Junctional adhesion molecule (JAM) is involved in tight junction (TJ) formation in epithelial cells. Three JAMs (A, B, and C) are expressed in rat hepatocytes, but only rat JAM-A is present in polarized WIF-B cells, a rat-human hepatic line. We used knockdown (KD) and overexpression in WIF-B cells to determine the role of JAM-A in the development of hepatic polarity. Expression of rat JAM-A short hairpin RNA resulted in ϳ50% KD of JAM-A and substantial loss of hepatic polarity, as measured by the absence of apical cysts formed by adjacent cells and sealed by TJ belts. When inhibitory RNA-resistant human JAM-A (huWT) was expressed in KD cells, hepatic polarity was restored. In contrast, expression of JAM-A that either lacked its PDZ-binding motif (hu⌬C-term) or harbored a point mutation (T273A) did not complement, indicating that multiple sites within JAM-A's cytoplasmic tail are required for the development of hepatic polarity. Overexpression of huWT in normal WIF-B cells unexpectedly blocked WIF-B maturation to the hepatic phenotype, as did expression of three huJAM-A constructs with single point mutations in putative phosphorylation sites. In contrast, hu⌬C-term was without effect, and the T273A mutant only partially blocked maturation. Our results show that JAM-A is essential for the development of polarity in cultured hepatic cells via its possible phosphorylation and recruitment of relevant PDZ proteins and that hepatic polarity is achieved within a narrow range of JAM-A expression levels. Importantly, formation/ maintenance of TJs and the apical domain in hepatic cells are linked, unlike simple epithelia.partitioning-defective polarity protein/atypical protein kinase C complex
Sacroiliac (SI) joint disease is a common cause of low back pain. It is not easily diagnosed by physical examination, as the joint has limited mobility and referral patterns are not sufficiently delineated from other pathological conditions implicated in low back pain. The accuracy of provocative testing of the sacroiliac joint is controversial. Many physicians use injection of the SI joint with local anesthetic and/or steroid as a diagnostic and therapeutic tool in treating SI joint–related pain. Historically, SI joint intra-articular injections have been performed without imaging guidance. Imaging-guided techniques, often using CT fluoroscopy, increase the precision of these procedures and help confirm needle placement while achieving better results and reduced complications rates. Sacroiliac joint injection is routinely performed on an outpatient basis. The patient is questioned regarding previous steroid use (oral, cutaneous, or injected) to avoid iatrogenic Cushing syndrome. Repeat injections can be administered depending on patient’s response.
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