Loss of reaction time specificity for movement direction in Parkinson's disease

Electromyographic (EMG) reaction times (RTs) of the right biceps brachii muscle and its integrated EMG (iEMG) from the onset until 50 msec after the start of activities for elbow flexion and forearm supination in the condition with or without warning signal were examined in seven patients with Parkinson's disease and seven age- and sex-matched normal subjects. In the control group RT of forearm supination with warning tended to be faster than that of elbow flexion and the reverse occurred without warning, and iEMG of forearm supination were significantly small compared to those of elbow flexion in each condition. In the Parkinson group both RT and iEMG of elbow flexion were nearly the same as that of forearm supination regardless the presence or absence of warning signal, indicating the loss of RT and iEMG specificity for the two direction of movement in Parkinson's disease.     

Active infective endocarditis remaining latent for six weeks after discontinuation of antibiotic therapy: a case report

A 75-year-old man was treated for 4 weeks with penicillin administration for infective endocarditis in the mitral valve caused by Enterococcus faecalis. The infection recurred, so he received penicillin administration for a further 6 weeks. He remained afebrile and all laboratory examinations were within normal limits for 6 weeks after the antibiotic treatment was discontinued, but the vegetation remained large and highly mobile. Since the onset, possible embolic episodes had occurred three times. He underwent mitral valve repair with annuloplasty. Although the infection appeared to have healed by antibiotic therapy, resected tissue was strongly positive for Enterococcus faecalis. This case suggests that surgery should be aggressively considered if the vegetation does not shrink markedly.     

Virus-induced neuronal apoptosis as pathological and protective responses of the host

Extensive efforts have been made to elucidate mechanisms by which viruses induce apoptosis in cultured neuronal cells. However, little is yet understood about the mechanisms of neuronal apoptosis in vivo as well as interpretations of this active host response. Here we review recent advances toward understanding these topics. The c-Jun N-terminal protein kinase cascade may be an important apoptotic mediator in virally infected neurons, which comes in focus as a therapeutic target for protecting neurons from death. A novel concept can be proposed that virus-induced neuronal apoptosis in the central nervous system may represent a pathological host response, while that in the peripheral counterpart, especially olfactory receptor neurons, may mediate a protective host response.     

The association between tumour necrosis factor-alpha gene polymorphism and the susceptibility to rugal hyperplastic gastritis and gastric carcinoma

OBJECTIVES: Some subjects infected by Helicobacter pylori have enlarged folds in the gastric body, the precise mechanism of which remains obscure. The aim of this study was to clarify the association of tumour necrosis factor-alpha (TNFA) gene polymorphism with susceptibility to hyper-rugosity. We also examined the association of TNFA polymorphism with gastric carcinoma. SUBJECTS AND METHODS: Four hundred and seventy-two subjects (male/female = 351/121, aged 26-81 years) without gastric carcinoma (control group), and 300 patients (male/female = 218/82, aged 32-91 years) with gastric carcinoma. Barium meal roentgenograms were performed in 396 subjects in the control group and fold width was measured at the greater curvature of the middle portion of the gastric body. Fasting plasma anti-H. pylori IgG titres, pepsinogens (PGs) I and II were analysed, and TNFA -857 promoter polymorphism was distinguished by the 5' nuclease polymerase chain reaction assay and polymerase chain reaction restriction fragment length polymorphism using HincII in both groups. RESULTS: Adjusted odds ratios of TNFA -857 T/T genotype and H. pylori seropositivity for hyper-rugosity (fold width = 6.0 mm) were 6.7 (95% confidence interval (CI) 1.5-28, P < 0.01) and 18.2 (95% CI 4.2-78, P < 0.0001), respectively. There were no significant differences in any genotype or allele frequencies between the control and total gastric carcinoma group. In a subgroup of gastric carcinoma patients who were negative for the PG assay, however, the odds ratio of the T allele was 1.4 (95% CI 1.0-2.0, P < 0.05). CONCLUSION: The TNFA -857 T/T genotype and H. pylori infection were strongly associated with rugal hyperplastic gastritis. The TNFA -857 T allele may promote gastric carcinoma without severe atrophy.     

Non-steroidal anti-inflammatory drug,nabumetone, prevents indometacin-induced gastric damage via inhibition of neutrophil functions

Nabumetone is a non-steroidal anti-inflammatory drug (NSAID). It works as a prodrug and is extensively metabolized to an active metabolite, 6-methoxy-2-naphthylacetic acid (6MNA). It is well known that neutrophil infiltration and activation are critical in the pathogenesis of NSAID-induced gastric injury, and nabumetone shows less incidence of gastrointestinal irritancy. We examined the effects of nabumetone on neutrophil activation and on indometacin-induced gastric damage. In the indometacin-induced gastric mucosal injury, rats were treated with indometacin and then nabumetone or 6MNA was orally administered. Nabumetone prevented gastric damage accompanied by the reduction of neutrophil infiltration into gastric mucosa, but such an effect was not observed with 6MNA. Nabumetone reduced the formyl methionyl leucyl phenylalanine (fMLP)-induced respiratory burst of human neutrophils to 30% of the control level in-vitro, but 6MNA did not. In addition, nabumetone prevented the fMLP-induced migration of neutrophils. Nabumetone did not inhibit O2- generation in the xanthine-xanthine oxidase system. These results suggest that nabumetone prevents gastric damage induced by the active metabolite, 6MNA, via the suppression of neutrophil activation in gastric mucosa.     

Enhancement of antitumor radiation efficacy and consistent induction of the abscopal effect in mice by ECI301, an active variant of macrophage inflammatory protein-1alpha.

PURPOSE: We studied whether i.v. administration of a chemokine after local tumor site irradiation could prevent remaining, as well as distant, nonirradiated tumor cell growth by leukocyte recruitment. EXPERIMENTAL DESIGN: Tumors were implanted s.c. in the right or both flanks. After local irradiation at the right flank, ECI301, a human macrophage inflammatory protein-1alpha variant was injected i.v. Tumor volumes were measured every 3 days after treatment. RESULTS: In Colon26 adenocarcinoma-bearing BALB/c mice, repeated daily administration (over 3-5 consecutive days) of 2 mug per mouse ECI301 after local irradiation of 6 Gy prolonged survival without significant toxicity, and in about half of the treated mice, the tumor was completely eradicated. Three weekly administrations of ECI301 after local irradiation also led to significant, although less effective, antitumor radiation efficacy. ECI301 also inhibited growth of other syngenic tumor grafts, including MethA fibrosarcoma (BALB/c) and Lewis lung carcinoma (C57BL/6). Importantly, tumor growth at the nonirradiated site was inhibited, indicating that ECI301 potentiated the abscopal effect of radiation. This abscopal effect observed in BALB/c and C57BL/6 mice was tumor-type independent. Leukocyte depletion studies suggest that CD8+ and CD4+ lymphocytes and NK1.1 cells were involved. CONCLUSIONS: Marked inhibition of tumor growth at the irradiated site, with complete tumor eradication and consistent induction of the abscopal effect, was potentiated by i.v. administration of ECI301. The results of this study may offer a new concept for cancer therapy, namely chemokine administration after local irradiation, leading to development of novel therapeutics for the treatment of advanced metastatic cancer.     

A clinical study of tuberculous colitis.

During the last 8 years, the diagnosis of tuberculous colitis has been made radiologically in 22 cases. Twelve were confirmed by histological or bacteriological evidences. The X-ray findings are classified into three types as follows: Type A, showing an extensive scarred area in the ileocecum and ascending colon. Type B, showing annular stricture in the ascending colon and dilatation of its oral side. Type C, showing pouchformation (pseudo-diverticulum) and deformity in the cecum. We emphasize that histological examination and culture of the biopsy specimens by endoscopy were useful for the diagnosis of tuberculous colitis. Furthermore, radiologic changes of the colon by administration of antituberculous drugs were observed.