Development and loss of toluene diisocyanate reactivity: immunologic,pharmacologic, and provocative challenge studies

Toluene diisocyanate (TDI) sensitivity accompanied by nonspecific bronchial hyperresponsiveness occurs in approximately 5% of occupationally exposed workers. We report the case of a 32-yr-old worker followed longitudinally after removal from isocyanate exposure. TDI reactivity was lost 11 mo after removal from exposure and nonspecific bronchial hyperresponsiveness resolved after 17 mo. Bronchial reactivity to radishes (Raphanus sativus), which developed concurrently with TDI reactivity, was lost 2 yr later. Immunopharmacologic results show that the worker's initial decreased ability of lymphocytes to produce cyclic AMP returned to near normal after 2 yr. IgE antibodies to a human serum albumin tolyl monoisocyanate conjugate were still present at this time.     

MR technology: effect of even-echo rephasing on calculated T2 values and T2 images

In multiple spin-echo image sequences of blood flow, the "even-echo" phenomenon produces an absolute increase in signal magnitude from first- to second-echo images of normal vessels harboring slow flow. Distinguishing this from the apparent relatively high signal intensity seen on second-echo images in pathologic foci of stationary tissue is important to the diagnostician. Selected case material containing two tissue types was reviewed retrospectively: tissues known to harbor slow flow, such as normal veins and venous sinuses and vascular malformations, and tissues that have long transverse (T2) relaxation times and appear as intense structures on second-echo images, such as neoplasms, infarcts, and regions of demyelination. Calculations of T2 parameters were made by computer for defined regions of interest. T2 images were also generated. Visual inspection of the acquired images did not reliably distinguish increased intensity due to even-echo rephasing from the relative changes between adjacent tissues seen on second-echo images. More definitive differentiation of the even-echo phenomenon was provided by calculated values of T2 and computer-synthesized T2 images representing acquired intensity data of two-echo sequences. The synthesized images were especially useful when stationary tissue with lengthened T2 values was adjacent to or in proximity to vessels or vascular lesions. A five spin-echo image sequence was valuable for separating slow flow from stationary tissue by a technique of synthesizing T2-difference images using three consecutive echoes.     

Sizes, laminar and topographic origins of cortical projections to the major divisions of the red nucleus in the monkey

The retrograde transport of horseradish peroxidase was used to study the topographic and laminar origins of the cortical projections to the parvocellular and the magnocellular divisions of the red nucleus in Macaca mulatta and Macaca fascicularis. Approximately 90% of the corticorubral projection is directed to the parvocellular division of the nucleus. Corticoparvocellular (CRp) neurons are pyramidally shaped, are smaller in size than corticospinal neurons, and are more numerous. They are found principally in sublamina Va of cytoarchitectonic areas 4 and 6, and in moderate quantities in sublamina Vb of posterior area 8 and area 5. In areas 4 and 6, the cells are grouped in clusters of three to 15 neurons each and are arranged in cellular bands of varying rostrocaudal thickness which course mediolaterally. With respect to functionally defined zones, CRp neurons are found throughout the supplementary motor area and the precentral motor cortex. In addition, they are found in parts of areas 5, 6, and 24 that project to these cortical motor areas, and that are thought to have "premotor" or movement-programming functions. The corticomagnocellular (CRm) projection arises principally from cells in sublamina Vb of the precentral arm and leg areas (area 4), and from adjacent parts of posterior area 6, CRm cells are pyramidally shaped, and their size distribution is bimodal, with peaks that correspond, respectively, to the modal diameters of CRp and of corticospinal neurons. These results and those of previous studies suggest that CRm neurons are involved principally in the control of hand and foot movements, with little effect on more proximal musculature. The massive CRp projection, however, is clearly part of a large cerebrocerebellar communication system, with motor and/or movement programming functions that have yet to be clearly defined.     

Safety and Efficacy of a Steroid Avoidance Immunosuppression Regimen in Renal Transplant Patients With De Novo or Preformed Donor-Specific Antibodies: A Single-Center Study

Although interest in the role of donor-specific antibodies (DSAs) in kidney transplant rejection, graft survival, and histopathological outcomes is increasing, their impact on steroid avoidance or minimization in renal transplant populations is poorly understood. Primary outcomes of graft survival, rejection, and histopathological findings were assessed in 188 patients who received transplants between 2012 and 2015 at the Scripps Center for Organ Transplantation, which follows a steroid avoidance protocol. Analyses were performed using data from the United Network for Organ Sharing. Cohorts included kidney transplant recipients with de novo DSAs (dnDSAs; n = 27), preformed DSAs (pfDSAs; n = 15), and no DSAs (nDSAs; n = 146). Median time to dnDSA development (classes I and II) was shorter (102 days) than in previous studies. Rejection of any type was associated with DSAs to class I HLA (P < .05) and class II HLA (P < .01) but not with graft loss. Although mean fluorescence intensity (MFI) independently showed no association with rejection, an MFI >5000 showed a trend toward more antibody-mediated rejection (P < .06), though graft loss was not independently associated. Banff chronic allograft nephropathy scores and a modified chronic injury score were increased in the dnDSA cohort at 6 months, but not at 2 years (P < .001 and P < .08, respectively). Our data suggest that dnDSAs and pfDSAs impact short-term rejection rates but do not negatively impact graft survival or histopathological outcomes at 2 years. Periodic protocol post-transplant DSA monitoring may preemptively identify patients who develop dnDSAs who are at a higher risk for rejection.     

Chromogranin A: osmotically active fragments and their susceptibility to proteolysis during lysis of the bovine chromaffin granules

Osmotically active fragments of chromogranin A (Chr A) were studied in lysates from bovine chromaffin granules (CG) disrupted in the presence or absence of inhibitors of endogenous proteolytic activities. The effects of various methods of lysis were examined by micro-osmometry, PAGE-SDS electrophoretic techniques and immunoblots with polyclonal anti-Chr A sera. Osmotically active 'small' Chr A fragments (below 30 kDa) were conspicuous in lysates containing cocktails of leupeptin, pepstatin A, pHMB, PMSF and aprotinin. The osmotically inactive native Chr A in the 68-100 kDa range and the osmotically active fragments below 47 kDa were degraded in lysates at neutral or acid pH in the absence of inhibitors. However, degradation of the native Chr A and intermediates below 47 kDa could be prevented by extraction directly from intact CG, notably in cold or boiling distilled water. On the other hand, the main product after large-scale extraction of CG in 1 M acetic acid (pH 1.9, 100 degrees C) was a novel, osmotically active fragment (22 kDa), immunostaining only for the N-terminal sequence (Chr A1-40). The heat-stable fraction (Mr,n 23 kDa) exhibited concentration-independent colloid osmotic pressures even in the absence of phosphate, a property which may distinguish this N-terminal-containing fragment from the larger intermediates, probably containing the pancreastatin sequence, and other regions at the C-terminal side of the prohormone molecule. The functional roles of these osmotically active intermediates in the processing of Chr A are not yet known.     

Quantification of children's hand and mouthing activities through a videotaping methodology.

A videotaping methodology has been developed for use in quantifying the types and frequencies of children's hand and mouthing activities that could lead to exposure to environmental pollutants via dermal and ingestion pathways. Twenty children in day care, ages 3-6 years and 10 children in residences, ages 2-5 years, were videotaped during their waking hours for 1 day. Parents of each child completed questionnaires for the purpose of evaluating the accuracy of parental reports of hand-to-mouth rates. Videotapes were translated as quantifiable activities by two trained observers whose reporting reliability was checked throughout the investigation. Results determined that reliability of the videotaping method was very good, even over a year post-training. From videotape data, the average hand-to-mouth frequency rate was determined to be 9.5 contacts/h. These values are considerably higher than the current default value of 1.56 contacts/h under consideration by the EPA.