Just another dubious virus in cells from a patient with multiple sclerosis?
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Adult↗
Biomedical subjects
S Haahr
Publications and source records attributed to S Haahr.
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↗
[New knowledge on the pathogenesis of multiple sclerosis].
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Humans↗
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↗
[Virus as the cause of disseminated sclerosis?].
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Antibodies, Viral↗
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↗
X-linked resistance of mice to high doses of herpes simplex virus type 2 correlates with early interferon production.
Mice inoculated intraperitoneally with herpes simplex virus type 2 develop focal necrotizing hepatitis and eventually die from ascending myelitis and encephalitis. The genetics of resistance to the infection were analyzed in crosses between resistant C57BL/10 mice and susceptible BALB/c mice. It was shown that the resistance of C57BL/10 mice to hepatitis induction was influenced by an X-linked dominant gene as previously shown for the GR mouse strain. The course of infection in the liver pointed to early, natural defense mechanisms as being responsible for the difference between the mouse strains, whereas the clearance of virus from the liver, probably mediated by specific immunity, was exerted at the same time and with equal efficiency for all groups of mice. In mortality experiments, resistance was shown to be an autointerference phenomenon in that a considerable number of C57BL/10 mice survived an intraperitoneal injection of 10(6) PFU, whereas all mice were killed by 10(5) PFU. This resistance of C57BL/10 mice to high doses of HSV-2 was retrieved in all groups of F1 mice in crosses between C57BL/10 and BALB/c mice except the (BALB/c female X C57 male) male group, in which the mice receive the X chromosome from the susceptible BALB/c female. Thus, the autointerference phenomenon also seems to be influenced by loci on the X chromosome. A similar pattern of inheritance was observed when early interferon induction (4 to 5 h after infection) in response to HSV-2 was measured. The possible relevance of this early interferon response in conjunction with other potential natural defense mechanisms is discussed.
Animals↗
Hodgkin's disease: in vitro susceptibility of skin fibroblasts to infection with virus and to lysis by autologous lymphocytes.
Fibroblast cultures established from the skin of 16 untreated stage 1 and stage 2 Hodgkin's patients (HD) and 60 healthy controls were studied in their 3rd, 4th and 5th in vitro passage. HD cultures were similar to control cultures with respect to transformation with Simian sarcoma virus (SSV) and SV40 and with respect to interferon release. HD cultures, however, showed a depressed replication of both herpes simplex virus (HSV) type 1 and type 2. Preliminary evidence for enhanced immune interaction with fibroblasts in HD was a more frequent injury of HD than control fibroblast cultures when incubated 4 hours with autologous mononuclear leucocytes in the presence of autologous serum.
Adolescent↗
Immunological parameters in multiple sclerosis patients with special reference to the herpes virus group.
A group of multiple sclerosis (MS) patients (n = 50), most of them in a stable or slightly progressive phase was studied together with a group of neurological control (NC) patients with CNS lesions (n = 38) comparable in age and disability and an age matched group of healthy persons (n = 46). On stimulation of lymphocytes with herpes simplex virus (HSV), cytomegalovirus (CMV) and varicella zoster virus (VZV) a significantly lower interferon production was found in MS patients compared with the NC patients and the healthy controls; when the NC patients were compared with the healthy controls a significantly lower production was also found. The lymphocyte transformation reaction in seropositive MS patients was significantly lower than that seen in the seropositive control groups when HSV was used as antigen. Lower responses, although insignificant, were found when CMV and VZV were used as antigens. There were no differences among the three groups when Con A was used as mitogen in three different concentrations. Likewise spontaneous lymphocyte transformations were equal. The lower interferon production and the lower transformation reactions in MS patients could not be correlated to age, duration of disease, disability, disease activity or impairment. No significant differences in humoral immunity to HSV, CMV and VZV were found in the three groups, a few MS patients were 'true' seronegative to HSV type 1 and 2. Suppressor cell activity induced by Con A and measles virus was comparable in the three groups, although a few MS patients in an active relapsing phase were found to have low suppressor cell activity. Natural killer cell activity against two different cell lines was found equal in the three groups, and there was no difference in the potentiating effect of interferon.
Adult↗
The influence of general anesthesia and surgery on cell-mediated cytotoxicity and interferon production.
The effect on cell-mediated cytotoxicity of surgery and anesthesia for removal of a primary malignant melanoma was studied in 47 patients. The cytotoxic ability of peripheral blood lymphocytes has been investigated using 2 melanoma cell lines or 2 leukemia cell lines as target cells, with or without addition of interferon or specific antibodies. The cytotoxic ability was clearly reduced in all assays 1 day after the operation. After 6 days about half the patients were totally restored; others showed increase in cytotoxicity without reaching the initial values, whereas one fourth of the patients were still heavily depressed with only a small or no increase at all. The number of macrophages in the effector cell population was followed, and the ability to produce interferon on stimulation with viral or melanoma antigens was investigated, as alterations in these parameters could influence cytotoxicity. There were no fluctuations in these parameters.
Anesthesia, General↗
Severe acquired immunodeficiency in European homosexual men.
Four previously healthy Danish homosexual men developed Kaposi's sarcoma or opportunistic infections with fever of unknown origin and lymphadenopathy. One patient died of a Pneumocystis carinii pneumonia. Three patients had defective cell-mediated immunity with absent leucocyte interferon production and decreased proliferative response to mitogens and antigens. T lymphocyte helper subsets and natural killer cell activity were reduced. Unstimulated mononuclear cells produced leucocyte migration inhibitor factor. Two patients were sexual partners and three had never been to the USA, where cases of severe acquired immunodeficiency have been reported. Thus, the syndrome must also be suspected in European homosexual men who present with fever of unknown origin, opportunistic infections, or Kaposi's sarcoma.
Adult↗
Interferon production, cellular and humoral immunity in splenectomized patients.
Undetectable levels of circulating interferon were found in 35 splenectomized patients and in 14 controls. In addition, no differences in virus, purified protein derivative (PPD), and phytohaemagglutinin (PHA) induced interferon production were observed between the patients and the controls. Virus induced lymphocyte transformation tended to be reduced after splenectomy, but only the herpes simplex virus (HSV) induced transformation index was significantly reduced in splenectomized patients without residual splenic tissue (P less than 0.05). In contrast, the PHA lymphocyte transformation was unchanged in patients and controls. The number of natural viral antibodies in splenectomized patients did not differ from that of controls. Furthermore, there were no major differences in the magnitude of the titers of the sero-positive cases between the various groups. Thus, splenectomy does not interfere with interferon production in vitro, and as seen from natural viral antibodies, no impairment of humoral immunity was observed. The reduced HSV lymphocyte transformation may indicate an impaired lymphocyte function after splenectomy.
Adolescent↗
Interferon in rabbit sera after inoculation with Treponema pallidum suspensions contaminated with PED virus.
Paired rabbits sera were examined for the presence of interferon and pathogenicity for rabbits. The sera were obtained before and 48 hours after inoculation with Treponema pallidum suspensions of rabbit origin in 12 selected laboratories. Classical interferon, detectable in dilutions from 1/9 to 1/81, were found in 27 out of 39 postinoculation sera from which the pleural effusion disease (PED) virus was isolated. Serum interferon was not detectable in dilutions greater than or equal to 1/9 in 16 virus-negative postinoculation sera or in any of the 55 preinoculation sera. Interferon was found more often in sera from which highly virulent strains of PED virus were isolated than in sera from which strains of low virulence were isolated. The serum interferon assay provides useful presumptive evidence of contamination of rabbit-passaged treponemes with PED virus, but the assay is least useful when PED virus is present subclinically.
Animals↗