Decreased Bone Mass and Strength in Ovariectomized Cynomolgus Monkeys (Macaca fascicularis)

Agents for prevention or treatment of osteoporosis must now be tested in a large animal species that exhibits bone remodeling. Ovariectomized, nonhuman primates provide one such model, and they consistently develop osteopenia accompanied by high bone turnover rates. The goal of this study was to further characterize this model, and particularly to determine the effect of ovariectomy on bone strength in vertebrae and femoral necks. Longitudinal evaluations of spinal bone mass and serum markers of bone turnover were performed in 19 sham-ovariectomized (SHAM) and 18 ovariectomized (OVX), domestically reared cynomolgus monkeys, aged >9 years. OVX monkeys lost bone relative to both baseline values and SHAM controls. Serum markers of bone turnover were increased by OVX. After 72 weeks, both vertebral bone compressive strength and femoral neck breaking strength were significantly decreased in OVX animals compared with SHAM. Ovariectomized cynomolgus monkeys, like postmenopausal women, develop accelerated bone loss, increased bone turnover, and reduced bone strength, and provide a suitable large animal model for efficacy studies with agents for prevention or treatment of osteoporosis. Received: 24 June 1996 / Accepted: 3 September 1996     

Specific Changes of Urinary Excretion of Cross-Linked N-Telopeptides of Type I Collagen in Pre- and Postmenopausal Women: Correlation with Other Markers of Bone Turnover

Urinary excretion of cross-linked N-telopeptide of type I collagen (NTx) has been reported to be a specific marker of bone resorption [18]. We assessed a new immunoassay for NTx as an indicator of changes in bone resorption caused by spontaneous menopause and compared cross-sectionally the levels of urinary NTx, hydroxylysylpyridinoline (HP), lysylpyridinoline (LP), hydroxyproline (OH-Pr), other serum biochemical indices, and lumbar spine and proximal femur bone mineral density (BMD). Eighty-one Japanese women aged 22–77 participated in this study; 36 were premenopausal and 45 were postmenopausal. Urinary HP, LP, and NTx stayed at low levels in the premenopausal period and rose 21%, 30%, and 67% in the postmenopausal period, respectively. The rise in LP and NTx was statistically significant (P < 0.01), suggesting that NTx is mostly released from bone matrix when bone resorption is accelerated. When premenopausal women were divided into two age groups and postmenopausal women were divided into two groups according to years since menopause (YSM) there were significant differences in LP and NTx between women <4 YSM and women aged <40 and those women aged 41+ (P < 0.01 and P < 0.05, respectively). A significant 110% increase in urinary NTx and a 48% increase in urinary LP were observed in postmenopausal women compared with age-matched premenopausal women aged 45–55. All biochemical markers other than serum PTH correlated significantly with each other (r = 0.243–0.858, P < 0.05–0.0001). Urinary NTx inversely correlated with lumbar spine BMD. When postmenopausal women were divided into three groups, the correlation between bone resorption and formation markers in women 0-1 YSM was greater than in women 2–10 YSM and in women 11 + YSM, indicating that resorption and formation are coupled at the early postmenopausal period. We conclude that urinary NTx is responsive to changes in bone metabolism caused by estrogen deficiency and may be a more sensitive and specific marker than HP, LP, or OH-Pr in the early postmenopausal years. Received: 15 February 1995 / Accepted: 18 October 1996     

骨与关节肿瘤和瘤样病变1084例统计分析

目的：分析青海高原地区骨与关节肿瘤及瘤样病变的发病情况。方法：对１９６３～１９９５年１０月的１０８４例骨与关节肿瘤及瘤样病变进行了统计分析。结果：良性骨肿瘤７２２例（６６．６１％），恶性骨与关节肿瘤２４９例（２２．９７％），瘤样病变１１３例（１０．４２％），良、恶性肿瘤之比为２．９∶１，男女之比为１．２２∶１，好发年龄为１１～３０岁，好发部位为胫骨（２７．３％），其次为股骨（２１．８％）。良性骨肿瘤以骨软骨瘤（５４．４３％）、软骨瘤（２１．１９％）、骨巨细胞瘤（９．９７％）多见。原发恶性骨肿瘤以骨肉瘤（３３．３％）、软骨肉瘤（１０．８５％）、骨髓瘤（１０．０５％）多见。瘤样病变则以孤立性骨囊肿（４６．０１％）和骨纤维结构不良（３０．９７％）多见。结论：本组结果与国内文献对比有许多相似之处，但良性骨肿瘤与恶性骨肿瘤之比与国内文献有较大不同，可能与高原环境有关。     

MRI gadolinium enhancement of bone marrow: age-related changes in normals and in diffuse neoplastic infiltration

 Objective: To quantify gadolinium-related enhancement in the bone marrow of the spine in normals and in patients with homogeneous diffuse malignant bone marrow infiltration. Design and patients: The patients consisted of two groups: group 1 comprised 94 healthy adults (18–86 years) without bone marrow disease and group 2 comprised 30 patients with homogeneous diffuse malignant bone marrow infiltration due to myeloma (n=20) or breast carcinoma (n=10). All patients received intravenous gadopentetate dimeglumine (Gd-DTPA), 0.1 mmol/kg body weight. Pre- and postcontrast signal intensity (SI) on T1-weighted spin-echo (SE) images (TR/TE: 572 ms/15 ms) was measured over a region of interest (ROI) and the percentage SI increase was calculated. The results were confirmed by bone marrow biopsy (n=20) and clinical parameters (n=10). Dynamic contrast-enhanced studies using a spoiled gradient-recalled-echo (GRE) sequence (TR/TE/α: 68 ms/6 ms 75°) were performed in 10 controls with normal bone marrow. Results and conclusion: Contrast material enhancement in healthy persons can vary greatly (range 3–59%, mean 21%, SD 11%). With increasing age there is a significant decrease in contrast enhancement (Pearson’s correlation, P<0.01). The percentage SI increase in patients with intermediate-grade (biopsy 20–50 vol%) and high-grade (biopsy >50 vol%) diffuse malignant bone marrow infiltration was significantly higher than in normals (mean 67%, SD 34%, P<0.001). Low-grade (biopsy <20 vol%) diffuse malignant bone marrow infiltration can not be assessed by non-enhanced T1-weighted SE images or Gd-DTPA application. In conclusion, contrast material enhancement in healthy persons can vary greatly and is dependent on age, while intermediate-grade and high-grade diffuse malignant bone marrow infiltration can be objectively assessed with SI measurements.     

高压氧对家兔面神经撞击伤后面神经核内生长相关蛋白变化的影响(论著)

目的：研究面神经撞击伤后面神经核内生长相关蛋白（ＧＡＰ－４３）的变化及高压氧（ＨＢＯ）治疗的影响。方法：利用ＢＩＭ－Ⅱ型生物撞击机致家兔右侧面神经干损伤，应用ＳＰ免疫组化染色法观察损伤后１、３、７、１４和２１天（分别用ＨＢＯ治疗及不用ＨＢＯ为对照）面神经核内ＧＡＰ－４３的变化，并用电镜观察面神经干超微结构变化。结果：面神经损伤第１天，伤侧面神经核区ＧＡＰ－４３样免疫反应性神经元（ＧＬＩＮ）开始增多，第１４天其增多达到高峰，第２１天逐渐下降。ＨＢＯ治疗组伤后不同时期ＧＬＩＮ的增多明显高于对照组。伤后第２１天，与对照组相比ＨＢＯ组面神经干电镜观察可见较多的新生髓鞘。结论：ＨＢＯ治疗可使伤后面神经核内ＧＬＩＮ增多，因而有助于面神经损伤后的修复与再生。     

核仁形成区嗜银蛋白定量对结肠癌分型、分级的诊断意义

对１１４例不同类型和级别的结肠癌进行银染核仁形成区嗜银蛋白（Ａｇ－ＮＯＲｓ）形态定量研究．结果表明，Ａｇ－ＮＯＲｓ数量、大小和分布在结肠未分化癌和印戒细胞癌组与管状腺癌和粘液腺癌组比较，有明显差异．管状腺癌随分化程度的降低，Ａｇ－ＮＯＲｓ的数量、形态、大小和分布也发生等级性变化．结果提示，Ａｇ－ＮＯＲｓ形态定量的数量、形态、大小和分布４项指标对结肠癌分型有一定意义，对管状腺癌分级有较好的诊断价值。     

肝豆状核变性RFLP连锁分析的建立及症状前诊断和杂合子检出的研究

ＲＢ１基因位于ＤＩ３ｑ１４－２１，与Ｗｉｌｓｏｎ氏病基因紧密连锁，遗传距离为４．４ｃｍ（ｃｅｎｔｉｍｏｒｇａｎ），其３＇端第１７号内含子中ｐ６８ＲＳ２．０标记的等位片段与白种人相同，但基因频率存在差异，杂合子频率为４３％。应用该标记对１１个ＷＤ家系进行ＲＦＬＰ连锁分析，检出３名症状前患者，１１名杂合子及３名正常纯合子，证实ｐ６８ＲＳ２．０标记可用于Ｗｉｌｓｏｎ氏病的症状前诊断及杂合子筛选。     

病理性损伤因素对肾小管上皮细胞表型转化的影响

目的 :观察低血清、高糖、高蛋白刺激下肾小管上皮细胞向间叶性细胞的表型转化 ,探讨损伤的肾小管上皮细胞在肾小管间质纤维化中的作用。方法 :以体外培养的人近端肾小管上皮细胞为对象 ,分别用含低血清(0 .2mol·L-1小牛血清 )、高葡萄糖 (4.5 g·L-1)、高白蛋白 (15 g·L-1)的培养液培养 7d ,透射电镜检测细胞形态变化 ;免疫组化和Westernblot检测细胞表型改变 ,包括CK、Vimentin、α SMA、Ⅰ和Ⅲ型胶原 ,原位杂交检测Ⅰ型胶原mRNA表达 ,同时检测细胞TGFβ1蛋白表达。 结果 :低血清、高糖、高蛋白直接刺激下 ,肾小管上皮细胞出现明显形态学改变 ,包括细胞变为长梭形 ;透射电镜下细胞内线粒体明显减少 ,粗面内质网明显增加 ,并出现actin样微丝。免疫组化染色和Westernblot显示CK表达明显减弱 ,Vimentin、Ⅰ、Ⅲ型胶原、α SMA和TGFβ1表达增强。原位杂交显示Ⅰ型胶原mRNA表达增强。结论 :低血清、高糖、高蛋白可直接引起人近端肾小管上皮细胞TGFβ1表达增加 ,并发生向间叶性细胞的表型转化     

人骨髓间充质干细胞体外分化为雪旺样细胞的方法

目的 :建立人骨髓间充质干细胞体外向雪旺样细胞定向诱导分化的方法。方法 :取健康人骨髓血标本 ,利用percoll(密度为 1.0 73 g·ml-1)分离骨髓单个核细胞 ,在DMEM LG + 10 % (体积分数 )FBS中培养 ,通过流式细胞术对培养细胞进行表型测定 ,对第 2、3、5、8代间充质干细胞进行定向诱导分化 ,用单抗S 10 0、神经胶质纤维酸性蛋白 (glialfibrillargacidicprotein ,GFAP) ,通过免疫组化方法对诱导的细胞进行鉴定。 结果 :经 percoll分离的间充质干细胞可传 16代 ,细胞数增加了大约 6× 10 7倍。流式细胞术结果显示 :percoll分离出来的未经培养的细胞 ,其CD2 9+CD4 4 +CD3 4 -CD4 5 -细胞数为 3 2 .4 7%± 3 .4 9% ,而培养后贴壁细胞中CD2 9+CD4 4 +CD3 4 -CD4 5 -细胞数为 94 .3 8%± 1.5 0 %。诱导后免疫组化染色结果显示 :由 β ME +bFGF预诱导、β ME +bFGF诱导的S 10 0阳性细胞最多 ,可达 90 %± 4 % ,GFAP阳性细胞为 2 1%± 5 %。结论 :人骨髓中间充质干细胞能定向诱导分化成雪旺样细胞。     

尺骨鹰嘴骨折皮质骨加压螺钉固定的实验研究及临床应用

比较尺骨鹰嘴骨折加压螺钉与常用的4种内固定的强度,为临床选择内固定方法提供实验依据。用22具新鲜尸体肘关节做成横型、斜形和粉碎形鹰嘴骨折模型。用5种内固定后置于MD—10E万能电子力学试验机上,测定骨折处的位移与压力的关系;结果:钢丝内固定强度最小,钩钢板最大。髓内加压螺钉固定欠可靠。横形骨折皮质骨加压螺钉与张力带钢丝比较,统计学上无显著差异(P〉0.05),斜形骨折皮质骨加压螺丝钉强于张力带钢丝(P〈0.01)。粉碎形骨折使用钩钢板尤佳(P〈0.01)。临床应用24例中,22例平均随访14个月。骨折全部愈合,优良率达90.91％;认为皮质骨加压螺丝钉治疗横、斜形尺骨鹰嘴骨折,创伤小,操作简便,固定确切,是一种安全可靠的方法。