Solid‐type poorly differentiated adenocarcinoma of the stomach: Deficiency of mismatch repair and SWI/SNF complex

ARID1A, one of the subunits in SWI/SNF chromatin remodeling complex, is frequently mutated in gastric cancers with microsatellite instability (MSI). The most frequent MSI in solid‐type poorly differentiated adenocarcinoma (PDA) has been reported, but the SWI/SNF complex status in solid‐type PDA is still largely unknown. We retrospectively analyzed 54 cases of solid‐type PDA for the expressions of mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6), SWI/SNF complex subunits (ARID1A, INI1, BRG1, BRM, BAF155, and BAF170) and EBER, and mutations in KRAS and BRAF. We analyzed 40 cases of another histological type of gastric cancer as a control group. The solid‐type PDAs showed coexisting glandular components (76%), MMR deficiency (39%), and complete/partial loss of ARID1A (31%/7%), INI1 (4%/4%), BRG1 (48%/30%), BRM (33%/33%), BAF155 (13%/41%), and BAF170 (6%/2%), EBER positivity (4%), KRAS mutation (2%), and BRAF mutation (2%). Compared to the control group, MMR deficiency and losses of ARID1A, BRG1, BRM, and BAF155 were significantly frequent in solid‐type PDAs. Mismatch repair deficiency was associated with the losses of ARID1A, BRG1, and BAF155 in solid‐type PDAs. In the MMR‐deficient group, solid components showed significantly more frequent losses of ARID1A, BRG1, BRM, and BAF155 compared to glandular components (P = .0268, P = .0181, P = .0224, and P = .0071, respectively). In the MMR‐proficient group, solid components showed significantly more frequent loss of BRG1 compared to glandular components (P = .012). In conclusion, solid‐type PDAs showed frequent losses of MMR proteins and the SWI/SNF complex. We suggest that loss of the SWI/SNF complex could induce a morphological shift from differentiated‐type adenocarcinoma to solid‐type PDA.     

Addiction Mindsets and Psychological Processes of Quitting Smoking

Background: Lay belief systems about the malleability of human attributes have been shown to impact behavior change in multiple domains. Addiction mindset—i.e., beliefs about the permanence (vs. malleability) of addiction — may affect cigarette smokers’ ability to quit, but this has never been examined. Objectives: The aims of the present research were to develop a measure of addiction mindset (study 1) and examine its associations with various psychological aspects of quitting smoking (study 2). Methods: In Study 1, using factor analysis of current smokers’ and nonsmokers’ (n?=?600) responses to 22 items designed to measure addiction mindset, we developed a reliable six-item Addiction Mindset Scale (AMS). In Study 2, adult smokers (n?=?200) completed the AMS, and measures of a number of psychological processes related to smoking. Results: Higher scores on the AMS, indicative of the belief that addiction is malleable (referred to as a growth mindset), were positively and significantly associated with greater motivation to quit, greater commitment to quitting, greater self-efficacy to abstain, less attribution of failure to lack of ability to change addiction, and fewer self-reported barriers to cessation (all p’s < .05). Conclusions: The results of this study show a relationship between the beliefs about the permanence of addiction and psychological processes relevant to quitting smoking. The findings underscore the potential of future research exploring how addiction mindsets relate to successful smoking cessation as well as other types of addictive behavior and how they can be applied to change people’s behavior.     

Association of gBRCA1/2 mutation locations with ovarian cancer risk in Japanese patients from the CHARLOTTE study

Whether germline (g) breast cancer susceptibility gene (BRCA) mutations are located within or outside the ovarian cancer cluster region (OCCR) (1380‐4062 bp for gBRCA1, and between 3249‐5681 bp and 6645‐7471 bp for gBRCA2) may influence risk variations for ovarian cancers. This ad hoc analysis of the CHARLOTTE epidemiological study in Japan assessed the distribution of gBRCA1/2 mutations in patients with newly diagnosed ovarian cancer, and investigated an association between gBRCA1/2 mutation locations and ovarian cancer risk. Differences in patient background and clinical characteristics in subgroups stratified by gBRCA1/2 mutation locations were also evaluated. We analyzed the data of 93 patients (14.7%) from the CHARLOTTE study who were positive for gBRCA1/2 mutations. After excluding 16 cases with L63X founder mutation, 28 (65.1%) of gBRCA1 mutations were within the OCCR. Of 30 gBRCA2 mutations, 15 (50.0%) were within the OCCR. Of 27 patients (one patient excluded for unknown family history) with gBRCA1 mutations located in the OCCR, 11 (40.7%) had a family history of ovarian cancer; the proportion of patients with a family history of ovarian cancer and gBRCA1 mutations outside the OCCR was lower (13.3%). Sixty percent of patients with gBRCA1 mutations outside the OCCR had a family history of breast cancer; the proportion of patients with a family history of breast cancer and gBRCA1 mutations within the OCCR was relatively lower (33.3%). Understanding the mutation locations may contribute to more accurate risk assessments of susceptible individuals and early detection of ovarian cancer among gBRCA mutation carriers.     

Stochastic resonance with differential code in feedforward network with intra-layer random connections.

We examined stochastic resonance with a differential coding scheme using a multilayer feedforward neural network which is composed of intra-layer connections. We show that the network, with random synaptic connections in each layer, encodes an input signal into a spike coherence that represents temporal differences among the inputs. We also demonstrate that both internal and external noise enhance the detection of weak signals. Finally, we discuss how the feedforward network with intra-layer random connections is similar to a membrane in its sensitivity to and amplification of a change in stimulus and suggest that the intensity of internal noise may be tuned in a real brain.     

Steroid pulse therapy impaired endothelial function while increasing plasma high molecule adiponectin concentration in patients with IgA nephropathy.

BACKGROUND: Decreased plasma adiponectin is associated with impaired endothelial function and, thereby, increased risk for cardiovascular events. Glucocorticoid (GC) affects vascular endothelial cells either favourably or harmfully depending upon the dosages and duration. We examined the effect of GC pulse therapy on vascular endothelial function. METHODS: Fourteen young patients with IgA nephropathy were evaluated for flow-mediated vasodilation (FMD), plasma levels of adiponectin both in high molecular weight (HMW adiponectin) form and in single molecular form (total adiponectin), hepatocyte growth factor (HGF), asymmetric dimethylarginine (ADMA), and high-sensitive C-reactive protein, before and after a course of GC pulse therapy. RESULTS: GC pulse therapy significantly decreased FMD (from 7.2 +/- 2.6 to 5.7 +/- 2.5%, P < 0.01). Meanwhile, plasma adiponectin levels were significantly augmented (total adiponectin: from 10.2 +/- 4.0 to 12.1 +/- 6.3 microg/ml, P < 0.05; HMW: from 6.5 +/- 3.2 to 7.7 +/- 3.3 microg/ml, P < 0.05). In parallel, elevated concentrations of serum HGF (from 0.28 +/- 0.12 to 0.63 +/- 0.38 ng/ml, P < 0.01) and plasma ADMA (from 0.45 +/- 0.07 to 0.53 +/- 0.04 nmol/ml, P < 0.05) were observed. CONCLUSIONS: GC pulse therapy impaired endothelial function while increasing plasma adiponectin levels, which may in turn restore the endothelial function in patients with IgA nephropathy.     

Myosin heavy chain composition of tongue muscle in microphthalmic (mi/mi) mice before and after weaning.

To elucidate the effects of teeth on muscle fibers in the tongue during the developmental process, we examined the expression of muscle contractile proteins and the genes for those proteins in normal mice and microphthalmic (mi/mi) mice with impaired tooth eruption. The mice were observed during the growth period, including weaning, which is when feeding movements undergo major changes. Expression of the myosin heavy chain (MyHC)-2a protein, whose contraction speed is relatively slow, disappeared after weaning in normal mice, while it remained in high concentrations even after weaning in mi/mi mice. The presence of MyHC-2a after weaning in mice with no tooth eruption was attributed to a compensation for lack of proper masticatory function and sucking-like movements, as MyHC-2a is necessary for these movements.