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Biomedical subjects

Israel Steiner

Publications and source records attributed to Israel Steiner.

At least 19 recordsLinked to original sources
PubMed2006

Neurotropism of herpes simplex virus type 1 in brain organ cultures.

The mechanism of herpes simplex virus type 1 (HSV-1) penetration into the brain and its predilection to infect certain neuronal regions is unknown. In order to study HSV-1 neurotropism, an ex vivo system of mice organotypic brain slices was established and the tissue was infected with HSV-1 vectors. Neonate tissues showed restricted infection confined to leptomeningeal, periventricular and cortical brain regions. The hippocampus was the primary parenchymatous structure that was also infected. Infection was localized to early progenitor and ependymal cells. Increasing viral inoculum increased the intensity and enlarged the infected territory, but the distinctive pattern of infection was maintained and differed from that observed with adenovirus and Vaccinia virus. Neonate brain tissues were much more permissive for HSV-1 infection than adult mouse brain tissues. Taken together, these results indicate a complex interaction of HSV-1 with different brain-cell types and provide a useful vehicle to elucidate the mechanisms of viral neurotropism.

Adenoviridae↗
PubMed2005

Involvement of cellular death signals in the reactivation of herpes simplex virus type 1 and lambda bacteriophage from a latent state.

Herpes simplex virus (HSV) 1 has adapted to the human host through two modes of infection, the acute-transient infection that may cause diseases (such as encephalitis) and the latent state, which is a source for recurrent infection and disease. While much information has been gathered on the cellular and molecular concomitants of establishment and maintenance of HSV-1 latent state, the biological basis of viral reactivation is still unclear. Despite their obvious differences, HSV-1 and the bacterial temperate virus, the bacteriophage lambda, shares four distinct features that may help understand the viral latency phenomenon: (i) two modes of life cycle and a decision point to choose either latency (HSV-1) and lysogeny (bacteriophage lambda), or active replication, that results in cell destruction, (ii) establishment of lysogeny/latency of the respective virus is associated with protection from cell death, (iii) immunity/resistance to super-infection, (iv) agents that trigger mammalian and bacterial cell death also induce reactivation of both HSV-1 and lambda bacteriophage. Thus, despite their differences, these two viruses might display analogous mechanism(s) of reactivation. Based on clinical and experimental data, we propose in this hypothesis that while HSV-1 latency, like bacteriophage lambda lysogeny, is associated with protection from cell death and restriction to super-infection, viral reactivation from the latent state is triggered by exogenous stress signals that interfere with cellular viability and may eventually lead to cell death.

Bacteria↗
PubMed2005

Experimental allergic encephalomyelitis: a misleading model of multiple sclerosis.

Despite many years of intensive research, multiple sclerosis (MS) defies understanding and treatment remains suboptimal. The prevailing hypothesis is that MS is immune mediated and that experimental allergic encephalomyelitis (EAE) is a suitable model to elucidate pathogenesis and devise therapy. This review examines critically the validity that EAE is an adequate and useful animal model of MS and finds credible evidence lacking. EAE represents more a model of acute central nervous system inflammation than the counterpart of MS. We propose to reconsider the utilization of EAE, especially when this model is used to define therapy. This will also force us to examine MS without the restraints imposed by EAE, as to what it is, rather than what it looks like.

Animals↗
PubMed2005

Statins lower the risk of developing Alzheimer's disease by limiting lipid raft endocytosis and decreasing the neuronal spread of Herpes simplex virus type 1.

Many possible risk factors for Alzheimer's disease (AD) have been investigated, with only a very few showing positive associations and none defining the etiology of the neurodegenerative disease. The presence of herpes simplex virus type 1 (HSV-1) DNA in the brain, coupled with apolipoprotein E allele e4 (ApoE e4), has been suggested to confer an increased risk for AD. Studies have shown that pathogens, including viruses, utilize clathrin-independent endocytosis, i.e., lipid rafts that contain cholesterol, as part of their structure. Moreover, cholesterol-lowering statins have recently been linked with a reduced risk of developing Alzheimer's dementia. We, therefore, posit that long-term statin therapy protects individuals from AD by reducing the neuronal spread of HSV-1 via lipid raft domain pathways. Although the mechanism by which statins reduce AD risk is unknown, they reduce the amount of cholesterol in the plasma membrane and, thus, may decrease the availability of lipid raft pathways to spread HSV-1 within the brain.

Alzheimer Disease↗
PubMed2005

Synchronized infection of cell cultures by magnetically controlled virus.

To override the diffusion-limited adsorption step of viral infection, we magnetically synchronized cell attachment. Human immunodeficiency virus type 1-based lentivirus preparations were rendered magnetically reactive by association with magnetite nanoparticles, 50 nm in diameter. Application of a magnetic field resulted in immediate redistribution of the viral inoculum to the cell-associated state and completion of the productive adsorption process within 1 min. Independent of adsorption time, viral concentration, and diffusion rate, infection subsequently progressed by the receptor-mediated entry mechanism. Synchronization of this rate-limiting step of infection may now be applied to analyze isolated events in the viral replication sequence.

Adsorption↗
PubMed2004

Recurrence of Sydenham chorea: implications for pathogenesis.

BACKGROUND: Sydenham chorea (SC), a major sign of rheumatic fever (RF), is related to systemic streptococcal infection and is treated with antibiotics. Recurrence usually occurs within a short interval following the initial event and is considered part of RF. OBJECTIVE: To evaluate the rate, nature, and course of recurrent SC during an extended follow-up period. DESIGN: Prospective assessment of a cohort of patients with SC who were admitted between 1985 and 2002. SETTING: General community hospital. METHODS: Diagnosis of RF was based on the revised Jones criteria. Other causes of chorea were excluded. Recurrence was defined as the development of new signs, lasting more than 24 hours and separated by a minimum of 2 months from the previous episode. Patients were observed from 1 to 14 years following the initial SC episode and for at least 1 year after recurrence. At recurrence, patients were assessed for RF clinical and laboratory activity, including change in cardiac involvement. RESULTS: Twenty-four patients had SC. In 19 patients (79%), the chorea was associated with other RF signs, and 5 suffered from pure chorea. Ten patients (42%, 7 women) developed 11 recurrent episodes of chorea 3 months to 10 years after the initial episode. Association of recurrent chorea with RF could be suspected in only 6 episodes: cessation of prophylactic antibiotic treatment or poor compliance in 4 patients and rise in antistreptolysin O titers in 2. In an 18-year-old woman, chorea recurred during her first pregnancy. At recurrence, chorea was the sole rheumatic sign in all 9 patients who had 1 recurrent episode. In the patient with 2 recurrent episodes, mitral regurgitation developed into mitral stenosis. No statistical differences in previous RF activity and rheumatic cardiac involvement between patients with recurrent SC and patients with a single episode could be found. CONCLUSIONS: In a significant subgroup of patients, SC recurrence might not be a true relapse of rheumatic fever. It might represent either a primary underlying abnormality that renders patients susceptible to developing such a movement disorder or the outcome of permanent subclinical damage to the basal ganglia following the initial SC episode.

Adolescent↗
PubMed2004

Complete mitochondrial DNA sequence analysis in a family with early-onset dystonia and optic atrophy.

The combination of optic atrophy and dystonia has been etiologically associated with mitochondrial DNA (mtDNA) mutations. We report here on the complete mtDNA sequence from the proband of a consanguineous family exhibiting "mitochondrial-like" optic atrophy and dystonia. A candidate tRNA(Gly) mutation was identified that was unique to the family. However, the mutation was homoplasmic in both affected and unaffected family members and we were unable to demonstrate a biochemical defect in patient mitochondria. Hence, it is unlikely that a mtDNA mutation accounts for the phenotype in this family.

Adult↗
PubMed2004

Neurological abnormalities associated with celiac disease.

BACKGROUND: Celiac disease (CD) is a gluten-sensitive enteropathy in genetically susceptible individuals. Anecdotal reports suggest that the nervous system might be affected in the disorder, but the severity and prevalence of such an involvement have not been systematically evaluated. MATERIALS AND METHODS: Analysis of files of CD patients diagnosed between 1980 and 1999 for neurological abnormalities. Diagnosis of CD was based on the modified criteria of the European Society for Pediatric Gastroenterology and Nutrition. RESULTS: Of 148 CD patients, 18 (12%) had 21 neurological disorders that could not be attributed to any other condition including muscle abnormality (3), epilepsy (3), psychiatric disease (4), peripheral neuropathy (3), cerebrovascular disease (1), myelopathy (1) and Down syndrome (2). Other disorders probably unrelated to CD were present in 8 patients. CONCLUSION: If this association is not coincidental, both the central and the peripheral nervous systems may be affected in CD by a spectrum of neurological disorders that are either the outcome of CD or share the same pathogenesis with the enteropathy.

Adolescent↗
PubMed2004

Chronic intracranial hypertension with unexplained cerebrospinal fluid pleocytosis.

In a retrospective review of all cases with a diagnosis of idiopathic intracranial hypertension in two academic departments of neurology over a nine-year period, the authors identified six patients with a clinical course typical of idiopathic intracranial hypertension (IIH) except for the finding of cerebrospinal fluid pleocytosis. There were five women and one man with a mean age at presentation of 25.7 years (range, 25-32 yr). All were obese but had no other associated medical conditions or identifiable risk factors for IIH. In five patients, all or most cerebrospinal fluid cells were lymphocytes. Cerebrospinal fluid pleocytosis persisted for several months in all patients. Patients underwent a thorough laboratory and neuroimaging evaluation that did not reveal a primary cause. Medical treatment directed solely at lowering intracranial pressure was effective in five patients; one patient required lumboperitoneal shunting. Ophthalmic manifestations of increased intracranial pressure stabilized or remitted after treatment was withdrawn with a mean follow-up period of 33 months (range, 14-55 mo). Some patients may present with idiopathic chronic meningitis and elevated intracranial pressure that responds to treatment used for IIH.

Acetazolamide↗
PubMed2003

Transgenic mouse with the herpes simplex virus type 1 latency-associated gene: expression and function of the transgene.

During herpes simplex virus type 1 (HSV-1) latent infection in human peripheral sensory ganglia, the major viral gene transcribed is the latency-associated transcript (LAT) gene. In order to facilitate the study of this gene, we generated a transgenic mouse that contains the DNA fragment that transcribes the LAT RNAs (2.0 kb and its 1.5-kb spliced transcript) under control of the cytomegalovirus promoter. The tissue distribution of these transcripts and their effects upon HSV-1 replication, latency, and reactivation in the transgenic-mouse model were examined. Different steady-state amounts of both transcripts were found in various tissues. While the highest levels of the 2.0-kb RNA were detected in heart and skeletal muscle, the 1.5-kb transcript was found at elevated levels in the brain and at much higher levels in the trigeminal ganglia (TG). Replication of both the wild-type and a LAT-negative mutant virus was suppressed in primary embryonic fibroblasts obtained from LAT-expressing transgenic mice compared to that in cells obtained from normal mice. HSV-1 DNA amounts in latently infected TG of transgenic mice were similar to those in normal mice. Reactivation of latent HSV-1 LAT-negative mutants by explant cocultivation of TG from transgenic mice was more efficient than reactivation from normal-mouse TG. Considering our present and previous results, we propose that the significantly higher steady-state level of the 1.5-kb RNA in the TG may link this transcript to latency functions and that by inhibition of virus replication, the LAT gene may protect ganglion cells and thereby increase the probability of reactivation.

Animals↗