The clinical course of two sisters with myasthenia initially published in La Revue Neurologique in 1960 has been followed. Both had secondary severe respiratory impairment requiring a tracheotomy and mechanical ventilation. Thymectomy was performed in both and revealed residual thymic tissue. Complete remission was observed long after thymectomy even with the persistence of antiacetylcholine receptor antibodies which are still present in the older sister despite intercurrent autoimmune thyroiditis and in the younger sister despite the development of mediastinal lymphosarcoma leading to death 32 years after the onset of myasthenia.

Cancers are the most frequent and at the same time the most complicated of somatic genetic diseases. Technical progress in the last fifteen years has enabled to analyse the acquired genetic abnormalities found in the vast majority of cancers. This molecular dissection of cancer has led to an understanding of this disease that can basically be viewed as a rupture of the balance between two class of genes, the oncogenes and the antioncogenes. This article defines the properties of these cancer genes and gives through a few examples an insight into the various mechanisms of cancerogenesis.

The BCL2 gene is the most representative member of a family of genes that control cell homeostatic processes in the course of the developmental and adult life. Some members of the BCL2 family (bcl-2 alpha, bcl-xL) inhibit apoptosis, whereas some other (Bax, Bclxs) induce it. The biological activity of these proteins is dictated by: 1) their capacity to be integrated in specific membranes of the cytoplasm; 2) their ability to homo- or hetero-dimerize, due to the presence of two highly conserved domains which are a signature of this gene family. The bcl-2 protein exhibits two main biochemical properties: it acts in an antioxidant metabolic pathway aimed at eliminating oxygene free radicals that induce lesions in DNA, lipids and proteins; it modulates intracellular Ca++ fluxes. BCL2 (and presumably its congeners) interplay with other genes involved in the tight control of cell proliferation and programmed cell death (c-myc, p53). A more comprehensive view of BCL2 functions should benefit to cancer chemotherapy by improving rational approach of the antitumor drug mechanisms.

The expression of the cytokine genes in human spleen was studied using reverse transcriptase-polymerase chain reaction (RT-PCR) method capable of detecting low levels of mRNA. Total RNA was prepared from human spleen by acid guanidinium thiocyanate-phenol-chloroform (AGPC) method. cDNA was synthesized by M-MLV RTase using oligo (dT)16 primer, and amplified using the oligonucleotide primers specific for IL-1 alpha, IL-1 beta, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, TNF-alpha, IFN-alpha, IFN-beta and IFN-gamma by PCR method. Although IL-1 beta, IL-4, IL-5, IL-6, IL-7, IL-8, TNF-alpha, IFN-alpha and IFN-gamma mRNA were detected in all the samples tested, IL-3 and IFN-beta mRNA was not detected at all. These results suggest that many kinds of cytokines may be produced constitutionally in human spleen, and its pattern of cytokine production was similar to that in mice.

The p53 gene codes for a nuclear phosphoprotein which is capable of modulating the expression of certain genes implicated in the regulation of cell division. The mutation of an allele on the p53 gene with loss of the healthy allele, in different tissues such as lung, larynx, bladder, liver, skin, colon and breast, which may or may not be exposed to chemical or physical carcinogens (tobacco, radon, ultraviolet, aflatoxin B1), is associated with the occurrence of cancer. Indeed, the mutated p53 protein loses its anti-proliferative properties favouring a de-regulation of cellular multiplication with the accumulation of genetic aberrations. The homozygous deletion of the p53 gene in germ cells in the members of certain family cancers (Li-Fraumeni syndrome) leads to an increased incidence of cancers in the child or young adult. The most frequent mutations of the p53 gene end in a stabilisation of the mutated protein with immuno-histochemical nuclear marking of the cells carrying such an alteration. In certain patients this stabilisation of the mutated protein ends in auto-immunisation with anti-p53 serum antibodies. Bronchial cancer is a cancer of which the mutations of p53 are the most frequent (45-65% of bronchial cancer) as result of the mutagenic effect of tobacco smoke. These mutations seem to be associated with a bad prognosis and indeed to chemo-and radiotherapeutic resistance. The early diagnosis of p53 alterations (in dysplastic lesions or tumours which are only slightly developed) would enable new therapeutic interventions in bronchial cancer such as gene therapy or radio-immunotherapy to either restore the p53 gene to normality or to eliminate the cells expressing the mutated p53 protein respectively.

Multiple endocrine neoplasia type I, also known as Wermer's syndrome, is characterized by the presence of functioning or nonfunctioning tumors or hyperplasia of the parathyroid glands, pancreatic islet cells and pituitary gland. MEN I syndrome may be either familial or sporadic. MEN I locus has recently been mapped to chromosome 11, and further characterization of the abnormal gene appears imminent. The GENEM I, a multidisciplinary study group is in the process of formation. Pathologists have to specify the morphological criteria of hyperplasia vs tumor. Further characterization of the gene and its product requires the application of molecular biology methods to the pathologic tissues of these patients.

In this present work, the authors discuss some recent advances in the pathogenesis of pituitary tumours. The model of transgenic mice suggest that chronic hormonal stimulation and some growth factors could sustain pituitary tumour development. However, these data are not suitable for human pituitary adenomas. The evidence that most pituitary adenomas are monoclonal in origin has prompted a search for somatic mutations. The mutated Gs alpha are found in only 30-40% of somatotroph adenomas and the ras mutations seem to be associated with the malignant transformation. In some prolactinomas resistant to the bromocriptine treatment, quantitative and qualitative alterations of the dopamine receptor D2, have been described. Mutations of protein kinase C have been identified in some invasive pituitary tumours. Molecular abnormalities have been reported in some cases (allele loss at the 11q13 locus, retinoblastoma gene mutation, aberrant expression of hst gene, Pit-1 overexpression) but none by itself can explain the tumour formation. The pituitary tumorigenesis is certainly a multistep process with the intervention of multiple promoting factors.

The Buschke-Ollendorff syndrome (BOS) is a rare connective tissue disorder inherited in an autosomal dominant pattern characterized by cutaneous lesions, dermatofibrosis lenticularis disseminata, and osteopoikilosis. We report a new case of this syndrome in a 66 year old man, interesting by its association with a protein C deficiency, another rare genetically transmitted disease. Diagnosis of the BOS is difficult on the mere cutaneous lesions; it is therefore important to systematically practice bone X-rays in the presence of atypical pseudoxanthoma elasticum, disseminated collagenoma or disseminated connective tissue or elastic nevi. The radiologically detectable osteopoikilotic bone lesions, evoking Paget's disease, easily sign the diagnosis. In our case, the association of a protein C deficiency with the BOS may not be fortuitous because both the elastin and protein C genes are localized on chromosome 2q.

Hirschsprung's disease is a frequent congenital malformation of the hindgut. The existence of Hirschsprung's families favors the role of an autosomal dominant gene with a reduced penetrance. We have successively localized and identified the RET proto-oncogene as the gene responsible for familial Hirschsprung's disease. Interestingly, other mutations of the RET proto-oncogene have been described in inherited predisposition to endocrine cancers. This observation shows that, depending on their nature, mutations of the RET proto-oncogene could lead either to early developmental defects or to tumor predisposition.

These studies were designed to assess the influence of sun exposure on nevi in white people. In order to eliminate the confounding effect of age, sex and phenotype, two parallel studies were conducted in people of the same age (17 to 24 years), sex (males) and phenotype: one in people with "red" phenotype and one in people with "dark" phenotype.

The xenograft of human cancers into athymic nude mice makes it possible to obtain abundant tumour material and deepen biological characterization. Usually, the tumours are grafted into the subcutaneous tissue whose environment is indeed different from that of original colon cancer.

Hemangioblastoma may arise in isolation ("sporadic" cases) or as a major manifestation of von Hippel-Lindau (VHL) disease, an autosomal dominant disorder with a prevalence of at least 1/36,000. In addition of central nervous system hemangioblastomas (cerebellum, spinal cord and retina), affected patients may develop renal cysts or carcinomas, pheochromocytomas and pancreatic cysts. A multidisciplinary group including neurosurgeons, geneticists, pathologists and clinicians from all involved specialities has been organized to develop a national registration of all hemangioblastoma and VHL patients. The findings of a preliminary 10-year study (1983-1993) conducted in France are presented. Two hundred thirteen cases of hemangioblastoma were reviewed for their location and genetic features. The majority (77%) of the tumors were located in the cerebellum whereas 23% were located inside the spinal canal. By thorough clinical examination of the patients and systematic genetic inquiry of their family background, it was found that 34.3% of the total (58.7% before age 30) were afflicted with VHL disease. Spinal hemangioblastomas were more often related to VHL disease than infra-tentorial locations (50% versus 36.6%). In addition, mean age at diagnosis in VHL disease was significantly younger than in sporadic cases (33.5 +/- 10 versus 43.6 +/- 15 years). Recent progress in VHL molecular genetics led to the identification of the mutated gene to the distal part of the short arm of chromosome 3 (3p25-3p26), paving the way to presymptomatic diagnosis and, hopefully, to elucidation of pathogenesis, which may offer a further glimpse into tumorigenesis in general. Because of the usually early adulthood onset, accurate presymptomatic diagnosis of affected members would be of great benefit to VHL families. However, the fact that very few mutations in the VHL gene are identified precludes molecular diagnosis of "sporadic" hemangioblastomas. In summary, this study reveals that VHL-related hemangioblastoma is a more common clinical problem that it was previously reported. Thus, all patients with an apparently isolated central nervous system hemangioblastoma should be investigated for evidence of VHL disease.

A case of trilateral retinoblastoma in a male child of 29 months is described, using a clinical and imaging approach. The patient was first presented with a proptosis, more pronounced in the left eye and with signs of a bilateral glaucoma. Ophthalmologic examination, echography and computed tomography were used to confirm the diagnosis. The importance of clinical examination associated with an imaging approach to evaluate intraocular tumors was emphasized and also the necessity of identifying trilateral retinoblastoma as a distinct entity and to differentiate it from intracranial metastasis or from a single retinoblastoma associated with pineal tumors.

The authors are reporting a case of papillary and cystic neoplasm of the pancreas. This rare malignant epithelial neoplasm occurs mostly in young women and has a more favorable prognosis than the adenocarcinoma. Radiologic investigations showed a well demarcated, heterogeneous, hypovascular mass. The histological study showed the proliferation of epithelial cells in a papillary pattern. The immunochemistry was negative for markers of adenocarcinoma but positive for vimentin, alpha-1-antitrypsin, alpha-1-antichymotrypsin and neuron specific enolase. Receptors of progesterone were also detected. By flow cytometric analysis, the tumours was hypoploid. The histogenesis of these tumours remained controversed. Ultrastructural details of the neoplastic cells suggest that these tumours originate from small duct cells; detection in several cases of markers for endocrine neoplasm suggests that they originate from primitive multipotential cells, that may show exocrine or endocrine differentiation.