Purpose: Glioblastoma (GBM) is a malignant brain tumor with poor prognosis. Radioresistance is a major challenge in the treatment of brain tumors. The development of several types of tumors, including GBM, involves the phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT) signaling pathway. Upon activation, this pathway induces radioresistance. In this study, we investigated whether additional use of selective inhibitors of PI3K isoforms would enhance radiosensitivity in GBM. Materials and Methods: We evaluated whether radiation combined with PI3K isoform selective inhibitors can suppress radioresistance in GBM. Glioma 261 expressing luciferase (GL261-luc) and LN229 were used to confirm the effect of combination of radiation and PI3K isoform inhibitors in vitro. Cell viability was confirmed by clonogenic assay, and inhibition of PI3K/AKT signaling activation was observed by Western blot. To confirm radiosensitivity, the expression of phospho-γ-H2AX was observed by immunofluorescence. In addition, to identify the effect of a combination of radiation and PI3K-α isoform inhibitor in vivo, an intracranial mouse model was established by implanting GL261-luc. Tumor growth was observed by IVIS imaging, and survival was analyzed using Kaplan–Meier survival curves. Results: Suppression of the PI3K/AKT signaling pathway increased radiosensitivity, and PI3K-α inhibition had similar effects on PI3K-pan inhibition in vitro. The combination of radiotherapy and PI3K-α isoform inhibitor suppressed tumor growth and extended survival in vivo. Conclusion This study verified that PI3K-α isoform inhibition improves radiosensitivity, resulting in tumor growth suppression and extended survival in GBM mice.

NgR1, a Nogo receptor, is involved in inhibition of neurite outgrowth and axonal regeneration and regulation of synaptic plasticity. P19 embryonal carcinoma cells were induced to differentiate into neuron-like cells using all trans-retinoic acid and the presence and/or function of cellular molecules, such as NgR1, NMDA receptors and STAT3, were examined. Neuronally differentiated P19 cells expressed the mRNA and protein of NgR1, which could stimulate the phosphorylation of STAT3 when activated by Nogo-P4 peptide, an active segment of Nogo-66. During the whole period of differentiation, mRNAs of all of the NMDA receptor subtypes tested (NR1, NR2A-2D) were consistently expressed, which meant that neuronally differentiated P19 cells maintained some characteristics of neurons, especially central nervous system neurons. Our results suggests that neuronally differentiated P19 cells expressing NgR1 may be an efficient and convenient in vitro model for studying the molecular mechanism of cellular events that involve NgR1 and its binding partners, and for screening compounds that activate or inhibit NgR1.
Axons ; Central Nervous System ; Embryonal Carcinoma Stem Cells* ; Mass Screening ; N-Methylaspartate ; Neurites ; Neurons ; Phosphorylation ; Plastics ; Receptors, N-Methyl-D-Aspartate ; Regeneration ; RNA, Messenger ; Tretinoin*

PURPOSE: The goal of this article was to characterize and explain the etiology of a left-sided gallbladders with intrahepatic portal vein anomalies, and these cases of this unusual anatomy were all encountered at a single center. METHODS: We reviewed the movies recorded during surgery, the database information and the preoperative radiologic examinations of 1,141 patients who underwent cholecystectomies at our institution between August 2007 and July 2010 to assess the presence of left-sided gallbladder and its combined anomalies. RESULTS: Four of 1141 patients (0.35%) were diagnosed with left-sided gallbladder. In all the cases, the gallbladder was located on the left side of the falciform ligament, under the left lobe of the liver with typical abnormal intrahepatic portal venous branching. The right posterior portal vein came directly from the main portal vein, and the right anterior portal vein originated from the left portal vein, but the ligamentum teres joined to the left branch of the portal vein in the liver. CONCLUSION: Left-sided gallbladder with intrahepatic portal venous branching anomaly resulted from the defective development of the central portion of the liver rather than from abnormal regression of the left umbilical vein with persistence of the right umbilical vein.
Cholecystectomy ; Gallbladder ; Gallbladder Diseases ; Humans ; Ligaments ; Liver ; Porphyrins ; Portal Vein ; Umbilical Veins

OBJECTIVE: To investigate the effect of action related visual and auditory stimuli on the motor evoked potential (MEP) of hand. METHOD: Right handed fifteen healthy adults without neurological deficit were included. Visual lingual stimulation was given on the computer monitor with the sentence and auditory lingual stimulation was given 10 repetitions of the above sentence using computer speaker with eyes closed. MEPs from transcranial and transcervical magnetic stimulation were recorded on the abductor pollicis brevis of the right hand. RESULTS: The latency of MEPs was shortened and the amplitude of MEPs with transcranial magnetic stimulation after lingual stimulation (p<0.05). However, the latency and amplitude of with transcervical stimulation did not show significant changes. CONCLUSION: Cortical excitability was enhanced by action related visual or auditory stimuli. Exercise accompanied by visual or auditory lingual stimulation rather than simple exercise might be useful for facilitating cortical excitability.
Adult ; Evoked Potentials, Motor ; Eye ; Hand ; Humans ; Magnetics ; Magnets ; Organothiophosphorus Compounds ; Transcranial Magnetic Stimulation

Severe hypoglycemia leading to permanent brain damage is rare in non-diabetic population. We present one case where chronic alcoholism combined with prolonged fasting lead to such a state. A 51-year-old male patient, a chronic alcoholic, was found unconscious and brought to the emergency room. At the time of hospitalization, consciousness was stupor and he had a blood glucose of 5 mg/dl and MRI of the brain showed high signal density of the inner temporal gyrus and both hippocampus in T2 weighted imaging. There was no history of diabetes. After two months of rehabilitation, improvements were showed to Rancho Los Amigos recognition scale IV, fair grade of muscular strength in upper and lower limbs, FIM score of 21, and dysphagia was improved and nutrition supply was intaken orally. An alcoholic for a long period of time without adequate nutrient supply was experienced to develop into hypoglycemic encephalopathy and therefore reported.

BACKGROUND: There are different models of skin substitutes, but no skin substitutes have the characteristics of native skin. It was reported that the incubation of skin substitutes in medium containing ascorbic acid extends cellular viability and promotes formation of an epidermal barrier in vitro. OBJECTIVE: The purpose of this study is to observe the effects of ascorbic acid on the proliferation of keratinocytes and on the reconstruction of epidermis. MATERIALS AND METHODS: Normal human keratinocytes and fibroblasts were isolated and used for culturing living skin equivalent (LSE). RESULTS: When ascorbic acid was added, the expression of p63 and a6 integrin was definitely increased compared to control models. In addition, ascorbic acid increased the proliferation of normal human keratinocytes at a dose dependent manner. Especially, ascorbic acid induced the phosphorylation of ERK and up-regulation of EGF-R CONCLUSION: Results suggest that ascorbic acid is essential in the control of keratinocyte proliferation and basement membrane formation. Ascorbic acid-related keratinocytes proliferation is seemed to be mediated by ERK phosphorylation and EGF-R up-regulation.
Ascorbic Acid* ; Basement Membrane ; Epidermis ; Fibroblasts ; Humans ; Keratinocytes* ; Phosphorylation ; Skin* ; Skin, Artificial ; Up-Regulation

PURPOSE: Unilateral ureteral obstruction(UUO), a well established experimental model of renal injury, gives rise to tubulointerstitial fibrosis, tubular dilatation and cellular atrophy. Angiotensin(ANG) II may take the prime role in the regulation of this response. The objectives in the current investigation were to determine whether the renal response to UUO involves the dedifferentiation of tubular epithelial cells to mesenchymal cells(expressing vimentin, V) whether the response implicates the transformation of fibroblasts to myofibroblasts(expressing alpha-smooth muscle actin, SMA), and whether these responses depend on the action of ANG II or not. METHODS: Unilateral ureteral ligation and sham operations were performed in 12 adult male Sprague-Dawley rats. An additional 18 rats received exogenous ANG II at 50 ng/min or vehicle for one week using an osmotic minipump inserted into the interscapular area. Rats were sacrificed on postoperative day seven or day 14. To know the expression of vimentin(V) and alpha-smooth muscle actin (SMA) proteins, immunohistochemical staining and Western blot assay were done. RESULTS: In immunohistochemical staining, following UUO, V-positive cells appeared markedly in the interstitium and tubular cells within dilated tubules. UUO also markedly increased alpha-SMA expression in the interstitium surrounding dilated tubules. In Western blotting, UUO increased V(five times of Sham) and alpha-SMA(2.5 times of Sham) expression. ANG II infusion increased alpha-SMA significantly(two times of control), but not V expression in Western blotting. CONCLUSION: Phenotypic transformation of fibroblasts to myofibroblasts following UUO may depend on ANG II, but dedifferentiation of tubular epithelial cells may depend on other mechanisms rather than ANG II.
Actins ; Adult ; Angiotensin II* ; Angiotensins* ; Animals ; Atrophy ; Blotting, Western ; Dilatation ; Epithelial Cells* ; Fibroblasts* ; Fibrosis ; Humans ; Ligation ; Male ; Models, Theoretical ; Myofibroblasts ; Rats* ; Rats, Sprague-Dawley ; Ureter* ; Ureteral Obstruction* ; Vimentin

PURPOSE: Long-term prognosis of Henoch-Schonlein purpura(HSP) is determined by the existence and severity of renal involvement. We evaluated the relationship between various clinical features of HSP and the development of renal involvement using univariate and multivariate analyses for early detection and proper management of HSP nephritis. METHODS: We performed a retrospective study of 200 children who were diagnosed as HSP and were initially free from renal involvement, from 1998-2003. Clinical features of each patient as risk factors of renal involvement were evaluated by univariate and multivariate analysis. Significant risk factors proven by univariate analysis were paired and re-analyzed to see if there are any interactions between them. RESULTS: A univariate analysis showed that sex, previous disease, severe abdominal symptoms, persistent purpura and steroid administration were associated with developing renal involvement. Among them, severe abdominal symptoms, persistent purpura, and male sex were statistically significant when they were re-analyzed after pairing, and they also increased the risk of renal involvement in a multivariate analysis. CONCLUSION: Severe abdominal symptoms, persistent purpura, and male sex are independent risk factors of renal involvement in HSP and it is presumed that interaction between them could be another factor of HSP nephritis.
Abdominal Pain ; Child ; Humans ; Male ; Multivariate Analysis* ; Nephritis ; Prognosis ; Purpura ; Purpura, Schoenlein-Henoch* ; Retrospective Studies ; Risk Factors*

Schinzel-Giedion syndrome is a rare, distinct dysmorphic syndrome characterized by congenital hydronephrosis, skeletal dysplasia, and severe developmental retardation, likely to be inherited as an autosomal recessive trait, but not yet confirmed. This syndrome is characterized by coarse facial features such as midfacial retraction, bulging forehead, short nose with anteverted nostrils, low-set malformed ears, protruding large tongue, and hypertelorism. Skeletal and limb defects, choanal stenosis, simian creases, hypospadias, microphallus, hypertrichosis, and intractable seizures are the frequently associated clinical findings. Urogenital involvement is a major component of the syndrome, and this problem sometimes is associated with nephrocalcinosis and urinary tract infection in the clinical course of the disease. We report a 22 month-old girl with Schinzel-Giedion syndrome complicated by medullary nephrocalcinosis and urinary tract infection due to Klebsiella pneumoniae. This patient had also been suffering from postnatal growth deficiency, intractable seizure, spastic tetraplegia, delayed development and severe mental retardation.
Constriction, Pathologic ; Ear ; Extremities ; Female ; Forehead ; Humans ; Hydronephrosis ; Hypertelorism ; Hypertrichosis ; Hypospadias ; Infant ; Intellectual Disability ; Klebsiella pneumoniae ; Male ; Nephrocalcinosis ; Nose ; Quadriplegia ; Seizures ; Tongue ; Urinary Tract Infections

The deficiency of enzyme hypoxanthine-guanine phosphoribosyltransferase(HPRT) results in hyperuricemia and subsequently manifests in diverse symptoms. Lesch-Nyhan syndrome is a disorder characterized by hyperuricemia, mental retardation, choreoathetosis, spasticity and self-mutilation, resulting from complete deficiency of the enzyme, whereas partial deficiency of the enzyme shows symptoms of milder forms more often without abnormal neurologic signs. A 7-year-old boy with normal growth and psychomotor development presented with a uric acid stone accompanied by a disproportionate increase of serum/urine uric acid level. The stone was removed by nephrolithotomy and further enzymatic study on lysed erythrocytes showed less than 1% of the normal HPRT activity. After initiation of treatment with allopurinol, the uric acid level was rapidly decreased to a normal range and the patient has not shown hyperuricemia or nephropathy since. Although partial HPRT deficiency is not commonly seen, this possibility should be considered whenever urolithiasis is accompanied by disproportionately high levels of serum uric acid.