Effects of cyclosporin A on functions of specific murine T cell clones: inhibition of proliferation, lymphokine secretion and cytotoxicity

Allospecific T lymphocyte clones with different functions were generated from spleen cells of C 57/Bl6 mice following sensitization in vitro by a one-way mixed lymphocyte culture (MLC) with irradiated DBA/2 spleen cells. The clones were propagated in vitro in the presence of interleukin 2 (IL 2) and restimulation with stimulator cells. In these clones Cyclosporin A (CSA) was tested for its suppressive effect on different T lymphocyte functions. The antigen-dependent proliferation of a helper clone (HTL) was totally inhibited by 50 ng/ml CSA. Proliferation induced by simultaneous administration of antigen and IL 2 was partially suppressed in all helper and cytotoxic clones (CTL). The IL 2-driven proliferation in the absence of antigen was also suppressed between 25-70% by the immunosuppressive drug. Secretion of macrophage activating factor (MAF) and interferon (IFN) by HTL and CTL in response to antigen or mitogen was reduced dose dependently by CSA. Concentrations of 50 ng/ml CSA diminished lymphokine secretion to approximately 10% of controls, also when excess IL 2 was present. Cytotoxicity, previously described to be insensitive to the drug, could be suppressed by 50 ng/ml CSA to a various extent, from 40-70%, in different cytotoxic clones when the effector cells were preincubated with CSA for 1 h or more. Conclusively, the data suggest that CSA interferes generally with the activation of T lymphocyte clones.     

Interleukin 1 induces specific phosphorylation of a 41 kDa plasma membrane protein from the human tumor cell line K 562

An in vitro system was established to investigate the early effects of interleukin 1 (IL 1) on a clearly defined subcellular system, the plasma membrane. Murine IL 1 was obtained from the macrophage tumor line P 388 D1 and purified to apparent homogeneity. Plasma membranes from the human leukaemic tumor cell line K 562 were highly purified by differential ultracentrifugation. The monokine induced the specific phosphorylation of a 41 kDa plasma membrane protein. This could be demonstrated by incubating the plasma membranes in the presence of IL 1 and (gamma-32P)-ATP, separating the proteins by SDS-PAGE and subsequent autoradiography. A first biochemical reaction caused by IL 1 in the target organelle of the cell, the plasma membrane, was discovered, yielding a clue of how signal transmission may take place finally resulting in the stimulation of the responding cell.     

Organization of central hyperthermic mechanisms in helium-cold hypothermic hamsters

We have investigated the ability of three hyperthermic stimuli (PGE2, 5-HT and ACh) to elicit hyperthermia in the Helium-Cold (He-Cold) hypothermic hamster. Hamsters in these conditions are poikilothermic and will passively follow room temperature in a regulated cold room. Animals were injected centrally at AH/POA sites via an indwelling guide tube at body temperatures maintained between 9-12 degrees C. Active sites in the AH/POA were determined prior to the experiment by PGE2 injection. PGE2 injection at an effective AH/POA site immediately reversed the anesthetic induced hypothermia in warm air. Hamsters were induced into hypothermia by the He-Cold induction method and body temperatures were maintained in a 9 degrees C cold room. Colonic temperatures were monitored at 5 minute intervals by a YSI thermistor probe and telethermometer. Central injections of 5-HT (2 micrograms/microliter) and ACh (50 micrograms/microliter) at effective AH/POA sites evoked significant increases in colonic temperature in He-Cold hamsters. PGE2 injections were not different from saline control injections and did not elicit pronounced temperature changes in these animals. Specific blockade of the 5-HT and ACh temperature increases was demonstrated with specific antagonist injections. The results suggest that the central organization of heat-gain mechanisms in the AH/POA is the same as normothermic animals even at temperatures well below those previously investigated.     

Results of flexor-to-extensor and extensor brevis tendon transfer for correction of the crossover second toe deformity

Between 1990 and 1995, 38 patients (42 feet) underwent repair for crossover toe deformity, 31 (35 feet) of whom returned for final examination at an average of 51.6 months (range, 24-81 months). Causes included trauma, iatrogenic, and unknown. Presenting complaints included dorsal pain with either metatarsalgia or joint pain, isolated metatarsophalangeal (MP) joint pain, metatarsalgia, painful plantar callus, metatarsalgia and joint pain, and painful dorsal callus. All patients were treated with one of two operative techniques, either the flexor-to-extensor tendon transfer or the extensor brevis tendon transfer. Choice of procedure depended on the stage of preoperative deformity. Twenty-four patients were completely satisfied with the surgical correction, 6 were satisfied with reservations, and 1 was dissatisfied. The average postoperative AOFAS score for all patients was 85 points (range, 54-100 points), which correlated strongly with patient satisfaction. Twenty-two patients stated that they had no postoperative pain, 8 reported some pain, and 1 had frequent pain at the corrected toe. In 30 feet, there was no recurrence; three patients had mild residual crossover toe deformity, and two patients had recurrent deformity, although all MP joints were stable. Follow-up radiographs demonstrated substantial reduction in MP joint angles in both the AP (from 7 degrees to -1 degree) and lateral (from 45 degrees to 25 degrees) projections. This article reviews the surgical technique of both procedures, proposes specific indications for each, and presents outcomes. Based on our findings, the extensor brevis tendon transfer is appropriate for stage 1, stage 2, and flexible stage 3 deformities. Flexor-to-extensor tendon transfer is appropriate for rigid stage 3 and stage 4 deformities and for all patients with a symptomatic neuroma of the second web space (where the extensor brevis transfer is not possible). Stiffness of the MP joint is a potential problem with the flexor-to-extensor tendon transfer.     

Die Operation nach Bankart —“Bohrlochtechnik”

Operationsprinzip Beseitigung der am vorderen unteren Pfannenrand gelegenen sogenannten Bankart-L?sion durch Reinsertion der Gelenkkapsel am Pfannenrand mit U-N?hten.     

Interleukin I and the glomerular mesangium. II. Monokine stimulation of mesangial cell prostanoid secretion.

Monocytic (MC) infiltration is a prominent feature of many forms of immune-mediated glomerulonephritis. Through the release of interleukin-1, (IL-1), monocyte/macrophages have been shown to induce the proliferation of mesangial cells and to stimulate the secretion of a glomerular basement membrane-degrading neutral proteinase. In addition, mesangial cells release a cytokine that expresses many of the biologic properties of monocyte IL-1, including stimulation of mesangial cell proliferation. Because many of the actions of IL-1 are mediated by the induction of prostanoid prostaglandin (PG) synthesis, the authors determined the effects of purified macrophage and mesangial IL-1 on the secretion of prostaglandin E (PGE), prostacyclin, and thromboxane. The results indicated that cycling MCs release primarily PGE in response to purified IL-1. The local release by either monocytes or mesangial cells of IL-1 during glomerular inflammation, with subsequent mesangial cell generation of vasodilatory PGE, may be responsible in part for the alterations in the glomerular microcirculation observed in these disorders.