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Biomedical subjects

B Benyahia

Publications and source records attributed to B Benyahia.

At least 19 recordsLinked to original sources

Cell-mediated autoimmunity in paraneoplastic neurological syndromes with anti-Hu antibodies.

Paraneoplastic encephalomyelitis or subacute sensory neuronopathy associated with small-cell lung cancer (SCLC) and high titers of anti-HuD antibodies, also called the "anti-Hu syndrome," is believed to result from an immune response triggered by tumor antigens and misdirected to the neurons. To further assess the issue of cell-mediated immunity in this disease, the peripheral blood lymphocyte surface phenotype was studied in 15 patients suffering from the anti-Hu syndrome (seropositive group) and in two control groups consisting of 12 seronegative SCLC patients without neurological syndrome and 15 healthy volunteers. In addition, the recombinant human HuD protein was used to stimulate in vitro peripheral blood mononuclear cells of 10 seropositive patients and of 10 patients from each control group. Phenotypic analysis of the peripheral blood lymphocytes revealed a significant increase of the memory helper (CD45RO+CD4+) T cells in the seropositive group in comparison with the two control groups. Antigen-specific proliferation of peripheral blood mononuclear cells, measured by [3H]thymidine uptake after HuD antigen stimulation, was much higher in the seropositive group than in the two control groups, and phenotypic analysis of proliferating cells revealed a significant expansion of the CD45RO subpopulation of T cells in the seropositive group. Furthermore, after HuD stimulation, a significant increase of the interferon-gamma/interleukin-4 ratio was found in culture supernatants of the seropositive group compared with seronegative SCLC patients and normal controls. Taken together, these results indicate that HuD protein is an antigenic target for autoreactive CD4+ T cells, presumably of the Th1 subtype, which could therefore be directly involved in cell-mediated injury of the nervous system as well as in antitumoral immunity.

Autoantibodies

[Asphyxiating intra-alveolar hemorrhage: a rare form of fat embolism syndrome].

We report a case of a 23-year-old patient admitted for a right femur fracture resulting from a traffic accident. An intra-alveolar haemorrhage occurred 48 hours later, with asphyxia anaemia, haematic bronchial aspirations, and bilateral alveolar opacities at chest X-ray. This symptomatology was associated with fever, sub-conjunctival petechiae, major hypocholesterolemia, deterioration of renal function, and cholestasis. All these features suggested a fat embolism. Other possible aetiologies were discarded because of normal cardiovascular and immunologic systems and absence of infection. The outcome under symptomatic treatment was satisfactory within 15 days. The occurrence of intra-alveolar haemorrhage in post-traumatic fat embolism is a rare event caused by pulmonary capillary obstruction by fat emboli.

Accidents, Traffic

The pathophysiology of paraneoplastic neurological syndromes.

Paraneoplastic neurological diseases are a group of neurological disorders associated with neoplastic tumors but not due to tumoral extension, metabolic, infectious, vascular or toxic complications of these tumors or their treatment. In the majority of paraneoplastic neurological disorders, circulating autoantibodies directed against neurons have been found in the serum and/or the CSF suggesting, and in some cases implicating, autoimmunity in the pathophysiology of these diseases. The finding of autoimmune phenomena during the course of paraneoplastic neurological disorders is of importance: from a practical point of view, since the detection of anti-neuronal autoantibodies is of great diagnostic help and should lead to the thorough search of the associated tumor often at an early stage of its development; from a theoretical point of view, these disorders represent a peculiar type of molecular mimicry. Tumoral neontigens having structural homology or identity with neuronal autoantigens elicit autoreactivity. The immunological effector mechanisms involved in the pathophysiology of paraneoplastic syndromes appear to differ according to the disease: autoantibodies are pathogenic in Lambert-Eaton syndrome whereas, in paraneoplastic cerebellar degeneration and in the Hu syndrome, the cellular immune response might play a greater role.

Encephalomyelitis

[Arterial thrombosis in the course of nephrotic syndrome. Report of three cases].

Vascular thrombosis remains severe complication in patients with nephrotic syndrome. Both venous and arterial thrombosis are observed. We report three new cases of arterial thrombosis in patients with nephrotic syndrome. The role of acquired hemostasis disorders, inducing hypercoagulability, is predominant. Extramembranous glomerulonephritis remains the most frequent cause of nephrotic syndrome, complicated by vascular thrombosis. Treatment is based on anticoagulation and corticosteroid therapy. Search for proteinuria should be part of the etiology work-up in all patients with vascular thrombosis of undetermined origin.

Adult

[Paraneoplastic intestinal pseudo-obstruction revealing small cell lung carcinoma: "the anti-Hu syndrome"].

A 67-year-old woman was admitted for intestinal pseudoobstruction associated with peripheral sensitive neuropathy. Jejunal biopsies performed during laparotomy, showed axonal degeneration and lympho-plasmocytic infiltration in myenteric plexus. High titer of seric anti-Hu antibodies suggested a paraneoplastic syndrome. Thoracic CT scan showed mediastinal lymph nodes. Their histological examination confirmed the diagnosis of metastatic small-cell lung carcinoma. Her condition gradually deteriorated despite supportive parenteral nutrition, chemotherapy, steroids and intravenous immunoglobulins. She died 12 months after the onset of symptoms.

Aged

[Arterial complications of Behcet's disease. Report of 13 cases].

Vascular involvement, usually venous thrombosis, is common in Behçet's disease. Arterial manifestations, usually aneurysms or more rarely occlusion, are less common. We analyzed 13 cases of Behçet's disease with arterial complications. This fourth series in the literature was collected over 11 years. There were 12 men and 1 woman, mean age 41 +/- 7 years. Mean delay to arterial complications was 5.8 years (maximum 20 years) after the first sign of the disease. In the 13 patients in our series, there were a total of 18 arterial lesions, including one aneurysm and one stenosis of the internal carotid artery. There were 2 cases (10%) with lesions of the aorta (aneurysms). Approximately half of the arterial lesions (7/18) involved the femoral artery. There were 11 localizations on the femoropopliteal axis (11 aneurysms). One aneurysm of the humeral artery was the only localization in the upper limb. Vascular involvement was limited to arterial lesions in 9/13 patients with multiple lesions at different localizations in 2 patients. In two others, a second arterial localization occurred secondarily. All patients except one were operated. Mid-term complications are: 1 death and 4 thrombi including 3 with good results after reoperation. In these patients with Behçet's disease, risk of severe complications is important, requiring long-term surveillance.

Adult

[Glomangioma of the popliteal fossa. Apropos of a case].

Glomus tumours are relatively uncommon lesions most frequently found in the extremitis, usually in the digits. They are most often solitary lesions but multiple tumours have been reported. If the triad of pain, tenderness and cold intolerance should raise the clinical suspicion of a digital glomus. The histological exam is necessary in the extra digital glomus. We reported a case of fossa poplitea glomangioma with tibialis nerve compression. The treatment of choice was a surgical exision. But the tumour have been redivided a year later without malign transformation.

Follow-Up Studies

Imaging and biodistribution of 125I tyramine oligonucleotide in nude mice bearing human breast tumor. Preliminary report.

Although the range of applications for antisense oligonucleotides is vast, current research concentrates mainly on virology and oncology. We have conducted in vivo and in vitro investigations of radiolabelling and biodistribution of a 22-mer phosphodiester oligonucleotide injected in athymic mice bearing xenograft of human mammary tumor (coculture: MCF7 and fibroblasts strain AF-11). Tumor/healthy tissue ratio of the 22-mer phosphodiester oligonucleotide fixation is high during the 24 hours after injection instead of fast elimination.

Animals

[False hydatic aneurysm of the thoraco-abdominal aorta].

Arterial complications of hydatic disease are rarely encountered. We report a false hydatic aneurysm of the thoracoabdominal aorta revealed by ischemic embolism of the lower limbs. Surgical treatment included aorto-aortic prosthesis and albendazol for 6 months. Results at 18 months are excellent with negative hydatic serology. In endemic areas, hydatic disease is a possible cause of false aneurysms. Long-term surveillance is required after curative surgery and medical treatment.

Adult

Erythema gyratum repens. A case studied with immunofluorescence, immunoelectron microscopy and immunohistochemistry.

We report a patient with erythema gyratum repens (EGR), in whom a bronchial carcinoma was found. Direct immunofluorescence revealed granular deposits of immunoglobulins at the basement membrane zone (BMZ) in the skin, and in the lung tumour. Direct immunoelectron microscopy showed that the immune deposits were localized just beneath the lamina densa. Indirect immunofluorescence revealed circulating anti-BMZ antibodies. Immunohistochemical staining, using anti-transforming growth factor-beta, anti-epidermal growth factor receptor, anti-vimentin and anti-alpha-actin, was found to be more intense in the lesional skin and the lung tumour than in normal tissues. Possible mechanisms in the pathogenesis of EGR are discussed.

Autoantibodies

Transforming growth factor-beta and megakaryocytes in the pathogenesis of idiopathic myelofibrosis.

Although the disease is well described, the pathogenesis of bone marrow fibrosis in idiopathic myelofibrosis still remains unclear. We previously reported elevated intraplatelet transforming growth factor-beta (TGF-beta) levels in patients with this myeloproliferative disorder, compared with healthy subjects. Here, in a series of 16 patients, we show that TGF-beta expression is also increased in patients' peripheral blood mononuclear cells (PBMC): (i) at the mRNA level analysed by Northern blot hybridization and/or reverse transcription-polymerase chain reaction (RT-PCR); (ii) and/or at the secreted peptide level as evaluated in conditioned media from patients' mononuclear cells by a growth inhibition assay on CC164 cells. By immunostaining with a polyclonal anti-TGF-beta 1 antibody, TGF-beta was localized in morphologically heterogenous cells; these cells were characterized as megakaryocytes by labelling with a gpIIbIIIa monoclonal antibody. Thus we provide evidence that both TGF-beta and megakaryocytes are linked in the pathogenesis of idiopathic myelofibrosis.

Aged

[Applications of antisense oligonucleotides in oncology].

The development of biotechnologies offers considerable potential for new therapeutical approaches, targetting nucleic acids as information bearing molecules responsible for various pathologies. Gene therapy has, up to now, mainly aimed at compensating deficiencies of gene expression, through complex molecular and cellular constructions. Recently, an increasing interest has focused on short nucleotidic sequences (thus relatively easy to synthetize), or oligonucleotides, which could be able to specifically block the expression of mutated or overexpressed genes. When the target of these oligonucleotides is the mRNA of such genes, the strategy is called "antisense". This strategy has already led to a number of successful results in experimental models in vitro. Much more rare are actual effects in animal models and clinical trials are just being sketched. A review on the current state of the art will enlighten the physiological potential of these new molecules but also underline the still numerous issues before controlling therapeutical applications.

Animals

Breast cancer proliferation measured on cytological samples: a study by flow cytometry of S-phase fractions and BrdU incorporation.

Cell kinetics have been shown to be an important predictor of clinical evolution of operated breast cancer. We established a method for the estimation of the proliferative activity of tumour cells obtained by fine needle sampling without aspiration (FNS), using simultaneously S-phase fractions (SPF) measured on DNA histograms and 5-bromodeoxyuridine (BrdU) labelling index (BLI) measured by flow cytometry. Biparametric BrdU/DNA flow cytometry could be performed in 122 of 189 (65%) consecutive patients. The mean BLI of the cytologically malignant FNS (118) was of 3.0 and the median of 2.2%. One hundred and forty-eight DNA histograms (78%) were suitable for SPF analysis, of which 141 presented malignant cells, showing a mean of 4.5 and a median of 3.5%, comparable to BLIs. These results were obtained from fluorescence peak area histograms with doublet discrimination and background subtraction allowing the measurements of SPFs as low as 0.4%. An excellent correlation was thus observed between BLIs and SPFs, for the 94 cases for which both results were available (r = 0.85). Infrequent discordances (9%) were noted with SPFs considerably higher than BLIs. Seven patients had three consecutive FNS of their tumour at weekly intervals before treatment. Some variability in the proportions of multiple subpopulations of tumour cells was observed on the DNA histograms. In contrast, proliferation indices (SPF or BLI) were reproducible, suggesting homogeneous growth rates. We conclude that an estimation of the proliferative activity of breast tumours at any stage of the disease is possible routinely by SPF and/or BLI analysis of FNS. At least one quantitative proliferation index could be obtained for 91% of patients.

Biopsy, Needle

[Arteriopathies of the lower limbs in adults under 40 years of age].

In Morocco, thromboangiitis obliterans (TAO) is the most common cause of obliterating arteriopathy in subjects under 40 years: 252 cases out of 291, versus 21 cases of diabetic arteritis and 18 miscellaneous causes. The anatomo-clinical appearance is in keeping with the criteria for Buerger's disease with the exception of superficial migratory thrombophlebitis. The absolute basis of treatment has been the total definitive discontinuation of smoking. Platelet anti-aggregant agents have also been used. Aside from limited resections of distal gangrenous regions (168 cases), surgery has been limited to lumbar sympathectomy without adrenalectomy (154 cases). Out of 133 patients regularly followed up for more than one year, results were good in 102 patients. The 39 poor results occurred exclusively in patients who continued or restarted smoking.

Adult

Arterial manifestations in Behçet's disease: four new cases.

Four new arterial lesions observed with Behçet's disease are reported: two popliteal aneurysms, one carotid aneurysm and one carotid stenosis. The clinical features, therapeutic modalities and postoperative complications of these uncommon lesions are reviewed briefly.

Adult

New approach for visualizing estrogen receptors in target cells using inherently fluorescent ligands and image intensification.

Four fluorescent estrogen ligands were investigated as agents for visualization of estrogen receptors in cells: 2-(2,4-dihydroxyphenyl)-6-hydroxy-3-benzofurancarboxylic acid delta-lactone (coumestrol) and 9(11)-dehydro-12-oxoestradiol [12-oxo-1,3,5-(10),9(11)-estratetraene-3, 17 beta-diol] (12-oxoestradiol), which are inherently fluorescent compounds; and tamoxifen [Z)-1-[4-(2-dimethylaminoethoxy)phenyl]-1,2-diphenyl-1-butene) and 4-hydroxytamoxifen [Z)-1-[4-(2-dimethylaminoethoxy) phenyl]-1-(4-hydroxyphenyl)-2-phenyl-1-butene), which become maximally fluorescent only after ultraviolet irradiation. By conventional fluorescence techniques, these agents can be detected down to 10(-8) M in water, but only to 10(-6) to 10(-7) M in protein solutions; however, by photon-counting spectrofluorimetry, coumestrol and 12-oxoestradiol can be detected in protein solutions down to 5 X 10(-10) M. Three of these compounds have good affinity for the estrogen receptor: coumestrol (20%); 12-oxoestradiol (12%); and 4-hydroxytamoxifen (37%), relative to estradiol (100%). Under conditions where autoradiographic controls indicate that most of the estrogen receptor of MCF-7 human breast cancer cells is in the nucleus, we could demonstrate nuclear fluorescence using 10(-9) M concentrations of coumestrol, 12-oxoestradiol, and 4-hydroxytamoxifen. This nuclear fluorescence was abolished by a 200-fold excess of diethystilbestrol and could only be observed through a fluorescence microscope equipped with a microchannel image intensifier and a video camera detector that together provide a sensitivity enhancement of approximately 10(4). These studies indicate that the estrogen receptor in breast cancer cells can be visualized by fluorescence techniques, provided that the visualizing ligands have adequate affinity and specificity for the receptor and appropriate fluorescence characteristics, and provided that the fluorescence instrument has adequate sensitivity to observe fluorescence emission from cells treated with nM concentrations of the fluorescent agents.

Breast Neoplasms

[Fine-needle aspiration biopsy and analysis of estrogen receptors in breast cancer].

Estrogen receptor concentration was measured in fine needle aspirates from 98 human mammary carcinomas. We performed a biochemical radiolabeled assay by the Charcoal-Dextran procedure on cytosols obtained after homogenization in a saline hypertonic buffer (0,4 M KCl) and centrifugation at 105,000 g. DNA content of the pellets was measured by fluorimetry. A sample of about 10(6) cells, containing at least 10 micrograms of DNA, was needed to obtain a reliable result. In this report, 74 samples were over 10 micrograms of DNA each. The analysis of these samples showed that, in 39 cases (52,8%), the estrogen receptor level was over the limit of 500 fmol/mg of DNA. In 5 cases (6,7%), the range was between 500 to 600 fmol/mg DNA and, in 30 cases (40,5%), it was under 500 fmol/mg DNA and was considered as negative. For 15 patients, estrogen receptors were determined on the same tumor, as removed by fine needle aspiration and by a surgical procedure (6 cases) or drill-biopsy (9 cases). There was a good correlation between the receptor content in needle aspirates and in tissue specimens for 13 cases out of 15.

Biopsy, Needle