Methods for a public health response to birth defects clusters

Few resources are available to guide public health officials in investigations of reported birth defects clusters. The majority of published resources focus on the investigation of cancer and infectious disease clusters and do not address clinical and epidemiologic concerns specific to birth defects research. This document aims to address these concerns, discuss the needs of the affected community, and provide suggestions for the development of a standardized protocol to be used as a guide in the investigation of birth defects clusters. We suggest that health departments and birth defects registries that may receive reports of birth defects clusters establish a protocol for responding that includes the following steps: develop a proactive plan for future birth defects cluster reports (step I), receive report of a birth defects cluster (step II), verify diagnoses and complete case ascertainment (step III), compare the observed rate to a reference rate (step IV), ascertain exposures among cases from available records (step V), interview case mothers (step VI), initiate further epidemiologic study-selection of controls (step VII), and communicate results to the community (step VIII). Specific criteria for continuing or terminating an investigation should be established before receiving cluster reports. The recommendations in this report should be carefully considered to ensure that the specific needs of the region, agency and affected community are met.     

Characterization of Trichodesmium spp. by genetic techniques

The genetic diversity of Trichodesmium spp. from natural populations (off Bermuda in the Sargasso Sea and off North Australia in the Arafura and Coral Seas) and of culture isolates from two regions (Sargasso Sea and Indian Ocean) was investigated. Three independent techniques were used, including a DNA fingerprinting method based on a highly iterated palindrome (HIP1), denaturing gradient gel electrophoresis of a hetR fragment, and sequencing of the internal transcribed spacer (ITS) of the 16S-23S rDNA region. Low genetic diversity was observed in natural populations of Trichodesmium spp. from the two hemispheres. Culture isolates of Trichodesmium thiebautii, Trichodesmium hildebrandtii, Trichodesmium tenue, and Katagnymene spiralis displayed remarkable similarity when these techniques were used, suggesting that K. spiralis is very closely related to the genus TRICHODESMIUM: The largest genetic variation was found between Trichodesmium erythraeum and all other species of Trichodesmium, including a species of KATAGNYMENE: Our data obtained with all three techniques suggest that there are two major clades of Trichodesmium spp. The HIP1 fingerprinting and ITS sequence analyses allowed the closely related species to be distinguished. This is the first report of the presence of HIP1 in marine cyanobacteria.     

Growth hormone enhances effects of endurance training on oxidative muscle metabolism in elderly women

The present study investigated whether recombinant human (rh) growth hormone (GH) combined with endurance training would have a larger effect on oxidative capacity, metabolism, and body fat than endurance training alone. Sixteen healthy, elderly women, aged 75 yr, performed closely monitored endurance training on a cycle ergometer over 12 wk. rhGH was given in a randomized, double-blinded, placebo-controlled design in addition to the training program. GH administration resulted in a doubling of serum insulin-like growth factor I levels. With endurance training, peak oxygen uptake increased by approximately 18% in both groups, whereas the marked increase in muscle citrate synthase activity was 50% larger in the GH group compared with the placebo group. In addition, only the GH group revealed an increase in muscle L-3-hydroxyacyl-CoA dehydrogenase activity. Body weight remained unchanged in both groups, but the GH group showed significant changes in body composition with a decrease in fat mass and an increase in lean body mass. Twenty-four-hour indirect calorimetry performed in four subjects showed a marked increase in energy expenditure with increased relative and absolute fat combustion in the two subjects receiving rhGH. In conclusion, rhGH adds to the effects of endurance training on muscle oxidative enzymes and causes a reduction in body fat in elderly women.     

Cyanobacterial diversity in geographically related and distant host plants of the genus Gunnera

The diversity among 45 cyanobacterial isolates from 11 different Gunnera species originating from different geographical areas was examined. By means of polymerase chain reaction (PCR) fingerprinting with short tandemly repeated repetitive (STRR) sequences as primers, ten groups of symbiotic cyanobacteria and five unique isolates not belonging to a particular group were identified. Most groups were restricted to one geographical area, indicating a limited distribution of related cyanobacterial strains. An extensive cyanobacterial diversity was found both within and between the 11 different Gunnera species. Within a particular plant and even within the same stem gland, more than one cyanobacterial strain at a time could be present. These results indicate a low specificity in Gunnera-Nostoc symbiosis.     

2-(oxalylamino)-benzoic acid is a general, competitive inhibitor of protein-tyrosine phosphatases

Protein-tyrosine phosphatases (PTPs) are critically involved in regulation of signal transduction processes. Members of this class of enzymes are considered attractive therapeutic targets in several disease states, e.g. diabetes, cancer, and inflammation. However, most reported PTP inhibitors have been phosphorus-containing compounds, tight binding inhibitors, and/or inhibitors that covalently modify the enzymes. We therefore embarked on identifying a general, reversible, competitive PTP inhibitor that could be used as a common scaffold for lead optimization for specific PTPs. We here report the identification of 2-(oxalylamino)-benzoic acid (OBA) as a classical competitive inhibitor of several PTPs. X-ray crystallography of PTP1B complexed with OBA and related non-phosphate low molecular weight derivatives reveals that the binding mode of these molecules to a large extent mimics that of the natural substrate including hydrogen bonding to the PTP signature motif. In addition, binding of OBA to the active site of PTP1B creates a unique arrangement involving Asp(181), Lys(120), and Tyr(46). PTP inhibitors are essential tools in elucidating the biological function of specific PTPs and they may eventually be developed into selective drug candidates. The unique enzyme kinetic features and the low molecular weight of OBA makes it an ideal starting point for further optimization.     

An analytical approach to the implementation of genetically modified crops

Public scepticism towards genetically modified (GM) crops is increasing. To address this, the risks and benefits of GM crops must be examined across scientific disciplines, and be discussed with the authorities, the agricultural industry and the consumers. In a feasibility study we have systematically analysed the challenges of the development and marketing of GM crops in Europe. A life-cycle inventory was used together with established technology foresight techniques in an interdisciplinary and empirical framework. The approach taken in this study established a dialogue between stakeholders and provided a framework for discussions about the future direction of GM crops.