In vivo receptor occupancy of the angiotensin II receptor by nonpeptide antagonists: relationship to in vitro affinities and in vivo pharmacologic potency.

The affinities of 13 angiotensin II antagonists for the AT1 subtype determined in vitro with tissue homogenates were shown not to correlate well with in vivo pharmacologic potency. The addition of human serum albumin to the in vitro assay to mimic in vivo plasma protein interactions reduced the measured affinity by reducing the effective free concentrations of antagonists, but the resulting affinities were not predictive of the in vivo effects. Using an in vivo radioligand competition assay, in which receptor occupancy is demonstrated via competitive blockade of the in vivo binding of [125I][Sar1,Ile8]angiotensin II to AT1 receptors in rat kidney cortex, we demonstrated that the in vivo pharmacologic potencies reflect receptor occupancy. By comparing the effects of rat plasma and bovine serum albumin on the in vitro affinity of two antagonists, we suggest that the use of plasma would alter free plasma concentrations in a manner more consistent with in vivo measures of potencies.

Receptor binding radiotracers for the angiotensin II receptor: radioiodinated [Sar1, Ile8]Angiotensin II.

The potential for imaging the angiotensin II receptor was evaluated using the radioiodinated peptide antagonist [125I][Sar1, Ile8)angiotensin II. The radioligand provides a receptor-mediated signal in several tissues in rat (kidneys, adrenal and liver). The receptor-mediated signal of 3% ID/g kidney cortex should be sufficient to permit imaging, at least via SPECT. The radiotracer is sensitive to reductions in receptor concentration and can be used to define in vivo dose-occupancy curves of angiotensin II receptor ligands. Receptor-mediated images of [123I][Sar1, Ile8]angiotensin II were obtained in the rat kidney and Rhesus monkey liver.

The role of closed pleural needle biopsy in the diagnosis of malignant mesothelioma of the pleura.

Malignant mesothelioma of the pleura is a disease that requires a biopsy procedure for a definitive diagnosis. In the past, closed pleural needle biopsy (CPNB) has given poor yields due to the small amount of tissue obtained, and the patient has subsequently been subjected to a diagnostic thoracotomy. In recent years, the availability of more accurate histopathologic tests have enabled the pathologist to make a diagnosis more easily on samples obtained at CPNB. In this retrospective study of 20 consecutive cases of malignant mesothelioma of the pleura diagnosed between 1980 and 1990, we found that a blind CPNB was diagnostic in five of seven procedures and CT-guided CPNB was diagnostic in five of six procedures. An open pleural biopsy (OPB) was diagnostic in ten of ten procedures performed. There were no complications associated with any of the CPNB procedures. We conclude that CPNB is a safe and effective manner of diagnosing malignant mesothelioma of the pleura, and should be attempted prior to OPB.

Community outbreak of adenovirus type 7a infections associated with a swimming pool.

In July 1982, an outbreak of pharyngitis caused by adenovirus type 7a occurred among children in a small town in western Oklahoma. Predominant symptoms were fever and sore throat (by case definition), headache (83%), abdominal pain (64%), and conjunctivitis (51%). At least 77 persons were identified whose symptoms met the case definition for illness. Onsets of illness peaked during the week of July 5 to 12, and the outbreak resolved within three weeks. A systematic telephone survey of the town revealed that persons who had swum at the community swimming pool were more likely to be ill than those who had not (P less than .001). A second survey of families with season passes to the pool showed that among swimmers, illness was directly related to average number of hours of exposure to the pool each week (P less than .001 by chi-square for trend). In addition, swimmers who reported swallowing pool water were more likely to be ill (29 of 56, 52%) than persons who did not (ten of 41, 24%) (P = .01). Throat-swab specimens from five of seven ill persons (71%) grew adenovirus 7a compared with one of 12 well persons (8%) (P = .01). The pool chlorinator had reportedly malfunctioned during early July. The outbreak resolved with proper operation of the chlorination system. Swimming pools continue to be a potential source of community-wide outbreaks of adenovirus infections.

Comparison of polyclonal antiserum versus monoclonal antibodies for the rapid diagnosis of influenza A virus infections by immunofluorescence in clinical specimens.

A pool of monoclonal antibodies was compared with polyclonal antiserum for the rapid detection of influenza A virus in 28 clinical specimens by immunofluorescence. Monoclonal antibodies showed higher sensitivity (69 versus 46%) and accuracy (86 versus 75%) and easier slide interpretation than did polyclonal antiserum. The procedure proved useful for rapid detection of a community outbreak of influenza A virus infection.

Write-read-erase in situ optical memory using thermoplastic holograms.

A method of using a thermoplastic hologram array for a write-read-erase in situ optical memory is proposed. A model of the proposed memory consisting of an array of 3 x 3 holograms was constructed. The experimental results of the model demonstrated that (1) thermoplastic holograms can be organized into an array on a single glass plate with adequate thermal isolation, (2) the number of recording-erasure cycles of a thermoplastic hologram can be well over 100, and (3) because of the absence of Bragg diffraction from thermoplastic holograms, the input and the output planes of the memory can be conveniently separated without any imaging lens and mechanical movement. Photographs of some images obtained from one hologram of the model array are shown.