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Biomedical subjects

J W Adelson

Publications and source records attributed to J W Adelson.

At least 19 recordsLinked to original sources
PubMed2001

From aardvarks to apples and orchids to ostriches: the simple evolutionary roots of a world of biological complexity and biodiversity.

Most genes arise by gene duplication, a process that has allowed the evolutionary development of new proteins and peptides with diverse functions, based on modifications of pre-existing sequences. Gene duplication creates both new DNA substrate for the encoding of information, and an information substrate for further modification of already evolved information. Because DNA "wants" to copy itself, both vertically from generation to generation and horizontally due to gene duplication, it creates a great deal of nonsense within the genome called "junk" or "selfish" DNA, which has no present function. However, it acts as an inadvertent evolutionary library and as an autocatalytic substrate for the creation of more DNA containing already-preselected sequences. The process, over evolutionary time, has created large families of related hormones, regulatory peptides, and their receptor and signaling systems, for many of which the functions have yet to be described.

Animals↗
PubMed1996

Cystic fibrosis. Gastrointestinal complications and gene therapy.

The gastrointestinal and nutritional complications of cystic fibrosis are diverse. As longevity improves in patients with cystic fibrosis, management of these complications is becoming increasingly important . This article provides overviews of the molecular aspects of the pathogenesis of cystic fibrosis, the current status of gene therapy, and a review of the gastrointestinal manifestations and nutritional care.

Adolescent↗
PubMed1996

Fundamental cellular heterogeneity of the exocrine pancreas.

Homogeneity in structure and function are broadly assumed to be characteristics of the acinar pancreatic digestive enzyme-secreting tissue. In recent years, physiological studies have shown that the pancreas stores the digestive enzymes in heterogeneously composed pools and releases them from these pools in a cyclic and secretagoguec fashion. The cellular basis for pancreatic heterogeneity is unknown; classical light and electron microscopic preparations appear homogeneous. We applied a panel of biotinylated lectins to pancreatic tissue sections; acinar cell glycoconjugates were localized in situ with peroxidase and fluorescent techniques and lectin-gold complexes. The lectin-binding properties of both fasting rabbit and rat pancreas revealed extensive and specific heterogeneity of the acinar cell population. Light and electron microscopy demonstrated highly heterogeneous labeling of the zymogen granule contents of specific acinar cells with the lectins Ulex europaeus agglutinin (UEA) and Erythrina cristagalli (ECA), which also showed preferential labeling of peri-insular acini. Other lectins also demonstrated heterogeneous binding to specific cellular regions. The striking acinar cell heterogeneity confirms earlier predictions, and may eventually prove to be the cellular basis for the secretion of different enzyme mixtures from heterogeneous sources within the pancreas.

Animals↗
PubMed1995

Pancreatic digestive enzyme secretion in the rabbit: rapid cyclic variations in enzyme composition.

The role and mechanism of nonparallel pancreatic secretion of digestive enzymes, in which enzyme proportions change in rapidly regulated fashion, remain controversial. Secretion was collected from male 2.2-kg New Zealand rabbits in 5-min intervals for 3 h under basal conditions or constant stimulation with cholecystokinin (CCK; 0.1 microgram per kg per h i.v.) or methacholine chloride (MCh; 40 micrograms per kg per h i.v.). Both CCK and MCh produced an 8-fold stimulation of protein output. Enzymes were separated by SDS/PAGE and quantitated by densitometry of Coomassie blue-stained gels. Under both basal conditions and constant MCh infusion, rapid neurosecretory-like 12-min cyclic changes occurred in the proportions of amylase, lipase I, chymotrypsinogen, and trypsinogen. During constant infusion their percentages changed as much as 10-fold, and their ratios cycled by as much as 30-fold. The mean percentage for the entire infusion period for lipase I declined > 25% with CCK or MCh, for amylase it rose approximately 30%, and for chymotrypsinogen and trypsinogen it doubled (for all, P < 0.05). CCK and MCh elicited subtly but significantly different mean enzyme percentages and enzyme ratios (P < 0.05) for amylase, chymotrypsinogen, and trypsinogen; these differences were also confirmed by regression and correlation analyses. The changes in enzyme percentages and ratios were explicitly consistent with secretagogue-caused shifts in the intrapancreatic enzyme secretory sources. Nonparallel secretion of digestive enzymes occurs routinely, even during constant stimulation, and is due to cyclic neurosecretory-like secretion from heterogeneous intrapancreatic sources.

Activity Cycles↗
PubMed1995

Stability of circadian and minor cycles of exocrine pancreatic secretion in atropine- and MK-329-infused rats.

We previously demonstrated the existence of a circadian rhythm of pancreatic secretion of fluid and digestive enzymes, which was superimposed on by a regular 1.84-h minor cycle of exocrine pancreatic secretion of fluid and total protein, amylase, and chymotrypsinogen (25). Direct control of these daily and hourly rhythms of pancreatic secretory function has not been addressed. Cholinergic and cholecystokinin (CCK)-associated influences on these two rhythms of exocrine pancreatic secretion were investigated in rats provided with pancreatic, biliary, duodenal, and jugular vein cannulas, allowing separate drainage of bile and pure pancreatic juice, as well as intravenous infusions of atropine sulfate and/or MK-329. Rats were kept in restraint cages under controlled temperature and humidity, with a regular 12-h light cycle, and divided into five groups. The first group of fed rats was constantly infused with 200 micrograms.kg-1.h-1 atropine, the second with 0.5 mg.kg-1.h-1 MK-329, and the third with both. In the group where both drugs were simultaneously infused, 500 micrograms.kg-1.h-1 atropine was intraperitoneally administered, whereas MK-329 was infused by intravenous cannula. Two groups consisted of fasted rats, of which one was also given atropine (100 micrograms.kg-1.h-1). Three-day experiments were performed separately with fed rats, and 2-day experiments were performed with fasted rats; atropine and/or MK-329 infusion, starting on day 2, was constant over 48 h in both fed and fasted rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Maternal knowledge, attitude and practices regarding childhood acute respiratory infections in Kumasi, Ghana.

Acute respiratory infections (ARI) are a major cause of paediatric mortality and morbidity, particularly when associated with delays in treatment. A study of mothers' knowledge, attitudes and practices regarding ARI in their children aged less than 5 years was conducted in an urban Ghanaian population. One hundred and forty-three women traders were interviewed in open air markers in Kumasi, Ghana. Based on Western standards, there was a poor maternal understanding of the aetiology of ARI. A variety of herbal and home care therapies, including some which have potentially harmful effects, were routinely employed for the prophylaxis and treatment of ARI. For example, castor oil and enemas (25.9%) were reported as agents to prevent ARI, and antibiotics were prescribed by the parents in 39.9% for treating coughs. While the mothers exhibited an understanding of symptoms which differentiate between mild and severe ARI, a substantial number indicated that they would delay accessing a health care facility in the presence of the following symptoms which signify severe respiratory distress: dyspnoea (11.2%); tachypnoea (18.9%); chest retraction (21.7%); cough, fever and anorexia (30.0%); and cough, fever and lethargy (57.3%). These findings support the need for an ARI health education programme in Ghana.

Acute Disease↗
PubMed1993

Circadian rhythm of exocrine pancreatic secretion in rats: major and minor cycles.

The circadian variations of exocrine pancreatic secretion were studied in conscious rats provided with pancreatic, biliary, duodenal, and peritoneal cannulas and kept in restraint cages under controlled conditions, with a regular 12-h light cycle. Rats were divided into fed and fasted groups, and experiments were performed separately. During a 4-day post-surgical recovery period, rats were fed ad libitum. During the experiment, fed rats had free access to food and water. Food, but not water, was denied fasted rats 10 h before the experiment and for its 48-h duration. During the experiment, pancreatic juice was continuously collected for 4 and 2 days from fed and fasted rats, respectively. Every 30 min, a 20-microliters aliquot of sampled pancreatic juice was removed for total protein, amylase, and chymotrypsinogen assays. The remainder was mixed with bile collected simultaneously, and the mixture was recirculated into the duodenum. Over the 4- and 2-day periods there was a clear circadian rhythm of 24-h duration; for all measured parameters, secretory rates increased in the dark period and decreased during the light period. This major circadian rhythm was unexpectedly found to be superimposed on by a remarkably constant neurosecretory-like minor cycle of 2-h duration present in both fed and fasted states. The amplitude of the minor cycle was diminished by fasting. The outputs of fluid, total protein, and amylase were found to be only modestly correlated with each other, whereas chymotrypsinogen output was virtually completely independent of the others. The results suggest that the spontaneous major increase of exocrine pancreatic secretion in the dark was at least partially independent of food intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Activity Cycles↗
PubMed1990

The amino acid sequence of chymodenin, a hormone-like peptide from porcine duodenum, is identical to cytochrome C-oxidase, peptide VII.

The amino acid sequence of chymodenin, a hormone-like peptide from porcine duodenum is reported. The molecule is known to rapidly alter the proportions of digestive enzymes secreted by the rabbit pancreas in vivo and in vitro, by selection of the specific intra-pancreatic source from which the preset mixture of digestive enzymes is secreted. The sequence is identical to that of cytochrome C-oxidase peptide VII (cCoVII) from bovine heart, with the exception of a substitution of threonine for alanine at position 6 and a second substitution of alanine for threonine at position 71. Disulfide bridges link positions 29-64 and 39-53. cCoVII-chymodenin has a pentapeptide (-Ala-Glu-Gly-Thr-Phe-) near the carboxy-terminus which is immediately preceded by an -Arg-Arg- sequence in the porcine and bovine sequences of cCoVII. This peptide is identical to a pentapeptide found close to the amino terminus of the hormones gastric inhibitory peptide (GIP) and glucagon-like peptide I. The identity to cCoVII means chymodenin as isolated is itself unlikely to be a gastrointestinal hormone. However, the partial commonality of sequence with the glucagon-secretin family immediately adjacent to a pro-hormone-like activation site, and the specific actions on the exocrine pancreas, means that the molecule probably mimics the natural actions of an as-yet uncharacterized member of the glucagon family, which exerts a unique action on exocrine pancreatic secretion.

Amino Acid Sequence↗
PubMed1989

Heterogeneity of the exocrine pancreas.

The exocrine pancreas is generally considered to be a homogeneous organ at the morphological and functional levels. Recent work, reviewed here, has provided multiple reasons to question this. Morphologically, differences have been found in cell size and digestive enzyme content in "peri-" vs. "teleinsular" acini by methods including acinar separation, enzyme assay, and both light and electron microscopic immunocytochemistry. Detection of several blood group antigens in human acinar tissue showed striking cellular heterogeneity in a mosaic pattern. Stimulation of pancreatic lobules by specific secretagogues and separation of individual zymogen granules with microfluorometric assay of enzyme content also confirmed heterogeneity at the lobular and organellar level. Functionally, evidence that nonparallel digestive enzyme secretion can be taken as direct support for acinar heterogeneity is reviewed, as is the work leading to direct demonstration of secretagogue-specific heterogeneous sequestration and storage of nascent digestive enzyme protein. A general overview of pancreatic acinar cell specificity is presented; the model incorporates temporal changes in secretion from eligible acini, with secretagogue specificity of whole acini containing specific preset mixtures of digestive enzymes.

Animals↗
PubMed1987

Proteins are secreted from heterogeneous prestored sources in the exocrine pancreas.

Recent studies demonstrating nonparallel regulated secretion of prestored digestive enzymes in tightly linked groups consistent with the exocytosis mechanism led us to predict that digestive enzymes would be found to be secreted from heterogeneous sources within the exocrine pancreas (J. W. Adelson, and P.E. Miller, Science Wash. DC 228: 993-996, 1985). We explored whether the gland was heterogeneous with respect to its sources of prestored secretory proteins with a double isotopic label method not dependent on activity of secreted digestive enzymes. Rabbit pancreatic proteins were double labeled in vivo by injection of each animal with chemically identical but isotopically distinct mixtures of 3H- and 14C-labeled amino acids, which were administered separately or together on consecutive days after partial depletion of prestored proteins by administration of cholecystokinin (CCK), methacholine chloride, or saline in a protocol in which order of both isotope and secretagogue administration was varied. Three days after labeling, proteins were recovered by collection from cannulated pancreatic ducts of anesthetized animals after stimulation with alternating increasing doses of CCK and methacholine chloride. Pooled secretory data were analyzed to determine whether secretagogue pretreatment resulted in specific and heterogeneous sequestration of proteins after synthesis; data after final secretory stimulation with methacholine chloride and CCK were individually analyzed to determine whether presequestered proteins were mobilized from heterogeneous compartments during secretion. Correlation and regression analysis of isotopic outputs and variance analysis of specific radioactivities of secreted proteins showed sequestration into and secretion from heterogeneous pools of secretory proteins, directly confirming out hypothesis. These results provide a cell biological mechanism explaining regulated nonparallel secretion of digestive enzymes.

Animals↗
PubMed1986

Purification and characterization of chymodenin. A hormone-like peptide from porcine duodenum.

Chymodenin, a hormone-like duodenal peptide which rapidly alters the proportions of secreted pancreatic digestive enzymes to a mixture relatively richer in chymotrypsinogen than that found in basal secretion, has been purified to homogeneity. The starting material was an acidic methanol-soluble, neutral pH-insoluble fraction of an acetic acid extract of porcine duodenum; the purification consisted of cation-exchange chromatography on SP-Sephadex and CM-Sephadex in ammonium bicarbonate gradients, and gel filtration on Sephadex G-75 in dilute acetic acid. The yield of material was followed by radioimmunoassay. Homogeneity was determined from chymodenin's behavior in disc gel electrophoresis in an acidic counter-migration-of-dye system, sodium dodecyl sulfate-urea gels, gel filtration, dansyl-Edman reaction, reversed-phase high pressure liquid chromatography, isotachophoresis, and sedimentation equilibrium ultracentrifugation. The electrophoretic mobility, the molecular weight of 9,000-10,000, and the biological activity differed from those of other gastrointestinal peptide hormones. The amino acid composition was unique. Chymodenin is the first purified hormone-like substance reported capable of altering the composition of the mixture of secreted digestive enzymes, independent of the stimulation of massive pancreatic protein output.

Amino Acids↗
PubMed1985

Pancreatic secretion by nonparallel exocytosis: potential resolution of a long controversy.

The idea that pancreatic digestive enzyme secretion can occur in a nonparallel manner has been controversial because of its presumed incompatibility with the exocytosis secretory mechanism. Correlation and regression analysis of enzyme output by the rabbit pancreas after it is stimulated with cholecystokinin and chymodenin revealed that digestive enzymes are secreted in a highly linked fashion, compatible with exocytosis and with nonparallel secretion. Thus, exocytosis and nonparallel secretion are not contradictory processes, but rather nonparallel secretion is due to exocytosis from heterogeneous sources within the pancreas.

Amylases↗
PubMed1985

Thrombosis as a complication of inflammatory bowel disease in children: a report of four cases.

Thrombosis and thromboembolism have rarely been reported in inflammatory bowel disease (IBD) in children. Four cases of thrombosis, two with apparently serious thromboembolism, are reported in three patients with ulcerative colitis and one with Crohn's disease. Two patients were on steroid treatment at the time of the initial thromboembolic event. Thrombosis may result from a "hypercoagulable state" that occurs in IBD, brought about by a combination of altered clotting factors and the presence of a thrombogenic gastrointestinal mucosa, the risk of which is increased by steroid medications. Children and adolescents with IBD are at risk for serious thromboembolic complications.

Adolescent↗
PubMed1978

Studies on intestinal enzyme secretion; the action of cholecystokinin-pancreozymin, pentagastrin and bile.

Intravenous administration of 1 U cholecystokinin-pancreozymin (CCK-PZ) to rats caused the release of enteropeptidase, alkaline phosphatase (AP), and sucrase to the intestinal lumen in the absence of a concomitant increase in luminal DNA. Thus, the hormone elicited hydrolase secretion was not due to cell desquamation. Pentagastrin also stimulated hydrolase release. Following CCK-PZ administration enteropeptidase was released preferentially over sucrase and AP and showed a linear correlation with total protein output. The specific enteropeptidase activity was higher in the perfusate following secretion than in the mocosa. Enteropeptidase was found mainly in soluble form in both mucosa and perfusate; addition of bile following enteropeptidase release further increased its activity. In contrast, sucrase and AP were found mainly in insoluble form in both mucosa and perfusate and their specific activities were higher in the mucosa. The presence of bile rendered both sucrase and AP more soluble in the perfusate. The data indicate that enteropeptidase is released by a specific secretory process and that its subcellular site of origin is different from that of sucrase and AP. By eliciting the coordinated release of trypsinogen, enteropeptidase and bile, CCK-PZ plays a central role in the initiation of protein digestion.

Alkaline Phosphatase↗