Metastatic Tumors of the Stomach Detected by Endoscopy

Thirteen patients with gastric metastasis were examined endoscopicallyand their diseases were diagnosed histologically at the NationalCancer Center Hospital from 1962 to 1980. Their endoscopic findings were analyzed. The metastatic lesionwas solitary in 10 of the 13 cases and multiple (9 lesions)in three. Although 12 of the 13 cases showed elevated lesionsendoscopically, ulcerated hemispherical nodules, which correspondto the "bull's-eye sign" of Pomerantz roentgeno-graphically,were observed in only four cases. In the remaining nine casesthe endoscopic findings were submucosal tumor without centraldepression (2 cases), a cancer-like appearance (6 cases) orextragastric compression (1 case). The majority of these metastatic lesions (9 of the 19; 47.3%)were located along the greater curvature of the stomach. Fromthese results, the elevated lesion of the greater curvaturemight suggest a metastatic tumor regardless of the conventionalcriteria (multiplicity or ulcerated hemispherical nodule) whenthe patient has cancer in other organs.     

Nonulcerative Lesion Detected by Endoscopy as an Early Expression of Gastric Malignancy: --Retrospective Observation of 72 Cases of Gastric Carcinoma--

To evaluate the endoscopic criteria for early malignant findingsof gastric carcinoma more precisely, a retrospective examinationof endoscopic pictures of 72 patients with gastric carcinomawas carried out. The patients had received endoscopic examinationsrepeatedly for years and proceeded finally to surgery on thebasis of a diagnosis of carcinoma by gastric biopsy. The macroscopicas well as microscopic findings of the resected specimens werecompared with the previous endoscopic observations. Ulcerative lesions were predominantly found at the initial endoscopyin patients whose final diagnosis was the lie type of earlygastric cancer or IIc-like advanced cancer. These patients usuallyreceived endoscopic examinations repeatedly and their lesionswere diagnosed as malignant by the adopted criteria of earlygastric cancer 2 to 6 yr after the initial examination. In contrast, nonulcerative lesions were observed more frequentlyat the initial examination in patients with the final diagnosisof the IIa+IIc type of early gastric cancer or Borrmann typeof advanced cancer. In most of those patients endoscopic examinationwas not carried out so frequently, and in some of those whohad been closely followed the malignant findings appeared rathersuddenly with tumorous formation as well as deeper invasionduring less than a few years from the previous examination atwhich the tumor had been considered benign. These data indicate that the nonulcerative lesions which wereconsidered benign could be the early expression of gastric carcinoma.It should be stressed that nonulcerative lesions such as "irregularerythematous change, discoloration, flat granular change" and"simple mucosal depression" observed in some parts of the stomachwould be important site for the detection of early gastric carcinoma,and that these lesions need to be biopsied more frequently.     

Effects of glycyrrhizin on immune-mediated cytotoxicity

Intravenous administration of glycyrrhizin is known to decrease elevated plasma transaminase levels in patients with chronic viral hepatitis, in which immune-mediated cytotoxicity by cytotoxic T lymphocytes and tumour necrosis factor (TNF)-α is considered to play an important pathogenic role. However, the immunological interpretation of the transaminase-lowering action of glycyrrhizin is not known. Studies were performed to elucidate this action immunologically by assessing the effects of glycyrrhizin on immune-mediated cytotoxicity using an antigen-specific murine CD4⁺ T hybridoma line, which exhibits cytotoxicity against antigen-presenting cells after stimulation with specific antigen, and a murine TNF-α-sensitive fibroblast line. Glycyrrhizin inhibited the cytotoxic activity of the T cells against antigen-presenting cells and also suppressed TNF-α-induced cytotoxicity in the TNF-α-sensitive cell line in vitro. These results suggest that the decrease of elevated transaminase levels by glycyrrhizin in patients with chronic viral hepatitis is mediated in part by inhibition of immune-mediated cytotoxicity against hepatocytes.     

Treatment of Mouse Preimplantation Embryos with Adriamycin, Methyl Methanesulfonate and Retinoic Acid Results in Congenital Defects

ABSTRACT Treatment of mouse preimplantation embryos with adriamycin (ADM), methyl methanesulfonate (MMS) and all -trans retinoic acid (RA) on their later development including implantation, growth and organogenesis were investigated. ICR mice were treated intraperitoneally with ADM or MMS on day 3 of gestation, or with RA on day 4 of gestation. The uterine contents were examined on day 18 of gestation. The viable fetuses were inspected for external and skeletal malformations. Irrespective of the kind of chemical agents tested, frequencies of total malformed fetuses were significantly increased, whereas the frequencies were considerably lower than those of malformations in fetuses of dams treated with ADM, MMS or RA during the period of organogenesis. In the fetuses of ADM-treated mice, the most common abnormality was umbilical hernia, followed by cleft palate. In the MMS-treated fetuses, the most common abnormality was cleft palate. Among the malformations observed in this study, duplication of hindlimb (5/193 fetuses) induced by the treatment with RA at the preimplantation stage was a quite unique abnormality. This type of malformation has never before been found in our historical control embryos and in embryos treated with various kind of teratogens. Based on these results and other data, it is concluded that embryos at the preimplantation stage are susceptible to environmental chemical-induced congenital malformations.     

Oral Tolerance Induced by Enterobacteria Altered the Process of Lymphocyte Recruitment to Intestinal Microvessels: Roles of Endothelial Cell Adhesion Molecules,TGF‐beta and Negative Regulators of TLR Signaling

Objective: Although enterobacteria are implicated in intestinal immune response, there has been no report on how intraluminal pathogens affect lymphocyte recruitment. The aim of this study was to determine how the presence of intestinal flora affects lymphocyte migration to intestine under physiological and lipopolysaccharide (LPS)‐induced inflammatory conditions. Methods: Interaction of T‐cells with ileal microvessels was monitored by using an intravital microscope in mice under germ‐free (GF) and specific pathogen‐free (SPF) conditions. LPS was administered into either the peritoneal cavity or duodenum before lymphocyte injection. Results: Adherence of T‐cells was greater in SPF than in GF mice, indicating that the presence of enterobacteria upregulated migration under physiological conditions. Intraperitoneally administered LPS significantly increased the adherence of T‐cells in both GF and SPF mice accompanied by the expression of adhesion molecules and proinflammatory cytokines. However, intraluminally administered LPS did not enhance the adherence of T‐cells in SPF mice. A significant induction of increase in mRNA expression of IRAK‐M, a negative regulator of TLR4 signaling, and transforming growth factor beta (TGF‐beta), a regulatory cytokine, was observed in SPF mice after luminal LPS treatment. Conclusions: Tolerance to intraluminally administered LPS in the lymphocyte recruitment process was induced by enterobacteria, possibly via the induction of IRAK‐M and TGF‐beta.     

The Synergistic Purgative Action of Aloe-emodin Anthrone and Rhein Anthrone in Mice: Synergism in Large Intestinal Propulsion and Water Secretion

This study aimed to explore the mechanism involved in the synergistic purgative action of aloe-emodin anthrone and rhein anthrone, the active metabolites of sennoside C. Aloe-emodin anthrone and rhein anthrone, and their equimolar mixture, induced excretion of an approximately equal number of faeces by intracaecal administration at a dose of 23.2 μmol kg^?1 in mice (= 10 standard dose). The number of wet faeces induced by aloe-emodin anthrone was less than those of rhein anthrone and the mixture. At the same dose, rhein anthrone and the mixture significantly stimulated large intestinal propulsion, though aloe-emodin anthrone had little stimulatory effect. Aloe-emodin anthrone and rhein anthrone decreased net water absorption but could not reverse it to the net secretion at 1/2 dose. The mixture significantly decreased net water absorption and reversed it to the net secretion at this dose. These anthrones did not stimulate mucus secretion in the colon at 1/2 dose. We concluded that the synergistic purgative effect of aloe-emodin anthrone and rhein anthrone in mice results from synergistic stimulation of large intestinal transit and large intestinal water secretion.     

Sexual function and clinical features of patients with Klinefelter's syndrome with the chief complaint of male infertility

In this report, we present the overall sexual function and clinical features of patients with Klinefelter's syndrome with the chief complaint of male infertility. The study consisted of 40 patients with a control group of 55 infertile non-azoospermic males with a normal 46,XY karyotype who visited the Reproduction Center of Toho University Hospital during the 5.5-year period between January 1991 and June 1996 with the chief complaint of male infertility. Among the 40 patients with Klinefelter's syndrome, 38 cases were pure 47,XXY, one case was 47,XXY with a pericentric inversion of chromosome 9 and one case was a mosaic of 46,XY/47,XXY(2:28). Thirty-nine of these 40 patients were azoospermic and one (47,XXY) had severe oligoasthenozoospermia. The sexual function of the patients was evaluated according to their responses to a preliminary questionnaire devised by our department. There was no significant difference in the frequency of sexual function disturbances between the patients with Klinefelter's syndrome and the control group (67.5% vs. 60.0%; χ² analysis; p = 0.454). The mean frequency of sexual intercourse per month in the patients with Klinefelter's syndrome was significantly higher than in the control group (4.4 ± 2.8 vs. 3.3 ± 1.6: Welch's t -test, p < 0.05). A possible explanation for this variation may lie in the fact that many of these patients were diagnosed with azoospermia prior to the administration of the questionnaire and may have wished to continue to have relations as a couple.     

Exposure to Ethylnitrosourea Before Implantation Induces Congenital Malformations in Mouse Fetuses

Abstract The effects of ethylnitrosourea (ENU) on the development of preimplantation mouse embryos were investigated. ICR mice were treated intraperitoneally with single doses of 25, 50 or 100 mg ENU/kg body weight on day 0, 1, 2 or 3 of gestation, or with single doses of 25, 50 or 75 mg ENU/kg on day 8 of gestation. The uterine contents were examined on day 18 of gestation, and viable fetuses were inspected for external and skeletal malformations. No significant differences were observed in the number of implants between the ENU-treated groups on day 1, 2 or 3 of gestation and controls, while the number of implants in all of the groups treated with ENU on day 0 of gestation was significantly decreased compared to that in the control group. The frequencies of early postimplantation deaths were significantly increased in all of the groups treated with ENU on each gestational day before implantation, compared to the control frequencies. ENU treatment before implantation caused dose-dependent increases in the incidence of externally or skeletally malformed fetuses. Cleft palate, exencephaly and umbilical hernia were the most common types of external malformations in the groups treated with ENU before implantation and in the control group. The skeletal malformations seen in the ENU-treated groups were malformed vertebrae, malformed ribs, and bending of appendicular skeleton. Fused ribs was the most common skeletal malformation seen in the control fetuses. The type distributions of external and skeletal malformations induced by the treatment with ENU before implantation is quite different from those of fetal malformations induced by the treatment with ENU at the organogenesis stage. The results in the present study demonstrate that embryos before implantation in the uterus are susceptible with regard to the induction of congenital malformations by chemicals, and I propose that a large portion of the external malformations in fetuses treated at the preimplantation stages is the result of increased yields of spontaneously-occurring malformations.