Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism of cellular swelling induced by extra-cellular lactic acidosis and the effect of diuretics were studied using neuroblastoma-glioma hybrid (NG108-15) cells. The cells were incubated in one of three lactate concentrations (0, 15, or 30 mM), each of which was randomized to one of three pH groups (7.4, 6.2, or 5.0). Analysis of the swelling was measured using a Coulter counter technique. Cellular swelling was most prominent at pH 6.2 at all lactate levels. Cellular swelling was noted to be pH dependent but not lactate dependent. The addition of 1 mM amiloride completely blocked cellular swelling, suggesting that the main mechanism of neuronal cellular swelling induced by extracellular lactic acidosis was the activation of Na+/H+ exchange. Second, three dissimilar diuretic drugs were used for cellular swelling: amiloride (Na+/H+ exchange inhibitor), mannitol (osmotic diuretic), and bumetanide (loop diuretic). Amiloride and mannitol were found effective in reducing the lactic acidosis-induced cellular swelling. Furthermore, the combination of these drugs had additive effects. However, bumetanide was not effective. The results indicate that the direct inhibition of Na+/H+ exchange and/or removal of water from the cell by mannitol was effective against cellular swelling induced by the activation of Na+/H+ exchange in NG108-15 cells.
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PMID:Mechanism of cellular swelling induced by extracellular lactic acidosis in neuroblastoma-glioma hybrid (NG108-15) cells. 889 76

The m.3243A>G variant in the mitochondrial tRNA(Leu(UUR)) gene is a common mitochondrial DNA (mtDNA) mutation. Phenotypic manifestations depend mainly on the heteroplasmy, i.e. the ratio of mutant to normal mtDNA copies. A high percentage of mutant mtDNA is associated with a severe, life-threatening neurological syndrome known as MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes). MELAS is described as a neurovascular disorder primarily affecting the brain and blood vessels, but the pathophysiology of the disease is poorly understood. We developed a series of cybrid cell lines at two different mutant loads: 70% and 100% in the nuclear background of a neuroblastoma cell line (SH-SY5Y). We investigated the impact of the mutation on the metabolism and mitochondrial respiratory chain activity of the cybrids. The m.3243A>G mitochondrial mutation induced a metabolic switch towards glycolysis in the neuronal cells and produced severe defects in respiratory chain assembly and activity. We used two strategies to compensate for the biochemical defects in the mutant cells: one consisted of lowering the glucose content in the culture medium, and the other involved the addition of l-arginine. The reduction of glucose significantly shifted the 100% mutant cells towards the wild-type, reaching a 90% mutant level and restoring respiratory chain complex assembly. The addition of l-arginine, a nitric oxide (NO) donor, improved complex I activity in the mutant cells in which the defective NO metabolism had led to a relative shortage of NO. Thus, metabolically induced heteroplasmy shifting and l-arginine therapy may constitute promising therapeutic strategies against MELAS.
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PMID:Metabolically induced heteroplasmy shifting and l-arginine treatment reduce the energetic defect in a neuronal-like model of MELAS. 2230 5

Acute disseminated encephalomyelitis (ADEM) is an immune-mediated monophasic inflammatory demyelinating disorder of the central nervous system which poses a diagnostic challenge. We report on six cases of different etiologies that mimicked the clinical and radiologic findings of ADEM. The cases were collected from four different reference hospitals in Turkey. The same radiologist from the Akdeniz University Faculty of Medicine examined the magnetic resonance images of all patients. Three (50%) patients had antecedent infections. Initial symptoms of the patients were as follows: fever in 50%, altered consciousness in 33.3% and convulsions in 16.7% of patients. Neurologic examination showed long tract signs in 83.3%, ataxia in 50% and altered consciousness in 50% of patients. Cerebrospinal fluid examination revealed lymphocytic pleocytosis only in case 6. Four patients received steroid pulse therapy and one of these initially underwent intravenous immunoglobulin therapy. The patients' definitive diagnoses were as follows: paraspinal neuroblastoma-associated paraneoplastic syndrome; histiocytic sarcoma; mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes; and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in one patient each, while two patients had hemophagocytic syndrome. The present case series demonstrated difficulties in diagnosing ADEM while revealing extremely rare disorders that mimic ADEM radiologically and clinically.
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PMID:UNUSUAL CLINICAL CASES THAT MIMIC ACUTE DISSEMINATED ENCEPHALOMYELITIS. 2666 11

A 22-month-old female with high-risk neuroblastoma completed 5 cycles of chemotherapy then underwent high-dose chemotherapy with autologous stem cell rescue (ASCR). Parenteral nutrition was administered from day +2 following ASCR, as she was unable to tolerate nasogastric feeds because of grade IV mucositis and vomiting. On day +12, she developed worsening metabolic acidosis with above reportable levels of lactic acid. Given the patient's well clinical appearance and paucity of evidence of end-organ dysfunction on physical examination and on laboratory studies, there was high suspicion that the patient's lactic acidosis did not result from tissue hypoxia and was, in fact, a type B lactic acidosis. Thiamin was empirically administered, with rapid improvement in lactic acidosis. Thiamin deficiency was later confirmed by laboratory studies drawn prior to thiamin administration.
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PMID:Lactic Acidosis Secondary to Thiamin Deficiency Following Autologous Stem Cell Transplantation. 3270 Apr 22