Biomedical subjects
Publications and source records attributed to S W Young.
Evidence is presented that incubation of rat liver cells with glucagon leads to an increase in the phosphorylation of specific serine residues within insulin receptors, particularly in the presence of insulin. However, no changes in either the tyrosine phosphorylation of the receptors or the tyrosine kinase activity towards a synthetic peptide substrate was detected.
Complete and homogeneous distribution of gastrointestinal (GI) contrast media are important factors for their effective use in computed tomography as well as in magnetic resonance (MR) imaging. A radiographic method (using fluoroscopy or spot films) could be effective for monitoring intestinal filling with GI contrast agents for MR imaging (GICMR), but it would require the addition of a radiopaque agent to most GICMR. This study was conducted to determine the minimum amount of barium additive necessary to be radiographically visible and to evaluate whether this additive influences the signal characteristics of the GICMR. A variety of barium sulfate preparations (3-12% wt/vol) were tested in dogs to determine the minimum quantity needed to make the administered agent visible during fluoroscopy and on abdominal radiographs. Solutions of 10 different potential GI contrast agents (Gd-DTPA, ferric ammonium citrate, Mn-DPDP, chromium-EDTA, gadolinium-oxalate, ferrite particles, water, mineral oil, lipid emulsion, and methylcellulose) were prepared without ("nondoped") and with ("doped") the barium sulfate additive. MR images of the solutions in tubes were obtained at 0.38 T using 10 different spin-echo pulse sequences. Region of interest (ROI) measurements of contrast agent signal intensity (SI) were made. In addition, for the paramagnetic contrast media, the longitudinal and transverse relaxivity (R1 and R2) were measured. A 6% wt/vol suspension of barium was the smallest concentration yielding adequate radiopacity in the GI tract. Except for gadolinium-oxalate, there was no statistically significant difference in SI for doped and non-doped solutions with most pulse sequences used. In addition, the doped and nondoped solutions yielded R1 and R2 values which were comparable. We conclude that barium sulfate 6% wt/vol added to MR contrast agents produces a suspension with sufficient radiodensity to be viewed radiographically, and it does not cause significant alteration in the MR signal appearance of most GICMR. These formulations can be useful for achieving optimal filling of the gastrointestinal tract prior to MRI.
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Ninety-six patients with known or suspected focal hepatic disease were evaluated in a multiinstitutional study of manganese (II) N,N'-dipyridoxylethylenediamine-N,N'-diacetate 5,5'bis(phosphate) (DPDP) as a hepatic-specific contrast agent for magnetic resonance (MR) imaging. The patients were divided into four dose groups, receiving 3, 5, 8, or 10 mol/kg of Mn-DPDP. Half of the patients in each dose group received Mn-DPDP as an intravenous bolus (0.25 mL/sec) and the other half as an infusion (1 mL/min). Patients were evaluated with T1-weighted imaging parameters. No serious side effects were noted. In 76 patients, both Mn-DPDP-enhanced and nonenhanced T1-weighted images depicted the same number of lesions, but one additional lesion was depicted with enhanced imaging in 12 patients, two additional lesions in three patients, and three additional lesions in three patients. Enhanced, T1-weighted images depicted no more lesions than nonenhanced, T2-weighted images in 77 patients, but one more lesion was depicted in nine patients, two more lesions in two patients, three more lesions in one patient, and four more lesions in one patient.
Comparison of the effectiveness of various gastrointestinal (GI) contrast agents for magnetic resonance (MR) imaging is often complicated by varying amounts intraluminal filling with the orally administered agents. To achieve more uniform and reproducible imaging results with GI contrast agents for MR imaging (GICMR), we evaluated a radiographic method for monitoring intraluminal filling and distribution. Solutions of Mn-DPDP (2 mM), to which a small amount of barium sulfate (6 wt/vol%) was added, were administered orally to dogs. Gastric emptying and small bowel transit were monitored fluoroscopically. MR imaging was performed either 1) at a fixed time after administration of the contrast agent or 2) at a variable interval when the contrast agent was observed fluoroscopically to be in the terminal ileum. When initiation of MR imaging was guided by fluoroscopic monitoring of intestinal contrast distribution, uniform and reproducible intestinal contrast enhancement by GICMR was achieved. However, when MR imaging was performed at a fixed time interval after oral administration, non-uniform and variable GI visualization was obtained, and this corresponded to the variable intestinal distribution observed fluoroscopically. We conclude that reproducible intestinal filling with orally administered contrast agents can be accomplished with a radiographic monitoring technique, and this promotes more consistent GI visualization on MR images. Such standardized and reproducible methods are necessary for studies in which the effectiveness of GI contrast media for MR imaging is evaluated and compared.
The primary purpose of this exploratory study was to examine differences between exercisers and nonexercisers in self-esteem, perceived benefits of exercise, and perceived barriers to exercise. Second, we investigated how much variation in group membership as an exerciser or nonexerciser could be explained by the relationship among self-esteem, perceived benefits of exercise, and perceived barriers to exercise. A sample of 105 university students completed four questionnaires. Using t tests, a significant difference was found between exercisers and nonexercisers on self-esteem, perceived benefits of exercise, and perceived barriers to exercise. It was found that the three variables successfully accounted for 32% of the variation in group membership as an exerciser or nonexerciser.
The healing of large fractural defects is a difficult clinical problem, especially if it occurs in elderly or otherwise debilitated patients. The objective of this study is to determine if a new formulation of fibrous calcium phosphate crystals would induce fracture healing in vivo. Fibrous calcium phosphate (FCP) can be grown with unique size, shape, and surface area characteristics as a resorbable or nonresorbable, osteoconductive or osteoinductive material. In comparison with other conventional calcium phosphate particulates, FCP particles possess approximately x 100 to x 1000 more surface area. One-and-one-half centimeter sections were removed from the ulnas of 12 rabbits. Three groups had fibrous calcium phosphate spherulites (4-8 microns, 150-300 microns, 400-600 microns) mixed with collagen and a growth factor-bonding agent injected into the ulnar defect. One site per group was not treated. X-rays were obtained during the study and the percentage of the ulna defect filled in by callous was measured. The percentage was recorded as the amount of fracture healing for each site. Histologic examination of the ulnas was performed following sacrifice at 12 weeks. Fracture sites treated with fibrous calcium phosphate showed significantly greater healing (0.79 +/- 0.3) than control animals (0.36 +/- 0.1) (P less than .05, unpaired t-test) radiographically. Histologic examination showed that the spherulites remain in situ and become embedded within the new growth of fibrous tissue, collagen and new bone. Radiographically and histologically, FCP preparations appear to accelerate fracture healing by inducing new bone formation, into which they often become embedded.
Bioabsorption of synthetic apatite compounds used to promote bone healing and remodeling has been difficult to evaluate. In this study, solid-state phosphorus-31 nuclear magnetic resonance (NMR) has been used to characterize and quantitate bone mineral and a synthetic apatite in order to establish a model for bioabsorption studies. Pulverized solid samples of cortical rabbit bone and a synthetic fluoridated apatite were examined in vitro at variable degrees of hydration. A 9.4 T superconducting spectrometer was used to obtain 31P magic angle spinning NMR spectra and T1 relaxation times. Quantitation was attempted in mixed samples using T1 recovery data. Bone mineral and synthetic apatite could be distinguished by chemical shift and T1 relaxation time in variable hydration states, and were readily differentiated in mixtures by their T1 relaxation time. NMR estimates of relative proportions of components in mixed samples were accurate within 2% of evaluations based on weight. Solid-state 31P NMR therefore provides a suitable method for monitoring the bioabsorption of synthetic apatites.
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If proton nuclear magnetic resonance (1H NMR) spectroscopy is to provide a clinically useful modality for monitoring tumor growth and treatment, the technique must be able to unambiguously detect steady-state metabolite concentrations in human tumors and differentiate these from normal tissue levels. To address this problem, a two-dimensional double quantum coherence transfer spectroscopy (2DDQCT) method was developed and tested in a series of tumor cell lines implanted in mice. Lactate-edited proton NMR spectra were determined from a roughly 1-cm3 region of interest in EMT6, RIF-1, and fibroma. In two-dimensional data matrix representations of the 2DDQCT experiments (double quantum frequency on the vertical axis and chemical shift on the horizontal axis) the lactate signal (330 Hz with the transmitter set at the water resonance) was well-resolved from lipid (480 Hz, 600 Hz). The resolution in the double quantum dimension was also sufficient to conclude that a detectable level of alanine, which would reside at 358 Hz, was not present in the three tumor types. Following the NMR experiment, tumors were chemically assayed for lactate giving 8.17, 9.1, and 6.73 mumols/g wet wt for RIF-1, EMT6, and fibroma, respectively. This technique is likely to provide a noninvasive method for monitoring the steady-state lactic acid levels in small tumors before and after therapy, as well as in tissues with impaired oxygen delivery using clinical and research NMR systems.
A new hepatobiliary contrast agent (Mn-DPDP) was used in the detection of liver metastases in six rabbits with seven hepatic V2 carcinomas. This contrast agent is derived from pyridoxyl-5-phosphate which is biomimetically designed to be secreted by the hepatocyte. After Mn-DPDP administration, a 105% increase in liver signal to noise was obtained using a 200/20 (TR/TE) pulsing sequence, and a 62% decrease in intensity was observed using a 1200/60 pulsing sequence. Liver V2 carcinoma contrast enhancement increased 427% using the 200/20 pulsing sequence and 176% using the 1200/60 pulsing sequence. Four of seven V2 carcinomas were not detectable prior to the administration of Mn-DPDP (50 mumol/kg). Two neoplasms were only detectable in retrospect (after Mn-DPDP) on the 1200/60 sequence. The smallest neoplasms detected in this study were 1-4 mm. Mn-DPDP appears to be a promising MRI contrast agent.
Newly developed ferromagnetic catheters (Fe-Caths) are more conspicuous than conventional radiographic catheters (Rad-Caths) on magnetic resonance (MR) images because they produce recognizable ferromagnetic signal patterns (FSPs). To determine how MRI parameters influence these patterns, the imaging characteristics of nine Fe-Caths (ferromagnetic concentration 0.01 to 1.0 weight/weight %) were studied systematically and compared with three Rad-Caths. All catheters were studied in stationary and moving phantoms at mid-field (0.38 T) and high-field (1.5 T) strength using spin-echo and gradient-echo pulse sequences. Rad-Caths always produced a signal void. Fe-Caths produced FSPs, the size of which depended on the orientation of the catheter with respect to the main magnetic field, the concentration of ferromagnetic agent in the catheter, and the direction and strength of the frequency encoding gradient. When Fe-Caths were positioned perpendicular to the main magnetic field, they produced FSPs; however, when they were parallel to the main magnetic field, Fe-Caths produced no FSP, thus having a similar appearance to the Rad-Caths. Ferromagnetic catheters produce conspicuous patterns on MR images that depend on catheter orientation in the main magnetic field and vary predictably with the MRI parameters.
Identification of the junction of the posterior band with the bilaminar zone is important to detect anterior displacements of the temporomandibular joint (TMJ) meniscus on magnetic resonance (MR) images. However, significant differences in tissue characteristics within the meniscus itself may cause a confusing appearance that is not easily reconciled with available anatomic references. Six cadaveric TMJ specimens were imaged sagittally at 1.5 T with various combinations of repetition time and echo time and with use of both standard surface coils and a specially developed solenoidal specimen coil. Corresponding histologic sections were correlated with the in vitro MR images to identify the anatomic structure and tissue characteristics. Comparison of these in vitro images with in vivo images of 100 joints identified a vertical, linear, low-signal-intensity band as an important landmark of the junction of the posterior band and bilaminar zone. Recognition of the signal-intensity characteristics of the center and the surfaces of the posterior band as well as the appearance of the insertion of the bilaminar zone also increased confidence of visualization and helped avoid possible false-positive diagnoses.
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This study reports the first in vivo results using an MR contrast agent manganese dipyridoxal diphosphate (Mn-DPDP) designed to estimate the functional status of the hepatocyte. Thirty New Zealand white rabbits were studied in groups of 5 as follows: No. 1, control, MRI scans only; No. 2 MRI before and up to 90 min following 50 mumol/kg of Mn-DPDP iv; No. 3, rabbits received 9.3 g ethanol/kg and MRI; No. 4, as in No. 3 but following Mn-DPDP; No. 5, MRI as in No. 2 but 18 h. following 1000 mg/kg D-galactosamine used to induce hepatocyte necrosis; and No. 6, rabbits received D-galactosamine and MN-DPDP. In this study significant ethanol- and D-galactosamine-induced hepatocyte damage was indicated by the increased SGPt serum levels in the rabbit. The use of Mn-DPDP allowed detection of early hepatocyte necrosis in these animals whereas conventional spin-echo MRI did not. The fact that D-galactosamine curves with and without Mn-DPDP were not significantly different indicated virtually no membrane transport or metabolism of Mn-DPDP in the liver. Ethanol curves were not normal, but there was still considerable residual Mn-DPDP metabolism. Mn-DPDP appears to be an attractive agent in assessing hepatocyte function.
Insulin has metabolic, growth, and differentiation effects in chicken embryos in vivo and it is required for normal development. Whether the pancreas is the sole source of insulin in embryogenesis is controversial. In the present study we investigated (1) the developmental pattern of expression of the chicken insulin gene in the pancreas; (2) the expression of the insulin gene in three nonpancreatic tissues, liver, brain, and lower limb, during chicken development; and (3) the expression of the insulin gene at prepancreatic stages and during chicken embryo organogenesis. Hybridization of synthetic species-specific insulin oligonucleotides to pancreatic frozen section in situ and to Northern blots revealed a major increase in insulin messenger RNA (mRNA) levels during the third week of embryonic development. The hybridization histochemistry showed both an increase in the levels of insulin mRNA per pancreatic islet and, in addition, an increase in the number of insulin mRNA containing islets with development. By Northern analysis there was a major polyadenylated transcript of 0.6 kb, which increased in abundance approximately 30-fold during this interval. Under the same stringency conditions used for pancreatic RNA an insulin transcript was detected in liver RNA blots. The abundance of this hepatic insulin mRNA was about 100-fold less than the pancreatic insulin mRNA and, in contrast to the latter, did not increase in late development. Primer extension experiments demonstrated that the insulin transcripts of pancreas and liver had similar 5' ends. No insulin mRNA was detected by Northern analysis or primer extension either in whole brain or lower limb total RNA from several developmental stages. A very low abundance insulin mRNA was detected in whole embryo at Day 8 and body regions at Day 4 and Day 5 when organogenesis of the pancreas takes place. Interestingly, a polyadenylated insulin transcript was detected, as well, in whole Day 2 and Day 3 embryos (stages 10 to 20, with 20 to 40 somites) before differentiation of beta cells occurs. Thus, there is differential developmental regulation of the insulin gene in several chicken embryo tissues and the expression of insulin precedes pancreatic maturation. These findings support the proposed role of insulin in differentiation and development in vivo and suggest a paracrine type of action of the hormone in early embryos before blood circulation begins.
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