Increased plasma LIGHT levels in patients with atopic dermatitis.

LIGHT [the name of which is derived from 'homologous to lymphotoxins, exhibits inducible expression, competes with herpes simplex virus glycoprotein D for herpes simplex virus entry mediator (HVEM), and expressed by T lymphocytes'], is a member of the tumour necrosis factor superfamily that is involved in various inflammatory diseases. We aimed to estimate the relevance of plasma LIGHT levels as a biomarker for atopic dermatitis (AD). In order to understand the putative role of LIGHT in AD pathogenesis, we also investigate the effects of LIGHT on a monocytic cell line, human acute monocytic leukaemia cell line (THP-1). We examined plasma LIGHT levels, total serum IgE, serum value of CCL17 and peripheral blood eosinophil counts in patients with AD and healthy subjects. The effects of LIGHT on activation and apoptosis in THP-1 cells were also investigated. The plasma concentrations of LIGHT in AD patients were significantly higher than those in healthy individuals and the concentrations decreased as the symptoms were improved by treatment. The LIGHT plasma concentrations correlated with IgE levels and the Severity Scoring of AD (SCORAD) index. In addition, LIGHT stimulation increased expression of CD86 and induced production of interleukin-1ß in THP-1 cells. Apoptosis was inhibited, the Bcl-2 level increased and the caspase-3 level decreased in THP-1 cells stimulated with LIGHT, compared to unstimulated control cells. These results suggest that plasma LIGHT levels may be one of the promising biomarkers for AD.

Amelioration of glucose tolerance by hepatic inhibition of nuclear factor kappaB in db/db mice.

AIMS/HYPOTHESIS: Recent studies have identified the involvement of inhibitor IkappaB kinase (IKK) in the pathogenesis of insulin resistance. To investigate the mechanism involved, we examined the role of nuclear factor kappaB (NF-kappaB), the distal target of IKK, in hepatic glucose metabolism. METHODS: To inhibit NF-kappaB activity, db/db mice were infected with adenovirus expressing the IkappaBalpha super-repressor. RESULTS: The IkappaBalpha super-repressor adenovirus infection caused a moderate reduction of NF-kappaB activity in liver. The treatment was associated with improved glucose tolerance, reduction in the serum insulin level, and increased hepatic triacylglycerol and glycogen contents, but had no effect on insulin-stimulated phosphorylation of Akt. On the other hand, quantification of mRNA in the liver revealed marked reduction of expression of gluconeogenic genes, such as those encoding phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase, concurrent with reduced expression of gene encoding peroxisome proliferator-activated receptor gamma coactivator-1alpha (PPARGC1A, also known as PGC-1alpha). Furthermore, the production of super-repressor IkappaBalpha suppressed the increase in blood glucose level after pyruvate injection. CONCLUSIONS/INTERPRETATION: Our results indicate that moderate inhibition of NF-kappaB improved glucose tolerance through decreased gluconeogenesis associated with reduced PGC-1alpha gene expression in db/db mice, and suggest that inhibition of NF-kappaB activity in liver is a potentially suitable strategy for the normalisation of blood glucose concentration in type 2 diabetes.

Polymorphism of the solute carrier family 12 (sodium/chloride transporters) member 3, SLC12A3, gene at exon 23 (+78G/A: Arg913Gln) is associated with elevation of urinary albumin excretion in Japanese patients with type 2 diabetes: a 10-year longitudinal study.

AIMS/HYPOTHESIS: We have shown previously that the SLC12A3 +78G/A polymorphism in exon 23 (Arg913Gln) was a new candidate for conferring susceptibility to diabetic nephropathy. The aim of this study was to confirm the effect of this polymorphism on the elevation of urinary albumin excretion in type 2 diabetic patients. METHODS: We retrospectively studied 264 Japanese patients with type 2 diabetes over a ten-year period. The subjects were classified into two groups: (1) persistent normoalbuminuria or microalbuminuria, or improvement from microalbuminuria to normoalbuminuria (group N); and (2) progression from normoalbuminuria to microalbuminuria or overt proteinuria, or progression from microalbuminuria to overt proteinuria (group P). They were assessed for association with the +78G/A polymorphism. RESULTS: The frequency of the +78A allele was significantly higher in group N than in group P (10% vs 1%, p=0.021). By logistic regression analysis and discriminant analysis, the substituted allele was shown to be an independent factor correlating negatively to the elevation of albumin excretion (p=0.043 and 0.022, respectively). CONCLUSIONS/INTERPRETATION: The SLC12A3 +78A(+) genotype may have a protective effect against the development and/or progression of diabetic nephropathy in Japanese type 2 diabetic patients.

Eosinophilic pustular folliculitis in association with nevoid basal cell carcinoma syndrome.

This study reports on the clinical and light microscopic features of a nevoid basal cell carcinoma syndrome with the complication of eosinophilic pustular folliculitis. To the authors' knowledge, this is the first report of such an association, which is possibly due to immune dysregulation. Moreover, the patient experienced remission of eosinophilic pustular folliculitis after removal of the jaw cyst. One possible explanation for the remission is that a long-lasting TH, type inflammatory response as a result of the bone defect produces effective cytokines such as interferon-gamma.

Investigations on the liver toxicity of a blend of HCFC-123 (2,2-dichloro-1,1,1-trifluoroethane) and HCFC-124 (2-chloro-1,1,1,2-tetrafluoroethane) in guinea-pigs.

2,2-Dichloro-1,1,1-trifluoroethane (HCFC-123) has been developed as a substitute for ozone-depleting chlorofluorocarbons (CFCs). It is a structural analogue of halothane and similarities in the metabolic pathways and liver toxicity of both compounds have been described. The present study was initiated after an accidental outbreak of hepatitis in an industrial setting to examine whether concomitant exposure to 2-chloro-1,1,1,2-tetrafluoroethane (HCFC-124), which is not hepatotoxic, could enhance the liver toxicity of HCFC-123. Male Hartley guinea-pigs were exposed for 4 h to 5,000 ppm HCFC-123 alone or blended with 5,000 ppm HCFC-124, either once (single exposure) or on 5 consecutive days (repeated exposure). The animals were killed either 24 or 48 h after the last exposure. A transient cytolytic action of HCFC-123 was evident by increased mean serum levels of alanine aminotransferase at 24 h and isocitrate dehydrogenase at 24 and 48 h, both after a single or repeated exposure. The liver toxicity of HCFC-123 was confirmed by pathological examination of liver tissue, which showed mild (foci of necrotic hepatocytes) to moderate (multifocal random degeneration and necrosis) damage. Steatosis was also observed and was more pronounced after repeated exposure than after single. One animal out of 6 that were repeatedly exposed to the blend and sacrificed at 24 h showed liver lesions similar to halothane hepatitis. Although a few other animals responded markedly in the blend-treated group, on average, no significant difference in the biochemical or pathological lesions was found between the groups treated with HCFC-123 alone or with the blend. Urinary excretion of trifluoroacetic acid and chlorodifluoroacetic acid increased dose-dependently upon exposure to HCFC-123 and indicated accumulation after repeated exposure. No difference in metabolite excretion was found between animals treated with HCFC-123 alone or blended with HCFC-124. Treatment with HCFC-123 depleted hepatic glutathione levels by about 40 and 25% after single and repeated exposure, respectively; the amplitude of this reduction was not modified by co-exposure to HCFC-124. In conclusion, this study confirmed the hepatotoxicity of HCFC-123, based on biochemical, histopathological and metabolite studies, and found only very limited indication of a potentiation by HCFC-124 of this hepatotoxic effect.

Evidence on N-acetyltransferase allele-associated metabolism of hydrazine in Japanese workers.

Hydrazine (N2H4), which has been categorized as a weak carcinogen, is a chemical with the one of the largest production rates in Japan. We have investigated the effects of acetylation phenotypes on the metabolism of hydrazine. Genotypes of N-acetyl transferases, NAT2*, were determined using polymerase chain reaction for 297 male workers. Biological and exposure monitoring were also conducted. The rapid and intermediate acetylators accounted for 45% each, and the slow acetylators accounted for 10%. Biological half-lives were significantly different among the three acetylation phenotypes (analysis of variance, P < 0.05): 3.94+/-1.70 hours for slow acetylators, 2.25+/-0.37 hours for intermediate acetylators, and 1.86+/-0.67 hours for rapid acetylators. Among Japanese, rapid and intermediate acetylators are the major phenotypes, which is in sharp contrast with those among Caucasians. We conclude that biological monitoring should take genetic factors, which may vary dramatically among different populations, into account.

Acute hepatitis in an adult with acquired rubella infection.

We report a case of acute hepatitis in a 28-year-old male with acquired rubella infection. Serological tests revealed acute rubella virus infection and ruled out infection by other common viruses, including type A and type B hepatitis viruses. The patient showed not only marked increase of lactate dehydrogenase (LDH) activity, with only slight liver dysfunction, but also platelet and kidney injury, suggesting systemic rubella virus infection. Because the liver dysfunction was slight, liver biopsy was not performed. When a patient has mild, transient hepatitis accompanied by high LDH activity in comparison with both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, we should take a common viral infection such as rubella into consideration when making a diagnosis.

Combination chemotherapy for a senile patient with adenoid cystic carcinoma of the esophagus: a case report.

Adenoid cystic carcinoma of the esophagus with multiple liver metastases was found in a 77-year-old Japanese female in October, 1991. Combination chemotherapy, including etoposide (VP-16) and tegafur (FT) allowed the patient to survive for approximately a year after the onset of the initial symptoms. During her course of treatment, the patient improved greatly with minimal toxicity, and declines in the elevated levels of GOT and LDH were also noted. Since no other therapy, such as surgery or radiation, was given to the patient, the response to chemotherapy as well as the survival advantage for the patient have been evaluated.

Hyperplastic cellular components of a hemangiopericytoma. An ultrastructural study.

Based on ultrastructural features of cellular components of a hemangiopericytoma, hyperplastic cells are classifiable into fibroblast-like (group I), endotheloid (group II) and pericyte-like (group III) cells. The transformation of the group I cells to the group II, or to the group III cells, is pronounced in our electron micrographs and this may imply that the group I cell is the principal cell of origin in this neoplasm. The smooth muscle-like (group IV) cells comprising the media of the arteries and veins in this neoplasm may represent modified, possibly de-differentiated smooth muscle cells reacted to the neoplastic proliferation of the surrounding adventitial (group I) cells.

Bifid tail of the pancreas: a case presenting as a gastric submucosal tumor.

A 49-yr-old male was admitted to our hospital because of epigastric discomfort and a suspected tumor of the stomach on barium meal examination at the Center for Automated Multiphasic Health Test and Services. The tumor shadow of the stomach was initially considered as the "type II" gastric carcinoma according to the Borrmann's classification. Multiple endoscopical and electrocautery cutting biopsies revealed that the tumor occurred in the submucosal layer and was composed of normal pancreatic tissue. A computed tomogram showed a large mass on the pancreatic body which was adjacent to gastric wall. Selective angiography of the celiac trunk revealed that the gastric submucosal lesion was supplied by the transverse pancreatic artery. Endoscopic retrograde pancreatography showed that Wirsung's duct had a divergence in the body of the pancreas and one of the branched ducts headed for the posterior wall of the gastric body. On the basis of these results, a diagnosis was made of the rare pancreatic anomaly, "bifid tail of the pancreas." One of the tails formed the gastric submucosal tumor. This report emphasizes the potential diagnostic value of combined study of endoscopic retrograde pancreatography and computed tomography in determining the presence of pancreatic anomaly.

Epidemio-hygieological aspects of gastric neoplasms in aged patients.

A 100-year-old male who died of gastric carcinoma was discussed and illustrated epidemiohygieologically. According to dynamic population statistics of the Health and Welfare Ministry of Japan, 418 persons over the age of 100 years died in 1979. Among them, 157 (38%) died of cardiovascular diseases and 49 (12%) died of pulmonary diseases, but only six died of neoplasms including two with gastric carcinomas (0.48%). To our knowledge no such case has been reported previously in the literature.

Gastric acid secretion and plasma gastrin response to test meal in patients with gastric cancer.

Gastric acid secretion and plasma gastrin response to test meals were examined in 110 patients with gastric cancer and a comparative study was made in accordance with depth of invasion, macroscopic shape, histological type, location and size of the lesion. Cases were classified into two large groups by the depth of invasion: early cancer (invasion was limited to the mucosa and submucosa) and advanced cancer (invasion reached the muscularis propria or deeper). Patients showed hypoacidity on the whole. Cases of early cancer showed significantly higher acid secretion than cases of advanced cancer, although no significant differences were observed in gastrin release. Among the cases of early cancer, cases of the elevated shape showed significantly lower acid secretion and higher gastrin release than cases of the depressed shape, and cases of the histologically differentiated type showed significantly higher acid secretion than cases of the undifferentiated type although no significant differences were observed in gastrin release. Among the cases of advanced cancer, cases with large carcinomas in the corpus tended to show low acid secretion and cases with large carcinomas in the antrum tended to show low gastrin release. High gastrin release was observed in cases of the Borrmann IV type with giant folds.

A comparative study on application of Nd-YAG laser radiation and electrocautery in canine gastric mucosa--magnified observations by dissecting microscopy and scanning electron microscopy, and histological examinations.

The mucosal change, the depth of injury and the healing process in the canine gastric wall after Nd-YAG laser (YAG) exposure and electrocautery were studied comparatively by magnified observations. The results were as follows: 1. Mucosal changes caused by the YAG laser beam were more localized within the exposure area than those by electric current. 2. The depth of tissue damage to the canine gastric wall by YAG laser exposure was easy to control when compared to that caused by electrocautery. 3. The healing time of the ulcer caused by the YAG laser was shorter than that caused by high frequency current. 4. In the present study on the mucosal changes due to laser exposure and electrocautery using endoscopy, dissecting microscopy and SEM, it was found that these examinations appear to be helpful as experimental procedures to clarify the detailed appearance of the mucosal surface. It was suggested that endoscopic application of the YAG laser to the gastrointestinal tract was safe and effective when compared with other procedures which have been applied endoscopically for diagnosis and treatment.

The PFD test for pancreatic disease patients.

The PFD test was performed on various pancreatic disease patients. The urinary PABA excretion rate was significantly lower in chronic pancreatitis patients and in pancreatic carcinoma patients than in the controls, but no difference was observed between PABA excretion in the two diseases. After surgery, PABA excretion values of pancreatic carcinoma patients were significantly lower than those of non-pancreatitis non-pancreatic carcinoma patients. This was thought to be caused by the difference in residual anastomosed pancreatic tissues. Mild to severe pancreatitis, fibrosis and/or fat necrosis were seen in the pancreatic tissues of carcinoma patients, but these changes were minimal in non-pancreatitis non-pancreatic carcinoma patients. The PFD test is useful in detecting decreases in pancreatic exocrine functions or measuring the grade of pancreatic disorders in various pancreatic diseases, although it can not be used to differentiate pancreatic diseases.

Hematemesis and Melena: gastritis.

The records of a total of 60 gastritis patients who showed hematemesis and/or melena are reviewed. The mean age was 40. The ratio of males to females was two to one. During the examination, 19 upper G-I lesions were confirmed in addition to gastritis. Sixteen patients had severe underlying diseases which were thought to be the cause of the bleeding tendency. Thirteen patients took alcohol or drugs which induced bleeding. Prognoses of the patients were relatively good when they were treated medically.

The coexistence of gastric cancer and duodenal ulcers.

The records of 356 gastric carcinoma patients who were treated surgically were reviewed. Among them, six patients (1.7%) had duodenal ulcers. Five cancers of the six patients were "early" gastric cancers classified as type "IIc" or "IIc + III" according to "The general rules for the gastric cancer study in surgery and pathology". The cancers of the six patients were located in the lower half of the stomach. Gastric secretion activity was normal in four and above normal in two cases. Three had signet ring cell carcinomas, two had poorly differentiated adenocarcinomas and one had a well differentiated adinocarcinoma. Our results were similar to other results reported in many papers. In Japan gastric carcinomas coexisting with duodenal ulcers were more often confirmed in the "early" gastric cancer stage. This is probably because endoscopic examinations of the stomach were more often performed in Japan than in other countries because of te large number of gastric disease patients. In addition, it is assumed that the growth of gastric cancer in the stomach is slow because of the very active gastric secretion.

Hematemesis and melena: Endoscopic examination.

Today, gastrointestinal endoscopy has become a routine examination. In our "Endoscopy center", about five hundred gastroscopies are performed every month. It has been said in many reports that endoscopy, especially emergency endoscopy, is an effective method of discovering sources of bleeding. In this report, we also emphasize that emergency endoscopy is effective in diagnosing upper gastrointestinal bleeding on the basis of reviewing 318 endoscopic examinations.

Hematemesis and melena: Mallory-Weiss syndrome.

The records of 29 patients with Mallory-Weiss tears diagnosed by endoscopy are reviewed. Ingestion of alcohol was a chief cause of bleeding. Single tears were the largest in number and 68% of the lacerations were seen just distal to the esophago-cardial junction. Lacerations occurred more frequently on the right lateral wall of cardia than on the left lateral wall. Most of these lesions were mild and could be treated medically except for two cases which were surgically treated.