It has been found that ultrasonic effects upon mammalian CNS chemical synapses are among the earliest morphologic changes that occur. This provides a possible explanation for the earlier findings which showed that a functional effect can be recorded almost immediately following certain ultrasonic exposures while no morphological abnormalities were observed with the light microscope.
Small heterodimer partner (Shp) regulates several metabolic processes, including bile acid levels, but lacks the conserved DNA binding domain. Phylogenetic analysis revealed conserved genetic evolution of SHP, FXR, CYP7A1 and CYP8B1. Shp, although primarily studied as a downstream target of Farnesoid X Receptor (Fxr), has a distinct hepatic role that is poorly understood. Here we report that liver-specific Shp knockout (LShpKO) mice have impaired negative feedback of Cyp7a1 and Cyp8b1 upon bile acid challenge and demonstrate that a single copy of the Shp gene is sufficient to maintain this response. LShpKO mice also exhibit elevated total bile acid pool with ileal bile acid composition mimicking that of CA-fed control mice. Agonistic activation of Fxr (GW4064) in the LShpKO did not alter the elevated basal expression of Cyp8b1 but lowered Cyp7a1 expression. We found that deletion of Shp led to an enrichment of distinct motifs and pathways associated with circadian rhythm, copper ion transport, and DNA synthesis. We confirmed increased expression of metallothionein genes that can regulate copper levels in the absence of SHP. LShpKO livers also displayed a higher basal proliferation that was exacerbated specifically with bile acid challenge either with cholic acid or 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine but not with another liver mitogen, TCPOBOP (TC). Overall, our data indicate that hepatic SHP uniquely regulates certain proliferative and metabolic cues.
Abstract-Mouseovaries were exposed in uiuo to I MHz continuous wave ultrasonic energy at spatial peak intensities ranging from 5 to 100 W/cm' for times varying from 300 to 15 s depending on the intensity. Following exposure the ovaries were surgically removed at times ranging from immediately (within 60 s) to 7 days and prepared histologically for light microscopic analysis. The observed tissue alterations varied from severe, at the higher intensities to subtle, at the lower intensities. Lesions were manifested by pyknosis of cells, vacuolization of cells and tissue, eosinophilic cytoplasm, and general cellular disruption. Subtle alterations showed large numbers of polyovular follicles and increases in the amount of PAS positive material in the interstitial tissue. Various ovarian structures showed differing sensitivities to the insult with luteinized structures being preferentially altered.
Canine thyroid carcinomas are relatively common malignant endocrine neoplasms in dogs derived from either thyroid follicular cells (forming follicular thyroid carcinomas) or medullary cells (parafollicular, C-cells; forming medullary thyroid carcinomas). Older and recent clinical studies often fail to discriminate between compact cellular (solid) follicular thyroid carcinomas and medullary thyroid carcinomas, which may skew conclusions. The compact subtype of follicular thyroid carcinomas appears to be the least differentiated subtype of follicular thyroid carcinomas and needs to be differentiated from medullary thyroid carcinomas. This review includes information on the signalment, presentation, etiopathogenesis, classification, histologic and immunohistochemical diagnosis, clinical management, and biochemical and genetic derangements of canine follicular and medullary carcinomas, and their correlates with human medicine.
Earlier studies [Science 127, 83 (1958)] showed that functional changes-appear virtually instantaneously in response to appropriate ultrasonic exposure of CNS structures, though structural changes, as observed by optical microscopy, did not become manifest until approximately 10–15 min later [A.M.A. Arch. Neurol. Psychiatry 75, 15 (1956)]. It was thus believed that the ultrasound acted initially upon structures too small to be observed in the light microscope, and that time was required for the physiological progression to proceed to appropriate dimensions for observation [Am..!. Phys. Med. 37, 148 (1958)]. Recent studies [Ultrasound Med. Biol. 5, 167 (1979); 6, 1239 (1980)] have shown that ultra-structural organelles such as mitochondria, nuclei, endoplasmic reticulum, lysosomes, and attached ribosomes are indeed affected by ultrasound. It has now been observed that ultrasound also affects, within very short periods of time, synapses. thus providing an explanation for functional changes observed virtually instantaneously with the ultrasonic insult. Dosage conditions are in the neighborhood of 300 W/cm2 for 1 s at 1 MHz. Changes have also been observed in microtubules, neurofilaments and free ribosomes, in addition to previously unreported morphological alterations in nuclei and mitochondria. [This research was supported by the National Science Foundation.]
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