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Biomedical subjects

J P Jones

Publications and source records attributed to J P Jones.

At least 19 recordsLinked to original sources

Visualization of myocardial cellular architecture using acoustic microscopy.

The resolution of an ultrasound transducer depends on its frequency. The resolution improves when higher frequency transducers are used. A 1000 MHz transducer has a resolution of approximately 1 micron. Acoustic microscopy utilizes very high-frequency ultrasound (600 to 1000 MHz) to visualize structures on a microscopic level. Unstained, deparaffinized, 5 microns sections of myocardial biopsy specimens from 10 patients were placed on a slide and imaged using an Olympus UH3 scanning acoustic microscope. To compare with light microscopy, the section used for acoustic microscopy was subsequently stained with hematoxylin and eosin and a serial section from the paraffin block was stained with PTAH stain. Myocytes, myofibrils, and interstitial tissue were accurately imaged. Pathologic phenomena such as cell fallout, interstitial fibrosis, and lymphocytic infiltration were identified by acoustic microscopy. Intramural vessels, nuclei of endothelial cells, and the media were clearly identified by this technique. There was close correlation between findings by acoustic microscopy and light microscopy. Acoustic microscopy permitted the visualization of cardiac cellular detail with a resolution similar to that of light microscopy. Unlike light microscopy, acoustic microscopy requires no staining of the specimen.

Biopsy

Laparoscopic diverticulectomy: preliminary report of a new approach for the treatment of bladder diverticulum.

Laparoscopic techniques have expanded the possibilities of endo-surgically approaching urological abnormalities that would otherwise be managed via an open operation. We report on another useful application of the laparoscope, bladder diverticulectomy. A large bladder diverticulum, responsible for incomplete bladder emptying and recurrent urinary tract infections in an 87-year-old man, was successfully excised endoscopically. The technique and possible future indications are described.

Aged

Laparoscopic cystectomy: initial report on a new treatment for the retained bladder.

The retained bladder of a 27-year-old paraplegic woman suffering from recurrent pyocystis was removed laparoscopically. Operative time was 130 minutes. Postoperative hospital stay was 5 days, which was significantly less than that in 5 similar patients undergoing open cystectomy for vesical empyema in whom the mean hospital stay was 20.6 days. We believe that laparoscopic cystectomy represents a plausible, minimally invasive alternative to standard cystectomy for the symptomatic bladder left behind after supravesical urinary diversion.

Adolescent

Cine magnetic resonance imaging of the temporomandibular joint.

Magnetic resonance imaging (MRI) provides a significant amount of information about both the position of the meniscoligamentous complex and the osseous structures in evaluation of internal derangements of the temporomandibular joint (TMJ). With the advent of computer-driven cine displays, dynamic information is now available, providing cost-effective diagnostic evaluation similar to cine fluoroscopy with arthrography, but without the ionizing radiation exposure or discomfort. Using a bite block, a series of sagittal images are obtained with the patient "posing" at different degrees of jaw opening. The subsequent cine MRIs with "posed" motion are striking and very helpful in evaluating various types of TMJ dysfunction. At the authors' institution, 205 patients were examined with a history of TMJ arthralgia. Correlation of imaging studies and surgical findings reveals a sensitivity (98%) and specificity (96%) for identifying the meniscoligamentous complex.

Adolescent

Insulin-induced hypoglycemia in fed and fasted exercising rats.

To determine running performance and hormonal and metabolic responses during insulin-induced hypoglycemia, fed and fasted male rats (315 +/- 3 g) were infused with insulin (100 mU/ml, 1.5 ml/h) or saline (1.5 ml/h) for 60 min and then killed at rest or after running on the treadmill (21 m/min, 15% grade). Insulin-infused fed rats ran poorly during the second 10 min of a 20-min exercise test. They were capable of running a total of 43 +/- 5 min, compared with 138 +/- 6 min for saline-infused fed rats. Fasted insulin-infused rats were able to run only 12.8 +/- 0.8 min, compared with 122 +/- 15 min for fasted saline-infused rats. In fasted rats, blood glucose was 1.6 +/- 0.1 mM after 60 min of insulin infusion and 1.2 +/- 0.1 mM after running to exhaustion. Artificial increase of plasma free fatty acids had no effect on performance. Intravenous infusion of glucose at the time of fatigue produced an immediate recovery, allowing the formerly fatigued rats to run 20 min without development of fatigue. These results provide evidence that severe hypoglycemia can be a significant cause of fatigue, even if it occurs early in the course of an exercise bout.

Animals

Laparoscopic intraperitoneal marsupialization: report on a new treatment for lymphoceles.

Lymphocele formation, a common complication of pelvic surgery, can produce considerable morbidity. Treatment is problematic, with no single procedure considered optimal. We recently treated a 67-year-old man with a symptomatic lymphocele by laparoscopic internal marsupialization. Total operative time was 45 min, and the patient was discharged home the same day with minimal need for pain medications. Total resolution of the symptoms occurred within 24 h. In comparison to other methods compiled and analyzed from the literature, this highly effective, minimally invasive procedure offers a significant advantage to the patient.

Aged

Intravascular coagulation and osteonecrosis.

Current evidence suggests that intravascular coagulation (IC), an intermediary mechanism, is the most likely final common pathway by which intraosseous fat embolism causes nontraumatic osteonecrosis (ON). Stage 1A lesions (fatty osteocytic necrosis) appear to progress to classic Stage 1B lesions (ischemic degeneration of necrotic osteocytes and adipocytes) when the ischemic threshold is exceeded by absolute subchondral fat overload with insufficient local clearance of procoagulants, especially tissue thromboplastin. The result is vascular stasis, hypercoagulability, endothelial damage (by free fatty acids) and IC, especially if there is coexistent subchondral vasoconstriction and impaired secondary fibrinolysis. Osteonecrosis can be produced in animals by IC, which begins in the vulnerable subchondral microcirculation (Arthus phenomenon). Cartography (embolic scintimetry with superselective angiography) indicates early complete devascularization of the femoral head, suggesting progressive venous and retrograde arterial thrombosis. Increased plasma fibrinopeptide A and direct histologic evidence of intraosseous thromboses and peripheral hemorrhages further indicate that IC is the final pathway. Best evidence are 51 ON lesions complicating disseminated IC in eight children (Shwartzman phenomenon), with collateral histologic evidence of intraosseous thrombosis and ON.

Animals

Modification by focused ultrasound pulses of electrically evoked responses from an in vitro hippocampal preparation.

The application of short pulses of focused ultrasound was studied as a method of modifying electrically evoked responses in the mammalian brain. The in vitro hippocampal preparation was employed to facilitate delivery and dosimetry of ultrasound, and assessment of mechanisms of ultrasound effects. Cellular and dendritic field potential responses evoked by electrical stimulation of the Schaffer/Commissural afferents were examined before, during and after exposure of a portion of the CA1 region to focused ultrasound pulses for periods ranging from 2 to 15 min. Focused ultrasound with a repetition rate of 150 kHz was delivered in pulses comparable in duration to an electrical pulse that could initiate activity in the nervous system. The pulses had a center frequency of 750 kHz, durations of about 6 microseconds, and spatial-peak-temporal-averaged intensities of about 80 W/cm2. These parameters are markedly different from those employed in conventional diagnostic ultrasound. Temperatures in the bath and tissue were monitored. Extracellular field potentials reflecting the presynaptic fiber volley, dendritic response and cellular discharge were significantly reduced by exposure to ultrasound. Recovery occurred to varying degrees, and in one experiment was complete. Average temperature changes observed were less than 1 degree C. The present study demonstrates that the electrically evoked response in mammalian brain can be altered by ultrasound in a non-thermal, non-cavitational mode, and that such effects are potentially reversible.

Action Potentials

Secondary 18O isotope effects for hexokinase-catalyzed phosphoryl transfer from ATP.

Secondary 18O isotope effects in the gamma-position of ATP have been measured on phosphoryl transfer catalyzed by yeast hexokinase in an effort to deduce the structure of the transition state. The isotope effects were measured by the remote-label method with the exocyclic amino group of adenine as the remote label. With glucose as substrate, the secondary 18O isotope effect per 18O was 0.9987 at pH 8.2 and 0.9965 at pH 5.3, which is below the pK of 6.15 seen in the V/K profile for MgATP. With the slow substrate 1,5-anhydro-D-glucitol, the value was 0.9976 at pH 8.2. While part of the inverse nature of the isotope effect may result from an isotope effect on binding, the more inverse values when catalysis is made more rate limiting by decreasing the pH or switching to a slower substrate suggest a dissociative transition state for phosphoryl transfer, in agreement with predictions from model chemistry. The 18O equilibrium isotope effect for deprotonation of HATP3- is 1.0156, while Mg2+ coordination to ATP4- does not appear to be accompanied by an 18O isotope effect larger than 1.001.

Adenosine Triphosphate

Scanning acoustic microscopy of neoplastic and inflammatory cutaneous tissue specimens.

Acoustic microscopy utilizes high frequency ultrasound to generate microscopic images. The current study was designed to examine representative disorders of the skin by use of a reflective scanning acoustic microscope (R-SAM), and to determine whether the obtainable resolution was sufficient to render a microscopic diagnosis. An Olympus UH3 Scanning Acoustic Microscope was utilized with lenses producing burst wave frequencies at 600 and 800 MHz (600 and 800 million cylces/sec). Cutaneous tissue specimens representing 12 different neoplastic and inflammatory disorders were examined. Acoustic images of unstained sections were compared with conventional light microscopic study of sections stained with hematoxylin-eosin. In most neoplasms examined, it was possible to make a specific diagnosis primarily from low magnification pattern analysis. Although individual cells could be visualized, cytologic atypia was poorly defined. In the inflammatory disorders, a specific diagnosis was possible in all but bullous pemphigoid and lichen planus, because the composition of the inflammatory infiltrate was difficult to determine. The advantages of the R-SAM include the capability of producing an acoustic profile of the tissue and the future possibility of in situ diagnosis.

Humans

Intrinsic isotope effects suggest that the reaction coordinate symmetry for the cytochrome P-450 catalyzed hydroxylation of octane is isozyme independent.

The mechanism of the omega-hydroxylation of octane by three catalytically distinct, purified forms of cytochrome P-450, namely, P-450b, P-450c, and P-450LM2, was investigated by using deuterium isotope effects. The deuterium isotope effects associated with the omega-hydroxylation of octane-1,1,1-2H3, octane-1,8-2H2, and octane-1,1,8,8-2H4 by all three isozymes were determined. From these data the intrinsic isotope effects were calculated and separated into their primary and secondary components. The primary intrinsic isotope effect for the reaction ranged from 7.69 to 9.18 while the secondary intrinsic isotope effect ranged from 1.13 to 1.25. Neither the primary nor secondary isotope effect values were statistically different for any of the isozymes investigated. These data are consistent with a symmetrical transition state for a mechanism involving initial hydrogen atom abstraction followed by hydroxyl radical recombination which is essentially independent of the specific isozyme catalyzing the reaction. It is concluded that (1) in general the porphyrin-[FeO]3+ complex behaves as a source of a triplet-like oxygen atom, (2) the regioselectivity for the site of oxidation is dictated by the apoprotein of the specific isozyme of cytochrome P-450 catalyzing the reaction, and (3) the maximum primary intrinsic isotope effect for any cytochrome P-450 catalyzed oxidation of a carbon center is about 9, assuming no tunneling effects.

Cytochrome P-450 Enzyme System

Frequency measurements in real-time US equipment: variations from expected values.

The frequency responses of nine real-time mechanical probes and two pulsed Doppler probes from four manufacturers were measured. The reflected frequency was measured in a clinical environment by evaluating the pulser, transducer assembly, and receiver as a system. Two independent systems were used for these measurements: a spectrum analyzer and a data acquisition system that computed the fast Fourier transform of the reflected waveform. Results showed that probe frequency (calibrated by the manufacturer in the transmit mode with a hydrophone) was as much as 30% higher than that found by means of frequency measurement procedures with the probe attached to the ultrasound system and evaluated in the receive mode. Such large discrepancies indicate that if acceptance testing of the frequency spectrum is not performed at a clinical facility, prolonged clinical evaluation of new equipment should be arranged.

Ultrasonics

Low-dose digital computed radiography in pediatric chest imaging.

A prototype digital computed radiographic imaging system that uses laser-stimulated luminescence was evaluated for its ability to achieve reproducible, high-detail, low-dose pediatric chest radiographs. Using this system, we performed a total of 401 examinations in infants and children, and achieved an 85% reduction in radiation dose, as compared with that delivered when film-screen techniques were used. We also achieved satisfactory image resolution, and the images obtained were of acceptable diagnostic quality. A direct comparison of analog and digital radiographs showed that comparable quality and clinical acceptability could be readily maintained between the two techniques. This study shows that high-quality images can be produced by this system at radiation doses reduced by 85% when compared with doses from standard radiographic techniques.

Adolescent

The two-dimensional spatial structure of simple receptive fields in cat striate cortex.

1. A reverse correlation (6, 8, 25, 35) method is developed that allows quantitative determination of visual receptive-field structure in two spatial dimensions. This method is applied to simple cells in the cat striate cortex. 2. It is demonstrated that the reverse correlation method yields results with several desirable properties, including convergence and reproducibility independent of modest changes in stimulus parameters. 3. In contrast to results obtained with moving stimuli, we find that the bright and dark excitatory subregions in simple receptive fields do not overlap to any great extent. This difference in results may be attributed to confounding the independent variables space and time when using moving stimuli. 4. All simple receptive fields have subregions that vary smoothly in all directions in space. There are no sharp transitions either between excitatory subregions or between subregions and the area surrounding the receptive field. 5. Simple receptive fields vary both in the number of subregions observed, in the elongation of each subregion, and in the overall elongation of the field. In contrast with results obtained using moving stimuli, we find that subregions within a given receptive field need not be the same length. 6. The hypothesis that simple receptive fields can be modeled as either even symmetric or odd symmetric about a central axis is evaluated. This hypothesis is found to be false in general. Most simple receptive fields are neither even symmetric nor odd symmetric. 7. The hypothesis that simple receptive fields can be modeled as the product of a width response profile and an orthogonal length response profile (Cartesian separability) is evaluated. This hypothesis is found to be true for only approximately 50% of the cells in our sample.

Animals

The two-dimensional spectral structure of simple receptive fields in cat striate cortex.

1. A quantitative, general purpose method was developed for measuring the responses of visual neurons to stimuli distributed with high resolution over the two-dimensional (2D) spatial frequency domain. The stimuli consisted of drifting sinusoidal gratings of nonsaturating contrasts whose spatial frequency and orientation were drawn in random order from a 16 X 16 array of coordinates covering each neuron's responsive area. This method was applied to a population of 36 simple cells in area 17 of cat. 2. The response of each simple cell to drifting sinusoidal gratings appeared as a rectified sinusoidal modulation of the spike frequency. The degree of rectification varied from cell to cell, but for each cell, the form of the response was constant irrespective of stimulus spatial frequency, orientation, or contrast. The amplitude of the average response at the stimulus temporal frequency was used as the response metric at all spectral coordinates. Variations in this amplitude over two spectral dimensions forms a surface that we call the 2D spectral response profile. 3. For each cell, the 2D spectral response profile was localized to a limited region of the complete 2D spatial frequency domain. In bidirectionally responsive cells, there were two lobes in the surface disposed with mirror symmetry about the origin. In all cells, each lobe exhibited a single maximum and the response decayed smoothly in every direction away from the maximum. Isoresponse amplitude contours were elliptical and often, but not always, elongated about an axis of symmetry passing through the origin. 4. We tested the hypothesis that orientation and spatial frequency tuning are independent by forming scaled radial and angular sections through 2D spectral response profiles. In virtually every case polar separability did not obtain, that is, orientation selectivity depended on spatial frequency and vice versa. 5. In contrast, more than half the cells had 2D spectral response profiles that were Cartesian separable. The 2D spectral response profiles of most of the remaining cells were neither polar nor Cartesian separable, because the response profiles were elongated about an axis of symmetry that did not pass through the origin. 6. These results are discussed in terms of the constraints they place on models of the contributions simple cells make toward the neural representation of images.

Animals

An evaluation of the two-dimensional Gabor filter model of simple receptive fields in cat striate cortex.

1. Using the two-dimensional (2D) spatial and spectral response profiles described in the previous two reports, we test Daugman's generalization of Marcelja's hypothesis that simple receptive fields belong to a class of linear spatial filters analogous to those described by Gabor and referred to here as 2D Gabor filters. 2. In the space domain, we found 2D Gabor filters that fit the 2D spatial response profile of each simple cell in the least-squared error sense (with a simplex algorithm), and we show that the residual error is devoid of spatial structure and statistically indistinguishable from random error. 3. Although a rigorous statistical approach was not possible with our spectral data, we also found a Gabor function that fit the 2D spectral response profile of each simple cell and observed that the residual errors are everywhere small and unstructured. 4. As an assay of spatial linearity in two dimensions, on which the applicability of Gabor theory is dependent, we compare the filter parameters estimated from the independent 2D spatial and spectral measurements described above. Estimates of most parameters from the two domains are highly correlated, indicating that assumptions about spatial linearity are valid. 5. Finally, we show that the functional form of the 2D Gabor filter provides a concise mathematical expression, which incorporates the important spatial characteristics of simple receptive fields demonstrated in the previous two reports. Prominent here are 1) Cartesian separable spatial response profiles, 2) spatial receptive fields with staggered subregion placement, 3) Cartesian separable spectral response profiles, 4) spectral response profiles with axes of symmetry not including the origin, and 5) the uniform distribution of spatial phase angles. 6. We conclude that the Gabor function provides a useful and reasonably accurate description of most spatial aspects of simple receptive fields. Thus it seems that an optimal strategy has evolved for sampling images simultaneously in the 2D spatial and spatial frequency domains.

Animals

In vivo measurement of attenuation.

We propose a new technique for the in vivo measurement of attenuation. The method is conceptually simple and can also be easily implemented on a real-time ultrasound unit. The technique is suggested by an analysis of the propagation of a Gaussian pulse in a medium which has frequency-dependent attenuation as well as dispersion (frequency-dependent velocity). If the medium has a loss factor which can be described by H(f) = exp(-eta[f]pX), where f is the frequency and O less than or equal to p less than or equal to 2 (valid for tissues and other objects of interest), then the pulse retains its Gaussian shape, shifting only its centre frequency and bandwidth. This suggests that by measuring the mean frequency of the reflected rf waveform in a window which is moved in depth we can obtain an estimate of the attenuation. Here we describe a particular hardware implementation of this technique which we have completed (based on measurement of zero-crossings) and present some preliminary in vivo measurements.

Humans

111In-labeled eosinophils: localization of inflammatory lesions and parasitic infections in mice.

Based upon recent development of practical isolation techniques for eosinophils, labeling and in vivo imaging of eosinophils has been achieved. Isolation of cells was performed utilizing a Percoll density gradient. The eosinophils were subsequently labeled by a modified 111In-oxine method. Migration of eosinophils in response to intradermal ear-pinna injections of SEA (soluble schistosoma egg antigen), S. mansoni eggs, E. coli, and turpentine was followed with gamma-ray camera imaging from 4 to 48 h. Maximal localization, determined by Gamma 11 data processing, occurred by 4-h post-injection of radiolabel. SEA and S. mansoni eggs provided a greater stimulus for localization than E. coli or turpentine. Neutrophils did not preferentially accumulate. Tissue distribution of labeled eosinophils was greatest in the spleen, followed by liver and bone. 111In-labeled-eosinophil scans are sensitive to parasitic infections, although somewhat nonspecific.

Animals