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Biomedical subjects

R G Steen

Publications and source records attributed to R G Steen.

At least 19 recordsLinked to original sources
PubMed1998

Age-related changes in brain T1 are correlated with iron concentration.

Age-related changes in brain T1 from 115 healthy subjects (range, 4.5-71.9 yr) were analyzed in relation to published regional brain iron concentration in cortex, caudate, putamen, and frontal white matter. The relaxation rate in these structures was linear with respect to iron concentration (P < 0.001). The iron relaxivity, k1 (s(-1)/mg iron/g wet weight), was much higher in cortex (5.5) and white matter (6.1) than in caudate (1.7) and putamen (1.0). These results are consistent with evidence that iron is an important factor in determining the relaxation properties of brain tissue. Iron relaxivity may reflect regional differences in the physical state of brain iron or in the interaction of brain iron with tissue water.

Adolescent↗
PubMed1998

Abnormalities of the central nervous system in very young children with sickle cell anemia.

OBJECTIVE: To determine whether abnormalities of the CNS are present in very young children with sickle cell anemia. STUDY DESIGN: Thirty-nine children with hemoglobin SS between the ages of 7 and 48 months were examined with magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). No child had a history of clinical stroke, although 3 had a history of seizures (2 neonatal). Twenty-one patients underwent developmental testing with the Bayley or McCarthy Scales. RESULTS: The overall prevalence of CNS abnormalities in asymptomatic children was 4 of 36 (11%, confidence interval 3, 26%). One patient had a silent infarct observed on MRI and a stenotic lesion on MRA; 3 other patients had stenotic lesions on MRA. The 3 patients who had a history of seizures all had lesions consistent with infarcts on MRI. Of the asymptomatic patients who had psychometric testing, 1 of 18 was developmentally delayed. One of 3 with a history of seizures had mild developmental delay. CONCLUSIONS: Very young children with sickle cell anemia (and no history of clinical stroke) have infarction in the brain and/or stenosis of major cerebral arteries, similar to those reported in older children. These findings indicate a need for larger studies to define the incidence of CNS lesions in this age group and to determine the need for early therapeutic intervention to prevent CNS sequelae of sickle cell disease.

Anemia, Sickle Cell↗
PubMed1997

Effects of p53 mutations on apoptosis in mouse intestinal and human colonic adenomas.

We have examined the effects of inactivation of the p53 tumor suppressor gene on the incidence of apoptotic cell death in two stages of the adenoma-to-carcinoma progression in the intestine: in early adenomas where p53 mutations are rare and in highly dysplastic adenomas where loss of p53 occurs frequently. Homozygosity for an inactivating germ-line mutation of p53 had no effect on the incidence or the rate of progression of ApcMin/+-induced adenomas in mice and also did not affect the frequency of apoptosis in the cells of these adenomas. To examine the effect of p53 loss on apoptosis in late-stage adenomas, we compared the incidence of apoptotic cell death before and after the appearance of highly dysplastic cells in human colonic adenomas. The appearance of highly dysplastic cells, which usually coincides during colon tumor progression with loss of heterozygosity at the p53 locus, did not correlate with a reduction in the incidence of apoptosis. These studies suggest that p53 is only one of the genes that determine the incidence of apoptotic in colon carcinomas and that wild-type p53 retards the progression of many benign colonic adenoma to malignant carcinomas by mechanism(s) other than the promotion of apoptosis.

Adenoma↗
PubMed1997

Phenotype of mice lacking functional Deleted in colorectal cancer (Dcc) gene.

The DCC (Deleted in colorectal cancer) gene was first identified as a candidate for a tumour-suppressor gene on human chromosome 18q. More recently, in vitro studies in rodents have provided evidence that DCC might function as a receptor for the axonal chemoattractant netrin-1. Inactivation of the murine Dcc gene caused defects in axonal projections that are similar to those observed in netrin-1-deficient mice but did not affect growth, differentiation, morphogenesis or tumorigenesis in mouse intestine. These observations fail to support a tumour-suppressor function for Dcc, but are consistent with the hypothesis that DCC is a component of a receptor for netrin-1.

Animals↗
PubMed1997

Establishing norms for age-related changes in proton T1 of human brain tissue in vivo.

The goal of this study was to determine the expected normal range of variation in spin-lattice relaxation time (T1) of brain tissue in vivo, as a function of age. A previously validated precise and accurate inversion recovery method was used to map T1 transversely, at the level of the basal ganglia, in a study population of 115 healthy subjects (ages 4 to 72; 57 male and 58 female). Least-squares regression analysis shows that T1 varied as a function of age in pulvinar nucleus (R2 = 56%), anterior thalamus (R2 = 51%), caudate (R2 = 50%), frontal white matter (R2 = 47%), optic radiation (R2 = 39%), putamen (R2 = 36%), genu (R2 = 22%), occipital white matter (R2 = 20%) (all p < 0.0001), and cortical gray matter (R2 = 53%) (p < 0.001). There were no significant differences in T1 between men and women. T1 declines throughout adolescence and early adulthood, to achieve a minimum value in the fourth to sixth decade of life, then T1 begins to increase. Quantitative magnetic resonance imaging provides evidence that brain tissue continues to change throughout the lifespan among healthy subjects with no neurologic deficits. Age-related changes follow a strikingly different schedule in different brain tissues; white matter tracts tend to reach a minimum T1 value, and to increase again, sooner than do gray matter tracts. Such normative data may prove useful for the early detection of brain pathology in patients.

Adolescent↗
PubMed1997

Age-related changes in the pediatric brain: quantitative MR evidence of maturational changes during adolescence.

PURPOSE: To determine whether a quantitative MR imaging method to map spin-lattice relaxation time (T1) can be used to characterize maturational changes in the normal human brain. METHODS: An inversion-recovery technique was used to map T1 transversely at the level of the basal ganglia in a study population of 19 healthy children (4 to 10 years old) and 31 healthy adolescents (10 to 20 years old), and in a normative population of 20 healthy adults (20 to 30 years old). RESULTS: Nonparametric analysis of variance showed that T1 decreases with age in the genu, frontal white matter, caudate, putamen, anterior thalamus, pulvinar nucleus, optic radiation, cortical gray matter (all P < .0001), and occipital white matter. There was a significant reduction in T1 between childhood (mean age, 7.1 +/- 1.4) and adolescence (mean age, 13.5 +/- 2.6) in all brain structures, but there was also a significant reduction in T1 between adolescence (mean age, 13.5 +/- 2.6) and adulthood (mean age, 26.5 +/- 3.4) in all brain structures except occipital white matter. Regression shows that T1 declines to within the range (mean +/- 2 SD) of young adult T1 values by about 2 years in the occipital white matter, by about 4 years in the genu, by 11 years in the cortical gray matter, by 11 years in the frontal white matter, and by 13 years in the thalamus. CONCLUSION: Brain structures mature at strikingly different rates, yet the ratio of gray matter T1 to white matter T1 does not change significantly with age. Thus, conventional MR imaging methods based on inherent contrast are insensitive to these changes. Age-related changes tend to reach completion sooner in white matter than in gray matter tracts. Such normative data are essential for studies of specific pediatric disorders and may be useful for assessing brain maturation in cases of developmental delay.

Adolescent↗
PubMed1996

Genetic mapping of a murine locus controlling development of T helper 1/T helper 2 type responses.

Genetic background of the T cell can influence T helper (Th) phenotype development, with some murine strains (e.g., B10.D2) favoring Th1 development and others (e.g., BALB/c) favoring Th2 development. Recently we found that B10.D2 exhibit an intrinsically greater capacity to maintain interleukin 12 (IL-12) responsiveness under neutral conditions in vitro compared with BALB/c T cells, allowing for prolonged capacity to undergo IL-12-induced Th1 development. To begin identification of the loci controlling this genetic effect, we used a T-cell antigen receptor-transgenic system for in vitro analysis of intercrosses between BALB/c and B10.D2 mice and have identified a locus on murine chromosome 11 that controls the maintenance of IL-12 responsiveness, and therefore the subsequent Th1/Th2 response. This chromosomal region is syntenic with a locus on human chromosome 5q31.1 shown to be associated with elevated serum IgE levels, suggesting that genetic control of Th1/Th2 differentiation in mouse, and of atopy development in humans, may be expressed through similar mechanisms.

Animals↗
PubMed1996

Genetic susceptibility to Leishmania: IL-12 responsiveness in TH1 cell development.

The genetic background of T lymphocytes influences development of the T helper (TH) phenotype, resulting in either resistance or susceptibility of certain mouse strains to pathogens such as Leishmania major. With an in vitro model system, a difference in maintenance of responsiveness of T cells to interleukin-12 (IL-12) was detected between BALB/c and B10.D2 mice. Although naive T cells from both strains initially responded to IL-12, BALB/c T cells lost IL-12 responsiveness after stimulation with antigen in vitro, even when cocultured with B10.D2 T cells. Thus, susceptibility of BALB/c mice to infection with L. major may derive from the loss of the ability to generate IL-12-induced TH1 responses rather than from an IL-4-induced TH2 response.

Animals↗
PubMed1995

Growth rate, labeling index, and radiation survival of cells grown in the Matrigel thread in vitro tumor model.

Six rodent cell lines (36B10 rat glioma cells, 9L rat gliosarcoma cells, V79 Chinese hamster lung fibroblasts, EMT6/UW and EMT6/Ro mouse mammary sarcoma cells, and RIF-1 mouse fibrosarcoma cells) were tested for growth in cylindrical threads of Matrigel. These cells grew in the threads with doubling times of 17-23 h, reaching maximum cell densities on the order of 10(8) cells/ml. Histological sections of these threads showed a heterogeneous cell distribution: cells grew to confluence at the thread surface and at somewhat lower cell densities in the thread core. [H-3]thymidine labeling index and radiation sensitivity were measured for 9L and EMT6/UW cells in Matrigel threads. For both cell types, the labeling index in Matrigel was lower than observed in cell monolayers, with higher labeling indexes at the thread periphery than in the thread core. When these threads were grown in stirred medium, lower thread diameters, higher cell yields per thread, and higher labeling indices were obtained. EMT6 cell monolayers coated with Matrigel were less radiosensitive than cells in uncoated monolayers. This protective effect was eliminated by irradiating in the presence of 1 mg/ml misonidazole. EMT6 cells consume nearly three times as much oxygen (mole/cm3-sec) as do 9L cells, which are equally radiosensitive in monolayers with or without a Matrigel coating. The radiation sensitivity of EMT6/UW cells in Matrigel threads was similar to that for monolayers of plateau phase cells, whereas for 9L cells, the response in threads was more similar to exponentially growing cells. We conclude that Matrigel threads provide an alternative in vitro model for studying the radiation response of cells in a three-dimensional geometry.

Animals↗
PubMed1994

In vivo measurement of tumor blood oxygenation by near-infrared spectroscopy: immediate effects of pentobarbital overdose or carmustine treatment.

Near-infrared (NIR) spectroscopy was used to measure blood oxygen saturation (SO2) in vivo, in normal rat brain and in subcutaneously-implanted rat 9L gliosarcoma. Changes in cranial and tumor blood SO2 were measured during lethal pentobarbital overdose. After sacrifice, SO2 of cranial blood fell rapidly to a mean of 5.0% of the pre-sacrifice values, whereas SO2 of tumor blood stabilized at a mean of 72.4% of the pre-sacrifice values. This suggests that oxygen consumption by tumor is very low compared to brain. Cranial blood had a higher SO2 than tumor blood before sacrifice (p = 0.03), and a lower SO2 after sacrifice (p = 0.02). The magnitude of the change in SO2 after sacrifice was greater in normal brain than in tumor (p = 0.02), showing that brain tissue uses a greater proportion of the oxygen in ischemic blood than does tumor tissue. To determine the effect of carmustine (BCNU) treatment on tumor and cranial blood SO2, we compared BCNU-treated rats with sham-treated rats. Continuous NIR measurements before and immediately following treatment (ie. over 30-60 min) showed that tumor blood SO2 tended to increase after BCNU treatment, whereas SO2 tended to decrease following sham-treatment. The difference in SO2 between treated and control tumors was significant at 60 min (p = 0.02). Thus BCNU treatment can potentially result in immediate increases in tumor oxygenation. The increase in treated tumor blood SO2 occurred despite the fact that there was no change in cranial blood SO2 even at day 4 following treatment. Tumor blood SO2 was inversely correlated with tumor size (p = 0.001), confirming that blood is more poorly oxygenated in large tumors.

Animals↗
PubMed1994

A genetic map of the mouse with 4,006 simple sequence length polymorphisms.

We have constructed a genetic map of the mouse genome containing 4,006 simple sequence length polymorphisms (SSLPs). The map provides an average spacing of 0.35 centiMorgans (cM) between markers, corresponding to about 750 kb. Approximately 90% of the genome lies within 1.1 cM of a marker and 99% lies within 2.2 cM. The markers have an average polymorphism rate of 50% in crosses between laboratory strains. The markers are distributed in a relatively uniform fashion across the genome, although some deviations from randomness can be detected. In particular, there is a significant underrepresentation of markers on the X chromosome. This map represents the two-thirds point toward our goal of developing a mouse genetic map containing 6,000 SSLPs.

Animals↗
PubMed1993

A genetic linkage map of the mouse: current applications and future prospects.

Technological advances have made possible the development of high-resolution genetic linkage maps for the mouse. These maps in turn offer exciting prospects for understanding mammalian genome evolution through comparative mapping, for developing mouse models of human disease, and for identifying the function of all genes in the organism.

Animals↗
PubMed1993

Relationship of perfusion to edema in the 9L gliosarcoma.

The relationship between tumor perfusion and edema was analyzed, with edema characterized as tumor wet/dry weight ratio. Perfusion of subcutaneous 9L gliosarcoma was measured by injection of 133Xe in saline into the tumor core, followed by gamma camera imaging of 133Xe washout kinetics. A significant inverse correlation was found between edema and tumor perfusion (p < 0.0002), suggesting that edema can limit tumor perfusion, perhaps through a mechanism of increased interstitial fluid pressure. The perfusion rate of highly edematous tumors was reduced to less than 10% of the perfusion rate of less edematous tumors (p < 0.001). It was also found that tumor edema increased significantly with increasing tumor volume (p < 0.001), which could account for the finding that perfusion declined significantly with increasing tumor volume (p < 0.02). These findings are potentially important because it is possible to quantify tumor edema in vivo, with millimeter resolution, using 1H magnetic resonance imaging (MRI). Thus MRI may provide a non-invasive technique for characterizing tumor perfusion or tumor drug delivery.

Animals↗
PubMed1992

In vivo phosphorus NMR spectroscopy of skin using a crossover surface coil.

A modified crossover surface coil with minimal B1 field penetration was used for collection of skin phosphorus NMR spectra. Projection imaging experiments show that the coil-sensitive volume is uniform at the phosphorus frequency, but strikingly nonuniform at the proton frequency. Experiments with an in vitro phosphorus phantom, designed to simulate skin and underlying tissue, demonstrated that 45.1% (+/- 1.2%) of total signal was derived from Sprague-Dawley rat skin and 19.3% (+/- 1.4%) of total signal was derived from Fischer-344 rat skin. 31P MR spectra of rat skin in vivo permitted resolution of four phosphorus compounds: nucleoside triphosphates, phosphocreatine (PCr), inorganic phosphate (Pi), and phosphomonoester. Spectra collected after skin flap surgery in Fischer-344 rats showed a 50.1% (+/- 7.6%) reduction in the ratio of PCr/Pi within 30 min of surgery, compared to presurgical PCr/Pi levels (P less than 0.01). Skin phosphorus spectra are potentially useful for assessment of skin flap and skin graft viability.

Animals↗
PubMed1992

Edema and tumor perfusion: characterization by quantitative 1H MR imaging.

Tumor perfusion is of central importance to the clinical oncologist because it has a direct effect on the success of cancer therapy. Yet determining whether a tumor is well or poorly perfused is difficult without the use of invasive techniques, because the variables that affect tumor perfusion are poorly understood. Quantitative MR imaging of tumor edema may provide a means of characterizing tumor perfusion, of studying heterogeneity of perfusion within the tumor mass, or of monitoring changes in tumor perfusion after therapy. A combination of factors often results in production of a large amount of edema within cranial or extracranial tumors. Any tumor that is encapsulated, whether by a fibrous tumor capsule or by a structure such as the cranium, will have an elevation in interstitial fluid pressure because dissipation of fluid is hindered. Elevated pressure of interstitial fluid acts to occlude tumor capillaries, so edema can cause a striking reduction of tumor perfusion. Because MR imaging can potentially be used for quantitative imaging of tumor edema, it may provide a means of indirectly measuring tumor perfusion. A review of the literature suggests that diffusion-weighted MR imaging may be better than T1- or T2-weighted MR imaging for quantitative imaging of tumor edema. I do not propose that diffusion-weighted imaging can measure perfusion directly; rather I hypothesize that a diffusion-weighted image can be correlated with tumor edema. Because edema indirectly regulates perfusion through the mechanism of interstitial fluid pressure, I propose an indirect correlation between the diffusion-weighted image and regional tissue perfusion. If the relationship between tumor perfusion and the pharmacokinetics of chemotherapeutic agents is better understood, MR imaging of tumor edema may even aid in predicting the delivery of drugs to a tumor.

Brain Edema↗
PubMed1992

Applications of magnetic resonance spectroscopy to the investigation of neuropsychiatric disorders.

Magnetic resonance spectroscopy (MRS) can noninvasively characterize tissue composition and metabolism in vivo without the need for radioactive isotope administration. For the neuropsychiatrist interested in the functional basis of disease, MRS offers an investigative tool capable of studying a wide variety of neuropsychiatric disorders. This report provides an overview of how MRS works, current and potential clinical applications for specific psychiatric populations, and limitations of the technology.

Brain Chemistry↗