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Biomedical subjects

L C Altman

Publications and source records attributed to L C Altman.

At least 73 records · Page 4Linked to original sources
PubMed1982

Severe recurrent bacterial infections associated with defective adherence and chemotaxis in two patients with neutrophils deficient in a cell-associated glycoprotein.

We studied two patients with delayed umbilical cord detachment, recurrent bacterial infections, inability to form pus, rapidly progressive periodontitis, and persistent leukocytosis. The phagocytes of both patients were strikingly abnormal in their ability to adhere to surfaces. The adherence of polymorphonuclear leukocytes to endotoxin-coated glass coverslips, glass beads, or nylon wool was markedly reduced. Scanning electron microscopy of the few adherent polymorphonuclear leukocytes from both patients showed a failure to flatten and form fine pseudopods. In vivo polymorphonuclear leukocyte and monocyte chemotaxis assessed by skin window and skin chamber methods was dramatically impaired, and in vitro chemotaxis was severely depressed. Chemiluminescence of zymosan- but not phorbol-stimulated polymorphonuclear leukocytes was markedly reduced. Allogeneic polymorphonuclear leukocytes transfused into these patients functional normally, indicating that the defect is intrinsic to the cells and not a secondary phenomenon. A 180-kilodalton glycoprotein normally present in the particulate fraction of polymorphonuclear leukocytes was found to be completely absent in Patient 1 and present in low concentration in Patient 2. We postulate that the glycoprotein deficiency interferes with the migration of polymorphonuclear leukocytes from the bloodstream into the interstitial space and to the site of infection.

Bacterial Infections↗
PubMed1982

Exacerbation of a lupus-erythematosus-like syndrome during treatment of non-C1-esterase-inhibitor-dependent angioedema with danazol.

A 70-yr-old man presented with symptoms of angioedema and a lupus erythematosus-like syndrome. Because initial studies showed a functional deficiency of C1 esterase inhibitor and low C4 levels, he was treated with danazol, an attenuated androgen that has proven to be effective in the treatment of angioedema associated with C1 esterase inhibitor deficiency. After treatment, the patient's C4 levels returned to normal and his angioedema resolved, but concurrently he experienced clinical and laboratory exacerbations of his lupuslike illness. Specifically, on two occasions after danazol treatment he developed arthralgias, myalgias, hematuria, and pleuritic chest pain, accompanied by increased titers of antinuclear antibodies and circulating immune complexes. Serum testosterone levels were decreased during these episodes. Because treatment with danazol was temporally associated with recurrent exacerbations of a lupuslike illness and low serum testosterone levels, we believe that this case is an example of sex hormonal modulation of a lupuslike disease in man.

Aged↗
PubMed1982

Effect of decreased salivation and pH on the adherence of Klebsiella species to human buccal epithelial cells.

To assess the role of reduced salivary flow and intraoral pH on gram-negative bacterial colonization of the oropharynx, we studied in vitro Klebsiella adherence to normal human buccal epithelial cells at various pH values and to buccal cells from patients with pathological xerostomia (decreased saliva flow). Reduced pH significantly increased adherence of Klebsiella pneumoniae 84 to normal buccal epithelial cells (P less than 0.001). In contrast, two clinical isolates of K. oxytoca showed no significant pH-dependent change in adherence. A corollary of this was that patients with pathological xerostomia had significantly increased adherence of K. pneumoniae 84 to their buccal epithelial cells as compared with normal controls (P less than 0.01). These results suggest that reduced salivary flow and the concomitant reduction of intraoral pH may predispose patients to bacterial colonization with K. pneumoniae.

Adhesiveness↗
PubMed1982

Alveolar macrophage kinetics and function after interruption of canine marrow function.

To study the kinetics and function of alveolar macrophages after interruption of marrow function, we performed serial bronchoalveolar lavages in dogs. The studies were performed before and after 9.0 to 9.5 Grey total body irradiation and marrow infusion. Monocytes had disappeared from the bloodstream by Day 7 after the irradiation. Alveolar macrophages were significantly decreased at Day 21. At Days 14 and 21 myeloperoxidase-positive alveolar macrophages were also significantly decreased. Beyond Day 30 the number of circulating monocytes, myeloperoxidase-positive and total alveolar macrophages had returned. Sex chromatin stains of alveolar macrophages obtained from a male dog that received female marrow indicated that the repopulating macrophages were of marrow origin. In vitro studies of alveolar macrophage migration and phagocytosis demonstrated increased activities beyond Day 30. These studies suggest that in this model the alveolar macrophage is dependent on the bone marrow for support and that the alveolar macrophage depletion may impair lung defense mechanisms.

Animals↗
PubMed1981

Role of cell-mediated immunity in Hymenoptera allergy.

Currently there is little information regarding the immunologic mechanisms responsible for large local reaction (LLR) after Hymenoptera stings. To investigate this question, we measured in vitro lymphocyte proliferation and delayed skin reactivity to venom antigens in 10 subjects with LLR (six with LLR only and four with LLR and systemic reactions), seven subjects with systemic reactions, and eight nonallergic controls. The lymphocyte response to venoms in the LLR group was greater than that in either the systemic reactor group (p less than 0.05) or the control group (p less than 0.001). In contrast, lymphoproliferative responses to Candida albicans, streptokinase-streptodornase, and phytohemagglutinin were comparable in the three groups. Forty percent of the LLR group had positive delayed skin tests to venom antigens, and none of the patients in the systemic reactor group had such responses. These findings suggest that cellular immune mechanisms play a role in the pathogenesis of LLR after Hymenoptera stings.

Candida albicans↗
PubMed1981

Glucocorticoid receptors in normal human eosinophils: comparison with neutrophils.

Saturation analysis with [3H]-dexamethasone was employed to measure glucocorticoid binding in purified preparations of human eosinophils and neutrophils. Eosinophils contained 10.8 +/- 1.3 x 10(3) high-affinity receptor sites per cell, with a dissociation constant (Kd) of 15.3 +/- 0.6 nM dexamethasone. Cortisol was capable of competing with [3H]-dexamethasone in the binding reaction, whereas progesterone, estradiol, estriol, and testosterone were less effective. Saturable glucocorticoid binding in neutrophils had a Kd of 17.7 +/- 0.8 nM dexamethasone with 11.1 +/- 0.8 x 10(3) sites per cell and displayed similar steroid specificity. These data indicate that normal human eosinophils have glucocorticoid receptors with characteristics similar to those in neutrophils and that in these cells ligand-receptor interaction can occur at physiologic glucocorticoid concentrations. Furthermore, these results suggest that certain glucocorticoid effects on eosinophils and neutrophils may be mediated through specific receptors.

Binding Sites↗
PubMed1981

Effects of corticosteroids on eosinophil chemotaxis and adherence.

Therapeutic doses of corticosteroids frequently induce eosinopenia; however, the mechanism(s) involved remain obscure. To investigate this question, we studied the effects of corticosteroids on eosinophil adherence and migration. Eosinophils from normal donors were prepared by dextran sedimentation and Hypaque gradient centrifugation to 45-96% purity. Adherence was measured by filtration of whole blood and isolated eosinophils through nylon wool columns. Before prednisone administration, adherence was 83.8+/-3.2% for eosinophils in heparinized blood and 82.1+/-3.2% for isolated eosinophils. 4 h after oral prednisone administration whole blood eosinophil adherence was reduced to 53.9+/-10.7%; at 24 and 48 h adherence was normal. In contrast, isolated eosinophils showed no decrease in adherence 4, 24, or 48 h after corticosteroid administration. Similarly, in vitro addition of hydrocortisone to isolated eosinophils at 0.01 and 2.0 mg/ml did not reduce adherence. Eosinophil migration was tested in modified Boyden chambers by "lower-surface" and "leading-front" methods, using zymosan-activated serum and buffered saline to assess chemotactic and random migration, respectively. In vitro incubation of eosinophils with hydrocortisone or methylprednisolone produced a dose-dependent inhibition of chemotaxis. Using lower-surface methods the minimal concentration effecting substantial inhibition was 0.01 mg/ml for both drugs. At 2.0 mg/ml hydrocortisone and methylprednisolone inhibited eosinophil chemotaxis 82.6+/-4.4% and 85.0+/-3.5%, respectively. Using leading-front chemotaxis techniques significant inhibition was detected at 0.001 mg/ml hydrocortisone. Eosinophils incubated and washed free of corticosteroids responded normally to chemoattractants, indicating that the inhibitory effect of these drugs was reversible. Hydrocortisone at 2 mg/ml inhibited random eosinophil migration, although this effect was not apparent at lower concentrations. Corticosteroids did not act as chemotactic factor inactivators and were not toxic as measured by trypan blue exclusion. Eosinophils obtained from donors who had received 40 mg of prednisone orally for four days showed normal chemotactic responses, probably reflecting the fact that the cells were washed free of plasma before testing. In contrast, incubation of eosinophils in plasma from donors who had received a 300-mg bolus of hydrocortisone induced 46.1+/-4.5% more inhibition of chemotaxis than did incubation in normal plasma. These results indicate that: (a) eosinophil adherence is transiently reduced following in vivo corticosteroid administration, (b) eosinophil chemotaxis is inhibited by both in vitro and in vivo administration of corticosteroids, and (c) the chemotaxis inhibiting effect is nontoxic, cell-directed, dose-dependent and reversible. Inhibition of eosinophil adherence and chemotaxis may in part explain how corticosteroids produce eosinopenia and decrease the local accumulation of eosinophils.

Cell Adhesion↗
PubMed1980

Lymphocyte-derived chemotactic factor synthesis in initial genital herpesvirus infection: correlation with lymphocyte transformation.

Lymphocyte transformation and production of lymphocyte-derived chemotactic factor in response to herpes simplex virus antigen were studied in 15 patients with initial genital herpes and 10 controls. The patients underwent frequent genital examinations, viral cultures, and weekly immunological studies for a period of 11 weeks. The production of lymphocyte-derived chemotactic factor was maximal in week 1 of the disease and declined to control levels by week 6. In contrast, lymphocyte transformation was lowest in week 1, reached a maximum by week 4, and declined to control levels by week 11. Production of lymphocyte-derived chemotactic factor in week 1 was significantly lower in nine patients who developed signs or symptoms of systemic herpes infection than in six who had localized disease. In addition, a marked but transient decline in the production of this lymphokine was observed in patients at the time of clinical recurrence. Virus-specific lymphocyte transformation correlated inversely with the duration of genital pain and lesions and did not correlate with the presence of systemic signs or symptoms. These findings indicate that during initial genital herpes infection the dynamics of lymphocyte transformation and those of lymphocyte-derived chemotactic factor production are different, and that the generation of this lymphokine is an early component of the cellular immune response in this disease. Furthermore, adequate produce of lymphocyte-derived chemotactic factor may be important in restricting herpes simplex virus to the genital area and preventing disease recurrence.

Adult↗
PubMed1979

Impaired alveolar macrophage chemotaxis in patients with acute smoke inhalation.

Pulmonary infection is a leading cause of death in patients with smoke inhalation; however, few studies have evaluated the effects of inhaled smoke on the host defense mechanisms of the lung. In this study we investigated the effects of acute smoke inhalation on the random and chemotactic (stimulated unidirectional) migration of human pulmonary alveolar macrophages. Fiberoptic subsegmental pulmonary lavage was performed in 19 normal subjects (12 nonsmokers and 7 smokers) and 7 patients with smoke inhalation. After quantification of lavaged cell populations, random and chemotactic migration was measured using modified Boyden chambers. Zymosan-activated serum was used as a chemotactic stimulant. Mean +/- SE random migration was 6.2 +/- 0.8 cells per 20 microscopic fields in smoking control subjects, 5.7 +/- 0.7 in nonsmoking control subjects, and 5.2 +/- 0.7 in patients with smoke inhalation. These values are not significantly different. In contrast, the mean directed (chemotactic) migration of pulmonary alveolar macrophages was 26.5 +/- 1.9 in smoking control subjects, 22.7 +/- 3.0 in nonsmoking control subjects, and 11.4 +/- 1.4 in patients with smoke inhalation; the latter response was significantly different from that of the smoking (P less than 0.001) and nonsmoking (P less than 0.025) control subjects and the combined average of the 2 control groups (P less than 0.001. In vitro exposure of pulmonary alveolar macrophages to nontoxic doses of smoke produced similar impairment of chemotaxis. These findings may partially explain the enhanced susceptibility of patients with smoke inhalation to pulmonary infection.

Adult↗
PubMed1978

Defective monocyte and polymorphonuclear leukocyte chemotaxis in atopic disease.

Monocyte (MN) and polymorphonuclear (PMN) leukocyte chemotaxis was studied in 17 atopic children with hyperimmunoglobulinemia E (IgE), 9 age- and diagnosis-matched children with normal IgE levels, 10 pediatric controls, and 45 adult controls. Twenty-one of the 26 atopic patients had eczema, while 5 had only respiratory allergies. All patients were free of infection and receiving no systemic corticosteroids. Depressed PMN chemotaxis was found in only one patient. Defects of MN chemotaxis were detected in 8 of 17 atopic children with IgE and 2 of 9 with normal IgE values. Seven of 21 patients with atopic eczema and 3 of 5 with respiratory allergies had depressed MN chemoatxis. No evidence was found for a cell-directed chemotactic inhibitor in the plasma of patients with abnormal MN chemotaxis. These data demonstrate that: (1) MN chemotaxis is frequently depressed in uninfected atopic patients; (2) this abnormality occurs in patients with respiratory allergies as well as in those with eczema and is more prevalent in atopics with IgE; and (3) PMN chemotactic defects are uncommon in allergic patients. Whether abnormal MN chemotaxis is a primary or a secondary event in atopy requires further investigation.

Adolescent↗