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L C Altman

Publications and source records attributed to L C Altman.

At least 55 records · Page 3Linked to original sources
PubMed1985

Defective neutrophil and monocyte motility in patients with early onset periodontitis.

Several studies have documented suppressed polymorphonuclear neutrophil (PMN) chemotaxis in most patients with juvenile periodontitis. In contrast, data regarding PMN chemotaxis in patients with rapidly progressive periodontitis are very limited, and monocyte (MN) chemotaxis and random migration of PMNs or MNs from these patients have not been studied previously. Accordingly, we examined cell motility of PMNs and MNs from 27 patients with rapidly progressive periodontitis, 5 patients with juvenile periodontitis, and 37 normal control subjects by using a microchamber technique and the synthetic peptide N-formylmethionyl-leucyl-phenylalanine (FMLP) as the chemoattractant. As a group, PMNs and MNs from patients with rapidly progressive periodontitis manifested significantly enhanced random migration relative to control cells (P less than 0.001), suppressed directed migration (chemotaxis) at FMLP doses of 10(-9) and 10(-8) M (P less than 0.05), and enhanced directed migration at a dose of 10(-6) M FMLP (P less than 0.01). In contrast, PMNs from patients with juvenile periodontitis exhibited normal random migration, and directed migration was significantly suppressed at all doses of FMLP tested (P less than 0.05). An abnormality of either PMN or MN motility was observed in 26 of 27 patients with rapidly progressive periodontitis. Enhanced random migration was seen in PMNs in 63%, MNs in 39%, and both cell types in 26% of the patients. Suppressed chemotaxis was seen in PMNs in 85%, in MNs in 74%, and in both cell types in 69% of the patients. The prevalence and magnitude of abnormalities in motility were somewhat lower in treated than in untreated patients. Thus, most, if not all, of this subgroup of patients with early onset, highly destructive periodontitis have abnormalities in PMN or MN motility, and these defects may differ from those seen in cells from patients with the juvenile form of the disease.

Adolescent↗
PubMed1985

Clinical and laboratory studies of a family with a high prevalence of juvenile periodontitis.

The form of periodontitis with onset at puberty and affecting predominantly the first molars and incisors is called juvenile periodontitis (JP). The disease has been the object of intense study because from its analysis may come insights into understanding other, more common, forms of periodontitis. We recently had the opportunity to study an unusual family in which both parents developed JP in their teens. We did clinical examinations, measured leukocyte chemotaxis, analyzed the pocket microflora, looked for serum antibodies against a large panel of putative periodontal pathogens and correlated the results. The couple had two affected and two unaffected children. One of the unaffected children was not available for study. Neutrophil chemotaxis was abnormal in both parents and in the two affected children, but not in the unaffected child. Actinobacillus actinomycetemcomitans accounted for 17.5% of the pocket flora isolated from one affected child and 2.5% of that from the unaffected child, but was not detected in the remaining family members. Antibodies specific for A. actinomycetemcomitans, Hemophilus aphrophilus and Eikenella corrodens were present in the serum of both affected children and for Capnocytophaga sputigena and C. ochracea in the father, but no antibodies directed against any of the species studied were found in the mother and the unaffected child. The distribution of disease in this family was more compatible with an X-linked dominant than with an autosomal recessive mode of inheritance. The correlations among presence or absence of disease, abnormal neutrophil chemotaxis and presence of serum antibodies reacting with A. actinomycetemcomitans were excellent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

Interferon production and tumor cell killing by human lymphocytes stimulated in mixed-lymphocyte culture.

The in vitro synthesis of interferon (IFN) by human lymphocytes stimulated in mixed-lymphocyte culture (MLC) was examined. The production of IFN in MLC was restricted to T lymphocytes and maximum levels of IFN were detected in supernatants from cells incubated for 5 to 7 days. The IFN produced was identified as IFN-gamma by antibody neutralization. To identify the T cell responsible for IFN production, purified T lymphocytes were separated into subpopulations after incubation in 5 mM theophylline. Theophylline-resistant (T-res) T cells retain the ability to form sheep erythrocyte (SRBC) rosettes and are depleted in IgG Fc receptor-positive T cells (T gamma cells). Theophylline-sensitive (T-sens) T cells fail to form rosettes after theophylline treatment and are enriched in T gamma cells. In addition, analyses using monoclonal antibodies showed that T-sens cells were enriched in OKM1-, HNK-1-, and 7.2-positive cells and T-res cells contained increased numbers of 9.6- and OKT4-positive cells. Following MLC stimulation, equivalent levels of IFN-gamma were produced by T-res and T-sens cells and both subpopulations maintained natural killer (NK)-like cytotoxicity against K562 target cells. Addition of partially purified IFN-gamma to unstimulated T-res and T-sens cells resulted in the maintenance of NK-like cytotoxicity in a manner analogous to that observed after MLC. Additional experiments indicated that peripheral blood lymphocytes depleted of 9.6- or OKM1-positive cells by complement-mediated lysis were devoid of cytotoxicity against K562 cells. Furthermore, MLC stimulation of 9.6- or OKM1-depleted cells failed to restore cytotoxic activity. In summary, these experiments demonstrate that the maintenance of NK-like cytotoxicity by MLC-stimulated T cells is associated with the synthesis of IFN-gamma, that MLC stimulated T-res and T-sens T-cell subsets produce equivalent amounts of IFN, and that 9.6- or OKM1-positive cells are required for the maintenance of NK-like cytotoxicity in MLC.

Antibodies, Monoclonal↗
PubMed1984

Pulmonary bronchoalveolar cell and protein kinetics in dogs given total-body irradiation, autologous marrow grafts, and methotrexate.

Patients receiving allogeneic marrow transplantation for hematologic malignancies commonly are conditioned with total body irradiation (TBI) and given methotrexate (MTX) in an attempt to prevent graft-versus-host disease. To study the effects of TBI with or without MTX on bronchoalveolar cells and proteins, we performed sequential bronchoalveolar lavages in dogs before and after irradiation. Ten dogs received 9 Gy TBI followed by autologous marrow grafts. Six dogs were given no additional treatment and four also received MTX at 0.4 mg/kg on days 1, 3, 6, and 11- and then weekly until day 100. TBI alone resulted in a significant decrease in alveolar macrophages and lymphocytes with recovery after day 30. The addition of MTX resulted in a more profound and prolonged decrease in alveolar macrophages and lymphocytes. The addition of MTX was also associated with a significant increase in alveolar granulocytes with a concomitant rise in lavage protein content in one animal. Lavage fluid IgA levels remained constant. We conclude that the irradiation and chemotherapy used in marrow transplantation has significant pulmonary effects and may contribute to the pulmonary complications following marrow transplantation.

Animals↗
PubMed1984

Leukotriene B4 production by the human alveolar macrophage: a potential mechanism for amplifying inflammation in the lung.

Leukotriene B4 (LTB4) is a lipoxygenase product of arachidonic acid that has potent chemotactic activity for blood leukocytes. To assess the potential role of LTB4 in lung inflammatory responses, we investigated the production of LTB4 by human alveolar macrophages and determined its chemotactic activity for lung and blood phagocytes in vitro and in vivo. Human alveolar macrophages were stimulated with the calcium ionophore A23187 (10 micrograms/ml), and lipoxygenase products in the supernatants were isolated by high-performance liquid chromatography. Leukotriene B4 was the predominant arachidonate lipoxygenase product from the alveolar macrophages of 2 nonsmokers (17.3 +/- 2.7 ng/10(6) cells) and 3 of 4 smokers (23.4 +/- 14.8 ng/10(6) cells). Alveolar macrophages produced more LTB4 than did similarly treated peripheral blood neutrophils. Stimulated alveolar macrophages also produced 5-hydroxyeicosatetraenoic acid (HETE) and 2 isomers of LTB4: 5-(S),12-(R)-6-trans-LTB4 and 5-(S),12-(S)-6-trans-LTB4. Leukotriene B4 showed little chemotactic activity for alveolar macrophages in vitro and was a more potent chemoattractant for peripheral blood neutrophils than for monocytes (p less than 0.05). When instilled into the airways of anesthetized rats, LTB4 was less potent as an attractant for neutrophils and mononuclear cells than either zymosan-activated serum or bacterial-derived chemotactic factors. Leukotriene B4 production by alveolar macrophages may provide a mechanism by which phagocytes are recruited to the human lung during inflammatory processes.

Adult↗
PubMed1984

The injurious effect of neutrophils on pneumocytes in vitro.

Neutrophils have been implicated in the pathogenesis of pulmonary injury in many clinical entities, but in vitro studies of neutrophil-mediated pneumocyte damage are limited. To study the role of neutrophils in mediating pulmonary injury, we cocultured these cells with monolayers of human A549 pneumocytes and rat type II alveolar cells. As indexes of injury, we measured cell detachment from monolayers, frank cytolysis, and the effect on pneumocyte protein and DNA synthesis. Unstimulated neutrophils effected minimal lysis or detachment of both pneumocyte targets, but neutrophils stimulated with phorbal myristate acetate and other secretogogues produced marked target cell detachment without lysis, which was time- and dose-dependent. Supernatants of activated neutrophils were similarly effective, suggesting that the mediator was a stable, soluble substance. Catalase and superoxide dismutase were minimally inhibitory to neutrophil-mediated detachment, and neutrophils from patients with chronic granulomatous disease produced detachment comparable to that produced by normal neutrophils. Furthermore, target cells were quite resistant to reagent H2O2 and non-neutrophil-derived toxic oxygen species, further suggesting that oxidative injury was not a major factor in causing detachment. Target cells were susceptible to detachment by the neutral proteases, elastase and collagenase, whereas neutrophil-mediated detachment was markedly inhibited by neutral protease and elastase inhibitors. Human and bovine serum were also inhibitory, but not albumin or pepstatin A, an acid protease inhibitor. Furthermore, we found that activated neutrophils inhibited protein and DNA synthesis of pneumocyte targets, providing additional evidence that neutrophils cause nonlytic injury to pneumocytes. These studies indicate that stimulated neutrophils cause nonlethal injury to pneumocytes, as measured by detachment from monolayers, and inhibition of vital intracellular synthetic functions. The mechanism of detachment is through the action of granule neutral proteases, rather than toxic oxygen metabolites, and is probably due to degradation of the extracellular matrix of the pneumocytes. In vivo, detachment could lead to desquamation of alveolar cells and increased permeability of the epithelial barrier of the lung. Similarly, inhibition of protein and DNA synthesis could have profound effects on the normal function and replication of alveolar epithelium.

Animals↗
PubMed1984

The comparative toxicity of volcanic ash and quartz. Effects on cells derived from the human lung.

To evaluate the effects of volcanic ash and free crystalline silica on cells derived from the air space of the human lung, we compared the effects of these minerals on human alveolar macrophages and A549 cells, which are derived from human type II pneumocytes. The quartz was markedly cytotoxic to alveolar macrophages and A549 cells and stimulated the release of neutrophil chemotactic activity from alveolar macrophages. By contrast, volcanic ash was much less toxic to human alveolar macrophages and A549 cells and did not stimulate the release of neutrophil chemotactic activity from alveolar macrophages. The results with A549 cells were similar to findings with isolated type II pneumocytes recovered from rat lungs. Secretory IgA, IgG, and albumin, which are normally present in the air spaces of the lung, reduced the cytotoxicity of quartz in a dose-dependent manner. These results suggest that in the human lung quartz, but not volcanic ash, may cause direct damage to cells in the alveolar spaces and lead to the recruitment of phagocytes from the bloodstream to the lung.

Adult↗
PubMed1984

Clinical, microbiological and immunological studies of a family with a high prevalence of early-onset periodontitis.

Extensive clinical, laboratory and microbiological studies were performed on members of a family with an unusually high prevalence of early-onset severe periodontitis. Clinical observations included intraoral photographs and assessment of inflammation, plaque, probing depths and bone loss. Pocket bacteria were sampled, cultivated and identified. Immunological studies included assessment in vitro of neutrophil (PMN) and monocyte (MN) chemotaxis, assessment of PMN phagocytosis and other functions using the iodination assay, measurement of serum opsonic and chemoattractant activities and determination of levels of serum antibodies specific to various putative periodontal pathogens. The proband, a 19-year-old white woman, had rapidly progressive periodontitis (RP). Of her six siblings available for study, all had juvenile periodontitis (JP), and both parents had been edentulous since early adulthood. Early edentulism and recurrent infections, especially otitis media, were prevalent in the forebearers, especially on the maternal side. Two married sisters of the proband had young male children with recurrent infections. Abnormalities in leukocyte chemotaxis were found in the proband, in two of her siblings and in both parents. The pocket flora was predominantly Gram-negative, anaerobic rods with a high prevalence of Bacteroides species, and serum antibodies specific to Bacteroides species were detected in the sera of five of the seven patients studied. Actinobacillus actinomycetemcomitans was not found in any of the pockets studied, nor were antibodies specific to any of the three known serotypes of this bacterium detected in the serum of any of the patients. There was a relatively good correlation between the bacterial species isolated from the periodontal pockets and the antibodies found in the serum. PMN iodination and serum opsonic activity were normal in all of the patients. Thus not all JP patients have detectable Actinobacillus species in their periodontal pockets, nor do all have antibody detectable with the techniques we used specific to these bacteria in their serum. In contrast, JP patients may have Bacteroides species in their periodontal pockets and antibody specific to Bacteroides species in their serum. Although abnormal leukocyte chemotaxis is generally common in RP and JP patients, in this family the correlation between this defect and the presence of these diseases was poor.

Adolescent↗
PubMed1983

Spontaneous and alloantigen-induced cytotoxicity by human T-lymphocyte subpopulations.

Freshly isolated human T lymphocytes were separated into two subpopulations on the basis of their ability to form E rosettes after treatment with the phosphodiesterase inhibitor, theophylline. T cells that retained the ability to form E rosettes (T-res cells) and those that failed to form E rosettes (T-sens cells) were assayed for natural killer (NK) cell activity against 51Cr-labeled K562 tumor cells and for the ability to proliferate and kill allogeneic cells in mixed-lymphocyte culture (MLC). T-sens cells were highly enriched for NK activity. In contrast, T-res cells exhibited much less activity than either T-sens or unseparated T cells (T-sens greater than unseparated T cells approximately equal to unseparated PBL approximately equal to non-T cells greater than T-res cells). T-sens cells were poorly responsive to allogeneic cells in proliferation assays and demonstrated greater levels of cytotoxicity against allogeneic cells than T-res cells. T cells stimulated with allogeneic lymphocytes for 7 days were cytotoxic for K562 targets while comparably stimulated non-T cells and T cells cultured with medium were not cytotoxic. Cold target inhibition experiments suggested that within the T-sens subset there are overlapping populations which mediate cytotoxicity against K562 and allogeneic cells. These studies demonstrate that freshly isolated human T cells are composed of heterogeneous populations which differ in their ability to mediate NK and to generate cytotoxic T lymphocytes in culture.

Binding, Competitive↗
PubMed1983

Comparative effects of inhaled volcanic ash and quartz in rats.

To investigate the relative toxicities of inhaled volcanic ash and quartz, we exposed matched groups of rats to either respirable volcanic ash (100 mg/m3), quartz (100 mg/m3), or clean air only for 6 h daily for 10 days. Thereafter, we examined animals sequentially for as long as 9 months, and measured changes in lung histopathologic aspects, air-space cells and lipids, and lung density. Neutron activation studies demonstrated that 3.3% of the inhaled daily dose of volcanic ash was detectable in the lung parenchyma. Volcanic ash was less toxic to the lung than quartz. Immediately after exposure, the lungs of animals treated with volcanic ash had ultrastructural evidence of damage to type I pneumocytes and early alveolar edema formation. By contrast, quartz-treated animals had an intense acute injury, with intraalveolar accumulation of lipid, protein, macrophages, and granulocytes. Six months after exposure, animals treated with volcanic ash had moderate interstitial thickening and fibrosis, whereas the quartz-treated animals had severe pulmonary fibrosis. Quartz, but not volcanic ash, caused a marked increase in lavage granulocytes, protein, and phospholipids. Lung density increased in quartz-exposed, but not in volcanic-ash-exposed animals. These data indicate that volcanic ash is less harmful to the lung parenchyma than is quartz. Persons exposed to volcanic ash for short periods are at much less risk of subsequent lung damage than are those who are exposed to similar amounts of quartz in the workplace.

Absorptiometry, Photon↗
PubMed1983

The effects of severe protein-calorie malnutrition on antibacterial defense mechanisms in the rat lung.

Protein-calorie malnutrition (PCM) impairs systemic immunity in humans and animals, but its effects on regional defense mechanisms in the lung are not clear. Therefore, we investigated lung phagocytic antibacterial defenses in vivo and in vitro in an animal model of PCM. Matched groups of weanling rats consumed Isocaloric diets containing either 0.8% (PCM) or 24% protein (Control, C). A third group of animals was fed the C diet in restricted amounts to match the daily caloric intake of the PCM animals (pair-fed control, PF). After 4 wk on the diet, PCM animals were hypoproteinemic, hypoalbuminemic, and anemic and had depressed systemic cell-mediated immunity. In vivo, the lung clearance rate of Listeria monocytogenes was markedly delayed in PCM animals (% bacterial recovery at 9 days, mean +/- SE:PCM = 120 +/- 25.1; PF = 5.2 +/- 3.0; C = 0.6 +/- 0.6; p less than 0.001 for PCM versus C). Only 36% of the PCM animals survived for 9 days after Listeria exposure, whereas more than 94% of the C and PF animals survived (p less than 0.01). Recruitment of macrophages to the lungs of PCM animals after Listeria aerosolization was markedly impaired compared with that in the PF and C animals (p less than 0.001). By contrast, lung clearance rates of 2 pyogenic organisms, Staphylococcus aureus 502a and Pseudomonas aeruginosa 177, were similar in all groups. In vitro, alveolar macrophage chemotaxis toward zymosan-activated serum, and microbicidal activity against Staphylococcus epidermidis were also similar in all groups of animals. Our findings indicate that in the rat, PCM impairs the pulmonary clearance of L. monocytogenes, and that this defect is associated with impaired macrophage recruitment to the lung after Listeria inhalation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Rapidly progressive periodontitis. A distinct clinical condition.

We report radiographic, clinical, historical, and laboratory observations on seven patients selected to illustrate the features and characteristics of rapidly progressive periodontitis, with the aim of establishing this disease as a distinct clinical entity. This form of periodontitis is seen most commonly in young adults in their twenties, but it can occur in postpubertal individuals up to approximately 35 years of age. During the active phase, the gingival tissues are extremely inflamed and there is hemorrhage, proliferation of the marginal gingiva, and exudation. Destruction is very rapid, with loss of much of the alveolar bone occurring within a few weeks or months. This phase may be accompanied by general malaise, weight loss, and depression, although these symptoms are not seen in all patients. The disease may progress, without remission, to tooth loss, or alternatively, it may subside and become quiescent with or without therapy. The quiescent phase is characterized by the presence of clinically normal gingiva that may be tightly adapted to the roots of teeth with very advanced bone loss and deep periodontal pockets. The quiescent phase may be permanent, it may persist for an indefinite period, or the disease activity may return. Most patients with rapidly progressive periodontitis have serum antibodies specific for various species of Bacteroides, Actinobacillus, or both, and manifest defects in either neutrophil or monocyte chemotaxis. Affected patients generally respond favorably to treatment by scaling and open or closed curettage, especially when accompanied by standard doses of antibiotics for conventional time periods. A small minority of patients do not respond to any treatment, including antibiotics, and the disease progresses inexorably to tooth loss even in the presence of aggressive periodontal therapy and maintenance. At the present time it is not possible to distinguish prior to treatment which individuals will respond to therapy and which will not.

Adult↗