Magnetic resonance imaging. Detecting enzyme activity in live animals.
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Animals↗
Biomedical subjects
E Straus
Publications and source records attributed to E Straus.
IV. Neuroanatomy of Williams syndrome: a high-resolution MRI study.
Williams syndrome (WMS), a genetic condition resulting from a contiguous deletion on the long arm of chromosome 7, is associated with a relatively consistent profile of neurocognitive and neurobehavioral features. The distinctiveness and regularity of the profile of learning and behavioral characteristics in this genetic condition suggests that underlying neurobiological correlates may be identifiable. In this initial study, we report findings derived from a high-resolution neuroimaging study of 14 young adult subjects with WMS and an individually matched normal control group. Compared to controls, subjects with WMS were noted to have decreased overall brain and cerebral volumes, relative preservation of cerebellar and superior temporal gyrus (STG) volumes, and disproportionate volume reduction of the brainstem. Analyses also suggested that the pattern of cerebral lobe proportions in WMS may be altered compared to normal controls with a greater ratio of frontal to posterior (parietal+occipital) tissue. Assessment of tissue composition indicated that, relative to controls, individuals with WMS have relative preservation of cerebral gray matter volume and disproportionate reduction in cerebral white matter volume. However, within the cerebral gray matter tissue compartment, the right occipital lobe was noted to have excess volume loss. Combined with our growing knowledge of the function of genes in the commonly deleted region for WMS, more detailed information regarding the structure and function of the WMS brain will provide a unique opportunity for elucidating meaningful correlations amongst genetic, neurobiological, and neurobehavioral factors in humans.
Adult↗
Gastrointestinal hormones.
Solomon A. Berson, M.D., the first Murray M. Rosenberg Professor and Chair of the Department of Medicine at Mount Sinai from 1968 until his death in 1972, and Rosalyn S. Yalow, Ph.D., 1977 Nobel Laureate in Medicine or Physiology and Solomon A. Berson Distinguished Professor-at-Large, brought meticulous quantitation and new vistas to all of clinical medicine and biomedical science through the application of their technique of radioimmunoassay. I was fortunate to know and work with them for many years. In 1972, while I was an NIH Fellow in gastroenterology at Mount Sinai, Dr. Berson suggested that I pursue my research in their laboratory at the Bronx Veterans Administration Hospital. Dr. Berson died one month after I began my research in the Bronx. Yalow and Berson had already discovered big gastrin (G-34), but much work with gastrin remained to be done. Challenging work with secretin, cholecystokinin, and a host of other gut peptides, would keep the Mount Sinai group at the forefront of this exciting field.
Gastrointestinal Hormones↗
New frontiers in gastrointestinal hormones.
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Gastroenterology↗
Cat gastrinoma and the sequence of cat gastrins.
Following the curative resection of a pancreatic gastrinoma in a cat, gastrin peptides were purified from the tissue and sequenced. The sequence of cat gastrinoma G17 (18-34) confirms the previously published sequence. The sequence of cat G34 (1-34) is reported for the first time. The NH2-terminal portion of cat G34 differs from that of dog by having a Q (Gln) for L (Leu) at position 10 from the NH2-terminus.
Amino Acid Sequence↗
The Brooklyn gastrinomas.
During the past seven years we have diagnosed and treated 12 patients with the Zollinger-Ellison syndrome (ZES), some of whom have had virtually unique manifestations. Among these are a 74-year-old man who was cured after endoscopic removal of a submucosal duodenal gastrinoma, suggesting the usefulness of an operative approach using intraoperative endoscopic transillumination; a 33-year-old man in whom the manifestations of ZES brought him into conflict with the law; and a 10-year-old domestic cat who was cured surgically, the gastrinoma providing material for the first determination of the sequence of cat gastrins.
Adult↗
Gastropathy and ketoconazole malabsorption in the acquired immunodeficiency syndrome (AIDS).
STUDY OBJECTIVE: To correlate oral ketoconazole absorption with gastric acid secretion in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Prospective measurement of maximal acid output and oral ketoconazole absorption with and without 0.1-N hydrochloric acid. SETTING: Hospital in-patients in university medical center. PATIENTS: Ten consecutive male patients with AIDS. INTERVENTION: Maximal acid output was determined after pentagastrin stimulation in all patients. Serum ketoconazole levels were measured the day after ingestion of a 200-mg ketoconazole tablet in the fasted state. On the final day, ketoconazole was ingested with 200 mL of 0.1-N hydrochloric acid. MEASUREMENTS AND MAIN RESULTS: Maximal acid output was below 15 mEq/h in 7 of 10 patients. In all 7, the area under the serum ketoconazole concentration-time curve was below normal (1.4 +/- 0.9 mg/h.L; mean +/- SE), and absorption was normalized by hydrochloric acid (9.9 +/- mg/h.L). Two of three patients with maximal acid outputs above 15 mEq/h had normal ketoconazole absorption (15.1 +/- 6.7 mg/h.L). CONCLUSIONS: The bioavailability of oral ketoconazole is reduced in patients with AIDS, largely as a result of gastric hypochlorhydria. Ketoconazole tablets should therefore be given with acid in these patients.
Acquired Immunodeficiency Syndrome↗
Stimulation of human pancreatic polypeptide and gastrin by Boots and GIH secretin: in vitro and in vivo studies.
We have studied the concentration of various gastrointestinal peptides in a crude porcine secretin (Boots) preparation and pure natural porcine secretin (GIH, Kabi) preparation. Boots secretin was found to contain 140.3 ng secretin, 1.27 ng human pancreatic polypeptide (hPP), 1.03 ng gastrin, 137.4 ng cholecystokinin (CCK), 241 microU insulin, 1.86 ng vasoactive intestinal polypeptide (VIP), 2.22 ng glucagon and 6.60 ng somatostatin (SRIF) per Crick Harper unit Boots secretin. Sephadex gel filtration demonstrated that the immunoreactivity was due to the hormone per se. GIH secretin contained 240 ng secretin per clinical unit (CU) and less than detectable concentrations of hPP, gastrin, CCK, insulin, VIP, glucagon and SRIF. To determine the clinical significance of having contaminating peptides in Boots secretin, we investigated the effect(s) in 4 subjects. Determined in a highly gastrin-specific assay, the mean plasma gastrin response to Boots secretin administration was slightly, but not significantly greater than the GIH secretin response at 1 and 2.5 minutes. However, in some subjects false positive elevations in plasma gastrin immunoreactivity occurred when some commercially available kit gastrin assays were employed. After intravenous injection of Boots secretin, mean plasma hPP levels rose significantly more than after GIH secretin administration. The mean peak plasma insulin level after GIH secretin administration was significantly higher than after Boots secretin. Neither secretin preparation caused a change in plasma glucose, glucagon and SRIF levels. From these results, it is suggested that GIH secretin be used as the preparation of choice in provocative testing for diagnosing gastrinoma or deficiencies of exocrine pancreatic function.
Adult↗
Distribution, molecular forms, and bioactivity of immunoreactive gastrin in a patient with metastatic gastrinoma.
A patient with metastatic gastrinoma whose plasma gastrin ranged from 7.6 nmol X ml-1 at presentation to 18.9 nmol X ml-1 just before death 4 yr later has been studied. The presence of such high circulating levels facilitated study of the biological and immunological activities as well as the molecular forms of gastrin in plasma, ascitic fluid, urine and cerebrospinal fluid. The results indicate: 1) the 34 amino acid gastrin (G34) was the only molecular form detectable in the body fluids studied; 2) bioactivity of G34 is maintained despite passage across the renal endothelium and the blood brain barrier; 3) the blood brain barrier significantly limits diffusion of G34.
Adult↗
Increases in cellular calcium concentration stimulate pepsinogen secretion from dispersed chief cells.
Intracellular calcium concentration ([Ca]i) and pepsinogen secretion from dispersed chief cells from guinea pig stomach were determined before and after stimulation with calcium ionophores. [Ca]i was measured using the fluorescent probe quin2. Basal [Ca]i was 105 +/- 4 nM. Pepsinogen secretion was measured with a new assay using 125I-albumin substrate. This assay is 1000-fold more sensitive than the widely-used spectrophotometric assay, technically easy to perform, rapid, and relatively inexpensive. The kinetics and stoichiometry of ionophore-induced changes in [Ca]i and pepsinogen secretion were similar. These data support a role for calcium as a cellular mediator of pepsinogen secretion.
Aminoquinolines↗
A new rapid gastrin radioimmunoassay.
A 45-min gastrin assay with a minimum detection limit of 50 pg/ml plasma has been developed which makes use of delayed addition of labeled tracer. The precision of the rapid assay compares favorably with standard methods for measurement of plasma gastrin concentrations in excess of 100 pg/ml. The rapid method can be used for emergency preoperative diagnosis of Zollinger-Ellison syndrome and as an aid in localizing gastrinomas before or during surgery.
Fasting↗
Comparison of mammalian VIP bioactivities in dispersed acini from guinea pig pancreas.
Mammalian VIP is identical in pig, cow, human, rat, dog and goat but differs in the guinea pig (GP) in positions 5, 9, 19, and 26. We now demonstrate that GP, goat, rat and synthetic mammalian VIP are indistinguishable in their inhibition of binding of 125I-labelled synthetic VIP to dispersed acini from GP pancreas and that GP, pig, dog, goat and synthetic VIP are also similar in their efficacy and potency in stimulating amylase release from these acini. Thus in spite of the differences in amino acid sequence, GP VIP appears to have full biologic potency in its action on dispersed acini from GP pancreas.
Animals↗
Low acid output in Pima Indians. A possible cause for the rarity of duodenal ulcer in this population.
Duodenal ulcer has not been observed in full-heritage Pima Indians, while gastric cancer is relatively frequent. To investigate possible underlying factors for this phenomenon, we determined gastric acid output, gastric emptying rate, and plasma levels of gastrin, pepsinogen I, and pepsinogen II in apparently healthy Pima Indians and in Caucasian controls. The Pimas had significantly lower basal and stimulated outputs of gastric acid and higher fasting and postprandial plasma gastrin concentrations than the Caucasians. Plasma pepsinogen I levels were similar in the two groups, but plasma pepsinogen II was significantly higher and the ratio of pepsinogen I to pepsinogen II was significantly lower in the Pima Indians. In addition, gastric emptying of acaloric liquid meal was significantly delayed in the Pimas. The results suggest that the absence of duodenal ulcer in Pima Indians may be related to low gastric acid production and a slow rate of gastric emptying in this population. The associated findings of hypergastrinemia, hyperpepsinogenemia II, and a low ratio of pepsinogen I to pepsinogen II suggest that the hypochlorhydria may reflect an increased prevalence of chronic gastritis in full-heritage Pima Indians. This, in turn, could represent a risk factor for the development of gastric cancer in this population.
Achlorhydria↗
Gastric function and obesity: gastric emptying, gastric acid secretion, and plasma pepsinogen.
Because rapid gastric emptying and a shortened satiety period might contribute to development of obesity, this study compared gastric emptying of acaloric liquid, gastric acid production, and plasma levels of gastrin and pepsinogen I (PG I) and II (PG II) among obese and nonobese Pima Indians. Rates of fractional gastric emptying and of gastric acid secretion were similar in the two groups, basally and after an acaloric liquid meal. Basal and postprandial plasma gastrin levels did not differ significantly in obese and nonobese Pimas , but peak betazole-stimulated gastric acid output was greater in the obese group, except when normalized by body weight. The plasma PG I and PG II concentrations and PG I/PG II ratio did not differ significantly between the two groups, but the PG I/PG II ratio had a positive correlation with peak acid output. No correlation was found between fractional gastric emptying rate and degree of obesity. We conclude that an increased gastric emptying rate for liquid does not contribute to the pathogenesis of obesity in Pima Indians.
Adolescent↗
Inhibitory effect of intragastric glucose on gastric acid secretion and gastric emptying of liquids in man. Role of endogenous somatostatin, gastrin, and insulin.
Intragastric glucose inhibits gastric acid secretion and gastric emptying in man. To determine if these effects are mediated by somatostatin--a known inhibitor of gastric acid production, gastrin secretion, and gastric motility--the plasma somatostatin-like immunoreactivity (SLI) levels were determined in healthy human subjects after an intragastric load of 30% glucose solution. These findings were compared with results after an instillation of distilled water. Following the glucose load, the intragastric acid concentration, the acid output, and the fractional gastric emptying rate declined significantly (P less than 0.01) before either the plasma glucose or plasma insulin levels had increased. Neither the gastrin nor SLI plasma concentrations changed after the water or glucose load. These findings suggest that the suppression of gastric acid secretion and inhibition of the rate of gastric emptying that occur with intragastric glucose are mediated by factors other than changes in the peripheral circulating levels of SLI, gastrin, insulin, or glucose.
Adult↗
The role of CCK-like peptides in appetite regulation.
The physiological dose levels for the classically defined functions of CCK peptides, i.e., their effect on gall bladder contraction and release of pancreatic enzymes, are well established. However, the reported effects of peripheral administration of these peptides on regulation of satiety are achieved only at levels greatly in excess of the physiological range achieved in response to feeding. Thus, endogenous peripheral CCK alone would appear not to be the physiological satiety factor. The observations by Della-Fera et al. (1981) that lateral ventricular infusion into sheep of antibody to CCK results in increased feeding, if confirmed by other investigators and in other species, is the strongest evidence for a CSF-mediated role for CCK peptides in the regulation of satiety. However, numerous reports now delineate a variety of other CNS functions for these peptides. With so many effects reported, it is difficult at present to be certain which are real, which are direct or acting indirectly through another system, or which are the physiologically important functions. It can be expected that another decade will be required to sort out and define fully the multiple roles of CCK peptides that are synthesized independently in mucosal and in neuronal tissues.
Animals↗
Hypergastrinemia in obese noninsulin-dependent diabetes: a possible reflection of high prevalence of vagal dysfunction.
To elucidate the relation of noninsulin-dependent (type II) diabetes mellitus to plasma levels of gastrin, pepsinogen I, and pepsinogen II, gastric acid secretion, and gastric emptying, we studied diabetic and nondiabetic obese Pima Indian subjects. Fasting and postprandial plasma gastrin concentrations were significantly higher (P less than 0.02) in diabetic than in nondiabetic subjects, but gastric acid outputs basally, after an acaloric liquid meal, and in response to betazole were similar in the two groups. Plasma pepsinogen I and pepsinogen II levels were also similar in both groups. A significant negative relation (r = -0.84; P less than 0.01) was found between basal gastrin levels and gastric acid production in nondiabetic Indians, but not in diabetic Pimas. The fractional gastric emptying rate of an acaloric liquid meal was significantly decreased in diabetic Pimas (P less than 0.01); and at least one test showing abnormal vagal function, as estimated by the Valsalva maneuver, heart rate changes between deep expiration and inspiration, and postural hypotension, was found in every diabetic subject. These findings suggest that hypergastrinemia in type II diabetes is not related to hypochlorhydria, but, instead, results from autonomic dysfunction with slow gastric emptying.
Adult↗
Secretin responses to feeding and acid load.
Secretin can be readily concentrated from 10 ml of plasma by adsorption to and elution from octadecylsilyl silica columns (C18 Sep-Pak cartridges). This method of concentration is more expedient than either ethanol extraction or adsorption to and elution from precipitated silica (QUSO G32) and permits detection of secretin in plasma at concentrations of 1 pg/ml or greater. Basal secretin in normal subjects was found to be less than 4 pg/ml of plasma. In response to an STM, plasma secretin increased on the average to twice the fasting level, but in response to an oral SAL, it generally increased about 10-fold.
Acids↗