Antithymocyte globulin reacts with many normal human cell types

Antithymocyte globulin (ATG) is frequently effective therapy for aplastic anemia. Its mechanism of action is often assumed to be upon a lymphocyte inhibitor of hematopoiesis. However, specificity for T lymphocytes would not be anticipated from consideration of the method of preparing ATG. In fact, using flow microfluorometry and fluorescence immunohistochemistry, we have found that ATG binds to virtually all circulating lymphocytes, granulocytes, and platelets, as well as to bone marrow cells. Extensive absorption of ATG with either granulocytes or lymphocytes does not eliminate reactivity with the opposite cells, indicating that ATG recognizes some distinct antigens on each cell type. Treatment of cells with ATG blocks the binding of monoclonal antibodies directed against either lymphocyte differentiation or histocompatibility antigens. ATG also binds to visceral tissues, including thymus and testis cell membranes and the nuclear and cytoplasmic components of tonsil, kidney, liver, breast, lung, and intestine. In vitro cytotoxicity of ATG was demonstrated for both T and non- T lymphocytes and platelets. Despite its name, ATG is not specific for a particular cell type, and it would be premature to conclude that its effect is mediated through a specific lymphocyte population.     

Renovascular hypertension: quantitative renography as a screening test

The accuracy and reliability of quantitative gamma camera renography in screening for functionally significant renovascular hypertension was investigated. Renal perfusion, total and relative renal function, and parenchymal transit times were measured in 141 patients with recently diagnosed or severe hypertension. Renal angiography was performed in 13 of the 15 patients diagnosed as having evidence of renovascular hypertension. In all 13 either occlusion or significant stenosis of the renal artery was correctly predicted. Previous studies utilizing static images, playback buffers, and renograms have shown that these methods have excellent sensitivity, but relatively low specificity because of false-positive results. The addition of computer quantitation, including measurement of parenchymal transit times, has greatly improved the accuracy of this test. Quantitative renography can now be regarded as a reliable means of selecting patients for transluminal dilatation of stenosed renal arteries and for follow-up after this procedure.     

Cutaneous territory of the posterior branches of spinal nerves. A review of Dejerine's scheme

This report concerns not only anatomical study of posterior branches of the spinal nerves, but has also a clinical aim. The cutaneous territories and the sites of pain irradiation are precised. In the cervico-thoracic region emphasis is placed on the importance of the fourth cervical posterior branch and of the second dorsal posterior branch. At the lumbar and sacral levels the authors distinguish three pain pathways: from up to down and from outside to inside: the first corresponding to posterior branches of 11th and 12th dorsal nerves, the second to those of first, second and third lumbar nerves and the third to sacral nerves.     

High-resolution longitudinal screening with magnetic resonance imaging in a murine brain cancer model

One of the main limitations of intracranial models of diseases is our present inability to monitor and evaluate the intracranial compartment noninvasively over time. Therefore, there is a growing need for imaging modalities that provide thorough neuropathological evaluations of xenograft and transgenic models of intracranial pathology. In this study, we have established protocols for multiple-mouse magnetic resonance imaging (MRI) to follow the growth and behavior of intracranial xenografts of gliomas longitudinally. We successfully obtained weekly images on 16 mice for a total of 5 weeks on a 7-T multiple-mouse MRI. T2- and T1-weighted imaging with gadolinium enhancement of vascularity was used to detect tumor margins, tumor size, and growth. These experiments, using 3D whole brain images obtained in four mice at once, demonstrate the feasibility of obtaining repeat radiological images in intracranial tumor models and suggest that MRI should be incorporated as a research modality for the investigation of intracranial pathobiology.     

Angiogenesis in nervous system disorders

Angiogenesis is a crucial requirement for embryonal development and new vessel formation during adult life. Various disease processes such as cancer, ischemia, vascular malformations, and inflammatory processes also depend on pathological angiogenesis. A better understanding of the complex and coordinated interactions among various angiogenic pathways involved in pathological angiogenesis is necessary to improve our therapeutic approaches to the various disease processes observed in the central nervous system. This review summarizes the current understanding of the role of principal angiogenic factors relevant to neurosurgical abnormalities.     

Evidence for apoptosis of the majority of T cells activated in vitro with Actinobacillus actinomycetemcomitans

Our previous studies had demonstrated that nearly half of all T cells stimulated with Actinobacillus actinomycetemcomitans are activated within a few hours. However, it was not known whether all of these T cells survive. The aim of the present study was to determine whether the T cells activated in response to A. actinomycetemcomitans undergo apoptosis. To that end, peripheral blood mononuclear cells were cultured at different time points in the presence of A. actinomycetemcomitans. Flow cytometric analysis demonstrated that, following exposure to a preparation of A. actinomycetemcomitans, T cells progressively externalized their plasma membrane phosphatidylserine, as measured by annexin V binding. Approximately half of all T cells bound annexin V by 96 h. During this period, Annexin V-positive T cells also incorporated propidium iodide suggesting loss of membrane integrity. The externalization of phosphatidylserine occurred at a higher rate among activated (CD69+) T cells, where roughly two-thirds became Annexin V-positive. Flow cytometric analysis also demonstrated shrinkage of the Annexin V-positive and propidium iodide-positive T cells. The data presented here provides evidence for the induction of apoptosis among the majority of the T cells responding to A. actinomycetemcomitans.