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Biomedical subjects

E Berntorp

Publications and source records attributed to E Berntorp.

161 records · Page 9Linked to original sources

HIV seroconversion in Swedish haemophiliacs: relation to type and dosage of factor concentrate.

Human immunodeficiency virus (HIV) seroconversion among 40 Swedish haemophilia A patients has been investigated by retrospective sera testing. 22/40 patients had developed HIV antibodies before 1983, i.e., when heat-treatment of American factor concentrates was introduced. All patients had received American and Swedish factor concentrates, thus no case of seroconversion was seen among patients treated exclusively with non-heat-treated Swedish concentrates. Of 79 patients with severe or moderate haemophilia, all of whom had received both American and Swedish concentrates, the 36 seropositives were compared with the 43 seronegatives. The total number of units received did not differ between the two groups, though the seropositive group had received significantly more American concentrate. Two batches of concentrate were proved to have been infected. 29 seropositive and 13 seronegative patients had been treated with at least one of these batches. As expected, and unlike most of the seronegative patients, patients in the seropositive group generally had abnormal lymphocyte subsets.

Acquired Immunodeficiency Syndrome↗

(3H)ouabain binding to leukaemic cells and intralymphocytic sodium content in chronic lymphocytic leukaemia; no evidence for alterations of the Na+/K+-pump.

The number of specific (3H)ouabain binding sites and dissociation constants (Kd) were determined by Scatchard analysis of values for leucocytes from patients with B-cell chronic lymphocytic leukaemia (CLL), chronic myeloid leukaemia (CML), acute blastic leukaemia (AL) and healthy subjects. CLL lymphocytes and normal B-cells bound significantly less (3H)ouabain than did normal T-lymphocytes. CML granulocytes showed the same binding characteristics as normal granulocytes, while blast cells from AL patients bound significantly more (3H)ouabain than did normal granulocytes or B-cells. The increased binding capacity in blast cells might, at least partly, reflect their larger cell size. A decrease in Kd values was only found in CLL lymphocytes, as compared with normal B-cells. Intralymphocytic sodium content in CLL lymphocytes was significantly increased, as compared with that in T-cell-enriched normal lymphocytes. (3H)ouabain binding did not show any relationship to different prognostic variables in CLL. The present data mainly argue against altered Na+/K+-ATPase enzyme activity as an indicator of malignancy.

Acute Disease↗

Lymphocyte transglutaminase function may be impaired in type 2 diabetes mellitus.

A method for capping of beta 2-microglobulin involving the transglutaminase inhibitor monodansylthiacadaverine was applied to lymphocytes from 17 patients with Type 2 diabetes mellitus and from a matched control group of 16 normoglycaemic healthy subjects. Monodansylthiacadaverine strongly inhibited the capping, which points to the involvement of transglutaminase in the redistribution of beta 2-microglobulin on the cell surface. The inhibition was more pronounced in lymphocytes from diabetic patients, indicating impaired transglutaminase function in Type 2 diabetes mellitus.

Cadaverine↗

Induction of split tolerance and clinical cure in high-responding hemophiliacs with factor IX antibodies.

An approach to the problem of inducing tolerance in patients with hemophilia complicated by high-responding antibodies is described. Thus, in four patients with severe hemophilia B and high-responding antibodies against factor IX, it has been possible to modify the immune response by giving high doses of intravenous IgG in combination with cyclophosphamide and factor IX, followed by regular factor IX treatment. In three of the patients, the in vivo recovery and half-life of infused factor IX coagulant activity (IX:C) are now normal, while the fourth patient has been converted to a low responder. Hip replacement surgery has been performed successfully in one patient. The tolerant state in these four patients is characterized, and they have all been found to have complexes between factor IX antigen and a "new" antibody without IX:C inhibitory activity. The disappearance rate of the complexed factor IX antigen (i.e., lacking IX:C activity) is considerably prolonged, and the persistence in the circulation of this (probably modified) factor IX molecule may be crucial, since tolerance to factor IX treatment was only induced when immunocomplexes were produced. Since earlier treatment of the patients with cyclophosphamide and factor IX, but without IgG, failed to induce tolerance, it appears to be the IgG that is the prerequisite.

Adolescent↗

Effects of insulin on the total number of [3H]ouabain binding sites in normal human lymphocytes and after stimulation in vitro with concanavalin A.

The effects of insulin in vitro on the total number of [3H]ouabain binding sites were studied in normal and concanavalin A-stimulated human T-lymphocytes after incubation for 18 and 42 h with 0, 10(2) and 10(5) mIU/l of insulin. While no effect on [3H]ouabain binding could be demonstrated in non-stimulated cells, a significant decrease could be produced in concanavalin A-stimulated cells. Mean +/- SD for the total number of [3H]ouabain binding sites per cell after 18 h incubation time with concanavalin A in the absence of insulin was 46,099 +/- 6,620 as compared with 44,783 +/- 8,347 in the presence of 10(2) mIU/l of insulin (non-significant) and 42,406 +/- 7,066 in the presence of 10(5) mIU/l (p = 0.031). The corresponding 42-h values were 47,075 +/- 9,412, 43,761 +/- 9,273 (p = 0.033) and 43,824 +/- 9,312 (p = 0.005).

Binding Sites↗

Transmission of HIV infection to heterosexual partners but not to household contacts of seropositive haemophiliacs.

The prevalence of HIV antibodies in 44 heterosexual female partners and 56 nonsexual family household contacts of 61 HIV seropositive haemophiliacs (41 adults and 20 children or adolescents) was determined to evaluate the risk of transmission of HIV infection. HIV antibodies were determined by enzyme-linked immunosorbent assay and positive reactions were confirmed by Western blotting. HIV antibodies were demonstrated in 4/40 (10%) regular heterosexual partners of 40 seropositive patients with haemophilia A. Four temporary heterosexual partners of one additional seropositive haemophiliac were seronegative. 56 nonsexual household contacts including 30 parents, 13 siblings and 13 children of 29 seropositive haemophiliacs were all negative for HIV antibodies. Thus transmission of HIV occurred from seropositive haemophiliacs to their heterosexual partners but not to nonsexual household contacts.

Acquired Immunodeficiency Syndrome↗

von Willebrand's disease characterized by increased ristocetin sensitivity and the presence of all von Willebrand factor multimers in plasma.

In eight members of one family, platelets in platelet-rich plasma aggregated at much lower ristocetin concentrations than normal. Ivy bleeding time was variously prolonged, and von Willebrand factor antigen (vWF:Ag), ristocetin cofactor activity, and factor VIII coagulant activity were decreased. Most of the affected members had had slight to rather severe bleeding symptoms. Platelet-type von Willebrand's disease (vWD) could be ruled out. All multimers of vWF:Ag were found in plasma as well as platelets. Administration of 1-desamino-8-D-arginine vasopressin (DDAVP) to the propositus did not cause thrombocytopenia, and platelet-poor plasma obtained immediately after did not aggregate normal platelets. The molecular defect in this family, inherited as an autosomal dominant, resembles the one in type IIB because of the response to ristocetin but differs from IIB because all vWF:Ag multimers are present in plasma and the response to DDAVP is atypical. We conclude that this family has a new subtype of vWD and propose that structural as well as functional criteria should be used for a proper classification of vWD.

Blood Platelets↗

[3H]ouabain binding and sodium content in lymphocyte sub-populations and the demonstration of increased binding in type 2 diabetes mellitus.

The number of specific [3H]ouabain binding sites in T-lymphocytes was determined and linear Scatchard plots were obtained. The number of sites was 30088 +/- 3039 (mean +/- SD) per lymphocyte in 14 healthy males and 33939 +/- 3185 in 11 males with type 2 diabetes (P less than 0.01). No difference between the dissociation constants were found (Kd = 3.91 and 3.86 mmol/l). The number of binding sites in lymphocytes from 15 healthy males with normal glucose tolerance but with a strong family history of type 2 diabetes did not differ from the controls. In T-lymphocytes a significantly higher number of specific ouabain binding sites was found than in non-T-lymphocytes (P less than 0.01). There was no difference between the dissociation constants. (Kd = 3.69 and 3.97 mmol/l). Intra-lymphocytic sodium was measured in 18 healthy individuals and the mean content was 8.1 +/- 2.3 mmol/kg lymphocytes. A lower content of sodium in T- compared to non-T-lymphocytes was also found (5.9 +/- 0.8 mmol/kg vs 15.5 +/- 0.8 mmol/kg, P less than 0.001). There was no correlation between lymphocytes and erythrocytes concerning [3H]ouabain binding sites or sodium concentration.

Blood Glucose↗

Characterization of transglutaminases in normal and malignant human leukocytes.

Using the fluorescent activity staining procedure, transglutaminases in human monocytes, granulocytes and lymphocytes have been characterized with respect to agarose gel electrophoretic mobility and thrombin dependence. A thrombin dependent transglutaminase was found in concanavalin A stimulated peripheral monocytes. The electrophoretic mobility of this zymogen and of platelet and plasma factor XIII was similar. With stimulated peripheral lymphocytes a similar pattern was observed. However, the potential transglutaminase activity in the lymphocyte factor XIII was lower than that in monocytes. Similar results were obtained when lymphocytes from chronic myeloid and chronic lymphocytic leukaemia patients were examined. Quantitatively, the transglutaminase activity in the leukaemic cells was estimated to be lower than the activity in normal cells. With respect to agarose gel electrophoretic mobility, a similar transglutaminase was found in concanavalin A stimulated human peripheral granulocytes. Although electrophoretically clearly separated from tissues transglutaminase, the granulocyte enzyme did not seem to require thrombin for activation.

Acyltransferases↗

High expression of lymphocyte surface immunoglobulin in chronic lymphocytic leukaemia may be a bad prognostic sign.

Lymphocytes from 27 patients with B-type chronic lymphocytic leukaemia (CLL) were tested with immunofluorescence for expression of surface membrane immunoglobulin (SmIg) and the B cell antigen 7420. When age at time of testing, sex, clinical stage according to Binet, disease progression according to Levin and percentage of SmIg and 7420 antigen-expressing cells were used as explanatory variables for survival in a linear logistic regression model, only the SmIg variable was significant (p less than 0.025). A high proportion of SmIg bearing cells (greater than 61%) was associated with short survival, large tumour mass and aggressive disease. The tentative conclusion is drawn that the differentiation stage of the tumour cells in CLL determines the clinical course of the disease and is inversely correlated to the SmIg expression.

Aged↗

Cellular expression of the non-HLA-DR B-cell antigen 7420: studies on non-lymphoid cells and on lymphocytes from different species.

We recently reported on a heterologous antiserum (antiserum 7420), raised against chronic lymphocytic leukaemic lymphocytes, that reacts with B-lymphocyte antigen(s) different from known B-cell markers such as HLA-DR (Ia-like) antigens, surface immunoglobulin, and the Fc receptor. This antiserum is now shown to react also with a C3-receptor-positive population of lymphocytes from the dog, monkey, ox and sheep but not from rodents and avians. The antiserum does not react with the non-lymphoid human cells mature granulocytes, thrombocytes, erythrocytes, or spermatozoa, nor with the cultured cell lines tested, i.e. fibroblasts, melanoma cells, HeLa cells and green monkey kidney cells. This reactivity pattern differs somewhat from that reported for HLA-DR antiserum. The antigen(s) defined by the 7420 antiserum and the C3 receptor are different, since they redistribute independently on the lymphocyte surface.

Absorption↗

Heterologous B-cell antisera may detect non-Ig, non-HLA-DR antigens.

A heterologous antiserum (antiserum 7420) against B-lymphocyte antigen(s) was raised in a rabbit by immunization with peripheral blood lymphocytes from a patient with chronic lymphocytic leukaemia (CLL). After absorptions with pooled normal human serum, IgA, IgD, and IgM M-components, the fluorescein isothiocyanate-conjugated F(ab')2 fragments were prepared and further absorbed with normal peripheral blood leucocytes. The F(ab')2 fragments, studied in direct immunofluorescence, reacted with both normal and CLL B lymphocytes but not with T lymphocytes. Comparative studies with an HLA-DR antiserum showed that the antigen(s) detected by 7420 antiserum did not redistribute together with HLA-DR antigens in cocapping experiments, nor did the HLA-DR antiserum block the reaction of 7420 F(ab')2 fragments with B lymphocytes. The 7420 F(ab')2 fragments prcipitated detergent-solubilized B-cell membrane material with a molecular weight of around 40,000 and 150,000 daltons. The conclusion drawn is that the 7420 and HLA-DR antigens are different. The 7420 antigen was also shown to be different from classical HLA antigens, beta 2-microglobulin, surface immunoglobulin, the Fc receptor, and HC protein.

Animals↗

Social support and the development of immune function in human immunodeficiency virus infection.

A psychosocial investigation offered to all human immunodeficiency virus (HIV)-infected men with moderately severe or severe hemophilia in Sweden was made in 1986. Most of these men had been infected in the years 1980 to 1984 and told about their infections in 1985. Forty-nine subjects had answered questions in regard to sources of emotional support in their life situation. Based on the responses to these questions a score of "availability of attachment" (AVAT) was calculated, and two groups of patients were identified: one with high AVAT and one with low AVAT scores. The subjects were followed with regard to the state of their immune system, as reflected by CD4 counts, until 1990. The results indicated that a low AVAT score in 1985 was associated with a significantly more rapid progressive deterioration in CD4 count during subsequent years. The mechanism behind this association is unknown. Several possible confounders were not studied. However, if the association between a poor AVAT score and rapid CD4 deterioration after HIV infection is replicated in other samples, it could be important to the future clinical care of HIV-infected subjects.

Adolescent↗

Plasma product treatment in various types of von Willebrand's disease.

Four different virus-inactivated factor VIII concentrates (Haemate P, Behring; Profilate, Alpha, FVIII-VHP-vWF, CRTS), near-pure von Willebrand factor (Facteur Willebrand, CRTS) or one recombinant FVIII preparation (Recombinate, Baxter) were given to one or more patients with different forms of von Willebrand's disease. Duke bleeding time, VIII:C, vWF:Ag, RC of activity, and the multimeric pattern of plasma vWF were monitored. Both Duke bleeding time and the multimeric pattern were normalized after treatment with Haemate P, FVIII-VHP-vWF, or Facteur Willebrand, and to a lesser extent after Profilate. Except in one case, the reduction in bleeding time lasted longer after Haemate P than after the other concentrates. Recombinate had no effect on primary hemostasis, and the half-life of VIII:C was very short. If prompt hemostasis is required, and when pharmacological correction of the defect is impossible, we recommend a concentrate containing both FVIII and the full complement of vWF multimers, but for prophylactic treatment pure von Willebrand factor may be used.

Adolescent↗