The effects of nucleotides and potassium channel openers on the SUR2A/Kir6.2 complex K+ channel expressed in a mammalian cell line, HEK293T cells

 The effects of potassium channel opening drugs and intracellular nucleotides on the ATP-sensitive K+ (K_ATP) channel composed of SUR2A and Kir6.2 in HEK293T cells were examined using the patch-clamp technique. The SUR2A/Kir6.2 channel was activated effectively by pinacidil, marginally by nicorandil but not by diazoxide. The pinacidil-activated channel currents were inhibited by glibenclamide with a K _i value of 160 nM. Upon formation of inside-out (I-O) patches, spontaneous openings of the channels appeared, which were inhibited by intracellular ATP (ATP_i) equipotently in the presence and in the absence of intracellular Mg²⁺ (Mg²⁺ _i). The channel activity ran-down gradually in I-O patches. The run-down channels could be reactivated by ATP_i only in the presence of Mg²⁺ _i. Uridine 5’-diphosphate (UDP) antagonized the ATP_i-mediated inhibition of the channel activity before run-down. After run-down, UDP activated the channel without antagonizing ATP_i-mediated channel inhibition. Thus, the SUR2A/Kir6.2 reproduced the major properties of the native cardiac K_ATP channel well in terms of nucleotide regulation and pharmacology, and therefore can be a useful tool with which to elucidate the molecular mechanisms characterizing the K_ATP channel. Received: 24 October 1997 / Received after revision and accepted: 4 December 1997     

Online parameter identification of second-order systemic circulation model using the delta operator

To develop effective medical care with the artificial heart, we proposed a new method that can calculate the time varying and unmeasured hemodynamics of the human body from measured physiological data: aortic pressure, aortic flow, and pump flow in real time. This method comprises first, the second order of systemic circulation model, which consists of aortic compliance (Ca), aortic resistance (Ra), aortic inertia (L), and total peripheral resistance (Rp); and second, system identification using the delta operator. In the computer simulation, we confirmed the effectiveness of this method. During the animal experiment with the left ventricular assist system, the physiological parameters could be identified online: mean Ra = 0.04 mm Hg s/ml, mean Ca = 0.65 mm Hg/ml, mean L = 0.004 mm Hg s(2)/ml, and mean Rp = 0.3 mm Hg s/ml. This new method efficiently identified the physiological parameters, which are important not only to support the medical care but also to develop the control method adapted to the physiological behavior.     

A prospective study on the possible association between having children and colon cancer risk: findings from the JACC Study

If having children is regarded as an exposure in life, its effect on a host could be considered as being due to female sex hormones associated with pregnancy in women and some lifestyle factors associated with large families in both men and women. To explore the roles of having children in the etiology of colon cancer, we examined 36,629 women and 24,877 men aged 40–79 years who completed a questionnaire on the number of children and other lifestyle factors from 1988 to 1990 in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk. During 291,080 and 200,648 person-years of follow-up, we documented 198 female and 202 male incident colon cancers, respectively. After adjusting for some factors known or suspected to modify the risk of colon cancer, compared with the women with no children, the multivariate-adjusted relative risks of colon cancer were 0.74 (95% confidence interval [CI]: 0.30–1.84) for one child, 1.00 (95% CI: 0.46–2.20) for two, 0.70 (95% CI: 0.31–1.55) for three, and 0.59 (95% CI: 0.26–1.33) for four or more. The risk of colon cancer showed a significantly monotonic decrease with increasing number of children (P value for trend=0.047). There was no association between the number of children and colon cancer risk among men. From these prospective data, having children may reduce risk of colon cancer among women, but not among men, suggesting that modifications of hormone profiles secondary to pregnancies may influence female colon cancer risk.     

External-beam radiation therapy for age-related macular degeneration: two years' follow-up results at a total dose of 20 Gy in 10 fractions

PURPOSE: The efficacy of external-beam radiation therapy (RT) was evaluated in the treatment of eyes with subfoveal or juxtafoveal choroidal neovascularization in age-related macular degeneration (ARMD). MATERIALS AND METHODS: Twenty-one eyes of 18 patients with occult or mixed-type ARMD received a total dose of 20 Gy of 6 MV X-rays in 10 fractions. The follow-up time was 24 months. Fifteen non-treated eyes of 13 patients who had been followed served as a control. RESULTS: In the RT group, visual acuity was improved in three eyes, maintained in 14 eyes, and worsened in four eyes. In the control group, it was not improved in any eyes, was maintained in six eyes, and worsened in nine eyes. The improved or maintained rate in visual acuity was 81% in the RT group and 40% in the control group (p=0.0342). In the RT group, fundoscopic and angiographic findings were improved in five eyes, unchanged in seven eyes, and worsened in nine eyes, while they were not improved in any eyes, unchanged in two eyes, and worsened in 13 eyes in the control group(p=0.0342). CONCLUSION: RT at a total dose of 20 Gy in 10 fractions is effective for ARMD for at least two years. RT may be effective treatment for occult or mixed-type ARMD compared with the classic type.     

Existential concerns of terminally ill cancer patients receiving specialized palliative care in Japan

Background Although alleviation of existential distress is important for terminally ill cancer patients, the concept of existential distress has not been fully understood. The aim of this study was to categorize existential concerns of Japanese terminally ill cancer patients and explore care strategies based on the categorizations.Methods A multicenter cross-sectional study in 88 terminally ill cancer patients receiving specialized inpatient palliative care was performed. The nurses explored patient existential concerns by asking several key questions, and recorded the answers that they considered typically described the patients concerns. All statements recorded by the nurses were analyzed using content analysis methods.Results A total of 89 statements were subjected to analysis. The categories and their prevalence were: relationship-related concerns (22%; isolation, concerns about family preparation, conflicts in relationship), loss of control (16%; physical control, cognitive control, control over future), burden on others (4.5%), loss of continuity (10%; loss of role, loss of enjoyable activity, loss of being oneself), uncompleted life task (6.8%), hope/hopelessness (17%), and acceptance/preparation (25%).Conclusions Existential concerns of Japanese terminally ill cancer patients were categorized as relationship-related concerns, loss of control, burden on others, loss of continuity, uncompleted life task, hope/hopelessness, and acceptance/preparation. These themes seemed to encompass universal human suffering beyond cultural differences, and this conceptualization may contribute to the development of effective therapeutic interventions to alleviate existential distress.This is work is presented on behalf of the Japan Pain, Rehabilitation, Palliative Medicine, and Psycho-Oncology (J-PRPP) Study Group.The study was supported by Health and Labor Sciences Research Grants, Clinical Research for Evidenced Based Medicine (2002).