Publications

Clinical trials constitute one of the main sources of medical knowledge, yet trial reports are difficult to find, read, and apply to clinical care. Reasons for these difficulties include the lack of a common, standardized, structure for trial reports; the restricted length of reports; and limited computer support for use of the literature. We propose a new model of reporting clinical trials, in which trials are published as both prose commentary and as data in electronic "trial banks." The prose will allow authors to discuss their trials in writing; the electronic database will allow readers easy access to well-defined data about the trials. We are developing a formal conceptual model of the clinical trials domain for integrating the use of multiple trial banks. We will then focus on validating this conceptual model with clinical literature users.

The nef gene product of human immunodeficiency virus type 1 (HIV-1) promotes more-rapid kinetics of viral replication in primary peripheral blood mononuclear cells. We have previously shown that these enhancing effects of Nef on HIV-1 replication reflect an increase in viral infectivity detectable both in limiting dilution assays and through a single-cycle infection of the HeLa-CD4-long terminal repeat-beta-galactosidase indicator cell line. We now demonstrate that nef-defective HIV-1 can be rescued to near wild-type levels of infectivity by coexpressing Nef in trans in the cell line producing the virus. This observation indicates that HIV-1 virions produced in the presence of Nef are intrinsically different. However, we show that the major viral structural proteins are quantitatively similar in purified viral preparations. We also demonstrate the functional equivalence of the gp120-gp41 envelope glycoprotein complexes of Nef+ and Nef- HIV-1 through an assay for viral entry. Finally, we show that env-defective Nef+ HIV-1 pseudotyped with an amphotropic envelope is also more infectious than similarly pseudotyped Nef- HIV-1. Thus, the production of HIV-1 in the presence of Nef results in viral particles that are more infectious, and this increased infectivity is manifested at a stage after viral entry but prior to or coincident with HIV-1 gene expression.

The present study examined whether neutrophil recruitment in dog airways by Staphylococcus aureus is mediated by interleukin-8 (IL-8). S. aureus culture supernatant was superfused into an isolated tracheal segment in six dogs, and neutrophil recruitment and IL-8 concentrations were measured in the superfusate. Dog IL-8 was cloned, expressed in Escherichia coli, purified by chromatography, and shown to be biologically active. With the use of an enzyme-linked immunoabsorbent assay (ELISA) for the measurement of dog IL-8, we showed that S. aureus supernatant induced neutrophil recruitment and increased IL-8 concentration in the superfusate in a time-dependent manner. The chemotactic activity present in the superfusate 6 h after superfusion with S. aureus was inhibited by an anti-IL-8 antibody. S. aureus supernatant also stimulated IL-8 production and gene expression by cultured canine tracheal epithelial cells. These results provide evidence that IL-8 plays a major role in S. aureus-induced neutrophil recruitment in the airways by stimulating IL-8 production in airway cells.

OBJECTIVE

The lining cell layer of the synovium proliferates strongly in rheumatoid arthritis. It has been suggested that it has a central role in the destruction of cartilage. We have analyzed the structure of the extracellular matrix and the adhesion molecules of normal, osteoarthritic and rheumatoid lining cell layer.

METHODS

We localized the alpha v integrin subunit and its 4 putative partner beta subunits in synovial samples by using indirect immunofluorescence. The specimens were also analyzed by confocal microscopy. Indirect immunofluorescence was also used to analyze the ligands of alpha v integrins, namely fibronectin and vitronectin.

RESULTS

The alpha v integrin was abundant in the lining cell layer of normal and osteoarthritic synovia, whereas it was not expressed in the proliferating rheumatoid lining cell layers. A similar expression pattern was found for beta 5 subunit, suggesting that it is the major partner for alpha v. However, also some alpha v beta 1 and alpha v beta 3 heterodimers may be present. The confocal microscopy revealed the presence of both alpha v beta 5 positive and negative lining cells. The putative ligands for alpha v integrins, namely fibronectin and vitronectin were found in the lining cell layer of all the synovial specimens.

CONCLUSION

In spite of the proliferation of the lining cell layer in rheumatoid inflammation, the extracellular matrix stays very similar to that in normal and osteoarthritic synovium, whereas the pattern of the adhesion receptors is completely altered.

OBJECTIVE

The likelihood of interstitial lung disease being detected on high-resolution CT scans and having functional significance is often related to the severity of the disease. The extent and severity of the abnormalities seen on high-resolution CT are usually assessed subjectively. This study was undertaken to investigate whether a subjective semiquantitative scoring method or a method using a cumulation of the different high-resolution CT features of asbestosis were comparable in suggesting asbestosis in a group of patients with histopathologic confirmation of disease. A secondary objective was to compare the results of these two high-resolution CT methods with chest radiographs in the same population.

MATERIALS AND METHODS

This study group consisted of 24 patients and six lungs obtained at autopsy. Histopathologic asbestosis was present in 25 of the 30 patients or lungs. The patients or lungs were imaged using selected high-resolution CT scans. The high-resolution CT scans were assessed in two ways. One used a subjective semiquantitative extent and severity score consisting of four levels of severity, while the other was a cumulative score adding the different types of high-resolution abnormalities in asbestosis. The commonest high-resolution CT abnormalities in the cases with confirmed asbestosis were interstitial lines (84%), parenchymal bands (76%), and architectural distortion of secondary pulmonary lobules (56%). Subpleural lines and honeycombing were less frequent. The histopathologic severity of asbestosis was independently graded on a four-point scale. Chest radiographs, when available, were classified according to the International Labor Organization (ILO) classification of pneumoconioses.

RESULTS

With the subjective semiquantitative high-resolution CT severity score, asbestosis was suggested in 16 (64%) instances, all with disease. With the cumulative method, any one type of abnormality was present in 88% of cases with asbestosis, two types in 78%, and three in 56%. However, to include only cases with asbestosis, three different abnormalities had to be present. The high-resolution CT scans were normal or near normal in five instances of asbestosis. Chest radiographs using the ILO classification predicted asbestosis with a lesser frequency than high-resolution CT in this selected population.

CONCLUSION

We conclude that a subjective semiquantitative grading system of the extent and severity of asbestosis and a method using a cumulative addition of the different findings in asbestosis give similar results in suggesting the presence of disease. Thus, for the high-resolution CT detection of asbestosis, a combination of the cumulative number of different findings and an assessment of the extent and severity of the abnormalities could be complimentary. We also conclude that asbestosis can be present histopathologically with a normal or near normal high-resolution CT scan.

We analyzed CK and CK-MB levels over 24 h in 15 male subjects admitted for alcohol detoxification following recent heavy ingestion. None had clinical or electrocardiographic evidence of myocardial ischemia or infarction. The mean 0-hour serum alcohol level +/- SD was 342 +/- 101 mg/dl. CK levels were measured by Kodak Ektachem and Abbott IMx assays, and CK-MB levels were determined by these assays and the Hybritech isoenzyme test. In 36% of the patients elevated 0-hour CK levels by the IMx and Ektachem assays were observed. The CK levels measured every 8 h decreased so that by 24 h CK was elevated in 1 patient by the Ektachem assay and in 2 by the IMx assay. Only 1 patient (7%) had an elevated 0-hour CK-MB value by two of the three assays, and it is unclear whether the source was cardiac or extracardiac. We conclude that: (1) elevated CK levels are common in heavy alcohol use patients without evidence of myocardial ischemia; (2) CK values over the first 24 h are decremental, not rising and falling as is typical of myocardial infarction and (3) current isoenzyme immunoassays eliminate a cardiac cause for elevated CK in most of these patients. These findings may assist in the evaluation of alcoholic patients with chest pain.