Frost-bite lesions were produced in five Hanford Miniature Swine exposed to - 75 degrees C air for 1, 3, 5, 10 or 20 min. Biopsies were taken at 0, 3, 6, 12, 24 and 48 h and 1 and 2 weeks. Two hundred slides were evaluated microscopically: pyknosis, vacuolation, individualization of cells, and degeneration were graded from 0-5; 0, no change; 5, severe change. Necrosis, new epithelium, and microabscesses were recorded as present or absent. Early changes of vacuolation of keratinocytes, individualization of cells and pyknosis increased with biopsy time until 1 week, at which time more severe changes predominated. Intermediate changes of advanced degeneration and dermoepidermal microabscesses were seen at 48 h and 1 and 2 weeks. Late changes of necrosis and epithelial regeneration occurred, both separately or together in the same tissue, at 1 and 2 weeks. Regeneration occurred either as complete replacement of epithelium, or as crescents of new epithelium beneath degenerating epithelium. The results show that necrosis is a late development, so prognosis based on early skin biopsies must be guarded to unfavourable. Furthermore, these findings suggest that cold has a direct effect on epithelial cell membranes.
The distribution of copper and related changes have been studied in copper-loaded rat kidneys at the ultrastructural level by X-ray electron probe microanalysis, in order to clarify the pathogenesis of copper-induced damage and subsequent recovery in this organ. Male rats fed a high copper diet (1500 ppm) for 16 weeks were killed at intervals; their kidneys were removed and portions of kidney cortex fixed in 4% paraformaldehyde and 2% glutaraldehyde for electron microscopy: other samples were analysed for copper by AA spectrophotometry. Increasing copper accumulation was associated with progressive PCT cell disarray and characterized by irreversible nuclear damage coincident with the intranuclear accumulation of Cu, S, P, and Ca. Copper was also identified within structurally intact lysosomes associated with Zn and Fe (Type I lysosomes) or P and S (Type II lysosomes, putative Cu-MT). Subsequent copper decline and tubular recovery was associated with the facilitated lysosomal sequestration of copper and excretion of copper-containing cell products into the tubule lumina, Cu-MT and alpha-2 urinary protein-copper. The cytotoxicity of copper in the kidney, as well as the liver, is associated primarily with irreversible nuclear damage, whereas lysosomal copper sequestration protects the cell from injury.
Simian adenovirus type 7 (SA-7) was found to induce tumours originating from nerve-supporting or paraneural cells in newborn hamsters, regardless of injection site or tissues. SA-7 induces glioblastomas characterized by definite localization (subependymal regions) and its main cell type, bipolar spongioblast-like cells, in the brain of hamsters inoculated as newborns. When the eyes of newborn hamsters were directly inoculated, SA-7 failed to induce retinoblastoma (0/27), but retro or peri-bulbar SA-7 tumours frequently occurred in tissues closely related to the peripheral nerve apparatus, including the oculomotor nerve or ciliary ganglion. These tumour cells were situated like stromal cells in these nerve tissues. The histological features of the orbital tumours were similar to those of SA-7-induced subcutaneous tumours but not to brain tumours. In contrast with other hamster brain tumours induced by human adenovirus type 12 or human papova JC virus, medulloepithelioma or medulloblastoma, SA-7 induced tumours exhibit distinctive histological and localization characteristics.
The pathological effect of parainfluenza type I (Sendai virus) is known to be a bronchopneumonia, which becomes a chronic pneumonia in the immunodeficient athymic (nude) mouse. The severity of this established chronic pneumonia can be dramatically altered by providing the nude mouse with humoral monoclonal antibodies which are neutralizing, and are directed against the fusion protein, of the virus. The alveolitis, which is a significant part of the pathology, is suppressed due to a reduction (greater than 90%) in the number of virus-infected alveolar macrophages present in the alveoli. This clearly identifies the infected alveolar macrophage as the primary effector cell in the pathogenesis of alveolitis caused by parainfluenza virus type I. The implications of using virus-neutralizing monoclonal antibodies, which have little immunomodulatory toxicity, in the treatment of viral pneumonias are discussed.
Cells within the central nervous system were identified as containing immunoglobulin G, A and M using immunocytochemistry in mice previously infected with Semliki Forest virus, a togavirus causing primary immune-mediated demyelination. Cells positive for these immunoglobulins were counted in cerebellar white matter, parenchyma, meninges and choroid plexus/ventricles. No positively staining cells were seen on day 6 after infection although other inflammatory cells were present at this time and virus-specific immunoglobulin was found in serum. Cells positive for IgG appeared in all areas by day 9 and remained dominant in numbers throughout. IgM-secreting cells appeared in small numbers in the parenchyma first on day 9 and subsequently in other areas, their numbers rising to a maximum on day 12 in all areas and falling thereafter. The number of IgA-secreting cells was small. They appeared by PID 12 and continued to rise on successive sampling days. Initially IgG-positive cells were seen in the perivascular cuffs but by day 12 a few had moved away from the cuffs into the adjacent parenchyma. IgG-positive cells were seen both in and away from cuffs within areas of demyelination. IgM and IgA-positive cells tended to follow the distribution of IgG-positive cells, but in fewer numbers.
