Clinicopathological significant and prognostic influence of cadherin-17 expression in gastric cancer

Cadherin-17 (CDH17), also called liver–intestine cadherin, is a structurally unique member of the cadherin superfamily. Our serial analysis of gene expression demonstrated that CDH17 was one of the most up-regulated genes in advanced gastric carcinomas. CDH17 expression is known to be regulated by Cdx2. In the present study, we examined the expression of CDH17 in primary gastric carcinoma tissues by immunohistochemistry, and analyzed the correlation of CDH17 expression with clinicopathological characteristics and patients prognosis. CDH17 expression was detected in 63/94 (67%) of gastric adenocarcinomas in addition to intestinal metaplasia. The expression of CDH17 tended to be associated with intestinal type carcinoma, and carcinomas with CDH17 expression was significantly more frequent in advanced stage cases (80%) than in early stage (53%). The prognosis of patients with positive CDH17 expression was significantly poorer than that of the negative cases (P=0.0314). However, multivariate analysis revealed that CDH17 was not an independent prognostic factor. Six of seven cases that showed positive expression of Cdx2 simultaneously expressed CDH17 protein. These results suggested that the expression of CDH17 was characteristic of the advanced gastric carcinoma that is associated with poor prognosis.     

Influence of ionic disturbances produced by gastric washing on cortical spreading depression

Summary The ionic composition of the internal environment was altered in rabbits by means of gastric washing, combined with intramuscular administration of 3-Beta-aminoethylpyrazole. The effects of this treatment on cortical spreading depression (SD) were studied. C1^- and Na⁺ concentrations decreased significantly in serum and in cerebrospinal fluid after the treatment. This made the animals much more susceptible to SD, as established by the high incidence of spontaneous SD, increased SD velocity of propagation and facilitated its interhemispheric transfer. An intensification of the epileptiform activity associated with SD was also observed. Intravenous replacement of NaCl abolished the above effects on SD. When the intravenous replacement was done with Na-Isethionate, those effects were enhanced. It is concluded that chloride deficiency was the main factor responsible for the observed facilitating effects.This work was supported by grants from the BNDE (FUNTEC-74 e 143), CNP_q and CAPES     

Effect of stretch on calcium channel currents recorded from the antral circular myocytes of guinea-pig stomach

The effect of membrane stretch on voltage-activated Ba²⁺ current (I _Ba) was studied in antral circular myocytes of guinea-pig using the whole- cell patch-clamp technique. The changes in cell volume were elicited by superfusing the myocytes with anisosmotic solutions. Hyposmotic superfusate (202 mosmol/l) induced cell swelling and increased peak values of I _Ba at 0 mV (from −406.6 ± 45.5 pA to −547.5 ± 65.6 pA, mean ± SEM, n = 8) and hyperosmotic superfusate (350 mosmol/l) induced cell shrinkage and decreased peak values of I _Ba at 0 mV (to −269.5 ± 39.1 pA, n = 8). Such changes were reversible and the extent of change was dependent on the osmolarity of superfusate. The values of normalized I _Ba at 0 mV were 1.43 ± 0.04, 1.30 ± 0.06, 1.23 ± 0.04, 1.19 ± 0.04, 1 and 0.68 ± 0.06 at 202, 220, 245, 267, 290 and 350 mosmol/l, respectively (n = 8). I _Ba was almost completely blocked by nicardipine (5 μM) under hyposmotic conditions. The values of steady-state half-inactivation voltage (−37.7 ± 3.3 and −36.5 ± 2.6 mV, under control and hyposmotic conditions, respectively) or the half-activation voltage (−13.6 ± 2.3 and −13.9 ± 1.9 mV) of I _Ba were not significantly changed (P > 0.05, n = 6). Cell membrane capacitance was slightly increased from 50.00 ± 2.86 pF to 50.22 ± 2.82 pF by a hyposmotic superfusate (P < 0.05, n = 6). It is suggested that cell swelling increases voltage-operated L-type calcium channel current and that such a property is related to the response of gastric smooth muscle to mechanical stimuli. Received: 14 November 1995/Received after revision and accepted: 8 January 1996     

Intramucosal Helicobacter pylori in the human and murine stomach: its relationship to the inflammatory reaction in human Helicobacter pylori gastritis

Intramucosal Helicobacter pylori (H. pylori) has been described in biopsy tissues and culture systems. However, the association of intramucosal H. pylori with histopathologic features has not been evaluated. The purpose of this study is to investigate the relationship between intramucosal H. pylori and inflammatory reactions in H. pylori infection. In 113 randomly selected human gastric biopsies and 20 murine stomachs, which were inoculated with SSI every day for a week, immunohistochemical analysis for intramucosal H. pylori was done and correlated with histologic parameters. Electron microscopic examination was done on murine stomachs. H. pylori infection was present in 104 gastric biopsies and 17 murine stomachs. Intraepithelial immunopositivity for H. pylori was detected in 27 of 104 (26%) biopsies and in 11 of 17 (65%) murine stomachs. Lamina proprial immunopositivity for H. pylori was present in 51 of 104 (48%) biopsies. Neutrophil-associated immunopositivity for H. pylori was observed in 22 of 90 (24%) biopsies with H. pylori chronic active gastritis. Lamina proprial and neutrophil-associated immunopositivity for H. pylori correlated significantly with the density of H. pylori and the grade of acute inflammatory reaction in H. pylori gastritis. Intramucosal location of H. pylori itself or its antigen is closely associated with acute inflammatory reactions and may play an important role in establishing a persistent infection in chronic H. pylori gastritis. Furthermore, lamina proprial and/or neutrophil-associated H. pylori appears to be more important than intraepithelial H. pylori in acute inflammatory reactions of H. pylori gastritis.     

Interepithelial cells of the oral mucosa in mice

Summary Non-epithelial mesenchymal and neuroectodermal cells occur between the keratinocytes in the stratified squamous epithelium of the oral mucosa. These cells cannot be classified adequately by light microscopy. In the present study the oral mucosa of the lip, cheek and tongue of 50 mice were studied by light and electron microscopy. 3,025 mononuclear interepithelial cells were documented and analysed.Monocytogenic macrophages, plasma cells and mast cells were not found interepithelially and cannot be regarded as a regular constituent of the epithelium. Only a few neuroectodermal cells — in mice these are exclusively Merkel cells, with no melanocytes — were localized in the epithelium. The majority of the interepithelial cell population is made up of lymphocytes (22.8%) and Langerhans cells (56.8%). They are an integral constituent of the epithelium. Lymphocytes with rounded and indented nuclei can be identified. The larger and dendritic Langerhans cells are a specific cell of squamous epithelium and also occur in the oral mucosa. Not all cells which feature the cytological characteristics of Langerhans cells contain Langerhans or Birbeck granules. Accordingly these granules cannot be considered an exclusive identification characteristic. Two types of Langerhans cells can be differentiated. 80.9% have the more or less typical appearance known from the epidermis and were termed macrophagocytoid Langerhans cells. The nuclei are irregularly indented and moderately heterochromatic. 19.1% possessed conspicuous large, spherical, euchromatic nuclei and an electron-lucent cytoplasm. These were termed reticuloid Langerhans cells. About 20% of the interepithelial cell population could not be identified, neither as typical lymphocytes nor as Langerhans cells. These were small to medium sized cells with deeply indented cerebriform strongly heterochromatic nuclei. They are similar to the Sézary cells or mycosis fungoides cells of epidermotropic human T-cell lymphomas. The lymphocytic nature of these cells has been confirmed. It seems likely that differentiation of lymphocytes to cerebriform cells occurs within the epithelium. It is further discussed whether cerebriform cells are precursors of Langerhans cells, a conclusion suggested morphologically by transitional forms. This would imply that Langerhans cells originate from lymphocytes, and that the cerebriform cell is an intermediate step of differentiation. The microenvironment of the squamous epithelium may play a role in the process of differentiation, which could explain the epitheliotropy of lymphocytes. The possibility is considered that Langerhans cells and interdigitating reticulum cells of the T-cell area of lymph nodes are identical. The close functional cooperation of Langerhans cells, lymphocytes, and interdigitating reticulum cells in immunological defenses against external antigens is discussed.The authors wish to express their sincere appreciation to Miss P. Starck and Miss I. Brandt for invaluable technical assistance in this project.     

Exogenous carbohydrate oxidation from maltose and glucose ingested during prolonged exercise

Summary Intestinal perfusion studies have shown that glucose absorption from maltose occurs faster than from isocaloric glucose. To determine whether ingested maltose might be a superior source of carbohydrate (CHO) for endurance athletes, we compared the rates of gastric emptying, absorption and oxidation of 15 g · 100 ml^–1 solutions of maltose and glucose. Six endurance-trained cyclists drank 1200 ml of either U-¹⁴C maltose or U-¹⁴C glucose as a 400-ml loading bolus immediately before exercise, and as 8 × 100-ml drinks at 10-min intervals during a 90-min ride at 700% of maximal oxygen consumption. The rates of gastric emptying [maltose 690 (SD 119) ml · 90 min^–1; glucose 655 (SD 93) ml · 90 min^–1], the appearance of U-¹⁴C label in the plasma, and the peak rates of exogenous CHO oxidation [maltose 1.0 (SD 0.09) g · min^–1; glucose 0.9 (SD 0.09) g · min^–1] were not significantly different. Further, the 51 (SD 8) g of maltose and the 49 (SD 9) g of glucose oxidised during exercise were similar. Each accounted for approximately 2001o of the total CHO oxidised during the 90 min of exercise. Since only half of the CHO delivered to the intestine was oxidised in the 90-min ride (maltose 49%; glucose 50%), we conclude that neither the rate of gastric emptying, nor digestion limited the rate of ingested CHO utilisation during the early stages of exercise. Rather, we hypothesise that, initially, it could be the rate at which the CHO diffuses across the unstirred water layer of the brush-border of the intestinal villi that limits the utilisation of soluble CHO ingested during prolonged exercise.     

Prognostic significance of standardized AgNOR analysis in early and advanced gastric carcinomas

 To assess the prognostic significance of silver-stained nucleolar organizer region (AgNOR) proteins, a standardized AgNOR analysis was performed on 78 patients affected by early (EGC, n=24) or advanced (AGC, n=54) gastric carcinomas. The histopathological diagnosis, grading and staging were done according to WHO and UICC recommendations; the mean follow-up time was 56.9 months. Visualization and quantification of AgNORs were made in formalin-fixed, paraffin-embedded sections as specified in the guidelines of the Committee on AgNOR Quantification (1995). Statistical analysis was performed on the mean AgNOR area values (NORA). Highly significant differences (P<0.001) were found in NORA values between EGC and AGC, between low- and high-grade gastric carcinomas and between patients dead from gastric cancer and living patients. In addition, significant P values were found on comparison of NORA values relating to pT status, pN status and stage. Comparison of Kaplan-Meier survival curves revealed that patients affected by gastric carcinomas with higher NORA values (>5.213 μm²) had a worse prognosis. Finally, using Cox multiple regression analysis, the AgNOR quantity emerged as a useful independent prognostic variable to predict the final outcome of patients affected by EGC or AGC. Received: 26 September 1997 / Accepted: 26 January 1998     

Hydration during exercise

Summary Five young unacclimatised subjects were exposed for 4 h at 34 C (10 C dew-point temperature and 0.6 m · s^–1 air velocity), while exercising on a bicycle ergometer: 25 min work — 5 min rest cycles for 2 hours followed by 20 min work — 10 min rest cycles for two further hours. 5 experimental sessions were carried out: one without rehydration (NO FLUID) resulting in 3.1% mean loss of body weight ( M_b), and four sessions with 20 C fluid ingestion of spring water (WATER), hypotonic (HYPO), isotonic (ISO) and hypertonic (HYPER) solutions to study the effects of fluid osmolarity on rehydration. Mean final rehydration (±SE) after fluid intake was 82.2% (±1.2). Heart rate was higher in NO FLUID while no difference among conditions was found in either M_b or hourly sweat rates. Sweating sensitivity was lowest in the dehydration condition, and highest in the WATER one. Modifications in plasma volume and osmolarity demonstrated that NO FLUID induced hyperosmotic hypovolemia, ISO rehydration rapidly led to plasma isoosmotic hypervolemia, while WATER led to slightly hypoosmotic normovolemia.It is concluded that adequate rehydration through ingestion of isotonic electrolyte-sucrose solution, although in quantities much smaller than evaporative heat loss, rapidly restored and expanded plasma volume. While osmolarity influenced sweating sensitivity, the plasma volume changes ( PV) within the range –6% PV+4% had little effect on temperature adjustments in our conditions.     

应用免疫组化技术检测胃癌组织p53、c-erbB-2、p21、nm23基因表达产物及其临床意义

目的：为探讨胃癌组织p53、c-erbB-2、p21、nm23联合基因表达产物对胃癌诊断与治疗方面的价值。方法：应用免疫组化技术检测了手术切除胃癌组织p53、c-erbB-2、p21、nm23基因产物表达。结果：p53蛋白表达阳性率37．6％-46．2％，c-erbB-2为34．6％-56．8％，p21为37．8％。61．5％，nm23为30．8％-70．3％；非胃癌组织(胃、十二指肠溃疡、胃息肉、重度不典型增生)未见c-erbB-2、p21、nm23基因表达。c-erbB-2、p21的表达与胃癌的分化程度有关，p21、nm23基因表达与肿瘤浸润深度、肿瘤转移程度有关。p53、c-erbB-2、p21、nm23四种肿瘤蛋白在胃镜活检标本和手术切除标本中表达是一致的，无显著性差异。结论：对胃癌组织检测p53、c-erbB-2、p21、nm23基因表达产物在胃部的良恶性肿瘤鉴别、非手术临床分期的判断及指导胃癌的临床诊断与治疗等方面具有一定价值。