Arsenite-induced thymus atrophy is mediated by cell cycle arrest: a characteristic downregulation of E2F-related genes revealed by a microarray approach.

Thymus atrophy is induced by a variety of chemicals, including environmental contaminants and is used as a sensitive index to detect their adverse effects on lymphocytes. In the present study we adopted a toxicogenomics approach to identify the pathways that mediate the atrophy induced by arsenite. We also analyzed gene expression changes observed in the course of thymus atrophy by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), dexamethasone (DEX), and estradiol (E2), to determine whether arsenite induces atrophy by activating an arsenite-specific pathway or the same pathways as other chemicals. These compounds were intraperitoneally administered to C57BL/6 mice at doses that reduce thymus weight by approximately 30% within 3 days, and gene expression changes in the thymus 24 h after the administration were analyzed by using microarrays and real-time PCR. The microarray analysis showed that arsenite specifically downregulates a variety of E2F target genes that are involved in cell cycle progression. The same genes were also downregulated when mouse B-cell lymphoma A20 cells were exposed to arsenite. Arsenite exposure of the A20 cells was confirmed to induce cell cycle arrest, mainly in the G(1) phase, and reduce cell number. Cell cycle arrest in the G(1) phase was also confirmed to occur in the thymocytes of the arsenite-exposed mice. These results indicate that arsenite induces thymus atrophy through E2F-dependent cell cycle arrest. The results of this study also show that analysis of gene expression in thymuses is a useful method of obtaining clues to the pathways that mediate the effects of atrophy-inducing chemicals.     

Gastrin Receptor Gene Expression in Several Human Carcinomas

Gastrin has been shown to enhance the growth of various human tumors. The present study was designed to examine the gastrin receptor gene expression in various human carcinoma cell lines and in surgically resected carcinoma tissues. By Northern blot analysis, gastrin receptor mRNA was detected in 3 out of 7 small cell lung carcinoma cell lines. Gastrin receptor mRNA was also expressed in one out of 8 colon carcinoma cell lines and 2 out of 10 colon carcinoma tissues. Moreover, one of two small cell carcinoma cell lines of the stomach clearly expressed gastrin receptor mRNA. However, none of the gastric adenocarcinoma cell lines or surgically resected gastric adenocarcinomas tested had any detectable expression of gastrin receptor gene. These findings may suggest a role of gastrin receptor in the growth and differentiation of certain human carcinomas.     

An integrated inpatient therapy for type 1 diabetic females with bulimia nervosa: a 3-year follow-up study

OBJECTIVE: To describe an "integrated inpatient therapy" for type 1 diabetic patients with recurrent binge eating and to assess its effectiveness for females with bulimia nervosa (BN). METHODS: At the first visit to our outpatient clinic for treatment of an eating disorder and diabetes, type 1 diabetic females with BN underwent single session "outpatient counseling." All patients then returned to the referring physician for further treatment and observation. None of the BN patients had the minimum expected 1% fall in HbA1c and all were therefore encouraged to undergo our "integrated inpatient therapy." However, only patients accepting inpatient treatment on their own volition were admitted. An "INPATIENT" group (n=9) consisted of those who underwent inpatient therapy and had a 3-year follow-up period after discharge. The clinical course was assessed by the HbA1c and BMI course and by comparison of psychological/behavioral factors between baseline and follow-up. For reference, the clinical course of a "NON-INPATIENT" group (n=10), who did not have the inpatient therapy for at least 2 years after first visit, was also assessed. RESULTS: The "INPATIENTs" had significantly lower HbA1c; lower psychological test scores related to eating disorder psychopathology, depressiveness, and anxiety-proneness; a reduced frequency and amount of binge eating; and fewer patients exhibited purging behaviors at follow-up than at first visit. At follow-up, seven (78%) "INPATIENTs" no longer fulfilled any criterion for clinical or subclinical eating disorders. The "NON-INPATIENTs" had no significant improvement. CONCLUSION: The findings give interesting insights into the possibilities of "integrated inpatient therapy" as an effective treatment for type 1 diabetic females with BN.     

Increased oxidative stress with elevated serum thioredoxin level in patients with coronary spastic angina

BACKGROUND: Increased oxidative stress has been implicated in the pathogenesis of coronary vasospasm. Thioredoxin (TRX) is a redox-active protein that is known to be induced by oxidative stress. HYPOTHESIS: The serum TRX level may be high in patients with coronary vasospasm. METHODS: The serum TRX level was determined using an enzyme-linked immunosorbent assay in 21 patients with the active stage of coronary spastic angina (CSA), in 18 patients with the inactive stage of CSA (iCSA), in 24 control subjects without coronary artery disease (Control), and in 20 patients with stable effort angina (SEA). RESULTS: Serum TRX levels (mean +/- standard deviation ng/ml) were significantly higher in CSA (64 +/- 44) than in iCSA (28 +/- 26), in Control (34 +/- 15), and in SEA (36 +/- 16). In contrast, serum alpha-tocopherol levels (mg/g lipids) were significantly lower in CSA (2.8 +/- 0.7) than in Control (4.0 +/- 1.2) and in SEA (3.2 +/- 0.4). Current smoking was significantly more prevalent in CSA (76%) than in any of the other groups. No significant correlation was found between the serum level of TRX and alpha-tocopherol in the study subjects. In nine patients with CSA, the serum TRX level decreased (93 +/- 41 --> 41 +/- 35 ng/ml) and the alpha-tocopherol level increased (2.7 +/- 0.6 --> 3.2 +/- 0.7 mg/g lipids) significantly under medication with calcium entry blockers after an at least 3-month angina-free period. CONCLUSIONS: Patients with coronary spastic angina had a higher serum TRX level associated with a lower serum level of antioxidant vitamin E, with redox equilibrium appearing to be related to the disease activity of coronary vasospasm in these patients. Oxidative stress may be related to the genesis of coronary vasospasm.     

Low dose exposure to cadmium and its health effects (1). Genotoxicity and carcinogenicity

We reviewed studies on genotoxicity and carcinogenicity of cadmium (Cd). Salmonella typhimurium and Escherichia coli exposed to Cd did not show mutagenicity, whereas cultured mammalian cells exposed to Cd showed mutation, DNA strand breaks, and chromosomal aberrations. Carcinogenicity tests showed that exposure to Cd increased the occurrence of tumors in testis, lung, prostate, hematopoietic tissues, and injection sites. On the other hand, recent epidemiologic studies are not supportive of earlier observations on the association between Cd and prostate cancer. The US NIOSH data on a possible association between Cd and lung cancer may need reevaluation. No studies which show a positive relationship between oral Cd exposure and carcinogenesis have been reported. All available data suggest that Cd should be reassigned to IARC Group 2A (probably carcinogenic to humans) from the current Group 1.     

A new medical education using a lung sound auscultation simulator called "Mr. Lung"

We developed a lung sound auscultation simulator "Mr. Lung" in 2001. To improve the auscultation skills of lung sounds, we utilized this new device in our educational training facility. From June 2001 to March 2002, we used "Mr. Lung" for our small group training in which one hundred of the fifth year medical students were divided into small groups from which one group was taught every other week. The class consisted of ninety-minute training periods for auscultation of lung sounds. At first, we explained the classification of lung sounds, and then auscultation tests were performed. Namely, students listened to three cases of abnormal or adventitious lung sounds on "Mr. Lung" through their stethoscopes. Next they answered questions corresponding to the portion and quality of the sounds. Then, we explained the correct answers and how to differentiate lung sounds on "Mr. Lung". Additionally, at the beginning and the end of the lecture, five degrees of self-assessment for the auscultation of the lung sounds were performed. The ratio of correct answers for lung sounds were 36.9% for differences between bilateral lung sounds, 52.5% for coarse crackles, 34.1% for fine crackles, 69.2% for wheezes, 62.1% for rhonchi and 22.2% for stridor. Self-assessment scores were significantly higher after the class than before. The ratio of correct lung sound answers was surprisingly low among medical students. We believe repetitive auscultation of the simulator to be extremely helpful for medical education.     

DNA damage triggers imbalance of proliferation and apoptosis during development of preneoplastic foci in the liver of Long-Evans Cinnamon rats

The mutant strain Long-Evans Cinnamon (LEC) rat accumulates copper, resulting in spontaneous hepatitis and subsequent development of hepatocellular carcinomas (HCCs) in the liver, providing a promising model for investigation of the relationship between hepatitis induced by oxidative stress and hepatocarcinogenesis. We examined DNA strand breaks in peripheral blood cells and p53 expression in livers during acute and chronic hepatitis in LEC rats, along with preneoplastic lesions, and cell proliferation and apoptosis in non-cancerous portions of livers from LEC rats aged 7-115 weeks. Immunohistochemistry using antibodies against glutathione S-transferase placental-form (GST-P), proliferating cell nuclear antigen (PCNA), and in situ DNA nick labeling (TUNEL) were used. Long-Evans Agouti (LEA) rats, a sibling line of the LEC strain, were used as controls. In the LEC rats, DNA strand breaks and expression of p53 were significantly higher than that of LEA rats at 24 weeks of age. The number of GST-P-positive (GST-P+) foci/cm2 increased and peaked at 48 weeks old, and the areas rapidly expanded thereafter. The level of cell proliferation increased with the development of hepatitis and was highest at about 48 weeks old. The induction of apoptosis in LEC rats was transiently higher than that in LEA rats during the period from 24 to 34 weeks of age. However, the ratio of PCNA-positive cells to the apoptotic index showed a growth imbalance in favor of cell proliferation, supporting sustained net growth in LEC rats. These findings suggest that DNA damage, reflected in DNA strand breaks, plays a critical role in the development of hepatocellular preneoplastic foci, with an imbalance between high proliferation and relatively low apoptosis.     

Body shape preference and body satisfaction in Taiwanese college students

This study examined differences in measures of perception of body shape and body satisfaction among 25 male and 165 female undergraduates. The students completed a body image questionnaire, comprised of four parts: (1) anthropometric data; (2) figure rating scale; (3) cognitive attitude toward body size; and (4) satisfaction with body characteristics. This study found that male ratings of the Ideal figure, the figure of how they currently thought they looked, and the figure of how they felt most of time were almost identical, as were the figure of what they thought most attractive to women and the figure of how they thought others saw them. On the contrary, female ratings of the Ideal figure were significantly thinner than their perception of their current figure, the figure as others saw them, and the figure they felt most of time. Furthermore, the female figure that women rated as most attractive to males was thinner than the figure that males actually preferred. On the other hand, male judgments of the male figure most attractive to females were heavier than female ratings of the same. Both males and females erred in estimating what the opposite sex would find attractive. Males overestimated and females underestimated the body size attractive to the other sex. Although over half of the male and female subjects reported their body size as 'In-between', more males wanted to gain weight and more females wanted to lose weight to present their Ideal body shape. Furthermore, males were biased toward being satisfied with their body and females were biased toward being dissatisfied with their body. Additionally, the number of females satisfied with hands and dissatisfied with upper thighs and buttocks was higher than that of males.     

Oral L-arginine prevents murine coxsackievirus B3 myocarditis

We have previously demonstrated that administration of nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), aggravated murine coxsackievirus B3 myocarditis. In the present study, we evaluated the effects of L-arginine, a precursor of NO, upon acute and chronic myocarditis. Dietary L-arginine and L-arginine plus L-NAME (L-arginine+L-NAME group) were administered to coxsackievirus B3 (CB3)-infected C(3)H/He mice for 2 weeks (experiment I), and to CB3-infected mice from the second week until the fourth week after virus inoculation (experiment II). Infected control was prepared in each experiment. In experiment I, survival was higher in the L-arginine group compared with the other two groups, and cardiac damage was less. In addition, plasma concentrations of L-arginine and NO were elevated in the L-arginine group. In experiment II, cardiomyopathic lesion in the L-arginine group was less prominent associated with lower plasma catecholamine and lower myocardial collagen concentrations compared with the other two groups. Thus, L-arginine treatment may be effective not only in preventing the development of acute CB3 myocarditis but in ameliorating cardiac dysfunction in chronic myocarditis.     

Psychological changes and group dynamics during confinement in an isolated environment

PURPOSE: Cultural and personal traits will become important as the number of short-duration spaceflights of international crews supporting the International Space Station (ISS) increases and more people begin staying aboard ISS for longer durations. This project investigated the interpersonal and personal changes of Japanese subjects during a 1-wk stay in the Japanese Experiment Module. The Giebetaen Test (GT) was used to determine if the cultural background and personality traits of the subjects become more explicit and stronger during isolation. METHODS: Six males and two females aged 22-28 yr participated in the study. They stayed 7 d in the isolation chamber at the National Space Development Agency of Japan (NASDA). The GT was chosen as an individual and group diagnostic instrument; it was administrated four times during, and one time after, isolation. RESULTS: According to the GT-self-picture, subjects exhibited a change toward negative social resonance and social withdrawal. Subgroups formed but caused no isolation or tension. The GT-foreign-pictures showed that the judgment of other subjects changed toward hedonic and permeability directions. The common interpersonal relationships of the Japanese subjects influenced the group dynamics. These relationships tend to be integrative and tend to support the network and value systems, emphasizing connectedness and minimizing differences. CONCLUSION: The cultural background became more explicit and stronger during isolation. Based on this, isolation studies with international crews and intercultural training will be necessary for international crews performing both short- and long-duration missions.