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Biomedical subjects

H M Wolf

Publications and source records attributed to H M Wolf.

49 records · Page 3Linked to original sources
PubMed1990

Prophylaxis of necrotizing enterocolitis by oral IgA-IgG: review of a clinical study in low birth weight infants and discussion of the pathogenic role of infection.

Necrotizing enterocolitis, a severe gastrointestinal disease in the neonatal period, affects primarily premature infants. Perinatal complications that predispose the neonate to systemic hypoxia are frequent in infants with necrotizing enterocolitis. Ischemia of the intestinal mucosa may facilitate the invasion of enteric microorganisms in stressed low birth weight infants. Geographical and temporal clustering of outbreaks of the disease and the termination of epidemics by standard infection control underline the importance of infectious agents in the development of this disease. Several studies have established the immunoprotective effect of orally administered antibodies against infection of the gastrointestinal mucosa in children and adults. Anecdotal evidence suggested that feeding of human immune globulin might have a positive effect on the incidence of necrotizing enterocolitis in premature infants. This paper reviews a prospective, randomized, controlled trial of the efficacy of an oral immune globulin preparation (published in detail in the New England Journal of Medicine, Vol. 319, pp 1-7, 1988) and discusses the pathogenic role of infection in necrotizing enterocolitis.

Administration, Oral↗
PubMed1990

Multiple infusions of human intravenous immunoglobulin in chimpanzees do not lead to immune elimination.

Administration of human i.v. immunoglobulins was shown to lead to a permanent increase in IgG1 and IgG2 levels in chimpanzees. Half-lives of human IgG1 and IgG2 in chimpanzees were comparable to those found in humans, and no signs of immune elimination were observed. Furthermore, long-term treatment of chimpanzees had no effect on the percentage of immunoregulatory T cells (CD2+, CD4+ and CD8+ T cells) as determined by FACS analysis. In addition, serum IgM levels in chimpanzees were found to be comparable to those in humans, whereas the chimpanzees' IgG levels are slightly elevated due to higher concentrations of IgG2 and, in particular, IgG4.

Animals↗
PubMed1989

Interleukin-1 production in acute viral hepatitis.

The in vitro production of interleukin-1 in 15 children with acute hepatitis A and five children with acute hepatitis B was determined by measuring lymphocyte activating factor secreted by peripheral blood monocytes in a thymocyte proliferation assay. Aluminium hydroxide induced production of lymphocyte activating factor was significantly lower in patients with acute hepatitis A as well as patients with hepatitis B as compared with healthy control subjects. In both forms of acute viral hepatitis production of lymphocyte activating factor was severely depressed during the first week, increased gradually during the further course of the illness, but did not reach normal concentrations within the first three weeks after onset of the acute symptoms of the disease. No correlation could be found between in vitro production of lymphocyte activating factor and the severity of liver disease as estimated by the rise of serum concentrations of transaminases, bilirubin, or several parameters of acute phase reaction (alpha 1 antitrypsin, C reactive protein, erythrocyte sedimentation rate). The reduced production of interleukin-1, as assessed by determination of lymphocyte activating factor, could explain the only moderate acute phase reaction seen during acute viral hepatitis.

Acute Disease↗
PubMed1988

Phagocytosis of serum-opsonized zymosan down-regulates the expression of CR3 and FcRI in the membrane of human monocytes.

The effect of iC3b receptor (CR3)-mediated phagocytosis on the expression of CR (C3b receptor, CR3) and IgG FcR (FcRI, FcRII) has been investigated by using serum-opsonized zymosan as a multivalent ligand for CR3. Sixteen hours after a short (1-h) pretreatment of human monocyte monolayers with zymosan opsonized with human AB serum (250 micrograms/ml), CR3 expression (as assessed by flow cytometric analysis with mAb Mo1) was significantly reduced by 59 +/- 3% (mean +/- SEM, n = 15, p less than 0.001). Concomitant with CR3 down modulation, FcR binding activity (as assessed by binding of IgG-coated E) was also found to be decreased to 41 +/- 4% of control (n = 7, p less than 0.001). Reduced FcR function was paralleled by a decrease in the expression of FcRI (as assessed with mAb 32.2). This FcRI modulation was not caused by zymosan-bound IgG because zymosan opsonized with agammaglobulinemic serum equally down regulated CR3 and FcRI expression. Pretreatment with zymosan opsonized with human AB serum, however, did not change the expression of other IgG and C-binding sites such as FcRII (examined with mAb IV.3 and 2E1) and CR1 (assessed with mAb 57F) as well as of unrelated cell membrane structures (beta 2m, MHC class II). In contrast, co-modulation for FcR function and CR3 expression induced by polymeric IgG is accompanied by a decreased expression of FcRII. These data indicate that interaction of a specific receptor with its ligand not only changes the expression of the receptor triggered, but has also a modulating effect on other receptor systems on the same cell.

Antigens, Differentiation↗
PubMed1988

Prevention of necrotizing enterocolitis in low-birth-weight infants by IgA-IgG feeding.

In a randomized clinical trial, we evaluated the efficacy of an oral immunoglobulin preparation (73 percent IgA and 26 percent IgG) in reducing the incidence of necrotizing enterocolitis in infants of low birth weight for whom breast milk from their mothers was not available. A total of 434 infants weighing between 800 and 2000 g were eligible for entry in the study. Of these, 255 were withdrawn - 234 during the first week of the study because breast milk from their mothers became available (123 in the treatment group and 111 in the control group), and 21 because of violations of protocol or because breast milk became available after the first week. The duration of follow-up was 28 days. Among the infants for whom breast milk did not become available during the study, there were no cases of necrotizing enterocolitis among the 88 receiving oral IgA-IgG, as compared with six cases among the 91 control infants (P = 0.0143). Of the infants withdrawn from the study, two assigned to the control group had necrotizing enterocolitis. We conclude that the oral administration of IgA-IgG may prevent the development of necrotizing enterocolitis in low-birth-weight infants.

Administration, Oral↗
PubMed1988

Identification of individuals at increased risk for AIDS among clinically asymptomatic homosexuals and abusers of intravenous drugs.

Immunological parameters previously shown to constitute an increased risk for progression towards AIDS have been observed in clinically asymptomatic individuals considered to be at risk for this syndrome. These parameters include severely decreased numbers of T helper cells (count below 400/mm3 blood for CD4+ cells were detected in 7 our of 33 HIV antibody-positive, asymptomatic homosexuals and in 3 out of 29 HIV antibody-positive, asymptomatic drug abusers) and elevated serum IgA and IgM levels (found in 7 to 30 percent of these subjects). Furthermore, up to 60% of risk group members showed a decreased lymphoproliferative response to tetanus toxoid as compared to only 11% of so-called low responders in the simultaneously tested healthy controls. Finally, the capacity to mount an immune response to viral glycoproteins was found to be impaired in individuals at risk for AIDS, as indicated by a low serum level of antibodies to tick-borne meningoencephalitis virus antigen in recently vaccinated subjects.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Comparable modulation of human monocyte functions by commercial factor VIII concentrates of varying purity.

Our previous observation on immune modulation induced by a given factor VIII (F VIII) concentrate preparation was extended by showing that the immune-modulating capacity is a more general feature of F VIII products and is independent of product purity. Interaction of human monocytes with therapeutic concentrations of various F VIII concentrates (0.2 to 2 IU F VIII/mL, six different F VIII concentrates from four manufacturers) led to a significant reduction in the expression of IgG Fc receptors in the membrane of these cells (F VIII concentrate-induced downmodulation of the receptor). This Fc receptor downmodulation was achieved by a short (1-hour) incubation of human monocytes with F VIII concentrates 16 hours prior to the Fc receptor assay and did not correlate with the respective product's IgG content. Although the IgG concentrations of the different products varied greatly (from 1.0 to 177.3 mg/1,000 IU F VIII), all products behaved comparably with respect to Fc receptor downmodulation (F VIII-treated monocytes: 34% +/- 7% to 44% +/- 4% rosette-forming cells; controls in the absence of F VIII: 83% +/- 5%). Furthermore, we also were able to demonstrate that heat treatment of F VIII, now used by virtually every manufacturer to eliminate contaminating viruses, had no effect on the respective products' Fc receptor-modulating capacity. The immune-modulating component was characterized as being a high-molecular-range compound containing IgG, IgM, F VIII, and blood group substances (most likely a combination of immune complexes and immunoglobulin aggregates). This compound is present in comparable amounts in both high-purity and intermediate-purity products and apparently copurifies with F VIII during the manufacturing process.

Antigen-Antibody Complex↗
PubMed1987

Results of a prospective controlled two-dose crossover study with intravenous immunoglobulin and comparison (retrospective) with plasma treatment.

Results of a two-dose (150 vs 500 mg/kg/month) crossover study with intravenous immunoglobulin (Endobulin, Immuno) (IVIG) carried out on 12 children with primary immunodeficiency syndromes over a period of 2 years are reported. Eight children had received human plasma (20 mg/kg/month) during the 2 years prior to the IVIG study. As these children had been thoroughly monitored during plasma treatment, a retrospective analysis of these data allowed for comparison with IVIG treatment. Children on low-dose IVIG therapy had significantly (P less than 0.01) fewer days with clinical illness, e.g., sinusitis, pneumonia, diarrhea, and arthritis, than did those receiving plasma treatment. High-dose IVIG therapy led to further significant clinical improvement. Lung function tests (MEF25) improved significantly as well. The difference between high- and low-dose therapy with respect to the improvement in clinical symptoms (e.g., cold, fever, otitis) was more pronounced in children with severe clinical symptoms at the initiation of the study. Children with fewer symptoms did comparably well on high- and low-dose treatment, except for those with acute febrile illness, which was less frequent in children on high-dose IVIG. Regular monitoring of liver enzymes in the group of patients on IVIG therapy gave no indication of the transmission of viral hepatitis in the course of the 2-year IVIG treatment.

Adolescent↗
PubMed1987

Effect of polymeric IgG on human monocyte functions.

Fc and iC3b receptors are involved in various biological functions of phagocytic cells, such as immune adherence and phagocytosis of opsonized particles, degranulation and superoxide generation. In the present study we examined the expression of specific receptors for the Fc portion of IgG (FcR) and for iC3b (CR3), a cleavage product of the third complement component, on human monocytes following in vitro treatment with polymeric and monomeric IgG. Interaction of polymeric IgG (fluid phase) with the monocyte membrane led to a concomitant modulation of both Fc and iC3b receptors. Monomeric IgG, however, down modulated Fc receptor expression only if surface bound. Under these conditions, no concomitant modulation of the iC3b receptor could be observed. The down modulation of Fc and iC3b receptors induced by fluid-phase IgG polymers was also accompanied by a decrease in monocyte functions as expressed by reduced Fc receptor-mediated phagocytosis, decreased release of oxygen metabolites following stimulation by aggregated IgG and opsonized zymosan, as well as in impaired killing of bacteria. These data suggest that a down modulation of Fc and iC3b receptors might have important implications for host defense mechanisms, since interaction with these receptors is required for the proper elimination of many pathogens.

Blood Bactericidal Activity↗
PubMed1987

A component of factor VIII preparations which can be separated from factor VIII activity down modulates human monocyte functions.

In this study we investigated different aspects of monocyte functions following interaction of monocytes (Mo) with therapeutic concentrations of factor VIII (F VIII) concentrate. A short (one-hour) treatment of normal Mo with F VIII concentrates led to a significant (P less than 0.001) down modulation of Fc receptors expressed in the Mo plasma membrane. This down modulation was accompanied by a decrease of Mo effector functions that was expressed by a reduced capacity of F VIII-treated Mo to release O2 radicals (40% of controls) and to kill bacteria (% killing: control Mo, 65%; F VIII-treated Mo, 24% to 51%). Further studies showed that the modulating activity was due to a contaminant present in F VIII concentrates (immune complexes or IgG aggregates). Fractionation using molecular sieving revealed that the modulatory activity was confined to a high-molecular range fraction (Mr greater than 1,270,000 daltons), while the fraction containing monomeric IgG had no effect. Further fractionation by affinity chromatography on protein A-Sepharose separated the coagulation activity (effluent) from the Mo function-modulating activity (eluate). We conclude that treatment with F VIII concentrates might contribute to an immunocompromised state in some hemophiliacs and facilitate opportunistic infections in these patients.

Antigen-Antibody Complex↗
PubMedDate not supplied

Immunomodulatory effect of immunoglobulins.

IVIG is clearly indicated as the treatment of choice on the basis of large clinical trials in a number of inflammatory and autoimmune diseases, e.g. Kawasaki disease, ITP, Guillain-Barré syndrome, etc. According to in vitro studies various mechanisms have been identified whereby IgG could modify immunologically mediated and inflammatory diseases. Fc-receptor blockade as well as true down-modulation of Fc-receptors, acting as a sump for activated complement components, have been demonstrated at the cellular level and in experimental animals. The possibility of interfering with the idiotype network has been discussed in connection with autoimmune diseases. Down-regulation of inflammatory cytokines as well as an increase in the production and release of IL-1 receptor antagonist appears to be of importance in inflammatory processes. Clinical studies have proven the efficacy of IVIG. Basic research has demonstrated its possible mechanisms of action; however, the question of exactly which mechanisms are responsible for the clinical efficacy in certain diseases still awaits clarification.

Animals↗