[A case of pedunculated colonic sm cancer showing unusual form of features of a submucosal tumor].
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Biomedical subjects
Publications and source records attributed to M Komatsu.
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Ascites 13762 rat mammary adenocarcinoma cells express abundantly on their cell surfaces a heterodimeric glycoprotein complex composed of a sialomucin ascites sialoglycoprotein (ASGP)-1 and a transmembrane subunit ASGP-2. The latter, which contains two epidermal growth factor-like domains, binds the receptor tyrosine kinase p185(neu), suggesting that the complex is bifunctional as well as heterodimeric. Immunoblot analyses using monoclonal antibodies prepared against the complex demonstrate high levels of expression in rat lactating mammary gland and colon. Immunolocalization studies with anti-ASGP-2 indicate that ASGP-2 is present in these two tissues in the apical regions of secretory epithelial cells. Both mammary gland and colon contain a soluble, secretable form of ASGP-2, which is not found in the ascites cells; milk and mammary gland also have the membrane form. Immunoblot analyses using a COOH-terminal-specific polyclonal antibody indicate that the soluble form of ASGP-2 is missing its COOH-terminal domains. Both the soluble and membrane forms of ASGP-2 are similar to the membrane-associated form from the 13762 adenocarcinoma with respect to Mr, antigenicity, and association with ASGP-1. The presence of ASGP-1 in milk suggests that it is a candidate for the uncharacterized high Mr milk mucin, MUCX. ASGP-2 expression is up-regulated in mammary gland during pregnancy, because it is undetectable in virgin and early pregnant rats but abundant in the gland from late pregnant and lactating animals. However, compared with the lactating mammary gland, the 13762 ascites cells overexpress ASGP-2 by more than 100-fold, which may contribute to their malignancy. These combined results indicate that sialomucin complex is a unique secreted product in the mammary gland and colon, whose behavior is different from that in the mammary ascites tumors, and which may play important roles in mammary and intestinal physiology.
This is the first systematic study on the pancreatic beta cell function in the heterozygous mouse with targeted disruption of the beta cell glucokinase gene. The heterozygotes' beta cell displayed the following characteristics: (1) impaired glucose sensitivity with normal glucose responsiveness, (2) poor discrimination of alpha and beta glucose anomers, and (3) normal response to glucose in the presence of 25 mM K+ and 150 microM diazoxide. Both the first and the second phases of glucose-stimulated insulin release were depressed. Although the heterozygotes were mildly hyperglycemic, insulin treatment further suppressed beta cell function, implying the beta cell glucose toxicity is not the cause of impaired glucose sensitivity. The data are compatible with the glucokinase glucose sensor concept inasmuch as glucose sensitivity is reduced in the heterozygotes' beta cell. The anomeric malaise and preservation of the ATP-sensitive K+ channel-independent glucose action were considered due to chronic hyperglycemia.
In vivo L-band electron spin resonance (ESR) system was used to measure the decay of nitroxide radicals in the living rat cerebrum containing a cortical area with an iron-induced epileptogenic region. Carbamoyl-PROXYL (3-carbamoyl-2,2,5,5-tetramethyl-1-pyrrolinyloxy) was injected intraperitoneally. The decay of nitroxide radicals in the iron-injected regions at the subacute stage of epileptogenesis was prolonged. The Japanese herbal medicine, sho-saiko-to-go-keishi-ka- shakuyakuto (TJ-960), a compound known to have free radical scavenging activity, inhibited the delay of nitroxide radical decay in the rat cerebrum with an iron-induced epileptic focus following injection of carbamoyl-PROXYL. TJ-960 did not affect the decay of nitroxide radicals in the control rats' brain. These data show that TJ-960 has the scavenging activity for free radicals generated within an iron-induced epileptogenic regions of rat brain.
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Asteroids display four distinct modes of developmental patterns: the indirect mode, the nonbrachiolarian mode, the direct mode, and the mode with a barrel-shaped larva. Among them the former two are planktotrophic, whereas the latter two are lecithotrophic. The direct mode and the mode with a barrel-shaped larva are thought to have evolved from the more primitive planktotrophic mode, the nonbrachiolarian and the indirect mode, respectively. However, whether the nonbrachiolarian mode or the indirect mode is the more primitive in asteroids is unresolved, despite discussion since early this century. A key aspect of this problem is the phylogenetic status of paxillosidans, since the nonbrachiolarian mode and the mode with a barrel-shaped larva are seen only in paxillosidans. To resolve this problem, we performed a molecular phylogenetic study of asteroids, based on the nucleotide sequences of mitochondrial rDNAs. Phylogenetic trees support a close relationship between the Asterinidae and the Solasteridae. We suggest that the paxillosidans are not a monophyletic group; rather, the Luidiidae (one family of Paxillosida) is a sister group to the rest of the asteroids. Although some aspects of our results contradict a recent study by Lafay et al. (1995, Syst. Biol. 44: 190-208) based on 28S rRNA sequences, both studies agree on a paraphyletic nature for the paxillosidans. We conclude that characters shared by paxillosidans are primitive; hence the primitive mode of development in asteroids is the nonbrachiolarian mode.
We report the unusual case of a 77-year-old man with cervical Castleman's disease associated with benign M-proteinemia. The patient was found to have an anterior cervical tumor during a follow-up examination after surgery for early gastric cancer, at which time blood biochemistry tests revealed M-proteinemia at the position of beta-globulin with a high level of IgG and low levels of IgA and IgM. Serum protein immunoelectrophoresis revealed M-protein consisting of the IgG-k chain, and urine protein immuno-electrophoresis demonstrated Bence Jones protein consisting of the chain. No abnormalities were noted in bone marrow aspiration or bone scintigram. The results of imaging and fine-needle aspiration biopsy of the tumor led to a pre-operative diagnosis of cervical malignant lymphoma with suspected M-proteinemia derived from this disease, and resection of the anterior cervical tumor with bilateral neck dissection was performed. Histopathological examination subsequently demonstrated four mixed-type tumors of Castleman's disease. The pathogenesis of Castleman's disease remains unknown; however, we speculate that the complication of benign M-proteinemia in this patient was not incidental, but caused by an underlying immunological abnormality of the B cells.
Leiomyomatosis peritonealis disseminata (LPD) is a rare condition, reported to occur chiefly in premenopausal women. In fact only five cases of LPD in postmenopausal women have been documented in the English literature. We report herein a case of LPD occurring in a postmenopausal woman who had undergone a total hysterectomy 15 years earlier and received no subsequent hormonal therapy. At laparotomy, a cystic mass measuring 10.0 x 12.0 cm was found adhering to the jejunum. There were also innumerable tumor nodules ranging from 0.5 to 5.0 cm in diameter attached to the antimesenteric borders of the intestine and the parietal peritoneum. We resected the cystic main tumor together with 20 cm of jejunum to release the intestinal obstruction. Several daughter tumors were also resected as biopsies for histological examination. Histologically, the lesions were multiple and consisted of proliferating smooth muscle cells with rod-like nuclei showing extremely rare mitotic figures, confirming a diagnosis of LPD.
A 55-year-old woman was treated at our hospital for multiple sclerosis. Therapy consisted of glucocorticosteroids and cyclosporin. In the 7th week after these drugs were discontinued the patient developed acute liver failure due to fulminant hepatitis (FH) and died. Post-mortem examination showed massive liver necrosis. Serologic examination was negative for hepatitis B virus-related markers. Antihepatitis C virus (anti-HCV) antibody and serum HCV RNA were negative on admission, but HCV RNA appeared concurrently with the onset of FH. Although HCV infection rarely causes FH, it was considered to be the cause of FH in this patient, since there were no other causes of acute liver injury. We suspect that underlying immunologic abnormalities in conjunction with HCV infection may have precipitated the FH.
We report a rare case of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and carbohydrate antigen (CA) 19-9-producing gallbladder cancer with high levels of CA125 and protein induced by vitamin K absence or antagonist II (PIVKA II). A 63-year-old man was diagnosed with gallbladder cancer with metastases to the liver, based on ultrasonography and computed tomography of the abdomen showing multiple tumorous lesions in the liver and a thickened gallbladder wall. Laboratory data showed high levels of tumor markers: 4647.4 ng/ml AFP, 9987.1 ng/ml CEA, 11,704.0 U/ml CA19-9, 847.6 U/ml CA125, and 0.2 AU/ ml PIVKA II. AFP in the present case showed an increase in Concanavalin A-nonbinding fraction and an increase in Lens culinaris lectin-binding fraction by affinity column chromatography. The patient died of hepatic failure. Autopsy revealed gallbladder cancer consisting of papillary adenocarcinoma and moderately differentiated tubular adenocarcinoma. By immunohistochemical staining, AFP was detected in the papillary adenocarcinoma portion of the primary focus and metastatic tumor cells in the liver, but was not detected in noncancerous liver tissue. CEA and CA19-9 were detected mainly in the tubular adenocarcinoma portion.
The free radical scavenging activity of the Japanese herbal medicine, Toki-Shakuyaku-San (TJ-23; TSUMURA & Co., Tokyo, Japan), was examined using electron spin resonance (ESR) spectrometry. TJ-23 scavenged 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH), superoxide (O2-), and hydroxyl radicals (.OH) dose-dependently. It also diminished carbon centered radicals (.C) generated by oxidative stress and inhibited thiobarbituric acid-reactive substances (TBARS) formation in mouse cortex homogenate. In addition, the effect of TJ-23 on the concentration of neurotransmitters and TBARS formation, and superoxide dismutase (SOD) activity in the cortex, hippocampus and striatum of the aged rat brain was studied. The concentrations of the metabolites of monoamines, glutamate and glutamine were decreased by 4 weeks of oral administration of TJ-23. The SOD activity of mitochondrial fraction was increased and TBARS formation was significantly suppressed. These results suggest that TJ-23 has an antioxidant action and would have a prophylactic effect against free radical-mediated neurological diseases associated with aging.
Density gradient ultracentrifugation and anion-exchange chromatography combination were effective for the purification of the eel vitellogenin from the plasma of estradiol-treated eels. The vitellogenin was very high density glycolipoprotein (P = 1.27 g/ml) and its apolipoprotein was M(r) 196 k in both reduced and non-reduced conditions by SDS-PAGE. The major lipid component was phospholipid. The N-terminal amino-acid sequence of the vitellogenin was as follows: (Ac)Thr-Pro-Ala-Leu/Ala-Asp-Tyr. Amino-acid composition of the eel vitellogenin was similar to those of other teleosts. The protease activity appeared in the trypsinized vitellogenin, but was not detected in the purified vitellogenin. The protease was separated from the used trypsin and the other cleaved vitellogenin by a dextran sulfate cellulose column. The molecular weight of the protease was determined by zymogram using SDS-polyacrylamide gel containing casein and was 50 k. It was concluded that the eel vitellogenin possesses the protease activity as a latent form.
The antioxidant effect of Fructus Momordicae extract, FME (mogrosides 75 approximately 80%), was studied. FME reduced the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH) and scavenged superoxide radicals (O2-) generated by a hypoxanthine and xanthine oxidase system. It also scavenged hydroxyl radicals (.OH) generated by Fenton reaction. In addition, FME inhibited Fe(II) induced lipid peroxidation in rat cortex homogenates in a dose-dependent manner, as indicated by decreased thiobarbituric acid-reactive substances (TBARS) formation. Oral administration of FME inhibited TBARS and malonaldehyde (MDA) formation in the ipsilateral cortex 30 min after iron-salt injection into the left cortex of rat. FME showed inhibitory effect on 4-hydroxy-2(E)-nonenal (4-HNE) formation induced by Fe(III) injection into the rat cortex. These data suggest that Fructus Momordicae extract has an antioxidant activity against free radicals and lipid peroxidation.
Although hepatitis C virus (HCV) has now been classified into several subtypes, the clinical significance of HCV subtypes is not well known. Typing of HCV is now routinely performed in Japan. In the present study, HCV subtypes in hepatocellular carcinoma (HCC) patients were analysed from nationwide data collected in Japan using a standard questionnaire. Answers to the questionnaire concerning HCV subtypes in patients with chronic hepatitis (CH), liver cirrhosis (LC) and HCC were obtained from 14 hospitals. The prevalence of the 1b-related subtype, which includes the mixed subtype of 1b and 2a or 2b, in patients with LC and HCC in each hospital was higher than in patients with CH, with few exceptions. However, the differences were not statistically significant because of the small number of patients in each hospital. In summarized data from all 14 hospitals, the 1b-related subtype was found in 1370 of 1922 patients with CH (71.2%). In 356 LC and 426 HCC patients, the prevalence of the 1b-related subtype was 79.8 and 80.5%, respectively. The prevalence of the 1b-related subtype in patients with LC and HCC was significantly higher than in patients with CH. There was no significant difference between the prevalence of the 1b-related subtype in patients with HCC and LC. These results indicate that the oncogenic activity of subtype 1b, although not yet clearly characterized, may be stronger than subtypes 2a and 2b.
Interferon (IFN) is now commonly used for the treatment of type C hepatitis; however, its effects differ depending upon the subtype of hepatitis C virus (HCV) being treated. It has been recently confirmed in many studies in Japan that the effectiveness of IFN treatment is poor in patients having type 1b and better in patients having type 2a HCV. However, the effects of IFN treatment on other subtypes of HCV were not clear because of the small number of patients in each hospital. In the present study, the effects of IFN treatment in patients with other HCV subtypes were analysed from nationwide data collected in Japan using a standard questionnaire. From this questionnaire, local differences in the distribution of HCV subtypes in Japan were also analysed. A standard questionnaire, consisting of questions about the number of patients with chronic type C hepatitis with different HCV subtypes and the number of patients showing different responses to IFN treatment, was sent to over 40 study groups in Japan. Answers to the questionnaire concerning HCV subtypes and the effects of IFN treatment were obtained from 26 and 22 hospitals, respectively, throughout Japan. The incidence of HCV type 1b was highest in the Kinki area (south-central Japan). The incidence of type 1b HCV decreased in parallel with distance from this area. The mortality rates of hepatic cancer in different areas were significantly correlated with the incidence of HCV type 1b. The efficacy of IFN treatment was significantly better for both types 2a and 2b HCV than for type 1b HCV; the efficacy of IFN treatment was poor in the mixed type of 1b and 2a and tended to be better in type 1a. The efficacy of IFN treatment for other types of HCV was also better. These results indicate that there are local differences in the distribution of HCV subtypes in Japan and that these differences may be closely associated with the clinical features of HCV-related liver disease. The efficacy of IFN treatment was significantly poorer in patients with the 1b-related type HCV than in patients with other types of HCV.
Gene therapy based on gene-specific nucleic acids has moved from theory to a practical possibility in a very short time. The new DNA and RNA therapeutic reagents are intended to stop the growth of cancerous cells or the production of viruses. At the practical level, the efficacy of antisense oligomers as therapeutic reagents has been carefully examined in various clinical contexts. For the efficient use of antisense nucleic acids as pharmaceutical agents, a complete analysis of their mechanisms of action is necessary. The use of antisense oligomers always involves the following problems: basepair specificity, stereoisomer specificity, stability and resistance to nucleases of sense-antisense duplexes, permeability of the cell membrane and targeting of the oligomer, safety, and the preparation of large amounts of oligomer. Herein, we review the basic concepts and problems associated with the exploitation of antisense technology. We have identified a new transcription factor triple-helix-binding zinc-finger protein-1 (THZif-1) induced by antisense c-myc RNA in the antisense-transformed HL60 cells. The encoded protein functions as the repressor of c-myc to achieve the reduction of the endogenous expression of c-myc gene. Therefore, the introduction of THZif-1 gene into HL60 cells in conjunction with antisense c-myc oligomers may result in the efficient repression of the expression of the c-myc gene. The molecular features of this factor are herein discussed.
Rapid detection and identification method of mycobacteria from specimen with infected mycobacteriosis was established by the combination of polymerase chain reaction and alkaline phosphatase labeled oligonucleotide probe (PCR-ALPDH). We prepaired four kinds of probes: Mycobacterium tuberculosis complex, M. avium, M. intracellulare, and mycobacterial-probe other than tuberculosis. PCR-ALPDH was compared with conventional methods using 234 specimens which suspected mycobacteriosis. In culture, 68 specimens (29.1%) were positive and 166 specimens (70.9%) were negative. In PCR-ALPDH, 88 specimens (37.6%) were positive and 146 specimens (62.4%) were negative. In 68 specimens which were positive in culture, the agreement of results of conventional identification and PCR-ALPDH for each probes were: 39/40 (PCR-ALPDH/Culture, 97.5%) in M. tuberculosis 5/9 (55.6%) in M. avium, 6/6 (100%) in M. intracellulare and 22/28 (88.6%) in MOTT isolation. Among 166 negative culture specimens, 27 specimens were positive in PCR-ALPDH. The results indicated that PCR-ALPDH method was applicable for the establishment of rapid and sensitive mycobacterial diagnostic system.
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