Pit cells in extrahepatic organs of the rat

Electron microscopic examination of the extrahepatic distribution of pit cells, a cell type found in the liver, revealed their existence in several other organs of the rat. They were relatively frequent in lungs, spleen (red pulp), small intestine, epididymis, trachea, and peripheral blood; much fewer in bone marrow and thymus (medulla); and nonexistent in lymph nodes, spleen (white pulp), and thymus (cortex). The pit cells in these organs, as well as in the liver, contained characteristic dense granules and rod-cored vesicles in the cytoplasm. Our observations suggest that pit cells circulating in the peripheral blood adhere to the endothelium of capillaries in the various organs and migrate into the tissue, where they have some special immunological function.     

The ability to predict weight gain,individual organ weight,and corresponding food intake in the rat by the four-parameter model for physiological responses

The applicability of the four-parameter model for physiological responses to the prediction of food intake and corresponding weight gain and individual organ weight gain was studied further in 40-day postpartum male rats. Seven groups of animals were maintained on diets in which protein content ranged from 0 to 23.54% casein. Food intake and weight gain were recorded every other day for each animal for 21 days. At the termination of the experiment the following organs were removed and weighed: liver, heart, lungs, spleen, kidneys, adrenals, and testes. When these weight values are fitted by use of the four-parameter model, food intake and total animal and organ weight gains can be predicted in relation to the amount of protein in the diet. It was found that liver, heart, lungs, spleen, and whole animal had similar K(0.5) values. However, it was also shown that there is variation in response of organs when relating organ weight as a percentage of body weight. For example, heart, lungs, and testes show an increased ratio on low protein diet while liver, kidneys, and adrenals maintain a fairly constant ratio and the spleen shows a decreased ratio. Additionally, it was noted that the animals on low protein diet consumed more food per gram body weight but did so at a slower rate. Possible future applications of the four-parameter model for physiological reponses are discussed.     

Histopathologic and ultrastructural studies of disseminated cytomegalovirus infection in strain 2 guinea pigs

Inbred strain 2 guinea pigs developed severe disseminated disease during acute experimental guinea pig cytomegalovirus (GPCMV) infection. A high mortality rate (100%) resulted, with most animals dying between 10 and 14 days after high dose (7.5 X 10(5) TCID50) virus inoculation. Infectious virus was recovered from many tissues, including spleen, lungs, liver, pancreas, heart, adrenals, kidneys, and salivary glands. The rate of GPCMV isolation from these tissues ranged from 50 to 100%. Gross lesions were observed in the spleen, liver, and lungs. On histologic examination, lesions were also seen in many other organs, including heart, pancreas, kidneys, adrenals, brain, intestines, and salivary glands. Intranuclear viral inclusions were present in many cell types of various organs. Under electron microscopic examination, cells with viral inclusions were easily found in the spleen, and liver, but less readily in the lungs, kidneys, salivary glands, and other organs. Most of the intranuclear inclusions consisted of electron-dense fibrils (10 nm diameter), viral nucleocapsids (100 nm), and tubular structures (60 nm diameter). Dense bodies and enveloped dense virions containing single or multiple capsids were present in the cytoplasm of many infected cells. The morphologic developments of GPCMV in these visceral tissues of strain 2 guinea pigs resembled those seen in GPCMV-infected cultured guinea pig cells but differed from those observed in the infected salivary gland duct cells. Strain 2 guinea pigs are a useful animal model for studying disseminated infection in CMV-associated human diseases.     

Pathological, immunohistochemical, and in-situ hybridization studies of natural cases of postweaning multisystemic wasting syndrome (PMWS) in pigs

Fifteen pigs from five farms on which there had been a previous clinical and histopathological diagnosis of postweaning multisystemic wasting syndrome (PMWS) were investigated. At necropsy, enlargement of lymph nodes was the most obvious lesion; other lesions were non-collapsed lungs, ulceration of the gastric pars oesophagica, and cranioventral pulmonary consolidation. Microscopical lesions attributable to PMWS were found in lymphoid organs (including lymph nodes, tonsil, Peyer's patches and spleen), liver, kidney and lungs. Varying degrees of lymphocellular depletion, affecting both lymphoid follicles and parafollicular zones, and progressive multifocal to diffuse infiltration of lymphoid tissue by large histiocytic cells were the characteristic lesions. Syncytial cells were seen frequently, especially in lymphoid organs. A prominent finding was the presence of sharply demarcated, spherical, basophilic, cytoplasmic inclusions in histiocytic cells. The lymphoid lesions were suggestive of immunosuppression. Non-lymphoid lesions included interstitial pneumonia, periportal mononuclear inflammatory infiltration of the liver in varying degrees, and interstitial nephritis. Porcine circovirus (PCV) antigen and nucleic acid were regularly found in lymphoid organs, lung, liver and, to a lesser degree, kidney. Target cells for PCV replication included monocyte/macrophage lineage and antigen-presenting cells. To a lesser extent, epithelial cells such as renal tubular, bronchial and bronchiolar cells, endothelial cells, hepatocytes and lymphocytes were also labelled. One pig did not show PCV nucleic acid; sequence differences among different viral isolates are discussed as the probable cause of this lack of labelling by the in-situ hybridization PCV-specific probe.     

Immunocytochemical analysis of cellular responses to BCG.

The study reported here was performed to find out whether changes in the number of mycobacteria in various organs of BCG-infected mice can be related to changes in the phenotype of monocytes, macrophages and lymphocytes in the blood, various tissues, and peritoneal cavity and to the formation of granulomas in the spleen, liver and lungs. The relative amounts of various antigens on the leukocytes were assessed semi-quantitatively after immunocytochemical detection of the binding of monoclonal antibodies. Granuloma formation was determined after immunocytochemical staining of cells in sections of liver and lung tissue with a monoclonal antibody against the common leukocyte antigen and in sections of the spleen with a monoclonal antibody against the Mac-2 antigen. The results showed that during the first week of infection the number of BCG in spleen, liver and lungs declined considerably. Multiplication of mycobacteria during the second week of infection was associated with decreased expression of antigen F4/80 and increased expression of Ia antigen and Mac-2 antigen by blood monocytes and macrophages. Reduction of the numbers of BCG in the spleen and liver during the third week after i.v. injection of BCG and in lungs during the fourth week of the infection was found to be correlated with the degree of granuloma formation in these organs. After intravenous injection of killed BCG no changes were observed in the phenotype of monocytes and the macrophages in spleen, liver, lungs and peritoneal cavity. These mice showed considerably less granuloma formation than BCG-infected mice. The present results indicate that live but not killed mycobacteria induce macrophage activation.     

Comparative study of the distribution of 7,12-dimethylbenz(a)anthracene in pregnant rats and their fetuses

On the 21st day of pregnancy rats were given an intravenous injection of 7,12-dimethylbenz(a)anthracene (DMBA) in a dose of 15 mg/kg, and its concentration in the organs of the mothers (liver, kidneys, lungs, brain, spleen, and placenta) and of their fetuses (liver, kidneys, lungs, brain, intestine, carcass, and whole fetus) was determined by a fluorescence-spectral method 30, 60, and 180 min later. The highest concentration of DMBA in the mothers at all times was found in the lungs. With an increase in the time of injection the DMBA concentration fell in all organs of the pregnant rats, except in the brain, in which it rose. In the fetuses an irregular distribution of the carcinogen in the organs was found only 60 min after injection of DNBA, when the highest concentration was detected in the liver. In all fetal organs the maximal concentration was found after 60 min. Accumulation of DMBA in the various fetal organs did not correlate with the observed highest frequency of tumors in the kidney and nervous system of rat fetuses following transplacental exposure to DMBA in the same dose.Laboratory of Biophysics and Laboratory of Experimental Tumors, N. N. Petrov Research Institute of Oncology, Ministry of Health of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR L. M. Shabad.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 3, pp. 334–335, March, 1980.     

Tissue stages of<Emphasis Type="Italic"> Hepatozoon canis</Emphasis> in naturally infected dogs from São Paulo State,Brazil

A total of 222 dogs were examined by blood smear examination and Hepatozoon canis infection was detected in 13 dogs (5.9%). Five H. canis-infected dogs were necropsied to observe tissue stages in the organs. Fragments of spleen, liver, lungs, heart, kidneys, lymph nodes, bone marrow and skeletal muscles were used to made touch-impression smears. No macroscopic lesions were found in the organs. Two dogs had gamonts within polymorphonuclear cells and schizonts in various stages of development within the spleen and the bone marrow. Nevertheless, no mature meronts were found.     

Systemic injection of products of activated neutrophils and H2O2 in myeloperoxidase-immunized rats leads to necrotizing vasculitis in the lungs and gut.

The strong association of anti-neutrophil cytoplasmic antibodies with various forms of systemic vasculitis suggests a role for these autoantibodies in the pathophysiology of systemic vasculitis. In the present study, we tested the hypothesis that release of neutrophil lysosomal enzymes in the presence of an anti-myeloperoxidase (anti-MPO) immune response may underlie the development of systemic vasculitis. Brown Norway rats were immunized with MPO in complete Freund's adjuvant or complete Freund's adjuvant alone. Two weeks after immunization, rats bad developed antibodies to human and rat MPO as measured by enzyme-linked immunosorbent assay. Next, rats were intravenously infused with 400 micrograms of a human neutrophil lysosomal extract containing 200 micrograms of MPO followed by 0.5 ml of a 1 mmol/L solution of H2O2 through a cannula inserted into the right jugular vein. Rats were sacrificed at 4 hours, 24 hours, 7 days, or 14 days, and several organs (lungs, heart, liver, spleen, gut, and kidneys) were examined for vasculitic lesions and inflammatory cell infiltrates. Macroscopically, patchy hemorrhagic spots were observed in the lungs and gut of MPO-immunized rats at days 7 and 14 after systemic infection of the neutrophil lysosomal extract and H2O2. Such changes were not observed at earlier time points or in control immunized rats. Histologically, the lungs of MPO-immunized rats sacrificed at days 7 and 14 showed patchy inflammatory cell infiltrates associated with vasculitis, granuloma formation, giant cells, and foci of hemorrhage. At 14 days, early signs of fibrosis were found with deposition of collagen and proliferation of fibroblasts. Furthermore, a prominent leukocytoclastic vasculitis was found in the small intestine of these rats characterized by fibrinoid necrosis and an extensive neutrophilic infiltrate. No inflammatory changes were found in the other organs studied (heart, liver, spleen, and kidneys). Control immunized rats, sacrificed at days 7 and 14 showed only some small foci of inflammatory infiltrates in the lungs whereas no inflammatory changes were found in the gastrointestinal tract. These studies show that release of products from activated neutrophils in the presence of anti-MPO autoantibodies may be relevant to the pathogenesis of anti-MPO-associated vasculitides.     

The Effect of 1-(o-Chlorophenyl)-1-(p-Chlorophenyl)-2,2-Dichloroethane(o,p′-DDD) on the Immune Response in Malnutrition

The drug o,p′-DDD diminished the body weight as well as the weights of the thymus, spleen and adrenals of rats. There was minimal fatty infiltration of the liver. In well-nourished rats o,p′-DDD produced atrophy of both the adrenal cortex and the thymolymphatic organs, but no changes could be detected in kidneys, heart and lungs. The numbers of plaque-forming cells (PFC) and rosette-forming cells (RFC) in the spleen and thymus of the o,p′-DDD treated rats were lower than the controls. The effect of o,p′-DDD was greatest on the adrenal cortex of the malnourished rats with a diminution of plasma corticosteroid concentration and less impairment of the immune response. The numbers of PFC and RFC in the spleen and thymus of the o,p′-DDD-treated malnourished rats were almost equal to that of their controls. It was interesting to observe that o,p′-DDD seemed to affect PFC more adversely than RFC. In comparison to the controls, thymocytes and spleen cells of the o,p′-DDD-treated rats responded better to phytohaemagglutinin (PHA) than to pokeweed mitogen (PWM).     

Persistence of Adenovirus 5 in Guinea Pigs

One intracardiac inoculation of adenovirus 5 in guinea pigs leads to virus persistence in different organs, viz., 5 days in lungs and liver, 14 days in blood and lymph nodes, and 56 days or more in the spleen. After cultivation of tissue cells for 1 week, virus was recovered from blood, lymph nodes, or spleen lymphocytes, but virus could be detected directly in cells only when organs were removed within 48 h of inoculation. To determine how the virus persisted in low concentrations and as a latent infection, spleens were primarily selected for study by three techniques: homogenization of spleens, suspended Maitland fragment cultures, and in vitro cultivation of spleen cells. The last procedure showed virus in fibroblast-like cells (probably macrophages or reticuloendothelial cells) for 56 days after infection of guinea pigs. With other methods, the virus was found only within the first 2 days after inoculation.     

Bone marrow transplantation in the rat. Lytic functions of inflammatory leukocytes during acute graft-versus-host disease

We have isolated inflammatory leukocytes from various lymphoid and parenchymal organs after total body irradiation and bone marrow transplantation from either an allogeneic or syngeneic strain and tested their ability to perform lytic functions in vitro. No direct lytic activity (i.e. cytotoxic T lymphocytes, CTL) to relevant strain-derived target cells in the lymphoid or parenchymal target organs was seen preceding or during acute graft-versus-host disease (aGVHD). Instead, the leukocytes of the spleen and blood and the inflammatory cells of liver and lungs were efficient effector cells against recipient-derived target cells in the presence of relevant antibody (antibody dependent cellular cytotoxicity, ADCC). The NK activity against YAC-1 (natural killer, NK) target cells was first high in the spleen, but when the aGHVD appeared in the allograft marrow recipients the NK activity decreased in the spleen with a concomitant increase in the liver, but not in the other parenchymal target organs. At the same time no NK activity was seen in the syngeneic marrow graft recipients' parenchymal organs. These observations suggest functional differences in the structure of inflammation in the different target organs of aGVHD.     

Experimental pathogenesis of buffalo pox virus in rabbits: clinico-pathological studies

Buffalo pox virus produced typical pock lesions on the skin of rabbits at the site of primary inoculation following an incubation period of 48-72 hr. Gross lesions in internal organs, characterized by focal or diffuse necrotic areas on lung, liver and spleen were seen from day 5 post-inoculation (p. i.). Isolated lesions of approximately 2 mm diameter appeared in skin, stomach, intestine and uterus from day 7 p. i. Histopathological changes, i. e. intra-alveolar and intra-bronchial haemorrhages were seen in lungs and severe fatty changes were found in the liver. Multinuclear cells were detected in liver during recovery. Virus particles were demonstrated by electron microscopy in skin, lung, liver and spleen lesions.     

Macrophage development: II. Early ontogeny of macrophage populations in brain, liver, and lungs of rat embryos as revealed by a lectin marker.

Earliest origins of macrophage populations in the central nervous system, the liver, and the lungs were studied in rat embryos aged between 10.5-11 days and 14 days of gestation, based on light and electron microscopic identification of macrophages using peroxidase-coupled isolectin B4 of Griffonia simplicifolia (GSA I-B4), which recognizes alpha-D-galactose groups on the cell membrane. During embryonic life macrophages and their precursors are GSA I-B4-positive and generally bereft of peroxidase-positive granules. At 10.5 days the yolk sac and embryonic circulations have just become joined, the brain has five vesicles but nerve cells are little differentiated, the liver exists as a diverticulum of the gut with fingerlike extensions of hepatocytes, and the lungs as a laryngotracheal groove. Macrophages and/or their precursors occurred in small numbers in embryonic mesenchyme and blood vessels but showed no special affinity for either liver or lung rudiments. The developing brain was the first organ to be colonized, beginning on prenatal day 12. The liver followed between days 12 and 13 and was succeeded by the lungs, beginning between days 13 and 14. Dividing macrophages were present in these organs at the outset of colonization and throughout the duration of the embryo series, indicating that from the beginning, replication of resident cells contributes to growth of the local population. Granulocyte precursors were first apparent in the liver around day 13; they are also GSA-positive but are distinguished from macrophages by their content of peroxidase-positive granules. Organ cultures of 13-day liver and lungs, and 14-day brain tissue, indicate that whereas isolated liver fragments support the formation of both granulocytes and macrophages, only the latter develop in brain or lung cultures. A resident population of macrophages evidently is set up very early in these organs, well before white cells colonize the spleen, bone marrow, and other future blood forming regions. The events outlined are seen as stages in an embryo-wide process that leads to establishment of macrophage populations in various organs.     

全反式维甲酸对生长发育期大鼠实质器官的损伤

目的 探讨体内过量全反式维甲酸（ATRA）对生长发育期SD大鼠的脑、心、肺、肝、肾和脾的影响。方法 以48只3周雄性SD大鼠为实验对象,随机分为对照组和3个实验组,ATRA剂量分别为40、60、80 mg/(kg·d),每组12只,进行连续10 d ATRA灌胃处理,记录SD大鼠每日体重,于灌胃第10天解剖称量各器官的重量以及计算脏器指数,然后对各器官进行HE染色。结果 ATRA灌胃后,与对照组比较,40 mg/(kg·d) ATRA组肾指数升高,体重变化差异无统计学意义;60 mg/(kg·d) ATRA组体重降低,心、肾指数升高,脾脏重量降低;80 mg/(kg·d)ATRA组体重明显降低,脑、心、肾指数升高,脑、脾重量降低;HE染色显示,与对照组比较,ATRA处理组的肺泡壁增厚,肾小管上皮细胞有空泡样改变,脾脏红髓出现较多巨噬细胞,而大脑、肝脏、心肌无明显组织学变化。结论 体内过量全反式维甲酸能够对生长发育期SD大鼠的肺、肾和脾有一定的损伤作用。     

Macrophage development: II. Early ontogeny of macrophage populations in brain,liver, and lungs of rat embryos as revealed by a lectin marker

Earliest origins of macrophage populations in the central nervous system, the liver, and the lungs were studied in rat embryos aged between 10.5–11 days and 14 days of gestation, based on light and electron microscopic identification of macrophages using peroxidase-coupled isolectin B₄ of Griffonia simplicifolia (GSA I-B₄), which recognizes alpha-D-galactose groups on the cell membrane. During embryonic life macrophages and their precursors are GSA I-B₄-positive and generally bereft of peroxidase-positive granules. At 10.5 days the yolk sac and embryonic circulations have just become joined, the brain has five vesicles but nerve cells are little differentiated, the liver exists as a diverticulum of the gut with fingerlike extensions of hepatocytes, and the lungs as a laryngotracheal groove. Macrophages and/or their precursors occurred in small numbers in embryonic mesenchyme and blood vessels but showed no special affinity for either liver or lung rudiments. The developing brain was the first organ to be colonized, beginning on prenatal day 12. The liver followed between days 12 and 13 and was succeeded by the lungs, beginning between days 13 and 14. Dividing macrophages were present in these organs at the outset of colonization and throughout the duration of the embryo series, indicating that from the beginning, replication of resident cells contributes to growth of the local population. Granulocyte precursors were first apparent in the liver around day 13; they are also GSA-positive but are distinguished from macrophages by their content of peroxidase-positive granules. Organ cultures of 13-day liver and lungs, and 14-day brain tissue, indicate that whereas isolated liver fragments support the formation of both granulocytes and macrophages, only the latter develop in brain or lung cultures. A resident population of macrophages evidently is set up very early in these organs, well before white cells colonize the spleen, bone marrow, and other future blood forming regions. The events outlined are seen as stages in an embryo-wide process that leads to establishment of macrophage populations in various organs.     

Immunohistochemical study of arginase 1 and 2 in various tissues of rats

Arginase 1 and arginase 2 catalyze the hydrolysis of arginine to ornithine and urea. The localization of these enzymes was studied in various tissues in Sprague-Dawley rats by immunohistochemistry and Western blotting. Western blot analysis showed that both arginase 1 and 2 were differentially expressed in the various organs examined. Arginase 1 was expressed at high levels in the liver, at moderate levels in the pancreas, and at low levels in the cerebrum, cerebellum, spinal cord, stomach, small and large intestines, kidneys, lungs, and spleen. The levels of arginase 2 immunoreactivity were high in the kidneys and pancreas, and moderate in the cerebrum, spinal cord, stomach, small intestine, large intestine, and lungs; the levels were very low in the liver and spleen compared with that in the cerebellum. Immunohistochemical analysis largely confirmed the results of the Western blot analysis. These findings indicate that the levels of arginase 1 and 2 varied among organs, suggesting that the arginase isoforms may play organ-specific roles in the urea cycle.     

A light and electron microscope study on the origin of Foà-Kurloff cells.

Numerous Foà-Kurloff (FK) cells have been found in the circulation, spleen, bone marrow, thymus and placenta of guinea pigs under endogenous or exogenous oestrogenic stimulation. The origin of these cells is obscure. In the present experiment, the distribution of FK cells in organs other than those stated above was studied following gonadectomy and hexoestrol administration in guinea pigs of both sexes for either 1 or 10 weeks. More FK cells than those expected from the vascularity of the organ were found in the liver and lungs of male and female animals. The number of FK cells in these organs was larger after the long-term treatment with hexoestrol and it was accompanied by a significant decrease in the number of Kupffer cells of the liver. The latter observation is in contrast to previous reports of increased numbers of Kupffer cells in the liver of oestrogen-receiving mice, a species not producing FK cells. These observations suggest a relation between the two types of cells. No transformation of mature Kupffer cells into FK cells was seen with the electron microscope. However, other findings suggest that both Kupffer cells and FK cells may well be derived from a common precursor of MPS in the bone marrow.     

实验性家兔动脉粥样硬化血管外器官的病理学变化

对50办家兔实验性动脉粥样硬化的血管及血管以外心、肝、脾、肺、肾等脏器,进行了系统的病理形态学观察,试图探讨动脉粥样硬化形成过程中高脂血症对内脏器官的影响。结果表明,高脂血症不仅可以诱发家兔动脉粥样硬化,也可使受试动物产生肺炎,肝细胞广泛脂变和水变,以及全身单核巨噬细胞系统反应。并着重讨论了内脏器官病变的发病机理。     

Porphyrobilinogen biosynthesis from δ-aminolevulinic acid by the viscera of albino rats

Ability to synthesize porphyrobilinogen (PBG) from -aminolevulinic acid (ALA) was determined in homogenates of tissues of the lungs, heart, liver, kidneys, spleen, pancreas, and small intestine of 77 albino rats. All these organs were found to be able to synthesize PBG. Highest ALA dehydratase activity was found in the liver tissue, followed in descending order by the kidneys, lungs, pancreas, small intestine, heart, and spleen. On the addition of a lead solution to the synthesizing system a significant decrease in enzyme activity was observed in the liver tissue, but in kidney tissue its activity was unchanged. On the addition of lead and D-penicillamine simultaneously no changes were found in the toxic effect of lead.M. F. Vladimirskii Moscow Regional Clinical Research Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR S. S. Debov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 86, No. 12, pp. 687–689, December, 1978.     

The distribution of immunoreactive interferon-alpha in formalin-fixed paraffin-embedded normal human foetal and infant tissues.

Human foetal and infant tissues were studied to test the hypothesis that microbes have a role in switching on interferon-alpha (IFN-alpha) synthesis. Foetal tissues were essentially 'germ free', while the infants had been exposed to a normal microbial environment in life. IFN-alpha was first seen at 9 weeks gestation in macrophages in the liver and thereafter was seen in macrophages in most other organs. When infant lungs were compared with foetal lungs, a statistically significant increase in the number of macrophages and the percentage of these cells expressing IFN-alpha was noted in the infant lungs. No such change was observed in spleen, liver and thymus following birth. These findings suggest that there is a basal production of IFN-alpha by macrophages that is not dependent on microbial products, but that such products can enhance synthesis of this cytokine.