Proliferation of dendritic cells in the bronchioles of sudden infant death syndrome victims.

Sudden Infant Death Syndrome (SIDS) victims have significantly thickened bronchiolar walls with increased mononuclear cells in the adventitia. An immunohistochemical study was performed on 25 SIDS and 18 aged-matched control infants to characterize these cells. The panel of antibodies included alpha-1-antitrypsin, lysozyme, actin, vimentin, Leu M1, NSE, S-100, Leu 6, bombesin, serotonin, anti-substance P, vasoactive intestinal peptide, MAC 387, and Factor XIIIa. The bronchiolar cells stained with S-100 antibody and demonstrated slender processes similar to dendritic cells, such as Langerhans' cells, and interdigitating reticulum cells, present in normal tissues as well as in certain tumors and inflammatory diseases. Manual counting of the S-100 positive cells and fibers revealed both of these to be significantly increased in SIDS infants as compared to age-matched control infants. Morphologically, the bronchiolar dendritic cells closely resembled Langerhans' cells and therefore may have similar immunologic functions, such as antigen presentation and viral and neoantigen immunosurveillance. We hypothesize that the proliferation of these dendritic cells in SIDS victims is a result of exposure to environmental antigens, resulting in a thickening of the bronchiolar walls, narrowing of the lumen, and reduction in airflow, thus causing a chronic or persistent hypoxia.

Asbestos in organs and placenta of five stillborn infants suggests transplacental transfer.

Digests of lungs, liver, and placenta from five stillborn infants of 22 to 38 weeks gestational age were examined for asbestos and other fibers using light and electron microscopy, energy dispersive X-ray analysis, and selected area diffraction analysis. Uncoated chrysotile asbestos fibers were found in the digests of at least one of the three tissues examined from each stillborn infant. The asbestos fiber burdens ranged from 71,000 to 357,000 fibers/g wet tissue. Most of the fibers were small, with the mean length ranging from 0.83 to 2.53 microns. While appreciable numbers of uncoated chrysotile fibers were present, no coated asbestos fibers were found in any of the stillborns. Both coated and uncoated nonasbestos fibers were found in at least one of the tissue digests of all five stillborns. The uncoated nonasbestos fibers were characterized as aluminum silicates, diatomaceous earth fragments, or other fibers. The coated nonasbestos fibers or ferruginous bodies were consistent with being formed on diatomaceous earth fragments, black carbon cores, or sheet silicate cores. Since the placenta is the only route of communication between the fetus and the outside environment, our findings strongly suggest a transplacental transfer of asbestos and other fibers in humans.

Bronchiolar wall changes in sudden infant death syndrome: morphometric study of a new observation.

Sudden infant death syndrome (SIDS) infants have significantly thicker and more cellular bronchiolar walls than control infants of similar age. A morphometric study of 25 SIDS and 18 control infants was undertaken to measure the bronchiolar wall thickness using a Cue-2 image analysis system. A mathematical formula (relative index) was used to compare the thickness of bronchioles of varying diameter. Data analysis using a nested design two-way analysis of variance and covariance of the measured bronchioles showed a significant difference between the SIDS and control infants with a P value less than .001. Manual counting of the cells in the bronchiolar walls and data analysis using an unpaired two-tailed t test showed that the SIDS infants had a significantly greater number of cells than control infants (P less than .01). Our preliminary results indicate that the cells in the bronchiolar wall are either peripheral nerve-derived (Schwann cells) or Langerhans cells. We postulate that these cells are increased in number in response to chronic hypoxia in SIDS infants.

Identification of new cryoprotective agents for cultured mammalian cells.

Thirty-one compounds have been identified that act as cryoprotective agents for cultured mammalian cells. Eight compounds were comparable to dimethylsulfoxide (DMSO) in cryoprotective effectiveness. Many of the cryoprotective compounds studied also (a) promote cell fusion and (b) induce cell differentiation in erythroleukemia and other cell systems. Thus, previously unrecognized effects on the differentiated state of cells may occur when cells are treated with cryoprotective agents.

Enhancement of polyethylene glycol-mediated cell hybridization by inducers of erythroleukemia cell differentiation.

Dimethyl sulfoxide (DMSO) has many biological effects, which include enhancement of polyethylene glycol (PEG) -mediated cell fusion, induction of cell differentiation in erythroleukemia and other cell systems, and cryoprotection of cells from freezing damage. In this study, compounds which induce erythroleukemia cell differentiation were tested for their ability to enhance PEG-mediated cell fusion. It was found that many compounds which induce erythroleukemia cell differentiation also promote cell membrane fusion as well as protect cells against freezing damage. Hence, many inducers of erythroleukemia cell differentiation have direct and similar effects on cell membranes. This study also demonstrates previously unrecognized effects of cryoprotective agents and cell fusogens on the differentiated state of cultured cells.

Two-dimensional spectroscopy of electrophoretic gels.

Optical techniques are described which permit one to analyze two-dimensional electrophoretic gels in a fashion which is analogous to the one-dimensional spectroscopy of solutions. In the methods described, an electrophoretic gel is irradiated with monochromatic light and isozyme patterns are detected by the absorption of light or the fluorescent emission of light. The system described can both generate and detect monochromatic light in a range from 200 to 1100 nm. Without the use of histochemical stains, several isozymes have been visualized by purely optical means. Five methods for the visualization of lactate dehydrogenase and five methods for the demonstration of trypsin isozymes are described. In addition, general methods have been formulated for hydrolases and oxidases. Gel spectroscopy should permit the investigation of a wide range of new isozymes.

Chemicals which promote cell hybridization.

In order to identify new compounds with cell hybridization properties similar to poly(ethylene glycol), the standard method for PEG-induced cell hybridization has been employed as a screening procedure. Of 118 membrane-active agents studied, over 20 compounds were identified which promoted cell hybridization with nearly the same efficiency as PEG. PEG derivatives which retained cell hybridization activity included polymers with branched and charged structures as well as polymers with chemical alterations of the PEG monomer itself. PEG derivatives with hydrophobic moieties were generally inactive. Several chemically modified derivatives of poly(ethylene glycol), which are commercially important in the pharmaceutical and cosmetic industries, were found to be highly efficient cell hybridization agents. The biohazard of such compounds is discussed. A simplified method is presented for the preparation and use of PEG in cell hybridization procedures.