Defects in neurofibromatosis 2 protein function can arise at multiple levels

Neurofibromatosis 2 (NF2) is an inherited cancer syndrome resulting from mutations in the NF2 tumor suppressor gene. Analysis of NF2 mutations has revealed some general genotype-phenotype correlations. Severe disease has been associated with mutations that produce a premature termination while more mild disease has been associated with missense mutations. Here, we provide experimental proof for these genotype-phenotype correlations by demonstrating that nonsense mutations fail to produce stable merlin protein while missense mutations result in the generation of merlin proteins defective in negative growth regulation. This inability to suppress cell growth may result from defects in the function of merlin at several levels, including failure to form an intramolecular complex. Based on these findings, we propose a model for merlin growth suppression that provides a framework for analyzing NF2 patient mutations and merlin function.      

Uterine myomata and outcome of assisted reproduction

The aim of this work was to study the effect of uterine myomata on the implantation rate and outcome in in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Among 406 patients, 51 (12.6%) were found to have uterine corporeal myomata. Twelve patients were excluded from the study as they had large myomata, submucous myomata or intramural myomata encroaching on the cavity. These patients were advised to have myomectomy before being enrolled in the IVF/ICSI programme. The remaining patients (n = 39) were sorted according to the number, site and size of the myomata as assessed by transvaginal sonography. Three patients had more than one myoma. Most of the myomata were subserous (72.7%) and the mean diameter of the myomata was 3.5 +/- 0.9 cm. A control group (n = 367) was chosen with normal uteri and no history of uterine reconstruction surgery. The mean age of myoma patients was 34.7 +/- 3.6 years as compared to 34.0 +/- 4.4 years in the control group. The age, period of infertility, body mass index, duration and number of human menopausal gonadotrophin ampoules needed for stimulation, oestradiol levels, number of oocytes retrieved and the fertilization rate were not significantly different in the myoma patients compared to the control group. Fifteen myoma patients (38.5%) subsequently showed one or more pregnancy sacs on ultrasonography of which three (20%) spontaneously aborted during the first trimester and two (13.3%) had preterm labour, as compared to 123 (33.5%), 19 (15.5%) and nine (7.3%) respectively, among the control group (P = 0.27, 0.33 and 0.21). In conclusion, uterine corporeal myomata, not encroaching on the cavity and <7 cm in mean diameter, do not affect the implantation or miscarriage rates in IVF or ICSI.      

Covariances of Mitogenic Responses in Leukaemic Blood Lymphocytes: a Functional Marker System for the Human B Lymphocyte Differentiation

Various polyclonal activating substances have been shown to stimulate human chronic lymphatic leukaemic (CLL) cells to undergo blast transformation, to divide and to secrete monoclonal immunglobulin. CLL cells from different patients show distinct response patterns to these ligands. We have statistically analysed these response patterns and found that responses to certain ligands demonstrate covariance; that is, a high response to one ligand is statistically associated with a high response to another ligand. A factor analysis of these data on the basis of responses of CLL cells from twenty-one patients and from the use of five different ligands in three different concentrations has shown that as few as two factors can account for as much as 63% of the total variance of these responses. On the assumption that these two factors were T-cell dependency of CLL responses and stage of maturity of the responding CLL cell, we have formulated a theory that explains the basis for this functional marker system for CLL cells. It is possible application to the characterization of individual CLL clones has been discussed.     

THE EFFECT OF PROSTAGLANDIN E1 ON PULMONARYBLOOD FLOW AFTER RETROGRADE FLUSH ANDCOLD STORAGE OF LUNGS

ReSllm6 Objectif Nos studes Precedentes out montrd une panne fonCtion de la greffe pulmonaire traitde Prdalablementper perfusion forcde retrograde et un stockage d froid inns ~. L' etude Prdsente a pour but de determiner l' effet de ~ surlefiot mngUin du poumon trait4 Prdalablement per perfusion retrograde forcde et un stockage d froid. met~. 12poumons donneurs canins out ate trait4s per perfusion r4tFograde de solution UW. Chez 6 animaux du grouch A, 250ng furent injectes dans l' artrdre…