Interleukin-6 dimers produced by endothelial cells inhibit apoptosis of B-chronic lymphocytic leukemia cells.

Tumoral lymphocytes from patients with B-chronic lymphocytic leukemia (B-CLL) are long-lived cells in vivo, but they die rapidly by apoptosis in vitro. Here, it is reported that endothelial cells (ECs) inhibit the apoptosis of B-CLL cells, as determined by 4 different flow cytometric methods, and that this antiapoptotic effect is mediated mainly by soluble factor(s), as can be deduced from the following findings. First, EC-conditioned medium (ECCM) inhibited the apoptotic rate in B-CLL to approximately 50% of control. Second, the antiapoptotic effect mediated by EC/B-CLL cell contact was more apparent than real; using a fluorescence-based phagocytosis assay, it was demonstrated that this effect was due to the phagocytic capacity of ECs, which internalized apoptotic cells. Third, the protective effect of ECCM was associated neither with proliferation nor differentiation signals. Fourth, the survival factor was a dimeric form of IL-6 because anti-IL-6 antibodies completely neutralized the antiapoptotic effect mediated not only by the crude ECCM but also by the 45- to 55-kd active fractions obtained after gel filtration, which contained high levels of IL-6. These IL-6 dimers (IL-6(D)) were noncovalently associated. Sixth, human recombinant IL-6(D) (hrIL-6(D)) inhibited B-CLL apoptosis, whereas hrIL-6 monomers (hrIL-6(M)) did not. Binding and functional competition experiments showed not only that monomers and dimers had similar affinity for the IL-6R, but also that hrIL-6(M) inhibited the antiapoptotic activity of hrIL-6(D). These data suggest that IL-6(D) derived from ECs promote the survival of B-CLL cells.

[Erotic hallucinations associated with the use of propofol]. / Alucinaciones eróticas asociadas al uso de propofol.

A 42-year-old woman underwent outpatient surgery to remove vocal cord polyps. She had a history of depressive syndrome and had previously undergone surgery without complications. Before surgery she received 3.5 mg of midazolam orally. General anesthesia was provided with propofol: one initial bolus of 1 mg/kg followed by an infusion of 6 mg/kg/h. Surgery was uneventful. Upon arrival in the postanesthetic recovery ward, the patient, greatly agitated, accused the orderlies pushing the gurney of forcing her to touch his genitals. Twenty-four hours after surgery she did not remember the incident. Since 1987 various cases of postoperative sexual hallucination have been associated with the use of propofol. Usually the patients are women undergoing minor gynecological procedures and involve male health-care providers in the surgical area. The incidents are characteristically followed by amnesia. This clinical picture has also been described for midazolam and nitrous oxide, but the frequency is higher for propofol owing to its pharmacodynamic and pharmacokinetic properties (rapidly recovered awareness and lowering of inhibition). Given the legal implications, the presence of someone of the same sex as the patient is recommended when the patient awakens.

Alucinaciones eróticas asociadas al uso de propofol / Sexual hallucinations related to propofol

Una mujer de 42 años fue intervenida de polipectomía en cuerda vocal en régimen de cirugía ambulatoria. Tenía antecedentes de síndrome depresivo y había sido intervenida anteriormente sin incidencias. Preoperatoriamente recibió 3,5 mg de midazolam por vía oral. Se realizó anestesia general con propofol: un bolo inicial de 1 mg/kg de peso, seguido de una perfusión de 6 mg/kg/h. La intervención se desarrolló sin ninguna incidencia. Al llegar al área de recuperación postanestésica, la paciente, muy agitada, acusó delante del personal de enfermería al camillero de obligarla a tocarle los genitales. A las 24 h postoperatorias presentaba amnesia del incidente.Desde el año 1987 se han referido diversos casos de alucinaciones postoperatorias con contenido sexual asociadas al uso de propofol. Principalmente han sido mujeres sometidas a procesos ginecológicos menores y con involucración de personal masculino del área quirúrgica. Es característica la amnesia posterior.Este cuadro también se ha descrito con otros fármacos (midazolam, óxido nitroso), pero su frecuencia de aparición es mayor con el propofol debido a sus propiedades farmacodinámicas y farmacocinéticas (rápida recuperación de consciencia, carácter desinhibido). Dadas las implicaciones legales asociadas se recomienda la presencia, en el momento del despertar, de una tercera persona del mismo sexo del paciente (AU)

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Derivatives of gallic acid induce apoptosis in tumoral cell lines and inhibit lymphocyte proliferation.

The effect of gallic acid (3,4,5-trihydroxybenzoic acid) and its alkyl esters (methyl, propyl, octyl, and lauryl) has been studied on several tumoral and nontumoral cells. Three types of behavior have been observed; the first type is represented by the mouse B cell lymphoma Wehi 231 cell line in which death occurs according to the biochemical characteristics of classical apoptosis showing the DNA ladder fragmentation pattern. The second type is represented by the mouse fibroblast L929 cell line in which morphological characteristics such as cell shrinkage, chromatin condensation, and appearance of apoptotic bodies can be evidenced by microscopical observation. However, the typical DNA fragmentation is absent. Peripheral blood lymphocytes are representative of a third type of behavior. In a resting state they can withstand higher concentrations of these compounds. If the drug is washed, they proliferate normally upon the addition of the mitogen phytohemagglutinin (PHA). However, if the drug is added in the presence of PHA, a clear antiproliferative effect can be demonstrated. A special interest for these compounds stems from the fact that some of them are currently used as antioxidant food additives with the European Community codes E-310 (propylgallate), E-311 (octylgallate), and E-312 (laurylgallate).

Quantification of soluble serum HLA class I antigens in healthy volunteers and AIDS patients.

A solid-phase enzyme immunoassay (ELISA) has been used to quantify human soluble Class I histocompatibility antigens in serum samples from voluntary blood donors and AIDS patients. Statistical analysis of the results showed significantly raised levels (p less than 0.01) of free HLA Class I in sera from AIDS patients (2.95 +/- 1.80 micrograms/ml) when compared with the blood donors (1.06 +/- 0.6 micrograms/ml). The assay is specific, reproducible and easy to perform. Potential uses of this determination are discussed.

Studies on the quaternary structure of class I major histocompatibility complex antigens. Effect of different agents on the interaction between subunits.

The effect of temperature, urea, guanidine HCl, ionic and nonionic detergents, organic solvents, chaotropic salts, pH, and divalent cations has been investigated on purified human histocompatibility antigens solubilized by papain (HLApap) or solubilized by sodium cholate (HLAchol). HLApap and HLAchol are fairly stable proteins to agents acting predominantly on hydrogen bonds (temperature, urea) or hydrophobic forces (ionic and nonionic detergents). However, agents which affect ionic interactions (pH, salts, divalent cations) dissociate the molecules into subunits. A single binding site for beta 2-microglobulin with an affinity constant of 1.0 X 10(7) M-1 was found for the alpha chain of HLAchol. The dissociated subunits can be separated by affinity chromatography on Sepharose-rabbit IgG anti-human beta 2-microglobulin and reassociate in vitro when incubated under the appropriate conditions. The results point toward an important role of ionic interactions between subunits in the stabilization of the quaternary structure of HLA.