Inflammatory cell infiltrate in a responding metastatic nodule after vaccine-based immunotherapy

A patient with von Hippel Lindau disease, bilateral symmetric renal cell carcinoma and pulmonary metastases treated with immunotherapy is the subject of this study. A left kidney and tumour mass were removed and the tumour cells used to make an autologous tumour/bacille Calmette–Guérin (BCG) vaccine as part of the treatment protocol. The patient's pulmonary nodules responded, but the remaining renal nodule subsequently grew. Samples of both tumours were obtained allowing for an internally controlled evaluation of the histological and immunohistologic differences between a responding and non-responding tumour nodule after therapy. The immunotherapy protocol is designed to promote a T cell response to autologous tumour. Cellular infiltrates were demonstrated in both responding and non-responding nodules compared with the pretreatment tumour specimen, but the responding nodule contained proportionately more T cells as well as markedly increased numbers of plasma cells and granulocytes. This suggested that several arms of the immune system may have been operative in the responding nodule.     

Psychometric Properties of Resting Anterior EEG Asymmetry: Temporal Stability and Internal Consistency

We examined whether resting anterior electroencephalographic (EEG) asymmetry in the alpha frequency band has psychometric properties that would be expected of a measure assessing individual differences. In each of two experimental sessions, separated by three weeks, resting EEG in midfrontal and anterior temporal sites was recorded from 85 female adults during eight 60-s baselines. Resting alpha asymmetry demonstrated acceptable test-retest stability and excellent internal consistency reliability. Analyses including other frequency bands indicated that degree of stability varied somewhat as a function of band and region. In addition, asymmetry was less stable than absolute power. Discussion focuses on the implications of the present findings for the measurement and conceptualization of resting anterior asymmetry.     

Recurrent Poisoning in Children: A Review

The literature on poisoning accidents or ingestion of toxicsubstances in children is reviewed. Special emphasis is givento the phenomenon of recurrent or repeat episodes. Recommendationsare made concerning means for identifying children who are atrisk for repeat poison episodes, as well as for developing methodsof intervention to prevent such occurrences.     

Potentiation of mossy fiber-evoked EPSPs in turtle cerebellar Purkinje cells by the metabotropic glutamate receptor agonist 1S,3R-ACPD.

1. The effects of the metabotropic glutamate receptor (mGluR) agonist 1S,3R-ACPD on excitatory postsynaptic potentials (EPSPs) evoked by stimulation of mossy fibers (MF) and parallel fibers (PF) were examined in turtle cerebellar Purkinje cells. 2. 1S,3R-ACPD (1-25 microM) reversibly potentiated the amplitude of the MF-evoked EPSPs and revealed a late, slow EPSP component, but was without effect on PF-evoked EPSPs. The potentiation of both components of MF-evoked EPSPs was dose dependent, with an ED50 of approximately 3 microM. At higher doses (15-25 microM) 1S,3R-ACPD produced a direct depolarization of Purkinje cells in 57% of cells examined. 3. The enhancement of MF EPSPs by 1S,3R-ACPD was blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonovalerate (AP-5), but not by the mGluR antagonist L-2-amino-3-phosphonopionic acid (L-AP3; 1 mM), or the 1R,3S isomer of ACPD (25-500 microM). 4. The results demonstrate that mGluR activation by 1S,3R-ACPD produces a potent, stereospecific facilitation of NMDA receptor-mediated transmission at the MF-granule cell synapse.     

Ultimate tensile strength of dentin: Evidence for a damage mechanics approach to dentin failure

Dentin structure and properties are known to vary with orientation and location. The present study explored the variation in the ultimate tensile strength (UTS) of dentin with location in the tooth. Hourglass specimens were prepared from dentin located in the center, under cusps, and in the cervical regions of human molar teeth. These were tested in tension at various distances from the pulp. Median tensile strengths ranged from 44.4 MPa in the inner dentin near the pulp, to 97.8 MPa near the dentino-enamel junction (DEJ). This increase in the median UTS with distance from the pulp to the DEJ was statistically significant (P <.001). Of particular importance was the observation that the UTS measurements followed a Weibull probability distribution, with a Weibull modulus of about 4.5. The Weibull behavior of the UTS data strongly suggests that the large variances in fracture strength data result from a distribution of preexisting defects in the dentin. These findings justify a damage-mechanics approach to studies of dentin failure.     

Blurring artifacts in megavoltage radiography with a flat-panel imaging system: comparison of Monte Carlo simulations with measurements

Originally designed for use at medical-imaging x-ray energies, imaging systems comprising scintillating screens and amorphous Si detectors are also used at the megavoltage photon energies typical of portal imaging and industrial radiography. While image blur at medical-imaging x-ray energies is strongly influenced both by K-shell fluorescence and by the transport of optical photons within the scintillator layer, at higher photon energies the image blur is dominated by radiation scattered from the detector housing and internal support structures. We use Monte Carlo methods to study the blurring in a notional detector: a series of semi-infinite layers with material compositions, thicknesses, and densities similar to those of a commercially available flat-panel amorphous Si detector system comprising a protective housing, a gadolinium oxysulfide scintillator screen, and associated electronics. We find that the image blurring, as described by a point-spread function (PSF), has three length scales. The first component, with a submillimeter length scale, arises from electron scatter within the scintillator and detection electronics. The second component, with a millimeter-to-centimeter length scale, arises from electrons produced in the front cover of the detector. The third component, with a length scale of tens of centimeters, arises from photon scatter by the back cover of the detector. The relative contributions of each of these components to the overall PSF vary with incident photon energy. We present an algorithm that includes the energy-dependent sensitivity and energy-dependent PSF within a ray-tracing formalism. We find quantitative agreement (approximately 2%) between predicted radiographs with radiographs of copper step wedges, taken with a 9 MV bremsstrahlung source and a commercially available flat-panel system. The measured radiographs show the blurring artifacts expected from both the millimeter-scale electron transport and from the tens-of-centimeters length scale arising from the scattered photon transport. Calculations indicate that neglect of the energy-dependent blurring would lead to discrepancies in the apparent transmission of these wedges of the order of 9%.     

Fusion protein vesicle-associated membrane protein 2 is implicated in IFN-gamma-induced piecemeal degranulation in human eosinophils from atopic individuals

BACKGROUND: Exocytosis is an integral event during IFN-gamma-induced piecemeal degranulation in eosinophils. In many tissues soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs), including vesicle-associated membrane protein (VAMP), act as specific intracellular receptors to allow granule fusion with the membrane during degranulation. However, the mechanisms underlying eosinophil piecemeal degranulation induced by IFN-gamma are not well understood. OBJECTIVE: We sought to assess whether eosinophils express the vesicular SNARE protein VAMP-2 and to determine the involvement of VAMP-2 in IFN-gamma-induced piecemeal degranulation. METHODS: Human peripheral blood eosinophils (> or =97%) from atopic subjects were subjected to RT-PCR and sequence analysis with specific primers for VAMP-2 mRNA. Western blotting and flow cytometric analysis were carried out to confirm the identity of VAMP-2 and its susceptibility to cleavage by tetanus toxin. Confocal laser scanning microscopy imaging was conducted on double-labeled cytospin preparations of eosinophils at 0, 5, 10, 30, and 60 minutes and 16 hours of IFN-gamma (500 U/mL) stimulation. RESULTS: Eosinophils expressed VAMP-2 mRNA (n = 4 donors), which exhibited 100% homology with human VAMP-2 cDNA on sequencing. Eosinophils were also found to express tetanus toxin-sensitive VAMP-2 protein. RANTES and VAMP-2 immunofluorescence were observed to colocalize to similar intracellular structures by means of confocal imaging. IFN-gamma induced a rapid translocation of VAMP-2(+) organelles toward the cell membrane in correlation with RANTES. CONCLUSIONS: These findings suggest that exocytosis in human eosinophils is regulated by SNAREs, with a specific role indicated for VAMP-2 in piecemeal degranulation.     

Oesophageal Pain and Catecholamine Mediated Ecg Changes Mimicking Myocardial Ischaemia

It is known that oesophageal pain can imitate angina and also that non specific ECG changes, probably catecholamine mediated, can be similar to those due to true myocardial ischaemia. Both of these can therefore pose a problem for the diagnosis of angina pain due to cardiac ischaemia. We report a patient who had both of these conditions simultaneously, pain on exertion appearing as angina but due to oesophagitis, and "ischaemic" ECG changes due to catecholamines—a double mimic of myocardial ischaemia.

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