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Non-small cell lung cancer (NSCLC) is a significant global health issue with diverse molecular profiles affecting treatment responses. Yet, NSCLC's molecular epidemiology in Morocco is largely unexplored. This study focuses on NSCLC genetic mutations, specifically in adenocarcinoma, among Moroccan patients to contribute to understanding NSCLC in this population. Ninety-four patients diagnosed with lung adenocarcinoma were analyzed. Formalin-fixed paraffin-embedded tissue samples were processed, and deoxyribonucleic acid (DNA)/ribonucleic acid (RNA) was extracted using standardized protocols. Mutations were detected using the AmoyDx Pan Lung Cancer Polymerase Chain Reaction (PCR) Panel kit, and their frequencies were assessed through statistical analysis. Epidermal Growth Factor Receptor (EGFR) mutations were detected in 22.34% of patients, predominantly exon 19 deletions (66.66%) and exon 21 L858R mutations (23.80%). Anaplastic lymphoma kinase (ALK) gene fusion was observed in 3.19% of patients, and KRAS mutations in 1.06%. No mutations were found in other tested genes. A slightly higher mutation rate was noted in females (54.16%) compared to males (45.84%). The study reveals a distinct mutation profile in Moroccan NSCLC patients, with a notable prevalence of EGFR mutations, albeit lower than in some Asian populations. The significance of EGFR mutations in treatment response aligns with global findings, highlighting the importance of understanding regional molecular variations for personalized therapy. Despite limitations in sample size and clinical data, this study sheds light on the genetic landscape of NSCLC in Morocco. The observed mutation rates, particularly in EGFR, underscore the potential for targeted therapies in Moroccan NSCLC patients, emphasizing the need for further research to refine treatment strategies tailored to this population., Competing Interests: The authors declare no competing interests., (Copyright: Ouafaa Morjani et al.)

Background: Neuromyelitis optica spectrum disorder (NMOSD) was suggested to be more frequent and have specific features among populations from Africa or North Africa. However, we could not find any large study about NMOSD in an African population in the medical literature., Objectives: To describe the characteristics of NMOSD in a Moroccan monocenter population., Patients and Methods: A retrospective study was conducted. Patients fromJanuary 1999 to December 2015 fulfilling the 2015 International Consensus Criteria for NMOSD were included., Results: Sixty four patients fulfilled the criteria. Mean age at onset was 35.7 ± 10.7 years, and the sex ratio was 1/3.57. First clinical event was represented by optic neuritis (38.1%), followed by myelitis (27.0%) and a Devic's syndrome (17.2%). Mean annualized relapse rate was 1.07 ± 1.23 and mean EDSS at last visit was 5.1 ± 2.8. Aquaporine 4 antibodies were positive in 47.1%. Brain lesions were found in 71.2%. Most patients (76.6%) received disease-modifying therapy, mainly cyclophosphamide (86.0%) and 49% remained relapse-free after treatment initiation CONCLUSION: Data from our study suggest more similarities between North African NMOSD patients and non-Caucasian populations. More studies are needed to assess other pathological patterns and compare disease course to other populations., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Cryoglobulins are immunoglobulins that precipitate at low temperature and dissolve when warmed. According to Brouet, their classification relies upon the immunochemical study: type I comprises monoclonal immunoglobulins (IGG), when types II and III include both monoclonal and polyclonal components. During C hepatitis, the presence of a cryoglobulin, essentially made of mixed G-IGG and M-IGG, is a common feature with a prevalence of 40 to 80%. The authors report a case of a 63-year patient who presented with a vascular purpura and a peripheral polyneuropathy in a context of C hepatitis infection. The cryoglobulin found was composed of a monoclonal kappa A-IgG associated with a biclonal kappa and lambda M-IgG. No decrease of normal IgGs was found. This type of cryoglobulin does not belong to Brouet's classification, and argues for a new and more pertinent classification to be proposed.

A bilateral leukemic hypopyon can be inaugural in the child's leukemia or reveal a relapse. A five years old child with acute lymphoblastic leukemia presented after 30 months of treatment a bilateral hypopyon. Anterior chamber paracentesis with cytological survey revealed leukemic cells and confirmed the ocular relapse. The treatment included the association of topical corticosteroids, chemotherapy and radiotherapy. This child died unfortunately 16 months later following a medullar relapse. We remind the different clinical aspects of leukemic invasion of the anterior segment and the therapeutic methods for this relapse.

The major immunogenic site of foot-and-mouth disease virus (FMDV) is contained in a disordered loop comprising residues 134-158 of capsid protein VP1, located on the surface of the viral particle. Peptides corresponding to this sequence generally elicit protective levels of neutralizing antibodies in guinea pigs. In some instances, however, the level of neutralizing antibodies is low although the level of antibodies against the peptide, determined by ELISA, is as high as that in the sera with high neutralizing antibody titres. In an attempt to ascertain the reason for this difference, we have synthesized on a cellulose membrane 10 overlapping decapeptides, offset by one residue, covering the segment 141-159 of VP1 of two viruses belonging to serotypes A12 and O1, and tested them with guinea pig antisera raised against peptide 141-159, VP1 and FMDV particles (SPOTscan method). With type A, some peptides which were strongly positive with highly neutralizing antisera did not include the RGD triplet located at residues 145-147. In contrast, antisera with low neutralization titres reacted only with decapeptides which included the RGD motif. Moreover, peptide 147-156 coupled to keyhole limpet haemocyanin, but not peptide 141-149 coupled to the same carrier, elicited high levels of neutralizing antibodies in guinea pigs. In the case of serotype O, highly neutralizing antisera to virus reacted in ELISA with peptides 141-150 (containing the RGD motif) and 135-144 (located upstream from the RGD motif). The results suggest that the RGD triplet is not an indispensable constituent of peptides able to elicit a neutralizing antibody response against the virus.

Monoclonal antibodies recognize antigens with high affinity and specificity, but the structural basis for molecular mimicry remains unclear. It is often assumed that cross-reactive antigens share some structural similarity that is specifically recognized by a monoclonal antibody. Recent studies using combinatorial libraries, which are composed of millions of sequences, have examined antibody cross-reactivity in a manner entirely different from traditional epitope mapping approaches. Here, peptide libraries were screened against an anti-carbohydrate monoclonal antibody for the identification of peptide mimics. Positional scanning libraries composed of all-l or all-d hexapeptides were screened for inhibition of monoclonal antibody HGAC 39.G3 binding to an antigen displaying N-acetyl-d-glucosamine (GlcNAc) residues on a polyrhamnose backbone. Inhibitory activity by mixtures from the all-d hexapeptide library was greater than the activity from the all-l libraries. The most active d-amino acid residues defined in each of the six positions of the library were selected to prepare 27 different individual hexapeptides. The sequence Ac-yryygl-NH2 was specifically recognized by mAb HGAC 39.G3 with a relative affinity of 300 nM when measured in a competitive binding assay. The contributions to overall specificity of the residues of the all-d peptide (Ac-yryygl-NH2) in binding to mAb HGAC 39.G3 were examined with a series of truncation, l and d-amino acid substitution, and retro analogs. Dimeric forms of the all-d peptide were recognized with tenfold to 100-fold greater affinities relative to the monomer. The all-d peptide was found to inhibit mAb HGAC 39.G3 binding to an anti-idiotype antibody with approximately 1000-fold greater affinity than GlcNAc. As demonstrated here, the study of immune recognition using combinatorial chemistry may offer new insights into the molecular basis of cross-reactivity., (Copyright 1998 Academic Press.)

Retro-inverso (RI) peptides, also called all-D-retro peptides, have been shown to mimic the antigenic and immunogenic properties of L-peptides successfully. RI peptides corresponding to the loop 141-159 of the VP1 protein of foot-and-mouth disease virus (FMDV) have been synthesized and used to immunize rabbits and guinea pigs. These peptides induced longer-lasting and higher antibody titres in immunized animals than did the corresponding L-peptides and the antibodies cross-reacted strongly with virus particles and with L-peptides. Antisera raised to RI peptides had in vitro virus neutralization titres equal to or better than those obtained after immunization with classical FMDV antigens and L-peptides. In view of their increased stability, RI peptides may overcome some of the shortcomings of synthetic viral vaccines based on L-peptides.

Peptides corresponding to the immunodominant loop located at residues 135-158 on capsid protein VP1 of foot-and-mouth disease virus (FMDV) generally elicit high levels of anti-peptide and virus-neutralizing antibodies. In some instances, however, the level of neutralizing antibodies is low or even negligible, even though the level of anti-peptide antibodies is high. We have shown previously that the antigenic activity of peptide 141-159 of VP1 of a variant of serotype A can be mimicked by a retro-inverso (all-D retro or retroenantio) peptide analogue. This retro-inverso analogue induced greater and longer-lasting antibody titers than did the corresponding L-peptide. We now show that a single inoculation of the retro-inverso analogue elicits high levels of neutralizing antibodies that persist longer than those induced against the corresponding L-peptide and confer substantial protection in guinea pigs challenged with the cognate virus. In view of the high stability to proteases of retro-inverso peptide analogues and their enhanced immunogenicity, these results have practical relevance in designing potential peptide vaccines.

The binding specificity of a monoclonal antibody (MAb 12) known to recognize the surface antigen of hepatitis B virus (HBsAg) was studied using a positional scanning synthetic combinatorial library. A hexapeptide library totaling more than 30 x 10(6) sequences, made up of 120 mixtures having a single position defined with individual amino acids and the remaining five positions composed of mixtures of amino acids, was screened by competitive enzyme-linked immunosorbent assay (ELISA). This led to the identification of Ac-STTSMM-NH2 (IC50 = 170 nM), which specifically inhibited the interaction between HBsAg and MAb 12. One of the most active individual mixtures from the library was Ac-XXXPXX-NH2; however, none of the individual peptides synthesized containing proline at the fourth position showed significant activity (IC50 > 100,000 nM). To identify the individual peptide(s) responsible for the activity of Ac-XXXPXX-NH2, a bidirectional iterative synthesis and selection process was carried out. A completely different but active peptide sequence was identified (Ac-SVGPPH-NH2, IC50 = 165 nM). The two different hexapeptide sequences were prepared as linear homo- and heterodimer peptides in an attempt to improve the antigenicity. Of the four different sequences prepared, one heterodimer (Ac-STTSMMGGGSVGPPH-NH2) was found by ELISA to have a 10-fold improvement in activity over the two individual hexapeptides, and was equal to the inhibitory activity of the protein antigen. The equilibrium affinity constant of the MAb 12 toward this heterodimer sequence was 50-fold higher than the protein antigen when measured in a biosensor system. Since motifs from these two hexapeptides, namely, -STTS- and -GP-, were located in the primary sequence of the protein (residues 114-120, subtype ad), overlapping hexapeptides of this region were synthesized and assayed. The most active hexapeptide, namely, Ac-TTSTGP-NH2 (IC50 = 2.3 microM), was 10-fold less active than either hexapeptide found from the library. Extending the specific motif sequences to eleven residues resulted in an analog (Ac-STTSTGPSRTC-NH2) having an equilibrium affinity constant similar to the heterodimer. The combined use of positional scanning libraries and the iterative synthesis and selection process in this study illustrates the power of these methods for the identification of novel peptides that inhibit anti-protein antibodies. These methods can be directly applied to the development of improved immunodiagnostics.

The RP dipeptide motif is highly conserved in the third hypervariable region (V3 loop) of the extracellular envelope glycoprotein of different types of HIV isolates. In view of this, we have designed and synthesized a construction referred to as "template assembled synthetic peptide" (TASP), in which a lysine-rich short polypeptide was used as a template to covalently anchor arrays of tripeptides, such as RPR, RPK, or KPR. The pentavalent presentation, 5(RPR)-, 5(RPK)-, or 5(KPR)-TASP, molecules manifested maximum inhibitory activity on HIV infection with a 50% inhibitory concentration value of 1-5 microM, respectively. Structure and inhibitory-activity relationship studies using analogs of 5(KPR)-TASP indicated that the positively charged side chains of the K and R residues in the tripeptide molecules are critical for the optimal inhibitory activity of the pentavalent construct. Interestingly, replacement of L-amino acid residues by D-amino acids or reduction of the peptide bond between the first two amino acids of the tripeptide generated peptide-TASP analogs active at sub-microM, concentrations. The anti-HIV action of the peptide-TASP constructs is specific, since they inhibit infection of several types of CD4-expressing cells by HIV-1 Lai and HIV-2 EHO but not by the simian SIV-mac isolate. Our results suggest that these inhibitors block three post-CD4 binding functions of the HIV envelope glycoproteins, mediation of viral entry, syncytium formation, and triggering cell death by apoptosis. As the peptide-TASP derivatives with unnatural amino acid sequences in the tripeptide moiety retain full inhibitory activity, they should provide potent protease-resistant peptide inhibitors as potential therapeutic agents for treatment of AIDS patients.

Two major limitations to the use of peptides as synthetic vaccines are their poor immunogenicity and low antigenic cross-reactivity with the epitopes of virus particles. Recently it has been shown that retro-inverso peptides corresponding to an immunodominant epitope of foot-and-mouth disease virus (FMDV) are able to mimic the structure and antigenic activity of natural L-peptides [1]. A series of L- and retro-inverso peptides of the loop 141-159 of the VP1 protein of FMDV has been synthesized. Antibodies to these peptides were produced by injecting rabbits with peptides covalently coupled to small unilamellar liposomes containing monophosphoryl lipid A as adjuvant. The retro-inverso peptides led to higher serum antibody titres which appeared earlier after the start of immunization and lasted longer than those found with L-peptides. Antibodies to retro-inverso peptides cross-reacted strongly with L-peptides and with virus particles, while guinea pig antisera to VP1 protein and virions cross-reacted strongly with the retro-inverso peptides. In view of their increased stability compared to natural L-peptides, retro-inverso peptidomimetics have considerable potential as synthetic viral vaccines.

Pseudopeptide analogues of the C-terminal hexapeptide of histone H3 (-Ile-Arg-Gly-Glu-Arg-Ala-OH) were obtained by systematically replacing, in each analogue, one peptide bond at a time by a reduced peptide bond psi (CH2-NH). The resulting analogues were then examined, in ELISA and in the BIAcore system, for their ability to bind polyclonal and monoclonal antibodies generated against the parent natural peptide and the protein. The comparative results show that reduced bond pseudopeptide analogues can mimic the parent peptide. These results present the first unequivocal example for the potent applicability of reduced peptide bond pseudopeptides in the immunological field.

One case of transmural thoracic lipoma is reported. Thoracic lipomas are rare tumors. This report illustrates the usefulness of CT and MRI in the preoperative diagnosis and subsequent evaluation of transmural thoracic lipoma.