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Biomedical subjects

I Steiner

Publications and source records attributed to I Steiner.

At least 73 records · Page 4Linked to original sources

Serum Cu/Zn superoxide dismutase activity is reduced in sporadic amyotrophic lateral sclerosis patients.

Accumulated evidence implies that mutations in the gene coding for Cu/Zn superoxide dismutase (SOD) are associated with the pathogenesis of the familial form of amyotrophic lateral sclerosis (ALS). The clinical and pathological similarities of the familial and the sporadic forms of the disease may suggest that abnormal SOD activity takes also part in the pathogenesis of sporadic ALS. We therefore measured serum SOD activity in fifteen sporadic ALS patients. Mean serum SOD activity was 1.15 +/- 0.40 u/ml in ALS patients, 1.50 +/- 0.45 u/ml. in patients with other neurological disorders and 1.45 +/- 0.45 u/ml in.healthy controls (p < 0.021 and p < 0.031 respectively). If this sporadic ALS-related reduction in serum SOD activity will be confirmed in the diseased nervous system tissue, it may suggest that abnormal SOD activity is also associated with the motor neuron damage in the sporadic form of ALS.

Adult↗

Human herpes viruses latent infection in the nervous system.

The neurotropic herpes viruses, HSV-1, HSV-2 and VZV, colonize and establish latent infection in human peripheral sensory ganglia. Recurrent diseases due to reactivation of these viral pathogens can take place despite an effective immune response. Molecular, cellular, physiological and immune mechanisms work in concert to enable the establishment of latency, the maintenance of the latent state for the entire life of the host, and the reactivation infection. Although all three viruses belong to the same family and establish latent infection in the same tissue, the clinical pattern of their reactivation is quite different. This review covers current knowledge of the basis of these infections, and offers a theory explaining the basis of HSV-1 latent infection and the differences of the disorders caused by HSV-1 and VZV reactivation in humans.

Animals↗

Expression and splicing of the latency-associated transcripts of herpes simplex virus type 1 in neuronal and non-neuronal cell lines.

Herpes simplex virus type 1 (HSV-1) is transcriptionally active during latent infection in human peripheral sensory ganglia. This transcription has been linked to the ability of the virus to reactivate, but its potential gene products and mechanisms of action are unknown. To analyze the viral latency-related transcripts in neuronal and non-neuronal cell lines in an isolated cellular system, a 10.4 kb DNA fragment, which covers the entire viral transcriptionally active latency-associated region, was cloned under control of the constitutive cytomegalovirus promoter (pNM3). During transient transfection of a human embryonic kidney 293 cell line, pNM3 expressed high levels of the 2.0 kb latency-associated transcript (LAT) that was not polyadenylated. The 1.5 kb LAT as well as the minor hybridizing RNAs could not be identified by Northern blotting analysis. pNM3 expression was further analyzed following transfection of two neuronal, C1300 and ND7 cell lines. The 2.0 kb LAT was synthesized at high levels in these cell lines. The 1.5 kb LAT, which in vivo can be identified only during HSV-1 latent infection in tissues which facilitate reactivation, was present at very low amounts in 293 and C1300 cells using reverse transcription PCR analysis. Higher amounts of the 1.5 kb LAT were produced in ND7 cells, a neuronal cell line shown to possess neuronal-specific splicing proteins. However, the 1.5 kb LAT was present in ND7 cells in lesser amounts than produced during latent infection in peripheral sensory ganglia. This novel cellular system provides now a tool for future studies of the role of the 1.5 kb and the 2.0 kb LATs in HSV-1 latency.

Base Sequence↗

Neurologic aspects of inflammatory bowel disease.

UNLABELLED: To determine the frequency, spectrum, and clinical features of neurologic disorders associated with ulcerative colitis (UC) and Crohn's disease (CD). BACKGROUND: Extraintestinal manifestations of inflammatory bowel disease (IBD) are well documented, but the association of IBD with neurologic involvement is rare and often controversial. METHODS: Tertiary care center ambulatory and hospital services data bank retrospective computerized search with subsequent file review. PATIENTS: From among 638 IBD patients diagnosed from 1981 to 1991, we identified 10 CD patients and nine UC patients with neurologic involvement unrelated to a defined systemic or iatrogenic cause. Neurologic disorders diagnosed 15 or more years before the intestinal symptomatology were excluded. RESULTS: Three percent of IBD patients had neurologic involvement. In 14 of 19 (74%), it started within a mean of 5.7 years (range, 0.7 to 12 years) after the diagnosis of bowel disease, and in two of 19 (10%) it occurred at the time of IBD exacerbation. During the course of IBD, 10 of 19 patients (53%) exhibited other extraintestinal manifestations. Peripheral nerve disorders were observed in six UC patients. Myelopathy (5 patients), myopathy (3), and myasthenia gravis (1) were diagnosed in eight CD patients and one UC patient. Cerebrovascular disorders occurred in two UC and two CD patients. CONCLUSIONS: Neurologic disorders associated with IBD are more common than appreciated and follow a different pattern of involvement in UC and CD. A prospective study is required to define the nature of this association.

Adult↗

Herpes simplex virus latent infection in the nervous system.

Herpes simplex virus (HSV) establishes a latent infection in the human peripheral nervous system and can cause recurrent disease by reactivation. Intensive effort has been directed in recent years to unveil the molecular, cellular and immune mechanisms, as well as the virus-host interactions associated with latent HSV infection. The aim of this review is to summarize current knowledge regarding the site of latent infection, the molecular phenomena of latency, and the mechanisms of the various stages of HSV-1 latent infection in the nervous system, relating them where possible to the human situation. Specifically, the following biological questions are addressed: (1) How does this lytic virus survive in the nervous system and why can it establish a lifelong latent infection in nerve cells? (2) What advantage is conferred on HSV by establishing latent infection in nervous tissue? (3) What can be gathered from the accumulated knowledge on latency about the pathogenesis of herpes simplex encephalitis?

Gene Expression Regulation, Viral↗

[Endoluminal grafts in the therapy of aneurysms of the abdominal aorta. Experimental results].

In 1991 a new method of treatment of aneurysms of the abdominal aorta was published. The method is based on bridging the sac of the aneurysm by an endoluminal graft. The graft is a stent provided with a special vascular prosthesis. The endoprosthesis is inserted by means of a catheter from arteriotomy of the common femoral artery. The objective of the submitted work was to test the possibility to use a polyester covered spiral Z stent in the treatment of aneurysms of the abdominal aorta. For experiments six dogs were used weighing 12-18 kg. In the experimental animals an artificial aneurysm of the abdominal aorta was induced. Then the authors interposed surgically into the subrenal section of the abdominal aorta a special polyester knitted prosthesis imitating the shape of the aneurysm. Two weeks after surgery angiography of the abdominal aorta was performed. After angiography the authors introduced from arteriotomy of the superficial femoral artery an endoluminal graft into the artificial aneurysm. The graft bridged the aneurysm on the inside and this led to thrombosis of the sac of the aneurysm. The state of the graft and aneurysm was checked sonographically and angiographically. The graft was successfully used in all experimental animals. Angiographic check-up examinations revealed that application of the graft led to immediate exclusion of the sac of the aneurysm. In two experimental animals the graft was inserted in an excessively cranial position. It did not bridge the aneurysm throughout its length. Reflux of blood in the distal part persisted and filled the residual cavity of the sac of the aneurysm.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Herpes simplex virus type 1 gene expression and reactivation of latent infection in the central nervous system.

Restricted gene expression takes place during latent infection of herpes simplex virus type 1 (HSV-1) in the human peripheral nervous system and has been linked with viral reactivation. The state of HSV-1 gene expression in the central nervous system (CNS) during latency is unclear and we, therefore, examined gene expression in the brainstem of experimental mice and normal humans. Only part of the transcription pattern present during latent infection in peripheral sensory ganglia (PSG) was identified in the human brainstem by in situ hybridization and Northern blot analysis for HSV-1-specific transcripts. Instead of three HSV-1 latency-associated transcripts (LATs) present in PSG and demonstrated by Northern blot analysis, only one was identified in mouse brainstem and none was detected in human brainstem. These findings might be attributed to the relatively low amounts of HSV-1-specific latency-associated RNAs in brainstem tissue. Combined with our inability to reactivate HSV-1 from explanted mouse brainstem, these findings suggest that tissue levels of latency-associated gene expression play a role in HSV-1 reactivation and have relevance to the very low incidence of HSV-1-induced CNS disease compared with peripheral mucocutaneous disease.

Animals↗

A molecular and cellular model to explain the differences in reactivation from latency by herpes simplex and varicella-zoster viruses.

There are marked similarities in the biological properties of the human neurotropic herpesviruses herpes simplex virus type 1 (HSV-1) and varicella-zoster virus (VZV), including their ability to establish lifelong latent infections in human peripheral sensory ganglia (PSG). Despite this, their patterns of reactivation are quite different: HSV-1 reactivations occur many times during a lifetime, they are localized to the cutaneous distribution of a single sensory nerve, they are not associated with sensory symptomatology and their frequency decreases with age. VZV recurrence on the other hand is usually a single event which tends to appear with advancing age, its cutaneous eruption involves an entire dermatome and is usually extremely painful. To help explain these differences, we have formulated a model based on current knowledge of the molecular and cellular basis of latent infection in the nervous system. We suggest that the amount of latent viral DNA and RNA in the latently infected tissue (higher with HSV-1), the cellular location of latent virus (neuronal in HSV-1, probably non-neuronal in VZV), the presence or absence of viral replication in the PSG during reactivation together with the host immune response, are all key determinants of the clinical expression of viral reactivation.

DNA, Viral↗

Evidence for intrathecal synthesis of autoantibodies in systemic lupus erythematosus with neurological involvement.

The diagnosis of systemic lupus erythematosus (SLE) in a patient who presents with isolated central nervous system (CNS) abnormalities, is a difficult clinical challenge. The pathogenesis of such CNS involvement in SLE is unknown. Twelve patients with active SLE were examined for serum and cerebrospinal fluid (CSF) autoantibodies and compared with 21 patients with headache. Four of six patients with SLE and active CNS presentation had CSF autoantibodies while none of the other SLE patients and the controls had autoantibodies. We describe these four patients in whom immunological work-up revealed CSF antinuclear, anti-DNA, anti-SSA/Ro, anti-SSB/La and antineuronal autoantibodies. A newly devised antibody activity index provided means to demonstrate that the CSF autoantibodies in these patients were produced intrathecally. Beyond the importance of our finding of the potential role of autoantibodies in the pathogenesis of CNS damage in SLE, we propose that CSF analysis for autoantibodies should become an essential part of the diagnostic work-up in autoimmune diseases with CNS involvement.

Adolescent↗

[Infectious endocarditis--a study of 153 cases].

The study describes 153 necropsy cases of infective endocarditis (IE) encountered in a university hospital over a period of 23 years (1970-1992), with necropsy incidence of 0.63%. The average age of patients at the time of death was 51.7 years. Both the incidence and the average age tended to increase during the period studied. The location of infective vegetations was mostly in the left heart and univalvular (mitral in 41%, aortic in 33%). The mitral valves involved by IE were otherwise normal in 62%; the aortic valves were normal in 33%. The spectrum of microorganisms yielded by postmortem cultivations is compared with that obtained by blood cultures during life. Staphylococcus aureus comprised 60% of all positive clinical blood cultures and 40% of all organisms grown postmortally. Gram-negative bacilli, streptococci and mycoses appeared as further important etiologic agents. Discussed in more detail are the subgroups of tricuspid valve IE (5% of all cases), IE in patients on chronic hemodialysis (17%), and IE involving prosthetic valves (9%).

Adolescent↗