Reflux esophagitis is a common intractable postoperative complication, especially after procedures such as total gastrectomy, when it manifests itself as alkali esophagitis. Although medications such as proton pump inhibitors (PPI) are said to be efficacious in the treatment of reflux esophagitis, the mechanism of the curative effect of such drugs remains unclear. To address this issue, we performed esophago-duodenostomy on Wistar rats after total gastrectomy, to establish a rat model for reflux esophagitis. An esophagoduodenostomy with an end-to-side anastomosis was performed following a total gastrectomy, and animals were sacrificed at 4, 7, 14, 21, and 28 days after the operation. Esophageal epithelial lesions following histological sectioning were observed under the microscope after fixing the specimens in formalin, and the image analysis of the affected area was carried out on a computer. Lesions were detected as early as seven days after the operation. The total area of the lesions of the esophageal epithelium reached a peak 21 days following the operation, and consisted of sores, ulcers, cornification, mamilliform hyperplasia and hypertrophy. The results enabled us to establish a critical reflux esophagitis model following esophago-duodenostomy after total gastrectomy in rats.

View full abstract

Dyspnea has been implicated in the prognosis of patients with chronic obstructive pulmonary disease (COPD) . We examined the relationship between exertional dyspnea during walking and oxygen utilization, as well as the pulmonary hemodynamics at rest in patients with stable COPD. A sixminute walking test (6 MWT) and cardiac catheterization was performed in twenty-four subjects, whereby each patient was instructed to walk as far as possible for six minutes, during which the distance and degree of dyspnea were recorded each minute on a 150-mm visual analog scale (VAS) . In all patients there was a significant linear relationship between dyspnea and the distance walked over time. From these results, we obtained a ratio of induced dyspnea to distance (VAS I distance) during the 6MWT. There was significant correlation between VAS I distance and FEV1, oxygen extraction ratio (ER), PaO₂, and mixed venous oxygen tension (PvO₂) . However, the PaCO₂ and pulmonary arterial mean pressure (mPAP) showed no correlation with VAS / distance. These results suggest that COPD patients with severe exertional dyspnea have an impairment of oxygen utilization at rest.

View full abstract

Lidocaine inhibits the proliferative response and cytokine synthesis of peripheral blood mononuclear cells after allergen- and non-allergen-specific activation. In the present study, we investigated the role of apoptosis in the inhibitory effect of lidocaine on CD4⁺ T-cells. CD4⁺ T-cells from 8 patients with asthma and house dust mite allergy were cultured with lidocaine. Staining for Annexin V and propidium iodide was monitored by flow cytometry. The active forms of caspase-3 and caspase-9 were examined by flow cytometry and the expression of Bcl-2 was analyzed by immunoblotting. The inhibitory effects of lidocaine on CD4⁺ T-cell proliferation and interleukin-5 and interferon γ production after stimulation with phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore were also investigated. The extent of apoptosis in CD4⁺ T-cells stimulated with PMA plus calcium ionophore was examined. Addition of lidocaine (1mM) to resting CD4⁺ T-cells increased the percentage of Annexin V⁺ PI^- Tcells in the culture (P<0.01) ; expression of the active forms of caspase-3 and caspase-9 was increased (P<0.05), while expression of Bcl-2 was decreased. The proliferative response (P<0.01) and the production of interleukin-5 and interferon-γ (P<0.01) by CD4⁺ T-cells after stimulation with PMA plus calcium ionophore were inhibited upon incubation with 1 mM lidocaine. Furthermore, the percentage of Annexin V⁺ PI^- T-cells in activated CD4⁺ T-cells treated with 1 mM lidocaine was also increased. Thus, lidocaine induces apoptosis in CD4⁺ T-cells by activation of caspase-3 and caspase-9 and down-regulation of Bcl-2.

View full abstract

We evaluated the expression of cathepsin D (CD) in a series of colorectal tumor cells and stromal cells, in relation to the clinicopathological and histopathological features. Tissue samples were obtained from the archival surgical specimens of 72 primary colorectal adenocarcinomas and endoscopic mucosal resection (EMR) specimens of 53 colorectal adenomas and adenocarcinomas. The carcinomas were sited in the mucosa (M) in 23 patients, in the submucosa (SM) in 28 patients, in the muscularis propna (MP) in 16 patients, and in the subserosa (SS) in 39 patients. The adenoma samples comprised 19 severe dysplastic adenomas (AD) . High CD expression in the tumor cells was observed in 1 case (5.3%) of AD, 2 cases (8.7%) of M, 10 cases (35.7%) of SM, 7 cases (43.8%) of MP, and in 15 cases (38.4%) of SS. There was a significant correlation between the CD expression of M and SM samples (p<0.05) . High CD expression in the stromal cells was observed in 1 case (5.3%) of AD, in 1 case (4.3%) of M, in 12 cases (42.9%) of SM, in 12 cases (75%) of MP, and in 27 cases (69.2%) of SS. There was correlation between the CD expression of M and SM carcinomas (p<0.01) and between that of SM and MP (p<0.05) . In 72 surgical specimens, lymph nodes metastasis was proven histologically in 1 case (5.9%) of SM, 2 cases (12.5%) of MP, and in 17 cases (43.6%) of SS. In both tumor cells and stromal cells, there were no correlation between CD expression and lymph nodes metastasis. These results indicate that cathepsin D expression in carcinoma and stromal cells reflects a potential for invasive growth of colorectal tumors.

View full abstract

This study aimed to clarify the mechanisms by which selective portal vein occlusion can result in hypertrophy of the remnant liver and atrophy of the liver to be resected. The association between hepatic reduced glutathione (GSH) and malondialdehyde (MDA) in lobes supplied by branches of the portal vein that had been occluded (LPVO) or not occluded (LPVNO) were evaluated in rats. Changes in liver function in both groups were determined before and after portal vein occlusion (PVO) . Transaminase showed significantly higher levels in the PVO group than in the sham operation group on days 1 and 3, and the levels of prothrombin activity in the PVO group were significantly lower than in the sham group on day 1. GSH in the LPVNO increased significantly during the first 3 days in comparison to the sham group, and reached a peak on the 3rd day. In the LPVO, the levels of GSH decreased gradually relative to the sham group on days 3, 5, and 7 MDA levels in both LPVNO and LPVO were significantly higher on the first day than in the sham group. From the third day. MDA levels in the LPVNO were less than the lowest level in the sham group, while those in the LPVO continued to increase linearly throughout the observation period. The correlations between GSH and MDA levels in the LPVO were negatively significant. The regeneration in LPVNO was preceded by a temporary increase in MDA and a subsequent increase in GSH production, whereas LPVO showed atrophic changes with a continuous decrease in GSH and an increase in MDA.

View full abstract

The tyrosine kinase Syk plays an important role in the signal transduction pathway of hematopoietic cells, especially in activated platelets stimulated with collagen. We found that the translocation of tyrosine-phosphorylated Syk differed from that of the Src family protein tyrosine kinases (PTKs) . Furthermore, Syk was identified not only in the cytosolic fraction, but also in the membrane-bound subcellular fraction of platelets. Only the membrane-bound Syk was tyrosine phosphorylated and translocated one minute after stimulation. In resting platelets, Src was constitutively tyrosine phosphorylated in both the cytosolic and membrane-bound fractions, and translocated from the cytosolic fraction to the membrane fraction after stimulation. Platelet dysfunction after stimulation with collagen is quite common in myelodysplastic syndrome (MDS), and we demonstrated abnormal tyrosine phosphorylation and translocation of PTKs using platelets from six patients with MDS. In resting platelets, the distribution and constitutive tyrosine phosphorylation of PTKs (Syk, Src, Lyn, Fyn) was abnormal. After collagen stimulation, tyrosine phosphorylation and translocation of these PTKs became disrupted. However, these abnormalities were highly heterogeneous among individual patients. We postulate that membrane-bound Syk plays an important role in signal transduction and that anomalous signal transduction is a key source of platelet dysfunction in MDS patients.

View full abstract

The analysis of both the numbers and subsets of cerebrospinal fluid (CSF) -infiltrating leukocytes is useful for the diagnosis of meningitis ; however, the precise mechanism of leukocyte infiltration into the CSF has not been determined. Adhesion molecules play important roles in the recruitment of leukocytes to the site of inflammation. We therefore investigated the expression of the adhesion molecule L-selectin and its ligand sialyl Lewis X (sLe^x) on infiltrating CSF leukocytes. The CSF leukocytes from ten patients, including 6 cases of viral, 3 of bacterial, and 1 of tuberculous meningitis were examined by flow cytometry. In general, the ratios of cells positive for L-selectin and sLe X were higher in bacterial than in viral meningitis. In tuberculous meningitis, the expression of sLe^x was elevated in lymphocytes. The expression profiles of adhesion molecules on CSF leukocytes were different for each type of meningitis. Although we could not draw any definite conclusions from this study because of the limited number of patients, the range of molecular profiles on CSF leukocytes for different infectious agents might reflect differences in the activation and migration mechanisms of the leukocytes in the various meningitides.

View full abstract

A case of ovarian mucinous cystic tumor with mural nodules, containing reactive fibro-histiocytic lesions and a few small foci of anaplastic carcinomatous lesion, is reported. Macroscopically, the tumor was 19.5×6.3 cm and weighed 1800 g. The cut surface of the tumor was mucinous and multicystic with mural nodules. Microscopically, the inner surface of the cyst wall was lined with endocervical and intestinal type mucinous epithelium. In some areas, stratified atypical epithelium was seen, but as there was no evidence of stromal invasion, we considered it a borderline malignancy. In the mural nodules, a few granulomatous lesions consisting of atypical cells with multinucleated giant cells were seen. These atypical cells were positive for AE1 / AE3, cytokeratin 7, vimentin and periodic acid Schiff, and negative for cytokeratin 20, CD68, carcinoembryonic antigen and alcian-blue. These results suggested a diagnosis of anaplastic carcinoma. A foreign body reaction was seen surrounding the granulomatous lesions, most likely in response to mucin excursion. The prognosis for patients with sarcomatous mural nodules associated with cystic common epithelial tumors of the ovary is not good, however this patient is alive and free of disease two years postoperatively without additional therapy.

View full abstract