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Lymphatic drainage routes of the gastric cardia visualized by lymphoscintigraphy.

UNLABELLED: This study was undertaken to assess the feasibility of lymphoscintigraphy of the gastric cardia and to identify the incidence of paraesophageal lymphatic drainage, precluding total gastrectomy with esophagojejunostomy as a potentially curative therapy for gastric cardia cancer. METHODS: Ten patients scheduled for esophagectomy with high-grade dysplasia or with esophageal cancer at least 3 cm above the esophagogastric junction were enrolled in this study. Preoperatively, 111 MBq of(99m)Tc-labeled nanocolloid (n = 5) or sulfur colloid (n = 5) were injected into the submucosa of the tumor-free cardia. Subsequently, lymphoscintigraphy in combination with CT was obtained. Locoregional lymph node stations were measured for radioactivity by a gamma-probe intraoperatively and ex vivo in the resection specimen. RESULTS: In each patient, at least 1 radioactive lymph node station was detected. In total, 42 radioactive lymph node stations were detected by gamma-probe. Of those 42 areas, 38 (90%) were visible at preoperative lymphoscintigraphy. In the group of 5 patients in whom nanocolloid was used, a median of 2 (range, 1-4) node stations per patient was identified, whereas when sulfur colloid was administered a median of 6 (range, 4-8) active lymph node stations per patient could be detected (P < 0.002). Paraesophageal drainage was identified in 1 patient. CONCLUSION: Lymphoscintigraphy of the gastric cardia is feasible and can accurately determine the location of radioactive lymph nodes. Early paraesophageal lymphatic drainage is rare.

Adenocarcinoma↗

[The application of surface-enhanced laser desorption/ionization-time of flight-mass spectrometry in diagnosing dysplasia and chronic atrophic gastric-carditis in population with high risk of gastric-cardia adenocarcinoma].

OBJECTIVES: To evaluate the serum biomarkers for diagnosis of gastric cardia dysplasia (DYS) and chronic atrophic gastric-carditis (CAG) and to provide a novel screening method for high risk population of gastric-cardia adenocarcinoma (GCA). METHODS: Proteomic spectra were generated by surface-enhanced laser desorption/ionization-time of flight-mass spectra (SELDI-TOF-MS) and weak cation exchange protein chip system. A set of spectra derived from analysis of serum from 143 symptom-free subjects at high-risk area for GCA, including 63 cases with histologically normal gastric cardia epithelia, 57 of CAG and 23 of DYS, were analyzed by bioinformatics like decision tree classification algorithm. The sensitivity and the specificity for test group were performed by using 10-fold cross validation classification with the decision tree classification model. RESULTS: One protein spot with a ratio of mass to charge (M/Z) of M3894. 0 was selected to build a decision tree classification model to identify the case with DYS or normal. With this classification model, the sensitive rate for DYS identification was 87% (20/23). Two proteins with M/Z of M2942. 15 and M33316. 6 were used to build a decision tree classification model. With this model, the sensitivity for discriminating CAG from normal was 93% (53/57) and the specificity was 92 (58/63). CONCLUSIONS: The gastric cardia lesions of DYS and CAG could be identified by SELDI-TOF-MS technique specifically in symptom-free subjects at high incidence area for GCA. The present findings provide a new screening way for high-risk subjects with CGA.

Adult↗

[Re-surgical treatment for postoperative anastomotic recurrence of adenocarcinoma of gastric cardia].

OBJECTIVE: To evaluate indications and approaches of re-surgical treatment for postoperative anastomotic recurrence of adenocarcinoma of the gastric cardia. METHOD: Clinical date on 23 patients who had received re-surgical treatment for postoperative anastomotic recurrence of adenocarcinoma of the gastric cardia were analyzed retrospectively. RESULTS: The rate of tumor resection, incidence of complications, and mortality in the patients were 69.6%, 17.4% and 8.7% respectively. The percentage of patients with pleural and peritoneal adhesion was 87.0%. The mean survival time of the patients with tumors resected was 15.0 months, much longer than 4.1 months of the patients who underwent exploration (P < 0.05). The mean survival time of the patients with no lymph node metastasis and those with lymph node metastasis was 21.3 months and 10.2 months respectively (P > 0.05). The mean survival time of the patients with radical resection was 15.8 months, and that of the patients with palliative resection was 13.3 months (P > 0.05). CONCLUSIONS: Because of extensive pleural and peritoneal adhesion as well as re-building of the alimentary tract, the operation for anastomotic recurrence of adenocarcinoma of the gastric cardia is difficult and the mortality is high. Moreover, the prognosis of the patients with adenocarcinoma of the gastric cardia is poor. Indications for re-surgical treatment should be strictly selected. Operative approach should depend on the stage of disease.

Adenocarcinoma↗

[Postoperative respiratory failure in patients with cancer of esophagus and gastric cardia].

OBJECTIVE: We retrospectively analyzed the cause and death risk of 114 postoperative respiratory failure patients found in 3519 patients with esophageal cancer and 1495 patients with carcinoma of gastric cardia surgically treated between January 1992 and May 2003. METHODS: To analyze the reasons causing postoperative respiratory failure in surgically treated esophageal or gastric cardia cancer patients, and the correlation between the death risk of postoperative respiratory failure and preoperative pulmonary function tests, postoperative complications, operation modes, history of preoperative accompanying diseases and so on using Binary Logistic Regression analysis and Chi-square tests (chi(2)) in SSPS statistics software. RESULTS: In this series, postoperative respiratory failure developed in 97 of 3519 (2.76%) esophageal cancer patients and 17 of 1495 (1.14%) gastric cardia cancer patients, which were mainly caused by severe respiratory tract infection (37.7%, 43/114) and operative complications (35.1%, 40/114) such as: anastomotic leakage or perforation of thoracic stomach, extensive bleeding during operation, chylothorax, etc, totally accounting for 72.8% (83/114). In contrast with lung cancer patients, most of the postoperative respiratory failure (69.3%) occurred in the patients who had perioperative complications but almost always normal preoperative pulmonary function tests. Other reasons to cause postoperative respiratory failure were: extubation in unconscious patients at the end of general anesthesia; over-infusion during operation; pulmonary artery embolism; severe arrhythmia and so on. All patients except 2 were treated in ICU by mechanic ventilation through intubation and/or tracheotomy. Eighty patients (70.2%) were intubated and/or had tracheotomy within 3 days postoperatively. Seventy patients (61.4%) were rescued successfully, whereas 44 cases (38.6%) died of postoperative respiratory failure and/or other postoperative complications. Univariate analysis and multivariate analysis by binary logistic regression indicated that: severe perioperative complications, more postoperative complications, poor preoperative pulmonary function, radical preoperative radiotherapy, intubation and/or tracheotomy after the second postoperative day and long period of mechanic ventilation were the major risk factors leading to death once the postoperative respiratory failure developed. The former 3 factors were independent risk factors leading to death with OR of 2.50, 2.37, 1.68, respectively. Age, sex, operation modes, history of preoperative accompanying disease, prophylactic antibiotics were not demonstrated as statistically significant risk factors correlated with death. CONCLUSION: Severe perioperative complications and respiratory tract infection are the two major causes of postoperative respiratory failure in patients with cancer of esophagus and gastric cardia. Patients with severe perioperative complications or poor preoperative pulmonary function or association with more than two kinds of postoperative complications have much higher death risk than other patients when they develop postoperative respiratory failure. Careful manipulation during operation and effective perioperative management are the most important measures to avoid postoperative respiratory failure and high mortality.

Adult↗

[Multivariate prognostic analysis for patients with curative resection of gastric cardia cancer].

OBJECTIVE: To explore the factors affecting the long-term survival of patients with curative resection of gastric cardia cancer. METHODS: The data of 108 patients who underwent radical resection of gastric cardia cancer from Jul. 1994 to Dec. 2003 in our hospital were investigated retrospectively. The Kaplan-Meier method and long-rank test were used for bivariate comparisons of survival. Multivariate analysis was done by the Cox regression model (Backward Wald). RESULTS: Survival status of the 108 patients was ascertained in Dec. 2004. Among them, 68 were Siewert type II and 40 were Siewert type III. Seventy-four patients had lymph node metastases (68.5%). The mean follow-up time was 37 months (95% CI: 29.3-44.7 months) and the middle follow-up time was 26.6 months (95% CI: 25.8-34.2 months). The 1-,3- and 5-year cumulative survival rates were 77.2%, 33.6% and 21.8%, respectively. According to the Kaplan-Meier and log-rank methods, splenectomy, lesion size, depth of tumor invasion and regional lymph node status were prognostic factors. Multivariate regression analysis indicated that only depth of tumor invasion (P=0.009) and lymph node metastases (P=0.001) were independent prognostic factors. CONCLUSION: Depth of tumor invasion and lymph node metastases have negative effects on the survival of patients with gastric cardia cancer undergoing curative resection. Splenectomy may only be appropriate for patients with direct tumor invasion to the spleen and the extent of gastric resection does not influence survival in patients with curative gastric cardia cancer.

Adult↗

Fibrosis of gastric cardia after endoscopic sclerosis. Mechanism for control of experimental reflux?

Endoscopic sclerosis of the gastric cardia (ESGC) prevents experimental gastroesophageal reflux (GER) without changes in lower esophageal sphincter (LES) pressure and length. This study was performed to define the histologic appearance of the esophagus and stomach one year after ESGC. Four dogs were studied one year after ESGC with morrhuate sodium; ESGC had been performed at six sites, 1-3 cm distal to the esophagogastric junction. All animals had stable weight and eating habits at sacrifice. Light microscopy of the cardia and LES included morphometry of wall thickness (mm) and assessment of fibrosis (- to ). The esophagus had minimal changes; the gastric cardia had focal fibrosis, maximal on the greater curve, without any change difference in wall thickness. ESGC results in fibrosis of the gastric cardia, without significant changes in the esophagus. These changes prevent GER, possibly by preventing the initiation of a reflux event.

Animals↗

[Radical operation for carcinoma of gastric cardia--lymph node dissection by laparosternophrenotomy approach].

The adequate esophago-gastric resection and lymph node dissection can be performed without the necessity of a thoracotomy, by using the laparosternophrenotomy approach. For tumors restricted to lower esophagus of 4cm in localized tumors or 3cm in invaded tumors above the EG junction, the sternotomy approach is utilized. However, if the tumor extends to more than the above criteria, the thoracoabdominal approach must be utilized. For 14 years, 85 cases with tumor of gastric cardia were performed by sternotomy approach and 76 cases were performed by thoracotomy approach. The lymph node metastatic rate in the lower thoracic cavity was 26% in total. The lymph node metastatic rate of No. 110 was 22.6%, No. 111 was 17.4% and No. 112 was 12.5%. These results show the lymph node dissection in the lower thoracic cavity is very important in tumors of gastric cardia. The five year survival rate was 41% in patients who undergone curative operation by the sternotomy approach, and 45% in patients performed by the thoracotomy approach. According to our study of the lymph fluid stream in gastric cardia tumors using carbon, the lymph node dissection around the renal vein is important. This approach has less respiratory disturbance than the thoracotomy. This procedure is one of the best approaches for carcinoma of gastric cardia according to our criteria.

Cardia↗

[Experimental and clinical study on the lymphatic pathway draining from the distal esophagus and gastric cardia].

The intramural and extramural lymphatics draining from the distal esophagus and gastric cardia were studied in 140 mongrel dogs by dye injection technique. A clinical study was also performed on the lymphatic pathway in these regions by radio isotope uptake (RIU). The results were compared with that of lymph node metastases in 113 patients with carcinoma of the distal esophagus and 103 patients with carcinoma of the gastric cardia. The intramural lymphatics between the distal esophagus and gastric cardia were communicated at the central part of the muscularis mucosae. This finding coincided with the results of intramural RIU. The extramural lymphatics from the distal esophagus flowed both upward and downward. Those from the cardia entered the intraabdominal regional lymph nodes, but none was visualized either in the mediastinum or in the thoracic cavity. Similarly, few RIUs were detected in the mediastinal nodes. As the result of partial or total blockade at the cardiac portion of the stomach in dogs, ascending lymphatics reaching the thoracic cavity was observed in 6 of 27 cases. Clinically, the incidence of the mediastinal lymph node metastases were 17.0%. These results indicate that upward lymphatic spreads may occur in cases with cardiac cancer when the descending lymphatic pathway is blocked by the tumor invasion.

Adult↗

[Megaesophagus secondary to carcinoma of the cardia: apropos of 4 cases].

Four cases of megaesophagus with esophageal motor disturbances secondary to adenocarcinoma of the cardia are hereby reported. There were common characteristics to all cases such as: 1) short duration of symptoms, 2) grade II megaesophagus by X-Rays with narrowing of the cardia, 3) the endoscopy showed esophageal dilatation and inability to pass the cardia with the endoscope, 4) histology (obtained by endoscopy or surgery) and exfoliative cytology were positive for malignancy, 5) the esophageal motility tests showed aperistalsis of the whole esophagus in all cases, and lack of relaxation of the lower esophageal sphincter in two. The urecholine test was positive in one patient with neoplastic infiltration of the myenteric plexus, 6) in two cases where esophageal resection was performed, infiltration of the Auerbach's plexus by cancer cells was proven. We conclude that in the presence of aperistalsis of the esophagus with or without achalasia of the lower esophageal sphincter, the diagnosis of megaesophagus secondary to cancer of the gastric fundus should be suspected when it is not possible to pass the cardia with the endoscope, even if biopsy and cytology are negative for malignancy.

Adenocarcinoma↗

Laparoscopy and laparoscopic ultrasonography in staging of carcinoma of the esophagus and gastric cardia.

BACKGROUND: The objective of this prospective study was to assess the contribution of laparoscopy combined with laparoscopic ultrasonography (LLU) in the preoperative staging of patients with carcinoma of the esophagus and cardia. STUDY DESIGN: Preoperative LLU was performed in 56 patients who were selected for curative resection of carcinoma of the esophagus (n = 38) or gastric cardia with involvement of the distal esophagus (n = 18) after routine preoperative workup. During LLU, the peritoneal cavity was scrutinized for metastatic disease, and ultrasonography of the liver and celiac axis was performed. In all patients without histologically proven metastases, laparotomy was then performed. RESULTS: The morbidity rate of the procedure was 3.5 percent (two superficial wound infections). In three (5 percent) of the 56 patients, laparotomy was excluded by the presence of intra-abdominal metastases. In three other patients, laparotomy was necessary to confirm the suspected hepatic or peritoneal metastases, or both, because histologic proof was not obtained at laparoscopy. In one patient, LLU failed to detect a small hepatic metastasis in segment VII. The preoperative stage was altered by laparoscopy in nine (17 percent) patients (M1 in six, T4 in three). Laparotomy was avoided in two (11 percent) and the preoperative stage changed in seven patients (41 percent), all of whom had carcinoma of the gastric cardia, as occurred in one (3 percent) and two (6 percent) patients with middle and distal carcinoma of the esophagus, respectively. CONCLUSIONS: Preoperative staging by LLU is of little value in patients with carcinoma of the middle and lower esophagus. The probable role of LLU in the staging of patients with carcinomas of the gastric cardia remains to be confirmed in larger series.

Cardia↗

[Extent of radical surgery in cardia carcinoma--esophagectomy or gastrectomy?].

In patients with cardia cancer, showing a tumor center between 1 cm above to 2 cm below the anatomical cardia, the results of transhiatal esophagectomy with proximal gastrectomy versus total extended gastrectomy with distal esophageal resection were compared. For gastrectomy, postoperative mortality was significantly lower (2% vs. 8.6%), whereas the rates of R0 resection (81% vs. 68%) and 5-year survival rate (48 vs. 25%) were significantly higher than after esophagectomy. If in cardia cancer, according to the mentioned definition, R0 resection can be achieved by extended total gastrectomy and distal esophageal resection, this represents the procedure of choice for this strictly defined type of carcinoma of the cardia.

Adenocarcinoma↗

Body mass index and the risk of cancers of the gastric cardia and distal stomach in Shanghai, China.

The divergent incidence patterns of gastric cardia and distal stomach cancers suggest different etiologies. Although obesity has recently been linked to cardia cancer in Western populations, its association with distal stomach cancer remains unclear. This study examined the relation of anthropometric measurements to risk by subsites of stomach cancer in a Chinese population. We identified 1124 population-based cases of stomach cancer, ages 20-69 years, newly diagnosed between December 1988 and November 1989 in Shanghai, China. Controls (n = 1451) were randomly selected from permanent Shanghai residents and frequency-matched to cases by age and sex. Information on demographic characteristics, height and weight, diet, smoking, and other exposures was obtained by trained interviewers in person. The body mass index (BMI) was calculated as weight in kilograms divided by height in square meters and categorized into quartiles based on the distribution among controls. Odds ratios and 95% confidence intervals were estimated using logistic regression models, simultaneously adjusting for age, education, income, cigarette smoking (men only), alcohol drinking (men only), intake of total calories, and chronic gastric diseases. For gastric cardia cancer, the odds ratios among men were 1.4, 1.5, and 3.0 in the second, third, and fourth quartiles of usual BMI (P for trend, < 0.01). Among women, elevated risks also were associated with excess weight, but the gradient in risk was not smooth. Risk patterns for usual body weight, maximum BMI, and minimum BMI were similar to those found for usual BMI. For distal stomach cancer, no association with usual BMI was observed among men, but a slightly elevated risk was seen among women. Our observations in China support recent findings in Western populations that obesity contributes to the risk of gastric cardia cancer, especially among men.

Adult↗

An inverse relation between cagA+ strains of Helicobacter pylori infection and risk of esophageal and gastric cardia adenocarcinoma.

Gastric colonization with Helicobacter pylori, especially cagA+ strains, is a risk factor for noncardia gastric adenocarcinoma, but its relationship with gastric cardia adenocarcinoma is unclear. Although incidence rates for noncardia gastric adenocarcinoma have declined steadily, paralleling a decline in H. pylori prevalence, rates for adenocarcinomas of esophagus and gastric cardia have sharply increased in industrialized countries in recent decades. To clarify the role of H. pylori infection in these tumors with divergent incidence trends, we analyzed serum IgG antibodies to H. pylori and to a recombinant fragment of CagA by antigen-specific ELISA among 129 patients newly diagnosed with esophageal/gastric cardia adenocarcinoma, 67 patients with noncardia gastric adenocarcinoma, and 224 population controls. Cancer risks were estimated by odds ratios (OR) and 95% confidence intervals (CI) using logistic regression models. Infection with cagA+ strains was not significantly related to risk for noncardia gastric cancers (OR, 1.4; CI, 0.7-2.8) but was significantly associated with a reduced risk for esophageal/cardia cancers (OR, 0.4; CI, 0.2-0.8). However, there was little association with cagA- strains of H. pylori for either cancer site (OR, 1.0 and 1.1, respectively). These findings suggest that the effects of H. pylori strains on tumor development vary by anatomical site. Further studies are needed to confirm these results and to assess whether the decreasing prevalence of H. pylori, especially cagA+ strains, may be associated with the rising incidence of esophageal/gastric cardia adenocarcinomas in industrialized countries.

Adenocarcinoma↗

[Esophagogastric bypass anastomosis for benign stricture of cardia].

The aim of the study is to discuss our observations concerning oesophagogastric bypass anastomosis in cases with scar stricture of cardia in long-term achalasia (megaoesophagus). The Heller operation is ineffective in such patients and the resection of cardia with oesophagogastric anastomosis is a large and controversial operation. 16 patients were operated (6 of them after ineffective cardiomyotomy). In all cases long-term dysphagia, big loss of weight and large, S-shaped oesophagus lying on the diaphragm were found. The left side thoracotomy was performed and fundus of the stomach was dislocated to the chest through dilatatored oesophageal hiatus and with the oesophagus above the cardia. There were no postoperative complications. However, dysphagia regressed. The remote results (from 1 year to 7 years) in 11 patients were analysed. The general condition was satisfactory. No dysphagia and gastrooesophageal reflux was revealed. Anastomosis was efficient in X-ray examination. Our observations indicate that oesophagogastric anastomosis is a procedure of choice in the treatment of long-term achalasia with stricture of cardia and megaoesophagus.

Aged↗

Secretion of the type 2 peritrophic matrix protein, peritrophin-15, from the cardia.

The midgut of most insects is lined with a peritrophic matrix, which is thought to facilitate digestion and protect the midgut digestive epithelial cells from abrasive damage and invasion by ingested micro-organisms. The type 2 peritrophic matrix is synthesised by a complex and highly specialised organ called the cardia typically located at the junction of the cuticle-lined foregut and midgut. Although the complex anatomy of this small organ has been described, virtually nothing is known of the molecular processes that lead to the assembly of the type 2 peritrophic matrix in the cardia. As a step towards understanding the synthesis of the peritrophic matrix, the synthesis and secretion of the intrinsic peritrophic matrix protein, peritrophin-15 has been followed in the cardia of Lucilia cuprina larvae using immuno-gold localisations. The protein is synthesised by cardia epithelial cells, which have abundant rough endoplasmic reticulum, Golgi, and vesicles indicative of a general secretory function. Peritrophin-15 is packaged into secretory vesicles probably produced from Golgi and transported to the cytoplasmic face of the apical plasma membrane. The vesicles fuse with the plasma membrane at the base of the microvilli and release peritrophin-15 into the inter-microvilli spaces. The protein then becomes associated with the nascent peritrophic matrix, which lies along the tips of the epithelial cell microvilli. It is proposed that peritrophin-15 binds to the ends of chitin fibrils present in the nascent peritrophic matrix, thereby protecting the fibril from the action of exochitinases.

Amino Acid Sequence↗

Cardia carcinomas of intestinal type are associated with histologic changes in the gastric mucosa.

BACKGROUND: Previous studies of Japanese patients showed that distal gastric carcinomas (of the corpus or the antrum) were associated with histologic changes in the non-neoplastic gastric mucosa. These changes (cells with ciliated metaplasia, with large and small mucus-negative vacuoles, intramucosal glandular cysts, and extensive intestinal metaplasia) were often found in carcinomas of intestinal type.METHODS: In the present work, similar mucosal changes were searched for in surgical specimens carrying a carcinoma of the cardia. A total of 12 079 archival histologic sections, corresponding to 563 gastrectomies performed in Japanese patients, were analyzed.RESULTS: Of the specimens with cardia carcinoma of intestinal type seen in Tokyo ( n = 169) and in Matsuyama ( n = 168), 53.3% and 63.1% contained intramucosal cysts; 39.6% and 51.8%, ciliated metaplastic cells; 34.9% and 30.4%, large vacuolated cells; and 7.7% and 11.9%, small vacuolated cells; and 69.8% and 68.5% had high intestinal metaplasia scores, respectively. These percentages were significantly higher than those for cardia carcinomas of diffuse type in Tokyo ( n = 153) and in Matsuyama ( n = 73), in which 30.7% and 34.2% of the specimens had intramucosal cysts; 17.6% and 17.8%, ciliated metaplastic cells; 14.4% and 9.6%, large vacuolated cells; and 3.9% and 4.1%, small vacuolated cells; and 43.1% and 39.7% had high intestinal metaplasia scores, respectively.CONCLUSION: Thus, similarly to carcinomas of the corpus or the antrum, cardia carcinomas of intestinal type are associated with histologic changes in the gastric mucosa. The possibility that these changes are evoked by environmental factors was entertained.

Journal Article↗

A comparison of two methods to ascertain dietary intake: the CARDIA Study.

Data on dietary intake were collected in the Coronary Artery Risk Development in Young Adults (CARDIA) Study at the baseline examination in 1985-86 and again at the second examination 2 years later. At baseline, a diet history questionnaire developed for the CARDIA study was used; at the second exam the NCI (Block) food frequency questionnaire was used. The purpose of the present report is to compare the estimated nutrient intakes obtained with the two instruments; to compare correlations of nutrient intakes obtained at the two exams with those observed for other lifestyle and physiological variables also measured 2 years apart; and to assess ability to test hypotheses relating 2-year changes in risk factors to between-exam differences in reported nutrient intakes. Mean levels of reported intake were generally greater for both blacks and whites on the CARDIA diet history than on the Block food frequency. Rank order correlations of reported nutrient intakes between the two questionnaires indicated greater consistency between instruments for whites (r's ranging between 0.35 and 0.52) than for blacks (r's ranging between 0.29 and 0.45). Correlations over time for nutrients were smaller than those observed for body size measures and lipid levels but were similar in magnitude to those for blood pressure, physical activity, and life events. At both exams, total caloric intake was positively associated with physical activity (range of r's for CARDIA were 0.07 for white women to 0.23 for black men, the range of r's for Block were 0.06 for women to 0.11 for white men). Using data from the two examinations, 2-year changes in total plasma cholesterol were significantly related to 2 year changes in Keys scores. The results of this comparison are useful in that they show similarities and differences between two instruments developed to gather dietary intake data. The study also illustrates the need to monitor young adults during a time when rapid changes occur in many lifestyle and physiologic factors.

Adult↗

Wortmannin induces zebrafish cardia bifida through a mechanism independent of phosphoinositide 3-kinase and myosin light chain kinase.

Cardia bifida is an anomaly of the embryonic heart in which the bilateral myocardial rudiments fail to travel to the midline, resulting in the formation of two separate hearts in lateral positions. In zebrafish, eight loci responsible for the cardia bifida phenotype were identified in the large-scale genetic screen. Wortmannin has been reported to be a highly selective inhibitor of phosphoinositide 3-kinase and myosin light chain kinase activity. We provide the first evidence that wortmannin treatment of zebrafish embryos can induce cardia bifida in a dose-dependent manner and that wortmannin alters cardiac development between 6 and 16 h post-fertilization. In addition, we demonstrate that wortmannin induces zebrafish cardia bifida through a mechanism independent of phosphoinositide 3-kinase and myosin light chain kinase. Our findings may provide new insights into the cardiomyocyte function and disfunction.

Androstadienes↗