Endoscopic aspiration mucosectomy as curative endoscopic surgery; analysis of 24 cases of early gastric cancer.
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Biomedical subjects
Publications and source records attributed to M Okuma.
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To clarify the mechanism of in vivo proliferation of adult T cell leukemia (ATL) cells, we examined the organ distribution of ATL-43T cell line cells derived from original leukemic cells in severe combined immunodeficiency (SCID) mice using radiometric techniques. First, we injected 111In-oxine-labeled ATL-43T cells into SCID and CB17 mice. On day 6, significant accumulation of radioactivity was found in the spleen and thymus of SCID mice (33.3 +/- 9.4 and 10.0 +/- 3.6% injected dose/g of tissue [%ID/g], respectively) in comparison with that in CB17 mice (19.1 +/- 2.5 and 3.7 +/- 0.9%ID/g, respectively). Next, we injected radiolabeled anti-Tac monoclonal antibody (MoAb) recognizing human interleukin-2 receptor (IL-2R) alpha chain or isotype-matched control MoAb RPC5 in SCID mice bearing ATL-43T cells 4 weeks after cell inoculation. The amounts of radioactivity found in the spleen and thymus of SCID mice injected with 125I-labeled anti-Tac MoAb (22.5 +/- 6.9 and 22.8 +/- 9.6 %ID/g, respectively) were significantly higher than those in the corresponding organs of SCID mice injected with 125I-labeled RPC5 MoAb (12.0 +/- 5.1 and 7.5 +/- 4.6 %ID/g, respectively). Similar results were obtained with 111In-labeled anti-Tac MoAb. These results were consistent with the histological findings of SCID mice bearing ATL-43T cells, indicating that ATL-43T cells infiltrated preferentially into the lymphoid organs, such as the spleen and thymus, and proliferated there. Thus, the radiometric techniques employed in this study were very useful to evaluate the proliferation sites of ATL-43T cells in SCID mice. Furthermore, this murine model could give us an opportunity to test the feasibility of therapeutic application of radiolabeled anti-Tac MoAb.
Patients with idiopathic acquired sideroblastic anaemia (IASA) usually show macrocytic or normocytic anaemia and increased free erythrocyte protoporphyrin (FEP). The mean cell haemoglobin concentration is normal or slightly low. Here we report a pyridoxine-responsive IASA patient with microcytic and hypochromic anaemia and low FEL level; these features are usually seen in cases of hereditary sideroblastic anaemia. Microcytosis increased during therapy. There may be a subgroup of IASA with microcytic and hypochromic anaemia, low normal FEP and some response to pyridoxine like hereditary sideroblastic anaemia.
PURPOSE: To evaluate a magnetic resonance (MR) imaging technique for measurement of azygos blood flow volume, which is an important indicator of superior collateral circulation in patients with portal hypertension. MATERIALS AND METHODS: Azygos blood flow was measured by means of direct bolus (DB) imaging, an MR flow measurement technique. A presaturation pulse was applied in combination with electrocardiographic gating. RESULTS: The measured flow volume was 320 mL/min +/- 30 (mean +/- standard error of mean) in the control subjects, 550 mL/min +/- 130 in patients with cirrhosis of the liver and without varices, and 660 mL/min +/- 60 in patients with cirrhosis of the liver and with varices. The flow volume was significantly higher in each of the groups with cirrhosis of the liver than in the control group (P < .01). Furthermore, a significant correlation was shown between DB imaging and continuous thermodilution measurements (r = .707, P < .01). CONCLUSION: DB imaging, which is noninvasive, was useful in the monitoring of the effect of treatment and in determination of the prognosis in patients with portal hypertension.
The release of goblet cell mucus (GCM) was examined in immune reaction-system of colonic mucosa of rats (SD rats). We previously reported that in the immune reaction of normal colon of rats, the discharge of colonic GCM was not increased by intrarectal instillation (challenge) of several test-antigens after repeated immunization of single BSA antigen through rectal mucosa, and there was difference in local antigen-antibody reaction on the surface of normal mucosa between small intestine and colon. In the present study we investigated the release of colonic GCM in local antigen-antibody system in rats of damaged colon mucosa, who had repeated immunization of BSA after damage induction by intracolonic infusion of formalin. Consequently, the discharge of colonic GCM increased associated with local antigen-antibody reaction in animals after damage induction by formalin. It is suggested that when the mucosal barrier is disrupted, enhanced release of colonic GCM is occurred by the local immune reaction on the surface of colonic mucosa.
A clinical study to investigate the efficacy and safety of recombinant human G-CSF (rG.CSF) was performed in patients with acute myelogenous leukemia who had had protracted neutropenia. The drug was administered d.i.v. at a dose of 5 micrograms/kg. Sixty-four patients entered the study, of whom 61 patients were evaluable for safety and 58 patients evaluable for efficacy. The treatment produced an early recovery in neutrophil count in the patients who had had protracted neutropenia (< 1,000/microliters) of over 10 days. Among relapsed cases and cases showing > 20% blasts in the bone marrow, many showed blast stimulation in response to rG.CSF, suggesting difficulty in attaining complete remission by subsequent chemotherapy in such cases. The present data indicates that it is desirable to use the drug in lower-blast-count states in order to attain safe and sufficient therapeutic effects in patients with acute myelogenous leukemia who have had protracted neutropenia.
A randomized treated/non-treated study of rG.CSF (5 micrograms/kg/d, d.i.v.) in patients with acute myelogenous leukemia was conducted to assess its efficacy on fever (> or = 38 degrees C) or documented infection after induction therapy. Of 95 patients enrolled, 46 patients were evaluable for safety and 43 for efficacy in the treated group of 47 patients while 37 of 48 patients were eligible for data analysis in the untreated group. Mare patients showed a recovery in the blood neutrophil count (to > 1,000/microliters) during rG.CSF treatment (14 days) than in the non-treated group (p = 0.039) while the number of febrile patients and duration of fever did not significantly differ between the two groups. The treatment with rG.CSF enabled an early recovery in neutrophil count in the patients with neutropenia and overt signs of infection after induction therapy, but there was no hastened allevistion of symptoms of infection in these patients.
A multicenter, randomized, double-blind controlled study was performed to evaluate the efficacy and safety of recombinant human granulocyte colony-stimulating factor (rG.CSF) in reducing infectious morbidity and neutropenia induced by consolidation chemotherapy for acute myeloid leukemia (AML). One hundred and twenty-four eligible patients were randomized to receive either rG.CSF (5 micrograms/kg/d d.i.v.; 59 patients) or placebo (65 patients) for 14 days from the day after chemotherapy. All of them were included in the safety analysis, while 57 patients receiving rG.CSF and 64 patients receiving placebo were included in the efficacy analysis. The duration of neutropenia as well as the incidence of fever and febrile neutropenia, and frequency of antibiotic therapy required, were all significantly reduced in the rG.CSF group. No serious adverse reactions were encountered; there was no significant difference between the two groups in terms of incidence of adverse events. These results demonstrate that rG.CSF is beneficial to alleviate neutropenic episodes induced by consolidation chemotherapy in patients with AML.
Previously, we reported the establishment of a human lymphoma cell line, FL-318, carrying a t(14;18)(q32;q21) chromosomal translocation. FL-318 cells had mu-heavy chain on the cell surface, while they expressed 'sterile' germ-line gamma transcripts, suggesting that the chromatin structure of the immunoglobulin heavy chain (IGH) locus was 'accessible' to class switch recombination. After several months of in vitro cell culture, we found a small population of FL-318 cells expressing the gamma-chain. Using a limiting dilution method, a mu-producing cell clone FL-318M, and gamma-producing FL-318G were isolated. Hybridization studies with various DNA probes from the IGH locus as well as the BCL2 gene demonstrated that the mu-constant gene was deleted on the functional IGH allele of FL-318G cells, and that the cells produced abundant productive gamma-chain messages. These studies indicated that FL-318 cells underwent spontaneous class switching during in vitro cell culture, unrelated to T cell interaction or antigenic stimulation.
Autoimmune gastritis (AIG) develops spontaneously in BALB/c mice thymectomized 3 days after birth (3d-Tx). We first confirmed our previous observations that CD4+ splenic T cells in AIG mice induced AIG in nu/nu mice, while those in normal mice suppressed the development of the disease. In addition, we found that a quantitative balance between these effector (Te) and suppressor (Ts) T cells determined either onset or prevention of the disease. Peripheralization of Ts seemed to begin around 3 days after birth, since the incidence of AIG in mice that underwent Tx 6 days after birth (6d-Tx) decreased markedly, compared with that of 3d-Tx mice; 12% in the former, while 79% in the latter. Notably, Ts existed in the 6d-Tx mice that escaped AIG. We next examined the target specificity of such Ts using syngeneic parietal cells known as autoantigens and two kinds of T-cell lines established from an AIG mouse; one is gastritis inducible in vivo, termed A-II, while another is not, named AC-II. Intrathymic injection of parietal cells into mice 3 days after birth followed by 6d-Tx completely prevented the development of AIG. In contrast, injection of irradiated A-II, but not AC-II cells resulted in AIG in 67% of the mice. No autoimmune oophoritis (AIO) was induced in female mice, implying that the breakdown of tolerance is organ specific. Taken together, peripheral tolerance for organ-specific autoantigens seems to be maintained by CD4+ Ts responding to Te, which induces the disease.
A 25 year-old woman diagnosed as acute myelocytic leukemia (M0) suffered a fourth relapse in February 1992 at which time she already had anthracycline-induced cardiac dysfunction. Although remission was induced by low dose cytosine arabinoside and etoposide combined with pirarubicin, she developed acute heart failure followed by extreme elevation of transaminases level and DIC. Abdominal echography and CT revealed small round lesions in the liver. We diagnosed this episode as ischemic hepatitis because of the following clinical findings; serological markers of virus hepatitis were negative, hypotension and reduced blood flow to the liver were seen, and both transaminases and LDH were markedly elevated. Dobutamin and oxygen inhalation were started, her liver function returned to almost normal levels 8 days later.
We investigated the central effects of neuropeptide Y (NPY) on stress-induced gastric ulcers in water immersion rats. Intracisternally administered NPY dose-dependently aggravated, but intravenously administered NPY did not affect stress ulcers in rats. Intraperitoneal pre-treatment of atropine completely blocked the central effect of NPY, but neither pyrilamine nor cimetidine affected. Intracisternal administration of NPY aggravated stress ulcers not through histamine mediated mechanism but by parasympathetic pathway. It is suggested that centrally administered NPY acted by the inhibition on gastric motility and by the suppression on gastric mucosal blood flow rather than by the stimulation on gastric secretion in rats.
Rat colonic mucosa contains ETA and ETB receptors with Kd values for endothelin (ET)-1 of 32 and 11 pM and maximal binding capacities of 277 and 181 fmol/mg protein, respectively. In muscle-stripped rat colon without tonic nerve activity in Ussing chambers, the serosal addition of ET-1, ET-3 and IRL1620 inhibited amiloride-sensitive noncoupled Na+ entry and enhanced diphenylamine-2-carboxylate-sensitive Cl- secretion, producing a sustained decrease and a transient increase in the short-circuit current (Isc) and the transepithelial conductance, respectively. EC50 values of ET-1, ET-3 and IRL1620 and the maximal changes in Isc were 2.0, 10.2 and 10.9 nM and -12.7, -7.0 and -7.1 muA/cm2, respectively for the Na+ entry; these values were 50, 220 and 225 nM and +57.3, +47.3 and +21.3 muA/cm2, respectively, for the Cl- secretion. FR139317 (100 nM) inhibited ET-1-induced Na+ and Cl- movements, shifting the concentration-response curves to the right (EC50 = 25 nM and 1 microM, respectively), and inhibited ET-3 (> 100 nM)-induced Cl- movement, decreasing the maximal response to 35%, but it did not inhibit either ET-3-induced Na+ movement nor IRL1620-induced Na+ and Cl- movements. The removal of serosal Ca++ reduced 100 nM ET-1- and IRL1620-evoked changes in Isc by 50% and 70% for the Na+ entry and by 80% and 100% for the Cl- secretion, respectively. Indomethacin (1 microM) also reduced changes in Isc by 30% and 70% for the Cl- secretion but did not affect the Na+ entry. Our results show that ETA and ETB receptors regulate Na+ and Cl- transport by different mechanisms.
OBJECTIVES: There is still much debate about the indications and best technique for endoscopy for the treatment of esophageal leiomyomas. We developed a novel technique for endoscopic aspiration lumpectomy and used it in patients with esophageal leiomyomas derived from the muscularis mucosae. METHODS: Nine patients with esophageal leiomyomas were treated with informed consent. The indication for intervention was based on the endosonographic confirmation of a tumor originating from the 2nd layer of the esophagus. We attached a transparent cylinder to the tip of an endoscope and a snare-guide tube to the outer axis of the scope. After endoscopic suction of the tumor into the cylinder, the snare was pushed open. The tumor was grabbed at its base with the entire surrounding mucosa, and removed. RESULTS: The overall procedure time averaged 18 minutes, and there were no complications in any of the subjects. The resected specimens were elliptical with a mean long diameter of 22 +/- 4 mm and a mean short diameter of 17 +/- 4 mm. Complete resection was possible in eight of the nine tumors that were under 2 cm in diameter. After a follow-up period of 4 to 27 months (mean 11 months), no recurrence was found in any of the completely resected cases. CONCLUSIONS: Endoscopic aspiration lumpectomy has been proven to be a safe, effective, and less invasive procedure for small esophageal leiomyomas derived from the muscularis mucosae.
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