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Biomedical subjects

J P Merlio

Publications and source records attributed to J P Merlio.

At least 19 recordsLinked to original sources

Three cases of primary cerebral lymphoma in AIDS patients: detection of Epstein-Barr virus by in situ hybridization and Southern blot technique.

Three cases of primary cerebral lymphoma in acquired immunodeficiency syndrome were studied. Tumoral fragments taken at autopsy were frozen and studied by the Southern blot technique (SBT). Other tumoral fragments were fixed in formalin, embedded in paraffin and used for in situ hybridization (ISH) with biotinylated probes for DNA of Epstein-Barr virus (EBV). ISH was positive in each case with a spotty nuclear labelling of certain tumoral cells. SBT evidenced a clonal rearrangement of the immunoglobulin heavy chain gene in each case. In addition, EBV DNA was detected in each frozen fragment with only one restriction pattern, indicating that the EBV- infected cell population was a clonal expansion of a progenitor cell.

Adult

Benign lymphocytic angiitis and granulomatosis: a T-cell lymphoma?

Benign lymphocytic angiitis and granulomatosis is a T-cell lymphoproliferative disorder confined to the lung and corresponding to a low-grade angiocentric immunoproliferative lesion. Controversy remains as to whether these lesions are lymphomas. We report such a case in an 8-year-old patient with Burkitt's lymphoma in remission who presented with persistent bronchopneumopathy and bilateral pulmonary infiltrates on tomodensitometry. Surgical resection revealed the histologic changes of benign lymphocytic angiitis and granulomatosis. Immunohistochemistry showed no aberrant pan T-cell marker loss. Genetic analysis of frozen tissue by Southern blot DNA hybridization with probes to T-cell receptor beta- and gamma-chain genes and to the immunoglobulin heavy chain joining region gene (JH) identified no clonal rearrangement. Search for Epstein-Barr virus-DNA sequences by in situ hybridization and Southern blot analysis provided negative results. Our data imply that lowgrade angiocentric immunoproliferative lesions are not exclusively lymphomas but might represent a borderline lymphoproliferative disease (seen in the course of many diseases), perhaps corresponding to host immune response.

Burkitt Lymphoma

Molecular cloning of rat trkC and distribution of cells expressing messenger RNAs for members of the trk family in the rat central nervous system.

Tyrosine protein kinases trk, trkB and trkC are signal-transducing receptors for the neurotrophins nerve growth factor, brain-derived nerve growth factor, neurotrophin-3 and neurotrophin-4. Here we report on the isolation of cDNA fragments encoding a part of rat trk and trkB proteins, respectively, and characterization of a full-length cDNA clone encoding rat trkC. Cells expressing mRNAs for the different members of the trk family were identified in the rat central nervous system by in situ hybridization using oligonucleotide probes designed from the isolated cDNA sequences and complementary to mRNA sequences coding for the extracellular region of the receptors. The expression of trk mRNA was found to be restricted to neurons of the basal forebrain, caudate-putamen with features of cholinergic cells and to magnocellular neurons of several brainstem nuclei. In contrast, cells expressing trkB and trkC mRNAs were widely distributed in the brain. Areas expressing high levels of trkB or trkC mRNAs included olfactory formations, neocortex, hippocampus, thalamic and hypothalamic nuclei, brainstem nuclei, cerebellum and spinal cord motoneurons. A similar distribution for trkB and trkC mRNAs was shown in most areas but each probe specific for these mRNAs also provided distinct labeling patterns in different subregions, layers and cells. Comparison between our data and previous analyses of cells expressing mRNAs for neurotrophins and the low-affinity nerve growth factor receptor suggests that different modes of action and different combinations of receptors mediate biological responses to neurotrophins in the adult rat brain.

Animals

[Syndrome of macrophagic activation with hemophagocytosis in human immunodeficiency virus infection].

The authors report two cases of hematophagic histiocytosis in HIV positive patients. In the first case, a patient with Kaposi sarcoma and Mycobacterium avium infection had a rapidly deteriorating course with progressive pancytopenia and death, as generally described in the literature. In the second case, hematophagic histiocytosis appeared during HIV primo infection and reversed spontaneously. Although few cases of hemophagocytic syndrome have been reported in HIV positive patient, it could represent an underestimated cause of pancytopenia. Both opportunistic microorganisms and HIV are able to cause hematophagic histiocytosis.

Adult

[Non-Hodgkin's malignant lymphoma and human immunodeficiency virus. Apropos of 34 cases].

The characteristics of 34 HIV-associated non Hodgkin's lymphomas diagnosed and treated at Bordeaux hospitals are described. The patients represented 7% of the AIDS cases observed in the Bordeaux area. HIV-lymphomas were almost always high-grade malignancies, usually disseminated (70%) with extranodal disease at presentation (91%) primarily in the bone marrow, meninges, gastrointestinal tract and liver. Twenty-eight patients were treated with different chemotherapy protocols or radiation therapy alone. Complete remission was achieved in 11 patients and partial remission in 3. The median survival was 3.9 months. Despite utilization of low-intensity chemotherapy regimens, opportunistic infections were not prevented. The only factor that accurately predicted complete remission was the WHO performance index. The total number of CD4-positive lymphocytes, the Ann Arbor stage and the WHO performance index were prognostic factors influencing survival. These results justify the use of high-intensity regimens, but only for patients without opportunistic infection and with a WHO performance index below 3.

AIDS-Related Opportunistic Infections

Colocalization of NGF binding sites, trk mRNA, and low-affinity NGF receptor mRNA in primary sensory neurons: responses to injury and infusion of NGF.

The distributions of mRNAs for the protooncogene trk and the low-affinity NGF receptor (LNGFR) were studied by hybridization with oligonucleotide probes on sections of adult rat primary sensory and sympathetic ganglia. For comparison with high-affinity binding sites, adjacent sections were processed for NGF receptor radioautography. Among neurons in lumbar dorsal root ganglia and trigeminal ganglia, trk mRNA and NGF-binding sites were closely colocalized; this finding together with previous direct evidence in other cell types is taken to indicate that trk protein is an essential component of the high-affinity NGF receptor in adult sensory neurons. In lumbar dorsal root ganglia and trigeminal ganglia, abundant LNGFR mRNA was found in all neurons with strong 125I-NGF labeling and on additional neurons lacking high-affinity NGF-binding sites. The presence of abundant LNGFR in neurons with high-affinity receptors could be the cause and/or consequence of their ability to respond to NGF. Neurons with abundant LNGFR mRNA but few high-affinity NGF-binding sites may have receptors for other members of the neurotrophin family. In nodose ganglia, neurons with high concentrations of LNGFR mRNA greatly outnumbered the small percentage with abundant trk mRNA. Following intrathecal infusion of NGF to otherwise normal dorsal root ganglia, the concentrations of LNGFR mRNA but not those of trk mRNA and NGF-binding sites were increased in NGF-responsive neurons. The usual single normal pattern of frequency histograms of LNGFR labeling indices became bimodal in response to NGF. Concentrations of NGF-binding sites, LNGFR mRNA, and trk mRNA were all decreased by peripheral nerve transection and restored by exogenous NGF, the restoration being complete for LNGFR mRNA and partial for trk mRNA and NGF-binding sites. The data indicate that NGF can regulate both LNGFR and trk mRNAs but do not clarify the possible contribution of the LNGFR protein to high-affinity binding sites.

Amino Acid Sequence

[Tumor necrosis factor in graft rejection. In situ hybridization study].

The development of necrosis and macrophage infiltration increases the risk of renal graft rejection. But the macrophages secrete the alpha form of the tumour necrosing factor (TNF) which is also involved in several immunologic and inflammatory phenomena. We therefore studied the expression of the gene TNF alpha by in situ hybridization during advanced stage rejection after renal transplantation: the grafts were infiltrated with macrophage-like cells expressing the mRNA of the TNF alpha gene, particularly deep in the cortex and in the medulla. These cells then secrete the TNF alpha molecule since they are recognized by anti-TNF alpha antibodies. These antibodies also recognize certain other glomerular endothelial and tubular epithelial cells which do not express the TNF alpha gene: these cells are undoubtedly the TNF target cells. These findings confirm the synthesis of TNF alpha in advanced stage renal graft rejection.

Colorectal Neoplasms

Histiocytosis X of the hypothalamus.

An unusual case of cutaneous and hypothalamic histiocytosis X (HX) is reported. The hypothalamic involvement occurred as a tumor that mimicked a chiasm glioma on computed tomography angioscanning. Magnetic resonance imaging after gadolinium injection localized the tumor within the third ventricle floor. The HX origin of the tumor was confirmed by histological examination of hypothalamic biopsies obtained by transventricular endoscopy. The results of endocrine evaluation were consistent with anterior panhypopituitarism resulting from a multiple releasing-hormone secretory defect, but there was no diabetes insipidus. This unusual endocrine aspect has not been previously described in the field of hypothalamic HX. Lastly, the tumor was insensitive to low dose megavoltage radiation therapy. This unusual case stresses the superiority of magnetic resonance imaging over computed tomography scanning in the assessment of suprasellar tumors and emphasizes the usefulness of transventricular endoscopy in these cases.

Female

Eosinophilia associated with a composite lymphoma.

We report a case of composite lymphoma heralded by a hyper-eosinophilia syndrome. Combination of immunophenotyping and gene rearrangement analysis allowed us to confirm malignancy and to detect a minor oligoclone B within a malignant T-cell predominant population. No evidence of retroviral infection was found using western blot and gene amplification techniques.

Adult

[Non-Hodgkin's lymphoma associated with human immunodeficiency virus infection. Bordeaux experience with 26 cases].

We describe the clinical and histologic features of non-Hodgkin's lymphoma in 26 patients with human immunodeficiency virus 1 (HIV) infection. These represent 10 per cent of AIDS cases recorded in the Bordeaux area. Mean age was 42. Contamination was mostly related to homosexuality (50 per cent) and blood transfusion (27 per cent) with 5 female cases. The initial presentation of lymphoma was extranodal (69 per cent). Lymphoma spread was diffuse (65 per cent), involving the bone marrow (38 per cent), lymph nodes (35 per cent), central nervous system (27 per cent), oral and digestive mucosae (23 per cent), liver (19 per cent) and genital tract (12 per cent). Histologic types were of intermediate or high grade malignancy (88 per cent) with 38 per cent large, non cleaved-cell (centroblastic) subtype. Median survival was 4 months. Lymphoma caused death in 65 per cent of patients and opportunistic infection in 18 per cent. Lymphoma was the first manifestation of HIV infection in 10 patients (38 per cent) and was responsible for AIDS in 14 (54 per cent). Diagnosis of lymphoma could be established at an early stage on extranodal biopsy. In these patients a prolonged disease-free survival was obtained after chemotherapy alone or associated with radiotherapy.

Acquired Immunodeficiency Syndrome

[Cells of the phenotype HNK-1 + (CD 57 +) in reactive adenopathies, lymphomas and Hodgkin's disease].

The number and distribution of Leu-7 + cells, a subset of Natural Killer cells clustered as CD 57 + cells, were studied with an immunoperoxidase technique on reactive lymph nodes (n = 13), malignant lymphomas (n = 60) and Hodgkin's disease (n = 22). Results of paraffin-section immunocytochemistry were compared with those obtained of frozen sections of the same tissues. CD 57 + cells are small lymphocytes mainly located in the germinal centers of reactive lymph nodes and in their malignant counterpart, i.e. the follicular lymphomas. The paragranuloma of Hodgkin's disease, type I nodular, contained high numbers of CD 57+ cells. Nine cases of CD 57+ lymphomas are reported, which were of high grade of malignancy. Their histological subtypes were anaplastic (3 cases) immunoblastic (2 cases), pleomorphic medium and large cell (3 cases), unclassifiable (1 case). Their diverse T-cell (4 cases) or B-cell (2 cases) origin and the various expression of epithelial membrane antigen (EMA) or Kil/Ber-H2 (CD 30) suggest an aberrant CD 57+ phenotype of a subset of large cell lymphomas.

Antigens, Differentiation

[Colo-rectal spirochetosis: is it an anatomo-pathologic entity?].

Nineteen colorectal biopsy specimens, stained by Hematein-Eosin-Safran (HES), were examined by light microscopy and showed a thick, blue and fuzzy brush border. Without any further microbiologic investigation, this histologic feature is considered strongly suggestive of colorectal spirochetosis. Our study concerned 19 male patients aged between 35 and 68 years, who had no risk factor for HIV infection, but who belonged to these three groups: (a) those suffering from chronic diarrhea; (b) those without intestinal symptoms; (c) those who had a colonic tumor removed. Rectal biopsy specimens were also taken from a control group of 35 patients seropositive for HIV-1. This thickening, which measured 3-7 microns, showed some variation within the same patient but did not depend on the site of the biopsy. It appeared as a blue fuzzy band on HES stain, was purple on Periodic-Acid-Schiff stain and basophilic after Giemsa stain. Silver stain by Warthin-Starry method confirmed the presence in three cases of numerous spirochetes attached to the epithelial surface. Two of the three patients had no symptom. In the control group, a thickening of the brush border, was observed in only one case, but no spirochete by silver stain was seen. The thickened blue, fuzzy brush border of the colonic mucosa is not a specific criterion. The pathologist must be aware of the possible presence of spirochetes that can only be confirmed by a silver stain. The pathogenicity of spirochetosis remains to be defined.

Adult

An adult atypical fibromyxoid tumor of the urinary bladder.

A case of atypical fibromyxoid tumor of the urinary bladder in a 32-year-old woman is reported. The patient had never complained of urinary symptoms, and bladder tumefaction was revealed fortuitously at pelvic ultrasound. Cystoscopy revealed a peanut-sized mass. Microscopically, the lesion was composed of strap- and tadpole-shaped cells resembling rhabdomyoblasts. For this reason, the tumor was initially diagnosed as embryonal rhabdomyosarcoma. However, immuno-histochemical study was negative for muscle origin, and the tumor has subsequently proved benign. The reported case illustrates the value of immuno-histochemical study in the evaluation of the true type of bizarre stroma cells in this pseudo-sarcomatous lesion. Their recognition is important, because the therapeutic consequences of misinterpreting this tumor as a sarcoma are great.

Adult

Plasma cell granuloma of the adrenal gland and the thyroid: report of two cases.

The clinicopathologic features of two rare cases of plasma cell granuloma of the endocrine glands are described and compared with extrapulmonary cases reported in the literature. One was localized in the adrenal gland and was revealed by amenorrhea and a large inflammatory syndrome; it is the first case reported to our knowledge. The other case developed in the thyroid, was asymptomatic, and represents the third case in the literature.

Adolescent

Gastric large cell lymphoma expressing cytokeratin but no leukocyte common antigen. A diagnostic dilemma.

A case of undifferentiated malignant tumor of the stomach is reported. The immunohistochemistry of biopsy specimens pointed to a diagnosis of carcinoma, the tumor cells being cytokeratin positive and leukocyte common antigen (LCA) negative. After resection, however, histopathologic results showed that the tumor was a large cell lymphoma with plasmablastic differentiation. A new immunohistologic study confirmed, on the one hand, the diagnosis of lymphoma with its monotypic character IgA kappa and, on the other, positivity with three different cytokeratins of the lymphoma cells and their negativity with LCA. The aberrant immunophenotyping of this lymphoma is exceptional and must not undermine the recognized usefulness of LCA and cytokeratin, which both are basic antibody markers of immunohistochemistry in undifferentiated malignant neoplasms.

Antigens, Differentiation

[Isolated necrotizing angiitis of the cervix uteri. Apropos of a case].

A necrotizing arteritis isolated to the uterine cervix without multisystem disease was fortuitously discovered in a 52-year old woman after hysterectomy for uterine leiomyomas. This rare lesion discovered by routine histopathological examination was cured by surgery. The aetiology and pathogenesis of this arteritis are unknown.

Female