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Joab Chapman

Publications and source records attributed to Joab Chapman.

27 records · Page 2Linked to original sources
PubMed2003

Deficiency of nicotinic acetylcholine receptor beta 4 subunit causes autonomic cardiac and intestinal dysfunction.

Neuronal nicotinic acetylcholine receptors (nAChR) are composed of 12 subunits (alpha 2-alpha 10 and beta 2-beta 4), which play the central role in autonomic transmission. beta 4 subunits are abundantly expressed in autonomic ganglia, forming acetylcholine binding sites and ion channels with alpha 3 or alpha 3 and alpha 5 subunits as pentameric receptors. To investigate the physiological and pharmacological properties of beta 4 subunits in autonomic ganglia, we measured autonomic functions in knockout mice lacking nAChR subunit beta 4 (beta 4(-/-)) and wild-type mice. beta 4(-/-) mice had an attenuated bradycardiac response to high frequency (60 pulse/s) vagal stimulation, as well as an increased sensitivity to hexamethonium blockade at low dose (3 mg/kg) and a reduced ileal contractile response to the nicotinic agonists cytisine, dimethylphenylpiperazinium iodide, nicotine (10 mg/kg each), and epibatidine (0.1 mg/kg). The results suggest that beta 4 subunits are important components of nAChRs in autonomic ganglia. Deficiency of beta 4 subunits altered ion channel properties, conductance, and sensitivity and affinity of receptors to agonists and antagonists, affecting ganglionic transmission.

Acetylcholine↗
PubMed2002

Prevalence and clinical features of dementia associated with the antiphospholipid syndrome and circulating anticoagulants.

The increasing prevalence with age of antiphospholipid antibodies (aPL), of dementia and of stroke complicates the study of a causal relationship between antiphospholipid syndrome (APS) and dementia. Prolonged aPTT due to circulating anticoagulants (CAC) may serve as a more specific laboratory marker of APS. In a hospital-based study, we examined all patients with CAC and included 23 who fulfilled standard criteria for primary APS. These patients were assessed for dementia, vascular brain disease, autoimmune disease activity and dementia risk factors. Among CAC-positive APS patients, 13 of the 23 (56%) were demented and these were significantly older (mean age+/-S.E., 68+/-3 years) than the nondemented APS group (n=10, 51+/-4 years; p<0.01, Student's t-test). The demented patients had significantly more pathology on computerized brain tomography (CT) and electroencephalography (EEG) studies but six of them had no clinical or CT evidence of vascular brain disease. Erythrocyte sedimentation rate was significantly lower in the dementia group, in which there was also a significant negative correlation between levels of aPL and age. CAC-positive APS patients seem to be at risk for developing dementia with age, suggesting a pathogenic role for prolonged exposure to elevated aPL.

Aged↗
PubMed2002

Autonomic function in mice lacking alpha5 neuronal nicotinic acetylcholine receptor subunit.

Neuronal acetylcholine nicotinic receptors (nAChR) are composed of 12 subunits (alpha2-10, beta2-4), of which alpha3, alpha5, alpha7, beta2 and beta4 subunits are known to exist in the autonomic nervous system (ANS). alpha5 subunits possess unique biophysical and pharmacological properties. The present study was undertaken to examine the functional role and pharmacological properties of the nAChR alpha5 subunits in the ANS using mice lacking alpha5 nAChR subunits (alpha5-/-). These mice grew to normal size showing no obvious physical or neurological deficit. They also showed normality in thermoregulation, pupil size and resting heart rate under physiological conditions. The heart rate and rectal temperature did not differ between alpha5-/- and wild-type mice during exposure to cold stress. An impairment of cardiac parasympathetic ganglionic transmission was observed during high frequency vagal stimulation, which caused cardiac arrest in all wild-type animals while alpha5-/- mice were more resistant. Deficiency of alpha5 subunits strikingly increased the sensitivity to a low concentration of hexamethonium, leading to a nearly complete blockade of bradycardia in response to vagal stimulation. Such a concentration of hexamethonium only slightly depressed the effects of vagal stimulation in control mice. Deficiency of alpha5 subunits significantly increased ileal contractile responses to cytisine and epibatidine. These results suggest that alpha5 subunits may affect the affinity and sensitivity of agonists and antagonists in the native receptors. Previous studies revealed that alpha5 subunits form functional receptors only in combination with other alpha and beta subunits. Thus, the data presented here imply that alpha5 subunits modulate the activity of nAChR in autonomic ganglia in vivo.

Alkaloids↗
PubMed2002

Changes in axonal morphology in experimental autoimmune neuritis as studied by high b-value q-space (1)H and (2)H DQF diffusion magnetic resonance spectroscopy.

Experimental autoimmune neuritis (EAN) has been studied in rat sciatic nerves by a combination of high b-value (1)H and (2)H double quantum filtered (DQF) diffusion MRS. The signal decays of water in the (1)H and (2)H DQF diffusion MRS were found to be not monoexponential and were analyzed using the q-space approach. The q-space analysis of the (1)H diffusion data detected two diffusing components, one having broad and the other having narrow displacement profiles. These components were shown to be very sensitive to the progression of EAN disease. The q-space parameters were found to be abnormal at day 9 postimmunization before the appearance of clinical signs. The assignment of the component with the narrow displacement profile to axonal water has been corroborated by the (2)H DQF diffusion MRS results. The displacement and the relative population of this slow and restricted diffusing component followed the processes of demyelination, axonal loss, and remyelination that occur in EAN. The displacements extracted from the slow-diffusing component with the narrow displacement correlated well with the average size of the axons as deduced from electron microscopy (EM). The component with the broad displacement showed significant changes which were attributed to the formation of endoneurial edema. This observation was also corroborated by the (2)H DQF diffusion MRS experiments. It seems, therefore, that q-space analysis of high b-values diffusion MRS is a promising new approach for early detection and better characterization of the different pathologies associated with EAN. This study demonstrates the utility of high-b-value q-space diffusion MRS for studying white matter-associated disorders in general.

Animals↗
PubMed2002

Assessment of experimental autoimmune neuritis in the rat by electrophysiology of the tail nerve.

The assessment of experimental autoimmune neuritis (EAN) by electrophysiological studies of the sciatic innervation of the plantar muscle may be complicated by local inflammation. We therefore utilized the tail nerve-muscle system to monitor disease progression in 20 rats with EAN and 10 control rats. Early changes were detected in motor nerve conduction velocity (32.06 +/- 1.85 m/s versus 43.57 +/- 3.98 m/s in controls, P < 0.001) at 15 days postimmunization (DPI), and conduction block (70.6 +/- 9.4% compared to 12.4 +/- 3.4%, P < 0.001) at 22 DPI. No consistent conduction block (22.4 +/- 10.4%) was found in the plantar muscle measurements. The tail nerve response of EAN rats demonstrated severe temporal dispersion at 43 DPI, which returned to normal at 135 DPI, although motor nerve conduction velocity values were still lower than in controls (24.4 +/- 0.9 m/s, P < 0.001). The tail nerve may be a useful addition to electrophysiological studies in this model of the Guillain-Barré syndrome.

Animals↗
PubMed2002

Neurological and neuroendocrine-cytokine inter-relationship in the antiphospholipid syndrome.

Although many neurological deficits have been described in the antiphospholipid syndrome (APS), only stroke is well established and accepted as a diagnostic criterion in the disease. We presently review clinical data obtained from large series of cases regarding stroke, dementia, epilepsy, chorea, migraine, white-matter disease, and behavioral changes in APS, or linked-to-laboratory criteria such as antiphospholipid antibodies (aPL). The contribution of animal models to our understanding of these manifestations of APS is stressed, especially regarding the cognitive and behavioral aspects for which we have established model systems in the mouse. These models utilize immunization of mice with beta(2)-glycoprotein1, a central autoantigen in APS, which induces persistent high levels of aPLs. These mice develop hyperactive behavior after a period of four months, as well as deficits in learning and memory, and are potentially valuable as a system in which to study the pathogenesis and treatment of cognitive and behavioral aspects of APS. We have developed another model, in which IgGs from APS patients induce depolarization of brain synaptoneurosomes, and which may serve as a model for the pathogenesis of epilepsy in APS. Hormonal changes are another potential CNS manifestation of APS and this may be potentially linked to the systemic and central effects of cytokines such as interleukin-3. Better understanding of the link between APS and neurological or neuroendocrine manifestations other than stroke will reveal whether they can be used as clinical criteria for the diagnosis of APS and, it is hoped, lead to better treatment.

Abortion, Habitual↗
PubMed2002

[The use of alternative medicine by multiple sclerosis patients].

This paper aims to present the results of a study that explores the use of uncontrolled and unexamined alternative treatment methods with 37 MS patients, and to compare these results with previous studies. The studied variables were: (a) reasons and circumstances of referral, (b) self reported outcome effectiveness of alternative treatment, and (c) satisfaction with the conventional physician and alternative healer. From a group of 37 patients, 17 were referred to alternative healers. In comparison with those who were not referred to alternative medicine, the sub-group referred for alternative treatment reported more familial support and lower levels of satisfaction from their rapport with their conventional physicians.

Complementary Therapies↗
PubMedDate not supplied

Plasma homocysteine levels and Parkinson disease: disease progression, carotid intima-media thickness and neuropsychiatric complications.

OBJECTIVE: To determine whether plasma homocysteine (Hcy) levels are associated with clinical characteristics, neuropsychological and psychiatric manifestations and cardiovascular comorbidity in patients with Parkinson disease (PD). BACKGROUND: Elevated Hcy levels are linked to atherosclerosis, vascular disease, depression, and dementia. Patients with PD treated with L-dopa have been shown to have elevated Hcy levels. DESIGN/METHODS: Idiopathic PD patients were evaluated using the Unified Parkinson's Disease Rating Scale, Hoehn and Yahr stage, Parkinson Psychosis Rating Scale, Beck Depression Inventory, Frontal Assessment Battery, Mini-Mental Status Examination, and several tests for frontal type cognitive functions. Fasting blood samples were collected for the measurement of Hcy, and carotid B-mode ultrasound was performed to measure intima-media thickness of the common carotid arteries. RESULTS: Seventy-two consecutive PD patients (46 men; average age, 68.7 +/- 11.6 years; average disease duration, 7.0 +/- 4.7 years) were recruited. All but 10 patients were treated with L-dopa. The average level of Hcy was 16.4 +/- 7.8 micromol/L, and 38.9% of the patients had Hcy level above the reference range (>15.0 micromol/L). The Hcy levels were associated with PD duration as they were with L-dopa treatment duration but were not associated with the parameters of disease severity or with L-dopa dose. The Hcy levels were associated neither with the common carotid intima-media thickness nor with cardiovascular morbidity. No association was found between Hcy and the neuropsychiatric features of PD such as depression, cognitive performance, or psychosis. CONCLUSIONS: Hyperhomocystinemia is common in L-dopa-treatedPD patients but was not associated with neuropsychological complications (depression, dementia, and cognitive decline associated with frontal lobe functioning or psychosis), enhanced disease severity, or vascular comorbidity.

Adult↗