C620R mutation of the murine ret proto-oncogene: loss of function effect in homozygotes and possible gain of function effect in heterozygotes.

Germline RET mutations are responsible for different inherited disorders: Hirschsprung disease (congenital aganglionic megacolon), caused by loss of function mutations, familial medullary thyroid carcinoma and multiple endocrine neoplasia type 2, caused by gain of function mutations. Intriguingly, some RET mutations, including C620R, are associated with both types of diseases. To investigate the dual role of such RET mutations, a mouse model with a targeted mutation ret(C620R) was generated.

SH2D1A mutation analysis for diagnosis of XLP in typical and atypical patients.

X-linked lymphoproliferative disease (XLP) is a rare inherited immunodeficiency to Epstein-Barr virus (EBV). The gene responsible for XLP has recently been identified as the four-exon SH2D1A gene encoding a 128-amino-acid protein that contains an SH2-domain. Functional studies indicate the SH2D1A protein acts as a regulator of at least two signal transduction pathways initiated by the cell surface molecules SLAM and 2B4, respectively, and possibly related to the host immune response to EBV infection.

Genetic analysis of 24 French families with multiple endocrine neoplasia type 2A.

The gene for multiple endocrine neoplasia type 2A (MEN2A) has been mapped to the pericentromeric region of chromosome 10 by linkage analysis. Thirty-four families with multiple cases of medullary carcinoma of the thyroid (MTC), including 24 families with origins in France, have been typed with nine polymorphic markers spanning the centromere of chromosome 10. No recombination was observed between the MEN2A locus and either of the four loci D10Z1 (lod score 12.

The gene for MEN 2A is tightly linked to the centromere of chromosome 10.

We have examined 30 families with multiple endocrine neoplasia type 2a (MEN2A). Linkage studies indicate that the gene for MEN2A is located on chromosome 10, tightly linked to the D10Z1 locus.

Antibody response against the Epstein-Barr virus-coded nuclear antigen2 (EBNA2) in different groups of individuals.

Specific antibody responses against the 2 major subcomponents of EBNA, EBNA1 and EBNA2 were evaluated, in order to study whether this serological study was beneficial compared to classical EBV serology. During this investigation, 491 sera, obtained from blood donors and patients with Burkitt's lymphoma (BL), nasopharyngeal carcinoma (NPC), infectious mononucleosis (IM), Hodgkin's disease, renal transplantation, rheumatoid arthritis and Human Immunodeficiency Virus (HIV) infection, were tested. While the anti-EBNA1 response followed the classical anti-EBNA/Raji response (99% of anti-EBNA/Raji-positive sera also recognize EBNA1), the anti-EBNA2 response was much less frequent and did not correlate with either anti-EBNA/Raji or anti-EA antibodies.

Epstein-Barr viral serology in nasopharyngeal carcinoma patients in the USSR and Cuba, and its value for differential diagnosis of the disease.

Serological responses to Epstein-Barr virus (EBV)-associated antigens were studied in nasopharyngeal carcinoma (NPC) patients in 2 countries non-endemic for the disease: the USSR (77 cases) and Cuba (55 cases). Two age- and sex-matched control groups were available, one consisting of patients with other head-and-neck tumours (OHNT) (171 from the USSR and 56 from Cuba), and the other of normal individuals (blood donors) (83 from the USSR and 80 from Cuba). Unlike the control groups, NPC patients from both countries had high levels of IgG and IgA antibodies, similar to those seen in patients from endemic areas.

[Burkitt's lymphoma-Epstein-Barr virus association in western Algeria. Clinical, cytological and serological aspects apropos of 34 pediatric cases].

Burkitt's lymphoma (BL) and naso-pharyngeal carcinoma (NPC) are tumors generally believed to be associated with Epstein-Barr virus (EBV). Algerian population could be considered at high risk for BL-EBV association. In a series of 34 BL patients observed by us between 1982 and 1984 characteristics were: 70% of children were under 5 years age, abdominal location in 90% of cases (n = 30), 13% only isolated, massive tumor burden (70% stage III after Murphy, 30% stage IV after Murphy and Duque-Hammershaimb), EBV serology titers above or equal to 640 in 60% of cases (anti-EBNA and anti-VCA) and 50% (anti-EA) respectively, presence of EBNA antigen in tumor cells found in 63% of cases, no complete correlation between serology positivity and EBNA presence.

Induction of Epstein-Barr virus early antigen by phytohaemagglutinin in the presence of 5-iodo-2'-deoxyuridine: application to EBV serology.

Induction of EBV early antigens in the non-producer lymphoid cell line RAJI by treatment with PHA in the presence of IUdR has been shown to be a convenient and efficient procedure for the preparation of cells for EBV serology. This induction procedure results in significant levels of EA-D and EA-R positive cells. The serological titres obtained on cell preparations induced with PHA and IUdR were comparable to those obtained on smears prepared by the classical procedure requiring infectious EBV.

In vitro transforming activity of Epstein-Barr virus (EBV). II. Differences between M81 and B95-8 EBV strains.

Lymphocytes from 38 human cord blood and 9 adult circulating blood were aliquoted and infected in parallel either with the B95-8 EBV strain (produced by cotton-top marmoset lymphocytes transformed by EBV originating from an infectious mononucleosis line) or with the M81 EB virus (produced by callithrix jacchus marmoset lymphocytes transformed by EBV originating from a nasopharyngeal carcinoma (NPC) derived line). Significant differences were observed in the lymphoblastoid lines obtained and involved cell morphology, cell growth and synthesis of viral antigen. Cord blood lymphocytes infected with M81 virus resulted in lymphoblastoid lines where EA and VCA synthesis and production of virions took place, whereas this was not observed in B95-8 induced lines.

A comparison of the prognostic value of antibody-dependent lymphocyte cytotoxicity and other EBV antibody assays in Chinese patients with nasopharyngeal carcinoma.

Antibody titres to EBV-associated antigens in Chinese NPC patients were analysed according to length of survival after diagnosis and to disease stage. Geometric mean titres of ADLC antibody were highest in the long-term survivors, whereas VCA, EA and EBNA antibody titres showed an inverse relationship to survival. High VCA, EA and EBNA titres were less frequent, and high ADLC titres were more frequent in long-term survivors than in intermediate or short-term survivors.

[Epstein-Barr virus and infectious mononucleosis. A clinical study of Epstein-Barr antibodies (author's transl)].

Thirty-seven patients--aged 2 to 58--with clinical and hematological signs of infectious mononucleosis were studied. Thirty patients gave serologic evidence of Epstein-Barr virus infections; antibodies to viral capsid antigen (VCA) appeared very early (only two seroconversions and 4 cases of increased titer were detected); antibodies to early antigen (EA) occured in 25 patients, but only 9 had high titers; antibodies to nuclear antigen (EBNA) appeared late in the course of the disease. VCA-specific IgM antibodies occurred in 25 cases (they usually disappeared during the 2nd month).

Differences in EBV antibody titres of patients with nasopharyngeal carcinoma originating from high, intermediate and low incidence areas.

In order to assess the differences in serological reactivities of NPC patients from high, intermediate and low incidence areas, 288 NPC sera from Hong Kong, Singapore, Tunis, East Africa, Paris and Los Angeles, together with sera from patients with ear, nose and throat tumours other than NPC and with those from normal individuals from the same areas, were tested 'blind' with the same batches of antigen. Important differences (up to 3-fold) in the GMTs of antibodies directed against VCA, EA and EBNA were observed between different ethnic groups. Although the stages of the disease varied somewhat between groups, the main cause of the variations appeared to lie in the socio-economic environment of the patients.

Herpes simplex-RAJI(A44), a new cell line for serologic testing by immunofluorescence.

An IF technique for the detection of HSV antibodies by using a lymphoblastoid cell line, Raji(A44), which continuously produce a constant amount of HSV antigen, is described. IF and IH tests were found to be similar with respect to sensitivity and reproducibility. Sero-conversions detected by the CF test were detected with this cell line.

Sero-epidemiology of the Epstein-Barr virus: preliminary analysis of an international study - a review.

Samples of Chinese, Indian, African and Caucasian populations, randomly selected in Hong Kong, Singapore, the West Nile District of Uganda, and Nancy, France, were titrated for antibodies to EBV, viral capsid (VCA) and complement-fixing soluble (CF/S) antigens. The age-specific prevalence of infection (as reflected by the proportion of VCA-positive individuals) varied greatly up to the age of 10 years in the four populations studied, the West Nile District of Uganda being outstanding in having an early and massive infection rate. Differences were also observed between ethnic groups in Singapore, where the Chinese appeared to have a delayed infection rate compared to the Indians.

The variability in immunofluorescent viral capsid antigen antibody tests in population surveys of Epstein-Barr virus infections.

A comparative study of the extent of Epstein-Barr virus (EBV) infections in populations that differ with respect to the incidence of tumours associated with this virus is now in progress in different countries. In these surveys of antibody titres from the various study populations, it is of critical importance that strict comparability be maintained. Despite standardization of techniques and reagents in the cooperating laboratories, considerable variation in the results has remained.