Acute encephalopathy with a truncation mutation in the SCN1A gene: A case report

A girl aged 1 year 9 months had recurrent episodes of febrile status epilepticus. She recovered completely after the first three episodes. However, at 9 months she developed acute encephalopathy resulting in severe neurologic sequelae. Diffusion‐weighted magnetic resonance imaging revealed diffuse high‐intensity signals over the cortex and subcortical white matter in the acute phase and severe diffuse cerebral atrophy in the chronic phase. Mutations were detected in the neuronal voltage‐gated sodium channel alpha subunit type 1 (SCN1A) gene. SCN1A sequence analysis revealed a truncation mutation: ex1‐c.126Adel (D43fs). Our patient was likely afflicted by severe myoclonic epilepsy in infancy, and the fourth episode of status epilepticus was similar to acute encephalopathy. This report provides further insight into the molecular pathophysiology underlying acute encephalopathy.     

Preoperative estimation of asialoglycoprotein receptor expression in the remnant liver from CT/99mTc-GSA SPECT fusion images correlates well with postoperative liver function parameters

Background

Accurate preoperative estimation of remnant liver function is critically important for hepatic surgery, and the expression of asialoglycoprotein receptors (ASGPR) is associated with hepatic function.

Methods

Thirty-two patients with hepatocellular carcinoma who underwent surgical resection were studied. To estimate the expression of ASGPR in the remnant liver, simulated surgery was performed on fusion images that combined data from ^99mtechnetium-galactosyl human serum albumin (^99mTc-GSA)/single photon emission computed tomography (SPECT) and computed tomography (CT) scanning. The liver uptake ratio (LUR) of ^99mTc-GSA and the functional liver volume (FLV) in the remnant liver were predicted and were compared with postoperative liver function parameters.

Results

The LUR of ^99mTc-GSA was strongly correlated with the extent of hepatic ASGPR expression (r = 0.944, p = 5.01 × 10^?16), being confirmed to be a reliable parameter for the evaluation of liver function. The estimated remnant LUR, but not the estimated remnant FLV, was significantly correlated with postoperative liver function parameters, such as serum total bilirubin (r = ?0.430, p < 0.05), prothrombin activity (r = 0.515, p < 0.01), and serum cholinesterase activity (r = 0.546, p < 0.01) at 1 week.

Conclusion

Preoperative estimation of the extent of ASGPR expression in the remnant liver on CT/GSA-SPECT fusion images correlated well with postoperative liver function parameters, suggesting its usefulness for surgical decisions.     

Self-organization of the compositional gradient structure in hyaluronic acid and poly(N-isopropylacrylamide) blend film

A compositional gradient structure in hyaluronic acid (HA) and poly(N-isopropylacrylamide) (PIPAAm) blend film was self-organized from a homogeneous aqueous solution in a plasma-treated polystyrene dish (PTPSD), and the formation mechanisms of the gradient structure were studied by casting the same solution on PTPSD and a non-treated polystyrene dish (NTPSD) under ambient and vacuum conditions. The formation of a compositional gradient structure in HA/PIPAAm blend film was confirmed by scanning electron microscopy, energy dispersive X-ray (EDX) mapping analysis and step-scan photoacoustic Fourier transformed infrared spectroscopy (PAS-FT-IR) measurements. The EDX mapping measurements for Na element revealed that the HA component gradually decreases from the dish-side to the air-side of the film cast on PTPSD, while for the film cast on NTPSD no such obvious change was observed on the cross-section. Further studies on the films prepared on PTPSD and NPTPSD under ambient and vacuum conditions demonstrated that the hydrophilic interaction and the solvent evaporation rate were the most significant factors leading to the formation of a compositional gradient structure in the HA/PIPAAm blend system.     

Effects of mechanical properties of muscle and tendon on performance in long distance runners

The purpose of this study was to investigate the mechanical properties of muscle and tendon in long distance runners and their relations to running performance. Fifteen long distance runners (LDR) and 21 untrained subjects (CON) participated in this study. Muscle strength and activation level of knee extensors and plantar flexors were measured. Tendon elongation was determined using ultrasonography, while subjects performed ramp isometric knee extension and plantar flexion up to the voluntary maximum. Relative MVC (to body mass) of LDR was significantly lower than that of CON for knee extensors, but not for plantar flexors. No significant difference in the neural activation levels was found between LDR and CON for both sites. Maximal tendon elongation of LDR was significantly lower than that of CON for knee extensors, but not for plantar flexors. Furthermore, faster running time in a 5,000 m race (best official record of LDR) was associated with lower tendon stiffness for both sites. In conclusion, the tendon of long distance runners is less extensible than those of untrained subjects for knee extensors, but not for plantar flexors. For both sites, however, the lower tendon stiffness may be in favor of the running performance in long distance runners.     

Role of salvage cytoreductive surgery in the treatment of patients with recurrent ovarian cancer after platinum-based chemotherapy

OBJECTIVES: The role of cytoreductive surgery, which is well established in the primary treatment for epithelial ovarian cancer, is controversial in recurrent disease. The aim of this study was to assess the clinical benefit of salvage surgical cytoreduction in patients with recurrent ovarian cancer after platinum-based chemotherapy. METHODS: We conducted a retrospective analysis of 46 patients with recurrent epithelial ovarian cancer treated at our department between 1988 and 2003. Twenty-three patients underwent salvage cytoreductive surgery (cytoreductive group), and the other 23 patients were treated without surgery (control group). RESULTS: Patients in cytoreductive group had a median survival of 41.7 months after recurrence, which was significantly longer than control group (18.8 months; P < 0.01). The duration of stay at home and the period oral intake was preserved were significantly longer in the cytoreductive group. In the cytoreductive group, survival was influenced by the residual disease after surgery (residual tumor diameter, <2 cm vs >2 cm; median survival, 50 months vs 35.2 months; P < 0.05). However, the number of recurrent sites (solitary vs multiple) and the lengths of treatment-free intervals after primary treatment (<6 months vs >6 months) showed no significant influence on survival. CONCLUSIONS: The application of cytoreductive surgery might improve the prognosis of patients with recurrent ovarian cancer if the tumor was resectable. Preserved prognoses of platinum-resistant disease with short treatment-free interval demonstrated in this study suggest that the concept of maximum cytoreduction might be introduced in the treatment of recurrent disease in the future.     

Electrospun microfiber meshes of silicon-doped vaterite/poly(lactic acid) hybrid for guided bone regeneration

Silicon-releasable microfiber meshes consisting of silicon-doped vaterite (SiV) particles and poly(lactic acid) (PLA) hybrids were prepared by electrospinning. Due to their flexibility and porosity they formed ideal membranes or scaffolds for guided bone regeneration. In addition, a trace amount of silicon species has been reported to stimulate osteogenic cells to mineralize and enhance bone formation. We propose a new method of preparation of silicon-releasing microfiber meshes by electrospinning. Their structure and hydroxyapatite (HA)-forming abilities in simulated body fluid were examined. In addition, we studied their stimulatory effects on osteoblast-like cells in vitro and bone-forming ability in vivo, with a special emphasis on their ability to release silicon. The meshes consisted of a hybrid of carboxy groups in PLA and amino groups in siloxane, derived from aminopropyltriethoxysilane or calcium ions on the SiV surface. This hybrid exhibited an enhanced ability to form HA. The meshes coated with HA released 0.2–0.7 mg l^?1 silicon species into the culture medium over 7 days. Enhanced proliferation of osteoblast-like cells was observed using the meshes and new bone formed on the meshes when implanted into the calvaria of rabbits. These meshes, therefore, provide an excellent substrate for bone regeneration and exhibit enhanced bone-forming ability under both in vitro and in vivo conditions.     

Monocytes enhance cell proliferation and LMP1 expression of nasal natural killer/T-cell lymphoma cells by cell contact-dependent interaction through membrane-bound IL-15

Nasal natural killer (NK)/T-cell lymphoma (NNKTL) is an Epstein-Barr virus (EBV)-related malignancy with poor prognosis and has distinct histological features characterized by angiocentric and polymorphous lymphoreticular infiltrates including inflammatory cells such as granulocytes, monocytes, macrophages and lymphocytes. Here, we show that the monocytes enhance proliferation as well as LMP1 expression of NNKTL cells by cell contact-dependent interaction through membrane-bound interleukin (IL)-15. We used two EBV-positive NK-cell lines, SNK6 and KAI3, which originated from two patients-SNK6 from a patient with NNKTL and KAI3 from a patient with a severe mosquito allergy. We cocultured the cell lines with granulocytes or monocytes and examined whether proliferation, survival and LMP1 expression of the cells changed. Although cocultured granulocytes did not affect proliferation, survival or LMP1 expression of the cells, cocultured monocytes enhanced both proliferation and LMP1 expression in a dose-dependent manner. These phenomena were not seen when monocytes were placed in a separate chamber. Moreover, the monocyte-inducible proliferation and LMP1 expression were inhibited by treatment with an antibody against IL-15. Furthermore, production of interferon-gamma-inducible protein (IP)-10 were enhanced by coculture with monocytes and were inhibited by the antibody. Immunohistological studies confirmed that a number of infiltrating CD14-positive monocytes contacted CD56-positive lymphoma cells in all of 20 NNKTL tissues tested. These results suggest that monocytes enhance cell growth as well as LMP1 expression of NNKTL cells by cell contact-dependent interaction through membrane-bound IL-15. In the microenvironment of NNKTL tissue, a positive feedback loop of interaction between lymphoma cells and monocytes may be present and contribute to lymphoma progression.     

An ectopic ACTH-producing small cell lung carcinoma associated with enhanced corticosteroid biosynthesis in the peritumoral areas of adrenal metastasis

A 60-year-old Japanese male presented with swelling of bilateral cervical lymph nodes was subsequently diagnosed as the late stage of primary small cell lung carcinoma (SCLC). He was then treated with cisplatin and irinotecan as first-line chemotherapy, but hypokalemia with muscle weakness of the bilateral legs became gradually noticeable following two months of effective chemotherapy. A computed tomography (CT) scan revealed enlargement of bilateral adrenal glands and abdominal and mediastinal lymph nodes, though primary lung tumor remained the same in size. An ectopic ACTH-producing syndrome (EAS) was subsequently revealed by the following endocrinological studies. Hypokalemia was clinically improved by the treatment with metyrapone and the second-line chemotherapy with amrubicin for SCLC was started, but the patient died 12 days after the second-line chemotherapy. Post-mortem examination revealed ACTH immunoreactivity in tumor cells of all the metastatic lesions. Non-neoplastic adrenal cortex demonstrated hyperplasia associated with lipid depletion and marked expression of steroidogenic enzymes, especially in cortical cells around tumor infiltration, suggestive of paracrine ACTH stimulation of cortisol production. This is the first report evaluating expression of steroidogenic enzymes in adrenal cortex especially adjacent to the adrenal metastasis in the patients with EAS due to SCLC. These findings suggest that ACTH producing adrenal metastasis can induce EAS more frequently and severely, and that the symptoms and examination of EAS should be monitored carefully in the patients with adrenal metastasis of SCLC.     

Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming

Cancer cells consume large quantities of nutrients and maintain high levels of anabolism. Recent studies revealed that various oncogenic pathways are involved in modulation of metabolism. Nrf2, a key regulator for the maintenance of redox homeostasis, has been shown to contribute to malignant phenotypes of cancers including aggressive proliferation. However, the mechanisms with which Nrf2 accelerates proliferation are not fully understood. Here, we show that Nrf2 redirects glucose and glutamine into anabolic pathways, especially under the sustained activation of PI3K-Akt signaling. The active PI3K-Akt pathway augments the nuclear accumulation of Nrf2 and enables Nrf2 to promote metabolic activities that support cell proliferation in addition to enhancing cytoprotection. The functional expansion of Nrf2 reinforces the metabolic reprogramming triggered by proliferative signals.