Search

Nilsson K, Lukinius A, Påhlson C, Moron C, Hajem N, Ohlsson B, Lindquist O. Evidence ofRickettsiaspp. infection in Sweden: a clinical, ultrastructural and serological study. APMIS 2005;113:126–34.Sweden is an area potentially endemic for spotted fever rickettsioses.Rickettsia helveticahas been isolated from its tick vectorIxodes ricinus, and in a handful of cases linked to human disease. This study demonstrates for the first time in Sweden the transmission of rickettsial infection after a tick bite and the attack rate in an endemic area. We present three cases of documented rickettsial infection and a prospective serological study of Swedish recruits who were trained in the area where the patients lived and showed seroconversion to spotted fever rickettsiae. All patients showed a four-fold increase in antibody titer to the spotted fever rickettsia,R. helvetica,and immunohistochemical examination revealed rickettsia-like organisms in the walls of skin capillaries and veins. Electron microscopy showed organisms resemblingR. helveticaand immunogold labeling with two anti-rickettsial antibodies demonstrated specific labeling of the rickettsial organisms in the skin biopsy specimens. Eight of the thirty-five recruits showed a four-fold increase in IgG titer reflecting a high rate of exposure. The results of this study demonstrate that spotted fever rickettsioses should be taken into consideration in the diagnosis of tick-transmitted infections in Sweden. [ABSTRACT FROM AUTHOR]

Radioactive tumor targeting agents are highly interesting and for treatment of neuroendocrine tumors expressing somatostatin receptors, radiolabeled somatostatin analogues (including [[sup 111]In-DTPA-D-Phe[sup 1]]-octreotide) has been tried in a small number of patients with encouraging results. To increase our knowledge about the in vivo processing of administered [[sup 111]In-DTPA-D-Phe[sup 1]]-octreotide we have examined tumor and normal tissue material from a patient with a midgut carcinoid tumor. By ultrastructural autoradiography, silver grains indicating the presence of [[sup 111]In-DTPA-D-Phe[sup 1]]-octreotide could be identified within tumor cells, both in the primary tumor and in the mesenteric metastases. Silver grains were also found in leukocytes and in blood vessels. However, normal enterocytes did not show any specific radioligand uptake. This study indicates that the binding and endocytosis of [[sup 111]In-DTPA-D-Phe[sup 1]]-octreotide is a specific process that takes place in cells expressing somatostatin receptors. However, the importance of the number of somatostatin receptors and subtypes expressed will have to be further studied. [ABSTRACT FROM AUTHOR]

Selective targeting of endothelial cells in tumor vessels requires delineation of key molecular events in formation and survival of blood vessels within the tumor microenvironment. To this end, proteins transiently up-regulated during vessel morphogenesis were screened for their potential as targets in antiangiogenic tumor therapy. The molecular chaperone alphaB-crystallin was identified as specifically induced with regard to expression level, modification by serine phosphorylation, and subcellular localization during tubular morphogenesis of endothelial cells. Small interfering RNA-mediated knockdown of alphaB-crystallin expression did not affect endothelial proliferation but led to attenuated tubular morphogenesis, early activation of proapoptotic caspase-3, and increased apoptosis. alphaB-crystallin was expressed in a subset of human tumor vessels but not in normal capillaries. Tumors grown in alphaB-crystallin(-/-) mice were significantly less vascularized than wild-type tumors and displayed increased areas of apoptosis/necrosis. Importantly, tumor vessels in alphaB-crystallin(-/-) mice were leaky and showed signs of caspase-3 activation and extensive apoptosis. Ultrastructural analyses showed defective vessels partially devoid of endothelial lining. These data strongly implicate alphaB-crystallin as an important regulator of tubular morphogenesis and survival of endothelial cell during tumor angiogenesis. Hereby we identify the small heat shock protein family as a novel class of angiogenic modulators.