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Biomedical subjects

I Mansour

Publications and source records attributed to I Mansour.

At least 19 recordsLinked to original sources
PubMed2003

Effects of a short-term calcium and vitamin D treatment on serum cytokines, bone markers, insulin and lipid concentrations in healthy post-menopausal women.

In vitro studies have shown that 1,25 dihydroxyvitamin D3 [1,25(OH)2D3] decreases cytokine production by monocytes and lymphocytes. In addition, intravenous or oral pulse calcitriol treatment suppresses interleukin 6 (IL6) and interleukin1beta (IL1beta) in hemodialysis patients. We studied the effect of a daily 12-week course of 1000 mg calcium and 800 U cholecalciferol on circulating 25 hydroxyvitamin D [25(OH)D], PTH, cytokines, osteoprotegerin (OPG), C-reactive protein (CRP), bone markers, lipid parameters and insulin levels in 47 healthy post-menopausal women. Thirty-nine women completed the study. A significant increase in 25(OH)D and a significant decrease in PTH were observed (p=0.0043 and p<0.0001, respectively). In addition, alkaline phosphatase, osteocalcin and, to a lesser extent, urinary free deoxypiridinoline (DPD) decreased significantly (p<0.0001, p=0.0002 and p=0.026, respectively). No change in circulating IL6, tumor necrosis factor alpha (TNFalpha), CRP, OPG, triglycerides, LDL- and HDL-cholesterol, and insulin levels was observed. Correlation studies in the 47 women enrolled in the study revealed inverse significant correlations between OPG on one side and body mass index, LDL-cholesterol, IL6, CRP and insulin levels on the other (p=0.002, p=0.002, p=0.004, p=0.023 and p=0.0001). Also, IL6 was significantly correlated with insulin levels (p=0.0005). In a multivariate model, both insulin and LDL-cholesterol were independently associated with OPG, while only insulin was independently associated with IL6. Our results showed no effect of a short-term calcium-vitamin D treatment on circulating cytokines, CRP, insulin levels and lipid parameters. This could be related to the low circulating cytokine concentrations in healthy subjects or to the short duration of treatment. The interesting association we found between OPG and some cardiovascular risk markers deserves further investigation.

Aged↗
PubMed2002

Asymptomatic deficiency in the peptide transporter associated to antigen processing (TAP).

Human HLA class I deficiency is a rare disease which, in most of the patients described to date, results from a defect in subunit 1 or 2 of the peptide transporter associated with antigen processing (TAP). The clinical features of TAP deficiency include a chronic inflammation of the respiratory tract and/or granulomatous skin lesions. In this report, we describe two adult siblings with an HLA class I deficiency. One individual had only spontaneously-healing skin granulomatous lesions, while the second did not display any of the symptoms associated with HLA class I deficiency and could be considered to be healthy. We show that the patients display a homozygous TAP2 mutation which blocks the maturation of HLA class I molecules. Cell surface expression of these molecules is strongly reduced, but three times higher than on cells from other previously described TAP-deficient individuals. This higher expression results, at least in part, from the presence of HLA-B7 molecules which are probably empty of peptide. The numbers of CD8+ alphabeta T cells are almost normal in these patients. The anti-EBV T-cell response of one patient is mediated by HLA-B7 restricted CD8+ alphabeta T lymphocytes recognizing the BMRF1 nuclear EBV antigen, demonstrating that CD8+ alphabeta T cells can participate in anti-viral responses. This study shows that TAP deficiency can remain totally asymptomatic for several decades, and suggests that in some cases, TAP-independent immune responses provide efficient protection from most of the common intracellular pathogens.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

A new HLA-B*27 allele (B*2719) identified in a Lebanese patient affected with ankylosing spondylitis.

Eighteen different HLA-B*27 alleles (B*2701-B2718) have so far been recognized by the WHO Nomenclature Committee for Factors of the HLA System. Frequency and disease association of these alleles with spondyloarthropathies differ among ethnic groups. We describe here a novel HLA-B*27 subtype identified in a Lebanese patient suffering from ankylosing spondylitis (AS). This new variant differs from the common HLA-B*2705 DNA sequence at five different nucleotide positions. These nucleotide changes lead to three amino acid differences in the alpha2 domain; Thr to Ile at position 94, Leu to Ile at position 95 and Asn to Arg at position 97. Since this novel allele is encountered in an AS patient, the associated sequence changes are not expected to affect significantly neither the presentation of a putative arthritogenic peptide nor the conformation-dependent recognition by effector cells.

Amino Acid Sequence↗
PubMed2001

Familial Mediterranean fever in Lebanon: mutation spectrum, evidence for cases in Maronites, Greek orthodoxes, Greek catholics, Syriacs and Chiites and for an association between amyloidosis and M694V and M694I mutations.

Seventy-nine unrelated Lebanese patients were tested for 15 mutations in the MEFV gene: A761H, A744S, V726A, K695R, M694V, M694I, M694del, M6801 (G --> C), M680I (G --> A) in exon 10, F479L in exon 5, P369S in exon 3, T267I, E167D and E148Q in exon 2, using PCR digestion, ARMS, DGGE and/or sequencing. Mutations were detected in patients belonging to all communities, most interestingly the Maronite, Greek orthodox, Greek catholic, Syriac and Chiite communities. The most frequent mutations are M694V and V726A (27% and 20% of the total alleles respectively). M694I, E148Q and M680I mutations account respectively for 9%, 8% and 5%. Each of the K695R, E167D and F479L mutations was observed once and all the remaining mutations were not encountered. Of the alleles 33% do not carry any of the studied mutations. The mutation spectra, clinical features and severity of the disease differed among the Lebanese communities. The genotype-phenotype analysis showed a significant association (P < 0.001) between amyloidosis and the presence of mutations at codon 694 in exon 10 (both M694V and M694I). None of the patients carrying other mutations developed amyloidosis.

Amyloidosis↗
PubMed2001

Familial Mediterranean Fever: association of elevated IgD plasma levels with specific MEFV mutations.

Familial Mediterranean Fever (FMF) is a recessively inherited disorder, characterized by episodic fever, abdominal and arthritic pain, as well as other forms of inflammation. Some FMF patients present higher IgD serum levels, and it is not yet known whether such an elevation is related to specific genotypes or correlated with a specific phenotype. In order to evaluate the association between known FMF-related mutations and IgD levels in confirmed patients, as well as the correlation between those levels and the presence of specific clinical signs, genotypic analysis and IgD plasma measurements were performed for 148 Lebanese and Jordanian FMF patients. Most common mutational patterns were M694V heterozygotes (19%) and homozygotes (17%), and V726A heterozygotes (18%) and homozygotes (5%), with an additional 11% combining both mutations. Twenty-one patients had higher IgD levels (superior to 100 microg/ml). The risk for higher IgD levels was significantly associated with M694V homozygote status (OR = 6.25) but not with heterozygotic one (OR = 1). Similarly, the risk for higher IgD was also found with V726A homozygotes (OR = 2.2) but not with heterozygotes (OR = 1.05). The use of colchicine was not statistically associated with IgD levels. Clinically, hyper IgD was also found significantly associated with arthritis (OR = 18). Thus, homozygotic status for M694V, and to a lesser extent V726A, is associated with increased risk for higher IgD plasma levels, regardless of colchicine use. Elevated IgD plasma levels are also correlated with the severity of FMF manifestations, and especially with arthritis.

Cytoskeletal Proteins↗
PubMed2000

Genetic screening of fourteen mutations in Jordanian familial Mediterranean fever patients.

Familial Mediterranean fever is an autosomal recessive disorder characterised by episodic fever, abdominal and pleuritic pain, serositis and arthritis. The FMF gene (MEFV) has been mapped to chromosome 16p13.3 and generates a protein found exclusively in granulocytes. Seventeen mutations have been reported up to the present in FMF patients. This study involves the screening of 14 mutations in 42 Jordanian patients by two methods: RFLP and ARMS. The most frequent mutations were M694V and V726A (20% and 14% of the alleles respectively), followed by M680I and E148Q (9.5% and 7% of the alleles respectively). The A744S mutation accounts for 2.5% and the M694I, T267I and F479L mutations account each for 1% of the alleles. E167D, R761H, P369S, I692del and M694del mutations were not found in this population. Forty-four percent of the alleles did not have any of the 14 mutations. The results show the diversity and the frequency of the mutations in the Jordanian patients, and open the way for further investigations on patients diagnosed to have FMF and in whom no mutations were found. Hum Mutat 15:384, 2000.

Adolescent↗
PubMed1996

HLA phenotype polymorphism in the Lebanese population.

The HLA-A, -B, -DR and DQ phenotypes have been defined in a panel of 217 Lebanese. These subjects were all unrelated, belonged to different religious communities and originated from the various provinces of Lebanon. All the broad class I specificities tested, except splits A25(10), B54(22) and B56(22), were present in this panel. When HLA-A and -B antigen frequencies were compared with data on the Caucasoids, Negroids and Orientals, several similarities in antigen frequencies could be found between some frequencies observed in the Lebanese and those observed in the Negroids and/or Orientals. There were no frequencies equivalent to those particular to the Caucasoids. In addition, two groups of class I antigens could be distinguished: a first group (A32, B14, B18, B35, B38, B39, B41 and B50) showing higher frequencies, and a second group (A31, B27, B60 and B62) showing lower frequencies than those observed in the Caucasoids, Negroids and Orientals. However, when analysed separately, several mediterranean ethnic groups, notably the Greeks and Italians, have a frequency profile equivalent to that of the Lebanese, with the exception of the B41 specificity, which is particularly high in the Lebanese (14.2%). The data concerning the class II antigens are the most interesting. All the specificities were present in the panel. The HLA-DR5 is the highest frequency of DR antigens in the present panel (58.9%) and nearly all DR5 positive individuals are DR11. The DR11 allele accounts for 33.1% of the total DR gene frequency. The highest DQ antigen frequency is that of DQ3 (76.4%), the majority of which is DQ7 (66.4%). We observed a high DR11-DQ7 haplotype frequency (29.4%) with a significant delta value for linkage disequilibrium. There is no linkage disequilibrium between B41 and DR11. The commonly observed linkage disequilibrium between the DQ5 allele, and the DR1, DR2, DR10 and DR14 alleles are not significant in this Lebanese panel.

Adolescent↗
PubMed1996

[Hepatitis C virus in hemodialysis patients and blood donors in Lebanon].

The agent of the majority of parenterally transmitted non-A, non-B hepatitis is the hepatitis C virus (HCV). In this study, we estimate the HCV seropositivity in 7,771 blood donors and 317 patients on hemodialysis in 5 different centres, of which 4 are situated in Beirut. The used screening test consists of a second generation EIA technique. The study shows that 0.41% of blood donors are HCV seropositive. The mean percentage of seropositive patients is about 27% but the comparison of centres among them showed a high variability (10, 19, 21, 33 et 39%). The blood transfusion, the number of years on hemodialysis and the screening of blood donors seem to be the main risk factors. Reducing the number of transfusions to hemodialysed patients and screening antibodies anti-HCV in blood donations are primordial.

Adolescent↗
PubMed1994

Multiple labeling using two-color immunofluorescence with only one light source, two fluorescence photomultiplier tubes, and two light scatter detectors.

Multiple labeling is necessary for the detailed phenotyping of cells in many biological systems in human and animal species. In a previous report, we described an approach permitting the study of three labels simultaneously by using the two-color immunofluorescence and one light source (Mansour et al., Cytometry 11:636-641, 1990). This approach allowed enumeration of cell subpopulations positive for only one label and negative for many others (X+ A- B- ...). We here present an improvement of the previous approach to allow analysis of double positive phenotypes (X+ Y+ A- B- ...), using only two fluorescence photomultiplier tubes and light scatter detectors. It consists of a two-step analysis that does not require additional material than that used in the former technique. Briefly, all antibodies are conjugated to only two fluorochromes: either FITC or PE. For the analysis of the X+ Y+ A- B- ... phenotype, the Y, A and B labels are all coupled to the same dye (FITC, e.g.) and the X label to the other dye (i.e, PE). In a first step, cells are labeled with X, A, and B, and in a second step, the second positive (Y) label is added. Two examples are supplied: CD56+ CD2+ CD3- CD16- decidua infiltrating cells and CD3+ TCR delta+ CD4- CD8- peripheral blood lymphocytes. This technique is useful for qualitative as well as quantitative analysis, with cytometers that do not have the appropriate hardware to do true three-color immunofluorescence analysis.

Antigens, CD↗
PubMed1994

No evidence for the expression of the progesterone receptor on peripheral blood lymphocytes during pregnancy.

The expression of the progesterone receptor in human peripheral blood lymphocytes was analysed, using an enzyme linked immunosorbent assay (Abbott PgR-EIA monoclonal), in order to evaluate its prognostic character in the context of spontaneous abortion. Cytosols were prepared from lymphocytes of 24 healthy pregnant women (11 first, 10 second and three third trimester), seven healthy non-pregnant women, nine women with recurrent spontaneous abortion, and six healthy men. In addition, a human breast carcinoma cell line (ZR-75-1), which expresses the progesterone receptor, was analysed throughout. The ZR-75-1 cell line showed an expression of 642 fmol/mg whereas lymphocytes of pregnant women showed an expression < or = 4 fmol/mg. Lymphocytes of non-pregnant women, women with threatened pre-term delivery, and men showed equivalent levels: 3 +/- 1, 3 +/- 2 and 5 +/- 4 fmol/mg respectively. These results show that there is no evidence of specific expression of the progesterone receptor in pregnancy and exclude any prognostic character in spontaneous abortion. A role for the progesterone receptor in the mechanism of the known effect of progesterone on peripheral blood lymphocytes is also excluded.

Abortion, Habitual↗
PubMed1993

Circadian rhythms of circulating NK cells in healthy and human immunodeficiency virus-infected men.

Antiviral immunity involves NK cells, which circulate rhythmically every 24 hours. We have investigated circadian and 12-hour rhythms in the peripheral count of circulating NK cells in 15 men infected with human immunodeficiency virus (HIV) and 13 healthy controls. We analyzed three phenotypes using double-labeling with monoclonal antibodies and flow cytometry assessment: CD3- CD16+, CD3-CD57+, and CD2+CD3-. A statistical validation of time-dependent differences was achieved if significance (p < 0.05) was validated both with analysis of variance and cosinor. The circadian rhythm had a similar asymmetric waveform for the three phenotypes and is homogeneous on an individual basis. The circulating NK cell count peaked in the early morning and was low at night. A circadian rhythm and a circahemidian harmonic characterized all phenotypes in healthy subjects. We considered two groups of HIV-infected men: those who were asymptomatic (eight) and those with acquired immune deficiency syndrome (AIDS) (seven). Circadian changes in NK cell count were similar in both subgroups and in healthy controls. The circadian pattern was also consistent among individual patients. Asymptomatic HIV-infected men (early-stage disease) exhibited more pronounced 12-hour rhythmicity than did patients with AIDS or controls. The circulation of NK cells does not appear to share the same synchronizer(s) as other circulating T- or B-lymphocyte subsets. Thus, HIV infection gradually abolished circadian rhythmicity in circulating T and B cells, whereas it did not disturb that in NK cells.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Expression of CD11b (Leu15) antigen on CD3+, CD4+, CD8+, CD16+ peripheral lymphocytes. Estimation of CD3+8+11b+ and CD3+4-8-11b+ T-cell subsets using a single laser flow cytometer.

CD11b (Leu15) epitope is expressed on 20-30% of peripheral blood lymphocytes, including CD16+ large granular lymphocytes and CD8+ cells. This study confirms that 30% of CD8+ lymphocytes and virtually all CD16+ NK cells from healthy subjects express this determinant. In parallel, our data show that various proportions of CD3+4-8-, TCR-delta cytotoxic T lymphocytes and occasionally CD4+ lymphocytes subsets could also express this epitope. The CD8+11b+ phenotype is associated with suppression of T-cell proliferative response and has been extensively used to characterize suppressor T lymphocytes. Since about 25% of CD8 lymphocytes are non-T (CD3-) and express the CD16 NK antigen (CD8+16+3-), the expression of CD11b was also studied on CD8+3+ T-cell and CD8+16+ NK-cell subsets. To this end, we developed three methods using a flow cytometer equipped with a single laser and two fluorescence detectors. Results showed that T CD8+3+11b+ and NK CD8+16+11b+ lymphocytes account for 30% and 70% of CD8+11b+ cells respectively. Consequently, the CD8+3+11b+ phenotype would be more specific for suppressor T lymphocytes than the total CD8+11b+ phenotype which includes high proportions of CD16+ NK cells.

Antigens, Differentiation↗
PubMed1991

Dichotomy of two CD8+ lymphocyte subsets in HIV infection. Depletion of CD8+ CD3- and expansion of CD8+ CD3+ subsets: consequence on the CD4/CD8 ratio.

In order to highlight the underlying mechanism(s) of the CD8 lymphocyte expansion in the HIV infection, two distinct CD8 subsets were analysed: T CD8bright+ CD3+ with MHC-restricted activity, and non-T CD8dim+ CD3-, which performs natural killer (NK) activity. It consists of a cross-sectional study including 168 HIV-infected patients (74 CDC stage II, 48 CDC stage III and 46 CDC stage IV) compared among them and to 60 healthy individuals. We observed an expansion of CD8+ CD3+ cells which masks a depletion of CD8+ CD3-. The comparative study showed that the expansion of the CD8+ CD3+ is relatively higher than that of total CD8+ lymphocytes and that the depletion of the CD8+ CD3- subset is severe, begins early and remains constant through the HIV progression. The comparison of CD4/CD8 and CD4/CD8+ CD3+ ratios showed that the latter could possibly be a better indicator in the HIV infection. The mechanism of inverted CD4/CD8 ratio in healthy individuals was also clarified. The CD8+ CD3+, CD8+ CD3- and CD4/CD8+ CD3+ parameters would be more specific markers than total CD8 and CD4/CD8 ratio especially in therapy trials.

Adult↗