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Biomedical subjects

J A Winkelstein

Publications and source records attributed to J A Winkelstein.

At least 127 records · Page 7Linked to original sources
PubMed1979

Activation of the alternative complement pathway by L-phase variants of gram-positive bacteria.

The present studies were performed to investigate the potential role of the alternative complement pathway in the host's defense against bacterial L-phase variants and to gain insight into the subcellular component of gram-positive bacteria responsible for activation of the alternative pathway. L-phase variants of Staphylococcus aureus and Streptococcus faecalis were able to activate the alternative pathway and consume C3 in C4-deficient guinea pig serum in amounts comparable to their respective bacterial-phase parent organisms. Activation of the complement system via the alternative pathway resulted in death of the L-phase variants. Membranes prepared from S. faecalis L-phase variants, by either osmotic lysis or mechanical disruption, retained their ability to activate the alternative pathway. Treatment of the membranes by three different methods (water washes, hot trichloroacetic acid, and cold trichloroacetic acid) resulted in a greatly diminished ability of the membranes to activate the alternative pathway. In addition, the extracts derived from the membranes by water washes and by cold-trichloroacetic acid treatment were able to activate the alternative pathway. These studies indicate that these L-phase variants can activate the alternative pathway and suggest that membrane-associated factors play a role in the alternative pathway activation by S. faecalis L-phase variants.

Animals↗
PubMed1979

Defective activation of the third component of complement in the sera of newborn infants.

The activation of the terminal complement components, C3--9, plays an important role in the host's defense against infection. In the present study, the ability of bacteria to activate the third component of complement (C3) in newborn serum was examined. A variety of bacteria were incubated in test sera at 37 degrees C for 30 min and the percent of available C3 that was activated was measured. Using one strain of Escherchia coli (no. 3), 32% (mean) of the available C3 was activated in sera from 18 newborns, as compared to 85% in sera from their mothers and 79% in sera from 13 normal adults (P less than 0.005). In contrast, using another strain of E. coli (N70), the percent of C3 activated in newborn sera (83%) was the same as in sera from their mothers (81%) or in sera from normal adults (73%). The defective activation of C3 in newborn sera by E. coli was not related to the presence of the K1 antigen. Newborn sera were also challenged with other bacterial species and the activation of C3 was deficient when tested with klebsiellae, but not with staphylococci or streptococci. The defect in newborn sera appeared to be due to a deficiency of a serum factor rather than to the presence of an inhibitor.

Adult↗
PubMed1979

Serum opsonic activity in rodent malaria: functional and immunochemical characteristics in vitro.

The functional and immunochemical characteristics of serum opsonic activity in rodent malaria were examined in the present study. Schizont- and late trophozoite-enriched populations of Plasmodium berghei-infected red blood cells (IRBC) were isolated on a Ficoll density-gradient and used in an in vitro phagocytosis system composed of serum and monolayer cultures of rat peritoneal macrophages. Hyperimmune serum augmented the phagocytosis of IRBC to a greater degree than did nonimmune serum. When either IRBC or macrophages were pre-incubated with serum, the phagocytosis-promoting factors acted on the IRBC rather than on the macrophages in a manner characteristic of serum opsonins. The opsonic activity was specific for IRBC since noninfected red blood cells were rarely phagocytized and were unable to absorb opsonic activity from serum. The opsonic activity of both hyperimmune and nonimmune sera was heat stable, and unaffected by agents known to inactivate or inhibit complement (cobra venom factor and ethylenediaminetetraacetic acid). Finally, the opsonic activity was identified in preparations of purified IgG isolated from both hyperimmune and nonimmune sera.

Animals↗
PubMed1979

Non-candidal infections in children with chronic mucocutaneous candidiasis.

Chronic mucocutaneous candidiasis (CMCC) is a clinical syndrome characterized by persistent and recurrent Candida albicans infections of the mucous membranes and skin often associated with immunodeficiency. In order to gain insight into the frequency and severity of non-candidal infections in children with CMCC, four patients with CMCC are described in detail and 60 previously reported cases are reviewed. Fifty percent of children with CMCC had significant infections with other fungi, bacteria and viruses. Recurrent bacterial pneumonias and bronchiectasis were a major cause of morbidity and mortality. In addition, there were a large number of infections, in both the lung and other sites, due to opportunistic organisms. Thus the clincial syndrome of CMCC includes not only mucocutaneous candidiasis, endocrine failure and autoimmune phenomena, but patients with CMCC also show a remarkable susceptibility to non-candidal infections. These non-candidal infections represent a serious cause of morbidity for patients with CMCC.

Bacterial Infections↗
PubMed1978

Abnormalities of the peripheral blood as a presenting feature of immunodeficiency.

The predisposition of immunodeficient patients to the development of peripheral blood abnormalities is well documented. Less often recognized is the presence of immune defects in patients who initially present with "idiopathic" forms of thrombocytopenic purpura or autoimmune hemolytic anemia in the absence of symptomatology indicative of an immuno-deficiency. In this report we describe two children, each of whom had intermittent and at times severe hemolysis and thrombocytopenia secondary to formation of autoantibodies. Although the initial clinical impression was the presence of an "idiopathic" form of platelet or red cell destructive phenomenon, subsequent observations demonstrated abnormalities of the immune system which affected both B and T lymphocytes. In one of the patients there was a marked deficiency of IgA with a moderate but progressive decrease in IgM and IgG. The other patient had a moderate decrease in IgA and a failure to sensitize to dinitrochlorobenzene. Both exhibited dysmorphic features, including small stature, abnormal dentition, hyperelasticity of the skin, and hyperextensibility of the joints. Neither had significant problems with bacterial, fungal, or viral infections. These observations highlight the importance of evaluating the immune system in children with "idiopathic" forms of hemolytic anemia or thormbocytopenia. Demonstration of these abnormalities can have important therapeutic implications and may also provide information regarding the etiology of the blood abnormalities.

Adolescent↗
PubMed1978

Protective effect of residual splenic tissue after subtotal splenectomy.

Studies in animals and clinical experience in man have demonstrated that splenectomy leads to increased susceptibility to infection with encapsulated bacteria. Splenic tissue has an excellent ability to regenerate, even when implanted into subcutaneous tissue or the abdominal cavity. These implants, however, do not protect against bacterial challenge despite the fact that a number of other functions can be restored. We therefore studied the ability of residual splenic tissue to protect against challenge following subtotal splenectomy in Sprague-Dawley rats. Subtotal splenectomy was performed on 48 animals in which approximately 75% of the spleen was removed and left with a branch of its normal blood supply; 48 animals underwent total splenectomy and 48 had sham operations. Six months after surgery the groups were challenged intravenously with type 25 pneumococci to determine the LD50 for each group. Animals that had undergone subtotal splenectomy were more resistant to pneumococcal challenge than were asplenic animals, but they were not as resistant as normal animals. In addition, there was marked delay in death in the animals with subtotal splenectomy as compared with asplenic animals. Thus residual splenic tissue after subtotal splenectomy appears to confer some degree of protection against pneumococcal challenge.

Age Factors↗
PubMed1978

Lack of protective effect of autotransplanted splenic tissue to pneumococcal challenge.

Studies in animals and clinical experience in patients have demonstrated that splenectomy may lead to an increased susceptibility to infection. The infections are usually caused by encapsulated bacteria such as penumococcus. It has been shown in a variety of experimental animals that autotransplanted splenic tissue is capable of regenerating into implants that are microscopically indistinguishable from normal spleen and of restoring a number of normal splenic functions. The response to intravenous challenge with Streptococcus pneumoniae, type 25, was therefore studied in control, asplenic, and autotransplanted Sprague-Dawley rats. Despite previous observations that a number of immune functions can be restored in this animal model by autotransplanted splenic tissue, the present study indicates that splenic tissue autotransplants do not restore the ability to resist intravenous pneumococcal challenge.

Animals↗
PubMed1978

The effect of complement depletion on the course of Sindbis virus infection in mice.

The course of Sindbis virus infection in 12-day-old BALB/c mice was altered significantly in animals depleted of the third component of complement (C3) by treatment with purified cobra venom factor (CoVF). Although the same percentage of C3-depleted and normal animals died (30%) after the subcutaneous inoculation of 1000 PFU Sindbis virus, the mean day of death was later in C3-depleted mice (8.4 days) than in controls (6.5 days). In addition, morbidity was prolonged in C3-depleted mice. Growth of virus at the inoculation site in the foot was not different; however, viremia was prolonged and the amount of virus in the brain was 1000-fold greater 6 days after infection in C3-depleted animals. These studies demonstrated that complement plays an important role in the host's response to Sindbis virus infection by participating in both beneficial and immunopathologic responses to the infection.

Aging↗
PubMed1977

Myasthenia gravis. Study of humoral immune mechanisms by passive transfer to mice.

To study the role of humoral factors in the pathogenesis of myasthenia gravis, we employed passive transfer of human serum fractions to mice. Immunoglobulins from 16 patients with myasthenia gravis were injected into mice daily for one to 14 days. Typical myasthenic features of reduction in amplitude of miniature end-plate potentials (mean change more than 50 per cent, P less than 0.005) or reduction in acetylcholine receptors at neuromuscular junctions (mean change more than 50 per cent, P less than 0.005) (or both) were produced by immunoglobulin from 15 of the 16 patients. Some mice showed weakness or decremental responses to repetitive nerve stimulation as well. The active fraction was identified as IgG by three different purification methods. Its effect was enhanced by the third component (C3) of the complement system, but the fifth component (C5) had no effect. These data suggest that the pathogenesis of myasthenia gravis often involves and antibody-mediated autoimmune attack on the acetylcholine receptors of the neuromuscular junction.

Acetylcholine↗
PubMed1977

Conjuctivitis and keratoconjunctivitis associated with primary immunodeficiency diseases.

Nineteen patients with a variety of well-defined primary immunodeficiency diseases were examined for ocular abnormalities. Eight patients with low levels, or absence, of all the major serum immunoglobulins had conjunctivitis or keratoconjunctivitis associated with bacterial infection. The remaining 11 patients, who had at least one immunoglobulin class present in normal concentration in the serum, showed no inflammatory ocular lesion. Absence of only IgA, the major tear immunoglobulin, did not predispose the eye to these lesions.

Adolescent↗