PubMed HealthSearch

Biomedical subjects

S Haahr

Publications and source records attributed to S Haahr.

At least 19 recordsLinked to original sources

[Disseminated sclerosis and retrovirus].

Multiple sclerosis is a disease characterized by neurologic dysfunction due to focal CNS lesions with demyelination. The cause of the disease is unknown; but it may be due to a virus and/or autoimmune reactions. The latter cause is suspected on account of family- and ethnical studies, the first on account of locally produced antibodies in the cerebrospinal fluid, and also epidemiologic investigations. The newly discovered human retroviruses, especially HTLV-I which is the cause of tropical spastic paraparesis, has been suspected as a possible cause; but this has been disproved by multiple antibody- and PCR-studies. An uncharacterized exogenous or an endogenous retrovirus is still considered to be a possible cause or possibly partial cause of the disease which could be multifactorial.

Autoimmune Diseases

Is multiple sclerosis caused by a dual infection with retrovirus and Epstein-Barr virus?

Although the etiology of multiple sclerosis is as yet unknown, epidemiological observations strongly point toward one or more infectious agent(s) being involved in the disease. In recent years some studies have indicated involvement of retrovirus in multiple sclerosis (MS). However, an intrafamilial epidemiological study revealed that MS and the known human retroviruses had a divergent epidemiology. Some studies have shown the association of Epstein-Barr virus (EBV) with MS and one recent study revealed dual infection by retrovirus and EBV in a cell line established from a patient with an MS-like disease. Our hypothesis for the development of MS and MS-like diseases is that a hitherto uncharacterized retrovirus is the etiological agent, but development of neurologic disease is related to or even dependent on a delayed EBV infection. The dual infection hypothesis is analyzed and found to be consistent with the epidemiological characteristics of MS.

Cluster Analysis

Multiple sclerosis as a retroviral disease? Epidemiological considerations in relation to HTLV-I epidemiology.

The intrafamilial epidemiology of multiple sclerosis was compared with the known intrafamilial epidemiology of infections with HTLV-I. Infections with this retrovirus most often have a subclinical course, but can cause leukemia or a neurological disease resembling multiple sclerosis. Through the Danish Multiple Sclerosis Registry, information was obtained on 79 parent-child cases of multiple sclerosis, and in 55 cases further information was obtained through questionnaires. The study did not reveal any common intrafamilial pattern of MS and HTLV-I infections. It can be concluded that if multiple sclerosis is associated with a specific 'MS virus', it is hardly one with the same epidemiology as HTLV-I, maybe because MS could be a multifactorial disease only developing if various factors coincide in the same person.

Denmark

Search for a retrovirus in long-term cultured cerebrospinal fluid cells and peripheral blood mononuclear cells from patients with multiple sclerosis.

Long-term peripheral blood mononuclear cell (MNC) cultures stimulated with interleukin 2 (IL-2) or IL-2 + phytohemagglutinin were established from 33 multiple sclerosis (MS) patients, 9 with other neurological diseases (OND), and 24 normal controls (C). Cultures were analysed for growth characteristics, reverse transcriptase (RT) in the culture medium, 2'-5' oligoadenylate synthetase in the cells, and cell morphology. None of these parameters differed in the MS group compared with the OND and C groups. Furthermore, 11 cerebrospinal fluid cell cultures were established without feeder cells. Morphology studies of the cells and RT assays of the supernatants from these cultures were normal. Induction studies by dexamethasone and 2-bromo-5'-deoxyuridine in 2 of these cultures did not reveal any signs of a virus. The significance of these results for the retrovirus hypothesis is discussed.

Adult

Tubuloreticular inclusions in skin biopsies from patients with HIV infection.

Skin biopsies obtained from apparently normal skin from 15 HIV infected patients and 6 anti-HIV negative patients were examined by electron microscopy. Tubuloreticular inclusions (TRI) were detected within the cytoplasm of capillary endothelial cells in 5/5 AIDS patients and in 2/5 patients with AIDS related conditions. Biopsies from 5 asymptomatic HIV positive patients and the 6 control subjects were without ultrastructural alterations. The occurrence of TRI was related to low numbers of CD 4+ lymphocytes. 5/7 patients with TRI had elevated serum interferon activity, and in all of the patients without TRI, interferon activity was below detection level. The occurrence of TRI was not dependent on the presence of free p24 antigen in serum. It is concluded that the occurrence of TRI in entothelial cells of skin capillaries is associated with late stages of HIV infection and this may indicate a generalization of this change.

Acquired Immunodeficiency Syndrome

The phagocytic activity of monocytes and polymorphonuclear leucocytes against viral antigens as measured by chemiluminescence in patients with multiple sclerosis.

Twenty-two patients with Multiple Sclerosis in different stages of the disease were investigated in a chemiluminescence-assay and compared with a similar number of healthy individuals. The reactivity of peripheral blood monocytes to different viral antigens was followed by measurement of both the immediate oxidative activity and the development of activity through a 85-minutes period. The patients with a progressive course of the disease showed a high activity and reached maximum activity in a shorter time than the other groups, indicating an activation of the monocytes in these patients.--The patients in steady state showed a rather low activity, compared with both the other patient groups and the control group. A possible significance of these findings is discussed. The activity of the polymorphonuclear cells did not show differences in activity between the groups.

Adult

MS and the group-specific component.

Sera from 95 MS patients and 227 control persons were examined by IEF to determine the Gc genotype. There was no correlation between MS and the distribution of Gc genotype (0.70 less than P less than 0.80) nor Gc alleles (0.80 less than P less than 0.90) although such a correlation is generally accepted on the basis of a smaller material. Furthermore, Gc correlated with neither disease course nor with the age of disease onset.

Alleles

The influence of human allergic encephalitogenic peptide on cell-mediated cytotoxicity reactions in patients with multiple sclerosis.

Multiple sclerosis patients and normal control persons were assayed for cell-mediated cytotoxicity against target cells coated with human allergic encephalitogenic peptide. Coating of different types of target cells resulted in increased cytotoxicity, most clearly seen against homologous lymphocytes and virus-infected fibroblasts. Both patients and controls showed reactivity against coated targets. A possible role for this type of reaction in the pathogenesis of multiple sclerosis is proposed.

Adult

Interferon induction, 2'-5' oligo A synthetase and lymphocyte subpopulations in out-patients with multiple sclerosis in a longitudinal study.

Nine patients with multiple sclerosis, four with relapsing-remitting disease, and five with chronic progressive disease, together with eight healthy control, were followed for nearly a year with monthly clinical and laboratory examinations. Alpha- and gamma-interferon was induced in lymphocytes with different viruses and PHA, no differences were found between healthy controls and multiple sclerosis patients. The alpha- and gamma-interferon induced enzyme 2'-5' oligo A synthetase in lymphocytes was found to have a tendency to be lower in multiple sclerosis patients than in healthy controls. When medians of ratios of helper/suppressor blood lymphocytes in multiple sclerosis patients were compared with healthy controls, the same results were found, although higher values of ratios were found among the patients and the highest value was found in a patient with chronic progressive disease. No correlation to disease activity could be found in interferon inductions, 2'-5' oligo A synthetase concentrations and ratios of OKT4/OKT8. In particular no change in ratio was found in relation to five exacerbations taking place in the four multiple sclerosis patients with acute relapses.

2',5'-Oligoadenylate Synthetase

Late-onset rubella syndrome: coexistence of immune complex disease and defective cytotoxic effector cell function.

We studied a classical case of late-onset rubella syndrome characterized by multi-organ disease and persistence of live rubella virus in spite of high titres of specific antirubella antibodies and presence of large amounts of circulating immune complexes. When first studied at the age of 5 months there was a low proportion of T8+ lymphocytes. Functional studies revealed decreased activity of K and NK cells as well as alloreactive direct cytotoxic cells (CTL). Removal of cell-bound immunoglobulin and immune complexes tended to improve K and NK cell function in vitro. Plasma exchange transfusions carried out at 9 months of age resulted in clinical improvement. Normalization of cytotoxic effector cell functions and cessation of viremia accompanied recovery from active disease. The results indicate that defective cytotoxic effector cell function is the primary cause for the defective virus elimination in this syndrome.

Antibodies, Viral

Cell-mediated and humoral immune responses to herpes simplex virus and cytomegalovirus in renal transplant patients.

Cell-mediated immunity to herpes simplex virus and cytomegalovirus, using the lymphocyte transformation test and interferon induction in lymphocytes, was studied in 59 patients from 1 day to 7 years after allotransplantation and compared with the results in normal subjects. Both parameters were permanently depressed with regard to cytomegalovirus. With herpes simplex virus, interferon production was also permanently depressed, whereas the transformation reaction was normal during the first year after transplantation and only slightly depressed in patients more than 1 year after transplantation. In 6 patients the above-mentioned assays and the complement fixation reaction were performed serially and related to the clinical signs of herpes simplex virus and cytomegalovirus infection. The relationship between depression of the transformation reaction and interferon production in lymphocytes and the occurrence of clinically evident herpes simplex virus and cytomegalovirus infections was, however, equivocal. The humoral immune response to herpes simplex virus was measured by the complement fixation test and the more sensitive antibody-dependent, cell-mediated cytotoxicity reaction, and a good correlation was found between these two tests, although only a few persons were found to be negative in the antibody-dependent, cell-mediated cytotoxicity reaction. The suggestion is made that only a few adults are "true" herpes simplex virus seronegative.

Adolescent

Pleural effusion disease in rabbits. Interferon in body fluids and tissues after experimental infection.

The distribution of interferon in body fluids and tissues was studied in 18 rabbits infected experimentally with the agent of pleural effusion disease (PED). Circulating interferon of the classical type was demonstrable 12 h after inoculation, and a maximum response was attained 2-3 days later. Circulating interferon disappeared between 6 and 8 days after inoculation. Interferon titres of serum were closely correlated with the early phase of febrile response and probably also with the initial growth phase of the PED agent. The interferon titres of pleural fluid exceeded by far the titres of other body fluids and tissues. No interferon could be demonstrated in brain, liver and urine.

Animals