Brain–gut communication via vagus nerve modulates conditioned flavor preference

It is well known that the postingestive effect modulates subsequent food preference. We previously showed that monosodium L‐glutamate (MSG) can increase flavor preference by its postingestive effect. The neural pathway involved in mediating this effect, however, remains unknown. We show here the role of the vagus nerve in acquiring this learned flavor preference and in the brain’s response to intragastric glutamate infusion. Adult rats with an intragastric cannula underwent total abdominal branch vagotomies (TVX), common hepatic branch vagotomies (HVX), total abdominal branch vagotomies with the common hepatic branch intact (TVXh), or sham operations (Sham). Following recovery, rats were subjected to a conditioned flavor preference paradigm, in which they drank a flavored solution (CS+) paired with intragastric MSG or another flavored solution (CS?) paired with intragastric distilled water. After conditioning, the Sham and HVX groups demonstrated significantly higher intake of CS+ than CS?, whereas the TVXh and TVX groups showed no significant differences. We then conducted an fMRI study to identify the brain areas that responded to the intragastric glutamate in each group. In the Sham, HVX and TVXh groups, intragastric MSG significantly increased the BOLD intensity in the nucleus of the solitary tract. The amygdala, hippocampus and lateral hypothalamus were also activated in the Sham and HVX groups but not in the TVXh and TVX groups. These results indicate that the abdominal vagus nerve is necessary for acquiring preference and that the lateral hypothalamus and limbic system could be key areas for integrating the information on gut glutamate and oronasal stimuli.     

Percutaneous radiofrequency ablation as first‐line treatment for small hepatocellular carcinoma: Results and prognostic factors on long‐term follow up

Background and Aims: We evaluated the prognosis and associated factors in patients with small hepatocellular carcinoma (HCC; up to 3 nodules, each up to 3cm in diameter) treated with percutaneous radiofrequency ablation (RFA) as first‐line treatment. Methods: Eighty‐eight consecutive patients who underwent percutaneous RFA as first‐line treatment were enrolled, among whom 70 who had hypervascular HCC nodules which were treated by a combination of transcatheter arterial chemoembolization and RFA. RFA was repeated until an ablative margin was obtained. Results: The rate of local tumor progression at 1 and 3 years was 4.8% and 4.8%, respectively. The rate of overall survival at 3 and 5 years was 83.0% and 70.0%, and the rate of disease‐free survival at 3 and 5 years was 34.0% and 24.0%, respectively. On multivariate analysis, age (< 70 years; hazard ratio [HR] = 2.341, 95% confidence interval [CI] = 1.101–4.977, P = 0.027) and indocyanine green retention rate at 15 min (< 15%; HR = 3.621, 95% CI = 1.086–12.079, P = 0.036) were statistically significant determinants of overall survival, while tumor number (solitary, HR = 2.465, 95% CI = 1.170–5.191, P = 0.018) was identified for disease‐free survival. Overall survival of patients with early recurrence after RFA was significantly worse than that of patients with late recurrence. Tumor size was the only independent risk factor of early recurrence after RFA of HCC (tumor size > 2 cm; risk ratio [RR] = 4.629, 95% CI = 1.241–17.241, P = 0.023). Conclusion: Percutaneous RFA under the protocol reported here has the potential to provide local tumor control for small HCC. In addition to host factors, time interval from RFA to recurrence was an important determinant of prognosis.     

Effects of stimulus field size and coherence of visual motion on cortical responses in humans: an MEG study

Among various kinds of visual motion, wide field coherent visual motion should have characteristic physiological significance regarding the relationship between the external world and us. To detect veridical visual motion in the surrounding environment, specific mechanisms are necessary to differentiate it from the wide field coherent motion due to one's own movement. To disclose whether and how the neural process of wide field coherent motion is different from that of other motions, we measured cortical responses to visual motions in humans using magnetoencephalography (MEG) manipulating both field size and coherence. Results showed that an increase in field size enhanced the response at sensors around the parieto-occipital area, and that the difference in activity between coherent and incoherent motion tended to be larger for the wide field. These findings suggest that wide field coherent and incoherent motion is detected differently at least in part in the parieto-occipital area, and suggest the neural process of wide field coherent motion could be pronouncedly tapped by a combination of field size and coherence.     

Evaluation of the 'liking' and 'wanting' properties of umami compound in rats

Food reward is neurologically and psychologically divided into at least two properties; ‘liking’ and ‘wanting’. Although umami taste enhances food palatability, the liking and wanting properties of umami taste, and the underlying neural mechanisms for these properties are not clear. Here, we compared sucrose (0, 10, 30, 120 and 480 mM) and monosodium l-glutamate (MSG; 0, 10, 30, 60 and 120 mM) solutions using a taste reactivity test to evaluate liking, and fixed/progressive-ratio operant licking tasks to evaluate wanting. To determine the underlying neural mechanisms, we also conducted systemic blockade of opioid receptors in both tests. In the taste reactivity test, the hedonic reactions to 30, 60 and 120 mM MSG were greater than those to water (0 mM) but lower than those to 480 mM sucrose. In the operant task, the intake, number of licks, and breakpoint to MSG reached peaks at around 60 mM but they were lower than those to 30-480 mM sucrose. The systemic naloxone treatment decreased the hedonic responses to MSG and sucrose, and reduced the incentive salience of MSG but not sucrose. These findings indicate that the hedonic response and incentive salience of MSG is lower than those of sucrose when compared at the maximum response and that the incentive salience of MSG is lower than sucrose even where the hedonic response is similar. The present study also suggest that the hedonic response and incentive salience of umami compound is modulated by brain opioid signaling.     

Development of cortical orientation selectivity in the absence of visual experience with contour

Visual cortical neurons are selective for the orientation of lines, and the full development of this selectivity requires natural visual experience after eye opening. Here we examined whether this selectivity develops without seeing lines and contours. Juvenile ferrets were reared in a dark room and visually trained by being shown a movie of flickering, sparse spots. We found that despite the lack of contour visual experience, the cortical neurons of these ferrets developed strong orientation selectivity and exhibited simple-cell receptive fields. This finding suggests that overt contour visual experience is unnecessary for the maturation of orientation selectivity and is inconsistent with the computational models that crucially require the visual inputs of lines and contours for the development of orientation selectivity. We propose that a correlation-based model supplemented with a constraint on synaptic strength dynamics is able to account for our experimental result.     

Cytomegalovirus infection following renal transplantation in patients administered low-dose rituximab induction therapy

Anti-CD20 antibody (rituximab) is recently being used as a B cell-depleting agent in renal transplantation (RTx). However, the incidence of infectious complications associated with rituximab therapy remains uncertain. We evaluated the incidence of cytomegalovirus (CMV) infection associated with rituximab therapy in RTx. A total of 83 patients were enrolled. The immunosuppressive regimen consisted of tacrolimus or cyclosporin, mycophenolate mofetil, methylprednisolone and basiliximab. In 54 patients, only one dose of rituximab (200 or 500 mg/kg body weight) was given before RTx. A total of 25 of 43 (58.1%) recipients who were CMV seropositive prior to RTx and who received rituximab induction therapy developed CMV infection, compared to 18 of 24 (75%) CMV seropositive recipients who did not receive rituximab therapy ( P  = 0.1676). A total of 8 of 11 patients who were CMV seronegative prior to RTx and who received rituximab developed CMV infection. However, CMV seroconversion was seen in all 8 of these infected patients. Low-dose rituximab induction therapy in renal transplant recipients appears to have no influence on the incidence of CMV infection and CMV seroconversion. However, we have to consider anti-CMV prophylaxis therapy, because of high incidents of CMV infection, especially for CMV seronegative recipients who received rituximab.     

Useful detection of CD147 （EMMPRIN） for pathological diagnosis of early hepatocellular carcinoma in needle biopsy samples

AIM To make clear whether CD147 (EMMPRIN)expression in pathological tumor samples with a fineneedle aspiration biopsy is useful for pathological diagnosis of early hepatocellular carcinoma (HCC).METHODS Twenty-two patients (15 men and 7 women;median age 68 years, range 56-81 years) underwent a liver tissue biopsy in order to make a diagnosis of HCC.Paraffin-embedded liver biopsy tissue samples from 22 patients were stained with anti-CD147 antibody,murine monoclonal antibody 12C3 (MAb12C3) for immunohistochemical analysis. An immunohistochemical analysis of CD147 was performed and the degree of staining compared between tumor and non-tumor tissue. In addition, the degree of staining within tumor tissue was compared according to a number of clinicopathological variables.RESULTS The degree of staining of CD147 was significantly higher in tumor tissues than non-tumor tissues, even in tumors less than 15 mm in diameter.The expression of this protein was significantly elevated in HCC tissue specimens from patients with a low value of serum AST and γ-GTP.CONCLUSION CD147 serves potentially as a pathological target for cancer detection of early HCC.     

The hepatic sinusoidal endothelial lining and colorectal liver metastases

Colorectal cancer （CRC） is a common malignant disease and the severe nature of cases in men and women who develop colorectal cancer makes this an important socio-economic health issue. Major challenges such as understanding and modeling colorectal cancer pathways rely on our understanding of simple models such as outlined in this paper. We discuss that the development of novel standardized approaches of multidimensional （correlative） biomolecular microscopy methods facilitates the collection of （sub） cellular tissue information in the early onset of colorectal liver metastasis and that this approach will be crucial in designing new effective strategies for CRC treatment. The application of X-ray micro-computed tomography and its potential in correlative imaging of the liver vasculature will be discussed.     

A novel compound heterozygous mutation in the DAP12 gene in a patient with Nasu-Hakola disease

A 34-year-old woman showed clinical features characteristic of Nasu-Hakola disease (NHD), also designated polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL). The genetic analysis of the DAP12 gene (TYROBP) identified two heterozygous mutations composed of a previously reported single base deletion of 141G (141delG) in exon 3 and a novel single base substitution of G262T in exon 4, both of which are located on separate alleles. The protein sequence motif search indicated that both mutations encode truncated nonfunctional DAP12 polypeptides. This is the first case of NHD caused by compound heterozygosity for loss-of-function mutations in DAP12.