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…     

Antibacterial hydroxycinnamic esters from Piper caninum from Paluma, north Queensland, Australia. The crystal and molecular structure of (+)-bornyl coumarate

The crude chloroform bark extract of Piper caninum (Piperaceae) exhibits antibacterial activity against the Gram-positive bacteria, Bacillus cereus, Staphylococcus aureus, and Streptococcus pneumoniae. The antibacterial agents in this extract have been isolated using bioactivity-directed chromatographic techniques and identified by NMR spectroscopy as (+)-bornyl p-coumarate and bornyl caffeate. A single-crystal X-ray structure has been carried out on (+)-bornyl p-coumarate. The compound crystallizes in the orthorhombic space group P2(1)2(1)2(1) (#19) with a = 12.659(4), b = 13.281(4), and c = 10.177(3) A. Fullmatrix least-squares refinement converged at R = 0.047, and Rw = 0.058.     

Investigation of the transfection capability of cloned tandemly-repeated chicken anaemia virus DNA fragments

Summary Chicken anaemia virus (CAV) is an icosahedral virus, 25 nm in diameter, which, on the basis of its circular single-stranded DNA genome, has recently been classified in the family,Circoviridae. We have investigated whether infectious, monomeric CAV DNA from recombinant plasmids containing tandemly-repeated CAV replicative form (RF) DNAs, following transfection, was generated by homologous recombination or a replicational release mechanism involving rolling circle replication (RCR) of DNA. Experiments designed to locate the virus strand origin of RCR and/or sites of recombination were performed by sequence analyses of hybrid viruses generated after transfection with cloned tandemly-repeated RFs specified by the sequence-distinct Cux-1 and 26P4 isolates. Positive transfection results obtained from 2 recombinant plasmid constructs were shown to have resulted from homologous recombination occurring at different sites within the RF sequence. Three of 5 hybrid viruses analysed were circularised within the same 105bp sequence, that contains four 19bp repeats and with which promoter/enhancer activity has been associated. This region may represent a novel origin or recombination hot-spot within the CAV genome. A distinctive cruciform-loop structure within the non-coding region was shown to contain an S1 nuclease-sensitive site, detected in CAV RF and in recombinant plasmids containing RF inserts.     

Development and validation of clinical indicators for mental health nursing practice

A national study was undertaken in Australia to develop and validate a set of clinical indicators for mental health nursing. Using survey and action research procedures, the indicators were developed in two stages. During stage one, focus group interviews involving 39 nurses were conducted at national conferences in Australia and New Zealand in order to provide a pool of indicator statements. A Delphi survey of an Australian sample of mental health nurses (n = 33) was then conducted to refine the indicators. In stage two, the refined indicators were tested and validated in selected clinical settings. A total of 1751 mental health nurses employed at 14 sites were involved in the second stage of the study. The resulting data were used to establish the set of national indicators that the Australian and New Zealand College of Mental Health Nurses will use in practice accreditation and benchmarking.     

Prostate volume and serum prostate-specific antigen as predictors of acute urinary retention. Combined experience from three large multinational placebo-controlled trials

OBJECTIVES: We evaluated prostate volume and prostate-specific antigen (PSA) as predictors of acute urinary retention (AUR) in men with benign prostatic enlargement (BPE). METHODS: Data were pooled from 3 identical 2-year, multinational, multicenter, non-US, placebo-controlled finasteride trials in 4,222 men with BPE and no evidence of prostate cancer. RESULTS: The 2-year incidence of spontaneous AUR was higher in placebo patients with enlarged prostates (4.2% in men with prostate volume > or =40 ml vs. 1.6% in the <40 ml group) and higher PSA levels (3.9% in men with PSA > or =1.4 ng/ml vs. 0.5% in the <1.4 ng/ml group) at baseline. Finasteride reduced AUR incidence by 61% in men with larger prostates, by 63% in men with higher PSA levels, and by 47% in men with smaller prostates, compared with placebo. CONCLUSIONS: BPE patients with larger prostate volumes, higher PSA levels and no evidence of prostate cancer have an increased risk of developing AUR and therefore derive the greatest benefit from the risk reduction seen with finasteride therapy.