| ヒトゲノム研究と21世紀の医療 |
| 中村祐輔 東京大学医科学研究所ヒトゲノム解析センター |
| 現在、世界的規模で「ヒトゲノム解析計画」が進められている。この計画は人のすべての遺伝子の働きを解明することを目的としたものであり、生命科学のアポロ計画と称されている。その成果はわれわれの生活、とりわけ、医療分野に計り知れない影響をおよぽすことが確実である。「ゲノム」とは細胞核の中に含まれているすべての遺伝子の総称であり、われわれの「生命の設計図」に相当するものである。つまり、ゲノムにはあらゆる生命現象を支配する重要な全情報が書き記されていることになる。この設計図には生きていくために必要なタンパクを必要な臓器（細胞）で必要なだけ作るようにプログラムされており、このプログラムが正しく運用されているかぎり、われわれは健康な生活を送ることができる。しかし、先天的・後天的に設計図に傷が生じたり、プログラムが正しく働かないと、疾患の発症につなかったり、疾患を起こしやすくする要因となる。したがって、この設計図に書き込まれた全暗号を解読し、必要なタンパクを作るプログラムを調節する仕組みを解明することは、いろいろな疾患の原因を明らかにさせることにつながる。疾患の発症には上述したように遺伝的要因と後天的な環境要因が複雑に関与するが、突発的な事故を除き、ほとんどの疾患には程度の差はあるものの遺伝的要因が関係している。生活習慣病と言われるような高血圧・糖尿病なども、複数の遺伝的要因に環境要因が加わって発症に至ることが明らかにされてきている。疾患遺伝子の発見や疾患を起こしやすくする遺伝的要因の特定は、画期的な診断・予防・治療法の開発へとつながっていくことは確実であり、この成果は21世紀の医療を大きく変革する。ヒトゲノム解析研究は染色体地図の作製は終了し、現在は、大量のDNA配列の決定と遺伝子の機能解析が並行して驚異的なスピードで行われている。3−5年以内には30億塩基対からなるヒトの遺伝暗号のすべてが解読され、10−20年以内には10万種類と推測されている遺伝子やその産物の機能も解明されると予測されている。ゲノム研究に基づいての疾患原因遺伝子の解明法は、遺伝子の染色体上の位置を手がかりとして疾患遺伝子を探索していく方法と遺伝子産物の機能から類推して疾患との関係を調べていく方法に大別される。前者には、複数のアプローチ法があり、その代表的なものとして、多型マーカーを利用した連鎖解析法・同胞罹患対法やアソシエーション検索、染色体異常を指標とする方法などがある。これらのうち、疾患の性質や利用可能な症例に応じて最も適切な手法を選択することが重要である。また、ヒトの疾患と同じような症状を示すマウスなどの動物モデルを利用した方法もきわめて有効である。具体的な疾患例を示しつつ、疾患遺伝子単離法の概略とゲノム研究がもたらすであろう将来の医療像について紹介したい。 |
| Health care reform for the aging and childless Society |
| Michael R. Reich Ph.D. Taro Takemi Professor of International Health Policy Department Of Population and International Health, Harvard School of Public Health |
| Japan confronts a dilemma in reshaping its health care for children: the low birth rate is reducing the proportion of children in the overail population, while the health issues for children are becoming increasingly complex and connected to sociai behavior. This presentation will begin with a brief review of Japan's changing demographics , and the declining proportion of children in the population structure. This change has important implications for how the government sets priorities in the health sector, how physicians make decisions about specialization, and how children receive care for their health issues. Each of these implications is briefly discussed. Next, the presentation will consider how 'problems' are defined in society and how the agenda for health reform is determined. Attention will be directed to the political dimensions of these two processes of problem definition and agenda setting. Several exmples of health reform for children, in other countries, will be discussed, to show how these two processes have worked in practice. In the next section, the presentation will explore some of the new health issues for children in Japan. The final section will consider the challenges to Japanese pediatricians in shaping health policy to address these new health issues for children. |
| Raising heart health in children |
| Albert P. Rocchini M.D. Director of Pediatric Cardiology ,Professor of Pediatric Michigan Congenital Heart Center, C.S. Mott Children's Hospital, University of Michigan Health System |
| My topic is "Raising Heart Health in Children". The talk will center on ways of reducing cardiovascular risk in children. I will concentrate on the areas of obesity, hypertension, hypercholesterolemia, cigarette smoking, decreased physical activity and also spend a very brief time talking about maternal factors during pregnancy that may help to predict the future heart outcome of their off spring. Overall, the lecture will deal with a brief discussion in each of the topics. It is hoped that the audience of pediatricians and pediatric sub-specialists will find information that will be useful in the management of their patients. |
| Eating disorders |
| S.Jean Emans M.D. Associate Professor of Pediatrics, Harvard Medical School Division of Adolescent Medicine, Children's Hospital, Boston |
| Eating disorders are prevalent in contemporary society, and girls commonly worry about being overweight and exhibit dieting behaviors at ages as early as 8 or 9 years old. The criteria for the diagnosis of Anorexia Nervosa (AN) , Bulimia Nervosa (BN), and Eating Disorders Not Other Specified (EDNOS) are summarized in the Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV). The prevalence for AN is estimated at 0.1-1.0 % ; 95 % are females. It has been estimated that bulimia occurs in from 3-13 % of college women. For AN, the 4 criteria include weight 15% below normal weight/height, primary or secondary amenorrhea for >3 months, intense fear of becoming fat and distorted body image. Two peaks of presentation of anorexia nervosa have been noted, at age 13 years and at 18 years, the first associated with pubertal maturation and body image concerns and the second the age of separation and choices about jobs and college. The extreme pursuit of thinness can cause delayed pubertal development, delayed menarche , secondary amerorrhea and severe bone loss. There is also the recent recognition of the "female athlete triad" (eating disorders , amenorrhea, and osteoporosis) in highly competitive young athletes, The criteria for BN include 2 binges/week for 3 months, recurrent purging behaviors, and lack of control; affective illness in common in these patients and their families. Triggers of eating disorders include previous obesity, excessive teasing about weight, depression, mild illness which initiated weight loss, death or severe illness of a close relative, or recent change in family constellation. Presenting signs for AN and/or BN may include depressed vital signs (10w temperature, blood pressure, and pulse rate), dehydration, electrolyte imbalance, fatigue, muscle weakness. dry, yellow skin, Ianugo, bruises, edema (during refeeding), murmurs (mitral valve prolapse) , Mallory Weiss tears, dental cavities, abdominal bloating, constipation, cold intolerance, suicide attempts, and stress fractures. Selective Questions posed to the teen and the family are key in making the appropriate diagnosis, assessing co-morbid conditions, and formulating a diagnostic and treatment plan. The laboratory tests ordered depend on presentation and the history of the patient. Effective treatment requires a multidisciplinary approach including a pecliatrician, nutritionist, psychotherapist for the patient and the family, psychopharmacologist, and a school counselor/nurse. For AN, the goal is rapid nutritional improvement and return of menses (usually at 92ｱ7% of Ideal Body Weight) to prevent further bone loss; the patient must understand that her adolescent years are critical for her accruing normal bone mass and that normal weight/height, calcium and vitamin D intake, normal physical activity levels, genetic factors, and estrogenization play important roles in this process. Bone density needs to be monitored, and patients may desire to participate in research studies examining the role of estrogen, androgens and lgF-1 in the treatment of bone loss. Hospitalization is indicated for unstable vital signs, severe malnutrition, dehydration, electrolyte abnormality, acute food refusal, uncontrollable bingeing and purging and suicidality. The prognosis for AN in the U.S. is that 50% do well, 25% do poorly (mortality 5%), and 25% have an intermediate outcome. Prevention should include education of teens, families, coaches, and the media to lessen the emphasis on thinness as desirable in society and to provide positive and realistic images of women. New research directions include better screening tools for pediatricians and new treatment modalities (nutritional, behavioral , medical and pharmacologic) . |