The polymeric immunoglobulin A receptor is present on hepatocytes in human liver.

A monoclonal antibody raised against human colostrum secretory component produced even staining of hepatocyte plasma membranes, as well as bile duct lining cells, in all sections examined from eight normal and three abnormal human livers. Human bile samples incubated with free secretory component degraded it to varying extents, probably proteolytically; true levels of free secretory component will therefore often be higher than those reported. It seems likely that human liver resembles that of other mammals in transferring polymeric IgA through hepatocytes to the bile by means of the polymeric IgA receptor.     

Formaldehyde in cryoprotectant propanediol and effect on mouse zygotes

Cryopreservation of human zygotes and embryos has been routinely performed by in-vitro fertilization clinics for many years. Karran and Legge (1996) first reported that formaldehyde (FA) present in the cryoprotective solutions can have a deleterious effect on mouse oocytes. FA is a cytotoxic, carcinogenic and mutagenic chemical. The effect of FA on mouse zygotes was investigated. In addition, the concentrations of FA in propanediol (PROH) obtained from various sources were determined. Pooled 1-cell embryos were dispensed into droplets of modified Ham's F10 or human tubal fluid containing various concentrations of FA. Since bovine serum albumin (BSA) may minimize toxicity additional trials were done as above in the absence of BSA. FA concentration in the standard 1.5 M PROH, from different sources in water, was measured in the same assay using a standard curve of 0-100 microM FA. FA in a complex medium had a significant deleterious effect on embryo development and hatching but only at 1 mM concentration (P < 0.000001; see Tables I-III). There was no significant effect of FA at 100 microM. However, in a simple medium even 50 microM FA decreased embryo hatching. FA was present in 1.5 M PROH from different sources (range 1.0-35.3 microM concentration). It appears that FA concentrations do not increase with storage because FA concentrations were low even after opening and storage for 3 years on the shelf. This suggests that FA is a contaminant during the manufacturing process and may vary from manufacturer to manufacturer and batch to batch. Until further studies are done to confirm the lack of toxicity to embryos during cryopreservation (with or without FA scavengers) it may be prudent to screen all batches of cryoprotectants for FA as part of quality control.      

Stability of Th1 and Th2 populations

Using an in vitro model for the development of IFN-y-producIng(Th1) and IL-4-produclng (Th1) cells from CD4 T lymphocytesexpressing a transgenlc TCR, we show that IL-12 and IL-4 arethe most potent stimuli for the differentiation of naive T cellsto effector populations. When combinations of cytokines arepresent during T cell priming, the effect of IL-4 Is dominant.Furthermore, differentiated Th1 cells can be converted intoIL-4 producers by exposure to IL-4, but the Th2 phenotype Isnot reversible. The stability of Th2 populations may limit theability to regulate Th2-domlnant responses In pathologic situations.     

Laser tomography of heterogeneous scattering media using spatial and temporal resolution

Time-resolved tomography is performed in transillumination by using 527 nm picosecond pulses from a passively mode-locked doubled Nd/glass laser and a streak camera to select photons according to their flight time. This work reports on the increase in contrast of a time-resolved profile of a 2 mm radius opaque object embedded in a scattering medium, constituted of diluted milk in a 30 mm thick cell. For spatial analysis, the emerging photons are detected through a 6 mm slit at the outlet face of the cell. Transmission profiles obtained as a function of time show that the contrast is enhanced for the shortest flight times, while the ‘shadow’ of the object is no longer detected after about 100 ps. Moreover, improvements in contrast are studied for different configurations of the model, to analyse separately the role of collimated and scattered photons. It is expected that such a tomographic method based on time-resolved absorption could be applied to imaging for more complex biological structures in the red and near-infra-red range.     

Effects of overexpansion on stents' recoil, symmetry/asymmetry, and neointimal hyperplasia in aortas of hypercholesterolemic rabbits.

BACKGROUND: It is not known whether overexpansion modifies stent recoil, symmetric distribution of struts, and neointimal hyperplasia. OBJECTIVES: The objectives were (a) to evaluate whether stent overexpansion modifies the geometric configuration of the stent in the arterial wall, (b) to determine the relationship between overexpansion and stent recoil, and (c) to evaluate the relationship between the distribution of struts and neointimal hyperplasia. METHODS: Twenty tubular stainless steel 316L stents (3.0 and 3.5 mm in diameter) were implanted at 20 and 10 atm, respectively, in the abdominal aorta of New Zealand rabbits fed a hypercholesterolemic diet (1% cholesterol). Sham operations were also performed in seven animals. Eight weeks after implantation or sham operation, an intravascular ultrasound (IVUS) study was performed to measure stent recoil and aid in stent classification (symmetric or asymmetric) according to strut distribution. The degree of injury and neointimal hyperplasia were also evaluated in hematoxylin-eosin stained sections. RESULTS: The symmetry/asymmetry of stents assessed by IVUS, as well as the neointimal hyperplasia, was similar in both groups. Stent recoil was significantly greater in the 3.0-mm stent (overexpanded) group (0.28+/-0.02 mm), as compared with stent recoil in the 3.5-mm stent group (0.10+/-0.01 mm, P<.05). The neointimal hyperplasia in histological slices, independent of the implant technique, was predominantly in zones with higher strut concentration as compared with zones with fewer struts. CONCLUSIONS: Stent overexpansion enhanced stent recoil and did not modify symmetric and asymmetric strut distribution. Neointimal hyperplasia was not modified by the implant technique. Interestingly, significant hyperplasia was observed in locations with greater strut concentration, independent of overexpansion.     

Antibodies to the polymeric immunoglobulin receptor with different binding and trafficking patterns

The polymeric immunoglobulin receptor (pIgR) has been proposed as a therapeutic target, but its potential depends on the efficiency of uptake and trafficking of the receptor ligand. Mouse monoclonal antibodies (Mabs) directed against pIgR, selected for strong binding to secretory component (SC) and secretory IgA (sIgA), were tested in a transcytosis assay in 16HBEo--cells (human bronchial epithelial cell line) transfected with human pIgR. Intracellular trafficking was followed by confocal microscopy. Mabs fell into two classes. For two Mabs, transcytosis from basolateral to apical surface is rapid, unidirectional, and little Mab is retained in the cell. For three Mabs, basolateral to apical transcytosis occurs to a significantly lesser extent, reverse transcytosis is permitted, and some of the Mab is retained in the perinuclear region even after 24 h. When tested for their ability to recognize and immunoprecipitate pIgR with systematic truncations and deletions of the five immunoglobulin (Ig)-like domains, all Mabs bound to the fifth Ig-like domain, but three of them also bound to the C-terminal region of pIgR near the plasma membrane. Different binding sites probably account for the different trafficking of these Mabs and may predict differential therapeutic utility.     

Genotyping of Uruguayan Human adenovirus isolates collected between 1994 and 1998

Adenoviruses are one of the most frequent causative agents of acute lower respiratory infections in infants and young children. Twenty-three adenovirus isolates from nasopharyngeal aspirates of children hospitalized for acute lower respiratory infections in Uruguay between 1994 and 1998 were studied by restriction enzyme analysis. The genomic analysis showed that 60.9% (n = 14) of isolates belonged to the species Human adenovirus C (HAdV-C) and 31.9% (n = 9) to the species Human adenovirus B (HAdV-B). Whereas some isolates could be classified according to the published profiles into genotype or genomic variant, others displayed migration patterns not allowing classification. Eight isolates (89%) of HAdV-B corresponded to the Ad7h genotype that has been associated with severe and fatal pneumonia and necrotizing bronchiolitis in children in South America. The isolates of HAdV-C showed a great variability in accordance with the data published earlier.     

HL-A Antigens in Leprosy

HL—A phenotype frequencies were studied in 30 patients with leprosy and in 149 healthy controls. Leprosy patients had a significantly higher frequency of HL—A14. In addition, a majority of the HL—A14 patients gave a negative response to leproma antigen using the Mitsuda test.     

Tumor necrosis factor-mediated inhibition of interleukin-18 in the brain: a clinical and experimental study in head-injured patients and in a murine model of closed head injury.

Tumor necrosis factor (TNF) and interleukin-(IL)-18 are important mediators of neuroinflammation after closed head injury (CHI). Both mediators have been previously found to be significantly elevated in the intracranial compartment after brain injury, both in patients as well as in experimental model systems. However, the interrelation and regulation of these crucial cytokines within the injured brain has not yet been investigated. The present study was designed to assess a potential regulation of intracranial IL-18 levels by TNF based on a clinical study in head-injured patients and an experimental model in mice. In the first part, we investigated the interrelationship between the daily TNF and IL-18 cerebrospinal fluid levels in 10 patients with severe CHI for up to 14 days after trauma. In the second part of the study, the potential TNF-dependent regulation of intracerebral IL-18 levels was further characterized in an experimental set-up in mice: (1) in a standardized model of CHI in TNF/lymphotoxin-alpha gene-deficient mice and wild-type (WT) littermates, and (2) by intracerebro-ventricular injection of mouse recombinant TNF in WT C57BL/6 mice. The results demonstrate an inverse correlation of intrathecal TNF and IL-18 levels in head-injured patients and a TNF-dependent inhibition of IL-18 after intracerebral injection in mice. These findings imply a potential new anti-inflammatory mechanism of TNF by attenuation of IL-18, thus confirming the proposed "dual" function of this cytokine in the pathophysiology of traumatic brain injury.