Estimation of the developmental age of the ovine fetus and lamb

Fifty-six fetuses and 33 lambs were obtained from a flock of ewes at set gestational intervals between 50 to 180 days after conception. The fetuses and lambs were killed, disected and the sizes and weights of a wide range of skeletal and soft tissues were measured. Five morphological parameters emerged as most suitable for the determination of normal foetal developmental age. By plotting the mean value and ninety-five per cent tolerance limits, the rates of growth and the variability of each parameter were studied. Crown-anus length is useful for determining fetal developmental age from 50 to 100 days gestation; brain weight, long bone length and the number of appendicular ossification centres can be used to determine fetal development age from 50 days gestation until term.     

Identification of a novel complement-dependent serum-elicited inward current in the Xenopus oocyte provoking Ca2+ influx and subsequent activation of Cl- channels

The membrane spanning complement channel is assumed to be a nonselective ion 'pore', although little evidence is available to support this hypothesis. In this paper we provide evidence that Ca2+ entry and Cl- exit occur rapidly after complement activation and precede the development of a long-lasting complement-dependent inward current. Addition of rabbit serum (a source of heterologous complement) and mouse anti-human insulin receptor antibody to a single Xenopus oocyte expressing human insulin receptor was shown to stimulate an initial hyperpolarising current followed by a sustained depolarising current. On voltage clamping the oocyte, a novel long-lasting inward current generated by serum addition was detected. Complement classical pathway-stimulated calcium influx into the oocyte was directly demonstrated using 45Ca influx measurements. In addition, we found that Ca2+ influx was required for the stimulation of the complement alternative pathway-dependent inward current. The novel conductance elicited by the classical pathway was outwardly rectifying, had a reversal potential of -35 +/- 8 mV (or -52 +/- 7 mV in the presence of chloride channel inhibitors), was inhibited by nifedipine, and was observed in the presence but not in the absence of the pore-forming complement component C9. As overactivation of complement does play a role in many inflammatory or autoimmune diseases, inhibition of early complement-mediated ion flux might restrict tissue damage and aid recovery from such diseases.     

Application of nearest-neighbor and cluster analyses in pharmaceutical lead discovery

CASE REPORT: A case history of unanticipated radiation-induced bilateral optic neuropathy, 18 months after induction chemotherapy and radiation therapy for a locally advanced nasopharyngeal carcinoma, is presented. Retrospective reanalysis of the radiation therapy technique, with emphasis on the doses received by the optic pathway structures, was performed. These re-calculations revealed unexpectedly high doses in the range 79 to 82 Gy (cumulative external and brachytherapy dose) at the level of the optic nerves, which explained the observed radiation injury. CONCLUSION: Routine implementation of computed tomography for 3D dose planning purposes is therefore advocated. Review of the current literature confirms the importance of 3D dose planning in avoiding this complication and high-lights the role of MRI in establishing the diagnosis of radiation-induced optic neuropathy.     

Prediction tests by using ISF method for the geomagnetic disturbances

A so-called ISF method for predicting geomagnetic disturbances caused by solar wind storm blowing to the earth is suggested. The method is based on a combined approach to solar activity, interplanetary scintillation (IPS) and geomagnetic disturbance observations in 1966-1982, dynamics of disturbance propagation and fuzzy mathematics. Prediction test has been made for 24 large geomagnetic disturbance events that produced space disasters during the period of 1980 -1998, with the three-dimensional propagation characteristics, the best close degree of each radio source and the influence of the south-north components of interplanetary magnetic fields considered. The main results are (i) for onset time of the geomagnetic disturbance, events with relative error △Tpred/Tobs≤10% between the observation Tobs and the prediction Tpred, account for 45.8% of all events, ≤30% for 78.3% and >30% for only 21.7%; (ii) as for the magnetic disturbance magnitude, events with relative error ΔΣKp,pred/ΣKp,obs≤10% betwee     

Molecular Biology to Radiation Oncology: A Model for Translational Research? Opportunities in basic and translational research. From a workshop sponsored by the National Cancer Institute, Radiation Research Program, January 26-28, 1997, Bethesda, Maryland

Many exciting discoveries are being made that are providing new insights into how molecules, cells and tissues respond to ionizing radiation. There remains a need, however, to translate these findings into more effective treatments for cancer patients, including those treated with radiation therapy. This complex task will require the collaboration of scientists studying molecular, cellular and tissue responses, and those performing clinical trials of emerging therapies. The Radiation Research Program of the National Cancer Institute sponsored a workshop entitled "Molecular Biology to Radiation Oncology: A Model for Translational Research?" to bring together basic scientists and clinicians to exchange ideas and fundamental concepts and to identify opportunities for future research and collaboration. Four broad topics were addressed: signal transduction and apoptosis, the cell cycle, repair of radiation damage, and the microenvironment. The development, selection and use of appropriate experimental models is crucial to finding and developing new therapies, and opportunities exist in this area as well. This paper and the accompanying paper by Coleman and Harris that provides the viewpoint of radiation oncologists (Radiat. Res. 150, 134-147, 1998) summarize the background concepts and opportunities for translational research identified by the workshop participants.     

Upper bound risk estimates for mixtures of carcinogens

The excess cancer risk that might result from exposure to a mixture of chemical carcinogens usually is estimated with data from experiments conducted on individual chemicals. An upper bound on the total excess risk is estimated commonly by summing individual upper bound risk estimates. The degree to which this approach might overstate the true risk associated with the mixture has not been evaluated previously. This paper reports the results of a Monte Carlo simulation study on the degree of reduction in conservation that might be achieved using alternative methods for calculating mixture upper bounds. An unexpected finding is that for chemicals that exhibit strongly linear dose-response relationships, the summing of multistage-model-based upper bounds on excess risk can be anti-conservative, that is, it can provide less than the nominal 100(1-alpha)% coverage.     

Clinical, endocrine and neurochemical effects of moclobemide in depressed patients

A case of Fraser syndrome diagnosed prenatally is presented. Detection of oligohydramnios, hydrops fetalis and bilateral absence of the kidneys were the initial findings leading to further study. Specific IgM for cytomegalovirus in maternal serum and confirmed infection by fetal blood sampling was an associated finding. The importance of an etiologic diagnosis of nonimmune hydrops and the relevant aspects of genetic counselling are emphasized. The association of the Fraser syndrome with cytomegalovirus infection has not been previously reported.     

Occupational stress and health care use

This study investigated the relationship between health care use and (a) stressful work events; (b) strain; (c) social support; (d) type of job and industry; and (e) the individual characteristics of control, commitment, and length of time in position. A sample of 260 individuals (95 men, 165 women) from two different industries was used. Correlational analyses suggested that health care claims and costs were positively related to stressful work events and strain and negatively related to employees' length of time in position. Industry type also played a role in predicting the health care variables. Multivariate analyses suggested that environmental, stressor, and strain variables accounted for up to 16% of the variance in health care costs and 21.5% of the variance in number of health care claims.