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Biomedical subjects

M Khaled

Publications and source records attributed to M Khaled.

8 recordsLinked to original sources

PI3K mediates protection against TRAIL-induced apoptosis in primary human melanocytes.

Melanocytes are cells of the epidermis that synthesize melanin, which is responsible for skin pigmentation. Transformation of melanocytes leads to melanoma, a highly aggressive neoplasm, which displays resistance to apoptosis. In this report, we demonstrate that TNF-related apoptosis-inducing ligand (TRAIL), which was thought to kill only transformed cells, promotes very efficiently apoptosis of primary human melanocytes, leading to activation of caspases 8, 9 and 3, and the cleavage of vital proteins. Further, we show that stem cell factor (SCF), a physiologic melanocyte growth factor that activates both the phosphatidyl-inositol-3 kinase (PI3K) and the extracellular regulated kinase (ERK) pathways, strongly protects melanocytes from TRAIL and staurosporine killing. Interestingly, inhibition of PI3K or its downstream target AKT completely blocks the antiapoptotic effect of SCF, while inhibition of ERK has only a moderate effect. Our data indicate that protection evoked by SCF/PI3K/AKT cascade is not mediated by an increase in the intracellular level of FLIP. Further, only a sustained PI3K activity can protect melanocytes from apoptosis, thereby indicating that the PI3K/AKT pathway plays a pivotal role in melanocyte survival. The results gathered in this report bring new information on the molecular mechanisms involved in primary melanocyte apoptosis and survival that would help to better understand the process by which melanomas acquire their resistance to apoptosis.

Apoptosis↗

A prospective comparative study on IVF outcomes with either purified FSH or human menopausal gonadotrophin in downregulated normogonadotrophic women.

OBJECTIVE: In compare the use of purified follicle-stimulating hormone with that of a preparation containing follicle-stimulating hormone and luteinizing hormone in infertile females undergoing IVF. DESIGN: Open-labelled prospective controlled single-center study. SETTING: Nile Badrawy IVF unit. PARTICIPANTS: 153 infertile females undergoing their first cycle of IVF divided into 2 groups. INTERVENTIONS: Ovarian stimulation was done with either highly purified FSH for group 1 (n = 75) or human menopausal gonadotrophin group 2 (n = 78) after pituitary desensitization commenced in the midluteal phase of the preceding cycle. Monitoring was performed by ultrasound transvaginal oocyte retrieval followed by IVF and transfer of three embryos. OUTCOMES: Number of oocytes >18 mm at day of hCG, fertilization rate, embryo transfer rate, clinical pregnancy rate and incidence of ovarian hyperstimulation syndrome. RESULTS: The response to ovarian hyperstimulation was similar in both groups. The number of follicles >18 mm achieved at day of hCG was 12.3 +/- 0.9 (mean +/- SEM) following stimulation with 38.3 +/- 0.9 ampoules of Fostimon The Menogon-treated group needed 39.1 +/- 0.8 ampoules to produce 11.6 +/- 0.7 follicles. Fertilization rate (2PN/cell) was 58.6 vs. 64.2% in the Fostimon and Menogon group, respectively (p > 0.05). The number of embryos transferred per woman was 3.1 +/- 0.1 in the Fostimon group and 3.6 +/- 0.1 in the Menogon group. The pregnancy rate per woman was 33.3 vs. 25.6% in the Fostimon- and Menogon-treated groups, respectively (p > 0.05). Miscarriage rate was 16 vs 20%, respectively. However, the incidence of multiple pregnancies was significantly higher in the Fostimon-treated group (32%) vs. 10% only in the Menogon-treated group (p < 0.01). CONCLUSION: Purified FSH yields similar clinical outcome to hMG in terms of oocytes retrieved and clinical pregnancies in a standard IVF regimen.

Adult↗

[Conservative surgery for T2 > 3 cm, T3 N0 N1 M0 breast cancer after induction chemotherapy].

Induction chemotherapy (IC) provides in more than 20% of cases a complete shrinkage of the tumor. This down staging is a new challenge for the surgeons for breast conservative procedure. Although, IC has become the standard of care for breast cancer T2 > 3 cm T3 N0 N1 M0. No guidelines have devoted attention to the surgical problems due to this down staging after IC. Location and size of the tumor before IC have to be studied and outlined by the surgeon himself. During surgery, the residual tumor volume and how much mammary gland must be removed are very difficult to determine. The maximum volume of mammary gland to be removed after IC around the primary site of the tumor before IC is the volume which permits a good cosmetic reconstruction of the breast. After IC, in spite of an important downstaging, an axillary clearance must be done. For N0 patients, sentinel lymph node biopsy could be performed before IC. If the sentinel node is p N0, axillary clearance could be avoided.

Breast Neoplasms↗

Antigen inhalation as a triggering factor in systemic small-sized-vessel vasculitis. Four cases.

In order to identify small-sized-vessel vasculitis occurring immediately after massive inhalation of particles which could be considered antigenic, we performed a retrospective review of patients who consulted our Department of Internal Medicine between 1980 and 1998 and were diagnosed as having small-vessel vasculitis that developed immediately after massive exposure to inhaled particles. Four patients, 27 to 55 years old, presented with small-sized-vessel vasculitis (one with Wegener's granulomatosis and three with Churg-Strauss syndrome) which developed after massive inhalation of particles. Clinical manifestations occurred from a few hours to 10 days after inhalation of diesel fumes, cereal dust, flour or cereal dust and/or pigeon droppings. Three patients remain disease-free 8, 9 and 18 years after discontinuing treatment. One patient remains well after 3 years on low-dose corticosteroids and cyclophosphamide therapy. Our data suggest that primary antigens can cause small-sized-vessel vasculitides. Identifying such etiological factors could improve our understanding of the pathogenesis of systemic vasculitides and prevent relapses due to similar antigenic exposure.

Adult↗

[Lymph node mapping and axillary sentinel lymph node biopsy in 243 invasive breast cancers with no palpable nodes. The south Lyon hospital center experience].

STUDY AIM: To evaluate the effect of intraoperative lymph node mapping and sentinel lymph node dissection (SLND) on the axillary staging of patients with N0 breast carcinoma. Two techniques were used: blue dye alone (Evans Blue and Patent Blue) and combined technique (blue dye and isotope). METHODS: The incidence of axillary node metastasis in axillary lymph node dissection (ALND) and SLND was compared prospectively. Multiple sections of each SLN were examined by HPS staining and immunohistochemical techniques. Two sections of each non sentinel node in ALND specimens were examined by routine HPS staining. RESULTS: 243 patients underwent ALND after SLN biopsy. The SLN detection rate was 225/243 cases (92.59%): 89.94% with blue dye alone and 100% with the combined technique. The false-negative rate was less than 2%. CONCLUSION: SN biopsy is an accurate staging technique for N0 breast cancer. SLN biopsy with multiple sections and immunohistochemical staining of the SLN can identify significantly more patients with lymph node metastases than ALND with routine HPS staining.

Biopsy↗

Isolation of a second cryptic plasmid from Mycoplasma mycoides subsp. mycoides.

Plasmids have rarely been detected in organisms constituting the genus Mycoplasma. Recently, the isolation of a cryptic plasmid from Mycoplasma mycoides subsp. mycoides has been described, and we report here the isolation of a second cryptic plasmid from this species. Restriction map and Southern blot analyses show that the second plasmid is distinct from the previously described plasmid, although a limited region of homology was detected. The availability of mycoplasmal cryptic plasmids may lead to the development of cloning vectors that replicate in these organisms.

Genetic Vectors↗

Isoenzymes of beta-hexosaminidase from normal rat colon and colonic carcinoma.

N-Acetyl-beta-D-hexosaminidase isolated from normal rat colon was compared to that obtained from a transplantable rat colonic carcinoma. Levels of total hexosaminidase from purified epithelial cells of normal colon were similar to those from purified malignant cells from the transplantable tumor. Cultured malignant cells had significantly higher levels of activity than did freshly purified tumor cells. Isoelectric focusing of hexosaminidase from normal rat colon indicated approximately equal amounts of A (pI 5.0 ) and B (pI 8.1) isoenzyme activity. The B isoenzyme (normal cell) was more stable to heat inactivation than was the A isoenzyme and had significantly higher activity at low pH's. In contrast, the B isoenzyme from the tumor was relatively unstable to heat and low pH.

Animals↗