Interleukin 10 (IL-10) upregulates functional high affinity IL-2 receptors on normal and leukemic B lymphocytes

Interleukin 10 (IL-10) has recently been shown to induce normal human B lymphocytes to proliferate and differentiate into immunoglobulin (Ig)-secreting cells. Herein, we show that IL-10 also promotes DNA synthesis and IgM production by anti-CD40 activated B cell chronic lymphocytic leukemia (B-CLL). Most strikingly, IL-2 and IL-10 were found to synergize to induce the proliferation and differentiation of B-CLL cells. This synergy between IL-2 and IL-10 was also observed with normal B cells which proliferated strongly and secreted large amounts of IgM, IgG, and IgA. The observed synergy is likely to be due to the IL-10-induced increase of high affinity IL-2 receptors on both normal and leukemic B cells. This increase of high affinity receptor is associated to an increase of Tac/CD25 expression that can be detected by flow cytometric analysis. Taken together, these results indicate that IL-10 permits anti-CD40 activated B cells to respond to IL-2 through an induction of high affinity IL-2 receptors. This effect of IL-10 may partly explain how T cells, which activate B cells in a CD40-dependent fashion, induce B cell proliferation and differentiation mostly through IL-2.     

Two structural adaptations for regulating transmitter release at lobster neuromuscular synapses

The distal accessory flexor muscle (DAFM) in the lobster (Homarus americanus) walking leg consists of 5 muscle fiber bundles. All five bundles, one proximal, one distal, and 3 medial, are innervated by one excitatory and one inhibitory motor neuron. Both neurons release more transmitter on the distal bundle than on the proximal bundle. The aim of our studies was to investigate the structural basis of this differentiation. Thin sections cut at 50 microns intervals showed a similar number of excitatory synapses on the two bundles. Freeze-fracture views of excitatory synapses showed that synapse size, active zone number per synapse, and intramembrane particle density in the postsynaptic membrane are similar proximally and distally. Active zones at synapses on the distal bundle are larger and contain about 50% more large intramembrane particles, which are thought to include the voltage-gated Ca2+ channels that couple the action potential to transmitter release, than their counterparts on the most proximal bundle. This difference in channel number appears to produce a disproportionate increase in the probability of transmitter release sufficient to account for most of the proximal-distal disparity in the amplitude of the excitatory postsynaptic potential. In contrast, staining the inhibitor for antibodies to the inhibitory neurotransmitter, GABA, showed that it forms more varicosities on the distal bundle than on the proximal bundle. Because most of the synapses are located in the varicosities, differences in synapse number likely regulate the proximal-distal disparity in the amount of inhibitory transmitter released. Therefore, the regional differentiation in the amount of transmitter released in the DAFM appears to be based on two distinct mechanisms. In the inhibitor, transmitter release appears to be regulated differentially by differences in synapse number. In the excitor, transmitter release appears to be regulated differentially from a similar number of synapses by differences in active zone structure.     

An approximate model and empirical energy function for solute interactions with a water-phosphatidylcholine interface

An empirical model of a liquid crystalline (L alpha phase) phosphatidylcholine (PC) bilayer interface is presented along with a function which calculates the position-dependent energy of associated solutes. The model approximates the interface as a gradual two-step transition, the first step being from an aqueous phase to a phase of reduced polarity, but which maintains a high enough concentration of water and/or polar head group moieties to satisfy the hydrogen bond-forming potential of the solute. The second transition is from the hydrogen bonding/low polarity region to an effectively anhydrous hydrocarbon phase. The "interfacial energies" of solutes within this variable medium are calculated based upon atomic positions and atomic parameters describing general polarity and hydrogen bond donor/acceptor propensities. This function was tested for its ability to reproduce experimental water-solvent partitioning energies and water-bilayer partitioning data. In both cases, the experimental data was reproduced fairly well. Energy minimizations carried out on beta-hexyl glucopyranoside led to identification of a global minimum for the interface-associated glycolipid which exhibited glycosidic torsion angles in agreement with prior results (Hare, B.J., K.P. Howard, and J.H. Prestegard. 1993. Biophys. J. 64:392-398). Molecular dynamics simulations carried out upon this same molecule within the simulated interface led to results which were consistent with a number of experimentally based conclusions from previous work, but failed to quantitatively reproduce an available NMR quadrupolar/dipolar coupling data set (Sanders, C.R., and J.H. Prestegard. 1991. J. Am. Chem. Soc. 113:1987-1996). The proposed model and functions are readily incorporated into computational energy modeling algorithms and may prove useful in future studies of membrane-associated molecules.     

Involvement of vitamin E and protein thiols in the inhibition of microsomal lipid peroxidation by glutathione

Iron-ascorbate stimulated lipid peroxidation in rat liver microsomes can be inhibited by glutathione (GSH). The role of protein thiols and vitamin E in this process was studied in liver microsomes isolated from rats fed diets either sufficient or deficient in vitamin E and incubated at 37 degrees C under 100% O2. Lipid peroxidation was induced by adding 400 microM adenosine 5'-triphosphate, 2.5 to 20 microM FeCl3, and 450 microM ascorbic acid. One mL of the incubation mixture was removed at defined intervals for the measurement of thiobarbituric acid reactive substances (TBARS), protein thiols and vitamin E. In vitamin E sufficient microsomes, the addition of GSH enhanced the lag time prior to the onset of maximal TBARS accumulation and inhibited the loss of vitamin E. Treatment of these microsomes with the protein thiol oxidant diamide resulted in a 56% loss of protein thiols, but did not significantly change vitamin E levels. However, diamide treatment abolished the GSH-mediated protection against TBARS formation and loss of vitamin E during ascorbate-induced peroxidation. Liver microsomes isolated from rats fed a vitamin E deficient diet contained 40-fold less vitamin E and generated levels of TBARS similar to vitamin E sufficient microsomes at a 4-fold lower concentration of iron. GSH did not affect the lag time prior to the onset of maximal TBARS formation in vitamin E deficient microsomes although total TBARS accumulation was inhibited. Similar to what was previously found in vitamin E sufficient microsomes [Palamanda and Kehrer, (1992) Arch. Biochem. Biophys. 293, 103-109], GSH prevented the loss of protein thiols in vitamin E deficient microsomes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Coronary reoperations: indications and results

The aim of this study was to assess the results of coronary reoperations and to determine the indications. Between January 1972 and December 1990, 166 coronary reoperations were performed in 161 patients (5 patients were operated three times). The interval between the first and second operation was 93 +/- 46 months. The interval between recurrence of symptoms and reoperation was 27 +/- 40 months. Recurrence of symptoms was related to isolated problems with the bypass grafts in 23% of cases, to an aggravation of the coronary disease without problems with the bypass grafts in 17% of cases and to an association of the two conditions in 60% of cases. Mortality in the first 30 postoperative days was 7.8% (13/161). The predictive factors of mortality were age over 70 years and an interval between recurrence of symptoms and reoperation of over 12 months. The causes of death were myocardial infarction (n = 5), left ventricular failure (n = 4), sudden death (n = 3), and arrhythmias (n = 1). The average follow-up period of survivors (n = 134) was 40 +/- 32 months. Four patients have been transplanted. Seven patients died secondarily. The cause of death was cardiac in 4 cases and non-cardiac in 3 cases. The actuarial 5 year and 10 year survival rates were 85 +/- 3%. Actuarial absence of myocardial infarction, angina, Class III-IV cardiac failure and transplantation was 87 +/- 4% at 5 years and 69 +/- 10% at 10 years. These figures show that coronary reoperation gives good functional results and long-term survival.(ABSTRACT TRUNCATED AT 250 WORDS)     

The surgical treatment of Graves'' disease

The in vitro adherence of Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli to five commercially available prosthetic vascular graft materials was compared. The influence of precoating the segments with human plasma for 2 h was also studied. S35-methionine was used to radiolabel bacteria. The segments were exposed to bacterial suspensions of approximately 10(7) CFU/ml at 37 degrees C for 0.5-18h. Following repeated washing in phosphate buffered saline (PBS), radioactivity associated with the segments was measured. The adherence of the three clinically relevant bacterial species was higher to untreated Dacron than to gelatin or collagen impregnated/coated Dacron or to PTFE. Furthermore, precoating of grafts with human plasma reduced bacterial adherence to woven Dacron, had a little effect on gelatin coated Dacron, but increased the adherence to collagen treated Dacron and, in particular, to PTFE.     

Intravitreal large-cell lymphoma

Large-cell (non-Hodgkin's) lymphoma may occur in the eye as a cellular infiltrate in the vitreous, uveal tract (choroid), retina, or optic nerve. Lymphomatous involvement may be limited to the eye but also is frequently associated with lesions of the central nervous system. Ocular involvement may precede involvement of the central nervous system by months or, in some cases, years. Ocular large-cell lymphoma is bilateral in approximately 80% of cases but often is asymmetric. The mean age of patients with ocular large-cell lymphoma is 60 years, and women are affected almost twice as often as men. Intravitreal large-cell lymphoma may manifest as an infiltrate of large glassy-gray cells or clusters of cells, and it may mimic uveitis or other inflammatory and infectious conditions of the eye. The diagnosis is based on cytologic and immunocytochemical studies of a vitreous biopsy specimen obtained by aspiration or by vitrectomy through the pars plana. Advances in irradiation of the eyes and the central nervous system, supplemented with corticosteroids and intrathecally and intravenously administered chemotherapeutic agents, have resulted in improvement of the dismal prognosis for patients with large-cell lymphoma.