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Biomedical subjects

S Himeno

Publications and source records attributed to S Himeno.

At least 37 records · Page 2Linked to original sources
PubMed2000

Frequent expression of sialyl Le(a) in human esophageal squamous cell carcinoma.

Sialyl Le(a) antigen (CA19-9), a member of a family of high molecular weight glycoproteins, was originally described as a gastrointestinal- and pancreatic-specific tumor marker. Recent studies have demonstrated that sialyl Le(a) is a ligand for E-selectin and may play an important role in tumor metastasis. However, expression patterns of sialyl Le(a) have not yet been established in human esophageal carcinomas. In this study, we examined sialyl Le(a) expression and its histopathological localization in human esophageal squamous cell carcinoma. Sialyl Le(a) immunoreactivity was detected in 28 (51.9%) of the 54 esophageal squamous cell carcinomas, regardless of the depth of tumor invasion, vascular invasion or lymph nodal status. In 13 cases (29.5%), significant sialyl Le(a) expression was detected not only in the intramucosal carcinoma components, but also in the invasive carcinoma components. These observation suggested that sialyl Le(a) expression is associated with early-stage cancer progression.

CA-19-9 Antigen↗
PubMed1999

The involvement of microtubular disruption in methylmercury-induced apoptosis in neuronal and nonneuronal cell lines.

Methylmercury (MeHg) is known to interfere with cell cycle progression by disruption of microtubules. The relationship between the changes in cell cycle and the induction of apoptosis caused by MeHg was investigated in cultured mammalian cells. MeHg caused nuclear fragmentation and DNA ladder formation in rat pheochromocytoma (PC12) and mouse neuroblastoma cells exposed to MeHg. Flow cytometric analysis revealed that the occurrence of apoptosis was preceded by the accumulation of cells in G2/M after MeHg treatment. Exposure to colchicine, a well-characterized mitotic inhibitor, also caused G2/M-phase arrest followed by the appearance of apoptotic cells. These results suggest that G2/M-phase arrest through the disruption of microtubules is an important event in the development of apoptosis by MeHg. MeHg treatment led to G2/M-phase arrest followed by apoptosis in nonneuronal HeLa cells also. Bcl-2 was phosphorylated by MeHg treatment in HeLa cells but not in PC12 cells; however, p53 expression was not changed in either cell line. Thus, MeHg induces apoptosis via a p53-independent pathway in both cell lines, however, different pathways may be activated after the disruption of microtubules in PC12 and HeLa cells.

Animals↗
PubMed1999

Simian virus 40-transformed metallothionein null cells showed increased sensitivity to cadmium but not to zinc, copper, mercury or nickel.

Primary cultured embryonic cells derived from mice with disrupted metallothionein (MT) I and II genes and from control mice were transformed with a plasmid encoding the simian virus 40 (SV40) large T antigen. The resulting MT-/- and MT+/+ cell strains showed similar cell morphology, cell cycle and no significant differences in glutathione levels or in the activities of glutathione-related enzymes and antioxidant enzymes. The MT-/- cells were more sensitive to Cd than MT+/+ cells, though no increase in the sensitivity to Zn, Cu, Hg or Ni were observed in MT-/- cells. MT+/+ cells accumulated more Cd than MT-/- cells but showed less lesion, suggesting the role of MT induced by Cd in MT+/+ cells as a scavenger of toxic Cd ion. These results suggest a dominant protective role of MT against Cd compared with other metals. SV40-transformed MT-/- cells seem to be a useful tool for the investigation of cellular function of MT.

Animals↗
PubMed1999

Reduced uptake and enhanced release of cadmium in cadmium-resistant metallothionein null fibroblasts.

Metallothionein (MT) is known to play a predominant role in the protection of cells from cadmium (Cd) toxicity. To investigate other factors involved in Cd resistance, we established Cd-resistant cell lines from simian virus 40-transformed MT null fibroblasts. Cd-resistant MT null cells, Cd-rA7 and Cd-rB5, developed approximately 10-fold resistance to Cd compared to parental cells, but showed no cross-resistance to Zn, Cu, Hg, Ni, As, cisplatin or H2O2. Accumulation of Cd in the resistant cells was 13-18% of that of parental cells after treatment with Cd for 24 h. A short-term experiment revealed that the rate of Cd incorporation into the Cd-resistant cells was suppressed, and the rate of Cd release was enhanced in the resistant cells compared with that of parental cells. These results indicate that the altered transport of Cd, slow uptake and rapid release, may confer resistance to Cd on the Cd-resistant cells established from MT null fibroblasts.

Animals↗
PubMed1999

Gastric ulcer formation after the Hanshin-Awaji earthquake: a case study of Helicobacter pylori infection and stress-induced gastric ulcers.

BACKGROUND: Both Helicobacter pylori (H. pylori) infection and various stresses are known to induce peptic ulcer disease of the upper gastrointestinal tract. However, the pathogenetic relationship between the two factors has not yet been clarified. We conducted a case-control study to examine whether H. pylori infection played a role in the development of gastric ulcer (GU) induced by life-event stresses that were experienced after the Hanshin-Awaji earthquake. MATERIALS AND METHODS: Serum samples from patients in the devastated area who developed GUs during the 2 months following the Hanshin-Awaji earthquake and those from GU patients in the same area during the corresponding period of the previous year, and from gender-, age- and institute-matched ulcer-free controls were tested for the presence of the H. pylori IgG antibody. RESULTS: A significant association between H. pylori infection and the development of GU in uninjured patients was observed in all sets [matched odds ratio (OR) = 3.23, 95% confidence interval: 1.95-5.35]. Moreover, the prevalence of H. pylori infection in patients who developed GUs after the earthquake was not different from that for GU patients in the previous year. In contrast, there was no association between H. pylori infection and the development of GU in the physically injured patients after the earthquake. CONCLUSIONS: H. pylori infection may play an important role in the development of GUs that are induced by emotional life-event stresses.

Antibodies, Bacterial↗
PubMed1999

Metallothionein modulates the carcinogenicity of N-butyl-N-(4-hydroxybutyl)nitrosamine in mice.

We examined the carcinogenicity of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in transgenic mice deficient in the metallothionein (MT) I and II genes and in control (129/Sv) mice. Both strains of mice were given BBN for 8 weeks with or without Zn treatment. All mice were killed at 12 weeks after the cessation of BBN administration. BBN induced bladder tumors in 75% of MT null mice and in 43% of 129/Sv mice. The average number of bladder tumors per mouse was significantly higher in MT null mice (1. 18 +/- 0.27) than in 129/Sv mice (0.43 +/- 0.20). Zn treatment suppressed the carcinogenicity of BBN in 129/Sv mice but not in MT null mice. Histopathological examination of the tumors revealed that the malignant potential of bladder tumors in 129/Sv mice was greater than that in MT null mice. These results indicate that MT is an important modulator of carcinogenicity of BBN in the bladder of mice.

Animals↗
PubMed1999

Frequent expression of inducible nitric oxide synthase in esophageal squamous cell carcinomas.

Nitric oxide (NO) plays important biological roles in cardiovascular, nervous and immune systems, and is synthesized by nitric oxide synthase (NOS). Intracellular NO is known to cause DNA damage as a mutagen. We examined the expression of cytokine-inducible NOS (iNOS) in human esophageal squamous cell carcinomas. Weak iNOS immunoreactivity was seen in the basal and parabasal layers of non-neoplastic esophageal stratified squamous epithelium. iNOS expression was detected in 50 (87.7%) of the 57 esophageal squamous cell carcinomas, regardless of the depth of tumor invasion, histological differentiation and lymph node status. Early-stage cancers, i.e. mucosal squamous cell carcinomas, also showed significant iNOS expression. We speculate that increased iNOS expression is associated with the carcinogenesis of human esophageal cancer.

Adult↗
PubMed1998

Peptic ulcers after the Hanshin-Awaji earthquake: increased incidence of bleeding gastric ulcers.

OBJECTIVE: Although physical stresses are known to induce peptic ulcers in the upper gastrointestinal tract, it remains controversial whether emotional stress can cause peptic ulcers. Therefore, we examined retrospectively the influence of the Hanshin-Awaji earthquake that occurred in Japan in January 1995 on the occurrence of peptic ulcer disease among noninjured residents. METHODS: Sixty-one hospitals, covering 70% of all endoscopy examinations performed in this area, joined the study and were divided into three areas according to the severity of the damage. A comparison was made between a group of 10,831 patients who underwent upper gastrointestinal endoscopy within 2 months after the earthquake and 16,100 who did so in the same hospitals during the corresponding period in 1994. RESULTS: In the most devastated area, in spite of a dramatic decrease in the total number of endoscopies (50.0%), patients with gastric ulcer (GU) were increased in 1995, whereas those with duodenal ulcer were decreased, resulting in a higher ratio of gastric to duodenal ulcers than in 1994 (3.07 vs 1.88). In particular, there was a marked increase in bleeding GU. The mean age of patients with GU was significantly higher in 1995 than in 1994. CONCLUSION: The Hanshin-Awaji earthquake-induced life event stress not only triggered but also exacerbated GU, particularly in the elderly.

Adult↗
PubMed1998

Secondary aortoduodenal fistula complicating aortic grafting, as a cause of intermittent chronic intestinal bleeding.

Intermittent intestinal bleeding persisted in a 77-year-old male, who had undergone grafting for abdominal aortic aneurysm. Each attack lasted for a few weeks and spontaneously resolved. Only a minute abnormality was found in the third portion of the duodenum; barium studies showed a segmental narrowing, but endoscopy disclosed only a small erosion in that portion. Massive and fatal gastrointestinal hemorrhage broke out 6 months after the onset of bleeding. Autopsy revealed an adhesion area with a small fistula formation between the duodenum and aorta. Even slight endoscopic findings should be considered suggestive of aortoenteric fistula in patients after aortic surgery.

Aged↗
PubMed1997

Efficacy of combination therapy of interferon-alpha with ursodeoxycholic acid in chronic hepatitis C: a randomized controlled clinical trial.

The efficacy of interferon-alpha therapy in the treatment of chronic hepatitis C is still limited. A combination therapy of interferon-alpha with ursodeoxycholic acid (UDCA) was tested for its efficacy in the treatment of chronic hepatitis C by a randomized controlled study. Eighty consecutive Japanese patients with chronic hepatitis C were randomly divided into two groups: one group was treated with interferon-alpha (group A, n = 40) and the other with a combination of interferon-alpha and UDCA (group B, n = 40). In both groups, human interferon-alpha (6 million units per day) was intramuscularly injected daily for 2 weeks and then three times a week for 22 weeks: this 24-week period was followed by 24 weeks of observation. In group B, UDCA was also administered, daily at a dose of 600 mg orally, from the beginning of the interferon therapy and administration was continued for 48 weeks. The rates for ALT normalization and clearance of hepatitis C virus (HCV) viremia at the end of the 24-week interferon therapy were similar for groups A and B (58% vs 60% and 55% vs 48%, respectively). At the end of the 24-week follow-up, the sustained normalization rates for ALT levels for the two groups were not different (35% vs 43%), while the rate of clearance was higher in group B (40%) than in group A (23%), but the difference was not significant (P = 0.14). The sustained complete response, i.e., HCV RNA negativity at the end of the follow-up, as well as the maintenance of ALT normalization during the follow-up period, was more frequent in group B (38%) than in group A (18%) although the difference was not significant (P = 0.08). The rate of HCV reactivation after interferon was discontinued was significantly lower in group B (16%) than in group A (59%) (P < 0.01). Although this combination therapy did not lead to a sufficiently sustained complete response, it could serve as adjuvant antiviral therapy when a suitable dosage and administration period are determined.

Administration, Oral↗
PubMed1997

Recombinant interferon-alpha-2a for treatment of chronic hepatitis C: results of a multicenter randomized controlled dose study.

To compare the efficacy of low and relatively high dosages of recombinant interferon (IFN)-alpha-2a in Japanese patients with chronic hepatitis C, as well as to characterize the type of patients who will respond well to a low-dosage treatment, 88 patients with histologically proven chronic hepatitis C were randomly assigned to two treatment groups; one treated with IFN-alpha-2a 6 MU daily for 2 weeks followed by 6 MU three times weekly for 22 weeks (6-MU group), and another given the same initial treatment followed by 3 MU three times weekly for 22 weeks (3-MU group). The rate of sustained normalization of ALT 6 months after the cessation of treatment was 33% in the 3-MU group and 40% in the 6-MU group (p = 0.64). In addition, there was no difference in elimination of serum HCV-RNA 6 months after the cessation of treatment between the 3-MU group (26%) and 6-MU group (29%). Multivariate stepwise regression analysis revealed that serum HCV-RNA level (p = 0.0035) and platelet count (p = 0.0009) were independent variables useful in predicting a sustained response of ALT. The sustained response rate of ALT in patients with a serum HCV-RNA level less than 10(5) copies/ml and serum platelet level above 15 x 10(4)/microliter was 71%, whereas that in patients with a serum HCV-RNA level above 10(5) copies/ml and serum platelet level less than 15 x 10(4)/microliter was 12%. These results indicate that a high rate of sustained response to IFN therapy can be expected in chronic hepatitis C patients with a low serum level of HCV-RNA and a high level of platelets, even if treated with a low dose of IFN.

Antiviral Agents↗
PubMed1997

Follow-up after the Hanshin-Awaji earthquake: diverse influences on pneumonia, bronchial asthma, peptic ulcer and diabetes mellitus.

We evaluated the influence of the Hanshin-Awaji earthquake on the patients in our internal medicine department. After the initial rush of patients with injury, the number of respiratory diseases, largely pneumonia, increased within one month. This same event, however, seemed to decrease attacks among asthma patients. During the following three months, the number of peptic ulcer patients increased: 39.5% had a giant gastric ulcer and 34.8% had bleeding complications. Diabetic control of outpatients became worse after the earthquake. It is important to recognize that various disorders involving physical and psychological problems develop at different stages after a large-scale disaster.

Asthma↗
PubMed1997

Histological evaluation of destructive monoarthropathy in mixed connective tissue disease.

The synovium from a patient with mixed connective tissue disease and destructive ankle monoarthritis was studied in detail to determine its immunohistological characteristics. Fibrinoid necrotic tissue on the surface of the synovium, multi-layered lining cells, increased numbers of capillaries, interstitial edema, infiltration of macrophages, relatively small numbers of lympho-plasma cells and polymorphonuclear leukocytes, scattered bone fragments, and multinucleated giant cells were observed. Many cells in the lining and sublining area were positive for CD68 and MAC387. Lower layers of increased lining cells which had a spindle shape were positively stained with anti-HLA-DR antibody. The small arteries in the deeper part of the synovium revealed obstruction or highly stenotic change. These findings suggest that obstructive circulatory disturbance due to endothelial injury might influence the progression of arthritis.

Adult↗
PubMed1996

Isoforms of selenoprotein P in rat plasma. Evidence for a full-length form and another form that terminates at the second UGA in the open reading frame.

Several forms of selenoprotein P that share the same N-terminal sequence have been identified in rat plasma, but only one selenoprotein P mRNA has been characterized. The open reading frame of the mRNA contains 10 UGAs that presumably code for selenocysteine residues. Using heparin-Sepharose, we isolated two of the protein forms from immunoaffinity-purified selenoprotein P. One of the forms, Se-P45B, migrates at 45 kDa on SDS-polyacrylamide gel electrophoresis, and the other, Se-P57B, migrates at 57 kDa. These two forms were cleaved with cyanogen bromide, and both yielded 40-kDa fragments that were consistent with those fragments being an inter-methionine peptide near the N terminus of the predicted polypeptide. A 20-kDa fragment present in the cleavage products of Se-P57B was absent from the products of Se-P45B. This result suggested that Se-P45B lacks the C-terminal region of the predicted polypeptide. Carboxypeptidase P digestion of Se-P45B indicated that its C-terminal amino acid is Ser244, the amino acid immediately upstream from the predicted second selenocysteine. C-terminal analysis of Se-P57B indicated that its final residue is Asn366, the last amino acid predicted by the cDNA sequence. Amino acid composition analyses of the two forms were consistent with both arising from the same mRNA. Immunoaffinity-purified selenoprotein P was digested with proteases, and the resulting peptides were separated and sequenced. Only amino acid sequences predicted by the cDNA were found, and 80% of the predicted amino acid sequence was confirmed. These results are compatible with Se-P45B arising from termination of translation at the second in-frame UGA codon and all of the 10 in-frame UGA codons being read through to produce Se-P57B. These findings demonstrate that selenoprotein P isoforms of differing peptide lengths are present in plasma. They raise the possibility that the second UGA codon in selenoprotein P mRNA can have alternative functions: coding for the incorporation of selenocysteine or coding for termination of translation.

Amino Acid Sequence↗
PubMed1996

Multiple forms of selenoprotein P in rat plasma.

SDS-PAGE of immunoaffinity-purified rat seleno-protein P demonstrates a major band at 57 kDa and a less intense band at 45 kDa, suggesting the existence of more than one form of the protein. Separate experiments were carried out in which plasma from rats administered 75Se and immunoaffinity-purified 75Se-labeled selenoprotein P were applied to a heparin-Sepharose column at pH 7. In each experiment three peaks of 75Se-labeled protein were eluted during a continuous gradient from pH 7 to pH 8.5. The remaining 75Se-labeled material was eluted as a single peak by 1 M NaCl. Phosphorimaging of the SDS-PAGE gel of the peaks revealed that the first peak (1a) contained two bands (45 and 57 kDa) while the three remaining peaks each contained one band (peak 1b, 45 kDa and peaks 2 and 3, 57 kDa). N-terminal sequencing of the first eight amino acids of each band revealed that all five have the same N-terminal amino acid sequence and therefore are forms of selenoprotein P. Staining using a digoxigenin-based staining procedure revealed that all five forms contain carbohydrate. This demonstrates that plasma-derived selenoprotein P can be separated into five forms based on SDS-PAGE migration and heparin-Sepharose affinity and that at least two isoforms of selenoprotein P exist based on the presence of 45- and 57-kDa forms. The five forms have been given designations based on their order of elution from the heparin-Sepharose column and their M(r) on SDS-PAGE: selenoprotein P57A (peak 1a, 57 kDa), selenoprotein P45A (peak 1a, 45 kDa), selenoprotein P45B (peak 1b, 45 kDa), selenoprotein P57B (peak 2, 57 kDa), and selenoprotein P57C (peak 3, 57 kDa).

Amino Acid Sequence↗
PubMed1995

Evaluation of gastric ulcer healing by lansoprazole by measurement of ulcer diameter.

Ninety-three patients with gastric ulcers larger than 10 mm in diameter were randomly divided into two groups. Seventy patients received lansoprazole 30 mg once daily and 23 patients received cimetidine 400 mg twice daily. Ulcer healing was assessed by measuring changes in the longitudinal diameter of the ulcer at 2, 4, and 8 weeks after the start of treatment. In the lansoprazole group, ulcer diameters became significantly smaller than those in the cimetidine group. In the lansoprazole group, ulcer diameters did not differ significantly between patients younger than 65 years of age and those 65 or older at the evaluation points. However, in the cimetidine group, ulcer diameters became much smaller in patients younger than 65 years of age than in older patients. These results suggest that the potent acid suppression afforded by lansoprazole led to effective healing of gastric ulcers even in elderly gastric ulcer patients with defective mucosal protection.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

Selenium levels and glutathione peroxidase activities in blood in an andean high-altitude population.

Selenium (Se) levels in blood (whole blood, erythrocytes and serum) and blood glutathione peroxidase (GSH-Px) activity were investigated in people living at high altitude in Bolivia (4,000 m above sea level). These parameters were compared to those of people living at low altitude (300 m above sea level). The Se levels in whole blood of the high-altitude subjects did not differ significantly from those of the low-altitude subjects. However, the Se levels in erythrocytes were significantly lower in the high-altitude subjects than in the low-altitude subjects, whereas serum Se levels were higher in the high-altitude subjects than in the low-altitude subjects. GSH-Px activity (Unit/g Hb) was significantly lower in the high-altitude subjects than in the low-altitude subjects. The mean corpuscular Hb concentration (MCHC), an indicator of the age of erythrocytes, in the high-altitude subjects was significantly higher than in the low-altitude subjects. These results show that the GSH-Px activity in the blood of the high-altitude subjects is relatively low. This may be due to their aged erythrocytes and/or to relatively low Se intake in the high-altitude population compared with low-altitude population.

Adolescent↗