Functional roles of the NH 2 -terminal region of RGS (regulators of G protein signaling) 8 in G protein signaling were studied. The deletion of the NH 2 -terminal region of RGS8 (⌬NRGS8) resulted in a partial loss of the inhibitory function in pheromone response of yeasts, although G␣ binding was not affected. To examine roles in subcellular distribution, we coexpressed two fusion proteins of RGS8-RFP and ⌬NRGS8-GFP in DDT1MF2 cells. RGS8-RFP was highly concentrated in nuclei of unstimulated cells. Coexpression of constitutively active G␣ o resulted in translocation of RGS8 protein to the plasma membrane. In contrast, ⌬NRGS8-GFP was distributed diffusely through the cytoplasm in the presence or absence of active G␣ o . When coexpressed with G protein-gated inwardly rectifying K ؉ channels, ⌬NRGS8 accelerated both turning on and off similar to RGS8. Acute desensitization of G protein-gated inwardly rectifying K ؉ current observed in the presence of RGS8, however, was not induced by ⌬NRGS8. Thus, we, for the first time, showed that the NH 2 terminus of RGS8 contributes to the subcellular localization and to the desensitization of the G protein-coupled response. RGS1 (regulators of G protein signaling) proteins comprise a large family of more than 20 members that modulate heterotrimeric G protein signaling (1, 2). This protein family was originally identified as a pheromone desensitization factor in yeast (3). Many members of RGS protein family were subsequently identified by virtue of a common stretch of 120 amino acids termed the RGS domain in organisms ranging from yeast to human (1,2,4,5). It was shown that several RGS proteins (RGS1, RGS3, RGS4, and GAIP) attenuate G protein signaling in cultures (4,6,7). Biochemical studies demonstrated that RGS members function as a GTPase-activating protein for ␣ subunits of heterotrimeric G proteins (8, 9, 10). Therefore, RGS proteins are proposed to down-regulate G protein signaling in vivo by enhancing the rate of G␣ GTP hydrolysis.We previously searched for RGS proteins specifically expressed in neural cells using a culture system of neuronally differentiating P19 cells. We isolated cDNA of RGS8 and identified it as a RGS protein induced in differentiated P19 cells (11). In addition, since RGS7 had been reported to be expressed predominantly in the brain (5), we also isolated a full-length cDNA of RGS7 (12). Biochemical studies indicated that RGS8 binds to G␣ o and G␣ i3 , and that RGS7 binds to G␣ o , G␣ i3 , and G␣ z . To examine effects of each RGS protein on G protein signaling, we coexpressed a G protein-coupled receptor and a G protein-coupled inwardly rectifying K ϩ channel (GIRK1/2) (13-15) in Xenopus oocytes and analyzed the activation and deactivation kinetics. We observed that RGS8 significantly speeds up both activation and deactivation of GIRK current (11). Doupnik et al. (16) reported the similar accelerated kinetics of GIRK current by RGS1, RGS3, or RGS4. We further observed that RGS8 induces acute desensitization of receptor-activated GIRK current in th...

Abstract-The outcome of spontaneous intracranial hypotension has been unpredictable. The results of initial MRI were correlated to outcome of treatment in 33 patients with spontaneous intracranial hypotension. A good outcome was obtained in 25 (97%) of 26 patients with an abnormal MRI vs only 1 (14%) of 7 patients with a normal MRI (p ϭ 0.00004). These findings show that normal initial MRI is predictive of poor outcome in spontaneous intracranial hypotension. NEUROLOGY 2005;64:1282-1284 Wouter I. Schievink, MD; M. Marcel Maya, MD; and Charles Louy, MD Spontaneous intracranial hypotension is increasingly recognized as an important cause of new daily persistent headaches, although an initial misdiagnosis remains common.1 The cause of spontaneous intracranial hypotension is a spontaneous spinal CSF leak often associated with an underlying generalized connective tissue disorder.2 Most cases of spontaneous intracranial hypotension are believed to be selflimiting, and initial treatment is centered around a course of bedrest and hydration. Nevertheless, persistent symptoms are present in the majority of patients who come to medical attention; for those, a variety of treatment options are available, including epidural blood patching, 3 percutaneous fibrin sealant placement, 4 and surgical repair of the underlying CSF leak. 5 The reported results of these various treatments have generally been good, but the outcome of spontaneous intracranial hypotension is unpredictable and some patients have persistent and often incapacitating symptoms in spite of maximal medical and surgical treatments. The vast majority of patients with spontaneous intracranial hypotension undergo cranial MRI scanning early in their clinical course prior to any therapeutic intervention. It has been our experience that patients with recalcitrant symptoms generally have had normal MRI findings. We therefore investigated a large group of patients with spontaneous intracranial hypotension to determine whether abnormalities on initial MRI can predict outcome.Methods. The patient population consisted of a group of 33 consecutive patients with spontaneous spinal CSF leaks and intracranial hypotension who were referred to us for evaluation and treatment. The mean age of the 23 women and 10 men was 41 years (range 13 to 72 years). The presenting symptom was a positional headache in 31 patients, a nonpositional headache in one patient, and nonpositional neck pain in one patient. Cranial MRI was available for all patients, which was reviewed for features of intracranial hypotension. The presence of a spinal CSF leak was confirmed by CT myelography in all patients. Radionuclide cisternography was performed in only a few patients because CT myelography has almost completely replaced this nuclear medicine study in our practice. None of the patients had a cranial CSF leak. Treatment consisted of 1) conservative measures such as bedrest, oral hydration, oral caffeine, and use of an abdominal binder; 2) high-volume epidural blood patching (up to 80 mL) injected at th...

Aim This study aims to elucidate the foreign patient‐specific factors associated with emergency department length of stay (EDLOS) in a regional core hospital emergency department (ED) in Japan. Methods This retrospective observational study included non‐Japanese patients who visited the ED in a Japanese regional core hospital between April 1, 2018, and March 31, 2020. The effects on EDLOS were assessed using multivariate linear regression analysis, which included factors such as age, sex, consultation language, interpreter usage, arrival time, day of visit, mode of arrival, underlying disease, triage level, diagnosis of injury/noninjury, diagnostic investigations, consultation with specialists, and treatments or procedures. Results Of 65,297 ED patients, there were 777 study patients, with a median age of 37 years (interquartile range [IQR], 24.0–50.0). The median EDLOS was 101 min (IQR, 63.0–153.0). Multivariate linear regression analysis indicated that an extended EDLOS was associated with: language apart from Japanese, Chinese, or English (51.7 min; 95% confidence interval [CI], 17.8–85.6), helicopter arrival (115.6 min; 95% CI, 48.8–182.5), blood testing (60.5 min; 95% CI, 34.6–86.4), computed tomography (23.8 min; 95% CI, 3.7–43.9), consultation with specialists (36.2 min; 95% CI, 11.8–60.6), intravenous fluid/medication (29.7 min; 95% CI, 3.3–56.1), and surgical procedure/reduction/fixation in the ED (38.8 min; 95% CI, 14.2–63.4). Conclusions Consultation in a language other than Japanese, English, or Chinese was associated with a longer EDLOS in a regional core hospital in Japan. Devising ways to accommodate patients who speak various languages could be important.

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