Staurosporine, a protein kinase inhibitor, is known to mimic the effect of nerve growth factor (NGF) in promoting neurite outgrowth. To elucidate the mechanism by which staurosporine induces neurite outgrowth in PC-12 cells, we performed an in-gel kinase assay using myelin basic protein as a substrate, and found that staurosporine induced the activation of a kinase with an apparent molecular mass of 57 kDa. The dose of staurosporine required to activate this kinase was consistent with that required to induce neurite outgrowth. Interestingly, the staurosporine-activated kinase was immunoprecipitated by anti-c-Jun NH 2 -terminal kinase (JNK) isoforms antibody, but not by anti-JNK1-specific antibody or anti-ERK1 antibody, raising the possibility that this kinase is a novel JNK isoform. The substrate specificity of the kinase was distinct from those of osmotic shock-activated JNKs and NGF-activated ERK1. The kinase phosphorylates transcription factors including cJun, Elk-1, and ATF2, as well as myelin basic protein, suggesting that it plays a role in gene induction. Furthermore, staurosporine induced immediate-early genes including Nur77 and fos, but not jun. The activation of the staurosporine-activated kinase, as well as the induction of neurite outgrowth, did not require Ras function, while Ras was required for the activation of ERKs and neurite outgrowth induced by NGF. Taken together, these results indicate staurosporine specifically activates a JNK isoform, which may contribute to biological activities including neurite outgrowth.Neurotrophic factors play a key role in the normal development of the nervous system by regulating both differentiation and apoptosis of neurons (1). Nerve growth factor (NGF) 1 is the prototype of this family of neurotrophins and its intracellular signaling pathways have been intensely studied using rat pheochromocytoma PC-12 cells, which undergo neuronal differentiation in response to NGF stimulation (1, 2). NGF binds and activates its receptor, Trk, which leads to the activation of a guanine nucleotide-binding protein, Ras (3-5). Expression of oncogenic Ras in PC-12 cells induces neuronal differentiation (6), while introduction of anti-Ras antibody or dominant inhibitory Ras mutant into PC-12 cells blocks NGF-induced differentiation (7,8), suggesting that Ras is necessary and sufficient for neuronal differentiation in PC-12 cells. The formation of GTP-Ras is followed first by the activation of Raf and then by activation of MEK (9, 10). MEK in turn activates the ERK family of MAP kinases, which then phosphorylate a variety of proteins including Elk-1 transcription factor (11-13). The expression of a dominant inhibitory mutant of Ras inhibits activation of the Raf/MEK/ERK kinase cascade (14 -16). Furthermore, recent studies revealed that MEK and ERK play an important role in NGF-induced differentiation (17, 18). These results indicate the Ras/Raf/MEK/ERK signaling pathway plays a key role in NGF-induced differentiation in PC-12 cells.The molecular cloning of c-Jun NH 2 -terminal ki...

BackgroundConcerns about sodium overload when using sodium polystyrene sulfonate (Na-resin) as an ion-exchange resin for the treatment of hyperkalemia led our institution to gradually shift to the use of calcium polystyrene sulfonate (Ca-resin). However, as serum potassium levels were insufficiently controlled and patients experienced constipation, we returned to using Na-resin and observed better results than previously.ObjectiveAs few papers have examined the potassium adsorption ability of Ca-resin compared with Na-resin, we investigated this issue within our institution.MethodsWe studied potassium adsorption in patients who switched from Ca-resin to an equivalent amount of Na-resin (change group). We also investigated the incidence of sodium loading with Na-resin, including in patients newly commencing Na-resin treatment (new start group).ResultsMean (± standard deviation) serum potassium levels decreased significantly, from 5.5 ± 0.6 to 4.9 ± 0.6 mEq/l in the change group and from 5.9 ± 0.4 to 4.7 ± 0.6 mEq/l in the new start group. No changes were observed in blood pressure, weight gain or serum sodium levels in the change group, but serum sodium levels in the new start group increased significantly, from 137.4 ± 2.3 to 139.0 ± 2.5 mEq/l, although they remained within the normal range.ConclusionsOur results indicate that Na-resin exhibited an advantage in treating hyperkalemia when used in small amounts. However, when prescribing an ion-exchange resin at a higher dose, physicians should select the type and amount of resin according to the sodium and/or calcium load in each case.

ABSTRACT:We hypothesized that the stability and a larger stability area of the center of gravity in a single elbow support position are the factors that determine the ability of sitting up by way of a single elbow support position in patients with hemiparesis. The purpose of this study was to confirm this hypothesis. The locus of the center of pressure (COP) in a single elbow support position under the two conditions and sitting up time were measured in 17 patients with hemiparesis after stroke, and relations among these parameters were examined. Two conditions for measurements of COP were that subjects maintained a static position (static condition), and they moved their upper body to two directions (anterior and posterior)(dynamic condition). The sitting up time was the performance time from supine to long sitting by way of a single elbow support position. As a result, no correlation was observed between the static and dynamic conditions. The sitting up time was found to correlate significantly with the length of trajectory (LNG) of COP under the dynamic condition. It was indicated that patients with hemiparesis could sit up smoothly if dynamic stable area in a single elbow support position was larger, and that training to extend the dynamic stable area should be included in physical therapy.

Various factors are considered to be mechanisms of the increase in the sizes of cysts in patients with polycystic kidney disease. Vasopressin is one of the causes, and drinking large volumes of water shows an effect of suppressing an increase in cysts. On the other hand, it is known that hydrogen-rich water reduces oxidative stress and has a good effect on kidney injury. We examined whether drinking large volumes of hydrogen-rich water affected the increase in the sizes of cysts. Forty 5-week-old PCK rats were randomly assigned to four groups: C(Control), purified water; W(Water), water with sugar; H(Hydrogen), hydrogen-rich water; WH(Water+Hydrogen), hydrogen-rich water with sugar. They consumed water from 5 to 15 weeks of age. The intake of water in the groups in which sugar was added to the water (W, WH) significantly increased in comparison to C, but there was no significant change in the serum Creatinine concentration. The kidney weight per body weight in W was significantly decreased in comparison to C. The kidney weights in H and WH were significantly increased in comparison to W. There were no significant differences in the ratio of the cross-sectional area of the cysts to the whole area among the groups. This experiment showed that the effect of drinking large volumes of hydrogen-rich water was not significantly different from that of normal water, in terms of preventing an increase in the size of cysts in PCK rats. However, some papers acknowledge the influence of hydrogen water. Significant differences might become obvious if we change aspects such as the administration method or administration period.

A 67-year-old man complained of lower limb edema with a purpuric skin rash. Laboratory tests revealed proteinuria, elevated serum creatinine levels, and low serum albumin levels. The patient was also positive for cryoglobulin in serum, immunoglobulin (Ig) M gammopathy, hypocomplementemia, and rheumatoid factor. He was negative for anti-hepatitis C virus antibodies. A pathological analysis of the renal tissue revealed membranoproliferative glomerulonephritis, common histological features of cryoglobulinemic vasculitis (CV), and mucosa-associated lymphoid tissue lymphoma invasion. Although hematologic malignancy is a rare cause of type II CV, these clinical findings suggest that mucosa-associated lymphoid tissue lymphoma (MALT) lymphoma may have been the cause in the present case.