Biomedical subjects
Publications and source records attributed to T Tsuji.
We report a case of typical erythema gyratum repens lesions observed as a manifestation of idiopathic hypereosinophilic syndrome in a 63-year-old man. While erythema gyratum repens is usually associated with malignancy, an intensive search over a 30-month period failed to reveal any evidence of neoplasm. With administration of dapsone, the typical gyrate lesions disappeared as the subject's hypereosinophilia improved.
The binding of Escherichia coli heat-labile enterotoxin (LT) type I to glycosylated proteins with lactose (Gal beta 1-4Glc) by amino carbonyl reaction was studied by the Western blot assay and by the microtiter well binding assay. LT bound to a lactose-alpha-lactalbumin amino carbonyl product (Lac-LA), whereas cholera toxin did not. The binding ability of Lac-LA was abolished by beta-galactosidase treatment, indicating that the terminal galactose is essential for the binding of LT. The binding of LT to Lac-LA was inhibited by galactose and lactose, and most effectively inhibited by lactulose (Gal beta 1-4Fru), which is a structural analog of the Amadori rearrangement product of the amino carbonyl reaction between lactose and an epsilon-amino group of a lysine residue (lactuloselysine). The results suggest that LT recognizes the portion of lactuloselysine in Lac-LA. LT also bound to a melibiose (Gal alpha 1-6Glc)-alpha-lactalbumin amino carbonyl product (Mel-LA), but the binding ability of Mel-LA was weaker than that of Lac-LA, suggesting that the beta 1-4 linked terminal galactose is dispensable but preferable for the binding. Furthermore, LT bound to the amino carbonyl products of lactose with beta-lactoglobulin, caseins, bovine serum albumin, and ovalbumin. These results indicate that LT binds to the amino carbonyl products between proteins and sugars containing the terminal galactose, such as lactose.
Acute idiopathic thrombocytopenic purpura (ITP) often appears to be related to the sensitization by some viral infections. However, the causative viral agents are not identified in most cases. Although the primary infection with Epstein-Barr virus (EBV) occurs during early childhood in Japan, the majority of cases are usually asymptomatic. A minority are associated with acute infectious mononucleosis (IM), which is characterized by fever, tonsillitis, lymphadenopathy, splenomegaly and liver dysfunction. In this report, three cases are described of children with EBV-induced ITP who clinically had atypical findings of IM. Their primary EBV infections were confirmed by serological test and, in addition, were verified by the enhanced expression of activation antigens (HLA-DR and CD45RO) on T cells as well as the inverted ratio of CD4+ to CD8+ subsets. These observations imply that ITP can occur as one of the host responses during primary EBV infections, irrespective of clinical manifestations. Evaluation of lymphocyte subpopulations may be useful for the assessment of primary EBV infection in ITP.
A two year old boy exhibited not only clinical manifestations which suggested a recurrence of Kawasaki disease (KD) but also evidence of a primary infection by Epstein-Barr virus (EBV) including tonsillitis, splenomegaly and atypical lymphocytosis in the peripheral blood. An inverted CD4/CD8 ratio in lymphocyte subsets suggested the presence of infectious mononucleosis (IM). Epstein-Barr virus titers (viral capsid antigen-immunoglobulin G 1:20; Epstein-Barr virus-associated nuclear antigen < 1:10) showed an acute EBV infection and the presence of EBV genome in the blood was determined by the polymerase chain reaction technique. In Japan, the peak incidence of KD and IM is in children under 4 years of age. From the investigation of EBV titers, it has been reported that some patients with KD develop an associated, unusual primary EBV infection. Kawasaki disease concurrent with a primary EBV infection as in this case, suggests the possibility of an etiologic agent related to the KD rather than to the EBV infection itself.
Human serum albumin (HSA), formaldehyde-treated HSA (FHSA), and HSA polymerized with glutaraldehyde (pHSA) were conjugated with colloidal gold (15 (15G) or 50 (50G) nm in diameter). The labeled proteins were injected into the portal veins of rats and followed by electron microscopy. Both 15G-FHSA and 15G-pHSA were taken up by sinusoidal endothelial cells (Ec) and Kupffer cells (Kc). Five minutes after injection, gold particles were observed on the surface of Ec and Kc. At 10 min, most gold particles were gathered in the coated pits and vesicles of Ec. In Kc, gold particles were observed in both coated vesicles and macropinocytotic vesicles. At 15 min, the gold particles were localized mainly in the endosomes and some lysosomes of Ec and in the large vacuoles of Kc. At 30 min, the gold particles had been gathered into the secondary lysosomes and condensed. At 60 min, some gold particles were observed in the cytoplasm of Ec. The fate of 15G-pHSA was the same as that of 15G-FHSA. Simultaneous injection of 15G-pHSA and 50G-FHSA revealed that particles of both sizes were taken up together into the coated pits and vesicles of Ec. Preperfusion of livers with unlabeled FHSA, pHSA, or formaldehyde-treated bovine serum albumin (FBSA) inhibited the uptake of 15G-FHSA or 15G-pHSA by Ec. In a human liver biopsy specimen, both 15G-FHSA and 15G-pHSA were taken up by Ec and Kc through coated vesicles, as in the rat liver.(ABSTRACT TRUNCATED AT 250 WORDS)
To clarify the role of cytosolic Ca2+ in hepatocellular death, we exposed cultured hepatocytes to human serum and a monoclonal antibody directed against rat liver plasma membranes to produce complement-mediated cell injury. The change in cytosolic Ca2+ concentration was measured by fura2 and fluo3 fluorescence. With the addition of monoclonal antibody, an increase in cytosolic Ca2+ was observed, followed by cell death. Both the increase in intracellular Ca2+ and cell death were prevented by intracellular Ca2+ chelation or removal of extracellular Ca2+. We conclude that an increase in cytosolic Ca2+ plays a major role in hepatocellular injury induced by exposure of the cell membrane to monoclonal antibody.
Since 1984, we have performed extended radical resection combined with extended intraoperative radiation therapy (IORT) for pancreatic cancer. This approach has provided a dramatic improvement in long-term survival and control of local recurrence. Hepatic metastases, however, remain an unsolved problem. Among patients with this combined therapy, we found hepatic metastases in 8 of 22 patients postoperatively. Four of these 8 were considered candidates for further therapy and underwent treatment for their hepatic metastases, the other 4 had too extensive disease. Two patients with multiple hepatic metastases underwent percutaneous ethanol injection therapy and chemotherapy, but they died within a year. Two patients with a solitary hepatic metastases underwent hepatic resection. One patient died two years and six months after the first operation because of multiple metastases in the liver and both lungs, while the other patient is still alive over six years after the first operation with an excellent performance status. When a patient has no local recurrence and a solitary metastasis in the liver, surgical resection of the liver metastasis should be performed.
The Thomsen-Friedenreich antigen (T) is the core disaccharide of O-glycosylated complex carbohydrates and is presumed to be a cancer-associated carbohydrate antigen. However, we recently found that the expression of alpha-T and alpha 1-2 fucosyl alpha-T in the gastric surface epithelia was regulated allogeneically. In the present study we addressed their changes in gastric differentiation disorders. Expression of the T-related antigens was studied histochemically with monoclonal antibody MBrl and peanut agglutinin in 22 normal, 14 metaplastic, and 54 cancerous tissues. The sialylated antigens were detected after neuraminidase digestion. Gastric mucins were purified and examined to determine whether they were the carrier molecules of T. Expression of the normal antigens was decreased or not detected in about 80% of both disorders. Neosialylation of the T-related antigens was observed in the goblet cells of all metaplastic tissues. The absorptive cells did not express any T-related antigens. In gastric cancers, blocked synthesis, i.e., precursor accumulation or totally negative expression, was observed in approximately 66% and neosialylation in approximately 40%. The T-related antigens were carried by mucins. We conclude that blocked synthesis of the T-related antigens was found in a cancer-specific manner. Neosialylation was invariably associated with intestinal metaplasia and occasionally with cancer.
Human gastric surface epithelial cells display the ABH blood group antigens with the core structure of N-acetyllactosamine (NAcLc). Their expression is under the control of the secretor gene Se. The Thomsen-Friedenreich (T)-antigen (Gal beta 1-3GalNAc) is another core structure of the ABH antigens. We examined the gastric surface epithelial expression of T- and alpha 1-2 fucosylated T (FucT) histochemically with peanut agglutinin (PNA) and monoclonal antibody (MAb) MBr1, respectively. Eight of 24 individuals exhibited the PNA-reactive antigen (i.e., T-expressers) and others the MBr1-reactive antigen (i.e., FucT-expressers). alpha-L-fucosidase digestion of the FucT-positive tissues and beta-galactosidase digestion of the T-positive tissues, respectively, made them reactive with PNA and the antibody specific for GalNAc alpha-O-Ser/Thr. There was a remarkable correlation among reactivities with MBr1, Ulex europaeus lectin 1 (UEA1), and anti-Leb MAb CO-431. ABH blood group status had no correlation with this expression. We conclude that human gastric surface epithelial cells constitutionally synthesize T in alpha configuration (i.e., Gal beta 1-3GalNAc alpha-O-Ser/Thr) and that it was alpha 1-2 fucosylated only in the FucT-expressers. alpha 1-2 fucosylation of T is suggested to be regulated by the Se gene.
We studied the distribution of class 1 and class 2 major histocompatibility complex (MHC) antigens on bile duct epithelial cells in liver from patients with primary biliary cirrhosis (PBC) by an immunohistochemical method using monoclonal antibodies to HLA-ABC products and HLA-D subregion products (HLA-DR, -DP, -DQ). By light microscopy, the expression of MHC class 1 antigens (HLA-ABC antigens) was enhanced in PBC compared with controls. While negligible staining of MHC class 2 antigens was detected on the bile duct in controls, de novo expression of MHC class 2 antigens, as well as the coexpression of HLA-DR, HLA-DQ, and HLA-DP antigens on the bile duct epithelial cells, was observed in PBC. By electron microscopy, HLA-ABC and HLA-DR antigens were present preferentially along the basolateral domain of the cell surface of the bile duct epithelial cells and on the membrane of the endoplasmic reticulum in the cytoplasm, suggesting that these MHC antigens are synthesized by the bile duct epithelial cells in PBC. The distribution of these MHC antigens on the basolateral surface of the bile duct epithelial cells, where they are easily accessible to immunocytes, supports the idea that MHC-restricted cytotoxic T lymphocytes are involved in the bile duct injury in PBC.
Hepatitis C virus (HCV)-RNA in the blood was measured by polymerase chain reaction (PCR) in 37 subjects from eight families in which 2 or more persons tested seropositive for antibodies against C100-3 or CP9. HCV-RNA was positive in 17 of 37 subjects. Two or more HCV-RNA-positive subjects were observed in six of the families. Intrafamilial HCV infection was studied by determining the HCV-RNA type (I, II, III or IV) by PCR using type-specific primers. In two families, all of the subjects showed type III infection, and in three other families, all of the subjects showed type II infection, with different types of HCV infections being observed in only one family. The HCV type was uniform in all but one. These findings suggest a possibility of intrafamilial infection between husbands and wives and between members of the same household.
To clarify the events related to complement-mediated immune responses in human colorectal cancers, we immunohistochemically examined the distribution of decay-accelerating factor (DAF), CD59/homologous restriction factor 20 (HRF20), membrane cofactor protein (MCP) and terminal complement complex (TCC) in human colorectal adenomas and cancers, and then compared the findings with their distribution in normal colonic mucosa. In the normal mucosa, TCC was not present on epithelial cells. Whereas DAF and CD59/HRF20 were present only occasionally on the apical surfaces of normal epithelial cells, MCP was diffusely distributed on the basolateral surfaces of most epithelial cells of the colon. These findings suggest that MCP has a primary role in the regulation of complement activation on these cells. In adenoma cells, the expression of both DAF and CD59/HRF20 was enhanced. In cancer cells, the expression of CD59/HRF20 and MCP was diminished, whereas DAF expression was markedly enhanced. Since DAF was frequently stained in the lumen of the cancer glands, it was suggested that DAF was released into the colonic lumen in patients with colorectal cancer.
To identify diffuse mucosal changes which may precede the development of colorectal cancer and a possible indicator for detecting high-risk populations, we immunohistochemically studied cell-cycle events in crypts of normal-appearing rectal mucosa of patients with colorectal adenoma and cancer using an in vitro labeling method with bromodeoxyuridine (BrdU). Biopsy specimens of endoscopically normal-appearing rectal mucosa were obtained during colonoscopy from 20 patients with colorectal adenocarcinoma, 20 with adenoma, and 15 without apparent colorectal diseases. The specimens were incubated with BrdU in vitro, and labeled S-phase cells were identified immunohistochemically using a monoclonal antibody to BrdU. Modification of the BrdU-labeling pattern in the normal appearing rectal mucosa, such as the presence of BrdU-labeled cells at the mucosal surface or in the upper one-fifth of the crypt column, was observed in 15 of the 20 patients with adenocarcinoma, 17 of the 20 patients with adenoma and 6 of the 15 controls. This upward shift in the frequency of proliferating cells in the crypt was significantly higher in the patients with colorectal adenoma and cancer than in the controls, and may be used to identify subjects at high risk for colorectal cancer.
Recently, factors predicting the response to interferon (IFN) therapy against hepatitis C virus (HCV) have received much attention. To evaluate the usefulness of the quantitation of intrahepatic HCV RNA as a predictive marker of the response to IFN therapy, we compared the amount of intrahepatic HCV RNA with serum levels in 16 patients. Eleven patients who had 10(10) copies/g or more of intrahepatic HCV RNA had increased level of serum alanine aminotransferase (ALT) after IFN therapy, while 4 of 5 patients who had less than 10(10) copies/g of intrahepatic HCV RNA achieved sustained normalization of serum ALT level and were designated as complete responders. Four complete responders possessed significantly less HCV RNA in the liver parenchyma than partial and nonresponders (P = 0.010, Mann-Whitney U-test), but the amount of HCV RNA in the serum was not significantly different between those groups. In conclusion, the results suggest that the quantitation of intrahepatic HCV RNA is a better indicator of the response to IFN therapy than serum HCV RNA.
Of the eight patients with fulminant hepatitis placed under total parenteral nutrition with an amino acid solution rich in branched chain amino acids and treated by plasma exchange, four survived and four died from hepatic failure. Serum uric acid levels in the non-survived group were significantly lower on days 1-6 compared with the survived group. The concentration ratios of uric acid to creatinine and prothrombin time were significantly lower on days 5-8 and days 3-8, respectively, in a similar comparison. Thus, the uric acid to creatinine ratio, which corrects for the possible renal dysfunction associated with acute hepatic failure, may serve as a clinically useful prognostic indicator for patients with fulminant hepatitis.
Endoscopical segmental piecemeal tumorectomy (ESPT) for nodular elevation of colorectal tumor is advantageous in terms of minimizing both surgical invasion and postoperative burden to the patients. Nodular elevation of colorectal tumors is said to occur when the body of the tumor is adenomatous and the surface of the focal cancer grows more horizontally into the lumen than vertically. We report here four cases of nodular elevation of colorectal tumors which were each treated by different surgical procedures.
We investigated the specificities and characteristics of anti-cytoskeleton antibodies in 13 anti-smooth muscle antibody (ASMA)-positive patients with chronic liver disease C (CLD-C), and compared them with those in 7 ASMA-positive patients with autoimmune hepatitis (AIH), and 6 ASMA-positive patients with chronic liver disease B (CLD-B). Anti-microfilaments (anti-MF) were found not only in 6/7 AIH patients (85.7%), but also in 8/13 CLD-C patients (61.5%) with a relatively high incidence, when compared with 1/6 CLD-B patients (16.7%), while, there was no significant difference in the incidence of anti-intermediate filaments (anti-IMF), especially anti-IMF IgM, among these patient groups. Among the patients with CLD-C, the mean levels of serum gammaglobulin and IgG in the anti-MF-positive patients were 2.46 +/- 1.03 g/dl and 3277 +/- 1089 mg/dl, respectively, which were higher than those in the anti-MF-negative patients (1.60 +/- 0.53 g/dl, 2245 +/- 610 mg/dl) and those in the patients with CLD-B (1.60 +/- 0.57 g/dl, 2192 +/- 339 mg/dl). Furthermore, 4 of the 8 anti-MF-positive patients with CLD-C satisfied the serological criteria for the diagnosis of AIH. These findings suggest that autoimmune mechanisms might be involved in the pathogenesis of anti-MF-positive CLD-C, and that anti-MF might be used as a marker.
We administered a branched-chain amino acid (BCAA) infusion to 16 patients with hepatic failure and two healthy subjects, and then evaluated its effects on ammonia metabolism and amino acid metabolic pool. Immediately after the BCAA infusion, the venous blood ammonia concentration increased in 12 of 15 patients with hepatic failure and in both two healthy subjects. Glutamine (Gln) also rose in all cases following the BCAA infusion, and this rise was particularly marked in the hepatic failure group. The increase in Gln due to the BCAA infusion and the arteriovenous difference in the pre-administration ammonia concentration showed a good correlation. These results suggest an increase in glutamine cycle capacity in patients with hepatic failure.