Decreased lung capillary blood volume post-exercise is compensated by increased membrane diffusing capacity

The diffusing capacity of the lung for carbon monoxide (DLCO) decreases to below the pre-exercise value in the hours following a bout of intense exercise. Two mechanisms have been proposed: (1) development of pulmonary oedema and (2) redistribution of central blood volume to peripheral muscles causing a reduction in pulmonary capillary blood volume (V_c). In the present study DLCO, V_c and the membrane diffusing capacity (D_m) were measured in nine healthy females using a rebreathing method, in contrast to the single breath technique employed in previous studies. DLCO, V_c and D_m were measured before and at 1, 2, 3, 16 and 24 h following maximal treadmill exercise. Compared with pre-exercise values, DLCO was depressed by up to 8.9 (3.0)% (P<0.05) for the first 3 h following exercise, but had returned to pre-exercise values by 16 h post-exercise. V_c fell by 21.2 (4.1)% (P<0.05) at 3 h post-exercise, but at the same time D_m increased by 14.7 (9.1)%. It was concluded that: (1) the increase in D_m made it unlikely that the fall in DLCO was due to interstitial oedema and injury to the blood gas barrier; (2) on the other hand, the reduction in DLCO following exercise was consistent with a redistribution of blood away from the lungs; and (3) the trend for D_m and V_c to reciprocate one another indicates a situation in which a fall in V_c nevertheless promotes gas transfer at the respiratory membrane. It is suggested that this effect is brought about by the reorientation of red blood cells within the pulmonary capillaries following exercise.     

Delay between pregnancy confirmation and sickle cell and [corrected] thalassaemia screening: a population-based cohort study.

BACKGROUND: Antenatal sickle cell and thalassaemia screening sometimes occurs too late to allow couples a choice regarding termination of affected fetuses. The target gestational age for offering the test in the UK is 10 weeks. AIM: To describe the proportion of women screened before 70 days' (10 weeks') gestation and the delay between pregnancy confirmation in primary care and antenatal sickle cell and thalassaemia screening. DESIGN OF STUDY: Cohort study of reported pregnancies. SETTING: Twenty-five general practices in two UK inner-city primary care trusts offering universal screening. METHOD: Anonymised data on all pregnancies reported to participating general practices was collected for a minimum of 6 months. RESULTS: There were 1441 eligible women intending to proceed with their pregnancies, whose carrier status was not known. The median (interquartile range [IQR]) gestational age at pregnancy confirmation was 7.6 weeks (6.0-10.7 weeks) and 74% presented before 10 weeks. The median gestational age at screening was 15.3 weeks (IQR = 12.6-18.0 weeks), with only 4.4% being screened before 10 weeks. The median delay between pregnancy confirmation and screening was 6.9 weeks (4.7-9.3 weeks) After allowing for practice level variation, there was no association between delay times and maternal age, parity, and ethnic group. CONCLUSION: About 74% of women consulted for pregnancy before 10 weeks' gestation but fewer than 5% of women were screened before the target time of 10 weeks. Reducing the considerable delay between pregnancy confirmation in primary care and antenatal sickle cell and thalassaemia screening requires methods of organising and delivering antenatal care that facilitate earlier screening to be developed and evaluated.     

Recognition surfaces of MHC class I

Summary: Recent crystallographic results have provided dose to atomic resolution views of the recognition events mediated by MHC class I molecules. The specificity-conferring interaction of MHC class I/peptide with a T-cell antigen receptor (TCR) appears dependent on certain key interactions with the MHC scaffold. These interactions, in particular those of the TCR Va domain, define a standard orientation for TCR binding. Previous studies on biologically significant variations in the TCR recognition surface presented by a series of MHC/variant peptide complexes can be reassessed in the light of this TCR-building mode. The interaction of CDS with MHC class I resembles that between antibody and antigen in the use of loops from the CD8 structure. The interaction is of very low affinity and buries equivalent surface area to that between the TCR and MHC class I but while the TCR/MHC interface shows poor surface shape complementarity the match in the conservative interaction between MHC and CDS is precise.     

Mutagenicity of some benzidine congeners and their N-acetylated and N,N'-diacetylated derivatives in different strains of Salmonella typhimurium

The Ames Salmonella/microsome test was used to compare the mutagenic response of Salmonella typhimurium TA100, TA98, TA1538, and TA1535 to 12 benzidine derivatives, ie, benzidine, 3,3'-dimethoxybenzidine, 3,3'-dimethylbenzidine, 3,3'-dichlorobenzidine, and the corresponding N- and N,N'-diacetylated derivatives. With a few exceptions, the mutagenic response to this series of compounds varied in the order TA98 greater than TA1538 greater than TA100 greater than TA1535 = 0, and the N-monoacetylated derivatives were more mutagenic than either the parent diamines or the N,N'-diacetyl derivatives. The relative mutagenicities of the parent amines for TA98 were 3,3'-dichlorobenzidine much greater than 3,3'-dimethoxybenzidine greater than benzidine greater than 3,3'-dimethylbenzidine.     

Pulmonary artery remodeling and pulmonary hypertension after exposure to hyperoxia for 7 days. A morphometric and hemodynamic study.

This study shows by morphometric and hemodynamic techniques that exposure to hyperoxia at normobaric pressure causes rapid structural remodeling of rat pulmonary arteries and pulmonary hypertension. After 7 days of 90% O2, pulmonary artery cross-sectional area is reduced by a striking loss of intraacinar arteries (control, 13 +/- 1 sq mm; exposed, 8 +/- 1 sq mm; P less than 0.001), the ratio of arteries to alveoli being 4:100 in control rats and 2.5:100 after hyperoxia. The lumen of preacinar and intraacinar arteries is narrowed by a reduction of vessel external diameter (ED) and an increased medial wall thickness (MT). There is a significant reduction in the percent medial thickness [( 2 X 100 X MT]/ED) in both regions. The proportion of muscular and partially muscular intraacinar arteries increases at the expense of nonmuscular ones (P [chi 2] less than 0.01), and fully muscular arteries appear in the alveolar wall where they are not normally found. Intimal thickening occurs in 19% of alveolar duct and 34% of alveolar wall nonmuscular arteries. Right ventricular hypertrophy occurs, the ratio of the left ventricle plus the septum to the right ventricle being significantly reduced (control, 4.07 +/- 0.26; exposed, 3.23 +/- 0.10; P less than 0.02). After 3 days of 87% O2, pulmonary artery pressure is still normal (17.0 +/- 0.9 mmHg) but after 7 days it is significantly increased (26.2 +/- 0.9 mmHg; P less than 0.01), as is pulmonary vascular resistance (control, 0.033 +/- 0.003; exposed, 0.065 +/- 0.015 U/kg; P less than 0.05). Return to air breathing (after 7 days at 87% O2) causes pulmonary vasoconstriction and a further rise of the pulmonary artery pressure (to 38.3 +/- 3.3 mmHg after 60 minutes).     

DNA analysis for donor screening of Dombrock blood group antigens

Due to the scarcity of reliable antibodies, RBC typing for Doa and Dob is notoriously difficult. Inaccurate typing can place patients at risk for hemolytic transfusion reactions. The molecular basis of the DOA/DOB polymorphism is associated with three nucleotide changes:378 C>T, 624 T>C,and 793 A>G of DO. While the 378 C>T and 624 T>C are silent mutations, the 793A>G polymorphism in codon 265 encodes asparagine for Doa and aspartic acid for Dob. We describe here the use of a PCR-RFLP assay as an alternative to traditional hemagglutination for typing donor blood for Dombrock. Primers were designed to amplify the region of DO containing the 793A>G polymorphism. DNA samples from blood donors were amplified and subjected to RFLP analysis. A total of 613 samples were tested for the Dombrock polymorphism (793 A>G) by PCRRFLP. PCR-RFLP can be used to screen for Do(a-) or Do(b-) donors. This approach overcomes the scarcity of the reagents required for testing by hemagglutination.     

Pharmacological evidence for stimulation of growth hormone secretion by a central noradrenergic system in dogs

The role of brain catecholamines in the regulation of growth hormone secretion was investigated in pentobarbital-anesthetized dogs by using drugs which modify the function of adrenergic neurons and receptors. Intravenous administration of L-dopa produced a prompt, statistically significant increase in plasma growth hormone concentration. This response was not significantly reduced by blockade of peripheral dopa decarboxylase activity with carbidopa. Clonidine, an alpha-agonist which penetrates the brain, increased plasma growth hormone secretion. Norepinephrine, epinephrine, dopamine and isoproterenol, catecholamines which do not penetrate the blood-brain barrier, failed to affect plasma growth hormone concentration when administered intravenously. Apomorphine did not produce a statistically significant increase in plasma growth hormone concentration when administered directly into the the third ventricle, and pimozide failed to abolish the increase in plasma growth hormone produced by L-dopa. The increase in plasma growth hormone concentration produced by intravenous L-dopa and clonidine was prevented by administration of phentolamine or phenoxybenzamine directly into the third ventricle. The response to L-dopa was also abolished by intraventricular procaine. In dogs in which central beta-adrenergic blockade was produced by intraventricular L-propranolol, the growth hormone response to L-dopa was greater than it was in control dogs treated with intraventricular D-propranolol. The data indicate that in pentobarbital anesthetized dogs, the increase in growth hormone secretion produced by L-dopa is mediated by norepinephrine, rather than dopamine, that the site of action of the norepinephrine is central, above the median eminence and inside the 'blood-brain barrier', and that the norepinephrine acts via alpha-adrenergic receptors.