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Biomedical subjects

Alireza Minagar

Publications and source records attributed to Alireza Minagar.

At least 37 records · Page 2Linked to original sources
PubMed2005

Hereditary ataxia and behavior.

Recognizing cognitive deficits and psychiatric disorders in patients with autosomal dominant ataxias is relatively new. At this time, the percentage of patients with these disorders who experience changes in cognition or psychiatric symptoms is unknown. Cognitive impairment, when seen, is often found on tests of executive function, probably reflecting disruption of afferent and efferent pathways of the prefrontal cortex and subcortical structures, including the cerebellum. Widespread global dysfunction does occur in some cases, especially later in the disease course. Psychiatric symptoms including depression, aggression, irritability, and psychosis have all been reported. As these behavioral changes receive further study, one hopes that guidelines for treating these symptoms will emerge. Clinicians should be mindful of the psychosocial effects that genetic testing for the hereditary ataxias may have, especially in cases of predictive testing for those who are asymptomatic but at risk because of family history. Guidelines established for genetic testing in HD may be helpful when approaching these cases.

Behavior↗
PubMed2004

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↗
PubMed2004

Brain RNA expression in obese vs lean mice after LPS-induced systemic inflammation.

Mortality of obese patients with severe sepsis is higher than non-obese patients. Thus far, a pathophysiologic mechanism has not been identified that explains this higher mortality. The central nervous system is now becoming increasingly recognized as a target organ in sepsis and the systemic inflammatory response syndrome and may hold clues to the deleterious affects of obesity in patients with sepsis syndrome. In this study, obese and non-obese mice were given LPS IP and the brains were harvested 2 hours after injection. The brains were processed and mRNA isolated and hybridized to a microarray chip and processed. Analysis of gene expression demonstrated distinct expression difference between the lean and obese animals. Ontology data supports clear differences between the lean and obese groups in the coagulation system, neuro-endocrine system, lipid transport and insulin receptors. Approximately eighty genes were identified to show 10-fold differential expression between the obese and lean mice.

Animals↗
PubMed2004

Endothelial microparticles (EMP) bind and activate monocytes: elevated EMP-monocyte conjugates in multiple sclerosis.

Elevated plasma endothelial microparticles (EMP) have been documented in MS during exacerbation. However, the role of EMP in pathogenesis of MS remains unclear. We investigated the formation of EMP-monocyte conjugates (EMP-MoC) and their potential role in transendothelial migration of inflammatory cells in MS. EMP-MoC were assayed in 30 MS patients in exacerbation, 20 in remission and in 35 controls. EMP-leukocyte conjugation was investigated flowcytometrically by employing alpha-CD54 or alpha-CD62E for EMP, and alpha-CD45 for leukocytes. EMP-MoC were characterized by identifying adhesion molecules involved and their effect on monocyte function. In vivo (clinical): EMP-MoC were markedly elevated in exacerbation vs. remission and controls, correlating with presence of GD+ MRI lesions. Free CD54+ EMP were not elevated but free CD62E+ EMP were. In vitro: EMP bound preferentially to monocytes, less to neutrophils, but little to lymphocytes. Bound EMP activated monocytes: CD11b expression increased 50% and migration through cerebral endothelial cell layer increased 2.6-fold. Blockade of CD54 reduced binding by 80%. Most CD54+ EMP bound to monocytes, leaving little free EMP, while CD62+ EMP were found both free and bound. These results demonstrated that phenotypic subsets of EMP interacted differently with monocytes. Based on our observations, EMP may enhance inflammation and increase transendothelial migration of monocytes in MS by binding to and activating monocytes through CD54. EMP-MoC were markedly increased in MS patients in exacerbation compared to remission and may serve as a sensitive marker of MS disease activity.

Adult↗
PubMed2004

Sepsis associated encephalopathy (SAE): a review.

Sepsis associated encephalopathy (SAE) is a poorly understood condition that is associated with severe sepsis and appears to have a negative influence on survival. The incidence of encephalopathy secondary to sepsis is unknown. Amino acid derangements, blood-brain barrier disruption, abnormal neurotransmitters, and direct CNS effect are possible causes of septic encephalopathy. Research has not defined the pathogenesis of SAE.

Amino Acids↗
PubMed2004

Elevated expression of IFN-gamma in the HIV-1 infected brain.

We determined the extent of expression of three cytokines (IFN-gamma, IL-4, and TNF-alpha ) in brain tissue infected with human immunodeficiency virus-1 (HIV-1). The selections were IFN-gamma as a Th1 cytokine, IL- 4 as a Th2 cytokine, and TNF-alpha as a pro-inflammatory cytokine (and because of its prior implication in brain tissue damage due to HIV-1 infection). Based on current models for pathogenesis of HIV-1-associated dementia (HAD), in the periphery, Th1 cytokines are considered to be salutary, whereas Th2 cytokines are regarded as deleterious. However, we hypothesized that in the CNS these roles are reversed. Post-mortem temporal lobe tissue specimens from 16 HIV-1-seropositive patients and 11 HIV-1-seronegative controls were stained for IFN-gamma, IL-4, and TNF-alpha utilizing immunohistochemistry and alkaline phosphatase. HIV-1 infection causes alterations of brain cytokine expression that include increased IFN-gamma expression for HIV-1-seropositive vs. HIV-1-seronegative individuals. There was increased expression of IFN-gamma for HIV-1-seropositive individuals with or without HAD, with or without the broader category of neuropsychiatric impairment (NPI), and with or without opportunistic infections (OIs) compared to HIV-1-seronegatives. A significant inverse correlation between IFN-gamma vs. IL-4 in HIV-1-seropositives with HAD and in seronegative individuals was observed. There was an inverse correlation in seropositives between IFN-gamma vs. TNF-alpha, a positive trend with HAD, significant without HAD, significant with NPI and significant without OIs. Between IL-4 vs. TNF-alpha there was a correlation (trend) in seropositives, a trend with NPI, significant without NPI, and a trend without OI. Due to HIV-1 infection of the brain and neurological disease there is a prominent increased expression of IFN-gamma, an inverse expression of IFN-gamma vs. TNF-alpha, and TNF-alpha vs. IL-4. The inverse correlation between increased IFN-gamma and decreased IL-4 expression is consistent with the stimulation of activated macrophages, and T cells, greater toxicity in the HIV-1-infected brain, and is supportive of the significance of IFN-gamma in HIV-1-infected patients.

Adolescent↗
PubMed2004

Stereotactic radiosurgery using the Leksell Gamma Knife: current trends and future directives.

Stereotactic radiosurgery is the extremely precise administration of a radiation dosage in three-dimensional space to treat an increasingly broad spectrum of intracranial and skull-base lesions. 455 patients with various indications were treated using the 201 Source Co-60 Leksell Model "B" Gamma Knife(r) at Louisiana State University Health Sciences Center in Shreveport, Louisiana. 273 (60.2%) patients received radiosurgery as the first line of treatment for their disease. The mean Karnofsky Performance Score (KPS) of the patients was 70. Cerebral metastases were the main indications for radiosurgery at our center accounting for 27% of the patients, while meningioma, AVM, trigeminal neuralgia, movement disorders, and primary CNS malignant tumors were the other indications. Our institutional experience and results indicate that low incidence of complications coupled with a high tumor control rate makes Gamma Knife stereotactic radiosurgery a viable option for patients who must undergo neurosurgery. As the Gamma Knife continues to prove itself as a first-line treatment of many complex brain disorders, new indications for this technology will continue to emerge, further broadening the scope of patient care.

Forecasting↗
PubMed2004

Movement disorders.

Explore the source record for details and available documents.

Essential Tremor↗
PubMed2004

CYP450 dietary inhibitors attenuate TNF-alpha-stimulated endothelial molecule expression and leukocyte adhesion.

Enhanced expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and other endothelial cell adhesion molecules (ECAMs) are associated with the onset and progression of inflammatory bowel disease (IBD). We show in this study that two cytochrome p-450 (CYP450) inhibitors from Citrus paradis (grapefruit), bergamottin, and 6',7'-dihydroxybergamottin (DHB) block tumor necrosis factor (TNF)-alpha-stimulated expression of MAdCAM-1 in cultured endothelial cells and also reduce alpha(4)beta(7)-dependent lymphocyte adhesion. Bergamottin (20-50 microM) or DHB (10-30 microM) pretreatment dose-dependently reduced TNF-alpha-mediated expression of MAdCAM-1 and lymphocyte adhesion. Bergamottin and DHB also prevented expression of two other ECAMs, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 (but not E-selectin). SKF-525a, a specific CYP450 inhibitor, also blocked the expression of MAdCAM-1 mediated by TNF-alpha. Similar to SKF-525a (20 microM), bergamottin (20 microM) and DHB (20 microM) directly inhibited the activity of CYP450 3A4. These results suggest that natural CYP450 inhibitors may be effective in reducing ECAM expression and leukocyte adhesion and therefore be useful in the clinical treatment of inflammatory states like IBD.

Animals↗
PubMed2004

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↗
PubMed2004

Gamma knife surgery in the management of brain metastases from lung carcinoma: a retrospective analysis of survival, local tumor control, and freedom from new brain metastasis.

OBJECT: The objective of this retrospective study was to analyze the results of stereotactic radiosurgery performed using a gamma knife in the treatment of 44 consecutive patients with brain metastases from lung carcinoma. METHODS: Forty-four patients with lung carcinoma were treated for metastatic brain tumors by performing radiosurgery with a Leksell Gamma Knife. Twenty-one patients (47.7%) were women and 23 were men. The mean age of the patients was 56 years (range 35-77 years). Twenty-two patients (50%) had solitary tumors and the rest had multiple tumors (two-six lesions). Eighteen patients (40.9%) presented with a recurrent and/or progressive brain disease that previously had been treated with other modalities (surgery, external-beam radiotherapy, or both). Fifteen patients had controlled lung disease and 19 patients had systemic metastases (in lymph nodes, liver, and/or bones) at the time of radiosurgery. The median follow-up period was 18.25 months. All patients were followed up for three different end points: 1) death caused by the disease; 2) clinical and/or radiological evidence of progression of the tumor that had been treated with radiosurgery; and 3) appearance of new lesions. At the last follow-up review, 17 patients (38.6%) were alive and 27 (61.4%) had died. Ten patients (22.7%) died as a result of brain disease (failure of local control or new metastases). Controlled primary disease at the time of detection of metastases and the ability to achieve local tumor control after radiosurgery significantly improved the patient survival (p < 0.01). Control of the treated tumor(s) was achieved in 32 of 44 patients (72 tumors) and 10 patients experienced treatment failure. In addition to the 44 patients comprising the study population, two other patients were treated, but died of lung disease too early in the follow-up period to have been assessed. As of the last follow-up review, no new brain metastasis had occurred in 36 patients (81.8% [includes surviving and nonsurviving patients]). The median duration of overall survival was 7 months, the median period of controlled brain disease was 21 months, and the median period of freedom from new brain metastases was 17 months (95% confidence interval 13-19 months). CONCLUSIONS: Gamma knife surgery has significantly reduced the incidence of mortality from brain disease by effectively accomplishing local tumor control in patients with metastatic lung cancer. Local control and freedom from new brain metastases is not influenced by prior external-beam radiotherapy.

Adult↗
PubMed2004

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↗
PubMed2003

Soluble HLA-I (s-HLA-I) synthesis in systemic lupus erythematosus.

Our objective was to study a possible contribution of major histocompatibility complex (MHC) genes to soluble HLA-I synthesis in patients with systemic lupus erythematosus (SLE). Solid-phase enzyme-linked immunoassay (ELISA) was used to measure sHLA-I in the sera of 20 patients with SLE and 76 normal controls with known HLA phenotypes. Serial serum samples ( n=108) from the above group of patients ( n=19) were further investigated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. Soluble HLA-I levels were abnormally higher in patients with SLE than normal controls ( P<0.0002). No complete HLA haplotype has been identified to be correlated with high or low sHLA-I secretion. Only the sera of HLA-A23- or -A24- (splits of HLA-A9) positive individuals were found to contain high sHLA-I concentrations in both populations studied. The difference between sHLA-I of HLA-A24 patients ( n=7) and HLA-A24 normal controls ( n=19) was statistically highly significant ( P<0.0079). The results suggest that HLA-A24 may confer additional risk of more severe disease expression in female patients with SLE. The data imply that SLE patients carrying 39-kDa sHLA-I have increased risk of developing renal disease. A higher prevalence of 35-37 kDa was observed in patients with mild disease. Interestingly, 44-46 kDa was the predominant molecular form of sHLA-I in SLE patients with lymphocytosis with no evidence of organ involvement. Notably, all these variations were not reflected by differences in HLA phenotypes, with the exception of HLA-A24-positive patients, in whom the 44-46-kDa form occurs consistently but not exclusively. In summary, the results show a genetic heterogeneity of SLE with MHC control of the expression of sHLA-I concentrations and possible involvement of disease-associated factors that might potentiate a specific sHLA-I molecule synthesis.

Adult↗
PubMed2003

Nonmalignant pediatric brain tumors.

Brain tumors are the most common solid neoplasms in the pediatric population. Each year in the United States, approximately 1500 to 2000 children are affected by one of these tumors. About 50% of pediatric brain tumors are malignant. Nonmalignant pediatric brain tumors comprise an eclectic group of pathologic entities that have fascinating clinical features. Many of these tumors demonstrate a favorable prognosis. In this report, we review the epidemiology, histopathology, genetics, clinical presentation, neuroimaging, and treatment of the common nonmalignant pediatric brain tumors, including low grade astrocytomas (such as cerebellar astrocytoma and optic pathway glioma), subependymal giant cell astrocytomas, central neurocytomas, dysembryoplastic neuroepithelial tumor, choroid plexus papilloma, and craniopharyngioma. Advances in the therapeutic management of patients with these tumors have considerably improved their prognosis.

Adolescent↗