Burn sepsis

Sepsis in the burned individual can arise from multiple causes. However, the unique source is the burn wound itself. It is clear that health is association with maintenance of a bacterial equilibrium in the wound and that infection is a result of an imbalance in favor of the bacteria. The primary host defense mechanism, an intact epithelial barrier, has been lost at the time of burning. A portal of entry has been created, and the bactericidal defenses have been neutralized. All of the host defense mechanisms associated with inflammation are evoked but may be limited by the avascular isolation of much of the wound. In addition to alteration in vascular response associated with the burns, there are adverse changes in the neutrophils themselves. The alterations in nutrition that may follow burn injury further reduce systemic host resistance. Associated diseases, such as diabetes, may present a further hazard. All of the local factors influencing host resistance are adversely affected in the burn wound. There is necrotic tissue, decreased local tissue perfusion, and loss of the mechanical barrier. Quantitative techniques have demonstrated that bacteria are present in the depths of the wound from the time of injury. Infection and burn wound sepsis are clearly represented by the quantitative increase in bacteria to numbers exceeding 10(5) per gram of tissue. In no other instance has the importance of the "amphibiont" organisms been more clearly demonstrated than in the burn wound. Today's nonpathogen has all too often become tomorrow's killer. As therapeutic control becomes effective against the current organism, the ecologic void is filled by another, which, by definition, is resistant to the treatment being employed.     

Pulmonary artery catheterization: a modified technique

A modified technique for catheterization of the pulmonary artery was developed. It involves the passage of a tapered, movable-core, J-tipped guide wire across the right ventricle into the pulmonary artery followed by the advancement of a straightened Grollman pigtail catheter. The technique was successful in 34 of 34 pulmonary artery catheterizations. The method avoids prolonged catheter manipulation within the right ventricle. In addition, since the catheter does not cross the tricuspid valve until the guide wire has been advanced, the occasional complication of the pigtail "hooking" on a tricuspid valve leaflet or chordae tendineae during catheter withdrawal and manipulation is prevented.     

Giant cell tumor of the scapula

This study reviews the demographic, radiologic, and histologic characteristics of 13 cases of an important primary skeletal neoplasm, giant cell tumor of bone, occurring in an uncommon location, the scapula. that eight of 13 patients presented prior to 20 years of age contrasts significantly with the typical age distribution (between 20–40 years) encountered in giant cell tumors arising in long bones. As it does elsewhere in the skeleton, giant cell tumor of the scapula frequently demonstrates cystic and/or telangiectatic components on histologic examination. The radiologic appearances of giant cell tumor in the scapula and in more typical locations are similar and include: (1) well-defined (geographic) margins, occasionally with a delicate sclerotic rim, (2) prominent trabeculations, (3) expanded bone contour, (4) frequent extension to the subchondral plate, and (5) absence of internal mineralization. Tumor sites within the scapula included: coracoid process, acromion, and body (three cases each); glenoid (two cases); and superior and inferior angles (one case each).The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army, the Department of Defense, or the Uniformed Services University of the Health Sciences.     

PJA-BP expression and TCR delta deletion during human T cell differentiation

Recombination of deltaRec to psiJalpha will delete the TCR delta gene, which is thought to play an important role in the bifurcation of the TCR alphabeta versus TCR gammadelta differentiation lineages. We recently detected a DNA-binding protein in human thymocytes, the so- called PJA-BP, which recognizes the psiJalpha gene segment and might be one of the factors involved in the regulation of preferential deltaRec- psiJalpha rearrangements. We now investigate PJA-BP expression and its correlation with TCR delta gene deletion in thymocytes. Our electrophoretic mobility shift assay experiments showed that the PJA-BP is evolutionary conserved in human, murine and simian thymocytes. Using a large series of human hematopoietic malignancies (n = 30), we conclude that PJA-BP expression is thymocyte specific and seems to be restricted to thymocytes committed to the TCR alphabeta lineage. Analysis of seven well-defined human thymocyte subpopulations showed that preferential deltaRec-psiJalpha rearrangements as well as PJA-BP expression can be detected from the immature CD34-/CD1+/CD3- /CD4+/CD8alpha+beta- thymocyte differentiation stage onwards. These experiments indicate that expression of PJA-BP in human thymocytes starts simultaneously with preferential deltaRec-psiJalpha rearrangements, which supports our hypothesis that PJA-BP is one of the factors involved in the preferential recombination of deltaRec to psiJalpha.      

Angiotensin-(1–7) stimulates water transport in rat inner medullary collecting duct: evidence for involvement of vasopressin V2 receptors

The peptide angiotensin-(1–7) [Ang-(1–7)] is known to enhance water transport in rat inner medullary collecting duct (IMCD). The aim of this study was to determine the mechanism of the Ang-(1–7) effect on osmotic water permeability (P _f). P _f was measured in the normal rat IMCD perfused in vitro in presence of agonists [Ang-(1–7), arginine vasopressin (AVP) and Ang-(3–8)], and antagonists of the angiotensin and the vasopressin cascade. Ang-(1–7), but not Ang-(3–8), increased P _f significantly. The effect of Ang-(1–7) on P _f was abolished by its selective antagonist, A-779, added before or after Ang-(1–7). Prostaglandin E₂ and the protein kinase A inhibitor H8 also blocked the Ang-(1–7) effect. Blockade of vasopressin V₁ receptors by antagonists did not change the Ang-(1–7) effect, but pre-treatment with a V₂ antagonist abolished the effect of Ang-(1–7) on P _f. Similarly, pre-treatment with A-779 inhibited AVPs effect on P _f. Forskolin-stimulated P _f was blocked both by A-779 and by the V₂ antagonist. Finally, Ang-(1–7) increased cAMP levels in fresh IMCD cell suspensions whilst the forskolin-stimulated cAMP synthesis was decreased by A-779 and the V₂ antagonist. These data provide evidence that Ang-(1–7) interacts via its receptor with the AVP V₂ system through a mechanism involving adenylate-cyclase activation.     

Lack of directed Vα14-Jα281 rearrangements in NK1+ T cells

NK1.1⁺ T cells are an unusual subset of TCRαβ cells distinguished by their highly restricted Vβ repertoire and predominant usage of an invariant Vα14-Jα281 chain. To assess whether a directed rearrangement mechanism could be responsible for this invariant α chain, we have analyzed Vα14 rearrangements by polymerase chain reaction and Southern blot in a panel of cloned T-T hybrids derived from thymic NK1.1⁺ T cells. As expected a high proportion (17/20) of the hybrids had rearranged Vα14 to Jα281. However, Vα14-Jα281 rearrangements always occurred on only one chromosome and were accompanied by other Vα-Ja rearrangements (not involving Vα14) on the homologous chromosome. These data argue that rigorous ligand selection rather than directed rearrangement is responsible for the high frequency of Vα14-Jα281 rearrangements in NK1.1⁺ T cells.     

Organization of suppression in receptive fields of neurons in cat visual cortex.

1. The response to an optimally oriented stimulus of both simple and complex cells in the cat's striate visual cortex (area 17) can be suppressed by the superposition of an orthogonally oriented drifting grating. This effect is referred to as cross-orientation suppression. We have examined the spatial organization and tuning characteristics of this suppressive effect with the use of extracellular recording techniques. 2. For a total of 75 neurons, we have measured the size of each cell's excitatory receptive field by use of rectangular patches of drifting sinusoidal gratings presented at the optimal orientation and spatial frequency. The length and width of these grating patches are varied independently. Receptive-field length and width are determined from the dimensions of the smallest grating patch required to elicit a maximal response. 3. The extent of the area from which cross-orientation suppression originates has been measured in an analogous manner. Each neuron is excited by a patch of drifting grating the same size as the receptive field. The response to this stimulus is modulated by a superimposed patch of grating having an orthogonal orientation. After selecting the spatial frequency that produces maximal suppression, the response of each cell is examined as a function of the length and width of the orthogonal (suppressive) grating patch. Results from 29 cells show that the dimensions of the orthogonal grating patch required to elicit maximal suppression are similar to, or smaller than, the dimensions of the excitatory receptive field. Thus cross-orientation suppression originates from within the receptive field. 4. For some cells the spatial frequency tuning of the suppressive effect is much broader than the spatial frequency tuning for excitation. In these cases it is possible to find a spatial frequency that produces suppression but not excitation. With the use of a suppressive stimulus having this spatial frequency, we examined the strength of suppression as a function of orientation for 11 cells. These tests show that suppression occurs at all orientations, including the preferred orientation for excitation. In some cases, suppression is somewhat stronger at the preferred orientation for excitation than at any other orientation. 5. For 12 cells we varied the relative spatial phase between the optimally oriented and orthogonal gratings. In all cases the magnitude of suppression is largely independent of the relative spatial phase. 6. For three binocular cells we examined whether the suppressive effect of a grating oriented orthogonal to the optimum could be mediated dichoptically.(ABSTRACT TRUNCATED AT 400 WORDS)     

Inactivation of Notch1 impairs VDJbeta rearrangement and allows pre-TCR-independent survival of early alpha beta Lineage Thymocytes

Notch proteins influence cell fate decisions in many developmental systems. During lymphoid development, Notch1 signaling is essential to direct a bipotent T/B precursor toward the T cell fate, but the role of Notch1 at later stages of T cell development remains controversial. We have recently reported that tissue-specific inactivation of Notch1 in immature (CD44(-) CD25(+)) thymocytes does not affect subsequent T cell development. Here, we demonstrate that loss of Notch1 signaling at an earlier (CD44(+)CD25(+)) developmental stage results in severe perturbation of alpha beta but not gamma delta lineage development. Immature Notch1(-/-) thymocytes show impaired VDJ beta rearrangement and aberrant pre-TCR-independent survival. Collectively, our data demonstrate that Notch1 controls several nonredundant functions necessary for alpha beta lineage development.     

A novel dicentric deleted chromosome 21 arising from tandem translocation

We present a 26-year-old patient with myelodysplastic syndrome (MDS). Initial bone marrow cytogenetics with G-banding showed a rearranged chromosome 21, which was dicentric and bisatellited on CBG- and NOR-banding. Fluorescence in situ hybridization helped to characterize the structure, using a whole chromosome 21 paint and the locus specific AML1 gene probe. The rearranged 21 consisted solely of chromosome 21 material, contained only one copy of AML1, and was not a trisomy, but a deleted tandem translocation. The MDS transformed to acute myeloid leukemia (AML), and the patient died almost 12 months post-diagnosis. Cytogenetics was performed three times during the course of the disease, and the dicentric chromosome 21 was present throughout. Although there are a number of published rearrangements of chromosome 21 in MDS and AML, most are isodicentrics. We could not find another case of an abnormal chromosome 21 with the same structure as reported here.