The immune response of the Chacma baboon to Bacille Calmette Guerin: development of a primate model for BCG-based vaccine research

Mycobacterium bovis Bacilli Calmette-Guerin (BCG) is used increasingly as an efficient vector for expression of recombinant proteins to induce a strong cell-mediated immunity. Here, we tested the immune response of Chacma baboons to the Tokyo and Pasteur strains of BCG in order to obtain base-line information on the response of this primate to BCG. While a humoral immune response to BCG was detected only in some vaccinated baboons, a cellular immune response characterized by a PPD-specific delayed hypersensitivity response and BCG-specific IFN-γ production from PBMC was a consistent finding. These responses were long-lived and could be detected beyond a year after a booster inoculation at 20 weeks. The results thus suggest that the Chacma baboon may be used as a non-human primate for the evaluation of recombinant BCG vaccines.     

Quantification and cellular localization of expression in human skin of genes encoding flavin-containing monooxygenases and cytochromes P450

The expression, in adult human skin, of genes encoding flavin-containing monooxygenases (FMOs) 1, 3, 4, and 5 and cytochromes P450 (CYPs) 2A6, 2B6, and 3A4 was determined by RNase protection. Each FMO and CYP exhibits inter-individual variation in expression in this organ. Of the individuals analysed, all contained CYP2B6 mRNA in their skin, 90% contained FMO5 mRNA and about half contained mRNAs encoding FMOs 1, 3, and 4, and CYPs 2A6 and 3A4. The amount of each of the FMO and CYP mRNAs in skin is much lower than in the organ in which it is most highly expressed, namely the kidney (for FMO1) and the liver (for the others). In contrast to the latter organs, in the skin FMO mRNAs are present in amounts similar to, or greater than, CYP mRNAs. Only the mRNA encoding CYP2B6 decreased in abundance in skin with increasing age of the individual. All of the mRNAs were substantially less abundant in cultures of keratinocytes than in samples of skin from which the cells were derived. In contrast, an immortalized human keratinocyte cell line, HaCaT, expressed FMO3, FMO5, and CYP2B6 mRNAs in amounts that fall within the range detected in the whole skin samples analysed. FMO1, CYP2A6, and CYP3A4 mRNAs were not detected in HaCaT cells, whereas FMO4 expression was markedly increased in this cell line compared to whole skin. In situ hybridization showed that the expression of each of the FMOs and CYPs analysed was localized to the epidermis, sebaceous glands and hair follicles.     

Strength training for wheelchair users.

Sedentary adult males with spinal lesions, all habitual wheelchair users, were allocated to exercise (n = 11) and control (n = 4) groups. A Cybex II dynamometer was used to assess peak power, average power, total work and muscular endurance for elbow flexion/extension, shoulder flexion/extension and shoulder abduction/adduction at five angular velocities, on recruitment and after eight and 16 weeks of forearm ergometer training (three days/week). Small sub-groups of the exercised subjects were assigned to high or low intensity endurance effort (70 or 40 per cent of maximal oxygen intake) and long or short training sessions (40 or 20 minutes per session). Despite the aerobic nature of the activity, gains of average power were registered by the two muscle groups most involved in the ergometer task (shoulder extension and elbow flexion). In keeping with current theories of training, gains were largest with prolonged, high intensity activity at angular velocities approximating those adopted during training.     

Occupational demand and human rights. Public safety officers and cardiorespiratory fitness

The issue of discrimination in physically demanding employment, such as police, firefighters, prison guards and military personnel, is contentious. In terms of oxygen transport, the 'action limit' (calling for personnel selection or task redesign) is a steady oxygen consumption of 0.7 L/min, while the maximum permissible limit is 2.1 L/min. Note is taken of the commonly expressed belief that public safety duties are physically demanding, calling for personnel with an aerobic power of at least 3 L/min, or 42 to 45 ml/kg/min. The actual demands of such work can be assessed on small samples by physiological measurements (using heart rate or oxygen consumption meters), but the periods sampled may not be typical of a normal day. A Gestalt can also be formed as to the heaviness of a given job, or a detailed task analysis can be performed; most such analyses of public safety work list distance running and other aerobic activities infrequently. An arbitrary requirement of 'above average fitness' is no longer accepted by courts, but a further approach is to examine the characteristics of those currently meeting the demands of public safety jobs satisfactorily. Young men commonly satisfy the 3 L/min standard, but this is not usually the case for women or older men; in the case of female employees, it also seems unreasonable that they should be expected to satisfy the same standards as men, since a lower body mass reduces the energy cost of most of the tasks that they must perform. A second criterion sometimes applied to physically demanding work (a low vulnerability to heart attacks) is examined critically. It is concluded that the chances that a symptom-free public safety officer will develop a heart attack during a critical solo mission are so low that cardiac risk should not be a condition of employment. Arbitrary age- and sex-related employment criteria are plainly discriminatory, since some women and 65-year-old men have higher levels of physical fitness than the average young man of 25 years. Neither laboratory nor field tests offer a satisfactory means of distinguishing such individuals, and the only equitable basis of selecting personnel for physically demanding work seems a probationary period of employment.