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Biomedical subjects

H Valdimarsson

Publications and source records attributed to H Valdimarsson.

At least 127 records · Page 7Linked to original sources

Prospective study of early rheumatoid arthritis. II. Association of rheumatoid factor isotypes with fluctuations in disease activity.

Thirty-three patients with early peripheral synovitis were followed up for two to four years in order to study the relationship between fluctuations in rheumatoid factor (RF) levels and indices of clinical activity. Twenty-eight of these patients developed classical/definite rheumatoid arthritis (RA). Seventeen patients developed erosive disease of their hands and wrists and thirteen had a positive RF agglutination test. Nineteen patients had raised levels of IgM, RF, IgA, RF, or IgG RF as measured by isotype-specific ELISA techniques. The within-patient fluctuations in IgA RF levels correlated significantly with the corresponding fluctuations in grip strength (p less than 0.05), erythrocyte sedimentation rate (ESR) (p less than 0.01), and a composite index of disease activity (p less than 0.02). IgG RF levels were also associated with changes in ESR and grip strength, but IgM RF showed only a weak association with fluctuations in ESR and not with any other clinical parameters. It is suggested that serum IgA RF may be a useful marker of disease activity in rheumatoid arthritis.

Adult↗

Human polyomavirus in pregnancy. A model for the study of defence mechanisms to virus reactivation.

We have carried out a longitudinal study of human polyomavirus infection in 71 pregnant women and correlated the virological findings with changes in the defence system in the same patients. As reactivation of human polyomaviruses generally occurred late in the second trimester it was possible to distinguish between the immunological changes which preceded the onset of reactivation and those which were secondary to the infection. Evidence of reactivation was detected in 26 women; all had high or rising antibody titres against BK or JC virus, but only five of these developed viruria. A positive correlation was observed between a high monocyte count in early pregnancy and subsequent virus reactivation. The virus excretors had significantly lower neutrophil counts than the women who had no evidence of virus reactivation. In contrast, women with serological evidence of virus activity but no viruria has significantly higher neutrophil counts than the non-activators. They also had stronger lymphocyte responses to PHA than the virus excretors. Virus activators were found to have a significant lymphopenia in the third trimester compared to the non-activators. High antibody levels did not appear to inhibit virus excretion. These findings suggest that monocytosis may predispose to reactivation of human polyomaviruses in pregnancy. On the other hand, ability to contain the virus once it has been activated, was associated with neutrophilia, and relatively vigorous in vitro reactivity of lymphocytes to PHA. Persistent lymphopenia was probably secondary to virus reactivation. The model on which this study is based could be adapted to investigate the causes of reactivation of other viruses. It may also help to identify risk factors in patients who are particularly susceptible to infection with opportunistic viruses.

Animals↗

A longitudinal study of leucocyte blood counts and lymphocyte responses in pregnancy: a marked early increase of monocyte-lymphocyte ratio.

Seventy-seven pregnant women were studied repeatedly from the first trimester until 4 weeks after delivery. Neutrophil count was increased but constant in all stages of pregnancy. In contrast, there was a marked increase in monocyte numbers in the first and early second trimester, followed by a gradual decrease towards normal before term. A progressive decrease in total lymphocyte count was observed up to 25-28 weeks, when it increased again, although not reaching the non-pregnant level before term. These fluctuations in monocyte and lymphocyte numbers have not been described before and could explain contradictory findings of previous studies. They may also be important in relation to the mechanisms which prevent rejection of the fetal allograft. Absolute T cell counts were not significantly decreased, but a striking reduction was observed in B cell numbers in early pregnancy. Lymphocyte response to T cell mitogens was decreased throughout pregnancy. It is concluded that immunological studies of pregnancy must take account of the dynamic nature of this condition.

B-Lymphocytes↗

T-dependent antigens are more immunogenic in the subarachnoid space than in other sites.

Systemic antibody responses were compared in mice injected with antigens into the subarachnoid space (SAS) and into conventional sites. Introduction of T-dependent antigens into the SAS induced higher systemic antibody responses than injections into any other sites. This applied to both soluble and particulate antigens and was more apparent in secondary than in primary responses. The effect was not observed with a T-independent antigen and not consistently with high doses of sheep red blood cells (SRBC). It was concluded that the subarachnoid space is a highly efficient site for the induction of systemic antibody production, in particular to low amounts of T-dependent antigens.

Animals↗

Interaction between a synthetic analogue of vasopressin and human peripheral blood lymphocytes.

The interaction between 1-desamino-8-D-arginine vasopressin (DDAVP) and human peripheral blood lymphocytes was investigated in vitro, using DDAVP concentrations ranging between 1 pg and 10 microgram per ml. DDAVP did not display any mitogenic activity in the absence of phytohaemagglutinin (PHA). Neither did DDAVP have any significant effect on the PHA-stimulated incorporation of 3H-thymidine into DNA, provided that optimally mitogenic concentrations of PHA were present. However, DDAVP either enhanced or inhibited lymphocyte transformation initiated by suboptimally mitogenic concentrations of PHA: the direction of the response depended on the magnitude of the transformation response induced by the PHA alone. Experiments employing 125I-DDAVP demonstrated that DDAVP bound reversibly to untransformed lymphocytes, and that at 20 degrees C, the amount bound increased rapidly to reach a plateau value after 60 minutes. The binding of DDAVP was inhibited in the presence of Pitressin or arginine vasopressin suggesting that human peripheral blood lymphocytes have surface receptors for the vasopressins which also react with DDAVP.

Adult↗

Dual action of leucocyte dialysates and of thymosin on the recovery of sheep-cell-rosetting capacity in trypsinized human lymphocytes.

Trypsinization of human blood lymphocytes abolishes their capacity to form rosettes with sheep erythrocytes (E-rosettes) and this is regained in part on incubation of the cells at 37 degrees C for 3 hr. The recovery of rosetting capacity was found to be accelerated in the presence of dialysable extracts of human leucocytes (DLE) or bovine thymosin fraction 5 (THFV). For both DLE and THFV two types of effect were demonstrated. At lower concentrations the stimulation of recovery was dependent on the presence of the agent during incubation and it presumably comes about through an effect on the metabolic process required for regeneration of the E-receptors. At higher concentrations another mechanism is apparent since the agents were now effective when added after incubation. This last phenomenon is wholly dependent on prior incubation of the trypsinized lymphocytes in medium alone and it probably involves attachment of components of DLE and THFV to incompletely recovered cells, thereby providing a more favourable charge environment for E-rosette formation. A similar process of adhesion-promotion may be occurring in certain in-vitro tests with THFV which are carried out on lymphocytes from immunodeficient patients. On the other hand, it is the other mechanism, that of metabolic action, which is likely to be the predominant consideration in relation to treatment of such patients with DLE or THFV.

Cell Extracts↗

Idiopathic pyoderma gangrenosum and impaired lymphocyte function: failure of azathioprine and corticosteroid therapy.

A 58-year-old man with chronic "idiopathic' pyoderma gangrenosum, recurrent secondary staphylococcal infection, nail candidiasis, markedly impaired lymphocyte function and a serum blocking factor is described. Despite an initially favourable response to immunosuppressive therapy, the patient later relapsed whilst on high dose systemic corticosteroids and azathioprine. Immune function remains abnormal 3 years cessation of azathioprine. Attempted immunostimulation with Corynebacterium parvum proved unsuccessful. A striking but transient increase in lymphocyte function followed parenteral iron therapy for an unexplained iron-deficiency anaemia. Gradual reduction in prednisone dosage to 5 mg daily has coincided with a period of clinical resolution and modest improvement in lymphocyte reactivity. Prolonged immunosuppressive therapy may be inadvisable in chronic idiopathic pyoderma gangrenosum associated with defective cellular immunity.

Azathioprine↗

A radiometric assay for the combined measurement of phagocytosis and intracellular killing of Candida albicans.

A radiometric assay for combined measurement of phagocytosis and intracellular killing of Candida albicans by human polymorphonuclear leucocytes (PMNs) is presented. The assay, based upon the incorporation of 3H-uridine into the micro-organisms, makes it possible to measure phagocytosis and intracellular killing simultaneously but independently in a single sample. Thus it is possible to determine in a single assay whether increased survival of the micro-organism is due to reduced ingestion or reduced ability of the PMN to kill. The assay is objective, quantitative and convenient for clinical application. It is also suitable for analysing the effects of various agents, including serum factors and drugs, on PMN function.

Adult↗

Development of human granulocyte and monocyte Fc receptors.

Bone marrow cells were examined for the presence of IgG-Fc receptors using a red cell rosette technique. Receptors were demonstrated on some of the neutrophil promyelocytes, almost all of the neutrophil myelocytes, and a few of the eosinophil myelocytes. Cells which appeared on morphological grounds to be promonocytes also expressed Fc receptors.

Bone Marrow↗

Use of an antiserum specific for human T lymphocytes as a diagnostic reagent: comparison with E rosette formation and mitogenic response to PHA.

An antiserum with specificity for human T lymphocytes was evaluated as a diagnostic reagent in the clinical immunology laboratory. The antiserum was used in indirect immunofluorescence to detect T cells in blood samples from normal controls and patients with various disorders involving the immune system. The same samples were also examined using two established tests for T cells, the rosette reaction with sheep red blood cells (E rosette assay) and the proliferative response to phytohaemagglutinin (PHA). The antiserum and the rosette assay detected approximately the same numbers of T cells in controls, but the antiserum indicated T cell deficiency in several patients who appeared normal by rosetting or PHA reactivity. PHA stimulation in autologous plasma was depressed in a further group of patients who had normal T cell numbers by the other two tests. In vitro experiments with normal lymphocytes indicated that the E-rosette receptor was distinct from determinants detected by the T-cell specific antiserum. The immunofluorescence test with the anti-T serum provides an additional assay which appears to be more sensitive than the other two tests in detecting certain cases of T lymphocyte deficiency.

Antibody Specificity↗

A new semiquantitative radiometric opsonin assay. Selective measurement of opsonizing capacity of the alternative pathway.

A new semiquantitative radiometric opsonin assay is described. It was found that the opsonin activity generated by incubating brewer's yeast, Saccharomyces cerevisiae, in medium containing less than 5% human serum was exclusively complement dependent. In contrast, C. albicans was effectively opsonized in the absence of complement. Antibodies and the early classical complement pathway did not contribute to the opsonization of S. cerevisiae and neither did C5-9. The brewer's yeast assay can therefore be used for measuring selectively the opsonizing capacity of the alternative pathway. Sera from approximately 7% of apparently healthy adult controls consistently failed to generate significant opsonin activity while 8 out of 26 patients with suspected immune deficiency of unknown cause were defective in this assay. All opsonin deficient sera so far tested had haemolytically normal alternative pathway and Factor B activity.

Adult↗

Phagocytosis measured as inhibition of uridine uptake by Candida albicans.

Inhibition of 3H-uridine incorporation into Candida albicans can be used as a sensitive index of phagocytic function because: 1) there is a linear correlation between uridine incorporation and yeast number; 2) phagocytic cells do not incorporate significant amounts of uridine in short term cultures; and 3) C. albicans replicating inside phagocytic cells does not take up uridine from culture medium. Appropriate conditions for measuring phagocytic capacity of human polymorphonuclear cells (PMN's) were 5 x 10(5) C. albicans and 5 x 10(4) PMNs in 0.5 ml of medium containing 2.5% AB serum. This mixture was incubated for 30 min at 37 degrees C. Aliquots were then transferred into microtiter wells and incubated for a further 60 min in the presence of 3H-uridine. Under these conditions PMN leucocytes from 25 healthy individuals caused suppression of uridine incorporation ranging from 33 to 75% (50 +/- 12).

Candida albicans↗

Participation of C3 in intracellular killing of Candida albicans.

Using new objective methods for measuring, independently, phagcytosis and killing, it was demonstrated that Candida albicans opsonized by C3-deficient serum was ingested by not killed in vitro by human polymorphonuclear leukocytes. Killing could be induced by adding purified C3 to the C3-deficient serum. It is concluded that C3 participates directely in the intracellular process leading to phagocytic killing of C. albicans.

Candida albicans↗

Crude transfer-factor preparations stimulate trypsinized human lymphocytes to form rosettes with sheep red cells.

The binding sites for sheep red cells (E) on human lymphocytes are trypsin-sensitive but regenerate in vitro on incubation at 37 degrees C. The rate of this regeneration was increased in the presence of dialysates of human leucocyte extracts (DLE). Thus incubation of trypsinized lymphocytes for 3 hr in appropriate dilutions of DLE resulted in a 2- to 6-fold increase of E-binding activity above that observed in medium-incubated control lymphocytes. Dialysates prepared from human thymus and brain similarly accelerated recovery of E-binding activity whilst dialysates of human fibroblasts and liver cells were inactive. The regeneration of trypsinized membrane immunoglobulin was slightly delayed in the presence of DLE. These findings indicate that leucocyte dialysates contain an activity which preferentially stimulates the regeneration of a T-lymphocyte membrane component. It is suggested that this activity may account for the immunological restoration observed in some patients with T-lymphocyte deficiency after injection of leucocyte dialysates.

Humans↗