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Biomedical subjects

S Ogata

Publications and source records attributed to S Ogata.

At least 19 recordsLinked to original sources
PubMed1995

Immune sera and monoclonal antibodies define two configurations for the sialyl Tn tumor antigen.

Sialyl Tn (sTn) is a mucin-associated carbohydrate antigen expressed in most types of human adenocarcinoma. Defining the configuration of tumor cell surface sTn recognized by antibodies is important for understanding the basis for the cancer cell specificity of sTn-reactive mAbs, for the development of more effective mAbs, and for designing cancer vaccines against sTn. In this study, we compared the immunogenicity of synthetic single sTn disaccharide epitopes and clusters [sTn(C)] of 3 sTn epitopes covalently linked via serine to keyhole limpet hemocyanin [KLH; sTn-KLH and sTn(C)-KLH, respectively]. The cell surface sTn configurations were analyzed with the use of sera from mice immunized with these neoglycoproteins and a panel of sTn-reactive mAb. Sera from mice immunized with sTn-KLH reacted in direct and inhibition assays with sTn-human serum albumin (HSA) but only weakly with sTn(C)-HSA, whereas sera from mice immunized with sTn(C)-KLH reacted with sTn(C)-HSA but not with sTn-HSA. Both anti-sTn and anti-sTn(C) sera reacted with ovine submaxillary mucin (a natural source of sTn) and with sTn-positive human tumor cell line LS-C but not with sTn-negative LS-B cells. With regard to the sTn-reactive mAbs, B72.3 reacted exclusively with clustered sTn, whereas mAb B195.3R11 reacted preferentially with unclustered sTn. Results with mAbs TKH2, B239.1, and CC49 were less clear, although all reacted more strongly with clustered sTn than with unclustered sTn. These results suggest that sTn is recognized at the tumor cell surface in at least two quite distinct configurations, as clustered and nonclustered arrays.

Animals↗
PubMed1995

Tumor-associated sialylated antigens are constitutively expressed in normal human colonic mucosa.

Immunohistochemical studies have indicated that sialylated carbohydrate antigens such as sialyl-Tn, sialyl-Le(a), and sialyl-Le(x) are expressed in a tumor-associated fashion in human colon. Since sialic acid residues are O-acetylated more extensively in normal colonic epithelium than in colon cancer cells, we examined whether deacetylation of colonic tissues might enable monoclonal antibodies to recognize these tumor-associated sialylated antigens. In normal colon, deacetylation turned most cases (82%) positive with anti-sialyl-Tn mAb TKH2; and in colon cancers, it increased the number of TKH2-positive cells. Sialyl-Le(a) and sialyl-Le(x) detection was also increased after deacetylation of normal and malignant colonic tissues so that the frequency of positive cases in normal tissues was similar to that in the cancers. However, in the stomach and pancreas, the same treatment rarely increased the detection of the sialylated epitopes in normal or cancerous tissues. Thus, the same sialylated epitopes can be expressed in a tumor-associated fashion by different mechanisms in different gastrointestinal organs; in the colon, these antigens are constitutively expressed and O-acetylated, whereas in the upper gastrointestinal tract, they are rarely O-acetylated, suggesting that other mechanisms such as differences in glycosylation account for the cancer-associated expression.

Adenocarcinoma↗
PubMed1995

Changes in surgical strategies for peptic ulcers before and after the introduction of H2-receptor antagonists and endoscopic hemostasis.

A total of 902 surgical patients with peptic ulcer disease were evaluated to clarify the effects of H2-receptor antagonists and endoscopic hemostasis on surgical treatment. Following the introduction of these treatments to our institute in 1982, the number of operations performed annually decreased by 40%, or 36 cases per year. However, a remarkable increase in the frequency of surgical emergency intervention since 1982 was concurrently observed, with the ratio of emergency procedures to the total number of operated cases increasing to 72.5% in the last 5 years of the study. Moreover, intractability as an indication for surgery decreased to 34.1%, compared with an increase in the number of patients with bleeding and perforated ulcers requiring operation. There were 13 postoperative deaths recorded (1.4%). All of the deaths were in patients who had undergone emergency surgery in poor health. Of these 13 patients, 10 had bleeding ulcers. A study of bleeding ulcers for which endoscopic hemostasis had been unsuccessful revealed that shock on admission and a concomitant medical condition had been evident in all the patients who died, and in 52.2% and 30.4% of the survivors, respectively. The current study suggests that the frequency of high-risk patients requiring surgery is increasing since the introduction of H2-receptor antagonists and endoscopic hemostasis, and thus, prompt surgical treatment and intensive management for such patients is essential.

Emergencies↗
PubMed1995

Immunogenicity of synthetic TF-KLH (keyhole limpet hemocyanin) and sTn-KLH conjugates in colorectal carcinoma patients.

Mucins of colorectal carcinomas overexpress the cancer-associated disaccharides Thomsen-Friedenreich antigen (TF) and sialyl-Tn antigen (sTn), making these antigens suitable for active specific immunotherapy. Patients at high risk for recurrent colon cancer, but free from disease after surgical resection, were immunized with synthetic TF and sTn covalently attached by a two-carbon crotyl linker to keyhole limpet hemocyanin (KLH). Four groups of patients were treated with TF-KLH without adjuvant, TF-KLH plus the immunological adjuvant Detox, sTn-KLH plus Detox, or sTn-KLH plus the immunological adjuvant QS-21, and the serological response was monitored. Enzyme-linked immunosorbent assay (ELISA), dot-blot immunostains, and inhibition assays were used to identify antibody responses against synthetic TF and sTn epitopes and against natural antigens, including asialoglycophorin expressing TF antigen, and ovine submaxillary mucin and the human colon cancer line LS-C expressing sTn antigen. Our results demonstrate that vaccines containing TF or sTn-KLH conjugates plus immunological adjuvants Detox and especially QS-21 induced high IgM and IgG antibody titers against the respective synthetic disaccharide epitopes. However, when tested against natural antigens expressing these disaccharide epitopes, IgM antibodies showed weak to moderate reactivity, while IgG antibodies were almost totally unreactive. On the basis of these results we are continuing to test modifications of synthetic TF and sTn epitopes to identify those that induce IgM and IgG antibodies that are more reactive with these antigens as they are expressed on tumor mucins.

Antibodies, Neoplasm↗
PubMed1995

Newly synthesized histamine accelerates ornithine decarboxylase activity in rat intestinal mucosa after ischemia-reperfusion.

We previously demonstrated that both histamine synthesis (histidine decarboxylase activity) and polyamine synthesis (ornithine decarboxylase activity) increased in the rat intestinal mucosa after ischemia-reperfusion, whereas the relationship between these two factors remains unclear. To elucidate this relationship, we performed the present study. The superior mesenteric artery was occluded for 15 min followed by reperfusion. After ischemia-reperfusion, histidine decarboxylase activity and ornithine decarboxylase activity in the rat jejunal mucosa were measured in a time-dependent manner. Histidine decarboxylase activity increased 1 hr after ischemia-reperfusion, although ornithine decarboxylase activity did not; however, its activity did increase 6 hr after. The increase of ornithine decarboxylase activity was attenuated when the increase of histamine synthesis was suppressed by the inhibition of histidine decarboxylase activity caused by pretreatment with alpha-fluoromethylhistidine, a suicide inhibitor of histidine decarboxylase. Pretreatment with H1-receptor antagonist attenuated the increase of ornithine decarboxylase activity after ischemia-reperfusion. These results indicate that the newly synthesized histamine, as indicated by an increase of histidine decarboxylase activity, increases ornithine decarboxylase activity after ischemia-reperfusion of the rat intestinal mucosa.

Animals↗
PubMed1995

Human urinary kallikrein can generate angiotensin II from homologous renin substrates.

We previously proposed the "kinin-tensin system," a unique vasoregulatory system that can produce both angiotensin II and kinins. To verify whether tissue kallikrein is a part of this system in humans, we examined the ability of human urinary kallikrein (HUK) to generate angiotensin (ANG) II directly from homologous renin substrates such as purified human angiotensinogen (AOGEN) and authentic human tridecapeptide renin substrate (13 RS). HUK released ANG II not only from ANG I but also directly from both AOGEN and 13RS at an optimum pH of 7.0. The amount of generated ANG II from 7.5 nmol of each of the three substrates at pH 7.0 was as follows: ANG I, 292.7 +/- 67.2; 13 RS, 1951.7 +/- 239.6; AOGEN, 2.2 +/- 0.3 (pmol/3h, n = 3 mean +/- SE). HUK cleaved Phe-His and His-Leu bonds in 13 RS, and Tyr-Ile and Phe-His bonds in ANG I. These results suggest that HUK is a part of the "kinintensin system", i.e., HUK can not only release kinins, but can also generate ANG II mainly through ANG I conversion and from AOGEN, the latter being a minor source of ANG II. Furthermore, HUK may play a role in regulating vascular tone under certain conditions in vivo.

Angiotensin I↗
PubMed1995

Human EEG responses to classical music and simulated white noise: effects of a musical loudness component on consciousness.

The main purpose of the present study was to investigate the psychophysiological effects of music on human EEG. For this purpose, a sound modulator was developed which simulates the sound-pressure variations of a given piece of music by white noise (sim-music). Using this apparatus, the author tested the psychophysiological effects of music on human EEG. The electroencephalograms (EEG), electrocardiograms (ECG), and electrooculograms (EOG) of eight normal volunteers were recorded for a total of 21 min., 5 sec. per session for each subject under three sound conditions: silence for 5 min., two types of music (music) or two types of simulated noise (sim-music) for 11 min., 5 sec., followed by silence for another 5 min. Each subject was exposed to a total of 10 music and 10 sim-music conditions. At the low consciousness level (drowsiness, Stage S1), higher delta component power densities were observed with sim-music than with music. Thus, even in the same Stage S1, entire physiological consciousness levels may be higher when listening to music than to sim-music. While listening to music, many subjects reported that they felt pleasantly relaxed or comfortable. However, with the sim-music, they reported feeling unpleasantly weary and sleepy. It seems that the mental set toward two sound conditions differed greatly for many subjects. In Stage S1, the differences in EEG slow components showed that the differences in consciousness had a physiological aspect and indicated differences in mental set toward both sound conditions and mental activity during the listening conditions.

Adult↗
PubMed1995

Clinical abnormalities in adults with pancreaticobiliary maljunction with and without bile-duct dilatation.

OBJECTIVE: To study clinical diseases associated with pancreaticobiliary maljunction with or without bile-duct dilatation. DESIGN: A retrospective study over 16 years. SETTING: A single university surgical service in Japan. PATIENTS: Thirty-three patients with pancreaticobiliary maljunction. MAIN OUTCOME MEASURES: Gallstones and cancer in patients with and without bile-duct dilatation. RESULTS: Twenty-five patients had dilatation of the bile duct, 8 did not. Seven (28%) of the 25 patients with bile-duct dilatation had gallstones compared with 1 (12%) of the 8 patients with no dilatation. Seven (88%) of the 8 patients with no dilatation had carcinoma (all of the gallbladder), but only 3 (12%) of the 25 patients with bile-duct dilatation had carcinoma (1 of the gallbladder, 2 of the bile duct). CONCLUSION: Prophylactic cholecystectomy is recommended for patients with pancreaticobiliary maljunction and no dilatation of the bile duct because of the high incidence of gallbladder cancer.

Adolescent↗
PubMed1994

Structure of the glycosylphosphatidylinositol membrane anchor of human placental alkaline phosphatase.

The glycosylphosphatidylinositol membrane anchor of human placental alkaline phosphatase was isolated by exhaustive proteolysis followed by hydrophobic interaction chromatography. The resulting glycosylphosphatidylinositol-peptide was subjected to compositional analysis and chemical and enzymic modifications. The neutral-glycan fraction, prepared by dephosphorylation followed by HNO2 deamination and reduction, was sequenced using exoglycosidases and acetolysis. The phosphatidylinositol moiety was analysed by fast-atom bombardment mass spectrometry and gas chromatography-mass spectrometry. Taken together the data suggest the structure, Thr-Asp-ethanolamine-PO4-Man alpha 1-2Man alpha 1-6Man alpha 1-4GlcN-(sn-1-O- alkyl-2-O-acylglycerol-3-PO4-1-myo-D-inositol), which contains an additional ethanolamine phosphate group at an unknown position.

Alkaline Phosphatase↗
PubMed1994

Lysosomal targeting of Limp II membrane glycoprotein requires a novel Leu-Ile motif at a particular position in its cytoplasmic tail.

A class of integral membrane glycoproteins specific to lysosomes has been identified, and they are classified into two separate groups depending on whether or not their cytoplasmic sequence contains a tyrosine residue. Lamp-1 and lamp-2 have a tyrosine-containing motif in their cytoplasmic segments, and this motif was found to direct the glycoproteins to lysosomes. Limp II glycoprotein, on the other hand, lacks a tyrosine in its cytoplasmic segment and it must be directed to lysosomes by a different signal (Fukuda, M. (1991) J. Biol. Chem. 266, 21327-21330). In order to elucidate the targeting signal of Limp II, a cDNA encoding its cytoplasmic segment was fused with a reporter molecule, a chimeric protein of human gonadotropin alpha chain-vesicular stomatitis G-protein transmembrane. After various mutations its expression was examined by immunofluorescence. First it was shown that a chimeric protein with a Limp II wild-type tail is transported to lysosomes. Deletion of the three amino acids of the cytoplasmic tail at the carboxyl terminus abolished this sorting to lysosomes. Substitution of individual amino acids revealed that the Leu-Ile motif in the Leu-Ile-Arg-Thr sequence at the carboxyl terminus is crucial to the sorting signal. When this motif was brought closer to the transmembrane domain by deletion of nine amino acids next to the transmembrane domain, this sorting function was abolished. In addition, substitution of alanine for the serine, which is at 5 residues from the transmembrane also abolished the sorting capacity, although there was no evidence that the phosphorylation of serine is involved in sorting. Altered proteins that were not transported to lysosomes were found to accumulate at the cell surface and, unlike proteins with a wild-type cytoplasmic tail, were unable to undergo endocytosis. These results indicate that the carboxyl-terminal amino acid sequence, including the Leu-Ile motif and the sequence that connects the motif to the transmembrane domain, is critical for the sorting of Limp II to lysosomes.

Amino Acid Sequence↗
PubMed1994

Isolation of thermosensitive mutants of Yersinia enterocolitica by transposon insertion.

During bacterial infection, pathogens are exposed to a variety of stimuli, e.g., sudden temperature increase on entering mammalian host or oxidative stress associated with exposure to phagocytes. Yersinia enterocolitica, which is a facultative intracellular bacteria, responds to macrophage phagocytosis by the production of a set of stress proteins; which are also induced by heat shock (Yamamoto et al., 1994, Microbiol. Immunol. 38, 295-300). To examine the role of bacterial stress proteins in the adaptation to environmental changes encountered during infectious processes, we have isolated stress-sensitive mutants from Y. enterocolitica in which mini-Tn10 transposon insertions allow bacterial growth at 28 degrees C but prevent growth at an elevated temperature, 39 degrees C. Eight independent insertions were obtained and preliminarily characterized by Southern blot hybridization and morphological analysis.

Bacterial Proteins↗
PubMed1994

Impalement injury of the thorax: report of a case.

We report herein the case of a 33-year-old man who survived an impalement injury of the thorax involving the heart, esophagus, and spinal cord. The patient was transported to our hospital with the impalement object left in situ and it was extracted under cardiopulmonary bypass in an operating room. The important principles of surgical management contributing to the successful outcome of such patients are discussed following the presentation of this case.

Adult↗
PubMed1994

Extended central bisegmentectomy--an en bloc resection of hepatic segments 4, 5, 8 and 7: report of a case.

We herein present an example of an extended central bisegmentectomy in a patient with a large hepatocellular carcinoma. According to a magnetic resonance imaging study, the right hepatic vein was displaced and narrowed at its origin and a large inferior right hepatic vein was revealed. In this case, owing to the only slightly functional remaining hepatic reserve, an extended central bisegmentectomy was selected as the optimum treatment. The postoperative course was uneventful except for some bile leakage. Twelve months after operation, the patient is still alive and no sign of recurrence has been detected. The extended central bisegmentectomy is an en bloc resection of hepatic segments 4, 5, 7, and 8. When the large inferior right hepatic vein is present, segment 6 can be preserved even when the right hepatic vein is sacrificed at its origin.

Carcinoma, Hepatocellular↗
PubMed1994

Induction of Yersinia enterocolitica stress proteins by phagocytosis with macrophage.

Yersinia enterocolitica is a facultative intracellular pathogen which invades to epithelial cells and survives in phagocytes. Since the internal environment of phagocytes should be stressful conditions for the phagocytosed Yersinia, the bacteria should respond to protect themselves from otherwise lethal results. We analyzed the stress-induced proteins which possibly contribute to survival of Yersinia within the phagocytes. Y. enterocolitica was radiolabeled during the growth in macrophage-like J774-1 cells, and the bacterial proteins were analyzed by two-dimensional gel electrophoresis. At least 16 proteins were selectively induced in response to phagocytosis, and several out of 16 proteins were also induced by heat shock at 42 C or oxidative stresses in vitro. Of those, two major stress proteins were identified to be homologues of DnaK and CRPA by immunoblotting analysis. These results have indicated that Y. enterocolitica exhibits a global stress response to the hostile environment in the phagocytosed macrophage.

Animals↗
PubMed1994

Detection and characterization of antibodies to bacterial heat-shock protein 60 in sera of patients with primary biliary cirrhosis.

The enzyme-linked immunosorbent assay (ELISA) with bacterial heat-shock protein 60 (HSP60) purified from Yersinia enterocolitica (Ye) revealed that the antibodies directed against YeHSP60 existed in sera of patients with primary biliary cirrhosis (PBC). To characterize the epitope specificity of the antibodies in patients, the epitope mapping of HSP60 by means of the antibodies was performed. The results have suggested that the epitope recognized with anti-HSP60 antibodies in PBC relates to the amino acid sequence of YeHSP60 molecule as follows: DLGQAKRVVINKDTTIIIDGVGDEAAIQGRLAQIRQQIEEATSDYDKEK.

Amino Acid Sequence↗
PubMed1993

Sporulation-inhibitory gene in pock-forming plasmid pSA1.1 of Streptomyces azureus.

A plasmid, pSA1.1, of Streptomyces azureus elicited conjugative pocks and inhibited the sporulation of its host mycelia. pSA1.1 was studied with a kanamycin resistance gene derived from S. kanamyceticus as a selective marker. The deletion analysis and sequencing of the derivative plasmid found an open reading frame (ORF909b) that was involved in the sporulation-inhibitory function of pSA1.1 and in pock formation. The nucleotide sequences of ORF909b were compared with those of the genes registered in GenBank, but no similarity was found. However, the predicted amino acid sequence of ORF909b showed a significantly high similarity with that of the spoIIIE gene of Bacillus subtilis. This detected gene might be a new sporulation-regulatory gene in streptomycetes.

Amino Acid Sequence↗