Experimental axonopathy induced by immunization with campylobacter jejuni lipopolysaccharide from a patient with guillain‐barré syndrome

Campylobacter jejuni (C. jejunj) infection is the most common antecedent in the axonal variant of Guillain‐Barré syndrome (GBS). Antibodies against nerve gangliosides found in GBS patients recognize cross‐reactive epitopes in the lipopolysaccharide (LPS) of C. jejuni. This led to the molecular mimicry hypothesis of GBS. We immunized eleven rabbits with a LPS extracted from HS:19 C. jejuni strain isolated from a patient with GBS and complete Freund's adjuvant (CFA)(group I). In a second experiment we immunized seven rabbits with LPS, CFA and keyhole limpet hemocyanin (KLH)(group II). All group I rabbits developed high titers of anti‐LPS, anti‐GM1, anti‐GD1b antibodies and lower titers of anti‐GD1a. One rabbit, 50 days after initial inoculation, showed tremor and weakness. All rabbits of group II developed high titres of antiganglioside antibodies and six animals showed weakness 59–113 days after initial inoculation. Two rabbits died. Pathology showed mild to moderate, tendentially grouped, axonal degeneration in sciatic nerves of four out of five animals. Control rabbits of group I (immunized with CFA only) did not develop antibodies, controls of group II (immunized with CFA + KLH) developed low titers of IgG anti‐GM1. None developed neurological signs or showed axonal degeneration. C. jejuni LPS is a potent B‐cell stimulator capable to induce a strong antiganglioside response in rabbits. However, to induce the neuropathy is crucial to employ KLH, a glycoprotein known to stimulate both humoral and cellular responses. This animal model reproduces the pathogenetic process hypothesized in axonal GBS with antiganglioside antibodies post C. jejuni infection.     

Effect of cordarone on the eye (results of long-term follow-up of the treatment and prevention of arrhythmia)

Thirty-one patients who received a prolonged maintenance therapy with cordarone to treat and prevent cardiac arrhythmias underwent an ophthalmologic examination. The treatment lasted 1.5 to 51 months. The signs of keratopathy were detected in 24 (77.4%) patients using a slit lamp biomicroscopy. There is a relationship between the severity of keratopathy and a daily dose of cordarone: in most cases signs of stage I keratopathy were detectable when the daily dose was up to 200 mg. Keratopathy appears to be reversible after the drug has been discontinued.     

Disorders of perfusion of the anterior segment of the eye

Background: We have investigated the vascular perfusion of a wide variety of conditions of the anterior segment using fluorescein angiography.
Methods: The conditions were classified and findings reported according to the system set out below. Patients underwent full ocular examination. Fluorescein angiography of the anterior segment was carried out when indicated to investigate iris atrophy and neovascularisation. Specular microscopy of the corneal endothelium was used to detect changes in this tissue.
Results: The hypoperfusion was variable in degree and accompanied by varying degrees of iris hypoplasia and atrophy with neovascularisation. The degree of neovascularisation depended upon its rapidity of development, the pre-existing state of vascular perfusion and the underlying pathological condition.
Conclusions: Hypoperfusion with resultant ischaemia and neovascularisation is common in conditions of the anterior segment. An understanding of the changes is valuable in treating many conditions affecting the anterior segment. The changes observed may also occur elsewhere in the physical system and may be a significant part of the ageing process, either as scattered, disparate processes or as part of a general disease process.     

Postoperative radiation therapy in the management of lung cancer

Postoperative radiation therapy for lung cancer is still controversial. In a 9-year period, 69 patients with non-oat-cell carcinoma of the lung (16% stage I, 26% stage II, and 58% stage III) received such therapy. The radiation dose was less than 5,000 cGy in 42 patients, 5,000-5,900 cGy in 16, and 6,000 cGy or more in 11; follow-up ranged from 24 to 64 months. Actuarial survival at 2 and 4 years was 50% and 16%, respectively, for squamous cell carcinoma, and 40% and 26% for adenocarcinoma. The 5-year survival for stages I, II, and III cancer was 29%, 17%, and 19%, respectively. Histologic findings and type of surgery did not affect survival, but the radiation dose apparently did. The 3-year survival for patients who received less than 6,000 cGy was 35%, compared with 73% for patients who received higher doses. In eight patients, treatment failed within the irradiated volume: all had received doses of less than 6,000 cGy, and the volume in three was judged to be inadequate.     

Integrative and replicative transformation of Penicillium canescens with a heterologous nitrate-reductase gene

A wild isolate of Penicillium canescens was subjected to mutagenesis, and 150 chlorate-resistant mutants were isolated and classified in respect of their ability to utilize various nitrogen sources. Strains supposedly deficient in nitrate reductase have been transformed with the nitrate-reductase gene from Aspergillus niger. Transformation probably occurred by non-homologous integration of the transforming vector into the chromosome. Co-transformation with the AMA1 replicating element from A. nidulans enhanced transformation frequency up to 2000-fold, and was shown to result in autonomous maintenance of replicating concatenates, one of which was re-isolated by transformation of E. coli.     

Intergenic HA-NA interactions in influenza A virus: postreassortment substitutions of charged amino acid in the hemagglutinin of different subtypes

In our previous studies influenza A virus reassortants having neuraminidase (NA) gene of A/USSR/90/77 (H1N1) strain and hemagglutinin (HA) genes of H3, H4 and H13 subtypes were shown to produce a low virus yield and to exhibit a strong tendency to virion aggregation. More detailed studies with the use of a H3N1 reassortant and its high-yield non-aggregating variants revealed that NA of A/USSR/90/77 strain is inefficient in the removal of the terminal sialic acid residues from the virion components, and that the inefficiency of NA may be compensated by mutations in HA gene leading to a decrease of the receptor-binding affinity (Kaverin, N.V. , Gambaryan, A.S., Bovin, N.V., Rudneva, I.A., Shilov, A.A., Khodova, O.M., Varich, N.L., Sinitsin, B.V., Makarova, N.L., Kaverin, N.V., 1998. Postreassortment changes in influenza virus hemagglutinin restoring HA-NA functional match, Virology 244, 315-321). The present report describes studies performed with the use of H2N1 and H4N1 reassortants having HA genes of A/Pintail/Primorie/695/76 (H2N3) and A/Duck/Czechoslovakia/56 (H4N6) strains respectively and NA gene of A/USSR/90/77 strain. The low-yield reassortants and their high-yield non-aggregating variants were studied in both direct and competitive binding assays with sialic acid-containing substrates. The non-aggregating variants were shown to have a decreased affinity as compared to the initial reassortants toward high-molecular-weight sialic acid-containing substrates. The sequencing of HA genes revealed that all non-aggregating variants of H2N1 and H4N1 reassortants had amino acid substitutions increasing the negative charge of the HA molecule in the vicinity of the receptor-binding pocket. The results suggest that the influenza virus reassortants containing low-functional NA undergo similar postreassortment changes irrespective of the HA subtype: their receptor-binding activity decreased due to negatively charged amino acid substitutions in the vicinity of the receptor-binding pocket.     

Lineage-specific gene expansions in bacterial and archaeal genomes

Gene duplication is an important mechanistic antecedent to the evolution of new genes and novel biochemical functions. In an attempt to assess the contribution of gene duplication to genome evolution in archaea and bacteria, clusters of related genes that appear to have expanded subsequent to the diversification of the major prokaryotic lineages (lineage-specific expansions) were analyzed. Analysis of 21 completely sequenced prokaryotic genomes shows that lineage-specific expansions comprise a substantial fraction (approximately 5%-33%) of their coding capacities. A positive correlation exists between the fraction of the genes taken up by lineage-specific expansions and the total number of genes in a genome. Consistent with the notion that lineage-specific expansions are made up of relatively recently duplicated genes, >90% of the detected clusters consists of only two to four genes. The more common smaller clusters tend to include genes with higher pairwise similarity (as reflected by average score density) than larger clusters. Regardless of size, cluster members tend to be located more closely on bacterial chromosomes than expected by chance, which could reflect a history of tandem gene duplication. In addition to the small clusters, almost all genomes also contain rare large clusters of size > or =20. Several examples of the potential adaptive significance of these large clusters are explored. The presence or absence of clusters and their related genes was used as the basis for the construction of a similarity graph for completely sequenced prokaryotic genomes. The topology of the resulting graph seems to reflect a combined effect of common ancestry, horizontal transfer, and lineage-specific gene loss.