The human adrenal cortex consists of three functionally and structurally distinct layers; zona glomerulosa, zona fasciculata (zF), and zona reticularis (zR), and produces adrenal steroid hormones in ...a layer-specific manner; aldosterone, cortisol, and adrenal androgens, respectively. Cortisol-producing adenomas (CPAs) occur mostly as a result of somatic mutations associated with the protein kinase A pathway. However, how CPAs develop after adrenocortical cells acquire genetic mutations, remains poorly understood.
We conducted integrated approaches combining the detailed histopathologic studies with genetic, RNA-sequencing, and spatially resolved transcriptome (SRT) analyses for the adrenal cortices adjacent to human adrenocortical tumours.
Histopathological analysis revealed an adrenocortical nodular structure that exhibits the two-layered zF- and zR-like structure. The nodular structures harbour GNAS somatic mutations, known as a driver mutation of CPAs, and confer cell proliferative and autonomous steroidogenic capacities, which we termed steroids-producing nodules (SPNs). RNA-sequencing coupled with SRT analysis suggests that the expansion of the zF-like structure contributes to the formation of CPAs, whereas the zR-like structure is characterised by a macrophage-mediated immune response.
We postulate that CPAs arise from a precursor lesion, SPNs, where two distinct cell populations might contribute differently to adrenocortical tumorigenesis. Our data also provide clues to the molecular mechanisms underlying the layered structures of human adrenocortical tissues.
KAKENHI, The Uehara Memorial Foundation, Daiwa Securities Health Foundation, Kaibara Morikazu Medical Science Promotion Foundation, Secom Science and Technology Foundation, ONO Medical Research Foundation, and Japan Foundation for Applied Enzymology.
Dorsal root ganglion (DRG) neurons project their axons to specific target layers in the gray matter of the spinal cord, according to their sensory modality (Neuron 30 (2001), 707; Cell 101 (2000), ...485; Neuron 31 (2001), 59; J. Comp. Neurol. 380 (1997), 215; Sensory Neurons, Oxford Univ. Press, New York, 1992, p. 131). Expression of
runt-related
Runx/AML genes (Mech. Dev. 109 (2001), 413) on subtypes of DRG neurons suggests their involvement in lamina-specific afferent differentiation and maturation. Here we show that
Runx3−/− mice display severe limb ataxia and abnormal posture and that most of them die shortly after birth. They show that proprioceptive afferent axons fail to reach the ventral horn and have a smaller dorsal funiculus in their spinal cords. Despite the strong resemblance of this phenotype to that of knockout mice deficient in neurotrophin-3 (
NT-3) (Cell 77 (1994), 503; Nature 369 (1994), 658) and its receptor,
trkC, (Nature 368 (1994), 249), which show proprioceptive afferent loss through selective neuronal cell death,
Runx3−/− mice maintain normal number of TrkC/
trkC positive DRG neurons throughout development. Our results suggest that
Runx3 controls the target-specific axon pathfinding of
trkC-expressing DRG neurons in the spinal cord.
Background and Purpose: Appraisal of the current practice of intravenous thrombolysis with recombinant tissue plasminogen activator (tPA) for treatment of acute ischemic stroke in a large ...metropolitan city.Method: We analyzed demographic factors, ischemic stroke types, and outcomes of all patients who were treated with tPA between October 11, 2005 and October 10, 2010 in our hospital, which serves as a regional referral center located in the bay area of the metropolitan city of Osaka. We also divided our patients into those residing in the bay area and others residing outside the bay area. For statistical analysis, we used chi-square (Pearson) test or nonparametric Wilcoxon test as indicated. We considered p<0.05 to be significant.Results: The number of cases treated with tPA was 105 (69.2±14.4 years), accounting for 7.0% of all acute ischemic stroke and 0.0088% of local residents. While there were many embolic strokes among those living in the bay area, younger patients and the incidence of cervico-cerebral arterial dissections were encountered among those living outside the bay area.Conclusion: The rate of tPA treatment as per local population was higher than that reported in J-MARS. Regional differences encountered here likely reflected the increase of daytime population by an influx of people to metropolitan cities such as Osaka.
Four parameters of pupillary light reflex were investigated from May to December in 2011 to study the effects of low serum vitamin A level on pupillary light reflex in Japanese black cattle during ...their vitamin A controlled stage. A 2CCD camera was used to acquire the pupillary light reflex images. Constriction amplitude in 1 second, maximum constriction velocity, maximum velocity time and initial pupil roundness were used for pupillary light reflex analysis. Cattle in low vitamin A level period had larger constriction amplitude in 1 second (p=0.001), higher maximum constriction velocity (p=0.016) and thinner resting pupil (p=0.003). This result showed pupillary light reflex analysis can be used as indicators for cattle management during vitamin A controlled stage.
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