Biomedical subjects

H Watanabe

Publications and source records attributed to H Watanabe.

At least 19 recordsLinked to original sources

PubMed1992

Combined action of paraquat and superoxide on the peroxidation of detergent-dispersed linolenic acid.

We investigated the peroxidative effect of paraquat and active oxygens on detergent-dispersed linolenic acid in phosphate buffer (pH 7.5) from the malondialdehyde (MDA) level. Our complete system and further inclusion of catalase were effective in stimulating MDA formation. On the other hand, xanthine oxidase (XOD) or paraquat omission, superoxide dismutase (SOD) inclusion or anaerobic incubation inhibited the formation of MDA. Ferrous ion was weakly associated with phosphate of the buffer, forming a complex, and the release of ferrous ion from the complex intensified the MDA levels with the complete and catalase inclusion systems. The electron paramagnetic resonance (EPR) spectra using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) showed that superoxide, produced immediately after the addition of XOD, played a crucial role. We could obtain a DMPO-OOH signal at the starting stage whenever MDA stimulation was observed. The omission of paraquat, however, produced no increase in MDA level in spite of an appearance of DMPO-OOH signal, indicating that paraquat also plays an important role. On the other hand, Desferal, a ferric chelator, showed a concentration-dependent inhibition effect. There was an immediate strong intensity of DMPO-OOH and paraquat signals. We did not, however, observe MDA stimulation at 250 microM Desferal, which confirms that ferrous ion plays an essential role in the lipid peroxidation. These results indicate a combined action of paraquat (or its radical) and superoxide on the accessibility of ferrous ion, including its release from the complex with phosphate, which may be an endogenous chelator. The possibility of ternary complex participation is also discussed.

Cyclic N-Oxides↗

PubMed1992

Carcinoids and endocrine cell micronests of the minor and major duodenal papillae. Their incidence and characteristics.

BACKGROUND: There have been no reports about the incidence and characteristics of carcinoids and endocrine cell micronests (ECM) of the minor and major duodenal papillae. METHODS AND RESULTS: The minor and major duodenal papillae of 78 consecutive autopsy and 117 surgical specimens were examined histologically using mirror-image paraffin-embedded tissue samples. ECM were found frequently in these areas in hematoxylin and eosin-stained sections, and their aggregation patterns were classified into four types: nodular type (Type 1, 2 of 167 in the minor papilla and 1 of 145 in the major papilla), scattered type (Type 2, 39 of 167 and 6 of 145), orifice type (Type 3, 7 of 167 and 0 of 145), and islet-like type (Type 4, 14 of 145 and 0 of 145, respectively). Criteria of neoplastic or nonneoplastic ECM were defined tentatively by histologic and immunohistochemical analyses of the ECM. Type 4 was regarded to be atrophic or regenerating islets of Langerhans. Distinct carcinoids (Type 1), neoplastic ECM (39% of all Type 2 and 3), and nonneoplastic ECM (61% of all Type 2 and 3) were found in 1.2%, 9.0%, and 16.2% of 167 samples of the minor papilla and 0.7%, 1.4%, and 2.8% of 145 specimens of the major papilla, respectively. The endocrine cells composing the carcinoids and the ECM usually were immunoreactive for somatostatin and/or pancreatic polypeptide (PP). They were negative for S-100 beta. CONCLUSION: In duodenal papillae, especially in the minor duodenal papilla, carcinoids and ECM seem to occur more frequently than generally thought, and predominantly consist of somatostatin and/or PP containing cells.

Adolescent↗

PubMed1992

Histologic follow-up of ampullary adenomas in patients with familial adenomatosis coli.

BACKGROUND: The major duodenal papilla is a common site of extracolonic adenoma in patients with familial adenomatosis coli (FAC). However, there have been no reports which have systematically discussed histologic change in atypia of ampullary adenomas with time by their location in the papilla. METHODS AND RESULTS: The major duodenal papillae of 23 patients with FAC were followed endoscopically and histologically for an average of 7.7 years (range, 1 year to 14 years 7 months). Tubular adenomas were detected histologically in 17 of the 23 patients at the first (14) or following examinations (3). They occurred in the orifice and/or ampulla in 11 patients and in the surface of the papilla in 8 patients. Three of the 11 orifice and/or ampulla adenomas contained moderate to severe atypia. There was no histologic change in atypia or malignant transformation during the follow-up period. CONCLUSIONS: In the patients with FAC, the major duodenal papilla had adenoma, i.e., precancerous lesion, at a high incidence (74%), and it is reported that the ampulla of the papilla tended to have extracolonic carcinoma. Therefore, it is necessary to follow duodenal papillae of patients with FAC carefully and take biopsy specimens repeatedly from various sites, especially from the orifice or ampulla even if the papilla seems to be normal.

Adenoma↗

PubMed1992

Surgical treatment of thoracic esophageal carcinoma directly invading the lung.

BACKGROUND: The authors examined 63 patients with thoracic esophageal carcinoma directly invading the adjacent lung. Four of them had esophago-pulmonary fistulas. One patient received exploratory thoracotomy and exposure to radiation, and 62 underwent esophagectomy with mediastinal and abdominal lymph node dissection. A resection of the seized lung and the esophagus was performed in 39 patients (Group A), and 23 received esophagectomy with part of the tumor remaining intact (Group B). METHODS: The results of treatment were compared between the two groups. RESULTS: Operative blood loss, mortality, and complications in both groups showed no difference. The average number of dissected lymph nodes in Group A was significantly larger than that in Group B (P less than 0.01). Histologic examination revealed that 22 (56.4%) lesions in Group A invaded the pulmonary parenchyma, a finding that indicates the difficulty of gross diagnosis of tumor infiltration. Five-year survival rates for patients in Groups A and B were 21.1% and 8.7%, respectively. The survival curve for patients in Group A was significantly better than for those in Group B (P less than 0.05). CONCLUSIONS: Pulmonary resection and aggressive lymph node dissection are recommended for patients with esophageal carcinoma that invades the adjacent lung.

Aged↗

PubMed1992

Chemiluminescence in the crude extracts of soybean seedlings. Postulated mechanism on the formation of hydroperoxide intermediates.

It has been reported that weak chemiluminescence (CL) from crude extracts of soybean seedlings is remarkably enhanced with the addition of various aldehydes (Biochim. Biophys. Acta 1058, 209-216). The reactivity of certain emitter(s) with oxygen species was examined in the autoclaved extracts of seedlings. When samples were reduced by the addition of hydrosulfite, two different types of reactivities in CL were defined. One type showed an initial rapid increase and a subsequent fast decay in CL upon mixing with oxygen. This rapid increase in CL intensity was independent of the presence of aldehydes, and was significantly suppressed by SOD. However, the subsequent slow decay phase in CL was dependent on the presence of aldehydes. In the sample reduced more moderately by borohydride, the same slow decay of CL appeared upon mixing with acetaldehyde and oxygen. This second type of CL was not inhibited by active oxygen scavengers. Hydrogen peroxide added to unreduced (oxidized) samples also elicited CL. Three types of primary emitters may be oxidized to form transient hydroperoxide, and excited for light emission by slightly different ways: two of them are excited by abstraction of one atomic oxygen from the hydroperoxy intermediate with aldehyde or hydrogen peroxide, leading to formation of an excited hydroxide intermediate. The third is excited directly on the binding of superoxide anion to the reduced primary emitter.

Acetaldehyde↗

PubMed1992

Suppression of melanoma cell motility factor receptor expression by retinoic acid.

beta-All-trans-retinoic acid (RA) has been shown to inhibit the growth, enhance the differentiation, and suppress the transformed and metastatic properties of certain human and murine melanoma cells. This study examined the effect of RA on the level of a cell surface receptor (M(r) 78,000) (gp78) for an autocrine motility factor, which has been implicated in invasion and metastasis. Treatment of murine melanoma cell lines S91-C2, B16-F1, and K1735-P with RA (10 microM) for 5 days decreased the level of gp78 by 37, 72, and 92%, respectively, as revealed by immunoblotting with monoclonal antibodies raised against gp78. In contrast, RA had only a limited effect on gp78 levels in melanoma cell clones or variant cell lines that are resistant to the growth-inhibitory effects of RA (S91-C154, B16-F10, and K1735-Cl19). Further studies with K1735-P, the most sensitive cell line with respect to modulation of gp78, showed that the decrease in gp78 level required at least 1 microM RA and 4 to 5 days of treatment. The binding of anti-gp78 antibodies to the surface of intact RA-treated cells and to intracellular gp78 in permeabilized cells was also lower than in untreated cells. Furthermore, RA treatment decreased the induction of cell motility, on colloidal gold-coated glass coverslips, by anti-gp78 antibodies, which mimic the effect of autocrine motility factor. The RA-induced decrease in antibody-enhanced cell motility was similar to the time- and RA concentration-dependent decrease in the amount of gp78, suggesting that the two events are related. These results raise the possibility that the previously reported suppression by RA of tumor cell invasion and metastasis may be related, at least in part, to suppression of cell motility resulting from the decreased level of the autocrine motility factor receptor.

Animals↗

PubMed1992

[X-ray examination of the gastrointestinal tract in systemic cutaneous disease].

An X-ray examination of the gastrointestinal tract was performed on 56 patients with systemic cutaneous disease that is often considered associated with internal malignancies. Found were one case of esophageal cancer, two cases of gastric cancer, and two cases of colon cancer. The prevalence of gastric and colon cancer in these patients showed a statistically significant increase compared to the general population. The rate of gastric cancer was 16.26 times higher than the general population and that of colon cancer 32.26. X-ray examination of the gastrointestinal tract in patients with systemic cutaneous disease is useful for detecting malignancy.

Aged↗

PubMed1992

Age-dependent increase of extrathymic T cells in the liver and their appearance in the periphery of older mice.

The liver is a major site of generation of extrathymic T cells with unique properties (e.g., expressing intermediate TCR and containing self-reactive clones). We investigated herein whether the levels of extrathymic alpha beta T cells varied in various organs as a function of age. A systematic examination of the number of mononuclear cells in various organs of BALB/c mice revealed that the number of hepatic MNC increased with age whereas the number of thymocytes decreased. These changes were more striking in mice fed under conventional conditions than under specific pathogen-free condition. The age-dependent changes in the number of mononuclear cells in the spleen and lymph nodes were minimal. Although the total proportion of alpha beta T cells in each organ remained constant, the staining patterns of TCR-alpha beta as shown by immunofluorescence profiles varied. The most prominent change was that intermediate TCR-alpha beta cells, which constituted a small population in the liver of young mice, expanded in the liver of older mice. Intermediate TCR cells appeared even in the periphery of older mice. These findings were confirmed by the appearance of extrathymic T cells with other unique properties, e.g., double-negative CD4-8- phenotype and CD44 expression. In athymic nude mice, only intermediate TCR cells were present in the liver and periphery. An age-dependent increase of intermediate TCR cells was also seen in these mice. Taken together with the result of bromodeoxyuridine-injection experiment, which showed an intensive in vivo proliferation of cells in the hepatic sinusoids, extrathymic T cells may differentiate predominantly in the liver and appeared even to the periphery in older mice.

Age Factors↗

PubMed1992

Effect of anti-CD3 antibody on the generation of interleukin-2-activated lymphocytes from tumor tissues of gastrointestinal cancer.

BACKGROUND: The efficiency of anti-CD3 antibody (OKT3) for adoptive immunotherapy using lymphokine-activated killer (LAK) cells generated from tumor-infiltrating lymphocytes (TIL), regional lymph node lymphocytes (RLNL), and peripheral blood lymphocytes (PBL) was investigated. METHODS: TIL, RLNL, and PBL derived from 39 patients with gastrointestinal cancers (16 gastric cancers, 17 colorectal cancers, and 6 esophageal cancers) were cultured for 4 weeks with 200 U/ml of recombinant interleukin-2. To one group, solid-phase 10 micrograms/ml OKT3 was added during the initial culture period (day 2 or 4). Cytotoxicity against K562 cells (NK-like activity) and Daudi cells (LAK activity) and the phenotypes of effector cells generated after culturing for 2-3 weeks were studied. RESULTS: Proliferative responses were significantly increased by OKT3 in each type of effector cell (P less than 0.01); in particular, TIL expanded more by OKT3 than PBL and RLNL (P less than 0.01). The population of CD8+ CD11b- cytotoxic T-cells in OKT3-stimulated groups was significantly larger than that in unstimulated groups (P less than 0.01), whereas no differences were observed with CD4+ cells (helper/inducer T-cells) and CD8+ CD11b+ cells (suppressor T-cells). OKT3 enhanced the NK-like activity of TIL and PBL but did not affect their LAK activity. OKT3 suppressed the NK and LAK activity of RLNL. CONCLUSIONS: OKT3 stimulation did not significantly enhance the LAK activity, but the authors propose that OKT3 could be an effective addition to adoptive immunotherapy using TIL due to an increased proliferation and generation of a large cytotoxic T-cell population.

Aged↗

PubMed1992

Differences between solid and duct-ectatic types of pancreatic ductal carcinomas.

Macroscopically, 45 pancreatic ductal carcinomas were classified into two types: solid type (36 tumors) and duct-ectatic type (9 tumors). To disclose the biologic differences between these two types, they were compared by incidence, primary site, histologic types and grades, and biologic behavior. Although 20 solid type carcinomas arose from the branch duct, the duct-ectatic type carcinoma originated in the branch duct in three tumors, in a cyst in one, and in the main duct in one. The major component of the solid type was tubular (glandular) adenocarcinoma with high nuclear atypia and slight mucous secretion. The major component of the duct-ectatic type was papillary adenocarcinoma with low nuclear atypia and abundant mucous secretion. Thirty-four solid type carcinomas showed pancreatic stromal invasion, and 28 showed metastasis. Nine duct-ectatic type carcinomas spread intraductally and had not metastasized. It is concluded that the biologic differences between the two macroscopic type carcinomas are induced by the histologic types and grades.

Adenocarcinoma↗

PubMed1992

Details of an isolation method for hepatic lymphocytes in mice.

The liver comprises a unique lymphocyte population, i.e., extrathymic alpha beta T cells with TcR of intermediate intensity. In the present study, we attempted to determine what pretreatments were appropriate to isolate hepatic mononuclear cells (MNC) containing such intermediate alpha beta TcR cells in mice. Hepatic MNC were isolated from untreated mice and mice subjected to either bleeding or liver perfusion, and the intermediate alpha beta TcR cells in each preparation were identified. For reasons of simplicity, cell purity and cell yields, hepatic lymphocytes should be obtained from mice subjected to total bleeding. Additional information on extrathymic alpha beta T cells obtained by using the recommended method is also presented.

Animals↗

PubMed1992

Different effects of peptidase inhibitors on dermorphin- and on [D-Arg2]dermorphin-induced antinociceptive activity.

The antinociceptive effects produced by the intracerebroventricular (i.c.v.) injection of dermorphin and [D-Arg2]dermorphin were compared in conscious mice, using the combined administration of peptidase inhibitors. Nociception was assessed using a tail pressure assay. Dermorphin-induced antinociception was not potentiated by simultaneous administration of amastatin or captopril as judged from the ED50 values. Co-administration of dermorphin and amastatin gave a longer duration than with dermorphin alone, whereas there was no significant effect on duration with captopril. The antinociceptive activity of dermorphin was significantly enhanced when the heptapeptide was injected simultaneously with both peptidase inhibitors. This result indicates that the heptapeptide sequence is required for the full expression of intrinsic opioid activity of dermorphin. In contrast, co-administration of amastatin brought about a significant enhancement of the antinociceptive activity induced by i.c.v. administration of [D-Arg2]dermorphin, whereas the effect of [D-Arg2]dermorphin was markedly decreased by the concurrent administration of captopril or thiorphan. The potency of captopril was much greater than that of thiorphan. The present results suggest that [D-Arg2]dermorphin may be transformed metabolically to a peptide which has potent antinociceptive activity.

Analgesics, Opioid↗

PubMed1992

Weak chemiluminescence of bilirubin and its stimulation by aldehydes.

Bilirubin in an alkaline solution exhibits a weak chemiluminescence (CL) under aerobic conditions. This spontaneous CL was markedly enhanced by the addition of various aldehydes. The fluorescent emission spectrum of bilirubin, excited by weak intensity light at 350 nm, coincided with its CL emission spectrum (peak at 670 nm). CL emission from bilirubin was not quenched by active oxygen scavengers. This suggests that triplet oxygen reacts with bilirubin, and forms an oxygenated intermediate (hydroperoxide) as a primary emitter (oxidative scission of tetrapyrrole bonds in bilirubin is not involved in this CL). The Ehrlich reaction (test for monopyrroles) and hydrolsulphite reaction (test for dipyrroles) on the CL reaction mixture and unreacted bilirubin showed no differences. When the CL was initiated by singlet oxygen, rather than superoxide anion, monopyrrole, was detected in the reaction products by gel chromatography. The inhibitory effect of a scavenger of singlet oxygen on CL was eliminated in the presence of formaldehyde. Therefore, triplet carbonyl, formed by singlet oxygen through the dioxetane structure in bilirubin, is not an emitter. The reaction mechanism of bilirubin CL and the formation of a hydroperoxide intermediate is discussed in relation to the chemical structure of luciferin molecules from bioluminescent organisms.

Acetaldehyde↗

PubMed1992

Bilirubin chemiluminescence induced by the attack of active oxygen species.

Ultraweak chemiluminescence (CL) from bilirubin occurs in the presence of triplet oxygen and is stimulated by the addition of aldehydes. Active oxygen species also enhance bilirubin CL, in the absence of aldehydes. An inhibitory effect of active oxygen scavengers on the CL indicated that active oxygens generated from the decomposition of added hydrogen peroxide or from the xanthine-xanthine oxidase reaction contributed to the CL from bilirubin molecules. However, the contribution of singlet oxygen to the CL disappeared in the presence of formaldehyde. This suggested that the scission of tetrapyrrole bonds via a dioxetane intermediate or the production of triplet carbonyls from the oxidation of aldehydes by singlet oxygen was not involved in the CL, at least in the presence of formaldehyde. The spectrum of CL induced by the generation of active oxygen was the same as that from the aldehyde-enhanced CL reaction. We propose that the formation of a hydroperoxide (and/or hydroxide) bilirubin intermediate, but not a dioxetane, may be involved in the excitation of bilirubin molecules for CL.

Aldehydes↗

PubMed1992

Genetic control of nonresponsiveness to hepatitis B virus vaccine by an extended HLA haplotype.

We previously reported evidence for a statistical association between the serologically determined HLA-Bw54, DR4 and DRw53 alleles and the non-immune responsiveness to hepatitis B virus surface antigen (HBsAg) in the Japanese population. To identify the locus and allele within the HLA region associated with the nonresponsiveness to HBsAg, serological HLA typing, DNA typing of HLA-DQ and DP alleles using amplified HLA genes and sequence-specific oligonucleotide probes, and restriction fragment length polymorphism (RFLP) analysis of the fourth component of complement (C4) genes were performed in healthy unrelated Japanese vaccinees who were immunized subcutaneously three times with plasma-derived HBsAg vaccine. In nonresponders to HBsAg, the frequencies of HLA-Bw54 cross-reactive epitope group (CREG); (Bw54, Bw55, Bw56 and other Bw22), C4 RFLP (6.5 kb + 12.0 kb), DR4, DRw53 and DQw4 (DQA1*0301-DQB1*0401) were increased and the frequencies of HLA-DR1, DRw6 and DQw1 were decreased as compared with those in healthy unrelated controls. Further analysis revealed that the coexistence of HLA-Bw54CREG and DR4-DRw53-DQw4 (DQA1*0301-DQB1*0401) was associated with the nonresponder group, whereas, donors positive for exclusively either Bw54 CREG or DR4-DRw53-DQw4 (DQA1*0301-DQB1*0401) were not associated with the nonresponder group. Because there is a strong linkage disequilibrium between HLA-Bw54CREG, C4 RFLP (6.5 kb + 12.0 kb) and HLA-DR4-DRw53-DQw4 (DQA1*0301-DQB1*0401) in the Japanese population, the extended HLA-Bw54CREG-C4 RFLP (6.5 kb + 12.0 kb)-DR4-DR-w53-DQw4 (DQA1*0301-DQB1*0401) haplotype may well control nonimmune responsiveness to HBsAg. This extended HLA haplotype controls nonresponsiveness as a dominant genetic trait because all ten heterozygotes and two of three probable homozygotes of this extended HLA haplotype were nonresponders.

Adult↗

PubMed1992

Time course of hepatitis A virus antibody titer after active and passive immunization.

To investigate the antibody titer necessary to prevent hepatitis A virus infection, either 15 or 7.5 mg/kg of immune serum globulin was injected into 10 antihepatitis A virus negative volunteers and their serum antihepatitis A virus titers were observed for 28 wk. In addition, antibody titers were observed for 96 wk in a phase 1 clinical trial of a hepatitis A vaccine. The two studies were then compared to assess the immunogenicity of the vaccine and the persistence of the antibody. Serum-neutralizing antibody titers that were greater than or equal to 4 (considered as positive) persisted for 18 wk and 14 wk after the injection of 15 and 7.5 mg/kg of globulin, respectively. Hepatitis A virus vaccine recipients showed adequate neutralizing antibody titers, with the groups receiving 1, 0.5 and 0.25 micrograms/dose showing titers of 4(5.5), 4(4.7) and 4(4), respectively, at 18 mo after the third inoculation. These findings suggested that effective blood antibody titers were likely to be retained in the 1.0 micrograms or 0.5 micrograms/dose groups for at least several years. Moreover, the serum antihepatitis A virus titers demonstrated by a modified radioimmunoassay changed in parallel with the neutralizing antibody titers in the volunteers injected with globulin.

Adult↗

PubMed1992

Chemically humanized murine monoclonal antibody against a cell nuclear antigen: usefulness in autoimmune diagnostics.

The cellular nuclear antigen SS-B/La is known to be a major antigenic target to an autoantibody in patients with Sjogren's syndrome and systemic lupus erythematosus. It is useful to detect an anti-SS-B/La antibody from patients' sera in a clinical point of view. We purified SS-B/La from rabbit thymus acetone powder by affinity chromatography with a murine anti-SS-B/La monoclonal antibody (1C3-H7). An enzyme-linked immunosorbent assay method, in which SS-B/La was used to coat a plate, was also successfully established. It is difficult to obtain a large volume of patient's serum with high antibody titer and high specificity as a positive control. We investigated whether or not a positive control from human could be replaced by a murine monoclonal antibody to SS-B/La. The 1C3-H7 was conjugated with a human IgG Fc' fragment using N-gamma-maleimidobutyryloxysuccinimide as a cross-linker. The chemically humanized murine monoclonal antibody (1C3-Fc') was recognized by antiserum specific for human IgG Fc fragment. 1C3-Fc' reacted to SS-B/La but not to other antigens. Furthermore, the titration curve of this conjugate ran parallel with those of patients' sera specific for SS-B/La. It is concluded that a chemically humanized murine monoclonal antibody is useful as a positive control in place of a human patient's serum.

Animals↗

PubMed1992

Surgical treatment for thoracic esophageal carcinoma in patients after gastrectomy.

The clinicopathologic factors in 50 gastrectomized and 831 nongastrectomized patients with thoracic esophageal carcinoma were compared. The differences in various factors were not statistically significant except for the average duration of operation, which suggests that the association of esophageal carcinoma and previous gastrectomy is a chance finding. Thirty-four gastrectomized patients underwent abdominal lymphadenectomy and 16 did not. The postoperative survival curves for the two groups did not differ. In comparing the clinicopathologic factors between the two groups, only the tumor location differed significantly (P < .05). Nine patients (26.5%) with lesions in the mid- or lower thoracic esophagus in the gastrectomized group had positive nodes in the abdomen; the 5-year survival rate was 39.4%. Among them, 8 had gastrectomy for peptic ulcer. Abdominal lymphadenectomy is recommended for those patients with mid- or lower thoracic esophageal carcinoma who have had previous gastrectomy without lymphadenectomy.

Carcinoma, Squamous Cell↗