Soluble HLA: patterns of expression in normal subjects, autoimmune diseases, and transplant recipients.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
Roger E Kelley
Publications and source records attributed to Roger E Kelley.
Soluble HLA measurement in saliva and cerebrospinal fluid in Caucasian patients with multiple sclerosis: a preliminary study.
BACKGROUND: Measurement of soluble HLA in body fluids has a potential role in assessing disease activity in autoimmune disorders. METHODS: We applied a solid phase, enzyme-linked immunoassay to measure soluble HLA class I (sHLA-I) and class II (sHLA-II) molecules in the saliva and cerebrospinal fluid (CSF) in 13 untreated patients with relapsing-remitting form of multiple sclerosis (MS). For comparison purposes, we also studied saliva from 53 healthy subjects. RESULTS: Saliva from normal controls had detectable sHLA-I levels in 41 of 53 individuals studied, with values ranging from 9-100 ng/ml (mean = 41 +/- 2.8 ng/ml). sHLA-I was undetectable in the saliva in 11 of 13 MS patients, and in none of the CSF specimens. In contrast, mean sHLA-II concentration in the saliva of MS patients was significantly increased compared to controls (386 +/- 52 unit/ml vs. 222 +/- 18.4 unit/ml, t = 8.68, P < 0.005). The mean CSF sHLA-II level (369 +/- 16 unit/ml) was equivalent to the mean sHLA-II concentration measured in saliva (mean = 386 +/- 52 unit/ml) (P = 0.7). In patients with brain magnetic resonance imaging (MRI) enhancing lesions (n = 5), reflective of more active disease, CSF sHLA-II averaged 356 +/- 26 unit/ml compared to 380 +/- 51 in saliva. Similarly, in patients with non-enhancing lesions (n = 8), CSF sHLA-II averaged 377 +/- 18 unit/ml compared to 390 +/- 77 unit/ml in saliva. Thus, the mean sHLA-II concentration in saliva and CSF was essentially equivalent for MS patients with or without enhancing plaques. CONCLUSION: Our data suggest that the measurement of soluble HLA in saliva, specifically sHLA-II, correlates with the level found in the CSF. Therefore, if sHLA correlates with disease activity in MS, as has been proposed, saliva measurements provide a noninvasive correlate of CSF measurement.
Journal Article↗
Update on stroke prevention.
It is now well recognized that stroke-prone individual scan be identified in the majority of instances and that effective preventive therapy is available. Cumulative risk factors enhance the potential for stroke.The challenge is to effectively intervene to substantially reduce stroke risk.
Angioplasty, Balloon↗
HIV-associated dementia, Alzheimer's disease, multiple sclerosis, and schizophrenia: gene expression review.
RNA and protein gene expression technologies are revolutionizing our view and understanding of human diseases and enable us to analyze the concurrent expression patterns of large numbers of genes. These new technologies allow simultaneous study of thousands of genes and their changes in regulation and modulation patterns in relation to disease state, time, and tissue specificity. This review summarizes the application of this modern technology to four common neurological and psychiatric disorders: HIV-1-associated dementia, Alzheimer's disease, multiple sclerosis, and schizophrenia and is a first comparison of these diseases using this approach.
AIDS Dementia Complex↗
CNS vasculitis.
Vasculitis of the central nervous system can be of several varieties depending upon the vessel(s) involved and type of disorder. One can see primary CNS vasculitis as a distinct entity which is primarily manifested as central nervous system injury in a vascular distribution or the vasculitic process can be secondary to a systemic disorder such as systemic lupus erythematosus (SLE) or polyarteritis nodosa (PAN). The inflammation of the CNS vessels can be immune mediated or infectious in nature and a number of "triggers" have been identified including hypersensitivity states. It is quite probable that there is a genetic predisposition in certain individuals and this can lead to an enhanced risk of a vasculitic process when there is exposure to a particular antigen that "sets off" the immune system. The potential for response of the process to antimicrobials and/or immunosuppressants, and the potential for devastating consequences if the process is left untreated, has heightened the urgency in recognizing CNS vasculitis. Key to the recognition and treatment of CNS vasculitis is the evolution of newer insights into the pathogenesis. For example, it is evident that most vasculitides are cell-mediated. Antigen stimulation of CD4+T cells is believed to play a crucial role in giant cell (temporal) arteritis which is the most common type of CNS vasculitis. Identification of genetic susceptibility has also contributed to our understanding of the cascade of events that leads to vascular injury on an inflammatory basis.
Animals↗
Memory complaints and dementia.
Explore the source record for details and available documents.
Alzheimer Disease↗
Pathogenesis of brain and spinal cord atrophy in multiple sclerosis.
For more than a century, multiple sclerosis was viewed as a disease process characterized by oligodendrocyte and myelin loss, and research into the pathogenesis of multiple sclerosis was mainly focused on the mechanisms of inflammation. However, with development of more sophisticated neuroimaging and molecular biology techniques, attention has shifted to new aspects of pathogenesis of multiple sclerosis: axonal loss and neurodegeneration. Evidence is increasing that tissue destruction, primarily axonal loss and neurodegeneration, is a key element in the pathogenesis of multiple sclerosis. In addition, it is now known that brain and spinal cord atrophy begins early in the disease process of multiple sclerosis and advances relentlessly throughout the course of the disease. Cumulative data suggest that axonal loss is the major determinant of progressive neurologic disability in patients with multiple sclerosis. Magnetic resonance imaging and magnetic resonance spectroscopy in patients with multiple sclerosis for < 5 years indicate brain atrophy and loss of axonal integrity. Neurodegeneration and axonal loss in patients with multiple sclerosis are initially accompanied by a local response from oligodendrocyte progenitor cells and some remyelination. However, these repair mechanisms eventually fail, and patients typically develop generalized brain atrophy, cognitive decline, and permanent disability. Although the exact mechanisms underlying central nervous system atrophy in patients with multiple sclerosis are largely unknown, evidence exists that atrophy may represent an epiphenomenon related to the effects of dynamic inflammation within the central nervous system, including demyelination, axonal injury, neuronal loss, Wallerian degeneration, and possibly iron deposition. This article summarizes the potential mechanisms involved in central nervous system atrophy in patients with multiple sclerosis.
Apoptosis↗
Neuroimaging of the complications of epilepsy surgery.
BACKGROUND AND PURPOSE: Stroke-like symptoms can be associated with the invasive evaluation and surgical resection of epileptic foci in patients with intractable epilepsy. Neurological deficits following surgical procedures for epilepsy are not uncommon, but most are relatively minor and transient. The authors investigated the neuroimaging patterns of cerebral tissue insults in patients suffering neurological deficits directly related to procedures performed to evaluate and treat intractable epilepsy. They attempted to discern potential secondary vascular insults from the not unexpected tissue loss that can be associated with various epilepsy procedures. METHODS: The authors prospectively assessed 7 consecutive patients who underwent either the invasive electrocortigraphic monitoring or surgical resection of epileptic foci. All had some degree of neurological deficit postoperatively. The authors evaluated for tissue injury type with postoperative computed tomography and magnetic resonance brain imaging. They also review pertinent medical literature addressing potential complications of epilepsy surgery. RESULTS: Three patients had primarily ischemic tissue injuries, 2 had tissue loss with minor bleeding, and 1 transient deficit appeared to reflect the amount of tissue removed. Another patient had choreiform movements and gait ataxia 1 week after the procedure, but no follow-up neuroimaging was available. The primary ischemic insults appeared to be related to vascular traction or compression or possibly vasospasm. The tissue loss/hemorrhagic insults were presumably related to tissue loss, with seepage of blood or bleeding from a resected cavernous hemangioma. No patients died, but 1 was left with a persistent, moderately severe neurological deficit. CONCLUSIONS: It is important to distinguish the not unexpected neurological deficits associated with inadvertent trauma to normal brain tissue during procedures associated with epilepsy surgery from vascular insults. Postoperative neuroimaging can be useful in this endeavor.
Adolescent↗
Cardioembolic stroke: an update.
Cardioembolic stroke accounts for approximately 15% of all strokes and is thought to be one of the more preventable types of strokes. Features that have been reported to support cardioembolism as a mechanism for ischemic stroke have included documented cardiac source of embolism, maximal neurologic deficit at onset, multiple cerebrovascular territories involved, enhanced tendency toward hemorrhagic transformation, enhanced risk of syncope or seizure associated with presentation, and lower likelihood of premonitory transient ischemic attacks. Features that tend to make cardioembolic stroke less likely include significant cerebral atherosclerosis, step-wise progression of the neurologic deficit within a finite period of time, vascular distribution such as entire internal carotid artery territory with combined middle cerebral artery and anterior cerebral artery involvement or watershed distribution, and premonitory transient ischemic attacks. A number of cardiac conditions can promote thromboembolism, and there is risk stratification reflective of the specific condition or coexistent conditions. Anticoagulant therapy generally has been found to be the most effective means of preventing cardiogenic brain embolism, but the intensity of anticoagulation needs to be optimized to reflect the risk-to-benefit ratio for the particular patient.
Aged↗
The Edwin Smith surgical papyrus: description and analysis of the earliest case of aphasia.
The Edwin Smith surgical papyrus, which dates back nearly five millennia, is the oldest known medical text and contains the first written example of the word "brain", as well as the earliest known descriptions of the meninges and the cerebrospinal fluid. The papyrus describes 48 cases and gives the first accounts of several forms of brain injury and their associated complications. The Egyptian author presents an analytical approach to the reported cases and classifies them as favourable, uncertain or intractable, depending on prognosis. The authors believe that case 20 of the papyrus presents the first possible case of aphasia, which occurred following head trauma. The patient, frustrated by his inability to speak, developed nuchal stiffness, which might have been due to meningeal irritation. The case concludes with the advice that a patient with such a grave condition should only be comforted, not treated.
Aphasia↗
Serum from patients with multiple sclerosis downregulates occludin and VE-cadherin expression in cultured endothelial cells.
Disruption of the blood brain barrier (BBB) and transendothelial migration of inflammatory cells are crucial steps in the development of demyelinating lesions in multiple sclerosis (MS). Occludin and vascular endothelial-cadherin (VE-cadherin) are two major components of the tight junctions (TJs) in the brain microvasculature that help to create the BBB. In the present study, we investigated the effect of serum from MS patients on the expression of these two junctional markers and on the endothelial integrity. Serum from six MS patients in exacerbation, six in remission, and six normal controls (10% by volume) was incubated with cultured endothelial cells, and the expression of occludin and VE-cadherin was measured by immunoblotting. Serum from MS patients in exacerbation significantly reduced the expression of occludin and VE-cadherin compared with patients in remission and normal controls. This disintegrating effect was more pronounced for occludin than for VE-cadherin. We assume that the elevation in cytokines or other serum-soluble factors in MS patients in exacerbation likely provokes downregulation of occludin and VE-cadherin. This downregulation of TJs proteins may, therefore, contribute to the disruption of the BBB in this condition.
Adult↗
Acute verbal dyspraxia, a rare presentation in multiple sclerosis: a case report with MRI localization.
Cortical speech disorders rarely occur in multiple sclerosis (MS). We report a patient with relapsing-remitting MS, who presented with acute verbal dyspraxia. Magnetic resonance imaging (MRI) demonstrated an acute T2/Flair hyperintense, primarily white matter lesion underlying the middle third of the inferior frontal gyrus. The verbal dyspraxia cleared beginning 48 hours after the initiation of iv dexamethasone. Follow-up MRI demonstrated qualitative and quantitative diminution of the hyperintensity. This is the first report of a clinically definite MS patient with acute verbal dyspraxia. Moreover, there was a suggestive localization of verbal praxis to Brodmann areas 44/45.
Acute Disease↗
Trancranial Doppler monitoring of response to therapy for meningovascular syphilis.
Meningovascular syphilis is now quite uncommon, but there have been increasing reports in patients immunocompromised with human immunodeficiency virus. The response of syphilis affecting the central nervous system to antibiotic therapy remains a challenge. This is an even greater challenge in patients who have underlying compromise of the immune system. The authors present a 46-year-old male with recurrent stroke who was found to have cerebrospinal fluid compatible with syphilitic involvement of the central nervous system and a cerebral arteriogram, which revealed focal narrowing of the right middle cerebral artery. The baseline transcranial Doppler study demonstrated increased mean and peak flow velocity within the right middle cerebral artery. Despite a 10-day course of intravenous penicillin, with substantial improvement in the cerebrospinal fluid results, this flow velocity elevation persisted, in a remarkably consistent pattern, over a 4-month follow-up period. Thus, the involved vessel remained patent following treatment, but no clear resolution of the stenotic lesion was observed.
Blood Flow Velocity↗
Perioperative stroke: evaluation, management, and possible preventive measures.
Mechanisms of perioperative ischemic stroke include: hypotension, hypercoagulability, arrhythmias with embolism, or direct vascular insult. Mechanisms of perioperative hemorrhagic stroke include: use of antithrombotics, hypertension, or direct vascular insult.
Anticoagulants↗