The MAGE-A1 gene expression is not determined solely by methylation status of the promoter region in hematological malignancies

Tumor antigens such as MAGE-A1 are aberrantly expressed in many human tumors and could be recognized by CTL. Thus, they could be targets for cancer immunotherapy. It is presently considered that the expression of the MAGE-A1 gene is regulated by methylation of its promoter region. To estimate the possibility of activating the MAGE-A1 gene with demethylating agents with a view toward clinical use, we assessed the methylation status of its CpG-rich promoter by sodium bisulfite mapping both of samples that express the gene and those that do not. Cell lines and samples from patients with hematological malignancies were examined. Surprisingly, the methylation status of the MAGE-A1 gene did not clearly correlate with the expression of the gene. Our results indicate that the MAGE-A1 gene expression is not determined solely by the methylation status of the promoter region in hematological malignancies.     

High-tension electrical injury to the heart as assessed by radionuclide imaging

To evaluate cardiac complications associated with electrical injury, 7 patients with high-tension electrical injury (6,600 V alternating current) underwent 201Tl and 123I-metaiodobenzylguanidine (MIBG) imaging in addition to conventional electrocardiographic and echocardiographic assessments. Electrocardiography showed transient atrial fibrillation, second degree atrioventricular block, ST-segment depression, and sinus bradycardia in each patient. Echocardiography showed mild hypokinesis of the anterior wall in only 2 patients, but 201Tl and 123I-MIBG myocardial scintigraphy showed an abnormal scan image in 6/7 and 5/6 patients, respectively. Decreased radionuclide accumulation was seen primarily in areas extending from the anterior wall to the septum. Decreased radionuclide accumulation was smaller in extent and milder in degree in 123I. MIBG than in 201Tl imaging. These results suggest that even in patients without definite evidence of severe cardiac complications in conventional examinations, radionuclide imaging detects significant damage due to high-tension electrical injury, in which sympathetic nerve dysfunction might be milder than myocardial cell damage.     

Intestinal neuronal dysplasia-like pathology in Ncx/Hox11L.1 gene-deficient mice

BACKGROUND/PURPOSE: Ncx/Hox11L.1-deficient (Ncx-/-) mice specifically created by the authors had mega-ileo-ceco-colon (mega-ICC) with a caliber change in the proximal colon. The authors studied the nerve distribution in the bowel of these Ncx-/- mice to determine the cause of their bowel dysmotility. METHODS: Four-week-old Ncx-/- mice (n = 10; 5 with mega-ICC, 5 without mega-ICC) were killed and the bowel harvested. Half of each specimen was snap frozen for AchE and NADPH-diaphorase histochemistry, and the other half were fixed with 10% formalin for H&E staining and immunohistochemistry using PGP9.5 antibody (a marker for neurons), C-kit antibody (a marker for intestinal pacemaker cells), and stem cell factor antibody (a marker for C-kit ligand). Age-matched wild-type normal mice (n = 5) served as controls. RESULTS: In the ileum, cecum, and proximal colon from all Ncx-/- mice (irrespective of the association of mega-ICC), typical findings of human intestinal neuronal dysplasia (IND) ie, obvious hyperganglionosis in neuronal plexuses on PGP9.5 immunohistochemistry, ectopic ganglia in the mucosal and muscular layers on AchE histochemistry, and ghostlike ganglia on NADPH-diaphorase histochemistry were found. Likewise, in normal caliber distal colon from these mice, the distribution of ganglion cells, C-kit, and stem cell factor was normal. In control specimens, there was no ectopic ganglia or hyperganglionosis. CONCLUSIONS: These findings suggest that the Ncx/Hox11L.1 gene is required for the proper innervation of the enteric nervous system in mice, and our deficient strain may be useful as a model for studying IND in humans.     

Mild alkalinization and acidification differentially modify the effects of lidocaine or mexiletine on vasorelaxation mediated by ATP-sensitive K+ channels

BACKGROUND: The previous study by the authors showed that the class Ib antiarrhythmic drug lidocaine impairs but mexiletine augments vasorelaxation mediated by adenosine triphosphate-sensitive K+ channels. Lidocaine and mexiletine have different values of the negative logarithm of the drug-proton dissociation constant, indicating that the ion channel-blocking effects of these drugs under different pH levels may vary. However, the role of pH in the effects of lidocaine and mexiletine on vasodilation mediated by K+ channels has not been studied. Therefore, the current study was designed to examine whether the inhibition and augmentation of vasorelaxation in response to an adenosine triphosphate-sensitive K+ channel opener, levcromakalim, by the clinically relevant concentrations of lidocaine or mexiletine are modified by mild alkalinization or acidification in the isolated rat aorta. METHODS: Rings of the rat aorta without endothelium were suspended for isometric force recording. Three types of modified Krebs-Ringer solutions (pH 7.2, 7.4, and 7.6) were prepared by changing the composition of NaCl and NaHCO3. During contractions in response to phenylephrine (3 x 10(-7) M), relaxations in response to levcromakalim (10(-8) to 10(-5) M) were obtained. Lidocaine (10(-5) to 10(-4) M), mexiletine (10(-5) to 10(-4) M), or glibenclamide (10(-5) M) was applied 15 min before addition of phenylephrine. RESULTS: Relaxations in response to levcromakalim, which are abolished by the selective adenosine triphosphate-sensitive K+ channel antagonist glibenclamide (10(-5) M), were not different among the three pH groups. In the normal Krebs-Ringer solution of pH 7.4, lidocaine significantly reduced these relaxations in a concentration-dependent fashion. Alkalinization of pH 7.6 augmented the inhibitory effect of lidocaine on these relaxations, whereas acidification of pH 7.2 substantially abolished this effect. In contrast, mexiletine pH independently augmented relaxations in response to levcromakalim. Glibenclamide (10(-5) M) abolished these relaxations in arteries treated with mexiletine (10(-4) M) in any pH group. CONCLUSIONS: These results suggest that even under conditions of such mild alkalosis or acidosis, vasorelaxation via adenosine triphosphate-sensitive K+ channels is dependent on pH in the presence of clinically relevant concentrations of lidocaine but not mexiletine.     

Successful transplantation of a cadaveric kidney with post-infectious glomerulonephritis

This report describes a successful renal Tx in a patient with chronic renal failure, caused by dysplastic kidneys, who received a cadaveric kidney with post-infectious glomerulonephritis. Sequential renal biopsies were performed at 12 h before Tx, and at 1 h and on days 8 and 58 post-Tx. Post-operative hematuria disappeared on day 9 and proteinuria on day 13. Normal graft function was observed within 1 month, with histologic resolution. Our study suggests that while the donor kidney facilitates deposition of certain immune reactants, this is a host (environmental) problem and when transplanted into a new host (new environment), the problem is no longer sustained.     

Prognostic impact of cathepsin B and matrix metalloproteinase-9 in pulmonary adenocarcinomas by immunohistochemical study

The expression of Cathepsin B (CB) and matrix metalloproteinase-9 (MMP-9) in extirpated tissues of adenocarcinomas in non-small cell lung cancer from 90 cases was investigated immunohistologically, and the correlations between the extent of the expression and the clinicopathological features were assessed for investigating the process of tumor metastasis. It is important to reveal the mechanisms of destruction of the basal membrane and infiltration of tumor cells at the primary lesion. Sections were obtained from 10%-formalin-fixed and paraffin-embedded tissues. They were reacted with an anti-human CB polyclonal antibody or an anti-human MMP-9 polyclonal antibody. Of 90 patients, 58 (64.4%) and 39 (48.3) cases were found to be positive for CB and MMP-9 expression, respectively. A significantly higher extent of the CB expression was observed in the tissues of patients who showed postoperative recurrence of the tumor (P = 0.013). Especially, a similar observation was obtained among early cases of T1N0 (P = 0.023). In contrast, no such tendency was demonstrated in the expression profile of MMP-9. Furthermore, the enzyme expressions were compared among different types of metastases. Patients with higher extents of CB expression tended to show significantly higher rates of hematogenous and intrapulmonary metastases (P = 0.023 and P = 0.010, respectively). However, there was no significant correlation between MMP-9 expression and the prognostic factor of the patients. Therefore, we suggested that evaluation of CB expression in the tumor tissue might be useful as a postoperative prognostic factor of pulmonary adenocarcinoma. Especially, early cancer of T1N0 cases showing higher expression of CB may need postoperative adjuvant chemotherapy.     

Degenerative changes of vein grafts in preparation media: Preliminary studies by electron microscopy and fibrinolytic autography

Degenerative changes of saphenous vein grafts in four preparation media (heparinized whole blood at room temperature and 4°C, and heparinized normal saline at same temperatures) were examined by scanning and transmission electron microscopy and fibrinolytic autography. Following 60–90 min. storage in heparinized normal saline at room temperature, marked morphological changes were present in the media, accompanied by swellingof the endothelial cells, however the tunica media and adventitia were well preserved even after 120 minutes in all of the four preparation media. The decrease in fibrinolytic activity was comparable to the observed morphological changes. In heparinized whole blood at 4°C, degenerative changes were slow and mostly of a slight nature.