Indoor radon and lung cancer in China.
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Air Pollutants↗
Biomedical subjects
G A Johnson
Publications and source records attributed to G A Johnson.
Observation of a water-depletion region surrounding loblolly pine roots by magnetic resonance imaging.
Magnetic resonance imaging was used to study sand containing various amounts of water and roots of loblolly pine planted into similar sand. Spin-lattice (T1) relaxation times of sand with water contents ranging from 0 to 25% (wt/wt) ranged from 472 to 1265 ms and increased with water content. Spin-spin (T2) relaxation times ranged from 54 to 76 ms and did not change in a discernible pattern with water content. Based on water content and measured T1 and T2 values, the signal intensity of sand/water images was predicted to increase with water content in a linear fashion, with the slope of the lines increasing with the time of acquisition repetition (TR). Measured signal intensity from images of sand with various water contents was found to follow a similar pattern. This allows interpretation of dark images of sand/water to be regions of low water content, and bright images to have comparatively greater water content. Images of loblolly pine seedling roots planted in identical sand showed the formation of a distinct water-depletion region first around the woody taproot and later showed the region extended and expanded around the lateral roots and clusters of mycorrhizal short roots. This observation strongly suggests that water uptake is occurring through the suberized region of the woody taproot.
Journal Article↗
Immunohistochemical and autoradiographic findings suggest that minoxidil is not localized in specific cells of vibrissa, pelage, or scalp follicles.
Immunohistochemistry with a minoxidil antibody suggested that minoxidil-immunoreactivity is associated with the root sheaths, laterally orientated differentiating matrix cells, and dividing epithelial cells of cultured vibrissa follicles of pigmented and albino neonatal mice. The dermal papilla and connective tissue sheath were devoid of minoxidil-immunoreactivity. To verify that minoxodil-immunoreactivity in the follicles was specific, immunostaining was conducted with dissected whisker pads, formalin-fixed "dead" follicles, and sections of spleen, liver and kidney (non-haired organs) cultured with minoxidil. Microscopic examination revealed minoxidil-immunoreactivity in all of these tissues. Follicles and whisker pads cultured with minoxidil, then washed for one h in media were devoid of minoxidil-immunoreactivity. These data suggest that minoxidil-immunoreactivity in cultured vibrissa follicles is probably non-specific. Sections of skin from C3H and CF1 mice which were topically dosed with minoxidil (in vivo) showed no minoxidil-immunoreactivity. Autoradiography demonstrated that tritiated minoxidil was bound in vivo and in vitro only to melanin granules in pigmented follicles of rodent and human tissue. This is probably non-specific binding since melanin is known to accumulate several chemically and pharmacologically unrelated drugs. It is reasonable to conclude that, under the conditions of these experiments, minoxidil is not specifically localized in any cells of whisker, pelage or, scalp follicles.
Animals↗
Magnetic resonance imaging of the thoracic cavity using a paused 3DFT acquisition technique.
A new pulse sequence designed for magnetic resonance imaging of the entire thoracic cavity is described. This sequence, called 3DPAUSE, is a rapid three-dimensional Fourier transform (3DFT) sequences with periodic pauses for breathing and additional rf pulses after each pause to restore the magnetization to steady-state before data acquisition resumes. Cardiac motion artifacts are effectively removed by signal averaging. Respiratory motion artifacts are removed by breath hold. Image artifacts caused by an inadequate number of pauses or by inappropriate placement of the pauses within a scan are shown, and ways to avoid these artifacts are discussed. 3DPAUSE provides the ability to acquire three-dimensional arrays in the thoracic cavity with minimal artifacts from respiratory and cardiac motions in a clinically reasonable time.
Animals↗
Colonic perforation following mild trauma in a patient with Crohn's disease.
A 26-year-old man with a history of Crohn's disease was struck in the abdomen by an opponent's shoulder while playing basketball. He presented to the emergency department 3 hours later with the complaint of abdominal pain and was admitted to the hospital for observation. Nine hours after presentation a computed tomography scan showed he had pneumoperitoneum and then underwent laparotomy. A perforated segment of sigmoid colon with severe inflammatory disease was found and resected. The rest of his small and large bowels were otherwise unremarkable. His localized but severe inflammatory bowel disease predisposed him to bowel perforation with minimal trauma. This is the first report of a patient with inflammatory bowel disease and traumatic colon perforation; it is also the first report of a patient with a bowel perforation with minimal traumatic force.
Adult↗
Maximizing contrast to noise with inductively coupled implanted coils.
Magnetic resonance (MR) microscopy with inductively coupled implanted coils has been used previously to follow loss and return of intra-medullary contrast as a result of nephrotoxic acute tubular necrosis with 117 microns resolution over a 2000 microns thick slice. The purpose of the current study was to further investigate the capabilities of in vivo MR microscopy by combining the implanted coil imaging technique with spin echo pulse sequence optimization done through signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) modeling. These models included consideration of the effects of T2* and sampling time on signal-to-noise and contrast-to-noise ratios. They were initially tested with GdCl3 and agar gel phantoms constructed to the relaxation time and spin density specifications of the intra-medullary junction which bridges the outer and inner stripe of the outer medulla. In vivo microscopy was performed using single turn radiofrequency (RF) coils that were surgically implanted around the left kidney of two rats and inductively coupled to an external "birdcage" body coil. The models revealed maximum CNR per unit imaging time at a TR of 800 msec. A TE of 16 msec proved to be the best compromise between loss of transverse magnetization and decreased bandwidth. These CNR predictions were supported by the gel phantom and in vivo data. Maximizing the CNR in the current study enabled us to improve the resolution of in vivo MR microscopy to 78 microns over a 1000 microns slice with an SNR of 40 and a CNR of eight in a total imaging time of 54 minutes.
Animals↗
Minoxidil sulfate is the active metabolite that stimulates hair follicles.
An important step in understanding minoxidil's mechanism of action on hair follicles was to determine the drug's active form. We used organ-cultured vibrissa follicles to test whether it is minoxidil or its sulfated metabolite, minoxidil sulfate, that stimulates hair growth. Follicles from neonatal mice were cultured with or without drugs and effects were assessed by measuring incorporation of radiolabeled cysteine in hair shafts of the treated follicles. Assays of minoxidil sulfotransferase activity indicated that vibrissae follicles metabolize minoxidil to minoxidil sulfate. Dose-response studies showed that minoxidil sulfate is 14 times more potent than minoxidil in stimulating cysteine incorporation in cultured follicles. Three drugs that block production of intrafollicular minoxidil sulfate were tested for their effects on drug-induced hair growth. Diethylcarbamazine proved to be a noncompetitive inhibitor of sulfotransferase and prevented hair growth stimulation by minoxidil but not by minoxidil sulfate. Inhibiting the formation of intracellular PAPS with chlorate also blocked the action of minoxidil but not of minoxidil sulfate. Acetaminophen, a potent sulfate scavenger blocked cysteine incorporation by minoxidil. It also blocked follicular stimulation by minoxidil sulfate apparently by directly removing the sulfate from the drug. Experiments with U-51,607, a potent minoxidil analog that also forms a sulfated metabolite, showed that its activity was inhibited by both chlorate and diethylcarbamazine. These studies show that sulfation is a critical step for hair-growth effects of minoxidil and that it is the sulfated metabolite that directly affects hair follicles.
Acetaminophen↗
Toward regulation of gonadal function by a synthetic hybrid molecule composed of gonadotropin and Fc fragment of immunoglobulin G.
A conjugate of human chorionic gonadotropin (HCG) and Fc fragment of immunoglobulin G was prepared by covalent cross-linking using the heterobifunctional reagent, N-succinimidyl 3-(2-pyridyldithio) propionate. Mouse Leydig tumor cells expressing receptors for luteinizing hormone were specifically lysed in vitro as a consequence of complement fixation via the Fc component of the hybrid molecule. Furthermore, administration of HCG-Fc to rams caused an acute depression in circulatory testosterone. This novel concept of targeted inhibition of gonadal function could prove to have future applications in control of reproductive processes.
Animals↗
Implanted coil MR microscopy of renal pathology.
Inductively coupled implanted coils have been shown to provide up to a 10-fold increase in signal-to-noise ratio when compared to whole-body imaging of small animals. The current study was designed to extend the implanted coil imaging technique to a rodent model of renal pathology. Resonant radiofrequency (RF) coils were implanted around the left kidney of four rats and inductively coupled from within a birdcage body coil. All images were acquired at 2 T using a T1-weighted spin-echo sequence with TR = 500 ms and TE = 20 ms. In vivo MR microscopy with voxels of 117 x 117 x 2000 microns demonstrated cortex, inner and outer medulla, and major vascular structures on baseline images. Mercuric chloride-induced nephrotoxic acute tubular necrosis (ATN) diminished cortico-medullary contrast at 24 h after dosing with pathologic evaluation demonstrating nephrotoxic changes in the inner cortex. The kidney regained a baseline MR appearance 360 h after dosing and resolution of the damage was confirmed with histology. T1 data were gathered on excised kidneys as an adjunct to the images to help correlate the loss and return of cortico-medullary contrast with the pathology and pathophysiology of nephrotoxic ATN. With implanted RF coils we were able to demonstrate renal pathology and follow its subsequent resolution. Specifically, loss and return of cortico-medullary contrast as a result of nephrotoxic ATN were serially documented in four rats. Such serial in vivo studies performed on single animals should further the use of MR microscopy by minimizing the number of animals required for adequate biostatistics.
Animals↗
Relaxation measurements at 300 MHz using MR microscopy.
Previous data on changes in tissue T1 with field have suggested the convergence of tissue T1 values toward a common value at high (greater than 4.0 T) fields. Measures of T2 dependence have suggested reduction of T2 with field. The purpose of this study was to observe the T1 and T2 at 85.5 and 300 MHz of microstructures in excised rat kidneys by employing MR microscopy. This study represents the first attempt of MR microscopy at 7.0 T with regard to the subject of magnetic field dependence of T1 and T2. As expected, T1 did increase with increasing field strength but not as dramatically as might be expected. Subtle differences in the microstructures of the kidney and the binding of water in those structures were discernible on the basis of T1 differences at 300 MHz. T2 values decreased, raising speculation concerning the mechanism for this dependence. The improved SNR permits smaller samples to be examined at much higher resolutions (greater than 30 X 30 X 200 microns), further extending the potentials for MR microscopy.
Animals↗
Image optimization in a computed-radiography/photostimulable-phosphor system.
Photostimulable phosphor imaging is an exciting new technology that has several advantages over film/screen radiography, the most important of which is the linearity of the photostimulable phosphor system over a wide exposure latitude. The photostimulable phosphor image is digital, and as such, provides options of how the image is viewed by radiologists. This report discusses the various image-processing parameters available for a photostimulable phosphor system and describes a rational approach for selecting these parameters in portable chest radiography. As photostimulable phosphor imaging becomes more widely implemented, an understanding of the processing parameters will facilitate the production of images that take full advantage of the benefits of these systems.
Humans↗
Experimental determination of wall shear rate in canine carotid arteries perfused in vitro.
The mathematical model of Hung (Tsai and Hung, 1984) is employed to determine the wall shear rate acting on canine carotid arteries perfused in vitro. Model equations for pulsatile flow in a deformable vessel are coupled with experimental data of dynamic pressure drop, flow rate, vessel radius and radial wall motion. Derived quantities, e.g. velocity profiles and wall shear, are obtained for vessels exposed to 'normotensive' hemodynamics, 'hypertension' simulations and perfusions in which the compliance of the vessel wall is deliberately altered. Our results indicate that wall shear varies markedly as a function of the hemodynamic environment. The effects of vessel radius vs flow rate on the development of wall shear are also demonstrated. It is found that convective processes correlate with the magnitude of wall shear in the 'hypertension' simulations. The present findings and complementary published data may explain, at least in part, the variations in vessel wall transport and endothelial cell biology we observe as a function of the hemodynamic environment. For example we have documented that the exposure of canine carotids to 'hypertensive' (vs 'normotensive') hemodynamics is associated with an increased flux of lipoproteins (LDL) into the intima and luminal media. Alternations in wall compliance, on the other hand, profoundly influence endothelial shape, orientation and cytoskeletal array.
Animals↗
Estrogen regulation of methyl p-hydroxyphenyllactate hydrolysis: correlation with estrogen stimulation of rat uterine growth.
We have recently demonstrated that methyl p-hydroxyphenyllactate (MeHPLA) is the endogenous ligand for nuclear type II binding sites in the rat uterus and other estrogen target and non-target tissues. MeHPLA binds to nuclear type II binding sites with a very high binding affinity (Kd approximately 4-5 nM), blocks uterine growth in vivo, and inhibits MCF-7 human breast cancer cell growth in vitro. Conversely, the free acid (p-hydroxyphenyllactic acid, HPLA) interacts with type II binding sites with a much lower affinity (Kd approximately 200 nM) and does not inhibit estrogen-induced uterine growth in vivo or MCF-7 cell growth in vitro. On the basis of these observations, we suggested that one way that estrogen may override MeHPLA inhibition of rat uterine growth may be to stimulate esterase hydrolysis of MeHPLA to HPLA. The present studies demonstrate that the rat uterus does contain an esterase (mol. wt approximately 50,000) which cleaves MeHPLA to HPLA, and that this enzyme is under estrogen regulation. This conclusion is supported by the observations that MeHPLA esterase activity is increased 2-3-fold above controls within 2-4 h following a single injection of estradiol, and is maintained at high levels for 16-24 h following hormone administration. This sustained elevation of MeHPLA esterase activity correlates with estradiol stimulation of true uterine growth and DNA synthesis.
Animals↗
Chemical shift imaging of atherosclerosis at 7.0 Tesla.
Chemical shift imaging (CSI) was performed on cadaveric atherosclerotic fibrous plaques, periaortic adipose tissue, and cholesterol standards using a 7.0 Tesla horizontal bore prototype imaging spectrometer. Proton spectroscopy of intact tissue and deuterated chloroform extracted samples was done at the equivalent field strength of 7.0 Tesla on a vertical bore spectrometer, including studies of temperature dependence and T2 relaxation measurements. Spectra obtained using CSI on the imaging magnet were comparable with those from the conventional vertical spectrometer. Fibrous plaques and adipose tissue had unique spectral features, differing in the ratios of their water and various fat components. Chloroform extractions revealed a typical cholesteric ester spectrum for the fibrous plaque in contrast to the triglyceride spectrum of the adipose tissue. These two tissues also had different T2 relaxation measurements of their major fat resonances, with fibrous plaques having a short T2 compared to adipose tissue (15.9 milliseconds vs. 46.2 milliseconds). Temperature dependence studies showed that spectral signal intensity of the fat resonance of the fibrous plaque increased while linewidth decreased with increasing temperature from 24 degrees C to 37 degrees C. Atherosclerotic lesions may be studied at 7.0 Tesla, and NMR parameters defined in the present study may be used for further studies at other magnetic field strengths.
Adipose Tissue↗
Three-dimensional imaging of the thoracic cavity.
Three-dimensional (3D) surface reconstruction techniques were applied to sets of computed tomographic (CT) images of the thoracic cavity. Emphasis was placed on extracting lung images. High quality, detailed 3D images of the lung surface and internal bronchial and vascular structures were produced.
Humans↗
Decline in sialic acid composition of cellular membranes isolated from ovine corpora lutea during prostaglandin-induced luteolysis: apparent independence of autoimmune recognition.
Sialic acid was quantified in plasma membranes of corpora lutea isolated during prostaglandin (PG) F2 alpha-induced luteolysis in sheep. Concentrations of sialic acid within membranes decreased after injection of PGF2 alpha, and before signs of luteal regression (i.e., a decline in tissue concentrations of progesterone) were manifested. Removal of residues of sialic acid from luteal membranes was not associated with cellular binding of gamma globulin, as monitored by indirect immunofluorescence microscopy. We suggest that desialylation of luteal membranes could be an important aspect of the mechanism of luteolysis. Such a process does not appear to involve participation of autoantibody.
Animals↗
Magnetic resonance microscopy of chemically-induced liver foci.
Magnetic resonance imaging (MRI) is a new imaging technique used in clinical diagnosis. This paper describes extension of the technique to basic research applications--specifically detecting and characterizing chemically-induced liver neoplasms and foci of cellular alteration. Two systems have been built that allow spatial microscopic resolution--more than 100,000 x greater than that of earlier efforts. Use of spin-lattice (T1) and spin-spin (T2) relaxation times permits detailed characterization of the tissue.
Animals↗
Magnetic resonance imaging of hepatic neoplasms in the rat.
Magnetic resonance imaging (MRI) at microscopic resolution was done on a live rat that had chemically induced hepatic neoplasms. Beginning at the anterior aspect of the liver, 16 contiguous transaxial slices (each 1.25 mm thick) were produced using three-dimensional Fourier transform sequences. The rat had been treated with diethylnitrosamine (200 mg/kg) at 70 days of age, and, subsequently, received periodic implants of 17a-ethynylestradiol for 60 weeks. Carr-Purcell-Meiboom-Gill (CPMG) sequences (repetition time = 2,000 and echo time = 20, 40, 60, 80 ms) were done to give quantitative measures of spin-spin relaxation times (T2). Pixel-by-pixel curve fitting from these multiple images yielded calculated T2 images. Histologic evaluation of three abnormal areas in the liver revealed solid and cystic hepatocellular adenomas. Although lesions were evident in early-echo images of the CPMG sequence, they were more apparent in the late-echo images. This was consistent with longer T2 relaxation times for the lesions. The voxels of dimensions (230 x 230 x 1,250 microns) permitted resolution of volume elements less than 0.07 mm3. This in turn permitted clear delineation of focal lesions less than 3 mm in diameter. The potential for MRI at microscopic resolution in toxicologic research is clearly demonstrated.
Animals↗