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Respiratory compliance is obtained from the ratio of lung volume change to change in differential pressure across the chest wall, and is classically derived from the slope of the static, transrespiratory pressure-volume relationship. The need to remove subjectivity from the derivation of respiratory compliance, has prompted the development of a computer-based system which facilitates compliance measurement with minimal experimenter error. This paper outlines the basic algorithms necessary to analyse static, quasi-static and dynamic pressure-volume data, and describes how these data may be entered into a graphics package (Sigmaplot) to derive best-fit polynomial curves.

Variable decelerations are of frequent concern to the practicing obstetrician. Oligohydramnios resulting in cord and/or placental compression is probably the most common cause of variable decelerations. We performed intrauterine saline amnioinfusion in 42 patients having repetitive variable or prolonged decelerations that did not respond to conventional therapy, such as maternal position changes and oxygen administration. Saline amnioinfusion was effective for relief of repetitive variable decelerations in 19 of 28 patients and prolonged decelerations in 12 of 14 patients. No neonatal or maternal complications occurred. This preliminary study suggests that amnioinfusion therapy may become a useful adjunct in the management of repetitive variable and prolonged decelerations.

The effectiveness of 6 chemicals (benzo[a]pyrene, (BaP), cyclophosphamide (CP), diethylnitrosamine (DEN), methyl methanesulphonate (MMS), mitomycin C (MC) and procarbazine (PC) ) as inducers of micronuclei in foetal liver and maternal bone marrow erythroblasts has been determined, and related to that of gamma-radiation. CP, DEN, MMS and PC were all more effective in the foetal liver. The induction of micronuclei and SCEs by each chemical in foetal erythroblasts after in vivo exposure was measured. When expressed as induction of sister-chromatid exchanges (SCEs) per erythroblast/induction of micronuclei per erythroblast (/microM/kg), the ratios obtained were MC 580, BaP 470, DEN 430, CP 258, MMS 140 and PC 13. The lowest doses detected as potentially genotoxic by each test in foetal liver erythroblasts are (with the exception of PC which is a relatively ineffective inducer of SCEs) similar. When isolated foetal livers were exposed in vitro, SCE dose responses to BaP, MC, MMS and PC could be directly related to those from in vivo exposure, indicating the role of the foetal liver in metabolic activation, but CP was considerably more cytotoxic. The transplacental micronucleus test, and in vivo/in vitro method for SCEs in foetal liver erythroblasts, provide sensitive, complementary assays for genotoxic effects of chemicals during prenatal life. Since foetal liver possesses greater metabolic potential than adult bone marrow, the transplacental tests respond to genotoxic agents not detected by bone-marrow systems.

Upright immersion imposes a pressure imbalance between alveolar and mean external thoracic pressure. Lung centroid pressure (PLC) is defined as the breathing pressure required to remove this imbalance. Static transrespiratory pressure-volume relationships were determined in subjects immersed in upright (n = 17) and prone (n = 13) postures. Compliances measured during immersion (1.87 +/- 0.15 liter.kPa-1 upright, 1.87 +/- 0.17 liter.kPa-1) prone) were compared with compliances, obtained over the same volume range, while upright in air (1.84 +/- 0.17 liter.kPa-1). PLC was determined by the horizontal (pressure) displacement of immersed compliance curves. PLC was calculated to be +1.33 +/- 0.11 kPa (+13.6 cmH2O) relative to the sternal notch when upright and -0.69 +/- 0.12 kPa (-7.0 cmH2O) relative to the sternal plane when prone (mean +/- SEM). Upright PLC did not support the widely used value of +19 cmH2O (Jarrett AS. J Appl Physiol 1965;20:1261-1266). Analysis shows that when data from earlier investigations were adjusted for differences in reference pressure, the collective PLC supports the present results.

Postnatal skeletal muscle growth in humans is generally ascribed to enlargement of existing muscle fibres rather than to cellular proliferation. Some evidence of muscle fibre division or splitting was provided in the nineteenth century. This evidence has more recently been supported by fibres obtained from regenerating muscle, and from muscle which has undergone stress-induced growth. Numerous investigators have reported indirect evidence for exercise-induced hypertrophy and hyperplasia. These findings are largely founded on secondary observations of fibre size or number differences expressed relative to muscle cross-sectional area. Since these observations in humans are open to methodological criticism, researchers have developed 3 animal models to represent exercise-induced human muscle growth. These include compensatory hypertrophy, stretch-induced hypertrophy, and weight lifting in trained animals. The results and criticisms of the experiments which have used these models are discussed in this review. In studies of muscle cross-sectional area, errors are created by fibres terminating intrafascicularly. Longitudinal growth of such fibres result in an overestimation of fibre number, and with the use of penniform muscles where fibres do not run parallel to the longitudinal axis of the muscle, the error is compounded. It was concluded that hyperplasia is not yet substantiated, and that new fibres, if present, may be the result of the development of satellite cells. Further experiments are required before a definitive answer can be provided. It is suggested that rigidly controlled exercise studies using contralateral control, fusiform muscles with analysis of individually teased muscle fibres be performed.

Heat dissipation, under conditions of thermal stress, is mediated primarily by evaporation of sweat. Physical training has been shown to enhance sweat production by eliciting changes in the sensitivity of eccrine glands, total sweat output and distribution of gland activity. These adaptations afford partial acclimation. Heat acclimation produces similar changes, and also results in reduced sweat thresholds. To account for these different responses it has been hypothesised that physical training induces peripheral adaptations, while acclimation produces both peripheral and central modifications. It is suggested that repeated cutaneous heat detection may be essential to the development of central sudomotor changes.

Two endopeptidases are involved in the conversion of proinsulin; a type I activity directed at the B chain, Arg31,Arg32, C-peptide junction, and type II which cleaves the C-peptide, Lys64,Arg65, A chain junction. To define further the substrate specificities of these enzymes, a series of mutant preproinsulin cDNAs were generated by site-directed and deletion mutagenesis. These were inserted into pT7 plasmids and capped cRNA transcripts synthesized, that were then microinjected into Xenopus oocytes. Oocytes were biosynthetically radiolabeled with [3H]leucine and the secreted peptides (greater than 95% present as unprocessed proinsulins) then incubated with types I and II endopeptidase activities prepared from isolated insulinoma secretory granules. The reaction products were analyzed by high performance liquid chromatography. Des-38-62-proinsulin, in which all but six amino acids of C-peptide were deleted was not processed by either enzyme. The mutant Lys64,Arg65 to Thr64,Arg65 was not cleaved by the type II enzyme but was still a substrate for the type I enzyme. The mutant Arg31,Arg32 to Arg31,Gly32 correspondingly was not cleaved by the type I enzyme; however, in this case it was not attacked by the type II enzyme. These results indicate that not only is the presence of a dibasic sequence essential, but also that the secondary structure of the protein is important in determining whether the prohormone is susceptible to proteolytic processing.

The biosynthesis and secretion of human proinsulin and a mutant human proinsulin with a major deletion in the C-peptide, (des 38-62)proinsulin, was studied in monkey kidney cells (Cos-7) transfected with cDNAs encoding the respective normal or mutant human preproinsulins. Transfected cells were labelled with [3H]leucine, and insulin-like material was immunoprecipitated and analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. It was found that the prepeptide was removed from both the normal and mutant preproinsulins, and that there was no further processing to insulin. The normal proinsulin was rapidly released from the transfected cells, with little intracellular accumulation, while the mutant proinsulin was retained within the cell, with only small quantities of radio-labelled material in the medium. The intracellular mutant proinsulin was membrane bound and located predominantly within a microsomal fraction. These results suggest that C-peptide plays an important role in the efficient transfer of proinsulin through the early stages of the secretory pathway.