Acute effects of methyl bromide gas in rats and mice--studies on survival time

Wistar male rats and ddY male mice were exposed to 500-10,000 ppm of methyl bromide gas up to 8 hours, and the survival time and weights of brain, lung, liver, kidneys, spleen and tests were measured. The survival time decreased with the gas concentration almost exponentially. In general, rats had a longer survival time than mice under the same exposure concentration. Difference of survival time between rats and mice was remarkable at low concentrations but small at high concentrations. Spleen weight decreased significantly and kidney weights tended to increase at 2000 ppm or greater exposure concentrations. Difference between wet and dry lung weight in the exposure group was significantly greater than that in the control group, especially for high concentrations, which suggested pulmonary edema or bronchopneumonia.     

Semisynthesis of new sarcophine derivatives with chemopreventive activity

The natural cembranolide sarcophine (3) and its lactone ring-opened analogue (10) were oxidized using selenium dioxide under different reaction temperatures to prepare hydroxylated derivatives. Nine new compounds were obtained, six of them targeted hydroxylated derivatives. The determination of regio- and stereochemistry as well as the mechanistic considerations on the selectivity observed in these reactions are discussed on the basis of 2D NMR and molecular modeling. In preliminary in vitro tests on inhibition of EBV-EA activation, compounds 10 and 12-15 have shown higher activity than the known chemopreventive agent sarcophytol A.     

Preoperative diagnosis of lymph node metastases in gastric cancer by magnetic resonance imaging with ferumoxtran-10

Background Knowledge regarding the presence and location of lymph node metastasis in gastric cancer is essential in deciding on the operative approach. Lymph node metastases have been diagnosed with imaging tests such as computed tomography (CT) and ultrasonography (US); however, the accuracy of such diagnoses, based on size and shape criteria, has not been adequate. Ferumoxtran-10 (Combidex; Advanced Magnetics) is a lymphotropic contrast agent for magnetic resonance imaging (MRI) whose efficacy for the detection of metastatic lymph nodes in various cancers has been reported by several investigators; however, its efficacy for this purpose has not been reported for gastric cancer. We investigated the efficacy of ferumoxtran-10-enhanced MRI for the diagnosis of metastases to lymph nodes in gastric cancer. Methods Seventeen consecutive patients who were diagnosed with a nonearly stage of gastric cancer were enrolled in the study. All the patients were examined by MRI (Signa Horizon 1.5 T; GE Medical; T2*-weighted images) before and 24 h after the intravenous administration of ultrasmall particles of superparamagnetic iron oxide — ferumoxtran-10 (2.6 mg Fe/kg of body weight) — and the presence or absence of metastasis was determined from the enhancement patterns. The imaging results were compared with the corresponding histopathological findings following surgery. Results Of 781 lymph nodes dissected during surgery, the imaging results of 194 nodes could be correlated with their histopathological findings. Fifty-nine lymph nodes from 11 patients had histopathological metastases. In nonaffected normal lymph nodes, we observed dark signal intensity on MRI caused by the diffuse uptake of the contrast medium by macrophages resident in the lymph nodes, which phagocytose the iron oxide particles of ferumoxtran-10. The number of phagocytic macrophages was decreased in metastatic lymph nodes, and they showed various patterns of decreased uptake of ferumoxtran-10. Three enhancement patterns were observed in lymph nodes: (A) lymph nodes with overall dark signal intensity due to the diffuse uptake of ferumoxtran-10; (B) lymph nodes with partial high signal intensity due to partial uptake; and (C) no blackening of lymph nodes due to no uptake of ferumoxtran-10. Patterns (B) and (C) were defined as metastatic. The sensitivity, specificity, positive predictive value, negative predictive value, and overall predictive accuracy of postcontrast MRI were 100% (59/59), 92.6% (125/135), 85.5% (59/69), 100% (125/125), and 94.8% (184/194), respectively. These parameters for predictive accuracy were much superior to these parameters previously evaluated by CT or US. Nodes in the retroperitoneal and paraaortic regions were more readily identified and diagnosed on the MR images than those in the perigastric region. Conclusion The present study confirmed that ferumoxtran-10-enhanced MRI is useful in the diagnosis of metastatic lymph nodes and that the use of this modality will be helpful in treatment decision-making for gastric cancer patients.     

Tuberculous peritonitis defying diagnosis: Report of a case

(Received for publication on Feb. 10, 1999; accepted on Nov. 11, 1999)     

Expression of glycolipids bearing Lewis phenotypes in tissues and cultured cells of human gynecological cancers.

Transformation-associated expression of Le(b) (Lewis antigen-b) or Le(Y) in human colorectal carcinomas has been well described. To examine the expression of glycosphingolipids (GSLs) bearing Lewis-phenotypes in human gynecological carcinoma-derived cells, we determined the concentrations of all GSLs. Although neither Le(b) nor Le(Y) was present in HEC-108 cells established from the poorly differentiated type of endometrial adenocarcinoma, other cell lines from moderately or well-differentiated types expressed either Le(b) or Le(Y), or both, at concentrations of 0.01 to 0.03 microg per mg of dry cells, which comprised 0.3 to 1.3% of the total GSLs. In the cervical and ovarian carcinoma-derived cell lines, Lewis phenotypes tended to be carried by nLc(4)Cer, which was accumulated in the cells without sialylation or fucosylation. These results indicated that expression of Le(b)- or Le(Y)-phenotypes was strongly dependent on the metabolic ability to supply the precursor GSLs. Both Le(b) and Le(Y) were successfully detected by monoclonal antibody MSN-1, which was a useful probe for the simultaneous detection of Le(b) and Le(Y). On application of MSN-1, either Le(b) or Le(Y) was detected in tissues from patients with well- and moderately differentiated types of endometrial adenocarcinoma at concentrations of 0.01 to 0.04 microg per mg of dry tissues, but not in the tissues of poorly differentiated type. Normal endometria at the follicular and luteal phases also contained the antigens, but the concentrations and the frequency of antigen expression were lower than those in the well- and moderately differentiated types of endometrial adenocarcinoma.     

Expression of Glycolipids Bearing Lewis Phenotypes in Tissues and Cultured Cells of Human Gynecological Cancers

Transformation-associated expression of Le^b (Lewis antigen-b) or Le^Y in human colorectal carcinomas has been well described. To examine the expression of glycosphingolipids (GSLs) bearing Lewis-phenotypes in human gynecological carcinoma-derived cells, we determined the concentrations of all GSLs. Although neither Le^b nor Le^Y was present in HEC-108 cells established from the poorly differentiated type of endometrial adenocarcinoma, other cell lines from moderately or well-differentiated types expressed either Le^b or Le^Y, or both, at concentrations of 0.01 to 0.03 μg per mg of dry cells, which comprised 0.3 to 1.3% of the total GSLs. In the cervical and ovarian carcinoma-derived cell lines, Lewis phenotypes tended to be carried by nLc₄Cer, which was accumulated in the cells without sialylation or fucosylation. These results indicated that expression of Le^b- or Le^Y-phenotypes was strongly dependent on the metabolic ability to supply the precursor GSLs. Both Le^b and Le^Y were successfully detected by monoclonal antibody MSN-1, which was a useful probe for the simultaneous detection of Le^b and Le^Y. On application of MSN-1, either Le^b or Le^Y was detected in tissues from patients with well- and moderately differentiated types of endometrial adenocarcinoma at concentrations of 0.01 to 0.04 μg per mg of dry tissues, but not in the tissues of poorly differentiated type. Normal endometria at the follicular and luteal phases also contained the antigens, but the concentrations and the frequency of antigen expression were lower than those in the well- and moderately differentiated types of endometrial adenocarcinoma.     

Facial nerve near the external auditory meatus in man: Computer reconstruction study—Preliminary report

The anatomy of the facial nerve relative to its intratemporal and extratemporal courses varies over time with developmental changes. Otologic and parotid surgery in infants and children demands detailed knowledge of the precise anatomy of the facial nerve with respect to the tympanic ring and external auditory canal, The authors analyzed this area using our three-dimensional (3-D) computer-aided reconstruction and measurement method studying the spatial relations of the facial nerve to the tympanic ring and stylomastoid foramen. Temporal bones from five normal individuals aged 36 gestational weeks, 3 months, 8 months, 4 years, and 17 years were retrieved from the temporal bone collection stored at the Elizabeth McCullough Knowles Otopathology Laboratory in Pittsburgh. Three-dimensional reconstruction of the facial nerve comparing the developmental anatomy across the various age groups provides the surgeon with the technical information necessary to address problems in this area.     

Psychological distress following first recurrence of disease in patients with breast cancer: prevalence and risk factors

Purpose: To investigate the effect of understanding their own disease by patients with metastatic breast cancer on their survival potential after being informed by their physician. Patientsandmethods: Two hundred and fourteen women with metastatic breast cancer who participated in a multi-institutional, randomized phase III trial (Japan Clinical Oncology Group (JCOG) Study 8808) were asked whether they understood their own disease after being given information about the clinical trial. They were classified into two groups on the basis of whether they understood or not. We estimated their survival after the time of registration and derived relative hazard ratios from Cox's proportional hazards model. Results: There were 190 patients in the better understanding group and 24 in the poor understanding group. Median survival times after registration were 28.3 and 16.1 months, respectively. The better understanding group showed a significant difference from the poor understanding group (p=0.016). In multivariate regression analysis, patients who did not understand still showed poorer survival than those who understood (hazard ratio = 2.09; 95% confidence interval (CI) 1.16–3.78; p=0.014)