Genetic polymorphism in cytochrome P450 7A1 and risk of colorectal cancer: the Fukuoka Colorectal Cancer Study

Bile acids have long been implicated in the etiology of colorectal cancer, but epidemiologic evidence remains elusive. Cholesterol 7alpha-hydroxylase (CYP7A1) is the rate-limiting enzyme in the synthesis of bile acids from cholesterol in the liver, and thus may be an important determinant of bile acid production. We examined the association between the CYP7A1 A-203C polymorphism and colorectal cancer. The CYP7A1 A-203C polymorphism was determined by the PCR-RFLP method in 685 incident cases of colorectal cancer and 778 controls randomly selected from a community in the Fukuoka area, Japan. The CC genotype was slightly less frequent in the case group, and the adjusted odds ratio for the CC versus AA genotype was 0.88 (95% confidence interval, 0.65-1.20). In the analysis by subsite of the colorectum, a decreased risk associated with the CYP7A1 CC genotype was observed for proximal colon cancer, but not for either distal colon or rectal cancer. The adjusted odds ratios (95% confidence intervals) of proximal colon cancer for the CC genotype were 0.63 (0.36-1.10) compared with the AA genotype, and 0.59 (0.37-0.96) compared with the AA and AC genotypes combined. A decreased risk of proximal colon cancer in relation to the CC genotype of CYP7A1 A-203C, which probably renders less activity of the enzyme converting cholesterol to bile acids, is new evidence for the role of bile acids in colorectal carcinogenesis.     

Acetylcholine receptors in dissociated nucleus basalis of Meynert neurons of the rat

Electrical and pharmacological properties of acetylcholine (ACh)-induced currents in neurons dissociated from the nucleus basalis of Meynert (nBM) of immature (2-week-old) rats were investigated with the whole-cell mode of the patch-clamp technique. At a holding potential (V_H) of −50 mV, ACh (10⁻⁴M) evoked a transient inward current mimicked by nicotine (I_nACh), followed by a sustained outward current mimicked by carbamylcholine (I_mACh). The K_D values were 1.2 × 10⁻⁴ M for I_nACh) and 8.7 × 10⁻⁷ M for I_mACh. The reversal potenial of I_mACh was close to E_K. The I_mACh was determined to be elicited via the M₂ muscarinic receptor, based on the differences in sensitivity to muscarinic antagonists such as pirenzepine and AF-DX-116.     

Return to the Original Work Activity Following the Full-endoscopic Lumbar Surgery under the Local Anesthesia

Transforaminal full-endoscopic spine (TF-FES) surgery is minimally invasive and can be performed under local anesthesia. Thus, it is expected that the patient can return to work (RTW) quickly. However, information in the literature regarding this is sparse. The purpose of this study is to review the timing of RTW after TF-FES surgery. This study involved 50 patients (14 women, 36 men; mean age 44.5 years, age range: 20–65 years) who underwent TF-FES surgery between January 2016 and April 2018. All the patients were active workers. Occupations varied widely (e.g., physician, nurse, helper, clerk, construction worker, chef, and schoolteacher). There were no surgery-related complications. Median time to RTW was 21 days. More than half of the patients could RTW within 21 days. In all, 12 cases (24%) could have RTW within 7 days. Occupations of 12 patients who achieved RTW within 7 days included physician, company owner, and restaurant owner, with 11 in the Light work, 1 was in the Medium work, and none in the Heavy work. All 12 had a quick RTW because their work was Light and they could not take prolonged sick leave. Prompt RTW is possible with TF-FES surgery. The biggest merit of TF-FES surgery is minimal invasiveness to the muscles of the back. Also, it can be performed under local anesthesia. Our findings reveal quicker RTW after surgery, depending on occupational type.     

Phlegmonous gastritis associated with advanced esophageal cancer

Phlegmonous gastritis is a rapidly progressive bacterial infection of the stomach wall. It has a high mortality rate and aggressive treatment, either with antibiotics or surgical resection, is required. Here, we report an extremely rare case of phlegmonous gastritis associated with advanced esophageal cancer. A 65-year-old Japanese man was urgently admitted to the hospital due to pyrexia and gastrointestinal symptoms. Abdominal computed tomography revealed widespread diffuse thickening of the gastric wall. On endoscopic examination, an ulcerative mass was detected at the lower thoracic esophagus, and a markedly elevated submucosal lesion was present in the middle of the stomach body. Biopsy specimens taken endoscopically from the esophageal tumor confirmed a diagnosis of squamous cell carcinoma. Gastric biopsy cultures were positive for Streptococcus viridans, leading to a diagnosis of phlegmonous gastritis associated with esophageal cancer. After the patient’s condition improved with preoperative antibiotic administration, we performed a thoracoscopic esophagectomy, a total gastrectomy and a reconstruction of the gastrointestinal tract using a pedicled right colon. Histological examination of the resected specimen confirmed that the gastric mass was compatible with a phlegmon.     

Semi-Automated Quantification of Finger Joint Space Narrowing Using Tomosynthesis in Patients with Rheumatoid Arthritis

Journal of Digital Imaging - The purpose of the study is to validate the semi-automated method using tomosynthesis images for the assessment of finger joint space narrowing (JSN) in patients with...     

Globus sensation and increased upper esophageal sphincter pressure with distal esophageal acid perfusion

The aim of the present study was to determine whether acid perfusion into the distal esophagus causes a globus sensation and an increase in upper esophageal sphincter (UES) pressure. UES pressures were measured using a sleeve-type sensor in 20 healthy volunteers. A 0.1-N HCl solution, the same as gastric acid, was perfused into the distal esophagus at a rate of 20 mL/min. During perfusion, 4-channel pH monitoring was performed to determine whether the HCl reached the hypopharynx. The following parameters were measured: (1) changes in UES pressure before and during acid perfusion, (2) presence or absence of a globus sensation or heartburn, (3) the time at which a globus sensation or heartburn was noted by the patient and (4) the position of the electrode at which the pH drop was recorded. Ten subjects enrolled as the control group received perfusions of distilled water. Acid perfusion raised the UES pressure in 13 of the 20 subjects. All 13 complained of globus at about the same time as the UES pressure increased. Twelve of the 13 subjects who experienced globus also complained of heartburn, which preceded the globus sensation in ten such cases. None of the control subjects reported globus or had elevated UES pressure. In the acid perfusion group, no pH reduction at the two most cranial electrodes was observed in any subject. In conclusion, the globus sensation is due to elevated UES pressure, resulting from gastroesophageal reflux and does not require direct exposure of the hypopharynx to gastric acid. The incidence of heartburn in combination with a globus sensation would be much higher if the cause of the latter were acid reflux.     

Concurrent administration of chemo-endocrine therapy for postmenopausal breast cancer patients

Background  

We have been treating hormone receptor-positive, postmenopausal women with breast cancer with a regimen of neoadjuvant chemotherapy (NAC), FEC (fluorouracil, epirubicin, and cyclophosphamide), followed by weekly doses of paclitaxel combined with the concurrent administration of anastrozole. In this article, we compared our results retrospectively with those of past trials.     

Butyl pocket formation in the vitamin D receptor strongly affects the agonistic or antagonistic behavior of ligands

Previously, we reported that 22S-butyl-25,26,27-trinor-1α,24-dihydroxyvitamin D(3)2 represents a new class of antagonist for the vitamin D receptor (VDR). The crystal structure of the ligand-binding domain (LBD) of VDR complexed with 2 showed the formation of a butyl pocket to accommodate the 22-butyl group and insufficient interactions between ligand 2 and the C-terminus of VDR. Here, we designed and synthesized new analogues 5a-c and evaluated their biological activities to probe whether agonistic activity is recovered when the analogue restores interactions with the C-terminus of VDR. Analogues 5a-c exhibited full agonistic activity in transactivation. Interestingly, 5c, which bears a 24-diethyl group, completely recovered agonistic activity, although 3c and 4c act as an antagonist and a weak agonist, respectively. The crystal structures of VDR-LBD complexed with 3a, 4a, 5a, and 5c were solved, and the results confirmed that butyl pocket formation in VDR strongly affects the agonistic or antagonistic behaviors of ligands.