Background
With the widespread use of endoscopy, small and low‐grade type 3 gastric neuroendocrine tumours (NETs) are increasingly being detected. The clinicopathological features, biological ...behaviour and appropriate treatment strategy for these NETs remain unclear.
Methods
Patients with biopsy‐proven gastric NET and a normal fasting serum gastrin level were identified from a prospectively maintained database. Clinicopathological features and long‐term outcome of local resection for type 3 NETs were reviewed retrospectively and compared according to tumour grade.
Results
Some 32 patients with type 3 gastric NETs were included (25 patients with NET grade G1, 5 with G2 and 2 with G3). Pathological tumour size was 2·0 cm or less in 30 patients. All tumours were well differentiated, even G3 lesions, and all tumours but one were confined to the submucosal layer. G1 NETs were significantly smaller and had a significantly lower lymphovascular invasion rate than G2 and G3 NETs. Twenty‐two patients with a G1 NET without lymphovascular invasion were treated with wedge or endoscopic resection. After a median follow‐up of 59 (range 6–102) months, no patient with a G1 NET of 1·5 cm or smaller developed recurrence and one patient with a G1 NET larger than 1·5 cm had recurrence in a perigastric lymph node. Among seven patients with a G2 or G3 NET, two had lymph node metastasis and one had liver metastases.
Conclusion
Low‐grade type 3 gastric NET has non‐aggressive features and a favourable prognosis. Wedge or endoscopic resection may be a valid option for patients with type 3 gastric G1 NET no larger than 1·5 cm without lymphovascular invasion.
Limited resection suffices in selected patients
Peroxiredoxin (Prx) is a family of bifunctional proteins that exhibit peroxidase and chaperone activities. Prx proteins contain a conserved Cys residue that undergoes a redox change between thiol and ...disulfide states. 2-Cys Prx enzymes, a subgroup of Prx family, are intrinsically susceptible to reversible hyperoxidation to cysteine sulfinic acid during catalysis. Cysteine hyperoxidation of Prx was shown to result in loss of peroxidase activity and a concomitant gain of chaperone activity. Reduction of sulfinic Prx enzymes, the first known biological example of such a reaction, is catalyzed by sulfiredoxin (Srx) in the presence of ATP. Srx appears to exist solely to support the reversible sulfinic modification of 2-Cys Prx enzymes. Srx specifically binds to 2-Cys Prx enzymes by recognizing several critical surface-exposed residues of the Prxs, and transfer the γ-phosphate of ATP to their sulfinic moiety, using its conserved cysteine as the phosphate carrier. The resulting sulfinic phosphoryl ester is reduced to cysteine after oxidation of four thiol equivalents.
We measured the concentrations of nitrous oxide (N2O) and methane (CH4) in the marine boundary layer and surface waters of the Atlantic Ocean from ∼50°N to ∼50°S during the Atlantic Meridional ...Transect expedition (AMT‐7) in 1998. The cruise track transects a variety of meteorological and oceanographic regimes. Unusually high mixing ratios of atmospheric CH4 were observed in the extratropical Northern Hemisphere, coinciding with globally high levels of CH4 associated with the El Niño event of 1998. Atmospheric N2O remained nearly invariable during the expedition, with only a small hemispheric difference (0.82 ppb). Throughout the cruise, these gases were saturated or supersaturated in the water. The coastal region was observed to be a significant source of CH4, while upwelling regions acted as strong N2O emission sources. We estimated the global oceanic emission of CH4 to be 0.6–1.2 Tg a−1, comparable to previous estimates from basin‐wide observations. However, our estimate turns out to be ∼10 times lower than the value in the 1990 to 2007 Intergovernmental Panel on Climate Change (IPCC) reports, which essentially all relied on the estimate by Ehhalt (1974). A bias toward high CH4 saturation anomalies is probably responsible for the overestimation of the marine CH4 source in the IPCC reports. The CH4 saturation anomaly in the ocean appears to have remained constant over an interval of 20 years in spite of the increase of atmospheric CH4, suggesting that the increase of the surface water temperature driven by global warming may be a major factor. Meanwhile, the N2O emission from the ocean, estimated in the present study to be 0.9–1.7 Tg N a−1, is ∼3 times lower than the value in the recent IPCC report Denman et al., 2007, implying either weak upwelling activity or low amounts of dissolved N2O in upwelling subsurface waters, or both, in the Atlantic.
Brenninkmeijer et al discuss the isotope effect in the chemistry of atmospheric trace compounds. The emphasis is somewhat more in the direction of atmospheric instead of global biogeochemical cycles.
The removal of molecular hydrogen (H2) from the atmosphere is dominated by the uptake in soils. Notwithstanding, estimates of the magnitude of this important process on a global scale are highly ...uncertain. The CARIBIC aircraft observations of the seasonal variations of H2 and its D/H isotopic ratio in the Northern Hemisphere allow an independent, better constrained estimate. We derive that 82% of the annual turnover of tropospheric H2 is due to soil uptake, equaling 88 (±11)Tg a-1, of which the Northern Hemisphere alone accounts for 62 (±10)Tg a-1. Our calculations further show that tropospheric H2 has a lifetime of only 1.4 (±0.2) years – significantly shorter than the recent estimate of ~2 years – which is expected to decrease in the future. In addition, our independent top-down approach, confined by the global and hemispheric sinks of H2, indicates 64 (±12)Tg a-1 emissions from various sources of volatile organic compounds by photochemical oxidation in the atmosphere. This estimate is as much as up to 60% larger than the previous estimates. This large airborne production of H2 helps to explain the fairly homogeneous distribution of H2 in the troposphere.
The carbon monoxide (CO) in the marine boundary layer and in the surface waters and water column were measured along the western limb of the North Pacific from the Korean Peninsula to Alaska, USA, in ...summer 2012. The observation allows us to estimate the CO budgets in the surface mixed layer of the three distinct regimes: the East Sea (Sea of Japan) (ES), the Northwest Pacific (NP), and the Bering Sea (BS). CO photochemical production rates were 56(±15) µmol m−2 d−1, 27(±3) µmol m−2 d−1, and 26(±2) µmol m−2 d−1, while microbial consumption rates were 30(±8) µmol m−2 d−1, 24(±5) µmol m−2 d−1, and 63(±19) µmol m−2 d−1 in the ES, NP, and BS, respectively, both of which are the dominant components of the CO budget in the ocean. The other two known components, air–sea gas exchange and downward mixing, remained negligible (less than 3 µmol m−2 d−1) in all regimes. While the CO budget in the surface mixed layer of the NP was in balance, the CO production surpassed the consumption in the ES, and vice versa in the BS. The significant imbalances in the CO budget in the ES (25 ± 17 µmol m−2 d−1) and the BS (40 ± 19 µmol m−2 d−1) are suggested to be compensated by external physical transport such as lateral advection, subduction, or ventilation. Notably, the increase in the CO column burden correlated with the imbalance in the CO budget, highlighting the significant role of the physical transport in the marine CO cycles. Our observation, for the first time, underscores the potential importance of physical transport in driving CO dynamics in the marine environment.
Peroxiredoxins (Prxs) are a family of peroxidases that reduce hydroperoxides. The cysteine residue in the active site of certain eukaryotic Prx enzymes undergoes reversible oxidation to sulfinic acid ...(Cys-SO2H) during catalysis, and sulfiredoxin (Srx) has been identified as responsible for reversal of the resulting enzyme inactivation in yeast. We have now characterized mammalian orthologs of yeast Srx with an assay based on monitoring of the reduction of sulfinic Prx by immunoblot analysis with antibodies specific for the sulfinic state. Sulfinic reduction by mammalian Srx was found to be a slow process (kcat = 0.18/min) that requires ATP hydrolysis. ATP could be efficiently replaced by GTP, dATP, or dGTP but not by CTP, UTP, dCTP, or dTTP. Both glutathione and thioredoxin are potential physiological electron donors for the Srx reaction, given that their Km values (1.8 mm and 1.2 μm, respectively) are in the range of their intracellular concentrations, and the Vmax values obtained with the two reductants were similar. Although its pKa is relatively low (∼7.3), the active site cysteine of Srx remained reduced even when the active site cysteine of most Prx molecules became oxidized. Finally, depletion of human Srx by RNA interference suggested that Srx is largely responsible for reduction of the Cys-SO2H of Prx in A549 human cells.
Various proapoptotic stimuli increase the production of superoxide and H 2 O 2 by mitochondria. Whereas superoxide impairs mitochondrial function and is removed by Mn 2+ -dependent superoxide ...dismutase, the role and metabolism of mitochondrial H 2 O 2 during apoptosis have remained unclear. The effects on apoptotic signaling of depletion of peroxiredoxin (Prx) III, a mitochondrion-specific
H 2 O 2 -scavenging enzyme, have now been investigated by RNA interference in HeLa cells. Depletion of Prx III resulted in increased
intracellular levels of H 2 O 2 and sensitized cells to induction of apoptosis by staurosporine or TNF-α. The rates of mitochondrial membrane potential collapse,
cytochrome c release, and caspase activation were increased in Prx III-depleted cells, and these effects were reversed by ectopic expression
of Prx III or mitochondrion-targeted catalase. Depletion of Prx III also exacerbated damage to mitochondrial macromolecules
induced by the proapoptotic stimuli. Our results suggest that Prx III is a critical regulator of the abundance of mitochondrial
H 2 O 2 , which itself promotes apoptosis in cooperation with other mediators of apoptotic signaling.
Hydrogen peroxide (H
2O
2) accumulates transiently in various cell types stimulated with peptide growth factors and participates in receptor signaling by oxidizing the essential cysteine residues of ...protein tyrosine phosphatases and the lipid phosphatase PTEN. The reversible inactivation of these phosphatases by H
2O
2 is likely required to prevent futile cycles of phosphorylation–dephosphorylation of proteins and phosphoinositides. The accumulation of H
2O
2 is possible even in the presence of large amounts of the antioxidant enzymes peroxiredoxin I and II in the cytosol, probably because of a built-in mechanism of peroxiredoxin inactivation that is mediated by H
2O
2 and reversed by an ATP-dependent reduction reaction catalyzed by sulfiredoxin.
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