PubMed Health⌕ Search

Biomedical subjects

B Hofmann

Publications and source records attributed to B Hofmann.

At least 145 records · Page 8Linked to original sources
PubMed1987

Kinetic analysis of interleukin 2 (IL-2) production and expression of IL-2 receptors by uraemic and normal lymphocytes.

The in vitro immune response of lymphocytes from uraemic patients was studied by comparing the in vitro kinetics of interleukin 2 (IL-2) production, the mitogen-induced proliferative response, and the expression of IL-2 receptors by T lymphocytes. The IL-2 production in 26 uraemic cell cultures decreased significantly after 48 h of stimulation with mitogen compared with that of 24 control cultures. The lymphocyte responses to phytohaemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM) increased linearly with time, but the responses of the uraemic cell cultures were significantly lower than those of the control cultures. The relative numbers of cells double-stained for both Tac (IL-2 receptor)/HLA-DR or Tac/Leu 2 were significantly increased in the uraemic cultures as compared with the control cultures at 48 and 72 h. A similar, but not significant, trend was also demonstrated for uraemic cells positive for Tac/Leu 3. These findings were also seen in uraemic lymphocyte cultures supplemented with exogenous IL-2. Thus, the IL-2 production of uraemic lymphocytes seems to be exhausted more rapidly than that of normal lymphocytes, and there is no evidence that the poor proliferative response of uraemic lymphocytes is due to a decreased relative number of cells positive for IL-2 receptors.

Adult↗
PubMed1987

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↗
PubMed1987

The immunodeficiency of bone marrow-transplanted patients. II. CD8-related suppression by patient lymphocytes of the response of donor lymphocytes to mitogens, antigens, and allogeneic cells.

Lymphocytes from 21 patients sampled 1-6 months after bone marrow transplantation (BMT) were tested for functional suppressor activity against marrow-donor lymphocytes in the lymphocyte transformation test. Suppression of donor responses to allogeneic (i.e. mixed lymphocyte reaction, MLR) and antigenic stimulation by irradiated (7600 rad) post-BMT cells was observed in about two-thirds of the combinations tested (N = 20 and N = 9). The suppression of donor MLR and antigen responses ranged between 5-52% and 10-46%, respectively. Irradiated post-BMT cells significantly suppressed donor responses to suboptimal concentrations of phytohaemagglutinin (PHA) (median suppression: 28%; P less than 0.05; N = 7) and concanavalin A (Con A) (median suppression: 31%; P less than 0.05; N = 6). A clearly suppressive effect of post-BMT cells was observed when the ratios of CD4+/CD8+ post-BMT cells were lower than 0.5 (P less than 0.01). In three experiments, the depletion of the CD8- but not of the CD4-positive subset abrogated the suppression of the donor MLR by post-BMT cells. The suppression by post-BMT cells (irradiated) of MLR and mitogen responses was comparable whether the responding cells were derived from the donor or from HLA-DR-incompatible, unrelated individuals. The proliferative capacity of post-BMT cells compared to that of donor cells was assayed in the MLR with unrelated, HLA-DR-incompatible stimulator cells. A significantly decreased proliferative capacity (median 20% of that of donor cells) was found (P less than 0.01; N = 16). A weak inverse correlation (P less than 0.05; N = 16) between the proliferative and the suppressive capacity of post-BMT cells in the MLR was observed. These findings indicate that the decreased proliferative capacity upon mitogen, antigen, and alloantigen stimulation observed in most patients within 1-6 months after BMT may be partly due to non-specific suppression by CD8+ cells.

Adolescent↗
PubMed1987

A "new" supertypic HLA-DP related determinant detected by primed lymphocyte typing (PLT).

Primed Lymphocyte Typing (PLT) with local (CDP) and the 9th International Histocompatibility Workshop reagents (GNN) revealed "cross-reactions" between HLA-DPw6 and the GNN2B but not other DPw2 PLT-cells (GNN2A, CDP2A, CDP2B). We raised and bulk-expanded a well discriminating PLT-reagent (the JET-reagent) from an HLA-DR identical, DP, GNN2A, CDP2A, CDP2B compatible and GNN2B incompatible responder/stimulator combination. The JET-reagent defined a "new" determinant, JET, which was present in 11% of Danes. The JET determinant was associated with DPw2, w6, and DP-blank: 66% of DPw6 and DP-blank and 20% of DPw2-positive individuals were JET-positive. All JET-positive individuals belonged to this group, and six of these had two DP-antigens. JET segregated with DP-blank in three and with DPw6 in two informative families. In an HLA-DR/DPw6 recombinant family, JET segregated with DPw6 in the recombinant haplotype. The JET PLT-responses against all of six different JET-positive stimulators including the specific stimulator were strongly inhibited by the monoclonal antibody (MoAb) Tü39, which preferentially reacts with DP-molecules, but not by other HLA-specific MoAbs. The results indicate that JET is either a "new" supertypic DP-related specificity or a determinant, which shares epitopes with DP, of a "new" locus and in linkage disequilibrium with DP.

Antibodies, Monoclonal↗
PubMed1987

Flucloxacillin in chronic leg ulcers. Penetration of flucloxacillin into chronic leg ulcer exudate and the effect on the bacteria.

The penetration of flucloxacillin into ulcer exudate was investigated in six patients with chronic leg ulcers. The flucloxacillin dosage used was 1 g orally three times daily for three days, and the serum and exudate concentrations were measured repeatedly during a 10 h-period following the first and the seventh dose. All the ulcers were contaminated with (S. aureus) Staphylococcus aureus either in pure culture (three ulcers) or in culture mixed with Gram-negative bacteria (three ulcers). Bacterial counting in the ulcers was performed twice before and twice during the antibiotic treatment. The flucloxacillin concentrations measured in the ulcer exudate were found to be lower than the corresponding serum concentrations. However, the exudate concentrations were found to be above the minimum inhibitory concentration (MIC) for the contaminating S. aureus during an average of 7 h after each dose, and the number of S. aureus during the treatment period was reduced to less than 0.01% of the initial number. The Gram-negative bacteria were not susceptible to flucloxacillin. The number of these bacteria decreased before flucloxacillin treatment but increased again during treatment, probably owing to the changed conditions in the ulcers following the marked decrease in the number of S. aureus.

Aged↗
PubMed1987

Increased prevalence of late stage T cell activation antigen (VLA-1) in active juvenile chronic arthritis.

The presence of activated T cells as judged from the reaction with monoclonal antibodies (MoAb) against (a) a late stage T cell activation antigen (VLA-1), (b) the interleukin 2 (IL2) receptor (CD25), and (c) four different HLA class II molecules (HLA-DR, DRw52, DQ, and DP) was studied in 15 patients with active juvenile chronic arthritis (JCA), 10 patients with JCA in remission, and 11 age matched, healthy controls. In addition, the distribution of T 'helper/inducer' (CD4+), T 'suppressor/inducer' (CD4+, Leu8+), T 'suppressor/cytotoxic' (CD8+), and 'natural killer' (NK) cells (CD16+) was studied. Twenty patients and six controls were investigated for the capability to stimulate alloreactivated primed lymphocytes. The prevalence of VLA-1 positive, large cells was significantly increased to 5% (median value) in active JCA as compared with JCA in remission (2%, p less than 0.05) and controls (1%, p less than 0.05), whereas no significant difference between JCA in remission and controls was observed. Except for two patients with active JCA, less than 1% IL2 receptor bearing cells were found in patients with JCA and controls. No significant difference in the prevalence and expression of the various HLA class II antigens was observed between the groups. Similarly, no significant differences in stimulatory capability in secondary mixed lymphocyte culture (MLC) were seen. The distribution of T helper/inducer (CD4+), T suppressor/cytotoxic (CD8+), and NK cells was similar in active JCA, JCA in remission, and controls. The prevalence of T suppressor/inducer (CD4+,Leu8+) cells was higher in remission JCA (17%) than in active JCA (11%) and controls (10%). This increase, however, did not reach statistical significance. In conclusion, late stage but not early stage T cell activation antigens were increased in patients with active JCA as compared with patients with JCA in remission and control, whereas some patients in remission had an increased prevalence of T suppressor/inducer cells.

Adolescent↗
PubMed1987

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↗
PubMed1987

The effect of foscarnet (phosphonoformate) on human immunodeficiency virus isolation, T-cell subsets and lymphocyte function in AIDS patients.

Foscarnet was administered by continuous intravenous infusion in 15 patients with the acquired immunodeficiency syndrome (AIDS) in an open, uncontrolled study. Mean steady state serum concentrations of foscarnet was 261 mumol/l. Treatment was given for 6-21 days, median 14 days, being interrupted prematurely due to renal function impairment in seven patients, and due to other reasons in three patients. Foscarnet therapy was accompanied by improvement of some, probably cytomegalovirus (CMV) related, symptoms but did not otherwise affect the clinical condition of the patients. The occurrence of positive CMV cultures decreased significantly during therapy. Human immunodeficiency virus (HIV) detection by culture was positive in 70-80% of cultures and was unaffected by foscarnet treatment. Eight patients had detectable, free HIV antigen in serum before therapy, and in five of these HIV antigen disappeared during therapy, but reappeared 4-23 weeks after therapy. No patient lost HIV antigen, except during foscarnet therapy. No patient became HIV antigen positive during foscarnet therapy. Immunological parameters did not change during or after foscarnet therapy. Renal function impairment was seen in 9 patients (95% confidence limits, 32-84%), apparently due to reversible tubular damage. At follow-up, serum creatine was normal in all surviving patients. Concomitant medication may have contributed to the renal side-effects. Severe renal function impairment, i.e. serum creatinine above 0.25 mumol/l, was only seen in patients who at the start of foscarnet therapy were chronically affected by their disease. Thus, foscarnet reduces HIV antigen production in AIDS patients. Renal function impairment limits foscarnet use in AIDS patients, but in individuals with less severe manifestations of HIV infection, this side effect may be less frequent.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Immunological studies in acquired immunodeficiency syndrome: effect of TCGF and indomethacine on the in vitro lymphocyte response.

We studied the effects of exogenous T cell growth factor (TCGF) (= interleukin-2) and indomethacine on the lymphocyte transformation response in vitro to allogeneic cells, mitogens, and antigens in AIDS patients, those with AIDS-related complex (ARC), and in healthy controls. While low amounts of TCGF reduced the response of peripheral blood mononuclear cells (PBMC) to allogeneic cells in both healthy controls and AIDS patients, large amounts of TCGF augmented the response in both groups, although the response of the patients' cells were still subnormal. By depleting the PBMC for either CD4-positive or CD8-positive cells, the effect of TCGF on suboptimally mitogen-stimulated PBMC from controls was shown to be due to an increased response in both the CD4-positive and the CD8-positive cells. In contrast, with patient cells, TCGF only increased the response of the CD4-positive cells, while that of the CD8-positive cells was largely unchanged. Thus, the lack of normalization of the mitogen response of patient cells upon addition of TCGF may be largely due to unresponsiveness of CD8-positive cells to TCGF. This observation further supports the idea that CD8-positive cells are abnormal. To investigate the role of the inhibitor of TCGF production, PGE2, in AIDS, indomethacine was added to cultures of mitogen-stimulated PBMC from controls and patients. No differences were found between the three groups: the responses to PHA were slightly increased and those to Con A were unchanged.

AIDS-Related Complex↗
PubMed1986

Acetylcholinesterase activities in association with congenital malformation of the terminal ureter in infants and children.

Acetylcholinesterase activity was found to be higher than normal in intravesical segments of ureters taken from children with vesicoureteral reflux. The ratio of acetylcholinesterase activity to total cholinesterase activity was also found to be high. Acetylcholinesterase activity was normal in intravesical segments taken from the constricted area of ureters from children with obstructive megaureter but it was high in segments taken from the juxtavesical part, immediately adjacent to the constricted area. These findings complement histological studies which have revealed a hyperplasia of cholinergic nerve fibres in the tunica muscularis of reflux ureters whereas obstructive megaureters show a hypoplasia of the beta-adrenergic system.

Acetylcholinesterase↗
PubMed1986

Immunological studies in the acquired immunodeficiency syndrome. II. Active suppression or intrinsic defect--investigated by mixing AIDS cells with HLA-DR identical normal cells.

The lymphocyte transformation responses to mitogens (phytohaemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM)), allogeneic cells, and the antigen-purified protein derivative (PPD) were studied in six acquired immunodeficiency syndrome (AIDS) patients and in six healthy controls, each of whom was HLA-DR- and mixed lymphocyte culture (MLC)-identical with one of the AIDS patients. No evidence of suppression was observed when irradiated or non-irradiated AIDS peripheral blood mononuclear cells (PBMC) were added to cultures of HLA-DR-identical PMBC from healthy controls stimulated with the strong mitogens PHA and Con A or with allogeneic cells, but suppression may be involved in the decreased responses in cultures stimulated with PWM or PPD. Addition of supernatants from macrocultures of AIDS cells did not suppress responses of control PBMC. Thus, suppression by any lymphocyte subset or soluble factor alone cannot explain the generally severely depressed transformation responses in AIDS. Addition of heavily irradiated HLA-DR-identical PBMC from healthy controls or supernatants from these cultures led to increased responses in cultures of mitogen-stimulated AIDS PBMC and in some cultures of antigen or allogeneic cell-stimulated AIDS PBMC, which were of the same magnitude as seen after the addition of commercially obtained T-cell growth factor (TCGF). This indicates that AIDS cells are deficient in producing TCGF. Heavily irradiated AIDS PBMC were capable of restoring the transformation responses to mitogens and antigens of purified HLA-DR-identical normal T cells, indicating that AIDS cells have a normal antigen-presenting capacity and interleukin (IL-1) production. However, AIDS PBMC had a very poor capacity to stimulate normal PBMC in MLC. Together, our experiments suggest that the immune deficiency in AIDS cells may be partially due to a decreased capability of T lymphocytes to produce TCGF and that a decreased number and/or function of dendritic cells may also be involved.

Acquired Immunodeficiency Syndrome↗
PubMed1986

HLA-DP related suppression of mixed lymphocyte reaction with alloactivated lymphocytes.

We studied the influence of HLA class I and class II antigens on the suppression of the MLR induced by primed lymphocytes (PLs) alloactivated in vitro. The suppression of 14 different PLs of 83 MLRs was analyzed. The PLs were primed against (i) HLA-DP (SB) (ii) HLA-DR/DQ or (iii) both HLA-DP and DR/DQ. The suppression was analyzed with special reference to the sharing of HLA-antigens between (i) the stimulator in the MLR and (ii) the stimulator generating the PL. HLA-DP and HLA-DR/DQ antigens were equally capable of generating suppressor cells. When these cells were added to MLRs, the specific stimulators induced the strongest suppression (74%), while allogeic cells sharing class II antigens induced a slightly weaker suppression (66%). The suppression related to HLA-DP (60%) was almost identical to that related to HLA-DR/DQ (59%). The HLA-A, B, C related suppression was of the same magnitude (58%). The unspecific suppression (40%), i.e. no relation to known HLA-antigens, was significantly lower than the class II related suppression, but not significantly lower than the class I related suppression. The suppression of the MLR did not seem to be caused by cytotoxic cells, consumption of lymphokines, nor changes in the kinetics of the MLR. Thus, HLA-DP antigens can-like DR/DQ antigens - induce PLs with the ability to suppress the MLR in an HLA-class II (DP or DR/DQ) related, and possibly a class I related, as well as an unspecific fashion.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1985

Immunological studies in acquired immunodeficiency syndrome. Functional studies of lymphocyte subpopulations.

The lymphocyte transformation response in vitro to mitogens (phytohaemagglutinin, concanavalin A, and pokeweed mitogen) and antigens (purified protein derivative and tetanus) was studied in three patients with acquired immunodeficiency syndrome (AIDS), three patients with pre-AIDS, and six healthy controls before and after depletion of T4- or T8-positive cells. In controls, T8-depleted lymphocytes responded as well as peripheral blood mononuclear cells (PBMC) when monocytes were added, whereas T4-depleted cells gave about 50% of this response to mitogens and no response at all to antigens. No evidence of suppression was seen when various mixtures of T4- and T8-depleted cells were made. In particular, there was a virtually linear relationship between the percentage of T8-depleted cells and the response to antigens. The PBMC of all AIDS and pre-AIDS patients had very low or absent responses to mitogens and antigens, and except in one case, this response did not increase after depletion of T8-positive cells (and addition of monocytes), indicating that these patient cells also lack suppressor activity in this assay. However, a significantly increased response to mitogens was seen when the T8-depleted suspensions were adjusted to contain 20,000 T4-positive cells per well, but the response was still significantly lower than that of similar suspensions from controls. Thus, not only are the poor responses of PBMC from AIDS and pre-AIDS patients due to a low concentration of T4-positive cells, but the responsiveness of these cells also seems deficient. Furthermore, T8-positive patient cells also have an impaired responsiveness. Our experiments do not exclude the possibility that the low response is due to a T8-negative suppressor cell, but it seems more likely that both the T4- and the T8-positive cells are deficient and/or that there is a deficiency in accessory cells. These possibilities are currently under study.

Acquired Immunodeficiency Syndrome↗
PubMed1985

The immunodeficiency of bone marrow-transplanted patients. The effect of patient lymphocytes on the response of donor lymphocytes to mitogens and allogeneic cells.

Lymphocytes from patients after bone marrow transplantation (BMT) are in most cases predominantly of the Leu-2+ (cytotoxic/suppressor) phenotypes and are almost unresponsive to mitogens. In contrast, normal Leu-3+-depleted, Leu-2+-enriched lymphocyte suspensions retain approximately 50% of the mitogenic response compared with that of unseparated cells. To investigate whether this discrepancy was due to active suppression, we selected nine BMT patients from whom sufficient numbers of cells were available and whose lymphocyte phenotypes were predominantly Leu-2+ after BMT. These post-BMT lymphocytes were tested for functional suppressor activities against donor and recipient pre-BMT lymphocytes in the lymphocyte transformation test. None of these post-BMT cells suppressed the response of donor or pre-BMT cells to phytohaemagglutinin A or concanavalin A. In contrast, the response of donor cells in mixed lymphocyte cultures to HLA-DR-different third-party cells was suppressed by highly X-irradiated post-BMT cells by approximately 40%. Addition of T-cell growth factor (= interleukin 2 (IL-2)) or X-irradiated donor cells to post-BMT lymphocytes partially restored the mitogenic response. These findings indicate that the early post-BMT cells lack production of IL-2 but are capable of responding to IL-2 and that the almost extinct mitogen response of these cells is due to immaturity rather than active suppression. The suppression of the allogeneic but not the mitogenic response might be explained by differences in the modes of activation; for example, the allogeneic response must involve the T-cell receptor, while the mitogenic response may not.

Bone Marrow Transplantation↗
PubMed1985

[Maxillofacial reflection of choanal atresia. Apropos 11 cases].

The authors study the maxillofacial repercussions of choanal imperforation based upon 11 cases (8 unilateral and 3 bilateral). Skeletal abnormalities are defined using teleradiographic and tomographic techniques. The origin of these abnormalities is sought: malformations, deformities or sequelae of surgical treatment.

Adolescent↗