Neurological Improvement Associated with Resolution of Irradiation-Induced Myelopathy: Serial Magnetic Resonance Imaging and Positron Emission Tomography Findings

We document serial magnetic resonance imaging (MRI) and [¹⁸F] 2-fluoro-2-deoxyglucose (FDG)-positron emission tomography (PET) findings in the process of improvement from delayed radiation necrosis of the spinal cord. A 61-year-old woman underwent radiotherapy for an oral carcinoma. Forty-six months later she developed a left-sided Brown-Séquard syndrome, suggesting incomplete cervical cord transection below the cervico-thoracic junction. Two months after starting steroid therapy, she had gradual clinical improvement, which continues 8 years after the termination of radiotherapy. Neurological improvement was associated with gradual resolution of an extensive high-intensity area within the cervico-thoracic spinal cord on MRI. Initially, the FDG-PET showed linear and uniform increase in FDG uptake throughout the cervical spinal cord with standardized uptake value of 2.68 ± 0.16 (mean ± SD), but it returned to normal value (1.90 ± 0.14) at final follow-up. Considering that the normalization of FDG uptake correlated with neurological recovery, the uniform- and diffuse-increased FDG uptake noted in the initial course of myelopathy could reflect the metabolic activity of the compromised spinal cord.     

Overexpression of CD-11b and CXCR1 on circulating neutrophils: its possible role in COPD

BACKGROUND: It has been shown that the beta2-integrin molecule is up-regulated in circulating neutrophils in COPD subjects. However, little has been reported about the expression of the cell surface molecules in such patients and their relationship with pulmonary function. The aim of the present study was to investigate the surface expression of molecules in circulating neutrophils and to clarify their possible role in the airflow limitation of COPD. METHODS: The surface expression of Mac-1 cells (ie, CD-11b and CD-18 cells) and CXC chemokine receptor (CXCR) 1 and CXCR2 of circulating neutrophils obtained from COPD patients and healthy subjects (HSs) was measured by flow cytometry analysis. The serum levels of interleukin (IL)-8 were measured by enzyme-linked immunosorbent assay. RESULTS: Both CD-11b and CXCR1 expression were significantly higher in COPD patients than in HSs (mean [+/- SE] CD-11b concentration: HSs, 9.7 +/- 1.0; COPD patients, 14.2 +/- 1.8 [p < 0.05]; mean CXCR1 concentration: HSs, 9.6 +/- 0.5; COPD patients, 11.9 +/- 0.4 [p < 0.01]). Although aging was positively correlated with the expression of CXCR1 (r = 0.440; p < 0.01), none of the other background factors, including smoking and body mass index, showed a correlation with the expression of the molecules. Although serum IL-8 levels were higher in patients with COPD than in HSs, no significant correlation between serum IL-8 levels and the expression of any molecule was seen. The expression of CD-11b (r = -0.317) and CXCR1 (r = -0.383) showed a significant negative correlation with the severity of airflow limitation (both p < 0.05). CONCLUSIONS: The overexpression of CD-11b and CXCR1 in circulating neutrophils may be associated with the development of airflow limitation in COPD patients.     

Adenovirus-mediated retrograde transfer of neurotrophin-3 gene enhances survival of anterior horn neurons of twy/twy mice with chronic mechanical compression of the spinal cord

Chronic mechanical compression of the spinal cord causes neural tissue damage, including loss of anterior horn cells around the level of injury. Exogenous delivery of neurotrophins to neuronal cells could provide neuroprotection to a spinal cord subjected to mechanical injury. We investigated the efficacy of retrograde gene delivery of adenoviral vector (AdV) carrying neurotrophin-3 (NT-3) gene into twy (twy/twy) mouse spinal cord anterior horn neurons with chronic and progressive mechanical compression at C1-C2 level. AdV-NT-3 was used for retrograde delivery via the sternomastoid muscle to the cervical spinal accessory motoneurons in 16-week-old adult twy mice with relatively mild spinal cord compression. Four weeks after the AdV-NT-3 or AdV-beta-galactosidase cDNA (LacZ) as a marker gene injection, the compressed cervical spinal cord was examined histologically, immunohistologically, and by immunoblot analysis. Immunoreactivity to NT-3 was significantly enhanced in the AdV-NT-3-injected twy mice compared with the AdV-LacZ-injected mice. The numbers of anterior horn neurons of Nissl-, choline acetyltransferase (ChAT)-, and trkC-stained and wheat germ agglutinin-horseradish peroxidase (WGA-HRP)-labeled neurons at the spinal cord level with maximum compression were significantly higher in AdV-NT-3-transfected than in AdV-LacZ-transfected twy mice. Retrograde NT-3 gene transfer to twy mouse anterior horn neurons increased neurite axonal length and arborization of WGA-HRP-labeled neurons. Our results suggest that targeted retrograde NT-3 gene delivery is feasible in the intact animal and that it enhances neuronal survival even under chronic mechanical compression of the spinal cord.     

Atlantoaxial subluxation-induced myelopathy in cleidocranial dysplasia. Case report

The authors describe the clinical course and treatment of a patient with cleidocranial dysplasia in whom spastic myelopathy developed due to atlantoaxial subluxation. This 27-year-old woman with cleidocranial dysplasia and a history of atlantoaxial subluxation presented with spastic myelopathy. Surgery was performed twice for cervical myelopathy and atlantoaxial subluxation, including laminectomy at the atlas and cervicooccipital fusion in which the Luque rod system was used, as well as C1-2 fusion via the transpharyngeal route. Solid bone fusion was achieved by 7 months postsurgery. Postoperative magnetic resonance imaging studies demonstrated that spinal cord compression was relieved, but atrophy persisted. At 2 years postsurgery there was no neurological disease progression, but spasticity persisted. The patient could walk with a cane. Cleidocranial dysplasia is an extremely rare cause of myelopathy in patients with atlantoaxial subluxation; the authors know of only two reports of this condition. When managing cleidocranial dysplasia, the practitioner should always be aware that atlantoaxial subluxation may be the cause of cervical myelopathy.     

Trans-4-lodo,4′-boranyl-chalcone induces antitumor activity against malignant glioma cell lines <Emphasis Type="Italic">in vitro</Emphasis> and <Emphasis Type="Italic">in vivo</Emphasis>

Chalcones are considered the precursors of flavonoids and have been identified as interesting compounds with antitumor properties. Boronic-chalcone derivatives are more toxic to breast cancer cells compared to normal breast cells. Here, we studied the antitumor activities of trans-4-lodo,4′-boranyl-chalcone (TLBC), which is a boronic-chalcone derivative, in several glioma cell lines. TLBC showed a dose-dependent inhibition with inhibitory concentration 50% value in the μM range (5.5–25.5 μM) in various glioma cell lines. Flow cytometric and western blot assay demonstrated that TLBC induced apoptosis independent of changes to the tumor suppressor p53. This cytotoxic effect was the caspase-dependent manner. Also, TLBC lowered levels of anti-apoptotic Bcl-2 and/or Bcl-X_L protein in several of the cell lines. To examine the antitumor effect of TLBC in vivo, we used a malignant glioma xenograft model. This result showed that in the mice treated with TLBC at 20 mg/kg, mean tumor volume was reduced by 43.9% (P < 0.01) in comparison with the control group. Immunohistochemical and western blot analysis showed that Bcl-2 protein levels were decreased and Bax protein levels were slightly increased in the tumors injected with 20 mg/kg TLBC compared with the control tumors. Therefore, we conclude that TLBC may be a potential chemotherapeutic agent for human glioma.     

In vitro activity of methylrosaniline chloride (gentian violet) as disinfectant against Candida spp. and Trichosporon spp. isolated from blood samples

OBJECTIVE: Methylrosaniline Chloride (MRC) is recognized as a disinfectant, but recently is rarely used in the clinic, because of its cytotoxicity when used continuously with conventional concentrations (1% MRC). We have reported the antibacterial activity of MRC with lower concentration against Methicillin-resistant Staphylococcus aureus (MRSA). In this study, we evaluated the antifungal activity of MRC with lower concentrations. MATERIAL AND METHODS: Antifungal activities of MRC against Candida spp. and Trichosporon spp. were tested. All strains tested were isolated from 106 blood or intravenous catheter samples at Juntendo University Hospital from 1995 to 2004. Minimum inhibitory concentrations against fungi were assayed by agar dilution, under both aerobic and anaerobic conditions. RESULTS: A 0.01% or less concentration of MRC solutions showed marked antifungal activity against Candida spp. and Trichosporon spp. under aerobic or anaerobic conditions. CONCLUSION: A 0.01% or less concentration of MRC should be reevaluated for the control of fungal infection and MRSA infection control.     

Complete genome analysis of a novel intertypic recombinant human adenovirus causing epidemic keratoconjunctivitis in Japan

For 4 months from September 2008, 102 conjunctival swab specimens were collected for surveillance purposes from patients across Japan suspected of having epidemic keratoconjunctivitis (EKC). Human adenovirus (HAdV) DNA was detected in 61 samples by PCR, though the HAdV type for 6 of the PCR-positive samples could not be determined by phylogenetic analysis using a partial hexon gene sequence. Moreover, for 2 months from January 2009, HAdV strains with identical sequences were isolated from five conjunctival swab samples obtained from EKC patients in five different regions of Japan. For the analyses of the 11 samples mentioned above, we determined the nucleotide sequences of the entire penton base, hexon, and fiber genes and early 3 (E3) region, which are variable regions among HAdV types, and compared them to those of other HAdV species D strains. The nucleotide sequences of loops 1 and 2 in the hexons of all 11 samples showed high degrees of identity with those of the HAdV type 15 (HAdV-15) and HAdV-29 prototype strains. However, the fiber gene and E3 region sequences showed high degrees of identity with those of HAdV-9, and the penton base gene sequence showed a high degree of identity with the penton base gene sequences of HAdV-9 and -26. Moreover, the complete genome sequence of the 2307-S strain, which was isolated by viral culture from 1 of the 11 samples, was determined. The 2307-S strain was a recombinant HAdV between HAdV-9, -15, -26, -29, and/or another HAdV type; however, the recombination sites in the genome were not obvious. We propose that this virus is a novel intertypic recombinant, HAdV-15/29/H9, and may be an etiological agent of EKC.