Biomedical subjects

A Janin

Publications and source records attributed to A Janin.

At least 19 recordsLinked to original sources

PubMed1998

Squamous cell carcinomas after allogeneic bone marrow transplantation for aplastic anemia: further evidence of a multistep process.

BACKGROUND: Secondary solid tumors are rare events occurring in patients who underwent allogeneic marrow transplantation for aplastic anemia and Fanconi's anemia. Human herpes virus 8 (HHV8), Epstein-Barr virus (EBV), and human papillomaviruses (HPV) sequences have been found in squamous cell carcinoma (SCC) occurring in organ transplant recipients. The tumor suppressor gene p53 has been strongly linked to the occurrence of SCC in the nonimmunocompromised population. PATIENTS AND METHODS: In eight patients with SCC, we searched for HHV8, EBV, varicella zoster virus, adenovirus, and HPV sequences from DNA extracted from selected areas of SCC. We also looked for p53 expression in those specimens as well as the presence of anti-p53 antibodies in the serum of these patients at the onset of SCC. RESULTS: In one patient, we found the presence of both HHV8 and EBV sequences, and in another patient we found HPV16 sequences. All five tumors that could be studied disclosed evidence of p53 accumulation, but none of the eight patients had anti-p53 antibodies in the sera. CONCLUSION: SCC developing in marrow transplant recipients seems to occur via a multistep process. Genetic predisposition may be present, as in patients with Fanconi's anemia. Transplantation-related factors, such as irradiation and chronic graft-versus-host disease, also have a role. In this article, we add two more potent risk factors: p53 alteration(s) and in some cases the presence of oncogenic viruses.

Anemia, Aplastic↗

PubMed1998

Transgenic mice for MTCP1 develop T-cell prolymphocytic leukemia.

T-cell prolymphocytic leukemia (T-PLL) is a rare form of mature T-cell leukemia associated with chromosomal rearrangements implicating MTCP1 or TCL1 genes. These genes encode two homologous proteins, p13(MTCP1) and p14(TCL1), which share no similarity with other known protein. To determine the oncogenic role of MTCP1, mice transgenic for MTCP1 under the control of CD2 regulatory regions (CD2-p13 mice) were generated. No abnormality was detected during the first year after birth. A late effect of the transgene was searched for in a cohort of 48 CD2-p13 mice aged 15 to 20 months, issued from 3 independent founders. Lymphoid hemopathies, occurring in the three transgenic lines, were characterized by lymphoid cells with an irregular nucleus, a unique and prominent nucleolus, condensed chromatin, a basophilic cytoplasm devoid of granules, and an immunophenotype of mature T cells. The molecular characterization of Tcrb rearrangements demonstrated the monoclonal origin of these populations. Histopathological analysis of the cohort demonstrated early splenic and hepatic infiltrations, whereas lymphocytosis and medullar infiltrations were found infrequently. The engraftment of these proliferations in H2-matched animals demonstrated their malignant nature. Cumulative incidence of the disease at 20 months was 100%, 50%, and 21% in F3, F4, and F7 lines, respectively, and null in the control group. The level of expression of the transgene, as estimated by Western blotting in the transgenic lines correlated with the tumoral incidence, with the highest expression of p13(MTCP1) being found in F3 mice. CD2-p13 transgenic mice developed an hemopathy similar to human T-PLL. These data demonstrate that p13(MTCP1) is an oncoprotein and that CD2-p13 transgenic mice represent the first animal model for mature T-PLL.

Animals↗

PubMed1998

Hodgkin's disease of donor origin after allogeneic bone marrow transplantation for myelogeneous chronic leukemia.

Secondary malignancies (lymphomas, leukemias, and solid tumors) occurring after bone marrow transplantation are now more frequently reported, as the patients surviving the early phase of the graft and remaining free of their original disease are more numerous. Besides early Epstein-Barr virus-associated B-cell lymphoproliferative diseases, which are the most common type and most often of donor origin, few late-occurring lymphomas have been described that might represent a distinct entity. We report here a case of Hodgkin's disease developing 8 years after allogeneic bone marrow transplantation for chronic myelogeneous leukemia. Only two Hodgkin's diseases after allogeneic bone marrow transplantation have been reported in the literature so far. The case we report is of interest because of its donor origin and its association with Epstein-Barr virus infection.

Adult↗

PubMed1998

Similar IL-5, IL-3, and GM-CSF syntheses by eosinophils in the jejunal mucosa of patients with celiac disease and dermatitis herpetiformis.

Celiac disease (CD) and dermatitis herpetiformis (DH) are gluten-sensitive diseases with different clinical features that can initiate similar intestinal changes. The flat-destructive stage corresponds to severe lesions involving activated T-cells. However, other inflammatory cells such as eosinophils are also abundant. The mechanisms for the intestinal recruitment of eosinophils in patients with CD and DH remain unknown. Eosinophil recruitment and activation are induced in vitro by three main cytokines: interleukin-3 (IL-3), interleukin-5 (IL-5), and granulocyte-macrophage colony-stimulating factor (GM-CSF). In this study, IL-3, IL-5, and GM-CSF were detected by immunohistochemistry in all patients with CD and DH but not in the control group. By ultrastructural immunogold staining, these three cytokines had the same subcellular localization in the granule matrix of eosinophils. This result suggests that eosinophils may be involved in the immune response at the flat-destructive stage of both CD and DH.

Adolescent↗

PubMed1998

Adverse events in phase-I studies: a report in 1015 healthy volunteers.

OBJECTIVE: This report describes all clinical, laboratory and electrocardiographical adverse events detected in healthy volunteers in a phase-I centre over a 10-year period: 54 phase-I studies are involved, including 1015 healthy young volunteers (993 males) who received 1538 treatments (23 different active drugs or placebo) corresponding to 12143 days of follow-up. This updates a similar report published previously in the European Journal of Clinical Pharmacology. METHODS: Adverse events were defined as all events noted in case-report forms. Incidence of adverse events was defined as the ratio between the number of adverse events and the number of follow-up days. Severity was rated as death, life-threatening, severe or minor. Incidences or occurrence rates were compared using the Chi-squared test with Yates' correction. RESULTS: The overall incidence of adverse events was 12.8% with a significant difference between active-drug (13.7%) and placebo (7.9%) treatments. There were 1558 adverse events of 110 distinct kinds. Only for three (headache, diarrhoea and dyspepsia) was the incidence superior to 10 per thousand. Most of these adverse events were also observed with placebo. Ninety-seven percentage of adverse events were of minor intensity; forty three (3%) were rated as severe, including nine worrying cases - six malaises with loss of consciousness, one atrial fibrillation, one hyperthyroidism and one bicytopenia. Some of the adverse events were not related to the tested drugs, but to a vagal reaction or to study conditions. There was no death or life-threatening event. The global rate of occurrence was one adverse event per treatment, one and a half per subject and one out of eight follow-up days. No difference in the overall incidence with placebo was observed between the two successive 5-year periods. CONCLUSIONS: This report confirms that adverse events in phase I studies are very common, usually of minor intensity and rarely severe; even though exceptional, life-threatening adverse events are possible. Adverse events occurring in phase I are rarely published, leading to lack of information. Thus, authors invite clinical research organization (CROs) and phase-I centres to regularly publicise at least severe adverse events; they also suggest that the life-threatening adverse events reported to health authorities should be publicised, for example by the World Health Organization (WHO).

Adult↗

PubMed1998

[Primary biliary cirrhosis and systemic scleroderma (Reynolds syndrome): apropos of 8 new cases. The contribution of accessory salivary gland biopsy].

PURPOSE: We report eight new cases of the association primary biliary cirrhosis--systemic sclerosis (Reynolds' syndrome) and study the contribution of labial salivary gland biopsy to the disease diagnosis. METHODS: We retrospectively collected clinical and biological data as well as results of labial salivary gland biopsies in eight patients with Reynolds' syndrome. RESULTS: The eight patients were female. Systemic sclerosis corresponded to a CREST syndrome in three patients, while in two other patients two features of the CREST syndrome were observed. Anticentromere antibodies were detected in these five cases. The last three patients had systemic sclerosis with bilateral pulmonary fibrosis in two cases. All patients presented with Sjögren's syndrome. Labial salivary gland biopsies performed in six patients showed in five cases an inflammatory infiltrate and focal sialadenitis typically associated with Sjögren's syndrome. In four cases, organic microangiopathy and fibrosis were suggestive of systemic sclerosis, and in four other cases, the presence of a pericanalicular infiltrate of lymphocytes and necrosis of the excretory ducts epithelial cells suggested the existence of primary biliary cirrhosis. In three patients, all histological lesions were found in the same labial salivary gland biopsy. CONCLUSION: Coexistence of histological lesions on the same labial salivary gland suggestive of primary biliary cirrhosis, systemic sclerosis and Sjögren's syndrome has never been described previously. The diagnostic value of labial salivary gland biopsy has to be assessed in this context.

Adult↗

PubMed1998

[The correlation between salivary endothelial expression of E-selectin and clinical and biological parameters in systemic scleroderma].

OBJECTIVES: A body of evidence suggests the pivotal role of endothelial cells in the pathophysiology of systemic sclerosis. E-selectin is an adhesion molecule specifically expressed by activated endothelial cells. In previous studies we noticed that E-selectin was frequently expressed in the salivary gland tissue of patients with systemic sclerosis. Moreover, E-selectin expression was detectable very early in the course of the disease. To better define the role of E-selectin in the pathogenesis of systemic sclerosis, we conducted a study aimed at determining whether E-selectin expression was correlated to clinical and biological features in patients with systemic sclerosis. METHODS: Thirty-one patients presenting with systemic sclerosis were included in the study. The following parameters were systematically assessed: duration and cutaneous extent of the disease, presence of secondary Sjögren's syndrome, antinuclear antibodies, and pulmonary and esophagus involvement. E-selectin expression was assessed by immunocytochemistry on minor labial salivary glands. RESULTS: E-selectin expression was detected in 21 out of 31 patients (67%). The disease duration was significantly shorter in patients with E-selectin expression (mean 9.1 +/- 8.5 years versus 4.2 +/- 3.3 years, P < 0.05). No significant difference was found for other features. CONCLUSIONS: This study shows that endothelial E-selectin expression is mainly detectable early in the course of systemic sclerosis, when active and non-cicatrical sclerosis may be evidenced. No correlation was found between E-selectin expression and immunological disorders (antinuclear antibodies, secondary Sjögren's syndrome).

Adolescent↗

PubMed1998

Meningioma in long-term survivors after allogeneic bone marrow transplantation.

Late complications occurring after allogeneic bone marrow transplant (BMT) are increasingly reported, since more patients survive. Among these late complications, solid tumors are of particular clinical concern. Only malignant brain tumors have been reported (astrocytoma, glioblastoma). We describe two cases of meningiomas developing 13 and 15 years after the graft. Occurrence of such benign tumors has been described after treatment of ALL, but not following allogeneic BMT. It is important to consider the diagnosis of meningioma in long-term survivors presenting with neurological symptoms.

Acute Disease↗

PubMed1998

Increased interleukin-6 production during the acute phase of the syndrome of episodic angioedema and hypereosinophilia.

BACKGROUND: The Gleich syndrome is rare and associates recurrent angioedema, urticaria, fever, weight gain and blood hypereosinophilia, underlying systemic and local inflammation. The pathogenesis of those symptoms remains unclear. OBJECTIVE: We wanted to address the possible implication of Interleukin-6 (IL-6) in the development of those clinical features, and to identify the cells involved in its production. METHODS: A 26-year-old man suffering of this disease was referred in hospital. During an acute attack with weight gain, fever and a diffuse oedema, a marked increase in eosinophils count (42700/mm3 was observed. Serum ECP was elevated at 47 microg/L (normal less than 16). Corticosteroid therapy administrated on the 7th day was followed by a rapid remission. Blood samples were collected (before, during the attack and under corticosteroid therapy) for measurements of serum IL-6 (ELISA, Immunotech, Marseille, France) and plasma histamine (RIA, Immunotech, Marseille, France). Blood monocytes and eosinophils were isolated and a skin biopsy was performed during the attack. RESULTS: The plasma histamine level was within normal range. The level of IL-6 in sera peaked to 74 pg/mL, concomitant with the peak of eosinophilia at the acute phase phase of the attack. Under corticosteroids, we observed a drop in the IL-6 serum level to 29 pg/mL, concomitant with the clinical remission. During the attack, an increase in IL-6 production was observed in 24 h blood monocyte supernatants (11.10(3) pg/mL compared with 2.4+/-0.8.10(3) pg/mL for BM from controls) as well as in skin endothelial cells but not in the blood and skin eosinophils. In vitro, when endothelial cells were incubated in eosinophils supernatants of the patient, liberation of IL-6 was observed (3.3 10(3) pg/mL compared with controls: 2.1 10(3) pg/mL) CONCLUSION: Serum IL-6 elevation may be related to an increased production by blood monocytes and endothelial cells, possibly stimulated by eosinophil mediator during the acute phase of the disease, and might participate in the inflammatory reaction of this syndrome.

Acute-Phase Reaction↗

PubMed1998

Sequencing-based typing reveals six novel MHC class I chain-related gene B (MICB) alleles.

The MHC class I chain-related gene A (MICA) is highly polymorphic. In this paper we demonstrate polymorphism in the other expressing member of the MIC family of genes: MICB. Using a sequencing-based typing approach on cDNA, analysis of exons 2 through 6 revealed eight polymorphic sites resulting in six unique MICB sequences. Although MICB has high nucleotide homology with MICA, its polymorphism is restricted and at different sites compared to those in MICA.

Alleles↗

PubMed1998

Abnormal mucus in cap polyposis.

BACKGROUND: Cap polyposis is a rare disease characterised by mucoid and bloody diarrhoea, with polyps covered by a cap of mucoid and fibrinopurulent exudate. The pathogenesis is not known. AIMS: To pour some light on cap polyposis pathogenesis, by examining the mucus of patients and analysing the expression of five mucin genes, MUC2, MUC3, MUC4, MUC5AC, and MUC5B. PATIENT AND METHODS: The study was performed on biopsy specimens taken from a patient with recurrent cap polyposis. Histochemical examination, electron microscopy, and mRNA in situ hybridisation were used. RESULTS: The mucus of cap polyposis differed in three respects from that of normal adult colon: abnormal ultrastructure of the mucus in the goblet cells, predominance of non-sulphated mucins, abnormal expression of the MUC4, MUC3, and MUC5AC genes. CONCLUSIONS: Most of these abnormalities have been reported for other pathological situations, suggesting that the abnormalities observed in the mucus of this patient with cap polyposis are probably secondary phenomena rather than primary. However, the mucin abnormalities detected, which reflect deregulation of the expression of three apomucin genes, abnormal glycosylation, and abnormalities of the secretion process, are also probably involved in the clinical manifestations of cap polyposis.

Adult↗

PubMed1998

Variability of immunohistochemical reactivity on stored paraffin slides.

AIMS: To investigate the effects of slide storage on immunohistochemical staining, since recent reports have indicated that storage of unstained paraffin slides for up to 12 weeks may lead to false negative immunostaining of tumour markers. METHODS: 11 antibodies (anti-cytokeratin, epithelial membrane antigen (EMA), vimentin, smooth muscle actin, PS100, chromogranin, CD45, CD20, CD3, CD30, and oestrogen receptor (OR) were tested on unstained paraffin slides of breast carcinomas, lymphomas, and neuroendocrine tumours that had been stored for three to 10 years. All the paraffin blocks were recut less than one week before immunostaining. Immunostainings of years old slides were compared with those of recent slides in at least five cases for each antibody. For three antibodies (antichromogranin, anti-CD3, and anti-OR) we also tested one year old and three months old slides. RESULTS: Intensity of staining on years old slides was strikingly reduced for chromogranin and CD3 in several cases and was slightly stronger for vimentin. In some cases a significant decrease of OR positivity was observed after three months storage, and a complete loss of OR immunostaining after 12 months. No significant difference was noted with the other antibodies. CONCLUSIONS: Immunohistochemical detection of some antigens located either in the nucleus, in the cytoplasm, or on the cytoplasmic membrane could be impaired by storage of paraffin slides as short a time as three months. One should be cautious of doing retrospective immunohistochemical studies on stored unstained slides.

Antigens, Neoplasm↗

PubMed1998

Secondary hyperparathyroidism: detection with I-123-Tc-99m-Sestamibi subtraction scintigraphy versus US.

PURPOSE: To compare iodine-123-technetium-99m-sestamibi subtraction scintigraphy with ultrasonography (US) for detection of parathyroid abnormalities in uremic patients with secondary hyperparathyroidism. MATERIALS AND METHODS: Fourteen adult uremic patients with severe secondary hyperparathyroidism underwent subtraction scintigraphy before total or subtotal parathyroidectomy. Subtraction scintigrams were acquired with a double-energy-window technique. US was performed with high-frequency transducers and standard methods. RESULTS: 1-123-Tc-99m-sestamibi subtraction scintigraphy correctly demonstrated 41 of 50 surgically confirmed enlarged parathyroids; US demonstrated 27. Sensitivity for detection of hyperplastic glands was 82% for scintigraphy and 54% for US. Scintigrams were correct in seven patients, and US scans were correct in five. Scintigraphy demonstrated all four enlarged parathyroids in six of 12 patients who were to undergo first surgery, whereas US demonstrated all four enlarged glands in three of the 12 patients. Gland weight was correlated with likelihood of detection with either method. Glands undetected at scintigraphy were significantly (P < .01) smaller (mean weight, 257 mg) than those undetected at US (mean weight, 467 mg). CONCLUSION: I-123-Tc-99m-sestamibi subtraction scintigraphy is efficient for detection of enlarged parathyroid glands in uremic patients with secondary hyperparathyroidism and is more sensitive than US.

Adult↗

PubMed1998