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Sex chromatin counts performed on the endothelial cells of 40 human kidneys transplanted to recipients of the opposite sex showed that the donor endothelium had persisted except in three poorly functioning and severely damaged grafts. In these a high proportion of the endothelial cells in peritubular capillaries and veins were derived from the host. Endothelial repopulation of organ allografts probably occurs only after severe tissue injury, and it cannot explain the phenomenon of graft adaptation. Repopulated endothelium may be derived from circulating cells.

This paper is the third in a series reporting our studies on the effect of hyperoxia on the growing retinal vessels of the rabbit. It deals with the in vitro behaviour of the rabbit retinal complex in a normal tissue culture environment, a necessary preliminary to an investigation of the effect of hyperoxia on such cultures, which is reported in the fourth and last paper of this series. An account is given of the materials and methods employed, including timelapse cinephotomicrography, phase contrast light microscopy, conventional light microscopy and electron microscopy. The origin and mode of growth of the cells composing the vascular complex, their differentiation and formation into capillaries, and the behaviour of their associated cells are described. It was found that growth began both as a budding of mesenchymal-like cells, arising from endothelium and pericytes, and as a direct growth of endothelial cells. In either case the cultures eventually assumed the typical appearances of endothelial growth with the formation of interlacing cords or strands which very occasionally differentiated into capillaries. The outgrowth was associated with an active proliferation of macrophages, but there was no evidence that these arose from the mesenchymal or endothelial cells or vice versa. Since this is the only reported work on tissue cultures of retinal endothelium the findings are compared and contrasted with tissue culture studies of endothelium from other tissue sources.

This is the final paper in a series reporting our studies on the effect of hyperoxia on the retinal vessels of the rabbit. It deals with the in vitro behaviour of the adult andimmature retinal vascular complex and of growing endothelial cells in tissue culture when exposed to anoxic, hypoxic and hyperoxic atmospheres. Comparison is made with growth in air, described in the previous paper, and the influence of added carbon dioxide and of changes in temperature and pH is reported. An account is given of the materials and methods employed, including time-lapse cinephotomicrography, phase-contrast light microscopy, conventional light microscopy and electron microscopy. Immature retinal capillaries exposed to pure oxygen showed, after 4–6 hr, shrinkage of the whole complex and individual capillary retraction. Movement of macrophages became sluggish and after 8–12 hr exposure the endothelial cells became swollen and broke down into granular debris. Within 24–30 hr the complex had entirely disintegrated: no growth occurred. Comparable experiments with 10% oxygen showed less breakdown than in air and outgrowth was profuse. Mature retinal capillaries exposed to pure oxygen showed much greater resistance to hyperoxic injury. Growing cells from the capillaries exposed to pure oxygen showed arrest of growth and contraction after 4–5 hr exposure; disintegration of cells began to appear after 18–22 hr and by 48 hr cellular death was complete (that is, some hours later than the immature capillaries). Macrophages in the culture were somewhat more resistant. This effect was obtained in all concentrations of oxygen above 30% at which level injury was minimal. Cells grew well in 10% oxygen and for short periods in pure nitrogen, but with cellular abnormalities and, in the case of the latter gas, with variable degrees of degeneration after 72-hr exposure. The ultrastructural evolution of the oxygen injury is described. Granular degeneration is largely due to the formation of autophagic vacuoles and it is thought that lysosomal injury is an important early change. These findings are discussed and related to cognate work in the literature. It is concluded that the reactivity of retinal vascular endothelium to oxygen in vitro is closely comparable to that of retinal vessels in vivo, both in animals and man, showing a uniform mode of cellular breakdown and parallel relationships between the degree of cellular maturity, the period of exposure and the concentration of oxygen. It follows that injury to the retinal endothelium in all these circumstances is most probably due to the direct action of oxygen.

The presence of fenestrations or “pores” in the endothelium of small blood vessels has been reported in numerous tissues and in several different animals. However, on only one occasion has a fenestrated blood capillary been described in muscle and the author of that paper considered the structure to be transient ( Karrer, 1960 ). In this paper the structure of fenestrated blood vessels in various ocular sites in rats and mice is compared and the presence of fenestrated blood capillaries in the extraocular muscles is reported. These fenestrations are found in about half of the capillaries occurring in the area of insertion of the recti muscles into the globe.

The endothelium of the corneoscleral trabeculum is an important part of the filtration apparatus of the human eye.1-4Minute details of structure and pathology are valuable, since they may eventually help to understand, prevent, and treat glaucoma. In this paper a new technique is introduced to demonstrate the trabecular meshwork with its endothelium and the supplying nerve fibers. The examination of the trabeculum of the normal eyes of a small child confirmed the findings of earlier authors. The studies of the trabeculum of eyes with two different types of angle closure following cataract surgery revealed extensive atrophy of the endothelium and changes of the trabeculae. The present paper represents my first report on the pathology of the chamber angle. More papers on this subject are intended. The reported findings are given with a short clinical description of the cases used for the demonstration. This is necessary, since this paper

Injection into varicose veins of the lower extremities has become the most popular and is undoubtedly the best method of treatment in most cases. In a previous paper by Garside and one of us (Ochsner) 1 and in a previous paper by us 2 the results of histologic studies of the effects of intravenous injection of twenty-nine sclerosing solutions are reported in detail. In each of those papers attention was called to the fact that the endothelium was partially or completely destroyed by an effective thrombosis-producing agent, and mention was made of the fact that such destruction was essential for the precipitation of a thrombus. In our last paper 2 we also showed that the effect of some sclerosing agents was not only the destruction of the intima but also at times the production of coagulation necrosis of the media. The intima, when sufficiently injured, disappeared so that it was

Dec. 4, 1915, the writer presented before the Biological Society of Washington a paper on the identification of the asexual stages of Bacrtonella bacilliformis, the causative organism of verruga, which was published in the Dec. 19, 1915, issue of the Journal of the Washington Academy of Sciences. Jan. 7, 1916, he presented the same subject before Section VIII of the Second Pan-American Scientific Congress, during which presentation he announced certain points additional to those previously announced. This second paper will be published in due course in the Proceedings of the Congress, but it is desirable to place on record at once the additional points announced therein. They are as follows, and should be added to the paper published Dec. 19, 1915: The toxin resulting from the extensive asexual multiplication of Bartonella in the vascular endothelial cells of the subcutaneous tissues is liberated in quantity into the blood, causing the rise of temperature which marks the fever stage of verruga, the anemia following through hemolysis. The proliferation of vascular endothelial cells incited by this toxin not only imprisons the toxin itself, thus arresting the hemolysis, but also prevents the erythrocytes from coming into direct contact with endothelial cells containing merozoites of Bartonella, thus cutting short the infection of the erythrocytes. As the natural result, the fever and anemia both subside, and the gametes of Bartonella are no longer to be found in the peripheral blood. The infected endothelial cell, in situ in the capillary wall, is positively chemotropic for uninfected freshly oxygenated erythrocytes, attracting and holding them in contact with itself until transfer of a certain number of merozoites of Bartonella has been effected, the presence of which reduces the oxygen tension in the substance of the erythrocytes, thereby transforming their tropic qualities, the sufficiently infected erythrocytes being set free through negative chemotropism. The localized proliferation of vascular cells following verruga eruption-tissue inoculations is not due to any new activity of a living organism or virus. The reason why Drs. Strong ct al. were unable to obtain proliferation lesions by injection of a filtrate from these tis

This paper generalizes a diffusion model of endothelial vesicular transport, previously described, to the case in which the plasmalemma is considered to behave as an imperfectly absorbing, or “elastic,” barrier for vesicles. The consequences of various anatomical and physiological assumptions, and of assumptions as to the probability of absorption, α, are studied. It was found that for a constant transiting vesicular flux the concentration of free vesicles is relatively insensitive to changes in α unless α ⪡ 1; the consequences of this finding for another diffusion model of vesicular transport are discussed. The recent publication of values estimating the mean attachment time of sessile vesicles in the endothelium of muscle capillaries makes it possible to use this generalized diffusion model to estimate the probability of fusion of free vesicles on collision with the plasmalemma, and for the first time to calculate the diffusion constant for endothelial vesicles and the cytoplasmic viscosity of capillary endothelial cells, if this model is valid. The confidence to be placed in such estimates is limited, however, by uncertainty as to the accuracy of the estimates currently available in the literature for two morphometric parameters of muscle capillaries: The surface density (cm2/cm3) of capillary endothelium and the density of free vesicles in the cytoplasm of endothelial cells.

The main findings reported in the paper are as follows. 1. The cells, including endothelial and smooth-muscle cells, came to associate closely with each other, and elastic (membranes) layers intervening among them were interrupted by the cytoplasmic projections of endothelial and muscle cells before birth. In the next stage (just before birth), disorder of cellular arrangement occurred remarkably. Some of the endothelial and smooth-muscle cells protruded into the vascular lumen. Later the central part of the obliterated D. a. was occupied by modified smooth-muscle cells, and most of them became necrotic. However, some of the smooth-muscle cells did not degenerate and seemed to change into fibroblast-like cells in the peripheral regions. During these processes, mitosis of intimal cells was found in a few cases. 2. During the obliteration, mucoid substance appeared in the cytoplasm of the smooth-muscle cells instead of myofilaments, and fusion of smooth-muscle cells sometimes occurred in the inner and middle parts of the muscle cell layers. Just after birth, inclusion bodies identified as lysosomes were found randomly distributed in the cytoplasm of the smooth-muscle cells. 3. Nerve endings, fibroblasts and mast cells were scarcely seen in the ductus arteriosus at the early stage of the closure. 4. In embryos treated with cortisone and vitamin A by the authors' method, unlike the untreated controls, mucoid substance did not appear in the smooth-muscle cells, and the myofibrils remained vigorous, till a later stage. Further, two sets of myofibrils were observed in a single cell. Generally speaking, endothelium and smooth-muscle cells in treated embryos were thin compared with those of controls. However, the obliteration of ductus arteriosus was rather accelerated in treated embryos.

The unsteady response of the rabbit cornea to the normal periodic variations in tear tonicity which accompany the sleep-wake cycle is examined quantitatively in terms of a physical description of corneal mechanics and transport. Two different sets of experimental epithelial and endothelial flow conductivities and reflection coefficients are used, and the effect of variations in epithelial solute permeability and sodium pump rate is examined. The use of a set of experimental corneal parameters chosen earlier provides good agreement between calculated and observed in vivo corneal thickness dynamics when the tear tonicity is within the physiologic range. The factors affecting the time-course of corneal thickness dynamics are discussed, including the osmometric quality of the corneal stroma, the role of the epithelial sodium pump, the flow resistance of the limiting corneal layers, and cyclic changes in aqueous tonicity. The unsteady solutions presented here are related to the steady-state solutions given in earlier papers through the concept of the time-average steady state. Any realistic description of the normal in vivo cornea must recognize its unsteady character and the potential for transepithelial flow. On the average, the hypertonicity of the tears relative to the stromal fluid can be sufficient to account for rabbit corneal deturgescence. The absence of endothelial “pumping” from the in vivo rabbit cornea cannot be proven; neither is there any certain need to postulate such transport in the normal state.

This paper is a histochemical and ultrastructural study of a case of mucopolysaccharidosis with certain clinical and morphological peculiarities. The patient was a 3-year-old girl with a congenital cataract of the right eye; the onset at the age of one was marked by epileptic seizures, accentuated hypotonia, and progressive psychic degradation. Optical microscopy of a cerebral biopsy specimen revealed ballooning of the neurons, swollen dendrites, vacuolized cytoplasm, and excentric nucleus. PAS staining showed an intensely positive material in the grey matter. Ultrastructural aspects were the presence of lamellar bodies, granulo-membrano-vacuolar bodies, low electron-dense vacuoles, and a special aspect of membranous body conglomerates with a peculiar orientation of the membranes. The presence of nuclear bodies in the astrocytes is described. Listing of this case among the existing classification types is discussed.

In 1923 Levaditi and Nicolau,1 in a rather extensive report on their neurovaccine, came to the conclusion that the vaccinia virus possesses an elective affinity for tissues derived from the ectoderm as well as certain organs of endodermic origin, while it has practically no affinity for mesodermic tissue. They also determined that a proliferation of the epithelium generally occurs. Soon afterwards, Ledingham2 published a series of papers attempting to disprove Levaditi's assertion that the primary reaction against an injection of vaccinia virus is a proliferation of the epithelium. He considered vaccinia as the type of a virus whose affinities are almost solely toward cells of the mesoderm. A preeminent affinity of the vaccinia virus for epiblastic tissue did not seem consistent with the appearance of antiviral substances in the blood of an immunized animal. Ledingham concluded that the primary reaction against an injection of the virus is an accumulation of the cells of the reticulo-endothelial system and that any epithelial proliferation that may appear is of secondary importance. Ledingham agreed that there is a definite tendency on the part of the basal layer of the epithelium to proliferate, giving rise sometimes to irregular outgrowths. However, he considered such happenings to be the result of the injection of any foreign material which has to be eliminated.

In a previous paper, we reported on phagocytosis of hematoxylin and its loss of color reaction after entering cells. The technic employed was to insert into muscles, catgut threads which had been soaked in hematoxylin solution and subsequently dried. A similar catgut technic was used in the present investigation for studying another aspect of phagocytosis, namely lipophagia. In some recent work on experimental cholesterol arteriosclerosis we were occupied with the problem of lipophagia and cholesterol phagocytosis. I t is not necessary to discuss here the adequacy of the term arteriosclerosis; suffice it to say that some species (rabbits, and to a slighter degree and less regularly, guinea pigs) react to the oral or percutaneous administration of cholesterol with the formation of foam cells and lipoid deposits in blood vessels as well as in other tissues and organs. Rats and cats, however, are refractory. Altschul showed that golden hamsters also are susceptible to cholesterol arteriosclerosis while, according to our recent experiences, prairie gophers are not. The foam cells of arteriosclerosis are believed to develop from endothelium (Wacker and Hueck), macrophages (Duff and many others), sessile elements of the reticulo-endothelial system (Leary) or from other cell types as well (Hueper, Altschul). I t is not established with certainty whether such cells become foamy by phagocytosis or whether they undergo fatty degeneration. There is the possibility that the variable susceptibility to lipoidosis in cholesterol arteriosclerosis may be somehow correlated to lipophagia in general and, we have, therefore, undertaken to investigate the latter in those species whose reaction to cholesterol feeding, whether positive or negative, is sufficiently known. As may be expected, lipophagia has been already studied experimentally, e.g., by Clark and Clark and more recently by Tompkins, whose experiments were restricted to cholesterol. However, to our knowledge, the problem has not yet been viewed from the standpoint of species differences. This new approach has little or no relation to former experiments and we, therefore, omit a discussion of the literature.

This paper represents the third part of a monograph on the development of the lymphatics and lymph hearts of Anura. In this part are considered the origin and development of the subvertebral, lateral, and dorsal lymphatics of the trunk, the caudal lymphatics, and the posterior lymph hearts. The chief lymphatic trunks arise along the veins from a series of small, spindle-shaped, and discontinuous anlagen which subsequently coalesce and thus establish continuity with one another. Lymph plexuses are formed from which emerge the main secondary lymph channels. After such trunks are laid down as indicated, smaller branches and capillaries spring from them by sprouting or extension, due to their actively proliferating endothelium. The posterior lymph hearts ‘crystallize,’ so to speak, from localized areas of the lateral lymphatic plexus. During its reorganization and differentiation, it temporarily separates from the surrounding lymph plexus. Other genetic details, such as the formation of its valves, histogenesis of its walls, number of hearts laid down, etc., are also considered. Twenty-two figures (microphotographs and reconstructions) accompany the text.

Previous work has shown that endogenous chemical mediators, of which histamine is the prototype, increase the permeability of blood vessels by causing gaps to appear between endothelial cells. In the present paper, morphologic and statistical evidence is presented, to suggest that endothelial cells contract under the influence of mediators, and that this contraction causes the formation of intercellular gaps. Histamine, serotonin, and bradykinin were injected subcutaneously into the scrotum of the rat, and the vessels of the underlying cremaster muscle were examined by electron microscopy. To eliminate the vascular collapse induced by routine fixation, in one series of animals (including controls) the root of the cremaster was constricted for 2–4 min prior to sacrifice, and the tissues were fixed under conditions of mild venous congestion. Electron micrographs were taken of 599 nuclei from the endothelium of small blood vessels representing the various experimental situations. Nuclear deformations were classified into four types of increasing tightness (notches, foldsl closing folds, and pinches. In the latter the apposed surfaces of the nuclear membrane are in contact). It was found that: (1) venous congestion tends to straighten the nuclei in al groups; (2) mediators cause a highly significant increase in the number of pinches (P < 0.001), also if the vessels are distended by venous congestion; (3) fixation without venous congestion causes vascular collapse. The degree of endothelial recoil, as measured by nuclear pinches, is very different from that caused by mediators (P < 0.001). (4) Pinched nuclei are more frequent in leaking vessels, and in cells adjacent to gaps (P < 0.001); (5) mediators also induce, in the endothelium, cytoplasmic changes suggestive of contraction, and similar to those of contracted smooth muscle; (6) there is no evidence of pericyte contraction under the conditions tested. Occasional pericytes appeared to receive fine nerve endings. Various hypotheses to explain nuclear pinching are discussed; the only satisfactory explanation is that which requires endothelial contraction.

The purpose of this paper is to clarify relationship between venous thrombosis and microthrombi on the intact endothelium. ADP-infusion caused a remarkable adhesion of platelets to the apparently unbroken endothelium of dog femoral vein and enhanced the development of microthrombi under partial stasis, and by these procedures, occlusive venous thrombus occurred very frequently under the serum-induced hypercoagulability without endothelial injury. It is concluded that ADP acts on platelets not only to aggregate to each other but to adhere to the intact endothelium and increased microthrombi play an im-portant role to promote formation of venous thrombus without endothelial injury.

The paper presents information about the fine structure of the sinusoids, the space of Dissé, the development of the bile canaliculi and some compartments of the hepatocytes in the liver of the carp. The sinusoids are covered completely by flat endothel cells. The plasma of these cells contains numerous vesicles. The endothelial cells possess plasmatic processes, which extend into the space of Dissé. The fine structure of the space of Dissé corresponds to that of mammals, the existence of fibrebundles included. The bile canaliculi don't develop intracellularly as described by other authors. They run intercellularly as in mammals, but they form diverticles which reach into the plasma sideways. The rough ER was found in two types. Outwardly the liver is limited by a layer of connective tissue existing in two different layers.

cesses affecting the cornea. Diagnosis and treatment of corneal disease de¬ mand an understanding of the events occurring in the reparative processes in the cornea. Widespread clinical interest has engendered intense re¬ search activity, and the resultant lit¬ erature is voluminous. The appli¬ cation of the techniques of electron microscopy, in particular, has given considerable aid to our understanding of corneal healing. This review will concentrate on re¬ search in the past two decades and is limited, in the main, to English lan¬ guage sources. The interest in corneal wound heal¬ ing extends back well into the 19th century. Early studies described basic events in corneal wound healing in excellent detail. A subsequent lull in research in this subject is evident un¬ til the 1940s, when a series of fine papers extending our knowledge ap¬ peared; many of these studies were the result of World War II research directed to the effects of noxious agents on the cornea. Periodic studies appeared in the 1950s describing ex¬ perimental histological and histochemical findings; application of the techniques of electron microscopy in the 1960s has added a new dimension

Chronic serum sickness was produced in rabbits by intravenous injections of bovine serum albumin. Rabbits making a hyperactive antibody response to multiple injections each day of high doses of bovine serum albumin developed glomerulonephritis and extra-glomerular lesions characterized by accumulation of inflammatory cells in the interstitium, in Bowman's capsule, in the walls of peritubular capillaries and by tubular atrophy and interstitial fibrosis. Granular deposits of bovine serum albumin, rabbit IgG, IgM and C3 were seen by immunofluorescence microscopy in these structures, corresponding to electron-opaque deposits observed by electron microscopy. The deposits presumably contained antigen-antibody complexes. Extra-glomerular renal changes were not reported in previous studies of experimental serum sickness in rabbits. Therefore it is likely that the different system of immunization used in these experiments may produce formation of larger amount of immune complexes and/or longer persistence of critical levels of complexes in the circulation than in rabbits receiving daily a single injection of bovine serum albumin. The lesions described in this paper are comparable to those observed in the kidneys of patients with active systemic lupus erythematosus glomerulonephritis.

This paper presents an overview of the problem of measuring the conductance of biological tissues by an analysis of the transient voltage response to step currents of constant magnitude. In general, the voltage response of tissues is characterized by a small step change in voltage followed by an exponential like rise. In the case of the gastric mucosa the voltage appears to level off after about 20 msec but this is only apparent; it actually continues to increase for about 100 sec. In the case of the frog cornea the voltage response levels off in about 1 sec. The response of the cornea with the endothelium removed is essentially similar to that of the intact cornea. The response of the cornea with the epithelium removed leaving the endothelium plus stroma behaves like an ohmic resistor with the usual sweep speeds in the msec range. The response of the above tissues are analyzed in light of the problem of determining the resistance of biological tissues.

The experiments presented in this paper support the idea that the output of small lymphocytes from the thoracic duct of the rat (about 109/day) is normally maintained by a large-scale re-circulation of cells from the blood to the lymph. It has been shown that the main channel from blood to lymph lies with in the lymph nodes and that small lymphocytes enter the nodes by crossing the walls of a specialized set of blood vessels, the post-capillary venules. In order to trace the fate of small lymphocytes, cells from the thoracic duct of rats were incubated for 1 hin vitrowith tritiated adenosine. This labelled theRNAof about 65% of the small lymphocytes and more than 95% of the large lymphocytes; it also labelled theDNAof a proportion of the large lymphocytes. The mixture of small and large labelled lymphocytes was transfused into the blood of two groups of rats which belonged to the same highly inbred strain as the cell donors. At various times after the transfusions the thoracic ducts in one group of rats were cannulated to determine the proportion of labelled cells which could be recovered in the lymph; at corresponding times, the rats in the other group were killed and autoradiographs prepared from their tissues to determine the location of the labelled cells. The radioactive label in theRNAof small lymphocytes was stable enough to ensure that the labelled small lymphocytes which were recovered in the lymph several days after a transfusion were those which had originally been transfused into the blood. When the thoracic duct was cannulated 20 to 27 h after a transfusion, about 70% of the labelled small lymphocytes which had been transfused into the blood could be recovered from the thoracic duct over a 5-day period of lymph collection. During the first 36 to 48 h after cannulation, while the total output of small lymphocytes was falling rapidly, the proportion of labelled cells in the lymph remained approximately constant. The pool of the animal’s own cells with which the labelled cells had mixed contained between 1·5 and 2 × 109small lymphocytes; this was identified as the re-circulating pool. An autoradiographic study showed that after their transfusion into the blood the labelled small lymphocytes ‘homed’ rapidly and in large numbers into the lymph nodes, the white pulp of the spleen and the Peyer’s patches of the intestine. The concentration of labelled cells in other tissues was trivial in comparison. Labelled small lymphocytes were seen penetrating the endothelium of the post-capillary venules in the lymph nodes within 15 min of the start of a transfusion; they were traced into the cortex of the nodes and finally into the medullary lymph sinuses. Labelled small lymphocytes did not migrate into the adult thymus but a few entered the thymus of newborn rats. It was concluded that the re-circulating pool of small lymphocytes was located in the lymphoid tissue, the thymus excepted, and that the rapid ‘homing’ of cells into the lymph nodes had its basis in the special affinity of small lymphocytes for the endothelium of the post-capillary venules. The interpretation of these experiments was not complicated by the presence of large, as well as of small lymphocytes in the suspensions of labelled cells which were transfused. Other experiments, in which the large lymphocytes alone were labelled with tritiated thymidine, showed that most of them migrated from the blood into the wall of the gut where they assumed the appearance of primitive plasma cells; very few divided to form small lymphocytes.

This paper describes a method for the short-term preservation of rat aortic endothelium and presents evidence that such endothelium is capable of DNA synthesis in vitro. The method consists of relatively nontraumatic surgical removal of rat aorta and incubation of 2–5 mm segments in medium 199 with 10% fetal calf serum. DNA synthesis was assessed by autoradiography of en face preparations of endothelium after exposure to 3H-thymidine in vitro and endothelial structure was studied by electron microscopy. The percentage of labeled cells in uninjured aortic segments incubated with 3H-thymidine in vitro varied according to the age of the rat, being highest in younger rats and lowest in old retired breeders. The length of survival in culture was determined by ability of endothelium, that had been stimulated by in vivo crushing of the aorta, to incorporate 3H-thymidine at intervals after in vitro culture: labeled endothelial cells were readily identified 24–48 h after culture, when up to 90% of the endothelium appeared to be preserved in en face preparations. Subsequently there was progressive detachment of endothelial cells, but patches of endothelium and labeled cells were seen as late as 6 days after culture. Trauma to the aorta in vitro, after removal from the animal, also resulted in stimulation of DNA synthesis in endothelial cells of aortic segments in culture. Electron microscopic observations confirmed adequate preservation of endothelial structure after 24 and 48 h of culture. The relative simplicity of the method and the demonstration of the ability of cultured endothelial cells to incorporate 3H-thymidine after both in vivo and in vitro trauma make it suitable for studies on endothelial regeneration.

In the paper the author describes the fine structure of terminal vascular branches in various organs of animals and human under normal physiological and experimental conditions and some pathological processes. Vesicles in various functional states of the capillaries are described as well as some more rarely encountered inclusions such as fatty drops, lipofuscyne granules anf glycogen storages, Microruptures of the vessels are found in inflammatory processes as well as disappearance of membranes of some fenestrations in the capillaries of the thyroid gland in thyreotoxicosis.

Summary Unfixed endothelium can be peeled off the inside of the aorta in a number of mammalian species with cellulose acetate paper.

This paper discusses the possibility that fenestrated capillaries may be induced by the presence or action of epithelial cells.

The passage of substances across the endothelial barrier may occur—theoretically at least [1]—by two main pathways: a) Through the cells. Particles of colloidal gold [2] or molecules of ferritin [3] injected into the plasma are taken up by the pinocytic vesicles of the endothelial cells, and thereafter appear in the extravascular spaces. This and other forms of trans-cellular passage will not be dealt within this paper, b) Between the cells. Interest in the intercellular junction as a potential pathway is stimulated by physiologic studies, which indicate that traus-endothelial passage of ions and small molecules is a passive process. Dyes injected intra-arterially escape at discrete points along venules and capillaries [4], in a manner which could not be adequately explained by pinocytic transfer [1]. It has been stated that the endothelial cells are connected by “tight junctions” or zonulae occludentes [5, 6]. It has not, however, been shown that these junctions form a continuous band around each cell, and that they do indeed represent a tight seal. The zone of membrane “fusion” could represent, rather than a seal, a very fine filter permeable to water and to very small molecules [7, 8]. By electron microscopy, the passage of tracer particles along junctions which appeared to be still “closed” has been observed [9] : these studies were done in vitro, on rat hearts perfused with a saline solution containing particles of saccharated iron oxide (S.I.O.).

Publisher Summary The blood–brain barrier (bbb) includes all structures between the capillary lumen and the central nervous tissue: the endothelium of the capillaries, the basement membrane, and the surrounding glial foot processes. Functionally, the bbb should be regarded as a system limiting the free exchange between blood and brain; it further exerts its function on transport processes essential for the nutrition of the brain and on those in the opposite direction, from the brain into the blood. The bbb is also effective as an intermediate system in humoral regulations of peripheral vegetative functions. Alterations of the bbb with increased permeability cause enhanced exchange between blood and brain which is dependent on the intensity of the disturbance; by this means the penetration of viruses and bacteria from the blood into the brain may be facilitated. This increased permeability may be followed by cerebral edema and by an increased predisposition for epileptic seizures. This paper demonstrates the increased permeability of the bbb in pathological conditions, that is, pathological conditions involving a reduced exchange between blood and brain. Under normal conditions glucose is the most important if not the only source of energy for the brain. Because glucose cannot enter the brain from the blood by a process of diffusion, glucose uptake is independent of the glucose level of the blood, over a wide range. The nutrition of the brain depends on a transport mechanism specific for glucose in the bbb system. As a conclusion, results of measurements of cerebral metabolism in patients with mental disturbances and in older men without great mental disturbance have also been mentioned.