The effect of exogenous nitric oxide on endothelial dysfunction in two-kidney, one-clip renovascular hypertensive rats

Previous studies have shown that hypertension causes endothelial dysfunction. To study the influence of exogenous nitric oxide(NO) on endothelial dysfunction produced by hypertension, we administered a non-depressor dose of nipradilol to two-kidney, one-clip renovascular hypertensive rats(2K1C). Sprague-Dawley rats underwent either sham surgery(G-1) or clipping of the left renal artery. From day seven, 2K1C were randomized into 3 groups, placebo treatment(G-2), nipradilol treatment(G-3,) and propranolol treatment(G-4). Urinary NO2- + NO3-(NOx) excretion (UNOx V) was measured 4 weeks after clipping, and then, acetylcholine(Ach), A23187, or sodium nitroprusside(SNP)-induced relaxation were measured in the aorta. Blood pressure was increased in G-2, G-3, and G-4 compared to G-1. UNOx V was lower in G-2, G-3, and G-4 compared to G-1, but UNOx V was higher in G-3 compared to G-2 and G-4. Although Ach or A23187-induced relaxation was significantly decreased in isolated artery from G-2, G-3, and G-4 compared with those from G-1. Ach- or A23187-induced relaxation was improved in G-3. SNP-induced relaxation did not differ among the 4 groups. These results suggest that exogenous NO from nipradilol reduces the endothelial dysfunction caused by hypertension without changing the blood pressure.     

S-1 plus cisplatin combination chemotherapy in patients with advanced non-small cell lung cancer: a multi-institutional phase II trial.

PURPOSE: To evaluate the efficacy and toxicity of a novel combination chemotherapeutic regimen including cisplatin with an oral anticancer agent, S-1 that consisted of tegafur, 5-chloro-2, 4-dihydroxypyridine, and potassium oxonate, for non-small-cell lung cancer (NSCLC) patients. EXPERIMENTAL DESIGN: In this phase II trial, patients with locally advanced and metastatic NSCLC were treated with the oral administration of S-1 at 40 mg/m(2) twice a day for 21 consecutive days while cisplatin (60 mg/m(2)) was administered intravenously on day 8. This schedule was repeated every 5 weeks. RESULTS: Of 56 patients enrolled in the study, 55 patients were eligible and analyzed. The median number of cycles administered was 3 (range, 1-12 cycles). Among these 55 patients, one complete response and 25 partial responses were observed with an overall response rate of 47% (95% confidence interval, 34-61%). The median survival time was 11 months and the 1-year survival rate was 45%. Hematologic toxicities of grades 3 and 4 included neutropenia (29%) and anemia (22%). No grade 4 nonhematologic toxicity was observed. Grade 3 toxicity included anorexia (13%), vomiting (7%), or diarrhea (7%). CONCLUSIONS: S-1 plus cisplatin combination chemotherapy showed a promising effectiveness with acceptable toxicity rates in patients with advanced NSCLC. These results warrant further investigations of this regimen including a randomized controlled trial for its use as a first line treatment for NSCLC.     

Non-contrast-enhanced MR angiography using 3D ECG-synchronized half-Fourier fast spin echo

A non-contrast-enhanced three-dimensional (3D) magnetic resonance angiography (MRA) technique, which acquires images in a reasonably short scanning time and requires no contrast agent, is developed. An electrocardiographically (ECG) synchronized 3D half-Fourier fast spin-echo (FSE) technique with an appropriate ECG delay time for every slice encoding in 3D terms was used to examine the thoracic and iliac regions in 16 healthy volunteers at both 0.5 and 1.5 T. Prior to each 3D fresh blood imaging (FBI) experiment, an ECG preparation (ECG-prep) scan was acquired, and an appropriate ECG triggering time was selected for 3D FBI acquisition to optimize visualization of the vessel of interest. In the thoracic and abdominal regions, good-quality 3D MRA images were obtained. Furthermore, the weighted subtraction of two images in different phases provides contrast enhancement between arteries and veins.     

A case of urachal abscess mimicking a tumor in the retrovesical space

A 14-year-old girl was admitted to our hospital because of umbilical erythema and discharge. She had had an appendectomy at the age of twelve. Abdominal ultrasonography and cystoscopy revealed a large tumor-like mass at the posterior wall of the bladder. Computed tomography and magnetic resonance imaging revealed urachal sinus. The diagnosis of urachal abscess had been confirmed and conservative treatment had been continued by drainage via umbilicus and the administration of antibiotics. Total excision of the urachus was performed about one month later because the bladder mass was not reduced. Pathological findings revealed an inflammatory thickened wall of the urachus and no evidence of malignancy. We report this rare case of urachal abscess with a large mass in the retrovesical space.     

Identification of the HLA-Cw*0702-restricted tumor-associated antigen recognized by a CTL clone from a lung cancer patient.

PURPOSE: A large number of tumor-associated antigens have been used in vaccination trials for mainly melanomas. Our purpose of this study is to identify a novel tumor antigen useful for immunotherapy of lung cancer patients. EXPERIMENTAL DESIGN: Analysis of an autologous tumor-specific CTL clone F2a that was established from regional lymph node lymphocytes of a patient with lung cancer (A904) by a mixed lymphocyte-tumor cell culture. RESULTS: F2a recognized and killed autologous tumor cells (A904L), whereas it did not respond to autologous EBV-transformed B cells, phytohemagglutinin-blastoid T cells, and K562 cells. cDNA clone 31.2 was isolated by using cDNA expression cloning method as a gene encoding antigen. This gene was identical to the reported gene whose function was unknown. The antigen encoded by the cDNA was recognized by the CTL in a HLA-Cw*0702-restricted manner. Furthermore, a 9-mer peptide at positions 659 to 685 in cDNA clone 31.2 was identified as a novel epitope peptide. The CTL recognized some allogeneic cancer cell lines with HLA-Cw*0702 as well as some HLA-Cw*0702-negative cell lines when transfected with HLA-Cw*0702, thus indicating that the identified antigen was a cross-reactive antigen. CONCLUSIONS: Although exact mechanism to process the encoded protein and present the antigen in the context of HLA class I remains to be elucidated, the CTL recognized some of tumor cells in the context of HLA-Cw*0702 but did not recognize a variety of normal cells and also autologous EBV-transformed B cells. These results indicated that the antigen identified in this study may therefore be a possible target of tumor-specific immunotherapy for lung cancer patients.     

Effect of N-methyl-2-pyrrolidone on skin permeation of estradiol.

N-Methyl-2-pyrrolidone (NMP) increased the skin permeation of estradiol (E2) in Yucatan micropig epidermis using a modified Franz-type diffusion cell. The addition of NMP significantly increased the fluxes of E2 from water and soybean oil. The flux and skin concentration of E2 were higher from soybean oil than from water and increased with increasing NMP concentrations in soybean oil. Correlation was observed with E2 flux and skin concentration (R(2) = 0.804) NMP enhanced E2 skin permeation because NMP made E2 skin concentration higher. Thus, NMP (10%) was added to the oily gel made by isocetyl isostearate and hydrogenated phospholipid. E2 permeation from the gel without NMP was the same as that from soybean oil suspension. The flux of E2 from the gel with NMP was 0.6 microg/h per cm(2) and might be sufficient for estrogen replacement therapy.     

A thoracoscopic resection of pulmonary metastasis from breast cancer: a case report with a 27-year disease-free interval

A 70-year-old woman, who had undergone a right radical mastectomy for breast cancer 27 years previously, was found to have a tumor measuring 15 mm in diameter between the S5 area and the S8 area of the left lung. We suspected it to be either metastatic or primary lung cancer based on preoperatively any conclusive diagnosis. We thus performed a thoracoscopic partial lung resection and pericardial resection. The pathological diagnosis of the resected specimen was pulmonary metastasis from the previous breast cancer, since the pathological findings of the lung lesion were closely similar to those of the previous breast lesion. Using immunohistochemical methods, the tumor cells show positive staining for anti-estrogen receptor antibody. In lung tumor cases in which the patient has undergone a breast cancer resection, even more than 20 years previously, surgeons must not rule out the possibility of recurrence. Thoracoscopic surgery is considered to be most effective method for both making a definitive diagnosis and for performing curative treatment.     

Unfolded protein response in keratinocytes: Impact on normal and abnormal keratinization

The unfolded protein response (UPR) is a signaling pathway from the endoplasmic reticulum (ER) to the nucleus that protects cells from stress caused by misfolded or unfolded proteins. As such, ER stress is an ongoing challenge for all cells, given the central biologic importance of secretion as part of normal physiologic functions. Mild UPR is activated by mild ER stress, which occurs under normal conditions. Abnormal UPR is activated by severe ER stress, which occurs under pathological conditions. Abnormal UPR activation is associated with a number of diseases, including diabetes mellitus and Alzheimer's disease. Within skin tissues, keratinocytes in the epidermis are especially dependent upon a mild UPR for normal differentiation in the course of their differentiation into secretory cells in the uppermost granular layers. Association between abnormal UPR activation and hereditary keratoses, including Darier's disease, keratosis linearis with ichthyosis congenita and keratoderma syndrome, erythrokeratoderma variabilis, and ichthyosis follicularis with atrichia and photophobia syndrome, have been elucidated recently. This review describes the UPR in normal and abnormal keratinization and discusses the regulation of abnormal UPR activation by chemical chaperones as a potential treatment for one of the hereditary keratoses.