Cyclosporine A Prevents the Generation of Single Positive (Lyt2+ L3T4−, Lyt2− L3T4+) Mature T Cells, but not Single Positive (Lyt2+ T3−) Immature Thymocytes, in Newborn Mice

The influence of cyclosporine A (CsA) on T-cell maturation was investigated in newborn mice. CsA treatment during the pre- and postnatal periods resulted in a hypoplasia of peripheral lymphatic organs, and absence of mature T3+ T cells in lymph nodes and spleens; no functional T-cell reactivity was observed. In thymuses of CsA-treated mice, no T3+ single positive Lyt2+ or T3+L3T4+ thymocytes could be found, but double positive (DP) cells were readily detected. A thymocyte subset with the phenotype Lyt2+L3T4-T3- was still discernible; this population was non-functional in vitro. The data show that the maturation of single positive (SP) T cells is critically influenced by CsA; under the conditions used here we found no evidence that 'leaky' autoreactive SP T cells develop in CsA-treated newborn mice.     

Host-Reactive Cytotoxic T Lymphocyte Precursors in Long-lived Fully Allogeneic Mouse Bone Marrow Chimeras

Fully H-2-incompatible chimeric mice were constructed by grafting lethally (950 rad) irradiated germ-free (GF) CBA (H2k) mice with anti-Thy 1 antibody plus complement-treated allogeneic C57Bl/6 (B6) (H2b) bone marrow cells. These chimeric mice were kept for more than 11 months, either under GF conditions or under barrier-sustained specific-pathogen-free (SPF) conditions. Controls included nonirradiated, nontransplanted, sex- and age-matched CBA and B6 mice raised under SPF conditions, and syngeneic chimeric mice of the CBA----CBA type kept under GF and SPF conditions. All chimeric mice were completely repopulated with donor-type lymphoid cells and showed no clinical or histological evidence of graft-versus-host disease. From the fully allogeneic chimeric mice, we enumerated the numbers of splenic cytotoxic T lymphocyte precursors (CTL-p) that could be clonally expanded under limiting dilution conditions in response to third-party alloantigens, or nonmodified and trinitrophenyl (TNP)-modified stimulator cells bearing host or donor H-2 antigens. The existence of high numbers of alloreactive and host- or donor-type H-2-restricted TNP-specific CTL-p in the spleens of fully allogeneic chimeras indicated almost normal immunocompetence. The surprising finding, however, was that large numbers of host (CBA)-reactive splenic CTL-p were inducible under limiting dilution conditions in healthy long-lived allogeneic chimeras, although these chimeric mice were devoid of any histological or clinical signs of graft-versus-host disease.     

Effectiveness of Oximes 2-PAM and HI-6 in Recovery of Muscle Function Depressed by Organophosphate Agents in the Rat Hemidiaphragm: An in Vitro Study

Effectiveness of Oximes 2-PAM and HI-6 in Recovery of MuscleFunction Depressed by Organophosphate Agents in the Rat Hemidiaphragm:An in vitro Study. REDDY, V. K., DESHPANDE, S. S., CINTRA, W.M., SCOBLE, G. T., AND ALBUQUERQUE, E. X. (1991). Fundam. Appl.Toxicol. 17, 746–760. Phrenic nerve diaphragm musclesof young adult rats were used to study the ability of the oximes2-PAM and HI-6 to recover muscle function depressed by organophosphate(OP) agents. The single twitch of diaphragm muscles which wereexposed to soman (0.2 mm) recovered after washing with salinefor 3 hr, but the muscles pretreated with sarin (0.4 µM),VX (0.2 µM), or tabun (0.4 µM) showed only partialrecovery. In addition, after 3 hr washing, the muscles pretreatedwith soman as well as with tabun did not recover the tetanussustaining ability (TSA), yet complete recovery was observedwith muscles pretreated with sarin and VX. These results indicatethat the OPs have different effects on muscle contractile propertiesand that VX- and sarin-pretreated muscles recover equally wellafter wash with physiological solution. The recovery of twitchtension of diaphragm muscles by 2-PAM and HI-6 was similar tothat achieved by washing with saline for 3 hr for sarin- andsoman-exposed muscles. The most remarkable differences wereseen in the recovery of TSA. Both 2-PAM and HI-6 recovered theTSA of muscles that were pretreated with sarin and VX. Although2-PAM recovered the TSA after tabun pretreatment, HI-6 had nodiscernible effect. On the other hand, HI-6 recovered the TSAof soman-pretreated muscles but 2-PAM did not. The effectivenessof muscle function recovery was not related to the oximes' abilityto reactivate AChE, thus indicating that the recovery of musclecontractility may be attributed to a direct effect of thesecompounds on the muscle.     

Metal deposition in post-surgical granulomas of the urinary tract

Fourteen cases of post-surgical granulomatous inflammation of the urinary tract were studied to investigate the possible deposition in the tissues of metals derived from the diathermy instruments used. The granulomas showed central necrosis, palisaded histiocytes and giant cells. On electronmicroscopy both amorphous material and electrondense particles were seen in the granulomas. The former appeared to be necrotic tissue. The particles were metallic in nature. Energy dispersive analysis of X-rays showed the presence of tungsten, iron, copper, nickel, chromium, zinc and vanadium. Tungsten particles were always pure. Other single particles contained two or more of the remaining elements, indicating the presence of alloy metals. Analysis of the diathermy instruments showed the cutting loops to be pure tungsten and the 'rollerballs' to be of nickel silver containing copper, zinc, nickel, manganese and iron. Both the loops and balls are supported on stainless steel wires containing iron, chromium, nickel, manganese, molybdenum, copper and vanadium. It is proposed that metallic fragments from the instruments were deposited in the tissues during the surgical procedures and elicited an immunological reaction with granuloma formation. Tungsten is probably inert but nickel, chromium, copper and zinc are immunogenic. Under certain circumstances both nickel and chromium may also be carcinogenic.     

An Analysis of 114 Consecutive Patients with Complete One-Year Follow-Up

This study assesses the clinical and electrode complications associated with the use of the epicardial screw-on electrode technique for permanent ventricular pacing. The records of 114 consecutive patients who received screw-on epicardial electrodes were analyzed in-hospital and at one year following implantation. We compared two techniques of implanting the screw-on electrode: 72 transmediastinal (TM) and 42 subxiphoid (SX) procedures. Baseline clinical inequalities were not apparent between the SX and TM patients. There was one operative death in the SX series and none among the TM patients. Total hospital mortality was 4% in the SX group and 2% in the TM group. In-hospital morbidity in the SX series (13/72-18%) was less than the TM group (14/42-33%), largely due to pleural entry and necessity for more frequent chest tube placement in TM patients. Electrode complications were low in both groups (3% in-hospital and 3% late; total 6/114, or 5%). Morbidity and mortality of these approaches to direct myocardial pacing remain noticeably higher than reported results of some transvenous series. Excellent electrode stability can be attained using the screw-on electrode, however, and the SX approach offers lower hospital morbidity than the TM method.