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Biomedical subjects

S Poser

Publications and source records attributed to S Poser.

At least 37 records · Page 2Linked to original sources

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

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

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

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

[Early retirement and occupational rehabilitation of patients with multiple sclerosis].

Statistical data are set out describing the situation of persons with multiple sclerosis (MS) relative to early pensioning and vocational rehabilitation. Findings show that MS gives rise to extraordinarily early pensioning, also when compared to other conditions. From 1980-1990, a total of 14,811 persons with MS were pensioned prematurely; average age at the time, in 1990, was 44.2 years for men and 41.1 years for women with MS. The number of temporary disability pensions has been decreasing since 1985. Vocational rehabilitation (VR) services are relatively rarely provided in MS; in 1990, a total of 626 rehabilitees with MS were registered at the Federal Employment Institute. The majority of VR benefits provided to persons with MS concentrated on mobility allowances to facilitate placement or continued employment. Concluding, the findings are discussed, also touching on the possibilities for persons with MS being paid greater attention concerning VR service provision.

Adult

Differential diagnosis of HTLV-I-associated myelopathy and multiple sclerosis in Iranian patients.

Two Iranian patients with chronic progressive spastic paraparesis and urinary dysfunction were referred to our hospital with the presumptive diagnosis of multiple sclerosis (MS). Routine CSF analysis and magnetic resonance imaging of the two patients were only partially characteristic of MS. Testing for antibodies to human T-cell leukemia virus type I [HTLV-I] in serum using a radioimmune precipitation assay revealed antibodies to HTLV-I in both patients. The infection with HTLV-I was confirmed by polymerase chain reaction (PCR) and liquid hybridization analysis using primers to the tax/rex region and a corresponding probe, demonstrating proviral DNA in peripheral blood mononuclear cells of both patients. On the basis of these findings demonstrating the presence of proviral HTLV-I DNA in the two Iranian patients, the initial diagnosis of MS was corrected to that of HTLV-I-associated myelopathy (HAM). In contrast, several patients with definite MS (nine from Germany, two from Iran) with a relapsing and remitting form of the disease were tested for HTLV-I infection by enzyme-linked immunosorbent assay and PCR, which yielded negative results. However, the mother of one HAM patient was found to be infected with HTLV-I. To support an association between HTLV-I infection and CNS disease in the two HAM patients, we analyzed the production of specific IgG antibodies within the CNS based on a simple enzyme immunoassay for viral IgG antibodies in CSF and serum. In the two HAM patients there was significant intrathecal antibody production directed against HTLV-I, but this was not found in any of the samples from MS patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Deltaretrovirus Antibodies

Mortality in patients with dependence on prescription drugs.

In 1974 we started a follow-up of patients with different psychoactive substance use disorders (PSUD) according to DSM-III; 2082 cases out of 2127 were analyzed; 1370 patients had taken legal drugs (i.e. prescription drugs and/or over-the-counter drugs); 444 patients suffered from abuse or dependence of legal drugs alone; 678 combined legal drugs and ethanol, and 248 cases combined legal and illegal drugs, often together with ethanol. A group of 712 alcoholics were included for comparison. Mean time under observation was 6.5 +/- 5.4 years, and 269 patients died. Mortality and survival were calculated and compared with expected survival from the normal population of the former Federal Republic of Germany. Mortality in all subgroups of PSUD was increased, the standardized mortality ratio (SMR) for patients on legal drugs alone being 2.1. Patients with legal plus illegal drugs had a SMR as high as 20.7; those with legal drugs plus ethanol 3.4; and alcoholics 4.2. The increased mortality seemed to be constant over the years. Mortality decreased in patients with stable abstinence. There was no clear sex difference. Abuse had a better prognosis than dependence. An estimation of potential life lost by the different PSUDs was attempted. Patients on legal drugs died from suicides, malignancies or accidents (including intoxication). In alcoholics or patients on legal drugs plus ethanol malignoma, liver cirrhosis, accident and suicide were the most prominent causes of death.

Adult

Early prognostic factors for disability in multiple sclerosis, a European multicenter study.

The effects of initial clinical variables on short-term prognosis are analyzed in a cross-sectional study of 574 multiple sclerosis patients from 7 centers in 5 European countries. Patients with a primary progressive course had a 2.3 higher mean disability score (EDSS) than the primary remittent group after a mean duration of disease of 6.6 years. High age at onset was associated with a primary progressive course, and was also related to increased risk of a rapid shift to a secondary progressive course. Among the remittent patients without a secondary progressive course a high age at onset was significantly correlated to a higher disability score. In the whole remittent group the presence of pyramidal and cerebellar symptoms at onset predicted both a high disability score and a rapid shift to a secondary progression, while the effect was reverse for sensory and visual symptoms. No difference between the sexes was found.

Adult

Acute demyelinating disease. Classification and non-invasive diagnosis.

Five young patients are described with biopsy-proven acute demyelinating disease. Two cases are classified as Schilder's disease, a particular childhood form of multiple sclerosis (MS) with atypical clinical manifestation, normal or atypical CSF-findings and large bilateral lesions in magnetic resonance imaging (MRI). Two further cases presented with a fulminant bout of MS with typical clinical picture and CSF-findings; they are classified as Marburg's disease. The last case was an acute second bout of classical MS. The biopsy seemed to be justified in 4 cases, but unnecessary in the last case. Localized proton magnetic resonance spectroscopy (MRS) performed in one case allowed us to examine the focal cerebral abnormalities directly and non-invasively. The spectra revealed a pattern typical of acute demyelination suggesting potential for a replacement of biopsy in the future.

Adult

The use of recombinant antigens in ELISA procedures for the quantification of intrathecally produced HIV-1-specific antibodies.

An ELISA procedure is described for the quantification of intrathecally synthesized immunoglobulin G antibodies to human immunodeficiency virus (HIV) antigens. Recombinant p17, p24, endonuclease (END), reverse transcriptase (RT), a peptide from the transmembrane region of gp41 (ENV80) and a fusion protein containing HIV-1 and HIV-2 epitopes were compared with a commercially available ELISA. Using a reference serum, antibodies in serum and cerebrospinal fluid (CSF) to all of the antigens could be measured quantitatively in a reliable and reproducible fashion. Despite the fact that the titer varied up to 10(5)-fold between CSF and serum, interassay variability ranged from 3.87% for p17 to 8.41% for RT and intra-assay variability varied from 3.9% +/- 1.2% for p17 to 14.3% +/- 3.9% for the commercial ELISA. Antibody specificity indices (ASI) obtained by relating CSF/serum titers with reference to the corresponding IgG concentrations can be used to detect intrathecal synthesis of virus specific antibodies.

Enzyme-Linked Immunosorbent Assay

Impact of magnetic resonance imaging (MRI) on the epidemiology of MS.

The availability of MRI has turned out to have less impact on the epidemiology of MS than originally expected. Only 3/69 patients diagnosed between 1986 and 1990 in the epidemiologic area of South Lower Saxony (Germany) would have been missed without MRI. However in 18/50 patients the diagnostic classification changed, mostly from possible to probable MS. As we included possible cases from the beginning of our studies, the overall figures remain essentially unchanged. Epidemiologists who excluded possible cases from their surveys may experience more problems with the introduction of MRI.

Brain

Analysis of oligoclonal antibody bands against individual HIV structural proteins in the CSF of patients infected with HIV.

Intrathecal antibody responses to HIV were investigated by a highly sensitive immunoblot assay. Serum and CSF specimens were tested for reactivity with the recombinant HIV gag proteins p15, p17 and p24 and with the recombinant transmembrane protein p41. Autochthonous production of virus-specific IgG to one or more HIV structural proteins was seen in 8 of 10 asymptomatic seropositive subjects, in 3 of 4 men with AIDS-related complex, and in 9 of 13 patients with AIDS. These results were consonant with an elevated CSF/serum antibody ratio to total HIV antigen. The high frequency of local HIV-specific antibody synthesis in seropositive individuals without related clinical symptoms indicates an early involvement of the CNS in HIV infections.

Acquired Immunodeficiency Syndrome

Survival in multiple sclerosis.

Survival from onset of symptoms was calculated for two series of MS patients, a population-based epidemiologic series from southern Lower Saxony of 224 cases, and a revised hospital series of 1429 cases from 11 neurologic centers throughout the Federal Republic of Germany. Median survival for the epidemiologic series was 35-42 years, with no finer estimate possible. Observed survival was 3/5 expected survival after 35 years of illness. Survival in this series was similar to that from two other population-based reports. No significant difference was found between the sexes, though patients with onset at age 35 + had a significantly shorter survival than those with onset at age under 35 years. The much larger hospital series, where median survival was 30 years, demonstrated significant differences separately favoring females and young onsets. However, the ratios of observed to expected survival from population life tables were strikingly similar among all four subgroups defined by sex and age at onset. While overall there is a substantial reduction in the expectation of life in MS, the differential survival by sex and age appears to be a reflection of the expected survival by sex and age per se, and not that of the disease.

Adult