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Biomedical subjects

R A Brooks

Publications and source records attributed to R A Brooks.

At least 55 records · Page 3Linked to original sources
PubMed1999

T1 and T2 in the brain of healthy subjects, patients with Parkinson disease, and patients with multiple system atrophy: relation to iron content.

PURPOSE: To investigate the potential of magnetic resonance imaging for identification and quantification of brain iron in healthy subjects, patients with Parkinson disease, and patients with multiple system atrophy. MATERIALS AND METHODS: Forty-nine subjects were studied at 1.5 T. Regional T1 and T2 values were compared among groups and also with histopathologic estimates of iron concentration. RESULTS: In healthy subjects, interregional T1 and T2 differences in the cortex and basal ganglia showed a good correlation with reported values for iron concentration, and intraregional variations were generally consistent with reported variability of iron concentration. Patients with multiple system atrophy had T1 and T2 shortening in the globus pallidus consistent with reported increases in ferritin-bound iron and changes in the putamen consistent with accumulation of hemosiderin (posterior portion) and neuromelanin (remainder). Both groups of patients had changes in the cortex that are consistent with decreased ferritin concentration and T2 changes in white matter consistent with demyelination. Patients with Parkinson disease also had a (nonsignificant) T2 shortening in the substantia nigra that was suggestive of iron accumulation. CONCLUSION: Most of the T1 and T2 findings appear to be related to changes in iron content and form and may possibly be used as indicators of such changes.

Aged↗
PubMed1999

Assisting persons living with HIV/AIDS to return to work: programmatic steps for AIDS service organizations.

The objective of this study was to develop a comprehensive picture of the concerns and needs of persons living with HIV/AIDS who are interested in returning to work. To collect information in this new area, a series of focus groups was conducted with a random sample of clients from AIDS Project Los Angeles who were currently unemployed and expressed a desire to return to work. The results indicate a range of concerns among individuals with HIV/AIDS about returning to work, such as a loss of or change in medical benefits, the need for flexibility in employment to address ongoing medical needs, concerns regarding disclosure of their HIV/AIDS status, the possibility of job related discrimination, and the need to address the practical aspects of reentering the labor market after a prolonged absence. The findings suggest a series of action steps for AIDS service organizations and others to address the needs of persons with HIV/AIDS in this new area.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Analysis of DNA damage and repair accompanying differentiation in the intestinal crypt.

The ability to process damaged DNA may vary between cells depending on their differentiated status. However, there is little in vivo data available and it is not intuitively obvious how the activity of specific repair pathways may vary between different subpopulations (e.g. stem cells and proliferative, committed and differentiated cells) of a particular tissue. To obtain such information for the intestinal epithelium, we have developed an assay that detects differences in the way different regions of the crypt (stem, proliferative and maturation zones) respond to DNA damage. The assay is a variant of the 'comet' assay, which detects DNA strand breaks by measuring the proportion of DNA migrating from individual cells, or in this case intact isolated crypts, in an electrophoretic field. The method is quantitative, with the amount of migrating DNA being proportional to the number of strand breaks. Isolated crypts are repair competent and spatial differences are apparent with some agents. The assay has the potential to characterize the repair properties of cells at different stages of differentiation within the crypt, determine the characteristics that might predispose them to damage and may help in understanding the route of stem cell mutation.

Animals↗
PubMed1998

Relaxometry and magnetometry of ferritin.

By combining nuclear magnetic relaxometry on 39 ferritin samples with different iron loading with magnetometry, results were obtained that suggest a new interpretation of the core structure and magnetic properties of ferritin. These studies provide evidence that, contrary to most earlier reports, the ferritin core is antiferromagnetic (AFM) even at body temperature and possesses a superparamagnetic (SPM) moment due to incomplete cancellation of antiparallel sublattices, as predicted by Néel's theory. This moment also provides a likely explanation for the anomalous T2 shortening in ferritin solution. However, the number of SPM moments derived from this model is less than the number of ferritin molecules determined chemically, and a similar discrepancy was found by retrospectively fitting previously published magnetometry data. In other words, only a fraction of the ferritin molecules seem to be SPM. The studies also provide evidence for paramagnetic (PM) Curie-Weiss iron ions at the core surface, where the local Néel temperature is lower; these ions are apparently responsible for the weaker T1 shortening. In fact, the conversion of uncompensated AFM lattice ions to PM ions could explain the small number of SPM particles. The apparent Curie Law behavior of ferritin thus appears to be a coincidental result of different temperature dependences of the PM and SPM components.

Ferritins↗
PubMed1998

The tension cord plaster: a method of immobilising the swollen elbow.

A method of immobilising the swollen elbow in a child is described. A length of traction cord is used to block extension, whilst a plaster backslab protects the point of the elbow. Constructive dressings in the cubital fossa may be avoided. This minimises the risk of further swelling and allows assessment of circulation in the elbow, forearm and hand without interfering with the integrity of the cast. Should increasing swelling threaten circulation, the traction cord may simply be cut on the ward to allow elbow extension. Use of this plaster is recommended when flexion of the elbow is necessary to maintain reduction of a fracture, such as following reduction of an extension-type supracondylar fracture.

Casts, Surgical↗
PubMed1998

Iron uptake by ferritin: NMR relaxometry studies at low iron loads.

Twenty ferritin samples were prepared at pH 6.5 with average loadings of 0-89 Fe atoms per molecule. Nuclear magnetic relaxation times T1 and T2 were measured at 3 degrees C, 23 degrees C, and at 37 degrees C and at field strength from 0.025 to 1.5 T. The field dependence, temperature dependence, and approximate equality of T1 and T2 at low fields all suggest that nuclear magnetic relaxation in this range is caused primarily by solitary Fe3+ ions. The relaxivity (relaxation rate per mM ferritin) increases quickly with initial iron loading, reaches a peak at 13-14 Fe atoms per molecule, and then declines. This provides supportive evidence for the formation of antiferromagnetically-coupled clusters during early stages in iron loading; the failure to see a similar peak in an earlier study may be related to the nonphysiological pH that was used. Above 50 atoms per molecule, the relaxivity remains approximately constant, except that 1/T2 at high fields increases slightly, consistent with early core growth. The residual ionic relaxivity in this region is consistent with about three solitary Fe3+ ions remaining on the protein shell, indicating that spin cancellation is not complete. A similar value is obtained by extrapolating relaxation data at high loadings (up to 3000 Fe atoms per molecule), suggesting that these uncoupled spins persist on the protein shell even after an appreciable core has been built.

Animals↗
PubMed1998

Dysprosium-DOTA-PAMAM dendrimers as macromolecular T2 contrast agents. Preparation and relaxometry.

RATIONALE AND OBJECTIVES: The authors have investigated dysprosium [Dy]-DOTA-PAMAM, generation 5 (G = 5) dendrimers as a possible new class of macromolecular T2 contrast agents. The use of DOTA provides a metal complex with greater stability than can be achieved using DTPA as ligand, an important factor in the design of blood pool agents with long half-lives. METHODS: Generation 5 ammonia-core PAMAM dendrimers were linked to the bifunctional ligand p-SCN-Bz-DOTA. After determination of the number of conjugated DOTA molecules by 1H nuclear magnetic resonance, Dy3+ was titrated at a 90% molar ratio. For comparison, single ionic chelates of Dy-DTPA and Dy-DOTA also were prepared. Using a variable field relaxometer, T1 and T2 relaxation times were measured at 13 different field strengths from 0.05 to 1.5 T and temperatures of 3, 10, 20 and 37 degrees C. RESULTS: The synthesis resulted in a preparation with 76 DOTA and 68 Dy3+ ions per dendrimer molecule. The T1 relaxivity values for Dy-DTPA, Dy-DOTA, and the Dy-DOTA-based dendrimer all were independent of field strength, with values between 0.12 and 0.20 mM-1 sec-1. At lower fields (0.05-0.1 T), 1/T2 was identical to 1/T1. At higher fields, however, 1/T2 increased quadratically with field strength, with a strong dependence on temperature. The field-dependent component of 1/T2 was up to three times higher for the Dy-DOTA-based dendrimer compared with the single chelate molecules, with coefficients of 0.37 to 0.03 sec-1/Tesla2 for T = 3 to 37 degrees C. CONCLUSIONS: The results are interpreted with the "inner sphere" theory of susceptibility effects (Curie spin relaxation). The large temperature dependence suggests that the dominant mechanism of relaxation is the contact interaction effect, with the proton residence time as the primary time constant. This largely unexplored relaxation mechanism has the potential to create a new class of T2-selective contrast agents.

Contrast Media↗
PubMed1997

Hepatic hemosiderosis in non-human primates: quantification of liver iron using different field strengths.

Using a non-human primate model of idiopathic hemochromatosis, hemosiderin-induced T2 shortening of the liver was assessed at nine different field strengths over a range of 0.05 to 1.5 Tesla. The 1/T2 values increased linearly with field strength, with all specimens having approximately the same zero-field intercept. The slope of the field increase, termed "field-dependent T2 proton relaxation enhancement (PRE)", appeared to be proportional to the chemically determined tissue iron content, viz. 10.8 s-1T-1(mg Fe/g wet tissue)-1. The correlation between iron content and field-dependent T2 PRE (r = 0.94) was better than the correlation between iron content and 1/T2 values obtained at single field strengths. For livers containing > or = 2 mg Fe/g wet weight, biexponential T2 relaxation behavior emerged at higher field strengths, with the short T2 component (intracellular water) exhibiting a linear dependence of 1/T2 on field, while T2 of the long component (extracellular/sinusoidal water) was nearly field-independent. After maceration of the specimens, all T2 relaxation curves became monoexponential, including those for high iron content at high field strengths. The present data suggest that the use of double-field MR imaging to assess the field-dependent T2 PRE has potential for specific quantification of (liver) tissue iron stores.

Animals↗
PubMed1996

The relation between brain iron and NMR relaxation times: an in vitro study.

T1 and T2 relaxation times and iron concentrations were measured in 24 specimens of gray matter from fresh human and monkey brains at magnetic fields from 0.05 to 1.5 Tesla. Three different effects were found that correlate with iron content: a T1-shortening that falls off somewhat at high fields, a T2-shortening that is field-independent and thus important at low fields, and a contribution to 1/T2 that increases linearly with field strength. This linear field dependence has been seen only in ferritin and other ferric oxyhydroxide particles. Our results are in agreement with in vivo MRI studies and are generally consistent with values for ferritin solution, except for differences such as clustering of ferritin in tissue. A cerebral cavernous hemangioma specimen showed similar T2-shortening, but with a 2.7 times larger magnitude, attributed to larger clusters of hemosiderin in macrophages. The dependence on interecho time 2 tau was measured in three brains; 1/T2 increased significantly for tau up to 32 ms, as expected from the size of the ferritin clusters. These findings support the theory that ferritin iron is the primary determinant of MRI contrast in normal gray matter.

Adult↗
PubMed1996

T1 and T2 of ferritin solutions: effect of loading factor.

Proton magnetic relaxation times T1 and T2 were measured at field strengths from 0.05 T to 1.5 T in solutions of ferritin with loading factors from 90 to 3600 iron atoms per molecule. 1/T2 increased linearly with field strength, as previously observed, and the slope per unit iron was approximately the same in all samples. This latter finding indicates that the field dependence of T2 may be used as a measure of ferritin-bound iron, regardless of loading factor. A possible explanation is presented, based on the presumed antiferromagnetic structure of the ferritin core and the linear dependence of 1/T2 on core magnetization. A nonzero contribution to 1/T2 in the limit of low field and a contribution to 1/T1 were also found, both of which increase linearly with loading factor for constant protein concentration; these effects represent quantum mechanical dipole-dipole relaxation of water protons either by iron atoms on the surface of the core or by the iron core itself. Finally, the extrapolated intercept at LF = 0 for both 1/T1 and 1/T2 indicates a contribution from a small number of iron ions bound to the protein shell. These results may help in the use of MRI to measure brain iron and possibly even ferritin loading factor.

Animals↗
PubMed1996

Determination of spatial patterns of DNA damage and repair in intestinal crypts by multi-cell gel electrophoresis.

We have developed a method to quantitate DNA strand breaks as a measure of DNA damage and repair in intact, isolated intestinal crypts. The assay is a modified form of the single-cell gel electrophoresis or 'comet' assay. By maintaining the spatial relationship between the cells we were able to characterise the repair response and the susceptibility to DNA damage of cells as a function of their position in the crypt. All cells were equally repair competent over the first 30 minutes of the repair of UV-C and gamma-radiation induced lesions. DNA damage was equally distributed following gamma-radiation but following incubation with the topoisomerase II inhibitor etoposide, damage was greater in the lower crypt with an unusual component to the comet tall which was tapered, implying an incremental change in susceptibility by cell position. This tapered component of the comet tail resolved rapidly after removal of etoposide. The pattern of damage produced by hydrogen peroxide was dose dependent with lower doses producing more strand breaks in the base of the crypt-an effect lost at higher doses. The assay has the ability to detect differences between cells in their susceptibility to DNA damage and their subsequent repair response which may vary with their proliferative or differentiative status.

Animals↗
PubMed1996

T1 and T2 alterations in the brains of patients with hepatic cirrhosis.

PURPOSE: To determine whether previously reported T1-weighted MR hyperintensities in the brains of patients with hepatic cirrhosis are accompanied by changes in T2. METHODS: We measured T1 and T2 in the brains of 10 patients with chronic liver disease and 7 age-matched healthy volunteers, using classic spin-echo sequences with multiple saturation recovery times and multiple echoes. RESULTS: Both T1 and T2 were shortened in the basal ganglia, cortex, and white matter of the patients, with the greatest shortening in the globus pallidus, where 1/T1 was increased by 0.76 s-1 or 74% and 1/T2 by 1.45 s-1 or 11%. CONCLUSIONS: The T1 changes were accompanied by T2 changes of greater magnitude that were not as visible because T2 is normally much shorter than T1, especially in the globus pallidus.

Adult↗
PubMed1995

Magnetic resonance imaging of brain iron in health and disease.

Brain iron is a major contributor to magnetic resonance imaging (MRI) contrast in normal gray matter, and its role in the pathogenesis of different neurological disorders has also become apparent. Non-heme brain iron is present in the brain mainly in the form of ferritin. The unique magnetic properties of ferritin determine different signal changes on both T1- and T2-weighted images, and the T2 relaxation rates have a linear dependence on applied field strength. This finding is typical for ferric oxyhydroxide cores. The resulting T2-shortening also depends on echo-spacing used in the imaging sequence as well as on the water diffusion coefficient and the size of the ferritin cluster. Quantitation of non-heme brain iron by MRI aids in the diagnosis and monitoring of different neurological diseases.

Brain↗
PubMed1994

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine is a potent mutagen in the mouse small intestine.

Mutations in long lived stem cells are critical events in carcinogenesis. The Dlb-1 assay detects intestinal stem cell mutation at the Dlb-1 locus in Dlb-1a/b heterozygous mice by visualizing mutated clones of epithelial cells in situ which do not bind the lectin Dolichos biflorus agglutinin. We have used this assay to show that the food-derived heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a potent intestinal mutagen when administered either i.p. or p.o. This contrasts with the inactivity of the structurally related mutagen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in the assay which we have described previously. Immunocytochemical localization of the P-450 enzyme CYP1A2, which is responsible for the primary activation of these mutagens, shows that in untreated mice it is present in liver hepatocytes and in occasional villus epithelial cells but is absent from the target intestinal stem cell population. In addition, liver microsomes, unlike intestinal microsomes, were able to convert PhIP to the proximate mutagen N-hydroxy-PhIP. CYP1A2 immunoreactivity in beta-napthoflavone-induced animals was elevated in liver hepatocytes and increased to a lesser extent in duodenal villus epithelial cells. Treatment with beta-napthoflavone produced an unexpected 46% decrease in the number of Dlb-1 mutations in response to PhIP. Following treatment with PhIP, there was no difference in the number of Dlb-1 locus mutations between the proximal and distal ends of the small intestine in uninduced animals, indicating that the bile duct is unlikely to be responsible for transport of mutation inducing metabolites of PhIP to the small intestine. Our results demonstrate that metabolic activation of an indirect acting genotoxic agent can occur at a site other than the target tissue, and absence of the enzymes required for activation of a mutagen does not necessarily protect that tissue from its genotoxic effects.

Animals↗
PubMed1993

A study of the effects of human blood derivatives and individual growth factors on [3H]thymidine uptake in bovine retinal pericytes and endothelial cells.

Pericytes disappear early, selectively and specifically from retinal capillaries in diabetic microangiopathy, but little is known of their growth and turnover in health and disease. We have studied the effects of human blood derivatives and of a panel of individual growth factors on [3H]thymidine incorporation in bovine retinal pericytes and endothelial cells. Human serum and platelet-rich plasma stimulated incorporation of the nucleotide in a dose-dependent manner in both cell types, and did so more potently than platelet-free plasma. Consistent and significant stimulation of DNA synthesis in pericytes was observed with basic fibroblast growth factor (ED50 = 1.8 x 10(-13) mol/l), acidic fibroblast growth factor (7.4 x 10(-12) mol/l), insulin-like growth factor 1 (8.6 x 10(-10) mol/l), insulin (158 microU/ml) and endothelin-1 (6.1 x 10(-10) mol/l). Transforming growth factor beta 1 inhibited DNA synthesis (ID50 = 3.6 x 10(-10) mol/l) and so did heparin (1.4 x 10(-6) mol/l) and low molecular weight heparin (2.9 x 10(-6) mol/l). Retinal endothelial cells were stimulated by basic fibroblast growth factor (3.2 x 10(-13) mol/l) and acidic fibroblast growth factor (1.3 x 10(-9) mol/l), and inhibited by transforming growth factor beta 1 (1.6 x 10(-12) mol/l). Neither cell type was stimulated by platelet-derived growth factor (A + B chain heterodimer), epidermal growth factor, growth hormone, or nerve growth factor (7S complex). The characteristics and active concentrations of the above growth factors suggest that none is solely responsible for the pericyte mitogenic activity of platelets, serum or plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

T1 and T2 of ferritin at different field strengths: effect on MRI.

Nuclear magnetic relaxation times T1 and T2 were measured in ferritin solutions at field strengths from 0.04 to 1.5 T. T1 was relatively constant, but 1/T2 increased linearly with field strength, in agreement with earlier MRI observations in the monkey brain. This finding supports the theory that ferritin is responsible for T2 shortening in brain nuclei containing iron. The linear dependence of 1/T2 on magnetic field is unique and not explained by present theories of the magnetic properties of ferritin.

Animals↗