Glycosylation and Cross-linking in Bone Type I Collagen

Fibrillar type I collagen is the major organic component in bone, providing a stable template for mineralization. During collagen biosynthesis, specific hydroxylysine residues become glycosylated in the form of galactosyl- and glucosylgalactosyl-hydroxylysine. Furthermore, key glycosylated hydroxylysine residues, α1/2-87, are involved in covalent intermolecular cross-linking. Although cross-linking is crucial for the stability and mineralization of collagen, the biological function of glycosylation in cross-linking is not well understood. In this study, we quantitatively characterized glycosylation of non-cross-linked and cross-linked peptides by biochemical and nanoscale liquid chromatography-high resolution tandem mass spectrometric analyses. The results showed that glycosylation of non-cross-linked hydroxylysine is different from that involved in cross-linking. Among the cross-linked species involving α1/2-87, divalent cross-links were glycosylated with both mono- and disaccharides, whereas the mature, trivalent cross-links were primarily monoglycosylated. Markedly diminished diglycosylation in trivalent cross-links at this locus was also confirmed in type II collagen. The data, together with our recent report (Sricholpech, M., Perdivara, I., Yokoyama, M., Nagaoka, H., Terajima, M., Tomer, K. B., and Yamauchi, M. (2012) Lysyl hydroxylase 3-mediated glucosylation in type I collagen: molecular loci and biological significance. J. Biol. Chem. 287, 22998–23009), indicate that the extent and pattern of glycosylation may regulate cross-link maturation in fibrillar collagen

Sympathetic overactivityを伴った重症破傷風の2例

破傷風は,Clostridium tetaniの産生毒素tetanospasminに起因する神経系疾患である.今日我が国では,予防接種の普及等により稀となった反面,軽微な外傷でも発症する本疾患は,外傷領域においては常に念頭に置くべき疾患である.その治療管理において痙攣,sympathetic overactivityに対する対処が重要となる.今回我々はsympathetic overactivityを伴った重症破傷風の2例を経験した.1例に対してはphenobartital,diazepam持続投与下の管理を約15日間要し,また他の1例はpancuronium bromide, midazolamを使用すると共に,循環動態安定のためfentanyl citrateを追加し,人工呼吸器管理期間は約28日を要した.いずれも軽快退院したものの,抗痙攣療法後の回復期に,筋力低下によるリハビリテーション,あるいはせん妄・自殺企図がみられ精神科的治療を要した.呼吸管理の進歩により生命予後は改善されたものの,抗痙攣療法後にも注意すべき合併症があり,全経過を通じ慎重な全身管理が必要である.Tetanus is a nervous system disease caused by tetanospasmin, a toxin produced by Clostridium tetani. In Japan, tetanus, which occurs in association with even a slight injury, should always be taken into consideration in the traumatology field, although there are rare cases of tetanus owing to the spread of vaccination, etc. Treatment of spasm and sympathetic overactivity plays an important role in the therapeutic control of this disease. We had an experience of treating two patients suffering from severe tetanus with sympathetic overactivity. For one patient, it took about 15 days to control the disease by continuous administration of phenobartital and diazepam. For the other patient, pancuronium bromide and midazolam were used and fentanyl citrate was added for circulatory dynamic stabilization, and control with a ventilator required about 28 days. Although both patients were cured from the tetanus and discharged, reduced myodynamia required rehabilitation, and delirium and suicide attempts required psychiatric treatment during the recovery period following the anti-spasm therapy. Careful systemic control of tetanus patients is necessary throughout the course of disease as complications to be watched may occur following the anti-spasm therapy as well, although the progress in respiratory control has contributed to the improvement in prognosis of tetanus patients

多発外傷患者の予後判定における甲状腺ホルモン測定の有用性について

T_3,T_4(甲状腺ホルモン)の低下する,いわゆるeuthyroid sick syndromeは慢性疾患や心筋梗塞などで見られ,その値が予後をよく反映したと報告されている.その一方,多発外傷は強い外力により生じることが多く,単独外傷に比べて著しく死亡率が高いのが特徴であり,多発外傷の予後には診断,治療を含めて複雑な因子が多いが甲状腺ホルモン値と予後に関する報告はほとんどない.今回我々はそれらにつき検討した.1996年9月より1999年2月まで福井医科大学病院救急部に入院した,多発外傷症例55例(男性34名,女性21名,平均年齢50.7歳)をsurvivors(生存群,S群),non-survivors(死亡群,N群)の2群に分け,それぞれの群で平均年齢,平均ISS(injury severity score),平均APACHEII(acute physiology and chronic health evaluation svstem II),と死亡率につき検討し,S群37例,N群18例において第0,1,3,7病日にTSH値,TBG,T_3,T_4,FT_3,FT_4値を測定した.2群間の有意差検定は第0病日のみの値で,paired-t検定で行った.S群37例とN群18例の間で,ISS,APACHE IIはそれぞれ危険率1%以下で有意差を認めた.2群間の第0病日のホルモン値の比較では,平均血清TSH値では有意差が見られず,平均血清T_3値は低下し,特にN群で著明に低下し,2群間では危険率0.01%以下で有意差を認め,平均血清FT_3値では有意差は見られなかった.平均血清T_4,FT_4値は0.01%以下の危険率で有意差を認めた.以上の結果より,多発外傷の予後の予測に関して,受傷後早期の甲状腺ホルモン,特に,T_3,T_4,FT_4値の測定は有用であると考えられた.To determine the usefulness of thyroid hormones measurement in predicting the prognosis of patients with severe multiple injuries, a total of 55 patients with severe multiple injuries (34 males and 21 females, with a mean age of 50.7 years) were evaluated between September 1996 and February 1999. The patients were evaluated within 2 hours of admission, and the serum free thyroxin (FT_4), thyroxin (T_4), free triiodothyronine (FT_3), triiodothyronine (T_3), thyroxin-binding globulin (TBG), injury severity score (ISS), and the acute physiology and chronic health evaluation (APACHE II) score were determined. The same tests were repeated with the exception of the APACHE II on day 1, day 3 and day 7. A comparison was made of these variables between the survivors (37 patients) and non-survivors (18 patients). The mean ISS was 35.1±15.3 and the mean APACHE II score was 17.7±12.0. The best predictors of the prognosis in a descending order were T_4 (p<0.0001), T3 (p<0.0001), FT_4 (p<0.0001), ISS (p<0.01), and APACHE II score (p<0.01). Measuring the thyroid hormones (T_4, T_3 and FT_4) within 2 hours of admission together with ISS and APACHE II score appear to be useful in predicting the prognosis of patients with severe multiple injuries

Sympathetic overactivityを伴った重症破傷風の2例

破傷風は,Clostridium tetaniの産生毒素tetanospasminに起因する神経系疾患である.今日我が国では,予防接種の普及等により稀となった反面,軽微な外傷でも発症する本疾患は,外傷領域においては常に念頭に置くべき疾患である.その治療管理において痙攣,sympathetic overactivityに対する対処が重要となる.今回我々はsympathetic overactivityを伴った重症破傷風の2例を経験した.1例に対してはphenobartital,diazepam持続投与下の管理を約15日間要し,また他の1例はpancuronium bromide, midazolamを使用すると共に,循環動態安定のためfentanyl citrateを追加し,人工呼吸器管理期間は約28日を要した.いずれも軽快退院したものの,抗痙攣療法後の回復期に,筋力低下によるリハビリテーション,あるいはせん妄・自殺企図がみられ精神科的治療を要した.呼吸管理の進歩により生命予後は改善されたものの,抗痙攣療法後にも注意すべき合併症があり,全経過を通じ慎重な全身管理が必要である.Tetanus is a nervous system disease caused by tetanospasmin, a toxin produced by Clostridium tetani. In Japan, tetanus, which occurs in association with even a slight injury, should always be taken into consideration in the traumatology field, although there are rare cases of tetanus owing to the spread of vaccination, etc. Treatment of spasm and sympathetic overactivity plays an important role in the therapeutic control of this disease. We had an experience of treating two patients suffering from severe tetanus with sympathetic overactivity. For one patient, it took about 15 days to control the disease by continuous administration of phenobartital and diazepam. For the other patient, pancuronium bromide and midazolam were used and fentanyl citrate was added for circulatory dynamic stabilization, and control with a ventilator required about 28 days. Although both patients were cured from the tetanus and discharged, reduced myodynamia required rehabilitation, and delirium and suicide attempts required psychiatric treatment during the recovery period following the anti-spasm therapy. Careful systemic control of tetanus patients is necessary throughout the course of disease as complications to be watched may occur following the anti-spasm therapy as well, although the progress in respiratory control has contributed to the improvement in prognosis of tetanus patients