[Comparison of two red-emitting fluorochromes for their use in lectin histochemistry].
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Biomedical subjects
Publications and source records attributed to B Borisch.
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A major hypothesis to explain the immunodeficiency associated with bone marrow transplantation states that thymic epithelial damage due to graft-versus-host disease (GVHD) abrogates or delays the recovery of normal immunologic function. This study evaluated the thymus glands of 36 human bone marrow transplant recipients dying between 4 and 1742 days after transplant using histology, histochemistry, and immunohistology. The observations lead to a model of thymic damage by irradiation, chemotherapy, and GVHD in which early injury by all three of these agents results in profound thymic atrophy followed by long-delayed restitution. Patients undergoing total body irradiation showed more severe damage to thymic cortical and medullary epithelium than did patients undergoing chemotherapy alone as preparation for transplantation. Patients with GVHD showed additional damage in the form of individual thymic epithelial cell death and showed HLA-DR surface protein expression on thymic epithelium during GVHD. Longer-term survivors showed a profoundly delayed restitution of normal thymic epithelium and delayed evidence of restored lymphopoiesis. A few patients dying late after transplant showed evidence of reconstitution of normal thymic structure or nodules of lymphopoiesis in focal areas of epithelial-cell reconstitution. Evidence of such lymphopoiesis was seen at times ranging between 90 and 1742 days after grafting. The data are consistent with a model of long-standing thymic damage caused by GVHD which is reversible after the development of tolerance.
Twenty-nine consecutive patients with suspected primary hyperparathyroidism were examined preoperatively using ultrasound, sonographically guided fine needle aspiration, and aspirate immunostaining for PTH. In 25 patients, localization of enlarged parathyroid glands was successful. In 2 patients, the tumors were located retrosternally and, thus, could not be detected by ultrasound. One patient had a multinodular goiter which impeded localization. In 1 patient with renal osteodystrophy, 2 enlarged parathyroid glands in the neck were not visualized preoperatively. Cytology was not diagnostic, although some cytological features were suggestive of parathyroid cells. Immunostaining of the aspirated smears for PTH, however, correctly diagnosed all preoperatively localized lesions. Ultrasound should be the routine procedure of choice for preoperative localization of abnormal parathyroid glands in primary hyperparathyroidism. Fine needle aspiration and immunocytochemistry can supply confirmation, if necessary.
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The microvasculature of lymph nodes of 55 cases of T-cell lymphoma was studied by light microscopy, immunohistochemistry and electron microscopy. A modified peroxidase-antiperoxidase (PAP) method was used for staining paraffin sections with lectin I of Ulex europaeus (UEA-I), which is a specific marker for vascular endothelial cells. The T-cell nature of each case was proven by immunohistochemistry, including immunoperoxidase staining of frozen sections with monoclonal T-cell antibodies. The cases were subclassified according to previously established criteria, but with the addition of a separate group showing a high content of clear cells. For the purpose of the present study, the small blood vessels were separated into two main variants, viz.: high endothelial venules (HEV) and all other types of vessels with flat endothelium (SVFE). The development of each of these variants and the extent of lymphocyte migration through the vascular wall were assessed semiquantitatively. The findings suggest that the blood microvasculature, as a whole, is similar in all types of T-cell lymphoma. There were distinct differences, however, in the development of the two main categories of small vessels between the various types. Chronic lymphocytic leukaemia of T-type (T-CLL) and Sézary's syndrome were poor in SVFE and rich in HEV, and there was considerable lymphocyte traffic through the latter. In contrast, T-immunoblastic and especially T-lymphoblastic lymphocyte traffic. The appearance of the microvasculature varied markedly in the various subtypes of "pleomorphic T-cell lymphoma". In the small cell subtype HEV predominated and SVFE represented only a small or moderate fraction of the microvasculature. As the size of the neoplastic lymphoid cells increased towards the medium-sized and large cell subtype, there was a decrease in the number of HEV and an increase in the number of SVFE accompanied by a decrease in lymphocyte migration. In T-cell lymphoma of the clear cell type the microvasculature showed features between those of T-CLL and the small cell subtype of pleomorphic T-cell lymphoma. Electron microscopy confirmed the light microscopic findings and revealed many similarities in vascular changes between "pleomorphic T-cell lymphomas" and lymphogranulomatosis X.
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Transmembrane signaling requires modular interactions between signaling proteins, phosphorylation or dephosphorylation of the interacting protein partners and temporary elaboration of supramolecular structures, to convey the molecular information from the cell surface to the nucleus. Such signaling complexes at the plasma membrane are instrumental in translating the extracellular cues into intracellular signals for gene activation. In the most straightforward case, ligand binding promotes homodimerization of the transmembrane receptor which facilitates modular interactions between the receptor's cytoplasmic domains and intracellular signaling and adaptor proteins. For example, most growth factor receptors contain a cytoplasmic protein tyrosine kinase (PTK) domain and ligand-mediated receptor dimerization leads to cross phosphorylation of tyrosines in the receptor's cytoplasmic domains, an event that initiates the signaling cascade. In other signaling pathways where the receptors have no intrinsic kinase activity, intracellular nonreceptor PTKs (i.e. Src family PTKs, JAKs) are recruited to the cytoplasmic domain of the engaged receptor. Execution of these initial phosphorylations and their translation into efficient cellular stimulation requires concomitant activation of diverse signaling pathways. Availability of stable, preassembled matrices at the plasma membrane would facilitate scaffolding of a large array of receptors, coreceptors, tyrosine kinases and other signaling and adapter proteins, as it is the case in signaling via the T cell antigen receptor. The concept of the signaling platform has gained usage to characterize the membrane structure where many different membrane-bound components need to be assembled in a coordinated manner to carry out signaling. The structural basis of the signaling platform lies in preferential assembly of certain classes of lipids into distinct physical and functional compartments within the plasma membrane. These membrane microdomains or rafts (Figure 1) serve as privileged sites where receptors and proximal signaling molecules optimally interact. In this review, we shall discuss first how signaling platforms are assembled and how receptors and their signaling machinery could be functionally linked in such structures. The second part of our review will deal with selected examples of raft-based signaling pathways in T lymphocytes and NK cells to illustrate the ways in which rafts may facilitate signaling.