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Biomedical subjects

M Alaibac

Publications and source records attributed to M Alaibac.

At least 19 recordsLinked to original sources
PubMed2005

Tumour necrosis factor alpha is expressed in refractory skin lesions from patients with subacute cutaneous lupus erythematosus.

OBJECTIVES: To investigate whether tumour necrosis factor alpha (TNFalpha) is expressed in subacute cutaneous lupus erythematosus (SCLE) skin lesions. METHODS: The in situ expression of TNFalpha in refractory lesional and non-lesional skin biopsy specimens from patients with SCLE was analysed using an immunohistochemical approach. At the time of biopsy these patients were receiving treatment with systemic medications such as antimalarial agents, immunosuppressive drugs, and thalidomide. Expression of TNFalpha was also evaluated in cutaneous lesions of patients with other inflammatory and neoplastic skin diseases as controls. RESULTS: The data showed that refractory lesional skin tissue from patients with SCLE displays a strongly positive distribution of TNFalpha, particularly within the epidermis. No prominent staining was seen in non-lesional skin from the same group of patients or in cutaneous lesions from the control group. CONCLUSIONS: These findings suggest that TNFalpha is localised and produced by epidermal cells within SCLE skin lesions and support its potential role in the pathogenesis of SCLE. The tissue localisation of TNFalpha may represent a potential therapeutic target providing a new perspective in the treatment of refractory skin lesions in patients with SCLE.

Adult↗
PubMed2001

Immunoglobulin heavy chain variable region family expression in primary cutaneous follicle centre cell lymphomas.

BACKGROUND: Primary cutaneous follicle centre cell lymphomas (PCFCCL) are the most common type of primary cutaneous B-cell lymphomas. Patients with this disorder develop one or a few clinically indolent tumour nodules, plaques, or papules confined to a circumscribed area. Only limited data have so far been published on the use of immunoglobulin heavy chain variable region (VH) families by these tumours. OBJECTIVES: Because the definition of the repertoire of VH genes could have significant biological and diagnostic implications, we evaluated a group of patients with PCFCCL for VH family use. METHODS: DNA obtained from 15 cases of PCFCCL was amplified by polymerase chain reaction (PCR) using a panel of VH family-specific amplimers. RESULTS: The pattern of VH family usage was similar to that reported in both normal peripheral blood B cells and the most common low grade non-Hodgkin's lymphomas, where VH region utilization is essentially random with frequent usage of the VH3 family. CONCLUSIONS: These findings support the hypothesis that PCFCCL may derive from the mature peripheral lymphoid compartment. Our results may also have implications for the routine analysis of B-lymphoid clonality in PCFCCL.

DNA, Neoplasm↗
PubMed2001

PIBI(D)S: clinical and molecular characterization of a new case.

The term PIBI(D)S has been used to indicate a rare recessively inherited genetic disorder characterized by photosensitivity, mild non-congenital ichthyosis, brittle sulphur-deficient hair with trichoschisis (trichothiodystrophy), impaired intelligence, occasionally decreased fertility and short stature. To the best of our knowledge, about 20 cases have been reported in the literature. Here we report the characterization of the hair, brain, ultraviolet sensitivity and DNA excision repair defects of a new patient affected by PIBI(D)S. The diagnosis of PIBI(D)S syndrome was made in our patient on the basis of the clinical features and then confirmed by hair microscopy and biochemical analysis. Our patient has increased muscular tone, alteration of the deep tendon reflexes and psychomotor retardation, all consistent with hypomyelination of the brain showed by magnetic resonance imaging and computed tomography. A deficiency of DNA repair capacity was demonstrated in our patient. Furthermore, complementation analysis by cell fusion assigned our patient to xeroderma pigmentosum group D. The nucleotide excision repair defect of the other reported patients with PIBI(D)S falls generally into the same group as xeroderma pigmentosum group D and carry a mutation on the same repair gene (XPD). The relationship between these molecular characteristics and the clinical spectrum of PIBI(D)S is discussed.

Child↗
PubMed2000

Skin cancer in heart transplant recipients: risk factor analysis and relevance of immunosuppressive therapy.

BACKGROUND: The frequency of skin tumors of all types and specifically of squamous cell carcinoma (SCC) is increased in heart transplantation (HT), but the predisposing risk factors are controversial. METHODS AND RESULTS: We studied 300 patients (age 49+/-15 years, 258 men, mean follow-up 4.6 years, follow-up range 1 month to 12 years) who were receiving standard double (cyclosporin plus azathioprine) or triple (cyclosporin plus azathioprine plus prednisone) therapy. The first-year rejection score was calculated for endomyocardial biopsy samples (International Society for Heart and Lung Transplantation grade 0=0, 1A=1, 1B=2, 2=3, 3A=4, 3B=5, and 4=6) and used as an indirect marker of the level of immunosuppression. Multivariate analysis (Cox regression) included age at HT, sex, skin type, first-year rejection score, presence of warts and solar keratosis, lifetime sunlight exposure, and first-year cumulative dose of steroids. The incidence of skin tumors of all types increased from 15% after 5 years to 35% after 10 years after HT according to life-table analysis. Age at HT of >50 years (P:=0.03, RR=5.3), skin type II (P:=0.05, RR=2.6), rejection score of 19 (P:=0.003, RR=5.7), solar keratosis (P:=0.001, RR=6.9), and lifetime sunlight exposure of >30 000 hours (P:=0.0003, RR=7.6) were risk factors for SCC. CONCLUSIONS: Older age at HT, light skin type, solar keratosis, greater sunlight exposure, and high rejection score in the first year were independently associated with an increased risk of SCC. The progressive increase in cancer frequency during follow-up and the association with high rejection scores suggest that both the length and level of immunosuppression may be relevant. Because cumulative immunosuppressive load is cumbersome to calculate, a high rejection score in the first year may provide a useful predictor for patients at risk.

Age Distribution↗
PubMed2000

The expression pattern of the AML1 gene in non-Hodgkin's B-cell lymphomas and normal B lymphocytes.

We have studied the expression of the three human acute myeloid leukemia (AML) genes in primary samples of non-Hodgkin's B-cell lymphomas in which translocations involving these loci were not present. We found a widespread expression of the three AML genes in all the lymphoma samples as well as in the purified normal B-lymphocytes. Thus, the presence of the three mRNAs "per se" does not allow the identification of the pathological status. However, AML1 showed a different transcription pattern in the neoplastic tissues with respect to the normal B-cells. The AML1b isoform proved to be peculiar to this lymphoma. Our data support the idea that qualitative and quantitative alterations of AML1 gene expression deriving from deregulating mechanisms other than translocations may be involved in this malignancy. The usage of two differently regulated promoters driving the expression of the transcripts AML1b and AML1c may be one of these mechanisms. Finally, we report the presence of a new alternatively spliced transcript in normal B-cells.

B-Lymphocytes↗
PubMed2000

Skin cancer in heart transplant recipients: frequency and risk factor analysis.

BACKGROUND: The frequency of skin cancer is increased among organ transplant recipients, but the predisposing risk factors are controversial. It is also unclear whether heart transplant patients face an increased risk compared to recipients of other organs, e.g. kidney transplants. METHODS: We performed univariate and multivariate analysis of risk factors for skin cancer in 252 heart transplants and in a control series of 228 kidney transplants followed up at a single center. An extensive dermatologic examination was carried out; baseline features, type of immunosuppression, number of 3A rejection episodes, extent of sunlight exposure and skin type were recorded. Multivariate analysis (Cox regression) included: age at transplantation, sex, skin type (Fitzpatrick's criteria), presence of solar keratosis, presence of warts, type of organ, sunlight exposure. RESULTS: During follow up skin cancer was more common among heart transplants (40, 16 %) than in kidney transplants (16, 7%, p = 0.004). The cumulative incidence of skin cancer by life table analysis increased from 16% after 5 years to 33% after 10 years in heart transplant patients and from 6% to 17% in kidney transplants (p 10000 hours (relative risk = 2.8), but not organ type were significant risk factors. CONCLUSION: Age at transplant, skin type and sunlight exposure, but not type of organ and type of immunosuppressive regimen, are associated with increased risk of skin cancer in heart transplantation.

Adult↗
PubMed1997

Gamma delta T-cells in human cutaneous immunology.

Gamma delta T-Cells represent a minor subpopulation of T-lymphocytes in man and their role in normal and diseased human skin is unknown. This article is a comprehensive review of T-lymphocytes bearing the gamma delta T-cell receptor in normal and pathological human skin. Firstly, we have documented the occurrence of gamma delta T-cells in normal skin and in a range of reactive and malignant skin conditions. We have then discussed the experimental findings regarding the repertoire used by gamma delta T-cells in normal human skin and in cutaneous disorders with an increased percentage of gamma delta T-cells.

Animals↗
PubMed1997

The effect of fixation type on DNA extracted from paraffin-embedded tissue for PCR studies in dermatopathology.

BACKGROUND: Amplification of nucleic acids from paraffin-embedded material by the polymerase chain reaction (PCR) is widely used to detect viral genomes, clonal gene rearrangements and oncogene mutations in skin specimens. Fixation with embedding of skin tissue is a procedure that has a profound effect on its molecular arrangement. OBJECTIVE: The aim of this study was to determine the effect of different fixatives on the PCR amplification of DNA. METHODS: We fixed randomly chosen fresh pathologic skin specimens in formalin, ethanol and Histochoice for 24 and 72 h and then embedded the tissue in paraffin. DNA was extracted from the paraffin-embedded tissues and used as template for amplification, producing 530- and 760-bp fragments of the phosphoglycerokinase gene. RESULTS: Our results indicate that PCR can be performed with excellent results on ethanol- and Histochoice-fixed, paraffin-embedded skin tissue with a rate of success comparable to that using fresh tissues; formalin-fixed tissue gave slightly less satisfactory results. CONCLUSION: This investigation corroborates previous reports investigating the effect of ethanol and formalin fixation on DNA amplification by PCR. Moreover, this is the first study showing that DNA extracted from tissue fixed with Histochoice is suitable for PCR gene amplification.

Base Sequence↗
PubMed1997

Comparison of formalin, ethanol, and Histochoice fixation on the PCR amplification from paraffin-embedded breast cancer tissue.

The polymerase chain reaction (PCR) has been successfully employed for the laboratory analyses of genetic and infectious disorders using DNA extracted from paraffin-embedded tissues. However, fixative type and fixation time influenced PCR reactions and in some circumstances amplification fragments could not be efficiently generated. In this study, we determined the effects of three commonly used fixatives including ethanol, formalin and Histochoice, on the PCR amplification of DNA from paraffin-embedded breast cancer tissue. The effect of fixatives and fixation times was measured by the ability of the extracted DNA to serve as a template for the amplification of 280 and 530 base pair DNA fragments. On amplifying DNA, positive reactions were uniformly seen in the ethanol specimens. The next best fixative was Histochoice with positive results almost constantly observed in the PCR reactions performed. Formalin fixation sometimes compromised DNA amplification. Our results are consistent with previous reports investigating the effect of ethanol and formalin fixation on DNA amplification by PCR. Moreover, this is the first study showing that paraffin-embedded tissues fixed with Histochoice can be efficiently used for PCR gene amplification.

Breast Neoplasms↗
PubMed1996

High incidence of a T nucleotide at the second position of codon 97 in Vdelta2-(D)-Jdelta1 junctional sequences of human normal skin gamma delta T-cells.

In this investigation, we have demonstrated that in-frame polyclonal Vdelta2-(D)-Jdelta1 junctional sequences from human skin gammadelta T-cells contain a high incidence of T nucleotides at the second position of codon 97. Analysis of the deduced amino acid sequences based on in-frame Vdelta2-(D)-Jdelta1 junctional nucleotide sequences from normal skin gammadelta T-cells revealed a high incidence of the amino acids valine and leucine at position 97. These results are consistent with the studies in peripheral blood gammadelta T-cells, but not with previous findings in skin gammadelta T-cells, where random nucleotides were observed in the second position of codon 97 of Vdelta2-(D)-Jdelta1 junctional sequences and only a small minority of the deduced Vdelta2-(D)-Jdelta 1 amino acid sequences showed the amino acids valine and leucine at codon 97. Therefore, our findings indicate that the human skin gamma delta T-cells with a T-cell receptor consisting of a Vdelta2-(D)-Jdelta1-C delta1 chain are not a subset distinct from the subpopulation of human peripheral blood gammadelta T-cells expressing the same chain.

Codon↗
PubMed1996

A rapid polymerase chain reaction-based technique for detecting clonal T-cell receptor gene rearrangements in cutaneous T-cell lymphomas of both the alpha beta and gamma delta varieties.

T-cell receptor-gamma gene rearrangements provide specific clonal markers for a variety of lymphoid malignancies. T-cell receptor gene rearrangements in patients with cutaneous T-cell lymphoma were examined using conventional Southern blot analysis and a newly developed polymerase chain reaction (PCR)-based technique. The oligoprimers amplified a rearranged V gamma and J gamma segment (including the N region) of the T-cell receptor-gamma gene, and products were resolved using high-resolution nondenaturing polyacrylamide gel electrophoresis. Our results demonstrated concordance between the two techniques in 10 patients with cutaneous T-cell lymphomas (including nine cases of C beta and one case of delta 2 TCR gene rearrangements) and 10 negative controls. In the present study, we have shown that this PCR-based method provides a highly sensitive, specific technique for the detection of T-cell clones of both the alpha beta and gamma delta varieties and could be used in both fresh and formalin-fixed, paraffin-embedded tissues. It is estimated that this PCR-based technique is 10 to 50 times more sensitive than conventional Southern blot analysis in the detection of small T-cell clones.

Base Sequence↗
PubMed1995

Functional defect in cells involved in Langerhans cell histiocytosis.

The characteristic cell type involved in Langerhans cell histiocytosis, 'LCH cells', express most of the enzyme histochemical and immunocytochemical markers of normal epidermal Langerhans cells. It is not known, however, whether these LCH cells express the functional characteristics of normal epidermal Langerhans cells. We studied the alloantigen-presenting activity of LCH cells derived from lesional sites of three patients with the disease. Lesional cells expressing the CD1a molecule were enriched using either fluorescein-activated cell sorting or negative selection with indirect immunomagnetic beads, and functional activity was assessed using the 6-day primary allogeneic mixed-cell reaction. Compared to epidermal Langerhans cells from healthy controls, LCH cells showed minimal alloantigen-presenting activity on a per-cell basis. The diminished activity was not reversed by exogenous prostaglandin synthetase inhibitor or recombinant human IL-1 beta. This study confirms our previous report of a child, with fatal multisystem Langerhans cell histiocytosis suggesting that this disease represents a condition in which functionally defective cells of Langerhans cell phenotype accumulate and/or proliferate in various tissues. We postulate that the functional defect is a primary defect of these LCH cells that have acquired an as-yet-undetermined biological insult(s).

Adult↗
PubMed1994

Angioimmunoblastic lymphadenopathy with dysproteinemia and dermal T-cell lymphoma.

BACKGROUND: T-cell receptor (TCR)-gamma gene rearrangements provide a specific clonal marker for T-cell malignancies of both the alpha beta and gamma delta varieties. A polymerase chain reaction (PCR)-based method was used in this study for investigation of clonal TCR-gamma gene rearrangements in a patient with a classical presentation of angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) that subsequently progressed into an indolent form of dermal T-cell lymphoma. METHODS: TCR gene rearrangements in patients with cutaneous T-cell lymphoma (CTCL) were examined using conventional Southern blot analysis and a newly developed PCR-based technique for clonal TCR gene rearrangements. The oligoprimers amplified rearranged V gamma and J gamma segments (including the N region) of the TCR-gamma gene, and PCR products were resolved using high resolution nondenaturing polyacrylamide gel electrophoresis. RESULTS: The authors' results demonstrated good correlation between the two techniques in 10 patients with CTCL (9 patients with C beta and 1 patient with delta 2 rearrangements) and 10 control subjects. The PCR-based technique allowed the authors to detect the presence of an identical T-cell clone in all skin nodules, but not in the original lymph node affected by AILD. CONCLUSIONS: This PCR-based method for detecting clonal TCR rearrangements is a highly sensitive and specific technique for detecting T-cell clones in fresh and paraffin embedded tissues. The presence of a T-cell clone in all skin nodules of this patient, but not in the original lymph node affected by AILD, confirms previous findings that in some cases of AILD, clonal T-cell expansion may not be detectable until a later stage of the disease.

Adult↗
PubMed1994

Morphological and quantitative analyses of normal epidermal Langerhans cells using confocal scanning laser microscopy.

Confocal scanning laser microscopy (CSLM), when used in conjunction with computerized image processing systems, provides a powerful tool for morphological and quantitative analyses of biological tissues. In this study, normal human epidermal sheets were stained by an indirect immunofluorescence method using anti-CD1a monoclonal antibody. Positively stained epidermal Langerhans cells (LCs) were visualized using the Bio-Rad MRC-600 Confocal Imaging System. Images obtained from the confocal microscope were volumetrically rendered and quantitatively analysed using ANALYZE (Version 4.0) running on a Sun SPARC 2 Workstation. Normal epidermal LCs were shown to be large disc-like structures with five to nine long dendritic processes per cell, orientated with their flat surfaces parallel to the skin surface. LCs form a monolayer network of cells distributed evenly throughout the suprabasal layers of the epidermis, with no direct physical contact between dendritic processes. Mean LC density was estimated to be 582 per mm2 (95% confidence intervals, CI = 233-940), and mean cell volume was 612 microns3 (95% CI = 257-1020). LCs in sun-exposed sites were significantly lower in mean cell density, but larger in mean cell volume, than in covered sites. Mean surface area projected by LCs was estimated to be 26.8% (95% CI = 18.9-34.2), and this value did not show significant regional or individual variation. Our data support the notion that epidermal LCs are organized in such a way as to maximize their surface area for efficient trapping of antigens, and a reduction in LC density per unit area in sun-exposed sites is compensated for by an increase in the mean cell volume.

Cell Count↗
PubMed1993

T-Lymphocytes bearing the gamma delta T-cell receptor in cutaneous lesions of Langerhans' cell histiocytosis.

The aim of this study was to investigate the regional importance of gamma delta T cells in cutaneous lesions of Langerhans' cell histiocytosis. Six cases of Langerhans' cell histiocytosis were investigated by immunohistochemical techniques (alkaline phosphatase-antialkaline phosphatase complex and indirect immunoperoxidase). Increase of gamma delta T cells was observed in 3 cases of Langerhans' cell histiocytosis. In these cases up to 30% of CD3+ cells stained with an anti-TCR gamma delta monoclonal antibodies and in two of them gamma delta T cells showed a marked epidermotropism. In the specimens of the remaining three cases gamma delta T cells were found in an overall percentage of 5% of CD3+ cells, but in two cases a significant increase of epidermal gamma delta T cells was observed. The finding of numerous gamma delta T cells in Langerhans' cell histiocytosis is provocative and supports the suggestion of a functional relationship between gamma delta T cells and LCH cells.

Antibodies, Monoclonal↗