Takotsubo cardiomyopathy

Takotsubo cardiomyopathy (TC) is characterized by transient left ventricular apical wall motion abnormalities, chest pain with electrocardiographic changes, and modest myocardial enzymatic release mimicking acute coronary syndrome, but without significant coronary artery disease. TC is an increasingly recognized type of acquired cardiomyopathy occurring commonly after a recent stressful event, in particular emotional stress, and is relatively common in middle-aged and older women. The pathogenetic mechanism remains unknown. Catecholamine surge related to emotional distress seems to play a major role in the pathogenesis of this cardiomyopathy, rendering TC a type of neurocardiological disorder that manifests as acute but reversible heart failure. Clinicians should consider this syndrome in the differential diagnosis of patients presenting with clinical findings suggestive of acute coronary syndrome, especially in postmenopausal women with a recent history of acute emotional or physical stress.     

Hepatic tumors induced by carbon tetrachloride in transgenic mice carrying a human c-H-ras proto-oncogene without mutations

Hepatic tumors were generated in mice by repeated administration of carbon tetrachloride (CCI₄). Eight transgenic (Tg) mice carrying a human c-H-ras proto-oncogene (rasH2 line) and 9 non-Tg mice were killed at 20 weeks. Tg mice developed more tumors than did non-Tg littermates. Most tumors were neoplastic nodules, but I hepatocellular carcinoma (HCC) was found in a Tg mouse at 20 weeks. Three Tg and 2 non-Tg mice were kept without further administration of CCI₄. Two Tg mice died at 30 weeks of HCC with intra-abdominal bleeding, and I Tg mouse developed HCC with a mesenteric metastasis at 32 weeks. No HCC was found in 2 non-Tg mice at 32 weeks. Although mutations at codon 12, 13, and 61 of the H-ras gene are often found in murine hepatocarcinogenesis, neither the tumors, including one HCC, nor the normal cells revealed any such mutations. These results showed that the unmutated human c-H-ras gene facilitates malignant transformation of hepatocytes when continuous liver-cell death and regeneration is caused by repeated administration of CCI₄. © 1994 Wiley-Liss, Inc.     

Rapid induction of more malignant tumors by various genotoxic carcinogens in transgenic mice harboring a human prototype c-Ha-ras gene than in control non-transgenic mice

In this study, we investigated the carcinogenic response oftransgenic mice carrying the human prototype c-Ha-ras gene,namely Tg rasH2/CB6F1 mice, to various genotoxic carcinogensand compared it with that of control non-transgenic CB6F1 mice(non-Tg mice). The present studies were conducted as the firststep in the evaluation of the Tg rasH2/CB6F1 mouse as a modelfor the rapid carcinogenicity testing system. Short-term (     

The mouse rasH2/BHT model as an in vivo rapid assay for lung carcinogens.

We have demonstrated the utility of a 9-week in vivo two-stage assay for lung cancer initiating agents, using transgenic mice carrying the human prototype c-Ha-ras gene (rasH2 mice) and butylhydroxytoluene (BHT) as a potent lung promoter (rasH2/BHT model). In the present study, to ascertain appropriate conditions for BHT administration in this model, the effects of exposure on proliferation of alveolar type II cells in male rasH2 mice were examined. Additionally, use of BHT was validated for promotion of urethane (UR) carcinogenesis in male and female rasH2 mice. In a time-course study of a single intragastric administration of BHT at a dose of 400 mg/kg, increased bromodeoxyuridine-labeling index (LI) reached a maximum 3 days after treatment and was still observed after 7 days. In a dose-response study, effects were dose-dependent, the dose of 400 mg/kg causing eight-fold elevation as compared to the control. With repeated administration, whereas the LI was increased dramatically at first, effects gradually diminished with further exposure, and finally six BHT treatments failed to induce cell proliferation. In a two-stage model using UR as the initiator, although up to five consecutive doses of BHT were able to exert continued enhancing effects in terms of adenoma yield, no increment was evident with further treatments. The data overall indicate that a rasH2/BHT model with five weekly administrations of BHT at a dose of 400 mg/kg is most efficacious.     

The Mouse rasH2/BHT Model as an in vivo Rapid Assay for Lung Carcinogens

We have demonstrated the utility of a 9–week in vivo two-stage assay for lung cancer initiating agents, using transgenic mice carrying the human prototype c-Ha- ras gene (rasH2 mice) and butylhydroxytoluene (BHT) as a potent lung promoter (rasH2/BHT model). In the present study, to ascertain appropriate conditions for BHT administration in this model, the effects of exposure on proliferation of alveolar type II cells in male rasH2 mice were examined. Additionally, use of BHT was validated for promotion of urethane (UR) carcinogenesis in male and female rasH2 mice. In a time-course study of a single intragastric administration of BHT at a dose of 400 mg/kg, increased bromodeoxyuridine-labeling index (LI) reached a maximum 3 days after treatment and was still observed after 7 days. In a dose-response study, effects were dose-dependent, the dose of 400 mg/kg causing eight-fold elevation as compared to the control. With repeated administration, whereas the LI was increased dramatically at first, effects gradually diminished with further exposure, and finally six BHT treatments failed to induce cell proliferation. In a two-stage model using UR as the initiator, although up to five consecutive doses of BHT were able to exert continued enhancing effects in terms of adenoma yield, no increment was evident with further treatments. The data overall indicate that a rasH2/BHT model with five weekly administrations of BHT at a dose of 400 mg/kg is most efficacious.     

In vivo gene transfer into the adult mammalian central nervous system by continuous injection of plasmid DNA–cationic liposome complex

Previously reported methods of liposome-mediated direct in vivo gene transfer have been inefficient, especially when performed with highly differentiated, quiescent cells of the adult mammalian central nervous system (CNS). We have therefore improved these procedures based upon a novel concept. Following continuous injection of plasmid DNA–cationic liposome complex which contained a reporter gene encoding E. coli β-galactosidase into the striatum of adult rats, the expression of transgene was dramatically elevated without any adverse effects. This new technique may enable a wide application of liposome-mediated gene transfer technology not only to basic analysis of gene functions in the brain but also for clinical treatment of certain CNS disorders.     

Effect of steroid on antiemetic for side effect of anticancer chemotherapy

The side effect of anticancer agents such as nausea and vomiting frequently interrupt chemotherapy. To reduce these side effects, 5-hydroxytryptamine (5-HT3) receptor antagonist or metoclopramide is administered combined with steroid. In this study, we examined the effect of 5-HT3 receptor antagonist on the frequency of nausea and vomiting in a male cancer patient treated with/without steroid. This patient in his sixties had esophageal cancer (stage IV). He was administered nedaplatin 100 mg/day for 1 day and then 5-fluorouracil (5-FU) 750 mg/day for 5 days combined with radiotherapy (60 Gy) as one cycle of this chemotherapy. In the first cycle, 5-HT3 receptor antagonist was administered, and in the second, the antagonist was administered after treatment with steroid. The blood levels of total bilirubin, GOT, GPT, BUN, Cre, Na, K and Cl were stable normally during both cycles of the chemotherapy, indicating that the hepatopathy and nephropathy which cause nausea and vomiting did not occur in these periods. The frequency and period of the nausea and vomiting were one-third decreased, respectively, by the combination of 5-HT3 receptor antagonist and steroid.