Genetics of programmed cell death in C. elegans: past, present and future

Genetic studies of the nematode Caenorhabditis elegans have defined a variety of single-gene mutations that have specific effects on programmed cell death. Analyses of the genes defined by these mutations have revealed that cell death is an active process that requires gene function in cells that die. Specific genes are required not only to cause cell death but also to protect cells from dying. Gene interaction studies have defined a genetic pathway for the execution phase of programmed cell death in C. elegans. Molecular and biochemical findings are consistent with the pathway proposed from these genetic studies and have also revealed that the protein products of certain cell-death genes interact directly. This pathway appears to be conserved among organisms as diverse as nematodes and humans. Important questions remain to be answered about programmed cell death in C. elegans. For example, how does a cell decide to die? How is cell death initiated? What are the mechanisms of action of the cell-death protector and killer genes? What genes lie downstream of the cell-death execution pathway? The conservation of the central cell-death pathway suggests that additional genetic analyses of programmed cell death in C. elegans will help answer these questions, not only for this nematode but also for other organisms, including ourselves.     

Detection and quantification of endolymphatic hydrops in the guinea pig cochlea by magnetic resonance microscopy

The experiments carried out on the model of immobilization stress permit establishing the antiulcer effect of preventive introduction of sodium succinate solution, milk serum solution and solution of milk serum with sodium succinate. A decrease in the degree and number of ulcers and in the integrative indices characterizing the ulcer process after introduction of the studied drugs was accompanied by a fall of the intensity of lipid peroxidation processes.     

Penetrating cardiac wounds: prospective study of factors influencing initial resuscitation

A prospective study of 66 consecutive patients with cardiac wounds seen over a 27-month period is reported. No patient was excluded. Patients were stratified by injury mechanism and by physiologic scoring at admission using the cardiovascular-respiratory elements of the Trauma Score (CVRS). Admission cardiac rhythm was obtained in patients with a CVRS of 0 and a Glasgow Coma Scale (GCS) score of 3. Information concerning the anatomic extent of the cardiac wound, the presence or absence of tamponade, and the degree of injury to other structures was also collected prospectively. Seventy percent of the cardiac wounds were caused by gunshots. The probability of successful resuscitation was significantly related to mechanism of injury and physiologic condition on arrival. Among patients arriving with a CVRS of 0 and a GCS score of 3, survival correlated with cardiac rhythm. Pericardial tamponade did not prove to be an independent predictor of early survival. The presence of tamponade was statistically linked to the mechanism of injury. Transport by non-official conveyance was associated with a higher CVRS on arrival. Intoxication with alcohol or cocaine had no evident effect on resuscitation probability.     

Reduced speed of sound in tibial bone of haemodialysed patients: association with serum PTH level

BACKGROUND: In end-stage renal disease, average bone mineral density has been reported to be normal or only modestly reduced, more so in the cortical bone. The purpose of the present study was to explore the potential use of quantitative ultrasound, a method reflecting both quantitative and qualitative properties of bone, in assessing bone status in patients on maintenance haemodialysis. METHODS: We studied 71 patients (age 17-81 years, time on dialysis 0-18 years). The speed of sound waves (tSOS; m/s) propagating along the cortical bone has been determined at the tibial shaft. tSOS results were expressed as Z scores, i.e. units of standard deviations from age- and sex-matched normal mean values, and correlated with relevant clinical and biochemical variables. RESULTS: SOS Z score averaged -2. 0 (range -6.8 to 0.6; P<0.001) and was negative in 93% of the patients. Significant inverse correlations were found between SOS Z score and both time on dialysis (r=-0.52; P<0.0001) and serum PTH (r=-0.39; P=0.0002). Markedly reduced SOS Z score, below -2, was found in 80% of the patients whose PTH levels exceeded 34 pmol/l (five times the upper normal limit), compared with 43% of the patients whose PTH levels were below 34 pmol/l(P=0.04). Compared to patients without bone pain (n=51), subjects with bone pain (n=20) had somewhat lower SOS Z scores -2.5+/-2.0 versus -1.8+/-1.4; P=0. 08), but this could be accounted for by longer time on dialysis. CONCLUSIONS: tSOS is substantially reduced in the majority of haemodialysed patients and is related to time on dialysis and serum PTH level. The clinical value of this novel method needs further exploration.     

Phenotypic analysis of antigen-specific T lymphocytes

Identification and characterization of antigen-specific T lymphocytes during the course of an immune response is tedious and indirect. To address this problem, the peptide-major histocompatability complex (MHC) ligand for a given population of T cells was multimerized to make soluble peptide-MHC tetramers. Tetramers of human lymphocyte antigen A2 that were complexed with two different human immunodeficiency virus (HIV)-derived peptides or with a peptide derived from influenza A matrix protein bound to peptide-specific cytotoxic T cells in vitro and to T cells from the blood of HIV-infected individuals. In general, tetramer binding correlated well with cytotoxicity assays. This approach should be useful in the analysis of T cells specific for infectious agents, tumors, and autoantigens.     

A manual on pediatric telephone triage

In 1985 in Zaire, a 12-week training course began in Kasongo district to prepare physicians to use sound management of primary and secondary health services, supervision of health centers, and commitment to team work to operate districts in an integrated way. Only 1 new physician trainee was accepted every 4 weeks. During the first week, trainees observed work at an outpatient clinic for 2-3 hours/day to learn about the links between the primary and secondary levels of health care. During the second week, they observed staff at an urban health center in Kasongo city so they could become familiar with strategies for diagnosis and treatment in curative consultations and with instructions for follow-up. During the third week, the trainees returned to the outpatient clinic to practice interviewing patients. During the fourth week, they observed work in a rural health center and in remote villages. During the second 4-week period, trainees worked in a hospital department of their choice to learn how to use files and to evaluate quality of care. They visited health centers 1-2 times/week to examine supervisory techniques of different resident physicians. Trainees were part of the health team during the third 4-week period. They were responsible for a hospital department and supervised health centers under a resident physician. The trainees also attended management committee meetings addressing quality of care, staff management, and feedback from health center supervisions. The cost for this health district management training was US $100/trainee. Between mid-1985 and mid-1988, 18 physicians underwent this training. 12 of these physicians are now working in health districts in Zaire. A follow-up survey in 1995 showed that most trainees were applying the requisite skills and knowledge acquired during the training. Further supervision or self-training, involving team analysis of problems and possible solutions, are needed. Factors contributing to the course's success include: an integrated health system under the direction of a health team, a large enough team to do student training but small enough to maintain communication, and active participation of trainees.     

Molecular characterization of erythrocyte glucose-6-phosphate dehydrogenase deficiency in Al-Ain District, United Arab Emirates

Operational skills involved in controlling a motor vehicle were measured in two groups of very healthy elderly drivers and a young control group to test the hypothesis that there are age-related declines in operational performance that may influence driver safety. An actual behind-the-wheel, standardized road test was employed using a motor vehicle equipped with sensors to record speed, braking activity, and lane position, as well as direction and magnitude of front-wheel and eye-movement excursions. The data from these sensors were used as dependent measures of operational performance. Older drivers made fewer steering and eye-movement excursions and drifted across the center line more frequently than the young control group. Younger drivers drove significantly faster and executed more braking applications than did their older counterparts. The motor-vehicle operational performance of older healthy drivers was related to visual-spatial attentional declines and the useful field of vision associated with the normal aging process.     

Lung cancer among steelworkers in Ontario

A population-based case-control study was carried out to follow up observations of increased lung cancer risk in the steel pouring areas of two Ontario steel mills. Study subjects were all men, aged 45-75 years, who died of lung cancer in the cities of Hamilton or Sault Ste-Marie, Ontario from 1979-1988. Nine hundred sixty-seven lung cancer victims were matched with 2,827 control subjects who died of other causes. Work histories were provided by the employers of steelworkers. In comparison with other residents of their cities, the relative risk of death from lung cancer was 0.85 (95% confidence interval [CI]: 0.58-1.23) for steelworkers in Sault-Ste Marie and was 1.10 (95% CI: 0.89-1.37) for steelworkers in Hamilton. In internal comparisons within the steel companies, increased lung cancer risk was observed among foundry, coke oven, and pouring pit workers. Retrospective hygiene assessment suggested that the increased risk of lung cancer among steel pourers might be related to the use of tar-based mold coating agents or to exposure to mineral fibers.