Association between recovery from Bell's palsy and body mass index.

BACKGROUND: Although many factors have been found to be involved in recovery from Bell's palsy, no study has investigated the association between recovery from Bell's palsy and obesity. This study therefore evaluated the association between recovery from Bell's palsy and body mass index (BMI). METHODS: Subjects were classified into five groups based on BMI (kg/m2 ). Demographic and clinical characteristics were compared among these groups. Assessed factors included sex, age, time from paralysis to visiting a hospital, the presence of comorbidities such as diabetes mellitus and hypertension, degree of initial facial nerve paralysis by House-Brackmann (H-B) grade and neurophysiological testing, and final recovery rate. RESULTS: Based on BMI, 37 subjects were classified as underweight, 169 as normal weight, 140 as overweight, 155 as obese and 42 as severely obese. Classification of the degree of initial facial nerve paralysis as moderate or severe, according to H-B grade and electroneurography, showed no difference in severity of initial facial paralysis among the five groups (P > 0.05). However, the final recovery rate was significantly higher in the normal weight than in the underweight or obese group (P < 0.05). CONCLUSIONS: Obesity or underweight had no effect on the severity of initial facial paralysis, but the final recovery rate was lower in the obese and underweight groups than in the normal group.

Clinically applicable human adipose tissue-derived mesenchymal stem cells delivering therapeutic genes to brainstem gliomas.

Pediatric brainstem glioma is an incurable malignancy because of its inoperability. As a result of their extensive tropism toward cancer and the possibility of autologous transplantation, human adipose-derived mesenchymal stem cells (hAT-MSC) are attractive vehicles to deliver therapeutic genes to brainstem gliomas. In this study, in a good manufacturing practice (GMP) facility, we established clinically applicable hAT-MSCs expressing therapeutic genes and investigated their therapeutic efficacy against brainstem glioma in mice. For feasible clinical applications, (1) primary hAT-MSCs were cultured from human subcutaneous fat to make autologous transplantation possible, (2) hAT-MSCs were genetically engineered to express carboxyl esterase (CE) and (3) a secreted form of the tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) expression vector for synergistic effects was delivered by a gene transfer technology that did not result in genomic integration of the vector. (4) Human CE and sTRAIL sequences were utilized to avoid immunological side effects. The hAT-MSCs expressing CE±sTRAIL showed significant therapeutic effects against brainstem gliomas in vitro and in vivo. However, the simultaneous expression of CE and sTRAIL had no synergistic effects in vivo. The results indicate that non-viral transient single sTRAIL gene transfer to autologous hAT-MSCs is a clinically applicable stem cell-based gene therapy for brainstem gliomas in terms of therapeutic effects and safety.

The effect of gadoxetic acid enhancement on lesion detection and characterisation using T2 weighted imaging and diffusion weighted imaging of the liver.

OBJECTIVES: To evaluate the effect of gadoxetic acid enhancement on the detection and characterisation of focal hepatic lesions on T(2) weighted and diffusion weighted (DW) images. METHODS: A total of 63 consecutive patients underwent T(2) weighted and DW imaging before and after gadoxetic acid enhancement. Two blinded readers independently identified all of the focal lesions using a five-point confidence scale and characterised each lesion using a three-point scale: 1, non-solid; 2, indeterminate; and 3, solid. For both T(2) weighted and DW imaging, the accuracies for detecting focal lesions were compared using the free-response receiver operating characteristic analysis; the accuracies for lesion characterisation were compared using the McNemar test between non-enhanced and gadoxetic acid-enhanced image sets. For hepatic lesions ≥ 1 cm, the lesion-to-liver contrast-to-noise ratio (CNR) and the apparent diffusion coefficient (ADC) were compared in the non-enhanced and enhanced image sets using the generalised estimating equations. RESULTS: For both T(2) weighted and DW images, the accuracies for detecting focal lesions (p ≥ 0.52) and those for lesion characterisation (p ≥ 0.63) did not differ significantly between the non-enhanced and enhanced image sets. The lesion-to-liver CNR was significantly higher on enhanced DW images than on non-enhanced DW images (p=0.02), although the difference was not significant for T(2) weighted imaging (p=0.65). The mean ADC values of lesions did not differ significantly on enhanced and non-enhanced DW imaging (p=0.75). CONCLUSION: The acquisition of T(2) weighted and DW images after administration of gadoxetic acid has no significant effect on the detection or characterisation of focal hepatic lesions, although it improves the lesion-to-liver CNR on DW images.

Therapeutic targeting of subdural medulloblastomas using human neural stem cells expressing carboxylesterase.

The prognosis of medulloblastoma has improved significantly because of advances in multi-modal treatments; however, metastasis remains one of the prognostic factors for a poor outcome and is usually associated with tumor recurrence. We evaluated the migratory potential and therapeutic efficacy of genetically engineered human neural stem cells (NSCs) that encode a prodrug enzyme in the subdural medulloblastoma model. We genetically modified HB1.F3 (F3) immortalized human NSCs to express rabbit carboxylesterase (rCE) enzyme, which efficiently converts the prodrug CPT-11 (Irinotecan) into an active anti-cancer agent (SN-38). To simulate clinical metastatic medulloblastomas, we implanted human medulloblastoma cells into the subdural spaces of nude mice. rCE expressing NSCs (F3.rCE) were labeled with fluorescence magnetic nanoparticle for in vivo imaging. The therapeutic potential of F3.rCE was confirmed using a mouse subdural medulloblastoma model. The majority of intravenously (i.v.) injected, F3.rCE cells migrated to the subdural medulloblastoma site and a small number of F3.rCE cells were found in the lungs, pancreas, kidney and liver. Animals that received F3.rCE cells in combination with prodrug CPT-11 survived significantly longer (median survival: 142 days) than control mice that received F3.rCE cells only (median survival: 80 days, P<0.001) or CPT-11 only (median survival: 118 days, P<0.001). In conclusion, i.v. injected F3.rCE NSCs were able to target subdural medulloblastomas and demonstrate therapeutic efficacy. Our study provides data that supports further investigation of stem-cell-based gene therapy against metastatic medulloblastomas.

The complete nucleotide sequence of the genome RNA of Lily symptomless virus and its comparison with that of other carlaviruses.

The complete genomic nucleotide sequence and genome structure of Lily symptomless virus (LSV), a lily-infecting carlavirus, have been obtained. The genome of the Korean strain of LSV, LSV-Kr, was 8394 nucleotides long and contained six open reading frames (ORFs) coding for proteins of Mr 220 kDa (1948 aa), 25 kDa (228 aa), 12 kDa (106 aa), 7 kDa (64 aa), 32 kDa (291 aa) and 16 kDa (140 aa) from the 5' to 3' end, respectively, which is typical of carlaviruses. Genetic heterogeneity was observed in the ORF1 gene. A total of 221 of 5,847 nucleotides (nt) were heterologous in the ORF1 of replicase; 162 nt portions were silent and 59 nt resulted in amino acid changes. This heterogeneity indicates that the LSV-infecting lily plants contained a genetically heterogeneous population of LSV (quasispecies). Overall similarities to those of other carlaviruses for the six ORFs of LSV were from 76.1% to 31.6% and from 87.3% to 13.7%, at nucleotide and amino acid levels, respectively. The ORF1 replicase gene of LSV shares 40.9% to 56.8% and 48.9% and 58.6% identities with that of 5 other carlaviruses at the amino acid and nucleotide levels, respectively. LSV was closest to Blueberry scorch virus (BlScV) in this ORF, among the carlaviruses for which sequence information is available. The three triple gene blocks (ORF2-4), ORF5 (coat protein) and 3'-proximal 16 kDa ORF6 genes were further analyzed, and phylogenetic trees for the coding regions indicate that the LSV was the most closely related to Kalanchoe latent virus and BlScV. This is the first report of the complete nucleotide sequence and genome structure of LSV.

Role of inducible heat shock protein 70 in radiation-induced cell death.

We previously demonstrated the protective effect of inducible heat shock protein 70 (Hsp70) against gamma radiation. Herein, we extend our studies on the possible role of Hsp70 to ionizing radiation-induced cell cycle regulation. The growth rate of inducible hsp70-transfected cells was 2-3 hours slower than that of control cells. Flow cytometric analysis of cells at G1 phase synchronized by serum starvation also showed the growth delay in the Hsp70-overexpressing cells. In addition, reduced cyclin D1 and Cdc2 levels and increased dephosphorylated phosphoretinoblastoma (pRb) were observed in inducible hsp70-transfected cells, which were probably responsible for the reduction of cell growth. To find out if inducible Hsp70-mediated growth delay affected radiation-induced cell cycle regulation, flow cytometric and molecular analyses of cell cycle regulatory proteins and their kinase were performed. The radiation-induced G2/M arrest was found to be inhibited by Hsp70 overexpression and reduced p21Waf induction and its kinase activity by radiation in the Hsp70-transfected cells. In addition, radiation-induced cyclin A or B1 expressions together with their kinase activities were also inhibited by inducible Hsp70, which represented reduced mitotic cell death. Indeed, hsp70 transfectants showed less induction of radiation-induced apoptosis. When treated with nocodazole, radiation-induced mitotic arrest was inhibited by inducible Hsp70. These results strongly suggested that inducible Hsp70 modified growth delay (increased G1 phase) and reduced G2/M phase arrest, subsequently resulting in inhibition of radiation-induced cell death.

Adaptive response is differently induced depending on the sensitivity to radiation-induced cell death in mouse epidermal cells.

We investigated the relationship between induction of radio-adaptive response and cell death in mouse normal and neoplastic epidermal cells. Mouse normal primary keratinocytes (PK), cancer-prone cells [v-rasHa-transfected mouse keratinocytes (ras-PK), and line 308 cells (mouse skin papilloma cells which have activated rasHa gene with A-to-T transversion at codon 61) were primed with a low dose of gamma-rays (0.01 Gy), and were challenged with a high dose (4 Gy) after a 4 or 7 h interval. The induction of cell death in PK was 2-10 times higher and was also more rapid in PK than in ras-PK or 308 cells. Low-dose pretreatment with a 4 h interval decreased cell death, and this adaptive response was prominent in PK, whereas it was less obvious in the cases of ras-PK and 308 cells. The response of each protein kinase C (PKC) isozymes to high-dose radiation, especially PKCalpha, PKCdelta, PKCepsilon, and PKCeta, were different between the normal and ras oncogene-activated neoplastic keratinocytes; translocation of these isozymes to membrane occurred more rapidly in normal than in neoplastic cells. Furthermore, low-dose pretreatment did not induce the translocation of PKCdelta in PK significantly more than in ras-PK and 308. Thus, the difference in the induction of radio-adaptive responses between mouse normal and neoplastic epidermal cells reflects difference in the rapidity of cell death, and responsiveness of PKC may affect this adaptive response.

Large cerebral infarction during praziquantel therapy in neurocysticercosis.

BACKGROUND: Large cerebral infarction is a rare complication of neurocysticercosis. Endarteritis by inflammation of the leptomeninges is known to be its cause. CASE DESCRIPTION: A 59-year-old man with known neurocysticercosis developed a large cerebral infarction during praziquantel therapy. A follow-up MRI obtained immediately after his cerebral infarction demonstrated notable decrease in the size of the cysts and more prominent enhancement around the peripheral margins of the cysts and the major vessels in comparison with the initial MRI. Cerebral angiography disclosed occlusions and narrowing of both internal carotid arteries at the supraclinoid portions, where multiple cysts were found on the MRI. CONCLUSIONS: Findings in our patient strongly suggest that a secondary inflammation reaction caused by the destruction of the cysts might have enhanced the process of endarteritis. The possible deleterious effects of praziquantel therapy should be considered in the treatment of patients with subarachnoid cysticerci.

Pure motor hemiplegia with conjugate lateral gaze palsy in pontine lacunar infarction.

The combination of pure motor hemiplegia and horizontal gaze palsy is a rare but identifiable lacunar syndrome. Among horizontal gaze palsies, one-and-a-half syndrome and abducens nerve palsy are reported to be associated with pure motor hemiplegia in pontine lacunar infarction. Although conjugate lateral gaze palsy is also hypothesized, pure motor hemiplegia with conjugate lateral gaze palsy has never been reported. We present a 75-year-old man who showed right hemiparesis and impaired left horizontal conjugate eyeball movement. Both the findings of the brain CT scan and those of the MRI study were consistent with a small infarction in the left midpontine tegmentum. Magnetic resonance angiography revealed no stenotic narrowing of the vertebrobasilar artery. Radiological findings suggested that pure motor hemiplegia with conjugate lateral gaze palsy, in our patient, might have been produced by the occlusion of a single penetrating branch of the basilar artery.