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Biomedical subjects

B Hofmann

Publications and source records attributed to B Hofmann.

At least 127 records · Page 7Linked to original sources
PubMed1989

Immunodeficiency after allogeneic bone marrow transplantation in man. Effect of phorbol ester (phorbol myristate acetate) and calcium ionophore (A23187) in vitro.

This study was undertaken to clarify the mechanism behind the severely decreased lymphocyte proliferative response upon stimulation with mitogens and antigens seen after allogeneic bone marrow transplantation (BMT) in man. We investigated eight BMT patients and eight controls and found that the proliferative response of patient cells was reduced both when the cells were stimulated with phytohaemagglutinin (PHA) and when they were stimulated with a combination of phorbol myristate acetate (PMA), which is an activator of protein kinase C (PKC), and the calcium ionophore A23187, which irreversibly opens for calcium transport into the cell (median relative responses were 41 and 37%, respectively). However, the PHA-induced increase in the concentration of intracellular free calcium in post-BMT cells was not significantly different from the values found in control cells and the expression of interleukin 2 (IL-2) receptors (CD25) was only slightly decreased. However, the production of IL-2 was severely decreased in patient cells after stimulation with A23187/PMA (median 3541 units), although it was higher than in PHA-stimulated control cells (median 354 units). These results show that a direct activation of PKC by PMA combined with an increase in intracellular free calcium by A23187 cannot overcome the lymphocyte proliferation deficiency in cells from patients after allogeneic BMT. The data suggests that the defect is affecting the diacylglycerol pathway considerably more than the inositol triphosphate pathway.

Adolescent↗
PubMed1989

Enhanced degradation of platelet-activating factor in serum from diabetic patients.

The degradation of platelet-activating factor (PAF) and lipid concentrations were measured in sera from 20 patients with insulin-dependent diabetes mellitus and from 20 age- and sex-matched healthy volunteers. The PAF-degrading capacity as well as triglycerides and total and very low density and low-density lipoprotein cholesterol were found to be significantly increased in the patients group, whereas the difference observed in high-density lipoprotein cholesterol was statistically nonsignificant. There were also a series of close relationships between the degradation of PAF and some lipid variables in the control group. These results confirm the parallel changes of lipoproteins and PAF-degrading capacity described previously in serum from atherosclerotic patients and extend it to patients suffering from diabetes mellitus.

Adult↗
PubMed1989

Prognostic value of immunologic abnormalities and HIV antigenemia in asymptomatic HIV-infected individuals: proposal of immunologic staging.

The prognostic value of various immunologic tests was investigated in 150 HIV-seropositive homosexual men, who were initially without HIV-related symptoms or AIDS and who were followed for a median of 12 months (range 3-28 months). The laboratory investigations included HIV antigen in serum, total lymphocyte count, T-helper (CD4) and T-cytotoxic/suppressor (CD8) counts, and lymphocyte transformation responses to the mitogens phytohemagglutinin (PHA) and pokeweed mitogen (PWM), and to antigenic extracts from Candida albicans and cytomegalovirus. 24 individuals developed HIV-related symptoms or AIDS (11 cases). All parameters except the CD8 count were of prognostic value, but a multivariate analysis of symptom-free survival showed that HIV antigenemia, a CD4 count less than 0.5 x 10(9)/l, and relative response to PWM below 25% of controls contained all the prognostic information. Individuals abnormal at entry for these 3 variables had a theoretical 36 times as high hazard of developing symptoms within the observation period as had individuals with normal parameters. There was no significant covariation between HIV antigenemia on the one hand and CD4 count and response to PWM on the other. Although, the latter 2 variables covaried, each of them provided independent information, and both were used to classify the degree of the immunodeficiency in 3 stages: Im-0 with normal values, Im-1 with one, and Im-2 with both tests abnormal. Individuals in stage Im-2 had a 10 times increased risk of developing symptoms. The immunologic staging correlated significantly with the clinical grouping (CDC criteria). This staging improved in only 1, but deteriorated in half of 36 individuals observed for at least 18 months. Thus, the staging is likely to prove useful when attempts to arrest the immunodeficiency of HIV-infected individuals has to be monitored.

Biomarkers↗
PubMed1989

Independent clinical significance of HIV antigen determination and CD4 counts in anti-HIV positive patients.

HIV antigenemia was found in 52/243 HIV antibody positive individuals attending 2 AIDS-screening clinics, giving a prevalence of 13, 25 and 76% in CDC groups II, III and IV, respectively. No correlation was found to decreased CD4 lymphocyte values in the individual groups. HIV antigen therefore identified a separate subpopulation. For 138 asymptomatic patients followed prospectively both laboratory parameters predicted HIV-related events, the relative risk factor being 4 for low CD4 value and 6 for presence of HIV antigen. Individuals presenting with HIV antigen and decreased CD4 count all developed disease within 18 months, the relative risk factor being 24. Thus the 2 markers, when measured together, effectively separated asymptomatic HIV-infected patients into 1 of 3 risk categories.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

Effect of thapsigargin on cytoplasmic Ca2+ and proliferation of human lymphocytes in relation to AIDS.

The tumor-promoting sesquiterpene lactone, thapsigargin, induced a dose-dependent increase of the cytoplasmic Ca2+ concentration ([ Ca2+]i) in human lymphocytes from a resting level between 100 and 150 nM up to about 1 microM. Half-maximum response was found at about 1 nM of thapsigargin, full response at 100 nM. The effect of thapsigargin on [Ca2+]i exceeded that of phytohaemagglutinin (PHA) which raised [Ca2+]i to maximum 300 nM. In combination with phorbol 12-myristate 13-acetate (PMA), thapsigargin stimulated the proliferation of normal lymphocytes to the same extent as did PHA, whereas the thapsigargin/PMA treatment could not restore the defective proliferation of AIDS lymphocytes in spite of the increased [Ca2+]i. Thapsigargin or PMA added separately had no stimulatory effects on cell proliferation. The thapsigargin/PMA treatment caused an increase in the interleukin-2 (IL-2) production of the lymphocytes, which was much higher than that caused by the PHA treatment, even in AIDS lymphocytes. Moreover, the thapsigargin/PMA treatment stimulated the expression of the IL-2 receptors on both normal and AIDS lymphocytes, similar to the effect of PHA. It is concluded that thapsigargin exerts its effects on lymphocyte proliferation by increasing [Ca2+]i, and that the general defect of AIDS lymphocytes, rather than being ascribed to the initiating signal systems, is associated with later events related to DNA synthesis and proliferation.

Acquired Immunodeficiency Syndrome↗
PubMed1988

[Serum magnesium and heart arrhythmias in patients with pelvic-leg arteriosclerosis].

In 122 male patients with arteriosclerosis of pelvis and legs up to 5 resting electrocardiograms were registered in the course of 4 years. 5.2% of these electrocardiograms showed disturbances of rhythm. In these cases no significant differences in the serum magnesium level could be ascertained between patients with and without disturbances of rhythm.

Arrhythmias, Cardiac↗
PubMed1988

Proaggregatory and inhibitory effects of 2-O-ethyl analogues of platelet-activating factor (PAF) on human and rabbit platelets.

A series of 8 analogues of platelet-activating factor (PAF) in which both the acetyl group and the polar head are changed, were tested for biological activities on human and rabbit platelets in plasma. Two of these compounds, 1-O-hexadecyl-2-O-ethyl-rac-glycero-3-phosphoric acid-5'-trimethylammoniumpentyl ester and 1-O-hexadecyl-2-O-ethyl-rac-glycero-3-phosphoric acid-6'-trimethylammoniumhexyl ester inhibit selectively the PAF-induced aggregation response without showing any agonistic activity. Schild analysis revealed a competitive antagonism and KB values of 4.4 and 10.5 mumol/l, respectively. These results point to a crucial role of the distance between the phosphoryl group and the polar head for expression of PAF-antagonistic properties. Moreover, the substituent at the 2-position was found to influence predominantly the agonistic behaviour.

Animals↗
PubMed1988

Serological response in patients with chronic asymptomatic human immunodeficiency virus infection.

To examine a possible relationship between decreased immune function and serological parameters, such as human immunodeficiency virus (HIV) antigenaemia and the quality and quantity of whole virus antibodies and antibodies against the major core protein p24, we investigated 160 healthy HIV infected individuals (CDC classification II and III). According to the number of T-helper lymphocytes (CD4 cells) these were divided into two groups (CD4 cell counts above or below 500/microliter), which according to the lymphocyte transformation response to pokeweed mitogen (response above or below 20% of control value) were further subdivided into two groups. Both the presence of HIV antigen (p = 0.022) and the absence of p24 antibodies (p = 0.001) correlated to a decreased CD4 cell count. Lack of p24 antibodies was more frequent than was the presence of HIV antigen among persons with decreased CD4 cell count and decreased response to pokeweed mitogen, indicating that absence of p24 antibodies may be an earlier marker of immune dysfunction than the presence of HIV antigen. In persons with p24 antibodies present, a low such titer was associated with a decrease of both immune parameters. Presence of HIV antigen and absence of p24 antibodies thus seems to correlate with the severity of immune dysfunction in healthy HIV infected individuals.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Differences between primed allogeneic T-cell responses and the primary mixed leucocyte reaction. Primed T cells become independent of the blocking effects of monoclonal antibodies against IL-1 beta and the CD5, CD11a (LFA-1), and CD11c (p 150,95) molecules.

Recent investigations have demonstrated that the primary mixed lymphocyte reaction (MLR) is dependent on certain accessory molecules, e.g. CD4 and LFA-1. We have compared the requirements of the primary MLR and the responses of alloreactive, primed lymphocytes (PL) by inhibition studies using monoclonal antibodies (MoAb) directed against (i) adhesion molecules belonging to the CD11 cluster of leucocyte antigens (CD11a, LFA-1; CD11b, MAC1 = CR3; and CD11c, p 150,95); (ii) various T cell-related antigens (CD2, CD4, CD5 and CD8); and (iii) recombinant IL-1 beta. The CD5-, CD11a- and CD11c-reactive MoAb significantly inhibited the primary MLR (inhibition = 25%, P less than or equal to 0.01; 48%, P less than or equal to 0.01 and 13%, P less than or equal to 0.05, respectively) but these MoAb did not inhibit the primed lymphocyte reaction (PLR). The CD11b-reactive MoAb had no significant influence on either of the responses. CD2- and CD4- reactive MoAb significantly inhibited both primary MLR (greater than 80%, P less than or equal to 0.01) and to a lesser extent the PLR (40-65%, P less than or equal to 0.01). A MoAb reactive with IL-1 beta inhibited the primary MLR (38%, P less than 0.01) and the purified protein derivative (PPD) induced lymphocyte transformation response (42%, P less than or equal to 0.01) of peripheral blood mononuclear cells (PBMC), whereas primed allogeneic responses to PBMC and Epstein-Barr virus (EBV) cell lines were unaffected by this MoAb. In addition, preliminary data indicated that PL seemed neither to bind exogenous IL-1 (as opposed to CD4+ PBMC) nor to possess membrane-bound IL-1. The differences between 'virgin' and primed, allogeneic T-cell responses indicate that profound changes in the functional capability of the responding T-cell population take place during the bulk expansion. The results indicate that during repeated priming with alloantigen and bulk expansion, the proliferative response of T lymphocytes becomes independent of (i) the interaction with the CD11 adhesion molecule(s), (ii) the CD5 molecule, and (iii) the cytokine IL-1 beta.

Antibodies, Monoclonal↗
PubMed1988

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↗
PubMed1988

A platelet disorder due to a structural abnormality of membrane glycoprotein Ib.

In a patient with mild bleeding symptoms, decreased platelet spreading and defective aggregation, an abnormal membrane glycoprotein (GP) was detected. Staining and surface labelling characteristics, cleavage by calcium-activated protease and decreased content of normal GP Ib in the platelets of the patient and 3 related carriers of the abnormal glycopeptide suggest that the additional component is a genetic GP Ib variant structurally characterized by an increase of about 20,000 in apparent Mr of the large subunit GP Ib alpha. The observed hereditary membrane GP abnormality although present in heterozygous state may be causally related to the defect of platelet function.

Adult↗
PubMed1988

Effects of synthetic analogues of platelet-activating factor (PAF) on fibrinolytic activity in the rat.

PAF and structural analogues were investigated for their in vivo effects on fibrinolytic activity (FA) in the rat. The i.v. administration of 1 and 4 micrograms/kg PAF caused a dose-dependent increase in FA which was shown to be attributable to the release of tissue-type plasminogen activator (t-PA). 1-O-hexadecyl-2-O-ethyl-glycero-3-phosphoric acid-2'-N-propargyl-N,N'- dimethylammoniumethyl ester (I) and 1-O-hexadecyl-2-(n-propyl)-propanediol-3-phosphocholine (II) increased FA according to their proaggregatory activity. In contrast, 1-O-hexadecyl-2-O-ethyl-rac-glycero-3-phosphoric acid-5'-trimethylammoniumpentyl ester (III), a competitive antagonist of PAF, reduced the PAF induced increase of FA by 30%. Under identical conditions BN 52021 given at 1 and 10 micrograms/kg amounts diminished the effect of PAF by 47 and 77%, respectively. These results indicate that the PAF induced PA release in vivo is receptor mediated.

Animals↗
PubMed1988

[Use of a tooth graft in mentoplasty. Apropos of a case].

The author reports the case of a young female patient who consulted for mentoplasty, during which a dental fragment, derived from the germ of a wisdom tooth, was used as an interposed graft. The result at 8 months revealed perfect tolerance and a tendency to osteo-integration of the tooth and demonstrates the simplicity of the procedure.

Adolescent↗
PubMed1988

Effect of specific antagonists on PAF-induced platelet aggregation and release of plasminogen activator.

We investigated the inhibitory effects of two synthetic phospholipids KO-286,001 and KO-286,006 on the platelet-activating factor (PAF) induced release of plasminogen activator (PA) in the isolated pig ear preparation as well as aggregation of pig platelets. The action was compared with that of the natural PAF antagonist BN 52021. The activator release induced by 5 x 10(-9) mol/l PAF was inhibited by 10(-6) mol/l KO-286,006, whereas BN 52021 and KO-286,001 had no effect. All three PAF antagonists tested inhibited the aggregation in a dose-dependent manner. Comparison of the IC50 values confirmed the considerably lower inhibitory action of BN 52021 and KO-286,001. Our results suggested that similar receptor sites are involved in both PAF activities tested and furthermore, that are species differences in the inhibition of PAF effects.

Animals↗
PubMed1987

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↗