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Human esophageal cancers have been shown to express high levels of epidermal growth factor receptor (EGFR) and a relationship between high EGFR expression and local advance, the number of lymph node metastases, life expectancy, and sensitivity to chemo-radiotherapy has been demonstrated. We examined the use of gefitinib, an orally active EGFR-selective tyrosine kinase inhibitor, as a new strategy for treatment of esophageal carcinoma. The effects of gefitinib were evaluated in monotherapy and in combination with radiotherapy in human esophageal carcinoma cell lines. Gefitinib produced a dose-dependent inhibition of cellular proliferation in all of the 8 esophageal carcinoma cell lines examined, with IC50 values ranging from 5.7 microM to 36.9 microM. In combination, gefitinib and radiotherapy showed a synergistic effect in 2 human esophageal carcinoma cell lines and an additive effect in 5 cell lines. Western blotting demonstrated that gefitinib blocked activation of the EGFR-extracellular signal-regulated kinase (Erk) pathway and the EGFR-phosphoinositide-3 kinase (PI3K)-Akt pathway after irradiation. These results suggest that further evaluation of EGFR blockade as a treatment for esophageal cancer should be performed, and that radiotherapy combined with EGFR blockade may enhance the response of esophageal carcinoma to therapy.

We attempted to prepare colloidal iron within tissues by means of microwave irradiation. Mouse tissue blocks were fixed with a mixture of paraformaldehyde and ferric chloride in a cacodylate buffer, immersed in a cacodylate buffered ferric chloride solution, and irradiated in a microwave processor. Colloidal iron was prepared within tissues or cells, and was observed in the form of electron dense fine granules (1-2 nm in diameter) by transmission electron microscopy. Collagen fibrils in the connective tissue showed colloidal iron deposition at regular periodical intervals. Cells in the splenic tissue showed that fine colloidal granules were deposited on the ribosomes but not on the nuclear chromatin. This finding suggests that ferric ions could not diffuse into the nucleus, which was surrounded by the nuclear envelope. The podocyte processes of the renal glomerulus were stained diffusedly. Though this microwave in situ colloidal iron preparation method has some limitations, it is convenient for use in biomedical specimen preparation in transmission electron microscopy.

To evaluate recent improvements in lung cancer screening, we compared the results of recently conducted lung cancer screening with those of a previous screening. This study compared the survival of lung cancer patients detected by lung cancer screening conducted between 1976 and 1984 (early period) with that conducted between 1989 and 1997 (late period). Two hundred seventy-six patients with lung cancer were detected in the early period and 541 patients with lung cancer were detected in the late period. The median survival time (late : 49.8 vs. early : 27.8 months) and the 5-year survival rate (late : 47.8 vs. early : 34.8%) of the patients with lung cancer detected in the late period were significantly better than those in the early period (p = 0.0054). Among patients undergoing resection, the proportion of pathological stage I patients in the late period was significantly higher than that in the early period (late : 60.8 vs. early : 54.9%, p = 0.005). Multivariate analysis showed that the screening time period was a significant prognostic factor (hazard ratio = 0.685, 95% confidence interval : 0.563-0.832, p = 0.0002). These results were consistent with the findings of case-control studies of lung cancer screening programs in the late period recently conducted in Japan, which also showed a greater efficacy for screening than for previous case-control studies in the early period.

We describe here a patient with a recurrent hemangiopericytoma of the superior mediastinum 23 years after an initial complete resection. In the current biopsy specimen, the tumor cells were much more anaplastic than those seen 23 years ago. Although the patient was treated with chemotherapy, which consisted of ifosfamide and epirubicin, the tumor was unresponsive and he died 6 months later from disease progression. Careful long-term follow-up is mandatory for patients with hemangiopericytomas because recurrence with greater malignancy can develop following an extended disease-free interval.

We report herein the disappearance of macular hard exudates after the introduction of hemodialysis in diabetic patients. A 62-year-old woman and a 52-year-old man with diabetes mellitus showed hard exudates in the macula of the left eyes. Both patients had previously undergone panretinal photocoagulation in both eyes. During the follow-up, hemodialysis was introduced for deteriorating chronic renal failure caused by diabetic nephropathy. Half a year later, macular hard exudates in the left eyes disappeared dramatically in both patients, but the visual acuity remained the same. No additional laser treatment was done during the observation period. Hemodialysis is considered to have accelerated the resolution of macular hard exudates in both patients. The deposition of macular hard exudates in diabetic patients is due in part to concurrent poor renal function.

The inflamed synovial tissue (ST) of rheumatoid arthritis (RA) is characterized by the selective accumulation of interferon gamma-producing Th1-type CD4+ T cells. In this study, we investigated whether the predominance of Th1-type CD4+ cells in the ST lesion is mediated by their selective recruitment through Th1 cell-associated chemokine receptors CXCR3 and CCR5. The lymphocyte aggregates in the ST of RA contained a large number of CD4+ T cells, which mostly expressed both CXCR3 and CCR5, but not CCR4. In contrast, the frequencies of CD4+ and CD8+ T cells expressing CXCR3 and CCR5 in the blood were significantly decreased in RA patients, compared with healthy controls (HC), although there was no difference in the frequencies of CCR4-expressing CD4+ and CD8+ T cells between RA and HC. CXCR3, CCR5, and CCR4 expression in blood CD4 + T cells and CXCR3 expression in CD8+ T cells were increased after interleukin-15 (IL-15) stimulation. Therefore, the distribution of Th1-type CD4+ T cells into the ST from the blood in RA may be associated with the local expression of chemokines, both CXCR3 and CCR5 ligands, and IL-15 may play a role in enhancing these chemokine receptors on CD4+ T cell infiltrates.

Type III collagen is found in fetal skin and blood vessels. Previously, we characterized the proximal promoter of the human alpha1(III) collagen gene (COL3A1) using the human rhabdomyosarcoma cell line, A204, and NIH3T3 cells (Yoshino et al., Biochim Biophys Acta, 2005). In the present study, we further analyzed this promoter using additional cell lines, namely a human embryonal rhabdomyosarcoma cell line (RD) and bovine vascular smooth muscle cells (vSMCs), both of which show high expression of type III collagen. Using a luciferase assay, electrophoretic mobility shift assays (EMSA), and DNase footprinting assay, 2 types of multifactor complexes were shown to bind to the DNA region in the vicinity of the B element (- 80 to - 58), depending on the cell type. Next, we used cells stably transfected with a GFP-linked type III collagen promoter fragment for analysis of promoter expression. Usually, transfected cells retained the characteristics of the original cells. However, in several clones derived from RD cells, promoter expression as well as cell shape changed to patterns characteristic of the A204 cell line. Nuclear factors expressed by these clones were also characteristic of the A204 line.

This study included 45 patients with intentional insecticide intoxication and 21 with accidental intoxication who were treated at the First-Aid and Emergency Department of Balcali Hospital at the Faculty of Medicine in the Cukurova University, Adana, Turkey, while the control group consisted of 25 people selected from university personnel known to be healthy. Patients with a history of X-ray exposure in the last 6 months or of any virus disease as well as continuous drug users and smokers were excluded, leaving a total of 49 patients. Acetylcholine esterase (Pseudocholinesterase) enzyme (AchE), sister-chromatid exchanges (SCE), the mitotic index (MI), and the replication index (RI) were evaluated. Blood samples were cultured for SCE evaluation and sera separated for AchE levels. Insecticide exposure was generally intentional for suicide in adolescents and at older ages, but accidental for children. AchE levels were found to be significantly lower in organophosphorus (OP) and carbamated (CB) insecticide poisoning groups in comparison with the control group (p<0.001), while the pyrethroid (PY) group was not statistically different for the AchE effect (p>0.05). SCE was found to be significantly higher in OP and CB groups (p<0.001), while the PY and control groups were statistically similar for SCE levels (p>0.05). This study showed an increase in SCE in response to orally ingested insecticides. These findings indicate that insecticide exposure results in cell abnormalities, with resulting impediments to the division and replication of cells, as suggested by MI decreases and RI increases, while the speed of the division cycles of stimulated cells increases.

A 61-year-old man, who was diagnosed with superior vena cava syndrome by papillary thyroid carcinoma, was referred to our hospital. A bulky thyroid tumor with tracheal invasion extended from the left neck to the right atrium without distant metastases. The risk of sudden death due to airway occlusion, tumor embolism or obstruction of the tricuspid valve led us to elect surgery. Extended resection of thyroid cancer was performed with cardiopulmonary bypass. Peritoneal dissemination was found via laparotomy. A histological diagnosis of anaplastic carcinoma arising from transformation of papillary carcinoma was made. After the operation, bilateral ureteral occlusion by peritoneal dissemination and multiple lung metastases were detected. The patient died with acute renal failure on postoperative day 12. Intraatrial extension of thyroid cancer is rare, and only 12 cases have been reported in the literature. We present a case of thyroid cancer with intraatrial extension.

Deficiency of glucose-6-phosphate dehydrogenase (G6PD) causes acute hemolytic anemia triggered by oxidative drugs such as primaquine. It is therefore essential in malaria-endemic areas for malaria patients to be confirmed for their G6PD activity before taking primaquine. The WST-8 method, a newly established screening method for G6PD deficiency, has been demonstrated to be suitable for field conditions, particularly for on-site malaria surveys. Here we report a laboratory evaluation by this method of the reactivity of blood-spotted filters. A time-course experiment was conducted to evaluate the reactivity of blood samples spotted onto 4 types of filter paper, Whatman 31ET Chr (ET), 3MM Chr (3MM), P81, and Advantec No. 2 (AD2). The rank of the relative reaction intensity was ET > 3MM = AD2 > P81. Blood-spotted filters stored at 4 degrees centigrade gradually decreased G6PD reactivity with the passage of storage time, whereas those stored at room temperature rapidly reduced their reactivity. Unexpectedly, saponin supplementation reduced the reactivity of blood-spotted filters. In conclusion, 1) ET is the most suitable filter for the WST-8 method ; 2) blood-spotted filters stored in cold condition can be assayed within 14 days, or those stored at room temperature should be tested within 3 days ; and 3) reaction mixtures should not contain saponin.

This study was conducted to develop a simple surrogate index comprised of routinely available laboratory tests to reflect the histological fibrosis stage. Clinical characteristics and laboratory data from 368 and 249 consecutive patients with chronic hepatitis C, a training cohort and a validation cohort, respectively, were retrospectively evaluated. Platelet (Plt) count and albumin (Alb) level contributed to the discrimination of the respective fibrosis stages. We derived the fi brosis index (FI), FI = 8.0-0.01 x Plt (10 multiply 3/microliter) - Alb (g/dl), from a multiple regression model. FI significantly correlated with the histological fibrosis stage in both the initial and validation cohort at p=0.691 and p=0.661, respectively (Spearman's rank correlation coefficient, p<0.0001). The sensitivity and positive predictive value of FI at a cutoff value < 2.10 for predicting fibrosis stage F0-1 were 66.8% and 78.8% in the initial cohort and 68.5% and 63.6% in the validation cohort, respectively. Corresponding values of FI at a cutoff value >- 3.30 for the prediction of F4 were 67.7% and 75.0% in the initial cohort and 70.8% and 81.0% in the validation cohort. The fibrosis index comprised of platelet count and albumin level reflected the histological fibrosis stage in patients with chronic hepatitis C.