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Biomedical subjects

A Williamson

Publications and source records attributed to A Williamson.

At least 19 recordsLinked to original sources
PubMed1992

Driving in Alzheimer's disease.

OBJECTIVE: To determine if the impaired mental skills in Alzheimer's Disease (AD) may adversely affect driving ability. DESIGN: Retrospective survey. SETTING: The Alzheimer's Clinic of the University of Kansas Medical Center. PATIENTS: We interviewed 67 AD patients and their families and compared them with 100 elderly, non-spousal controls. MEASURES: The questionnaire was designed to obtain information on their driving habits, with emphasis placed on whether they were still driving, and the number of accidents per year for the past 10 years. RESULTS: Forty-six of the AD subjects had stopped driving because of safety concerns expressed by the subjects, their families, or health care providers, and two had stopped for other reasons. Only two of the normal controls had stopped driving (P < 0.0001, Chi-square test). Over the past 3 years, the 19 AD subjects who were still driving had 263.2 motor vehicle accidents per million vehicle miles of travel compared with 14.3 for the controls (P < 0.002, Mann-Whitney U test) and 5.7 for the general driving population age > or = 55 years (P < 0.05, Students one group, two-tailed t test). CONCLUSION: This study suggests that a significant traffic safety problem exists in subjects with AD who continue to drive. Efforts should be directed to detect patients with AD whose driving presents a traffic safety problem.

Accidents, Traffic↗
PubMed1992

Role of psychosocial risk factors in work-related low-back pain.

The experience of low-back pain and its psychosocial associates were directly compared among sufferers drawn from three populations, a blue-collar working group, a white-collar working group, and a patient group. Sufferers drawn from the patient population revealed the expected psychological disturbance. There was no evidence of such involvement for sufferers still at work. Disability resulting from low-back pain was positively linearly related to severity of pain for sufferers drawn from working groups, irrespective of psychological disturbance. For patients, on the other hand, the presence of psychological disturbance modified the relationship between severity and disability such that no simple linear relationship existed between the two variables. Work dissatisfaction was not found to be related to the presence of, and did not account for disability resulting from, low-back pain in working subjects.

Adult↗
PubMed1992

Neurotransmitters and their receptors in human temporal lobe epilepsy.

Patients with medically intractable temporal lobe epilepsy (TLE) undergo medial temporal lobectomy with hippocampectomy for one of two reasons. (1) A lesion (tumor or arteriovenous malformation) adjacent to, but not invasive of, the hippocampus, results in the removal of the lesion and adjacent hippocampus in order to ensure a tumor-free margin. This group will be referred to as tumor-related TLE (TTLE) patients. (2) The operation is performed when depth electrode recordings and other evaluative techniques point to the hippocampus as the focus of seizure initiation. This group will be referred to as cryptogenic TLE (CTLE) patients. Analysis of the hippocampi of these two groups of patients reveals that the TTLE hippocampus is quite similar to that of autopsy subjects in its chemical neuroanatomy. However, the dentate gyrus of the CTLE patients shows considerable morphological and cytochemical reorganization. This reorganization is characterized by a number of features. (1) There is a loss of granule cells which occurs either as a patchy loss and/or a thinning of the granule cell layer. (2) Remaining granule cells which contain dynorphin appear to produce recurrent collaterals into the inner molecular layer of the dentate gyrus. (3) In the subgranular region of the hilus (the polymorphic layer) there is a selective loss of interneurons immunoreactive for somatostatin, neuropeptide Y and substance P. (4) There appears to be an increase in fibers immunoreactive for somatostatin and neuropeptide Y which extend throughout the dentate molecular layer. Somatostatin fibers being less numerous than neuropeptide Y fibers (5). The distributions of a number of neurotransmitter receptors also show striking reorganization in the dentate gyrus of the CTLE hippocampus. (6) Second messenger systems protein kinase C and adenylate cyclase, and Na+, K(+)-ATPase activity, as determined by ouabain binding, is increased in the molecular layer of CTLE. This remodeling of the CTLE hippocampus may hold the key to the mechanisms of hyperexcitability of the granule cells in the hippocampus of this group, and consequently the generation of seizures. The removal of the hippocampus in CTLE patients results in good control of seizures, whereas removal of hippocampi that do not show such reorganization, in a group of patients classified as atypical CTLE patients, results in inadequate seizure control. These findings suggest a complex series of processes in converting the properly regulated granule cells into hyperexcitable ones.

Afferent Pathways↗
PubMed1991

Endogenously synthesized peptide with an endoplasmic reticulum signal sequence sensitizes antigen processing mutant cells to class I-restricted cell-mediated lysis.

The HLA-A2-positive human mutant cell line T2 is not lysed by influenza virus-specific HLA-A2-restricted cytotoxic lymphocytes after virus infection. However, lysis does occur when cells are incubated with the antigenic influenza matrix protein-derived peptide M57-68. To examine the nature of this defect, T2 cells were transfected with two different plasmids. One plasmid encoded the peptide M57-68, and the other encoded the same peptide preceded by an endoplasmic reticulum translocation signal sequence. Mutant T2 cells expressing the M57-68 peptide without the signal sequence were not susceptible to lysis by M57-68-specific HLA-A2-restricted cytotoxic T lymphocytes, whereas T2 cells expressing the M57-68 peptide plus signal sequence were lysed effectively. Lysis of parental T1 cells with either plasmid was equally effective. These results suggest that the T2 mutant cells are defective in the transport of antigenic peptides from the cytosol into the secretory pathway.

Amino Acid Sequence↗
PubMed1991

Actions of norepinephrine in the cerebral cortex and thalamus: implications for function of the central noradrenergic system.

Norepinephrine (NE) has potent and long-lasting ionic effects on cortical and thalamic neurons. In cortical pyramidal cells, activation of beta-adrenergic receptors results in an enhanced excitability and responsiveness to depolarizing inputs. This enhanced excitability is expressed as a reduction in spike frequency adaptation and is mediated by a marked suppression of a slow Ca(++)-activated potassium current known as IAHP. In the thalamus, application of NE results in the suppression of ongoing rhythmic burst activity and a switch to the single spike firing mode of action potential generation. This effect is mediated through an alpha 1-adrenergic suppression of a resting leak potassium current, IKL, and through a beta-adrenoceptor-mediated enhancement of the hyperpolarization activated cation current Ih. Together with the actions of other neuromodulatory neurotransmitters (i.e., acetylcholine, histamine, serotonin) these effects facilitate the switch of these neurons from a state of rhythmic oscillation and low excitability during drowsiness and slow-wave sleep to a state of increased excitability and responsiveness during periods of waking, attentiveness and cognition.

Action Potentials↗
PubMed1991

Modulation of neuronal firing mode in cat and guinea pig LGNd by histamine: possible cellular mechanisms of histaminergic control of arousal.

The thalamus is innervated by histaminergic fibers presumably arising from neurons in the tuberomammillary nucleus of the hypothalamus. The possible function of this histaminergic projection was addressed through investigation of the cellular actions of histamine on guinea pig and cat dorsal lateral geniculate (LGNd) relay neurons maintained as a slice in vitro. Local application of histamine to LGNd relay neurons resulted in a slow depolarization that was associated with a decrease in membrane conductance and was blocked by the H1-antagonists pyrilamine, triprolidine, or diphenhydramine. Current versus voltage relationships revealed that the slow depolarization was associated with an inward current that reversed near EK, indicating that it was due to a decrease in a potassium current. The slow depolarizing response to histamine was occluded by maximal activation of the slow depolarizing responses resulting from stimulation of alpha 1-adrenergic or muscarinic receptors, suggesting that they are all mediated by reduction in the same potassium current and/or alteration of a common second messenger. In the presence of H1-receptor antagonists, application of histamine resulted in a small depolarization that was associated with a marked increase in apparent membrane conductance. Voltage-clamp recordings revealed that this response was associated with enhancement of the hyperpolarization-activated cation current Ih. This response to histamine was blocked by local or bath application of the H2-antagonists cimetidine or tiotidine. The functional consequences of these actions of histamine were addressed with extracellular and intracellular recordings in guinea pig and cat LGNd relay neurons. Extracellular recordings in cat LGNd revealed the occurrence of highly regular 1-4 Hz rhythmic burst discharges. Application of histamine halted rhythmic bursting and replaced it with a prolonged period of single-spike activity. Intracellular recordings indicate that the histamine-induced switch in firing mode is due largely to the slow depolarizing response mediated by H1-receptors, but is also facilitated by the enhancement of Ih mediated by H2-receptors. These postsynaptic actions indicate that increased activity in the tuberomammillary histaminergic system may result in a switch of thalamic neuronal activity from rhythmic burst firing to single-spike activity and thereby promote the accurate transmission and processing of sensory information and cognition.

Acetylcholine↗
PubMed1991

Aortic counterpulsation for up to 28 days with autologous latissimus dorsi in sheep.

This article reports the development and assessment of an entirely autologous extraaortic counterpulsation system using skeletal muscle (latissimus dorsi). The technique has been performed and assessed in 16 sheep to quantify the effectiveness of counterpulsation over periods up to 28 days and to optimize the stimulation regimens for muscle contraction and fiber-type transformation. Hemodynamic changes have been quantified by calculation of the endocardial viability ratio. This has shown an increase of between 12% and 89% for 28 days. The wide variety of increase observed has been related to the development of an optimum flap configuration. The technique of surface impedance monitoring of flap blood flow has allowed the start of electrical stimulation after 48 hours with the introduction of hemodynamic benefit (1:4 mode) during the process of fiber-type transformation (in situ training). Extraaortic counterpulsation with autologous latissimus dorsi has been shown to be effective and safe for as long as 28 days. It has not been associated with any thromboembolic or infective complications, which we attribute to the exclusion of any foreign material in the design.

Animals↗
PubMed1991

The management of otitis media with effusion.

Otitis media with effusion is one of the most common otologic diseases encountered by the clinician. This is primarily a pediatric problem although it can be seen in all age groups. The etiology, diagnosis, and treatment of this disorder will be discussed in this manuscript.

Humans↗
PubMed1990

A prolonged post-tetanic hyperpolarization in rat hippocampal pyramidal cells in vitro.

The post-tetanic sequelae of trains of synaptic stimuli (50 pulses at 5 or 10 Hz) were studied with intracellular recordings from rat hippocampal neurons in vitro. In a large proportion of CA1 neurons, stimulation of afferent fibers was followed by a prolonged membrane hyperpolarization (peak amplitude approximately 6 mV) that was associated with a decrease in neuronal input resistance (approximately 33%) that lasted from tens of seconds to over 1 min. Antidromic stimulation or activation of cells with intracellular current injection did not elicit this post-tetanic hyperpolarization (PTH). The PTH could be elicited in chloride (Cl-)-loaded cells, its null potential shifted in response to changes in extracellular potassium ([K+]o), and it was significantly reduced by 5-10 mM extracellular cesium (Cs+). The K(+)-dependent PTH may also be calcium (Ca2+) dependent as its amplitude and associated conductance increase were sensitive to changes in [Ca2+]o. The PTH was enhanced by treatments that increase Ca2+ entry into cells including perfusion with elevated [Ca2+]o, with picrotoxin or with tetraethylammonium ion (TEA). The K+ conductance blocker 4-AP had no consistent effect on the PTH. The PTH was potently blocked by the membrane-permeant forms of cAMP, dibutyryl- and 8-bromo-cAMP. However, phorbol esters that activate protein kinase C and carbachol, which usually block the same potential that is blocked by cAMP, did not depress the PTH. The cardiac glycosides dihydro-ouabain and strophanthidin had only small and variable effects on the PTH.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1990

Sexual dysfunction in Parkinson's disease.

Sexual functioning was investigated in 50 parkinsonian male and female patients using a questionnaire. A loss of sexual interest and functioning was reported in a high percentage of patients. Depression was not prevalent but 70% had some evidence of autonomic nervous system dysfunction that may be related to sexual dysfunction. It is concluded that the sexual function is frequently impaired in Parkinson's disease.

Aged↗
PubMed1990

Characterization of an early afterhyperpolarization after a brief train of action potentials in rat hippocampal neurons in vitro.

1. In rat hippocampal pyramidal cells in vitro, a brief train of action potentials elicited by direct depolarizing current pulses injected through an intracellular recording electrode is followed by a medium-duration afterhyperpolarization (mAHP) and a longer, slow AHP. We studied the mAHP with the use of current-clamp techniques in the presence of dibutyryl cyclic adenosine 3',5'-monophosphate (cAMP) to block the slow AHP and isolate the mAHP. 2. The mAHP evoked at hyperpolarized membrane potentials was complicated by a potential generated by the anomalous rectifier current, IQ. The mAHP is insensitive to chloride ions (Cl-), whereas it is sensitive to the extracellular potassium concentration ([K+]o). 3. At slightly depolarized levels, the mAHP is partially Ca2+ dependent, being enhanced by increased [Ca2+]o and BAY K 8644 and depressed by decreased [Ca2+]o, nifedipine, and Cd2+. The Ca2(+)-dependent component of the mAHP was also reduced by 100 microM tetraethylammonium (TEA) and charybdotoxin (CTX), suggesting it is mediated by the voltage- and Ca2(+)-dependent K+ current, IC. 4. Most of the Ca2(+)-independent mAHP was blocked by carbachol, implying that IM plays a major role. In a few cells, a small Ca2(+)- and carbachol-insensitive mAHP component was detectable, and this component was blocked by 10 mM TEA, suggesting it was mediated by the delayed rectifier current, IK. The K+ channel antagonist 4-aminopyridine (4-AP, 500 microM) did not reduce the mAHP. 5. We infer that the mAHP is a complex potential due either to IQ or to the combined effects of IM and IC. The contributions of each current depend on the recording conditions, with IC playing a role when the cells are activated from depolarized potentials and IM dominating at the usual resting potential. IQ is principally responsible for the mAHP recorded at hyperpolarized membrane potentials.

Action Potentials↗
PubMed1990

Tinnitus.

Although tinnitus is usually a benign finding, it can have an extremely adverse effect on a patient's life. Tinnitis is a symptom that can have many different etiologies. This communication deals with the etiology, diagnosis, and available treatment of the condition.

Humans↗
PubMed1989

Opioid peptides (DAGO-enkephalin, dynorphin A(1-13), BAM 22P) microinjected into the rat brainstem: comparison of their antinociceptive effect and their effect on neuronal firing in the rostral ventromedial medulla.

The highly mu-selective agonist Tyr-D-Ala-Gly-MePhe-Gly-ol-enkephalin (DAGO) produces potent, dose-dependent naloxone-reversible antinociception when microinjected into the ventrolateral periaqueductal gray (PAG) (ED50 = 0.72 nmol) or rostral ventromedial medulla (RVM) (ED50 = 0.05 nmol) as measured on the rat tail flick (TF) assay. In single-unit recording experiments, DAGO microinjected into the PAG also affected On- and Off-Cell firing in the RVM in the same way as previously demonstrated by our group for morphine. PAG-microinjected DAGO inhibits spontaneous and noxious-evoked On-Cell firing (attenuating the characteristic On-Cell burst) (n = 19), and excites spontaneous Off-Cell firing, preventing the characteristic Off-Cell pause (n = 12) at doses which suppress the TF. These results support a major role for the mu receptor in PAG and RVM mechanisms of opiate antinociception. In our experiments using BAM22P, an endogenous weakly mu-selective opioid peptide, we could not demonstrate a dose-dependent antinociceptive effect, whether the peptide was microinjected supraspinally into the PAG (n = 9) or RVM (n = 11), or intrathecally at the lumbar cord (n = 4). In two animals, a naloxone-reversible antinociceptive effect was observed following the microinjection of 10 nmol BAM 22P into the RVM; however, no effect was seen in 3 animals microinjected with 20 nmol. Dyn A(1-13), a putative endogenous ligand for the kappa receptor, had no antinociceptive effect when microinjected into the ventrolateral PAG, and no effect on the firing (spontaneous or noxious-evoked) of RVM On (n = 3)- or Off (n = 2)-Cells.

Action Potentials↗
PubMed1989

Some characteristics of a retrovirus isolated from transformed bovine cells.

A novel retrovirus has been isolated from bovine cells transformed after cocultivation with leukocytes from an animal suffering from sheep-associated bovine malignant catarrhal fever. Morphologically and in its morphogenesis the virus resembles the type D Mason-Pfizer monkey virus (MPMV) as well as the ovine jaagsiekte retrovirus (JSRV). It is also serologically related to these two viruses, whereas a relationship to other known bovine retroviruses was not detected. However, its density of 1.16 g/ml in sucrose and the preference of its reverse transcriptase for manganese ions are closer to the characteristics of type C retroviruses. Unsuccessful attempts at transmission suggest that the virus may be defective in some function affecting its infectivity.

Animals↗
PubMed1989

Convergence and divergence of neurotransmitter action in human cerebral cortex.

The postsynaptic actions of acetylcholine, adenosine, gamma-aminobutyric acid, histamine, norepinephrine, and serotonin were analyzed in human cortical pyramidal cells maintained in vitro. The actions of these six putative neurotransmitters converged onto three distinct potassium currents. Application of acetylcholine, histamine, norepinephrine, or serotonin all increased spiking by reducing spike-frequency adaptation, in part by reducing the current that underlies the slow after hyperpolarization. In addition, application of muscarinic receptor agonists to all neurons or of serotonin to middle-layer cells substantially reduced or blocked the M-current (a K+ current that is voltage and time dependent). Inhibition of neuronal firing was elicited by adenosine, baclofen (a gamma-aminobutyric acid type B receptor agonist), or serotonin and appeared to be due to an increase in the same potassium current by all three agents. These data reveal that individual neuronal currents in the human cerebral cortex are under the control of several putative neurotransmitters and that each neurotransmitter may exhibit more than one postsynaptic action. The specific anatomical connections of these various neurotransmitter systems, as well as their heterogeneous distribution of postsynaptic receptors and responses, allows each to make a specific contribution to the modulation of cortical activity.

Adenosine↗
PubMed1988

Assessment of the use of transfusion therapy perioperatively in patients with sickle cell hemoglobinopathies.

During the period of 1978 to 1986, 66 patients (31 men, 35 women) with a mean age of 28.4 years and various sickle cell hemoglobinopathies underwent 82 surgical procedures; 28 were emergencies. Fifty of the 66 patients had HbSS, 13/66 had HbSC, and 3/66 had HbS-thalassemia. All 66 patients received transfusions, although not for all procedures. In 48 patients, transfusion therapy was only administered preoperatively. Simple transfusions (1 to 10 units) were administered in 31 of 48 procedures. Exchange transfusions (1 to 6 units) were performed in nine of 48 procedures. Preoperative hematocrit ranged from 7.0% to 54.2%; of those receiving transfusions the hematocrit ranged from 22.6% to 53.7%. Intraoperative transfusions (1 to 10 units) were performed in 14 of 82 procedures; postoperative transfusions (1 to 6 units) were performed in 13 of 82 procedures. No advantage was noted in preoperative exchange transfusion as measured by a decrease in postoperative complications; a slight increase was seen in atelectasis in this group of patients with preoperative transfusions. An increase was reported in the complication rate of patients with an hematocrit of less than 30%. The type of transfusion (preoperative, intraoperative, or postoperative) administered did not appear to be related to postoperative morbidity rates. The complication rate for simple transfusions was 51.6% and for multiple transfusions, 55.6%. HbSS hemoglobinopathy had the higher complication rate. The hepatitis B surface antigen was demonstrated in four of 66 (6.1%) patients; ten of 66 (15.2%) developed alloantibodies. The benefits of transfusion therapy should be judged according to clinical needs; not all sickle cell patients need exchange or preoperative transfusion.

Adult↗
PubMed1988

A transient calcium-dependent potassium component of the epileptiform burst after-hyperpolarization in rat hippocampus.

1. The epileptiform burst potential produced by picrotoxin is a model of the interictal spike potential seen in epilepsy. We have studied the epileptiform burst after-hyperpolarization (epileptiform burst AHP) using intracellular recording from rat CA1 hippocampal pyramidal cells in the slice preparation. In most experiments burst potentials were induced by electrical stimulation of afferent fibres, but in some experiments bursts that arose spontaneously were also investigated. 2. Previous evidence suggested that the epileptiform burst AHP has two slow K+-dependent components and that both components would be blocked by phorbol esters that activate protein kinase C. We found that phorbol esters indeed blocked the slow components, but also uncovered a transient hyperpolarizing component of the epileptiform burst AHP. This phorbol-ester-insensitive component (the transient AHP) peaked approximately 65 ms after the onset of the stimulus and lasted approximately 150 ms. The transient AHP is K+ dependent since its reversal potential shifted in elevated [K+]o, whereas Cl- loading of the cell had no effect on either its development or reversal potential. 3. The transient AHP was either greatly reduced or abolished by 5-10 mM-tetraethylammonium (TEA) and by 15-20 nM-charybdotoxin (CTX), both of which block a particular Ca2+-dependent K+ current. Concomitant with the block of the transient AHP was a significant increase in burst duration. The transient AHP was not blocked by up to 1 mM-4-aminopyridine (4-AP), 1 mM-N'-2'-O-dibutyryl-adenosine 3':5'-cyclic monophosphate (dBcAMP) or 50 microM-carbamylcholine (carbachol), and burst duration was relatively unaffected by these agents. 4. The transient AHP is Ca2+ dependent: (1) it was often associated with the occurrence of a slow, Ca2+-dependent spike; (2) its amplitude was increased in either elevated [Ca2+] saline or in (3) Bay K 8644 (5-10 microM), a compound that prolongs the open time of certain Ca2+ channels. 5. We conclude that a Ca2+-dependent K+ conductance is transiently activated by the epileptiform burst potential. Its distinctive pharmacological profile indicates that it is fundamentally different from the slow Ca2+-dependent K+ conductance. The Ca2+-dependent K+ current, IC, may mediate the transient AHP. Our data also suggest that the transient AHP conductance plays an important role in repolarizing the membrane after bursts of action potentials.

Action Potentials↗