1型プロコラーゲンC末端プロペプチドおよび1型コラーゲン・cross-linked carboxyterminal telopeptideを用いた胎児期骨代謝の特徴の検討

我々は,胎児の生理的な骨代謝を検討するため,骨形成および骨吸収に関する指標を検討した.検査の意義と方法を説明し,母から承諾の得られた74例の新生児(何も合併症のない早期産児34例,満期産児40例)における臍帯血および1歳未満の健康乳児8例の末梢血の血中P1CP(1型プロコラーゲンC末端プロペプチド)と1CTP(1型コラーゲン・cross-linked carboxyterminal telopeptide)を測定した.新生児74例における膀帯血中P1CP,1CTP値は,それぞれ,1423.5±611.6,95.8±34.2ng/ml(mean±SD)であった.P1CPあるいは1CTP値と,妊娠週数,出生時体重,身長,頭囲の間にはそれぞれ有意な負の相関を認めた.(p<0.0001).妊娠週数に伴うP1CP,1CTP値の変化と,標準胎児体重増加率との関係を比べると,血中P1CPおよび1CTP値の曲線と標準胎児体重増加率の曲線はほぼ平行であった.血中P1CP,1CTP値は,出生時平均体重を等しくした妊娠週数の異なる2群間比較では,妊娠週数が少ない群ほど高値であった.また,出生時平均妊娠週数を等しくした体重の異なる2群比較では,体重が少ない群ほど高値であった.1歳未満の健康乳児8例におけるP1CP,1CTPの分析結果では,新生児の値に比し,P1CPが高値で,1CTPが低値であり,P1CP/1CTP比の平均値は新生児のそれに比べて4倍も高値であった.それに対し,出生児のP1CP/1CTP比の平均値は早期産児,満期産児に関係なく一定であった.我々の今回の検討結果から,胎生児期における骨代謝は著しく活発であり,その身体の発育と妊娠週数が骨代謝に強く関連している.また未熟児の骨代謝は未熟性が強いほど高回転性であり,!歳までの乳児では骨形成が優位に起こっている.In an effort to elucidate the physiology of fetal bone metabolism, we studied markers of bone formation and resorption. Cord blood levels of P1CP (the carboxy-terminal propeptide of type 1 procollagen) and 1CTP (the pyridinoline cross-linked carboxy-terminal telopeptide of type 1 collagen) were measured in 74 newborns (40 healthy newborns, 34 preterm newborns with no complications) at birth and 8 healthy infants during the first year of life. The cord blood levels of P1CP and 1CTP in the 74 newborns were 1423.5 ± 611.6 and 95.8 ± 34.2 ng/ml (mean ± SD), respectively. There were significant negative correlations between the concentra-tions of P1CP or 1CTP and gestational age, birth weight, birth length and head circumference (p<0.0001). Comparisons among the levels of P1CP and 1CTP and the rate of standard fetal weight gain, revealed the curves of P1CP and 1CTP levels to nearly parallel the curves of the standard fetal weight gain rate in male and female newborns. P1CP and ICTP levels corresponded to birth weight as well as gestational age, with the influences of other factors being negligible. We also assayed P1CP and 1CTP in 8 healthy infants under one year of age, and found that a high P1CP value and low 1CTP value resulted in a 4-fold increase in the mean P1CP/1CTP ratio, as compared to the newborns. In contrast, the P1CP/1CTP ratio was nearly constant during the preterm and term periods. The results suggest that high turnover reflects high bone remodeling activity which corresponds to rapid morphological changes in the fetal period, that high turnover processes are strongly associated with physical growth as well as gestational age in immature fetal bone and that bone formation is the dominant process in healthy infants during the first year of life

1型プロコラーゲンC末端プロペプチドおよび1型コラーゲン・cross-linked carboxyterminal telopeptideを用いた胎児期骨代謝の特徴の検討

我々は,胎児の生理的な骨代謝を検討するため,骨形成および骨吸収に関する指標を検討した.検査の意義と方法を説明し,母から承諾の得られた74例の新生児(何も合併症のない早期産児34例,満期産児40例)における臍帯血および1歳未満の健康乳児8例の末梢血の血中P1CP(1型プロコラーゲンC末端プロペプチド)と1CTP(1型コラーゲン・cross-linked carboxyterminal telopeptide)を測定した.新生児74例における膀帯血中P1CP,1CTP値は,それぞれ,1423.5±611.6,95.8±34.2ng/ml(mean±SD)であった.P1CPあるいは1CTP値と,妊娠週数,出生時体重,身長,頭囲の間にはそれぞれ有意な負の相関を認めた.(p<0.0001).妊娠週数に伴うP1CP,1CTP値の変化と,標準胎児体重増加率との関係を比べると,血中P1CPおよび1CTP値の曲線と標準胎児体重増加率の曲線はほぼ平行であった.血中P1CP,1CTP値は,出生時平均体重を等しくした妊娠週数の異なる2群間比較では,妊娠週数が少ない群ほど高値であった.また,出生時平均妊娠週数を等しくした体重の異なる2群比較では,体重が少ない群ほど高値であった.1歳未満の健康乳児8例におけるP1CP,1CTPの分析結果では,新生児の値に比し,P1CPが高値で,1CTPが低値であり,P1CP/1CTP比の平均値は新生児のそれに比べて4倍も高値であった.それに対し,出生児のP1CP/1CTP比の平均値は早期産児,満期産児に関係なく一定であった.我々の今回の検討結果から,胎生児期における骨代謝は著しく活発であり,その身体の発育と妊娠週数が骨代謝に強く関連している.また未熟児の骨代謝は未熟性が強いほど高回転性であり,!歳までの乳児では骨形成が優位に起こっている.In an effort to elucidate the physiology of fetal bone metabolism, we studied markers of bone formation and resorption. Cord blood levels of P1CP (the carboxy-terminal propeptide of type 1 procollagen) and 1CTP (the pyridinoline cross-linked carboxy-terminal telopeptide of type 1 collagen) were measured in 74 newborns (40 healthy newborns, 34 preterm newborns with no complications) at birth and 8 healthy infants during the first year of life. The cord blood levels of P1CP and 1CTP in the 74 newborns were 1423.5 ± 611.6 and 95.8 ± 34.2 ng/ml (mean ± SD), respectively. There were significant negative correlations between the concentra-tions of P1CP or 1CTP and gestational age, birth weight, birth length and head circumference (p<0.0001). Comparisons among the levels of P1CP and 1CTP and the rate of standard fetal weight gain, revealed the curves of P1CP and 1CTP levels to nearly parallel the curves of the standard fetal weight gain rate in male and female newborns. P1CP and ICTP levels corresponded to birth weight as well as gestational age, with the influences of other factors being negligible. We also assayed P1CP and 1CTP in 8 healthy infants under one year of age, and found that a high P1CP value and low 1CTP value resulted in a 4-fold increase in the mean P1CP/1CTP ratio, as compared to the newborns. In contrast, the P1CP/1CTP ratio was nearly constant during the preterm and term periods. The results suggest that high turnover reflects high bone remodeling activity which corresponds to rapid morphological changes in the fetal period, that high turnover processes are strongly associated with physical growth as well as gestational age in immature fetal bone and that bone formation is the dominant process in healthy infants during the first year of life

小児期の近位型脊髄性筋萎縮症の臨床像と分子遺伝学的診断

脊髄性筋萎縮症(SMA)は脊髄の前角細胞の変性,脱落により,筋萎縮や筋力低下を呈する常染色体性劣性の遺伝病である.本疾患は発症年齢,最高到達運動能力,経過により3つの型に分類される.分子遺伝学的には,1990年に3型ともに5q13に存在することが証明され,さらに1995年SMAの候補遺伝子としてSMN(survival motor neuron)遺伝子とNAIP(neuronal apoptosis inhibitory protein)遺伝子が報告された.本研究ではSMA患者を臨床的に分類し,SMN遺伝子,NAIP遺伝子について解析した.また,臨床型と遺伝子学的解析結果の関係を検討した.対象はSMA患者39名と精神遅滞,心肥大を各々伴つたatypical SMA2名である.1990年のInternational SMA Collaboration Workshop Reportの臨床型分類をもとに39名を分類した.この分類における発症年齢,最高到達運動能力,経過の3つの基準のすべてを満たし,臨床型に分類できたのは39例中20例であった.発症年齢,運動能力,経過のそれぞれについて分類した結果,発症年齢,経過では幅拡い臨床像を示し,臨床的に分類するのには最高到達運動能力および経過が有用であった.また,遺伝子解析の結果,全体の85%(33/39:I型90%,II型100%,III型54%)においてSMN遺伝子のexon 7のみ,またはexon 7および8のホモ接合性の欠失を認めた.また,I型の2名(5% 2/39)においてSMN遺伝子の欠失と同時にNAIP遺伝子のexon 5および欠失が認められた.両遺伝子の認められた2例ともに1型の重症例であったが,その他のSMN遺伝子のみの欠失した症例は臨床症状にかなりの幅が認めれていた.いずれの欠失も認められなかつた7例のうち5例は皿型であった.以上より臨床的重症度と遺伝子の欠失サイズの相関が示唆された.atypical SMAのうち1例にSMN遺伝子の欠失が認められた.また,精神遅滞をともなつた1例は欠失が認められず,異なる疾患の可能性も考えられた.Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by degenration of anterior horn cells in the spinal cord, leading to symmetrical proximal muscle weakness and atrophy. Affected individuals are classified into three types depending on the onset age, highest motor functional ability and clinical course. In 1990, the gene for SMA was mapped to chromosome region 5g13 for all three types of SMA. In 1995, the SMN (survival motor neuron) and NAIP (neuronal apoptosis inhibitory protein) genes were reported as candidate genes for SMA. In this study, we analyzed clinical features of SMA patients and deletions of these two candidate genes. The subjects included 39 SMA patients and two atypical SMA cases, one with mental retardation and the other with cardiomegaly. We classified 39 SMA cases based on the classification devised by the International SMA Consortium Meeting Report. Twenty cases satisfied all three criteria of this classification, and could clearly be classified as one of the three types. Our results of classifying cases according to each criterion suggested that clinical features of SMA constitute a broad spectrum encompassing the three types. Thus, it is most useful to classify patients according to their highest motor functional ability. Thirty-three cases of typical SMA (85% of all, 90% of type I, 100% of type II and 54% of type III) showed deletions of exons 7 and 8 or only exon 7 of the SMN gene. Two of type I (5% of all) showed deletions of exon 5 and 6 of the NAIP gene with deletions of the SMA genes. The other cases (2 of type I and 5 of type III) had no deletions of these genes. Involvement of the SMN and NAIP genes appears to be related to the severity of SMA. The one atypical case showed deletion of the SMN gene. The other one with mental retardation may be heterogeneous

小児期の近位型脊髄性筋萎縮症の臨床像と分子遺伝学的診断

脊髄性筋萎縮症(SMA)は脊髄の前角細胞の変性,脱落により,筋萎縮や筋力低下を呈する常染色体性劣性の遺伝病である.本疾患は発症年齢,最高到達運動能力,経過により3つの型に分類される.分子遺伝学的には,1990年に3型ともに5q13に存在することが証明され,さらに1995年SMAの候補遺伝子としてSMN(survival motor neuron)遺伝子とNAIP(neuronal apoptosis inhibitory protein)遺伝子が報告された.本研究ではSMA患者を臨床的に分類し,SMN遺伝子,NAIP遺伝子について解析した.また,臨床型と遺伝子学的解析結果の関係を検討した.対象はSMA患者39名と精神遅滞,心肥大を各々伴つたatypical SMA2名である.1990年のInternational SMA Collaboration Workshop Reportの臨床型分類をもとに39名を分類した.この分類における発症年齢,最高到達運動能力,経過の3つの基準のすべてを満たし,臨床型に分類できたのは39例中20例であった.発症年齢,運動能力,経過のそれぞれについて分類した結果,発症年齢,経過では幅拡い臨床像を示し,臨床的に分類するのには最高到達運動能力および経過が有用であった.また,遺伝子解析の結果,全体の85%(33/39:I型90%,II型100%,III型54%)においてSMN遺伝子のexon 7のみ,またはexon 7および8のホモ接合性の欠失を認めた.また,I型の2名(5% 2/39)においてSMN遺伝子の欠失と同時にNAIP遺伝子のexon 5および欠失が認められた.両遺伝子の認められた2例ともに1型の重症例であったが,その他のSMN遺伝子のみの欠失した症例は臨床症状にかなりの幅が認めれていた.いずれの欠失も認められなかつた7例のうち5例は皿型であった.以上より臨床的重症度と遺伝子の欠失サイズの相関が示唆された.atypical SMAのうち1例にSMN遺伝子の欠失が認められた.また,精神遅滞をともなつた1例は欠失が認められず,異なる疾患の可能性も考えられた.Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by degenration of anterior horn cells in the spinal cord, leading to symmetrical proximal muscle weakness and atrophy. Affected individuals are classified into three types depending on the onset age, highest motor functional ability and clinical course. In 1990, the gene for SMA was mapped to chromosome region 5g13 for all three types of SMA. In 1995, the SMN (survival motor neuron) and NAIP (neuronal apoptosis inhibitory protein) genes were reported as candidate genes for SMA. In this study, we analyzed clinical features of SMA patients and deletions of these two candidate genes. The subjects included 39 SMA patients and two atypical SMA cases, one with mental retardation and the other with cardiomegaly. We classified 39 SMA cases based on the classification devised by the International SMA Consortium Meeting Report. Twenty cases satisfied all three criteria of this classification, and could clearly be classified as one of the three types. Our results of classifying cases according to each criterion suggested that clinical features of SMA constitute a broad spectrum encompassing the three types. Thus, it is most useful to classify patients according to their highest motor functional ability. Thirty-three cases of typical SMA (85% of all, 90% of type I, 100% of type II and 54% of type III) showed deletions of exons 7 and 8 or only exon 7 of the SMN gene. Two of type I (5% of all) showed deletions of exon 5 and 6 of the NAIP gene with deletions of the SMA genes. The other cases (2 of type I and 5 of type III) had no deletions of these genes. Involvement of the SMN and NAIP genes appears to be related to the severity of SMA. The one atypical case showed deletion of the SMN gene. The other one with mental retardation may be heterogeneous

Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation A Report From the GARFIELD-AF Registry

IMPORTANCE Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes