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Biomedical subjects

K Yamaguchi

Publications and source records attributed to K Yamaguchi.

At least 577 records · Page 32Linked to original sources

Provirus load in patients with human T-cell leukemia virus type 1 uveitis correlates with precedent Graves' disease and disease activities.

We previously demonstrated the increased provirus load in the peripheral blood of patients with human T-cell leukemia virus type 1 (HTLV-1) uveitis (HU). To delineate the relevance of the increased provirus load to clinical and immunologic parameters, we studied the correlation between them. Seventy-nine HU patients (24 male and 55 female) were included in the study, with their informed consent. Plasma samples and genomic DNA of the peripheral blood mononuclear cells were isolated and the provirus load was estimated by semi-quantitative polymerase chain reaction of the gag region sequence. Serum levels of anti-HTLV-1 antibodies and soluble IL-2R were determined by electrochemiluminescence immuno assay and by ELISA, respectively. Disease activities were assessed and graded 0 to 4 according to the evaluation system. Recurrence of the disease during the follow-up period was diagnosed ophthalmologically. The provirus load was significantly higher in the HU patients after Graves' disease (GD) than in those without GD (P<0.05). It correlated with disease activities assessed in terms of vitreous inflammation and interval to recurrence (both P<0.05). In the HU patients without GD, it correlated with the serum levels of soluble IL-2 receptor (P<0.01), and nearly with those of HTLV-1 antibody (P=0.063). These correlations were not found in the HU patients after GD under methimazole treatment. The results suggested a direct involvement of HTLV-1-infected cells in the pathogenesis of uveitis, and raise the possibility that hyperthyroidism may contribute to the clonal expansion of HTLV-1-infected cells.

Graves Disease↗

The association between serum levels of Th cytokines and rhinoconjunctivitis caused by methyltetrahydrophthalic anhydride.

BACKGROUND: There are few epidemiologic studies on the association between serum levels of T helper (Th) cytokines and allergic symptoms caused by sensitizing agents. METHODS: A population of 147 workers from two condenser plants using epoxy resin with methyltetrahydrophthalic anhydride (MTHPA) underwent a questionnaire survey and serologic investigations. Total and MTHPA-specific IgE levels were measured by the Pharmacia CAP System, and serum levels of interleukin (IL)-4, IL-13, and interferon-gamma (IFN-gamma) by enzyme immunoassay. RESULTS: A significant association was found between work-related eye and nasal symptoms and a range of atopic characteristics, including the frequency of positive specific IgE, specific and total IgE levels, and IL-4 levels. A positive correlation was observed between levels of IL-4 and IL-13 (r=0.42). Furthermore, multiple logistic analysis revealed significant contributions of specific IgE and IL-13 to the work-related symptoms. A similar but nonsignificant association was also found for IL-4 (P=0.07). On the other hand, a multiple regression model with specific IgE levels as a dependent variable showed a significant association with total IgE, but not with IL-4, IL-13, and IFN-gamma. CONCLUSIONS: These results suggest that work-related eye and nasal symptoms are closely related to specific IgE antibodies, and that allergic responses, mediated by IgE, to MTHPA may lead to a shift in the balance between Th1 and Th2 cells.

Adult↗

Patient background of the Pokemon phenomenon: questionnaire studies in multiple pediatric clinics.

Many children in Japan developed various neuropsychological problems, including seizures, while watching the program Pocket Monster, televised on 16 December 1997. To examine the basis for this incident, we have performed a survey of volunteering children and their parents who visited our pediatric clinics for other reasons from 8 January to 28 February 1998. Children and their parents filled out questionnaires. Among the total of 662 children surveyed, the great majority (603, 91.1%) was found to have watched the Pocket Monster program and 30 individuals (5.0% of viewers) complained of variable degrees of neuropsychological abnormalities. These included seizures (two cases), headache (nine cases), nausea (eight cases), blurred vision (four cases), vertigo (two cases), dysthymia (two cases) and vomiting (one case). Nearly half (14) of these children developed symptoms during or immediately after watching the program, while the remainder did so later. Representative cases are reported and other statistical aspects are discussed.

Adolescent↗

Adenosquamous carcinoma of the pancreas: report of two cases.

Adenosquamous carcinoma of the pancreas is a rare variant of pancreatic exocrine carcinoma. We herein report two patients with this entity. One patient was a 60-yr-old Japanese man complaining of a palpable mass, 5.5 cm in the greatest diameter, in the epigastrium. Serum CA 19-9 was increased (2010 U/ml). Ultrasonography and computed tomography showed a mass in the pancreatic tail with central necrosis and invading the posterior wall of the stomach. Angiography showed an encasement of the splenic artery and complete obstruction of the splenic vein. Distal pancreatectomy, splenectomy, and partial resection of the stomach were done. The patient died of uncontrolled bleeding from the duodenal ulcer four months after operation. The other patient was a 73-yr-old man who presented with jaundice. The CA 19-9 was also elevated (354.8 U/ml). Ultrasonography showed a pancreatic head mass of heterogeneous echogeneity and computed tomography demonstrated a cystic mass with an enhanced rim, indicating necrosis in the tumor center. Angiography showed a hypervascular mass in the head of the pancreas. Pylorus-preserving pancreatoduodenectomy was done, but the patient died of multiple liver metastases 10 months after the operation. From our experience with the two patients, the presence of central necrosis in an infiltrative huge pancreatic tumor seems to be suggestive of the diagnosis of adenosquamous carcinoma of the pancreas.

Aged↗

Telomerase activity detected in pancreatic juice 19 months before a tumor is detected in a patient with pancreatic cancer.

We report a patient with pancreatic cancer in whom telomerase activity had been detected in the pancreatic juice 19 months before he was diagnosed as having pancreatic cancer. A 61-yr-old alcoholic man complaining of epigastric and back pain was diagnosed as having groove pancreatitis based on the presence of inflammation in the pancreatic head and its extension to the duodenal mucosa with an associated elevated serum amylase level. All imaging modalities showed no sign of a tumor. However, high telomerase activity was detected in the pancreatic juice collected during endoscopic retrograde pancreatography. His symptoms subsided due to abstinence from alcohol. A tumor, however, was recognized on computed tomography 19 months later, at which time the patient immediately underwent a pylorus-preserving pancreaticoduodenectomy. The carcinoma was located mainly in the Santorini duct region. High telomerase activity in the pancreatic juice may precede clinical detection of pancreatic cancer and thus could be a useful early diagnostic marker for pancreatic cancer.

Biomarkers, Tumor↗

Pleomorphic carcinoma of the pancreas: reappraisal of surgical resection.

Pleomorphic carcinoma is a rare variant of pancreatic exocrine carcinoma. The aim of this communication is to reappraise surgical resection of pleomorphic carcinoma of the pancreas. Clinicopathological findings of four Japanese patients with pleomorphic carcinoma of the pancreas were reviewed and compared with those of 24 Japanese patients with adenocarcinoma of the pancreas to clarify possible surgical implications of pleomorphic carcinoma. Of the four patients, three were female and one male, aged 64, 65, 66, and 74 yr, respectively. Two carcinomas were located in the head of the pancreas, one in the body, and the other in the tail. Ultrasonography demonstrated a well defined hypoechoic mass measuring 5-10 cm, with central necrotic area in all of the patients. Computed tomography showed a low density tumor with sharp margin and heterogeneous internal structure in all. On angiography, three tumors were hypervascular and another was hypovascular. Extensive vascular encasement was observed in all. Pancreatoduodenectomy was done in two patients and distal pancreatectomy in the other two. Multiple liver metastases occurred 1 month after surgical resection in two patients and local recurrence 1 month in one and 2 months in the other, leading to death either 2 (2 patients) or 3 months (2 patients) after pancreatectomy. Significantly differentiating features of the four pleomorphic carcinomas of the pancreas and the 24 adenocarcinomas of the pancreas were the mean diameter (6.6 +/- 1.3 cm vs 3.5 +/- 0.3 cm, p = 0.0007), margin of the tumor (expansive in the four pleomorphic carcinomas versus infiltrative in 21 of the 24 adenocarcinomas, p = 0.003) and vascularity on angiography (hypervascular in three of the four pleomorphic carcinomas versus hypovascular in 21 of the 23 adenocarcinomas, p = 0.013). The 1-yr and 3-yr survival rates of the four patients with pleomorphic carcinoma were 0% and 0%, whereas those of the 24 patients with adenocarcinoma of the pancreas were 42% and 13%, respectively (p < 0.0001). These findings suggest that the clinical course of patients with pleomorphic carcinoma of the pancreas is so poor even after surgical resection that pleomorphic carcinoma of the pancreas is not a candidate for pancreatectomy despite its locally expansive growth.

Adenocarcinoma↗

Plasma from patients with cirrhosis increases tissue plasminogen activator release from vascular endothelial cells in vitro.

AIMS/BACKGROUND: In patients with severe liver disease, blood levels of many coagulation and fibrinolytic factors are lowered due to a diminished synthetic capability in the liver. Tissue plasminogen activator (t-PA) is synthesized by the vascular endothelial cells, however, and is increased in such patients. METHODS: Amounts of t-PA secreted were determined by immunosorbent assay after plasma from patients with cirrhosis was added to cultured human umbilical vein endothelial cells to determine whether a plasma factor directly enhanced t-PA secretion from vascular endothelial cells. RESULTS: Release of t-PA was significantly higher with exposure to plasma from patients with decompensated cirrhosis than when plasma from patients with compensated cirrhosis or normal subjects was used (p < 0.01 and p < 0.05, respectively). Plasminogen activator inhibitor 1 (PAI-1) concentrations were measured similarly but did not differ among the three groups. CONCLUSIONS: Our results indicate that factors in plasma from patients with decompensated cirrhosis directly stimulate t-PA release from the vascular endothelial cells, while any increased PAI-1 release observed in comparable in vivo situations is probably an indirect response to an increase of t-PA or a result of impaired hepatic clearance.

Cells, Cultured↗

Goniodomin A, an antifungal polyether macrolide, increases the filamentous actin content of 1321N1 human astrocytoma cells.

Goniodomin A, a polyether macrolide isolated from the dinoflagellate Goniodoma pseudogoniaulax, caused morphological change in 1321N1 human astrocytoma cells. Observation by scanning electron microscopy revealed that the shape of the cell became refractile from flat in response to goniodomin A. This morphological change was accompanied by the outgrowth of a needle-like structure from the cell surface. Goniodomin A increased the intracellular content of filamentous actin in a concentration- and time-dependent manner. It also caused the change in filamentous actin distribution in the cells. The elongation of filamentous actin was observed in goniodomin A-treated cells. These results suggest that goniodomin A induces morphological change by increasing the content of filamentous actin in non-muscle cells.

Actins↗

In vitro and in vivo antibacterial activities of S-4661, a new carbapenem.

The in vitro and in vivo antibacterial activities of S-4661, a new 1beta-methylcarbapenem, were compared with those of imipenem, meropenem, biapenem, cefpirome, and ceftazidime. The activity of S-4661 against methicillin-susceptible staphylococci and streptococci was comparable to that of imipenem, with an MIC at which 90% of the strains tested were inhibited (MIC90) equal to 0.5 microg/ml or less. S-4661 was highly active against members of the family Enterobacteriaceae, Haemophilus influenzae, and Moraxella catarrhalis, with MIC90s ranging from 0.032 to 0.5 microg/ml. Against imipenem-resistant Pseudomonas aeruginosa, S-4661 was the most active among test agents (MIC90, 8 microg/ml). Furthermore, S-4661 displayed a high degree of activity against many ceftazidime-, ciprofloxacin-, and gentamicin-resistant isolates of P. aeruginosa. The in vivo efficacy of S-4661 against experimentally induced infections in mice caused by gram-positive and gram-negative bacteria, including penicillin-resistant Streptococcus pneumoniae and drug-resistant P. aeruginosa, reflected its potent in vitro activity and high levels in plasma in mice. We conclude that S-4661 is a promising new carbapenem for the treatment of infections caused by gram-positive and -negative bacteria, including penicillin-resistant S. pneumoniae and drug-resistant P. aeruginosa.

Animals↗

Effect of interleukin-10 on gut-derived sepsis caused by Pseudomonas aeruginosa in mice.

We evaluated the protective effect of interleukin-10 (IL-10) against murine gut-derived sepsis caused by Pseudomonas aeruginosa. Gut-derived sepsis was induced by administering cyclophosphamide and ampicillin while feeding P. aeruginosa to specific-pathogen-free mice. Treating mice with recombinant human IL-10 (rhIL-10) at 1.0 or 5.0 microg/mouse twice a day following the second cyclophosphamide administration significantly increased the survival rate compared to that of control mice treated with saline; however, treatment with rhIL-10 at 0.1 microg/mouse did not result in significant protection. Bacterial counts in the liver, spleen, and blood were all significantly lower in mice treated with rhIL-10 than in saline-treated control mice. Treatment with rhIL-10 significantly suppressed tumor necrosis factor alpha, interleukin-1beta, interleukin-6, and gamma interferon levels in the serum of mice following induction of gut-derived sepsis. We also studied the effect of IL-10 on leukocyte recovery after cyclophosphamide treatment of mice. Administration of rhIL-10 intraperitoneally at 1. 0 microg/mouse significantly accelerated the recovery of leukocytes in comparison with that of the group of saline-treated controls. These results indicate that IL-10 shows a protective effect against gut-derived P. aeruginosa sepsis. We suspect that the mechanism of this effect is that IL-10 regulates in vivo production of inflammatory cytokines. Furthermore, acceleration of leukocyte recovery by IL-10 after cyclophosphamide-induced depression may also play an important role in this protection.

Animals↗

In vitro and in vivo antibacterial activities of CS-834, a new oral carbapenem.

CS-834 is a prodrug of the carbapenem R-95867, developed by Sankyo Co., Ltd., Tokyo, Japan. To investigate the possibility that CS-834 may be the first carbapenem usable in an oral dosage form, its in vitro antibacterial activity (as R-95867) and in vivo antibacterial activity were compared with those of cefpodoxime proxetil, cefditoren pivoxil, cefdinir, ofloxacin, imipenem, and amoxicillin. R-95867 had high levels of activity against methicillin-susceptible staphylococci and streptococci, including penicillin-resistant Streptococcus pneumoniae, as well as Neisseria gonorrhoeae, Moraxella catarrhalis, the members of the family Enterobacteriaceae (with the exception of Serratia marcescens), Haemophilus influenzae, and Bordetella pertussis; for all these strains, the MICs at which 90% of tested strains are inhibited (MIC90s) were 1.0 microg/ml or less. Against methicillin-resistant staphylococci, enterococci, Serratia marcescens, Burkholderia cepacia, Stenotrophomonas maltophilia, and Acinetobacter calcoaceticus, R-95867 showed activity comparable to or slightly less than that of imipenem, with MIC90s ranging from 2 to >128 microg/ml. The in vivo efficacy of oral CS-834 against experimental mouse septicemia caused by gram-positive and gram-negative bacteria was better than that of comparative drugs. In murine respiratory infection models, the efficacy of CS-834 reflected not only its potent in vitro activity but also the high levels present in the lungs.

Animals↗

In vivo activity of HSR-903, a new fluoroquinolone, against respiratory pathogens.

The in vivo activity of HSR-903, a new fluoroquinolone, against major bacteria which cause respiratory tract infections was evaluated. HSR-903 was active against experimental respiratory tract infections in mice challenged with penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae and Haemophilus influenzae strains. Treatment with HSR-903 reduced the bacterial numbers in infected murine lungs. In accord with the pulmonary clearance results, the rates of survival for mice treated with HSR-903, sparfloxacin, levofloxacin, ciprofloxacin, and benzylpenicillin were 50, 30, 10, 0, and 0%, respectively, 14 days after being infected with penicillin-resistant S. pneumoniae. A pharmacokinetic study with pneumonic mice showed that the levels of HSR-903 in the lungs were seven to eight times higher than those in the plasma. These results indicate that clinical studies of HSR-903 against respiratory tract infections may be warranted.

Animals↗

Cloning and sequencing of the gene encoding Toho-2, a class A beta-lactamase preferentially inhibited by tazobactam.

Escherichia coli TUM1083, which is resistant to ampicillin, carbenicillin, cephaloridine, cephalothin, piperacillin, cefuzonam, and aztreonam while being sensitive to cefoxitin, moxalactam, cefmetazole, ceftazidime, and imipenem, was isolated from the urine of a patient treated with beta-lactam antibiotics. The beta-lactamase (Toho-2) purified from the bacteria hydrolyzed beta-lactam antibiotics such as penicillin G, carbenicillin, cephaloridine, cefoxitin, cefotaxime, ceftazidime, and aztreonam and especially had increased relative hydrolysis rates for cephalothin, cephaloridine, cefotaxime, and ceftizoxime. Different from other extended-spectrum beta-lactamases, Toho-2 was inhibited 16-fold better by the beta-lactamase inhibitor tazobactam than by clavulanic acid. Resistance to beta-lactams was transferred by conjugation from E. coli TUM1083 to E. coli ML4909, and the transferred plasmid was about 54.4 kbp, belonging to the incompatibility group IncFII. The cefotaxime resistance gene for Toho-2 was subcloned from the 54.4-kbp plasmid. The sequence of the gene was determined, and the open reading frame of the gene was found to consist of 981 bases. The nucleotide sequence of the gene (DDBJ accession no. D89862) designated as bla(toho) was found to have 76.3% identity to class A beta-lactamase CTX-M-2 and 76.2% identity to Toho-1. It has 55.9% identity to SHV-1 beta-lactamase and 47.5% identity to TEM-1 beta-lactamase. Therefore, the newly isolated beta-lactamase designated as Toho-2 produced by E. coli TUM1083 is categorized as an enzyme similar to Toho-1 group beta-lactamases rather than to mutants of TEM or SHV enzymes. According to the amino acid sequence deduced from the DNA sequence, the precursor consisted of 327 amino acid residues. Comparison of Toho-2 with other beta-lactamase (non-Toho-1 group) suggests that the substitutions of threonine for Arg-244 and arginine for Asn-276 are important for the extension of the substrate specificity.

Amino Acid Sequence↗

In vivo antibacterial activities of sanfetrinem cilexetil, a new oral tricyclic antibiotic.

The in vivo antibacterial activities of a new oral trinem, sanfetrinem cilexetil (a prodrug of sanfetrinem), were evaluated in comparison with those of cefdinir and amoxicillin. Sanfetrinem cilexetil showed potent efficacy against experimental murine septicemia caused by Staphylococcus aureus, Streptococcus pyogenes, and Escherichia coli and against murine respiratory infections caused by Streptococcus pneumoniae. Likewise, in murine models of respiratory infection by penicillin-susceptible and penicillin-resistant S. pneumoniae, sanfetrinem cilexetil was more effective than amoxicillin in reducing the number of bacteria in infected lungs. These results were reflected in its potent in vitro activity and high levels in plasma.

Animals↗

Serum cytokines in patients with Legionella pneumonia: relative predominance of Th1-type cytokines.

Serum samples from 14 patients with Legionella pneumonia were examined for the presence of cytokines. In spite of high levels of serum C-reactive protein in all patients during the acute phase in only four cases (one involving interleukin-1beta [IL-1beta], three involving IL-6, and none involving tumor necrosis factor alpha) was the concentration of cytokines more than 100 pg/ml. Th2 cytokines IL-4 and IL-10 were detected in only one patient each. In contrast, significant increases of serum gamma interferon (IFN-gamma) and IL-12 levels were observed during the acute phase in 6 and 11 cases, respectively. Interestingly, although serum IFN-gamma levels diminished thereafter, in seven cases IL-12 levels remained high or increased further during the convalescent phase. In an additional 22 cases clinically suspected to be but not diagnosed as Legionella pneumonia, increases of serum IL-12 levels were observed in 16 cases, whereas the remaining 6 cases showed no detectable IL-12. Our results demonstrate the relative predominance of Th1 cytokine production in Legionella pneumonia. Although the role and significance of prolonged increases in IL-12 levels in Legionella disease are unknown, our results should prompt further investigation of the host immune response in terms of Th1 and Th2 balance in legionellosis.

Cytokines↗

Adherence to and penetration of human intestinal Caco-2 epithelial cell monolayers by Pseudomonas aeruginosa.

Clinical isolates of Pseudomonas aeruginosa from blood adhered to and penetrated intestinal Caco-2 cell monolayers to a greater degree than did isolates from sputum, with a concomitant drastic decrease in transepithelial electrical resistance. PAO-PR1, an avirulent exotoxin A mutant of PAO1, did not cause a decrease in the resistance. The Caco-2 monolayer system may be useful for the evaluation of certain P. aeruginosa virulence factor activities.

Bacterial Adhesion↗

Retinal degeneration in hereditary ceruloplasmin deficiency.

A 56-year-old Japanese man was diagnosed as having hereditary ceruloplasmin deficiency. His ceruloplasmin concentration was below the lower limit of detection. Serum copper and iron concentrations were below normal, but the ferritin concentration was highly elevated. An ophthalmoscopic examination showed retinal degeneration with yellowish discoloration of the fundus in both eyes. Fluorescein angiography demonstrated a dark choroid in the posterior pole. Geographic areas of window defects were seen in the midperipheral fundus. The retinal degeneration in this patient was thought to be caused by the cellular iron deposition that occurred as a result of ceruloplasmin deficiency.

Ceruloplasmin↗