Regulation of myosin light chain phosphatase (MLCP) via protein kinase C (PKC) and the 17 kDa PKC-potentiated inhibitor of myosin light chain phosphatase (CPI-17) has been reported as a Ca2+ sensitization signaling pathway in smooth muscle (SM), and thus may be involved in tonic vs. phasic contractions. This study examined the protein expression and spatial-temporal distribution of PKCα and CPI-17 in intact SM tissues. KCl or carbachol (CCh) stimulation of tonic stomach fundus SM generates a sustained contraction while the phasic stomach antrum generates a transient contraction. In addition, the tonic fundus generates greater relative force than phasic antrum with 1 µM phorbol 12, 13-dibutyrate (PDBu) stimulation which is reported to activate the PKCα – CPI-17 pathway. Western blot analyses demonstrated that this contractile difference was not caused by a difference in the protein expression of PKCα or CPI-17 between these two tissues. Immunohistochemical results show that the distribution of PKCα in the longitudinal and circular layers of the fundus and antrum do not differ, being predominantly localized near the SM cell plasma membrane. Stimulation of either tissue with 1 µM PDBu or 1 µM CCh does not alter this peripheral PKCα distribution. There are no differences between these two tissues for the CPI-17 distribution, but unlike the PKCα distribution, CPI-17 appears to be diffusely distributed throughout the cytoplasm under relaxed tissue conditions but shifts to a primarily peripheral distribution at the plasma membrane with stimulation of the tissues with 1 µM PDBu or 1 µM CCh. Results from double labeling show that neither PKCα nor CPI-17 co-localize at the adherens junction (vinculin/talin) at the membrane but they do co-localize with each other and with caveoli (caveolin) at the membrane. This lack of difference suggests that the PKCα - CPI-17 pathway is not responsible for the tonic vs. phasic contractions observed in stomach fundus and antrum.

Background Hyperintensities in the splenium of the corpus callosum (CCS) have been proposed as a radiographic diagnostic criterion for fragile X‐associated tremor ataxia syndrome (FXTAS). Methods Magnetic resonance images from patients with FXTAS and from nonpremutation carriers with movement disorders were viewed by a radiologist who was blinded to gene status, and radiographic criteria for FXTAS were scored. Phenotypic data used for diagnosis of FXTAS also were collected. Results Twenty‐two patients with FXTAS and 23 controls were included. Hyperintensity in the CCS (the CCS sign) was more common in men with FXTAS versus controls (87% vs. 40%) but not in women with FXTAS (100% vs. 50% in controls). The CCS sign had higher sensitivity compared with the middle cerebellar peduncle sign (white matter lesions in middle cerebellar peduncle) in both men (0.87 vs. 0.67) and women (1 vs. 0.29) with FXTAS, but it had lower specificity in both men (0.6 vs. 0.8) and women (0.5 vs. 1). Conclusions The CCS sign is common in patients with FXTAS, but it is not significantly more prevalent in women with FXTAS compared with controls. This may be due to small sample sizes in the current study. Other signs, such as brainstem white matter disease, were more common in women with FXTAS and differed from those in men with FXTAS. This finding suggests that additional studies evaluating the diagnostic criteria for FXTAS need to be conducted, ideally with neuropathological confirmation of the disease.

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Purpose To describe a case of massive spontaneous subconjunctival hemorrhage in a patient taking warfarin with a therapeutic international normalized ratio (INR). Observations Massive circumferential hemorrhagic chemosis, extensive periorbital and facial ecchymosis, and active arterial extravasation in the subconjunctiva which required cessation and reversal of anticoagulation. Findings gradually resolved over several months after discharge. Conclusions and importance While subconjunctival hemorrhage, even in anticoagulated patients, is usually benign, rare examples of severe presentations exist. We present, to our knowledge, the first documented case of a subconjunctival hemorrhage necessitating cessation and reversal of anticoagulation in the setting of a therapeutic INR.