Photo-crosslinking analysis of preferential interactions between a transmembrane peptide and matching lipids.

In this study, a novel method is presented by which the molecular environment of a transmembrane peptide can be investigated directly. This was achieved by incorporating a photoactivatable crosslinking probe in the hydrophobic segment of a model transmembrane peptide. When this peptide was incorporated into lipid bilayers and irradiated with UV light, a covalent bond was formed between the crosslinking probe and a lipid.

DNA-templated catalysis using a metal-cleavable linker.

Catalytic release of carboxylates from their 8-hydroxyquinoline esters by Cu(II) complexes, both attached to peptide nucleic acid strands, is triggered by complementary DNA.

Activity of single-agent melphalan 220-300 mg/m2 with amifostine cytoprotection and autologous hematopoietic stem cell support in non-Hodgkin and Hodgkin lymphoma.

High-dose chemotherapy using melphalan (HDMEL) is an important component of many conditioning regimens that are given before autologous hematopoietic stem cell transplantation (AHSCT). In contrast to the situation in myeloma, and to a lesser degree acute leukemia, only a very limited published experience exists with the use of HDMEL conditioning as a single agent in doses requiring AHSCT for lymphoma, both Hodgkin lymphoma (HL) and especially non-Hodgkin lymphoma (NHL). Thus, we report results of treating 26 lymphoma patients (22 with NHL and four with HL) with HDMEL 220-300 mg/m(2) plus amifostine (AF) cytoprotection and AHSCT as part of a phase I-II trial.

Establishment and characterization of an angiosarcoma-derived cell line, AS-M.

A novel human endothelial cell line, AS-M, has been established from a cutaneous angiosarcoma on the scalp. The cells expressing platelet endothelial cell adhesion molecule-1 (CD31) were isolated using magnetic beads and subsequently cultured for a year. To date, the cells have undergone more than 100 population doublings (PDs).

Differential interactions between a twin-arginine signal peptide and its translocase in Escherichia coli.

The twin-arginine translocation (Tat) machinery of the Escherichia coli inner membrane is dedicated to the export of proteins harboring a conserved SRRxFLK motif in their signal sequence. TatA, TatB, and TatC are the functionally essential constituents of the Tat machinery, but their precise function is unknown. Using site-specific crosslinking, we have analyzed interactions of the twin-arginine precursor preSufI with the Tat proteins upon targeting to inner membrane vesicles.

DNA-templated metal catalysis.

Hydrolysis of an ester substrate by a CuII complex catalyst, both attached to oligo-peptide nucleic acids (PNA), is accelerated up to 485-fold in the presence of a complementary DNA template. The approach combines the sequence selectivity of DNA-templated reactions with signal amplification by multiple turnover and the versatility of metal catalysis.

Ligand crowding at a nascent signal sequence.

We have systematically analyzed the molecular environment of the signal sequence of a growing secretory protein from Escherichia coli using a stage- and site-specific cross-linking approach. Immediately after emerging from the ribosome, the signal sequence of pOmpA is accessible to Ffh, the protein component of the bacterial signal recognition particle, and to SecA, but it remains attached to the surface of the ribosome via protein L23. These contacts are lost upon further growth of the nascent chain, which brings the signal sequence into sole proximity to the chaperone Trigger factor (TF).

Molecular basis of endothelial dysfunction in sepsis.

Sepsis is one of the major causes of mortality in critically ill patients and develops as a result of the host response to infection. A complex network of events is set into motion in the body by the infection and results in the pathogenesis of sepsis. This review article focuses on the molecular mechanisms and components involved in the pathogenesis of sepsis with a major emphasis on the endothelium.

[Excessive hyperferritinemia as an indication of a reactive hemophagocytosis syndrome].

History And Admission Findings: A 17-year-old girl with a history of a polyarthritis of unknown etiology was admitted because of acute fever and general weakness. There were palpable cervical lymph nodes and her body temperature was 39.5 degrees C.

Interplay of signal recognition particle and trigger factor at L23 near the nascent chain exit site on the Escherichia coli ribosome.

As newly synthesized polypeptides emerge from the ribosome, they interact with chaperones and targeting factors that assist in folding and targeting to the proper location in the cell. In Escherichia coli, the chaperone trigger factor (TF) binds to nascent polypeptides early in biosynthesis facilitated by its affinity for the ribosomal proteins L23 and L29 that are situated around the nascent chain exit site on the ribosome. The targeting factor signal recognition particle (SRP) interacts specifically with the signal anchor (SA) sequence in nascent inner membrane proteins (IMPs).

Multiple splice variants of lactate dehydrogenase C selectively expressed in human cancer.

We applied a combined data mining and experimental validation Approach for the discovery of germ cell-specific genes aberrantly expressed in cancer. Six of 21 genes with confirmed germ cell specificity were detected in tumors, indicating that ectopic activation of testis-specific genes in cancer is a frequent phenomenon. Most surprisingly one of the genes represented lactate dehydrogenase C (LDHC), the germ cell-specific member of the lactate dehydrogenase family.

Restless legs syndrome probably induced by risperidone treatment.

Background: According to some reports, patients treated with risperidone may develop akathisia. Restless legs syndrome (RLS), which shares some clinical features with akathisia, is a distinct movement and sleep disorder that may be induced by various drugs that act on the CNS.

Methods: We studied a 31-year-old patient suffering from a schizoaffective disorder including auditory hallucinations who developed symptoms typical of the RLS during treatment with risperidone, using polysomnography to objectify sleep disturbances and associated periodic leg movements during sleep (PLMS).

YidC and SecY mediate membrane insertion of a Type I transmembrane domain.

YidC has been identified recently as an evolutionary conserved factor that is involved in the integration of inner membrane proteins (IMPs) in Escherichia coli. The discovery of YidC has inspired the reevaluation of membrane protein assembly pathways in E. coli.

Adaptive Support Ventilation (ASV).

Adaptive Support Ventilation is a novel ventilation mode, a closed-loop control mode that may switch automatically from a PCV-like behaviour to an SIMV-like or PSV-like behaviour, according to the patient status. The operating principles are based on pressure-controlled SIMV with pressure levels and SIMV rate automatically adjusted according to measured lung mechanics at each breath. ASV provided a safe and effective ventilation in patients with normal lungs, restrective or obstructive diseases.

Particulate matter contamination of intravenous antibiotics aggravates loss of functional capillary density in postischemic striated muscle.

Through the increased use of less expensive and counterfeit medicines, the contamination of parenteral fluids and drugs by particulate matter poses an increasing health hazard worldwide. However, the mechanism of action of such contamination has never been conclusively demonstrated. We have systemically injected the particles contained in three different 1-g preparations of the antibiotic cefotaxime into hamsters and visualized the functional capillary density in striated skin muscle, using intravital fluorescence microscopy.

Targeting, insertion, and localization of Escherichia coli YidC.

YidC was recently shown to play an important role in the assembly of inner membrane proteins (IMPs) both in conjunction with and separate from the Sec-translocon. Little is known about the biogenesis and structural and functional properties of YidC, itself a polytopic IMP. Here we analyze the targeting and membrane integration of YidC using in vivo and in vitro approaches.

Nonmyeloablative conditioning allows for more rapid T-cell repertoire reconstitution following allogeneic matched unrelated bone marrow transplantation compared to myeloablative approaches.

Nonmyeloablative pretransplantation conditioning regimens have resulted in durable engraftment of allogeneic hematopoietic stem cells. In contrast to conventional fully myeloablative approaches, nonmyeloablative regimens are associated with a marked reduction of morbidity and mortality in the early posttransplantation period. Consequently, such reduced-intensity transplantation approaches can be used in older and frailer patients who would not tolerate fully ablative regimens.

Field attraction of the stink bug Euschistus conspersus (Hemiptera: Pentatomidae) to synthetic pheromone-baited host plants.

The attraction of the stink bug Euschistus conspersus Uhler to sources of the synthetic pheromone component methyl (2E,4Z)-decadienoate was investigated in a series of field experiments in native vegetation surrounding commercial apple orchards in Washington. In experiments with pheromone lures placed inside two different tube-type traps, stink bugs were attracted to the immediate area around traps in large numbers, but very few were caught in the traps. Pheromone lures attached directly to the host plant mullein, Verbascum thapsus L.

Automated molecular weight assignment of electrospray ionization mass spectra.

Process improvements in the synthesis of therapeutic agents and their intermediates are often facilitated by identification of reaction by-products. Analysis by liquid chromatography/mass spectrometry (LC/MS) with electrospray ionization is a powerful approach for obtaining molecular weight information for these compounds. Such analyses are well suited for 'open-access' mass spectrometry using generic chromatographic conditions, provided spectral interpretation for unknown compounds is facile.

Membrane topography of the coupling ion binding site in Na+-translocating F1F0 ATP synthase.

A carbodiimide with a photoactivatable diazirine substituent was synthesized and incubated with the Na(+)-translocating F(1)F(0) ATP synthase from both Propionigenium modestum and Ilyobacter tartaricus. This caused severe inhibition of ATP hydrolysis activity in the absence of Na(+) ions but not in its presence, indicating the specific reaction with the Na(+) binding c-Glu(65) residue. Photocross-linking was investigated with the substituted ATP synthase from both bacteria in reconstituted 1-palmitoyl-2-oleyl-sn-glycero-3-phosphocholine (POPC)-containing proteoliposomes.