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Biomedical subjects

S Kam-Hansen

Publications and source records attributed to S Kam-Hansen.

At least 19 recordsLinked to original sources

Cell cycle-dependent expression of CD4 antigen in a monocytoid cell line.

The CD4 molecule has several biological functions, physiologically as a receptor for major histocompatibility complex class II molecules on antigen-presenting cells, and pathologically as a receptor for human immunodeficiency virus (HIV) by its binding to the HIV envelope glycoprotein gp 120. The frequency of CD4+ cells has been shown to correlate positively with both susceptibility and cytopathogenic effect by HIV. To determine if CD4 expression varied during the cell cycle, a CD4-expressing monocytoid cell line, U 937 clone 16, was synchronized with regard to cell growth. The CD4 antigen was analysed with regard to expression, density and rate of reappearance after treatment with trypsin, during the different phases of the cell cycle. The CD4 reappearance rate was found to be maximal during the S phase. This was followed by an increased expression and density in the late S/G2 phase. Thus a cell cycle-dependent expression of CD4 molecules on the cell surface was observed.

CD4 Antigens↗

Bone marrow cells in patients with multiple sclerosis.

Bone marrow cells from patients with multiple sclerosis (MS) were studied regarding proliferative capacity with and without mitogenic stimulation, immunohistochemical characterization of cellular phenotypes with monoclonal antibodies and morphology and compared to bone marrow cells from healthy individuals undergoing elective orthopaedic surgery. MS patients' bone marrow mononuclear cells (BM-MNC) showed higher spontaneous proliferation both in comparison with BM-MNC from controls and peripheral blood mononuclear cells (PBL) from MS patients. Phytohaemagglutinin (PHA) response was higher in MS BM-MNC than BM-MNC from controls. MS patients' BM-MNC proliferated more on interleukin-2 (IL-2) stimulation than their corresponding PBL. There was no significant difference in proliferative response of PBL between MS patients and controls. Higher levels of undifferentiated or activated cells, as measured by OKT10, were found in peripheral blood of patients with MS. Seven of 11 MS patients showed morphological signs of activation in their bone marrow. The results indicate a role for immune reactions in bone marrow in the pathogenesis of multiple sclerosis, a disease with symptoms and signs strictly confined to the central nervous system.

Adult↗

Primarily chronic progressive and relapsing/remitting multiple sclerosis: two immunogenetically distinct disease entities.

HLA class II gene polymorphism was investigated in 100 patients with clinically definite multiple sclerosis (MS) by restriction fragment length polymorphism analysis of Taq I-digested DNA using DRB, DQA, and DQB cDNA probes. Twenty-six patients had primarily chronic progressive MS and 74 had relapsing/remitting MS. The latter group included patients with a secondary progressive evolution of symptoms. Both clinical forms of MS were found to be associated with the DRw15,DQw6 haplotype. In addition, primarily chronic progressive MS was positively associated with the DQB1 restriction fragment pattern seen in DR4,DQw8, DR7,DQw9, and DRw8, DQw4 haplotypes, as well as negatively associated with the Taq I DQB1 allelic pattern corresponding to the serological specificity DQw7. Relapsing/remitting MS was positively associated with the DQB1 allelic pattern observed in the DRw17,DQw2 haplotype. These three DQB1 alleles are in strong negative linkage disequilibria with DRw15. The two susceptibility markers of each clinical form of MS act additively in determining the genetic susceptibility, as the relative risks for individuals carrying both markers roughly equal the sum of respective risks. Different alleles of the DQB1 locus defined by restriction fragment length polymorphisms contribute to susceptibility and resistance to primarily chronic progressive MS as well as to susceptibility to relapsing/remitting MS. The observed immunogenetic heterogeneity between the different clinical forms of MS favors the hypothesis that primarily chronic progressive MS and relapsing/remitting MS are two distinct disease entities.

Alleles↗

Estradiol potentiates poke-weed mitogen-induced B cell stimulation in multiple sclerosis and healthy subjects.

Female preponderance in many diseases suggested with autoimmune pathogenesis, multiple sclerosis (MS) being classified as one of them, indicates a role for hormonal factors such as estrogen in disease development. To bypass monthly hormonal fluctuations in females, we evaluated in male patients with MS and male blood donors the effect of 17-beta-estradiol on numbers of IgG, IgA and IgM producing cells in cultures of peripheral blood lymphocytes. While estradiol alone had no effect, estradiol in combination with poke-weed mitogen (PWM) yielded in both groups higher numbers of IgG and IgA producing cells when compared with numbers obtained by PWM stimulation alone, indicating an additory effect of estradiol to that of PWM on B cell maturation. This effect was less pronounced in MS than in blood donors, especially for IgG producing cells, probably reflecting higher B cell activation in vivo taking place in MS. On the contrary, cells producing IgG, IgA and IgM antibodies against myelin, myelin basic protein and measles virus were not detectable after stimulation with PWM, nor with PWM and estradiol. Estradiol can in many patients with MS and in blood donors be considered a potent co-activator of B cells in presence of B cell stimulating factor in the form of PWM.

Adult↗

Retrovirus in multiple sclerosis.

Presence of cytopathic effect and enzyme reverse transcriptase in cultures of peripheral blood mononuclear cells is described in 2 of 15 patients with multiple sclerosis and none of healthy controls. These findings might indicate: the presence of a new human retrovirus in these individuals, despite the low detection rate, and the shortcomings inherent in methodology used for detection of known human retroviruses in the study of new groups of diseases, such as those with possible autoimmune background.

Adult↗

Chronic progressive myelopathy associated with HTLV-I: oligoclonal IgG and anti-HTLV-I IgG antibodies in cerebrospinal fluid and serum.

Among 22 patients with human T-lymphotropic virus type I (HTLV-I)-associated chronic progressive myelopathy, agarose isoelectric focusing (AIF) revealed oligoclonal IgG bands in 21: in 3 in CSF only; in 11 in CSF and to some extent in serum; and in 7, identical patterns in CSF and serum. By immunoblot after AIF of CSF and serum, we observed bands of anti-HTLV-I IgG antibodies in 19 patients: in 5 in CSF only; in 9 in CSF and partly in serum; and in 5, identical in CSF and serum. Oligoclonal anti-HTLV-I IgG antibody bands could only partly be traced to oligoclonal IgG bands. If, prior to AIF, serum and CSF were absorbed with HTLV-I antigen, practically all oligoclonal HTLV-I-specific IgG antibody activity was abolished, while the oligoclonal pattern of total IgG was affected only to a minor extent. Alongside with HTLV-I-specific oligoclonal B cell response, HTLV-I myelopathy is regularly accompanied by production of oligoclonal IgG of unknown antibody specificities.

Adult↗

Tumor necrosis factor alpha in cerebrospinal fluid during bacterial, but not viral, meningitis. Evaluation in murine model infections and in patients.

To evaluate the potential role of cachectin/TNF-alpha in the pathogenesis of bacterial and viral meningitis, concentrations and kinetics of TNF-alpha were determined in cerebrospinal fluid (CSF). After intracerebral, but not systemic, infection with Listeria monocytogenes in mice, TNF-alpha was detected as early as 3 h after infection reaching maximum titers after 24 h. However, TNF-alpha was not found in serum during the course of Listeria infection. In contrast to bacterial meningitis, no TNF-alpha was detected at any time in CSF of mice suffering from severe lymphocytic choriomeningitis induced by intracerebral infection with lymphocytic choriomeningitis virus. This difference is striking since both model infections led to a massive infiltration of polymorphonuclear and mononuclear leukocytes into the meninges and CSF. The results found for the two model infections were paralleled by findings in humans; CSF from three out of three patients with bacterial meningitis examined during the first day of hospitalization showed significant levels of TNF-alpha; none of the CSF obtained later than 3 d after hospitalization was positive. In addition, similarly to what was found in mice with viral meningitis, zero out of seven patients with viral meningitis had detectable TNF-alpha in CSF.

Adolescent↗

Increased reactivity to HTLV-I in inflammatory nervous system diseases.

The presence of IgG antibodies reacting with purified and disrupted human T-lymphotropic virus type I (HTLV-I) was examined by an indirect enzyme-linked immunosorbent assay (ELISA) in sera from 49 patients with multiple sclerosis (MS), 21 patients with aseptic meningoencephalitis (AM), 12 patients with Guillain-Barré syndrome (GB), and 30 patients with tension headache (TH). This was also assessed in the concentrated cerebrospinal fluid (CSF) of most of these patients, as well as in sera of 60 blood donors (BD). Standardized amounts of serum IgG and CSF IgG were used in ELISA. For sera, higher reactivity with HTLV-I was found in all four patient groups compared with the BD group, but no significant differences were observed among the four groups. There was higher reactivity with HTLV-I in the CSF of patients with MS, AM, and GB compared to findings in patients with TH. Ten serum (2 MS, 3 GB, 3 TH, 2 BD) and 3 CSF (1 MS, 1 GB, 1 TH) specimens considered positive by ELISA for HTLV-I were found negative on confirmatory Western blot analysis. We extended this study to analyze the in vitro production of anti-HTLV-I-IgG antibodies by the 24-hour cultivation of unstimulated lymphocytes from peripheral blood and CSF of 6 additional patients with MS directly in HTLV-I antigen-coated wells of microtiter plates. This was followed by determination of specific antibodies by ELISA in the same wells. No antibody production was measurable. Our data do not favor the hypothesis of an HTLV-I-related human retrovirus in the etiology of MS.

Adolescent↗

Asymptomatic oligoclonal CSF IgG and progressive increase of intrathecal IgG synthesis in a patient with myasthenia gravis treated with thymectomy--a 4-years follow-up.

A young woman is described who had myasthenia gravis which was favourably influenced by thymectomy. Although there was no evidence for another neurological disease over 7.5 years of clinical observation and computed tomography as well as visual evoked response were normal, CSF studies over 0.5 years prior to and 3.5 years after thymectomy revealed persistent mononuclear pleocytosis, high CSF IgG index, oligoclonal IgG bands in CSF, and increasing IgG synthesis rate within the CNS, reflecting a continuous local humoral immune response. CSF/serum ratios of antibodies to acetylcholine receptors (AChR) were continuously lower than CSF/serum IgG ratios, contradicting intrathecal AChR antibody production. Proportion of total T cells was slightly higher in CSF than peripheral blood, while active T cells were lower in CSF. CSF lymphocytes did not proliferate on PHA stimulation but responded in allogeneic mixed lymphocyte culture. B cells were 4% in CSF and 4.5% in peripheral blood, but 227 IgG, 0 IgA and 0 IgM producing cells were detected among 20 X 10(3) CSF lymphocytes, compared to 5, 4 and 0 in 20 X 10(3) peripheral blood lymphocytes. This patient represents an in vivo 'experiment' regarding influence of thymectomy on CSF compartment constituents. The present study also shows that an individual can be clinically healthy despite continuous and pronounced intrathecal immune response.

Adult↗

Cerebrospinal fluid lymphocytes from patients with multiple sclerosis do not increase immunoglobulin or measles antibody production after stimulation with pokeweed mitogen.

Cerebrospinal fluid lymphocytes (CSF-L) and peripheral blood lymphocytes (PBL) from patients with multiple sclerosis (MS) and acute aseptic meningoencephalitis (AM) were cultured without and in the presence of pokeweed mitogen (PWM), a polyclonal B cell activator. IgG, IgA and IgM as well as measles IgG antibody production was measured in 7-day-culture supernatants by enzyme-linked immunosorbent assay. MS CSF-L did not respond with increased Ig production after PWM stimulation, in contrast to AM CSF-L which responded to PWM with a modest increase of production of all 3 Ig classes, especially IgG. PBL responded to PWM with a pronounced production of IgG, IgA and especially IgM, showing no difference between MS, AM and healthy controls. CSF-L from only 1 of 7 patients with MS showed increased measles IgG antibody production after PWM stimulation. The poor response of MS CSF-L might be due to maximal activation of B lymphocytes in vivo, thereby limiting further Ig production after stimulation in vitro.

Adult↗

Production of specific antibodies by cerebrospinal fluid lymphocytes in patients with herpes zoster, mumps meningitis and herpes simplex virus encephalitis.

We applied a new method consisting of short-term culture (18 h) of lymphocytes from cerebrospinal fluid (CSF-L) and peripheral blood (PBL) in viral antigen-coated ELISA plates and subsequent measurement of IgG and IgM antibodies bound to antigen. Utilizing mumps virus, herpes simplex virus (HSV), varicella zoster virus (VZV), and measles virus as antigens, we demonstrated production by CSF-L of antibodies against the aetiological agent only in all patients with mumps meningitis and HSV encephalitis and also in all patients with herpes zoster without central nervous system (CNS) symptoms. This might be considered as direct evidence that specific antibodies are produced within the CNS in inflammatory nervous system diseases. CSF-L usually produced higher amounts of antibodies than the corresponding number of PBL. In comparison with concentrations of free antibodies determined in parallel, our method had higher specificity and sensitivity and gave more precise information about the antibody response in infections of the nervous system.

Antibodies, Viral↗

IgM, IgA and IgG producing cells in cerebrospinal fluid and peripheral blood in multiple sclerosis.

The protein A plaque assay was used to enumerate IgM, IgA and IgG producing cells per 20 X 10(3) lymphocytes in cerebrospinal fluid (CSF) and peripheral blood (PB) from 37 patients with multiple sclerosis (MS) and in PB from healthy controls. Fifty-seven percent of the MS patients displayed in CSF cells producing IgM, 70% IgA and 89% IgG. IgM or IgA producing cells predominated in CSF from 10 patients, IgG in 27. Immunoglobulin producing cells were often present when the corresponding CSF Ig index was normal, confirming that enumeration of Ig producing cells is a more sensitive variable of the intrathecal immune status. No Ig producing cells were found in CSF from four patients with tension headache, indicating absence of intrathecal Ig synthesis in healthy individuals. The patients with MS had higher numbers of IgM, IgA and IgG producing cells in PB than healthy controls, confirming occurrence of an extrathecal B cell response in MS. Active and stable MS patients did not differ regarding Ig producing cells in CSF nor in PB, which speaks in favour of continuous immune activity within as well as outside the CNS independent of clinical symptoms.

Adolescent↗

Cerebrospinal fluid lymphocytes from patients with multiple sclerosis and aseptic meningo-encephalitis respond in mixed lymphocyte culture.

Proliferative responses of cerebrospinal fluid lymphocytes (CSF-L) and peripheral blood lymphocytes (PBL) from patients with multiple sclerosis (MS) and aseptic meningo-encephalitis (AM) were tested in allogeneic mixed lymphocyte culture (MLC). PBL from various sources (MS, AM, healthy subjects) were used as stimulator cells. CSF-L from 10 of 13 patients with MS and all 15 patients with AM were MLC-reactive to an extent not significantly different from that of PBL. No consistent differences in mixed lymphocyte reaction (MLR) patterns were registered in MS when clinical (exacerbation, age at onset, duration of disease, disability) and CSF variables (mononuclear cell count, CSF IgG index) or presence of HLA Dw2 were considered. The MLC response of PBL obtained from MS and AM patients did not differ significantly from that of healthy individuals. The results contrast with our previous observation of low proliferative response of MS CSF-L to mitogens. Clonal expansion of alloreactive CSF-L offers the possibility of further studies of their characteristics.

Adult↗