Distribution and significance of the oesophageal and gastric cardiac mucosae: a study of 131 operation specimens

AIMS: To clarify the distribution and significance of the oesophageal and gastric cardiac mucosae at the oesophago-gastric junction (EGJ). METHODS AND RESULTS: Oesophagectomy specimens from 131 consecutive patients with middle and upper thoracic oesophageal cancer were examined. The surgically resected specimens including the EGJ were cut into 5 mm thick serial sections and examined histopathologically for the length of the oesophageal and gastric cardiac mucosae and the incidence of columnar epithelial islands (CEIs). We also determined the presence of short-segment Barrett's oesophagus (SSBE) and goblet cell metaplasia in SSBE. Oesophageal cardiac mucosa was found in 125 cases (95%) and gastric cardiac mucosa was found in all cases. The mean length of the oesophageal and gastric cardiac mucosa was 4 mm (range 1-26 mm) and 13 mm (range 2-64 mm), respectively. CEIs were found in 75 cases (57%). SSBE was found in 70 cases (53%), among which goblet cell metaplasia was found in 28 cases (21%). No long-segment Barrett's oesophagus was found. The mean length of oesophageal cardiac mucosa (6 mm) and gastric cardiac mucosa (17 mm) in SSBE was significantly greater than that (3 mm and 8 mm, respectively) in non-SSBE cases (P < 0.0001 and P < 0.0001). The incidence (69%) of CEIs in SSBE was significantly higher than that (44%) in non-SSBE cases (P = 0.005). CONCLUSIONS: Oesophageal and gastric cardiac mucosae were found frequently. Oesophageal cardiac glands and CEIs might play an important role in the development of SSBE.     

Shift of motor activation areas during recovery from hemiparesis after cerebral infarction: a longitudinal study with near-infrared spectroscopy

Motor functional recovery after stroke may be attributable to cerebral reorganization. We used near-infrared spectroscopy, which measures non-invasively the changes in oxy- and deoxy-hemoglobin concentrations in response to neural activation, for monitoring cerebral activation in stroke patients, and investigated the longitudinal changes in functional laterality of activations in the primary sensorimotor cortex during unilateral audio-paced (1 Hz) hand movement. We examined five ischemic stroke patients (4 females and 1 male, 52-67 years old) with mild to moderate hemiparesis at acute stages and chronic stages at least 1 month later. Normal subjects (3 females and 2 males, 47-63 years old) were also included. Unilateral hand movement activated predominantly the contralateral primary sensorimotor cortex in the normal subjects and the stroke patients when they moved unaffected hand. Affected hand movements activated bilateral sensorimotor cortices early after stroke (< 25 days of stroke onset), whereas the activation pattern returned toward normal at later periods (> 35 days). The contralaterality index (0.34 +/- 0.12 in normal control) was reduced at early periods (0.00 +/- 0.03, p < 0.01) after stroke, and returned to normal (0.35 +/- 0.24) as motor function recovered. These findings suggest that a transient increase in motor activation in the ipsilateral intact hemisphere within 1 month may play an important role in the recovery from motor dysfunction after stroke.     

Characterization of voltage-gated ionic channels in cholinergic amacrine cells in the mouse retina

Recent studies have shown that cholinergic amacrine cells possess unique membrane properties. However, voltage-gated ionic channels in cholinergic amacrine cells have not been characterized systematically. In this study, using electrophysiological and immunohistochemical techniques, we examined voltage-gated ionic channels in a transgenic mouse line the cholinergic amacrine cells of which were selectively labeled with green fluorescent protein (GFP). Voltage-gated K(+) currents contained a 4-aminopyridine-sensitive current (A current) and a tetraethylammonium-sensitive current (delayed rectifier K(+) current). Voltage-gated Ca(2+) currents contained a omega-conotoxin GVIA-sensitive component (N-type) and a omega-Aga IVA-sensitive component (P/Q-type). Tetrodotoxin-sensitive Na(+) currents and dihydropyridine-sensitive Ca(2+) currents (L-type) were not observed. Immunoreactivity for the Na channel subunit (Pan Nav), the K channel subunits (the A-current subunits [Kv. 3.3 and Kv 3.4]) and the Ca channel subunits (alpha1(A) [P/Q-type], alpha1(B) [N-type] and alpha1(C) [L-type]) was detected in the membrane fraction of the mouse retina by Western blot analysis. Immunoreactivity for the Kv. 3.3, Kv 3.4, alpha1(A) [P/Q-type], and alpha1(B) [N-type] was colocalized with the GFP signals. Immunoreactivity for alpha1(C) [L-type] was not colocalized with the GFP signals. Immunoreactivity for Pan Nav did not exist on the membrane surface of the GFP-positive cells. Our findings indicate that signal propagation in cholinergic amacrine cells is mediated by a combination of two types of voltage-gated K(+) currents (the A current and the delayed rectifier K(+) current) and two types of voltage-gated Ca(2+) currents (the P/Q-type and the N-type) in the mouse retina.     

Quantitative analysis of hepatitis B virus precore mutant in hepatitis type B.

Active liver disease has been detected in chronic hepatitis B after seroconversion from positive HBe antigen to positive anti-HBe antibody. Active replication of HB virus (HBV) containing a precore stop-codon mutation has been implicated in this condition. The usual methods, such as direct sequencing, to characterize the responsible mutant of HBV are not suitable for routine clinical use. Here we employed the competitive mutation site specific assay (CMSSA) to detect precore mutant HBV-DNA in patients with positive HB surface antigen. In patients with HBe antigen, precore mutant HBV-DNA was significantly higher than in patients with HBe antibody. The level of precore mutant HBV-DNA in patients with elevated serum ALT was significantly higher than in patients with normal serum ALT. Sex, age and the level of serum HBV-associated DNA polymerase levels were not correlated with levels of precore mutant HBV-DNA. Ten of 11 negative patients for the precore mutant by polymerase chain reaction followed by restriction fragment length polymorphism assay (PCRRFLP) were positive for the precore mutant by CMSSA. These results suggest that the precore mutant has already emerged in the HBeAg-positive phase as determined by CMSSA, which is more sensitive than PCR-RFLP and is useful for evaluating the clinical course of patients with chronic hepatitis B.     

Association between Grit Scales and adherence to regular hospital visits among Japanese patients with type 2 diabetes: Prospective observational study

This study examined the association between Grit Scales and adherence to a schedule of regular hospital visits among Japanese type 2 diabetes patients. Patients with type 2 diabetes who visited the outpatient clinic as new patients comprised the study’s participants. Self-administered Short Grit Scale data were obtained from 122 patients at the first consultation and were then observed for 1 year. As the results, 21 participants failed to attend the hospital. In a logistic regression analysis, the Grit Scale as a continuous variable was positively associated with adherence to regular clinical visits. Its odds ratio and 95% confidential interval was 9.68 and 2.87–32.65 (P = 0.0003). In conclusion, it is likely that the Grit Scale is closely associated with adherence to regular hospital visits among Japanese type 2 diabetes patients.     

Long-term safety of subcutaneous immunotherapy with TO-204 in Japanese patients with house dust mite-induced allergic rhinitis and allergic bronchial asthma: Multicenter,open label clinical trial

Background

To evaluate the long-term safety of subcutaneous immunotherapy with TO-204, a standardized house dust mite (HDM) allergen extracts, we conducted a multicenter, open label clinical trial.

Molecular mimicry of mitochondrial and nuclear autoantigens in primary biliary cirrhosis

BACKGROUND & AIMS: The mechanism for development of primary biliary cirrhosis (PBC) remains enigmatic, but molecular mimicry has been implicated because of well-known cross-reactivity of human mitochondrial autoantigens and equivalent bacterial antigens. Virtually all patients with PBC have antimitochondrial autoantibodies (AMA), but, interestingly, approximately 50% also manifest antinuclear antibodies (ANA). METHODS: To determine whether generation of ANA are due to molecular mimicry of mitochondrial peptides, we established 6 T-cell clones selected by a peptide corresponding to the E2 subunit of mitochondrial pyruvate dehydrogenase complex and analyzed for reactivity to mimicry peptides derived from mitochondrial and nuclear autoantigens, including control sequences. RESULTS: For mitochondrial autoantigens, 1 peptide from the E2 subunit of the pyruvate dehydrogenase complex, 1 peptide from the E2 subunit of the oxo-glutarate dehydrogenase complex, 1 peptide from the E2 subunit of the branched-chain 2-oxoacid dehydrogenase complex, and 1 peptide from the E3-binding protein cross-reacted with these T-cell clones. For the nuclear autoantigens, 5 peptides from gp210 and 1 from Sp100 cross-reacted with these clones. Furthermore, 1 of 3 T-cell clones selected by recombinant gp210 protein reacted with a mimicry peptide corresponding to amino acids 188-201 of gp210, indicating that this part of the protein is a naturally processed immunodominant T-cell epitope. CONCLUSIONS: These results demonstrate molecular mimicry between mitochondrial and nuclear autoantigens in PBC and that a mimicry peptide may become an immunodominant T-cell epitope. These data have significance not only for PBC but also for the production of ANA in other disease processes.