MRI findings in pituitary-hypothalamic axis Langerhans cell histiocytosis

Pituitary-hypothalamic axis Langerhans cell histiocytosis is an uncommon entity. It is a rare disease in adults. The CT and MR study provides us the best anatomo-topographic evaluation and determine the precise size of the lesion which are necessary to the treatment. We report a case of hypothalamic involvement by Langerhans cell histiocytosis accompanied by lesions in bone affecting a 31-year-old woman. The clinical, histiotological and CT/MR findings of histiocytosis X are described in this article.     

Adult primary myelodysplastic syndromes. Report of 36 cases

Between 1989 and 1999, 36 cases with primary myelodysplastic syndromes were diagnosed. They were 15 male and 21 females, the median age was 62 years (range: 22 to 90 years). Eighty one per cent of patients were presented symptoms of anemia. Lymphadenopathy, splenomegaly and skin manifestations were noted in 25% of cases. Hemogram showed anemia, leucopenia and thrombocytopenia respectively in 97%, 44% and 55% of cases. Refractory anemia with excess blasts (AREB) is the most frequent FAB subtypes of MDS (17 cases). Cytogenetic study concerned 24 patients. In 13 cases the karyotype was pathological with deletion 5 q in 64% of cases. Seventeen patients have received a chemotherapy. Survival rate to 36 months is 11%. At the time, the only curative treatment is the bone marrow transplantation, which is proposed to young patients with HLA identical donor.     

An unusual lesion of the nasopharynx: oncocytic metaplasia

Oncocytic metaplasia of the nasopharynx is an exceptional lesion which exact etiopathogenesis, although largely discussed, still remains controversial. The purpose of this paper is to present the epidemiological characteristics and clinical signs of this lesion and to study its pathogenesis and its therapeutic modalities. We report two cases that occurred respectively in a 53- and 60-year-old woman. The first presented with pharyngeal dysesthesia and otalgia. The endoscopic examination revealed an irregularity of the posterior wall of the nasopharynx. The second patient presented with tinnitus, discomfort of the left ear and bilateral hearing loss. Endoscopic exam revealed a bilateral structural abnormality to the eardrum. Microscopy showed focal oncocytic metaplasia of the nasopharynx mucosa in both cases. There was a positive outcare for both patients after excisional biopsy. Oncocytic metaplasia seems to be in relation to the stimulation of sympathic neuropeptidergic nerve fibers which target epithelial, connective, endothelial and lymphoid cells.     

Herpes simplex virus type 1-induced FasL expression in human monocytic cells and its implications for cell death, viral replication, and immune evasion

Herpes simplex virus type 1 (HSV-1) is a ubiquitously occurring pathogen that infects humans early in childhood. The virus persists as a latent infection in dorsal root ganglia, especially of the trigeminal nerve, and frequently becomes reactivated in humans under conditions of stress. Monocytic cells constitute an important component of the innate and adaptive immune responses. We show here for the first time that HSV-1 stimulates human FasL promoter and induces de novo expression of FasL on the surface of human monocytic cells, including monocytes and macrophages. This virus-induced FasL expression causes death of monocytic cells growing in suspension, but not in monolayers (e.g., macrophages). The addition of a broad-spectrum caspase inhibitor, as well as anti-FasL antibodies, reduced cell death but increased viral replication in the virus-infected cell cultures. We also show here for the first time that the virus-induced de novo expression of FasL on the cell surface acts as an immune evasion mechanism by causing the death of interacting human CD4+ T cells, CD8+ T cells, and natural killer (NK) cells. Our study provides novel insights on FasL expression and cell death in HSV-infected human monocytic cells and their impact on interacting immune cells.     

Protective effects of pituitary adenylate cyclase-activating polypeptide (PACAP) against apoptosis

Apoptosis is a regulated process leading to cell death, which is implicated both in normal development and in various pathologies including heart failure, stroke and neurodegenerative diseases. Caspase-3, a key enzyme of the apoptotic pathway, is considered as a major target for the treatment of abnormal cell death. Many factors that inhibit cell death have been identified, but the mechanisms involved are not always fully understood. Pituitary adenylate cylase-activating polypeptide (PACAP) has been shown to exert neuroprotective activities during development. PACAP also inhibits apoptosis in cardiomyopathy, decreases glutamate-induced retinal injury, reduces neuronal loss in case of stroke, and prevents ethanol neurotoxicity. Most of the antiapoptotic effects of PACAP are mediated through the PAC1 receptor. This receptor activates a transduction cascade of second messengers to stimulate Bcl-2 expression which inhibits cytochrome c release and blocks in turn caspase activation. PACAP also acts through the PI3K/Akt pathway and inhibits the expression of proapoptotic factors such as c-Jun or Bax. The remarkable effect of PACAP on the apoptotic cascade suggests that innovative PACAP derivatives could potentially be useful for treatment of post-traumatic lesions, chronic neurodegenerative diseases, cardiac ischemia and/or retinopathy.     

c.1643_1644delTG XPC mutation is more frequent in Moroccan patients with xeroderma pigmentosum

Xeroderma pigmentosum is a rare autosomal recessive disease characterized by hypersensitivity to UV light which is due to alterations of the nucleotide excision repair pathway. Eight genes (XPA to XPG and XPV) are responsible for the disease. Among them, the XPC gene is known to be the most mutated in Mediterranean patients. The aim of this study was to determine the frequency of the most common XPC mutation and describe the clinical features of Moroccan patients with xeroderma pigmentosum. Twenty four patients belonging to 21 unrelated Moroccan families and 58 healthy subjects were investigated. After clinical examination, the screening for the c.1643_1644delTG (p.Val548AlafsX25) mutation in the XPC gene was performed by PCR and automated sequencing of exon 9 in all patients and controls. The molecular analysis showed that among the 24 patients, 17 were homozygous for the c.1643_1644delTG mutation and all their tested parents were heterozygous, whereas the others (7 patients) did not carry the mutation. The frequency of this mutation was estimated to be 76.19 % (16/21 families). None of the 58 healthy individuals carried this mutation. In addition, clinical investigation showed that the majority of the patients bearing this mutation have the same clinical features. Our results revealed that the p.Val548AlafsX25 mutation is the major cause (76.19 %) of xeroderma pigmentosum in Moroccan families. This would have an important impact on improving management of patients and their relatives.