牙型低碱性磷酸酶血症1例家系基因突变分析

正低碱性磷酸酶血症(hypophosphatasia,HPP)是一种罕见的遗传代谢性骨病,以组织非特异性碱性磷酸酶缺乏或活性降低,骨和牙齿矿化不全为主要临床特征[1]。该病临床表现变异较大,严重者可致胎儿死亡,轻型可仅表现为乳牙早脱。根据发病年龄及严重程度,HPP可分为6型:围生期致死型、围生期良性型、婴儿型、儿童型、成年型和牙型[2,3]。牙型HPP是低碱性磷酸酶血症中的少见类型,表现为     

全外显子测序对两例低磷酸酶症遗传病因研究

目的对2例低磷酸酶症(hypophosphatasia, HPP)患者及其家系进行临床分析及基因变异检测, 以探讨HPP的致病机制, 加强我们对HPP的诊治经验。方法收集2例HPP患者及其家属外周血提取基因组DNA, 采用全外显子组测序进行致病基因检测, 并通过Sanger测序和家系验证确认其遗传方式。利用生物信息学软件对变异位点进行功能分析。结果先证者1临床表现为发育迟滞、漏斗胸和乳牙过早脱落等临床表现, 血清碱性磷酸酶水平略低于正常值, 临床高度怀疑HPP进行基因检测, 结果发现先证者1的碱性磷酸酶基因ALPL上带有复合杂合变异(c.1120G>A和c.1334C>G), 分别遗传自父母, 符合常染色体隐性遗传;且两种错义变异经多种生物信息学预测均为有害, 美国医学遗传学与基因组学学会(ACMG)分级为疑似致病性;综合以上结果先证者1被诊断为儿童型HPP。先证者2临床表现为恒牙缺失3颗而无骨折史以及其他骨骼异常, 血清碱性磷酸酶水平明显低于正常值范围, 基因检测发现该患者携带c.1190-3C>G的单杂合变异, 遗传情况不明, ACMG指南初步判定为临床意义未明变...     

一例组织非特异性碱性磷酸酶基因突变所致的围生期致死型低磷酸酶症病例

目的对1例围生期致死型(新生儿型)低磷酸酶症(HPP)患者及其父母进行临床分析及基因突变检测,以期能更好地认识该病。方法对l例罕见的围生期致死型低磷酸酶症患者的临床表现、实验室及影像学检查结果进行总结。提取患儿及其亲属外周血基因组DNA,采用针对组织非特异性碱性磷酸酶(ALPL)基因调控区及编码区的特异性引物进行PCR扩增,直接对产物进行测序分析。结果患儿血碱性磷酸酶水平显著降低,血钙增高;骨骼显示骨软骨发育障碍类疾病样改变。ALPL基因测序结果显示患儿为复合杂合突变,同时携带位于第5外显子及第10外显子上c.346G>A(p.A116T)和c.1171C>T(p.R391C)的错义突变。临床表现正常的父亲、母亲为杂合子,分别携带c.346G>A(p.A116T)和c.1171C>T(p.R391C)的错义突变。该家系符合常染色体隐性遗传。结论围生期致死型HPP死亡率很高,骨骼发育异常、高血钙、血清低碱性磷酸酶在其鉴别诊断中非常重要。     

甲状腺功能低下及亢进大鼠血清ALP与BALP含量变化的研究

目的研究甲状腺功能低下(甲低)及甲状腺功能亢进(甲亢)时血清碱性磷酸酶(ALP)、骨型碱性磷酸酶(BALP)的含量的变化.方法复制出甲低及甲亢大鼠模型,用高效液相色谱法测定其血清ALP、BALP的含量.结果对照组大鼠血清ALP活性(10.75±1.63)U/L,BALP活性在(4.84±1.02)U/L;甲低组大鼠血清ALP含量是(7.73±1.03)U/L,BALP含量是(3.83±0.80)U/L与对照组相比均低于对照组(P＜0.01);甲亢组大鼠血清ALP是(15.12±1.98)U/L,BALP是(7.24±1.42)U/L,与对照组相比均明显升高(P＜0.001).结论ALP和BALP是甲低及甲亢诊断的重要生化指标,具有临床意义,且BALP更敏感.     

阿仑膦酸钠对老年男性血清骨转换指标及骨密度的影响

目的 观察阿仑膦酸钠对老年男性骨质疏松症患者的血清骨特异性碱性磷酸酶、抗酒石酸酸性磷酸酶5b、氨基端和中段骨钙素等血清骨转换指标及骨密度的影响.方法 临床选取符合骨量减少及骨质疏松诊断标准的老年男性病例70例,随机分为2组,治疗组34例,平均年龄(75.64±6.3)岁,服用阿仑膦酸钠;对照组36例,平均年龄(75.88±5.5)岁,为鲑降钙素针组;2组同时服用钙而奇D片和法能胶丸(阿法骨化醇)做为基础用药.分别于服药前及服药半年后,测定2组患者血清骨特异性碱性磷酸酶、抗酒石酸酸性磷酸酶、氨基端和中段骨钙素及骨密度,分析治疗前后以及治疗组与对照组间的差异.结果 治疗组患者治疗后血清骨特异性碱性磷酸酶、氨基端和中段骨钙素及骨密度较服药前显著升高(P均＜0.05);抗酒石酸酸性磷酸酶较服药前显著降低(P＜0.05);将上述指标与对照组比较,骨特异性碱性磷酸酶、氨基端和中段骨钙素、骨密度2组无显著差异(P均＞0.05);治疗组抗酒石酸酸性磷酸酶的降低程度不及对照组明显(P＜0.05).结论 阿仑膦酸钠能抑制骨吸收,促进骨形成,减缓骨量丢失,提高骨密度,可有效防治老年男性骨质疏松症.     

婴儿型低磷酸酶血症组织非特异性碱性磷酸酶基因突变检测

目的 对1例婴儿型低磷酸酶血症患者及其父母进行临床分析和基因突变检测,以探讨该病的致病机制.方法 针对1例罕见的婴儿型低磷酸酶血症患者进行实验室检验及影像学检查.进而提取患儿及其亲属外周血基因组DNA,采用针对组织非特异性碱性磷酸酶ALPL基因调控区及编码区的特异性引物进行PCR扩增,直接对产物进行测序,并对所鉴定的突变在无关人群中进行验证.结果 患儿血碱性磷酸酶水平显著降低,同时存在高钙血症、中度贫血及双肾钙化;骨骼具有佝偻病样改变.ALPL基因测序结果显示患儿为复合杂合突变,同时携带位于第7外显子的c.814C ＞T (p.R272C)错义突变及位于第9外显子的c.1101_1103 delCTC (p.S368 del)碱基缺失突变.临床表现正常的患儿母亲、父亲为杂合子,分别携带c.1101_1103 delCTC (p.S368del)碱基缺失突变及c.814C ＞T (p.R272C)错义突变.该家系符合常染色体隐性遗传,50例无关健康个体验证未发现上述两种突变存在.结论 ALPL基因c.814C＞T(p.R272C)和c.1101_1103 delCTC(p.S368del)突变与该家系婴儿型低磷酸酶血症临床表现密切相关.     

妊娠期高甘油三酯血症性胰腺炎的诊治分析

目的探讨妊娠期高甘油三酯血症性胰腺炎(HPP)的临床诊治分析。方法回顾性收集并分析榆林市中医医院2005年6月-2015年6月收治的29例HPP孕产妇患者的临床资料。结果 29例HPP患者中,孕早期5例(17.2%),孕晚期24例(82.8%);轻型胰腺炎8例(27.6%),中型胰腺炎14例(48.3%),重型胰腺炎7例(24.1%)。血清TG平均水平为15.5 mmol/L。孕产妇无死亡,胎儿死亡率为17.2%(5/29),均为胎死宫内。结论妊娠期HPP虽然少见,但其发病率逐年升高,多见于孕晚期。HPP常导致较高的胎儿死亡率,因此应及时诊断和治疗以改善母婴预后。     

厌食,不适和咳嗽(第16例)

临床讨论本例男病人无特殊病史,并有肺部感染的表现,对于这种情况,几乎必定有一种基础的病因存在。此外,病人有轻度贫血,并有红细胞沉降率增高。病人的(血清)白蛋白降低而球蛋白增高。病人有高钙血症,但部分被低白蛋白血症所掩盖,且其磷酸盐和碱性磷酸酶均正常。这就使病人不似是甲状旁腺功能亢进症或(肿瘤的)多处骨转移。病人的低钠血症与抗利尿激素(ADH=antidiuretic hormone——译者)分泌     

组织非特异性碱性磷酸酶基因突变与低磷酸酶血症：2个新突变位点

目的：对2例低磷酸酶血症（HPP）患者及家系进行分析和基因突变检测,拓展国人HPP致病基因库,探讨HPP的致病机制。方法对HPP家系先证者和其父母进行生化指标[血常规、肝肾功能、碱性磷酸酶（ALP）、甲状旁腺素（PTH）、钙、磷等]和骨密度检测。同时对所有研究对象进行alkaline phospatase,live/bone/kidney（ALPL）基因全部12个外显子和外显子内含子交界区直接测序。结果来自家系1的先证者为36岁成年男性,身高131.0cm,体重35.0kg。X线提示多发性胸腰椎骨折和骨盆畸形,生化检测示血清ALP27U/L。测序发现ALPL基因6号外显子532位杂合突变（c.532T＞C）,致ALPL成熟多肽中酪氨酸被组氨酸替代。该先证者母亲身高140.5cm,体重39.5kg,血清ALP30U/L,基因测序证明也是该杂合突变携带者。来自家系2的先证者5岁,其外祖父母为近亲结婚。该患儿身高100.0cm,体重18kg。血清ALP55U/L[低于同龄儿童正常范围（＜10岁）75～344U/L],牙齿发育不良并脱落,有左股骨中下端骨折史。测序发现该患儿存在ALPL基因2个错义突变,其中9号外显子c.871G＞A突变。4号外显子269位突变（c.269A＞G）是一个新的错义突变,该突变导致成熟ALPL多肽中天冬氨酸被甘氨酸所替代。该患儿母亲亦是4号外显子c.269A＞G错义突变携带者,但其生化指标正常,无骨骼和牙齿异常。结论ALPL基因6号外显子c.532T＞C突变和4号外显子c.269A＞G突变是以往未曾报道过的新错义突变,为上述2例HPP患者致病基因。     

曼氏血吸虫成虫碱性磷酸酶的抗原性

作者用直接固相碱性磷酸酶免疫吸附(APIA),蛋白质印渍及免疫染色法检测委内瑞拉JL和YT品系以及巴西品系(BH)曼氏血吸虫感染者及慢性感染鼠血清中抗碱性磷酸酶抗体,并对曼氏血吸虫成虫碱性磷酸酶(AP)的抗原性进行分析。结果:1.碱性磷酸酶免疫吸附的最适条件为(1)1:1000稀释的抗鼠血清或10μg/ml蛋白A作为人免疫球蛋白的捕获物;(2)用酪蛋白代替白蛋白进行饱和以防止平板的疏水吸附;(3)1:100稀释的人或鼠血清;(4)0.3mUAP/ml丁醇抽提物。     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.