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Biomedical subjects

J L Taylor

Publications and source records attributed to J L Taylor.

At least 109 records · Page 6Linked to original sources
PubMed1994

Conformers of acetylcholinesterase: a mechanism of allosteric control.

Rate control in acetylcholinesterase (AChE) involves a single anionic site whose anionic center controls rate-related biochemical and conformational changes in the E (free enzyme) and EA (acylated enzyme) conformers. Change in conformer structure and biochemistry affect binding, acylation, and hydrolysis. It is significant that the anionic-esteratic intersite distance is not altered during conformer change as E is converted to EA. In this enzyme system, cationic acetylcholine and anionic AChE are true structural, functional, and biochemical counterparts. The anionic center in the E conformer lies at the bottom of a sterically restricted, hydrophobic cleft < 8 A wide at the top and > 3 A wide at the bottom, while the anionic center in the EA conformer is relatively open. It is characterized by a decrease in the relative binding of hydrophobic cations and by an ability to bind large organic cations. Binding of acetylcholine, H+, or organic cations at the anionic site controls k2(acylation) in the E conformer and k3(hydrolysis) in the EA conformer. Acetylcholine binding forms the ES complex in which the cation maximizes k2. In the EAS complex, the cation reduces k3 and provides allosteric control. Anionic site structure and biochemistry and the effect of pH on k2 and k3 differentiates AChE from butyrylcholinesterase. This comprehensive study of kinetic and thermodynamic processes in AChE was made possible by the synthesis and/or use of families of over 30 cationic and acylation probes of known stereochemistry. They act as rulers of the E and EA conformers of AChE and provide comparative data on kinetic-based and thermodynamic-based constants. Cationic inhibitors affect decarbamylation rates in AChE and provide an additional set of comparative data related to the mechanism of substrate hydrolysis by AChE. Acridine araphanes are unique neural receptor and cholinergic enzyme probes. Their parallel plane and coplanar conformations are related to bridge length. Two parallel plane acridine araphanes are pure uncompetitive inhibitors of AChE. Scatchard plots of the binding of methylacridinium and 9-aminoacridine with the E conformer and 9-aminoacridine with the EA conformer indicate binding at a single anionic site. No ternary complex (EII or EAII) from two-site binding was detected. In AChE, nonspecific, low-level binding at surface ionic and hydrophobic areas is ubiquitous. Binding affinity differences greater than two orders of magnitude distinguish binding at the anionic site from low level binding at surface moieties. Surface binding provides environmental and stability changes in the enzyme but does not modify the fundamental biochemistry of the E and EA conformers.

Acetylcholinesterase↗
PubMed1993

An outbreak of cholera in Maryland associated with imported commercial frozen fresh coconut milk.

In August 1991, the first outbreak of cholera associated with an imported commercial food product occurred among persons attending a private picnic. An epidemiologic investigation showed infection with toxigenic Vibrio cholerae O1, biotype El Tor, serotype Ogawa, in 4 of 6 persons who had consumed coconut milk imported from Thailand. In addition, the US Food and Drug Administration recovered toxigenic V. cholerae O1, biotype El Tor, serotype Ogawa, from 1 of 6 unopened bags of the same brand (but different shipment) of coconut milk as that consumed by infected persons. Investigation in Thailand of the manufacturing process of the implicated coconut milk showed several sanitary violations, suggesting that contamination had occurred during production. This outbreak suggests a model of entrance of V. cholerae into a population and shows the need to evaluate current methods of maintaining the safety of imported foods in the United States.

Adult↗
PubMed1993

Interictal violence in epilepsy. Relationship to behavior and seizure variables.

Interictal violence among epileptic patients could result from factors other than epileptiform activity. We characterized 44 patients who presented for psychiatric evaluation because of violent behavior. Most violent acts consisted of verbal or minor physical aggression. Twenty (45%) of these patients met criteria for a schizophrenic disorder, and one committed murder during a paranoid schizophrenic relapse. In addition to schizophrenia, the violence patients had significantly more mental retardation when compared with 88 age- and sex-matched epileptic patients without prior violent behavior. However, violent and nonviolent patients did not differ on seizure variables such as type and frequency of seizures, auras, electroencephalographic changes, epilepsy age of onset, or anticonvulsant therapy. These findings suggest that interictal violence is associated more with psychopathology and mental retardation than with epileptiform activity or other seizure variables.

Adult↗
PubMed1993

Rural-urban differences in stigma and the use of care for depressive disorders.

Stigma may be a particularly important barrier to mental health care in rural communities where lack of anonymity increases the probability that someone who seeks care will be labeled "crazy." This study examined rural-urban differences in the stigma associated with depressive symptoms and the stigma associated with seeking treatment for depressive disorders. In addition, the study compared how the stigma associated with seeking treatment predicted use of care in rural and urban residents with a history of depressive symptoms. Two hundred subjects from metropolitan and adjacent non-metropolitan counties rated one of four randomly selected vignettes using 14-point semantic differential scales. The findings indicated that rural residents with a history of depressive symptoms labeled people who sought professional help for the disorder somewhat more negatively than their urban counterparts. Logistic models controlling for sociodemographic characteristics demonstrated that the more negative the labeling, the less likely depressed rural residents were to have sought professional help. Labeling was not associated with use of care among urban people with depressive symptoms. We concluded that prospective studies are warranted to inform the development of interventions to decrease the stigma associated with seeking treatment for depressive disorders in rural communities.

Data Collection↗
PubMed1993

A simple, sensitive, and rapid method for detecting seed contaminated with highly virulent Leptosphaeria maculans.

A primer-directed DNA amplification polymerase chain reaction assay for detection of seed contaminated with highly virulent Leptosphaeria maculans was developed. The primers were derived from a 5,238-bp repetitive sequence present only in the highly virulent isolates of the fungus. A procedure for isolating DNA from organisms infesting germinating seed was also developed. Seeds were added to liquid fungal minimal medium, and the culture was incubated for 3 days at room temperature with shaking. The organisms were collected from the cultures by centrifugation and lysed with a combination of sodium dodecyl sulfate and proteinase K. The DNA was extracted with organic solvents and with a high-salt-cetyltrimethylammonium bromide solution. It was also precipitated with a low-salt-cetyltrimethylammonium bromide solution. The extensive treatments used for minimizing polysaccharide contamination greatly improved the reliability of the assay. The minimum contamination level (2 of 1,000 seeds) that was tested was successfully detected with this DNA isolation procedure. The reliability of the assay was 96% at the 1 to 2% level of seed contamination. The described method is less laborious and requires only 4 to 5 days for completion in comparison to the 11 to 22 days required for the currently employed methods. In addition, large sample sizes can be easily handled, thus reducing the probability of contaminated seed escaping detection.

Ascomycota↗
PubMed1993

Cerebellar ataxia and muscle spindle sensitivity.

1. The cerebellum has long been known to participate in movement control. One of the enduring theories of cerebellar function is that it "tunes" and coordinates sensorimotor traffic in other parts of the CNS. In particular, it has been implicated in the control of the sensitivity of muscle spindle stretch receptors through the fusimotor system. 2. The stretch sensitivity of spindle primary endings can be varied approximately over a 10-fold range by fusimotor efferent action. For many years it has been believed that cerebellar dysfunction is associated with reduced drive to the fusimotor system and that this in turn causes hypotonia by reducing the reflex excitation of alpha-motoneurons by spindle afferents. 3. The data on which this hypothesis is based were obtained in anesthetized or decerebrate animals. Little direct information is available on animals or humans performing voluntary movements and exhibiting ataxia or other cerebellar symptoms. 4. We tested the hypothesis by recording from nine muscle spindle afferents in behaving cats before and during reversible inactivation of cerebellar interpositus and dentate nuclei. In normal cats fusimotor action varies with motor task, greatly altering spindle stretch sensitivity. We investigated whether this same range of task-related sensitivity manifested itself during ataxia. 5. We found that the full range of spindle sensitivity was still present during ataxia. We therefore conclude that the cerebellar nuclei studied are not primarily responsible for fusimotor control, nor is the ataxia primarily caused by disordered proprioceptive sensitivity.

Afferent Pathways↗
PubMed1993

Relationship of seizure variables to personality disorders in epilepsy.

Among epileptic patients, personality disorders may be associated with specific seizure manifestations. In an epilepsy clinic, we identified 42 idiopathic epilepsy patients diagnosed with various DSM-III-R personality disorders, including borderline, atypical or mixed, explosive, and dependent. When compared with 42 age- and sex-matched epileptic control subjects on six seizure variables, the personality disorder group had more patients with epileptic auras (P = 0.001), particularly "cephalic" auras, and fewer with secondarily generalized tonic-clonic seizures (P < 0.05). These findings suggest that the experience of epileptic auras contributes to the development of personality disorders, especially when auras are not masked by secondarily generalized seizures.

Adult↗
PubMed1993

Schizophrenia in epilepsy: seizure and psychosis variables.

Prior studies have incompletely established a relationship between epilepsy and schizophrenia, primarily because of methodological difficulties. We undertook a two-part retrospective investigation of neurology clinic patients with epilepsy and schizophrenia. Part I: Interictal schizophrenic disorders occurred in 149 (9.25%) of 1,611 epileptic outpatients, compared with only 23 (1.06%) of 2,167 migraine outpatients. Part II: Among age- and sex-matched groups, we compared 62 epilepsy-with-schizophrenia patients with 62 epilepsy patients on six seizure variables, and we compared them with 62 schizophrenia patients on 10 psychosis variables. The epilepsy-with-schizophrenia group had a later epilepsy age of onset with more complex partial seizures, more patients with auras, and fewer patients with generalized epilepsy. Except for increased suicidal behavior, epileptic patients did not differ from controls on psychosis variables; however, psychotic symptoms often emerged with increased seizure activity. Together these results support a distinct association of schizophrenic disorders with epilepsy, particularly with seizures emanating from the temporal limbic system.

Adult↗
PubMed1993

Depression in epilepsy. Relationship to seizures and anticonvulsant therapy.

Interictal depression is common among epilepsy patients and may have a relationship to seizure variables. Among 1339 epileptic outpatients, we identified 101 (7.5%) patients who had a depressive disorder that required psychiatric evaluation, compared with only 105 (5.3%) of 1991 migraine patients from the same clinic (p = .01). The 101 epilepsy-depression patients were compared retrospectively with 202 seizure patients without depression on six seizure variables. The epilepsy-depression group had significantly fewer patients with generalized tonic-clonic seizures, a decreased frequency of generalized tonic-clonic seizures, and more patients on multiple anticonvulsant medications. We conclude that interictal depression in epilepsy may result from the use of more anticonvulsant drugs resulting in the prevention of secondary generalization from a seizure focus.

Adult↗
PubMed1992

Correlates of memory decline: a 4-year longitudinal study of older adults with memory complaints.

Change in memory performance and its correspondence to change in speed of performance and self-reported memory functioning were investigated longitudinally in 30 older adults with memory complaints. Subjects were assessed by self-report questionnaires and cognitive tests 3 times, at near 2-year intervals. A significant decline in word-recall scores was found, which was accompanied at the group level by significant self-reported decline in everyday memory functioning and nonsignificant decline in Wechsler Adult Intelligence Scale Digit Symbol scores (alpha = .05). The oldest subjects showed the most substantial declines in memory performance. At the individual level, however, memory change did not significantly correlate with either change in self-reports or change in Digit Symbol scores. Although these results do not support a cognitive slowing model of decline at the intraindividual level, they do have implications for intervention of age-related memory decline.

Aged↗
PubMed1992

Nursing home outbreak of influenza A (H3N2): evaluation of vaccine efficacy and influenza case definitions.

OBJECTIVES: Describe an outbreak of influenza A (H3N2); provide an analysis of vaccine efficacy; measure the sensitivity, specificity, and positive predictive value of 3 clinical case definitions of influenza. SETTING: A nursing home in Washington County, Maryland. The outbreak involved 52 residents (attack rate = 47.7%) and at least 10 of 140 employees (minimum attack rate = 7.1%). RESULTS: Twenty-five residents exhibited a 4-fold or greater increase in titer to influenza A/Sichuan/2/87. Vaccine efficacy was measured at -7.1%, suggesting that the influenza vaccine in 1988/1989 did not offer optimal protection against influenza A infection for the institutionalized elderly. CONCLUSIONS: The outbreak was a clear indicator of the need for rapid diagnosis. With the use of rapid diagnostic tests, influenza A could have been detected in time to use amantadine.

Aged↗
PubMed1992

Physiological evidence for a slow K+ conductance in human cutaneous afferents.

1. The depression in axonal excitability that follows short trains of impulses (H1) may lead to spike frequency adaptation to a sustained stimulus, and has been attributed to a slow K+ conductance. The present experiments sought indirect evidence for slow K+ channels at the node of Ranvier of human cutaneous afferents based on the demonstration of post-tetanic changes in excitability typical of H1. 2. The excitability changes in low-threshold cutaneous afferents in the digital nerves of the index finger were explored using a submaximal test pulse conditioned by trains of supramaximal stimuli, containing up to 100 impulses. Changes in the amplitude of the compound sensory action potential set up by a constant test stimulus were used as a measure of the changes in excitability. These changes in amplitude were paralleled by inverse changes in latency. 3. When the conditioning stimulus was a single supramaximal pulse, excitability was enhanced at conditioning-test intervals of 4-40 ms, with a peak at 6-8 ms. When the conditioning stimulus consisted of a train of ten pulses delivered at 200 Hz, the recovery cycle was dominated by subnormality that was maximal at 20 ms and subsided gradually over 50 ms. 4. The post-train depression in excitability increased as the number of pulses in the conditioning train increased to ten but changed little with further increases in train duration. The degree of depression increased with the pulse frequency within the train. Cooling the hand from a skin temperature of 35 to 25 degrees C slowed the recovery processes but did not alter the magnitude of the post-train depression. 5. These characteristics are typical of the H1 phase of post-tetanic depression in axonal excitability. The extent of the depression in excitability suggests, first, that there may be a significant K+ conductance at the nodes of human cutaneous afferents and, secondly, that H1 may play a significant role in limiting repetitive discharge in normal and pathological afferents.

Axons↗
PubMed1992

Ankle stiffness of standing humans in response to imperceptible perturbation: reflex and task-dependent components.

1. It has been demonstrated that subjects can alter the reflex stiffness of the elbow and wrist in response to imperceptibly slow perturbations applied through a complaint coupling. We used this technique to measure ankle stiffness in standing subjects as a means of examining reflex activity. 2. During unperturbed stance, a linear relationship between ankle torque and ankle angle is expressed as a load stiffness. The load stiffness predicted from a subject's measured physical dimensions corresponds closely with the value measured by standing the subject on a force platform. 3. Slow perturbations were applied at waist level, through a spring, to standing subjects. The perturbations caused sway similar in magnitude and rate to the sway of normal stance. Ankle stiffness was measured during the period when the perturbations were unperceived. The contribution to ankle stiffness of reflexes that use visual information was assessed by eye closure. The ability of reflexes based on sensory information from the legs to maintain upright posture was assessed when subjects balanced a load equivalent to their own body, in a situation where neither visual nor vestibular information could assist. Ankle stiffness was measured while the load was perturbed. 4. The results show that a simple mechanical model of stance predicts the torque-angle relationship at the ankle. This relationship determines the minimal ankle stiffness required to stand, and reflex muscle stiffness is a necessary component of this ankle stiffness. Visual, vestibular and lower limb sensorimotor reflexes each contribute to ankle stiffness; however, the local sensory reflexes alone are sufficient to stand. For responses to unperceived perturbations, standing subjects can alter their reflex ankle stiffness according to intentional set.

Ankle↗
PubMed1992

Detection of slow movements imposed at the elbow during active flexion in man.

1. Subjects' ability to detect movements imposed at the elbow during active flexion was measured. Movements of three different angular velocities (0.04, 0.4 and 4.4 deg/s) were applied to the arm while subjects maintained one of two force levels of active flexion. The threshold magnitudes for detection of the direction of imposed movement were found. 2. All thresholds were very small. At the lowest velocity of movement the average threshold was 0.13 deg and no subject had a threshold of greater than 0.3 deg. This contrasts with thresholds of over 2 deg measured in a previous study when the muscles about the joint were relaxed. Thresholds decreased further with increasing velocity of movement. 3. No difference was found between the two levels of contraction of the elbow flexors. However, extension (stretch of the contracting muscle) and flexion thresholds were calculated separately, and smaller extensions than flexions could be detected. 4. These findings indicate that conscious detection of imposed movements is greatly enhanced during active muscle contraction. Movements which cause unloading of the contracting agonist, as well as movements which result in stretch, are more easily detected than when the muscle is contracting. The discussion focuses on possible mechanisms for this enhancement.

Elbow Joint↗
PubMed1992

Persistence of herpes simplex virus DNA in rabbit corneal cells.

Corneal cell cultures were established from the corneas of rabbits killed during a period of latency 118 d after ocular infection with the RE strain of herpes simplex virus (HSV). DNA was isolated from frozen cell pellets of 42 cell cultures that did not develop viral cytopathic effects during 44 d in culture. Using the polymerase chain reaction (PCR) to amplify HSV thymidine kinase (TK) gene sequences, HSV-specific DNA was detected in 15 of 42 culture-negative cell cultures. Subsequent reamplification, using nested primers that were complementary to HSV TK sequences internal to the orginal primers, resulted in eight additional culture-negative samples showing positive hybridization for HSV TK DNA. Twenty three of the 42 virus culture-negative corneal cell cultures tested by PCR were found to contain HSV genetic material. Detailed examination of the clinical histories of the eyes from which the corneal cultures were obtained showed no correlation between increased frequency or severity of epithelial disease, stromal disease, or virus shedding and more frequent isolation of virus or detection of HSV-specific DNA. These studies document that HSV DNA residues in the corneas of HSV-infected rabbits up to 118 d post-infection. About 10% of the eyes contained virus that could be reactivated in culture, whereas an additional 55% of the eyes contained DNA sequences homologous to a portion of the HSV TK gene.

Animals↗
PubMed1992

Radioimmunoscintigraphy of metastatic breast carcinoma.

Seventeen patients with breast cancer underwent preoperative radioimmunoscintigraphy (RIS). Planar and tomographic imaging techniques (single photon emission computerised tomography--SPECT) were studied using Indium-111-labelled anti-epithelial membrane antigen (EMA) antibodies for tumour localisation. Overall imaging sensitivities were reasonable with correct identification of around 90% of primary lesions and 50% of secondary lesions. Planar imaging was more sensitive than SPECT for identification of superficial lesions such as the primary lesions (88% vs 56%) and axillary metastases (59% vs 53%). SPECT was necessary, however, for detection of deeper lesions such as internal mammary chain metastases and often served as an adjunct rather than an alternative to planar imaging. RIS, therefore, may contribute to more accurate staging of breast cancer, although further technical advances in RIS would enhance this contribution.

Adult↗