Serological responses in chimpanzees inoculated with human immunodeficiency virus glycoprotein (gp120) subunit vaccine.

The major envelope glycoprotein of a human immunodeficiency virus (HIV) has been purified and was utilized as a prototype vaccine in chimpanzees. The 120,000-dalton glycoprotein (gp120) was purified from membranes of human T-lymphotropic virus (HTLV)-IIIB-infected cells and the final preparation contained low levels to no detectable HTLV-IIIB core antigen (p24) and low levels of endotoxin. Chimpanzees inoculated with gp120 responded by developing antibodies that precipitated radiolabeled gp120 and neutralized in vitro infection of HTLV-IIIB. Antibodies to HTLV-IIIB p24 were not detected in the gp120-immunized chimpanzees. Peripheral blood leukocytes from the vaccinated animals were examined for T4+ and T8+ cells, and no decrease in the T4/T8 ratio was found, indicating that immunization with a ligand (gp120) that binds to T4 has no detectable adverse effect on the population of T4+ cells. The only current animal model that can be reproducibly infected with HIV is the chimpanzee. Immunization of chimpanzees with HIV proteins will provide an experimental system for testing the effectiveness of prototype vaccines for preventing HIV infection in vivo.     

Diagnostic and therapeutic biomarkers in pancreaticobiliary malignancy

Pancreatic ductal adenocarcinoma(PDAC) and cholangiocarcinoma(CCA) are two malignancies that carry significant morbidity and mortality. The poor prognoses of these cancers are strongly related to lack of effective screening modalities as well as few therapeutic options. In this review, we highlight novel biomarkers that have the potential to be used as diagnostic, prognostic and predictive markers. The focus of this review is biomarkers that can be evaluated on endoscopically-obtained biopsies or brush specimens in the pre-operative setting. We also provide an overview of novel serum based markers in the early diagnosis of both PDAC and CCA. In pancreatic cancer, the emphasis is placed on prognostic and theranostic markers, whereas in CCA the utility of molecular markers in diagnosis and prognosis are highlighted.     

Comparisons of planar and tomographic gamma scintigraphy to measure the penetration index of inhaled aerosols

The quantitative measurement of regional aerosol deposition in human lungs using two-dimensional (2D) gamma scintigraphy has proven to be useful in therapeutic and diagnostic aerosol studies. The penetration index (PI) has been defined as the ratio of activity in a peripheral lung zone to a central lung zone, but the ability to discriminate between aerosol deposition in the large airways and lung parenchyma is reduced by the fact that the latter overlies the former in the central zone. To overcome this, we used a three-dimensional (3D) technique. Seven healthy subjects inhaled isotonic saline aerosols containing 99mTc-DTPA on two occasions. The droplets had a mass median aerodynamic diameter (MMAD) of either 2.6 or 5.5 microns (with geometric standard deviations [sigma g] of 1.4 and 1.7, respectively). Transmission tomography was performed on each subject to delineate lung boundaries in 2D and 3D. After inhalation, anterior (A) and posterior (P) images were collected and a tomographic study performed. Mid-lung slices were taken from coronal (CC) and transverse (TC) sections. PI was calculated on the 2D images (AP and P) and the 3D slices (CC and TC) using exactly defined regions. The PI values were smaller for the large droplet aerosol (5.5 microns) in all subjects and methods. The relative differences in PI between large and small (2.6 microns) droplet studies (d values) were greater and less variable for the 3D methods (TC, 56.5 +/- 11.4% and CC, 52.4 +/- 12.3%) compared to the 2D methods (P, 25.4 +/- 17.1% and AP, 38.3 +/- 15%; p less than 0.005). We found the 3D methods to be more sensitive for discriminating between aerosol deposition in large and small airways than were the conventional 2D methods.     

Activation of secondary cytotoxic lymphocytes by cell-free factors from I-region-primed and D-region-primed lymphocytes.

Cell co-operation in the generation of secondary cytotoxic responses was studied by selectively sensitizing lymphocytes in mixed lymphocyte culture (MLC) across I or D region difference and by combining the primed lymphocytes in the secondary MLC. Secondary cytotoxic responses were induced in D-region-primed lymphocytes by restimulation with the original priming D-region antigens, by co-culturing with the I-region-primed lymphocytes in the presence of the priming I-region antigens, or by cell-free supernatants obtained 24 h after the restimulation of D-region-primed lymphocytes and I-region-primed lymphocytes, The active MLC supernatants produced by both I-region-primed and D-region-primed cells also induced accelerated proliferative responses in D-region-primed lymphocytes. Heat-treatment or ultraviolet irradiation of the stimulator cells eliminated the capacity of the cells to induce the production of CTL-helper factor in I-region-primed and D-region-primed lymphocytes. It was concluded that both I-region-primed and D-region-primed lymphocytes produce a cell-free factor which induces proliferation and secondary cytotoxicity in D-region-primed lymphocytes. The possible participation of D-region reactive helper T cells and D-region reactive cytotoxic T cells in the cytotoxic responses to D-region antigens in the absence of I-region difference is discussed.     

A rapid method for the evaluation of diagnostic radioaerosol delivery systems

The effective delivery (ED) in MBq/min of a 100 MBq/ml nebuliser solution was defined as the rate of delivery of droplets in the respirable size range (aerodynamic diameter below 3.3 micron) to the mouthpiece of the aerosol delivery system (ADS). Wasted delivery (WD) was defined as the rate of delivery of droplets above 3.3 microns. ED and WD were measured on four types of commercially available ADS. The aerosols were sampled at the mouthpiece of each system and droplet size distribution measured with a seven stage cascade impactor. The effect of ambient air humidity on the droplet size produced by the Cadema delivery system was also evaluated. The ED values ranged from 6 to 15 MBq/min and WD values from 0.01 to 15 MBq/min. Two ADS produced low ED and WD values (6.1-9.0 and 0.01-0.07 MBq/min, respectively) due to a low output, while another produced higher ED and WD values [11.3 +/- 0.2 (SD) and 15.4 +/- 0.5 (SD) MBq/min, respectively] due to a larger droplet size. The Cadema delivery system gave the optimum characteristic of high ED [13.9 +/- 0.8 (SD) MBq/min] and low WD [1.24 +/- 0.61 (SD) MBq/min] values. The mass median aerodynamic diameter (MMAD) of the Cadema ADS fell by 22% (P less than 0.01) as the ambient dilution air was dried from a high relative humidity (RH) (88%-100%) to a low RH (12%-17%). The variability of both MMAD and geometric standard deviation (sigma g) was increased with dry dilution air (P less than 0.01).     

Disaccharide analysis of chondroitin sulfate in peri-implant sulcus fluid from dental implants

We collected peri-implant sulcus fluid by capillary tubes from sites around titanium osseointegrated implants and determined the chondroitin sulfate released into the peri-implant sulcus fluid by high-performance liquid chromatography. Chondroitin sulfate was found in all peri-implant sulcus fluid samples, and its content was similar to that in gingival crevicular fluid obtained around natural teeth. The predominant unsaturated disaccharide isomer was ΔDi-OS, followed by ΔDi-4S. ΔDi-6S was present in trace amounts. The amount of ΔDi-OS was greater in peri-implant sulcus fluid than in gingival crevicular fluid. Assaying chondroitin sulfate disaccharides in peri-implant sulcus fluid may be an effective method of monitoring the peri-implant condition of dental implants.