Infectious agents in bovine embryo production: hazards and solutions

Infectious agents in systems for producing bovine embryos might reduce the number and quality of embryos generated, result in transmission of disease to recipients and offspring, or confound findings of research. Embryo-associated pathogens might also jeopardize human health when the goal of embryo production is creating transgenic animals intended to be a source of pharmaceuticals or organs. This paper addresses risks and resulting hazards of pathogen and microbial contaminant introduction into in vivo or in vitro embryo production systems. Additionally, methods for prevention and quality control are discussed.     

Ceramic sculpture of Russell Aitken

Abstract

Pongioli's blowing, and the scraping of the anonymous fiddlers had shaken the air in the great hall. This moved the air in Lord Edward's membrana tympani; the interlocked malleus, incus, and stirrup bones were set in motion so as to agitate the membrana of the oval window and raise an infinitesimal storm in the fluid of the labyrinth. The hairy endings of the auditory nerve shuddered like weeds in a rough sea; a vast number of obscure miracles were performed in the brain, and Lord Edward ecstatically whispered ‘Bach!’—Aldous Huxley, Point Counterpoint

Music is the supreme mystery of human knowledge.—Claude Levi-Strauss     

Expression of lymphocyte cell surface markers in workers exposed to different respiratory hazards: biomarkers of occupational respiratory disease

This study was designed to evaluate the potential of flow cytometry to measure biomarkers of airways inflammation in the peripheral blood of two cohorts of workers reporting work related respiratory symptoms, who were exposed to different respiratory hazards. Nine bakers exposed to wheat flour and 10 glass bottle manufacturers exposed to a range of irritant chemicals were selected for study. Phenotypic and inducible cell surface markers were measured by flow cytometry. Results were compared with a control population of 58 volunteers reporting no respiratory problems. The bakers showed a significant increase above control values for cell types associated with inflammation; in particular CD3 CD4 cells p 0.005 and CD4 CD25 cells p 0.01 . In contrast, the workers reporting work related respiratory symptoms who were exposed to a range of irritant chemicals showed a different pattern of cell surface lymphocyte markers, with a significant decrease in the total T cell population p 0.05 . Comparison of results from a subset of smoking controls with the population of bakers who were all heavy smokers confirmed that the increase in CD3 CD4 cells and CD4 CD25 cells could not be ascribed to the effects of smoking alone. We have shown activation of helper T cells in the peripheral blood of bakers reporting work related respiratory symptoms consistent with the changes observed in mild to severe asthmatics. However, workers with similar symptoms who were exposed to irritant chemicals did not show this pattern of phenotypic or inducible cell surface markers, reflecting an absence of airways inflammation in these individuals. Our results suggest that flow cytometry may be of use as an objective test for detecting workers with airways inflammation to allow the identification of workers at risk of developing occupational asthma.     

Expression of lymphocyte cell surface markers in workers exposed to different respiratory hazards: biomarkers of occupational respiratory disease

This study was designed to evaluate the potential of flow cytometry to measure biomarkers of airways inflammation in the peripheral blood of two cohorts of workers reporting work related respiratory symptoms, who were exposed to different respiratory hazards. Nine bakers exposed to wheat flour and 10 glass bottle manufacturers exposed to a range of irritant chemicals were selected for study. Phenotypic and inducible cell surface markers were measured by flow cytometry. Results were compared with a control population of 58 volunteers reporting no respiratory problems. The bakers showed a significant increase above control values for cell types associated with inflammation; in particular CD3 CD4 cells p 0.005 and CD4 CD25 cells p 0.01 . In contrast, the workers reporting work related respiratory symptoms who were exposed to a range of irritant chemicals showed a different pattern of cell surface lymphocyte markers, with a significant decrease in the total T cell population p 0.05 . Comparison of results from a subset of smoking controls with the population of bakers who were all heavy smokers confirmed that the increase in CD3 CD4 cells and CD4 CD25 cells could not be ascribed to the effects of smoking alone. We have shown activation of helper T cells in the peripheral blood of bakers reporting work related respiratory symptoms consistent with the changes observed in mild to severe asthmatics. However, workers with similar symptoms who were exposed to irritant chemicals did not show this pattern of phenotypic or inducible cell surface markers, reflecting an absence of airways inflammation in these individuals. Our results suggest that flow cytometry may be of use as an objective test for detecting workers with airways inflammation to allow the identification of workers at risk of developing occupational asthma.     

Infectious exacerbations of chronic obstructive pulmonary disease associated with respiratory viruses and non-typeable Haemophilus influenzae

Infectious exacerbations of chronic obstructive pulmonary disease (COPD) have been reported to occur with both viral and bacterial pathogens. In this study, 35 exacerbations associated with the isolation of non-typeable Haemophilus influenzae from sputum were identified as part of a prospective longitudinal study. Samples from these patients were subjected to immunoassays to identify a new immune response to the homologous isolate of non-typeable H. influenzae to more accurately assess a bacterial etiology. These patients also were studied carefully for evidence of viral infection using viral culture, serology and polymerase chain reaction-based assays. Sixteen of 35 exacerbations (45.7%) were associated with evidence of acute viral infection and 11 of the 35 exacerbations (31.4%) were associated with the development of new serum IgG to homologous non-typeable H. influenzae. Overall, evidence of infection with a respiratory virus or non-typeable H. influenzae was seen in 24 of 35 exacerbations (68.6%). No association between viral infection and immune response to non-typeable H. influenzae was observed, although a trend toward an immune response to non-typeable H. influenzae and absence of viral infection was seen. The results show that exacerbations in adults with COPD were associated with infection caused by virus alone, non-typeable H. influenzae alone, or virus and non-typeable H. influenzae simultaneously.     

Taxonomic,evolutionary, and functional considerations ofCompositae pollen ultrastructure and sculpture

Two basic patterns of exine ultrastructure are found in theCompositae, the caveate Helianthoid pattern and the non-caveate Anthemoid pattern. TheHeliantheae, Astereae, Inuleae, Sececioneae, Calenduleae andEupatorieae all have pollen with caveate exines. TheMutisiseae, Vernonieae andCardueae have predominately Anthemoid pollen. TheAnthemideae, Arctoteae andLactuceae have pollen with exines of both patterns. Recent investigations of pollen in theVernonieae suggest that these exine ultrastructures in the family have evolved in response to mechanical stresses on the wall which are caused by changes in volume of the grain as it loses or gains water from its environment.     

Curette fat sculpture in rhytidectomy: improving the nasolabial and labiomandibular folds

The nasolabial and labiomandibular folds develop with facial aging by an anterior caudal descent of the fat prominences of the same name. Young patients with minimal folding can be corrected by substances inserted in the fold; however, this and other techniques have failed satisfactorily to improve the folds naturally and permanently. Identification of the prominences and removal of the fat superficial to the skin by curettes have proven safe and effective and superior to fat suction. Complications include small hematomas and visible depressions in the sculpted areas. There was no nerve or skin injury. Follow-up of this technique (an improvement of a previous technique) is 3 1/2 years.     

Infectious prions and proteinopathies

Transmissible spongiform encephalopathies (TSEs) are caused by an infectious agent that is thought to consist of only misfolded and aggregated prion protein (PrP). Unlike conventional micro-organisms, the agent spreads and propagates by binding to and converting normal host PrP into the abnormal conformer, increasing the infectious titre. Synthetic prions, composed of refolded fibrillar forms of recombinant PrP (rec-PrP) have been generated to address whether PrP aggregates alone are indeed infectious prions. In several reports, the development of TSE disease has been described following inoculation and passage of rec-PrP fibrils in transgenic mice and hamsters. However in studies described here we show that inoculation of rec-PrP fibrils does not always cause clinical TSE disease or increased infectious titre, but can seed the formation of PrP amyloid plaques in PrP-P101L knock-in transgenic mice (101LL). These data are reminiscent of the “prion-like” spread of misfolded protein in other models of neurodegenerative disease following inoculation of transgenic mice with pre-formed amyloid seeds. Protein misfolding, even when the protein is PrP, does not inevitably lead to the development of an infectious TSE disease. It is possible that most in vivo and in vitro produced misfolded PrP is not infectious and that only a specific subpopulation is associated with infectivity and neurotoxicity.     

Infectious Agents and Neurodegeneration

A growing body of epidemiologic and experimental data point to chronic bacterial and viral infections as possible risk factors for neurodegenerative diseases, including Alzheimer??s disease, Parkinson??s disease and amyotrophic lateral sclerosis. Infections of the central nervous system, especially those characterized by a chronic progressive course, may produce multiple damage in infected and neighbouring cells. The activation of inflammatory processes and host immune responses cause chronic damage resulting in alterations of neuronal function and viability, but different pathogens can also directly trigger neurotoxic pathways. Indeed, viral and microbial agents have been reported to produce molecular hallmarks of neurodegeneration, such as the production and deposit of misfolded protein aggregates, oxidative stress, deficient autophagic processes, synaptopathies and neuronal death. These effects may act in synergy with other recognized risk factors, such as aging, concomitant metabolic diseases and the host??s specific genetic signature. This review will focus on the contribution given to neurodegeneration by herpes simplex type-1, human immunodeficiency and influenza viruses, and by Chlamydia pneumoniae.