Immunological responses of astroglia in the rat brain under acute stress: interleukin 1 beta co-localized in astroglia.

In previous studies, we demonstrated that acute stress induces microglial activation, without inducing any inflammatory responses; however, the effect of acute stress on astroglia, another glial cell subtype in the brain, remains to be elucidated. We determined the effect of acute stress on astroglia, particularly in terms of morphological changes and inflammatory properties. In contrast to microglia, the morphology of astroglia was not altered following a 2-h period of acute stress. Interestingly, the number of astroglia immunoreactive to interleukin 1 beta (IL-1ß) significantly increased in several brain regions including the hippocampus, hypothalamus, amygdala, and periaqueductal gray following the acute stress. Confocal microscopy revealed that IL-1ß is exclusively co-localized in astroglia, and not in neurons or microglia. The present study demonstrates that exposing rats to acute stress increases IL-1ß immunoreactivity in astroglia in specific regions of the brain, and the mechanism of astroglial response to acute stress clearly differs from that of microglial response. Thus, astroglia may play important roles in neuroimmunomodulation through IL-1ß during times of acute stress.

Numerical evaluation method for catheter prototypes using photo-elastic stress analysis on patient-specific vascular model.

BACKGROUND: To date, no quantitative analysis has been developed to evaluate catheter performance inside the vascular lumen. METHODS: An evaluation system for endovascular tools was built with a polyurethane elastomer vascular model inside a polariscope and a catheter driving system. This robotic system reproduced a catheter insertion trajectory inside the vascular model, using a surgical catheter and three catheter prototypes used for motion capture on endovascular surgery simulation. Birefringence is produced by photo-elastic characteristics of the polyurethane elastomer when the material is submitted external stress. The birefringence produced by the catheter on the vascular model wall was recorded and represented numerically by the correlation between consecutive frames of the registered video. RESULTS: Correlation values between frames showed that the performance of the prototypes was lower than that of the medical use catheter. The performance of prototypes was reduced by microcoils on their tips. CONCLUSIONS: This methodology opens new options to evaluate medical catheters and physicians skills. opyright

Body image as a visuomotor transformation device revealed in adaptation to reversed vision.

People adapt with remarkable flexibility to reversal of the visual field caused by prism spectacles. With sufficient time, this adaptation restores visually guided behaviour and perceptual harmony between the visible and tactile worlds. Although it has been suggested that seeing one's own body is crucial for adaptation, the underlying mechanisms are unclear. Here we show that a new representation of visuomotor mapping with respect to the hands emerges in a month during adaptation to reversed vision. The subjects become bi-perceptual, or able to use both new and old representations. In a visual task designed to assess the new hand representation, subjects identified visually presented hands as left or right by matching the picture to the representation of their own hands. Functional magnetic resonance imaging showed brain activity in the left posterior frontal cortex (Broca's area) that was unique to the new hand representations of both hands, together with activation in the intraparietal sulcus and prefrontal cortex. The emergence of the new hand representation coincided with the adaptation of perceived location of visible objects in space. These results suggest that the hand representation operates as a visuomotor transformation device that provides an arm-centred frame of reference for space perception.

TT virus infection in patients with fulminant hepatic failure.

OBJECTIVE: A new DNA virus, which has been designated the TT virus, was discovered in 1997. It is not clear whether TT virus is a cause of any of the types of hepatitis. We conducted a case-control study to test the hypothesis that the presence of TT virus is a necessary condition for the development of fulminant hepatic failure in people who have non-A, -B, or -C hepatitis. METHODS: We studied 55 patients with fulminant hepatic failure [28 men, 27 women, mean (+/- SD) age, 47 +/- 15 yr], 32 patients with acute hepatitis (18 men, 14 women, mean age, 38 +/- 15 yr), and 200 healthy subjects (106 men, 94 women, mean age, 42 +/- 14 yr). TT virus DNA was detected in sera by a nested polymerase chain reaction using a primer set for genotype 1. RESULTS: TT virus was more frequently detected in patients with fulminant hepatic failure [in 33 of 55 (60%); 95% confidence interval (CI), 47-73%] than in those with acute hepatitis [in 8 of 32 (25%); 95% CI, 10-40%; p = 0.0016] or in healthy subjects [in 50 of 200 (25%); 95% CI, 19-31%; p < 0.0001]. TT virus was detected at a significantly higher rate in non-A, -B, or -C fulminant hepatic failure [in 18 of 22 (82%); 95% CI, 66-98%] than in fulminant hepatic failure of A, B, or C type [45%, 28-62%, 15/33; p = 0.007] or in non-A, -B, or -C acute hepatitis [24%, 3-44%, 4/17; p = 0.0003]. The logistic regression analysis selected TT virus (p = 0.0009), age (p = 0.0116), and etiology (p = 0.0309) as independent variables associated with fulminant hepatic failure (coefficient of determination, 0.2335). CONCLUSIONS: TT virus comparatively plays a role in the pathogenesis of non-A, -B, or -C fulminant hepatic failure.

Possible association between serum GB virus C RNA level and disease activity in fulminant hepatitis type G.

BACKGROUND/AIMS: Whether GB virus C causes serious liver diseases remains controversial. The aim of the present study was to determine whether there is an etiological relationship between GB virus C and fulminant hepatitis. METHODS: The level of GB virus C RNA in the sera of three patients with fulminant hepatitis was quantitatively determined using the newly developed real-time detection polymerase chain reaction method, which is based on Taq Man chemistry. The NS 3 region of the viral genome isolated from the sera was sequenced at several time points to confirm whether the same virus was responsible for fulminant hepatitis during the patients' clinical courses. RESULTS: The sensitivity of the PCR was comparable to that of nested PCR and a linear relationship between RNA copy number and threshold cycle was observed for 10(1) and 10(6) RNA copies/ml (r = 0.99). The serum level of GB virus C RNA closely paralleled that of ALT in all patients. Sequence analysis of the NS3 region isolated from the patients' sera revealed that the same GB virus C strain infected the patients during their entire clinical courses, despite plasma exchange therapy. CONCLUSIONS: These observations suggest that GB virus C may be etiologically associated with fulminant hepatic failure, and is not merely an inactive bystander introduced by therapeutic plasma exchange.

[Serial hepatic and splenic volumetry in acute severe hepatitis].

In this study, we elucidate a relationship between final outcome and changes in hepatic and splenic volume in patients with acute severe hepatitis. The subjects were 40 patients: 10 with sever acute hepatitis (prothrombin time < 40%) and 30 with fulminant hepatic failure (acute type in 12 and subacute type in 18). Liver and spleen volume were measured by CT initially on hospitalization and subsequently 1 to 40 days after hospitalization, and the scans were analyzed retrospectively. Liver volume decreased in 15 of 26 survivors, and all 14 non-survivors. Among 15 survivors and 14 non-survivors whose liver volume decreased, spleen volume increased in none of the survivors, whereas it increased in 11 of the 14 non-survivors. In survivors there was a close parallelism between changing rates of the liver volume and that of the spleen volume (r = 0.82, p < 0.0001). These observations suggest that the decrease of liver volume accompanied by that of spleen volume implies a good prognosis, while the decrease without such accompaniment implies a bad prognosis.

[A close association of prognosis with effect of interferon in HBV carriers developing acute severe exacervation].

We have treated 19 HBV carriers who developed acute severe exacerbation using interferon and immunosuppressive agents. Of these 14 patients developed fulminant hepatic failure. Of 10 patients with positive result for serum HBV DNA polymerase before the start of te treatment, five patients in whom HBV DNA polymerase turned negative and one patient whose HBV DNA polymerase level fluctuated in a low abnormal range after the start of the treatment survived. While, four patients whose HBV DNA polymerase level remained high after the start of interferon treatment died. Thus, it is suggested that suppression of HBV virus replication is closely related to prognosis in HB carriers developing acute severe exacervation of hepatitis.

Clinical and molecular virological differences between fulminant hepatic failures following acute and chronic infection with hepatitis B virus.

Clinical and molecular biological characteristics were compared between patients who presented with fulminant hepatic failure following acute infection with hepatitis B virus (HBV) and those who developed hepatic failure during they carried HBV. The 11 patients with acute HBV infection had higher levels of alanine aminotransferase (mean +/- SD: 4943 +/- 2867 vs 1157 +/- 678 IU/L, P < 0.01), more often with a single peak (91% vs. 0%, P < 0.001), and lower total bilirubin level (15.3 +/- 4.4 vs 28.1 +/- 14.3 mg/1000 ml, P < 0.01) than the 13 patients with chronic HBV infection. Hepatitis B surface antigen was detected less often (55% vs. 100%, P < 0.05) and viral DNA polymerase less frequently (0% vs. 46%, P < 0.05) in the patients with acute than chronic HBV infection. Hepatitis B e antigen was detected in one (9%) patient with acute infection, less frequently than in six (46%) patients with chronic infection (P < 0.05). Mutations in the precore region was detected in HBV DNA clones from ten (91%) patients with acute infection and only in those from eight (62%) patients with chronic infection. All HBV DNA clones from the five (38%) patients with chronic infection that did not have precore mutations, however, possessed mutations in the core promoter. These results indicate that HBV mutants incapable of translating hepatitis B e antigen would play a major role in fulminant hepatic failure occurring after acute HBV infection. In contrast, HBV variants with core promoter mutations for reducing the transcription of hepatitis B e antigen would play an additional role in fulminant hepatic failure developing during chronic infection.

Case report: primary hepatic lymphoma associated with chronic liver disease.

We report on a case of primary hepatic lymphoma that developed in a patient with chronic hepatitis C. Given that Japan is an area endemic for both hepatitis B and C viruses, we reviewed 51 Japanese cases of primary hepatic lymphoma, addressing the question as to whether the Japanese cases have unique characteristics and whether there is a causal relationship to the presence of chronic liver disease. Primary hepatic lymphoma most commonly affected middle-aged males. Presenting symptoms and physical findings were non-specific. Aminotransferases tended to stay in the low range compared with marked increases in lactate dehydrogenase. Sixteen patients (31%) had chronic liver disease, eight had liver cirrhosis and eight had chronic hepatitis, suggesting that there is a possible aetiological link between chronic liver disease and primary hepatic lymphoma.

[Causal relationship between GBV-C and fulminant hepatitis].

GBV-C is recently discovered RNA virus which appeared to be member of Flaviviridae. We previously reported the possible involvement of GBV-C in the etiology of fulminant hepatitis(FH). It is still controversial whether GBV-C cause FH. So far, the only reliable tool for the diagnosis of GBV-C is the detection of the viral genome using PCR. Detection of GBV-C in serum of patient with FH dose not necessarily mean that GBV-C is causal virus. Serial quantification of serum GBV-C RNA in patient with FH may reveal a pathogenetic role of GBV-C. Further study is needed to elucidate the relationship between FH and a specific strain of GBV-C.

Fulminant hepatic failure: observation with serial CT.

PURPOSE: To determine the imaging characteristics of fulminant hepatic failure at serial computed tomography (CT) and to assess if any CT findings have prognostic value. MATERIALS AND METHODS: In 40 patients, 207 CT scans were analyzed retrospectively. Thirty-four patients had fulminant hepatic failure (acute in seven and subacute in 27), and six had late-onset hepatic failure. Twenty-one patients died of hepatic failure. CT was performed soon after the onset of coma and repeated weekly. Liver volume was measured by tracing the hepatic contour and summing the areas to estimate whole-liver volume. RESULTS: Liver volumes in survivors (n = 19) and nonsurvivors (n = 21), respectively, were 1,090 cm3 +/- 300 and 830 cm3 +/- 240 at initial CT and 1,130 cm3 +/- 310 and 700 cm3 +/- 280 at last CT (P = .0001). III-defined hypoattenuating areas were noted in 20 patients and were distributed in a solitary (n = 13), multiple (n = 6), or diffuse (n = 1) pattern. At follow-up CT, the area of hypoattenuation increased in six patients (five nonsurvivors) and disappeared or markedly decreased in four survivors. An increase in or late occurrence of ascites was noted in 15 patients (14 nonsurvivors, P = .0001). CONCLUSION: Liver volumes at the initial and last CT examinations and an increase in or late occurrence of ascites are useful prognostic findings.

Cultural and linguistic factors in audiovisual speech processing: the McGurk effect in Chinese subjects.

The "McGurk effect" demonstrates that visual (lip-read) information is used during speech perception even when it is discrepant with auditory information. While this has been established as a robust effect in subjects from Western cultures, our own earlier results had suggested that Japanese subjects use visual information much less than American subjects do (Sekiyama & Tohkura, 1993). The present study examined whether Chinese subjects would also show a reduced McGurk effect due to their cultural similarities with the Japanese. The subjects were 14 native speakers of Chinese living in Japan. Stimuli consisted of 10 syllable (/ba/, /pa/, /ma/, /wa/, /da/, /ta/, /na/, /ga/, /ka/, /ra/) pronounced by two speakers, one Japanese and one American. Each auditory syllable was dubbed onto every, visual syllable within one speaker, resulting in 100 audiovisual stimuli in each language. The subjects' main task was to report what they thought they had heard while looking at and listening to the speaker while the stimuli were being uttered. Compared with previous results obtained with American subjects, the Chinese subjects showed a weaker McGurk effect. The results also showed that the magnitude of the McGurk effect depends on the length of time the Chinese subjects had lived in Japan. Factors that foster and alter the Chinese subjects' reliance on auditory information are discussed.

Chronic hepatitis A with persistent viral replication.

Hepatitis A virus (HAV) usually causes an acute self-limited illness. This report describes a patient with hepatitis A whose serum aminotransferase activities remained above normal and whose serum was persistently positive for immunoglobulin (Ig) M class anti-hepatitis A 31 months after the onset of hepatitis. Liver biopsy carried out 11 months after the onset of hepatitis showed histological changes consistent with chronic hepatitis of moderate severity. HAV RNA was detected by polymerase chain reaction (PCR) in feces collected at the time of the liver biopsy. Furthermore, the patient developed esophageal varices 25 months after the onset of hepatitis. We believe this to be the first reported case in which persistent replication of HAV is implicated in chronic hepatitis with the potential to develop into liver cirrhosis.

Favorable effect of new artificial liver support on survival of patients with fulminant hepatic failure.

The two most serious symptoms of fulminant hepatic failure are bleeding and hepatic coma. To overcome these problems, we developed an artificial liver support system comprising a combination of plasma exchange and hemodiafiltration using a high performance membrane. We treated 67 patients with fulminant hepatic failure. Of these, 65 patients (97.0%) regained normal consciousness, and 55 patients (80.9%) were kept alert as long as we continued to apply this system. All 7 patients (100%) with fulminant hepatitis caused by hepatitis A virus infection and 9 of 12 patients (75%) with fulminant hepatitis caused by acute hepatitis B (HB) virus infection survived. In addition, 7 of 15 HB virus carriers (46.7%) who developed fulminant hepatitis and 11 of 29 patients (37.9%) with fulminant hepatitis caused by non-A, non-B hepatitis viruses survived. The overall survival rate was 37 of 67 patients (55.2%). Our artificial liver support system allows as high a survival rate as liver transplantation.

Interferon and cyclosporin A in the treatment of fulminant viral hepatitis.

The prognosis of fulminant hepatitis due to non-A, non-B virus infection and acute reactivation of hepatitis B virus in HB carriers is generally poor, and the treatment of choice in Western countries is recognized as liver transplantation. In countries such as Japan where liver transplantation is not readily available, however, these intractable types of fulminant hepatitis have to be treated medically. Based on the assumption that persistent replication of causal viruses and enhanced host immune responses, especially cellular immunity, to eradicate the viruses are the key mechanism in progressive liver cell destruction and the poor prognosis, we attempted a combination treatment with interferon and cyclosporin A for these types of fulminant viral hepatitis. Subjects in the present study consisted of 1 patient with acute severe hepatitis without coma and 13 patients with coma (13 with fulminant hepatic failure) due to non-A, non-B virus and acute reactivation of hepatitis B virus. The patients were given interferon-beta, 300 x 10(4) U daily, and cyclosporin A, at an initial dose of 3 mg/kg, with tapering. Fourteen patients with coma received artificial liver support that we devised. The patient with acute severe hepatitis survived, showing histologically remarkable liver regeneration. Eight of the 14 patients with hepatic coma, all of whom were indications for liver transplantation according to the criteria of the King's College group, survived. Decreased transaminase level, increased liver volume, and histological liver regeneration were observed in all the survivors. The combination of interferon and cyclosporin A is worth attempting in fulminant hepatitis caused by non-A, non-B virus and acute reactivation of hepatitis B virus in HB carriers.