Just another dubious virus in cells from a patient with multiple sclerosis?
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Adult↗
Biomedical subjects
A Møller-Larsen
Publications and source records attributed to A Møller-Larsen.
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↗
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↗
Prognostic value of serial determinations of circulating immune complex levels in malignant melanoma.
A total of 50 melanoma patients free of distant metastatic disease and 54 healthy controls were analyzed for circulating immune complexes (cIC) and complement split product (C3d), using solid-phase Clq-anti-IgG radioimmunoassay (RIA), Clq-protein A RIA, and anti-C3d anti-IgG RIA for cIC detection. No significant differences in cIC and C3d levels could be demonstrated between the controls and the 31 patients with primary malignant melanoma analyzed before surgery. To evaluate the prognostic value of serial measurements, samples from the 50 patients were taken at regular intervals for 4 to 27 months (median, 20 months). Surgery was the only treatment given. Significant changes in the cIC and C3d levels were defined by reference to the changes that occurred in 23 of the 54 healthy controls observed for a period of 6 to 55 months (median, 23 months). During the period of serial sampling, recurrent disease developed in 8 of the patients. In only 3 of these 8 patients (versus 10 of 42 patients without recurrence) did significant changes occur, and the changes occurred either at the same time or after the clinical diagnosis of recurrence. During the entire clinical observation period of 6 years, a total of 11 patients developed recurrences. Significant changes were only observed in 4 of these 11 patients versus 8 of 37 patients without recurrence. In conclusion, changes in cIC and/or C3d levels were not found to be indicative of early or long-term recurrence of malignant melanoma.
Adolescent↗
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↗
Antibodies against herpes simplex virus in a group of healthy humans without reactions to herpes simplex virus antigens in blasttransformation assays.
22 healthy individuals with different reactions in humoral and cell-mediated immunity to herpes simplex virus (HSV), as found in complement-fixation, neutralization, and blasttransformation assays have been further investigated using antibody-dependent cell-mediated immunity (ADCC) as a serological test. Sera from all individuals were absorbed on HSV-infected, varicella zoster virus (VZV)-infected or uninfected cell monolayers, before they were used in ADCC with HSV-infected cells, as target. The results with absorbed sera were compared with the results from unabsorbed sera. Fresh uninactivated sera have also been used in some of the investigations. By these experiments a group of individuals was found, who were HSV-positive in ADCC, but negative in all other, above-mentioned tests. Because of these reactions they are proposed to be HSV-positives without a latent infection.
Adult↗
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↗
Cellular and humoral immunity in Hodgkin's disease. I Patients in continuous long-term remission.
Cell-mediated and humoral immunity to herpes simplex virus (HSV), cytomegalovirus (CMV) and varicella zoster virus (VZV) were examined in 37 patients with Hodgkin's disease in continuous long term remission. This group had lower blast-transformation than a matched control group to all 3 antigens. Patients originally showing B-symptoms had higher transformation to VZV than those with A-symptoms. Patients treated with irradiation only had higher transformation than those treated with either chemotherapy or a combination of chemotherapy and irradiation. There was a clear tendency towards lower transformation in patients having been in remission for 2 years or less. Phytohaemagglutinin (PHA) stimulation gave lower response in the patient group than in the control group. Patients with B-symptoms had lower response than those with A-symptoms. Interferon production was specially impaired in patients with B-symptoms. The patient group had higher CF titers against HSV and CMV while the control group had higher titers against VZV. B-symptom patients had higher titers against VZV than A-symptom patients. It is concluded that HD patients have impaired immune function many years after discontinuation of therapy, but there are certain differences regarding the in vitro immunity within the patient groups.
Antibody Formation↗
Cell-mediated and humoral immunity to herpesviruses during and after herpes zoster infections.
The influence of herpes zoster virus infection on cell-mediated and humoral immunity to varicella-zoster virus (VZV), cytomegalovirus, and herpes simplex virus (HSV) was followed in 17 zoster patients from the first week to 6 months after start of eruptions. The clinical responses were registered and correlated to the immune responses. A significant depression in blast transformation on stimulation of lymphocytes with all three antigens was found on days 1 to 5 compared with transformations later after zoster eruptions and compared with controls. Phytohemagglutinin exhibited the same stimulation in the different groups and controls. No significant differences in interferon production in the various groups and controls were found on stimulation with the VZV and HSV antigens. All zoster patients became seropositive by complement fixation to VZV a few days after start of the zoster eruption. Two zoster patients showed a fourfold rise in complement fixation antibodies to HSV. Three patients had changes in complement fixation titers to cytomegalovirus, which could indicate new infection or reactivation of infection with this virus. A significant lower transformation index to VZV was found during the first 9 days in zoster patients with fever compared with patients without fever. The relevance of this observation is discussed in relation to a previous similar observation from our group.
Adult↗
The effect of interferon on lymphocyte-mediated effector cell functions: selective enhancement of natural killer cells.
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Animals↗
Cell-mediated cytotoxicity during vaccinia virus revaccination in man: influence of antibodies and interferon.
Seven healthy human adults were revaccinated with vaccinia virus. Cell-mediated cytotoxicity to vaccinia virus-infected fibroblasts was investigated on the day of vaccination and on days with peak activity. Three donors were studied until day 30 after vaccination. The addition of interferon to cytotoxicity reactions resulted in an increase in killing. This increase was not seen when antibodies were added. When a mixture of lymphocytes from a revaccinated and a non-revaccinated donor was used as effector cells, the killing observed corresponded to the killing seen with lymphocytes from the revaccinated donor, when tested alone. This finding indicates that no antibodies or other soluble mediators capable of increasing cytotoxicity are released from the lymphocytes during the cytotoxicity assay.
Adult↗
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↗
Cellular immunity in herpes simplex and cytomegalovirus infections in renal allograft recipients.
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Adult↗
Humoral and cell-mediated immune responses in humans before and after revaccination with vaccinia virus.
Twenty-six healthy males vaccinated 15 to 18 years ago with vaccinia virus were revaccinated. Blood samples were collected before vaccination and 3 weeks after. The lymphocytes were tested in a blast transformation assay with vaccinia antigen and phytohemagglutinin, and interferon production was measured. The sera were subjected to neutralization and antibody-dependent cell-mediated cytotoxicity (ADCC) tests. All results were compared with clinical responses. The only test showing immunity in all donors before vaccination was the ADCC. The other tests showed a very limited residual immunity or no immunity at all. After revaccination, immunity reactions were found in all tests in most of the donors. None of the tests made before vaccination could be used to predict clinical reactions. The ADCC is recommended as a sensitive serological test.
Adult↗