Impaired cerebral autoregulation in obstructive sleep apnea.

Obstructive sleep apnea (OSA) increases the risk of stroke independent of known vascular and metabolic risk factors. Although patients with OSA have higher prevalence of hypertension and evidence of hypercoagulability, the mechanism of this increased risk is unknown. Obstructive apnea events are associated with surges in blood pressure, hypercapnia, and fluctuations in cerebral blood flow.

The integrity of esophagogastric junction anatomy in patients with isolated laryngopharyngeal reflux symptoms.

Background: Distortion of esophagogastric junction anatomy in patients with gastroesophageal reflux disease produces permanent dilation of the gastric cardia proportional to disease severity, but it remains unclear whether this mechanism underlies reflux in patients with isolated laryngopharyngeal reflux symptoms.

Method: In a prospective study, 113 patients were stratified into three populations based on symptom complex: laryngopharyngeal reflux symptoms, typical reflux symptoms, and both laryngopharyngeal and typical symptoms. Subjects underwent small-caliber upper endoscopy in the upright position.

[Health habits of patients with schizophrenia: a general pattern?].

Objective: Schizophrenia patients have in many aspects an unhealthier lifestyle than the general population. The aim of this study is to determine if disadvantageous health habits of schizophrenia patients present a general pattern that repeats itself in other regions and if psychosocial consequences of schizophrenia (singleness, unemployment) influence patients' health habits.

Methods: 95 schizophrenia outpatients from Germany and 97 from Austria were examined regarding eating-, drinking-, smoking- and physical-activity habits.

Optical resolution of 1-(1-naphthyl)ethylamine by its dicarboxylic acid derivatives: Structural features of the oxalic acid derivative diastereomeric salt pair.

Optical resolution methods were established for racemic 1-(1-naphthyl) ethylamine. The resolving agents were synthesized by N-derivatizing (R)-1-(1-naphthyl) ethylamine with dicarboxylic acids. Oxalic, malonic, and succinic acid derivatives were found to be suitable resolving agents.

Partial reduction of human FOXP3+ CD4 T cells in vivo after CD25-directed recombinant immunotoxin administration.

The regulation of tolerance to self-proteins and the suppression of T-cell responses have in part been attributed to the activity of CD25+CD4+ T regulatory (Treg) cells. Further, Treg cells can inhibit the antitumor effectiveness of adoptive immunotherapy and active immunization approaches in preclinical models. In an effort to selectively eliminate Treg cells from human peripheral blood mononuclear cell to potentially bolster antitumor responses, we have evaluated the Treg-cell depleting capacity of the CD25-directed immunotoxin, RFT5-SMPT-dgA.

Double-blind trial of recombinant gamma-interferon versus placebo in the treatment of rheumatoid arthritis. 1989.

One hundred five patients were enrolled in a 12-week, randomized, prospective, double-blind, placebo-controlled trial of recombinant human gamma-interferon (rHu gamma-IFN) for the treatment of rheumatoid arthritis. Fifty-four patients received rHu gamma-IFN and 51 received placebo. Forty-two patients in each group completed the 12-week trial.

Aqueous polymer two-phase systems for the proteomic analysis of plasma membranes from minute brain samples.

Comprehensive knowledge about the plasma membrane protein profile of a given brain region, at defined developmental stages, will greatly foster the understanding of brain function and dysfunction. Protocols are required which selectively enrich plasma membranes from small brain regions, thereby resulting in high yields. Here, we present a suitable protocol that is based on aqueous polymer two-phase systems.

p38 pathway kinases as anti-inflammatory drug targets.

Mitogen-activated protein kinases (MAPK) are intracellular signaling molecules involved in cytokine synthesis. Several classes of mammalian MAPK have been identified, including extracellular signal-regulated kinase, c-jun N-terminal kinase, and p38 MAP kinase. p38alpha is a key MAPK involved in tumor necrosis factor alpha and other cytokine production, as well as enzyme induction (cyclooxygenase-2, inducible nitric oxide synthase, and matrix metalloproteinases) and adhesion molecule expression.

Pyrrolopyridine inhibitors of mitogen-activated protein kinase-activated protein kinase 2 (MK-2).

A new class of potent kinase inhibitors selective for mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP-K2 or MK-2) for the treatment of rheumatoid arthritis has been prepared and evaluated. These inhibitors have IC50 values as low as 10 nM against the target and have good selectivity profiles against a number of kinases including CDK2, ERK, JNK, and p38. These MK-2 inhibitors have been shown to suppress TNFalpha production in U397 cells and to be efficacious in an acute inflammation model.

Reconstitution of FOXP3+ regulatory T cells (Tregs) after CD25-depleted allotransplantation in elderly patients and association with acute graft-versus-host disease.

Selective depletion (SD) of host-reactive donor T cells from allogeneic stem-cell transplants (SCTs) using an anti-CD25 immunotoxin (IT) is a strategy to prevent acute graft-versus-host disease (aGvHD). There is concern that concurrent removal of regulatory T cells (T(regs)) with incomplete removal of alloactivated CD25(+) T cells could increase the risk of aGvHD. We therefore measured T(regs) in the blood of 16 patients receiving a T-cell-depleted allograft together with anti-CD25-IT-treated SD lymphocytes, in 13 of their HLA-identical donors, and in 10 SD products.

The effect of genetic polymorphisms in the vinyl chloride metabolic pathway on mutagenic risk.

Vinyl chloride (VC) is a human carcinogen known to undergo metabolism by cytochrome P450 2E1 (CYP2E1) to reactive intermediates that can cause oncogene and tumor suppressor gene mutations and that are further metabolized by acetaldehyde dehydrogenase (ALDH2) and glutathione-S-transferases (GSTs) to non-mutagenic end products. These metabolic enzymes have known polymorphisms that could lead to increased levels of the VC reactive intermediates and thus an increased risk for mutations and cancer following exposure. Using restriction fragment length polymorphism (RFLP) analysis, we have examined a cohort of 597 French VC workers for polymorphisms in CYP2E1, ALDH2, GSTM1 and GSTT1 in relation to the occurrence of mutant oncogene and tumor suppressor gene biomarkers that are attributable to VC exposure.

Health habits of patients with schizophrenia.

Background: The aim of the study was to analyze the physical activity, dietary, drinking, and smoking habits of schizophrenia patients (SP).

Methods: Data from 194 schizophrenia outpatients collected using sections of the German National Health Interview and Examination Survey were compared with data from the German general population (GP). In addition to univariate data analyses, a multivariate regression analysis was performed.

Identification and quantification of high fluorescence-stained lymphocytes as antibody synthesizing/secreting cells using the automated routine hematology analyzer XE-2100.

Objectives: The aim of this study was to classify and quantify the high fluorescence lymphocytes area (HFL-count) from the SYSMEX XE-2100 leucocyte differential channel as antibody-synthesizing or -secreting cells (ASC, plasma cells or lymphoplasmacytoid cells) in reactive diseases. To unequivocally identify the HFL cells, all possibly eligible cell populations have been investigated: activated B-lymphocytes, activated T-lymphocytes, large granular lymphocytes (LGL), activated monocytes, and immature granulocytes.

Methods: In total, 85 patients were analyzed on the XE-2100 and compared with the automated image analysis system Cellavision Diffmaster 96 based on artificial neural network and immunophenotyping method with the BD FACSCalibur.

Enhanced efficiency due to the use of achiral additives in the optical resolution of 1-phenylethylamine by its glutaric acid derivative.

Racemic 1-phenylethylamine was optically resolved by its own derivative formed with glutaric acid namely (+)-(R)-N-(1-phenylethyl)glutaramic acid. The amide acid resolving agent was synthesized from (+)-(R)-1-phenylethylamine by N-derivatization. The glutaric acid derivative was the next in a homologous series of dicarboxilic acid derivatized resolving agents of racemic 1-phenylethylamine.

Advantages of structural similaritiesof the reactants in optical resolution processes.

Advantages and limitations of the use of structurally similar compounds in racemate resolution viadiastereoisomeric salt formation are discussed in this review. An effective conception on "derivativeresolving agents" (use of the optically active derivatives of a racemate as resolving agents)is presented by examples and the method is extended to the homologous series of the derivative resolvingagents and/or achiral additives. A recently developed distillation version of the family approachto optical resolution and the novel, solvent-free resolution methods using a half equivalent amountof resolving agent are also discussed.

Oligomerization of KCC2 correlates with development of inhibitory neurotransmission.

The neuron-specific K+-Cl- cotransporter KCC2 extrudes Cl- and renders GABA and glycine action hyperpolarizing. Thus, it plays a pivotal role in neuronal inhibition. Development-dependent KCC2 activation is regulated at the transcriptional level and by unknown posttranslational mechanisms.

Nonlinear chiral interactions in resolutions with benzylamine derivatives.

N-formylphenylalanine was subjected to optical resolution using a chiral agent such as phenylethylamine enantiomer, (R)-phenylglycine methyl ester, (S)-N-benzyl-2-aminobutanol, alone or in a mixture with each other or in a mixture with benzylamine.

Aqueous polymer two-phase systems: effective tools for plasma membrane proteomics.

Plasma membranes (PMs) are of particular importance for all living cells. They form a selectively permeable barrier to the environment. Many essential tasks of PMs are carried out by their proteinaceous components, including molecular transport, cell-cell interactions, and signal transduction.

Enrichment of integral membrane proteins from small amounts of brain tissue.

Subcellular fractionation represents an essential technique for functional proteome analysis. Recently, we provided a subcellular fractionation protocol for minute amounts of tissue that yielded a nuclear fraction, a membrane and organelle fraction, and a cytosolic fraction. In the current study, we attempted to improve the protocol for the isolation of integral membrane proteins, as these are particularly important for brain function.

Adoptive immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical stem cell transplantation.

Poor T lymphocyte reconstitution limits the use of haploidentical stem cell transplantation (SCT) because it results in a high mortality from viral infections. One approach to overcome this problem is to infuse donor T cells from which alloreactive lymphocytes have been selectively depleted, but the immunologic benefit of this approach is unknown. We have used an anti-CD25 immunotoxin to deplete alloreactive lymphocytes and have compared immune reconstitution after allodepleted donor T cells were infused at 2 dose levels into recipients of T-cell-depleted haploidentical SCT.

Neuroproteomics - the tasks lying ahead.

The brain is unquestionably the most fascinating organ. Despite tremendous progress, current knowledge falls short of being able to explain its function. An emerging approach toward improved understanding of the molecular mechanisms underlying brain function is neuroproteomics.

A pilot clinical trial of a recombinant ricin vaccine in normal humans.

Ricin, a highly potent toxin produced by castor beans, is classified by the Centers for Disease Control and Prevention as a level B biothreat because it is easily produced, readily available, and highly stable. There have been >750 cases of documented ricin intoxication in humans. There is no approved vaccine for ricin.

Proteomic analysis of brain plasma membranes isolated by affinity two-phase partitioning.

A comprehensive analysis of plasma membrane proteins is essential to in-depth understanding of brain development, function, and diseases. Proteomics offers the potential to perform such a comprehensive analysis, yet it requires efficient protocols for the purification of the plasma membrane compartment. Here, we present a novel and efficient protocol for the separation and enrichment of brain plasma membrane proteins.

Optical resolution by crystallization from melt using enantiomer derivatives as resolving agents: nonlinear behavior of resolving agent mixtures.

Substituted racemic 1-phenylethylamine derivatives were reacted in molten phase with chiral N-substituted 1-phenylethylamine dicarboxylic acid derivatives (4-9), and their mixtures (e.g., 4+6, 7+8, etc.