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Biomedical subjects

W A Murphy

Publications and source records attributed to W A Murphy.

At least 127 records · Page 7Linked to original sources
PubMed1985

The thoracic aorta studied by MR imaging.

Thirty-three patients with a variety of disorders of the thoracic aorta (aneurysm, dissection, Marfan syndrome, coarctation/pseudocoarctation, L-transposition, and Takayasu disease) were evaluated with magnetic resonance (MR) imaging. MR imaging delineated the presence and extent of thoracic aortic aneurysms and showed the relationship of the aneurysm to arch vessels; it also demonstrated intimal flaps and individual lumina in types A and B aortic dissection. Dilation of the ascending aorta in Marfan syndrome and focal narrowing of the aorta in coarctation were well visualized. The anteroposterior and side-to-side relationships of the aorta and pulmonary artery in L-transposition were demonstrated, as were aortic wall thickening and branch vessel narrowing in Takayasu arteritis. Initial experience suggests that MR imaging may provide a noninvasive method for evaluating thoracic aortic disease. Limitations include inferior spatial resolution, occasional difficulty in imaging the entire region of interest in one section, lack of signal from calcifications, and inability to monitor critically ill patients.

Adolescent↗
PubMed1985

US of the biceps tendon apparatus.

High-resolution real-time sonography of the biceps tendon was performed on 80 patients referred for shoulder arthrography. The arthrograms and sonograms were compared at the levels of the biceps tendon groove and distal tendon. Sonography and arthrography were equally successful in facilitating the evaluation of the bony configuration of the biceps tendon groove, but sonography gave a superior image of the biceps tendon within the groove. In 16 patients, biceps tendon sheath effusions or swelling was detected using sonography; 15 of these patients had associated pathologic conditions elsewhere in the joint. Arthrograms did not disclose a biceps tendon or sheath abnormality in any of these patients. We conclude that sonography could be the imaging method of choice in patients with suspected biceps tendon lesions and that the presence of a biceps tendon or sheath abnormality indicates an increased likelihood of abnormalities elsewhere in the joint.

Adolescent↗
PubMed1985

Adenohypophyseal response to hypophysiotropic hormones in male obese Zucker rats.

Description of the recessive, homozygote obese Zucker rat (fafa) includes disorders of growth and reproduction. The aim of this study was to compare responsiveness of adenohypophyseal cells, obtained from male fafa rats and from their lean siblings, to growth hormone-releasing factor (GRF) and to luteinizing hormone-releasing hormone (LHRH). Pituitary cells were cultured for 4 days and were then challenged with either GRF-29 (the NH2-terminal 29 amino acid GRF peptide that expresses full biological activity of its parent 44 amino acid molecule) or [D-Trp6]LHRH (LHRH-A, an LHRH agonist). Medium was assayed for growth hormone (GH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) by radioimmunoassay. Dose-response curves were compared using the computer program ALLFIT. The median effective GRF-29 concentration (EC50) computed for hypophyseal cells cultured from lean animals (0.30 +/- 0.01 fM; means +/- SE of 4 experiments) was less (P less than 0.01) than that calculated for cells obtained from fafa rats (15.8 +/- 6.7 fM). In contrast, cells derived from lean littermates required a larger (EC50) concentration of LHRH-A than did gonadotrophs cultured from obese rats [58.2 +/- 1.2 vs. 10.7 +/- 1.2 pM (P less than 0.01) and 59.4 +/- 10.4 vs. 15.7 +/- 7.6 pM (P less than 0.05)] to secrete LH and FSH, respectively. Our data describe an attenuated pituitary response to GRF-29 and an enhanced response to LHRH-A in the fafa.

Animals↗
PubMed1985

An extremely sensitive in vitro model for elucidating structure-activity relationships of growth hormone-releasing factor analogs.

An improved rat anterior pituitary primary cell culture technique for studying GH-releasing activity of human pancreatic GH-releasing factor (hpGRF) and its analogs is described. Male pituitaries, dispersed by a combination of trypsin digestion and mechanical agitation, were plated at a density of 200,000 cells per well and cultured for 4 days. The attached cells were then stimulated with synthetic hpGRF which was comprised of the first 29 residues of the larger, originally isolated forms and which was amidated at the C-terminal (hpGRF-29). Analogs of hpGRF-29 which were modified in positions 1, 2, 3, or 7, and other secretagogues were similarly tested. Medium was collected after 3 h, and secreted hormone was measured by RIA. The cells were extremely sensitive to hpGRF-29 stimulation, and this effect was specific. The minimal effective dose of hpGRF-29 was an unprecedented 0.4 X 10(-15)M. No stimulation of LH, FSH, or PRL by hpGRF-29 was observed. Bombesin and vasoactive intestinal peptide were ineffective in stimulating GH release. [D-Trp6]LHRH (a potent LHRH agonist), also did not release GH but did stimulate secretion of LH and FSH at doses ranging from 0.4 X 10(-10)M to 1.0 X 10(-9)M. Responses of the cells to hpGRF-29 analogs were characterized by distinct heterologous dose-response curves. [D-Ala2]hpGRF-29 was 50 times more active than its parent 29-amino-acid peptide. [D-Thr7]hpGRF-29, another analog that differed from hpGRF-29 by the insertion of a D-isomer for the naturally occurring L-residue, was about 10,000 times less effective in stimulating GH secretion than was hpGRF-29 itself. Potencies of these and other analogs with respect to GH release in vitro were similar to those estimated in vivo. Thus, this primary cell culture provides an extremely sensitive, selective, and reproducible system for studying hpGRF structure-activity relationships. Further, such tremendous sensitivity to hpGRF can provide a system to study changes in pituitary sensitivity to hpGRF during different physiological states.

Amino Acid Sequence↗
PubMed1985

Prolonged inhibition of growth hormone secretion by peripheral injection of bombesin is mediated by somatostatin in the rat.

Peripherally injected bombesin inhibits GH secretion in conscious, freely moving rats and in sodium pentobarbital-anesthetized rats. This inhibition of GH secretion is unusually prolonged, lasting up to 90 min after a single ip injection. The duration of inhibition of GH secretion by bombesin is greater than that observed for somatostatin (SRIF) in the same bioassay. The inhibition of GH release occurs concomitantly with stimulation of gastrin release and is independent of stimulatory effects of bombesin on plasma glucose. The structurally related mammalian gastrin-releasing peptide also inhibits GH secretion in the pentobarbital-anesthetized rat after peripheral injection. Peripherally administered bombesin blocks GH-releasing factor stimulation of GH secretion. Prior treatment of pentobarbital-anesthetized rats with SRIF-specific anti-serum blocks the inhibitory effect of bombesin on GH secretion. No effect of bombesin on GH secretion was observed in primary cultures of rat anterior pituitary cells. These data suggest that peripherally administered bombesin stimulates SRIF secretion, most probably of hypothalamic origin, which, in turn, inhibits pituitary secretion of GH. This sensitivity of the hypothalamus to a peripherally rather than centrally administered peptide has important mechanistic and therapeutic implications.

Animals↗
PubMed1985

Sonographic detection of rotator cuff tears.

Thirty-nine consecutive patients referred for shoulder arthrography underwent shoulder sonography to determine the ability of sonography to detect rotator cuff tears. Fifteen patients had arthrographically proven rotator cuff tears. Of these, 14 were detected by sonography, for a sensitivity of 93%. The three sonographic criteria indicative of rotator cuff tear were (1) discontinuity in the normal homogeneous echogenicity of the rotator cuff; (2) replacement of the normal homogeneous echogenicity by a central echogenic band; and (3) nonvisualization of the cuff. Twenty patients had normal sonographic examinations, 19 of which were normal by arthrography. Therefore, the predictive value of a negative sonogram was 95%. On the basis of these findings, sonography can provide a noninvasive means of screening patients with suspected rotator cuff tears.

Adult↗
PubMed1985

Hexabrix as a contrast agent for ascending leg phlebography.

Fifty patients were analyzed after a randomized double-blind study comparing Hexabrix and Hexabrix-20 in ascending phlebography. Measures of safety and patient tolerance indicated that both concentrations of Hexabrix appeared safe and were well tolerated. All studies were diagnostic, and the image quality was rated as excellent in 80% of the Hexabrix group and 72% of the Hexabrix-20 group. The authors conclude that Hexabrix and Hexabrix-20 are acceptable contrast media for ascending phlebography.

Adult↗
PubMed1985

Magnetic resonance imaging of mediastinal and hilar masses: comparison with CT.

Magnetic resonance imaging (MRI) was compared to computed tomography (CT) of the mediastinum and/or hila in 37 patients with bronchogenic carcinoma (35 unresectable for cure) and 11 patients with other masses. Spin-echo pulse sequences using a short pulse repetition rate (TR) and short echo delay (TE) were most helpful for detection of abnormal soft-tissue mediastinal and hilar masses. The accuracy of MRI and CT in staging bronchogenic carcinoma for curative resectability/nonresectability was comparable. CT staged 35 of 37 cases appropriately, while MRI correctly staged 36 of 37 cases. Several pitfalls in MRI evaluation of the mediastinum were identified. By MRI the esophagus may be misinterpreted as an enlarged retrotracheal lymph node unless serial scans are studied. Scattered calcifications in enlarged mediastinal and hilar lymph nodes due to old granulomatous disease are not detectable by MRI. Small adjacent lymph nodes shown individually by CT may appear as a single enlarged lymph node by MRI due to partial-volume averaging. Small lung nodules may be undetected by MRI due to respiratory motion and partial-volume averaging. Certain patients are unsuitable for MR scanning. Because of the requirement for patient selection and the identified pitfalls of MRI, CT remains the radiologic procedure of choice in the staging of patients with bronchogenic carcinoma and the evaluation of other mediastinal and hilar masses at present. However, because of the ability to show blood vessels without an intravascular contrast agent, MRI is useful in evaluating patients with potential contrast allergy and solving diagnostic problems not solved by CT.

Calcinosis↗
PubMed1985

Musculoskeletal applications of three-dimensional surface reconstructions.

We have applied computer programs originally developed for craniofacial surgical planning and evaluation to complex musculoskeletal problems. These computer programs reformat ordinary CT scans into black and white images of the three-dimensional osseous surfaces found in the scanned volume. These reformatted three-dimensional CT scan images increase the utility of CT scan examinations of complex osseous structures, such as the wrist, spine, hip, knee, and shoulder. The software, which operates on an unmodified commercially available CT scanner, can produce high-quality surface reconstructions from CT scan slices without operator intervention. No special knowledge of the principles used in the reconstruction methods is needed to successfully use the programs.

Adolescent↗
PubMed1984

Administration of human pancreatic growth hormone-releasing factor (GRF) analogs enhances responsiveness of cultured rat pituitary cells to GRF.

The aim of this study was to investigate whether anterior pituitary responsiveness to human pancreatic growth hormone-releasing factor containing 29 amino acids (GRF-29) can be modulated by GRF-29 itself. Male rats were injected (sc) daily for 3 days with 50 ug of GRF-29, or were treated twice daily for 14 days with 5 ug of [D-Ala-2]-GRF-29 (a potent GRF agonist). Control animals were injected with saline. After the last injection, pituitaries were removed, dispersed, cultured for 96 h and then challenged with either GRF-29 or [D-Trp-6]-LHRH (a LHRH agonist). Cultured cells from analog-treated rats were more responsive to GRF-29 stimulation than were cells obtained from controls. In contrast, neither treatment altered the response to [D-Trp-6]-LHRH. These studies indicate that periodic administration of GRF analogs can increase hypophyseal GRF responsiveness. Such control may be an important component in the physiological regulation of GH secretion and has important implications for potential therapeutic uses of GRF analogs.

Animals↗
PubMed1984

Super-active analogs of growth hormone-releasing factor (1-29)-amide.

Human pancreatic growth hormone releasing factor (1-29)-amide [hpGRF (1-29)-NH2] and the following analogs: [D-Tyr-1]-hpGRF(1-29)-NH2, [D-Ala-2]-hpGRF(1-29)-NH2, [D-Asp-3]-hpGRF(1-29)-NH2, and [N-Ac-Tyr-1]-hpGRF (1-29)-NH2 were synthesized using solid phase methodology and tested for their ability to stimulate growth hormone (GH) secretion in the rat and the pig in vivo. [D-Ala-2]-hpGRF (1-29)-NH2 was approximately 50 times more potent than the parent molecule in eliciting GH secretion in the rat. The other analogs were less active, but all were more potent than the 1-29 amide in the rat. [D-Tyr-1]-hpGRF(1-29)-NH2 was 10 times more potent, [D-Asp-3]-hpGRF(1-29)-NH2 7 times more potent, and the acetylated molecule approximately 12 times more potent than hpGRF(1-29)-NH2.

Animals↗
PubMed1984

Effect of oral 1,25-dihydroxyvitamin D and calcium on glucocorticoid-induced osteopenia in patients with rheumatic diseases.

Twenty-three rheumatic disease patients with glucocorticoid-induced osteopenia (defined by measurement of forearm bone mass) completed an 18-month double-blind, randomized study to assess the effect of oral calcium and 1,25-dihydroxyvitamin D (1,25-OH2D) or calcium and placebo on bone and mineral metabolism. Intestinal 47Ca absorption was increased (P less than 0.05) and serum parathyroid hormone levels were suppressed (P less than 0.01) by 1,25-OH2D (mean dose 0.4 micrograms/day); however, no significant gain in forearm bone mass occurred, and bone fractures were frequent in both groups. In the 1,25-OH2D group, histomorphometric analysis of iliac crest biopsy specimens demonstrated a decrease in osteoclasts/mm2 of trabecular bone (P less than 0.05) and parameters of osteoblastic activity (P less than 0.05), indicating that 1,25-OH2D reduced both bone resorption and formation. We conclude that 1,25-OH2D should not be used for treatment of glucocorticoid-induced osteopenia. Since patients receiving calcium and placebo did not exhibit a loss of forearm bone mass, elemental calcium supplementation of 500 mg daily might be useful to maintain skeletal mass in patients receiving long-term glucocorticord therapy.

Administration, Oral↗
PubMed1984

Musculoskeletal sporotrichosis.

Sporotrichosis is a chronic, indolent, fungal infection that rarely involves the musculoskeletal system. The etiologic agent, Sporothrix schenckii, is ubiquitous in nature and has been isolated from soil, timber, decaying vegetation, and a variety of foliage. The organism gains entrance to the body through trauma to the skin or, in rare instances, by inhalation. The vast majority of infections in humans is characterized by nodular or ulcerated lesions of the cutaneous tissues and adjacent lymphatics. Osteoarticular involvement may occur either by contiguous spread from a cutaneous focus, through direct inoculation of tissue by the organism, or by hematogenous dissemination. The rarity of musculosketetal sporotrichosis often causes a delay in diagnosis which leads to inappropriate therapy and permanent deformity in some patients. Three cases which show a spectrum of bone and joint involvement are presented.

Aged↗
PubMed1984

Phloretin inhibition of glucose transport by the tapeworm Hymenolepis diminuta: a kinetic analysis.

Phloretin non-competitively inhibits glucose and methionine absorption by Hymenolepis diminuta (Ki = 0.24 and 1.48 mM, respectively). Inhibition of glucose transport by phloretin is reversible. Phloretin and phlorizin binding sites on the surface of H. diminuta are distinct. Phloretin does not inhibit Na+ transport independent of glucose transport in H. diminuta. The data suggest that phloretin inhibits absorptive functions across the surface of H. diminuta via non-specific binding sites associated with the lipid portion of the worm outer membrane.

Animals↗
PubMed1984

A comparison of phlorizin and phloretin adsorption by the tapeworm Hymenolepis diminuta.

Phloretin and phlorizin adsorb to the tegument surface of Hymenolepis diminuta, with KDs of 2.39 mM and 14.7 microM, respectively, and Vmaxs of 1446 and 12.54 nmoles/g tissue per 2 min, respectively. Phloretin adsorption is not inhibited by phlorizin or glucose. Glucose partially inhibits phlorizin adsorption. Phlorizin, but not phloretin, adsorption to isolated tegument brush border membrane preparations is partially inhibited by N-ethylmaleimide. No indications of phlorizin hydrolysis to phloretin during incubation with H. diminuta were obtained. The data are supportive of spacially separate and distinct binding sites for phloretin and phlorizin in the tegument brush border.

Adsorption↗
PubMed1984

Structure-activity studies on the N-terminal region of glucagon.

Using solid-phase methodology and preparative medium- and high-performance reverse-phase liquid chromatography, we have synthesized glucagon and its Arg12 analogue in approximately 5% yields. The synthetic glucagon was fully active relative to natural material, and the Arg12 peptide exhibited 50% activity. Since perhaps the most critical part of the glucagon-family peptides is the N-terminal hexapeptide region, both batches of resin were split during synthesis in order to prepare two series of analogues based on glucagon and [Arg12]glucagon with changes in the His-Ser-Gln-Gly-Thr-Phe sequence. The following new analogues were tested for their effects on blood glucose levels in normal male rats relative to glucagon and gave the following activities: [Ac-His1,Arg12]glucagon, 46%; [3-Me-His1,Arg12]glucagon, 30%; [Phe1,Arg12 )glucagon, 31%; [Des-His1,Arg12]glucagon, 4%; [D-Ala2,Arg12]glucagon, 44%; [D-p-Cl-Phe1,D-Ala4,Arg12]glucagon, 9%; [D-Phe4]glucagon, 655%; [Ala2]glucagon, 9%. These data indicate that the amino or imidazole nitrogens of the histidine residue are not essential for biological activity. However, an aromatic group in position 1 may be important, since the Phe1 analogue is almost as active as glucagon in our bioassay. The superagonist activity with [D-Phe4]glucagon, which was synthesized to test the hypothesis that a beta-bend conformation occurs at this position in glucagon by analogy with luteinizing hormone-releasing hormone and other Gly-containing peptides, indicates that this is indeed the case and has important implications for the receptor-recognition requirements of the glucagon-secretin-vasoactive intestinal peptide family of peptides.

Adenylyl Cyclases↗
PubMed1984

Effect of Ala-2-D-Trp-8-D-Cys-14-somatostatin on the arginine induced release of insulin, GH and glucagon in normal men.

The effects of several doses of somatostatin (SS) and the analog Ala-2-D-Trp-8-D-Cys-14-SS on the arginine-induced release of insulin, glucagon, and GH were compared in a group of normal human subjects. Somatostatin suppressed the release of insulin, glucagon and GH when administered in a dose of 100 micrograms/hr. The same dose of Ala-2-D-Trp-8-D-Cys-14-SS inhibited GH and glucagon release, but although insulin levels were decreased about 24%, this inhibition was not significant statistically. Higher doses of Ala-2-D-Trp-8-D-Cys-14-SS (300 micrograms/hr) induced a partial inhibition of insulin secretion and completely blocked GH release. These results indicate that in humans this analog is a less potent inhibitor of insulin release than somatostatin.

Adult↗