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Biomedical subjects

H V Vinters

Publications and source records attributed to H V Vinters.

At least 55 records · Page 3Linked to original sources
PubMed1999

Postoperative seizure control and antiepileptic drug use in pediatric epilepsy surgery patients: the UCLA experience, 1986-1997.

PURPOSE: Young children with refractory symptomatic epilepsy are at risk for developing neurologic and cognitive disabilities. Stopping the seizures may prevent these disabilities, but it is unclear whether resective surgery is associated with adequate long-term seizure control. METHODS: This study determined pre- and postsurgery seizure frequency and antiepileptic drug (AED) use (6 months to 10 years) in children with symptomatic seizures from unilateral cortical dysplasia (CD; n = 64) and non-CD etiologies (i.e., ischemia, infection; n = 71), and compared them with older temporal lobe epilepsy (TLE; n = 31) patients with complex partial seizures. RESULTS: Compared with presurgery, postsurgery seizure frequencies were decreased for CD, non-CD, and TLE patients (p < 0.002), and there were no differences between the three groups from 6 to 24 months after surgery (p > 0.12). At 5 years after surgery, seizure frequencies were greater in CD compared with TLE cases (p = 0.009). Compared with presurgery, the number of AEDs declined after surgery in all three groups (p < 0.002), and positively correlated with seizure frequencies (p = 0.0001). CONCLUSIONS: This study indicates that seizure relief and AED use after resective surgery for symptomatic CD and non-CD etiologies was comparable with complex partial TLE cases up to 2 years after surgery. Furthermore, at 5 years after surgery, CD patients had outcomes better than those before surgery, but worse than TLE cases. In young children, these findings support the concept that early removal of symptomatic pathologic substrates is associated with seizure control and reduced AED use, similar to that noted in older TLE cases up to 2 years after surgery. Seizure control may reduce the risk of developing the seizure-related encephalopathy associated with severe symptomatic early-onset childhood epilepsy.

Age Factors↗
PubMed1999

Co-localization of TSC1 and TSC2 gene products in tubers of patients with tuberous sclerosis.

Two genes, mutations in which result in the phenotype of tuberous sclerosis (TSC), have recently been cloned. TSC2 on chromosome 16p13.3 encodes the protein tuberin, which appears to have growth regulating properties. TSC1 on chromosome 9q34 encodes hamartin which, as yet, has no specified cellular functions. Polyclonal antibodies were raised to synthetic peptides representing portions of tuberin and hamartin and used in immunoblots and immunohistochemical studies to localize the proteins in surgically resected neocortical tubers from four TSC patients. On Western blots of autopsy brain specimens, K-562 cell, and NT2 lysates, each antibody labelled a single band at the expected molecular weight. In immunohistochemical protocols on paraffin embedded tissue, antibodies to both tuberin and hamartin prominently labelled atypical and dysmorphic neuroglial cells that are a defining feature of TSC tubers. Some abnormal cells within cortical tuber sections were labelled with both tuberin and hamartin antisera. Our results suggest that tuberin and hamartin are both robustly expressed in similar populations of neuroglial cells of TSC tubers, even in the presence of TSC1 or TSC2 germline mutations. The roles of these gene products in normal and abnormal cortical development, tuber pathogenesis and the generation of seizures remain to be defined.

Adolescent↗
PubMed1999

Cortical dysplasia, genetic abnormalities and neurocutaneous syndromes.

Cortical dysplasia (CD) represents a common neuropathologic substrate of pediatric epilepsy, one frequently encountered in surgical resection specimens from infants and children with intractable seizure disorders, including infantile spasms. Severe CD shows similarities to structural features noted in tubers from individuals with tuberous sclerosis (TSC). The latter disorder, one with neurocutaneous and visceral manifestations, results from mutations in one of two recently cloned genes, TSC1 or TSC2, which encode (respectively) the proteins hamartin and tuberin. There is circumstantial evidence that both proteins may influence cell growth and differentiation, specifically that they may represent growth suppressors. Neither protein has a defined role in brain development. We discuss and illustrate neuropathologic features of both CD and TSC, and discuss the patterns and time course of hamartin/tuberin expression in normal brain, CD and TSC. Other recently cloned genes associated with cortical malformations encompassed by the term CD are briefly described.

Cerebral Cortex↗
PubMed1999

Cerebral cortical dysplasia: giant neurons show potential for increased excitation and axonal plasticity.

Cerebral cortical dysplasia (CD) is a common cause of intractable childhood epilepsy. Five cases of CD were analyzed for GABA(A) receptor subunit beta (GABA(Abeta)), glutamate decarboxylase, AMPA receptor subunit 1 (GluR1) and subunit 2/3 (GluR2/3), and NMDA receptor 2 (NMDAR2) immunoreactivity. Antisera to the highly polysialylated neural cell adhesion molecule (PSA-NCAM) and human unc-33-like phosphoprotein 1 (hUlip 1) were used to identify neurons with 'developmentally immature' characteristics. Differences between CD and comparison tissue (n = 3) included: (1) prominent GABA(Abeta) immunoreactivity of the cytoplasm of dysmorphic neurons in the subcortical white matter and cortex in 1 CD case; (2) increased immunolabeling with anti-GluR1 and GluR2/3 antisera in dysmorphic neurons compared with more normal-appearing adjacent neurons and neurons from nondysplastic cortex; (3) varying numbers of cortical dysmorphic neurons stained for NMDAR2 in all 5 CD cases, in contrast to a complete lack of cellular immunoreactivity in 2/3 of the cases of nondysplastic cortex; (4) PSA-NCAM and hUlip 1 expression (usually observed only in populations of neurons that undergo axonal growth) was observed in CD tissue, but not in normal brain tissue. In summary, dysmorphic neurons in cases of CD have increased immunoreactivity for several excitatory neurotransmitter receptor subunits, show variable immunoreactivity for GABA(Abeta) and show expression of several proteins that are normally expressed only in immature neurons or those with the potential for synaptic plasticity.

Axons↗
PubMed1999

A reexamination of the angiotoxicity of superselective injection of DMSO in the swine rete embolization model.

BACKGROUND AND PURPOSE: There are a variety of embolization applications for non-adhesive, liquid agents. We reevaluated the potential microvascular angiotoxicity of superselective infusions of dimethyl sulfoxide (DMSO) using very long infusion rates in a previously described animal model. METHODS: Twenty-six swine underwent percutaneous femoral puncture for superselective catheterization of the artery of the rete while being continuously monitored for ECG and intraarterial pressure. Two volumes (0.5 or 0.8 mL) and three durations (30, 60, and 90 seconds) of superselective infusion of DMSO were used to evaluate the effect of a single-dose rate within an ipsilateral rete. Contralateral control infusions of normal saline were also administered. Acute hemodynamic and angiographic outcomes were assessed. After recovery, follow-up angiography and sacrifice were performed at either 10 or 28 days. Brains and retia were harvested for gross and microscopic histopathologic evaluation. RESULTS: No significant hemodynamic alterations occurred acutely. Twenty-three of the 24 infused retia showed variable acute vasospasm that typically was mild to moderate in severity and transient (10 to 20 minutes). Follow-up angiography at sacrifice always showed normal retial arterial anatomy. No adverse clinical sequelae were noted. Gross inspection of brains showed no evidence of infarction or subarachnoid hemorrhage. Microscopic histopathologic examination of retia showed mostly nonspecific changes in both exposed and control samples. Possible causal histotoxicity was seen in four retia (three of four exposed to higher dose rates), in which involvement was limited to one to three retial arteries. CONCLUSION: Lower total dose and dose rates of superselective infusion of DMSO into the retial microarterial network resulted in substantially less angiotoxicity than that found in a previous study, as defined by clinical, angiographic, gross, and histopathologic criteria.

Angiography, Digital Subtraction↗
PubMed1998

Secondary microvascular degeneration in amyloid angiopathy of patients with hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D).

Various secondary microvascular degenerative and inflammatory alterations may complicate cerebral amyloid angiopathy (CAA) and contribute to the morbidity of CAA-associated stroke. We have investigated the severity of CAA-associated microangiopathy in a genetically determined Dutch form of CAA (HCHWA-D) that has major similarities to the type of CAA that more commonly occurs with aging or Alzheimer's disease (AD). The presence and extent of the following vascular abnormalities was assessed: (1) hyalinization/fibrosis, (2) microaneurysm formation, (3) chronic (especially lymphocytic) inflammation, (4) perivascular multinucleated giant cells/granulomatous angiitis, (5) macrophages/histiocytes within the vessel wall, (6) vessel wall calcification, (7) fibrinoid necrosis, and (8) mural or occlusive thrombi. (Of these, calcification of CAA-affected vessel walls has, to our knowledge, been described in only a single patient with CAA-associated cerebral hemorrhage.) Some of the changes, such as histiocytes in blood vessel walls and the relationship of vascular hyalinosis to amyloid beta/A4 protein deposition, were highlighted by immunohistochemistry. By assessing the numbers of sections in which the changes were present for each case, a 'score' reflective of CAA-associated angiopathy could be obtained. This 'score' was reproducible among several observers. We suggest that it might also be applicable to quantifying severe CAA and related microvascular degenerative changes in patients with AD. beta/A4 immunoreactivity was often sparse and adventitial (or almost absent) in severely hyalinized arterioles and microaneurysms. However, macrophages were prominent in the walls of such vessels and may play a role in the pathogenesis and progression of CAA-related microvasculopathy.

Amyloid beta-Peptides↗
PubMed1998

Congenital olivopontocerebellar atrophy: report of two siblings with paleo- and neocerebellar atrophy.

We report two sisters with congenital olivopontocerebellar atrophy, including immunohistochemical studies of autopsy brain tissue. Both cases showed microcephaly with disproportionately marked hypoplasia of the posterior fossa structures including pons, inferior olivary nuclei, and cerebellum. Microscopically, the pons was atrophic with near total loss of pontine nuclei and transverse pontocerebellar tracts (inferior and middle cerebellar peduncles). The medulla showed absent inferior olivary and arcuate nuclei. The cerebellum showed hypoplasia with rudimentary dentate nuclei, profound loss of Purkinje cells and external granule cell layer, a sparse internal granule cell layer of the entire dorsal vermis and the dorsal portions of the lateral folia, as well as markedly reduced underlying axon fibers in the white matter with marked astrogliosis. These features were highlighted by immunohistochemical study using antibodies against Purkinje cell epitopes, synaptophysin, neurofilament, glial fibrillary acidic protein, and tuberin. The cerebral hemispheres were unremarkable. Our cases are characterized by a pattern of diffuse posterior cerebellar involvement that has rarely been described in previous reports. An autosomal recessive pattern of inheritance is suggested. The abnormalities may result from antenatal degeneration or atrophy of neurons in the involved sites rather than hypoplasia or developmental arrest starting in the second and third month of late embryonic life.

Biomarkers↗
PubMed1998

Tuberous sclerosis-related gene expression in normal and dysplastic brain.

Cortical dysplasia (CD) broadly defines a complex cerebral malformative lesion associated clinically with intractable, pharmacoresistant epilepsy (including infantile spasms), especially in infants and children. In CD, the spectrum of structural brain abnormalities includes (at a minimum) neuronal dyslamination and (in severe cases) neuronal cytomegaly with cytoskeletal alterations and the presence of gemistocyte-like 'balloon cells'. In some CD variants, the neuropathological features are essentially indistinguishable from those of a tuber of tuberous sclerosis (TSC). Two genes associated with the autosomal dominant, multi-system disorder TSC have recently been cloned: TSC2 (on chromosome 16p13.3) encodes the protein tuberin and TSC1 (on 9q34) encodes hamartin. Tuberin has been immunolocalized to neurons and possibly astrocytes in normal brain and CD/TSC tubers, and is widely expressed in normal viscera; loss of heterozygosity and tissue culture studies suggest it functions as a growth suppressor. The TSC1 gene has been cloned within the last year and hamartin as yet has no well-defined cellular function, though its protein product may also function as a growth suppressor. This article focuses on the cellular pathogenesis of CD and TSC brain lesions and how the two may be biologically related. Studies of how TSC1 and TSC2 function in normal and dysplastic cerebral neocortex may provide a paradigm for understanding the neurobiology of other genes that determine epilepsy-associated cerebral malformations (e.g. lissencephaly, double cortex).

Brain↗
PubMed1998

Micronodular pneumocyte hyperplasia.

Tuberous sclerosis complex (TSC) is an autosomal-dominant disorder characterized by mental retardation, seizures, and central nervous system and visceral hamartomas. Pulmonary involvement manifesting as lymphangioleiomyomatosis (LAM) occurs in 1% of patients (all women) with TSC. Micronodular pneumocyte hyperplasia also has been described as a rare pulmonary manifestation of TSC. We report 14 patients with micronodular pneumocyte hyperplasia (MNPH). The patients ranged in age from 23 to 57 years (mean 37.5). There were 12 women and 2 men. Nine of the patients (one man and eight women) had documented clinical manifestations of TSC: seven with LAM, two without LAM (including one man). Of the five patients who did not have TSC, three had LAM and two did not (including one man). Histologically, all 14 cases demonstrated multiple well-demarcated nodules usually measuring up to 8 mm in size, but most were 1-3 mm. The nodules were produced by a proliferation of enlarged cytologically benign type II pneumocytes, with an associated increase in alveolar macrophages and interstitial reticulin. Immunoperoxidase studies showed the type II pneumocytes within lesions to be reactive with antibodies to cytokeratin (four of four), epithelial membrane antigen (EMA) (five of five), and surfactant apoprotein B (8 of 10). HMB-45 was negative in the MNPH lesions in all nine cases studied. Follow-up was available in 9 of 10 living patients and ranged from 1 to 14 years (mean 6 years). Nine patients are alive; six are clinically stable and three have repeated pneumothoraces related to LAM. Four patients have died. None of the deaths were attributable to MNPH. MNPH appears to be a hamartomatous proliferation occurring most frequently in patients with tuberous sclerosis, is separable from and not a manifestation of LAM, has been observed to occur in men, and, like other hamartomas of tuberous sclerosis, does not appear to possess malignant potential.

Adult↗
PubMed1998

Phenotypic variability of Gerstmann-Sträussler-Scheinker disease is associated with prion protein heterogeneity.

Gerstmann-Sträussler-Scheinker disease (GSS), a cerebello-pyramidal syndrome associated with dementia and caused by mutations in the prion protein gene (PRNP), is phenotypically heterogeneous. The molecular mechanisms responsible for such heterogeneity are unknown. Since we hypothesize that prion protein (PrP) heterogeneity may be associated with clinico-pathologic heterogeneity, the aim of this study was to analyze PrP in several GSS variants. Among the pathologic phenotypes of GSS, we recognize those without and with marked spongiform degeneration. In the latter (i.e. a subset of GSS P102L patients) we observed 3 major proteinase-K resistant PrP (PrPres) isoforms of ca. 21-30 kDa, similar to those seen in Creutzfeldt-Jakob disease. In contrast, the 21-30 kDa isoforms were not prominent in GSS variants without spongiform changes, including GSS A117V, GSS D202N, GSS Q212P, GSS Q217R, and 2 cases of GSS P102L. This suggests that spongiform changes in GSS are related to the presence of high levels of these distinct 21-30 kDa isoforms. Variable amounts of smaller, distinct PrPres isoforms of ca. 7-15 kDa were seen in all GSS variants. This suggests that GSS is characterized by the presence PrP isoforms that can be partially cleaved to low molecular weight PrPres peptides.

Adult↗
PubMed1998

Nonadhesive liquid embolic agent for cerebral arteriovenous malformations: preliminary histopathological studies in swine rete mirabile.

OBJECTIVE: To assess acute and chronic histopathological changes observed in a swine arteriovenous malformation model after endovascular delivery of Embolyx E (Micro Therapeutics Inc., San Clemente, CA) and its organic solvent dimethyl sulfoxide (DMSO). To develop standard endovascular delivery techniques of Embolyx through microcatheters into swine rete mirabile (RMB). METHODS: Forty RMBs in 22 swine were used to analyze acute and chronic angiographic and histological changes after superselective delivery of Embolyx E and/or its organic solvent (DMSO). Four RMBs (two for DMSO and two for Embolyx E study) were used as control specimens. Angiographic and histological evaluations were obtained 18 days, 1 month, 3 months, and 6 months after the procedure. Particular attention was paid to the presence of focal or diffuse angionecrosis, arterial revascularization, and perivascular inflammatory response. RESULTS: Staged and/or continuous delivery of Embolyx E were performed through the DMSO-compatible microcatheters without untoward catheter "gluing." All subacute/chronic specimens embolized with Embolyx E showed no evidence of angiographic recanalization. Twelve RMBs were used in acute studies, and all specimens showed no evidence of angionecrosis or aggressive inflammatory reaction. Subacute and chronic (total, n = 14) histological examinations of the RMBs showed mild inflammatory response manifested by monocellular infiltration and scattered foreign body giant cell reaction. In the 9 of 14 subacute and chronic specimens, focal disruption of elastica was observed along with embolic materials. Fourteen RMBs in eight swine were used to determine the safety range for DMSO injection. Two RMBs were used as control specimens. Rapid intra-arterial delivery (0.5 ml/5-15 s, n = 6) of DMSO caused angiographic vasospasm and histological endothelial necrosis. Slow injection (0.5 ml/30-120 s, n = 8) of DMSO showed minimum or no angiographic vasospasm, minimal adventitial inflammatory response, and no clinical complications. CONCLUSION: Embolyx E, an occlusive and nonadhesive embolic agent, is capable of producing permanent occlusion of swine RMB with the development of mild intra- and perivascular inflammatory changes and no clinical complications. The slow endovascular delivery of DMSO produces no untoward angiographic, pathological, or clinical changes. A fast injection of DMSO causes endothelial necrosis and severe inflammatory response in the arterial wall. This embolic material seems to have appropriate biochemical, anatomic, and histopathological characteristics to be used in the treatment of cerebral arteriovenous malformations or vascular cranial base tumors.

Animals↗
PubMed1998

Microvasculopathy is associated with the number of cerebrovascular lesions in hereditary cerebral hemorrhage with amyloidosis, Dutch type.

BACKGROUND AND PURPOSE: Microvascular changes such as microaneurysms and fibrinoid necrosis have been found in the presence of cerebral amyloid angiopathy (CAA). These CAA-associated microvasculopathies (CAA-AM) may contribute to the development of CAA-associated hemorrhages and/or infarcts, hereafter referred to as "cerebrovascular lesions." Hereditary cerebral hemorrhage with amyloidosis, Dutch type (HCHWA-D) is an autosomal dominant form of CAA, in which the amyloid angiopathy is pathologically and biochemically similar to sporadic CAA associated with aging and Alzheimer disease. To determine the significance of CAA-AM for CAA-associated cerebrovascular complications, we investigated the association between CAA-AM and cerebrovascular lesions in HCHWA-D patients. METHODS: In a previous autopsy study we semiquantitatively scored CAA-AM in 29 HCHWA-D patients. In the present study we reviewed clinical charts and autopsy protocols of these same patients. We investigated whether CAA-AM was associated with age at death, number of cerebrovascular lesions, duration of clinical illness, hypertension, and atherosclerosis. RESULTS: An association was found between CAA-AM and the number of cerebrovascular lesions (P = 0.009). The presence of microaneurysmal degeneration was most strongly associated with the number of cerebrovascular lesions (P < 0.001). In addition, we found an association between atherosclerosis and the CAA-AM score (P = 0.047). Hypertension was not associated with CAA-AM. CONCLUSIONS: Our findings support previous reports suggesting an important role of secondary microvascular degenerative changes in CAA-associated cerebrovascular lesions and suggest an aggravating effect of systemic atherosclerosis, but not hypertension, on the evolution of CAA-AM. These findings may be of relevance to understanding cerebrovascular complications of sporadic or Alzheimer disease-associated CAA.

Age Factors↗
PubMed1998

Alzheimer's disease: etiologies, pathophysiology, cognitive reserve, and treatment opportunities.

Alzheimer's disease (AD) can be diagnosed with a considerable degree of accuracy. In some centers, clinical diagnosis predicts the autopsy diagnosis with 90% certainty in series reported from academic centers. The characteristic histopathologic changes at autopsy include neurofibrillary tangles, neuritic plaques, neuronal loss, and amyloid angiopathy. Mutations on chromosomes 21, 14, and 1 cause familial AD. Risk factors for AD include advanced age, lower intelligence, small head size, and history of head trauma; female gender may confer additional risks. Susceptibility genes do not cause the disease by themselves but, in combination with other genes or epigenetic factors, modulate the age of onset and increase the probability of developing AD. Among several putative susceptibility genes (on chromosomes 19, 12, and 6), the role of apolipoprotein E (ApoE) on chromosome 19 has been repeatedly confirmed. Protective factors include ApoE-2 genotype, history of estrogen replacement therapy in postmenopausal women, higher educational level, and history of use of nonsteroidal anti-inflammatory agents. The most proximal brain events associated with the clinical expression of dementia are progressive neuronal dysfunction and loss of neurons in specific regions of the brain. Although the cascade of antecedent events leading to the final common path of neurodegeneration must be determined in greater detail, the accumulation of stable amyloid is increasingly widely accepted as a central pathogenetic event. All mutations known to cause AD increase the production of beta-amyloid peptide. This protein is derived from amyloid precursor protein and, when aggregated in a beta-pleated sheet configuration, is neurotoxic and forms the core of neuritic plaques. Nerve cell loss in selected nuclei leads to neurochemical deficiencies, and the combination of neuronal loss and neurotransmitter deficits leads to the appearance of the dementia syndrome. The destructive aspects include neurochemical deficits that disrupt cell-to-cell communications, abnormal synthesis and accumulation of cytoskeletal proteins (e.g., tau), loss of synapses, pruning of dendrites, damage through oxidative metabolism, and cell death. The concepts of cognitive reserve and symptom thresholds may explain the effects of education, intelligence, and brain size on the occurrence and timing of AD symptoms. Advances in understanding the pathogenetic cascade of events that characterize AD provide a framework for early detection and therapeutic interventions, including transmitter replacement therapies, antioxidants, anti-inflammatory agents, estrogens, nerve growth factor, and drugs that prevent amyloid formation in the brain.

Alzheimer Disease↗
PubMed1998

Antibody to caspase-cleaved actin detects apoptosis in differentiated neuroblastoma and plaque-associated neurons and microglia in Alzheimer's disease.

During apoptosis, activation of a family of cysteine proteases related to interleukin-1beta-converting enzyme (ICE)-related proteases or "caspases" results in endoproteolytic cleavage of multiple substrates at specific aspartate residues. We have sought to develop new antibody probes for the neoepitopes in protein fragments produced by ICE-related proteolytic cleavage as specific markers of events tightly linked to apoptotic mechanisms. Here, we demonstrate that an antibody probe specific for the C terminus of a 32-kd actin fragment produced by ICE-like activity specifically labels apoptotic but not necrotic, differentiated human neuroblastoma cells in culture. Unlike probes for nonspecific DNA strand breaks confined to the nucleus or cell body, this method allows the detection of cytoskeletal fragments in cell processes as well as the perikaryon long before DNA fragmentation and cell death and therefore serves as a novel marker of apoptosis-related events in distal parts of cells such as axons and dendrites. To illustrate this new tool, we show that the antibody detects the processes and cell bodies of degenerating neurons and plaque-associated microglia in Alzheimer's disease. In situ detection of caspase-cleaved actin provides a new means to evaluate the role of caspase activation in pathological and physiological processes.

Actins↗
PubMed1997

The trkC receptor is transiently localized to Purkinje cell dendrites during outgrowth and maturation in the rat.

In vivo studies of granule cell gene expression during corticocerebellar development and in vitro studies of Purkinje cell neurite outgrowth suggest that neurotrophin-3 may influence growth of Purkinje cell dendrites. To determine whether neurotrophic substances affect the growth of specific neuronal processes (i.e. axons and dendrites) or nonspecifically cause process development by exerting a trophic influence upon neuronal physiology we performed an immunohistochemical examination of trkC protein expression during early postnatal development of the rat cerebellum. Our findings indicate that Purkinje cells begin to synthesize trkC protein coincident with the onset of dendritic outgrowth. Robust immunostaining was evident throughout the entire somatodendritic domain of Purkinje cells during dendritic development but became faint and restricted to the cell body subsequent to the completion of dendritogenesis. These results suggest that growth and maturation of the Purkinje cell dendritic arbor may be influenced by neurotrophin-3 activation of trkC receptors distributed within developing dendrites.

Animals↗
PubMed1997

Local-clonal expansion of infiltrating T lymphocytes in chronic encephalitis of Rasmussen.

Rasmussen's syndrome is a progressive and intractable form of epilepsy characterized pathologically by focal brain inflammation with large numbers of infiltrating T lymphocytes. To better understand the nature of the T cell response in this disease, we analyzed TCR expression in the brain lesions using PCR for quantitative assessment of TCRBV gene transcripts, together with size and sequence analysis of the third complementarity-determining region (CDR3) of the dominant TCR rearrangements. Restricted (oligoclonal) BV family usage was not observed, as all of the 22 BV PCR products were usually detected at levels exceeding the background. However, significant individual biases in the frequencies of different TCR families was evident. The distinct pattern of BV expression by infiltrating lymphocytes detected in the original PCR screening suggested a specific immune response. The primary structure of the rearranged CDR3 sequences for the BV family expressed at highest level in each sample was studied by size and sequence analysis. The data showed that predominant TCR BV families expressed in diseased brain tissue displayed limited size heterogeneity and extensive repetition of in-frame CDR3 nucleotide motifs. These findings demonstrate that the local immune response in Rasmussen's syndrome includes restricted T cell populations that have likely expanded from a few precursor T cells responding to discrete antigenic epitopes.

Amino Acid Sequence↗
PubMed1997

High frequency of apolipoprotein E epsilon 2 allele in hemorrhage due to cerebral amyloid angiopathy.

From the somewhat conflicting published data on apolipoprotein E (apoE) genotype in hemorrhage due to cerebral amyloid angiopathy (CAA), it is unclear whether apoE genotype influences the risk of CAA-related hemorrhage independently of its association with concomitant Alzheimer's disease (AD). We determined the apoE genotypes of 36 patients presenting with cerebral hemorrhage associated with histologically confirmed CAA. The frequency of apoE epsilon 2 was 0.25 and the frequency of apoE epsilon 4 was 0.18. Patients with CAA-related hemorrhage and concomitant AD pathology (CERAD criteria, n = 17) had a high apoE epsilon 4 frequency, close to that in AD cases without hemorrhage. Patients in whom CAA-related hemorrhage occurred in the absence of significant AD pathology (n = 13) had an apoE epsilon 4 frequency somewhat lower than non-AD controls without hemorrhage. However, in CAA-related hemorrhage, the apoE epsilon 2 frequency was high regardless of whether significant AD pathology was present. We conclude that whereas possession of apoE epsilon 2 may be a risk factor for cerebral hemorrhage due to CAA, apoE epsilon 4 is a risk factor for concomitant AD but not an independent risk factor for CAA-related hemorrhage.

Aged↗