Routes to transplant tolerance versus rejection; the role of cytokines

The alloimmune response can be divided into specific junctures where critical decisions between tolerance and immunity are made which define the outcome of the transplant. At these "decision nodes" various cytokines direct alloresponsive T cells to develop either a proinflammatory response aimed at graft destruction or an immunoregulatory response facilitating graft acceptance. This review will focus on the role of these cytokines in influencing the progression of an alloimmune response leading ultimately to either allograft survival or rejection.     

Suppression of charge movement by calcium antagonists is not related to calcium channel block

The calcium channel-inhibiting drugs nitrendipine and diltiazem represent two important classes of organic calcium antagonists. In the present study, the effect of these drugs on calcium currents and charge displacement currents in bullfrog semitendinosus muscle fibers was examined using a vaseline gap voltage clamp. Nitrendipine (10 M) reduced the quantity of charge that moved both during the ON phase (Q_ON) and the OFF phase (Q_OFF) of charge movement. This action appeared to be most selective for Q_ON. However, at this same concentration, nitrendipine had no blocking action on inward calcium currents. In contrast to these findings, diltiazem blocked calcium currents in a concentration-dependent manner, while slightly increasing the quantity of charge moved during Q_ON and Q_OFF. The enhancement of charge movement by diltiazem resulted from two actions. First, diltiazem shifted the voltage-dependence of charge movement to more negative potentials. Second, diltiazem increased the maximum amount of charge moved. (Supported by NIH NS 03178 and HL 07382.)     

Supraependymal cells in the third ventricle of the neonatal rat

Supraependymal cells in the third ventricle of neonatal male and female rats were examined with scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Supraependymal cells in the third ventrical of adult male rats were also studied with SEM. Many neonate supraependymal cells were round to oval in shape and exhibited varying degrees of surface irregularity. Small finger-like processes or narrow pseudopodia projected from the cell bodies over the underlying ependymal cells. Some neonatal supraependymal cells exhibited flattened cell bodies with broad pseudopodia and few surface irregularities. TEM revealed a variety of cell profiles. Prominent within the cytoplasm of many supraependymal cells were lysosomes, smooth and coated vesicles suggesting pinocytosis, subplasmalemma vacuoles, and occasional lipid droplets. The morphological characteristics of neonatal supraependymal cells suggested they were mononuclear phagocytes. Adult supraependymal cells exhibited more pleomorphic cell shapes with numerous cell processes, varying widely in size and shape, and often extending over the ventricular surface for considerable distances. These observations, in combination with previous studies by other investigators, suggest that some adult supraependymal cells may also be phagocytic in nature. The differences in morphology between adult and neonatal supraependymal phagocytes may relate to the differing third ventricle environment between adult and neonates and/or differences in the origin of the phagocytes with age.     

In situ characterization of T lymphocyte subpopulations in leprosy in the mangabey monkey.

Leprosy in the mangabey monkey is an experimental model which is similar both clinically and histologically to human lepromatous leprosy. The immunopathology of these diseases was compared using monoclonal antibodies against T lymphocyte subpopulations in frozen tissue sections with an immunoperoxidase technique. In both mangabey and human lepromatous granulomas OKT4 (or Leu 3a) and Leu 2a cells were scattered among macrophages with greater numbers of Leu 2a as compared with OKT4 (or Leu 3a) cells. The results suggest that from an immunopathological standpoint experimental leprosy in mangabeys will provide a suitable model for the investigation of the pathogenesis of human lepromatous leprosy and for the evaluation of new antileprosy vaccines.     

Preoperative gentling does not attenuate septal-lesion induced hyperreactivity

Rats were either gentled or not gentled for 10 minutes a day for 7 days. At the end of this time a lesion was made in the region ventral to the anterior septum or in the lateral septum, or the rat was given a sham lesion. Reactivity to the experimenter was tested at 2, 7, and 14 days postoperatively. The reactivity scores of animals gentled preoperatively were not different from those of animals which had not been gentled but the animals of both groups were significantly more reactive than animals given a sham lesion. It is concluded that preoperative handling does not attenuate the increase in defensive behavior induced by lesions of the lateral septum or of the region ventral to the anterior septum.     

Maxillary artery embolisation in the management of epistaxis

Serious consideration needs to be given to the importance of early embolisation of the maxillary artery in severe and refractory epistaxis. This is particularly true in the young fit person with traumatic epistaxis and in the elderly person who is unfit for general anaesthesia. Embolisation is now a safe and reliable technique. Six patients were embolised. In the two institutions from 1999 - 2000. All responded well to embolisation without complication. This paper describes the technique used in our hospitals and suggests that with the advent of platinum coils and pre embolisation arteriography, the chances of cerebrovascular accident is very small.     

The influence of inspired oxygen on the oxygen uptake response to ramp exercise

The relation between and work rate (WR) was examined in seven male subjects who performed ramp (1 W·3 s^–1) two-legged cycle ergometry to exhaustion while inspiring either hypoxic (12% O₂), normoxic (21% O₂), or hyperoxic (40% O₂) air. The anaerobic threshold was estimated from respiratory gas exchange data and is thus referred to as the respiratory gas exchange threshold (RGET). Prior to the RGET, the was greater under normoxic [mean (SD); 10. 19(1.04) ml O₂·min^–1·W^–1] and hyperoxic [10.44 (0.72)] conditions compared with hypoxia [9.34 (0.89)]. Above the RGET, the for hypoxia [8.91 (0.63)], normoxia [10.40 (0.77)], and hyperoxia [11.08 (0.48)] were all significantly different from each other. These data indicated that for two-legged, cycle, ramp ergometry in normoxia below the RGET, both the and response time was constant. Above the RGET, the normoxic response was the net result of a declining and a longer response time to the unsteady state character of a ramp exercise protocol.     

Differential immunoglobulin G subclass antibody titers to respiratory syncytial virus F and G glycoproteins in adults

Two respiratory syncytial virus glycoproteins, F and G, which differ substantially in the amount of glycosylation were used as antigens in an enzyme-linked immunosorbent assay to determine immunoglobulin G (IgG) subclass titers in 30 experimentally infected healthy adults. The titers of antibodies to the F glycoprotein achieved in postinfection sera were highest in the IgG1 subclass, whereas those to the G glycoprotein were highest and comparable in the IgG1 and IgG2 subclasses. The high IgG2 response to the G glycoprotein suggests that it is seen by the immune system as a polysaccharide antigen, a hypothesis consistent with its large carbohydrate content.     

Selective vulnerability of unmyelinated fiber Schwann cells in nerves exposed to local anesthetics

When peripheral nerves of experimental rats are exposed to local anesthetics, distinctive and reproducible pathologic changes occur involving the perineurial sheath and endoneurial contents. Application of intermediate strength concentrations of the local anesthetics, 2-chloroprocaine, lidocaine, etidocaine, and intermediate or high concentrations of procaine to the surface of rat sciatic nerves resulted in the following changes. By 48 hours, the perineurial sheath exposed to the drug was disrupted and became permeable to granulocytes which infiltrated the subjacent endoneurium in conjunction with edema formation in the endoneurial interstitium. Application of 10% procaine to exposed nerve resulted in extensive demyelination. The most striking pathologic change occurring with either intermediate or high doses was accumulation of lipid droplets in Schwann cells, a phenomenon that occurred often in myelin-producing Schwann cells but much less frequently in unmyelinated fiber Schwann Cells. Lipid accumulation appears to be one of several reactive changes that affect Schwann cells of myelinated fibers and is dose-dependent. On the other hand, while reactive changes were infrequently seen in unmyelinated fiber Schwann cells, these cells appeared more susceptible to injury as shown by electron microscopy. Injury to Schwann cells by local anesthetics is temporary because these cells can replicate quickly. Autoradiographic studies of thymidine incorporation 1 week after procaine administration to the sciatic nerve showed intense proliferation of Schwann cells, but no such activity in controls. These findings support the view that their neurotoxic properties may account in some part for the function of local anesthetics, that Schwann cells of small unmyelinated fibers are more vulnerable to these agents than those of myelinated fibers, and that destruction of their supporting cells is followed by vigorous mitotic activity in the endoneurium.