Biomedical subjects

M Raphael

Publications and source records attributed to M Raphael.

At least 37 records · Page 2Linked to original sources

PubMed1998

Comparison of duplex imaging and arteriography in the evaluation of lower limb arteries.

BACKGROUND: The aim of this study was to assess the accuracy of duplex imaging, compared with arteriography, in detecting arterial disease distal to the renal arteries. METHODS: Some 177 legs were studied in 90 patients (59 men, 31 women; median age 68 years) with peripheral arterial disease. Each patient had conventional intra-arterial angiography and duplex ultrasonography. Each leg was divided into 17 arterial segments, and the disease in each segment was quantified by measuring the peak systolic velocity ratio across any arterial lesion that was identified. RESULTS: Compared with angiography, duplex imaging was able to detect arterial disease with an overall sensitivity of 92 per cent, specificity of 99 per cent, positive predictive value 91 per cent and negative predictive value 100 per cent, and with a kappa value of 0.87 (95 per cent confidence interval (c.i.) 0.81-0.93). Duplex was able to determine the length of the arterial lesion with a sensitivity of 89 per cent and a specificity of 98 per cent with a kappa value of 0.88 (95 per cent c.i. 0.86-0.90). When the surgeon's final management decision concerning each vascular lesion was used as the reference, duplex and arteriography were equivalent, with an accuracy of 84 per cent and 85 per cent respectively in identifying the management used. CONCLUSION: Duplex ultrasonography is reliable in detecting arterial lesions in peripheral arteries and could be used routinely in the initial evaluation of patients with lower limb arterial disease.

Aged↗

PubMed1998

CD80 expression is decreased in hyperplastic lymph nodes of HIV+ patients.

A centrofollicular hyperplasia is present within secondary lymphoid organs during all the asymptomatic phase of the HIV disease. Although this hyperplasia has been well characterized by histological studies, the nature of the phenotypic alterations in B cell populations occurring within HIV+ lymphoid organs remains to be established. By immunohistochemistry, we thus investigated whether a particular germinal center (GC) B cell population was increased during HIV-induced hyperplasia and whether any phenotypic change was specific to HIV-1 infection. As compared to normal tonsils (three cases) and HIV- hyperplastic lymph nodes (eight patients), we observed a loss of GC polarization in all HIV+ sections (11 patients), with no more delineation between dark and light zones, as shown by Ki67, CD10, CD77, CD95 and CD86 staining. In contrast to CD86 expression which remained as intensive in HIV+ as in HIV- lymph nodes, CD80 staining was strongly decreased in GC of HIV+ lymph nodes but not in their extrafollicular zones. The loss of CD80 expression from CD19+ B cells was also observed by cytometric analysis of cell suspensions of three HIV+ patients. Although we found no evidence of an increase in a particular GC B cell subset in HIV-1-induced hyperplasia, the strong GC disorganization observed may induce impaired cell-cell interactions and thus participate in the loss of CD80 antigen. In contrast to HIV- situations where CD80 and CD86 was similarly expressed on B cells, the lower level of CD80 expression in HIV+ GC may favor Th2 T cell responses through CD86-CD28 interactions.

Adult↗

PubMed1998

Posttransplant lymphoproliferative disorders not associated with Epstein-Barr virus: a distinct entity?

PURPOSE: Organ recipients are at a high risk of posttransplant lymphoproliferative disorders (PTLD) as a result of immunosuppressive therapy. Most B-cell lymphomas are associated with Epstein-Barr virus (EBV) infection. We describe a morphologically and clinically distinct group of PTLD in 11 patients that occurred late after organ transplantation and were not associated with EBV. PATIENTS AND METHODS: There were seven kidney, three heart, and one liver transplant recipients (group I). The clinical manifestations, pathologic findings, treatment, and outcome were compared with those in 21 patients with EBV-associated PTLD treated in our institution (group II). EBV was detected with at least two techniques: Epstein-Barr-encoded RNA (EBER) in situ hybridization with EBER 1 + 2 probes, Southern blotting, and detection of latent membrane protein 1 (LMP1) expression by immunohistochemistry. RESULTS: The time between transplantation and the diagnosis of lymphoma ranged from 180 to 10,220 days in group I (mean, 2,234; median, 1,800) and from 60 to 2,100 days in group II (mean, 546; median, 180), and was significantly shorter in group II (P = .02). Among 19 tumors diagnosed within 2 years after the graft, 16 were associated with EBV; among 13 tumors diagnosed after more than 2 years, only five were associated with EBV. All of the B-cell PTLDs in group I were classified as monomorphic, meeting the criteria of B diffuse large-cell lymphoma (B-DLCL) with a component of immunoblasts, and genotyping confirmed their monoclonality. Three tumors were T-cell pleomorphic lymphomas. Tumor sites were mainly bone marrow and lymph nodes. Overall median survival was 1 month in group I and 37 months in group II, with two patients still alive in group I and nine in group II. The survival time was significantly longer in group II (P < .01). CONCLUSION: EBV-negative PTLD may be a late serious complication of organ transplantation. Half the tumors observed after kidney transplantation in our center were not associated with EBV and emerged after more than 5 years, which suggests the number of EBV-negative PTLDs in organ recipients might increase with time.

Adolescent↗

PubMed1998

Mechanism involved in gallium-67 (Ga-67) uptake by human lymphoid cell lines.

The gallium-67 (Ga-67) is a radionuclide used for diagnostic imaging. It is known for its ability to accumulate in inflammatory lesions and tumors, especially in lymphomas. The intracellular distribution and the uptake mechanism of Ga-67 remains a subject of discussion. In this work, we studied the mechanism of Ga-67 uptake in 4 human lymphoid cell lines: 38658, Jurkat, DG75 and U715. Our results have pointed out the heterogeneity of Ga-67 uptake among these cell lines. Using flow cytometry analysis, we reported the expression of transferrin-receptor (TfR) in each lymphoid cell line, and found a positive correlation between TfR density and the Ga-67 uptake (r = 0.99) in lymphoid cells. The anti-TfR monoclonal antibody (MoAb) blocked significantly the Ga-67 uptake in all lymphoid cell lines indicating the Ga-67 uptake as a TfR-dependent mechanism. This mechanism has been saturated with different cold gallium concentrations. A total inhibition of Ga-67 uptake was obtained at a 10(-4) M cold gallium concentration. To conclude, we have shown that the Ga-67 uptake is TfR-dependent in lymphoid cells. Thus, the gallium penetrates in lymphoid cells by an active mechanism which can be saturated.

Antibodies, Monoclonal↗

PubMed1997

Nuclear Rel-A and c-Rel protein complexes are differentially distributed within human thymocytes.

Nuclear factor-kappa B (NF-kappa B)/Rel proteins are inducible transcriptional regulators of numerous cellular genes. They are particularly abundant in lymphoid tissues and are thought to be critical for the transcription of genes involved in immune and inflammatory responses. We have reported previously that a nuclear NF-kappa B activity was present in freshly extracted human thymocytes in the absence of in vitro treatment of these cells. In the present report, we identified NF-kappa B proteins extracted from human thymocyte nuclei as being p50/p65 and p50/c-Rel complexes. Immunochemical and immunofluorescent staining of thymus sections using specific Abs allowed visualization of nuclear NF-kappa B proteins in both thymocytes and nonthymocyte cells. This detection suggested a preferential activation of p50/c-Rel in medullary thymocytes, whereas p50/p65 was present in both cortical and medullary regions of human thymus lobules. However, the intensity of p65 labeling was much higher in several thymocytes from the medulla. p65, p50, and c-Rel activities were found in both CD4- and CD8-positive thymocytes. These observations suggest that p65 and c-Rel complexes play distinct roles in gene expression and that both forms of NF-kappa B play critical roles during late stages of the intrathymic maturation of T cells.

Cell Nucleus↗

PubMed1997

Hypercalcemia may indicate Richter's syndrome: report of four cases and review.

BACKGROUND: Hypercalcemia has rarely been reported in patients with Richter's syndrome (RS). In this article, the authors report four cases with complementary pathophysiologic examinations. METHODS: Four patients with hypercalcemia that indicated RS were admitted to the study unit between 1980 and 1994 with the following diagnoses: transformation of mixed follicular lymphoma, Waldenstrom's macroglobulinemia, and chronic lymphocytic leukemia, respectively, in 3 men ages 60 to 73 years, and chronic lymphocytic leukemia in a woman 73 years of age. Radiologic and histologic features were reported. Circulating levels of parathormone-related peptide (PTHrP), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) were measured. RESULTS: Radiologic skeletal abnormalities were found in three of three cases: osteopenia twice and multifocal osteolysis once. All four patients had large cell lymphoma (LCL). Bone resorption assessed histomorphometrically was elevated in two of two cases. Serum TNF-alpha and IL-6 levels were high in three of three and one of three cases, respectively. Elevated values were also found in four patients with LCL but without hypercalcemia. The serum PTHrP level was increased in the only hypercalcemic patient tested and values were normal in the three control patients. CONCLUSIONS: Hypercalcemia arising in a patient with a low grade lymphoproliferative disorder may indicate RS. Hypercalcemia is due to increased bone resorption, which may be caused by the secretion of osteoclast-stimulating factors by the LCL invading the bone marrow. Independently, TNF-alpha and/or IL-6 were unlikely causative factors of hypercalcemia in the patients in this study; however, synergism with PTHrP was suspected in one case.

Aged↗

PubMed1997

Production and roles of IL-6, IL-10, and IL-13 in B-lymphocyte malignancies and in B-lymphocyte hyperactivity of HIV infection and autoimmunity.

We analyzed the production and the roles of IL-6, IL-10, and IL-13 in B-lymphoid malignancies and in specific diseases with B-lymphocyte hyperactivity. Both IL-13 and IL-10 genes are expressed in B-cell lymphomas. However, their contribution to tumor progression is unclear. In certain lymphoproliferative disorders that develop in transplanted patients, IL-6 is produced by malignant cells and is a major factor of their proliferation. In other lymphomas, the IL-6 gene is expressed only in malignancies where differentiated malignant cells are present. In these lymphomas, IL-6 is produced by stromal cells, and the malignant cells express the IL-6 receptor. In patients with HIV infection, the level of production of IL-6, IL-10, and IL-13 is not higher than those of other conditions with immune activation. However, IL-6 contributes to increased production of IgG and IgA in vivo. In Castleman's disease, IL-6 is produced in the lymph node germinal centers, partly originating from follicular dendritic cells, which may explain some of the pathogenesis of this disease. In systemic lupus erythematosus, the critical cytokine is IL-10, which is produced in large amounts by B lymphocytes and monocytes and is responsible for autoantibody production. Taken together, these data emphasize the roles of IL-6 and IL-10, usually produced by nonlymphoid cells, on B lymphocytes, either malignant or hyperactivated.

Acquired Immunodeficiency Syndrome↗

PubMed1997

Thrombosis and restenosis after peripheral angioplasty: does acute 111indium-platelet accumulation predict angioplasty outcome?

OBJECTIVES: Use of platelet deposition to predict failure following angioplasty. DESIGN: Prospective study of angioplasty patients in a 9 months surveillance period. MATERIALS: Thirty-eight successful angioplasty patients. METHODS: Autologous 111indium-labelled platelets were re-injected immediately after angioplasty. Gamma camera and probe measures of radioactivity were obtained daily for 2-4 days and compared to a reference site to obtain a radioactivity ratio. Patient follow up was with duplex and arteriography from day 0 to 9 months or at angioplasty failure. RESULTS: Thirty-one patients remained asymptomatic; two developed acute occlusion and five developed restenosis. Platelet accumulation (increased mean radioactivity ratio) occurred at all angioplasty sites and was significantly higher after acute occlusion (camera: 2.93 and probe: 1.93) compared to asymptomatic patients (camera: 1.25 and probe: 1.15) and restenotic patients (camera: 1.31 and probe: 1.23). Radioactivity ratio was not different in patients who later developed restenosis. CONCLUSION: 111Indium platelet radioactivity effectively detected acute angioplasty reocclusions, but was unable to predict subsequent angioplasty restenosis.

Adult↗

PubMed1997

Pleomorphic medium-sized T-cell lymphoma following Hodgkin's disease (nodular sclerosis type).

We describe a 32-year-old woman who presented with Hodgkin's disease, nodular sclerosis type II, subtype I, which necessitated several treatments over 11 years. The patient then developed pleomorphic, medium-sized T-cell lymphoma, which had a fatal outcome within 13 months. The role of radiotherapy, splenectomy, and chemotherapy in second tumor induction is compared with other sequential T-cell lymphomas. The significance of rare Epstein-Barr virus-infected cells during the T-cell lymphoma extension is discussed.

Adult↗

PubMed1997

A hidden complication of out-patient arteriography.

Rapid progression of arterial disease may occur between out-patient diagnostic arteriography and therapeutic angioplasty. We have studied the incidence of this complication in our institution. Sixty-seven consecutive out-patient arteriograms were assessed. Thirty-four patients were re-admitted for angioplasty within a median interval of 4 weeks (range 5 days-3 months). We compared immediate pre-angioplasty arteriograms with the out-patient images. Twenty-five pairs of films showed disease progression. Three patients showed new disease, one remote from the site of the arterial lesion and two in the opposite limb. Six patients showed marked progression of the original disease. The policy of delayed treatment after out-patient arteriography may require reconsideration in the light of our complication rate of 18%.

Aged↗

PubMed1997

Lymphomas associated with HIV infection.

Lymphomagenesis in HIV positive patients is a complex phenomenon not yet completely understood (Karp and Broder, 1992). The great majority of NHL are of the B cell type. Burkitt lymphoma seems to develop early during the evolution of HIV infection in patients with a CD4 count above 200/microliter. MYC is rearranged in the majority of the cases. EBV latent infection is observed in 30-45%. EBV status is characterized by a negativity for EBNA2 and LMP1 The main sites of the tumour are the lymph node and the bone marrow. Diffuse large cell lymphomas, mostly represented by immunoblastic lymphomas with plasmacytoid differentiation and by centroblastic lymphomas rich in immunoblasts, are a late event in HIV infection, in patients with a low CD4 count (often below 50/microliter). The prognosis is worse than in Burkitt and Burkitt like lymphoma. MYC is rearranged in about 30-40% of the cases, whereas more than 70% are EBV positive. EBV status is characterized by a positivity for both EBNA2 and LMP1. B type ALC lymphomas are more frequently associated with EBV than in the general population and exhibit the same EBV status as diffuse large cell lymphomas. HD occurs at any stage of HIV infection. The majority of patients are in clinical stage III or IV at the time of diagnosis, and HIV associated HD shows a more aggressive course than non-HIV HD. Many cases remain difficult to classify; instead, the immunophenotype of neoplastic cells is similar to that in HD occurring in the general population. Histiocytes and epithelioid cells are even more numerous than T lymphocytes, and the CD4:CD8 ratio is low. Neoplastic cells are EBV positive in most or all cases, although they are consistently HIV negative by in situ hybridization. Lymphomagenesis seems to be very complex, with multiple agents acting together or successively. EBV, other viruses, rearrangement of various genes and production of cytokines all seem to have major roles in addition to immune deficiency.

Humans↗

PubMed1996

[Medication group for noncompliant patients in a psychiatric day unit--experiences during a one year period].

A group of noncompliant psychiatric patients was treated on a weekly basis over a 6-month period; 13 started but 3 dropped out. Results indicated greater feeling of security with medication; increased desire to maintain follow-up treatment in the outpatient clinic; greater likelihood of patients accepting their illness; and strong desire to discuss medication-related topics with staff. Our medication group appears to offer a convenient and organized method for addressing issues of psychiatric medication, especially for chronic patients, which we recommend to clinicians in other medical disciplines.

Adult↗

PubMed1996

VJ rearrangements of the TCR gamma locus in peripheral T-cell lymphomas: analysis by polymerase chain reaction and denaturing gradient gel electrophoresis.

Using Southern blotting for the diagnosis of clonality in peripheral T-cell lymphomas (PTCLs), analysis of the T-cell receptor (TCR) gamma gene rearrangement was shown to be more informative than that of the TCR beta gene rearrangement. In order to amplify every VJ gamma rearrangement, a polymerase chain reaction (PCR) procedure using newly designed GC-clamp primers has been developed. All primers can be mixed in a single multiplex PCR. PCR products are analysed by denaturing gradient gel electrophoresis (DGGE), providing tumour-specific imprints inasmuch as the procedure characterizes N sequence polymorphism at the VJ junctions. In a series of 30 PTCL cases, the PCR procedure demonstrated 27 cases to be clonally rearranged and failed in three cases. PCR was more accurate than Southern blotting, showing 47 rearranged gamma alleles, four of which were undetectable on the Southern blot. When lymphomas were studied at different sites and at relapse, the DGGE pattern remained unchanged. In PTCL, the proposed PCR is helpful for the diagnosis and staging of the disease and should improve the follow-up monitoring. The undetectability of clonal rearrangements in a few cases is discussed in the light of concepts of lymphomagenesis and T-cell differentiation.

Base Sequence↗

PubMed1996

Differential nuclear localization of p50, p52, and RelB proteins in human accessory cells of the immune response in situ.

The Rel/NF-kappa B proteins, p50, p52, p65, c-Rel, and RelB, constitute a family of transcription factors involved in the positive regulation of a variety of genes during the immune response. Recently, it has been shown that RelB knockout mice have no dendritic cells (DC). An overexpression of p50 has been described in follicular dendritic cells (FDC). A constitutive NF-kappa B activity has been reported in mature macrophages. This led to the hypothesis that some of the Rel/NF-kappa B proteins were key nuclear factors in functions of accessory cells of the immune response. Therefore, we investigated in situ the nuclear localization of Rel/NF-kappa B proteins in accessory cells of the immune system by immunohistochemistry and double labeling by immunofluorescence from five normal human tonsils and five lymph nodes with follicular hyperplasia. Nuclear p65 and c-Rel proteins were found in all cell types including lymphocytes. In germinal centers GC, p50, p52, and RelB were found in the nuclei of FDC only and were not detected in the nuclei of CD68+ cells. In T cell areas, p50, p52, and RelB were found in the nuclei of HLA-DR+ cells with an antigen-presenting cell (APC) morphology. p52 and RelB were detected in the nuclei in both CD1a+ and CD68+ cells from the T cell area, whereas p50 was found only in CD68- and CD1a- cells. Cells with nuclear p50 were negative for the CD38, CD20 and CD2 markers. These results show that, physiologically, high levels of nuclear of p50, p52 and RelB are restricted to accessory cells of the immune system, which include FDC in GC, and DC and macrophages in the T cell zone, that specialized scavenger macrophages from GC do not have detectable levels of p52 and RelB, whereas macrophages from the T cell area, known to present the antigen to T cells, do have both nuclear p52 and RelB, and that in the T cell zone, p52 and RelB are located in nuclei of both CD1a+, CD68+ or both, cells APC, whereas p50 is restricted to CD1a- and CD68- APC. The different patterns of p50, p52 and RelB protein nuclear localization may provide insight into their different roles during the immune response in vivo.

Adolescent↗

PubMed1996

Soft tissue sarcomas in HIV-infected adult patients.

Clinical and biological features of three HIV-infected adults with soft tissue sarcoma are reported. Epstein-Barr Virus (EBV) detection was negative using in situ hybridisation, PCR analysis and Southern blot analysis in the two cases for which tumour samples were available, contrary to all previously reported paediatric cases. All three patients developed metastases. Chemotherapy was feasible but only afforded tumour stabilisation. The cause of death in all three cases was distant spread and not AIDS. Soft tissue sarcoma associated with HIV infection are not exclusively found in children, do not appear to be EBV-related in adult patients, and fare dismally despite vigorous therapy.

Adult↗

PubMed1996

The significance of increased 111indium platelet accumulation at post-angioplasty sites.

We assessed prospectively the significance of 111indium labelled platelet accumulation following angioplasty procedures in 12 patients (9 femoral angioplasties (2 laser, 1 atherectomy) and 3 iliac stents). Autologous 111indium labelled platelets were re-injected immediately after angioplasty. Radioactivity was measured over treated and reference sites, by single probe and gamma camera, and expressed as a radioactivity ratio (RR). All patients had duplex ultrasound assessment and occlusions were confirmed by arteriography. RR was always raised after angioplasty. Three patients who had acute occlusions showed markedly raised average RRs (significant at 99% ANOVA). RR was not raised after laser assisted angioplasty, however, our numbers were small. 111Indium platelet radioactivity did not predict subsequent occlusion after angioplasty but effectively detected existing acute post-angioplasty occlusions.

Angiography↗

PubMed1996

Non-invasive assessment of arterial stenoses in angioplasty surveillance: a comparison with angiography.

OBJECTIVES: Comparison of non-invasive arterial measurements with angiography and their use for angioplasty surveillance. DESIGN: Prospective assessments of arterial stenoses in patients undergoing angioplasty in a 9 month surveillance period. MATERIALS: Fifty consecutive patients undergoing angioplasty. METHODS: (i) One hundred and thirty-one sets of clinical assessments, ankle brachial Doppler pressure indices and colour Duplex velocities and diameters were compared to time-matched angiographic diameter stenosis. (ii) Fifty patients undergoing femoropopliteal angioplasty (32 stenoses and 18 occlusions) were studied with ankle branchial Doppler pressure indices and colour Duplex and angiography during a 9 month surveillance period. RESULTS: (i) Symptoms, pulses, resting ABPI, and exercise ABPI showed no useful correlation with angiography. Duplex velocity ratio and Duplex diameters showed correlation and agreement with angiography respectively. (ii) On surveillance, restenosis was universal but not always clinically significant. Angioplasty caused a rapid improvement in ABPI and imaging studies which worsened at later times. ABPI did not predict clinical failure however, Duplex and angiography predicted all clinical failures. CONCLUSIONS: Restenosis should be assessed with imaging of the angioplasty site during angioplasty surveillance.

Adult↗

PubMed1996

Thymocyte and thymic microenvironment alterations during a systemic HIV infection in a severe combined immunodeficient mouse model.

OBJECTIVE: A new model for systemic and multifocal HIV-1 infection was developed in severe combined immunodeficient (SCID) mice to study the alterations of thymocytes and of the thymic microenvironment that occur during a disseminated HIV infection. DESIGN AND METHODS: We grafted SCID mice with the classical human fetal thymus/liver co-implants together with fragments of autologous lungs (SCID-huLLT). These organs achieved normal differentiation and were productively infected after an intraperitoneal inoculation of two HIV-1 primary isolates. At time of sacrifice, thymic biopsies and thymic cell suspensions were analysed by immunohistochemistry, flow cytometry and lymphocyte function assays. RESULTS: At weeks 2-4 post-inoculation we observed the following thymocyte abnormalities: a minor to severe depletion of the immature CD1+CD4+CD8+ T cells (range, 0-73% thymocytes), compared with the persistence of mature CD4+ cells (11-50%) and amplification of CD8+ T cells (6-92%). The immature subset depletion was inversely related to the thymic HIV-1 viral load, suggesting the preferential infection of this subset. The residual mature thymocytes were functional as assessed by their sustained proliferative responses to CD3-triggering which contrasted with the lack of HIV-specific cytotoxic activity. A quantitative analysis of immunostained thymic sections revealed a disorganization and a densification of the thymic epithelial cells (TEC) network which occurred in all HIV-infected SCID-hu mice independently of the thymic CD1+CD4+CD8+ T-cell depletion. CONCLUSION: These results suggest that a systemic HIV infection induces in human thymuses from SCID-huLLT mice a preferential depletion of the immature thymocytes in the absence of mature CD4+ T-cell depletion, HIV-specific cytotoxic T-lymphocyte activity or thymic epithelial cell death, but is associated with dysplasia of the thymic microenvironment, and is therefore opening new perspectives for studying immune cell reconstitution strategies in HIV infection.

Animals↗