Menkes Kinky Hair Disease Presenting with Pseudoperiodic Tonic Spasms during the Clinical Course

A case of Menkes kinky hair disease presenting with pseudoperiodic tonic spasms during the clinical course is described. The reported case had been treated by parenteral copper administration since 10 days of age. Although he gradually appeared to deteriorated mentally and developmentally and developed West syndrome at eight months of age, he had no convulsive seizures until four years of age. At four years of age, tonic spasms, which tended to be i.e. pseudoperiodic appeared. He had two types of tonic spasms, flexor spasms and extensor spasms. An ictal EEG also revealed different patterns, including diffuse desynchronization superimposed over the low voltage fast activities of during the flexor spasms and fast activities appeared only during extensor spasms. Both of these ictal events were dominantly in the left hemisphere on a EEG and each of the tonic spasms was easily controlled with phenytoin. The possibility must be entertained that the presented tonic spasms may have been partial seizures

Effects of valproic acid on the cell cycle and apoptosis through acetylation of histone and tubulin in a scirrhous gastric cancer cell line

Background. Management of peritoneal dissemination is the most critical problem in gastric cancer. This study was performed to investigate the inhibitory effects of valproic acid (VPA) on a highly peritoneal-seeding cell line of human scirrhous gastric cancer, OCUM-2MD3, and to explore the mechanism and the potential of VPA. Methods. The effects of VPA on the growth of OCUM-2MD3 cells were assessed by MTT assay. In addition, paclitaxel (PTX) was combined with VPA to evaluate their synergistic effects. HDAC1 and HDAC2 expression were evaluated by western blotting in OCUM-2MD3 cells and other gastric cancer cell lines (TMK-1, MKN-28). The acetylation status of histone H3 and α-tubulin after exposure to VPA were analyzed by western blotting. The activities of cell cycle regulatory proteins and apoptosis-modulating proteins were also examined by western blotting. The effects of VPA in vivo were evaluated in a xenograft model, and apoptotic activity was assessed by TUNEL assay. Results. OCUM-2MD3 cells showed high levels of HDAC1 and HDAC2 expression compared with TMK-1 and MKN-28. The concentration of VPA required for significant inhibition of cell viability (P < 0.05) was 5 mM at 24 h and 0.5 mM at 48 h and 72 h. The inhibition of VPA with PTX showed dose-dependent and combinatorial effects. VPA increased acetyl-histone H3, acetyl α-tubulin, and p21WAF1 levels accompanied by upregulation of p27, caspase 3, and caspase 9, and downregulation of bcl-2, cyclin D1, and survivin. In the xenograft model experiment, the mean tumor volume of the VPA-treated group was significantly reduced by 36.4%, compared with that of the control group at 4 weeks after treatment (P < 0.01). The apoptotic index was significantly higher in the VPA-treated group (42.3% ± 3.5%) than in the control group (7.7% ± 2.5%) (P < 0.001). Conclusions. VPA induced dynamic modulation of histone H3 and α-tubulin acetylation in relation with the anticancer effect and the enhancement of PTX in the OCUM-2MD3 cell line. Therefore, VPA in combination with PTX is expected to be a promising therapy for peritoneal dissemination of scirrhous gastric cancer. © 2010 Yagi et al; licensee BioMed Central Ltd

Single Photon Emission Computed Tomography of Neonatal Periventricular Leukomalacia

We describe herein single photon emission computed tomography (SPECT) with 99mTc HM-PAO of a patient with neonatal cystic periventricular leukomalacia (PVL). The patient, who was a low birth weight infant of 27 weeks gestation weighing 1,290 g, had suffered from respiratory distress syndrome. Following surfactant replacement therapy, mechanical ventilation were carried out six days after birth. Serial cranial ultrasonography (US) showed periventricular high-echoic lesions followed by cyst formation at three weeks of age. Although cystic PVL was markedly observed on both cranial US and MRI, a SPECT study initially revealed no abnormal distribution of rCBF. A chronological SPECT study at nine months of age revealed decreased rCBF of 10% in the left hemisphere as compared to the contralateral side. At the time decreased rCBF was observed on SPECT, periventricular cyst formation tended to disappear on simultaneous MRI. It is known that PVL is an infarction which affects all the cellular elements of the white matter and may lead to abnormal myelination. SPECT studies may also useful to clarify the cerebral function in neonatal PVL

A Case of Congenital Cytomegalovirus Infection Presenting with Lissencephaly

We report here a case of congenital cytomegalovirus infection presenting with lissencephaly-pachygyria and the evaluation of neuroradiological studies of this case including ultrasonography, cranial computed tomography and magnetic resonance imaging. We propose that congenital cytomegalovirus infection during the early gestational period is one of the important causes of lissencephaly-pachygyria. Therefore, virological and immunological studies should be performed during the early neonatal period

Evaluation of Source Generators in Partial Seizures : Availability of Neuroradiological Images Superimposed on the Dipole Tracing

To clarify the anatomical localization of epileptic foci in childhood partial seizures, the source generators of interictal focal spikes were analyzed using a dipole tracing method and the effectiveness of a composite image diagnostic technique using neuroradiological images obtained by magnetic resonance imaging and single photon emission computed tomography was evaluated. The localization of electric source generators approximately reflects the abnormal lesions on neuroradiological images. However, the source generators tended to be located in the deep and/or peripheral parts of the abnormal regions. Even though systemic shifts in the position of optimal dipoles from their true positions is a limitation that must be taken into consideration, composite image diagnostic technique may be useful for evaluating the epileptogenic regions in partial seizures, and particularly, in children where noninvasive methods are preferable

Spike Code Flow in Cultured Neuronal Networks

We observed spike trains produced by one-shot electrical stimulation with 8 × 8 multielectrodes in cultured neuronal networks. Each electrode accepted spikes from several neurons. We extracted the short codes from spike trains and obtained a code spectrum with a nominal time accuracy of 1%. We then constructed code flow maps as movies of the electrode array to observe the code flow of “1101” and “1011,” which are typical pseudorandom sequence such as that we often encountered in a literature and our experiments. They seemed to flow from one electrode to the neighboring one and maintained their shape to some extent. To quantify the flow, we calculated the “maximum cross-correlations” among neighboring electrodes, to find the direction of maximum flow of the codes with lengths less than 8. Normalized maximum cross-correlations were almost constant irrespective of code. Furthermore, if the spike trains were shuffled in interval orders or in electrodes, they became significantly small. Thus, the analysis suggested that local codes of approximately constant shape propagated and conveyed information across the network. Hence, the codes can serve as visible and trackable marks of propagating spike waves as well as evaluating information flow in the neuronal network

Paraspeckles are subpopulation-specific nuclear bodies that are not essential in mice

Mouse NEAT1 is required for paraspeckle formation in a subset of cells but is not essential for animal health and viability

Aging Is a Risk Factor for Utricular Dysfunction in Idiopathic Benign Paroxysmal Positional Vertigo

Benign paroxysmal positional vertigo (BPPV) is the most common cause of balance disorders in the elderly. Dislodgement of the otoconia in BPPV might have an association with damage to the otolith organs. The aim of this study was to investigate whether aging is a risk factor for otolith organ dysfunction in idiopathic BPPV. We retrospectively reviewed the medical records of 112 consecutive idiopathic BPPV patients who underwent cervical VEMP testing to air-conducted sound (ACS cVEMP), ocular VEMP testing to bone-conducted vibration (BCV oVEMP), and caloric testing. We performed binomial logistic regression analyses to see whether age, the side affected by BPPV or the canal affected by BPPV have an association with the presence of peripheral vestibular dysfunction in idiopathic BPPV patients. The elderly group (aged ≥65 years) had a significantly positive association with abnormalities in BCV oVEMPs (p = 0.0109), while the side affected by BPPV (p = 0.598) and the canal affected by BPPV (p = 0.576) did not. The odds ratio of the abnormal BCV oVEMPs for the elderly group compared with the non-elderly group (aged &lt; 65 years) was 2.676 (95% confidence interval, 1.254–5.079). The elderly group had no significant association with the abnormalities in ACS cVEMPs (p = 0.0955) or caloric testing (p = 0.488). Dysfunction of the utricle, where the dislodgement of the otoconia mainly occurs, is affected by aging in idiopathic BPPV

Emergence of a broad repertoire of GAD65-specific T-cells in type 1 diabetes patients with graft dysfunction after allogeneic islet transplantation.

Islet transplantation is one of the most promising therapies for type 1 diabetes (T1D). A major issue in islet transplantation is the loss of graft function at late phase. Several studies suggested the involvement of islet-specific T-cells in such islet graft dysfunction. In this study, we investigated the breadth and type of glutamic acid decarboxylase 65 (GAD65)-specific T-cells in T1D patients after allogeneic islet transplantation. Peripheral blood mononuclear cells (PBMCs) were obtained from islet-transplanted T1D patients during insulin-independent period and cultured for 7 days with pools of GAD65 overlapping peptides in the presence of IL-2. Cytokine secretion profiles of peptide-reactive T-cells were analyzed after a short-term restimulation with the same peptides by a multiplex bead-based cytokine assay and by an intracytoplasmic cytokine detection assay. Robust GAD65-specific CD4(+) and CD8(+) T-cell responses were detected in patients who eventually developed chronic graft dysfunction. Multiple GAD65 peptides were found to induce specific T-cell responses in these patients, indicating that the repertoire of GAD65-specific T-cells was broad. Furthermore, GAD65-specific CD4(+) T-cells were composed of heterogeneous populations, which differentially expressed cytokines including IFN-γ and type 2 cytokines, but not IL-10. In contrast, patients who showed only marginal GAD65-specific T-cell responses maintained substantially longer graft survival and insulin independence. In conclusion, our study suggests that the emergence of islet-specific T-cells precedes the development of chronic graft dysfunction in islet-transplanted patients. Thus, our observations support the hypothesis that these islet-specific T-cells contribute to the development of chronic islet graft dysfunction