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Biomedical subjects

E Dickmeiss

Publications and source records attributed to E Dickmeiss.

At least 73 records · Page 4Linked to original sources

Humoral and cellular responses to Pneumocystis carinii, CMV, and herpes simplex in patients with AIDS and in controls.

The titers of IgG and IgA to Pneumocystis carinii in 36 AIDS patients did not differ significantly from those in 31 controls. Only 2/15 patients (13%) with P. carinii pneumonia (PCP) had titers of IgM antibodies greater than or equal to 5, which is significantly less frequent than in 32 controls (62%) and in 21 AIDS patients without PCP (43%). The risk of PCP was 5 times higher in patients without IgM antibodies to P. carinii than in patients who had these antibodies. A significantly higher percentage of those without PCP (57%) showed increasing titers of IgM antibodies to P. carinii in the second of paired samples taken about 6 months apart, compared with whose with PCP (9%; p = 0.05). All patients had high titers of antibodies to CMV and HSV and normal total concentrations of immunoglobulins. None of the patients responded in lymphocyte transformation to P. carinii, CMV, or HSV antigens. There is no obvious explanation to the selective lack of IgM antibodies to P. carinii in patients with PCP. Lack of IgM antibodies may be a marker for an immunodeficiency to P. carinii.

Acquired Immunodeficiency Syndrome↗

Lymphocyte transformation response to pokeweed mitogen as a predictive marker for development of AIDS and AIDS related symptoms in homosexual men with HIV antibodies.

To identify factors that may predict the development of the acquired immune deficiency syndrome (AIDS) or AIDS related symptoms various immunological measurements were studied in a group of homosexual men attending screening clinics for AIDS in Copenhagen. Fifty seven men whose ratio of T helper lymphocytes to T suppressor lymphocytes (CD4:CD8 ratio) was less than 1.0 before the study began were included. Forty two were positive for antibody to the human immunodeficiency virus (HIV), of whom 38 were reinvestigated after a median observation period of 10 months. Among the seropositive men the transformation responses to pokeweed mitogen and cytomegalovirus and the absolute count of CD4 positive lymphocytes were the most common abnormal values. In particular, a low relative response to pokeweed mitogen on initial investigation correlated with a worsened clinical condition on reinvestigation. The risk of a worsened clinical condition was 55 times higher in seropositive men whose responses to pokeweed mitogen were low than in other seropositive men. The corresponding relative risks for low transformation responses to cytomegalovirus and for a decreased absolute count of CD4 positive lymphocytes were 18 and six. The relative response to pokeweed mitogen is therefore a very sensitive short term predictive marker of the clinical condition of seropositive patients who have a CD4:CD8 ratio of less than 1.0.

AIDS-Related Complex↗

Stages in LAV/HTLV-III lymphadenitis. II. Correlation with clinical and immunological findings.

The aim of the present study was to investigate the relation between the histopathological findings in LAV/HTLV-III lymphadenitis and immunological, clinical, and serological variables. The study group included 38 consecutive homosexual men with persistent generalized lymphadenopathy (PGL) in whom lymph node biopsy was performed. The histopathological lymph node changes were grouped into three stages. Opportunistic infections at the time of biopsy and their development during follow-up were significantly associated with stage III histology (follicular depletion). Analysis of blood from 10 patients with stage III histology revealed significantly (P less than 0.01) decreased proliferative responses of lymphocytes to mitogens and reduced absolute number of CD5+ and CD4+ lymphocytes compared with 17 patients with stage I histology (follicular hyperplasia), whereas patients with stage II histology (follicular involution) had intermediate values. The absolute number of CD8+ lymphocytes was increased in all three stages, as was IgG, while increase in IgM and IgA was restricted to stage III. No difference was observed between the different histopathological stages with respect to the specificity of the anti-LAV/HTLV-III antibody as measured by immunoblotting. In conclusion, the defects of lymphocytes from the blood of LAV/HTLV-III infected persons reflect alterations in secondary lymphoid tissue. Further, there is a close correlation between these alterations and the clinical status of the patients.

Acquired Immunodeficiency Syndrome↗

Combination of methylprednisolone pulse therapy and remission inducing drugs in rheumatoid arthritis.

Thirty patients with rheumatoid arthritis were allocated to either methylprednisolone pulse therapy or placebo at the beginning of treatment with either gold salts, penicillamine, or azathioprine. Methylprednisolone pulse therapy produced an immediate but temporary anti-inflammatory effect lasting for a maximum of four to eight weeks. It also caused a lasting depression of serum IgG, but no effect was observed on the proportion of T and B lymphocytes, proliferative responses, or on concanavalin A induced suppressor cell activity, and there was no effect on the amount of circulating immune complexes. The bone mineral content decreased similarly in the two groups, and methylprednisolone pulses had no effect on the progression of erosions on x rays during an observation period of eight months. A single pulse of methylprednisolone can give a short lasting anti-inflammatory effect but is of little or no value in the long term treatment of rheumatoid arthritis.

Adult↗

The immunological and clinical outcome of HIV infection: 31 months of follow-up in a cohort of homosexual men.

T-cell subsets, antibodies (Ab) against human immunodeficiency virus (HIV) and clinical status were evaluated during a 31 (24-35) month follow-up study of homosexual men. The study group included 50 homosexual men, with many sexual partners, who by 1982-83 were without symptoms and had a prevalence of HIV Ab of 38%. Among the men who were seropositive on the initial investigation a significant decrease occurred in the absolute number of CD4+ lymphocytes (p less than 0.01). 88% of these men experienced a decrease, and by follow-up 59% had CD4+ lymphocytes below the normal range. Also the men who seroconverted during the study had a significant decrease in CD4+ lymphocytes, while no changes were observed in the seronegative group. None of the subgroups had significant changes in CD8+ lymphocyte number. AIDS or AIDS related complex developed in 33% of the men seropositive at inclusion. None of these clinical syndromes developed in the seroconverting or the seronegative group. The men who eventually developed clinical symptoms did not differ significantly from the healthy HIV Ab positive persons, with respect to lifestyle parameters, presence of lymphadenopathy and isolation of cytomegalovirus. However, they had significantly lower CD4+ cells and CD4/CD8 ratio (p less than 0.01) at inclusion. It is concluded that in the majority of persons infected with HIV, phenotypic T-cell alterations will occur with a latency of years, but it remains to be seen if the alterations necessarily will result in clinical manifestations. Further, T-cell subset determination among healthy HIV Ab positive persons will provide prognostic information.

AIDS-Related Complex↗

HTLV-III antibody testing in three Danish blood banks.

The Organon Teknika Vironostika anti-HTLV-III/LAV test was evaluated in three Danish blood banks. The evaluation comprised in total 3,940 consecutive donors. In all three blood banks the tests were carried out exactly according to the manufacturer's instructions, using a low cut-off value defined as (4N + P)/5, where N and P are means of optical densities of known negative and positive samples. By this method the overall frequency of repeatably positive samples was 0.30%. When tested by Western blot, however, none of these samples were shown to contain specific antibodies against HTLV-III/LAV proteins. When testing different categories of patients, only sera containing HLA antibodies gave rise to false-positive reactions. Finally, important differences in the results were observed regarding sample preparation, single or dual wavelength optical density readings, and the experience of the technical staff.

Antibodies, Viral↗

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↗

The immunosuppressive potency of various steroids on peripheral blood lymphocytes, T cells, NK and K cells.

The immunosuppressive effect of natural and synthetic steroids was tested in vitro on phytohemagglutinin (PHA) stimulated T lymphocytes and peripheral blood lymphocytes (PBL), as well as on NK and K cell activity. Three groups of steroids, significantly different in their immunosuppressive activity, were identified. Fluorohydrocortisone, and methylprednisolone were highly potent in suppressing PHA stimulation of T lymphocytes and PBL. Hydrocortisone was of intermediate potency, whereas cortisone, dihydrocortisol, and tetrahydrocortisol were of low potency. T lymphocytes were more sensitive to the suppressive effect of fluorohydrocortisone and methylprednisolone than were PBL cultures. NK and K cell activity was suppressed only by the high potency synthetic steroids and even then the suppression of K cell activity was not significant except at high in vitro steroid concentrations. The present findings support the conception that different lymphocyte subpopulations have different susceptibility to the effect of highly potent steroids. Thus, lymphocyte heterogeneity must be taken into account when the immunosuppressive potencies of different glucocorticoids are studied. Furthermore, the findings in different lymphocyte populations ranked the relative in vitro immunosuppressive potency of glucocorticoids different from the relative anti-inflammatory potencies reported in the literature.

Adult↗

Antibodies to human T-cell lymphotropic virus type III in promiscuous healthy homosexual men. Relation to immunological and clinical findings.

Antibodies to human T-cell lymphotropic virus type III (HTLV-III Ab) were present in twenty-one out of sixty-four asymptomatic promiscuous homosexual men from Copenhagen. The presence of HTLV-III Ab was associated with lymphadenopathy (P less than 0.0005), cytomegalovirus isolation (P less than 0.01), low skin test reactivity (P less than 0.01) and episodes of fever within the 2 month period prior to investigation (P less than 0.05). No significant differences occurred in the total number of T-cells, T-suppressor cytotoxic cells, T-helper cells or helper to suppressor ratio (H/S ratio) between HTLV-III Ab positive and negative homosexuals. An H/S ratio less than or equal to 1.0 was significantly more frequent in homosexual men who both had HTLV-III Ab and excreted cytomegalovirus (P less than 0.01). The H/S ratio of HTLV-III negative homosexuals were significantly lower than that of the controls suggesting that a non-HTLV-III related immunosuppression occurs among homosexuals. Within 2 years after the investigation AIDS or the AIDS related complex developed in three of the men, who at the first investigation all had HTLV-III Ab, alterations in T-lymphocyte subsets and cutaneous anergy. It is suggested that a combination of T-cell subset determination and determination of HTLV-III Ab may provide more valuable prognostic information than isolated determination of HTLV-III Ab.

Acquired Immunodeficiency Syndrome↗

Cytotoxic capabilities of lymphocytes from patients with the acquired immunodeficiency syndrome.

Lymphocytes from 16 AIDS patients were tested in the cell-mediated lympholysis assay (CML). The ability to produce alloreactive cytotoxic lymphocytes in vitro was found to be substantially reduced when compared with concomitantly investigated normal controls. Addition of interleukin 2 (IL-2) to the inducer cultures increased the cytotoxic activity, but not to normal levels. The CML response did not correlate with the relative or absolute number of Leu 3+ cells or the proliferation in effector suspensions. The ability to produce cytotoxic cells in CML, and the degree of potentiation by IL-2, was positively correlated with the absolute number of Leu 2+ cells in peripheral blood of the patients, which was below normal in 56% of the patients. It is suggested that the low CML in AIDS patients is primarily caused by defective T-cell help. In addition patients with decreased absolute numbers of Leu 2+ cells may have a reduced number of CTL precursors. The natural killer (NK) activity of AIDS lymphocytes was reduced, but could be improved by incubation with IL-2 in vitro. The mononuclear cells from the patients showed a decreased ability to respond and to stimulate in the mixed lymphocyte culture. In one of the AIDS patients, the CML was found to induce autoreactivity in vitro.

Acquired Immunodeficiency Syndrome↗

Antibodies against HTLV-III in Danish haemophiliacs: relation to source of factor VIII used in treatment and immunological parameters.

18 out of 40 healthy Danish type A haemophiliacs had antibodies against HTLV-III as measured by an enzyme linked immunosorbent assay (ELISA). The overall seropositivity was 45%. A significant positive correlation was found between seropositivity and total lifetime dose of factor VIII and the age of the patients. 63% and 79% of the patients predominantly treated with commercial American and European preparations, respectively, had antibodies, compared with 11% among patients predominantly treated with Danish cryoprecipitate. Patients exclusively treated with preparations from a single source in the year prior to investigation showed 69% seropositivity when treated with American and European preparations. None of the patients treated with Danish cryoprecipitates prepared from voluntary Danish donors had antibodies. No difference between seropositive and seronegative groups was found in total lymphocyte count, leu 2+ cells, leu 3+ cells and leu 2+/leu 3+ ratio but the seropositive group had significantly higher total IgG and lower skin test score. It is concluded that treatment with local European preparation carries less risk of HTLV-III infection compared with commercial preparations from either the USA or Europe. The results also suggested that T-cell subset alterations among haemophiliacs are not primarily due to HTLV-III infection.

Antibodies, Viral↗

The acquired immunodeficiency syndrome (AIDS) in Denmark. A report from the Copenhagen study group of AIDS on the first 20 Danish patients.

Twenty Danish patients with the acquired immunodeficiency syndrome (AIDS) had been diagnosed by January 1984, 14 of them after 1982. Eighteen patients were male homosexuals, 8 of whom had visited the USA after 1979, 2 were heterosexual males with a history of sexual contacts in Central Africa, suggesting a transmission of AIDS from woman to man. AIDS has not been observed in drug abusers, hemophiliacs or transfused non-risk persons in Denmark. The clinical picture varied according to the presence of Kaposi sarcoma or the type of opportunistic infections, but was in general similar to that reported from the USA. Investigation of T-lymphocyte subsets revealed that the AIDS patients differed from controls and healthy homosexual men by having either a very low number of helper cells or a low helper/suppressor cell ratio. Functional immunological studies revealed a decreased natural killer cell activity and decreased blast transformation by mitogens. The survival two years after diagnosis was 16%.

Acquired Immunodeficiency Syndrome↗

T lymphocyte subsets in homosexual men from Copenhagen.

Screening of sixty-six asymptomatic homosexual men from Copenhagen revealed significantly lower Leu-3a/Leu-2a ratios as compared to controls. Ten (15%) of the homosexuals had a ratio less than or equal to 1.0. The low Leu-3a/Leu-2a ratios were the result of an increase in the absolute number of Leu-2a cells. Homosexuals with many partners and those who had been sexual partners of patients with the acquired immuno-deficiency syndrome (AIDS) had significantly lower ratios than those without these features. Cytomegalovirus was isolated from urine and/or sputum of 15% and this was associated with a Leu-3a/Leu-2a ratio less than or equal to 1.0. The observed immunological abnormalities could either represent latent infection with the putative AIDS agent or alternatively be caused by repeated infections and/or exposure to allogenic spermatocytes or lymphocytes.

Acquired Immunodeficiency Syndrome↗

The prognosis of asymptomatic homosexual men with decreased T-helper to T-suppressor ratio.

Screening of 70 asymptomatic homosexual men in Copenhagen revealed that 13 (19%) had T-helper to T-suppressor (H/S) ratios less than or equal to 1.0. Clinical and immunological follow-up examinations for 2-7 months (mean, 5.2 months) disclosed that none of the 13 men developed the acquired immunodeficiency syndrome (AIDS) or AIDS-like symptoms. An increase in H/S ratios to greater than 1.0 was observed in 11 of the 13 men during the time of observation. The decreased H/S ratios were due to an increase in the T-suppressor population. The T-helper population did not at any time differ from that found in 31 male control subjects. The biological relevance of the observed decrease in H/S ratios was supported by the demonstration of a positive correlation to a decrease in the proliferative response of the lymphocytes. Serological studies did not reveal any specific infectious background for the low H/S ratio found in the 13 men, and the reason for the 'spontaneous' increase during the time of observation remains unknown. The present results indicate that most asymptomatic homosexual men with a decreased H/S ratio will experience normalization of the immunological variables.

Acquired Immunodeficiency Syndrome↗

Alterations in T-lymphocyte subsets among Danish haemophiliacs: relation to source of factor VIII preparations and high dose factor VIII treatment.

Screening of 43 healthy Danish haemophiliacs revealed a significantly lower helper/suppressor (H/S) ratio than in controls. 8 of the haemophiliacs had an H/S ratio less than or equal to 1.0. A significant negative correlation occurred between the total lifetime factor VIII treatment and the H/S ratio. However, high-dose factor VIII treatment given to patients with antibodies against factor VIII was not associated with immunological abnormalities. Children had a significantly higher H/S ratio than the adult haemophiliacs. Patients exclusively treated with Danish cryoprecipitate during the last year had a significantly higher H/S ratio than patients receiving preparations from other sources. This difference might, however, be explained by lower age and lower total lifetime dose in the group receiving Danish preparations. Haemophiliacs treated with American preparations did not differ immunologically from those treated with preparations of other origin. Total serum IgG was increased in 23% of the patients. This parameter was negatively correlated with the H/S ratio. The possible relation of the observed immunological alterations among otherwise healthy haemophiliacs to the acquired immune deficiency syndrome warrants further attention.

Adolescent↗

Chronic lymphocytic leukaemia of T cell origin. Clinical variation possibly due to involvement of different T lymphocyte subpopulations.

Based on the literature and 2 patients studied, we suggest that at least 2 different clinical entities are included in the concept of T CLL: (i) a clinical variant characterized by a relatively benign course, splenomegaly without lymphadenopathy, low lymphocyte count and granulocytopenia; the proliferating lymphocyte is morphologically mature, of medium size and a cytoplasm with azurophilic granules staining positively for acid phosphatase and corresponding to parallel tubular arrays as demonstrated by electron microscopy. The cells form E-rosettes, have no surface-membrane-bound Ig, but Fc-receptors for IgG. With monoclonal antibodies, the phenotype is OKT3+, OKT4- and OKT8+, theoretically corresponding to the suppressor/cytotoxic T lymphocyte subset, but functionally the cells demonstrate killer cell (responsible for ADCC), but not natural or suppressor cell activity. (ii) another clinical variant with an aggressive course, massive hepato-splenomegaly, lymph node enlargement and very high lymphocyte counts; the lymphocytes are small without cytoplasmic granules; their immunological and functional characteristics have not been determined, but morphologically the cells correspond to the T helper/inducer lymphocyte subset. Thus, involvement of different T lymphocyte subsets may be the reason for the clinical variation in T CLL.

Aged↗

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↗