Repolarization of tumor infiltrating macrophages and increased survival in mouse primary CNS lymphomas after XPO1 and BTK inhibition

Journal of Neuro-Oncology - Patients diagnosed with primary central nervous system lymphoma (PCNSL) often face dismal outcomes due to the limited availability of therapeutic options. PCNSL cells...     

The photoionization-reduced energy in LSC.

The atomic rearrangement cascade that follows the electron-capture decay process in low-Z radionuclides involves X-rays which have high photoelectric interaction probabilities. When the K-shell binding energy of the ionized atom (e.g., hydrogen) is significantly lower than the energy of the X-ray photon, the detector response to a photon-equivalent energy electron and the whole photoionization process are very similar. This is not the case when the scintillator cocktail contains larger atoms (e.g., oxygen and phosphorus in Ultima Gold). For larger Z atoms, the reduced energy of the whole photoionization process is less than the reduced energy of the interacting photon due to the nonlinear effects of ionization quenching. This paper shows the convenience of including a more detailed simulation of the photoionization process in the atomic rearrangement detection model for electron-capture nuclides such as (55)Fe, (51)Cr and (54)Mn. The need for more elaborate atomic rearrangement models is a consequence of the analysis of (125)I data.     

Niflumic acid-induced increase in potassium currents in frog motor nerve terminals: effects on transmitter release

The actions of the nonsteroidal antiinflammatory drug niflumic acid were studied on frog neuromuscular preparations by conventional electrophysiological techniques. Niflumic acid reduced the amplitude and increased the latency of endplate potentials in a concentration-dependent manner. Neuromuscular junctions pretreated with niflumic acid (0.05–0.5 mM) showed much less depression than control when they were stimulated with trains of impulses. Inhibition of acetylcholine release was reverted by raising the extracellular Ca²⁺ concentration but not by simply washing out the preparations with niflumic acid-free solutions. Pretreatment with indomethacin (0.1 mM), another nonsteroidal antiinflamatory drug, did not affect the niflumic acid-induced inhibition of evoked responses. Niflumic acid (0.1 mM) did not change the amplitude of miniature endplate potentials and had a dual action on the frequency of miniatures: it decreased their frequency at 0.1 mM whereas it produced an enormous increase in the rate of spontaneous discharge at 0.5 mM. Niflumic acid (0.1–1 mM) reversibly increased the amplitude and affected the kinetics of presynaptic voltage-activated K⁺ current and Ca²⁺-activated K⁺ current in a concentration-dependent manner. Niflumic acid (0.1–1 mM) irreversibly decreased the amplitude and reversibly affected the kinetics of the nodal Na⁺ current. Indomethacin (0.1 mM) had no effect on presynaptic currents. In conclusion, niflumic acid reduces acetylcholine release by increasing presynaptic K⁺ currents. This may shorten the depolarizing phase of the presynaptic action potential and may reduce the entry of Ca²⁺ with each impulse.     

X-linked dominant chondrodysplasia with platyspondyly, distinctive brachydactyly, hydrocephaly, and microphthalmia

We describe a family with an X-linked dominant chondrodysplasia. Four males and six females were affected through four generations. Identification of skeletal abnormalities and hydrocephaly during the pregnancy of three male fetuses led to termination of the pregnancies. A fourth affected male died at 6 days of life. The four patients had chondrodysplasia, hydrocephaly, and facial features with microphthalmia. Radiographs showed severe platyspondyly and various bone abnormalities including a distinctive metaphyseal cupping of the metacarpals, metatarsals, and phalanges. The affected females were less affected and showed small stature, sometimes associated with body asymmetry and mild mental retardation. This condition appears to be a previously unrecognized X-linked dominant chondrodysplasia.     

C3 promotes clearance of Klebsiella pneumoniae by A549 epithelial cells

The airway epithelium represents a primary site for contact between microbes and their hosts. To assess the role of complement in this event, we studied the interaction between the A549 cell line derived from human alveolar epithelial cells and a major nosocomial pathogen, Klebsiella pneumoniae, in the presence of serum. In vitro, we found that C3 opsonization of poorly encapsulated K. pneumoniae clinical isolates and an unencapsulated mutant enhanced dramatically bacterial internalization by A549 epithelial cells compared to highly encapsulated clinical isolates. Local complement components (either present in the human bronchoalveolar lavage or produced by A549 epithelial cells) were sufficient to opsonize K. pneumoniae. CD46 could competitively inhibit the internalization of K. pneumoniae by the epithelial cells, suggesting that CD46 is a receptor for the binding of complement-opsonized K. pneumoniae to these cells. We observed that poorly encapsulated strains appeared into the alveolar epithelial cells in vivo but that (by contrast) they were completely avirulent in a mouse model of pneumonia compared to the highly encapsulated strains. Our results show that bacterial opsonization by complement enhances the internalization of the avirulent microorganisms by nonphagocytic cells such as A549 epithelial cells and allows an efficient innate defense.     

Release of ATP induced by hypertonic solutions in Xenopus oocytes

ATP mediates intercellular communication. Mechanical stress and changes in cell volume induce ATP release from various cell types, both secretory and non-secretory. In the present study, we stressed Xenopus oocytes with a hypertonic solution enriched in mannitol (300 m m ). We measured simultaneously ATP release and ionic currents from a single oocyte. A decrease in cell volume, the activation of an inward current and ATP release were coincident. We found two components of ATP release: the first was associated with granule or vesicle exocytosis, because it was inhibited by tetanus neurotoxin, and the second was related to the inward current. A single exponential described the correlation between ATP release and the hypertonic-activated current. Gadolinium ions, which block mechanically activated ionic channels, inhibited the ATP release and the inward current but did not affect the decrease in volume. Oocytes expressing CFTR (cystic fibrosis transmembrane regulator) released ATP under hypertonic shock, but ATP release was significantly inhibited in the first component: that related to granule exocytosis. Since the ATP measured is the balance between ATP release and ATP degradation by ecto-enzymes, we measured the nucleoside triphosphate diphosphohydrolase (NTPDase) activity of the oocyte surface during osmotic stress, as the calcium-dependent hydrolysis of ATP, which was inhibited by more than 50 % in hypertonic conditions. The best-characterized membrane protein showing NTPDase activity is CD39. Oocytes injected with an antisense oligonucleotide complementary to CD39 mRNA released less ATP and showed a lower amplitude in the inward current than those oocytes injected with water.     

Functional and structural conservation of CBS domains from CLC chloride channels

All eukaryotic CLC Cl⁻ channel subunits possess a long cytoplasmic carboxy-terminus that contains two so-called CBS (cystathionine β-synthase) domains. These domains are found in various unrelated proteins from all phylae. The crystal structure of the CBS domains of inosine monophosphate dehydrogenase (IMPDH) is known, but it is not known whether this structure is conserved in CLC channels. Working primarily with ClC-1, we used deletion scanning mutagenesis, coimmunoprecipitation and electrophysiology to demonstrate that its CBS domains interact. The replacement of CBS domains of ClC-1 with the corresponding CBS domains from other CLC channels and even human IMPDH yielded functional channels, indicating a high degree of structural conservation. Based on a homology model of the pair of CBS domains of CLC channels, we identified some residues that, when mutated, affected the common gate which acts on both pores of the dimeric channel. Thus, we propose that the structure of CBS domains from CLC channels is highly conserved and that they play a functional role in the common gate.     

Three-Year Follow-Up of the POIBA Intervention on Childhood Obesity: A Quasi-Experimental Study

Childhood obesity has increased worldwide over the past four decades. This quasi-experimental study aimed to assess the effectiveness of a multicomponent and multilevel school-based intervention (POIBA) at 3 years of follow-up. The nutrition intervention focused on food groups, food pyramid, nutrients, portions, and balanced menus. In total, 3624 children participated in the study. Anthropometric measurements and information on food frequency and behavior, physical activity, and daily screen use were collected in the intervention (IG) and comparison group (CG). Positive unadjusted changes toward adherence to recommendations were found for water, meat, sweets, and fried potato consumption, proper breakfast, not having dinner in front of the TV, out-of-school physical activity, and daily screen use. Three scores were used to calculate the proportion of children making more than one change to improve healthy habits regarding physical activity (global Activity score), nutrition (global Nutrition score), and both (global score). Students exposed to the intervention had a significantly better global Activity score (16.2% IG vs. 11.9% CG; p = 0.012) and Global score (63.9% IG vs. 58.5% CG; p = 0.025). Intervention effects on obesity incidence at 3-year follow-up lost significance but maintained the positive trend. In conclusion, school-based interventions including a family component could be useful to address the childhood obesity problem.     

Anatomic basis of vascular distribution in combined removal of liver and pancreas (28.5.93)

Summary Based on the study of the arterial distribution of 120 hepatic grafts removed from brain-dead patients, the authors assess the possibilities of vascular partition in cases of combined removal of the liver and pancreas. The discussion deals with the vascular distribution of each organ. The presence of a right hepatic artery arising from the superior mesenteric a. (SMA) requires preservation of the SMA with the hepatic graft, while the pancreas is removed with the celiac trunk (CT) and its branches. The presence of a left hepatic artery arising from the CT requires its preservation with the hepatic graft, the pancreas being removed with the SMA and the splenic artery.

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Partage vasculaire des prélèvements hépatiques et pancréatiques combinés : bases anatomiques (28.5.93)

Résumé A partir de l'étude de la distribution artérielle de 120 greffons hépatiques prélevés sur des patients en état de mort cérébrale, les auteurs apprécient les possibilités de partage vasculaire en cas de prélèvement combiné foie-pancréas. La discussion porte sur la distribution vasculaire de chaque organe. L'existence d'une artère hépatique droite naissant de l'artère mésentérique supérieure (AMS) nécessite de conserver l'AMS avec le greffon hépatique, le pancréas est prélevé avec le tronc coeliaque (TC) et ses branches. La présence d'une artère hépatique gauche naissant du TC impose de le conserver avec le greffon hépatique, le pancréas est prélevé avec l'AMS et l'artère splénique.