A case of acute disseminated encephalomyelitis (ADEM) associated with peripheral neuropathy]

A 17-year-old boy with high fever, headache, and neck stiffness was admitted to our hospital. Spinal fluid showed a protein level of 215 mg/dL with myelin basic protein (579 pg/mL), 347/ microl cells (330 mononuclear cells), and a glucose level of 53 mg/dL. One week later, urinary retention, flaccid paraplegia, and sensory disturbance below the 10th thoracic level developed. MRI of the spinal cord revealed swelling and T2-high intensity area in the cord at the 11th and 12th thoracic level. Although high-dose of methylprednisolone was administered, consciousness disturbance and respiratory failure that required mechanical ventilation occurred. Bilateral abducens nerve palsy, nystagmus, and flaccid tetraparesis also occurred. Brain MRI revealed T2-high intensity area in the midbrain and pons. Nerve conduction study showed diminished amplitudes and prolonged latencies or absence of F waves. The patient was administered a combination of intravenous immunoglobulin and a high-dose of methylprednisolone. He showed improvement within one week after the treatment. Two weeks later, he recovered from respiratory failure and weakness of the upper limbs. He remained paraplegic, but gradually improved and was able to walk with support one and a half years later. We suggest the combination therapy of intravenous immunoglobulin and a high-dose of methylprednisolone is effective for patients with combined ADEM and peripheral neuropathy.     

Superoxide dismutases of muscle in mitochondrial encephalomyopathies

Lmmunohistochemical analyses were made of the superoxide dismutases (Mn-SOD and CuiZn-SOD) in biopsied muscles from 7 patients with mitochondrial encephalomyopathies that included mitochondrial encephalomyopathy, lactic acidosis and strokelike episodes (MELAS), and chronic progressive external ophthalmoplegia (CPEO). Mn-SOD mainly was present in the subsarcolemmal region, but it also was found in a coarsely granular, reticular, or diffuse pattern of staining within the muscle fibers. These Mn-SOD-positive fibers corresponded almost completely to the ragged-red fibers. The immunoreaction for CuiZn-SOD was weakly positive in some of the muscle fibers positive for Mn-SOD. In CPEO, Mn-SOD-positive fibers predominantly showed decreased cytochrome c oxidase (COX) activity. In MELAS, Mn-SOD-positive fibers tended to be stained deeply for COX although a few were COX-negative. These findings suggest that Mn-SOD-positive fibers can be used to make a differential diagnosis between CPEO and MELAS and that in mitochondrial encephalomyopathies Mn-SOD in the raggedred fibers may protect against oxidative stress. © John Wiley & Sons, Inc.     

Proposal of a standard method for clinical evaluation of antimicrobial agents in prostatitis--specifications of patients and criteria for evaluation of clinical efficacy

The criteria for clinical evaluation of the efficacy of antimicrobial agents on prostatitis were proposed. Nomenclatural definition, specifications of patients and criteria were as follows. Acute prostatitis: Target infection is acute bacterial prostatitis with no underlying condition in urinary tract. The findings of swelling and tenderness of prostate by rectal examination are essential. The patients are between 16 and 69 years old. They have fever greater than 37 degrees C and pain on micturition. Microscopic examination reveals white blood cells (WBCs) in VB1 or VB2 before treatment greater than or equal to 10 cells/hpf. Viable bacteria in VB1 or VB2 before treatment are greater than or equal to 10(4) bacteria/ml. Period of treatment is for 7 days. To evaluate clinical efficacy, 3 days after administration, changes of symptoms (fever and pain on micturition) are recorded. Seven days after administration, changes of symptoms, microscopic examinations and number of bacteria are recorded. The overall clinical efficacy is graded as "excellent", "moderate" or "poor" by combining changes in the above 3 parameters. Chronic prostatitis: Target infection is chronic bacterial prostatitis with no underlying condition in urinary tract. The patients are between 16 and 69 years old. Microscopic examination reveals WBC in EPS or VB3 before treatment greater than or equal to 10 cells/hpf. Viable bacteria before treatment are greater than or equal to 10(3)/ml (GNR) or greater than or equal to 10(4)/ml (GPC). Treatment period is for 14 days. To evaluate clinical efficacy, after 14 days of administration, changes of symptoms, microscopic examinations and number of bacteria are recorded. The overall clinical efficacy is graded as "excellent", "moderate", or "poor" by combining the changes in the 2 parameters, microscopic examination and number of bacteria.     

Epidemiologic survey and genetic analysis of endemic hepatitis C virus infection in a Japanese town with a high prevalence of hepatitis B virus carriers

Mass screening for hepatitis C virus antibody was carried out in 875 inhabitants (313 men and 562 women) of a town in Japan with a high rate of hepatitis B virus infection. The overall rate of positivity for anti-HCV was 8.8% (6.4% in men and 10,1% in women). The rate of positivity for hepatitis B virus surface antigen was 11.2%. Five subjects (0.6%) were positive for both markers. HCV-RNA was detected in 65 (88.4%) of 77 individuals who were positive for anti-HCV and in 1 (1.5%) of 60 individuals negative for anti-HCV. The genotype of the HCV genome was determined by PCR analysis using type-specific primers in 60 individuals. HCV type 1b was detected in 51 subjects (85%), type 2a in 3 subjects (5%), and type 2b in 6 subjects (10%). None of the individuals was infected with more than one genotype. The nucleotide sequences of the partial nonstructural 5 region of HCV type 1b genotype obtained from 6 individuals showed at least 92.0% homology in the nucleotide sequence, and 94.8% homology in the amino acid sequence. Homology among these clones was greater than their homology with previously described type 1 b sequences. The findings suggest that there was a specific local origin of HCV infection, although it was not possible to identify any single source of HCV infection. The results also indicate the presence of asymptomatic HCV carriers. © 1995 Wiley-Liss, Inc.     

Marked sequence diversity in the putative envelope proteins of hepatitis C viruses.

The nucleotide sequences of cDNAs (414 base pairs) encoding parts of putative envelope proteins (gp35 and gp70) of 40 isolates of hepatitis C virus (HCV-J) derived from 30 independent plasma or liver specimens from Japanese patients (13 with chronic hepatitis, 14 with hepatocellular carcinoma and 3 hemophiliacs who had received imported clotting factors), were analyzed using the polymerase chain reaction. Approximately 29-38% of the nucleotide sequences of the HCV-J isolates examined differed from those of isolates from the United States (HCV-US). Furthermore, 12-24% and 8-17% sequence diversities were found within the isolates of HCV-J and HCV-US, respectively. The diversities of the amino acid sequences were the same or greater than those of the nucleotide sequences. We confirmed that two hypervariable regions (HVR1 and HVR2) were present in this amplified region, as described in our previous report (Hijikata et al., 1991a) and we found that the HVR1 regions of HCV-J and HCV-US were 27 and 21 amino acids in length, respectively, and began from the N-terminal amino acid of gp70. HVR2 was found in HCV-J, but not in HCV-US isolates, in which the corresponding region of the genome was conserved. During the analysis, plural HCV genomes were found in 6 of 30 specimens. These plural HCV genomes in a single specimen were concluded to be derived from the same HCV ancestor, because of their relative low sequence diversities (about 10% in their nucleotide sequences).(ABSTRACT TRUNCATED AT 250 WORDS)     

The expression of neuronal nitric oxide synthase and dystrophin in rat regenerating muscles

We investigated the expression of neuronal nitric oxide synthase (nNOS) and dystrophin in the regenerating skeletal muscles of rats after cardiotoxin-induced myonecrosis by immunohistochemical studies and western blot analysis. In normal muscles, nNOS was moderately immunostained on type 2B fibers, but was faintly immunostained on type 2A or type 1 fibers. In immunohistochemical studies of regenerating muscles, nNOS was first observed at the sarcolemma of type 2B fibers on day 10, when the type discrimination between types 2A and 2B was first detected by ATP reactions. Subsequently, the immunostaining of nNOS grew progressively stronger in type 2B fibers, with faint staining in type 2A and type 1 fibers until day 28. Meanwhile, the immunostaining of dystrophin grew stronger equally in all three fibers until day 21. In western blot analysis of regenerating muscles, nNOS regenerated more slowly than dystrophin. The present data suggest that the expression of nNOS is related to the muscle fiber type differentiation, and that the role of nNOS is related to the function of the type 2B fibers of the muscle. This revised version was published online in July 2006 with corrections to the Cover Date.     

Growth-suppressive activities of serine protease inhibitors, FOY-305, ONO-3403 and FO-349 toward human carcinoma cells

FOY-305 is a synthetic serine protease inhibitor and ONO-3403 and FO-349 are its derivatives. The effects of these compounds on the proliferation of several human carcinoma cell lines were investigated in vitro by MTT colorimetric assay. ONO-3403 showed the most potent growth-inhibitory activity among these protease inhibitors. The half maximum inhibition concentrations of ONO-3403 toward BxPC-3 pancreatic carcinoma, T24 bladder carcinoma and A431 epidermoid carcinoma cells were 20-30 mu g/ml whereas those toward pancreatic carcinomas, PANC-1 and Mia PaCa-2, were 60-80 mu g/ml. Since FOY-305 has been shown to be effective in chemotherapy for human oral cancer, ONO-3403 is expected to be a more effective anticancer drug.     

Enhancement of anti-proliferative activities of 5-FU, HCFU, SN-38, THP and ACNU by a serine protease inhibitor, FOY-305

The effects of a synthetic serine protease inhibitor, FOY-305, on the proliferation of normal and transformed mouse fibroblasts were investigated in vitro by MTT colorimetric assay. FOY-305 inhibited the growth of normal NIH3T3 cells and their src- and erbB2-transformed cells with a half maximum inhibitory concentration (IC50) of 1-1.2 mg/ml whereas it suppressed the growth of ras-transformed cells more effectively (IC50 was 0.5-0.6 mg/ml). Flow cytometric analysis using synchronized NIH3T3 cells has shown that the growth-inhibitory activity of FOY-305 was due to the suppression of G(1)/S transition. The synergistic effects between FOY-305 and traditional anticancer drugs were also investigated by the MTT assay and the results showed that FOY-305 significantly enhanced the antiproliferative activities of 5-fluorouracil (5-FU), 1-hexylcarbamoyl-5-fluorouracil (HCFU), 7-ethyl-1-hydroxy-7-ethyl-10-[4-(1-piperidino)-1-piperidino] camptothecin (SN-38), pirarubicin (THP) and 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU).