Purification of two secretin-releasing peptides structurally related to phospholipase A2 from canine pancreatic juice.

We previously showed that canine pancreatic juice contains a secretin-releasing factor activity. In this study, we carried out isolation of two secretin-releasing peptides (SRPs) from canine pancreatic juice. Through ultrafiltration, anion and cation exchange, and reverse-phase high-performance liquid chromatography (HPLC) steps and an in vitro bioassay in STC-1 cells, two SRPs, SRP-1 and SRP-2, were isolated and purified to homogeneity. Both SRPs dose-dependently stimulated secretin release from STC-1 cells. The results of mass spectral analysis indicated that SRP-1 and SRP-2 had molecular masses of 14,061 Da and 14,053 Da, respectively. N-terminal amino acid sequence analysis indicated that SRP-1 was identical to canine pancreatic PLA2 in the 25 residues determined; whereas SRP-2 had 71% sequence homology to the enzyme in the first 21 residues. Commercially available porcine pancreatic PLA2 dose-dependently stimulated secretin release from STC-1 cells. Porcine pancreatic PLA2 also stimulated secretin release from a secretin-producing cells-enriched preparation isolated from rat duodenal mucosa. These results suggest that pancreatic PLA2 and its related peptide may participate in regulation of secretin secretion.     

Toxins in everyday life

This article reviews the sources of exposure and health effects of common toxicants encountered by patients in primary care practice. The recognition and management of exposure to indoor and outdoor pollutants, heavy metals, pesticides, electromagnetic fields, and endocrine-disrupting chemicals are listed. A sample environmental history form is included.     

Allergic contact dermatitis from hair dye and development of lichen simplex chronicus

Those who dye their hair frequently manifest allergic contact dermatitis (ACD) from p-phenylenediamine (PPD)-containing hair dye. PPD is known to be the most frequent sensitizer in hair dye, but there has been no documentation of this sensitizer having a role in chronic dermatologic conditions. Our department experienced a case of a 62-year-old woman with lichen simplex chronicus (LSC), who complained of aggravation after hair dyeing and made such an association. We conducted a prospective and retrospective study to further evaluate the clinical associations between the two. In our prospective study, patch testing was performed in selected patients who regularly carried out hair dyeing and also had clinical manifestations of LSC. Also a retrospective examination was conducted in cases where patch testing had been performed with PPD in the past for suspected ACD and further selected cases with concurrent LSC and/or other neurodermatitis. 11 and 14 patients in our prospective and retrospective study, respectively, presented with both LSC and positive findings to PPD. 5 (45.5%) and 4 (28.6%) patients in our prospective and retrospective study showed clinical relevance from clinical improvement after stopping use and rechallenge. We report several cases of patients diagnosed as having LSC and/or prurigo nodularis who showed clinical improvement after discontinuing the use of hair dye. The suggestion can therefore be made that hair dye could be a possible aetiologic agent causing LSC in those using hair dyes.     

Gastric adenocarcinoma associated with fundic gland polyps in a patient with attenuated familial adenomatous polyposis

Familial adenomatous polyposis (FAP) is a rare autosomal dominant precancerous condition of the colon caused by mutations in the adenomatous polyposis coli (APC) tumor suppressor gene. FAP is characterized by the appearance of innumerable adenomatous polyps throughout the large bowel. Fundic gland polyps are the most common gastric lesion in FAP. It is generally believed that fundic gland polyps have little or no potential for malignant transformation in the population at large, and only a few case reports describe the development of high grade dysplasia or gastric adenocarcinoma associated with diffuse fundic gland polyposis in patients with FAP. We report the second case of gastric adenocarcinoma intimately associated with fundic gland polyposis in a family with an attenuated form of FAP. The patient had undergone routine screening per current guidelines because of his known mutation in the APC gene. This suggests that malignant transformation of fundic gland polyps in patients with FAP occur more frequently than previously believed. Current screening recommendations may not be sufficient for patients with FAP or its attenuated forms.     

Similarity in functional brain connectivity at rest predicts interpersonal closeness in the social network of an entire village

People often have the intuition that they are similar to their friends, yet evidence for homophily (being friends with similar others) based on self-reported personality is inconsistent. Functional connectomes—patterns of spontaneous synchronization across the brain—are stable within individuals and predict how people tend to think and behave. Thus, they may capture interindividual variability in latent traits that are particularly similar among friends but that might elude self-report. Here, we examined interpersonal similarity in functional connectivity at rest—that is, in the absence of external stimuli—and tested if functional connectome similarity is associated with proximity in a real-world social network. The social network of a remote village was reconstructed; a subset of residents underwent functional magnetic resonance imaging. Similarity in functional connectomes was positively related to social network proximity, particularly in the default mode network. Controlling for similarities in demographic and personality data (the Big Five personality traits) yielded similar results. Thus, functional connectomes may capture latent interpersonal similarities between friends that are not fully captured by commonly used demographic or personality measures. The localization of these results suggests how friends may be particularly similar to one another. Additionally, geographic proximity moderated the relationship between neural similarity and social network proximity, suggesting that such associations are particularly strong among people who live particularly close to one another. These findings suggest that social connectivity is reflected in signatures of brain functional connectivity, consistent with the common intuition that friends share similarities that go beyond, for example, demographic similarities.

Human social networks exhibit a high degree of homophily, such that individuals who are close together in their social network (i.e., friends or friends of friends, rather than people further removed from one another in social ties) tend to be exceptionally similar to one another with respect to physical and demographic traits, such as age, gender, and ethnicity (1). Yet, a common intuition is that friends are similar to each other in ways that go beyond readily observable and relatively coarse characteristics, such as demographics. The most common method to assess such similarities is the administration of self-report surveys measuring how people tend to think and behave (i.e., personality). However, past research has found no evidence, or only relatively weak evidence, for a relationship between similarity in personality and social network proximity (e.g., refs. 2 and 3).A separate body of research using functional MRI (fMRI) has shown that patterns of functional brain connectivity at rest comprise person-specific “fingerprints” that capture interindividual variability in a wide range of social, cognitive, and behavioral tendencies and capacities (4–10). These resting-state “functional connectomes” have also been shown to be predictive of individual differences in self-reported personality (11). Given that functional connectomes are predictive of an array of cognitive and behavioral phenotypes, interindividual similarities in functional connectomes may reflect similarities in how friends, and more generally people close to one another in their social network, think and behave. Such similarities may include those that are not sufficiently captured by widely used self-report surveys, such as measures of personality. Thus, fMRI can provide a window into the types of latent similarities that are associated with friendship. This approach is particularly promising given recent research integrating task-based fMRI and social network analysis, which has shown, for example, that when viewing videos, friends, and more generally, people closer together in their real-world social network, have exceptionally similar neural responses, which could be indicative of similarities in how friends attend to (12), understand (13), and interpret (14) the world (15, 16). Taken together with other recent work (17), these findings highlight the promise of integrating social network analysis and tools from cognitive neuroscience to improve our understanding of how individuals shape and are shaped by the real-world social networks in which they are embedded.Here, we tested if patterns of neural responding at rest (e.g., individuals’ functional connectomes) are associated with proximity between individuals in the social network of an entire village (Fig. 1). Specifically, we tested the hypothesis that greater similarity in individuals’ functional connectomes would be associated with greater proximity between those individuals in the social network. Given the large body of research demonstrating that links between interpersonal similarity in a number of cognitive, affective, and behavioral outcomes and social network proximity disappear beyond three or four “degrees of separation” (18–26), we focused our analyses on people four or fewer “degrees of separation” from one another in the village’s social network (Materials and Methods). We also tested if such relationships would persist after controlling not only for similarities in demographic characteristics but also for similarities in self-reported personality (i.e., the Big Five personality traits: extraversion, neuroticism, agreeableness, conscientiousness, and openness/intellect), which are thought to capture stable individual differences in people’s cognitive, affective, and behavioral tendencies (27). Although self-report personality questionnaires capture much variation in how people tend to think and behave, there is considerable variance in such tendencies that is unaccounted for by such questionnaires (28) and that may be encoded in individuals’ functional connectomes. Here, we tested if similarity in such latent traits is associated with proximity in a friendship network. Additionally, we examined which brain networks were particularly strongly associated with social network proximity to inform interpretations of the psychological significance of these results, as well as predictions for future research. Finally, given the well-established relationship between the physical distance between people and their distance from one another in social ties, we tested if geographic distance moderates the relationship between neural similarity and social network proximity.Open in a separate windowFig. 1.Social network characterization. Residents of a rural village located on a small island completed a survey in which they indicated their social ties with other individuals in their community. The complete social network (n = 798) of the village was reconstructed using this data, and a subset of residents (red nodes; n = 64) participated in the fMRI study. Lines (“edges”) indicate the existence of a reciprocated or unreciprocated social tie between individuals. For visualization purposes, unweighted edges were used to depict social ties. However, in our analyses, edges were weighted by individuals’ ratings of emotional closeness with one another (Materials and Methods).     

Effects of exogenous secretin on pancreatic and biliary ductal and sphincteric pressures in man demonstrated by endoscopic manometry and correlation with plasma secretin levels

An endoscopic manometric technique was used to investigate the effects of exogenous secretin on pancreatic duct, common bile duct, pancreatic duct sphincter, and bile duct sphincter pressures in 20 healthy volunteers. Synthetic secretin was infused intravenously at rates of 8.05, 16.1, 32.2, 64.4, 129, 258, and 516 ng/kg/hr, and plasma secretin concentrations were measured by a radioimmunoassay. Secretin produced a significant fall in peak and trough pancreatic duct sphincter pressures from basal values of 48.2±7.9 mm Hg (mean±sd) and 16.9±7.7 mm Hg, respectively, to 34.4±6.8 mm Hg and 11.2 ±5.8 mm Hg (P<0.005), respectively, at a mean plasma secretin concentration of 16 pg/ml (during an infusion rate of 32.2 ng/kg/hr). Higher infusion rates had no additional effect. Pancreatic duct pressure became significantly elevated above basal (11.5±4.0 mm Hg) at the two highest secretin rates. Secretin had no effect on common bile duct or bile duct sphincter pressures. Plasma secretin concentrations were within the postprandial range during the lowest four secretin infusion rates. We conclude that secretin produces selective physiological relaxation of the pancreatic duct sphincter.This work was supported by grants from the Katherine Gavriluk and Sara Jordan Funds, New England Baptist Hospital, Boston, Massachusetts; NIH Research Grant AM 25962. Dr. Carr-Locke is also in receipt of grants from the Wellcome Research Travel Fund, London, England, the Leicester Area Health Authority, Leicester, England, and the P&C Hickinbotham Trust, Leicester, England.