Importance of localized skin infection in tick-borne encephalitis virus transmission

Arboviruses are transmitted to vertebrates by the "bite" of infected arthropods. Events at the site of virus deposition are largely unknown despite increasing evidence that blood-sucking arthropods immunomodulate their skin site of feeding. This question is particularly relevant for ixodid ticks that feed for several days. To examine events under conditions mimicking tick-borne encephalitis (TBE) virus transmission in nature (i.e., infected and uninfected Ixodes ricinus ticks feeding on the same animal), infected adult and uninfected nymphal ticks were placed in one retaining chamber (skin site A) and uninfected nymphs were placed within a second chamber posteriorly (skin site B) on two natural host species, yellow-necked field mice (Apodemus flavicollis) and bank voles (Clethrionomys glareolus). Virus transmission from infected to uninfected cofeeding ticks was correlated with infection in the skin site of tick feeding. Furthermore, virus was recruited preferentially to the site in which ticks were feeding compared with uninfested skin sites. Viremia did not correspond with a generalized infection of the skin; virus was not detected in an uninfested skin site (C) of 12/13 natural hosts that had viremia levels > or = 2.0 log10 ic mouse LD50/0.02 ml blood. To characterize infected cells, laboratory mouse strains were infested with infected ticks and then explants were removed from selected skin sites and floated on culture medium. Numerous leukocytes were found to migrate from the skin explants of tick feeding sites. Two-color immunocytochemistry revealed viral antigen in both migratory Langerhans cells and neutrophils; in addition, the migratory monocyte/macrophages were shown to produce infectious virus. The results indicate that the local skin site of tick feeding is an important focus of viral replication early after TBE virus transmission by ticks. Cellular infiltration of tick feeding sites, and the migration of cells from such sites, may provide a vehicle for transmission between infected and uninfected cofeeding ticks that is independent of a patent viremia. The data support the hypothesis that viremia is a product, rather than a prerequisite, of tick-borne virus transmission.     

Physiological compensation in antisense transformants: specific induction of an "ersatz" glucan endo-1,3-beta-glucosidase in plants infected with necrotizing viruses

Plant class I glucan endo-1,3-beta-glucosidases (beta-1,3-glucanase; 1,3-beta-D-glucan glucanohydrolase, EC 3.2.1.39) have been implicated in development and defense against pathogen attack. Nevertheless, beta-1,3-glucanase deficiencies generated by antisense transformation of Nicotiana sylvestris and tobacco have little biological effect. We report here that another beta-1,3-glucanase activity is induced in these deficient mutants after infection with necrotizing viruses. Induction of class I beta-1,3-glucanase was markedly inhibited in leaves of N. sylvestris and tobacco antisense transformants infected with tobacco necrosis virus and tobacco mosaic virus, respectively. A serologically distinct beta-1,3-glucanase activity was present in the infected antisense transformants but was absent in both healthy and infected control plants and in antisense transformants treated with the stress hormone ethylene. Immunoblot analyses, localization studies, and measurements of antibody specificity indicate that this compensatory beta-1,3-glucanase activity is an intracellular enzyme different from known tobacco beta-1,3-glucanases. Therefore, plants can compensate for a deficiency in enzyme activity by producing a functionally equivalent replacement--i.e., "ersatz"--protein or proteins. The fact that compensation for beta-1,3-glucanase activity occurs in response to infection argues strongly for an important role of these enzymes in pathogenesis.     

A new technique for positioning tangential fields

PURPOSE: A technique that eliminates the use of a mechanical "breast-bridge" for positioning tangential fields for treatment of the intact breast or chest wall has been developed. METHODS AND MATERIALS: Treatment set-up parameters are determined using measuring capabilities (gantry angles and source-skin distances) available on a standard simulator unit. A programmable scientific calculator is used to determine field geometry from polar coordinates for various points on the patient's skin. The calculator program determines the field size, a depth and lateral shift from a skin reference point to the isocenter for the tangential fields, and the gantry angles. The program provides additional information which facilitates the simulation process: First, the coordinates of the isocenter for the tangential fields are expressed relative to couch coordinates for an initial arbitrary isocenter so that the "auto go to" capability available on some simulators can be used. Second, the coordinates of the medial and lateral entry points can be edited when the first set of tangents are not accepted. This part of the program allows quick and efficient adjustment of the fields to obtain adequate treatment volume coverage and a minimum of irradiated lung or heart. RESULTS: Simulation of more than 300 patients has shown the technique to be a practical and efficient method for positioning tangential fields for breast or chest wall irradiation. CONCLUSION: The technique described here takes full advantage of the capabilities of the new generation of computer controlled simulators, and offers an alternative to previous methods employing a mechanical "breast-bridge."     

Ultrastructural evidence for an innervation of epithelial enterochromaffine cells in the guinea pig duodenum

The innervation of the duodenal enterochromaffine cells (E.C.) of the guinea pig was studied at the electronmicroscopic level. Pretreatment with 5-OH-dopamine was performed to visualize catecholaminergic (CA) nervous elements. Near the basement membrane of all examined E.C. in the crypts, bundles of unmyelinated nerve processes were observed, only partly ensheathed in a Schwann cell cover. At least 4 types of processes could be observed. 1) Boutons containing only small clear vesicles, probably cholinergic fibres; 2) boutons with small clear vesicles, and in addition large (greater than 200 nm) granules with a dense matrix (P-type-fibres); 3) boutons with small electron-dense vesicles, probably CA-fibres; and 4) processes with few vesicles but having the appearance of dendrites. No typical synaptic arrangements were observed, but the minimal distance between the E.C. and the nerve bundles was 150 to 250 nm, thus well within the functional limits of the "autonomic gap". Thus epithelial E.C. may be influenced by several types of nervous elements, including CA-fibres.     

Rhinomanometry in myocardial infarction

Describing two new cases of so-called Central Core Disease, the authors revealed certain atypical features: The cores were formed in central as well as in peripheral position; they were observed in some apparently type II fibers; typical "structured" and "unstructured" cores coexisted with "reversed" core. Starting from this pictures a cycle of core formation was imaginated supposing to be initiated as the consequence of abnormal functional interrelationship between muscular and neural components in early myogenesis.     

Ion-pairs in proteins

A "working definition" for an ion-pair has been derived based upon analysis of the distance distributions for like- and oppositely charged groups in 38 proteins. Ion-pairs defined according to this criterion (less than or equal to 4 A between charged groups) have been analysed in respect of: (1) the frequencies of different pair types; (2) the residue separations and secondary structural locations of the residues involved; (3) the flexibility of the side-chains involved; (4) their conformation; (5) their environment (accessibility to solvent and proximity to active site or ligand binding regions); and (6) their conservation in related proteins. The results obtained indicate that on average one-third of the charged residues in a protein are involved in ion-pairs and 76% of these are concerned with stabilizing the tertiary (rather than the secondary) structure. Only 17% of ion-pairs are buried, and conservation of the interactions is generally low unless the residues involved have more specific functions to perform. In the light of the results obtained, the role of ion pairs in globular proteins is discussed.     

Imported measles. A potential control problem

From Dec 23, 1978, through Jan 31, 1979, an outbreak of five laboratory-confirmed cases and four clinical cases of measles occurred in a Vietnamese refugee population living in a single housing complex in Albuquerque, NM. The index cases were in two refugee siblings in whom measles was incubating on arrival in the United States. Despite spread through three subsequent generations of disease transmission within the Vietnamese population, there was no additional spread into the general Albuquerque population. Responsible factors included the age distribution of susceptible persons, the social isolation of the refugee population, and the physical structure of the housing complex. There is a need to identify the problem of imported measles in "ethnic islands" in need of vaccination.     

Experimental electrocoagulation of dog esophageal and duodenal mucosa

The per review system for the assessment of research proposals is widely respected by working scientists. Nevertheless two problems associated with the operation of this system by the US National Institutes of Health are identified. First the scientist has no control over which committee will review an application and it may be considered by a quite inappropriate group. Second analysis of the committee composition suggests that in some of the groups several members are not active scientists and therefore not the "peers" of the applicant.     

The psychological development of orphanage-reared infants: interventions with outcomes (Tehran)

This paper describes five successive interventions in the rearing of infants at an orphanage in Tehran, with their outcomes. The outcomes were assessed longitudinally. The first of the successive groups, here called "waves", numbered 15. These Ss constitute the controls. The only intervention consisted of examining the infants every other week during the first year and every fourth week thereafter with the ordinal, sensorimotor scales of Uzgiris and Hunt. The audio-visual intervention intended for the second wave of 10 infants was tape-recorded mother talk and music under the control of the infants and mobiles that the infants could activate. This plan was never adequately implemented because of inadequate supervision. The third wave of 10 infants got extra untutored human care. The fourth wave of 20 infants got the kind of audio-visual intervention originally intended for the second wave plus access to responsive inanimate materials. For the fifth wave, numbering 11, the infant-caretaker ratio was reduced to two or three to one and the caretakers were taught the Badger program supplemented with procedures to foster vocal imitation and semantic mastery of body parts, clothing, toys, and other objects and events regularly encountered. The results show that each successive wave, excepting the second, achieved the top steps of nearly all seven of the ordinal scales at mean ages younger than the preceding wave, and the fifth wave surpassed even home-reared American children from predominantly professional families in achieving the top steps on five of the seven scales. The findings show that infants need not advance along all branches simultaneously and that the kinds of experience encountered determine the branch along which advancement occurs. A number of theoretical implications are examined. Especially important is the idea that a dependable educational psychology for infancy and early childhood calls for much more knowledge than we now have of the kinds of experience that advance development along each of the various branches.     

Vascular endothelial growth factor (VEGF) induces rapid prourokinase (pro-uPA) activation on the surface of endothelial cells

Vascular endothelial growth factor (VEGF) is the pivotal angiogenic growth factor activating endothelial cells to migrate, proliferate, and form capillary tubes. For an ordered endothelial cell migration, tissue invasion, and degradation of the extracellular matrix, proteolytic machinery is indispensable. Such machinery, suitable for localized proteolysis, is provided by the prourokinase-urokinase-plasmin system. Prourokinase (pro-uPA), the initial component of this system, is, however, synthesized in its inactive precursor form and as such bound to its cellular receptor uPAR. Here we identify a mechanism via which VEGF(165) interacting with its receptor VEGFR-2 rapidly induces prourokinase activation that is dependent on a change in integrin affinity, activation of matrix metalloproteinase 2 (MMP-2), and pro-uPA being bound to its surface receptor uPAR. This VEGF-induced pro-uPA activation on endothelial cells is responsible for VEGF-dependent local fibrinolytic activity and might be one of the initial steps in the angiogenic process.