Multidrug resistance protein 3 loss promotes tumor formation by inducing senescence escape.

Oncogenic-stress-induced senescence (OIS) is a stress response allowing normal cells, when receiving oncogenic signals, to stably arrest their proliferation. OIS thus acts to prevent aberrant cell proliferation and tumor formation. To identify novel tumor suppressive pathways, we have recently completed a loss-of-function genetic screen to identify novel genes promoting escape from OIS and thus, potentially, tumor formation when their functions are lost. Using this approach, we unexpectedly found that loss of function of the multidrug resistance protein 3 (MRP3 or ABCC3) promotes escape from OIS in human epithelial cells. Importantly, ABCC3 expression is reduced in human skin tumors, and ABCC3-knockout mice display increased sensitivity to RAS-induced skin carcinogenesis, concomitantly with decreased OIS. ABCC3 participates in resistance to chemotherapy via its transporter activity. Our data show that this transporter activity is involved in ABCC3-induced senescence, demonstrating that this protein has a complex role in cancer, since its loss of function may promote escape from OIS and tumor formation whereas its gain of function promotes resistance to chemotherapy.

Multi-species sensing using multi-mode absorption spectroscopy with mid-infrared interband cascade lasers.

The application of an interband cascade laser, ICL, to multi-mode absorption spectroscopy, MUMAS, in the mid-infrared region is reported. Measurements of individual mode linewidths of the ICL, derived from the pressure dependence of lineshapes in MUMAS signatures of single, isolated, lines in the spectrum of HCl, were found to be in the range 10-80 MHz. Multi-line spectra of methane were recorded using spectrally limited bandwidths, of approximate width 27 cm-1, defined by an interference filter, and consist of approximately 80 modes at spectral locations spanning the 100 cm-1 bandwidth of the ICL output. Calibration of the methane pressures derived from MUMAS data using a capacitance manometer provided measurements with an uncertainty of 1.1 %. Multi-species sensing is demonstrated by the simultaneous detection of methane, acetylene and formaldehyde in a gas mixture. Individual partial pressures of the three gases are derived from best fits of model MUMAS signatures to the data with an experimental error of 10 %. Using an ICL, with an inter-mode interval of ~10 GHz, MUMAS spectra were recorded at pressures in the range 1-10 mbar, and, based on the data, a potential minimum detection limit of the order of 100 ppmv is estimated for MUMAS at atmospheric pressure using an inter-mode interval of 80 GHz.

Mid-infrared multi-mode absorption spectroscopy using interband cascade lasers for multi-species sensing.

An interband cascade laser (ICL) operating at 3.7 µm has been used to perform multimode absorption spectroscopy, MUMAS, at scan rates up to 10 kHz. Line widths of individual modes in the range 10-80 MHz were derived from isolated lines in the MUMAS signatures of HCl. MUMAS data for methane covering a spectral range of 30 nm yielded a detection level of 30 µbar·m for 1 s measurement time at 100 Hz. Simultaneous detection of methane, acetylene, and formaldehyde in a gas mixture containing all three species is reported.

Meal size can be decreased in obese subjects through pharmacological acceleration of gastric emptying (The OBERYTH trial).

BACKGROUND: Entry of nutrients into the small intestine activates neuro-hormonal signals that regulate food intake through induction of satiation. OBJECTIVE: To evaluate whether caloric intake can be decreased by pharmacologically accelerating gastric emptying (GE) of nutrients into the small intestine. METHODS: Subjects were tested in 2 days, at baseline (day1) and after randomly receiving, in a double-blind manner, a 1 h infusion of erythromycin (3 mg Kg(-1), to accelerate GE) or placebo (day 2). Ad libitum caloric intake and postprandial gastrointestinal symptoms were evaluated using a validated nutrient drink test, simultaneously measuring gastric emptying [corrected] by scintigraphy. Plasma levels of satiation factors were also measured to evaluate their role in the modification of caloric intake and postprandial symptoms. Acceleration of GE was assessed as the difference in percentage emptied between day 2 and day 1 (DGE). The effects of DGE on caloric intake and symptoms were evaluated using multiple (lineal) regression. RESULTS: Among 30 overweight/obese subjects (24F and 6 M), 15 received erythromycin and 15 placebo. The overall median age was 36 years (IQR: 30-42) and body mass index was 30 Kg m(-2) (IQR: 27-36). Subjects receiving erythromycin on day 2 presented accelerated GE as compared with placebo (P = 0.0002). DGE at 15 min after initiating eating had a significant effect on prospective caloric intake (P = 0.004). From the best-fitted regression model (R (2) = 81%, P < 0.0001), a 10% increase in GE at 15 min induced on an average a 135 ± 43.5 Kcal decrease in caloric intake. Postprandial increase in cholecystokinin (CCK) (P = 0.03) and insulin (P = 0.02) was associated with decreased caloric intake. Acceleration of GE at 60 min after initiating eating increased postprandial symptom scores measured 30 min after the completion of food consumption (P = 0.01). Postprandial increase in CCK (P = 0.002) and PP (P = 0.02) was associated with postprandial symptoms. CONCLUSION: Meal size can be reduced in overweight/obese subjects by pharmacologically accelerating GE. This may be a reasonable target in obesity management.

Seroepidemiology of human immunodeficiency virus in Africa.

Serum samples from 6015 African subjects without symptoms of the acquired immune deficiency syndrome (AIDS) or contact with the disease were examined for antibodies to the human immunodeficiency virus by a combination of an enzyme linked immunosorbent assay and radioimmunoprecipitation (2567 samples) or by immunofluorescence (3448 samples). Serum samples had been collected between 1976 and 1984 in Senegal (n = 789), Liberia (935), Ivory Coast (1195), Burkina Faso (299), Nigeria (536), Gabon (1649), Zaire (15), Uganda (164), and Kenya (433). Only four samples contained antibodies. Three of these were from attenders at the Lambarene clinic in Gabon and one from a villager in Senegal. By contrast, two out of six AIDS suspects from Guinea-Bissau, all 13 patients with AIDS from Kinshasa (Zaire), and two out of three of their contacts were seropositive, all these specimens having been collected in 1985. These data show that fewer than one in a 1000 subjects were seropositive for AIDS at the time of sampling before 1985 and do not support the hypothesis of the disease originating in Africa.

[Amniotic fibronectin in normal pregnancy and pregnancy with fetal anencephaly]. / Fibronectine amniotique au cours de grossesses normales et de grossesses avec anencéphalie foetale.

Fibronectin, which is an important protein in plasma and in surface cells was calculated in amniotic fluid using a laser ray nephelemetric technique. In normal pregnancies (in 72 samples studied) this protein which rises towards the 18th week of amenorrhoea (mean +/- S.D.: 60.8 +/- 16.0 mg/l), decreases steadily to term (mean 14.8 +/- 8.9 mg/l). In fetal anencephaly (10 samples tested) high levels were also found but the difference as compared with normal levels was not significant. This measurement does not therefore constitute an extra way of screening for closure of the neural tube.

[Comparative study of the fate of a pancreatic stump treated by ligature or by pancreatico-jejunal anastomosis (author's transl)]. / Etude comparative du devenir d'un moignon pancréatique traité par ligature ou anastomose pancréato-jéjunale.

The authors studied in a series of 23 dogs divided up into two groups the fate of the pancreatic stump treated either by pancreatico-jejunostomy with a Y loop, or by a simple ligature. They note that although the mortality is slightly higher in the anastomoses, histological lesions are constant in both series and are fairly similar. This agrees with the findings in man by Goldsmith and justifies ligature of the remaining pancreatic stump after cephalic duodeno-pancreatectomy.