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PubMed1998

New pyrrole alkaloids from Solanum sodomaeum.

Two new pyrrole alkaloids, solsodomine A and B, were isolated from the fresh berries of Solanum sodomaeum L., collected from the Libyan desert. The structures of these compounds were established by 2D-NMR, including 15N NMR spectroscopy and chemical degradation. Solsodomine A (1) shows activity against Mycobacterium intracellulare. This is the first report of pyrrole alkaloids from the genus Solanum.

Anti-Bacterial Agents↗
PubMed1999

Non-type I cystinuria caused by mutations in SLC7A9, encoding a subunit (bo,+AT) of rBAT.

Cystinuria (MIM 220100) is a common recessive disorder of renal reabsorption of cystine and dibasic amino acids. Mutations in SLC3A1, encoding rBAT, cause cystinuria type I (ref. 1), but not other types of cystinuria (ref. 2). A gene whose mutation causes non-type I cystinuria has been mapped by linkage analysis to 19q12-13.1 (Refs 3,4). We have identified a new transcript, encoding a protein (bo, +AT, for bo,+ amino acid transporter) belonging to a family of light subunits of amino acid transporters, expressed in kidney, liver, small intestine and placenta, and localized its gene (SLC7A9) to the non-type I cystinuria 19q locus. Co-transfection of bo,+AT and rBAT brings the latter to the plasma membrane, and results in the uptake of L-arginine in COS cells. We have found SLC7A9 mutations in Libyan-Jews, North American, Italian and Spanish non-type I cystinuria patients. The Libyan Jewish patients are homozygous for a founder missense mutation (V170M) that abolishes b o,+AT amino-acid uptake activity when co-transfected with rBAT in COS cells. We identified four missense mutations (G105R, A182T, G195R and G295R) and two frameshift (520insT and 596delTG) mutations in other patients. Our data establish that mutations in SLC7A9 cause non-type I cystinuria, and suggest that bo,+AT is the light subunit of rBAT.

Amino Acid Sequence↗
PubMed1996

Insoluble wild-type and protease-resistant mutant prion protein in brains of patients with inherited prion disease.

We studied prion proteins (PrP) in skin and brains of Libyan Jews carrying the E200K mutation who died of familial Creutzfeldt-Jakob disease (CJD). Unexpectedly, studies with brain showed that PrP molecules encoded both by the wild-type (wt) and mutant alleles exhibit altered properties characteristic of the prion protein associated with prion diseases (PrPSc). Using monospecific antisera, we found that wtPrP was insoluble in the brains of three patients who were heterozygous for the E200K mutation, whereas mutant PrP was both insoluble and protease-resistant. Our results argue that both wild-type and mutant PrP undergo conformational changes and are particularly intriguing, because the normal isoform PrPc is soluble in nondenaturing detergents and is readily digested by proteases, whereas PrPSc is insoluble and resistant to proteolytic digestion. Our findings indicate that insoluble wtPrP represents a conformational intermediate, the first to be identified, within a pathway in which PrPc is converted to PrPSc.

Amino Acid Sequence↗
PubMed1999

A novel allele in the promoter region of the human serotonin transporter gene.

The human serotonin transporter (hSERT) gene is a promising candidate for mediating the genetic susceptibility for various psychiatric conditions such as mood and obsessive-compulsive disorders. Two polymorphic sites in this gene attracted much interest: a VNTR of 17-bp repeats in intron two, and an insertion/deletion in the 5'-flanking promoter region (5-HTT gene-linked polymorphic region-5-HTTLPR) creating a short (S) and a long (L) allele. The 5-HTTLPR polymorphism is situated in a GC-rich region composed of 20-23 bp repeating units. The S and L alleles have 14 and 16 repeat-elements respectively. Positive associations of the 5-HTTLPR polymorphism with mood disorders, anxiety-related personality traits, autism and late-onset Alzheimer's disease have been published, although some non replications were also reported. Here we report a novel allele (termed LJ) in the 5-HTTLPR site. This allele is longer than the L allele by 43 bp, has 18 repeat units and contains two copies of the insertion/deletion sequence arranged in tandem. The LJ allele was found in individuals of Libyan and Tunisian Jewish origin but not in Moroccan or Ashkenazi Jews.

Base Composition↗
PubMed2002

Yeasts of the genus Candida are the dominant cause of onychomycosis in Libyan women but not men: results of a 2-year surveillance study.

BACKGROUND: The reported frequency of recovery of fungi from infected nails varies according to the geographical area. OBJECTIVES: To establish the nature of the causal agents in a sample of the Libyan population presenting with suspected onychomycosis. METHODS: Samples were taken from the infected fingernails of 648 patients attending the Tripoli Medical Centre. RESULTS: Samples from 500 patients proved positive for fungi following culturing, while 476 were potassium hydroxide and culture positive. Of the culture-positive samples, yeasts of the genus Candida (C. albicans, C. parapsilosis, C. glabrata, C. guillermondii and C. tropicalis) were the dominant cause of this condition in women (417 of 434, 96%) but were responsible for only a minority of cases in men (three of 66, 5%). In contrast, dermatophytes (Trichophyton violaceum, T. rubrum, T. mentagrophytes and Microsporum canis) were responsible for this condition in the majority of cases in men (53 of 66, 80%) but only 3% (15 of 434) of cases in women. The mould Aspergillus nidulans was isolated from the nails of 10 (15%) men and two (0.5%) women. CONCLUSIONS: The data obtained in this study reveal an almost total separation of the aetiological agents responsible for onychomycosis based on gender.

Adolescent↗
PubMed1998

Immunogenicity of Haemophilus influenzae-diphtheria CRM197 protein conjugate vaccine (HbOC) in Libyan infants.

The immunogenicity of the HbOC, a Haemophilus influenzae type b conjugate vaccine, was evaluated in a randomized clinical trial of Arab children resident in Tripoli. The HbOC vaccine was given as part of a three-dose series at 2, 3 and 4 months of age together with hepatitis B, OPV and DPT to 90 children. Anti-H. influenzae antibody levels were compared with 81 infants receiving hepatitis B, OPV and DPT but not the HbOC vaccine. The immunogenicity and safety of HbOC was as high as that observed in industrialised countries. There were no major complications, and fever and temporary local discomfort were observed in fewer than approximately 2% of the infants. Infants receiving the HbOC vaccine had an increase in Hib antibodies with only one dose. Geometric mean anti-Hib antibody levels were 0.41, 1.36 and 2.91 mg/ml after one, two and three doses. After two doses, all children had antibody levels above 0.20 mg/ml and the lowest antibody concentration was 0.80 mg/ml. Antibody levels in our children are similar to those observed in Europe and the USA and it is thus likely that HbOC will provide good clinical protection in this population. As most of the children develop antibody titres above or near 1 mg/ml, it is likely that they are protected even with two doses of the vaccine. The anti-Hib antibody levels observed are similar to those in studies from Europe where hepatitis B vaccine is not routinely given.

Antibodies, Bacterial↗