Prediction of apatite lattice constants from their constituent elemental radii and artificial intelligence methods

Lattice constants (LCs) of all possible 96 apatite compounds, A(5)(BO(4))(3)C, constituted by A[double bond]Ba(2+), Ca(2+), Cd(2+), Pb(2+), Sr(2+), Mn(2+); B[double bond]As(5+), Cr(5+), P(5+), V(5+); and C[double bond]F(1-), Cl(1-), Br(1-), OH(1-), are predicted from their elemental ionic radii, using pattern recognition (PR) and artificial neural networks (ANN) techniques. In particular, by a PR study it is demonstrated that ionic radii predominantly govern the LCs of apatites. Furthermore, by using ANN techniques, prediction models of LCs a and c are developed, which reproduce well the measured LCs (R(2)=0.98). All the literature reported on 30 pure and 22 mixed apatite compounds are collected and used in the present work. LCs of all possible 66 new apatites (assuming they exist) are estimated by the developed ANN models. These proposed new apatites may be of interest to biomedical research especially in the design of new apatite biomaterials for bone remodeling. Similarly these techniques may also be applied in the study of interface growth behaviors involving other biomaterials.     

Antimicrobial susceptibility and frequency of occurrence of clinical blood isolates in Sfax-Tunisia (1993-1998)

Antimicrobial susceptibility and frequency of occurrence of clinical blood isolates in Sfax-Tunisia (1993-1998). The choice of antimicrobial therapy for the treatment of bacteremia is often empirical and based on the knowledge of susceptibility profiles of the most common bacteria causing such infections. This study determines the bacterial etiology of bacteremic episodes and antimicrobial susceptibility patterns recorded at a teaching hospital, from January 1993 to December 1998. We collected 2979 strains responsible for bacteremia. Gram negative bacteria were predominant (60%). The organisms recovered most frequently were Staphylococcus aureus (18.9%), Escherichia coli (14.7%), Klebsiella pneumoniae (14%) and Pseudomonas aeruginosa (7.6%). The incidence of resistance to methicillin were 17.4% for Staphylococcus aureus and 26.8% for coagulase negative Staphylococcus. No resistance to glycopeptides was observed among the enterococci and staphylococci studied. 27.7% of enterobacteriaceae were resistant to third generation cephalosporins. Imipenem was the most active agent against gram negative bacteria. To carry out a surveillance of bacteremic episodes occurring at every hospital, it is necessary to provide valuable information which should be the basis for effective empiric therapy.     

A Huntington's disease CAG expansion at the murine Hdh locus is unstable and associated with behavioural abnormalities in mice

Huntington's disease (HD) is a dominant disorder characterized by premature and progressive neurodegeneration. In order to generate an accurate model of the disease, we introduced an HD-like mutation (an extended stretch of 72-80 CAG repeats) into the endogenous mouse Hdh gene. Analysis of the mutation in vivo reveals significant levels of germline instability, with expansions, contractions and sex-of-origin effects in evidence. Mice expressing full-length mutant protein display abnormal social behaviour in the absence of acute neurodegeneration. Given that psychiatric changes, including irritability and aggression, are common findings in HD patients, our data are consistent with the hypothesis that some clinical features of HD may be caused by pathological processes that precede gross neuronal cell death. This implies that effective treatment of HD may require an understanding and amelioration of these dysfunctional processes, rather than simply preventing the premature death of neurons in the brain. These mice should facilitate the investigation of the molecular mechanisms that underpin the pathway from genotype to phenotype in HD.     

High amounts of circulating interleukin (IL)-6 in the form of monomeric immune complexes during anti-IL-6 therapy. Towards a new methodology for measuring overall cytokine production in human in vivo.

A patient with plasma cell leukemia was treated with anti-interleukin (IL)-6 monoclonal antibodies (mAb) for 2 months. Using chromatography on protein A-Sepharose, anti-murine-IgG-Sepharose, anti-IL-6-mAb-Sepharose and gel filtration at pH 2.3, we have demonstrated that the anti-IL-6 mAb, by preventing the binding of IL-6 to its cell membrane receptor and its renal elimination, has induced huge amounts of IL-6 to circulate in the form of monomeric immune complexes. By using this observation, we have developed a mathematical modelling that allows the determination of the overall daily production of IL-6 in this patient, which was in the range of 15 micrograms per day. Overall in vivo production of cytokines has never been evaluated in animals or in humans before.     

Sexually dimorphic expression of protease nexin-1 and vanin-1 in the developing mouse gonad prior to overt differentiation suggests a role in mammalian sexual development

The mammalian sex-determining pathway is controlled by the presence or absence of SRY expression in the embryonic gonad. Expression of SRY in males is believed to initiate a pathway of gene expression resulting in testis development. In the absence of SRY, ovary development ensues. Several genes have now been placed in this pathway but our understanding of it is far from complete and several functional classes of protein appear to be absent. Sex-determining genes frequently exhibit sexually dimorphic patterns of expression in the developing gonad both before and after overt differentiation of the testis or ovary. In order to identify additional sex-determining or gonadal differentiation genes we have examined gene expression in the developing gonads of the mouse using cDNA microarrays constructed from a normalized urogenital ridge library. We screened for genes exhibiting sexually dimorphic patterns of expression in the gonad at 12.5 and 13.5 days post-coitum, after overt gonad differentiation, by comparing complex cDNA probes derived from male and female gonadal tissue at these stages on micro-arrays. Using in situ hybridization analysis we show here that two genes identified by this screen, protease nexin-1 (Pn-1) and vanin-1 (Vnn1), exhibit male-specific expression prior to overt gonadal differentiation and are detected in the somatic portion of the developing gonad, suggesting a possible direct link to the testis-determining pathway for both genes.     

Hyaluronan-related limited concentration by the immature kidney

The limited renal concentration performance by the immature kidney traditionally is thought to be attributed to blunted renal response to arginine vasopressin (AVP) and medullary hypotonicity. The diminished AVP-dependent osmotic water permeability of the collecting duct is the result of decreased AVP binding and adenylate cyclase activation, and low expression of aquaporin-2 (AQP2) mRNA and low levels of AQP2 protein. Moreover, the immature kidney fails to establish deep cortico-papillary osmotic gradient because of structural immaturity, limited solute transport and increased medullary blood flow. Based on indirect clinical and experimental evidences this article puts forward a hypothesis that during perinatal period the abundant hyaluronan (HA) content in the renomedullary interstitium has a primary role in antagonizing water reabsorption and limiting concentration performance. Hydration-related alterations in renal HA appears to be mediated by antidiuretic hormone.The concept of HA-mediated renal water transport may imply that interfering selectively with renal HA metabolism may provide a new therapeutic approach to promote diuresis or antidiuresis, respectively, according to the elevation or reduction in renomedullary HA.     

Needle necropsy in AIDS

The value of autopsy in understanding the natural course of any disease is beyond any argument. The reluctance of pathologists to perform autopsy in HIV infected cadavers is justified due to the risks involved to the prosector and the morgue attendants. A relative low risk needle necropsy protocol is proposed using fine needle aspiration cytology, tru-cut biopsies and microbiological examination. Diagnosis could be offered in all the forty-four needle necropsies performed. Disseminated tuberculosis in 18/44 (40.9%) cases, disseminated cryptococcosis in 12/44 (27.2%) cases, poly-microbial infections in 27.2% cases and non-Hodgkin's lymphoma in 9% cases were detected in the study. Infectious agents like Histoplasma capsulatum, Isospora belli, tachyzoites of Toxoplasma gondii, Candida sp and Cryptococcus sp could be demonstrated in the samples obtained in the study. Lack of material for study of gross pathology, inaccessibility of deep-seated lesions and risk of needle stick injury to the prosector though low are the limitations of this procedure.     

Mimotope and anti-idiotypic vaccines to induce an anti-IgE response

We have defined epitopes on human IgE by screening different phage display random peptide libraries with a monoclonal anti-IgE antibody termed BSW17. The selected mimotopes and epitopes within the Cepsilon3 and Cepsilon4 region of IgE induced antibodies that were nonanaphylactogenic and had biological activity similar to BSW17. The chemically synthesized and KLH-coupled IgE epitopes or mimotopes were used to induce an anti-IgE response in rhesus monkeys. The immunized rhesus monkeys were subsequently protected in a PCA test when sensitized with human IgE and triggered with the corresponding allergen. Furthermore, using the same monoclonal anti-IgE antibody, we also generated an anti-idiotypic antibody that showed sequence homology with the IgE epitope in the Cepsilon3 domain. This anti-idiotypic antibody as well as the mimotopes were then used in a mouse model to induce orally an anti-IgE immune response. For this purpose mice were fed by intragastric gavages with bacteriophages displaying the small IgE-homologous structures. Orally immunized mice produced serum anti-IgE antibodies that were inhibited by BSW17 suggesting that it may be possible to induce a systemic anti-IgE response orally.