Psychotic depression. An atypical initial presentation of multiple sclerosis

The Roussy-Lévy syndrome (MIM #180800) was described in 1926 as a disorder presenting with pes cavus and tendon areflexia, distal limb weakness, tremor in the upper limbs, gait ataxia and distal sensory loss. We report a family with affected members in four generations, showing these clinical signs of Roussy-Lévy syndrome and a partial duplication at chromosome 17p11.2. This genetic defect is commonly found in patients with the hypertrophic form of the Charcot-Marie-Tooth syndrome. Our finding provides evidence against the Roussy-Lévy syndrome as a distinct entity but suggests a close relation with the Charcot-Marie-Tooth syndrome. What causes the additional features of gait ataxia and essential tremor needs further clarification.     

An anti-IL-2 antibody increases serum half-life and improves anti-tumor efficacy of human recombinant interleukin-2

We examined the ability of anti-human recombinant interleukin-2 (hu rIL-2) monoclonal antibody DMS-1.10 to increase serum half-life of hu rIL-2, and the effect of this complex on inhibition of tumor progression in a B16-F10 murine melanoma model. In C57B1/6 mice, intravenous (i.v.) injection of DMS-1.10 premixed with 1 x 10(4) units (U) of hu rIL-2 at a 1:1 molar ratio extended serum half-life greater than 10-fold (222 min) when compared to the same dose of hu rIL-2 alone (20 min). In a murine tumor model, multiple intraperitoneal (i.p.) injections of non-neutralizing DMS-1.10 premixed with hu rIL-2 at a 5:1 molar ratio reduced the growth rate of subcutaneous (s.c.) B16-F10 tumor in C57B1/6 mice by 64% when compared to PBS and irrelevant antibody treated controls. Although similar treatment with hu rIL-2 alone reduced tumor growth rate by 46%, it was significantly less effective than the premixed treatment. Results from a flow cytometry assay confirm B16-F10 does not have IL-2 receptors, precluding direct inhibition of tumor growth by hu rIL-2 treatments. We propose that therapeutic efficacy of hu rIL-2 is improved by prolonging the in vivo half-life with an anti-IL-2 antibody, thus augmenting hu rIL-2 bioactivity and enhancing the hosts immune response against tumor.     

Photovoltaic-integrated building facades

Photovoltaic (PV) cells, when integrated within a building facade, offer the possibility of generating electric power and heat for local use or export. This paper reports on a project to investigate the practical operational efficiencies that might be delivered from such facades. The results from laboratory experiments and computer simulations are presented: the former were used to develop an empirical relationship between cell temperature and power output; the latter were undertaken to assess operational efficiencies under a range of climate conditions representative of the UK.     

Knowledge about asthma among Danish primary school teachers. Results of a questionnaire study

An anonymous questionnaire inquiry performed among 324 school teachers in the Randers area with the purpose of elucidating teachers' knowledge about asthma is presented. To a series of statements about asthma, the teachers should answer yes, no or don't know. A limited knowledge about asthma in children was found. The knowledge about medicamental treatment was particularly limited. Only 57 per cent knew that wheezing after physical exertion is a strong indicator of asthma. Only five per cent had received proper instruction. This latter group had a significantly better knowledge of medical treatment (p < 0.0001-0.05). It is recommended that instruction in children's diseases, especially asthma should be reintroduced in teachers' training colleges.     

Presence of Epstein-Barr virus in lymphoepithelioma-like carcinoma of the middle ear

AIM: To examine the association of Epstein-Barr virus (EBV) with carcinoma of the ear. METHODS: Five non-keratinising squamous cell carcinomas and two undifferentiated carcinomas of the ear were examined. In situ hybridisation was used to localised EBV-encoded RNAs (EBER). Immunohistochemical methods to detect LMP-1 and EBNA2 were performed in the EBER positive cases. RESULTS: Two cases were EBER positive, including one non-keratinising and one undifferentiated carcinoma. Both showed identical morphology to those arising from the nasopharynx, with abundant lymphoid stroma. They were both negative for LMP-1 and EBNA2. CONCLUSIONS: EBV associated carcinoma with the morphology of lymphoepithelioma can also arise from the middle ear.     

Caring for dying children: nurses' experiences

Interviews with 25 nurses in this grounded theory study show that when nurses recognized that a child's death was inevitable, they struggled with both grief distress and moral distress. Their distress occurred within the context of the nurse-patient relationship. Nurses employed a range of strategies to manage their distress. Several conditions facilitated or constrained nurses' strategies, and resulted in far-reaching implications both professionally and personally.     

Cooperation between glutathione depletion and protein synthesis inhibition against naturally occurring neuronal death

It is generally agreed that naturally-occurring neuronal death in developing animals is dependent on the synthesis of proteins. Oxidative stress, as when intracellular concentrations of free radicals are raised or when cell constituents such as membrane lipids or protein thiols are oxidized, is also involved in various types of neuronal death. In the present report, we show that the number of naturally dying retinal cells in the chick embryo can be reduced by intraocular injections of cycloheximide, an inhibitor of protein synthesis. L-buthionine-[S,R]-sulfoximine, an inhibitor of glutathione synthesis, can either enhance or diminish the cell death, depending on the conditions of treatment. Moreover, when the two inhibitors are combined, L-buthionine-[S,R]-sulfoximine potentiates the neuroprotective effects of cycloheximide. Measurements of retinal glutathione concentration and protein synthesis show the specificity of the treatments: buthionine-sulfoximine diminishes glutathione concentrations but not protein synthesis whereas cycloheximide inhibits protein synthesis without decreasing glutathione concentrations. Naturally-occurring neuronal death thus seems to involve the synthesis of proteins, and is also influenced by oxidative phenomena. Our results extend previous data in tectal-lesioned embryos, and suggest that a moderate, non-lethal oxidative stress can enhance the resistance of ganglion cells that might otherwise have died (spontaneously or following axotomy) owing to insufficient retrograde trophic support.     

PRMT 3, a type I protein arginine N-methyltransferase that differs from PRMT1 in its oligomerization, subcellular localization, substrate specificity, and regulation

Methylation is one of the many post-translational modifications that modulate protein function. Although asymmetric NG,NG-dimethylation of arginine residues in glycine-arginine-rich domains of eucaryotic proteins, catalyzed by type I protein arginine N-methyltransferases (PRMT), has been known for some time, members of this enzyme class have only recently been cloned. The first example of this type of enzyme, designated PRMT1, cloned because of its ability to interact with the mammalian TIS21 immediate-early protein, was then shown to have protein arginine methyltransferase activity. We have now isolated rat and human cDNA orthologues that encode proteins with substantial sequence similarity to PRMT1. A recombinant glutathione S-transferase (GST) fusion product of this new rat protein, named PRMT3, asymmetrically dimethylates arginine residues present both in the designed substrate GST-GAR and in substrate proteins present in hypomethylated extracts of a yeast rmt1 mutant that lacks type I arginine methyltransferase activity; PRMT3 is thus a functional type I protein arginine N-methyltransferase. However, rat PRMT1 and PRMT3 glutathione S-transferase fusion proteins have distinct enzyme specificities for substrates present in both hypomethylated rmt1 yeast extract and hypomethylated RAT1 embryo cell extract. TIS21 protein modulates the enzymatic activity of recombinant GST-PRMT1 fusion protein but not the activity of GST-PRMT3. Western blot analysis of gel filtration fractions suggests that PRMT3 is present as a monomer in RAT1 cell extracts. In contrast, PRMT1 is present in an oligomeric complex. Immunofluorescence analysis localized PRMT1 predominantly to the nucleus of RAT1 cells. In contrast, PRMT3 is predominantly cytoplasmic.     

Error handling in a parallel LR substring parser

Parallel parsing is currently receiving attention but there is little discussion about the adaptation of sequential error handling techniques to these parallel algorithms. We describe a noncorrecting error handler implemented with a parallel LR substring parser. The parser used is a parallel version of Cormack's LR substring parser. The applicability of noncorrecting error handling for parallel parsing is discussed. The error information provided for a standard set of 118 erroneous Pascal programs is analysed. The programs are run on the sequential LR substring parser.