Successful differentiation of herpes zoster‐associated erythema multiforme from generalized extension of herpes by rapid polymerase chain reaction analysis

The polymerase chain reaction (PCR) assay for varicella zoster virus (VZV), herpes simplex virus (HSV)‐1 and HSV‐2 is available for use. Sometimes the differential diagnosis of the generalized herpes zoster (HZ), HSV1/2, and drug eruption is difficult. We report a case of HZ followed by the vesicular erythema multiforme (EM)‐like lesion. In this case the use of PCR was of great assistance. A 78‐year‐old Japanese man without any significant previous history of disease was admitted to our hospital complaining of zosteriform vesicle on an erythematous base from his right shoulder to the upper arm. We diagnosed him with HZ at the level of right Th2. In spite of the prompt start of antiviral therapy, a secondary new vesiculous erythema developed on his trunk. Clinically, it was quite difficult to differentiate the lesion from the generalized HZ. Rapid PCR assay of effusion and crust for VZV was performed. A PCR assay of VZV was positive for the crust taken from the primary lesion, while it was negative for the effusion and crust of the secondary widespread lesion. We diagnosed the secondary widespread lesion as an EM‐type drug eruption induced by acyclovir, or an EM associated with herpes zoster. We then stopped the use of acyclovir and applied steroid ointment of a very strong class for the secondary lesions, which improved after a few days. A PCR assay for VZV was useful for ruling out the generalized HZ in our case with secondary developed vesiculous lesions.     

The free radical scavenger edaravone suppresses experimental dextran sulfate sodium-induced colitis in rats

Recent studies suggest that the enhanced release of reactive oxygen species (ROS) plays an important role in the pathogenesis of clinical inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease. In the present study, we investigated the effects of the free radical scavenger edaravone, which is used clinically as an anti-stroke agent, in the development of experimental dextran sulfate sodium (DSS)-induced colitis in rats. The rats were fed 4% (w/w of diet) DSS in standard powder chow for 8 days. The edaravone and vehicle saline were injected subcutaneously twice a day. After the experimental period, the wet colonic weight, macroscopic mucosal damaged area, histological damage score, mucosal myeloperoxidase (MPO) activity, mucosal tissue lipid peroxidate and serum interleukin-6 (IL-6) levels were measured. In the DSS-induced colitis model, edaravone treatment (1-20 mg/kg day) significantly reduced the wet colonic weight, macroscopic damaged area, and the histological damage score. Edaravone treatment also reduced mucosal MPO activity, mucosal tissue lipid peroxidate level and serum IL-6 level. In particular, edaravone at a dose of 20 mg/kg day significantly reduced mucosal MPO activity and serum IL-6 level. These results strongly support the involvement of ROS in the pathogenesis of DSS-induced colitis. A clinical effect for edaravone against IBD patients is strongly expected.     

Relationship between ambient sulfur dioxide levels and neonatal mortality near the Mt. Sakurajima volcano in Japan

We examined the association between neonatal mortality and ambient sulfur dioxide (SO2) levels in the neighborhood of Mt. Sakurajima, Yamashita public health district of Kagoshima City, during the period between 1978 and 1988. The analysis using Poisson regression models showed that the monthly average level of SO2 was positively associated with the neonatal mortality (P = 0.002). When the SO2 levels were categorized into four groups to estimate the relative risk (RR) of neonatal mortality using the lowest exposure category as a reference, the RR increased with elevated exposure levels (P for trend < 0.001) and was the highest in the group with the highest level of exposure (RR = 2.2, 95% confidence interval; 1.2-4.1). Other than SO2, we also examined the number of eruptions, the amount of ashfall, and the average level of suspended particulate matter. None of these factors was associated with neonatal mortality. Although the present study suggests that increase in SO2 levels has had an adverse effect on neonatal mortality in the neighborhood of Mt. Sakurajima, it is difficult to determine the source of the SO2. Further studies are necessary to elucidate the mechanisms of the excess neonatal mortality probably associated with the volcanic SO2 levels.     

Epithelial expression of caveolin-2, but not caveolin-1, is enhanced in the inflamed mucosa of patients with ulcerative colitis

Caveolae are vesicular invaginations of the plasma membrane that act as a scaffold of the assembly of many classes of signaling molecules. Caveolins are the principal structural component of caveolae membranes, and three distinct forms of caveolins have been identified: caveolin-1, caveolin-2, and caveolin-3. In this study, we evaluated the changes in the caveolin-1 and caveolin-2 expression in the inflamed mucosa of patients with IBD. Tissue samples were obtained endoscopically from patients with ulcerative colitis (UC) (n = 18), Crohn's disease (n = 10) and ischemic colitis (n = 8). Normal colorectal tissues were also obtained (n = 15). The caveolin expression was evaluated by standard immunohistochemical procedure. In normal colonic mucosa, caveolin-1 expression was detected in the smooth-muscle cells of the muscularis mucosae and the endothelial cells, but caveolin-2 expression was not detected. In the inflamed mucosa of patients with active UC, caveolin-2 expression was clearly detectable as small scattered foci on the luminal surfaces of epithelial cells, but caveolin-1 expression was similar to that in normal mucosa. Caveolin-2 expression increased in accordance with the disease activity of UC. This enhanced caveolin-2 expression was not detected in active Crohn's disease or ischemic colitis. In conclusion, we demonstrated that the epithelial expression of caveolin-2 is markedly enhanced in the inflamed mucosa of patients with UC. It is likely that the enhanced caveolin-2 expression in patients with UC was associated with the altered signal transductions in the intestinal epithelial cells. Furthermore, our results suggest that there are differences in the phenotypic features of epithelial cells between UC and Crohn's disease.     

Medium-chain triglyceride-rich enteral nutrition is more effective than low-fat enteral nutrition in rat colitis, but is equal in enteritis

Background. Although enteral nutrition (EN) therapy for Crohn's disease has been confirmed to be as effective as steroid therapy, the precise mechanism responsible for the effects of EN remains unclear, although some of the therapeutic effects of EN are believed to be due to a low dietary fat content. In order to elucidate the influence of fat in EN, it is important to investigate not only the quantity of fat, but also the source of the fat. Methods. We compared two enteral nutritional formulae: Elental (Ajinomoto) (elemental diet; ED), which contains only 1.5% fat, provided as long-chain triglycerides (LCT), versus Twinline (Snow Brand Milk Products) (TL), which contains a high percentage of fat (20.4%), provided mainly as medium-chain triglycerides (MCT). These formulae were tested on rat enteritis and rat colitis induced by trinitrobenzene sulfonic acid (TNBS). Results. Both ED and TL reduced the manifestations of enteritis. TL had a stronger anti-inflammatory effect than ED for colitis. TL also had nutritional advantages as compared with ED, as shown by the total serum protein in the TL group being significantly higher than that in the ED group. Conclusion. The results indicate that intraluminal MCT is suitable as a fat energy source during intestinal inflammation in rats. We suggest that Twinline may be more useful to improve nutritional status and to re-duce the mucosal inflammation in rat colitis, but that Twinline is equal in effect to Elental for rat enteritis. Received: November 10, 2000 / Accepted: April 13, 2001     

Identification of hepatitis B virus-specific CTL epitopes presented by HLA-A*2402, the most common HLA class I allele in East Asia

BACKGROUND/AIMS: The aim of this study was to identify and characterize hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTL) epitopes presented by human leukocyte antigen (HLA)-A*2402, most common HLA class I allele in East Asia. METHODS: HLA-A*2402-restricted CTL epitopes were identified by reverse immunogenetics. Immunogenecity of these epitopes was investigated using peripheral blood mononuclear cell (PBMC) from HLA-A24+ patients with acute hepatitis B. RESULTS: An HLA-A*2402 stabilization assay demonstrated that 36 of 63 HBV peptides carrying HLA-A*2402 anchor residues have high- and medium-HLA-A*2402 binding affinity. Two (C117-125 and P756-764) of the 36 peptides induced peptide-specific CTLs. CTL clones and lines specific for these peptides killed HBV recombinant vaccinia virus-infected target cells expressing HLA-A*2402, indicating that these two peptides are CTL epitopes presented by HLA-A*2402. These two peptides were able to induce specific CTLs in 7 and 11 of 12 HLA-A24+ patients with acute hepatitis B, respectively. CONCLUSIONS: We identified two immunodominant CTL epitopes restricted by HLA-A*2402. Because HLA-A*2402 is the most common allele in East Asia, a region in which there are approximately 200 million HBV carriers, these epitopes will be useful for analysis of CTL responses in patients from East Asia.     

Effects of synthetic serine protease inhibitors on proliferation and collagen synthesis of human pancreatic periacinar fibroblast-like cells

Protease inhibitors are currently used as therapeutic agents for chronic pancreatitis in Japan. We previously reported that human pancreatic periacinar fibroblast-like cells (hPFCs) could be cultured from isolated pancreatic acini, and those are thought to play a crucial role in pancreatic fibrosis correlating with platelet-derived growth factor (PDGF) and transforming growth factor beta1 (TGF-beta1) (Pancreas 1997;14: 373-82). The present study was designed to examine the effects of synthetic serine protease inhibitors (FOY-007 and FOY-305) on proliferation and collagen synthesis of hPFCs under cytokine stimulation. The cell proliferation and collagen synthesis were evaluated using assays of [3H]-thymidine incorporation and procollagen type I c-terminal peptide (PIP), and [14C]-proline incorporation to de novo synthesized collagen, respectively. The cell proliferation stimulated by PDGF was inhibited by the application of FOY-007 dose dependently (1-100 microM) and FOY-305 at 100 microM. FOY-007 attenuated the collagen synthesis and PIP production stimulated by TGF-beta1 dose dependently, but FOY-305 inhibited only PIP production. Both protease inhibitors demonstrated no effect on the proliferation and collagen synthesis of hPFCs when they were not stimulated by PDGF or TGF-beta1. Thus, serine protease inhibitors act on hPFCs to diminish the effects of PDGF on proliferation and the effects of TGF-beta1 on collagen synthesis.     

Terminal restriction fragment length polymorphism analysis of the diversity of fecal microbiota in patients with ulcerative colitis

BACKGROUND: Terminal restriction fragment length polymorphism (T-RFLP) analysis is a powerful tool to assess the diversity of complexed microbiota. This permits rapid comparison of microbiota from many samples. In this study, we performed T-RFLP analysis of the fecal microbiota from patients with ulcerative colitis (UC). METHODS: Forty-four patients with UC (23 women and 21 men, median age 25 years) and 46 healthy individuals (25 women and 21 men, median age 34 years) were enrolled in this study. DNA was extracted from their stool samples, and the 16S rRNA genes were amplified by PCR. The PCR products were then digested with HhaI and/or MspI restriction enzymes, and the length of the T-RF was determined. RESULTS: The fecal microbial communities were classified in 8 clusters. Almost all the healthy individuals (39 of 46) were included in cluster I, and most of the UC patients could be divided into the other 7 clusters, indicating that fecal bacterial communities are different between healthy individuals and active UC patients. Some T-RFs, derived from the unclassified bacteria, Ruminococcus, Eubacterium, Fusobacterium, gammaproteobacteria, unclassified Bacteroides, and unclassified Lactobacillus, were detected in the UC patients, but not in the healthy individuals. The T-RFLP patterns were also different between the active patients and inactive (remission) patients. The T-RF derived from the unclassified bacteria, Ruminococcus and Eubacterium, and the T-RFs derived from the unclassified bacteria, Eubacterium, and Fusobacterium were predominantly detected in the active patients not the inactive patients. In contrast, the T-RFs derived from Lactobacillus and unclassified Lactobacillus were more predominant in the inactive (remission) patients. In 4 patients with proctitis, the pattern of fecal microbial diversity was very similar. CONCLUSIONS: T-RFLP analyses showed that the diversity of fecal microbiota in patients with UC was different from that in healthy individuals. Unclassified bacteria, as well as known bacteria, can contribute to alterations in the bacterial diversity of UC patients.