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Biomedical subjects

A Khammari

Publications and source records attributed to A Khammari.

14 recordsLinked to original sources
PubMed2007

ECCA grading scale: an original validated acne scar grading scale for clinical practice in dermatology.

INTRODUCTION: The ECCA grading scale (échelle d'évaluation clinique des cicatrices d'acné) is a tool designed to help dermatologists to assess the severity of acne scars and to standardize the discussions about the treatments of scars. METHODS: We developed an acne scar clinical grading scale called ECCA, which consists of 6 items designed to assess easily and quickly the severity of acne scars by a global score. The interobserver reliability of the ECCA grading was statistically validated. RESULTS: The statistical analysis showed the interinvestigator reliability of the ECCA grading scale among 7 dermatologists who used it on the same group of 10 acne patients. CONCLUSION: ECCA is a new tool which will now be available for dermatologists to use in their everyday practice and for clinical trials evaluating the efficacy of treatments on acne scars.

Acne Vulgaris↗
PubMed2006

Loss of oncostatin M receptor beta in metastatic melanoma cells.

Oncostatin M (OSM) is an interleukin-6 (IL-6) type cytokine originally described by its capacity to inhibit melanoma proliferation in vitro. Here, the mechanisms involved in resistance to growth inhibition by OSM were analysed for the first time on a large panel of metastatic melanoma cell lines. OSM resistance did not strictly correlate with IL-6, interferon-gamma or tumor necrosis factor-alpha resistance. Rather, it correlated with a specific loss of the OSM receptor-beta (OSMRbeta) subunit, in conjunction with a lower level of histone acetylation in the OSMRbeta promoter region. Treatment of various OSM-resistant melanoma cells with the histone deacetylase inhibitor Trichostatin A increased activity and histone acetylation of the OSMRbeta promoter as well as expression of OSMRbeta mRNA and protein, allowing OSM to activate the signal transducer and activator of transcription 3 (STAT3) and to inhibit proliferation. Other defects associated with OSM resistance were identified at the level of OSMRbeta transcription or protein expression, as well as downstream of or parallel to STAT3 activation. Altogether, our results suggest a role for OSM in the prevention of melanoma progression and that metastatic melanoma cells could escape this growth control by the epigenetic silencing of OSMRbeta.

Acetylation↗
PubMed2006

Heredity: a prognostic factor for acne.

BACKGROUND: The role of heredity in acne severity and therapeutic response remains unclear. OBJECTIVE: A prospective epidemiologic study was performed to compare clinical and evolutive features of acne and response to treatment in 151 patients with acne with (A+) or without (A-) family history of acne. METHODS: A+ and A- patients were compared on clinical and therapeutic criteria. A+ patients were then distributed into subgroups (M+, F+, M+F+) following the origin of family history (father: F, mother: M). RESULTS: The clinical profile was similar in the A+ and A- populations. Acne occurred earlier and more often before puberty in the A+ population, in which oral treatments and relapse after isotretinoin were more frequent. Retentional lesions (number and extent) were more important in the M+ and M+F+ populations. CONCLUSION: This study confirms the importance of heredity as a prognostic factor for acne. Family history of acne is associated with earlier occurrence of acne, increased number of retentional lesions and therapeutic difficulties.

Acne Vulgaris↗
PubMed2005

Pathogenetic mechanisms of vitiligo in a patient with Sézary syndrome.

Patients exhibiting association between vitiligo and cutaneous T-cell lymphoma (CTCL) remain rare and it is not known whether some T-cell subpopulations of CTCL in the skin are able to recognize specific melanocytic epitopes and thus induce vitiligo. The aim of our study was to determine whether T cells specific to melanocyte differentiation antigens were detectable among tumour-infiltrating lymphocytes (TIL) in the hypopigmented skin of a patient with Sézary syndrome (SS). A 71-year-old patient presented with SS and developed vitiligo during the course of her disease. Immunohistochemical studies showed staining with HMB45 and MelanA antibodies in the pigmented skin biopsy, whereas no staining was observed in the hypopigmented skin biopsy. To analyse responses to melanocyte differentiation antigens, we used a transient COS transfection assay that permits an estimation of CD8 T-cell responses against a large number of HLA/antigen combinations. This technique allowed the detection of melanocyte differentiation antigen-specific T lymphocytes, directed mainly against Melan-A/MART1 antigen in the HLA-A*23 context. Our study supports the concept that vitiligo that has developed during the evolution of a CTCL is related to the presence of a T-lymphocyte subpopulation reactive against melanocyte differentiation antigens (mainly Melan-A/MART1) present in skin lesions. The role of interferon in the induction of this T-lymphocyte subpopulation is discussed.

Aged↗
PubMed2005

Induction of toll-like receptors by Propionibacterium acnes.

BACKGROUND: The bacterium Propionibacterium acnes is involved in the induction and maintenance of the inflammatory phase of acne. Recent studies have found that keratinocytes express toll-like receptors (TLRs) implicated in immediate immunity. No studies have, to date, been carried out on the action of P. acnes upon TLR activation in keratinocytes. OBJECTIVES: Focusing on the inflammatory phase of acne, to clarify the role of P. acnes in immediate immunity by inducing expression of TLR-2 and TLR-4 by keratinocytes. We also studied how the secretion and expression of matrix metalloproteinase (MMP)-9 is induced by P. acnes. METHODS: The work was carried out on two levels: in vivo with the study of the expression of TLR-2 and TLR-4 proteins in biopsies of acne lesions and in vitro on cultured keratinocyte monolayers to study the modulating effects of P. acnes on the expression of TLR-2 and TLR-4 and also on the expression and secretion of MMP-9. RESULTS: Our findings reveal that in vivo TLR-2 and TLR-4 expression is increased in the epidermis of acne lesions. In vitro, an increase in TLR-2 and TLR-4 expression by human keratinocytes occurred in the first hours of incubation with bacterial fractions as well as an increase of the expression and secretion by the keratinocytes of MMP-9, which plays a role in inflammation. CONCLUSIONS: This work demonstrates that P. acnes induces TLR expression and that this mechanism could play an essential role in acne-linked inflammation. These receptors could be involved notably in acute acne.

Acne Vulgaris↗
PubMed2001

Prognostic value of tyrosinase reverse-transcriptase polymerase chain reaction in metastatic melanoma.

BACKGROUND: Circulating tumor cells can now be identified in subjects with metastatic melanoma by using the reverse-transcriptase polymerase chain reaction (RT-PCR) to detect the messenger RNA of tyrosinase, a key enzyme of melanogenesis. AIM AND METHODS: The aim of this study was to determine whether the detection of positive tyrosinase cells in patients at metastatic stage was associated with a worse evolution. 32 patients were included with metastatic melanoma (AJCC IV). RESULTS: 66% had a positive tyrosinase RT-PCR and a shorter survival compared with patients with a negative RT-PCR, but this difference is not statistically significant. However, a positive test could appear indicative of rapid progression and poor prognosis. CONCLUSION: The prognostic value of this method could be improved by combining it with PCR of other melanoma markers (Melan A, Mage 3) or assays of serum markers (S 100 protein or lactate dehydrogenase).

Humans↗
PubMed1998

In situ study of the sarcoplasmic reticulum function in control and mdx mouse diaphragm muscle.

Sarcoplasmic reticulum (SR) calcium handling in diaphragm was compared between mdx mice (7-8 weeks old) and age-matched controls. The total SR Ca2+ load was released from the SR by rapidly cooling muscle bundles from 22 to -1 degree C. The plateau amplitude of the rapid cooling contracture (RCC) was considered as an index of the SR Ca2+ content. The steady-state RCC amplitude was significantly lower by 50% in mdx bundles mainly because of a decreased capacity of the dystrophic diaphragm to generate maximal tension. There was no significant difference between either RCC time to peak or the time to half-relaxation of the transient, spike-like, contractile response induced by muscle rewarming. The recovery process of RCC was studied by using a paired RCC protocol. In both groups, at the shortest interval (10 s) between two RCCs, the amplitude of the second RCC was decreased by 25% compared with the first RCC. Increasing the time interval led to progressive monoexponential recovery of the second RCC with similar time constants in control and mdx diaphragm. These results indicate that the dystrophic process does not significantly alter SR Ca2+ uptake nor Ca2+ redistribution within the muscular cell.

Animals↗
PubMed1996

Effects of perchlorate on myofibrillar calcium sensitivity in rat skinned skeletal muscles.

The effects of perchlorate (1-20 mM) on myofibrillar calcium responsiveness have been tested in Triton X-100-skinned fibre bundles from rat soleus (slow-twitch) and extensor digitorum longus (fast-twitch) skeletal muscles. In extensor digitorum longus and soleus, perchlorate dose-dependently shifted the pCa (-log[Ca2+])/tension relationship towards lower free calcium concentration (sensitizing effect) and maximal tension was unchanged. The degree of sensitization was greater in extensor digitorum longus than in soleus bundles. Reversibility after exposure to 12 mM perchlorate was complete in soleus but not in extensor digitorum longus muscles. In fact, the 'return' pCa/tension relationship in extensor digitorum longus was shifted to higher free calcium concentration (desensitizing effect) compared with control. Perchlorate (12 mM) also enhanced myofibrillar calcium responsiveness of frog semitendinosus skinned skeletal fibres. Assuming a passive distribution of perchlorate across the sarcolemma, this sensitizing effect is probably not involved in perchlorate-induced potentiation of contractile responses of intact muscles and thereby supports the specificity of perchlorate as an agonist of the excitation/calcium release sequence in skeletal muscle fibres.

Animals↗
PubMed1996

Perchlorate differentially potentiates excitation-contraction coupling of diaphragm muscle from mdx and control mice.

The effects of perchlorate (6-40 mM) on contractile properties and depolarization-contraction coupling of diaphragm have been tested in muscle fibre bundles from 8 to 12-week-old mdx and control mice. Twitch contractile properties were affected by perchlorate to a similar extent in mdx and control muscles. In the absence of perchlorate, voltage-dependent parameters of both activation and inactivation were similar in mdx and control muscles. In both mdx and control muscles, perchlorate induced a shift of activation and inactivation curves toward more negative potentials. However, mdx diaphragm fibres were less sensitive to perchlorate in the low range of concentrations (6-12 mM). These results are unlikely to be due to a possible effect of the lack of dystrophin on the excitation-contraction coupling voltage sensor or ryanodine receptor. However, necrosis and regeneration occur in mdx mouse diaphragm and it is postulated that the presence of a high proportion of not fully mature fibres could contribute to the reduced sensitivity of mdx diaphragm fibres to perchlorate.

Animals↗
PubMed1996

Differential effects of tert-butyl-benzohydroquinone, a putative SR Ca2+ pump inhibitor, on isometric relaxation during the staircase in the rabbit and rat ventricle.

1. The effects of 2,5 di-(tert-butyl)-1,4-benzohydroquinone (TBQ), a putative inhibitor of the sarcoplasmic reticulum Ca2+ pump, on mechanical relaxation and contraction-relaxation coupling have been studied at different frequencies (0.5-3 Hz) in isometrically contracting isolated right ventricular preparations of rabbit and rat at 37 degrees C. Two types of mechanical responses have been studied: the twitch tension and the force transient (rewarming spike, RSp) following a rapid cooling contracture (RCC, an index of sarcoplasmic reticulum Ca2+ content) on return to 37 degrees C. 2. The coupling between contraction and relaxation was assessed by two methods: (a) by evaluation of the variation of the slope relating the maximal rate of tension fall to twitch peak tension; (b) by modelling the twitch according to the following equation: TwT (t) = C x (t/A)B x exp(1-(t/AB) where TwT(t) is the time course of isometric tension, t is time, C and A are an inotropic and a chronotropic index respectively and B, a contraction-relaxation coupling index (Nwasokwa, 1993). 3. In the rabbit ventricle, 30 microM TBQ did not prevent the frequency-induced shortening of the twitch time to half-relaxation (t1/2) and of the time constant (tau) describing the final part of the RSp relaxation (tau decreased from 140 ms (0.5 Hz) to 133 ms (3 Hz) in control and from 253 ms (0.5 Hz) to 197 ms (3 Hz) after exposure to TBQ). By contrast, at a given frequency, the prolongation of relaxation induced by TBQ was proportional to its inotropic effect (unchanged slopes and B values) but TBQ did not prevent the acceleration of relaxation observed at high frequencies: B increased from 2.02 (0.5 Hz) to a peak value of 2.18 (1 Hz) in control and from 1.88 (0.5 Hz) to a maximum of 2.48 (2 Hz) after TBQ exposure. TBQ significantly attenuated the decay of RCCs elicited after increasingly longer periods of muscle quiescence as normally observed in control conditions. 4. In the rat ventricle, TBQ depressed relaxation more than expected on the basis of its negative inotropic effects (B decreased from 2.16 to 1.84 at 0.5 Hz and from 2.15 to 1.66 at 3 Hz). TBQ also slowed the rate of RSp relaxation (tau increased from 95 ms to 168 ms at 0.5 Hz, and from 109 ms to 149 ms at 3 Hz) and increased twitch t1/2. By contrast with the results obtained in the rabbit ventricle, B, tau and t1/2 were frequency-insensitive whether or not TBQ was present. 5. TBQ exerts negative inotropic effects consistent with inhibition of the SR Ca2+ pump. In the rabbit ventricle, the TBQ-induced potentiation of relaxation acceleration at high pacing frequencies suggests the involvement of counteracting Ca(2+)-mediated mechanisms probably via Ca(2+)-calmodulin-activated kinases. In the rat ventricle, TBQ did not have any differential effect on relaxation depending on the frequency, probably because the extent of the negative staircase was small in the present experimental conditions.

Action Potentials↗
PubMed1994

Changes in potassium contractures due to simulated weightlessness in rat soleus muscle.

Some contractile properties of soleus muscle (SOL) fibers isolated from tail-suspended (21 days) rats were compared with those determined in the slow-twitch SOL and the fast-twitch extensor digitorum longus muscle (EDL) of control rats. In SOL from suspended rats, the resting membrane potential and the intracellular Na+ activity were typical of fast-twitch muscles. The relationship between the amplitude of K+ contractures and the membrane potential was steeper for control SOL than for control EDL and suspended SOL. The inactivation curve was also shifted to more positive potentials after suspension. In the presence of perchlorate anions, the tension activation curves of control EDL and suspended SOL were similarly shifted to more negative potentials. Thus, in the present study, modifications induced by suspension in SOL, mainly related to changes in the voltage-sensing process involved in the excitation-contraction coupling mechanism, were that the SOL assumed some of the characteristics of fast-twitch muscles.

Animals↗
PubMedDate not supplied

Toll-like receptors 2, 4 and 9 expression in cutaneous T-cell lymphoma (mycosis fungoides and Sézary syndrome).

The aim of this work was to study Toll-like receptors (TLRs) 2, 4 and 9 expression patterns in parapsoriasis and in cutaneous T-cell lymphoma (CTCL): Mycosis fungoides (MF) and Sézary syndrome (SS) at different stages of the illness. The expression of TLRs was examined by immunohistochemistry on paraffin-embedded biopsies. Normal skin, atopic dermatitis and psoriasis, were used as controls. In cutaneous lesions of inflammatory diseases (atopic dermatitis, psoriasis) the expression of TLR2, TLR4 and TLR9 was low compared to normal skin. In parapsoriasis the expression of the three TLRs was similar to control. By contrast, in MF skin we observed a strong intensity of labelling with the three TLRs in the epidermis. Concerning SS, the expression of TLR2, TLR4 and TLR9 was intermediate between inflammatory lesions and MF. Thus, the development of skin lesions in MF appears associated with an increase of TLR2, TLR4 and TLR9 expression by keratinocytes in cutaneous lesions, which could play a role in the chronic activation of T lymphocytes in the skin.

Biopsy↗