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Biomedical subjects

J Hines

Publications and source records attributed to J Hines.

At least 37 records · Page 2Linked to original sources

Lipomas of the pancreas.

OBJECTIVE: The purpose of this study was to describe the CT findings of pancreatic lipomas in four patients. CONCLUSION: In all four cases, the lipoma was revealed incidentally on CT scans obtained for other reasons. CT scans were diagnostic, showing well-circumscribed masses within the pancreas composed almost entirely of fat, with a few scattered vessels or septa or both, which ranged in size from 1.4 x 2.0 cm to 4.5 x 5.3 cm in the axial plane. Pancreatic lipomas are rare, usually incidental tumors and, as with lipomas found elsewhere in the body, conservative management is often indicated.

Aged↗

Measurement of self-esteem in repeat assault victims.

Background characterization of assault-related injuries have demonstrated that lifestyle, substance abuse, education, employment, mental illness, and high-risk behavior contribute to low self-esteem in repeat assault victims. Recurrent-assault patients have never been studied with respect to self-esteem. This study evaluated self-esteem and assault-related injury in 28 consecutive male assault patients (11 first-assault and 17 recurrent-assault patients) and 19 controls with no previous assault history. Study participants were administered the Walmyr Assessment Scales Index of Self-Esteem (WASISE) as part of a three-item survey to determine the relationship between self-esteem and assault-related injury. No demographic differences were found between the groups. The mean (+/- standard error) WASISE score for recurrent-assault patients (34.9 +/- 3.4) was significantly higher than mean scores for no-assault and first-time assault-injured patients (14.7 +/- 1.4 and 15.0 +/- 2.3, respectively). The recurrent-assault patients had a lower mean education level than both no-assault and first-time assault-injured patients (2.1 +/- 0.26 and 1.9 +/- 0.57, respectively). Eighteen (2%) first-time assault-injured and 11 (7%) recurrent-assault patients were employed. These data suggest that self-esteem, education, and employment history need to be considered when evaluating and developing interventions for repeat-assault patients.

Crime Victims↗

Cloning and expression of angiotensin II type 2 (AT2) receptors from murine neuroblastoma N1E-115 cells: evidence for AT2 receptor heterogeneity.

Homology-based PCR was used to isolate angiotensin II type 2 (AT2) receptor cDNA from murine neuroblastoma N1E-115 cells. Despite subtle differences in the nucleotide sequence (the N1E-115 clone coded for Phe133 as TTC and Gln326 as CAG; base substitutions are in bold-italics), the AT2 receptor protein was identical to other reported murine AT2 clones. When transfected into COS-1 cells, the expressed AT2 receptor displayed high affinity for AngII and for AT2-selective compounds, GTP gamma S-insensitive agonist binding and enhanced agonist binding by dithiothreitol. Previously, we have demonstrated that N1E-115 cells possess two distinct subpopulations of AT2 receptors, defined as peak I and peak III receptors, that can be separated by heparin-sepharose chromatography. The two subpopulations differ pharmacologically, biochemically and immunologically. The binding properties of the cloned AT2 receptor closely resembled that of peak III receptors. Moreover, antisera raised against peak I AT2 receptors failed to immunoreact to either peak III receptors or cloned AT2 receptors expressed in COS-1 cells. Collectively, these data suggest that the cloned AT2 receptor is identical to peak III receptors from N1E-115 cells and that a novel AT2 receptor (peak I) remains to be cloned.

Angiotensin II↗

Female urethral diverticula.

Most urethral diverticula should be diagnosed on clinical grounds alone, but investigations may be used to confirm the diagnosis in difficult cases, delineate the extent of the disease and investigate other entities such as stress incontinence. A high index of suspicion is required when assessing women with lower urinary tract symptoms to ensure that cases of urethral diverticulum are not missed. The cases presented demonstrate that greater awareness of the signs and symptoms of this not uncommon disease may facilitate early diagnosis. Our cases also show that surgical treatment is effective and worthwhile.

Journal Article↗

Interaction of somatostatin receptors with G proteins and cellular effector systems.

Somatostatin induces its multiple biological actions by interacting with a family of receptors, referred to as sstr1-sstr5. To determine the molecular mechanisms of action of somatostatin, we have investigated the interaction of the different cloned receptors with G proteins and cellular effector systems. sstr2, sstr3 and sstr5 associate with pertussis toxin-sensitive G proteins and are able to mediate the inhibition of adenylyl cyclase activity by somatostatin. Two forms of sstr2, sstr2A and sstr2B, are generated by alternative splicing and differ in their C-terminal amino acid sequence. sstr2B couples to adenylyl cyclase whereas sstr2A does not. To investigate the basis for the differential coupling to adenylyl cyclase, we truncated sstr2B to the point of amino acid sequence divergence from sstr2A. The truncated sstr2B mediated the inhibition of cAMP formation by somatostatin, indicating that the C-terminus is not needed for coupling sstr2 to adenylyl cyclase. It is likely that the C-terminus of sstr2A hinders coupling to adenylyl cyclase. sstr2A associates with Gi alpha 3 and G(o) alpha but does not effectively interact with Gi alpha 1, a G protein that is necessary for coupling somatostatin receptors to adenylyl cyclase. The differential association of the splice variants with Gi alpha 1 may explain their contrasting effects on adenylyl cyclase activity. sstr3 also couples to adenylyl cyclase. Gi alpha 1 links sstr3 to adenylyl cyclase and mutagenesis studies have shown that the C-terminus of Gi alpha 1 is necessary for this coupling. The C-terminus of the Gi alpha proteins differ by only a few amino acid residues and only Gi alpha 1 couples sstr3 to adenylyl cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Payer and provider relationships: the key to reshaping health care delivery.

Though managed care is customarily thought of as the key point of connectivity for payers and providers, reshaping health care delivery requires a strong, united relationship between the two. The return to a health-related mission is a requirement of the new delivery system, which depends on moving beyond disease-based care and medical financing. In the future, community health status will be a strong indicator of success among payers and providers. Community-centered models of care for the underserved are illustrative of the opportunities for relationship building and strategic alignment between payers and providers.

Health Care Reform↗

Molecular mechanisms of agonist-induced desensitization of the cloned mouse kappa opioid receptor.

Prolonged exposure of opioid receptors to agonists can cause desensitization, a cellular event linked to tolerance. Although evidence exists for mu and delta opioid receptor desensitization, much less information is available concerning the in vitro regulation of kappa opioid receptors because no cell lines exist that specifically express this class of opioid receptor. Recently we have cloned the mouse kappa opioid receptor. After expression in COS-7 cells, this protein exhibits the pharmacological specificity of a kappa 1 receptor and mediates agonist inhibition of cAMP formation. Continuous exposure of COS-7 cells expressing the kappa receptor to the agonist trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]- benzeneacetamide methanesulfonate salt (U50,488) reduces the specific binding of the kappa-selective agonist [3H]U69,593. Furthermore, the potency of U50,488 to inhibit the binding of the opiate antagonist [3H]naloxone to the kappa receptor is reduced. However, total specific binding of [3H]naloxone is not altered, indicating that short-term (2-4 hr) agonist treatment of the kappa receptor reduces the affinity of the receptor for agonists but does not reduce the density of kappa receptors. The reduction in affinity of the kappa receptor for agonists is dependent on the time of agonist exposure and is reversible. The reduced affinity of the receptor for agonists is associated with kappa receptor desensitization, because kappa receptor-mediated inhibition of cAMP formation is lost in cells pretreated with U50,488. The desensitization of the kappa receptor is dependent on the time and concentration of agonist treatment, is blocked by the kappa-selective antagonist nor-binaltorphimine and is reversible.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Comparison of the adrenalytic activity of mitotane and a methylated homolog on normal adrenal cortex and adrenal cortical carcinoma.

Mitotane is an important adrenalytic drug for the treatment of adrenal cancer whose use is limited by toxicity. Reports from another laboratory indicated that a methylated homolog of Mitotane (Mitometh) tested in guinea pigs possessed comparable adrenalytic activity but was less toxic than Mitotane. This observation prompted us to undertake a comparative study of these two drugs on the basis that Mitometh may be a superior agent for the treatment of adrenal cancer. Preliminary studies in guinea pigs failed to show a significant adrenalytic effect for either Mitotane or Mitometh. Thus, we extended the study to 13 mongrel dogs weighing 12-15 kg that were treated daily with Mitometh or Mitotane (50-100 mg/kg) for 6 or 12 days. Cortisol decreased to undetectable levels and adrenocorticotropic hormone (ACTH) rose to 10 times the baseline levels within 72 h in Mitotane-treated animals. Despite the achievement of similar drug levels, Mitometh treatment in dogs failed to suppress cortisol or increase ACTH. To determine whether these differences were due to differences in bioavailability, we measured the relative concentration of Mitotane and Mitometh in homogenates of adrenal cortex obtained from Mitotane- and Mitometh-treated dogs. The adrenal concentration of Mitometh determined in Mitometh-treated dogs was 5 times higher than the concentration of Mitotane measured in Mitotane-treated animals. Whereas the adrenal glands of Mitotane-treated dogs showed hemorrhage and necrosis, the Mitometh-treated animals showed no adrenal damage. Despite the lack of adrenalytic activity, Mitometh maintained its toxicity as demonstrated by microscopic evidence of hepatic necrosis and an increase in hepatic enzymes. The adrenalytic effects of both agents was also studied in vitro using a human functioning adrenal cortical carcinoma cell line, NCI-H295. Whereas Mitotane strongly suppressed cell growth, Mitometh had a weaker effect. We conclude that Mitometh is not likely to be effective in the therapy of adrenal cancer. Moreover, the results of this study are supportive of the view that metabolic transformation of Mitotane is in some way linked to its adrenalytic action.

Adrenal Cortex↗

Evolution of morphologic changes after intravitreous injection of gentamicin.

Gentamicin shows retinal toxicity in rabbits, monkeys, and humans, but its mechanism of toxicity is not understood. Pig eyes, which are anatomically similar to human eyes, were examined with ophthalmoscopy, fluorescein angiography, and light and electron microscopy at time points ranging from 3 to 72 hours after intravitreous injection of 3 mg of gentamicin or vehicle to observe the sequence of toxicity-related changes that occur in the retina. The first ophthalmoscopic changes were retinal hemorrhages at 3 hours, followed by retinal whitening and thickening and vascular nonperfusion detected by fluorescein angiography 48 hours after injection. Vacuolization in the nerve fiber layer and perivascular swelling were seen at 6 hours, and subsequently, extended deeper into the retina. Vascular endothelial cells, photoreceptors, and the retinal pigment epithelium appeared to be spared from the toxic effects of gentamicin. At 48 and 72 hours after injection, numerous large and small retinal vessels showed congestion and leukocyte margination. These changes could not be prevented by increasing the pH of gentamicin to 7.2. These data suggest that gentamicin toxicity is not simply a pH-related phenomenon, that the primary targets of gentamicin toxicity are neurons and glia of the inner retina, and that retinal infarction occurs secondarily, possibly due to leukocytic plugging.

Animals↗

Analysis of autoantibody production in SCID-systemic lupus erythematosus (SLE) chimeras.

Mice with SCID disease have previously been successfully engrafted with human peripheral blood mononuclear cells (PBMC) obtained from normal individuals and from patients with various diseases. To determine whether SCID mice engrafted with SLE PBMC produced autoantibodies with specificities similar to those in the SLE donor, and to investigate which variables influence autoantibody production in the SCID recipients, we injected PBMC from 16 SLE patients into SCID mice and tested the recipients for autoantibodies to DNA and to five recombinant autoantigens. Ten out of 16 (68%) lupus and six out of nine (67%) normal grafts were successful as determined by the presence of human IgG greater than or equal to 5 micrograms/ml of SCID serum post-transfer. Autoantibodies to La/SSB, Ro/SSA, and RNP were detected in five out of 10 SCID-SLE recipients by ELISA and immunoblotting up to 22 weeks post-engraftment. The detection of autoantibodies in SCID-SLE mice was more closely related to autoantibody levels in donor sera than to total IgG concentrations in the SCID recipients. Autoantibody activity/mg IgG was similar in the donor and recipient sera. Histological evaluation of eight SCID-SLE mice killed 4-22 weeks post-transfer revealed population of the SCID thymus and spleen with mononuclear cells, but no evidence of lupus nephritis or dermatitis. These findings indicate that SCID mice can be engrafted with PBMC from patients with lupus and that specific autoantibodies are produced up to 5 months post-transfer. Failure to develop glomerulonephritis may be explained by low or absent anti-DNA antibodies or by changes in the cellular composition of the PBMC grafts.

Animals↗

The effect of head-down tilt and water immersion on intracranial pressure in nonhuman primates.

A headward fluid shift occurs in humans exposed to space-flight. This shift is thought to be the stimulus for the observed reduction in plasma volume, and may produce a sustained rise in intracranial pressure (ICP). In order to determine the effect of head-down tilt (HDT) and water immersion on intracranial pressure (ICP), five anesthetized rhesus monkeys were fitted with intracranial pressure-monitoring transducers and subjected to -6 degrees HDT followed by head-out thermoneutral (34.7 degrees) water immersion. ICP was elevated from 3.8 +/- 1.1 mm Hg in the horizontal control period to 5.3 +/- 1.3 mm Hg (p less than 0.05) during the 15 min pre-immersion HDT. When seated in the empty immersion tank, ICP stabilized at -6.3 +/- 1.3 mm Hg for the control period and increased to -2.2 +/- 1.9 mm Hg (p less than 0.05) when the water level was maintained for 30 min at the sternal notch. The ICP returned toward pre-immersion levels (-5.5 +/- 1.4 mm Hg) as the tank was drained. Mean blood pressure (MBP) remained constant during the pre-immersion tilt test. In the pre-immersion control period, MBP was 91 +/- 3 mm Hg compared to 90 +/- 4 mm Hg (p greater than 0.05) during immersion and 82 +/- 1 mm Hg (p less than 0.05) in the post-immersion recovery period. In summary, exposure of rhesus monkeys to either head-down tilt or water immersion produced a prompt rise in ICP during the stimulus period.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerospace Medicine↗

A calcium-selective optrode based on the fluorescence of dansylated troponin.

Troponin C (TnC) is covalently labeled with a fluorescent probe molecule dansylaziridine and immobilized on polyethyleneimine-impregnated cellulose. An optrode is constructed by attaching the treated cellulose membrane to the distal end of a bifurcated fiber-optic cable. Because fluorescence is enhanced as Ca+2 binds with the immobilized dansylated troponin (TnCDANZ), this system can be used as a calcium sensor for monitoring plasma Ca+2 levels.

Biosensing Techniques↗

Inhibition of growth factor effects in retinal pigment epithelial cells.

Several agents were examined for their effect on growth factor-stimulated processes in retinal pigment epithelial (RPE) cells. DNA synthesis was assessed by 3H-thymidine incorporation in density-arrested cells using previously determined maximally effective concentrations of various growth factors with and without test substances. Cell migration was assessed in Boyden chamber assays. For each test substance, trypan blue exclusion was used to determine noncytotoxic concentrations, and the effect of several concentrations were assessed on selected growth factors. The most effective, nontoxic concentration was then used for comparisons. Two cationic proteins, protamine and histone type II B, caused inhibition of RPE chemotaxis and 3H-thymidine incorporation induced by several growth factors, but a cationic polypeptide, polylysine, did not. Protamine and histone, were particularly effective inhibitors of acidic and basic fibroblast growth factors (FGF) but not if they were exposed to cells and then removed before growth factor addition. They had no effect on serum-stimulated chemotaxis or 3H-thymidine incorporation even when used in the presence of serum. Three anionic substances, heparin, pentosan polysulfate, and suramin, also inhibited RPE chemotaxis and 3H-thymidine incorporation induced by several different growth factors. They were less effective inhibitors of the FGFs than protamine and histone but were better inhibitors of serum-induced effects. Also unlike protamine and histone, the anionic substances maintained their inhibitory effect even when removed before growth factor addition. Since migration and proliferation of RPE cells are important processes in the pathogenesis of proliferative vitreoretinopathy, these agents and their mechanism of action deserve further study for potential therapeutic applications.

Adult↗

Stability of morphine sulfate in infusion devices and containers for intravenous administration.

The stability of morphine sulfate in one brand of polyvinyl chloride (PVC) container, one brand of glass syringe, and two brands of disposable infusion devices was determined. Solutions of morphine sulfate 2 and 15 mg/mL were used to fill the PVC containers and drug administration devices. Stability was determined for both concentrations of morphine sulfate at room temperature (23-25 degrees C) and 4 degrees C in the PVC containers, glass syringes, and disposable infusion devices; stability was also determined at 31 degrees C in the disposable infusion devices. At 0, 1, 2, 4, 7, 12, and 15 days, portions of the solutions were removed and assayed in triplicate by a stability-indicating high-performance liquid chromatographic method. At each time point the drug-infusion fluid combinations were inspected visually for color changes and the presence of particulate matter, and pH was measured. Morphine sulfate 2 and 15 mg/mL remained stable for at least 12 days in all the containers and devices at each temperature tested. No substantial changes in the pH or physical appearance of the solutions were observed. Morphine sulfate can be repackaged in the disposable glass syringe, PVC container, and both disposable infusion devices for routine clinical use.

Chromatography, High Pressure Liquid↗