Holmes tremor after brainstem hemorrhage, treated with levodopa.

Holmes tremor is a rare movement phenomenon, with atypical low-frequency tremor at rest and when changing postures, often related to brainstem pathology. We report a 70-year-old female patient who was presented with dystonic head and upper limb tremor after brainstem hemorrhage. The patient had experienced a sudden onset of left hemiparesis and right facial paralysis. Brain magnetic resonance imaging showed an acute hemorrhage from the brachium pontis through the dorsal midbrain on the right side. Several months later, the patient developed resting tremor of the head and left arm, which was exacerbated by a sitting posture and intentional movement. The tremor showed a regular low-frequency (1-2 Hz) for the bilateral sternocleidomastoid and cervical paraspinal muscles at rest. The patient's symptoms did not respond to propranolol or clonazepam, but gradually improved with levodopa administration. Although various remedies were attempted, overall, the results were poor. We suggest that levodopa might be a useful remedy for Holmes tremor. The curative or relieving effect of the dopaminergic agent in Holmes tremor needs more research.

PI3K/Akt and Stat3 signaling regulated by PTEN control of the cancer stem cell population, proliferation and senescence in a glioblastoma cell line.

Malignant gliomas are the most common primary brain tumor in adults. A number of genes have been implicated in glioblastoma including mutation and deletion of PTEN. PTEN is a regulator of PI3K-mediated Akt signaling pathways and has been recognized as a therapeutic target in glioblastoma. To achieve potent therapeutic inhibition of the PI3K-Akt pathway in glioblastoma, it is essential to understand the interplay between the regulators of its activation. Here, ectopic expression of PTEN in the U-87MG human glioblastoma-astrocytoma cell line is shown to result in the depletion of glioblastoma stem cells (GSCs) and to cause growth retardation and senescence. These effects are likely to be associated with PTEN-mediated cooperative perturbation of Akt and Stat3 signals. Using an in vivo rat model of glioblastoma, we showed that PTEN-overexpressing U-87MG cells failed to induce tumor formation, while untreated U-87MG cells did so. Furthermore, cells expressing the phosphorylated form of Stat3 were completely absent from the brain of rats implanted with PTEN-overexpressing U-87MG cells. Based on these results, PTEN appears to function as a crucial inhibitor of GSCs and as an inducer of senescence, suggesting that functional enhancement of the PTEN pathway will be useful to provide a therapeutic strategy for targeting glioblastoma.

Ell3 enhances differentiation of mouse embryonic stem cells by regulating epithelial-mesenchymal transition and apoptosis.

Ell3 is a testis-specific RNA polymerase II elongation factor whose cellular function is not clear. The present study shows that Ell3 is activated during the differentiation of mouse embryonic stem cells (mESCs). Furthermore, Ell3 plays a critical role in stimulating lineage differentiation of mESCs by promoting epithelial-mesenchymal transition (EMT) and suppressing apoptosis. Mouse ESCs engineered to stably express Ell3 were rapidly differentiated compared with control cells either under spontaneous differentiation or neural lineage-specific differentiation conditions. Gene expression profile and quantitative RT-PCR analysis showed that the expression of EMT markers, such as Zeb1 and Zeb2, two major genes that regulate EMT, was upregulated in Ell3-overexpressing mESCs. Remarkably, knockdown of Zeb1 attenuated the enhanced differentiation capacity of Ell3-overexpressing mESCs, which indicates that Ell3 plays a role in the induction of mESC differentiation by inducing EMT. In contrast to Ell3-overexpressing mESCs, Ell3-knock down mESCs could not differentiate under differentiation conditions and, instead, underwent caspase-dependent apoptosis. In addition, apoptosis of differentiating Ell3-knock out mESCs was associated with enhanced expression of p53. The present results suggest that Ell3 promotes the differentiation of mESCs by activating the expression of EMT-related genes and by suppressing p53 expression.

Sprouty1 regulates neural and endothelial differentiation of mouse embryonic stem cells.

Fibroblast growth factor (FGF) signaling is implicated in the control of pluripotency and lineage differentiation of both human and mouse embryonic stem cells (mESCs). FGF4 dependent stimulation of ERK1/2 signaling triggers transition of pluripotent ESCs from self-renewal and lineage commitment. In this study, Sprouty 1 (Spry1) expression was observed in undifferentiated mESCs, where it modulated ERK1/2 activity. Spry1 was confirmed as dispensable for the maintenance of self-renewal. However, suppression of Spry1 expression and subsequent activation of ERK1/2 signaling promoted neural differentiation and inhibited endothelial differentiation of mESCs. Moreover, evidence is presented which indicates that SHP2, a major determinant of balance between mESC self-renewal and differentiation, directly regulates Spry1 activity to modulate ERK1/2 signaling and lineage-specific differentiation in mESCs. Our results show that Spry1 has an essential role in the lineage specific differentiation of mESCs.

Nodular fasciitis in the forehead.

Histologically, nodular fasciitis is observed as similar to sarcoma in soft tissues, and it is referred to as pseudosarcomatous fasciitis. Its histologic findings can be summarized as spindle-shaped fibroblasts, intercellular space between fibroblasts, red blood cells released to the extravascular area, and deposition of mucus within the interstitium. The lesion looks similar to sarcoma histologically and shows the characteristic of rapid growth, which in result is readily misdiagnosed as malignancy. It occurs preferentially in the upper extremities, whereas rarely occurring in the head and neck region. When we encounter subcutaneous nodules of the head and neck region, it is important to keep nodular fasciitis in mind as a differential diagnosis to avoid unnecessary wide resection. In this article, we report a rare case of nodular fasciitis on the forehead and some reviews of the literature.

Depressive symptoms in elementary school children in Jeju Island, Korea: prevalence and correlates.

We investigated the prevalence and correlates of depressive symptoms in elementary school children in Jeju Island, Korea. The study participants were 2305 children enrolled in elementary schools in Jeju-si, Seogwipo-si, Namjeju-gun, and Bukjeju-gun and their parents who completed questionnaires about sociodemographics, health habits, family relationship information, and the Korean form of the Kovac's children's depression inventory (CDI) in September to December 2005. Multiple logistic regression showed that higher age (OR = 1.259, 95% CI 1.098-1.445), short time spent developing a relationship with the mother (OR = 2.770, 95% CI 1.280-5.944), and a low level of body image satisfaction (OR = 3.397, 95% CI 1.823-6.330) were correlates of depressive symptoms in children. Our results suggest that the following are essential to prevent depressive symptoms in elementary school children in Jeju, Korea: advanced education and social activity programs at home, in school, and in the community to help children have a positive self-image, and much time spent building a relationship with the mother.