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An outbreak of suspected iridovirus disease in cultured hybrid grouper (♀Tiger Grouper Epinephelus fuscoguttatus × ♂ Giant Grouper Epinephelus lanceolatus) occurred in the Guangxi Province in July, 2018. In this study, grouper iridovirus Guangxi (SGIV-Gx) was isolated from diseased hybrid grouper that were collected from Guangxi. Cytopathic effects were observed and identified in grouper spleen cells that were incubated with diseased tissue homogenates after 24 h, and the effects increased at 48 h postinfection. The transmission electron microscopy results showed that viral particles that were about 200 nm in diameter with hexagonal profiles were present in the cell cytoplasm of suspected virus-infected cells. The presence of SGIV-Gx (accession number: MK107821) was identified by polymerase chain reaction (PCR) and amplicon sequencing, which showed that this strain was most closely related to Singapore grouper iridovirus (AY521625.1). The detection of SGIV-Gx infection was further supported by novel aptamer (Q2c)-based detection technology. The effects of temperature and pH on viral infectivity were analyzed by using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and cell culture. The results indicated that SGIV-Gx was resistant to exposure to pH levels 5, 7, and 7.5 for 1 h, but its infectivity was remarkably lower at pH levels 3 and 10 after 1 h. The analyses showed that SGIV-Gx was stable for 1 h at 4°C and 25°C but was inactivated after 1 h at 40, 50, and 60°C., (© 2019 American Fisheries Society.)

Microvascular anatomy and histomorphology of larval and adult spleens of the Clawed Toad, Xenopus laevis were studied by light microscopy of paraplast embedded serial tissue sections and scanning electron microscopy (SEM) of vascular corrosion casts (VCCs). Histology showed i) that white and red pulp are present at the onset of metamorphic climax (stage 57) and ii) that splenic vessels penetrated deeply into the splenic parenchyma at the height of metamorphic climax (stage 64). Scanning electron microscopy of VCCs demonstrated gross arterial supply and venous drainage, splenic microvascular patterns as well as the structure of the interstitial (extravasal) spaces representing the "open circulation routes." These spaces identified themselves as interconnected resin masses of two distinct forms, namely "broccoli-shaped" forms and highly interconnected small resin structures. Arterial and venous trees were clearly identified, as were transitions from capillaries to interstitial spaces and from interstitial spaces to pulp venules. Venous sinuses were not diagnosed (nonsinusal spleen). The splenic circulation in Xenopus laevis is "open." It is hypothesized that red blood cells circulate via splenic artery, central arteries, penicillar arteries, and red pulp capillaries primarily via "broccoli-shaped" interstitial spaces, pulp venules and veins into subcapsular veins to splenic veins while lymphocytes circulate also via the interstitial spaces represented by the highly interconnected small resin structures in vascular corrosion casts. In physiological terms, the former most likely represent the fast route for blood circulation, while the latter represent the slow route. J. Morphol. 277:1559-1569, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: Lymphoid tissue remodeling is characteristic of chronic simian immunodeficiency virus infection., Methods: A rhesus macaque infected with SIVmac239 was necropsied and its lymphoid tissues subjected to histopathology characterization., Results: Germinal centers in spleen and lymph nodes contained PAS-positive, non-amyloid extracellular deposits, decreased T follicular helper cells, and normal density of Ki67(+) B cells., Conclusions: A possible mechanism for PAS-positive deposits includes exaggerated involution of SIV-induced follicular hyperplasia secondary to virus-associated immune reaction., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We studied the morphology and occurrence of splenic Langerhans-like (LL) cells in species representing 11 orders of ray-finned fishes, Actinopterygii. LL cells were frequent in spleen tissue of species among Cypriniformes, Esociformes, Salmoniformes, and Pleuronectiformes. These cells contained granules which resembled Birbeck granules known to occur in mammalian Langerhans cells. The ultrastructure of LL cells in Northern pike, Esox lucius, and in Atlantic halibut, Hippoglossus hippoglossus were similar to those reported in salmonids. LL cells found in cyprinids shared some characteristics with the LL cells in other Actinopterygii species, although unique structures distinguished them from the latter. They contained dense bodies within the Birbeck-like (BL) granules, a characteristic that was never observed in species outside the Cypriniformes. Two types of BL granules were characterized in cyprinid LL cells. The ultrastructure of BL granules across the species is discussed. LL cells in all Actinopterygii species demonstrated close contacts with nearby cells, characterized by adherens-like junctions. Additionally, multivesicular bodies were present within the cytoplasm and large aggregates of exosomes were observed closely associated with the plasma membrane suggesting their release from the cells. These structures are discussed in relation to mammalian dendritic cells. Macrophages found in European perch, Perca fluviatilis, blue gourami, Trichogaster trichopterus, and Atlantic halibut, Hippoglossus hippoglossus contained lysosomes and residual bodies with structures resembling Birbeck granules. These granules and cells were clearly distinct from LL cells., (© 2010 Wiley-Liss, Inc.)

Macrophage aggregate (MA) morphometry and pigment composition are believed to be dependent on the species, age, and health status of the fish. The aim of this study was to characterize a "normal" morphometry baseline of spleen and kidney MAs in blue gourami Trichogaster trichopterus and freshwater angelfish Pterophyllum scalare. Three size-classes of clinically normal fish were analyzed. Blue gourami and freshwater angelfish were obtained from three local ornamental fish farms; for each size-class, 10 fish from each farm were analyzed. Hematoxylin- and eosin-stained tissue sections were analyzed by light microscopy at 100x magnification and an image analysis program. The percentage of tissue occupied by MAs, MA size, and MA number were calculated on three arbitrarily selected fields of view from each spleen and kidney. In clinically normal blue gourami, increases in the percentage of tissue occupied by MAs and in MA size were associated with an increase in fish size, but in clinically normal angelfish no correlation was observed. Furthermore, in angelfish, a high variability in MA morphometry was observed, even among fish from the same sample group. In both species, a significant difference in the value of the morphometric parameters was observed among farms. Because iridoviruses inhibit macrophage activity and (possibly) proliferation, MAs in 25 clinical cases of iridovirus-infected blue gourami were analyzed. Preliminary data indicate that in iridovirus-infected blue gourami, there is a decrease in MA size and MA number compared with those of healthy fish.

Morphological and cytological alterations at the light microscope (LM) and transmission electron microscope (TEM) levels were observed in the thymus, spleen, head-kidney, and liver of cardinal fishes (Apogonidae, Teleostei) from the Gulf of Aqaba, Red Sea, sampled from a strongly polluted site at the northern end of the gulf, and compared to similar samples from a clean, reference site. At the polluted site, the most prominent change was the formation of numerous deposits of cells rich in phagosomes with lipofucin, melanin granules, and phagocytosed debris, including a high increase in number and dimensions of Hassall's corpuscles and melano-macrophage centers. The number of Hassall's corpuscles was 20 (+/-8.0)/mm(2) and of melano-macrophage centers 18 (+/-4.0)/mm(2) at the polluted site, and 7.0 (+/-4.0)/m(2) vs. 5.0 (+/-2.0)/mm(2) respectively at the reference site. In numerous instances the head kidney's melano-macrophage centers in fishes from the polluted site were encapsulated by reticulocytes, a phenomenon recognized as a marker of neoplasmosis and possible malignancy. In the spleens of fishes from the polluted site, numerous deposits of cell debris, peroxisomes, and enlarged lysosomes were also observed. The livers (hepatopancreas) of fishes from polluted waters demonstrated very strong hyperlipogeny. Many of their hepatocytes were laden with lipid vesicles, fragmented endoplasmic reticulula, and aberrant mitochondria. Although the observed alterations in the glands and liver do not indicate any immediate threat to the life of the fish, they can become crucial with respect to energy turnover and fecundity trajectories. This study strongly suggests the use of cytological alterations in vital organs, such as were observed, as pathological biomarkers to environmental stress., ((c) 2004 Wiley-Liss, Inc.)

Rainbow trout (Oncorhynchus mykiss) fry and fingerlings with clinical signs of rainbow trout fry syndrome, and rainbow trout (0.5 to 3.5 g) with experimentally induced infections with Flavobacterium psychrophilum, were examined histopathologically and electron microscopically. Severe hypertrophy of the spleen and cellular degeneration were consistently observed. Distinctive features of the disease were the loss of definition of the splenic border and its replacement by a loosely structured eosinophilic layer, fibrinous inflammation and intercellular oedema within the spleen, and the presence of numerous filamentous bacteria interspersed throughout the organ.

1. This study was done to characterize the functional role of alpha 1D-adrenoceptors in rat myocardium, aorta, spleen, vas deferens and prostate by use of the selective antagonist BMY 7378. 2. BMY 7378 inhibited [3H]-prazosin binding to aortic membranes with a potency (pKi 9.8 +/- 0.40) approximately 100 fold higher than in right ventricular membranes (pKi 7.47 +/- 0.11) and approximately 1,000 fold higher than that in plasma membranes of the prostate (pKi 6.62 +/- 0.39), vas deferens (pKi 6.67 +/- 0.15), salivary gland (pKi 6.46 +/- 0.38) and liver (6.58 +/- 0.06). 3. BMY 7378 antagonized the positive inotropic effects of phenylephrine (in the presence of 1 microM propranolol) on right ventricles (pA2 7.0 +/- 0.11), left atria (pKB 7.04 +/- 0.18) and papillary muscles (pKB 6.9 +/- 0.1) and inhibited phenylephrine-induced increase in inositol phosphates. 4. BMY 7378 was approximately 100 fold more potent as an antagonist of phenylephrine on aortic strips (pA2 9.0 +/- 0.13) than on vas deferens (pKB 7.17 +/- 0.08) and spleen (pKB 7.16 +/- 0.21); it was ineffective on the prostate. 5. Chloroethylclonidine suppressed the maximal effects of phenylephrine on spleen; 5-methylurapidil antagonized the effects of phenylephrine on aortic strips (pA2 7.98 +/- 0.08), vas deferens (pKB 8.89 +/- 0.07) and prostate (pKB 8.85 +/- 0.21). 6. BMY 7378 caused a dose (0.1-100 nmol kg-1)-dependent decrease in mean blood pressure of urethane-anaesthetized rats and its hypotensive efficacy was equal to that of hexamethonium. 7. The data suggest that alpha 1D-adrenoceptors play a significant role in rat aorta, a minor role in the heart, vas deferens and spleen and virtually no role in the prostate.

1. Our previous work has shown that injection into mice of lipopolysaccharide (LPS) and the cytokines interleukin 1 (IL-1) and tumour necrosis factor (TNF) induces histidine decarboxylase (HDC), the enzyme forming histamine, in various tissues such as liver, lung, spleen and bone marrow, but not in the blood. The induction of HDC also occurs in nude mice and mast cell-deficient mice. On the other hand, haematopoietic cytokines such as IL-3, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF) only induce HDC in the haematopoietic organs, i.e. bone marrow and spleen. In the present study, the effect of macrophage depletion on the induction of HDC was examined. 2. On day 1 after a single intravenous injection of a macrophage depletor (liposomes encapsulating dichloromethylene diphosphonate, which is toxic when ingested into macrophages), macrophages were almost completely depleted in the liver and reduced by about 50% in the spleen and bone marrow, but not significantly affected in the lung. On day 3, the degrees of the depletion were similar to those of day 1. In the spleen, macrophages were depleted in the red pulp, and there was a structural destruction. 3. In macrophage-depleted mice, the induction of HDC by LPS, IL-1 alpha or TNF-alpha was not impaired in the liver, and was potentiated in the lung and bone marrow. The induction of HDC was decreased only in the spleen at day 3. 4. HDC was not induced by LPS in the spleen of the adult rat, which is correspondingly inactive in haematopoiesis.5 These results indicate that the major cells in which HDC activity is induced in response to LPS, IL-1 and TNF are not circulating granulocytes, circulating monocytes, T cells derived from thymus, mast cells or phagocytic macrophages. Based on these results, we discuss the possibility that the major cells in which HDC was induced in non-haematopoietic and haematopoietic organs were endothelial cells and haematopoietic precursor cells respectively.

Lymphoid organs from belugas, Delphinapterus leucas, ranging in age from less than one to 16 years, were harvested during a sanctioned hunt to investigate morphology. The spleen is divisible into red and white pulp and a stroma consisting of a reticular network, a collagenous capsule, and trabeculae containing smooth muscle bundles. White pulp areas appear to be devoid of follicles and consist mainly of periarteriolar lymphatic sheaths (PALS), that are larger in younger than in older belugas. Definitive marginal zones between red and white pulp are difficult to discern in older belugas. Lymph nodes are similar to those of other mammals; they possess a follicular cortex surrounding a vascular medulla composed of lymphatic cords and sinuses. Smooth muscle is abundant in the medullary region, usually in close proximity to sinuses. The expansive nodular mass at the root of the mesentery, often referred to as the "pseudopancreas," is similar to lymph nodes in microscopic architecture. Pharyngeal tonsils and gut-associated lymphoid tissue (GALT) are found along the digestive tract and display an "active" morphology. Tonsils are comprised of lobules of follicles separated by vascular connective tissue. Epithelial-lined crypts communicate with the pharyngeal lumen. GALT consists of diffuse and follicular lymphocytes within the intestinal mucosa and submucosa. The thymus is well developed in the younger belugas, with lobules divisible into densely packed cortical zones of thymocytes and more loosely arranged medullary lymphocytes. Hassall's corpuscles are occasionally visible within the medulla. Cetaceans diverged evolutionarily from other mammals over 55 million years ago. This study investigates changes in lymphoid organ morphology in a species that now inhabits a unique ecological niche. This study also lays the groundwork for functional investigation of the beluga immune system, particularly as it relates to differences between healthy and stranded animals.

Epidermal growth factor (EGF) receptors were detected in plasma membrane preparations of equine hoof wall laminar tissue at concentrations comparable to that of equine liver. Scatchard analysis of the equilibrium binding data suggested the presence of two classes of EGF binding sites in most of the controls (plasma membranes from clinically normal horses); a high-affinity class and a more numerous low-affinity class. The dissociation constant of the low-affinity class of EGF-specific receptors (KD = 1 x 10(-9)M) is in reasonable agreement with other values established for the EGF receptor. The variability between individual estimates for the KD of the high-affinity receptor class precluded an accurate estimate for those sites. A possible explanation is discussed. The high-affinity binding sites were uniformly absent in plasma membranes prepared from horses affected by chronic laminitis. Autoradiographic analysis localised the EGF receptors primarily to the secondary epidermal laminae, with an apparent greater density over the proliferative basal keratinocytes. Little label was associated with the dermal or the keratinised primary epidermal laminae. Tissue from horses with chronic laminitis had EGF receptors located uniformly over the hyperplastic epidermal keratinocytes. These data suggest that an EGF-mediated response may be involved in the hyperproliferative response that is characteristic of chronic laminitis.

The spleen of Rana perezi is encapsulated by connective tissue and shows by light microscopy two areas with no obvious border: the white pulp and the red pulp. The white pulp-lymphoid clusters are scattered throughout the organ and contain lymphocytes, reticular cells, and some plasma cells. The red pulp displays two different portions. The predominant region consists of reticular cells, lymphocytes, a variety of other leucocytes, and cells undergoing division. This area possibly performs a haemopoietic function. The smaller portion of the red pulp is characterized by reticular-phagocytic cells and may be haemocaretic in its function. Macrophages and pigmented cells occur in both white and red pulp. The organization of the spleen of R. perezi can be considered as a transitional or intermediate state between the primitive condition seen in certain fishes and amphibians and the more complex organ of ammiotes.

Eosinophilopoiesis in the musk shrew, Suncus murinus, a representative of the order Insectivora, was studied by light and electron microscopy. To examine biochemical features of cytoplasmic granules, extraction with proteolytic enzymes was carried out on ultrathin sections of bone marrow. In this species, eosinophils are produced in the same manner in both spleen and bone marrow. Developing eosinophils were distinguished as belonging to four stages, recognized by ultrastructural changes in cytoplasmic organelles as well as the eosinophilic granules during maturation. Granulogenesis began by budding of vacuoles containing flocculent material from the concave face of the Golgi apparatus, in the promyelocyte to myelocyte stage. The matrix of developing granules transformed into a finely granular structure, and the large spherical granules of mature eosinophils were homogeneous without crystalline cores. It was shown by proteolytic enzyme extraction that the proteinaceous cores of mature granules were uniformly removed; there was no evidence that they contained crystalloid inclusions. These results indicate that shrew eosinophils can be regarded as cells that retain a prototype of eosinophil granules, probably like those of ancestral mammals rather than those of higher living Mammalia.

After infection with 10(3) T. brucei GUTat 3.1, C57BL/6 mice produced antibody responses and controlled the first parasitaemic wave whereas C3H/He mice did not. The inability of C3H/He mice to control parasitaemia resulted from an impaired ability of parasite-induced antibody-containing cells to secrete immunoglobulin. Antibody-containing cells in infected C3H/He mice regained the ability to secrete antibody within 24 h after trypanosome elimination by treatment with Berenil, suggesting that the block in antibody secretion was maintained by living parasites or short-lived components of degenerating parasites. Infected C3H/He mice also had an impaired ability to produce a rabbit erythrocyte-specific antibody response on challenge with rabbit erythrocytes and this response recovered when parasites were eliminated from the blood 24 h before analysis. It was not possible to inhibit secretion of antibody by rabbit erythrocyte-induced plasma cells either by incubating them with serum from infected C3H/He mice or by injecting large numbers of living trypanosomes into C3H/He mice already responding to rabbit erythrocytes. The process leading to failure of parasite and rabbit erythrocyte-induced antibody-containing cells to become high rate antibody-secreting cells was not identified but did not appear to correlate with any obvious change in the intra-cellular morphology of the antibody-containing cells.

1 The effects of some guanidine derivatives, (-)-N-(1-phenylethyl) guanidine (PEG), guanethidine and debrisoquine have been investigated on the content and subcellular distribution of noradrenaline in cat spleen and on the overflow of noradrenaline from this organ during stimulation of the splenic nerve.2 PEG and guanethidine, at a dose of 5 mg/kg, produced adrenergic neurone blockade within 15 min and the same dose of debrisoquine produced blockade within 30 minutes.3 All three compounds produced a decrease of similar magnitude in the noradrenaline content of the high-speed particulate (P(2)) and supernatant (S) fractions of splenic homogenates; these actions were temporally correlated with the adrenergic neurone-blocking action of the compounds.4 PEG did not produce any further decrease in the noradrenaline content of the subcellular fractions at times up to 18 h after its administration; adrenergic neurone blockade was maintained throughout this period but had disappeared after 7 days when the noradrenaline content of the subcellular fractions was restored to control levels.5 Guanethidine, in contrast, caused a marked progressive loss of the transmitter from all subcellular fractions-an effect which was maximal 18 h after its administration but continued, as did the adrenergic neurone-blocking action, for at least 72 hours. This additional loss of noradrenaline, over and above that seen after 15 min, is unlikely to be connected with the adrenergic neurone-blocking action of the drug.6 Dexamphetamine both prevented and antagonized the neurone blockade and the subcellular noradrenaline-depleting action of PEG and guanethidine. The restoration of nerve function after administration of dexamphetamine to animals pretreated with 5 mg/kg of either of these compounds was temporally correlated with a selective repletion of the noradrenaline content of the supernatant fraction of the spleen.7 Larger doses (15 mg/kg) of PEG or guanethidine produced a selective depletion of noradrenaline in only the supernatant fraction of the spleen. This depletion was temporally correlated with the adrenergic neurone-blocking action of these compounds. The lack of effect of the compounds at this dose level on the noradrenaline contained in the P(2) fraction may be due to ;stabilization' of the store of noradrenaline in vivo which gives rise to this fraction on homogenization.8 It is suggested that the guanidine-type adrenergic neurone-blocking agents displace the noradrenaline which is readily available for release by nerve impulses, and that it is this action that may account for their sympathomimetic properties.9 The ability of these guanidines to impair the release of noradrenaline by nerve impulses could occur because whilst they are present within the neurone the ;nerve-releasable store', which may in these experiments appear in the supernatant fraction after homogenization, may be unable to refill with transmitter.

A histological investigation of the filtering function of the spleen of the sunfish Lepomis spp. was conducted by light, scanning, and transmission electron microscopy. The parenchyma of the organ is predominantly red pulp, a system of splenic cords and sinuses. The white pulp consists of loose lymphoid tissue which forms a cuff around the pulp arteries. Filtering of particulate matter from the blood occurs in the red pulp by phagocytes of the pulp cords and ellipsoids (periarterial macrophage sheaths). The ellipsoids are pale-staining cuffs of macrophages and reticular cells in a framework of reticular fibres surrounding the arterial capillaries. Destruction of effete blood cells (especially erythrocytes) is confined to the pigment nodules; particulate matter is not taken up by the nodules. These yellow-brown bodies are dispersed throughout the red pulp and are bounded by a reticular capsule. They contain masses of phagocytes and have the appearance of a morula. They are associated with blood vessels and are surrounded by sinusoids. Prussian Blue stain shows the presence of haemosiderin within their phagocytes. The phagocytes of the pigment nodules are filled with inclusions such as residual bodies, siderosomes, and fragments of erythrocytes. The early filtering of particulate matter by the phagocytes of the pulp cords and ellipsoids may allow for a more efficient phagocytosis of erythrocytes by the pigment nodules, followed by storage and reutilization of iron-containing compounds uncontaminated by other phagocytosed material.

In the ultrastructural comparison of normal, unimmunized spleens with immunized spleens at key intervals after antigenic stimulation with keyhole limpet hemocyanin (KLH), we noted cellular and cytological features which reflect the cellular kinetics of the primary immune response, particularly with respect to plasma cell production. Although lymphoblasts and mature plasma cells are present in the white and red pulp, respectively, intermediate stages of the plasma cell line are rarely found in normal spleen. Following antigenic challenge, we found a marked increase in lymphoblasts in the white pulp, most of them containing short segments of rough endoplasmic reticulum suggesting initial differentiation toward plasma cells. Following an apparent migration of cells from the white to the red pulp, we found plasma cells in various stages of maturation in the red pulp cords and sinuses. The ultrastructural features of these cells reflect the differentiation of lymphoblasts into mature plasma cells. Both immature and mature plasma cells usually possess dilated cisternae of rough endoplasmic reticulum, suggesting that they are capable of producing and storing a secretory product, presumably antibody. We also noted a large number of immature macrophages and monocytes in immunized spleens. These cellular events and their cytological characteristics are compared to those described in other vertebrate classes.

Scanning electron microscopy of microcorrosion casts was used to visualize circulatory pathways in the sinusal spleen of dog. The examination of contracted versus dilated organs and variations of the volume of material injected gave an indication of flow dynamics. Minimal injections of material into contracted spleens produced filling of mainly the fastest routes for flow, whereas injections into dilated spleens primarily filled slower routes. This procedure yielded a more complete, three-dimensional picture of the arterial, intermediate, and venous pathways as a whole, and of the relative amounts of flow through different arterial routes. Evidence of flow from capillary lumina out into ellipsoid sheaths was plentiful in casts from dilated spleens, but rare in casts from contracted organs. The pattern of flow within and out of the marginal sinus has been elucidated: A circumferential filling occurs first, followed by a flow that radiates outward into the marginal zone and red pulp. Venous sinuses filled via two routes in addition to the generally accepted path from the reticular meshwork via fenestrations in sinus walls. First, many venous sinuses extending out from the marginal sinus and surrounding marginal zone originated as open-ended tubes continuous with the reticular spaces of the marginal sinus or marginal zone. Second, direct connections of arterial capillaries with venous sinuses in the red pulp were found. Evidence indicating that some mechanism is controlling the flow via these routes is discussed. The strikingly different arrangement of venous sinuses in the subcapsular region is demonstrated.

Spleen from nine patients with hairy-cell leukemia (HCL) were studied for ultrastructural alterations. In all cases, hairy cells with typical ultrastructural characteristics were observed within splenic cords and sinuses. Hairy cells had numerous cytoplasmic processes that interdigitated with cytoplasmic processes of other hairy cells. Hairy cells also adhered to sinus endothelial cells and ring fibers and protruded into spaces between endothelial cells. Some normal sinuses were filled with aggregated hairy cells. Other sinuses appeared dilated. Many sinuses were lined by hairy cells that covered thinned endothelial cells and ring fibers. In these abnormal sinuses, endothelial cells were decreased and many appeared injured. The splenic cords were expanded by an infiltration of hairy cells and by large blood-filled spaces. These findings suggest that hairy cells adhere to many cell surfaces, produce endothelial cell injury and death, and impede the venous flow of blood in the spleen. All of the factors appear to influence the formation of the abnormal splenic sinuses and the blood-filled spaces that characterize HCL.

Scanning electron microscopy of microcorrosion casts was used to visualize circulatory pathways of the intermediate circulation in nonsinusal spleen of cat. The marginal sinus (MS) around lymphatic nodules is a distinct vascular space which fills preferentially before the filling of the marginal zone (MZ) and surrounding red pulp occurs. The MS, which has a plentiful vascular supply, does not usually enclose the nodule completely. From the MS, flow occurs radially outwards into the MZ. Corrosion casts and histological sections both showed that a diversity of forms of the MZ exists: The thickness of MZ and the arrangement of its reticulum vary among nodules and between different areas of the same nodule, from a complete absence to a region of up to 50 microns in width. No direct arteriovenous connections were found (in contrast to dog spleen: Schmidt et al., '83b). Aside from capillary endings in the MS and MZ, all arterial capillaries terminate in the reticular spaces of the red pulp, i.e., the circulation appears to be entirely "open." From each capillary termination a great variety of flow pathways through the reticular meshwork to the pulp venules is available; some of these routes are quite long but others may involve distances as short as 15-25 microns. Evidence of flow into ellipsoid sheaths was abundant in casts from dilated spleens, but scarce in contracted spleens. In contrast to the extensive system of interconnected venous sinuses in dog spleen, the pulp venules found in cat spleen are nonanastomosing, shorter, and much smaller in caliber, and all receive flow freely from the reticular meshwork via open ends and fenestrations in their walls.

Six cases of angioimmunoblastic lymphadenopathy (AIBL) are presented, detailed ultrastructural and immunohistologic studies of several involved organs are described, and the literature is reviewed. The features of the lesion are of normal immune reactive cells containing polyclonal cytoplasmic immunoglobulin. Large numbers of dying and degenerating cells result in accumulations of cell debris, corresponding to the characteristic interstitial material seen by light microscopy. Our studies confirm that the vascular changes are unique to lymph nodes, appear confined to postcapillary venules, and consist of endothelial cell hypertrophy and expansion of the vessel wall by basement membrane-like material, cellular debris and collagen fibers. No deposits of amyloid or antigen-antibody complexes were noted by ultrastructural or immunologic techniques. Our data reveal morphologic and laboratory features of a hyperimmune state but with paradoxical cutaneous anergy and decrease in blood (T) lymphocytes. We postulate that AIBL is an abnormal, but non-neoplastic immune reaction related to the autoimmune disorders, resulting from a loss of suppressor T cells with hyperfunction of the B lymphocyte system.

Seven surgically removed spleens from patients with hairy cell leukemia and hypersplenism were examined ultrastructurally. In all spleens the pulp cords were diffusely and compactly infiltrated by hairy cells. Numerous hairy cells were also evident in the often distended sinuses. The hairy projections were readily visible in electron micrographs and tended to interdigitate to form syncytium-like aggregates. Compression of hairy cells within the cords flattened the projections against the cell bodies and may account for the surface alterations reported by scanning electron microscopic studies. Controversy over the cytogenesis of hairy cells has not been resolved by ultrastructural studies. Although all seven patients had hypersplenism, the hairy cells showed no evidence of phagocytic activity. However, active phagocytosis by cordal macrophages was observed and there is a probable absolute increase in their number contributing to the splenomegaly. The dense infiltrate of hairy cells causes marked widening of the cords and retards the passage of formed elements of the blood through the red pulp. Prolonged sojourn of these elements in a metabolically unfavorable environment results in cellular damage, increased exposure to cordal macrophages, and premature destruction with the evolution of a hypersplenic syndrome.