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Biomedical subjects

G E Bauer

Publications and source records attributed to G E Bauer.

At least 37 records · Page 2Linked to original sources
PubMed1982

Pancreatic polypeptide (PP)-like immunoreactivity in the pancreatic islets of the anglerfish (Lophius americanus) and the channel catfish (Ictalurus punctatus).

Pancreatic polypeptide (PP) immunoreactivity was demonstrated in the endocrine pancreas of the anglerfish (Lophius americanus) and the channel catfish (Ictalurus punctatus) using immunohistochemistry. In both species, PP-immunoreactive cells were localized at the periphery of endocrine tissue. In Lophius americanus, PP-immunoreactivity could be localized in the principal islet, the pyloric or secondary islet, and the mesenteric or tertiary islets. A peripheral localization of PP-immunoreactive cells having characteristic angular, or dendritic, appearance demonstrated in the above two species are a common finding among many teleost species. This peripheral localization of cells, particularly in principal (splenic) anglerfish islets, make them an ideal source of islet tissue which can be easily enriched or depleted of pancreatic polypeptide-containing cells for use in studying the synthesis and secretion of islet hormones.

Animals↗
PubMed1982

Reversal of diabetes by the isotransplantation of nicotinamide-streptozotocin-induced islet adenoma in rats.

The effect of syngeneic transplantation of islet tumors induced by streptozotocin-nicotinamide treatment into Fisher inbred diabetic rats was studied. Transplantation of 10 mg of tumor tissue under the kidney capsule of severely diabetic animals resulted in complete amelioration in 9 of 14 animals. Partial improvement was noted in three animals, whereas only one animal showed no change in diabetic condition within 4 months. Improvement in diabetes was accompanied by gain in body weight, decrease in blood sugar level and urinary glucose excretion, and normalization of glucose tolerance. After removal of the kidney containing the tumor grafts, the animals reverted to a severe diabetic condition, suggesting that the tumor graft supplied the insulin needs of the diabetic animals. The graft tissue exhibited in vitro insulin synthesis and secretion in response to 16.7 mM glucose.

Adenoma↗
PubMed1981

Characterization of proinsulin- and proglucagon-converting activities in isolated islet secretory granules.

The conversion of proglucagon and proinsulin by secretory granules isolated from both prelabeled and unlabeled anglerfish islets was investigated. Either granules isolated from tissue labeled with [3H]tryptophan and [14C]isoleucine or [35S]cysteine, or lysed granules from unlabeled tissue to which exogenously labeled prohormones had been added were incubated under various conditions. Acetic acid extracts of these granule preparations were analyzed for prohormone and hormone content by gel filtration. Both prelabeled and lysed, unlabeled secretory granules converted radiolabeled precursor peptides (Mr 8,000-15,000) to labeled insulin and glucagon. The accuracy of the cleavage process was established by demonstrating comigration of products obtained from in vitro cleavage with insulin and glucagon extracted from intact islets using electrophoresis and high-pressure liquid chromatography (HPLC). The pH optimum for granule-mediated conversion was found to be in the range of pH 4.5-5.5. Conversion of both proglucagon and proinsulin by secretory granules was significantly inhibited in the presence of antipain, leupeptin, p-chloromercuribenzoate (PCMB) or dithiodipyridine (DDP) but not chloroquine, diisopropyl fluorophosphate, EDTA, p-nitrophenyl guanidinobenzoate, soybean trypsin inhibitor, or N-p-tosyl-L-lysine chloromethyl ketone HCl. The inhibitory action of PCMB and DDP was reversed in the presence of dithiothreitol. Both membranous and soluble components of the secretory granules possessed significant converting activity. HPLC and electrophoretic analysis of cleavage products demonstrated that the converting activities of the membranous and soluble components were indistinguishable. The amount of inhibition of proinsulin and proglucagon conversion caused by 600 micrograms/ml porcine proinsulin was significantly lower than that caused by the same concentration of unlabeled anglerfish precursor peptides. These results indicate that the proinsulin and proglucagon converting enzyme(s) in the anglerfish pancreatic islet is a unique intracellular thiol proteinase(s) that may be granule membrane-associated and may require the presence of prohormone sequences in addition to the dibasic residues at cleavage sites for substrate recognition and/or binding.

Animals↗
PubMed1981

Insulin release in vitro from islet tissues and adenomas of rats treated with nicotinamide and streptozotocin. The effects of glucose.

Young male Holtzman rats injected with nicotinamide and streptozotocin develop grossly visible tumors of pancreatic islet tissue. Using an i.v. glucose tolerance test, some tumor-bearing animals exhibited a vigorous (or fast) response to glucose loading (Diabetic Index = 0.47), whereas others showed a subdiabetic (or slow) response (Diabetic Index = 2.34). In vitro perifusion studies demonstrate that tumor pieces from both groups of rats released immunoreactive insulin (IRI) in response to glucose; tumors from fast responding rats showed a rapid monophasic release of IRI (i.e., rapid transient release with little secondary phase), while tumors from slow responders released IRI in a biphasic pattern resembling that of normal islets. A population of large islet masses (or microscopic tumors), isolated from drug-treated rats by collagenase digestion of the pancreas of tumor-containing rats, exhibited glucose-stimulated IRI release that resembled the pattern of the tumor from the same animal. Isolated islets of Langerhans of ordinary size from the pancreas of tumor-bearing rats, on the other hand, usually exhibited a normal (biphasic) IRI release pattern in response to glucose. Analysis by gel filtration suggests that the predominant form of IRI released from perifused tumor preparations, under either basal or glucose-stimulated conditions, eluted at a rate corresponding to rat insulin.

Adenoma↗
PubMed1980

Evidence that somatostatin inhibits proinsulin synthesis and insulin release by isolated pancreatic islets of the rat.

Conflicting reports on the direction and magnitude of the effect of somatostatin on (pro)insulin synthesis prompted our investigation. Two assays for proinsulin synthesis were designed in which [4,5-3H]-L-leucine incorporation into proinsulin was normalized on the basis of postincubation insulin levels rather than on the number of islets incubated. Somatostatin at a concentration of 10 micrograms/ml inhibited 300 mg/dl glucose-stimulated proinsulin synthesis by 25% from 448 +/- 25 dpm/microunits insulin to 336 +/- 25 dpm/microunits insulin (disintegrations per minute in the proinsulin peak per microunit extractable insulin) (p less than 0.05). Glucagon (10 micrograms/ml) reversed the inhibitory effect of somatostatin on proinsulin synthesis from 336 +/- 25 dpm/microunits insulin to 480 +/- 44 dpm/microunits insulin (p less than 0.02). Somatostatin (10 micrograms/ml) had no significant effect on proinsulin synthesis in the presence of 70 mg/dl or 150 mg/dl glucose. Insulin release in 300 mg/dl glucose was inhibited 38% by 10 micrograms/ml somatostatin from 3.05 +/- 0.40 mU medium/mU tissue to 1.90 +/- 0.10 mU medium/mU tissue (p less than 0.01) over a 45-minute incubation period. These data suggest that somatostatin may act on glucose signal transduction on a level at which both insulin synthesis and secretion are affected. Further, the results are consistent with the hypothesis that cyclic AMP participates in mediating somatostatin effects on B-cell metabolism.

Animals↗
PubMed1980

Labetalol and propranolol in mild hypertensives: comparison of blood pressure and plasma volume effects.

Labetalol administered in a small to moderate dose (first month 400 mg/day, second month average 585 mg/day) was effective in lowering blood pressure (BP) (-21/-18 mmHg, recumbent) in 11 of 13 mild essential hypertensives over an eight-week period, despite a significant (+294 ml) increase in plasma volume. The effect of propranolol (first month 160 mg/day, second month average 234 mg/day) was significantly less on both blood pressure (-9/-9 mmHg) and plasma volume (+98 ml), although the pre-propranolol BP was lower and the final BP achieved on the two medications was comparable (labetalol 147/89 mmHg, propranolol 145/89). Six patients who continued labetalol for periods of up to 14 months had persistent plasma volume expansion. Three of these, taking a higher dose of labetalol, developed resistance to the drug's antihypertensive effect. Addition of a diuretic restored antihypertensive efficacy and led to a fall in plasma volume. No such plasma volume expansion was seen in six patients who were followed on long term propranolol therapy. Some plasma volume expansion with the combined alpha- beta-adrenoceptor blocker labetalol may be appropriate to its vasodilator action. Provided this effect is not excessive, it appears not to lead to resistance to its antihypertensive action. Small to moderate doses of labetalol would, therefore, seem effective without concomitant diuretic. Such sole use of labetalol could help minimise orthostatic symptoms which can be a major side effect of combination therapy.

Adult↗
PubMed1978

Side-effects of antihypertensive treatment: a placebo-controlled study.

1. A questionnaire, modified from Bulpitt & Dollery (1973), inquired about 20 symptoms commonly associated with hypertension or its drug therapy in 1017 subjects (age 30--69 years). Groups consisted of (a) active therapy, (b) placebo, (c) no tablets, and (d) a non-study control group. The response rate was 96% in the first three groups and 92% in group (d). 2. The subjects in groups (a), (b) and (c) constituted part of a placebo-controlled, patient-blind intervention study in the treatment of mild hypertension (The Australian National Blood Pressure Study). 3. After age/sex adjustment of the data, only sleepiness and self-assessed depression were found to be more common in the actively treated group. Impotence, failure of ejaculation and nocturia were age-related symptoms. Generally, complaint rate was higher in females. 4. The knowledge of a mild hypertensive condition or its modern drug therapy lead to very few symptoms in a non-hospital population who already have a fairly high 'complaint level'.

Adult↗
PubMed1978

Somatostatin biosynthesis occurs in pancreatic islets.

No information is at present available on the mode of SRIF biosynthesis. Since anglerfish pancreatic islet tissue is comprised of approximately 30% D cells, we have examined this tissue for SRIF synthesis . The following known differences in amino acid composition of islet peptides were used advantageously in this study: anglerfish proinsulin: Trp-0, Ile-2, Cys-6; anglerfish glucagon: Trp-1, Ile-0, Cys-0; mammalian SRIF: Trp-1, Ile-0, Cys-2. After incubating islet tissue with [3H]tryptophan and [14C]isoleucine or [35S]cystine for various time periods, proteins were extracted in 2 M acetic acid and desalted by Bio-Gel P-2 gel filtration. P-2 void volume proteins were then subjected to P-10 gel filtration and isolated by polyacrylamide gel electrophoresis (PAGE) at alkaline pH. The predominant amount of the immumoreactive SRIF in the extracts appeared in a peak eluting just before the salt volume on P-10 filtration and migrated slowly toward the cathode during PAGE. The behavior of synthetic SRIF was identical. The anglerfish SRIF immunoreactive peptide could be labeled with Trp and Cys but not Ile during incubations longer than 1 h. The Trp- and Cys-labeled peptide could be bound on columns to which the immunoglobulin fraction of antisera to SRIF had been complexed. Cycloheximide inhibited isotope incorporation into all islet proteins. These results indicate that islet SRIF is synthesized in situ. Moreover, the immunological activity, size, and charge characteristics of anglerfish islet SRIF appear to be similar to those of mammalian hypothalamic SRIF. When islets were subjected to short pulse incubations with labeled Trp and Cys, only peptides eluting in the 7,000-13,000 dalton portion of the filtration eluate became labeled. No appreciable isotope incorporation into SRIF was observed. However, when pulse incubations were followed by incubation in the presence of cycloheximide or excess unlabeled amino acids in isotope-free medium (chase), the incorporation of Trp and Cys into SRIF increased with the length of chase, suggesting the participation of a larger precursor in SRIF synthesis.

Animals↗
PubMed1977

The assessment of an antiarrhythmic agent, sustained-release procainamide, with the aid of Holter monitoring.

A sustained-release preparation of procainamide (PAD) was evaluated in a double-blind cross-over study. The preparation was found to reduce ventricular ectopic activity in all seven patients who completed the investigation in five patients the effectiveness reached the defined level of significance. A larger clinical trial to assess the long-term use of this preparation in terms of efficacy, safety and convenience is recommended.

Adult↗