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S Poser

Publications and source records attributed to S Poser.

At least 91 records · Page 5Linked to original sources
PubMed1997

S-100 protein concentration in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease.

We evaluated S-100 levels in paired cerebrospinal fluid (CSF) and serum samples in a group of 135 patients referred to the German Creutzfeldt-Jakob disease (CJD) surveillance unit from June 1993 to May 1995. The patients were seen in a prospective case control study. The diagnosis of probable CJD during life was made in any patient presenting with rapidly progressive dementia of less than 2 years' duration, typical periodic sharp wave complexes (PSWCs) in the EEG and at least two of the following findings: myoclonus, visual/or cerebellar symptoms, pyramidal and/or extrapyramidal signs and/or akinetic mutism. Patients presenting with the above clinical signs and symptoms but without PSWCs were classified as possible, while those with a dementia of a duration exceeding 2 years and without PSWCs were classified as other. S-100 was determined in paired CSF and serum samples by a commercially available enzyme-linked immunosorbent assay. In a group of 76 patients with definite and probable CJD, S-100 concentration (median 25 ng/ml, range 2-117) in CSF was significantly higher (P < 0.0001) than in 32 patients diagnosed as other (median 4 ng/ml, range 1-19). Serum levels of S-100 were below 0.5 ng/ml in all groups. At a cut-off of 8 ng/ml an optimum sensitivity of 84.2% with a specificity of 90.6% for the diagnosis of CJD by the determination of S-100 in CSF is obtained. S-100 levels exceeding 8 ng/ml in CSF support the diagnosis of CJD in any patient presenting with rapidly progressive dementia.

Adult↗
PubMed1996

Diagnosis of Creutzfeldt-Jakob disease by two-dimensional gel electrophoresis of cerebrospinal fluid.

BACKGROUND: The diagnosis of Creutzfeldt-Jakob disease (CJD) is based on clinical and electroencephalographic criteria which do not allow a reliable diagnosis to be made during life. METHODS: Serum and cerebrospinal fluid (CSF) samples were obtained after informed consent from relatives of suspected cases of CJD referred to the German CJD surveillance unit. CSF samples from 58 definite (neuropathologically verified), 46 probable, and 34 possible CJD cases, and from 44 patients without CJD were analysed by two-dimensional gel electrophoresis (2-DE). Two investigators blinded to clinical findings recorded the presence of two proteins, p130/131. The kappa value for the level of agreement between these investigators was calculated. Results obtained were compared with the determination of neuron-specific enolase (NSE) in CSF. NSE concentrations of more than 35 ng/mL were considered indicative of CJD. FINDINGS: p130/131 was detected in 81% of definite (47/58), 80% of probable (37/46), 68% of possible (23/34) CJD cases, and in none of the other 44 cases. NSE concentrations of more than 35 ng/mL were seen in 79% of definite (46/58), 80% of probable (37/46), 59% of possible (20/34) CJD cases, and 9% of other cases (4/43). The positive predictive value for 2-DE of CSF is 100% and the negative predictive value is 69%. The level of agreement for the detection of p130/131 by two evaluators in a subset of 141 2-DE gels was a kappa of 0.93 (95% CI 0.86-0.99). Of 13 cases initially classified as possible and later reclassified as definite, ten cases were identified correctly by the 2-DE analysis, indicating a better diagnostic accuracy of this test compared with the current clinical classification. None of nine cases classified as other by neuropathology had p130/131 in 2-DE. INTERPRETATION: 2-DE for p130/131 is a specific test for the diagnosis of CJD. These data suggest including detection of p130/131 as a criterion for the diagnosis of probable CJD in addition to the currently accepted criteria of a rapidly progressive dementia of less than 2 years duration, typical neurological signs, and periodic sharp-wave complexes in the EEG.

Adult↗
PubMed1996

A new variant of Creutzfeldt-Jakob disease in the UK.

BACKGROUND: Epidemiological surveillance of Creutzfeldt-Jakob disease (CJD) was reinstituted in the UK in 1990 to identify any changes in the occurrence of this disease after the epidemic of bovine spongiform encephalopathy (BSE) in cattle. METHODS: Case ascertainment of CJD was mostly by direct referral from neurologists and neuropathologists. Death certificates on which CJD was mentioned were also obtained. Clinical details were obtained for all referred cases, and information on potential risk factors for CJD was obtained by a standard questionnaire administered to patients' relatives. Neuropathological examination was carried out on approximately 70% of suspect cases. Epidemiological studies of CJD using similar methodology to the UK study have been carried out in France, Germany, Italy, and the Netherlands between 1993 and 1995. FINDINGS: Ten cases of CJD have been identified in the UK in recent months with a new neuropathological profile. Other consistent features that are unusual include the young age of the cases, clinical findings, and the absence of the electroencephalogram features typical for CJD. Similar cases have not been identified in other countries in the European surveillance system. INTERPRETATION: These cases appear to represent a new variant of CJD, which may be unique to the UK. This raises the possibility that they are causally linked to BSE. Although this may be the most plausible explanation for this cluster of cases, a link with BSE cannot be confirmed on the basis of this evidence alone. It is essential to obtain further information on the current and past clinical and neuropathological profiles of CJD in the UK and elsewhere.

Adolescent↗
PubMed1996

Accuracy and reliability of periodic sharp wave complexes in Creutzfeldt-Jakob disease.

OBJECTIVE: To assess the sensitivity, specificity, and interobserver reliability of periodic sharp wave complexes in the electroencephalograms of patients with Creutzfeldt-Jakob disease. DESIGN: Sixty-eight electroencephalograms in 29 patients who had been suspected of having Creutzfeldt-Jakob disease were reanalyzed by an investigator who was unaware of the clinical data. The incidence of periodic sharp wave complexes in neuropathologically confirmed Creutzfeldt-Jakob disease vs progressive dementia other than Creutzfeldt-Jakob disease was assessed. Blinded electroencephalogram analysis was performed by a second investigator. The interobserver reliability was assessed by the kappa value. SETTING: University hospital, base of the German National Creutzfeldt-Jakob Disease Surveillance Study. PATIENTS: Fifteen patients with neuropathologically confirmed Creutzfeldt-Jakob disease and 14 patients who had been suspected of having Creutzfeldt-Jakob disease because of rapidly progressive dementia but in whom other dementias were diagnosed by unblinded investigators based on clinical and electroencephalographic criteria. MAIN OUTCOME MEASURE: Sensitivity and specificity of periodic sharp wave complexes assessed by their incidence in Creutzfeldt-Jakob disease vs other dementias. Interobserver reliability of periodic sharp wave complexes was expressed by the kappa value. RESULTS: For periodic sharp wave complexes, blinded electroencephalographic analysis resulted in a sensitivity and a specificity of 67% and 86%, respectively. Interobserver reliability was excellent (kappa = 0.95). CONCLUSION: This blinded electroencephalographic study in Creutzfeldt-Jakob disease confirms the high diagnostic value of electroencephalography, as previously reported by open studies.

Aged↗
PubMed1996

Apolipoprotein E phenotype frequency and cerebrospinal fluid concentration are not associated with Creutzfeldt-Jakob disease.

OBJECTIVE: To analyze the distribution of apolipoprotein E (Apo E) phenotypes between patients with Creutzfeldt-Jakob disease (CJD) and control subjects. SETTING: University hospital, base of the German National CJD Surveillance Study. DESIGN: Prospective case-control study. SUBJECTS: Sixty-two patients with definite or probable CJD, 90 patients with initial suspected CJO, and 51 controls matched for age, sex, and place of residence. MAIN OUTCOME MEASURES: Phenotyping of Apo E in serum by isoelectric focusing, assessment of the gels by 3 independent investigators, measurement of of Apo E in cerebrospinal fluid using an enzyme-linked immunosorbent assay, and calculation of Kaplan-Meier cumulative survival plots. RESULTS: The most frequent phenotype was E 3-3 with 56% in patients and 59% in controls, followed by E 3-4 with a frequency of 29% vs 25%, respectively. The phenotype E 3-2 was much rarer (13% vs 16%, respectively). Patients with definite CJD had a mean (SD) Apo E concentration of 3.4 (2.0) mg/L; patients with probable CJD, 3.1 (1.6) mg/L; patients with possible CJD, 3.8 (2.2) mg/L; and subjects with other diseases, 3.0 (1.7) mg/L. Mean (SD) disease duration for patients with E 3-2 was 11.8 (9.8) months; for patients with E 3-3, 12.0 (9.02) months; and for patients with E 3-4, 14.2 (12.3) months. CONCLUSIONS: We found no significant difference in the distribution of Apo E phenotypes between patients with CJD and controls. The concentration of Apo E in cerebrospinal fluid cannot be taken as a biochemical marker for the disease. The Apo E phenotype had no influence on the duration of CJD. Our data do not support an association of Apo E4 with either the duration or time at onset of CJD.

Adult↗
PubMed1996

Pentoxifylline, a phosphodiesterase inhibitor, induces immune deviation in patients with multiple sclerosis.

The outcome of immune responses can be predicted by the lymphokine production pattern of the participating cells. Cytokines of the T helper type 1 (Th1) cells mediate inflammatory responses and delayed-type hypersensitivity (DTH), whereas Th2-like T cells predominantly produce cytokines, which stimulate antibody production by B cells. Immunoregulatory therapy of autoimmune diseases with unknown antigens may be achieved by inhibiting the production of inflammatory cytokines and induction of protective cytokines of Th2-like T cells. To determine the immunoregulatory capacity of the phosphodiesterase inhibitor pentoxifylline (PTX), which is known to suppress the production of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), this drug was used in mitogen and antigen-stimulated lymphocyte cultures as well as in patients with multiple sclerosis. PTX significantly decreased TNF-alpha and interleukin-12 (IL-12), whereas it increased IL-4 and IL-10 production. In addition, PTX inhibited cell proliferation, which was associated with a marked reduction in CD25 (IL-2 receptor alpha-chain) and CD54 (intercellular adhesion molecule-1; ICAM-1) expression. Increasing doses of PTX significantly reduced TNF-alpha and IL-12 mRNA expression of blood mononuclear cells, but increased IL-4 and IL-10 expression in eight patients with relapsing-remitting multiple sclerosis. These results indicate that PTX modulates immune reactions favouring a Th2-like response and may therefore be useful for the treatment of autoimmune diseases with a dominant Th1-like T cell response.

Autoimmune Diseases↗
PubMed1996

Induction of CRE-mediated gene expression by stimuli that generate long-lasting LTP in area CA1 of the hippocampus.

Gene expression regulated by the cAMP response element (CRE) has been implicated in synaptic plasticity and long-term memory. It has been proposed that CRE-mediated gene expression is stimulated by signals that induce long-term potentiation (LTP). To test this hypothesis, we made mice transgenic for a CRE-regulated reporter construct. We focused on long-lasting long-term potentiation (L-LTP), because it depends on cAMP-dependent protein kinase activity (PKA) and de novo gene expression. CRE-mediated gene expression was markedly increased after L-LTP, but not after decremental UP (D-LTP). Furthermore, inhibitors of PKA blocked L-LTP and associated increases in CRE-mediated gene expression. These data demonstrate that the signaling required for the generation of L-LTP but not D-LTP is sufficient to stimulate CRE-mediated transcription in the hippocampus.

Animals↗
PubMed1996

MR imaging of Creutzfeldt-Jakob disease.

PURPOSE: To describe the magnetic resonance (MR) imaging appearance of Creutzfeldt-Jakob disease (CJD). MATERIALS AND METHODS: MR images obtained in 29 patients who died of CJD (aged 53-77 years at death) were retrospectively reviewed by three neuroradiologists blinded to the diagnosis. RESULTS: Moderate to marked bilateral, symmetrically increased signal intensity was demonstrated in the putamen and caudate nucleus on T2- and proton-density-weighted MR images in 23 patients (79%). In six patients (21%), images showed no major signal intensity abnormalities. T1-weighted images revealed no signal intensity abnormalities and no contrast material enhancement. The degree of atrophy in the cortex and basal ganglia corresponded to the time between onset of symptoms and MR imaging. All patients with a disease duration of longer than 4 months had substantial volume loss. CONCLUSION: Although approximately 20% of the patients did not have MR imaging abnormalities, MR imaging did show signal intensity alterations due to gliosis and spongiform changes early in the course of CJD in the remaining 80%. The demonstration of bilateral areas of increased signal intensity that predominantly affected the caudate nuclei and the putamina on long-repetition-time MR images in an elderly patient with rapidly progressive dementia represents a specific finding and clearly should suggest the diagnosis of CJD.

Aged↗
PubMed1995

Prion disease associated with a novel nine octapeptide repeat insertion in the PRNP gene.

Some cases of spongiform encephalopathies are linked to mutations within the prion protein gene (PRNP). Repetitive octapeptide insertions of variable length in the PRNP gene are also associated with spongiform encephalopathies, mostly familial Creutzfeldt-Jakob disease (CJD). In this study we report on a novel insertion mutation comprising nine extra octapeptide repeats between codons 51 and 91 of the PRNP gene. The affected patient showed a slowly progressive dementia of at least 6 years duration and ataxia.

Adult↗
PubMed1995

Cerebrospinal fluid concentration of neuron-specific enolase in diagnosis of Creutzfeldt-Jakob disease.

Neuron-specific enolase (NSE) is among the biochemical markers in cerebrospinal fluid reported to be useful in the differential diagnosis of Creutzfeldt-Jakob disease from other dementing illnesses. In a group of 58 patients with definite and probable Creutzfeldt-Jakob disease, NSE concentrations (median 94.0, interquartile range 256 ng/mL) were significantly higher (p < 0.001) than in 26 control patients (9.5, 15.5 ng/mL). At a cut-off of 35 ng/mL an optimum sensitivity of 80% with a specificity of 92% for the diagnosis of Creutzfeldt-Jakob disease by NSE in cerebrospinal fluid was obtained.

Aged↗
PubMed1995

Tumor necrosis factor-alpha messenger RNA expression in patients with relapsing-remitting multiple sclerosis is associated with disease activity.

We determined the cytokine messenger RNA (mRNA) expression pattern of blood mononuclear cells in 29 patients with relapsing-remitting multiple sclerosis every 4 weeks over a period of 12 months. During this period 27 relapses occurred in 14 patients (48%). Progression of disease activity as assessed by the occurrence of new lesions on nonenhancing T2-weighted magnetic resonance images of the head was detected in 12 (48%) of 25 patients. Using a semiquantitative polymerase chain reaction we demonstrated significant increases in tumor necrosis factor-alpha mRNA expression in peripheral blood mononuclear cells prior to a relapse. In 24 (85%) of 27 relapses increased tumor necrosis factor-alpha mRNA expression preceded clinical symptoms by 4 weeks. A similar pattern was observed for lymphotoxin mRNA expression. At the same time, transforming growth factor-beta and interleukin-10 mRNA levels declined. Fluctuations in the mRNA expression of tumor necrosis factor-alpha were also observed in 6 patients with stable disease who had active magnetic resonance scans on follow-up. No correlation of disease activity was observed with interleukin-1 beta, -4, or -6, inferferon gamma or endothelin-1 mRNA expression. From these data it can be concluded that variations in cytokine mRNA expression in blood mononuclear cells are correlated with disease activity in relapsing-remitting multiple sclerosis. It may be a valuable parameter to monitor the immunological status of patients in future clinical trials.

Adult↗
PubMed1995

Monocyte/macrophage differentiation in early multiple sclerosis lesions.

Monocyte/macrophage differentiation was studied in biopsy samples of multiple sclerosis (MS) lesions obtained in the early course of the disease. Macrophages were identified by immunocytochemistry using a panel of antibodies recognizing different macrophage-activation antigens. The number of cells stained with each antibody was related to the demyelinating activity of the lesions as detected by the presence of myelin degradation products. The pan-macrophage marker Ki-M1P revealed the highest numbers of macrophages in early and late active lesions. Lower numbers were encountered in inactive, demyelinated, or remyelinated lesions. The acute stage inflammatory macrophage markers MRP14 and 27E10 were expressed in either only early active (MRP14) or early and late active (27E10) lesions, thus allowing the identification of actively demyelinating lesions. The chronic stage inflammatory macrophage marker 25F9, in contrast, showed increasing expression with decreasing lesional activity. These findings indicate a differentiated pattern of macrophage activation in MS lesions and allow the staging of demyelinating lesions in routinely fixed and paraffin-embedded tissue.

Adolescent↗
PubMed1994

Oligodendrocytes in the early course of multiple sclerosis.

The neuropathology of demyelinating lesions in multiple sclerosis was studied in specimens obtained by diagnostic needle biopsy during early stages of the disease. The lesions were characterized by a chronic inflammatory reaction dominated by lymphocytes and macrophages, plaque-like demyelination, and astroglial sclerosis. Oligodendrocytes within the lesions were studied by immunocytochemistry using antibodies against various myelin and oligodendroglia components. The expression of messenger RNA for proteolipid protein was determined by in situ hybridization. Our studies revealed that myelin-oligodendrocyte glycoprotein is a sensitive and reliable marker for identification of oligodendrocytes in demyelinated plaques. The results suggest that in the early course of the disease in some patients, oligodendrocytes may largely be preserved, whereas in others oligodendroglial loss is pronounced. Loss of oligodendrocytes was only marginally related to the stage of demyelinating activity within the lesions. These findings indicate that the pathogenesis of demyelination may vary within different multiple sclerosis patients.

Adolescent↗
PubMed1994

Acute diffuse leukoencephalitis in HIV-1 infection.

The clinical, neuroradiological, and cerebrospinal fluid findings of a case with acute diffuse leukoencephalitis, a demyelinating disease associated with human immunodeficiency virus infection of the brain, is reported. The patient presented with acute tetraparesis as the primary manifestation of a previously symptom free HIV infection. Cerebrospinal fluid analysis showed enhanced inflammatory abnormalities with high concentrations of P24 antigen. MRI showed diffuse white matter hyper-intensities in both hemispheres. In the follow up over 22 months, the neurological deficits disappeared after antiretroviral treatment in good correlation with improvements in MRI as well as in inflammatory cerebrospinal fluid abnormalities.

AIDS Dementia Complex↗
PubMed1994

Cytokine mRNA levels in mononuclear blood cells from patients with multiple sclerosis.

We determined the cytokine messenger RNA (mRNA) expression pattern of blood mononuclear cells in 45 patients with the relapsing-remitting form of MS and 32 patients with other neurologic diseases. Using a semiquantitative polymerase chain reaction method, we detected significantly higher levels of tumor necrosis factor-alpha and lymphotoxin mRNA in patients with relapsing compared to those with stable disease (p < 0.001), but transforming growth factor-beta and interleukin-10 mRNA expressions were higher in patients with stable disease.

Cytokines↗