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Biomedical subjects

A Amar

Publications and source records attributed to A Amar.

At least 19 recordsLinked to original sources
PubMed2005

Myotonic dystrophy: does it affect ovarian follicular status and responsiveness to controlled ovarian stimulation?

BACKGROUND: Myotonic dystrophy (MD) is characterized by myotonia, multisystemic lesions and hypogonadism. In women, the relationship between MD and infertility remains controversial. This study investigated the ovarian status and response to controlled ovarian stimulation (COS) in MD women entering our preimplantation genetic diagnosis programme. METHODS: We elected to compare MD patients with X-linked disorders (XLD) carriers, given that XLD have not been shown to affect ovarian status. On the one hand, we analysed all the cycles performed and, on the other hand, we conducted a subanalysis based on only first cycles. RESULTS: MD and XLD groups were similar with regard to women's ages, day 3 parameters, number of oocytes retrieved, embryos obtained and prevalence of top quality embryos. The day of HCG was significantly delayed and the prevalence of poor quality embryos was higher in the MD group. The subanalysis on first cycles only also showed significantly fewer mature follicles on the day of HCG in MD population. Implantation and pregnancy rates were similar in both groups; however, no pregnancy occurred at the first cycle in MD (0 out of 4), whereas 77% of pregnancies (10/13) occurred at the first attempt in XLD carriers. CONCLUSIONS: These results indicate that the responsiveness to COS was moderately hindered in MD women as compared to controls. Reassuring data about implantation and pregnancy rates support the feasibility of PGD in selected mildly affected MD women.

Adult↗
PubMed2005

[The use of implants in ptosis, hypertrophic and breast deformities].

Breast precise analysis, due to a partial or global diformity, total or minor tuberous breast allows an interesting appreciation of the skin and gland importance in breast modifications. This same analysis enables us to consider the ptosis and hypertrophies under a different angle. Thus, the relative proportions in between the various segments, their evolution in the time and especially the glandular distribution mode, sometimes leads to a different technical approach. To ensure a better glandular distribution, an important factor of the breast stability, the use of a mastopexy, which everyone knows the limits, appears under a new light and, more often than one thought, the use of a breast implant ensures homogeneity of consistency and a more long term result. Concerning the various skin modifications, their specific analysis permit to establish the type of incision used for a better-adapted scar result. The approach we suggest, (detailed analytic study of the breast, glandular distribution, relative proportion of the different breast levels and a more frequent use of an implant) which in any case should not be systematic, can obviously in certain situation optimize the quality of the result (long term projection and a better stability of the mammary shape).

Breast↗
PubMed2005

Internal fluid dynamics in levitated drops by fast magnetic resonance velocimetry.

Fluid motion inside a levitated drop is determined by the interface properties. Momentum transfer through a highly mobile interface results in stationary vortex patterns inside the drop that dramatically enhance mass transfer between both phases, while immobile interfaces suppress internal dynamics. The presence of small amounts of surface-active substances can result in a partial reduction of interface mobility, the so-called rigid cap. The time dependence of internal flow patterns is presented by means of NMR velocity images of levitated drops, and is compared to fast measurements of the velocity distribution along the three orthogonal coordinates.

Journal Article↗
PubMed2005

Visualizing flow vortices inside a single levitated drop.

The internal flow dynamics in single liquid drops, kept in place through levitation by a counterflowing continuous fluid phase in a suitably designed glass cell, is investigated by PFG NMR techniques. The positional stability of the drops was confirmed from series of one-dimensional profiles and was found to be below the spatial resolution of the experiment. Velocity distribution functions (propagators) along all three coordinates were obtained and demonstrated the long-time stability of the internal dynamics in terms of the velocity magnitudes occurring in the systems. Finally, velocity imaging was applied to visualize the internal vortex patterns in the drops either as projections onto different planes or within thin slices of selected orientations. Two different fluid systems were investigated in order to cover the principal cases of rigid and mobile interfaces. Different fast velocity imaging techniques were employed for monitoring the vastly differing velocity ranges of both cases, and the high sensitivity of the internal three-dimensional motion to the cell geometry is demonstrated.

Journal Article↗
PubMed2002

Allergy development after bone marrow transplantation from a non-atopic donor.

BACKGROUND: Transfer of allergy from atopic bone marrow donors to recipients is known to occur. Development of allergy in a non-atopic patient transplanted from a non-atopic donor is an unfamiliar phenomenon in clinical practice. OBJECTIVES: To clarify the course of events causing a bone marrow recipient to acquire an allergic disease in such non-conducive circumstances. METHODS: Full medical history, prick and intradermal skin tests, and serum IgE levels were obtained from both donor and recipient patients. DNA and red blood cell phenotype analyses were used to detect the degree of chimerism. RESULTS: Only the recipient patient showed positive specific IgE antibodies and skin tests to house dust mite. The recipient patient displayed 100% donor chimera, based on all engraftment markers sought. CONCLUSION: Full engraftment after allogeneic bone marrow transplantation may be associated with modulation of T and B cell function, which in turn could cause the onset of allergic disease after bone marrow transplantation.

Adult↗
PubMed2001

Anti-inflammatory, antithrombotic, and neuroprotective effects of activated protein C in a murine model of focal ischemic stroke.

BACKGROUND: Activated protein C (APC) contributes to systemic anticoagulant and anti-inflammatory activities. APC may reduce organ damage by inhibiting thrombin generation and leukocyte activation. Neutrophils and cerebrovascular thrombosis contribute to ischemic neuronal injury, suggesting that APC may be a potential protective agent for stroke. METHODS AND RESULTS: We examined the effects of APC in a murine model of focal ischemia. After middle cerebral artery occlusion/reperfusion, the average survival time in controls was 13.6 hours. Animals that received purified human plasma-derived APC 2 mg/kg IV either 15 minutes before or 10 minutes after stroke induction survived 24 hours and were killed for neuropathological analysis. APC 2 mg/kg given before or after onset of ischemia restored cerebral blood flow, reduced brain infarct volume (59% to 69%; P:<0.003) and brain edema (50% to 61%; P:<0.05), eliminated brain infiltration with neutrophils, and reduced the number of fibrin-positive cerebral vessels by 57% (P:<0.05) and 25% (nonsignificant), respectively. The neuroprotective effect of APC was dose-dependent and associated with significant inhibition of ICAM-1 expression on ischemic cerebral blood vessels (eg, 61% inhibition with 2 mg/kg APC). Intracerebral bleeding was not observed with APC. CONCLUSIONS: APC exerts anti-inflammatory, antithrombotic, and neuroprotective effects in stroke. Central effects of APC are likely to be related to improved maintenance of the blood-brain barrier to neutrophils and to reduced microvascular obstructions and fibrin deposition.

Animals↗
PubMed1999

Evaluation of lymph node reactivity in differentiated thyroid carcinoma.

CONTEXT: The development of metastases is the most notable characteristic of malignant neoplasias. The filter function of lymph nodes, which led to the idea of including lymphatic treatment in surgical management of metastases. OBJECTIVES: To evaluate morphological alterations in neck nodes in the presence of differentiated thyroid carcinoma (DTC): hyperplasia, histiocytosis, desmoplasia, capsular rupture, necrosis and their relation to the biological behavior of these neoplasias. DESIGN: Retrospective study. SETTING: University referral unit. PARTICIPANTS: 98 DTC patients, from 1977 to 1992, 18 cases were selected for histological analyses, of which 14 were female and 4 males, with an average age of 50.2 years. From these cases, 290 lymph nodes were analyzed (81 with metastasis), with an average of 16 lymph nodes/patient. MAIN MEASUREMENTS: Morphological evaluation of paraffin cuts stained by HE was done using an optical microscope, looking for presence of the above mentioned neoplasias and their UICC-TNM (1997) staging. RESULTS: Sinus histiocytosis was 2.4 times more frequent in the absence of lymph node metastasis (pNo). Disease recurrence occurred in 5 patients, all of whom were more than 40 years old (p= 0.24) and 4 of whom had necrosis (p= 0.02). Six patients with predominance of paracortical hyperplasia (p= 0.02) did not show as much relapse into disease as those with less than 6 metastasis lymph nodes (p= 0.009). CONCLUSIONS: The presence of paracortical hyperplasia is associated with a better prognosis. The existence of necrosis or metastasis in more than 6 lymph nodes in patients over 40 years of age is related to higher risk of relapse of disease in DTC.

Adolescent↗
PubMed1999

HLA class II susceptibility to multiple sclerosis among Ashkenazi and non-Ashkenazi Jews.

OBJECTIVE: To look for HLA class II alleles and haplotypes conferring susceptibility to multiple sclerosis (MS) in the Jewish population of Israel. DESIGN: Population-based cohort of clinically definite patients with MS tested prospectively over 7 years. SETTING: Referral center in a neurology clinic at a university hospital in the greater Jerusalem area in Israel. PATIENTS: A total of 162 consecutive patients with clinically definite MS from the 2 main ethnic Jewish groups in Israel: 104 Ashkenazi (80 with a relapsing remitting or secondary progressive and 24 with a primary chronic progressive course of the disease) and 58 non-Ashkenazi (36 with a relapsing remitting or secondary progressive course and 22 with a primary chronic progressive course of the disease), matched with 132 Ashkenazi and 120 non-Ashkenazi healthy controls. MAIN OUTCOME MEASURES: The relationship between the various HLA class II alleles and haplotypes and MS, as defined by the polymerase chain reaction and sequence-specific oligonucleotide probe hybridization, among the Ashkenazi and the non-Ashkenazi Jewish sections and with respect to the different clinical courses of the disease. RESULTS: The haplotype DRB1*1501, DQA1*0102, DQB1*0602 was found to be associated with MS among both Ashkenazi and non-Ashkenazi patients (P<.001 and P =.04, respectively). Among the non-Ashkenazi patients, a new association of haplotypes DRB1*1303, DQA1*05, and DQB1*030 with MS was detected (P = .03). The MS susceptibility alleles, DRB 1* 1501, DQA1*0102, and DQB1*0602 , were found in association with the Ashkenazi patients (P<.001, P=.02, and P=.01, respectively); DRB1*1501 and DRB1*1303 were more frequently observed among the non-Ashkenazi patients (P = .03, P = .04, respectively). On subdivision of the patients into clinical subgroups, associations of DRB1*0801, DQA1*0102, DQA1*0401, and DQB1*0602 with primary chronic progressive MS among the Ashkenazi patients were evident (P = .03, P = .04, P = .04 and P = .05, respectively), whereas DRB1* 1501, DRB1*03011, and DQB1*0602 were associated with relapsing remitting or secondary progressive among the non-Ashkenazi patients (P = .05, P = .05, and P = .03, respectively). CONCLUSIONS: This study, unlike previous ones, is the first to show a significant association between HLA class II alleles and MS in the Jewish population. The association with the HLA-DR2-related haplotype is similar to that among non-Jewish white patients with MS. Moreover, our data support the possibility that DRB1*1501 is the susceptibility allele responsible for the association between this haplotype and MS in the Jewish population. Our study also underscores differences in HLA profiles between Ashkenazi and non-Ashkenazi patients, and between the different clinical courses of the disease. The latter may indicate that the clinical courses of MS are influenced by the genetic background.

Alleles↗
PubMed1999

Molecular analysis of HLA class II polymorphisms among different ethnic groups in Israel.

The Jewish population in Israel comprises of inhabitants of heterogeneous ethnic backgrounds. Genetic studies classify the Israeli Jewish population into two major groups: Ashkenazi from Central and Eastern Europe and Sephardic or non Ashkenazi, from the Mediterranean and North Africa. The present study was aimed at elucidating the differential influx of HLA class II alleles in Ashkenazi, in various non-Ashkenazi subgroups and in Israeli Moslem Arabs. Using the PCR-SSOP technique, a large number of alleles were detected at each of the loci examined (DRB1, DQA1 and DQB1). In addition, gene frequencies, characteristic DR/DQ linkage disequilibria, population distance and their corresponding dendogram, were used to study the relationship between Israelis as a group, non Jewish Caucasians and Blacks. These populations could be grouped into three main clusters: the first consists of all the Israeli groups with the exception of the Ethiopian Jews; the second consists of non Jewish Caucasians, with a clear distinction seen between Israelis and non Jewish Europeans and U.S. Caucasians; the third, composed of Blacks, is distinctly different from the other populations. Ethiopian Jews were found to be closer to the Blacks than to any of the Israeli Jewish groups. We have shown that Jews share common features, a fact that points to a common ancestry. A certain degree of admixture with their pre-immigration neighbors exists despite the cultural and religious constraints against intermarriage.

Alleles↗
PubMed1999

Graft-versus-lymphoma effect after allogeneic peripheral blood stem cell transplantation for primary central nervous system lymphoma.

Allogeneic peripheral blood stem cell transplantation (allo PBSCT) is a recognized treatment modality for hematological malignancies resistant to conventional chemoradiotherapy. The post-transplant immune-mediated graft-versus-leukemia effect has major curative potential. In this case presentation, the allogeneic approach to resistant recurrent primary central nervous system (CNS) lymphoma using peripheral blood stem cells from an HLA identical sibling after immuno-suppressive non-myeloablative conditioning, was examined clinically. The patient in question had relapsing refractory primary CNS lymphoma and is the first to be treated with this modality. She developed early skin and liver-localized grade II graft-versus-host disease after allo PBSCT, which then responded to short-term treatment. Chimeric studies at the time showed 100% donor cells and repeated magnetic resonance imaging of the brain revealed gradual shrinkage of the tumor. Three months after transplant the cerebral mass was no longer evident and currently, 30 months after transplantation, the patient continues to be disease free. The absence of any signs of malignancy suggests the development of a durable graft-versus-lymphoma effect in this brain tumor and indicates that this effect may be achieved even after non-myeloablative conditioning.

Adult↗
PubMed1999

Genetic variation of three tetrameric tandem repeats in four distinct Israeli ethnic groups.

The allele frequency distributions of three STR loci amplified by PCR have been studied in four Israeli communities: Ashkenazi Jews and three non-Ashkenazi groups, namely Moroccan, Yemenite, and Ethiopian Jews. The loci analyzed were CSF1PO, TPOX, and HUMTHO1. The typing was performed in sequencing polyacrylamide gels under denaturing conditions that could separate alleles with differences of a single base. The population data were analyzed with respect to Hardy-Weinberg (H-W) equilibrium and found that all loci meet the H-W expectations. No-ticeable differences were encountered between the four Jewish ethnic groups studied hereby indicating the importance of establishing a local database to be used in human identity testing in these different Israeli Jewish groups.

DNA↗
PubMed1998

Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases.

Myeloablative conditioning associated with hazardous immediate and late complications is considered as a mandatory first step in preparation for allogeneic blood or marrow transplantation (allogeneic BMT) for the treatment of malignant hematologic disorders and genetic diseases. Immune-mediated graft-versus-leukemia (GVL) effects constitute the major benefit of allogeneic BMT. Therefore, we have introduced the use of relatively nonmyeloablative conditioning before allogeneic BMT aiming for establishing host-versus-graft tolerance for engraftment of donor immunohematopoietic cells for induction of GVL effects to displace residual malignant or genetically abnormal host cells. Our preliminary data in 26 patients with standard indications for allogeneic BMT, including acute leukemia (n = 10); chronic leukemia (n = 8), non-Hodgkin's lymphoma (n = 2), myelodysplastic syndrome (n = 1), multiple myeloma (n = 1), and genetic diseases (n = 4) suggest that nonmyeloablative conditioning including fludarabine, anti-T-lymphocyte globulin, and low-dose busulfan (8 mg/kg) is extremely well tolerated, with no severe procedure-related toxicity. Granulocyte colony-stimulating factor mobilized blood stem cell transplantation with standard dose of cyclosporin A as the sole anti-graft-versus-host disease (GVHD) prophylaxis resulted in stable partial (n = 9) or complete (n = 17) chimerism. In 9 patients absolute neutrophil count (ANC) did not decrease to below 0.1 x 10(9)/L whereas 2 patients never experienced ANC < 0.5 x 10(9)/L. ANC > or = 0.5 x 10(9)/L was accomplished within 10 to 32 (median, 15) days. Platelet counts did not decrease to below 20 x 10(9)/L in 4 patients requiring no platelet support at all; overall platelet counts > 20 x 10(9)/L were achieved within 0 to 35 (median 12) days. Fourteen patients experienced no GVHD at all; severe GVHD (grades 3 and 4) was the single major complication and the cause of death in 4 patients, occurring after early discontinuation of cyclosporine A. Relapse was reversed by allogeneic cell therapy in 2/3 cases, currently with no residual host DNA (male) by cytogenetic analysis and polymerase chain reaction. To date, with an observation period extending over 1 year (median 8 months), 22 of 26 patients (85%) treated by allogeneic nonmyeloablative stem cell transplantation are alive, and 21 (81%) are disease-free. The actuarial probability of disease-free survival at 14 months is 77.5% (95% confidence interval, 53% to 90%). Successful eradication of malignant and genetically abnormal host hematopoietic cells by allogeneic nonmyeloablative stem cell transplantation represents a potential new approach for safer treatment of a large variety of clinical syndromes with an indication for allogeneic BMT. Transient mixed chimerism which may protect the host from severe acute GVHD may be successfully reversed postallogeneic BMT with graded increments of donor lymphocyte infusions, thus resulting in eradication of malignant or genetically abnormal progenitor cells of host origin.

Adolescent↗
PubMed1998

Allogeneic cell-mediated and cytokine-activated immunotherapy for malignant lymphoma at the stage of minimal residual disease after autologous stem cell transplantation.

Immunocompetent donor-derived T lymphocytes play a crucial role in the elimination of residual leukemic cells post allogeneic bone marrow transplantation. Because this graft versus leukemia (GVL) effects is absent after autologous stem cell transplantation (ASCT), a high rate of relapse ensues. We introduced cell-mediated immunotherapy at the stage of minimal residual disease in lymphoma patients to help effect a GVL-like reaction by adoptive transfer of immunocompetent human leukocyte antigen-matched donor peripheral blood lymphocytes (PBL). Thirteen consecutive patients with high-risk lymphoma were treated with allogeneic cell therapy (AlloCT) after having undergone ASCT. In the absence of graft-versus-host disease, cell therapy-induced graft-versus-lymphoma reaction was amplified by human recombinant interleukin 2 (rIL-2) during 3 days to activate donor PBL in vivo, followed by infusion of in vitro rIL-2 activated donor lymphocytes combined with 3-day rIL-2 therapy. Nine of the patients underwent the treatment protocol well. In the four other patients, in whom the AlloCT resulted in marrow aplasia due to elimination of host hematopoietic cells, treatment with donor marrow cell infusion without further conditioning was performed. Adoptive cell therapy in the form of AlloCT may turn out to be an effective therapeutic modality for the treatment of resistant residual disease in lymphoma patients.

Adolescent↗
PubMed1998

Allogeneic cell-mediated immunotherapy for breast cancer after autologous stem cell transplantation: a clinical pilot study.

Allogeneic cell therapy (allo-CT) is emerging as an effective treatment for patients relapsing after allogeneic bone marrow transplantation (BMT), indicating that tumor cells resisting chemoradiotherapy may still respond to immunocompetent allogeneic lymphocytes. We investigated possible graft-versus-tumor (GVT) effects in six patients with metastatic breast cancer that would be comparable to the graft-versus-leukemia (GVL) phenomenon occurring after allogeneic BMT in hematologic malignancies. The patients were cytoreduced with high-dose chemotherapy and autologous stem cell transplantation (ASCT), and were treated ambulatory with allo-CT consisting of adoptive transfer of HLA-matched donor peripheral blood lymphocytes (PBL) activated in vivo with human recombinant interleukin-2 (rIL-2). If no graft-versus-host disease (GVHD) developed, allo-CT was augmented with infusion of donor PBL, preactivated in vitro with rIL-2. Treatment was well tolerated, with low therapy-related toxicity in all patients. Two patients developed signs and symptoms compatible with GVHD grade I-II, one of whom shows no evidence of disease at more than 34 months out. In the remaining patients, progression-free survival following allo-CT ranged between 7 and 13 months. Allogeneic cell-mediated, cytokine-activated immunotherapy might be utilized for induction of GVT in metastatic breast cancer. A search for techniques to boost chimerism without severe GVHD is indicated.

Adult↗
PubMed1998

Enhanced lymphoid cell recovery after bone marrow transplantation: correlation with the presence of costimulatory antibodies in serum.

We describe a patient with T cell deficiency who underwent bone marrow transplantation (BMT) from an HLA-identical brother. The patient's white blood cell count recovered with exceptional rapidity post-BMT: after 7 to 9 days it rose sharply to 98x10(9) cells/L, 76% of which were mononuclear leukocytes. It then decreased, and a second peak was observed 250 days post-BMT. Lymphocytes from both peaks displayed a phenotype of mature T cells together with characteristics of a constitutively activated state; that is, they 1) exhibited high levels of tyrosine-phosphorylated T cell receptor (TCR) zeta chain, 2) spontaneously secreted IL-2, 3) expressed activation specific cell surface markers, and 4) were unresponsive to in vitro stimuli. The increased cell counts in both peaks correlated with the presence of anti-lymphocytic antibodies in the patient's serum, which reacted with peripheral blood lymphocytes (PBLs) both from the donor and from unrelated individuals. These antibodies were present before BMT and reappeared post-BMT. Variable number tandem repeats analysis revealed that the patient's PBLs were chimeras for up to 2 years post-BMT. This finding could explain the newly synthesized post-BMT anti-lymphocytic antibodies and the appearance of the second WBC peak during that period. The patient's anti-lymphocytic antibodies displayed costimulatory activity, enhancing the in vitro proliferation of normal T cells suboptimally activated via the TCR. The unique characteristics of these antibodies could explain the enhanced T cell recovery observed post-BMT as well as the constitutive activation state of these cells. Furthermore, such antibodies may eventually facilitate development of a therapeutic method for inducing enhanced post-BMT recovery.

Adolescent↗
PubMed1997

Structure-activity relationships for a novel series of pyrido[2,3-d]pyrimidine tyrosine kinase inhibitors.

Screening of a compound library for inhibitors of the fibroblast growth factor (FGFr) and platelet-derived growth factor (PDGFr) receptor tyrosine kinases led to the development of a novel series of ATP competitive pyrido[2,3-d]pyrimidine tyrosine kinase inhibitors. The initial lead, 1-[2-amino-6-(2,6-dichlorophenyl)pyrido[2,3-d]pyrimidin-7-yl]-3- tert-butylurea (4b, PD-089828), was found to be a broadly active tyrosine kinase inhibitor. Compound 4b inhibited the PDGFr, FGFr, EGFr, and c-src tyrosine kinases with IC50 values of 1.11, 0.13, 0.45, and 0.22 microM, respectively. Subsequent SAR studies led to the synthesis of new analogs with improved potency, solubility, and bioavailability relative to the initial lead. For example, the introduction of a [4-(diethylamino)butyl]amino side chain into the 2-position of 4b afforded compound 6c with enhanced potency and bioavailability. Compound 6c inhibited PDGF-stimulated vascular smooth muscle cell proliferation with an IC50 of 0.3 microM. Furthermore, replacement of the 6-(2,6-dichlorophenyl) moiety of 4b with a 6-(3',5'-dimethoxyphenyl) functionality produced a highly selective FGFr tyrosine kinase inhibitor 4e. Compound 4e inhibited the FGFr tyrosine kinase with an IC50 of 0.060 microM, whereas IC50s for the inhibition of the PDGFr, FGFr, EGFr, c-src, and InsR tyrosine kinases for this compound (4e) were all greater than 50 microM.

Animals↗