The in vivo contribution of hematopoietic cells to systemic TNF and IL-6 production during endotoxemia.

Sepsis is a systemic inflammatory response syndrome resulting from an inappropriate innate immune response to infection. TNF and interleukin (IL)-6 are critically involved in this syndrome and although conclusive in vivo evidence is missing, innate immune cells are believed to be the principal producers of these cytokines. We investigated this assumption by performing bone marrow transplantations (BMT) between LPS-sensitive (C3H/HeN) and LPS-hyporesponsive (C3H/HeJ) mice.

Caspase inhibitors promote alternative cell death pathways.

The use of caspase inhibitors has revealed the existence of alternative backup cell death programs for apoptosis. The broad-spectrum caspase inhibitor zVAD-fmk modulates the three major types of cell death. Addition of zVAD-fmk blocks apoptotic cell death, sensitizes cells to necrotic cell death, and induces autophagic cell death.

New strategies in polypeptide and antibody synthesis: an overview.

The synthesis of radioligands can benefit considerably from optimized recombinant protein production, both on the aspect of economy of production and on the level of improving the targeting and pharmacokinetics of the ligand. This paper first describes a general production optimization strategy, and then elaborates on a protein design strategy tailored to targeting applications. Production in Escherichia coli will benefit from economy of goods and time as compared to other organisms.

Involvement of sialoadhesin in entry of porcine reproductive and respiratory syndrome virus into porcine alveolar macrophages.

Porcine reproductive and respiratory syndrome virus (PRRSV) shows a very restricted tropism for cells of the monocyte/macrophage lineage. It enters cells via receptor-mediated endocytosis. A monoclonal antibody (MAb) that is able to block PRRSV infection of porcine alveolar macrophages (PAM) and that recognizes a 210-kDa protein (p210) was described previously (MAb41D3) (X.

A novel homozygous missense mutation in the myotubularin-related protein 2 gene associated with recessive Charcot-Marie-Tooth disease with irregularly folded myelin sheaths.

Mutations in the myotubularin-related protein 2 gene on chromosome 11q22 are known to cause autosomal recessive Charcot-Marie-Tooth disease with irregularly folded myelin sheaths. We screened the coding region of the myotubularin-related protein 2 gene in a Turkish consanguineous Charcot-Marie-Tooth disease family compatible with linkage to chromosome 11q22. A homozygous cytosine to thymine missense mutation at nucleotide position 847, resulting in an amino acid substitution of arginine to tryptophan at codon 283, was detected in exon 9 of the MTMR2 gene.

Detection of the CMT1A/HNPP recombination hotspot in unrelated patients of European descent.

Charcot-Marie-Tooth type 1 disease (CMT1) and hereditary neuropathy with liability to pressure palsies (HNPP) are common inherited disorders of the peripheral nervous system. The majority of CMT1 patients have a 1.5Mb tandem duplication (CMT1A) in chromosome 17p11.

Increased stability of phage T7g10 mRNA is mediated by either a 5'- or a 3'-terminal stem-loop structure.

The mRNA encoding the major capsid protein of phage T7 (T7g10) is highly expressed in Escherichia coli. In common with other highly expressed T7 genes, the 5' end of this mRNA contains a stem-loop structure, while transcription termination at the phage T7 T phi terminator generates a stable 3'-end stem-loop structure. We assessed the influence of these structures on the expression level of T7g10 and on the functional stability of the mRNA.

Distal hereditary motor neuropathy type II (distal HMN II): mapping of a locus to chromosome 12q24.

The distal hereditary motor neuropathy (distal HMN) or the spinal form of Charcot-Marie-Tooth (CMT) disease is an exclusively motor disorder of the peripheral nervous system. The disorder clinically resembles the hereditary motor and sensory neuropathies (HMSN) type I and type II or CMT type 1 and type 2. Distal HMN might also be related to the spinal muscular atrophies (SMA) since, in both disorders, the lower motor neurons are affected.