Search PubMed⌕ Search

Biomedical subjects

R D Brown

Publications and source records attributed to R D Brown.

At least 235 records · Page 13Linked to original sources
PubMed1988

Relaxometry of calf lens homogenates, including cross-relaxation by crystallin NH groups.

We studied the magnetic field dependence of the longitudinal relaxation rates of water protons (1/T1 nuclear magnetic relaxation dispersion (NMRD) profiles) in transparent homogenates of calf lens. The samples included nuclear homogenates with total (heterogeneous) crystallin contents between 34% (v/v) (native) and 14% (diluted) as well as cortical homogenate, 21% (native) and 34% (concentrated). The NMRD profiles had two components: a monotonic dispersive component (analogous to that of both globular protein solutions and diamagnetic tissue) and "14N quadrupolar peaks." 14N peaks have never been reported for protein solutions, only for tissues and dehydrated proteins. These peaks occur between 0.5 and 5 MHz proton Larmor frequency and arise from interactions of solvent water protons with NH moieties of proteins. The 14N peaks in lens cytoplasm are very large and may correlate with the crystallin structure and interactions required to maintain short-range order and lens transparency. The monotonic and 14N quadrupolar components were largest in concentrated samples, but with different concentration dependencies. The dispersive components of samples above approximately 19% protein concentration had a fixed functional form, the amplitude of which varied with protein volume fraction, f, by the multiplicative factor f/(1 - f), suggesting spatial organization and dynamics of the solute proteins that are relatively independent of water content. In contrast, at concentrations less than 19%, the NMRD profiles are concentration dependent, indicating a dependence of the orientational relaxation time of the proteins on protein-protein interactions seen previously in other globular proteins at these concentrations. The 14N peaks are not resolved below approximately 19% protein and increase linearly with incremental volume fraction at protein concentrations above 19%. In addition, the 14N peaks in nuclear homogenates are 50-100% larger than those of cortical homogenates at the same concentrations. Partial substitution of solvent D2O for H2O decreases the peak heights, indicating that an exchangeable proton mediates the interaction between solvent protons and protein 14N nuclei.

Animals↗
PubMed1988

Number of inner-sphere water molecules in Gd3+ and Eu3+ complexes of DTPA-amide and -ester conjugates.

The inner-sphere water coordination number for Eu3+ and Gd3+ complexed with five DTPA analogs, in which one or two terminal carboxylate groups are functionalized as propyl amides or propyl esters, have been studied using phosphorescence lifetime and nuclear magnetic relaxation dispersion (NMRD) measurements. Both methods show that the water coordination number does not increase above that observed for the analogous DTPA complexes. The phosphorescence lifetime results indicate that all five Eu3+ complexes have one inner-sphere water molecule at 25 degrees C. The NMRD profiles for three of the Gd3+ complexes at 25 degrees C are also consistent with one inner-sphere water molecule, whereas two complexes have profiles consistent only with a mixture of complexes, 50% containing a single water molecule and 50% with none. Lowering the temperature alters the population of these species such that all five Gd3+ complexes have significantly less bound water on average at 5 degrees C. These results explain the anomalous temperature dependencies of the NMRD curves reported previously for the Gd(DTPA)-protein conjugates. We suggest that the Gd(DTPA)-conjugate systems have a fluxional coordination sphere whereby the amount of inner-sphere coordinated water varies from near zero at 5 degrees C to a high of two near 37 degrees C.

Chemical Phenomena↗
PubMed1988

Longitudinal proton relaxation rates in rabbit tissues after intravenous injection of free and chelated Mn2+.

The factors that determine the field-dependent increase in 1/T1 of tissue water protons were investigated for MnCl2 and Mn2+ (PDTA) (1,3-propylenediamine-N,N',N'',N'''-tetraacetic acid) introduced intravenously into rabbits. Mn2+ was used in preference to other paramagnetic ions in part because of the distinct NMRD profiles (magnetic field dependence of 1/T1) of free Mn2+ ions, their small chelate complexes, and their macromolecular conjugates, and in part because the relatively low toxicity of Mn2+ is favorable for animal studies. Tissue content of Mn2+ was determined in all samples by inductively coupled plasma analyses the state of Mn2+ in excised tissues was determined from the form of the 1/T1 NMRD profile of water protons; and distribution of contrast agent within tissue and access of water on a T1 time scale were determined by double-exponential analyses of proton relaxation behavior in intact doped tissue, as well as by the change of single-exponential relaxation rates and proton signal intensity upon gentle disruption of the tissue. MnCl2 is found in all tissues, except fat and skeletal muscle, but liver is most avid at low dose, and Mn2+ accumulates in spleen after high doses. Chelation targets Mn2+ to liver and kidney, saturating the liver chemically at relatively low dose. We suggest that pronounced increase in tissue relaxivity results from irrotationally bound Mn2+, ostensibly associated with the polar head groups of cell membranes. Compartmentalization of contrast agent and restricted diffusion of tissue water influences the maximum relaxation rates attainable, so that there is an optimal dose of these contrast agents which is rather low.

Animals↗
PubMed1988

Effect of atrial natriuretic peptide on ACTH, dibutyryl cAMP, angiotensin II and potassium-stimulated aldosterone secretion by rat adrenal glomerulosa cells.

We examined the effect of rat atrial natriuretic peptide (ANP) on ACTH, dibutyryl cAMP, angiotensin II and potassium-stimulated aldosterone secretion by dispersed rat adrenal glomerulosa cells. ANP inhibited ACTH, angiotensin II and potassium-stimulated aldosterone secretion with IC50's between 0.15-0.20 nM. Inhibition by 10 nM ANP could not be overcome with higher concentrations of these stimuli. ANP shifted the dibutyryl cAMP dose-response curve slightly to the right but did not blunt the maximal aldosterone secretory response. The sites of ANP inhibition in the aldosterone biosynthetic pathway for these stimuli were also examined. ANP inhibited activation of the cholesterol desmolase (CD) enzyme complex by ACTH, angiotensin II and potassium. Activation of the corticosterone methyl oxidase (CMO) enzyme complex by potassium was inhibited by ANP, however, activation by ACTH was not blocked. We concluded that: 1) ANP is a potent inhibitor of ACTH, angiotensin II and potassium-stimulated aldosterone secretion; 2) inhibition of ACTH stimulation is primarily due to lower cAMP levels and; 3) inhibition of angiotensin II and potassium stimulation reflects a block in the activating mechanism of the CMO and/or CD enzyme complexes, whereas CD but not CMO activation by ACTH is inhibited by ANP.

Adrenal Glands↗
PubMed1988

A technique for the in vitro incubation of deer antler tissue.

1. A procedure for the in vitro incubation of velvet deer antler tissue was developed. Biopsy samples were collected in June with a trephine from 2 adult white-tailed deer and incubated in modified BGJb medium up to 48 hr. Calcium (Ca) and hydroxyproline (OH-proline) concentrations in the tissue were determined. 2. A significant increase (P less than 0.05) in Ca was exhibited at 4 and 8 hr of incubation, and, after replenishment of media, at 48 hr. 3. Hydroxyproline concentrations continued to rise throughout the duration of the incubation period and were significantly higher than controls (P less than 0.05) at 16, 24, and 48 hr. 4. Results suggest antler tissue can be incubated in vitro with the protocol described, although length of incubation may vary with parameter measured.

Animals↗
PubMed1988

A new quantitative spectrophotometric assay of ischemia-reperfusion injury in skeletal muscle.

Characterization of ischemia-reperfusion injury of skeletal muscle remains poorly defined. A new quantitative assay to measure ischemic skeletal muscle injury is described and validated in a rat hindlimb model. This biochemical spectrophotometric technique measures triphenyltetrazolium chloride reduction in ischemic muscle. The reduction assay demonstrated significant injury after 3 hours of ischemia (25.4 +/- 9.7 percent of control activity; p less than 0.05). More severe injury occurred after 4 or more hours (less than 3 percent of control activity; p less than 0.05). This assay is an objective and quantitative method for characterizing ischemia-reperfusion injury.

Animals↗
PubMed1988

Localized amyloidosis of the urethra: diagnostic implications and management.

Localized amyloidosis of the urethra is a rare pathological entity that may resemble neoplastic disease. Biopsy is required to make the appropriate diagnosis. Although localized therapy is available for obstructing, symptomatic lesions, asymptomatic lesions may be followed with conservative management and spontaneous regression has been reported. In addition, an appropriate medical evaluation should be performed to determine the presence of systemic amyloidosis.

Amyloidosis↗
PubMed1988

Changing surgical aspects of urinary stone disease.

Surgical management of urinary calculous disease has changed dramatically in the past decade. The development of percutaneous nephrostomy techniques has allowed new access to upper tract stones. Percutaneous removal of large calculi was made possible by the development of ultrasonic and electrohydraulic lithotripsy. All upper tract calculi can now be removed in 70 to 100 per cent of cases with minimal complications. Nephrostolithotomy has reduced transfusion rates and hospitalization costs and has markedly shortened convalescence periods compared with open surgery. Ureteroscopy followed nephrostolithotomy as advanced fiberoptic technology allowed the development of the small-caliber instruments required for this procedure. With experience, successful stone retrieval has occurred in 90 per cent or more of cases, again with minimal complications. As nephrostolithotomy and ureteroscopy have become available, the subspecialty of endourology has emerged and significantly changed the management of urinary tract calculi. Perhaps the most significant advance in stone therapy has been the design and implementation of extracorporeal shock wave lithotripsy. With this noninvasive technique, most renal and proximal ureteral calculi can be effectively treated with minimal morbidity and convalescence. Research in lithotripter design is continuing, with more advanced and effective machines on the horizon. The applicability of extracorporeal therapy for the treatment of biliary tract calculi is currently under investigation. Finally, one should not disparage medical therapy for recurrent nephrolithiasis. A comprehensive metabolic evaluation combined with selective medical therapy provides almost complete relief from recurrent stone formation and makes medical therapy an integral component of treating the patient with renal or ureteral calculi.

Endoscopy↗
PubMed1988

A randomized placebo-controlled comparison of amlodipine and atenolol in mild to moderate systemic hypertension.

Amlodipine, a new long-acting dihydropyridine calcium antagonist, was compared with placebo and atenolol in 125 patients with mild to moderate systemic hypertension [supine diastolic blood pressure (DBP) 90-114 mm Hg]. Patients received placebo for 4 weeks, followed by a random allocation to an 8-week double-blind, once-daily treatment with amlodipine (n = 41), atenolol (n = 43), or placebo (n = 41). The changes in 24-h post-dose blood pressure (BP) from baseline to final visit for amlodipine (mean daily dose 8.8 mg, range 5-10 mg) were -12.8 +/- 2.0/ -10.1 +/- 1.2 mm Hg in supine BP and -11.5 +/- 2.3/-9.8 +/- 1.1 mm Hg in standing BP (p less than 0.001); for atenolol (mean daily dose 83.7 mg, range 50-100 mg), the changes from baseline were -11.3 +/- 2.3/-11.7 +/- 1.3 mm Hg in supine BP and -13.3 +/- 3.1/-12.3 +/- 1.5 mm Hg in standing BP (p less than 0.001); for placebo, the changes from baseline were -0.9 +/- 2.8/-3.5 +/- 0.9 mm Hg in supine BP and -1.6 +/- -2.6/-4.0 +/- 1.0 mm Hg in standing BP. In the study, goal response was defined as a supine DBP of less than 90 mm Hg or its decrease by greater than or equal to 10 mm Hg. The response rates were similar for atenolol (65%) and amlodipine (61%). Both active therapies were significantly more effective than placebo. Heart rate was significantly lowered by atenolol only.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Red cell ferritin and iron stores in patients with chronic disease.

Serum and red cell ferritin were determined in a heterogeneous group of 59 patients with chronic disease undergoing a bone marrow biopsy. There was very little correlation between serum and red cell ferritin (r = 0.53). Although serum ferritin increased in relation to increased bone marrow iron stores, only 1 out of 8 patients with absent marrow iron stores and none of 8 patients with reduced marrow iron stores had a decreased serum ferritin. In contrast, 6 of 8 patients with absent iron stores had a reduced red cell ferritin concentration. There was no significant difference between the mean red cell ferritin of the patients with reduced, normal and mild-moderately increased marrow iron stores (30, 26 and 34 ag/cell). Red cell ferritin was decreased in 78% of a group of 32 patients with a low mean cell volume. In the patients studied, red cell ferritin was a better indicator of absent iron stores than serum ferritin. However, red cell ferritin did not detect a reduction in the iron status until the marrow iron stores were completely depleted. Apparently, during normal erythropoiesis the primitive erythroblasts continue to take up iron irrespective of the amount of iron available in the stores.

Adolescent↗
PubMed1988

Circulating levels of 1,25 dihydroxyvitamin D, alkaline phosphatase, hydroxyproline, and osteocalcin associated with antler growth in white-tailed deer.

Alkaline phosphatase, hydroxyproline, osteocalcin, and 1,25(OH)2D were measured in biweekly serum samples obtained from 6 adult (greater than 4 years), 4 juvenile (1-4 years) and 4 fawn (less than 1 year) male white-tailed deer from Oct. 1983 to Oct. 1984. Antler length, from the pedicle to the tip, was measured at the time of serum sampling. Serum alkaline phosphatase activity and levels of hydroxyproline and osteocalcin were higher (P less than 0.05) in fawns compared with juveniles and adults reflecting increased bone metabolism in the younger deer. In adult deer serum alkaline phosphatase activity and hydroxyproline levels were elevated (P less than 0.05) during the period of antler growth, whereas serum osteocalcin and 1,25(OH)2D increased (P less than 0.05) during antler mineralization. Similar but less pronounced trends occurred in juvenile deer, possibly a reflection of skeletal growth in the younger animals. The data lend support for utilization of the deer antler cycle as a model for studies of bone disorders. Further work is needed to help clarify the role of hydroxyproline, osteocalcin, and 1,25(OH)2D in the antler cycle.

Age Factors↗
PubMed1988

The natural history of unruptured intracranial arteriovenous malformations.

The authors conducted a long-term follow-up study of 168 patients to define the natural history of clinically unruptured intracranial arteriovenous malformations (AVM's). Charts of patients seen at the Mayo Clinic between 1974 and 1985 were reviewed. Follow-up information was obtained on 166 patients until death, surgery, or other intervention, or for at least 4 years after diagnosis (mean follow-up time 8.2 years). All available cerebral arteriograms and computerized tomography scans of the head were reviewed. Intracranial hemorrhage occurred in 31 patients (18%), due to AVM rupture in 29 and secondary to AVM or aneurysm rupture in two. The mean risk of hemorrhage was 2.2% per year, and the observed annual rates of hemorrhage increased over time. The risk of death from rupture was 29%, and 23% of survivors had significant long-term morbidity. The size of the AVM and the presence of treated or untreated hypertension were of no value in predicting rupture.

Adolescent↗
PubMed1988

Post bone marrow transplant sera and persisting mast cell colonies.

Serum samples were collected from eight recipients of allogeneic bone marrow transplants (BMT) following the normalization of peripheral blood counts. Three patients (11 samples) were in the early engraftment period (less than 6 months post-BMT) and still receiving cyclosporin A or methotrexate and the remaining five patients (18 samples) were in stable engraftment (12-84 months post-BMT) and not on immunosuppressive therapy. All post-BMT serum samples supported the growth of increased numbers of mast cell colonies in long-term agar cultures when compared with normal controls (p less than 0.025-0.005), irrespective of the time from BMT or the presence of clinical graft-versus-host disease (GVHD). In contrast, the numbers of neutrophil, monocyte and eosinophil colonies were equivalent in test and control groups. It is proposed that post-BMT sera contain higher levels of a mast cell stimulating activity(s) than does normal sera. Such increased levels might be associated with clinical or subclinical GVHD.

Blood Physiological Phenomena↗
PubMed1988

Identification and characterization of human hemopoietic mast cell colonies.

Persisting mast cell colonies from human bone marrow and cord blood cells grown in semisolid agar cultures for over 56 days have been positively identified and characterized using morphology and cytochemistry. Mast cells demonstrated the following features: Cytoplasmic granules frequently contained the specific and characteristic papyrus rolls (transmission electron microscopy); mature cells were positive to the mouse monoclonal antibody YB5.B8 specific for human mast cells (raised against acute myeloid leukemia cells) and RPA-M1 specific for human monocytes but negative to the human basophil monoclonal antibody Bsp-1; morphologically the cells were large (diameter 20-25 micron), deeply basophilic, and contained granules that measured up to 2 micron in diameter (May-Grünwald-Giemsa stain); the presence of heparin by the thrombin clotting time and positive staining with toluidine blue and alcian blue; the presence of histamine by a positive fluorescent o-phthalaldehyde stain; the presence of IgE receptor sites with human IgE and a rabbit anti-human IgE second antibody; and a unique zone of lysis around mast cell colonies occurred when cultured on peripheral blood feeder layers in agar plates that was not present around monocytic, neutrophilic, or eosinophilic colonies under the same culture conditions. Our results identify the cells in persisting colonies as mast cells and describe some specific characteristics that distinguish these cells from basophils.

Bone Marrow Cells↗
PubMed1987

Electron paramagnetic resonance and magnetic susceptibility studies of dimanganese concanavalin A. Evidence for antiferromagnetic exchange coupling.

The double Mn2+ complex of concanavalin A with bound saccharide (SMMPL) was examined by electron paramagnetic resonance (EPR) spectroscopy and magnetic susceptibility measurements. A room temperature X-band (9 GHz) EPR spectrum of SMMPL revealed a relatively weak, broad resonance in contrast to the spectrum with a six-line hyperfine-split pattern observed for the mononuclear, high-spin Mn2+ complex found in Ca2+-Mn2+-concanavalin A with saccharide present (SCMPL). The EPR spectrum of SMMPL at 77 K, however, consisted of a series of overlapping patterns of 11 hyperfine-split lines near g = 2.0 with members of each pattern separated by 47 G, half the value of the hyperfine splitting of SCMPL. These 11-line patterns are preserved at Q-band (35 GHz), indicating that the manganese ions in SMMPL form a spin-coupled, binuclear center. As expected for an exchange-coupled system, the EPR signal of SMMPL at 77 K saturates at a higher microwave power than those for SCMPL or Mn2+ aquoion. There is also a marked loss of EPR signal intensity for SMMPL between 4.2 and 1.4 K, which supports the view that the pair of manganese ions is exchanged-coupled. The temperature dependence of both the magnetic susceptibility and the low-temperature EPR spectral intensity can be explained by a model in which the two high-spin Mn2+ ions of SMMPL are antierromagnetically exchanged-coupled with an isotropic coupling constant J = 1.8 cm-1 (for the spin Hamiltonian Hex = JS1.S2). Zero-field splitting D' was estimated to be 375 G from the EPR spectrum.(ABSTRACT TRUNCATED AT 250 WORDS)

Concanavalin A↗
PubMed1987

Decidium. A novel fluorescent probe of the agonist/antagonist and noncompetitive inhibitor sites on the nicotinic acetylcholine receptor.

We have examined the interaction of the nicotinic acetylcholine receptor with decidium diiodide, a bisquaternary analogue of ethidium containing 10 methylene groups between the endocyclic and trimethylamino quaternary nitrogens. Decidium inhibits mono-[125I]iodo-alpha-toxin binding, inhibits agonist-elicited 22Na+ influx in intact cells, augments agonist competition with mono-[125I]iodo-alpha-toxin binding, and enhances [3H]phencyclidine (PCP) binding to a noncompetitive inhibitor site. These effects occur over similar concentration ranges (half-maximum effects between 0.1 and 0.4 microM). Thus, decidium binds to the agonist site and converts the receptor to a desensitized state exhibiting increased affinity for agonist and heterotropic inhibitors. These properties are similar to metaphilic antagonists characterized in classical pharmacology. At higher concentrations decidium associates directly with the noncompetitive inhibitor site identified by [3H]phencyclidine binding. Dissociation constants of decidium at this site in the resting and desensitized states are determined to be 29 and 1.2 microM, respectively. Analysis of fluorescence excitation and emission maxima reveal that binding to both the agonist and noncompetitive inhibitor sites is associated with approximately 2-fold enhancement of fluorescence. The excitation maximum for decidium bound at the agonist site appears at 490 nm while that for decidium bound at the noncompetitive inhibitor site appears at 530 compared to 480 nm in buffer. These results suggest that decidium experiences a more hydrophobic environment upon binding to the nicotinic acetylcholine receptor sites, particularly to the noncompetitive inhibitor site. Fluorescence energy transfer between N'-fluorescein isothiocyanate-lysine-23 alpha-toxin (FITC-toxin), and decidium is not detected when each is bound to one of the two agonist sites on the receptor. This allows a minimal distance to be estimated between fluorophores. In contrast, energy transfer is observed between decidium nonspecifically associated with the membrane or with nonspecific sites and the FITC-toxin at the agonist sites.

Animals↗