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Biomedical subjects

E W Johnson

Publications and source records attributed to E W Johnson.

At least 73 records · Page 4Linked to original sources

"Central" and "peripheral" benzodiazepine receptors: opposite changes in human epileptogenic tissue.

We measured the density of two benzodiazepine (BZ) receptor subtypes in neurosurgically obtained hippocampal tissue from the seizure focus of patients with temporal lobe epilepsy (TLE) showing mesial temporal sclerosis, the most common pathologic finding in TLE. We performed quantitative in vitro receptor autoradiography with [125I]Ro 16-0154, a probe for the central-type BZ receptor and with [3H]PK 11195, a probe for the peripheral-type BZ receptor. In comparison with autopsy and neurosurgical control groups, patients with mesial temporal sclerosis had regionally selective decreased central-type and increased peripheral-type BZ receptors. These changes paralleled regional losses of neurons and proliferation of glia. Decreases of the inhibitory central-type BZ receptor may be a component of the enhanced excitability of the seizure focus and also may allow localization of the focus by in vivo neuroreceptor imaging. Single photon emission computed tomography (SPECT) imaging of two TLE patients with [123I]Ro 16-0154 suggests that this technique may provide a more sensitive means of localizing the seizure focus than current imaging methods relying on changes in blood flow or glucose metabolism.

Adult↗

Epidermis generated in vitro: practical considerations and applications.

The technology for culture of epidermis is one of the most advanced to date for generation of a tissue in vitro. Cultured epidermis is already used for a number of applications ranging from use as a permanent skin replacement to use as an organotypic culture model for toxicity testing and basic research. While simple epidermal sheets have been grafted successfully, more advanced models for skin replacement consisting of both dermal and epidermal components are in development and being tested in a number of laboratories. One of the most advanced in vitro models is the living skin equivalent, an organotypic model consisting of a collagen lattice contracted and nourished by dermal fibroblasts overlaid with a fully formed epidermis.

Culture Techniques↗

Calibration of [123I]iodine-labeled tissue standards for autoradiographic studies.

Autoradiographic images can be analyzed with computer-assisted microdensitometry relative to radioactive reference standards to provide quantitative measurements of regional radioactivity concentrations. [123I]Iodine containing sections of brain paste have been calibrated relative to plastic-embedded tritium(3H) and 125Iodine standards. For exposure times of 8, 12 and 24 h, plastic-embedded standards covered a range concentrations of [123I]iodine from 1000 to 100,000 dpm/mg wet weight. Iodine-123 radioactivity was linear with section thickness from 5 to 30 microns. These studies confirmed the feasibility of using commercially available longer-lived reference standards to provide [123I]iodine equivalent values in absolute units of dpm (or microCi) per mg tissue.

Animals↗

SPECT imaging of the benzodiazepine receptor: feasibility of in vivo potency measurements from stepwise displacement curves.

Iodine-123-labeled Ro 16-0154 is a high affinity, reversibly binding radiotracer for the benzodiazepine (BZ) receptor. Brain uptake of this radioligand was relatively stable and showed high ratios of specific-to-nonspecific uptake, with greater than 90% displaced by intravenous administration of BZ receptor agents. Repeated injections of increasing doses of each of five BZ drugs (Ro 16-0154, Ro 15-1788, clonazepam, alprazolam, and diazepam) yielded stepwise displacement curves, which were analyzed to measure the in vivo potencies of these agents. The relatively long half-life of 123I and the stable biologic uptake of the radiotracer allowed such potency estimations in just one experiment following a single injection of radioligand. The in vivo potencies of these five agents were highly correlated with their affinities for the BZ receptor determined with in vitro homogenate binding. A single crystal probe provided potency measurements virtually identical to simultaneously performed SPECT imaging studies. In conclusion, stepwise displacement by agents administered following the injection of the radioligand 123I-Ro 16-0154 provided a reliable means of measuring the in vivo potencies of BZ receptor agents. This in vivo determination may predict the clinical potency of BZ drugs than in vitro homogenate estimations, because the in vivo measure provides the summed effects of receptor affinity, plasma protein binding, penetration of the blood-brain barrier, and metabolism of the displacing agent.

Alprazolam↗

Asthmatic amyotrophy. Three cases.

Asthmatic amyotrophy is becoming a well established clinical phenomenon. A polio-like syndrome, it is characterized by an asymmetrical lower motor neuron paralysis after an acute asthmatic episode. We are presenting three additional cases of this syndrome to add to the literature describing this phenomenon. Our cases are similar to the 18 previously reported cases showing an asymmetrical flaccid paralysis accompanied by normal sensation. The prognosis for full recovery of function is poor. Anterior horn cell damage is postulated because no sensory loss has been found in any patients.

Asthma↗

Receptor binding characterization of the benzodiazepine radioligand 125I-Ro16-0154: potential probe for SPECT brain imaging.

The binding of an iodinated benzodiazepine (BZ) radioligand has been characterized, particularly in regard to its potential use as a neuroreceptor brain imaging agent with SPECT (Single Photon Emission Computed Tomography). Ro16-0154 is an iodine-containing BZ antagonist and a close analog of Ro15-1788. In tissue homogenates prepared from human and monkey brain, the binding of 125I-labeled Ro16-0154 was saturable, of high affinity (Kd = 0.5 nM at 37 degrees C), and had high ratios of specific to non-specific binding (approximately 40:1). Physiological concentrations of NaCl (150 mM) enhanced specific binding approximately 15% compared to buffer without this salt. Kinetic studies of association and dissociation demonstrated a temperature dependent decrease in affinity with increasing temperature. Drug displacement studies confirmed that 125I-Ro16-0154 binds to the "central" type BZ receptor: binding is virtually identical to that of 3H-Ro15-1788 except that 125I-Ro16-0154 shows an almost 10 fold higher affinity at 37 degrees C. These in vitro results suggest that 123I-labeled Ro16-0154 shows promise as a selective, high affinity SPECT probe of the brain's BZ receptor.

Animals↗

Spinal nerve stimulation in S1 radiculopathy.

The H reflex plays an important role in electrodiagnosis, but it does not give specific information about any particular segment of its long conduction pathway. Direct stimulation at the S1 spinal nerve might provide more complete information by dividing the H reflex pathway into its peripheral and spinal conduction portions. Patients with electromyographic evidence of S1 radiculopathy (n = 77) and normal control subjects (n = 56) were evaluated. Standard H reflex conduction studies were followed by monopolar needle stimulation of the first sacral spinal nerve. The ratio of the spinal nerve latency to the H reflex latency (S1 ratio) was calculated. The abnormal S1 ratio seen in 77% of the subjects suggested relative slowing within the spinal segment of the nerve. The remainder of the subjects with S1 radiculopathy had slowed conduction also affecting the peripheral segment that could have been caused by Wallerian degeneration. The S1 ratio can provide evidence that H reflex conduction slowing is the result of injury involving the intraspinal nerves. This technique should be especially useful in cases of acute lumbosacral injury when needle electromyographic study is often nondiagnostic.

Adult↗

First lumbrical latency and amplitude. Control values and findings in carpal tunnel syndrome.

It has been suggested that the nerve fibers to the first and second lumbrical muscles are relatively spared in patients with carpal tunnel syndrome compared with the fibers to the abductor pollicis brevis. Latencies and amplitudes of the first lumbrical and the abductor pollicis brevis (APB) muscles were compared with both wrist stimulation and midpalmar stimulation. The lumbrical latency at 12 cm and the APB at 8 cm were found to be similar at less than 4.3 ms. Amplitudes to the lumbrical were 0.6-8 mV compared with 4-13.6 mV for the APB. Three patients who had an abnormal sensory study, yet normal motor values to the APB, were found to have abnormal lumbrical latencies. This is an additional technique that could be useful for individuals suspected of carpal tunnel syndrome who have normal latencies and amplitudes to the APB.

Adult↗

Median to radial latency difference test in mild carpal tunnel syndrome.

Electrodiagnostic assessment of carpal tunnel syndrome (CTS) is hampered by the normal variability of conduction velocity, amplitude and duration of evoked responses, and hand temperature. Comparative testing of other nerves in the same hand may control for these variables and improve sensitivity for detection of mild focal entrapment. In consecutive cases referred for evaluation, antidromic sensory latencies were recorded from the thumb over 10 cm segments of the median and radial nerves, and the difference between these latencies was calculated. Median sensory antidromic conduction to digit III, ulnar sensory conduction, and median motor latency measurements were also made. Three hundred and thirty-three upper limbs were studied in 262 patients. All tests were normal in 73 arms. Mild conduction slowing was identified in 86 median nerves. The median-radial latency difference was increased in 87% of these mild cases. The median-ulnar latency difference was diagnostic in 88%. Either median-radial or median-ulnar latency differences were abnormal in all confirmed cases. The routine median motor and sensory distal latency tests had sensitivities of 29% and 52%, respectively. Radial responses were elicited in 99% of the hands studied. The median-radial latency difference in digit I is a sensitive indicator of mild CTS that can be measured quickly with a minimum of discomfort.

Adult↗