Search PubMed⌕ Search

Biomedical subjects

J J Ellner

Publications and source records attributed to J J Ellner.

At least 199 records · Page 11Linked to original sources
PubMed1982

Haemophilus influenzae meningitis: the spectrum of disease in adults.

Fifteen cases of Haemophilus influenzae (HI) meningitis in adults occurring of Cleveland during the last 11 years are presented. The majority of patients had factors predisposing to infection such as otitis, pneumonia, diabetes or alcoholism. In addition, 7 of the 15 patients developed meningitis at various intervals following head trauma and neurosurgery, and 3 patients required dural repairs for CSF rhinorrhea. The diagnosis of meningitis may be difficult to establish resulting in delay in appropriate therapy in some cases. Nuchal rigidity was absent frequently; CSF lymphocytosis can be seen initially. The CSF Gram stain may be negative or the pleomorphic nature of the organism on Gram-stain may make distinction from other gram-negative organisms difficult. The majority of patients had meningitis due to non-Type B HI in contrast to previous reports of this illness in children and adults. One of our patients had beta-lactamase producing HI isolated from CSF. We believe that chloramphenicol should be included in the initial empiric therapy for adults with meningitis and gram-negative coccobacillary rods on Gram-stain or negative CSF Gram-stains.

Adolescent↗
PubMed1981

Augmentation of selective monocyte functions in tuberculosis.

Four monocyte functions were studied in patients with pulmonary tuberculosis and in healthy subjects. Circulating monocytes from four of six patients with tuberculosis functioned as suppressor cells; depletion of adherent cells from mononuclear cells obtained from the peripheral blood of these patients resulted in a 37-fold enhancement in tuberculin purified protein derivative-induced incorporation of [3H]thymidine. Monocytes from patients with tuberculosis exhibited increased adherence to plastic. Plasma from patients with tuberculosis also increased the adherence of monocytes from healthy subjects. However, basal and lipopolysaccharide-stimulated production of prostaglandin E2 by monocytes and tumoricidal activity were not altered in patients with tuberculosis. Thus, tuberculosis in humans is associated with the enhancement of selective monocyte functions. The dissociation in monocyte effector functions in human mycobacterial infection has potential implications not only for the course of tuberculosis but also for immunoadjuvant therapy.

Adult↗
PubMed1981

Suppression of lymphocyte responses by tuberculous plasma and mycobacterial arabinogalactan. Monocyte dependence and indomethacin reversibility.

During tuberculosis, exposure of monocytes to circulating factors may induce the suppressor activity observed in some anergic patients. To explore this possibility, we examined the effects of plasma pooled from 28 untreated tuberculosis (TB) patients and the mycobacterial cell wall polysaccharide D-arabino-D-galactan (AG) on the in vitro function of peripheral blood mononuclear cells (PBMC) from healthy donors. In the [3H] thymidine incorporation assay, stimulated responses of PBMC incubated in culture medium supplemented with TB plasma or co-cultured with 3.0 microgram/ml AG were depressed significantly when compared with control responses. Cytotoxicity and altered kinetics of stimulated DNA synthesis did not contribute to the observed suppression. TB plasma and AG-induced suppression of the PBMC response to purified protein derivative was monocyte dependent and indomethacin reversible. In addition, TB plasma and AG directly inhibited the phytohemagglutinin-stimulated responses of T lymphocytes. In a quantitative assay of monocyte attachment to plastic, both TB plasma and AG significantly increased monocyte adherence from basal levels. These effects on monocyte adherence were reversed with indomethacin or antibody to mycobacterial polysaccharide. In addition, TB plasma passed over an immunoabsorbent column of Sepharose-linked antibody to mycobacterial polysaccharide was depleted of the suppressive and monocyte-adherence augmenting factors. 3.0 microgram/ml AG stimulated a fivefold increase in prostaglandin E2 production by cultured mononuclear cells. Our data suggest that AG circulating alone or bound in immune complexes may account for the observed effects of TB plasma. Similar in vivo exposure may contribute to the cell-mediated suppression of lymphocyte responses in tuberculosis.

Cell Adhesion↗
PubMed1981

Defective suppressor cell generation in juvenile onset diabetes.

Lymphocytes of juvenile onset, insulin-dependent diabetics failed to generate suppressor cell activity after preincubation with concanavalin A (Con A). The mean suppression of the autologous proliferative response to phytohemagglutinin (PHA) was 6.1 +/- 7.8% (mean +/- SEM) in the diabetics and 34.0 +/- 4.9% in 9 age-matched healthy controls (p less than 0.01). Cell mixing experiments identified the defect to be in the generation of suppressor cells rather than in the responses to their action. Plasma of insulin-dependent diabetics had no effect on the generation of suppressor activity. In contrast to our findings in insulin-dependent diabetics, Con A preincubation of lymphocytes from 4 maturity onset diabetics induced normal suppression of PHA responses. Defective immunoregulation is present in insulin-dependent diabetes and may underlie autoimmunity.

Adolescent↗
PubMed1981

Spontaneous cytotoxicity of human peripheral blood mononuclear cells for the lymphoblastoid cell line CCRF-CEM: augmentation by bacterial lipopolysaccharide.

Spontaneous cell-mediated cytotoxicity (SCMC) of human peripheral blood mononuclear cells for a poor target, CCRF-CEM, a lymphoblastoid cell line, was rapidly and markedly elevated by E. coli lipopolysaccharide (LPS). SCMC for K562, a myeloid cell line sensitive to SCMC, was only slightly elevated by LPS. The cytotoxicities of both adherent and non-adherent mononuclear cells for CCRF-CEM were elevated. A response to LPS was found in Fc gamma R-positive and Fc gamma R-negative T cells. LPS increased the binding of non-adherent cells to both targets, but analysis of the binding suggests that a subsequent step, either triggering of the cytotoxic mechanisms or susceptibility of the target was the basis for the increased SCMC.

Adult↗
PubMed1981

Amphotericin B-induced resistance to Schistosoma mansoni.

Amphotericin B (AmB) increases host resistance against several infectious agents and tumors. We evaluated its effect on infections with the helminth Schistosoma mansoni. A single dose of 500 microgram i.p. or 25 microgram i.v. increased resistance in mice to a challenge with 500 or 100 S. mansoni cercariae. Schistosomula recovery from the lungs, 5 days after challenge, was reduced 33 to 40%. Adult worm recovery 8 wk after infection was reduced 36 to 43%, AmB was effective in protecting mice when given from 9 days before until the day of cercarial challenge but was ineffective 2 wk before or at all intervals after S. mansoni infection. To examine the mechanism of this resistance, we obtained peritoneal exudate cells (PEC) from animals treated with AmB and assessed their ability to kill schistosomula, the migrating larval stage of the parasite. Killing by adherent PEC 1 or 2 days after AmB treatment was the same as that of resident macrophages from untreated animals. Adherent PEC from animals 3 to 7 days after AmB treatment showed enhanced killing of schistosomula (38.0 plus or minus 3.0% at day 4, which exceeded control of 8.1 plus or minus 4.0%, p less than 0.01). These PEC also displayed increased killing of Staphylococcus aureus. When AmB was added to cultures of resident peritoneal adherent cells from untreated mice at 0.5 microgram/ml to 2.0 microgram/ml (concentrations not toxic to the organism), schistosomula killing was increased 1- to 6- fold. These findings demonstrate activation of murine macrophages by AmB in vitro and in vivo, which results in greater killing of this multicellular parasite and potentially contributes to enhanced resistance to infection.

Amphotericin B↗
PubMed1981

Generation of a soluble immune response suppressor factor (IRSF) by unstimulated leukocytes of healthy subjects.

Supernatants derived from unstimulated cultures of mononuclear leucocytes obtained from healthy subjects contained a factor(s) which consistently suppressed lymphocyte proliferative responses to antigens and mitogens. This factor(s) is produced by a non-adherent cell and was generated in vitro after 4 hr of culture. Cells from almost all healthy subjects produced this substance(s). Cell number and viability were not affected by it. Kinetic studies suggested that interference with antigen presentation was not the mechanism of its action. The release of this immune response suppressor factor(s) (IRSF) was not blocked by indomethacin and its biological activity was unrelated to levels of prostaglandin E2. Experiments with low-specific-activity thymidine showed that suppression was not due to release of unlabelled nucleotide. Preliminary characterization of IRSF revealed that it is heat-stable and partially dialysable through membranes with an exclusion size of 12,000 daltons. IRSF differs from previously reported soluble suppressor substances and may play a role in immunoregulation in health.

Adult↗
PubMed1981

Dichotomies in the reactivity to worm antigen in human schistosomiasis mansoni.

3H-thymidine incorporation was studied using peripheral blood mononuclear cells (PBMC) from 41 Egyptians with Schistosoma mansoni infection. The individuals were preselected to fall into 3 age-matched categories: asymptomatic with light and heavy infections and those with schistosomal hepatosplenomegaly. Seven uninfected individuals served as controls. PBMC from all groups were comparable in their responsiveness to phytohemagglutinin (PHA), streptokinase-streptodornase (SKSD), and the schistosome soluble egg antigen (SEA). However, DNA synthesis induced by soluble worm antigenic preparation (SWAP) differed significantly among these groups. The mean response to SWAP (delta cpm = experimental cpm minus control cpm +/- standard error) was markedly decreased in individuals with heavy infections (1,963 +/- 509) compared with those with light to moderate egg excretion (4,646 +/- 790; p less than 0.01). Moreover, 2 subgroups were discernible among patients with hepatosplenomegaly. Seven were unresponsive to SWAP (7659 +/- 231), whereas 13 had vigorous responses (14, 617 +/- 2263; p < 0.01). This is the first demonstration of an inverse relationship between specific immune responsiveness to adult worm antigens and intensity of infection in humans with schistosomiasis mansoni. The depressed lymphocyte reactivity in patients with heavy infection, whether cause or consequence of the parasite load, may perpetuate large worm burdens. Furthermore, the observations on patients with hepatosplenomegaly may reflect differing pathogenetic mechanisms.

Adolescent↗
PubMed1980

Role of arginase in killing of schistosomula of Schistosoma mansoni.

Nonspecific resistance to the multicellular organism Schistosoma mansoni can be induced in mice by several infectious agents. We utilized the observed genetic restriction of such acquired resistance to study the mediators of killing of the larval stage of S. mansoni in vitro. Adherent peritoneal cell monolayers from Corynebacterium parvum-treated C57BL/6J but not from C. parvum-treated BALB/cJ mice killed an increased proportion of schistosomula in 24 h. Activated macrophages (Mphi) from both strains exhibited enhanced H(2)0(2) production after incubation with the parasites or phorbol myristate acetate. Thus H(2)0(2) production was not associated with schistosomula killing. Moreover, schistosomula killing was unaffected by catalase or superoxide dismutase. In contrast, activated C57BL/6J (but not BALB/cJ) Mphi released fourfold more arginase into supernates than control Mphi. Schistosomula killing by these Mphi correlated with arginase content of the supernates, was exaggerated in arginine-poor medium, and could be blocked by the addition of arginine. Exogenous bovine arginase added to Fischer's medium without macrophages produced comparable parasite mortality. Our data suggest that arginase is a critical mediator of in vitro killing of this multicellular organism by activated macrophages.

Arginase↗
PubMed1980

Invasive primary cutaneous phycomycosis in diabetic leg ulcers.

Two cases of cutaneous phycomycosis in the form of diabetic leg ulcers were diagnosed by culture and biopsy demonstration of invasive fungal infection. The first patient had an infected vesicular skin lesion. Systemic amphotericin B therapy and repeated debridement were curative. A posttraumatic leg ulcer developed in the second patient in the setting of hyperglycemia and renal insufficiency. Aggressive infection necessitated a curative amputation. Phycomycetes can cause or complicate diabetic leg ulcers and such infections may require biopsy for early recognition and subsequent successful therapy.

Aged↗
PubMed1980

Comparative stimulation of granulocyte adherence and chemotaxis by bacterial products.

Many inflammatory stimuli increase both in vitro granulocyte adhesiveness and motility. The present investigation compared the effects of bacterial products on in vitro granulocyte adherence to nylon fiber and granulocyte motility. Escherichia coli endotoxin and Staphylococcus aureus and E. coli culture filtrates enhanced both motility and granulocyte adherence to nylon. Column chromatography of S. aureus culture filtrate demonstrated that similar molecular weight components stimulated both motility and granulocyte adherence. In contrast, endotoxin stimulated granulocyte adherence but not chemotaxis in plasma-free medium. In addition, a group D streptococcal culture filtrate enhanced motility but not adhesiveness of plasma-free granulocytes. These studies indicate that inflammatory stimuli may interact with granulocytes in concert to enhance both adhesiveness and motility, or they may interact independently to stimulate one in vitro function preferentially.

Biological Products↗
PubMed1980

Thromboxane A2 mediates augmented polymorphonuclear leukocyte adhesiveness.

We examined the role of prostaglandins and thromboxanes as mediators of plasma-dependent increased polymorphonuclear leukocyte adhesiveness induced by Escherichia coli lipopolysaccharide. The cyclo-oxygenase inhibitors-indomethacin and d,l-6-chloro-alpha-methyl-carbozole-2-acetic acid (R020-5720)-reduced lipopolysaccharide-induced adherence of polymorphonuclear leukocytes by 74 and 62%, respectively. In addition, inhibitors of thromboxane synthetase-imidazole, 9,11-azoprosta-5,13-dienoic acid, and 1-benzylimidazole-suppressed the stimulation of adherence by 31, 66, and 83%, respectively. Exogenous prostaglandins E(1), E(2), and F(2)alpha did not increase polymorphonuclear leukocyte adherence, nor were they detected in significant quantities in supernates of polymorphonuclear leukocytes exposed to lipopolysaccharide. However, inhibitors of both cyclo-oxygenase and thromboxane synthetase reduced increases in adherence induced by arachidonic acid (10 mug/ml), suggesting that lipopolysaccharide-mediated increases in adherence were due to an arachidonic acid product other than prostaglandin E(2) or F(2)alpha. 8,11,14-Eicosatrienoic acid, a precursor of monoenoic prostaglandins, did not enhance polymorphonuclear leukocyte adhesiveness. We next demonstrated lipopolysaccharide-stimulated generation, by polymorphonuclear leukocytes, of a labile, low molecular weight, dialyzable substance capable of enhancing the adherence of unstimulated leukocytes. In parallel experiments, a 10-fold increase in immunoreactive thromboxane B(2) over basal levels was detected after exposure of leukocytes to lipopolysaccharide. The inhibition of lipopolysaccharide enhancement of adherence by specific rabbit antibodies to thromboxane B(2) strongly supported a primary role for thromboxane A(2) as the mediator of the observed increases in adherence. Lipopolysaccharide-stimulated purified platelets did not increase leukocyte adherence, whereas thrombin-stimulated platelets did increase adherence. These studies suggest that lipopolysaccharide stimulates polymorphonuclear leukocytes to produce thromboxane A(2), which enhances their adhesiveness to nylon.

Cell Adhesion↗