Tissue relaxation time: in vivo field dependence

Relaxation times (T1 and T2) were measured in vivo in mongrel dogs at fields of 0.3, 0.5, 1.0, 1.35, and 1.5 tesla (T). T1 was measured using nine values of inversion time ranging from 10 to 1,280 msec. T2 was measured with a four-point multiple spin-echo sequence. Relaxation times were calculated for muscle, kidney cortex, spleen, and adipose tissue. T2 is independent of field. A linear fit to the field dependence of T1 yields slopes of 400-500 msec/T for tissues in which the primary source of protons is water. The lower slope of adipose (approximately 150 msec/T) reflects the different mechanism of spin-lattice relaxation of the -CH2 protons.     

Purification and characterization of 26S proteasomes from human and mouse spermatozoa

We purified by fractionation on 10-40% glycerol gradients, 26S proteasomes from normal human spermatozoa. These proteasomes, which participate in the ATP-dependent degradation of ubiquitinated proteins, share a similar sedimentation coefficient to those purified from other human tissues. Fluorogenic peptide assays reveal they have chymotrypsin, trypsin and peptidyl-glutamyl-like peptide hydrolysing activities; the chymotrypsin activity is ablated by the specific 26S proteasome inhibitor MG132. Confirmation that these large proteases are 26S proteasomes is provided by detection of the 20S proteasome subunits HC2, XAPC7, RN3 and Z and regulatory ATPases MSS1, TBP1, SUG1 and SUG2 by Western analyses with monoclonal antisera. These antigens are found only in the gradient fractions enriched in proteolytic activities. We have also shown that, although mature spermatozoa from mice have considerably reduced amounts of a ubiquitin-conjugating enzyme (E2) and ubiquitin-protein conjugates in comparison with less mature germ cells, they retain relatively high values of 26S proteasome activity. This suggests that proteasomes may have further roles to play in normal sperm physiology.      

Insulin‐like growth factor‐II is produced by,signals to and is an important survival factor for the mature podocyte in man and mouse

Podocytes are crucial for preventing the passage of albumin into the urine and, when lost, are associated with the development of albuminuria, renal failure and cardiovascular disease. Podocytes have limited capacity to regenerate, therefore pro‐survival mechanisms are critically important. Insulin‐like growth factor‐II (IGF‐II) is a potent survival and growth factor; however, its major function is thought to be in prenatal development, when circulating levels are high. IGF‐II has only previously been reported to continue to be expressed in discrete regions of the brain into adulthood in rodents, with systemic levels being undetectable. Using conditionally immortalized human and ex vivo adult mouse cells of the glomerulus, we demonstrated the podocyte to be the major glomerular source and target of IGF‐II; it signals to this cell via the IGF‐I receptor via the PI3 kinase and MAPK pathways. Functionally, a reduction in IGF signalling causes podocyte cell death in vitro and glomerular disease in vivo in an aged IGF‐II transgenic mouse that produces approximately 60% of IGF‐II due to a lack of the P2 promoter of this gene. Collectively, this work reveals the fundamental importance of IGF‐II in the mature podocyte for glomerular health across mammalian species. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Evolution of the Dinosauriform Respiratory Apparatus: New Evidence from the Postcranial Axial Skeleton

Examination of the thoracic rib and vertebral anatomy of extant archosaurs indicates a relationship between the postcranial axial skeleton and pulmonary anatomy. Lung ventilation in extant crocodilians is primarily achieved with a hepatic piston pump and costal rotation. The tubercula and capitula of the ribs lie on the horizontal plane, forming a smooth thoracic “ceiling” facilitating movement of the viscera. Although the parietal pleura is anchored to the dorsal thoracic wall, the dorsal visceral pleura exhibits a greater freedom of movement. The air sac system and lungs of birds are associated with bicapitate ribs with a ventrally positioned capitular articulation, generating a rigid and furrowed rib cage that minimizes dorsoventral changes in volume in the dorsal thorax. The thin walled bronchi are kept from collapsing by fusion of the lung to the thorax on all sides. Data from this study suggest a progression from a dorsally rigid, heterogeneously partitioned, multichambered lung in basal dinosauriform archosaurs towards the small entirely rigid avian‐style lung that was likely present in saurischian dinosaurs, consistent with a constant volume cavum pulmonale, thin walled parabronchi, and distinct air sacs. There is no vertebral evidence for a crocodilian hepatic piston pump in any of the taxa reviewed. The evidence for both a rigid lung and unidirectional airflow in dinosauriformes raises the possibility that these animals had a highly efficient lung relative to other Mesozoic vertebrates, which may have contributed to their successful radiation during this time period. Anat Rec, 2011. © 2011 Wiley‐Liss, Inc.     

Characteristics of asbestos concentration in lung as compared to asbestos concentration in various levels of lymph nodes that collect drainage from the lung

Inhaled dust particulates are able to relocate to the extrapulmonary compartments, particularly the lymph nodes that drain the lung. There is little information about the concentration and type of asbestos in the lymphatics and lymph nodes. Quantitative analysis of asbestos lymph node burden conducted by light and analytical transmission electron microscopy has shown ferruginous bodies in lymph nodes that drain the lung and appreciable numbers of short asbestos fibers accumulate in lymph nodes in occupationally exposed individuals. The location of lymph nodes in the thoracic cavity was categorized according to the Naruke anatomical map. Tissue from eleven individuals with a history of asbestos exposure were selected for a comparative study of the asbestos content of lung with that found in the thoracic lymph nodes. The study used a digestion technique for tissue preparation and evaluated ferruginous body burden and concentration of asbestos fibers (> 0.5 microm in length). Comparison was made between sites and analysis was made as to the population of fibers detectable by light microscopy and defined as "Stanton fibers." The findings indicated the vast majority of all asbestos fiber types in all sites were shorter than 5 microm and would not have been counted in a light microscopy count scheme that included only those fibers > 5 microm. There were reproducible patterns of asbestos types of found in various lymph nodes, although there were variations in the amount of asbestos found in the sites sampled. In summary, asbestos fibers found in thoracic lymph nodes have predominately short fibers and, in this study group, consisted of a mixture of commercial and noncommercial amphiboles. When a long/thin fiber was found in the lung or lymph tissue, its detection required the use of analytical transmission electron microscopy for identification.     

Quality of routine spirometry tests in Dutch general practices

Background

Spirometry is an indispensable tool for diagnosis and monitoring of chronic airways disease in primary care.

Aim

To establish the quality of routine spirometry tests in general practice, and explore associations between test quality and patient characteristics.

Design of study

Analysis of routine spirometry test records.

Setting

Fifteen general practices which had a working agreement with a local hospital pulmonary function laboratory for spirometry assessment regarding test quality and interpretation.

Method

Spirometry tests were judged by a pulmonary function technician and a chest physician. Proportions of test adequacy were analysed using markers for manoeuvre acceptability and test reproducibility derived from the 1994 American Thoracic Society spirometry guideline. Associations between quality markers and age, sex, and severity of obstruction were examined using logistic regression.

Results

Practices performed a mean of four (standard deviation = 2) spirometry tests per week; 1271 tests from 1091 adult patients were analysed; 96.4% (95% confidence interval [CI] = 95.6 to 97.2) of all tests consisted of ≥3 blows. With 60.6% of tests, forced expiratory time was the marker with the lowest acceptability rate. An overall 38.8% (95% CI = 36.0 to 41.6) of the tests met the acceptability as well as reproducibility criteria. Age, sex, and severity of obstruction were associated with test quality markers.

Conclusion

The quality of routine spirometry tests was better than in previous reports from primary care research settings, but there is still substantial room for improvement. Sufficient duration of forced expiratory time is the quality marker with the highest rate of inadequacy. Primary care professionals should be aware of patient characteristics that may diminish the quality of their spirometry tests. Further research is needed to establish to what extent spirometry tests that are inadequate, according to stringent international expert criteria, result in incorrect clinical interpretations in general practice.