[Humoral factors and agents of tissue origin in the genesis of anaphylactic shock in the rat].
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Malignant fibrous histiocytomas were found in eight F344 rats and four Sprague-Dawley rats. They appeared to originate in skin or peritoneum and to have metastasized to liver and lung. Tumor cells appeared to be histiocytic in the light microscopic studies and fibroblastic after ultrastructural evaluation. The cell of origin was uncertain.
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A structural, ultrastructural and histochemical study in chick embryos indicates that the septum primum mesenchymal tissue originate between 3 and 5 days of development and that their origin may be related to an activation of endocardial cells that cover the septum primum. By day 3, endocardial cells display migratory appendages, cell hypertrophy and an increase in secretory and mitotic activity. In later stages (day 4) hypertrophic endocardial cells undergoing division seem to delaminate and translocate toward the subendocardial space to give rise to free mesenchymal-type cells. These results suggest that the endocardium makes up the bulk of the septum primum mesenchymal tissue as has been demonstrated during mesenchymal tissue formation in the atrioventricular canal and outflow tract. Before and during mesenchymal tissue formation an accumulation of extracellular matrix components like proteoglycans can be visualized using tannic acid. These extracellular components might be related to the promotion of cellular events described during endocardial activation. The fusion of the septum primum with the atrioventricular (AV) endocardial cushions which would obliterate the foramen primum, occurs between mesenchymal tissues. Therefore, any alteration in the normal development of these mesenchymal tissues could be related to pathological cases of persistent atrial communications. Light microscopy preliminary observations of embryonic mouse heart indicate that septum primum mesenchymal tissue formation occurs similarly between mouse and chick embryos.
Following activation within secondary lymphoid tissue, CD8 T cells must migrate to targets, such as infected self tissue, allografts, and tumors, to mediate contact-dependent effector functions. To test whether the pattern of migration of activated CD8 T cells was dependent on the site of Ag encounter, we examined the distribution of mouse Ag-specific CD8 T cells following local challenges. Our findings indicated that activated CD8 T cells migrated pervasively to all nonlymphoid organs irrespective of the site of initial Ag engagement. Using an adoptive transfer system, migration of nonlymphoid memory cells was also examined. Although some limited preference for the tissue of origin was noted, transferred CD8 memory T cells from various nonlymphoid tissues migrated promiscuously, except to the intestinal mucosa, supporting the concept that distinct memory pools may exist. However, regardless of the tissue of origin, reactivation of transferred memory cells resulted in widespread dissemination of new effector cells. These data indicated that recently activated primary or memory CD8 T cells were transiently endowed with the ability to traffic to all nonlymphoid organs, while memory cell trafficking was more restricted. These observations will help refine our understanding of effector and memory CD8 T cell migration patterns.
After activation within a lymphoid tissue, T lymphocytes enter the blood, where they circulate and then re-enter many organs. However, they predominantly end up in the tissue of origin, a phenomenon so far thought to be caused by organ-specific homing. We analyzed the fate of T cells from different sources stimulated via the T cell receptor and CD28 and then injected intravenously into rats. Our results showed that preferential proliferation and reduced apoptosis, rather than preferential immigration, were responsible for the accumulation of activated T cells in the tissue of origin, explaining how immune responses can spread from site to site but still be restricted to certain regions. Manipulating the life span of such cells might be a promising approach to influencing immune responses.
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A new technique is presented for the analysis of tissues which allows an exact, detailed comparison of light and electron microscopy. For this purpose, the previous techniques required the cutting of tissue pieces from the original tissue compound and the preparation of drawings as a rough localisation of the tissue pieces removed for analysis. Due to the processes of cutting and drawing, only an approximate localisation of the tissue investigated by electron microscopy was practicable. Specifically, the exact analysis of fetal cartilage-bone-tissue was mostly not possible due to the complicate arrangement of both tissue components. Therefore, the assessment of electron microscopic analyses was severely limited. The new technique, presented in this study, is characterised by a removal of punches 1 mm in diameter from the original tissue for electron microscopy. The remaining tissue with its exact defined punch-punctures is prepared for standard histology. Thus, the specific advantage of this new method is the precise attribution of the punched tissue to the original tissue group. Human fetal cartilage-bone-tissue has been used to demonstrate this punch-technique and the specific light- and electron microscopic preparations.
The cytosol and microsomal fractions of human adrenal cortex contain 3 isoforms of protein kinase C: alpha, zeta, and epsilon. The latter fraction is present in trace amounts. No isoforms beta1, beta2, gamma and delta were found in these cell fractions. The distribution of alpha-isoform between the cytosol and microsomal fraction is determined by tissue origin: in normal tissue its content differs by no more than 10%, while in most tumors this isoform is translocated into the microsomal fraction. The distribution of zeta-isoform did not depend on tissue origin.
Experimental data to determine time for restoration of intraarticular fluid are presented. Mature healthy domestic goats served as experimental animals. From the carpal joints under sterile conditions, synovial fluid was sucked out as completely as possible. Every four hours during the first day and further in 2, 3, 4 days synovial fluid was taken from one of the joints. Cellular elements, their percentage, pH, viscosity (determined on the amount of hyaluronic acid), common proteins and their fractions were determined. It was demonstrated that the process of synovial fluid restoration, in case it was removed completely, took four days. At first the amount of synovial fluid is restored at the expense of its liquid part, percentage of common protein and its fractions increase, and viscosity of synovial fluid decreases. After two days, a gradual restoration of all physiological indices mentioned occurs. By the fourth day they are completely restored. Data of synoviogram demonstrate that at first blood cells appear in a great amount, while cells of tissue origin are very scanty, and by the fourth day percentage of cellular elements is equal to the original: cells of tissue origin--70-72%, blood cells--28--30%.
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Previous studies suggest that the radiosensitivity and origin of tissue macrophage precursors differ from those of hemopoietic macrophage colony-forming units (CFU-Ms) committed to macrophage-lineage cells. We assessed the origins of tissue macrophage colony-forming cells (M-CFCs) in mice by comparing their kinetics and radiosensitivities in the normal steady state and under the conditions of bone marrow depletion by 89Sr-administration and/or splenectomy. The results indicate that the radiosensitive peritoneal M-CFCs elicited by thioglycollate are derived from bone marrow macrophage precursors; where as alveolar M-CFCs, which are radioresistant, are self-sustained locally and independent of hemopoietic macrophage precursors. In contrast, highly radiosensitive liver M-CFCs are probably derived from CFU-Ms that appear to be propagated in the spleen in association with hemopoietic responses.
The evaluation of peptide receptors in man is needed not only to discover the physiological target tissues of a given peptide but also to identify diseases with a sufficient receptor overexpression for diagnostic or therapeutic interventions. Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) receptors have been evaluated in human tumors and in their tissues of origin using in vitro receptor autoradiography with 125I-VIP or 125I-acetyl-PACAP-27 in tissue sections. The VIP/PACAP receptor subtypes VPAC1, VPAC2, and PAC1 were evaluated in these tissues by determining the rank order of potencies of VIP and PACAP as well as VPAC1- and VPAC2-selective analogues. The VIP/PACAP receptors expressed in the great majority of the most frequently occurring human tumors, including breast (100% receptor incidence), prostate (100%), pancreas (65%), lung (58%), colon (96%), stomach (54%), liver (49%), and urinary bladder (100%) carcinomas as well as lymphomas (58%) and meningiomas (100%), are predominantly of the VPAC1 type. Their cells or tissues of origin, i.e., hepatocytes, breast lobules and ducts, urothelium, prostate glands, pancreatic ducts, lung acini, gastrointestinal mucosa, and lymphocytes, also predominantly express VPAC1. Leiomyomas predominantly express VPAC2 receptors, whereas paragangliomas, pheochromocytomas, and endometrial carcinomas preferentially express PAC1 receptors. Conversely, VPAC2 receptors are found mainly in smooth muscle (i.e., stomach), in vessels, and in stroma (e.g., of the prostate), whereas PAC1 receptors are present in the adrenal medulla and in some uterine glands. Whereas the very wide distribution of VIP/PACAP receptors in the normal human body is indicative of a key role of these peptides in human physiology, the high VIP/PACAP receptor expression in tumors may represent the molecular basis for clinical applications of VIP/PACAP such as in vivo scintigraphy and radiotherapy of tumors as well as VIP/PACAP analogue treatment for tumor growth inhibition.
In the present study, we tried to detect the tissue of origin of herpes simplex virus type 1 (HSV-1) reactivated in tear film after artificial reactivation. The combined treatment consisted of iontophoresis on postinoculation day 35, followed by topical epinephrine on 2 days, after which the rabbits were killed. The ocular tissues and trigeminal ganglia were immediately dissected. Their cell-free supernatants were inoculated on CV-1 (African green monkey kidney cell) monolayers for infectious HSV-1 detection. The percentage of recovery from the cell-free supernatants was 50% (5 out of 10 samples) from the cornea, 0% from conjunctiva or lacrimal glands, and 20% (2 out of 10 samples) from trigeminal ganglia. The percentage of HSV-1 reactivation in the tear film was 50%. No infectious virus was detected from tissues or tear film in the control group. Four eyes showed HSV-1 reactivation simultaneously from the cornea and tear film, but only one eye from the trigeminal ganglion and tear film. These results demonstrate that the cornea might be the tissue of origin of HSV-1 reactivated in tear film.
Regenerative and degenerative changes of cartilage were studied in animals by micromorphological methods and autoradiography. Cartilage lesions of defined size were set in the femoral condyle of rabbits of variing age by means of an electrical drill developed by us. We used juvenile animals, 3 months old, and senile animals 4 years old. The lesions were studied by lightmicroscopy, electronmicroscopy and scanning electron microscopy. In young animals we were able to demonstrate prevailing reparative changes after injury and the potency for genuine regeneration originating from cartilage. Isolated chondral lesions develop reactive tissue originating mainly from superficial parts of the cartilage. When subchondral bone is exposed we see granulation tissue filling up the defect and change by metaplasia. The replacing tissue originating from superficial cartilage as well as from subchondral bone is able to fill the defect within 3 months. In the replacing tissue originating from cartilage we find fibroblasts and fibrocytes with many mitoses. Consecutively the cells are rounding increasingly. Finally chondrocytes are developing. At the same time as these reparative changes occur we see degenerative changes with decreased mucopolysaccharide synthesis, cell necroses with consecutive decrease in number of cells and singular small cluster. In old animals we could not demonstrate any reparative or regenerative changes after injuries; the artificial defect in cartilage persists. Instead, degenerative changes with signs of arthrosis are developing rapidly: chondroitin sulfate synthesis is decreased, there is ample cluster formation, cell necrosis, decrease in number of cells, and incorporation of paraplasmatic substances in cartilage. We could not demonstrate any mitoses. The causes for the inability of cartilage of aged individuals for reparative changes are discussed.