecylphosphocholine (HePC) is the first representative of the alkylphosphocholines, a novel group derived from the cytotoxic etherlysophospholipids. HePC shows a broad spectrum of antiproliferative effects in neoplastic cells in vitro and in vivo. HePC has been tested successfully in several clinical studies.

Successful transplantation and engraftment of peripheral blood stem cells after cryopreservation, positive and negative purging procedures, and a second cryopreservation cycle.

Transplantation of peripheral blood stem cells (PBSC), positively and/or negatively selected immediately after harvest, has become a widely applied therapeutic option in hematological or oncological patients. The following case of peripheral blood stem cell transplantation represents the first case of successful transplantation of PBSC, cryopreserved twice and purged after cryopreservation. PBSC were harvested in a 44-year-old female patient with a low-grade non-Hodgkin's lymphoma stage IV after mobilization with chemotherapy and G-CSF.

Cytogenetic subgroups in acute myeloid leukemia differ in proliferative activity and response to GM-CSF.

The current study was undertaken to search for differences in the biology of cytogenetic subgroups in patients with de novo acute myeloid leukemia (AML). In addition, factors influencing the metabolism of cytosine arabinoside (araC) as the key agent of antileukemic activity were assessed. Bone marrow aspirates from 91 patients with newly diagnosed AML in whom karyotypes were successfully obtained were analyzed: (1) for spontaneous proliferative activity by 3H-thymidine (3H-TdR) incorporation; (2) proliferative response to GM-CSF by in vitro incubation of blasts for 48 h with or without GM-CSF (100 U/ml) followed by an additional 4-h exposure to 3H-TdR (0.

Effects of amifostine in a patient with an advanced-stage myelodysplastic syndrome.

We report on a 63-year-old man with myelodysplastic syndrome at the stage of a refractory anemia with an excess of blasts in transformation (MDS-RAEB-T), first diagnosed in December 1996. After a period of stability, with no need for transfusions, the MDS progressed into acute myeloid leukemia (AML) in August 1998 with the emergence of a cytogenetic abnormality (11q-). Two courses of chemotherapy were given, resulting in prolonged pancytopenia; however, no clearance of bone marrow (BM) blasts was achieved.

[Imaging of vitreoretinal adhesions in the partner eye of patients with penetrating macular foramina in optical coherence tomography].

Background: Vitreoretinal adhesions play a crucial role in the development of a macular hole. To visualize vitreoretinal adhesion we used optical coherence tomography to investigate fellow eyes of patients with macular holes.

Methods: In a prospective study we scanned the retina in 188 patients with a macular hole stage III or IV (Gass classification).