Obstetrical magnetic resonance imaging: maternal anatomy

Eleven patients whose pregnancies were at 34-36 weeks of gestational development underwent magnetic resonance (MR) imaging. Images of the maternal pelvis were assessed for anatomical changes of pregnancy in comparison with MR images of five non-pregnant volunteers. The relationship of the fetal presenting part to the internal os of the cervix was seen in all patients. Effacement of the cervix was identified when present. The maternal spine demonstrated disk abnormalities in nine patients. Changes in venous flow patterns were readily identified in all patients. The inferior vena cava was flattened or obliterated, a high signal was present in the iliac vessels (TE 56), and large collateral vessels were present.     

Initiation of growth of baboon primordial follicles in vitro

Factors that cause some primordial follicles to enter the growth phase while the others remain quiescent are unknown. The hypothesis was tested that primate primordial follicles can survive and initiate growth in vitro in serum-free medium. Superficial pieces of ovarian cortex, containing mostly primordial follicles, were obtained from baboon fetuses during late gestation and cultured for 0, 2, 4, 7, 10 or 20 days in Waymouth MB 752/1 medium supplemented with insulin, transferrin, selenium, linoleic acid, and bovine serum albumin (ITS +). Histological examination of cortical pieces revealed that after 2 and 4 days in culture, the total number of primordial follicles had decreased by 55 and 76% (P < 0.01) respectively, relative to day 0 of culture. This was associated with a sustained, 5- to 8-fold increase in total primary follicles (P < 0.01) beginning on day 2 of culture. There was also a gradual increase in the total number of early secondary and secondary follicles. The average diameter of follicles and oocytes increased gradually throughout culture for all follicular categories (P < 0.01), except secondary follicles and oocytes. Immunohistochemical localization of proliferating cell nuclear antigen (PCNA), a marker for cell proliferation and growth, showed that PCNA was generally absent in primordial follicles on day 0, but was observed after 2 or 4 days in culture in both granulosa cells and oocytes of most growing follicles. Comparison of cortical pieces cultured for 10 or 20 days with ITS + versus 10% fetal bovine serum (FBS) showed a more pronounced decrease in the numbers of primordial follicles and more primary, early secondary and secondary follicles in ITS + compared to FBS-treated cortical pieces (P < 0.01 at 20 days). These results show that primordial follicles from non-human primates can survive and develop to the secondary stage in vitro in serum-free conditions.      

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.     

Function and structure of cilia in the fallopian tube of an infertile woman with Kartagener's syndrome

In Kartagener's syndrome (KS), primary defects of the ciliary axoneme cause dyskinetic ciliary motion. Because ciliary motion is an important factor in normal ovum transport, ciliary dyskinesia may cause infertility. On the other hand, the existence of some ciliary activity, albeit abnormal, may account for fertility in some women with KS. In this case study, an infertile woman diagnosed with KS had normal results in all usual infertility tests. Biopsies of tubal mucosa were obtained at laparoscopy for ovum recovery during an in-vitro fertilization cycle. Ciliary activity, measured by laser light- scattering spectroscopy, was detected in all tubal specimens; however the majority of regions sampled showed no activity. In active regions, beat frequency ranged from 5 to 10 Hz, approximately 30% of normal. Electron microscopy showed similar morphological defects in both tubal and nasal mucosa. The number of cilia per cell was approximately 20% of normal. The major ultrastructural abnormality of cilia was an absence of the central microtubules. The only demonstrable explanation for this patient's infertility was primary ciliary dyskinesia associated with KS.      

Concepts in hypoxia reborn

The human fetus develops in a profoundly hypoxic environment. Thus, the foundations of our physiology are built in the most hypoxic conditions that we are ever likely to experience: the womb. This magnitude of exposure to hypoxia in utero is rarely experienced in adult life, with few exceptions, including severe pathophysiology in critical illness and environmental hypobaric hypoxia at high altitude. Indeed, the lowest recorded levels of arterial oxygen in adult humans are similar to those of a fetus and were recorded just below the highest attainable elevation on the Earth's surface: the summit of Mount Everest. We propose that the hypoxic intrauterine environment exerts a profound effect on human tolerance to hypoxia. Cellular mechanisms that facilitate fetal well-being may be amenable to manipulation in adults to promote survival advantage in severe hypoxemic stress. Many of these mechanisms act to modify the process of oxygen consumption rather than oxygen delivery in order to maintain adequate tissue oxygenation. The successful activation of such processes may provide a new chapter in the clinical management of hypoxemia. Thus, strategies employed to endure the relative hypoxia in utero may provide insights for the management of severe hypoxemia in adult life and ventures to high altitude may yield clues to the means by which to investigate those strategies.     

Both CD80 and CD86 co-stimulatory molecules regulate allergic pulmonary inflammation

We examined the roles of CD80 (B7-1) and CD86 (B7-2) in a model of allergic pulmonary inflammation and airway hyper-responsiveness (AHR) by selectively inhibiting either CD80 or CD86. Inhibition of co- stimulation by either CD80 or CD86 affected multiple parameters of the allergic response. Specifically, blockade of either CD80 or CD86 in ovalbumin-sensitized and challenged mice resulted in reduced expression of IL-2Ralpha (CD25) on CD4+ T lymphocytes, decreased airway eosinophilia, lower serum IgE production and diminished AHR. Importantly, blockade of CD80 and CD86 inhibited production of IL-4 and IL-2, and enhanced IFN-gamma production. Our observations support a role for both CD80- and CD86-mediated co-stimulation in development of allergic pulmonary inflammation.