A case-control study of breast cancer among Japanese women: with special reference to family history and reproductive and dietary factors

Summary To study the effects of family history and reproductive, anthropometric, and dietary factors on the risk of breast cancer among low risk populations, we conducted a hospital-based case-control study involving 908 patients with breast cancer and their matched controls, in Japan. A positive family history of breast cancer significantly increased the risk of breast cancer (odds ratio = 1.52, 95% confidence interval: 1.14–2.03). The risk further increased with increasing number of family members affected. Obesity, single marital status, fewer births, a late childbirth, and less consumption of green-yellow vegetables and dairy products were also associated with an increased risk of breast cancer. These associations were independent in multivariate analyses. There was no increase in risk associated with consumption of high fat foods. When analyzed by menopausal status, the association with family history of breast cancer, especially in the first degree of relatives, was more evident for premenopausal breast cancer. The associations with obesity and lower consumption of dairy products were more pronounced for postmenopausal breast cancer, while those with lower parity and single marital status were stronger for premenopausal breast cancer.     

CCR1 acts downstream of NFAT2 in osteoclastogenesis and enhances cell migration.

We found that a chemokine receptor gene, CCR1, acts downstream of NFAT2 in RANKL-stimulated RAW264 and bone marrow cells. The upstream regulatory region of CCR1 showed RANKL-dependent and CsA-suppressible promoter activity. Downregulation of the expression and function of CCR1 suppressed cell migration. INTRODUCTION: We previously reported that the expression of NFAT2 induced by RANKL is a key process for progression to multinucleated cells in an in vitro osteoclastogenesis system. Identifying the target genes of NFAT2 would thus be informative about the differentiation process. We focused here on chemokine and chemokine receptor genes that act downstream of NFAT2 in RAW264 cells as well as osteoclast precursors prepared from bone marrow cells. MATERIALS AND METHODS: RAW264 mouse monocyte/macrophage line cells were cultured with or without cyclosporin A (CsA) in the presence of RANKL or glutathione S-transferase (GST). Osteoclast precursors were prepared from bone marrow cells. RANKL-inducible and CsA-suppressible genes were searched for by microarray analysis, and expression was confirmed by quantitative RT-PCR. Promoter activity was measured by luciferase gene reporter assay. Short interfering (si)RNA for CCR1 was introduced in RAW264 cells. Cell migration activity was examined using a Boyden chamber assay. RESULTS AND CONCLUSIONS: We identified the chemokine receptor gene CCR1 as a gene showing significant differential expression profiles in osteoclastogenesis in the presence versus the absence of CsA, an inhibitor of NFAT. This property was unique to CCR1 among the chemokine and chemokine receptor genes examined in both RAW264 and bone marrow cells. The upstream regulatory region was isolated from CCR1, and its RANKL-dependent and CsA-suppressible promoter activity was confirmed. The functional significance of CCR1 was assessed by monitoring the migration of cells in a transwell migration assay, and this activity was abolished when either CsA- or CCR1 siRNA-treated cells were used. Moreover, treatment with a Galpha inhibitor pertussis toxin (PTX) or methiolynated-regulated on activation, normal T cells expressed and secreted (Met-RANTES), an antagonist of CCR1, suppressed multinucleated cell formation in the bone marrow cell system. Together, these results suggest that the CCR1 signaling cascade is under the control of NFAT2 and seems to enhance the migration of differentiating osteoclasts.     

Anticonvulsant effect of liposome-entrapped superoxide dismutase in amygdaloid-kindled rats.

Amygdaloid-kindled rats received intravenous human copper-zinc superoxide dismutase (CuZn-SOD) either in free form or entrapped within liposomes (SOD-L), at 5, 10 or 20 mg/kg. The animals were stimulated at the generalized seizure-triggering threshold 5 min, 2 h and then every 24 h after the drug was given, until 5 consecutive stage 5 seizures were induced. Free CuZn-SOD had little or no effect. However, SOD-L, particularly at 10 mg/kg, had a prolonged anticonvulsant effect, although there was great individual variation in the onset and duration of seizure suppression. This effect of SOD-L may be due to the ability of liposomes to act as a depot for the sustained release of drugs.     

Relationship between the number of steps taken and body mass index for male workers in the metropolitan area]

The present study examined the relationship between number of steps and body mass index (BMI) among male workers in the metropolitan area. The number of subjects were 310 (aged 30-59) and they were studied for seven consecutive days. The number of steps was measured by a pedometer. Energy expenditure was assessed by the activity record method. Energy intake was assessed by a food frequency questionnaire. Height and body weight were examined by a self-administered questionnaire. BMI of 81 subjects (26.1%) was greater than 25 kg/m2. The number of steps was 10,682 +/- 4,365 on working days, and 7,135 +/- 4,536 on holidays. Average energy expenditure in seven days was 2,259 +/- 378 kcal/d. The physical activity level (PAL) was 1.5 +/- 0.1. There was a significant correlation between BMI and the number of steps in a working day (r=-0.188, p<0.01). In addition, there were significant correlations between PAL and daily steps on working days (r=0.301, p<0.001), and on holidays (r=0.296, p<0.001). Subjects were divided into four groups according to the median number of steps on working days and energy intake (I; > or =9,894 steps, <1,901 kcal, II; > or =9,894 steps, > or =1,901 kcal, III; <9,894 steps, <1,901 kcal, IV; <9,894 steps, > or =1,901 kcal). BMI of Group IV (24.7 kg/m2) was significantly higher than that of the other Groups. Group III had the highest proportion of subjects (15.7%) with lifestyle related diseases.     

Dental management of a patient with takotsubo cardiomyopathy: a case report.

Takotsubo cardiomyopathy (TCM) is a relatively new concept in cardiovascular disease. The clinical symptoms of TCM are similar to those of a myocardial infarction, but both the mechanism and the management of TCM are different from those of myocardial infarction. The cause of TCM is unclear, but it is suggested to occur in conjunction with excessive circulating catecholamines due to stress. Thus, control of the stress reaction and restriction of catecholamine levels are considered important for prevent of TCM onset. We report the dental management of a patient with intellectual disability who had anamnesis of TCM and cardiopulmonary arrest under restraint during a previous dental appointment in another dental clinic. We used intravenous sedation with both midazolam and propofol, by which the excessive hormonal reaction that caused TCM onset and cardiopulmonary arrest was controlled, for dental treatment in our facility. All planned dental treatment was then performed without any problems.     

Role of leukotrienes in airway hyperresponsiveness in guinea-pigs.

1. Repeated aerosolization of leukotriene C4 (LTC4) to guinea-pigs produced leftward shift in their pulmonary resistance (RL) dose-response curves to inhaled acetylcholine (ACh) without increasing the maximum responses. 2. Repeated LTC4 aerosolization did not increase airway eosinophils. 3. The 5-lipoxygenase-activating protein (FLAP) inhibitor, MK-886, prevented the leftward shift in RL dose-response curves to ACh following repeated antigen challenge in guinea-pigs. 4. MK-886 did not inhibit the increased maximal RL produced by repeated antigen challenge, nor inhibit the airway eosinophilia induced by repeated antigen challenge. 5. Our findings suggest that leukotrienes may account for the leftward shift in pulmonary resistance responses caused by antigen but do not cause the airway eosinophilia nor enhanced maximum broncho-constrictor response to antigen.     

Myasthenia gravis developing after discovery of thymoma

We report 4 cases of myasthenia gravis in which myasthenic symptoms developed after a thymoma was known to be present. They include 3 invasive thymomas and one thymoma. In 3 of them, myasthenic symptoms developed 2–7 months after removal of the thymoma; in 1 case, myasthenic symptoms developed 11 years after the thymoma was known to be present. We also discuss here the possible pathogenetic mechanism of post-thymomectomic myasthenia gravis, and propose that it is due to the natural course of the disease.     

Ventilatory response to the onset of passive and active exercise in human subjects.

Ventilatory responses at the onset of passive and active exercise with different amount of exercising muscle mass were studied in 10 healthy male subjects. Four exercise tests were performed for each subject with appropriate intervals on the same day, i.e., two voluntary exercises of one leg or both legs and two passive exercises of one leg or both legs. Inspiratory minute volume (VI), end-tidal CO2 and O2 partial pressures (PETCO2, PETO2) were measured breath-by-breath using a hot-wire flowmeter, infrared CO2 analyzer, and a rapid O2 analyzer. Average values of VI were obtained from 5 breaths at rest preceding exercise and the first and second breaths after the onset of exercise. The ventilatory response to exercise was calculated as the difference (delta) between the mean of exercise VI and mean of resting VI. In this study, the PETCO2 decreased by about 0.5 Torr in four exercise tests, though the decrement of PETCO2 was not statistically significant. The average values and standard deviation of delta VI were 4.22 +/- 1.63 l/min for the one leg and 6.46 +/- 1.80 l/min for the two legs in the active exercise, and were 2.46 +/- 1.12 l/min for the one leg and 3.44 +/- 1.55 l/min for the two legs in the passive exercise, respectively. These results suggest that in awake conditions, the ventilatory response at the onset of passive or active exercise does not increase additively with the increasing amount of muscle mass being exercised.