Calcitonin gene-related peptide and vasodilator nerves in large cerebral arteries of cats

Calcitonin gene-related peptide's (CGRP) role(s) was examined in the transmural nerve stimulation (TNS)-induced vasodilator response of the large cerebral arteries of the cat in vitro. Numerous CGRP-like immunoreactive nerves were demonstrated to be present in the adventitial layer of the middle cerebral, anterior communicating and basilar arteries of the cat. An electron microscopic study revealed that immunoreactive material was contained in not only nerve axons but also in the button-like structures, i.e., varicosities, which were located close to smooth muscle cells. Exogenously applied CGRP induced a dose-dependent vasodilator response which was independent of the presence of endothelial cells and of nerve components. Nerve stimulation elicited transient hyperpolarization, i.e., inhibitory junction potential, which was of nonadrenergic, noncholinergic origin. Likewise, CGRP produced hyperpolarization of smooth muscle cells. After incubation of the tissue with capsaicin in vitro, the intensity of the CGRP-like immunoreactivity diminished greatly. The TNS-induced vasodilator response and inhibitory junction potentials were also attenuated after the incubation with capsaicin. These results suggest that CGRP is involved in the TNS-induced vasodilator response of the large cerebral arteries of the cat.     

Genotype–phenotype relationships in familial amyotrophic lateral sclerosis with FUS/TLS mutations in Japan

Introduction: We investigated possible genotype–phenotype correlations in Japanese patients with familial amyotrophic lateral sclerosis (FALS) carrying fused in sarcoma/translated in liposarcoma (FUS/TLS) gene mutations. Methods: A consecutive series of 111 Japanese FALS pedigrees were screened for copper/zinc superoxide dismutase 1 (SOD1) and FUS/TLS gene mutations. Clinical data, including onset age, onset site, disease duration, and extramotor symptoms, were collected. Results: Nine different FUS/TLS mutations were found in 12 pedigrees. Most of the patients with FUS/TLS‐linked FALS demonstrated early onset in the brainstem/upper cervical region, and relatively short disease duration. A few mutations exhibited phenotypes that were distinct from typical cases. Frontotemporal dementia was present in 1 patient. Conclusions: This study revealed a characteristic phenotype in FUS/TLS‐linked FALS patients in Japan. FUS/TLS screening is recommended in patients with FALS with this phenotype. Muscle Nerve 54 : 398–404, 2016     

Endoscopic treatment for gastroesophageal reflux disease

The endoscopic treatment as a minimally invasive method to gastroesophageal reflux disease (GERD) came to be tried in addition to medication and laparoscopic antireflux surgery. Clinical trials, such as the Endoluminal Gastroplication method, the Full Thickness Plicator method, the Stretta method, the Enteryx method, and the Gatekeeper method, are advancing in the United States and Europe. It is necessary to consider the efficacy, safety, durability, cost effectiveness, an indication, etc. using data from a randomized controlled trial with sufficient observation period. If the usefulness of endoscopic treatment is confirmed in the future, the new minimally invasive strategy over GERD will be established.     

The Charlson Comorbidity Index as an Independent Prognostic Factor in Older Colorectal Cancer Patients

High-age patients have higher rates of comorbidity that are associated with a poor prognosis. It is important to correctly evaluate their preoperative status to avoid mortality. The aim of this study was to clarify whether the Charlson comorbidity index (CCI) was useful for predicting postoperative outcomes. This retrospective study collected data from 250 consecutive patients over 75 years of age. The CCI takes into account 19 comorbid conditions. Inflammation-based scores, including the Glasgow prognostic score (GPS) and the platelet to lymphocyte ratio (PLR), are other preoperative scoring systems. The relationships among these scores and postoperative outcomes were evaluated. The patients were classified according to their vital status (dead, n = 30 or alive, n = 220). Comorbidities, the presence of double cancer, and lymph node metastases were significantly different between the groups (p < 0.01, p = 0.01, and p < 0.01). In regard to the scoring systems, the CCI, GPS, and PLR were significantly different (p = 0.02, p = 0.03, and p = 0.05). Multivariate analysis identified CCI ≥ 2 (hazard ratio (HR) = 5.24, 95 % confidence interval (CI) = 1.30–12.1, p = 0.01) as a significant determinant of postoperative outcome (p < 0.01). The overall survival tended to be lower in patients with high CCI scores group (p = 0.03). The CCI was useful to predict postoperative outcomes in high-age colorectal cancer patients.     

Cerebral cortical dysfunction in patients with temporomandibular disorders in association with jaw movement observation

Temporomandibular disorders (TMD) represent a group of chronic painful conditions in the masticatory musculature and temporomandibular joint. To examine possible changes in cortical machinery in TMD patients, we compared neuromagnetic signals evoked by cortical neurons between healthy subjects and TMD patients while they were carefully observing the video frames of jaw-opening movements performed by another person. During the movement observation task in the healthy subjects, we found cortical activation in the following sequence with left hemisphere dominance: (1) the occipitotemporal region near the inferior temporal sulcus (human homologue of MT/V5 in monkeys), (2) the inferior parietal cortex (IPC), and (3) the anterior part of the inferior-lateral precentral gyrus (PrCG). In the TMD patients, however, we found deficit or marked attenuation of the neuromagnetic responses in the PrCG and IPC, while the activity of the MT/V5 showed no differences from that in the healthy subjects. In addition, we could not find any differences in cortical magnetic responses between healthy subjects and TMD patients when they were observing palm-opening movements, indicating that cortical dysfunction associated with jaw-movement observation is specific phenomena in the patients of TMD. Thus the present study provides new neuropathological evidence that TMD patients exhibit dysfunction of recognition mechanisms in cerebral cortex during motor observation, and suggests that disturbance of cortical functions regulating visuomotor integration would play a crucial role in development as well as aggravation of TMD.     

Hepatocyte growth factor gene transfer to alveolar septa for effective suppression of lung fibrosis.

We examined therapeutic gene transfer of human hepatocyte growth factor (hHGF) to alveolar septa in mouse bleomycin-induced lung fibrosis using macroaggregated albumin-polyethylenimine complex (MAA-PEI). Intravenous administration of MAA-PEI along with 1 microg pCAG.hHGF to C57BL/6 mice increased the uptake of plasmids into alveolar capillary endothelial cells and epithelial cells, prolonged hHGF expression in the lung, and induced a level of hHGF expression equal to that seen with 10 microg of hHGF-expression plasmids alone. The exogenous source of hHGF gene expression increased the endogenous mouse HGF in the lungs and significantly decreased TNF-alpha, IL-6, and collagen synthesis after bleomycin injury. Because GFP-labeled bone marrow-derived stem cells after bleomycin injury were reduced in number by HGF, the primary mechanism of HGF is likely to be the prevention of apoptosis, as has been suggested by in vitro experiments. This novel HGF gene transfer method to alveolar septa with nonstimulatory MAA-PEI conjugates may have promising clinical applications.