Inducible nitric oxide synthase inhibitors fromMelia azedarach var.Japonica

In bioassay-guided search for inducible nitric oxide synthase (iNOS) inhibitory compounds from higher plants of South Korea, two beta-carboline alkaloids, 4-methoxy-1-vinyl-beta-carboline (1) and 4,8-dimethoxy-l-vinyl-beta-carboline (2) have been isolated from the cortex of Melia azedarach var. japonica. The structures of these compounds were elucidated on the basis of spectroscopic data. Compounds 1 and 2 showed marked inhibitory activity of iNOS on LPS- and interferon-gamma-stimulated RAW 264.7 cells.     

Synthesis of benzo[c]phenanthridine derivatives and theirin vitro antitumor activities

Aiming at the development of anticancer agents by modification of phenolic benzo[c]phenanthridine alkaloid, additional hydroxyl group was put on C10 position of fagaridine (1) by a biomimetic synthetic procedure to afford 10-hydroxyfagaridine (12). All of the synthetic intermediates were also screenedin vitro antitumor activities against five different cell lines as well as12. Among them the representative cytotoxic results are shown as follows;p-quinone (11) [ED₅₀ (A549=0.22 μg/ml), (HCT15=0.21 μg/ml), fagaridine (1) (HCT 15=0.41 μg/ml), olefin (6) (HCT 15=0.06 μg/ml), acetal (7) (SKMEL-2=0.07 μg/ml), dihydrofagaridne (10) (A549=0. 38 μg/ml), 10-hydroxyfagaridine (12) (A 549=0.45 μg/ml). From these observation three main remarks can be drawn; (i) the iminium part of benzo[c]phenanthridine is not essential for showing acitvities, (ii) the additional hydroxyl group did not contribute to enhance the cytotoxicity, (iii) the 3-arylisoquinolin-1(2H)-one derivatives were found to display significantin vitro antitumor activity.     

Accuracy of college students' reports of parental handedness

College students' reports of their parents' handedness were compared with data provided by the parents themselves. The students' reports of their parents' writing hand were highly accurate, the reports of their parents' general handedness somewhat less so. For the latter measure, the students were asked, 'What is your mother's (father's) handedness?' and were given the choice 'left','either', 'right',and 'don't know'. Their answers were then compared with the investigators' classification based on the parents' answers to a 10-item hand-use questionnaire. For this measure, the accuracy of the students' reports was also found to be related to the students' own handedness.     

A case of subacute sclerosing panencephalitis showing various cerebral perfusion on 99mTc-ECD SPECT

We reported serial neuroradiological findings of a 20-year-old male with subacute sclerosing panencephalitis, who deteriorated from Jabbour stage 2 to stage 4 rapidly in spite of oral administration of inosine pranobex. At the stage 2, brain magnetic resonance imaging (MRI), computed tomography (CT) and [99mTc]-L, L-ethyl cysteinate dimer (99mTc-ECD) single photon emission computed tomography(SPECT) findings were normal. As the disease progressed, brain MRI and CT revealed diffuse cerebral white matter lesions as well as cerebral atrophy. 99mTc-ECD SPECT showed serially various perfusion of cerebrum. These findings in 99mTc-ECD SPECT may reflect the acute inflammatory process and consequent destruction of brain tissue.     

Pseudoepitheliomatous hyperplasia in lichen sclerosus of the vulva.

Small tentacles or separated nests of squamous cells in the dermis are not uncommonly seen in long-standing vulvar lichen sclerosus (LS) associated with epidermal thickening. We recently encountered a case where separated nests of well-differentiated squamous cells in the dermis were difficult to distinguish from squamous cell carcinoma (SCC). Further biopsies showed similar nests originating from every hair follicle. We postulated a diagnosis of multifocal pseudoepitheliomatous hyperplasia (PEH) to explain this phenomenon. Because we could find no reference to PEH in the setting of LS, we reviewed the biopsies of 92 women with extragenital and vulvar LS with and without carcinoma to determine its frequency and histological appearance. The study population, which excluded the index case, comprised 10 women with extra-anogenital LS, 58 with vulvar LS without carcinoma, and 24 with vulvar LS with carcinoma. The presence of PEH, epidermal thickness, predominant dermal collagen change, degree of inflammation, and presence of fibrin and red blood cells were recorded. The presence or absence of lichen simplex chronicus (LSC), squamous cell hyperplasia (SCH), and differentiated vulvar intraepithelial neoplasia (VIN) were recorded. PEH was identified only in vulvar LS, where it was seen in 7/58 (12.1%) women without carcinoma, 1/24 (8.3%) with carcinoma, and 0/10 (0%) with extra-anogenital LS. Two forms of PEH were seen: predominantly epidermal 7/8 (87.5%) and predominantly follicular 1/8 (12.5%). PEH was associated with increased epidermal thickness, less dermal edema, more dermal inflammation, fresh fibrin, and red blood cell extravasation. In all cases, there was associated LSC, but there was no SCH or differentiated VIN. In conclusion, PEH may explain many of the cases of dermal tentacles and separated squamous nests in vulvar LS with LSC. The association with fresh fibrin and red blood cells suggests that PEH might be a reaction to tissue damage. PEH is distinguished from SCC by its lack of atypia, confinement to the abnormal collagen, and limited growth. The pathologist must be careful about making a diagnosis of PEH in LS with epidermal thickening, looking carefully for basal atypia and other features of differentiated VIN in the overlying epidermis or dermal proliferation. We do not know whether PEH occurs in differentiated VIN and, if it does, how it could be distinguished from SCC.     

胃肠术后1号治疗急性弥漫性腹膜炎的研究

目的　探讨胃肠术后 1号治疗急性弥漫性腹膜炎的疗效。方法　测定 2 0例急性弥漫性腹膜炎患者 (随机分为 2组 :对照组 10例 ,治疗组 10例 )血中乳酸、DAO水平。结果　急性弥漫性腹膜炎患者血中乳酸、DAO呈现不同程度升高 ,经治疗随病情好转 ,血中乳酸、DAO呈现不同程度下降 ,而治疗组血中乳酸、DAO下降幅度显著 ,优于对照组 (P <0 .0 5 )。结论　血中乳酸、DAO在急性弥漫性腹膜炎患者病理过程中起重要作用 ,可作为评估急性弥漫性腹膜炎患者严重程度的指标 ,胃肠术后 1号使乳酸、DAO水平下降 ,促进疾病恢复     

A dendritic cell line genetically modified to express CTLA4-IG as a means to prolong islet allograft survival

BACKGROUND: Dendritic cells are potent antigen-presenting cells that bind allogeneic T cells. They are thus candidates for targeting immunoregulatory molecules to the alloreactive T cell compartment and suppressing the alloimmune response. METHOD: A dendritic cell line derived from the BALB/c mouse (H2d) was genetically modified to express the immunoregulatory molecule CTLA4-Ig. The ability of these dendritic cell transfectants to downregulate the alloimmune response was tested in an islet transplant model. Allogeneic C57Bl/6 (H2b) mice were rendered diabetic with streptozocin, and they received BALB/c islet (H2d) transplants. Mice were administered 25 million untransfected or CTLA4-Ig-transfected D2SC/1 cells i.v. on the day of islet transplantation and 6 days later[fnc]. RESULT: Mice treated with CTLA4-Ig-transfected D2SC/1 cells demonstrated prolonged allograft survival (mean = 20 days, median = 17 days, SD = 9.39) compared with mice treated with untransfected D2SC/1 cells (mean = 12 days, median = 11 days, SD=2.74) or untreated control mice (mean = 11 days, median = 11 days SD = 1.41). Third party allograft survival was not prolonged in mice receiving similar treatment. CONCLUSIONS: These results demonstrate that a genetically modified dendritic cell line can suppress the alloimmune response and prolong islet allograft survival in an allospecific manner. The findings also suggest that genetically modified dendritic cells may be useful in targeting alloreactive T cells and prolonging allograft survival.     

The attitudes of cancer patients and their families toward the disclosure of terminal illness.

PURPOSE:To ascertain the attitude of cancer patients and their families toward disclosure of terminal illness to the patient. PATIENTS AND METHODS: We constructed a questionnaire that included demographic and clinical information and delivered it to 758 consecutive individuals (433 cancer patients and 325 families that have a relative with cancer) at seven university hospitals and one national cancer center in Korea. RESULTS: 380 cancer patients and one member from each of 281 families that have a relative with cancer completed the questionnaire. Cancer patients were more likely than family members to believe that patients should be informed of the terminal illness (96.1% v 76.9%; P <.001). Fifty percent of the family members and 78.3% of the patients thought that the doctor in charge should be the one who informs the patient. Additionally, 71.7% of the patients and 43.6% of the family members thought that patients should be informed immediately after the diagnosis. Stepwise multiple logistic regression indicated that the patient group was more likely than the family group to want the patient to be informed of the terminal illness (odds ratio [OR], 9.76; 95% CI, 4.31 to 22.14), by the doctor (OR, 4.00; 95% CI, 2.61 to 6.11), and immediately after the diagnosis (OR, 3.64; 95% CI, 2.45 to 5.41). CONCLUSION: Our findings indicated that most cancer patients want to be informed if their illness is terminal, and physicians should realize that the patient and the family unit may differ in their attitude toward such a disclosure. Our results also reflect the importance of how information is given to the patient.     

A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer.

BACKGROUND: Capecitabine (Xeloda) is a novel, oral, selectively tumor-activated fluoropyrimidine with proven activity in the treatment of advanced colorectal cancer. This trial was conducted to evaluate the efficacy, safety and feasibility of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer, with a view to replacing 5-fluorouracil (5-FU) in such patients. PATIENTS AND METHODS: Forty-four patients received capecitabine 1250 mg/m2 twice daily (2500 mg/m2/day) for 14 days followed by 7 days of rest, for up to six cycles. RESULTS: Capecitabine produced an objective response rate of 34% (all partial responses) and stable disease in 14 patients (30%). The median time to disease progression (TTP) was 3.2 months [95% confidence interval (CI) 2.7-6.4 months] and median overall survival was 9.5 months (95% CI 6.9-13.2 months). Hand-foot syndrome (HFS), nausea, anorexia, diarrhea and vomiting were the most common adverse events. While HFS was the most frequent grade 3/4 toxicity (National Cancer Institute Common Toxicity Criteria), only 9% of patients experienced grade 3 HFS. Severe myelosuppression was not reported during the study. CONCLUSIONS: Capecitabine monotherapy is active and well tolerated as first-line therapy in patients with advanced/metastatic gastric cancer. Larger comparative trials investigating capecitabine-based combination regimens in patients with advanced gastric cancer are warranted.     

Smooth muscle distribution in the extrahepatic bile duct: histologic and immunohistochemical studies of 122 cases

The distribution of smooth muscle fibers in the extrahepatic bile duct (EBD) wall is not well characterized. We analyzed 101 consecutive Whipple's operation specimens and 21 autopsy specimens for the pattern of smooth muscle distribution in EBD using the Masson-trichrome stain and the desmin immunohistochemical stain. The patterns were categorized as continuous, interrupted, scattered, and no muscle layer. EBDs were divided into lower, middle, and upper portions, and the distribution pattern of smooth muscle fibers was analyzed separately in each portion. Because most surgically resected specimens contained the middle and lower EBDs with only a portion of the upper EBD, only the length of the middle and lower EBDs (common bile duct, CBD) was measured. The mean length of CBD in surgically resected specimens was 6.4 +/- 1.4 cm (men, 6.6 +/- 1.3 cm; women, 6.1 +/- 1.5 cm). The mean length of CBD in autopsy specimens was 6.8 +/- 1.0 cm. The predominant patterns of the lower third of the EBD were interrupted (49%) and continuous (43%). The predominant patterns of the middle third of the EBD were scattered (63%) and interrupted (23%). Those of the upper third of the EBD were no muscle fiber (58%) and scattered (39%). In conclusion, different patterns of smooth muscle distribution were observed in different portions of the EBD. Because scattered muscle fibers or no muscle fibers were the main features of the upper third of the EBD, understanding of this pattern may be helpful for assessment of the depth of invasion or staging of carcinoma of the upper third of the EBD.