Increased expression of manganese superoxide dismutase is associated with that of nitrotyrosine in myopathies with rimmed vacuoles

Oxidative stress has been suggested as one of the pathogenetic mechanisms of inclusion body myositis (IBM). To study the role of antioxidant enzymes in myopathies with rimmed vacuoles, we examined expressions of copper, zinc superoxide dismutase (Cu, Zn-SOD) and manganese superoxide dismutase (Mn-SOD), and the relationship between SODs and other proteins localized in rimmed vacuoles in muscle biopsy specimens from three cases of sporadic IBM and two of distal myopathy with rimmed vacuoles (DMRV) as well as eight control cases of myopathies without rimmed vacuoles. Immunoblot analysis showed distinct protein bands of both SODs in IBM and DMRV using subtype-specific antibodies. Intensities of immunoreactive bands for Mn-SOD in IBM and DMRV were stronger than those in the control cases. Immunohistochemistry disclosed accumulation of both SODs in vacuolated muscle fibers in all cases of IBM and DMRV. Immunoreactivity for Mn-SOD was often colocalized with that of nitrotyrosine, cytochrome oxidase, tau, and lysosome-associated membrane proteins 2 (LAMP-2) in vacuolated fibers. Some of the Cu, Zn-SOD-positive vacuolated fibers were associated with ubiquitin. The two SODs may have different roles for cell protection, and the expression of Mn-SOD is associated with nitric oxide-induced oxidative damage in myopathies with rimmed vacuoles.     

A network system of medical and welfare information service for the patients,their families,hospitals, local governments,and commercial companies in a medical service area

A service information system using the Internet, which connected the various people who are related to medical treatment and nursing welfare, was constructed. An intractable neurological disease patient who lives in the Onga district, Fukuoka, Japan, and the people who are related to the service were chosen as test users in an experimental model. The communicated service information was divided into open-use data (electronic bulletin board, welfare service, medical care service, and link to private company service home page) and closed-use data (the individual patient's hysterics). The open data server was installed in an Internet service provider The open data could be accessed not only by the patient, but also by the family, information center, companies, hospitals, and nursing commodity store related to patient's nursing and medical treatment. Closed data server was installed in an information center (public health center). Only patient and information center staff can access the closed data. Patients should search and collect the service information of various medical and welfare services by themselves. Therefore, services prepared for the patient are difficult to know, and they cannot be sufficiently utilized. With the use of this information system, all usable service information became accessible, and patients could easily use it. The electronic bulletin board system (BBS) was used by patients for knowing each other or each others' family, and was used as a device for exchange of wisdom. Also, the questions for the specialist, such as doctor, dentist, teacher, physical therapist, care manager, welfare office staff member, and public health nurse, and the answers were shown on the BBS. By arranging data file, a reference of various patients in question and answer, which appeared in this BBS, was made as "advisory hints" and was added to the open data. The advisory hints became the new service information for the patients and their family. This BBS discovered the possibility of becoming an important information source for companies, hospital and, administration to know the requirements of patients and their families and the kind of services to be served. Although suppliers provide medical and welfare services for the patient, there is a tendency that the service information is sent by the suppliers at their own convenience. The information system in which various people participated was constructed in order to collect information for the patient, taking a patient-oriented approach. The result of the model test showed that this information system using Internet technology is a good system for both the service supplier and its receiver.     

Diagnostic usefulness of diffusion-weighted magnetic resonance imaging in influenza-associated acute encephalopathy or encephalitis

A magnetic resonance imaging (MRI) study was performed for a 20-month-old girl with an influenza type A infection who presented acute encephalopathy. Conventional MRI performed 8 days after the onset of encephalopathy, including T1-weighted, T2-weighted, and fluid-attenuated inversion recovery imaging, revealed only vague lesions in the right frontal, temporal, and parietal lobes. In contrast, diffusion-weighted imaging (DWI) then demonstrated the lesions much more intensively. On the 26th day, the lesions previously observed on DWI had become less discernible. The hyperintensity observed on DWI might reflect cytotoxic edema. Thus, DWI may be useful for evaluation of acute influenzal encephalopathy/encephalitis.     

Renal tubular acidosis associated with zonisamide therapy

PURPOSE: We sought to report a previously undescribed adverse effect, renal tubular acidosis associated with zonisamide (ZNS) therapy. METHODS: Ammonium chloride, bicarbonate, and furosemide loading tests were performed in an epileptic patient with metabolic acidosis and episodic hypokalemia who was treated with ZNS. RESULTS: Distal renal tubular acidosis was diagnosed. On reexamination 7 weeks after ZNS had been replaced with phenytoin, the renal tubular acidosis disappeared. CONCLUSIONS: This case indicates, for the first time, that ZNS might be a potential cause of renal tubular acidosis. Blood gases and serum electrolytes should be measured in patients undergoing ZNS therapy.     

Neurotrophin-3 levels in cerebrospinal fluid from children with bacterial meningitis, viral meningitis, or encephalitis

Neurotrophin-3 levels were measured in the cerebrospinal fluid of 35 patients with bacterial meningitis, viral meningitis, or encephalitis by two-site enzyme immunoassay. Elevated cerebrospinal fluid levels of neurotrophin-3 were demonstrated in 8 of 18 patients with bacterial meningitis. Follow-up examination of the eight patients at the convalescent stage showed diminished cerebrospinal fluid levels of neurotrophin-3. In contrast, none of the 17 patients with viral meningitis or encephalitis showed an elevation of neurotrophin-3 levels in cerebrospinal fluid. No relationships were observed between neurotrophin-3 levels and cerebrospinal fluid cell numbers, cerebrospinal fluid protein levels, serum C-reactive protein concentrations, or outcome in bacterial meningitis. Since neurotrophin-3 is involved in the survival of neurons and the modulation of the immune system, neurotrophin-3 could play a neuroprotective or immunomodulatory role in bacterial meningitis.     

Cytotoxic T cell activity against the peptide, AYRARALEL, from Yo protein of patients with the HLA A24 or B27 supertype and paraneoplastic cerebellar degeneration

OBJECTIVE: To determine a peptide that reacts with cytotoxic T cells (CTL) of patients with paraneoplastic cerebellar degeneration and anti-Yo antibodies with either HLA A24 or B27 supertype. METHOD: We studied CTL activity of four patients, three were HLA A24-positive and one did not have HLA A24 but had B27 supertype. After an incubation of mononuclear cells with or without peptide and IL-2, CD8-rich fraction was prepared by treatment with Magnetic Cell Sorting system (MACS) twice. CTL activity was calculated by 51Cr release from transfectant, C1RA*2402 as target cells. The peptide-binding assay was examined by flow cytometry. RESULTS: Two of three HLA A 24-positive patients demonstrated CTL activity against the Yo peptide, AYRARALEL. CTL activity was found to be 19.5% and 11.7% at the effector/target (E/T) ratio of 23:1 and 11:1, respectively. A patient who did not have HLA A24 but had A2 and B27 supertype possessed a CTL activity of 19.4% with 15:1 as E/T ratio. The peptide could bind to HLA A*2402 molecules but not to A*0201. CONCLUSIONS: We showed CTL activity in two of three Japanese patients with HLA A24 by using HLA A*2402 transfectant cells as the target. In addition, we identified the first Japanese patient who had B27 supertype, and suggested that the same peptide, AYRARALEL, could be recognized by CTL in this patient.     

Quantitative renography with the organ volume method and interporative background subtraction technique

When quantification of renal activity is performed by planar imaging, many correction factors must be considered. To obtain quantitative renal images and renogram, we have examined our proposed method by using the organ volume for scatter, attenuation, and background activity, and the interporative background subtraction (IBS) technique in phantom and clinical studies. A renal phantom study was performed by varying the renal depth from 3 to 11 cm and the kidney-to-background activity concentration ratio from 5 to 80. Planar images were properly corrected for scatter, attenuation and background activity by our method and the corrected images were compared with the images obtained by the conventional method for the estimation of true renal activity. Clinical Tc-99m DTPA dynamic data for both a good and a poor renal function were also corrected by our method and volume-corrected renograms were obtained. For the phantom study, depth-independent images were obtained and these images gave a good estimation of the true count rate. In the clinical study, the conventional renogram was especially modified to allow for oversubtraction of background counts in the early phase (0–4 min). In conclusion, our proposed correction method can assess renal function qualitatively and quantitatively in both static and dynamic planar renal imaging.