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G A Johnson

Publications and source records attributed to G A Johnson.

At least 127 records · Page 7Linked to original sources
PubMed1994

Minoxidil sulfation in the hair follicle.

The in vivo model which may be the most accurate for the ability to predict hair growth in humans, and which was utilized in the preclinical development of minoxidil, is the adult stumptailed macaque. Previous reports have suggested that the enzyme activity which accounts for the activation of minoxidil, i.e., minoxidil sulfotransferase, is present in skin. We have demonstrated that scalp skin from the stumptailed macaque contains minoxidil sulfotransferase activity, and further with dissection of that scalp skin into epidermis, dermis and hair follicle, most of sulfotransferase activity was present in the follicle. Sulfotransferase activity in the hair follicle in freeze-dried scalp skin sections from 9 stumptailed macaques ranged from 47 to 84% of the total (mean 61 +/- 12%). Much less minoxidil sulfotransferase activity was measured in the epidermis (mean 18 +/- 11%, with a range of 2-37%) and the dermis (mean 21 +/- 8%, with a range of 4-35%) of these scalp sections. These results indicate that the scalp skin from the stumptailed macaque contains minoxidil sulfotransferase activity and this activity is largely localized in the hair follicle which may account for its ability to stimulate hair growth in this animal model.

Animals↗
PubMed1994

Magnetic resonance imaging of chronic myocardial infarcts in formalin-fixed human autopsy hearts.

BACKGROUND: In post-myocardial infarction patients, three-dimensional structure of the infarct as well as infarct size are likely to be important factors affecting mortality, cardiac function, and arrhythmias. Current morphological methods for determining three-dimensional infarct structure in autopsied hearts are inexact and time consuming. The cardiac magnetic resonance imaging techniques used in living patients have shown potential in determining infarct size and structure but have limited resolution for morphometric postmortem studies. The recent development of magnetic resonance microscopy raises the possibility that three-dimensional infarct structure can be quantified at microscopic levels in autopsied hearts. The purpose of this study was to determine the ability of magnetic resonance imaging at different spatial resolutions to differentiate infarcted from noninfarcted myocardium. METHODS AND RESULTS: Magnetic resonance imaging was performed at 2.0 T on cross sections taken from 10 autopsied hearts containing old myocardial infarcts. T1 was derived from six images with repetition times (TRs) for each image ranging from 100 to 3200 milliseconds. T2 was derived from multi-echo images with echo times (TEs) ranging from 10 to 60 milliseconds. Resolution was approximately 400 x 400 microns in 2-mm-thick slices. Sites of infarcted and noninfarcted tissue were identified from histological sections taken from each slice, and the T1 and T2 values of these sites were obtained. Microscopic images were acquired with voxels of 100 x 100 x 625 microns, representing tissue volumes more than 1000-fold smaller than conventional clinical images. In all cases, T1 of infarcted tissue (459 +/- 266 milliseconds, mean +/- SD) was greater than that of noninfarcted tissue (272 +/- 163 milliseconds). Also, in all cases, T2 of infarcted tissue (49 +/- 14 milliseconds) was greater than that of noninfarcted tissue (35 +/- 8 milliseconds). CONCLUSIONS: T1 and T2 values for infarcted tissue are significantly different from those of noninfarcted tissue (P < .001). Based on these findings, it should be possible to develop techniques to perform three-dimensional imaging and quantitation of infarcts with a resolution of 400 microns or less. When volumetric three-dimensional imaging was performed using a T1-weighted sequence, the resulting 256(3) arrays supported isotropic resolution at 400 microns (voxel volume, 0.064 mm3). Subsequent volume rendering using a compositing algorithm clearly shows the infarcted areas in three dimensions. The techniques demonstrate the potential for quantitative three-dimensional cardiac morphometry using magnetic resonance imaging.

Algorithms↗
PubMed1994

Utility of postmortem magnetic resonance imaging in clinical neuropathology.

Over 200 brains were examined by postmortem magnetic resonance imaging to determine the utility of this imaging procedure as an adjunct to the standard postmortem examination of the brain and spinal cord. One unembalmed cadaver was also studied using a conventional 1.5-tesla (T) field-strength unit, and three formalin-fixed sections of the hippocampus were imaged using a high field-strength (7.0-T) prototype imaging system. The postmortem magnetic resonance images proved to be an invaluable aid that complemented the standard pathologic examination of the brain and spinal cord. The compelling advantages of this postmortem radiographic procedure included the three-dimensional aspects of the images; the ability to detect mineral (ie, iron) deposits; small focal lesions such as hemorrhages or infarcts; and the ability to evaluate the extent of cerebral edema. For the same reasons, as well as its archival potential for documenting the topographic distribution of pathologic processes, this technique has great promise for forensic cases. High field-strength (7.0-T) imaging brought the resolution of magnetic resonance to the microscopic level and reaffirmed the potential value of magnetic resonance imaging for diagnostic and investigative studies in which both the histologic and fine radiologic features of lesions are of interest.

Autopsy↗
PubMed1993

A high-temperature superconducting receiver for nuclear magnetic resonance microscopy.

A high-temperature superconducting-receiver system for use in nuclear magnetic resonance (NMR) microscopy is described. The scaling behavior of sources of sample and receiver-coil noise is analyzed, and it is demonstrated that Johnson, or thermal, noise in the receiver coil is the factor that limits resolution. The behavior of superconductors in the environment of an NMR experiment is examined, and a prototypical system for imaging biological specimens is discussed. Preliminary spin-echo images are shown, and the ultimate limits of the signal-to-noise ratio of the probe are investigated.

Animals↗
PubMed1993

Ascertaining the true incidence of stroke: experience from the Perth Community Stroke Study, 1989-1990.

OBJECTIVE: To determine the age and sex specific incidence, and case fatality of stroke in Perth, Western Australia. DESIGN AND SETTING: A population-based descriptive epidemiological study. SUBJECTS: All residents of a geographically defined segment of the Perth metropolitan area (population 138,708) who had a stroke or transient ischaemic attack between 20 February 1989 and 19 August 1990, inclusive. MAIN OUTCOME MEASURES: Definite acute "first-ever-in-a-lifetime" (first-ever) and recurrent stroke classified according to standard definitions and criteria. RESULTS: During the 18-month study period, 536 stroke events occurred among 492 patients, 69% of which were first-ever strokes. The crude annual event rate for all strokes was 258 (95% confidence interval 231-285) per 100,000, and the overall case fatality at 28 days was 24% (95% CI, 20%-28%). The crude annual incidence for first-ever strokes was 178 (95% CI, 156-200) per 100,000; 189 (95% CI, 157-221) per 100,000 in males and 166 (95% CI, 136-196) per 100,000 in females. The corresponding rates, age-adjusted to the "world" population, were 132 (95% CI, 109-155) for males and 77 (95% CI, 60-94) for females. CONCLUSIONS: In contrast to mortality rates for ischaemic heart disease, the incidence of stroke in Australia appears little different from that for several other Western countries. For both males and females the incidence of stroke rises exponentially with increasing age. Although the sex-dependent difference in the risk of stroke is greatest in middle age, males are at greater risk of stroke even among the most elderly. To determine the incidence of stroke accurately, population-based studies of stroke need exhaustive and overlapping sources of case ascertainment. If only cases admitted to hospital had been used, we would have underestimated the rate of stroke among the most elderly by almost 40%. We estimate that approximately 37,000 people, about 50% of whom are over the age of 75, suffer a stroke each year in Australia.

Adolescent↗
PubMed1993

Determining the incidence of different subtypes of stroke: results from the Perth Community Stroke Study, 1989-1990.

OBJECTIVE: To determine the incidence and case fatality of seven distinct subtypes of stroke in Perth, Western Australia. DESIGN AND SETTING: A population-based descriptive epidemiological study. SUBJECTS: All residents of a geographically defined segment of the Perth metropolitan area (estimated population 138,708 persons) who had a stroke or transient ischaemic attack between 20 February 1989 and 19 August 1990, inclusive. MAIN OUTCOME MEASURES: The following subtypes of stroke were classified according to standard clinical, radiological and pathological criteria: types of cerebral infarction, namely, large artery (thrombotic) occlusive infarction (LAOI), cerebral embolic infarction (EMBI), lacunar infarction (LACI) and boundary zone infarction (BZI); primary intracerebral haemorrhage (PICH); subarachnoid haemorrhage (SAH); and stroke of undetermined cause. RESULTS: Over the 18-month study period 536 stroke events were registered, of which 86% (95% confidence interval, 83%-89%) had a defined "pathological" diagnosis on the basis of computed tomographic scanning, magnetic resonance imaging or necropsy. Cerebral infarction accounted for 71% of cases (95% CI, 68%-75%), PICH 11% (95% CI, 9%-14%) and SAH 4% (95% CI, 2%-5%). The 382 cases of cerebral infarction included LAOI (in approximately 71%), EMBI (15%), LACI (10%) and BZI (5%). While the incidence of all subtypes of stroke increased with age, there were age and sex differences in their proportional frequency, management and prognosis: patients with PICH, SAH and EMBI were more likely to be admitted to hospital, and these conditions carried the highest early case fatality. Over all, the 28-day case fatality was 24% (95% CI, 20%-28%), but varied from 0 for LACI and BZI, to 37% (95% CI, 15%-59%) for SAH and 35% (CI, 23%-47%) for PICH. CONCLUSIONS: In this study, we found considerable differences in incidence rates, the effect of age and sex on incidence rates, and prognosis for the different subtypes of stroke. Hospital-based studies are likely to be selectively biased by emphasising strokes that are severe and require admission to hospital. These data have important implications in the design and evaluation of clinical trials of therapy for stroke.

Adult↗
PubMed1993

MR microscopy of the rat lung using projection reconstruction.

Projection reconstruction has been implemented with self-refocused selection pulses on a small bore, 2.0 T MR microscope, to allow imaging of lung parenchyma. Scan synchronous ventilation and cardiac gating have been integrated with the sequence to minimize motion artifacts. A systematic survey of the pulse sequence parameters has been undertaken in conjunction with the biological gating parameters to optimize resolution and signal-to-noise (SNR). The resulting projection images with effective echo time of < 300 microseconds allow definition of lung parenchyma with an SNR improvement of approximately 15 x over a more conventional 2DFT short echo gradient sequence.

Animals↗
PubMed1993

High-field MR microscopy using fast spin-echoes.

Fast spin-echo imaging has been investigated with attention to the requirements and opportunities for high-field MR microscopy. Two- and three-dimensional versions were implemented at 2.0 T, 7.1 T, and 9.4 T. At these fields, at least eight echoes were collectable with a 10 ms TE from fixed tissue specimens and living animals, giving an eightfold improvement in imaging efficiency. To reduce the phase-encoding gradient amplitude and its duty cycle, a modified pulse sequence with phase accumulation was developed. Images obtained using this pulse sequence exhibited comparable signal-to-noise (SNR) to those obtained from the conventional fast spin-echo pulse sequences. Signal losses due to imperfections in RF pulses and lack of phase rewinders were offset in this sequence by reduced diffusion losses incurred with the gradients required for MR microscopy. Image SNR, contrast, edge effects and spatial resolution for three k-space sampling schemes were studied experimentally and theoretically. One method of sampling k-space, 4-GROUP FSE, was found particularly useful in producing varied T2 contrast at high field. Two-dimensional images of tissue specimens were obtained in a total acquisition time of 1 to 2 min with in-plane resolution between 30 to 70 microns, and 3D images with 256(3) arrays were acquired from fixed rat brain tissue (isotropic voxel = 70 microns) and a living rat (isotropic voxel = 117 microns) in approximately 4.5 h.

Animals↗
PubMed1993

Diffusion-weighted MR microscopy with fast spin-echo.

A diffusion-weighted fast spin-echo (FSE) imaging sequence for high-field MR microscopy was developed and experimentally validated in a phantom and in a live rat. Pulsed diffusion gradients were executed before and after the initial 180 degrees pulse in the FSE pulse train. This produced diffusion-related reductions in image signal intensity corresponding to gradient ("b") factors between 1.80 and 1352 s/mm2. The degree of diffusion weighting was demonstrated to be independent of echo train length for experiments using trains up to 16 echoes long. Quantitative measurements on a phantom and on a live rat produced diffusion coefficients consistent with literature values. Importantly, the eight- to 16-fold increase in imaging efficiency with FSE was not accompanied by a significant loss of spatial resolution or contrast. This permits acquisition of in vivo three-dimensional data in time periods that are appropriate for evolving biological processes. The combination of accurate diffusion weighting and high spatial resolution provided by FSE makes the technique particularly useful for MR microscopy.

Animals↗
PubMed1993

Enhanced in vitro hair growth at the air-liquid interface: minoxidil preserves the root sheath in cultured whisker follicles.

Inasmuch as hair follicles are difficult to maintain in culture, the study of hair biology using cultured hair follicles has met with only limited success. In our attempts to solve the problem of follicle degeneration, we cultured follicles at the air-surface interface on a modified collagen matrix (Gelfoam). In follicles cultured at the air-surface or submerged, we examined follicular morphology, hair shaft growth, sulfotransferase levels, cysteine incorporation, an expression of a tissue inhibitor of metalloproteinase (TIMP), and ultra-high sulfur keratin (UHSK). Follicles cultured at the air-liquid interface produced a 2.7-fold increase in hair growth and maintained an anagen-like morphology. Substrates such as nylon mesh seeded with fibroblasts, Full Thickness Skin, or 5-microns polycarbonate filter also supported hair growth, whereas Gelfilm, GF-A glass filter, filter paper, or 1-micron polycarbonate filter did not. The UHSK expression was significantly higher in the air-liquid interface cultures compared to the submerged culture. Several potassium channel openers, including minoxidil, a minoxidil analog, and the pinacidil analog (P-1075), all stimulated significant cysteine incorporation in follicles. Minoxidil and its analog specifically preserved the follicular root sheath, in contrast to P-1075 which did not, indicating a difference in the two drug types. The preservation of the root sheath was measured by increased TIMP expression and sulfotransferase activity and indicates that the root sheath is a target tissue for minoxidil. Our results show that follicles cultured at the air-liquid interface maintain a better morphology and produced greater hair growth than follicles cultured on tissue culture plastic.

Air↗
PubMed1993

Mathematical modeling of ligaments and tendons.

Ligaments and tendons serve a variety of important functions in maintaining the structure of the human body. Although abundant literature exists describing experimental investigations of these tissues, mathematical modeling of ligaments and tendons also contributes significantly to understanding their behavior. This paper presents a survey of developments in mathematical modeling of ligaments and tendons over the past 20 years. Mathematical descriptions of ligaments and tendons are identified as either elastic or viscoelastic, and are discussed in chronological order. Elastic models assume that ligaments and tendons do not display time dependent behavior and thus, they focus on describing the nonlinear aspects of their mechanical response. On the other hand, viscoelastic models incorporate time dependent effects into their mathematical description. In particular, two viscoelastic models are discussed in detail; quasi-linear viscoelasticity (QLV), which has been widely used in the past 20 years, and the recently proposed single integral finite strain (SIFS) model.

Animals↗
PubMed1993

In vitro MR microscopy of the hippocampus in Alzheimer's disease.

We used MR microscopy at 7 tesla to identify the anatomy of the degenerating hippocampus in Alzheimer's disease (AD), which we then correlated with the histopathologic findings in the same specimens. The specimens studied were resected postmortem from 13 patients with confirmed AD and from nine age-matched controls. We imaged the specimens in the coronal plane using either three-dimensional Fourier encoding or single-slice Carr, Purcell, Meiboom, Gill (CPMG) spin echo sequences. On all specimens imaged with the CPMG pulse sequence, we calculated the T2 relaxation times for subfields within the hippocampus. Histologic sections were taken from each specimen and compared with the corresponding MR image. Using histologic boundaries, we quantified the number of neuritic plaques and neurofibrillary tangles in each hippocampal subfield. We measured the area, morphometric characteristics, and width of identifiable signal variant regions on each image and compared these measurements with the histopathologic findings. The mean cross-sectional area of the hippocampus in AD was decreased by 31% compared with the control group. This atrophy was highly correlated with tangle counts within the hippocampus, but not with plaque counts. The width of the gray matter in hippocampal area CA1, as identified by MR, correlated with the total area of the hippocampus. An age-related decrease in the size of a low-signal region that corresponds histologically to input projections comprising part of the perforant pathway was identified. Measurements of the T2 relaxation times of hippocampal subfields showed little regional variability and were not accurate indicators of disease presence or severity (p > 0.05).

Aged↗
PubMed1993

A HPLC-based chloramphenicol acetyltransferase assay for assessing hair growth: comparison of the sensitivity of UV and fluorescence detection.

In our attempt to measure hair growth by hair-specific markers, we used transgenic mice to express the chloramphenicol acetyltransferase gene under the control of an ultrahigh sulphur keratin gene promoter. To quantitate expression of the keratin gene, we required a chloramphenicol acetyltransferase assay which could measure enzyme activity in a single follicle and also could be used to assay a large number of samples without loss of sensitivity. We achieved this objective by utilizing a fluorescent substrate for chloramphenicol acetyltransferase. With HPLC-fluorescence detection, this substrate provides a sensitivity of less than 1 x 10(-13) mol, which is 1000 times greater than that achievable with HPLC-UV detection in cultured follicles. Further, the assay was automated to facilitate the analysis of more than 100 samples/day. It should be possible to apply this fluorescent assay to a number of cell or tissue studies.

Animals↗
PubMed1993

Oscillometric blood pressures in the arm, thigh, and calf in healthy children and those with aortic coarctation.

Comparing blood pressure (BP) obtained in the arm with that obtained in the thigh or calf is important in the diagnosis of aortic coarctation. However, normative mean and range of differences in BP between the arm and lower extremity sites are not available for normal children. It is also not known how accurately the differences in BP between the arm and the lower extremity sites predict the pulsed Doppler estimation of systolic pressure (SP) gradient across an aortic coarctation. To resolve these questions, the authors obtained two BP measurements by an oscillometric (Dinamap) method in the arm, thigh, and calf in 74 healthy children aged 4 to 16 years. Oscillometric BP was also obtained in 21 children aged 3 to 17 years with preoperative or postoperative aortic coarctation and BP gradients were compared with that estimated by the pulsed Doppler method. Overall, SP was higher in the thigh and calf than in the arm. The gradients in SP expressed as arm SP minus calf SP [S(A-C)] and arm SP minus thigh SP [S(A-T)] were significantly greater in children 4 through 8 years old than in those 9 to 16 years old. The S(A-C) was -9.3 (+/- 7.4 SD) mm Hg in the 4- through 8-year group and -5.0 (+/- 6.9 SD) mm Hg in the 9- to 16-year group. The S(A-T) was -7.1 (+/- 6.8 SD) mm Hg in the 4- through 8-year group and -2.4 (+/- 7.7 SD) mm Hg in the 9- to 16-year group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Histology by magnetic resonance microscopy.

Magnetic resonance microscopy (MRM) has advanced from a technical challenge to a practical tool in a wide range of basic sciences. This article focuses on the use of MRM as a tool for histological studies. The technical challenges of limited signal to noise have been overcome by improved radio-frequency (rf) coil design and 3DFT encoding with large arrays. Resolution limits imposed by motion in in vivo studies have been overcome by improved physiologic monitoring and control and projection encoding. Integration of technologies now permits routine studies in vivo down to 50 microns. MRM has also been applied to in vitro studies of fixed tissues where absence of motion allows studies down to 10 microns. The nondestructive nature of the technique allows repeated studies of the same sample, retrospective studies through any arbitrary plane, registered studies using different contrast mechanisms, and examination of valuable specimens. The many and unique proton contrasts provided by MRM, i.e., T1, T2, and diffusion weighting, permit direct examination of the state of water in tissues, something not possible with other microscopic techniques. Finally, the inherent three-dimensional nature of MRM allows acquisition of perfectly registered isotropic 3D arrays that, when displayed with appropriate visualization tools, provide new perspectives to histologic examination. The technology of MRM continues to develop rapidly. New pulse sequences are reducing acquisition times. New computer architectures allow larger arrays. A new class of superconducting rf probe has increased the signal to noise ratio by 10 times. These developments promise routine use of MRM in histology studies with resolution to 1 micron in the near future.

Animals↗
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↗