Cyclosporine resistant effector cells in rabbit skin allografts

Summary Histoincompatible skin grafts in rabbits treated with cyclosporine can permanently engraft but show a transient mononuclear cellular infiltrate. This transient cyclosporine-resistant infiltrate consists of cells which are sensitive to steroids, radiation and cryopreservation. They have the same ACM-1 phenotype and the same characteristics as cyclosporine-sensitive cells.9 January 1987Supported by the Swiss National Research Foundation, Grant No. 3.908-0.83.     

Sustained and transient cortical neurones in area 18 of the cat

Summary The majority of the simple cells in area 18 of the cat's visual cortex gave pure transient responses to flashing slits of light. A few simple cells gave sustained responses to stationary slits of light. All of the complex cells encountered gave transient responses.     

B Lymphocytes in obesity-related adipose tissue inflammation and insulin resistance

Obesity-related insulin resistance is a chronic inflammatory condition that often gives rise to type 2 diabetes (T2D). Much evidence supports a role for pro-inflammatory T cells and macrophages in promoting local inflammation in tissues such as visceral adipose tissue (VAT) leading to insulin resistance. More recently, B cells have emerged as an additional critical player in orchestrating these processes. B cells infiltrate VAT and display functional and phenotypic changes in response to diet-induced obesity. B cells contribute to insulin resistance by presenting antigens to T cells, secreting inflammatory cytokines, and producing pathogenic antibodies. B cell manipulation represents a novel approach to the treatment of obesity-related insulin resistance and potentially to the prevention of T2D. This review summarizes the roles of B cells in governing VAT inflammation and the mechanisms by which these cells contribute to altered glucose homeostasis in insulin resistance.     

An initial phasic depolarization exists in the receptor potential of taste cells.

When frog taste cells were stimulated by varying salts after adaptation to water, quinine or acetic acid, a phasic depolarization appeared initially in the receptor potential of taste cells. The initial transient depolarization may be related to the enhancement of an initial phasic response in the taste nerve.     

Potassium currents in cardiac cells

The kinetic properties of the inwardly rectifying K current and the transient outward current in cardiac cells were investigated. In sheep Purkinje fibers superfused with Na-free K-free solution, time-dependent changes in the conductance of the inward rectifier are described. In patch clamp experiments the inward rectifier inactivates during hyperpolarization, as can be seen by a decrease in the open state probability. Using whole cell clamp on ventricular myocytes it is demonstrated that the inactivation during hyperpolarization is due to blocking of the channel by external Na, Mg and Ca. The channels responsible for the transient outward current in cow, sheep and rabbit Purkinje fibers are identified using single channel recording. It is demonstrated that in all three preparations the channels are K-selective. The channel in cow Purkinje cells has a large conductance and is regulated by voltage and internal Ca concentration. The channels identified in the sheep and rabbit cells have a much smaller conductance.     

Amino acid transport by small and large intestine of newborn pig

Summary Unidirectional fluxes of different amino acids have been determined across newborn pig small intestine and colon. The systems responsible for amino acid transport are present in the same proportion in both tissues. Colonic transport of amino acids appears to represent a transient overspill function of the small intestine.     

Host cell manipulation by the human pathogen Toxoplasma gondii

Toxoplasma gondii is an obligate intracellular parasite that can infect virtually any nucleated cell. During invasion Toxoplasma creates the parasitophorous vacuole, a subcellular compartment that acts as an interface between the parasite and host, and serves as a platform for modulation of host cell functions that support parasite replication and infection. Spatial reorganization of host organelles and cytoskeleton around the parasitophorous vacuole are observed following entry, and recent evidence suggests this interior redecorating promotes parasite nutrient acquisition. New findings also reveal that Toxoplasma manipulates host signaling pathways by deploying parasite kinases and a phosphatase, including at least two that infiltrate the host nucleus. Toxoplasma infection additionally controls several cellular pathways to establish an anti-apoptotic environment, and subverts immune cells as a conduit for dissemination. In this review we discuss these recent developments in understanding how Toxoplasma achieves widespread success as a human and animal parasite by manipulating its host.     

Biliverdin as an electron transfer catalyst for superoxide ion in aqueous medium

Stopped flow experiments gave evidence of the formation of a biliverdin-superoxide complex and/or a biliverdin radical anion by reaction of aqueous O2- with biliverdin. Such transient species are likely intermediates both in the bleaching of biliverdin, during exposure to the aerobic xanthine oxidase reaction, and in the reduction of ferricytochrome c under the same conditions.     

The potential importance of myeloid-derived suppressor cells (MDSCs) in the pathogenesis of Alzheimer’s disease

The exact cause of Alzheimer’s disease (AD) is still unknown, but the deposition of amyloid-β (Aβ) plaques and chronic inflammation indicates that immune disturbances are involved in AD pathogenesis. Recent genetic studies have revealed that many candidate genes are expressed in both microglia and myeloid cells which infiltrate into the AD brains. Invading myeloid cells controls the functions of resident microglia in pathological conditions, such as AD pathology. AD is a neurologic disease with inflammatory component where the immune system is not able to eliminate the perpetrator, while, concurrently, it should prevent neuronal injuries induced by inflammation. Recent studies have indicated that AD brains are an immunosuppressive microenvironment, e.g., microglial cells are hyporesponsive to Aβ deposits and anti-inflammatory cytokines enhance Aβ deposition. Immunosuppression is a common element in pathological disorders involving chronic inflammation. Studies on cancer-associated inflammation have demonstrated that myeloid-derived suppressor cells (MDSCs) have a crucial role in the immune escape of tumor cells. Immunosuppression is not limited to tumors, since MDSCs can be recruited into chronically inflamed tissues where inflammatory mediators enhance the proliferation and activation of MDSCs. AD brains express a range of chemokines and cytokines which could recruit and expand MDSCs in inflamed AD brains and thus generate an immunosuppressive microenvironment. Several neuroinflammatory disorders, e.g., the early phase of AD pathology, have been associated with an increase in the level of circulating MDSCs. We will elucidate the immunosuppressive armament of MDSCs and present evidences in support of the crucial role of MDSCs in the pathogenesis of AD.     

Effect of azimexon (BM 12.531) on mouse granulocyte-macrophage and monocyte-macrophage progenitor cells

Summary Treatment of mice with 25 mg/kg azimexon (BM 12.531) resulted in an increase in granulocyte-macrophage colony-forming cells (GM-CFC) in spleen and bone marrow after a transient depression in the cell populations. Bone marrow monocyte-macrophage colony-forming cells (MM-CFC) increased at 7 days after treatment, and splenic MM-CFC were least affected by azimexon treatment. The increase in granulocytic and monocytic colony-forming cells may play a role in the previously reported protection by azimexon against radiation and drug-induced toxicity.Supported by the Armed Forces Radiobiology Research Institute, Defense Nuclear Agency, under Research Work Unit MJ 00026.     

Adrenocorticotrophic hormone and cyclic adenosine monophosphate effect on mouse adrenal cortical cell membrane potential

Adrenocorticotrophic hormone (ACTH) and cyclic adenosine monophosphate (cAMP) both caused a rapid and transient depolarization of the resulting membrane potential of superfused rat adrenal cortical cells. The membrane depolarization to both secretagogues were very similar. The membrane potential changes occurred as early as 0.1 min and were dose dependent in both onset and extent of depolarization.     

In vitro proliferation of human large granular lymphocytes with v-raf/v-myc recombinant retrovirus

The effect of infection with a retrovirus carrying v-raf/v-myc oncogenes (J2 virus) on the in vitro proliferation of human large granular lymphocytes (LGL) was investigated. LGL infected with J2 virus (J2LGL), unlike uninfected cells, grew with a proliferation peak eight days after infection. Such cells retained the morphology and functional properties typical of LGL. Furthermore, 5% of J2LGL produced virus the day after infection, whereas non-virus production was detectable five days later. These data indicate that J2 virus provides a transient mitogenic signal for LGL.     

Biliverdin as an electron transfer catalyst for superoxide ion in aqueous medium

Summary Stopped flow experiments gave evidence of the formation of a biliverdin-superoxide complex and/or a biliverdin radical anion by reaction of aqueous O₂ ^– with biliverdin. Such transient species are likely intermediates both in the bleaching of biliverdin, during exposure to the aerobic xanthine oxidase reaction, and in the reduction of ferricytochromec under the same conditions.     

Changes in erythrocyte membrane lipid composition affect the transient decrease in membrane order which accompanies insulin receptor down-regulation.

We have recently demonstrated, using electron paramagnetic resonance (EPR) spectroscopy, that insulin receptor internalization in response to insulin incubation (down-regulation) in human erythrocytes is accompanied by a transient decrease in membrane order, as measured by the 2T' parallel order parameter. Since membrane lipids play such an important role in receptor internalization, we investigated the possible effects that an alteration of the normally-occurring lipid profile might have on down-regulation and the concomitant transient decrease in membrane order. Consequently, human erythrocytes enriched with cholesterol and erythrocytes from cirrhotic patients were examined, because both of these groups of cells have a higher cholesterol/phospholipid molar ratio (CH/PL) than controls. The 5-nitroxystearate spin label, which inserts into the lipid bilayer of cell membranes, was used to monitor changes in 2T' parallel for a 3-h period at 37 degrees C. We report here that both cholesterol-enriched and cirrhotic erythrocytes do not down-regulate, as demonstrated by binding assays, and that they do not show the typical transient decrease in membrane order observed in controls. The results seem to indicate that a more ordered membrane inhibits internalization of the insulin receptor in erythrocytes, and that an increase in membrane disorder is necessary for insulin receptor down-regulation.     

Cell-matrix contact structures

Cell-extracellular matrix contacts are points on cell surfaces where adhesion receptors tether cells to matrix and are linked intracellularly to cytoskeletal components. These structures integrate cell organisation within tissues, support cell motility and specialised activities of differentiated cells, and transduce extracellular signals. Current characterisations of matrix contacts are based on morphological and biochemical criteria, yet the levels of definition of different contact types are very varied. Some contacts are surprisingly little-studied given their likely importance in vivo. Here, I describe the general features of matrix contacts, review the functions and molecular composition of major types of transient and stable matrix contacts, and discuss the information that is emerging on contact integration and dynamics in single cells. Received 7 September 2000; received after revision 4 October 2000; accepted 6 October 2000     

Uninterrupted protein synthesis is essential for survival in the early stages of carbon tetrachloride-induced hepatocellular necrosis in the mouse

The fatal syndrome produced by cycloheximide given 6 h after a hepatonecrogenic dose of CCl4 is due neither to direct toxic synergism between CCl4 and cycloheximide nor to transient sinusoidal thrombosis. It is suggested that survival in the presence of unknown factors released from dying liver cells requires uninterrupted protein synthesis. The life-saving effect of sterilization of the intestine by antibiotics indicates that the gut flora or its products play a vital role in pathogenesis.     

Protective effect of interferon on the target cells of cytotoxic lymphocytes

Interferon treatment of sensitized T lymphocytes enhances cytotoxicity against target cells. On the contrary, the same treatment of the target cells alone protects them, whatever the cytotoxicity of effector cells might be. We suggest that the cells having once survived contact with cytotoxic T lymphocytes could become resistant to any new attack by the same cells.     

Differential stimulation of signaling pathways initiated by Edg-2 in response to lysophosphatidic acid or sphingosine-1-phosphate

Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are produced during cell activation and have multiple effects on cells. A family of seven transmembrane-spanning domain G-protein-coupled receptors, named Edg, mediate these effects of LPA and S1P. In this study, transient overexpression of Edg-2 sensitized MG63 human osteosarcoma cells to both LPA- and S1P-mediated stimulation of fibronectin matrix deposition and actin stress fiber formation. Both lipids were active in the 1-20 nM concentration range on cells transfected with Edg-2 as compared to the 10-200 nM range on mock-transfected cells. The signaling pathway for matrix deposition by Edg-2-transfected cells was Rho dependent. Overexpression of Edg-2 also caused a tenfold decrease in the concentration of either LPA or S1P that activated MAPKinase (Erkl/2) in MG63 cells. LPA- or S1P-stimulated activation of Erkl/2 was Gi dependent. These results indicate that, in MG63 cells, Edg-2 mediates actin stress fiber formation, fibronectin matrix assembly, and MAPKinase activation in response to either LPA or S1P.     

Adrenocorticotrophic hormone and cyclic adenosine monophosphate effect on mouse adrenal cortical cell membrane potential

Summary Adrenocorticotrophic hormone (ACTH) and cyclic adenosine monophosphate (cAMP) both caused a rapid and transient depolarization of the resting membrane potential of superfused rat adrenal cortical cells. The membrane depolarization to both secretagogues were very similar. The membrane potential changes occurred as early as 0.1 min and were dose dependent in both onset and extent of depolarization.The author gratefully acknowledges the generous financial support of the E.G. Schlieder Educational Foundation, the American Heart Association of Louisiana and the American Heart Association.