Search PubMed⌕ Search

Biomedical subjects

C Nezelof

Publications and source records attributed to C Nezelof.

At least 37 records · Page 2Linked to original sources
PubMed1993

The 5q35bp chromosomal abnormality characterizes certain CD30 positive anaplastic large cell lymphomas offering a new definition of malignant histiocytosis in childhood.

Anaplastic large cell CD30 positive lymphomas represent a heterogeneous group of lymphomas in which immunocytochemical and molecular investigations have demonstrated the existence of malignancies of T, B or undetermined origin. The recent identification, in a few cases, of a chromosomal 5q35 breakpoint may allow distinction of a specific disease. In these cases, the 5q35bp has been found to be a permanent abnormality present in 5 cell lines and associated with various translocations including most often t(2;5) but also t(7;5), t(5;6) and t(3;5). A primitive myelomonocytic origin of these 5q35bp cells is suggested on the basis of the following arguments: i) they spontaneously express CD68; ii) they reduce tetrazolium blue; iii) they express the c-fms proto-oncogene which encodes the macrophage growth receptor (CSF-1); iv) c-fms, which is not rearranged, has been mapped to 5q33 close to the 5q35 breakpoint; v) treatment by phorbol-diester of a 5q35bp cell line (DEL) induces immunodependent phagocytosis and modulation of the expression of c-fms, CSF-1 and TNF alpha. Since some 5q35bp cell lines also present rearrangements of TCR beta or Ig (jH), these data suggest an ancestral stem-cell origin, prior to T, B or myelomonocytic differentiation. Whatever its origin, the 5q35bp abnormality is mainly encountered in childhood malignancies. As it is constantly associated with the clinical and biological manifestations of a condition recognized by pediatricians as malignant histiocytosis, 5q35bp may today represent the best criterion for the identification of malignant histiocytosis in childhood.

Child↗
PubMed1992

Specific expression of the ras-related rab3A gene in human normal and malignant neuroendocrine cells.

BACKGROUND: The authors originally demonstrated the tissue-specific expression of the rab3A gene in the mouse brain. In the current study, they analyze the activity of this gene in fresh human tumors associated with neuronal phenotype compared with normal and malignant cells from other origins. METHODS: The authors studied the transcription levels of the rab3A gene by Northern blot in 81 fresh tumors. RESULTS: A high rab3A gene expression was observed in tumor samples derived from the neural tube (i.e., neuroblastomas, ganglioneuroblastomas, and adult nervous system neoplasms). In addition, this tissue-specific expression extended to neuroendocrine tumors of the gut, small cell lung cancers, and pheochromocytomas. CONCLUSIONS: These results suggest a specific restriction pattern to human cells derived from the neural tube and neural crests. The GTP/GDP-binding rab3A protein may be a useful differentiation marker of neuro-endocrine cells in the characterization of undifferentiated neoplasms.

Biomarkers, Tumor↗
PubMed1992

Thymic pathology in primary and secondary immunodeficiencies.

For the sake of clarity and in agreement with the World Health Organization immunodeficiency classification, it is important to distinguish the congenital, inherited malformative lesions called generically 'thymic dysplasia' from the secondary, acquired changes, designated under the broad term of 'severe thymic atrophy'. Thymic dysplasia represents the archetype of thymic changes in cellular immunodeficiency, since there is no example of a thymic dysplasia associated with a normal T-cell function. Thymic dysplasia is observed in several inherited diseases, the most frequent of them being severe combined immunodeficiency. More than the depletion of lymphoid cells, the lack of differentiation of the thymic epithelium, responsible for the absence of Hassal's corpuscles, is the main and constant feature of this condition. Thymic dysplasia underscores the crucial role of the thymic epithelium in the normal differentiation of the T-cell population. Severe thymic atrophy is secondary to various causes, including prolonged protein malnutrition and immunosuppressive or cytotoxic drugs, graft versus host reaction and, chiefly today, chronic viral infection, especially with HIV-1. The morphological changes are similar and are characterized by a partial lymphoid depletion, involving mainly the CD1+ population, necrosis and calcification of epithelial cells, the frequent presence of plasma cells and, more significantly, fibrohyaline changes of the basement membrane of the vessels and thymic epithelium. The severity of the atrophic changes and the immunodeficiency-related manifestations depend on the duration of the aetiological factors and, more significantly, with their early occurrence, within the first months of life. The mechanisms underlying thymic atrophy are poorly understood. A primary impairment of lymphoid cells seems at present to be the most likely hypothesis.

Animals↗
PubMed1992

Malignant histiocytosis in childhood: a distinctive CD30-positive clinicopathological entity associated with a chromosomal translocation involving 5q35.

The clinicopathological data on 20 cases of malignant histiocytosis (MH) collected over a period of 30 years at the Hôpital des Enfants Malades (Paris) are reported. Childhood MH was characterized by disseminated, frequently tender lymphadenopathy (19/20), skin (8/20), bone (6/20), and soft tissue localizations (7/20). These features were usually accompanied by fever, deterioration of general condition, and hematological abnormalities including anemia, thrombocytopenia, and occasionally fibrinopenia. These manifestations were clinically suggestive of a diagnosis of a severe neoplastic blood disease, although this hypothesis was not entertained for a long time because of the initial absence of abnormal cells in the blood and bone marrow. MH was characterized by the proliferation of large "histiocyte-like," usually mononucleated cells. When suitable material was available, MH cells appeared to react positively with acid-phosphatase, alpha-naphthyl acetate esterase (ANAE), alpha-antichymotrypsin, and antibodies directed against EMA, HLA DR, CD25, CD30, CD68, and CD71. No B- and T-cell antigens (except for one case) have been detected. Due to the frequent abundance of accompanying granulocytes, lymphoid, and plasma cells, and the presence of areas of necrosis, an initial correct diagnosis of MH was often difficult to establish on skin (four cases), bone (two), and soft tissue (three) biopsies. In lymph nodes, the sinusoidal and perifollicular topography of cell proliferation represented a highly reliable morphological feature. A permanent cell line (DEL) was obtained from a pleural effusion showing a t(5;6)(q35;p21) translocation and a monoallelic immunoglobulin (IgjH) rearrangement and consistent levels of expression of c-fms, c-myc, c-myb, c-ki-ras and c-fgr. Since an identical 5q35 breakpoint has been reported in four other MH cell lines with a comparable phenotype and in several isolated published cases, this chromosomal abnormality provides a highly valuable argument for individualizing an authentic malignancy of the mononuclear phagocyte system (MPS) in childhood, among the rather heterogeneous group of the CD30+ anaplastic large cell lymphomas.

Adolescent↗
PubMed1992

[Toward a new definition of malignant histiocytosis in children].

The anaplastic large cell, CD30 positive lymphomas represent a heterogeneous group of lymphomas in which immunocytochemical and molecular investigations have demonstrated the existence of malignancies of T, B or undetermined origin. The recent identification, in a few cases of this group of a chromosomal 5q35 breakpoint may allow the individualization of a peculiar disease entity. In these cases, the 5q35bp has been found to be a permanent abnormality, present in five human permanent cell lines and associated with various translocations including t(2;5), t(1;5) and t(5;6). A primitive myelo-monocytic origin of these 5q35bp cell is suggested on the basis of the following arguments: they express the c-fms proto-oncogene which encodes the macrophage growth receptor (CSF-1-R) the c-fms is mapped on 5q33,34 close to the 5q35bp the express spontaneously CD68 the treatment by phorbol-diester of a 5q35bp cell line (DEL cell line) induces an immunodependent phagocytosis and a modulation of expression of c-fms, CSF-1 and TNF alpha. Because some 5q35bp cell lines also presents rearrangements for TCR-bêta, or IgF, these data suggest an ancestral stem cell origin, prior to the T, B and myelomonocytic differentiation. Whatever its origin, the 5q35bp abnormality has been mainly encountered in children's malignancies. It has been constantly associated with clinical and biological manifestations of a condition recognized by paediatricians as malignant histiocytosis. For this reason, the 5q35bp may today represent the best criterion for the identification of malignant histiocytosis in childhood.

Child↗
PubMed1991

Human malignant histiocytosis CD30+ DEL cell line differentiates into macrophage-like cells when treated with a phorbol diester.

The histiocytic or lymphoid origin of human malignant histiocytosis is currently a subject of debate. The aim of this study was to investigate the in vitro effects of 12-O-tetradecanoylphorbol-13-acetate used as a differentiation inducer on the CD30, t(5;6)(q35;p21) DEL cell line, taken to be a reliable representative of the human malignant histiocytosis cell line. Treatment of DEL cells with 33 nM 12-O-tetradecanoylphorbol-13-acetate for 6-24 h resulted in cell surface attachment (up to 80%), decrease in dividing ability, enhancement of nitro blue tetrazolium reducing capacity (from 8 to 42%), occurrence of a limited immunodependent phagocytosis, and transient increase in expression of tumor necrosis factor alpha gene and in production of tumor necrosis factor alpha protein, whereas tumor necrosis factor beta remained undetectable. From these data, we can conclude that the malignant histiocytosis DEL cell line is not of lymphoid origin but stems from a myelomonocyte lineage.

Cell Differentiation↗
PubMed1991

Lingual localization of an inclusion body fibromatosis (Reye's tumor).

This report illustrates a lingual localization of an inclusion body fibromatosis, the so-called Reye tumor or infantile digital fibromatosis (IDF). The light microscopic features were identical to those found in IDF, showing eosinophilic perinuclear inclusions located in spindle-shaped cells arranged in interlacing fascicles. The immunocytochemical and ultrastructural findings suggested a fibroblastic and/or myofibroblastic nature of the proliferative cells. However, the inclusions in our case were strongly stained with vimentin and their ultrastructural appearance was in keeping with intermediate filaments. These findings have never been described in other reports of fibromatosis. Whereas most reviews state that IDF occurs exclusively on the digits, this unique case describes its possible occurrence in the tongue.

Fibroma↗
PubMed1991

Chronic omphalitis in a 4-month-old girl.

A case of chronic omphalitis present for birth in a 4-month-old girl is presented. The biopsy of the bud-like lesion failed to reveal a local malformation or remnants of umbilical cord but showed a common loose edematous tissue in which the inflammatory cells appeated remarkably scanty. The contrast existing between this poorly cellular local infiltrate and the high level of peripheral blood leucocytes (over 30,000/microliters) was in fact the most striking feature that allowed to evoke the diagnosis of Deficiency Leucocyte Adhesion molecules. Immunocytochemical investigations using anti CD11a, CD11b and CD18 monoclonal antibodies on fresh tissue or, better, peripheral leucocytes are necessary to confirm the diagnosis of this uncommon immunological autosomic recessive inherited disorder.

Cell Adhesion Molecules↗
PubMed1991

[Gonadal dysgenesis and agenesis: anatomical expression].

The term of gonadal dysgenesis designates generically any anatomical alteration due to abnormal embryological development of a gonad. The spectrum of these gonadal abnormalities is large and includes the following entities: The gonadal agenesis is characterized by a rudimentary streak gonad. It is composed of a dense, hyalinized fibrous tissue in which the germ cells or the germ structures are entirely missing. Usually the gonadal dysgenesis is a bilateral and symmetrical lesion. The gonadal dysgenesis is characterized by the presence of residual germ structures (follicles or tubules). These structures can be more or less easily identified within a dense fibrous tissue. The gonadal dysgenesis alterations are often unilateral and always asymmetrical. Usually the ipsilateral gonad is a testis. The ovotestis is characterized by the coexistence within the same gonad of differentiated germ structures. Most commonly, the gonadal dysgenesis are associated with sexual chromosome abnormalities and an increased risk of neoplastic change (gonadoblastoma). This risk can reach 30% in the asymmetrical gonadal dysgenesis.

Female↗
PubMed1991

[Disseminated mucormycosis in pediatrics].

The case of a 14 month-old infant presenting with hereditary lymphohistiocytosis is reported. After several days of post-chemotherapy aplasia a peritoneal, cutaneous (blackish necrosis), then pleuropulmonary involvement occurred. Fiberendoscopy showed an esophageal necrosis responsible for a pleural fistula. The child died after a few weeks, despite antifungal treatment. Post mortem examination found disseminated abscesses related to mucormycosis. The 41 pediatric cases in the world-wide literature are recorded.

Female↗
PubMed1990

Genotype markers and proto-oncogene analysis in the CD30-positive "malignant histiocytosis" DEL cell line with t(5;6)(q35;p21).

The DEL cell line isolated from a patient who died of malignant histiocytosis exhibits a reciprocal chromosomal translocation t(5;6)(5q35;6p21). The cells were analyzed for Ig(Jh), TCR beta-gene rearrangements and proto-oncogene expression pattern, using a panel of molecularly cloned probes that included c-fms, c-myc, c-myb, c-pim, c-fos, N-myc, c-sis, c-fgr as well as the virally derived probes v-ki-ras and v-src. Consistent levels of expression of c-fms, c-myc, c-myb, c-ki-ras and c-fgr were identified in cells from several in vitro passages as well as from the heterotransplanted tumors in nude mice. Transcripts homologous to the c-fos, c-src and c-sis were not observed. Southern blot study of DNA showed that the banding pattern of the screened proto-oncogenes was not altered. Furthermore, Southern blot analysis demonstrated monoallelic immunoglobulin heavy chain (IgJh) rearrangement but a normal germ-line configuration of the kappa light chain and TCR beta-genes. These results appear to imply that a T- or B-cell origin can be eliminated and that several activated proto-oncogenes, usually expressed in immature MPS cells (c-fms) and myeloblastic cells (c-fgr), may be implicated in the proliferative activity of the DEL cell line, the stem of which may be a primitive, ancestral myelomonocytic cell.

Antigens, CD↗
PubMed1990

DEL cell line: a "malignant histiocytosis" CD30+ t(5;6)(q35;p21) cell line.

A new cell line DEL, established in vitro, was isolated from a pleural effusion of a boy who died of malignant histiocytosis. Its principal characteristics are: strong positivity with monoclonal antibodies (MAbs) to CD25, CD30, CD45R, KiM7, EMA, HLA Cl I and II; constant presence of acid phosphatase, ANAE, alpha-anti-trypsin, alpha-anti-chymotrypsin and NBT reductase activity; rearrangement of the immunoglobulin heavy-chain gene (JH) and a germ-line configuration of the T-chain gene; and finally a translocation between chromosomes 5-6 with a breakpoint in 5q35. The DEL cell line is appropriate for studying the role of the 5q localized c-fms oncogene and of the genes of the mononuclear phagocyte growth factor (CSFI) and of their receptors in the dynamics and etiology of malignant hemopathies associated with a 5q35 breakpoint.

Antigens, Neoplasm↗
PubMed1990

Cell differentiation in Wilms' tumor (nephroblastoma): an immunohistochemical study.

Using an indirect immunoperoxidase technique, we tested frozen specimens from 12 Wilms' tumors with monoclonal antibodies (MoAbs) reacting against a large panel of molecules including laminin, fibronectin, cytokeratin, vimentin, villin, CD24, CALLA/CD10, CR1, CD26, class I and class II major histocompatibility complex (MHC) molecules, and endothelium factor VIII. These molecules were chosen because they are markers of specific segments of the mature kidney and because their loss or acquisition is indicative of different steps of human nephrogenesis. KI67 MoAb was used to evaluate the proliferating activity of the cells. The blastemal component (cell compact areas) of Wilms' tumors consisted of vimentin-positive cells with a fibronectin network. However, signs of epithelial maturation were present in compact areas where cytokeratin-positive cells producing laminin were observed. The cells exhibited a high degree of proliferating activity. The tubule formations consisted of cytokeratin-positive cells and had a defined laminin border. All the cells, whether in compact areas or in tubules, were strongly CD24-positive. Some tubular formations showed signs of proximal maturation with the presence of CALLA, CD26, and even villin. In four cases class I-MHC molecules were expressed by some tubular cells. Large cystic cavities present in five cases were edged by cytokeratin, CD24-positive cells, or by vimentin, CALLA, CR1-positive cells. Some glomeruloid bodies, present in two cases, were also composed of vimentin, CALLA, and CR1-positive cells which correspond to the mature podocyte phenotype. The interstitial tissue contained mainly laminin and fibronectin network with macrophages and few CD3 lymphocytes. The presence of large cells with muscular differentiation was noted; round vimentin and CD26-positive cells were also seen. The endothelial cells of the vessels exhibited vimentin, factor VIII, and class I and class II MHC molecules as do mature cells, but in some cases the endothelial cells lacked class II molecule expression and were CALLA-positive. These results which confirmed and extended those previously described show that cell differentiation in Wilms' tumor mimics that observed during metanephros development. Moreover, this study shows that tumoral cells in nephroblastoma share several antigens with cells from lymphoid lineage (CD24, CALLA, and CD26) as do developing and mature kidney cells. Such cell phenotype dissection provides a useful and reliable tool for testing the influence of various factors on the development of hetero-transplanted or cultured Wilms' tumors.

Antigens, CD↗
PubMed1990

CD30-positive large cell lymphomas ('Ki-1 lymphoma') are associated with a chromosomal translocation involving 5q35.

A chromosomal translocation involving a breakpoint on the long arm of chromosome 5 at position q35 has been reported previously in 17 cases of neoplasia. In 14 of these cases the translocation involves exchange of material between chromosome 2 p23 and chromosome 5. Most cases had been diagnosed histologically as malignant histiocytosis but it was suggested recently, following the study of three cases in one of the author's laboratories, that such tumours are in reality lymphoid tumours. In the present paper we report on 12 further neoplasms with a translocation involving the 5q35 breakpoint and show that all were large cell lymphomas expressing the CD30 (Ki-1) antigen, often classifiable histologically as 'Ki-1 lymphoma'. In five cases there was evidence, based on antigen expression and/or genotypic studies, that the neoplasm was of T lymphoid derivation. These findings provide further evidence that translocations involving 5q35 are associated not with histiocytic malignancy, but with large cell lymphoid neoplasms, including typical cases of 'Ki-1 lymphoma' or 'anaplastic large cell lymphoma'. Since cell lines have been established from five of these cases it may be possible in the future to clone the breakpoint on chromosome 5 and to investigate whether there is a gene in its vicinity with oncogenic potential.

Adult↗
PubMed1990

Different Epstein-Barr virus expression in lymphomas from immunocompromised and immunocompetent patients.

Eighteen tissue samples from lymphoproliferative lesions and lymphomas in immunodeficiency states were investigated for their content of Epstein-Barr virus (EBV) genome by dot blotting and for the distribution of EBV in tissue sections by in situ hybridization. Fourteen lymphomas from AIDS patients and four children with disorders of the immune system were available. For control reasons, six cases of infectious mononucleosis (IM) and eight Burkitt's lymphomas (BL) from malaria-free regions of Africa were included in the study. Two different patterns of EBV distribution are described: 1) heterogeneous scattered EBV-positive cells, as originally seen in IM and therefore called the IM-type pattern, 2) and a BL-type pattern seen in endemic Burkitt's lymphoma with homogeneous EBV-positive cells all over the tumor. In lymphomas in patients with inborn immunodeficiencies, an IM-type pattern was found. In lymphomas from AIDS patients, the two different patterns were found. There were lymphomas with the IM-type pattern as well as some with the BL-type pattern. In some AIDS-associated lymphomas, both patterns occurred in one tumor. The findings suggest that it is not the disease process that is the distinguishing feature between the two patterns of EBV infection but rather the patient's underlying disease and the extent of this disease.

Acquired Immunodeficiency Syndrome↗
PubMed1990

[Sudden infant death syndrome].

Over the last 20 years, the sudden infant death syndrome has become the leading cause of death in infants aged one month to one year in developed countries. The SIDS Referral Centers set up in France have been assigned the task of performing thorough clinical, metabolic, infectious and histologic studies. This post-mortem evaluation, whose results are difficult to interpret, is undertaken in an attempt to discriminate between the multiple causes of conditions present at the time of death. This classification task will improve the definition of a number of risk factors. Among these factors, prematurity, perinatal distress requiring resuscitation, and an unfavorable sociocultural environment are often mentioned. Other factors, including intrauterine growth retardation, dysmorphic disorders, impaired regulation of ventilation, heart rhythm anomalies, and inherited defects in fatty acid metabolism are still under study since they are all infrequent. Various combinations of these factors may result in increased vulnerability to stress during the first months of life, the period when SIDS is most common. This ongoing research is indispensable for providing advice and support of the family and developing appropriate individual preventive measures for newborn SIDS siblings.

Academies and Institutes↗
PubMed1990

[Primary interstitial pancreatitis or dyschylic pancreatitis in children. Apropos of 13 cases].

During a retrospective review of more than 1,000 pediatric pancreas specimens obtained by autopsy or biopsy, 13 cases of primitive interstitial pancreatitis (PIP) were identified. The morphologic diagnosis of PIP is based on the following histological features: presence of abundant, inspissated, PAS-negative intraductal secretions, overdistension and focal rupture of the intrapancreatic ducts, and presence of a focal, extensive inflammatory infiltrate. PIP should be distinguished from cystic fibrosis, necrotizing pancreatitis, and passive secondary interstitial infiltrates associated with extensive retroperitoneal cellulitis caused by septicemia or abdominal surgery. Clinical diagnosis is difficult and was not considered in the ten children under four years of age. In the three children over five, the presence of recurrent abdominal pain with mild ascitis and jaundice led to the correct diagnosis. Pathological findings suggest two possible pathophysiologic hypotheses: lesions may develop proximal to a mechanical malformative obstruction that is, however, only very rarely found, according to a more likely alternative, quantitative and qualitative modifications of pancreatic secretions may occur as a result of severe dehydration or use of drugs (corticosteroids, diuretics), justifying the term "dyschylic pancreatitis" coined by G. Seifert.

Child↗