PubMed Health⌕ Search

Biomedical subjects

J L Levin

Publications and source records attributed to J L Levin.

At least 37 records · Page 2Linked to original sources
PubMed1994

The effect of soluble complement receptor type 1 on hyperacute rejection of porcine xenografts.

The use of xenografts (Xgs) from distantly related species to relieve the increasing shortage of organs for clinical transplantation is prevented by the occurrence of hyperacute rejection (HAR). This process, in which C activation plays a central role, cannot be inhibited with currently available immunosuppressants. In two clinically relevant xenotransplantation models, this study evaluated the effect of C inhibition using recombinant soluble complement receptor type 1 (sCR1) on HAR. In an ex vivo model in which porcine cardiac Xgs were perfused with human blood, cardiac function ceased within 34 min when the perfusate blood was untreated (n = 3). When the perfusate blood was treated with sCR1 (300 micrograms/ml), cardiac Xg function was maintained for up to 4 hr (n = 3). Immunohistologic examination of these Xgs demonstrated deposition of C3b/iC3b and C3d in Xgs perfused with untreated human blood but only C3d deposition in those Xgs perfused with sCR1-treated human blood. These findings are consistent with the cofactor activity of sCR1 for factor I-mediated degradation of deposited C3b/iC3b to C3d. Treatment with sCR1 also prevented the histopathologic changes of HAR observed when untreated blood was used as the perfusate. In an in vivo pig-to-primate heterotopic cardiac xenotransplantation model, in which porcine Xgs transplanted into untreated cynomolgus monkey recipients underwent HAR in 1 hr or less (n = 3), a single intravenous bolus of sCR1 (15 mg/kg) administered to the recipient immediately before Xg reperfusion markedly inhibited total and alternative pathway serum C activity and prolonged Xg survival to between 48 and 90 hr (n = 5). These studies confirm the important role of C activation in HAR of porcine cardiac Xgs by primates and indicate that sCR1 may be a useful agent for xenotransplantation.

Animals↗
PubMed1994

Occupational chronic bronchitis: does it mean anything?

A good deal of ambiguity exists surrounding the term chronic obstructive pulmonary disease. Although much information has been uncovered concerning cellular epithelial mechanisms, the inflammatory response, and airflow obstruction, considerable research still needs to be conducted to offer better diagnostic categorization and definition of the role of occupational and environmental agents in the development of obstructive lung disease. This article will review these ambiguities of definition, as well as difficulties in estimating disease prevalence. The pathology of occupational bronchitis as well as occupational etiologic factors, including coal dust, will be reviewed. The significance of airways obstruction as a prognostic factor for future morbidity and its relevance for prevention are discussed.

Bronchitis↗
PubMed1993

Airflow obstruction in nonsmoking, asbestos- and mixed dust-exposed workers.

Obstructive changes in small airways have been described in patients exposed to asbestos and other mineral dusts. The physiologic significance of these small airways abnormalities and their relationship to dust burden and alveolitis remain unclear. We performed bronchoalveolar lavage (BAL) in 30 nonsmoking and 30 age-matched smoking subjects, all with mild asbestos and mixed dust exposure, to determine if parameters of lung dust burden correlated with spirometric evidence of airflow obstruction. Seventeen of 30 nonsmoking subjects and 24 of 30 smoking subjects met spirometric criteria for airflow obstruction. There were significantly more obstructed subjects in both dust exposed groups (P < 0.05) than in an age-matched nondust exposed group. There was, however, no significant difference in the number of obstructed subjects between the smoking and nonsmoking groups. There was no correlation in either group between airflow obstruction and total or differential cell counts, ferruginous bodies, total asbestos fibers, or the percent of free silica in the particulate fraction recovered by BAL. We conclude that evidence of small airways obstruction occurs commonly in occupationally dust exposed subjects and appears to be related to dust exposure per se and not to alveolar inflammation or fiber retention, important factors in the development of alveolitis and interstitial lung disease.

Asbestos↗
PubMed1993

Evaluation of the systemic toxicity and pharmacokinetics of the immunoconjugate anti-B4-blocked ricin in non-human primates. Delivered by multiple bolus injections and by continuous infusion.

The systemic toxicity of an immunoconjugate of blocked ricin and the anti-CD19 monoclonal antibody, anti-B4, was studied in cynomolgus monkeys to evaluate its safety for use in humans. Anti-B4-blocked Ricin (Anti-B4-bR) is a highly cytotoxic immunoconjugate which can kill up to 5 logs of antigen positive target cells at concentrations easily achievable in blood. Subacute toxicity studies with Anti-B4-bR were performed in 20 cynomolgus monkeys and 4 rhesus monkeys, which, unlike humans, do not express the CD19 epitope recognized by the anti-B4 antibody on their B-lymphocytes. Anti-B4-bR was administered to cynomolgus monkeys by 5 daily intravenous bolus injections of 10 or 100 micrograms/kg/day, and non-conjugated blocked ricin was administered by 5 daily intravenous bolus injections of 30 micrograms/kg/day. Total doses of the conjugate of 200, 500, 1000 or 1500 micrograms/kg were also delivered to rhesus monkeys by continuous intravenous infusion over seven days. The clinical signs of toxicity, clinical pathology parameters, and gross and microscopic tissue changes associated with Anti-B4-bR were minimal to moderate where present, and primarily hepatic. In monkeys treated with 5 x 10 micrograms/kg of Anti-B4-bR, lesions were noticeable on day 7 after the start of the treatment but were less severe or absent on day 14, suggesting that the toxic effects were reversible. Clearance of the conjugate from the serum after bolus injections of Anti-B4-bR was evaluated by ELISA and demonstrated an initial t 1/2(alpha) of 1.4-2.0 h and a secondary t 1/2(beta) of about 14 h. Serum concentrations of Anti-B4-bR were about 10-20-fold lower at 24 h as compared to 1 h after each of the 5 bolus injections in monkeys. Continuous infusion of Anti-B4-bR in primates achieved plateau levels of the immunotoxin in blood for almost the entire duration of the infusion. The therapeutic utility of the Anti-B4-bR is currently being evaluated in patients with B-cell malignancies.

Animals↗
PubMed1992

What is a specialist? The role of board certification in occupational medicine.

A shortage of occupational medicine physicians exists for which a number of solutions have been proposed. The lack of board-certified specialists to address the increasingly complex issues encountered in this area of medicine has contributed to a credibility and identity crisis within the occupational medicine community. This article will review the significance of board certification and its importance for enhancing and preserving the specialty of occupational medicine.

Certification↗
PubMed1991

The usefulness of bronchoalveolar lavage in identifying past occupational exposure to asbestos: a light and electron microscopy study.

Fiberoptic bronchoscopy has permitted the development of lavage procedures for the collection of lung washes. In certain disease states this material may contain large numbers of phagocytic cells (macrophages and neutrophils). Since these phagocytes are the predominant "dust scavenger cells" in the lung, the assessment of their particulate burden as well as that of the overall lavage material has been suggested as a potentially important diagnostic tool. The studies to date have shown that the presence of ferruginous bodies is an indication of past occupational exposure. In the present study, a digestion procedure was carried out on bronchoalveolar lavage material collected from individuals who were occupationally exposed to asbestos and from samples obtained from the general population. The parameters used for distinguishing the source of these samples included both light microscopy assessment of the filters for the presence of ferruginous bodies and electron microscopic screening for the presence of uncoated fibers.

Adult↗
PubMed1989

Respiratory effects of outdoor air pollution.

Outdoor air pollution adversely affects human health and the quality of the environment. However, epidemiologic studies of these effects are difficult to control because of confounding variables such as age and cigarette smoking and the difficulty in estimating doses of pollutants. Drs Griffith and Levin discuss the relationship between major types of pollutants and increased morbidity and mortality from respiratory disease.

Air Pollutants↗
PubMed1988

A naturally occurring epizootic of simian agent 8 in the baboon.

An epizootic of genital lesions was observed on baboons (four Papio sub-species) housed in two different outdoor breeding corrals. Serological analysis revealed strong prevalence of antibodies to Simian Agent 8 (SA8). This herpesvirus was subsequently recovered from skin lesions and identified by restriction endonuclease digestion of infected cell DNA. Observations of lesion type, frequency and location were suggestive of venereal transmission. The remarkable similarity between infection resulting from SA8 in baboons and herpes simplex virus in man suggests that the baboon is an excellent model in which to study genital herpes virus transmission and infection.

Age Factors↗
PubMed1984

Pseudocoarctation of the aortic arch in a patient with Turner's syndrome.

Pseudocoarctation of the aortic arch is a rare congenital anomaly which resembles true coarctation by the presence of a narrowing in the descending thoracic aorta immediately distal to the origin of the left subclavian artery. However, it is differentiated from that entity by the absence of a significant hemodynamic obstruction and by the presence of aneurysmal dilatation proximal and distal to the area of narrowing. As a result, the commonly observed clinical findings of coarctation such as a prominent collateral circulation and decreased blood pressure in the lower extremities are not observed. "Kinking" or "buckling" are common adjectives used to describe the roentgenographic appearance of the aortic arch in this condition. The association of various congenital cardiac abnormalities with pseudocoarctation has been reported, and are similar to those commonly seen with true coarctation. We now present the first reported case of pseudocoarctation associated with a probable bicuspid aortic valve in a patient with Turner's syndrome.

Aortic Coarctation↗
PubMed1983

In vivo metabolism of dihomo-gamma-linolenic acid to bronchoactive products in the canine lung.

We investigated the effects of dihomo-gamma-linolenic acid (DGLA), the fatty acid precursor to the monoenoic prostaglandins, on pulmonary mechanics in the intact chest, artificially ventilated dog. Under conditions of normal airway tone, intravenously administered DGLA produced a modest, dose-related increase in lung resistance and decrease in dynamic lung compliance. These responses were approximately 30-100 times less than those produced by arachidonic acid. The bronchoconstrictive responses to DGLA were abolished by prior inhibition of the cyclooxygenase with indomethacin. PGD1 was equal in activity to PGF1 alpha in causing constriction of central and peripheral airways of the dog. PGE1 was without significant airway effects in these animals under conditions of resting airway tone. We conclude that DGLA is a moderately good substrate for the cyclooxygenase pathway enzymes of the canine lung, producing products having a predominantly bronchoconstrictive effect. This bronchoconstriction is most likely due to the synthesis of PGD1 and PGF1 alpha and is not due to the synthesis of lipoxygenase pathway products.

8,11,14-Eicosatrienoic Acid↗
PubMed1981

6-keto-PGE1 exhibits more potent bronchodilatory activity in the cat than its precursor, PGI2.

In anesthetized, vagotomized an mechanically ventilated cats, we investigated the bronchodilatory activity of the PGI2 metabolite, 6-keto-PGE1, relative to PGI2 and PGE2. In a range of doses from 0.3-10.0 microgram, i.v. injection of 6-keto-PGE1 produced a dose-related decrease in central airway resistance (RL) in animals bronchoconstricted by 5-HT. This effect on RL was 3-10 times greater than that produced by i.v. PGI2. At the lower doses, 6-keto-PGE1 was also more potent than PGI2 in increasing dynamic lung compliance; their effects upon semi-static compliance were not significantly different. Comparison of the bronchopulmonary effects of the two prostanoids did not show any consistent difference in their temporal patterns. In contrast to PGI2 or PGE2, 6-keto-PGE1 had minimal pulmonary vasomotor activity. Inhibition of the cyclooxygenase pathway with sodium meclofenamate had no effect on the bronchopulmonary actions of 6-keto-PGE1 or on its duration of action. These data indicate that 6-keto-PGE1 is a more potent bronchodilator than PGI2 in the cat. They further suggest that conversion of PGI2 to 6-keto-PGE1, if it occurs to an appreciable extent in the lung in vivo, could enhance bronchodilatory activity.

Alprostadil↗