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picture is similar to that in the four-day lesion with some increase in the extent 
of the vesicle and in a more marked reaction in the corium beneath the lesion. 
(The polynuclear leucocyte infiltration of the corium is less intense, but the 
vesicle cavity shows a more even distribution of the pus cells. The reaction of 
the corium is more marked, being shown by the presence of oedema, necrosis, and 
an increase in the cellular content of the tissue. Aside from the polynuclear 
leucocyte the dominant element is a large cell with a vesicular nucleus surrounded 
by an abundant reticular protoplasm. These cells show a great variation in 
form, some being rounded, others irregular, the outline seemingly being condi- 
tioned by the space in which the cell lies. Many of these cells are found just 
outside of the capillaries and in the lymph spaces of the tissue, and by compar- 
ison of their morphology and staining reaction with that of the swollen endo- 
thelial cells, in situ in the capillaries and in the lymph spaces, it seems certain 
that they are identical with them. Many of these cells are phagocytic and in 
some mitosis is seen. In certain of these cells early stages of the cytoplasmic 
phases of Cytoryctes variolw are present. In addition to these endothelial cells, 
which have often wandered for some distance from their place of origin, a 
certain number of elements are found of the lymphoid and plasma cell series. 
The connective-tissue cells all through the corium about the lesion are swollen, and 
in some mitosis is in progress. The nerve bundles are frequently invaded by 
polymorphonuclear leucocytes. The cellular reaction of the corium is shared 
by the adjacent subcutaneous tissue and extends for a considerable distance from 
the line of inoculation. Necrosis is seen in the tissue beneath the center of the 
lesion, the cells losing their basic affinity and undergoing more or less fragmenta- 
tion or solution. Many deeply stained spherules of various sizes are scattered 
through the necrotic tissue, evidently the nuclear fragments of polynuclear 
leucocytes. 
Six days. The general relations of the vesicle cavities and the crust remain 
as before, although the outer limits of the vesicle often extend beyond the limits 
of the crust, being roofed by a layer of cornified epithelium which sweeps down- 
ward to form a part of the lateral wall of the cavity. In some instances the 
beginning of vesicle formation, shown by collection of fluid between tne cells, is 
apparent a short distance beyond the outer limits of the main vesicle. A similar 
condition is met with in the depths of the cellular sheaths of the hair follicles. 
The fusion of the middle portion of the crust with the underlying corium is 
often apparent, although in many places a collection of leucocytes is present here 
which is continuous with the lateral vesicles and with the purulent focus which 
forms in the corium along the line of inoculation. In such a lesion a roughly 
T-shaped cavity can be made out, the vertical portion being filled with leucocytes 
and extending from the crust for a variable distance into the corium, while the 
cross arm has for its extremities the vesicular cavities which extend laterally 
under the crust. The vertical portion of this T can often be traced to the focus 
of necrosis which lies in the lower layers of the corium and the upper portion of 
the subcutaneous tissue. The reaction of the corium is very marked at this 
stage. Study of the outer limits of the necrotic area shows that the large cells, 
which we believe to be endothelial in origin, seem to be resistant to the agent 
which is causing the necrosis. The large cells are frequently to be seen in an 
apparently normal condition in an area where all other cellular elements have 
been destroyed. It is hard to determine whether this apparent immunity from 
destruction is due to qualities of the cell or whether it is because the cells have 
migrated into the necrotic area. In one instance a small capillary was found in 
the corium near the necrotic area line by swollen endothelial cells, many of which 
were infected with early stages of the cytoplasmic phases of cytoryctes variole. 
Seven days. The lesions of this age and those collected later show a progres- 
