Biomedical subjects

G A Johnson

Publications and source records attributed to G A Johnson.

At least 19 recordsLinked to original sources

PubMed1992

In vivo magnetic resonance imaging of the blue crab, Callinectes sapidus: effect of cadmium accumulation in tissues on proton relaxation properties.

Nuclear magnetic resonance imaging (MRI) has been used to visualize the internal anatomy of a living blue crab. The resolution obtained in these studies was sufficient to distinguish individual organs by the differences in their proton densities and proton relaxation properties. T1 (spin-lattice relaxation time)-weighted imaging revealed the lipid-rich nature of the hepatopancreas and gonadal tissue. To evaluate the effect of metal-induced stress on the different organs, crabs were exposed to elevated levels of cadmium in their diet, which resulted in increased concentrations of both cadmium and copper in the hepatopancreas. The spin-spin relaxation time, T2, of mobile protons in the metal-exposed tissue was significantly greater than T2 in the control tissues. These measurements suggest that the excess copper in the exposed tissues was diamagnetic [Cu(I)], since the presence of paramagnetic copper [Cu(II)] would result in a decrease of observed T2 values. We hypothesize that the increased T2 value is a reflection of increased free water in the hepatopancreas. These studies show that magnetic resonance imaging is an important nondestructive tool for the study of morphological and physiological changes that occur in marine invertebrates in response to anthropogenic and natural stresses.

Animals↗

PubMed1992

A model of pulsatile flow in a uniform deformable vessel.

Simulations of blood flow in natural and artificial conduits usually require large computers for numerical solution of the Navier-Stokes equations. Often, physical insight into the fluid dynamics is lost when the solution is purely numerical. An alternative to solving the most general form of the Navier-Stokes equations is described here, wherein a functional form of the solution is assumed in order to simplify the required computations. The assumed forms for the axial pressure gradient and velocity profile are chosen such that conservation of mass is satisfied for fully established pulsatile flow in a straight, deformable vessel. The resulting equations are cast in finite-difference form and solved explicitly. Results for the limiting cases of rigid wall and zero applied pressure are found to be in good agreement with analytical solutions. Comparison with the experimental results of Klanchar et al. [Circ. Res. 66, 1624-1635 (1990]) also shows good agreement. Application of the model to realistic physiological parameter values provides insight as to the influence of the pulsatile nature of the flow field on wall shear development in the presence of a moving wall boundary. Specifically, the model illustrates the dependence of flow rate and shear rate on the amplitude of the vessel wall motion and the phase difference between the applied pressure difference and the oscillations of the vessel radius. The present model can serve as a useful tool for experimentalists interested in quantifying the magnitude and character of velocity profiles and shearing forces in natural and artificial biologic conduits.

Animals↗

PubMed1992

Surface coil imaging of rat spine at 7.0 T.

An inductively coupled surface coil for imaging the rat spine at 7 T is described. This planar circular probe was made from microwave substrate to limit the size of the coil and to minimize the magnetic susceptibility. The surface coil was used as a single transmit/receive coil and as a receive-only coil with a birdcage body coil for excitation. The signal-to-noise ratio (SNR) of the probe was compared to a 5-cm birdcage coil and exceeded the birdcage coil's SNR by three to six times at superficial structures. The main advantages of the probe are an improved SNR for superficial structures and a simple design and use. Images with 50 x 50 x 500 micron voxels were obtained of the rat spine with excellent anatomical detail.

Animals↗

PubMed1992

A probe for specimen magnetic resonance microscopy.

One of the primary limits to spatial resolution in magnetic resonance (MR) microscopy is the limited signal. The purpose of this study is to build a radiofrequency (rf) probe for MR microscopy of fixed specimens at 300 MHz. The design criteria for the probe were (1) high sensitivity; (2) good rf homogeneity; (3) minimization of BO variations. All probes were Helmholtz pairs operating at 300 MHz. Coils were constructed from copper/Teflon/copper microwave substrate which eliminated susceptibility problems from solder and discrete capacitors. Signal-to-noise ratio (SNR) was compared with a conventional solenoid. Phantoms of agar gels and saline-filled tubes were used to characterize the SNR and homogeneity. SNR measurements of the coil pairs showed a marked improvement (up to 60%) over that of the reference solenoid. The region of homogeneity was defined as a 10% variation in signal intensity. This correlated with the coil's inner diameter. Graphs of SNR versus diameter, separation, and copper foil width allowed for optimization of the structure. Using this coil, MR microscopy is now possible on small, fixed specimens with pixels as small as 20 x 20 x 30 microns. Work is currently under way exploiting the SNR and homogeneity provided by this probe to determine the degree to which MR microscopy might add to the pathologists' diagnostic tools.

Copper↗

PubMed1992

Potassium channel conductance: a mechanism affecting hair growth both in vitro and in vivo.

The opening of intracellular potassium channels has been suggested as a mechanism regulating hair growth. Enhancing the flux of potassium ions is a mechanism shared by several structurally diverse antihypertensive agents including minoxidil sulfate (the active metabolite of minoxidil), pinacidil, P-1075 (a potent pinacidil analog), RP-49,356, diazoxide, cromakalim, and nicorandil. Of these drugs, minoxidil, pinacidil, and diazoxide have been reported to elicit hypertrichosis in humans. This potassium channel hypothesis was examined by testing these drugs for effects on hair growth both in vitro and in vivo. For the in vitro studies, mouse vibrissae follicles were cultured for 3 d with drug and the effects on hair growth were measured by metabolic labeling. All drugs, except diazoxide, enhanced cysteine incorporation into the hair shafts of the cultured vibrissae. Diazoxide was poorly soluble and thus was tested only at low doses. Minoxidil, P-1075, cromakalim, and RP-49,356 were also evaluated in vivo by measuring hair growth effects in balding stumptail macaque monkeys. The drugs were administered topically to defined sites on balding scalps once per day for 4-5 months and the amount of hair grown was determined by monthly measurements of shaved hair weight. Three of the drugs produced significant increases in hair weight whereas, the RP-49,356 had no effect. These studies provide correlative evidence that the opening of potassium channels is an important regulatory mechanism for hair growth. This provides the impetus for further studies on this potentially important mechanism affecting hair biology.

Animals↗

PubMed1992

Minoxidil sulfotransferase, a marker of human keratinocyte differentiation.

The sulfation of minoxidil is catalyzed by a sulfotransferase activity in a number of tissues including skin. To investigate further the nature of the minoxidil sulfotransferase activity in epithelial tissue and to compare this activity to that of cholesterol sulfotransferase, which has already been shown to be induced during the differentiation of epithelial cells, we cultured normal human epidermal keratinocytes in a keratinocyte growth medium for 4 d, after which the media were replaced with either the same growth media or media with increasing Ca++ concentrations. Cholesterol sulfotransferase, minoxidil sulfotransferase, and transglutaminase were determined during the differentiation of the cells in the three media. Time-activity curves that suggested two different sulfotransferase activities were induced during the differentiation process. U-77581, a competitive inhibitor of minoxidil sulfotransferase activity, inhibited the sulfation of minoxidil sulfotransferase activity in the keratinocyte homogenates, but it did not inhibit the sulfation of cholesterol. These data indicate that at least two sulfotransferase activities are induced during the differentiation of epithelial keratinocytes and minoxidil sulfotransferase is an early marker of that differentiation.

Biomarkers↗

PubMed1992

Interaction of minoxidil with pigment in cells of the hair follicle: an example of binding without apparent biological effects.

To identify minoxidil target cells in hair follicles we followed the uptake of radiolabeled drug in mouse vibrissae follicles both in vitro and in vivo. Autoradiography showed that both 3H-minoxidil and 3H-minoxidil sulfate accumulated in the differentiating epithelial matrix cells superior to the dermal papilla, a distribution similar to that of pigment. Minoxidil localized in melanocytes, melanocyte processes, and areas of greater melanin concentrations within the epithelial cells. Although uptake of minoxidil was significantly less in unpigmented follicles, the drug stimulated proliferation and differentiation of both pigmented and unpigmented follicles. Labeled minoxidil bound to Sepia melanin and was displaced with unlabeled minoxidil and other electron donor drugs. This interaction with melanin acts as a targeting mechanism of minoxidil to pigmented hair follicles but has no apparent functional significance in hair growth. This work illustrates how measurement of drugs in hair may be biased by pigmentation.

Animals↗

PubMed1992

Mechanism of detection of acute cerebral ischemia in rats by diffusion-weighted magnetic resonance microscopy.

BACKGROUND AND PURPOSE: The aim of this study was to measure apparent diffusion coefficients in rat brain tissue exposed to ouabain, glutamate, and N-methyl-D-aspartate and to compare them with apparent diffusion coefficients found in acute cerebral ischemia. METHODS: The apparent diffusion coefficient was measured using magnetic resonance microscopy in four groups of Sprague-Dawley rats after occlusion of the right middle cerebral artery and ipsilateral common carotid artery (n = 7), after ouabain exposure (n = 6), during glutamate exposure (n = 7), or during N-methyl-D-aspartate exposure (n = 3). Ouabain, glutamate, and N-methyl-D-aspartate were applied via an intracerebrally implanted microdialysis membrane. RESULTS: Three hours after the induction of focal cerebral ischemia, a 33% reduction in the apparent diffusion coefficient was observed in the right dorsolateral corpus striatum and olfactory cortex. After ouabain exposure, reductions in the apparent diffusion coefficient were observed within a 1,500-microns radius of the microdialysis membrane. Quantitative analysis revealed that apparent diffusion coefficient values in ischemic and ouabain-exposed tissue fell within the same range. Glutamate and N-methyl-D-aspartate reduced the brain tissue apparent diffusion coefficient by 35% and 40%, respectively. CONCLUSIONS: On the basis of these findings, we conclude that ischemia-induced apparent diffusion coefficient reductions are likely caused by a shift of extracellular to intracellular water.

Acute Disease↗

PubMed1992

Hair growth effects of oral administration of finasteride, a steroid 5 alpha-reductase inhibitor, alone and in combination with topical minoxidil in the balding stumptail macaque.

A 5 alpha-reductase inhibitor, finasteride, was administered orally at 0.5 mg/day, alone or in combination with topical 2% minoxidil, for 20 weeks to determine the effects on scalp hair growth in balding adult male stumptail macaque monkeys. A 7-day dose-finding study showed that both 0.5- and 2.0-mg doses of the drug produced a similar diminution in serum dihydrotestosterone (DHT) in male stumptails. Hair growth was evaluated by shaving and weighing scalp hair at baseline and at 4-week intervals during treatment to obtain cumulative delta hair weight (sum of the 4-week changes in hair weight from baseline) for the 20-week study. The activity of the 5 alpha-reductase enzyme was assessed by RIA of serum testosterone (T) and DHT at 4-week intervals. The combination of finasteride and minoxidil generated significant augmentation of hair weight (additive effect) compared to either drug alone. Finasteride increased hair weight in four of five monkeys. When the data of the one nonresponsive monkey were excluded, finasteride elicited a significant elevation in hair weight compared to topical vehicle alone. Minoxidil also evoked a significant increase in hair weight compared to vehicle alone. Serum T was unchanged, whereas serum DHT was significantly depressed in monkeys that received either finasteride or the combination of finasteride and minoxidil. These data suggest that inhibition of the conversion of T to DHT by this 5 alpha-reductase inhibitor reverses the balding process and enhances hair regrowth by topical minoxidil in the male balding stumptail macaque.

5-alpha Reductase Inhibitors↗

PubMed1991

The use of gradient flow compensation to separate diffusion and microcirculatory flow in MRI.

This paper describes a new MR imaging technique termed Modified Stejskal Tanner versus Flow Compensation (MST/FC) for the separation of diffusion and microcirculatory flow. The theory behind the sequence is explained, along with a five-component model of microcirculation applicable to any "perfusion" imaging technique. Phantom data is presented showing that (1) diffusion effects can be matched between MST and FC (suggesting the possibility of flow-compensated diffusion imaging), and (2) the technique is a quantitative method of separating diffusion and slow (less than 0.25 mm/s) tortuous flow through a Sephadex column. Furthermore, animal images show the technique to be feasible and quantitative in measuring rat brain microcirculation under normal, vasodilated (hypercarbia), and no-flow (post mortem) conditions.

Acetone↗

PubMed1991

Three-dimensional MR microscopy with large arrays.

MR microscopy of fixed specimens is described using large (256(3] arrays. Images are acquired at 7.0 T with voxels as small as 70 x 70 x 70 microns (3.4 x 10(-4) mm3), more than 25,000 times smaller than routine clinical body imaging. Separation of the acquisition, reconstruction, archival, and analysis onto networked workstations provides flexibility and efficiency in handling the large data sets. The isotropic data can be interactively displayed through any plane without loss of in-plane resolution. The potential for applications of MR microscopy in clinical pathology is addressed.

Animals↗

PubMed1991

Diffusion/microcirculation MRI in the rat brain.

The CO2 fraction of an anesthetized rat's breathing mixture was changed (from 0 to 10%) to attempt to change the brain microcirculation and observe these changes in diffusion measurements of the neural tissue. Brain apparent diffusion coefficients were measured to be (0.71 +/- 0.01) X 10(-3) mm2/s before sacrifice and (0.39 +/- 0.01) X 10(-3) mm2/s after sacrifice. Multiple diffusion components were observed, consistent with flowing material, but the extra components did not increase with increased CO2. It is proposed that the additional components may be due to extracellular, extravascular water such as CSF.

Animals↗

PubMed1991

Pre- and postmortem diffusion coefficients in rat neural and muscle tissues.

Pulsed gradient diffusion-weighted spin-echo images (7 to 11 gradient strengths) were obtained in a coronal slice through the midbrain for five normal adult white rats before and after sacrifice in a 2-T CSI system with air temperature control. The pulse sequence was cardiac gated and respiratory synchronized in order to minimize motion artifacts (Tr greater than 2 s. Te = 30 ms). Diffusion coefficients reflecting several tissue compartments (D*) in brain and muscle were calculated and referenced to simultaneously imaged tubes of water. In the living animals, brain cortical matter had a value of D* = (0.82 +/- 0.02) x 10(-3) mm2/s. deeper brain regions had a value of D* = (0.73 +/- 0.02) x 10(-3) mm2/s, and the muscle had a value of D* = (1.4 +/- 0.1) x 10(-3) mm2/s. Postmortem the values in brain dropped by approximately 30%, while remaining constant in muscle. Signal intensity in the spin-echo images for muscle tissue rose by 50% over a 1- to 2-h interval after sacrifice while that of brain tissue remained relatively stable.

Animals↗

PubMed1991

Magnetic resonance microscopy of toxic renal injury induced by bromoethylamine in rats.

The alkylhalide 2-bromoethylamine hydrobromide (BEA) produces renal injury in rats that mimics analgesic-related renal injury in humans. Our purpose was to examine this injury, in vivo in rats, with magnetic resonance (MR) microscopy and correlate MR findings with findings from light microscopy of hematoxylin-eosin-stained sections. Rats (n = 48) were injected intravenously with BEA (150 mg/kg) or saline and imaged with MR 6, 48, and 336 hr later. The spin-spin relaxation time, T2, was measured from the cortex to the papilla. In other rats, we measured regional water content of the kidney. Renal injury was present 48 and 336 hr after BEA dosing based on increased renal organ weights, decreased urine specific gravity, and significant renal lesions (H & E). T2 was elevated in the inner stripe of the outer medulla in injured kidneys at 48 hr. The differences in T2 between cortex and outer medulla were also elevated 48 hr after BEA. In the inner medulla, there were no changes in T2 after BEA treatment. However, in all groups there were significant regional differences in T2. The value of T2 increased from outer to inner medulla and this gradient was directly correlated with water content. Thus, MR microscopy detected damage in the outer medulla after BEA injury but not the damage in the inner medulla. T2 appeared to reflect the water content in the different regions of the medulla. The noninvasive in vivo capability of MR microscopy, with its high sensitivity to tissue water, allows the toxicologist to monitor the progression and regression of toxic insult in the same animal. At present the technology is complicated. The precise and accurate measure of MR-sensitive parameters in live animals at microscopic resolution is difficult. However, as the technology matures, there will be significant improvements providing the toxicologist a unique in vivo tool.

Animals↗

PubMed1991

In vivo measurement of proton diffusion in the presence of coherent motion.

Measurement of the self-diffusion coefficient D of water in tissue has been performed traditionally using the technique proposed by Stejskal and Tanner. A variant of that technique is shown here, employing flow-compensated gradients that significantly reduce the sensitivity to small coherent motions that are common in body imaging. An interleaved sequence with four values of diffusion-sensitizing gradient (b) minimizes registration errors. Eddy currents and other systematic errors are reduced, permitting the measurement of standards in an imaging context within 5% of nonimaging values in the literature. The flow-compensated sequence permits the measure of D for tissues in the abdominal cavity of the rat. We present in vivo measurements of D for the following rat tissues; liver, kidney (cortex), kidney (medulla) muscle, brain, fat.

Acetone↗

PubMed1991

Small object contrast in AMBER and conventional chest radiography.

The ability of a commercially available scanning equalization system for chest radiography to render small object contrast in the lung-, mediastinum-, and subdiaphragm-equivalent regions of an acrylic chest phantom was quantitatively evaluated. Images from nine chest phantoms that represented a wide range of patient sizes and dynamic ranges of x-ray transmittance were analyzed. Subject contrast was measured with a photostimulable phosphor detector, and images were acquired in both equalized and nonequalized (conventional) imaging modes. Available subject contrast in the lung-equivalent region was 8%-15% lower in the equalized images compared with the nonequalized images in all phantoms (patient types); contrast in the mediastinum-, retro-cardiac-, and subdiaphragm-equivalent regions was 11%-63% higher in the equalized images, with the degree of improvement increasing as patient size and dynamic range increased. Images of each phantom were also acquired with the screen-film systems currently in use at the authors' institution, permitting an assessment of the relative performance (in terms of radiographic contrast) of these imagers with and without use of equalization.

Diaphragm↗

PubMed1991

Quantitative proton magnetic resonance imaging in focal cerebral ischemia in rat brain.

Proton magnetic resonance (MR) imaging has been recommended as a diagnostic tool for the detection of focal cerebral ischemia. We compared microscopic MR images of rat brains after focal cerebral ischemia with evidence of histological damage found on corresponding silver-impregnated or cresyl violet-stained brain sections. Ten male Wistar rats were subjected to permanent unilateral occlusions of the right middle cerebral and common carotid arteries under halothane anesthesia. Twenty-four hours later the area of injury on MR images amounted to 26% of the total slice area, whereas only 9% of the total slice area was necrotic on histological sections from the same animals. The infarcted areas on tissue sections were surrounded by regions of selective neuronal injury in the cerebral cortex and occasionally in the hippocampus. The area of injury on MR images was larger than the combined areas of infarction and selective neuronal injury on histological sections. Areas of increased T2 values on MR images extended medially into noninfarcted striatum and laterally and dorsally into noninfarcted cortex. The lateral and dorsal areas on MR images frequently coincided with cortical areas in which considerable selective neuronal injury was present in the upper cortical layers. We hypothesize that the abnormal areas on MR images above histologically normal brain tissue represent the ischemic penumbra. If true, this is the first demonstration of the ischemic penumbra by MR imaging and may reflect our use of Wistar rats, a new image analysis technique, and ultra-high resolution MR imaging.

Animals↗

PubMed1991

Research into psychiatric disorder after stroke: the need for further studies.

Attention is drawn to some shortcomings of previous findings with regard to the nature, prevalence and aetiology of psychiatric disorder after stroke, and in particular post-stroke depression. Reasons for and drawbacks of the emphasis on depression in studies to date are discussed. Inconsistencies amongst previous findings are examined and it is suggested that many further studies in the area are warranted providing methodological difficulties are addressed adequately.

Cerebrovascular Disorders↗