The Controversy of Pepsinogen A/Pepsin A in Detecting Extra-Gastroesophageal Reflux.

BACKGROUND: Pepsinogen A (PGA)/pepsin A is often used as a diagnostic marker of extra-gastroesophageal reflux. We aimed to explore whether its positivity in upper aerodigestive tract (UADT) was specific enough to diagnose reflux. METHODS: PGA/pepsin A protein levels were examined in 10 types of tissues and 10 types of body fluid by immunological staining, western blot or Elisa, using three different commercially available brands simultaneously. Liquid chromatography-tandem mass spectrometry parallel reaction monitoring (LC-MS/MS PRM) served as a gold reference for the detection of PGA/pepsin A proteins. PGA gene expression was analyzed by reverse transcriptase sequencing methods for tissue samples. Specifically, 24 hour pH monitoring technique was conducted for patients who donated saliva samples. RESULTS: Eight out of ten types of human tissue samples (stomach, esophagus, lung, kidney, colon, parotid gland, nasal turbinate and nasal polyps) were confirmed positive for PGA/pepsin A gene and protein by genetic and PRM technique, respectively. Two out of ten types of body fluid samples (gastric fluid, urine) were confirmed positive for PGA/pepsin A protein by PRM technique. The consistence rates of PGA/pepsin A positivity among three commercial antibody brands and Elisa kit were poor, and Elisa results of salivary did not match with 24-hour pH monitoring. CONCLUSIONS: Multiple tissues and body fluid could be detected baseline expression levels of PGA/pepsin A gene and protein. However, those commercially available PGA/pepsin A antibodies achieved poor sensitivity and specificity, therefore, relying on the detection of PGA/pepsin A in UADT by single antibodies to diagnose extra-gastroesophageal reflux without a specific positive cut-off value is unreliable.

Gastric adenocarcinoma of fundic gland (chief cell predominant type) coexisting with well differentiated intestinal adenocarcinoma: A case report.

RATIONALE: Gastric adenocarcinoma of fundic gland (chief cell predominant type) (GA-FG-CCP) is a new, rare variant of gastric adenocarcinoma, which is characterized by mild nuclear atypia and specific immunohistochemical markers. PATIENT CONCERNS: An 84-year-old Chinese man was referred to our hospital for endoscopic resection of a gastric lesion. INTERVENTIONS: We performed endoscopic submucosal dissection, and successfully removed the lesion. DIAGNOSIS: Esophago gastroduodenoscopy showed a slightly elevated lesion with a diameter of 22 mm in the posterior wall of cardia. Magnifying endoscopy with narrow band imaging revealed an abnormal microsurface and microvessels on the tumor surface. Endoscopic ultrasonography revealed a hypoechoic mass located in the first layer. The pathological diagnosis of the biopsy specimens indicated that the tumor was high grade intraepithelial neoplasia. The pathological diagnosis differed between the superficial and deeper part of the lesion. The superficial part was composed of a tubular structure with prominent atypia and was diagnosed as well differentiated intestinal adenocarcinoma. The deeper part was composed of a well-differentiated tubular adenocarcinoma mimicking the fundic gland cells, mainly the chief cells. The tumor cells showed mild nuclear atypia and was positive for pepsinogen-I (PG-I) and mucin-6 (MUC6). This deeper part was diagnosed as GA-FG-CCP. OUTCOMES: The tumor was successfully removed. This patient had no discomfort during the follow-up period (10 months). LESSONS: We present a rare case of GA-FG-CCP coexisted with well-differentiated tubular adenocarcinoma. GA-FG-CCP exists in the deep mucosal layer and the muscularis mucosa, which could not be found under endoscopy, but could be discerned in pathology with mild nuclear atypia and special biomarkers.

Gastric adenocarcinoma of the fundic gland type: A case report.

INTRODUCTION: Gastric adenocarcinoma of the fundic gland type (GA-FG) is a newly described entity that is characterized by well-differentiated neoplasm with unclear etiopathogenesis. PATIENT CONCERNS: A 60-year-old Chinese man was referred to our hospital for abdominal distension. DIAGNOSIS: Esophagogastroduodenoscopy (EGD) showed a depressed lesion found using in the greater curvature of the stomach. The pathological diagnosis of the biopsy specimens indicated that the tumor was GA-FG (chief cell predominant type, GA-FG-CCP). INTERVENTIONS: Endoscopic submucosal dissection (ESD) was performed. The histopathological examination of the ESD specimen revealed gastric hyperplasia of the fundic gland type around the adenocarcinoma cells. OUTCOMES: The surgical outcomes were good. The EGD showed a scar with no recurrence, and no symptoms were observed 1 year postoperatively during the follow-up. CONCLUSION: We present a rare case of a depressed lesion with a pathogenic expression suggesting gastric hyperplasia of the fundic gland type around the adenocarcinoma cells. Considering the origin of oxyntic mucosa, we consider that it may develop into GA-FG. To understand this issue better, similar cases should be monitored in the future.

Label-free detection of pepsinogen 1 and 2 by polyethylene coating Lamb microfluidic device.

Early screening of gastric cancer is a critical importance for the improvement of patients' survival rate. Here, a polyethylene coating Lamb (PE-Lamb) microfluidic device with immune layer for gastric cancer label-free detection was constructed. Two serum pepsinogen 1 (PG1) and pepsinogen 2 (PG2) biomarkers were applied to screen and predict the appearance of gastric cancer. Compared with enzyme-linked immunosorbent assay (ELISA), this method achieved a higher sensitivity and less time (40 min vs 120 min). The limit of detections (LOD) were reached 60 pg/mL for PG1 and 30 pg/mL for PG2, which have two orders of magnitude lower than traditional ELISA. The linearity coefficient indexes (R2) for PG1 and PG2 were 0.992 and 0.953 respectively, which is similar to that of ELISA. In addition, PG1 and PG2 mixed antigens sample with human serum was detected by PE-Lamb approach, and the frequency response showed high reproducibility and specificity. The results indicate that PE-lamb diagnostic technique is a novel and promising method for high-throughput screening and early diagnosis of gastric cancer.

Mid-season targeted selective anthelmintic treatment based on flexible weight gain threshold for nematode infection control in dairy calves.

The suitability of a single mid-season targeted selective treatment (TST) for gastrointestinal nematodes control, based on flexible average daily weight gain (ADWG) thresholds, was investigated in 23 groups of first grazing season calves. In each group, animals were weighed three times: before turnout, at mid-season and at housing. Just after the first weighing, each group was divided in two homogenous sub-groups in terms of age, breed and weight, and randomly allocated to one of two sub-groups intented for two different mid-season anthelmintic treatment strategies: (1) a treatment of all calves composing the sub-group (whole-group treatment (WT)) or (2) a targeted selective weight gain-based treatment (TST) of the animals showing an individual pre-treatment ADWG inferior to the mean pre-treatment ADWG of the corresponding WT sub-group. Anthelmintic treatment (levamisole 7.5 mg/kg BW) was performed 3 to 4 months after turnout. At housing, two parasitological parameters (the anti-Ostertagia ostertagi antibody level-Ostertagia optical density ratio (ODR) and the pepsinogen level) and a clinical parameter (the breech soiling score) were assessed at individual level in each group. Then, the high exposed groups to gastrointestinal nematode (GIN) were defined as groups for which untreated animals exhibited a mean Ostertagia ODR ⩾0.7 and among these groups, the ones characterized by high abomasal damage due to Ostertagia for which untreated animals exhibited a mean pepsinogen level ⩾2.5 U Tyr were also identified. Among TST sub-groups, the treatment ADWG thresholds varied from 338 to 941 g/day and the percentage of treated animals from 28% to 75%. Pre- and post-treatment ADWG as well as parasitological and clinical parameters measured at housing were similar between TST and WT sub-groups including the 17 high exposed groups to GIN. Within these 17 groups, the treatment allowed to significantly improve post-treatment ADWG compared with untreated animals. In the six high exposed groups showing mean pepsinogen level ⩾2.5 U Tyr, the average effect of treatment on post-treatment ADWG was the highest and estimated up to 14 kg after a grazing duration of 4 months. In contrast, in six other groups showing mean Ostertagia ODR<0.7 in untreated animals, no effect of treatment was seen suggesting an absence of production losses related to a low level of GIN infection. This study highlighted the suitability of a convenient mid-season TST strategy for first grazing season calves, based on the use of flexible thresholds of ADWG, allowing similar growth compared with a whole-group treatment while keeping a GIN population in refugia.

Associations among Gastric Juice pH, Atrophic Gastritis, Intestinal Metaplasia and Helicobacter pylori Infection.

BACKGROUND/AIMS: Gastric juice plays a crucial role in the physiology of the stomach. The aim of this study is to evaluate associations among the pH of gastric juice, atrophic gastritis (AG), intestinal metaplasia (IM), pepsinogen, and Helicobacter pylori infection. METHODS: Gastric biopsies and juice were collected from 46 subjects who underwent endoscopies at Seoul National University Bundang Hospital between November 2011 and March 2013. H. pylori, AG and IM were evaluated, and pepsinogen I or II, I/II ratio, and interleukin (IL)-1ß levels were measured. RESULTS: The mean pH of gastric juice was higher in the H. pylori-positive group (n=17) than that in the H. pylori-negative group (n=29) (4.54 vs 2.46, p=0.002). When patients were divided into pH ＜3 (n=28) and pH ≥3 (n=18) groups, H. pylori was lower in the pH ＜3 group (21.4%) than in the pH ≥3 group (61.1%) (p=0.007). The pH ≥3 group demonstrated AG and IM more frequently than the pH ＜3 group in the body (p=0.047 and p=0.051, respectively) but not in the antrum. There were no differences in pepsinogen I or II, I/II ratio, and IL-1ß levels between the two groups. CONCLUSIONS: There is a relationship between chronic H. pylori infection and gastric juice pH ≥3, which may originate from AG and IM in the body.

Cost-effectiveness of combined serum anti-Helicobacter pylori IgG antibody and serum pepsinogen concentrations for screening for gastric cancer risk in Japan.

BACKGROUND: A combination of assays for the presence of serum anti-Helicobacter pylori IgG antibody (HPA) and serum pepsinogen (PG) concentrations can be used to screen for gastric cancer risk. In Japan, this "ABC method" is considered an effective means of stratifying gastric cancer risk. This study aimed to ascertain its cost-effectiveness for assessing gastric cancer risk. METHODS: A Markov model was constructed to compare the cost-effectiveness of two strategies for gastric cancer-risk screening over a 30-year period: the ABC method, which uses a combination of assessing the presence of HPA and measuring serum PG concentrations and scheduling endoscopies accordingly, and annual endoscopic screening. Clinical and epidemiological data on variables in the model were obtained from published reports. Analyses were made from the perspective of the Japanese health care payer. RESULTS: According to base-case analysis, the ABC method cost less than annual endoscopic screening (64,489 vs. 64,074 USD) and saved more lives (18.16 vs. 18.30 quality-adjusted life years). One-way analyses confirmed the robustness of the cost-effectiveness results. The probability that the ABC method is cost-effective in Japanese individuals aged 50 years was 0.997. CONCLUSIONS: A combination of HPA and serum PG assays, plus scheduling endoscopy accordingly, is a cost-effective method of screening for gastric cancer risk in Japan.

Pepsinogen identification in the middle ear fluid of children with otitis media with effusion.

OBJECTIVES: This study aims to investigate the presence and concentration of pepsin/pepsinogen in middle ear fluid and to discuss the potential mechanisms involved in the pathogenesis of this condition. PATIENTS AND METHODS: A total of 33 children (21 boys, 12 girls; mean age 5.7±2.4 years; range 3 to 13 years) diagnosed with otitis media with effusion and scheduled for operation were enrolled into the study. Fluids aspirated from the middle ear were assessed for the presence of pepsinogen and albumin and blood samples were drawn simultaneously for comparison. RESULTS: Mean pepsinogen concentration was statistically significantly higher in middle ear fluids compared with serum samples (262.4 ng/mL [range: 211.7 ng/mL - 301.1 ng/mL] versus 102.6 ng/mL [range: 80.7 ng/mL - 134.5 ng/mL], respectively) (p<0.001). On the other hand, mean albumin concentration was significantly lower (1.1 g/dL [range: 0.01 g/dL - 9.5 g/dL] versus 5.8 g/dL [range: 0.9 - 9.5 g/dL], respectively) (p<0.001). The highest pepsinogen concentration was detected in patients with purulent effusion (275.3 ng/mL). CONCLUSION: Our findings support the theory of gastro-esophageal reflux related pepsinogen transition to the middle ear and indicate that pepsinogen may a reliable biochemical marker for the assessment of gastro-esophageal reflux.

[A Study to Determine the Optimum Antigens for the Serodiagnosis of Helicobacter Pylori Infection in Japanese Patients and the Association with IgG Subclass and Gastric Cancer].

Atrophic gastritis is caused by Helicobacter pylori infection, and is involved in gastric cancer. In this study, we investigated the association with total IgG and IgG subclass antibodies using several strains isolated from Japanese in H. pylori positive and negative individuals, and gastric atrophy using measuring pepsinogen I and II levels. We found that total IgG antibody measurement using typical Japanese genotype as an antigen was available for diagnosis of H. pylori infection, whereas IgG1 and IgG2 antibodies were not for diagnosis. Furthermore, the IgG1/G2 ratio was elevated in a patient with gastric cancer. The accuracy of serodiagnosis of H. pylori infection may increase when the optimal antigens are used, and measurement IgG subclass may provide additional prediction of gastric cancer.

[Characteristics of group A patients according to the ABC classification for gastric cancer risk screening].

In the ABC classification for gastric cancer risk screening, group A (Helicobacter pylori infection-negative, pepsinogen [PG]-negative) patients are assumed to be at low risk, but some patients do have atrophic gastritis and H. pylori infection. This study aimed to identify the characteristics of group A patients. Healthy adults in Yamagata City who underwent barium radiography and ABC classification participated in the survey. Patient radiographs were randomly interspersed and reviewed by two gastroenterologists who were blinded to the H. pylori and PG statuses. Group A patients (n=1462) was subclassified as follows: atrophic gastritis group, 21.5%; intermediate group, 15.7%; and no atrophic gastritis group, 62.8%. Elderly subjects and those with H. pylori antibody titers of 3.0-9.9U/ml should be carefully evaluated while interpreting the results of the ABC classification for gastric cancer risk screening.

Pepsin deteriorates prognosis of children with otitis media with effusion who undergo myringotomy or tympanostomy tube insertion.

OBJECTIVE: To investigate the concentrations of pepsin and pepsinogen within the middle ear cavity and determine whether pepsin and pepsinogen affect the prognosis of children with otitis media with effusion (OME). METHODS: All middle-ear lavage fluid from patients with OME undergoing myringotomy (M subgroup) or tympanostomy tube insertion (T subgroup) was collected and pepsin and pepsinogen were detected using enzyme-linked immunosorbent assay. After close follow-up over 2 years, the effects of pepsin and pepsinogen on the prognosis of the patients with OME in the M and T subgroups were analyzed. RESULTS: The average pepsin and pepsinogen concentrations were significantly lower in the M subgroup (n=54; 24.38±16.10mg/mL and 286.49±91.95mg/mL, respectively) than in the T subgroup (n=55; 45.56±16.60mg/mL and 664.92±107.06mg/mL; t=2.484, P=0.018 and t=2.670, P=0.011, respectively). In the M subgroup, the average time to tympanic membrane healing and tympanic pressure restoration to normal was much longer in pepsin(+) patients (17.0±2.0 days and 26.0±2.5 days, respectively) than in pepsin(-) patients (14.0±1.1 days and 22.0±1.0 days; t=3.871, P=0.001 and t=5.734, P=0.000, respectively), and the hearing level of pepsin(+) patients with OME ascended to 13.08±1.19dB, which was much lower than that of pepsin(-) patients (18.29±1.27dB; t=11.001, P=0.000). In the T subgroup, the complication rate including otorrhea and myringosclerosis was much higher in patients with high pepsin concentrations than in those with low pepsin concentrations (P<0.05). Finally, in both subgroups, the recurrence rates of OME in pepsin(+) or patients with high pepsin concentrations (34.6% [9/26] and 28.6% [10/35]) were significantly higher than those in pepsin(-) or low pepsin concentrations (10.7% [3/28] and 5.0% [1/20]; χ(2)=4.456, P=0.035 and χ(2)=4.420, P=0.036). However, pepsinogen had no significant effect on OME prognosis or recurrence. CONCLUSION: Pepsin but not pepsinogen could postpone tympanic membrane healing and pressure restoration in children with OME undergoing myringotomy and increase the incidence of recurrence and complications including otorrhea and myringosclerosis for those undergoing tympanostomy tube insertion. Therefore, pepsin could be considered a poor prognostic factor for OME, further emphasizing the important role of pepsin in OME pathogenesis.

Endoscopic diagnosis of gastric mucosal atrophy: multicenter prospective study.

BACKGROUND AND AIM: Gastric atrophy is one of the important pathological states that cause gastric cancer. As atrophic gastritis is related to the risk of gastric cancer, it is important to diagnose atrophic gastritis. In the present study, we tried to establish endoscopic criteria for atrophic gastritis. METHODS: A multicenter study of prospectively collected patients was conducted in 24 participating facilities. Two hundred and seventy-five patients received endoscopic examination and 15 endoscopic features, including diffuse redness, swelling of areae gastrica, and mucosal swelling, were evaluated. Biopsy specimens were taken from five points recommended by the Updated Sydney System, and evaluated by a single pathologist for atrophy. Sensitivity, specificity, positive predictive value, negative predictive value, area under the receiver operating characteristic curve (AUC/ROC) of each endoscopic finding to histological atrophy were calculated. Pepsinogen I/II ratios of these patients were measured and compared to the endoscopic features. RESULTS: There was no single endoscopic feature that is highly specific for histological atrophy. In the corpus, the combination of visibility of vascular pattern and swelling of areae gastrica by indigocarmine chromoendoscopy showed the highest AUC/ROC (0.83). In the antrum, the combination of visibility of vascular pattern and mucosal swelling showed the highest AUC/ROC (0.70). These endoscopic findings correlated very well to the pepsinogen I/II ratio. CONCLUSIONS: Combination of endoscopic findings can improve diagnostic accuracy, and endoscopic diagnosis of atrophy is improved especially with new endoscopic criteria, such as swelling of areae gastrica or mucosal swelling.

Gut peptide profile and chemotherapy-associated dyspepsia syndrome in patients with breast cancer undergoing FEC60 chemotherapy.

AIM: The association of motilin, ghrelin, leptin, gastrin, pepsinogen (PG) I and II with cancer chemotherapy-associated dyspepsia syndrome (CADS) was investigated in 35 patients with breast cancer receiving first cycle of 5-fluorouracil, cyclophosphamide, epirubicin (FEC60) chemotherapy. PATIENTS AND METHODS: The onset of dyspeptic symptoms on days 3 and 10 after chemotherapy identified patients with and without CADS. Gastrointestinal symptoms were scored with the Gastrointestinal Symptom Scoring Rate (GSRS) questionnaire. Gastrointestinal peptides were evaluated by enzyme-linked immunosorbent assay. RESULTS: Twenty-one patients (60%) had CADS. The area under the curve (AUC) of ghrelin was higher, whereas that of PGI, PGII and motilin were lower in patients with CADS compared to those without. In patients with CADS, the AUC of PGI and PGII negatively correlated with the GSRS indigestion cluster. CONCLUSION: Impairment of gastrointestinal motility suggested by low motilin concentrations and mucosal damage mirrored by an increase of ghrelin seem to be involved in the onset of CADS in patients during chemotherapy for breast cancer.

Clinical evaluation of pepsin for laryngopharyngeal reflux in children with otitis media with effusion.

OBJECTIVE: We sought to evaluate the clinical role of pepsin for laryngopharyngeal reflux (LPR) in children with otitis media with effusion (OME). METHODS: Pepsin/pepsinogen and fibrinogen were analyzed in fifty effusion and blood samples of children with OME using enzyme linked immunosorbent assay (ELISA). Ambulatory 24-h dual-probe pH monitoring was additionally performed in 31 children divided into two groups according to response of medical treatment. RESULTS: The effusion levels of pepsin/pepsinogen ranged from 8.5 to 1512 µg/dl and were up to 4-540 times higher than the concentrations found in plasma samples. The effusion levels of fibrinogen ranged from 0.05 to 4.1g/dl. Some effusion samples showed fibrinogen concentrations did not exceed 10 times higher than the concentrations found in plasma samples and others showed lower concentrations. The pH of effusion samples was 7.13 to 8.72. Dual-probe pH monitoring showed that 22/31 (71%) of the studied children had significant acid reflux documented by either the esophageal probe or the pharyngeal probe and all of them had LPR. There is a significant positive correlation between the level of pepsin assayed in the effusions and the number of pharyngeal reflux episodes measured by pH monitoring. CONCLUSIONS: Analysis of pepsin/pepsinogen in effusion samples of children with OME, using ELISA, can be considered as a reliable biochemical marker for assessment of laryngopharyngeal reflux.

Gastric cancer detection using gastric juice pepsinogen and melanoma-associated gene RNA.

OBJECTIVES: To develop a new method for gastric cancer detection with gastric juice using melanoma-associated gene (MAGE) RNA and pepsinogen (PG). METHODS: In total, 183 gastric juice and paired serum specimens were obtained from 134 patients with gastric cancer and 49 healthy individuals. The gastric juice specimens were analyzed with MAGE A1 to A6 nested reverse transcription-polymerase chain reaction. The serum and gastric juice PG were measured with a PG I and II immunoassay. RESULTS: The gastric juice PG I and PG I/II ratios were more accurate than those of serum. The combination test using the gastric PG I/II ratio and MAGE was the most accurate, with a sensitivity of 77.6% and a specificity of 87.8%. The sensitivity was 78.8% for stage I gastric cancer and not influenced by cancer location or pathologic type. CONCLUSIONS: The combination test is potentially an additional tool for gastric cancer detection.

Role of GERD in children with otitis media with effusion.

OBJECTIVES: To establish whether Gastroesophageal reflux disease (GERD) plays a significant role in the etiopathogenesis of otitis media with effusion (OME) patients and to find if there is any association between GERD symptoms and OME. Also, to detect presence of pepsinogen in the middle ear aspirate and to demonstrate pepsinogen band by electrophoresis. METHODS: This is a prospective study conducted in a tertiary care hospital. Middle ear effusion samples were collected from 32 children undergoing surgery for OME.The samples were measured for pepsinogen level as well as total protein content. Samples were subjected to electrophoresis study by SDS PAGE (Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis). RESULTS: A total of 21 patients out of 32 were found to have higher pepsinogen level in their middle ear effusion samples than the cut off value of 90 mg/ml.The lack of symptoms associated with GERD among the children in this study corroborates with other similar studies in the world literature. It was also statistically shown that the association between GERD score and pepsinogen level was insignificant (P = 0.512). CONCLUSIONS: OME appears to be multifactorial disease.GERD may be one of the contributing factors in the etiopathogenisis of OME.

Association between otitis media and gastroesophageal reflux: a systematic review.

OBJECTIVE: To systematically review the association between otitis media and gastroesophageal/laryngopharyngeal reflux in children. DATA SOURCES: Cochrane library, MEDLINE (1966-September 2011), EMBASE (1974-September 2011), proceedings of International Symposia on Recent Advances in Otitis Media, and reference lists of relevant selected articles. REVIEW METHODS: Studies with planned data collection, in children with chronic otitis media with effusion/recurrent acute otitis media, assessing gastroesophageal/laryngopharyngeal reflux, pepsin/pepsinogen in middle ear, or antireflux therapy, were included. RESULTS: Of 242 initial studies, 15 met inclusion criteria. The authors found a mean prevalence of gastroesophageal reflux disease in children with chronic otitis media with effusion of 48.4% (range, 17.6%-64%) and in children with recurrent acute otitis media of 62.9% (range, 61.5%-64.3%). A mean prevalence of laryngopharyngeal reflux of 48.6% (range, 27.3%-70.6%) was found in children with otitis media. Mean pepsin/pepsinogen presence in otitis media was 85.3% (range, 60%-100%) and of enzymatic activity was 34.2% (range, 14.5%-73%). Two randomized trials could not find benefit after antireflux treatment for 3 months, with an absolute rate difference (95% confidence interval) of 0.23 (0.023-0.42) and 0.13 (-0.086 to 0.34), respectively. Reporting of adverse events was limited, or absent, in most studies. CONCLUSION: The prevalence of gastroesophageal reflux disease in children with chronic otitis media with effusion/recurrent acute otitis media may be higher than the overall prevalence for children. Presence of pepsin/pepsinogen in the middle ear could be related to physiologic reflux. A cause-effect relationship between pepsin/pepsinogen in the middle ear and otitis media is unclear. Antireflux therapy for otitis media cannot be endorsed based on existing research.

Detection of pepsinogen in the neonatal lung and stomach by immunohistochemistry.

OBJECTIVE: Evaluate the hypothesis that the same pepsinogen C molecule produced in the stomach is also produced by the lung. PATIENTS AND METHODS: Pulmonary and gastric tissues collected postmortem were immunohistochemically stained for pepsinogen C and pepsinogen A. RESULTS: Sixteen patients with diverse causes of death were evaluated. Gestational age at birth ranged between 21 and 37 weeks. Pepsinogen A was detected in 12 of the 13 stomach sections, mainly in the chief cells, but not in any lung sections. Pepsinogen C was detected in all stomach sections in chief and mucus cells and in 9 of the 16 lung sections, mainly in type II pneumocytes. Pepsinogen C was not detected in the 3 lung cases with a gestational age <23 weeks. CONCLUSIONS: The same pepsinogen C molecule is produced in the stomach and in the lung. These findings potentially affect previous study results that used an enzymatic pepsin detection assay to evaluate for and associate gastroesophageal reflux disease with other morbidities.

Distribution of pepsinogen- and ghrelin-producing cells in the digestive tract of Japanese eel (Anguilla japonica) during metamorphosis and the adult stage.

Pepsinogen is the precursor form of the gastric-specific digestive enzyme, pepsin. Ghrelin is a representative gastric hormone with multiple functions in vertebrates, including the regulation of growth hormone release, stimulation of food intake and gastrointestinal motility function. We investigated chronological changes in the distribution of pepsinogen-expressing cells by in situ hybridization and ghrelin-immunoreactive cells by immunohistochemistry in the Japanese eel (Anguilla japonica) during metamorphosis from the leptocephalus sage to the elver stage. The ghrelin-producing cells first appeared in the gastric cecum and pyloric portion of the stomach in the late phase of metamorphosing leptocephali, whereas the pepsinogen-producing cells were first detected in the early phase of the glass-eel stage. These suggest that endocrine cells differentiated earlier than exocrine cells in the eel stomach. Accompanying eel development, the distribution of ghrelin-producing cells spread to the esophagus and other regions of the stomach, but not to the intestine. These results may be related to the changes in dietary habits during metamorphosis in the Japanese eel.