A case of superficial esophageal cancer complicated with idiopathic muscular hypertrophy of the esophagus

We hereby reported a case of 60-year old man with superficial esophageal cancer complicated with idiopathic muscular hypertrophy of the esophagus. Endoscopic ultrasonography and CT showed the thickness of esophageal muscular layer, but the accurate diagnosis could not be entertained before operation. Idiopathic muscular hypertrophy of the esophagus is an entity rarely encountered, and most cases are diagnosed at postmortem examination. Only a few cases have been reported regarding its clinical symptoms and images. The etiology remains to be elucidated, and the pathologic features are characterized by significant thickness of inner circular muscular layer of esophagus without degeneration of plexus and ganglionic cells. This case report deals with superficial esophageal cancer complicated with idiopathic muscular hypertrophy of esophagus. Literature review is also included.     

The risk of second malignancy after adjuvant chemotherapy for stomach cancer

Background. Although many trials have been conducted to evaluate the feasibility and effectiveness of adjuvant chemotherapy (ACT) for patients with stomach cancer, the benefits of ACT remain unclear. Moreover, some authors have reported that ACT increased the incidence of second malignancy. The risk of second malignancy was evaluated in patients who underwent treatment for stomach cancer in the past 20 years at Osaka Medical Center for Cancer and Cardiovascular Diseases. Methods. The study population consisted of 1925 patients who underwent gastrectomies for stomach cancer between the years 1978 and 1992 and who received follow-up examinations to check for second malignancies. They included 1114 patients who underwent surgery only (group A) and 811 who underwent surgery and received chemotherapy (group B). The observed incidence of second malignancy (O) was compared with the expected incidence (E), calculated by the person-year method, using data from the Cancer Registry in Osaka. Results. The average follow-up period was 7.99 years. The total number of patients with a second malignancy was 127 (men, 97; women, 30); 72 patients had the second malignancy in digestive organs; 27 in respiratory organs; and 28 in other organs. The relative risks of a second malignancy in group A and B patients were 1.05 and 1.02 (differences between the two groups were not significant). The relative risks of a second malignancy in patients who received ACT with 5-fluorouracil, Tegafur and Uracil, and FT207 were 0.79, 1.01, and 1.06, respectively (differences between the groups were not significant). Conclusion. The risk of second malignancy after chemotherapy for stomach cancer was not high in comparison with the expected incidence. Adjuvant chemotherapy did not increase the risk of a second malignancy. Received on April 16, 1999; accepted on Dec. 1, 1999     

Animal models for hepatitis C and related liver disease

Persistent infection with hepatitis C virus (HCV) is a major risk toward development of hepatocellular carcinoma (HCC). The elucidation of pathogenesis of HCV-associated liver disease is hampered by the absence of appropriate animal models: there has been no animal model for HCV infection/pathogenesis except for the chimpanzee. In contrast, a number of transgenic mouse lines carrying the cDNA of the HCV genome have been established and evaluated in the study of HCV pathogenesis. The studies using transgenic mouse models, in which the HCV proteins such as the core protein are expressed, indicate the direct pathogenicity of HCV, including oncogenic activities. HCV transgenic mouse models also show a close relationship between HCV and some hepatic and extrahepatic manifestations such as hepatic steatosis, insulin resistance or Sjögren's syndrome. A crucial role of hepatic steatosis and insulin resistance in the pathogenesis of liver disease in HCV infection has been demonstrated, implying hepatitis C to be a metabolic disease. Besides the data connecting liver fibrosis progression and the disturbance in lipid and glucose metabolisms in hepatitis C patients, a series of evidence was found showing the association between these two conditions and HCV infection, chiefly using transgenic mouse carrying the HCV genome. Furthermore, the persistent activation of peroxisome proliferator-activated receptor (PPAR)-α has recently been found, yielding dramatic changes in the lipid metabolism and oxidative stress overproduction in cooperation with the mitochondrial dysfunction. These results would provide a clue for further understanding of the role of lipid metabolism in pathogenesis of hepatitis C including liver injury and hepatocarcinogenesis.     

Emphysematous cystitis in a patient with type 2 diabetes mellitus

A 62-year-old woman with a history of poorly controlled type 2 diabetes mellitus was admitted to our hospital with a 3-week history of mild fever, vomiting, and anorexia. Abdominal computed tomography (CT) showed bilateral hydronephrosis and gas accumulation in the urinary bladder wall and left ureter. Laboratory tests showed leukocytosis and elevated C-reactive protein level. Urine culture showed heavy growth of Escherichia coli. The final diagnosis was emphysematous cystitis. The patient was treated with systemic antibiotics and drainage using a urethral catheter. The clinical and radiographic findings resolved rapidly, and she was discharged from the hospital on day 28. Emphysematous cystitis is a relatively rare urinary tract infection associated with gas formation, and has the potential for a serious outcome if untreated. Early detection by imaging studies such as CT is important in providing prompt treatment and favorable clinical outcome.     

IgG anti-GalNAc-GD1a antibody inhibits the voltage-dependent calcium channel currents in PC12 pheochromocytoma cells

We investigated the effects of IgG anti-GalNAc-GD1a antibodies, produced by immunizing rabbits with GalNAc-GD1a, on the voltage-dependent calcium channel (VDCCs) currents in nerve growth factor (NGF)-differentiated PC12 pheochromocytoma cells. VDCCs currents in NGF-differentiated PC12 cells were recorded using the whole-cell patch-clamp technique. Immunized rabbit serum that had a high titer of anti-GalNAc-GD1a antibodies inhibited the VDCCs currents in the NGF-differentiated PC12 cells (36.0+/-9.6% reduction). The inhibitory effect of this serum was reversed to some degree within 3-4 min by washing with bath solution. Similarly, application of purified IgG from rabbit serum immunized with GalNAc-GD1a significantly inhibited the VDCCs currents in PC12 cells (30.6+/-2.5% reduction), and this inhibition was recovered by washing with bath solution. Furthermore, the inhibitory effect was also observed in the GalNAc-GD1a affinity column binding fraction (reduction of 31.1+/-9.85%), while the GalNAc-GD1a affinity column pass-through fraction attenuated the inhibitory effect on VDCCs currents. Normal rabbit serum and normal rabbit IgG did not affect the VDCCs currents in the PC12 cells. In an immunocytochemical study using fluorescence staining, the PC12 cells were stained using GalNAc-GD1a binding fraction. These results indicate that anti-GalNAc-GD1a antibodies inhibit the VDCCs currents in NGF-differentiated PC12 cells.     

Overexpression of gamma-glutamyltransferase in transgenic mice accelerates bone resorption and causes osteoporosis

We previously identified gamma-glutamyltransferase (GGT) by expression cloning as a factor inducing osteoclast formation in vitro. To examine its pathogenic role in vivo, we generated transgenic mice that overexpressed GGT in a tissue-specific manner utilizing the Cre-loxP recombination system. Systemic as well as local production of GGT accelerated osteoclast development and bone resorption in vivo by increasing the sensitivity of bone marrow macrophages to receptor activator of nuclear factor-kappaB ligand, an essential cytokine for osteoclastogenesis. Mutated GGT devoid of enzyme activity was as potent as the wild-type molecule in inducing osteoclast formation, suggesting that GGT acts not as an enzyme but as a cytokine. Recombinant GGT protein increased receptor activator of nuclear factor-kappaB ligand expression in marrow stromal cells and also stimulated osteoclastogenesis from bone marrow macrophages at lower concentrations. Thus, GGT is implicated as being involved in diseases characterized by accelerated osteoclast development and bone destruction and provides a new target for therapeutic intervention.     

Usefulness of low- and medium-energy collimators in 123I-MIBG myocardial scintigraphy

The heart-to-mediastinum (H/M) ratio on myocardial scintigraphy with (123)I-metaiodobenzylguanidine (MIBG) is used as a semi-quantitative index. However, the scatter from a photopeak of 529 keV on (123)I is thought to affect the H/M ratio, and collimator selection is important as well. We attempted to determine the usefulness of low- and medium-energy general purpose (LME) collimators by comparing them with low-energy high-resolution (LEHR) and medium-energy low-penetration (MELP) collimators in phantom and clinical studies. In the phantom study, we used a thoracic phantom and plastic bottles filled with (123)I-MIBG solution as upper limbs. Phantom images were acquired with LEHR, LME, and MELP collimators. Regions of interest were placed on the lung, mediastinum, heart, and liver. The average counts in the lung, coefficient of variation (CV%) in the heart, mediastinum, and liver, and H/M ratio were calculated. The H/M ratios obtained with the LEHR collimator and LME collimator were compared in a clinical study. We found that the average count in the lung measured with the LME collimator was reduced to about 30% of that obtained with the LEHR collimator in the phantom study. CV% measured with the LME collimator improved about 10% compared with that determined with the MELP collimator. The H/M ratio measured with the LME collimator was close to that measured with the MELP collimator. In the clinical study, the H/M ratios measured with the LEHR and LME collimators showed a positive relationship (y=2.1x-1.3, x; H/M with LEHR, y; H/M with LME) . LME collimators provided improved contrast and signal-to-noise ratio in evaluation of the H/M ratio on (123)I-MIBG myocardial scintigraphy.     

Possible Relation of Hemin-Induced HO-1 Expression to the Upregulation of VEGF and BDNF mRNA Levels in Rat C6 Glioma Cells

Glial cells are generally considered to contribute to retaining the integrity of neural function through the protection of neuronal cells against neurodegenerative insults and also expected to play a potential role in the protection of cerebrovascular systems from various toxic insults of hemorrhaged blood, thus proposing a possible implication of glial cells in the recovery of brain function from the damage caused by cerebral hemorrhage. Based on this hypothetical idea, the direct effect of hemin on the expression of genes encoding heme oxygenase-1 (HO-1), vascular endothelial growth factor (VEGF), and brain-derived neurotrophic factor (BDNF) in glial cells was examined using rat C6 glioma cells as an in vitro model system. Hemin elevated both HO-1 and VEGF mRNA levels in the glioma cells at the concentration causing no critical damage to the cells, and the elevation of BDNF mRNA levels was also observed by exposing the cells to hemin under the same conditions. Furthermore, the elevation of VEGF and BDNF mRNA levels induced by hemin was blocked by pretreatment of the cells with the agents inhibiting not only HO-1 gene expression but also its enzymatic activity. These pharmacological studies indicate that hemin can induce the enhancement of VEGF and BDNF gene expression probably through the mechanism mediated by HO-1 activity in the glioma cells, proposing the possibility that glial cells are capable of contributing to the recovery of brain function from the damage caused by cerebral hemorrhage through the production of neurogenic and angiogenic factors.