无机活性元素骨组织工程支架材料修复山羊颌骨缺损

目的:应用无机活性元素骨组织工程支架材料,对山羊的下颌骨角部大型箱状缺损施行骨重建,观察支架材料骨构建效能和生物相容性的情况。方法:实验于2004-02/12在安徽医科大学附属省立医院实验中心及相关实验室完成。①实验材料:无机活性元素骨组织工程支架材料由美国波士顿大学分子生物相容学研究室研制提供;21只雌性健康山羊由安徽医科大学动物实验中心(皖医实动准字01号)提供,实验过程中动物处置符合动物伦理学标准。②实验方法:取山羊15只,按4,8,12周3个时间点分为3组,位下颌角部手术制备30 mm×25 mm×10 mm的大型箱状缺损。采用自身配对设计,左侧置入支架材料为实验组,右侧空白对照为对照侧;剩余6只山羊为对照组,不手术。③观察指标:术后4,8,12周应用X射线片、组织学和放射性核素显像观察缺损区新骨形成情况;并测定骨密度;应用血液学检查及骨髓基质细胞体外复合细胞培养评价材料的生物相容性。结果:①一般观察:实验山羊无手术死亡,创口Ⅰ期愈合。②X射线片:实验侧有渐进性骨密度增高,阻射影逐级增强,对照侧呈透光阴影。③放射性核素显像:实验侧有较明显的核浓聚和再生血管化现象,对照侧无骨重建,故无骨代谢变化。④骨密度测量系数:实验侧呈递增式上升,对照侧维持较低水平,提示无自发性成骨。⑤组织学观察:实验侧呈时间递增性骨重建现象,在12周时新骨已完全形成并钙化基本完成,而对照侧直到12周仍无成骨现象。⑥生物相容性:各组的血常规、细胞形态、生化和相关酶学指标均在正常范围内。结论:无机活性元素骨组织工程支架材料有良好的成骨和再血管化功能,且生物相容性好,提示由该支架材料诱导的组织工程化骨构建有望成为临床骨组织大型缺损的替代材料。     

Polymorphism of the h allele and the population frequency of sporadic nonfunctional alleles

BACKGROUND: Current polymerase chain reaction-based strategies for phenotype prediction often fail when sporadic nonfunctional alleles are encountered. The population frequency of such mutations was not known for any gene under low selection pressure and may be best examined in blood groups systems lacking prevalent nonfunctional alleles. The frequency of the very rare Bombay blood group (Oh, genotype hh sese) was recently determined in a systematic survey of more than 600,000 white individuals. STUDY DESIGN AND METHODS: With this survey used in conjunction with additional blood samples, the population frequency of nonfunctional alleles of the gene encoding the alpha (1,2)fucosyltransferase (H or FUT1) was determined. RESULTS: Seven different h alleles were found in five unrelated individuals, three of whom were homozygous for unique alleles. There was no prevalent h allele. Five missense and one frameshift mutations were observed, that were the presumptive causes of the null phenotype; the coding sequence of one h allele was identical to the H sequence. The average inbreeding factor alpha was 0.00116. The frequency of nonfunctional alleles at the H gene locus was calculated as 1 in 347 in a large white population (95% CI: 1:185-1:824). CONCLUSION: The Bombay blood group phenotype in white is due to diverse, sporadic, nonfunctional alleles without any prevalent allele. Assuming similar rates of nonfunctional alleles in glycosyltransferase genes like ABO, current genotyping strategies may fail as often as once in about 300 individuals of blood group O. Sporadic neutral alleles may also pose a serious obstacle for population-wide screening of many disease-associated genes.     

Viable lymphocytes in frozen washed blood

Samples of glycerolized, frozen, packed cells, were washed by each of three systems and then were cultrued for viable lymphocytes using the short-term culture method. Of the 39 samples, 17 (43.6%) showed definite evidence of growth of lymphocytes. Of the 17, 11(64.7%) were washed by Elutramatic, two (11.8%) by Haemonetics, and four (23.5%) by IBM. The 4 C prefreeze (two to five days) as well as the -80 C (21 To 40 days) storage times were the same for both positive and negative specimens. In all samples, clumps of distorted granulocytes with pyknotic nuclei were seen in addition to a number of well-preserved mononucleated white cells. In the 17 specimens which showed growth, incorporation of 3H-thymidine was seen only in the PHA-induced blast cells; typical mitotic figures were seen in some cultures. These observations demonstrate that lymphocytes remain viable in frozen blood stored at -80 C up to 40 days. The significant difference in removal of viable lymphocytes noted in specimens washed by different instruments requires further evaluation.     

Electrode migration after cochlear implantation.

OBJECTIVE: To review the occurrence of electrode migration after cochlear implantation. STUDY DESIGN: Review of public database and retrospective case series. SETTING: Tertiary academic referral center, ambulatory. PATIENTS: Retrospective review of electrode migration reported in association with the US Food and Drug Administration Manufacturer and User Facility Device Experience database and a single-institution case series between 1996 and 2006. INTERVENTION: Cochlear implantation. MAIN OUTCOME MEASURE: Occurrence of electrode migration. RESULTS: During the period 1996 to 2006, 151 reports of electrode migration were filed in the Manufacturer and User Facility Device Experience database. The most common association with migration was cochlear ossification, although 127 of 151 cases had no known association. During an equivalent period, 637 cochlear implant (CI) procedures were performed at the University of Miami. Of 580 primary CI operations, 2 cases of electrode migration were identified, both associated with reossification of a cochlea that was fully ossified at the first procedure. CONCLUSION: Electrode migration is an underrecognized complication of CI surgery and may be associated with cochlear ossification. Electrode stabilization techniques may reduce the incidence of CI electrode migration in nonossified or incompletely ossified cases.     

Electrophysiology and genetic testing in the precision medicine of congenital deafness: A review

Background:Congenital hearing loss is remarkably heterogeneous,with over 130 deafness genes and thousands of variants,making for innumerable genotype/phenotype combinations.Understanding both the pathophysiology of hearing loss and molecular site of lesion along the auditory pathway permits for significantly individualized counseling.Electrophysiologic techniques such as electrocochleography(ECochG)and electrically-evoked compound action potentials(eCAP)are being studied to localize pathology and estimate residual cochlear vs.neural health.This review describes the expanding roles of genetic and electrophysiologic evaluation in the precision medicine of congenital hearing loss.The basics of genetic mutations in hearing loss and electrophysiologic testing(ECochG and eCAP)are reviewed,and how they complement each other in the diagnostics and prognostication of hearing outcomes.Used together,these measures improve the understanding of insults to the auditory system,allowing for individualized counseling for CI candidacy/outcomes or other habilitation strategies.Conclusion:Despite tremendous discovery in deafness genes,the effects of individual genes on neural function remain poorly understood.Bridging the understanding between molecular genotype and neural and functional phenotype is paramount to interpreting genetic results in clinical practice.The future hearing healthcare provider must consolidate an ever-increasing amount of genetic and phenotypic information in the precision medicine of hearing loss.     

High glucocorticoid receptor content of leukemic blasts is a favorable prognostic factor in childhood acute lymphoblastic leukemia

We have previously shown that the number of glucocorticoid receptors (GR) per cell in malignant lymphoblasts from children with newly diagnosed pre-B- and early pre-B-cell acute lymphoblastic leukemia (ALL) has a positive correlation with the probability of successful remission induction (Quddus et al, Cancer Res, 45:6482, 1985). We report now on the long-term outcome for these patients treated on a single protocol with 3 different treatment arms, all of which included glucocorticoid pulses during maintenance therapy. GR were quantitated in leukemic cells from 546 children with ALL at the time of diagnosis. Immunophenotyping studies were performed on all specimens. Prior studies showed that in pre-B- and early pre-B-cell ALL, successful remission induction was associated with a median GR number of 9,900 sites/cell, whereas induction failure was associated with a median receptor number of 4,800 sites/cell. Long-term follow-up of these patients shows an association between higher GR number and improved prognosis. The 5-year event-free survival of 61.0% (SE 2.8%) for patients whose leukemic cells had greater than 8,000 receptors/cell and 47.3% (SE 3.3%) for those with less than 8,000 receptors/cell is significantly different (P < .001). This difference remains significant when adjusted multivariately for blast immunophenotype and clinical risk factors (P < .001) or for treatment type (P < .001). We conclude that GR number greater than 8,000 sites/leukemic cell is a favorable prognostic marker for children with acute lymphocytic leukemia. This finding offers deeper insights into molecular mechanisms of anti- leukemia therapy and suggests that manipulation of steroid receptor number might augment the antitumor response, thus opening new avenues for basic and clinical research.     

Structural Requirements in the Fc Region of Rabbit IgG Antibodies Necessary to Induce Cytotoxicity by Human Lymphocytes

Rabbit IgG anti-chicken erythrocyte antibodies were compared with the Fab/c or Facb fragments of IgG and with partially reduced and alkylated IgG for the capacity to induce cytotoxicity by normal human lymphocytes. The Fab/c antibody fragment, which lacks one Fab region, was still able to induce cytotoxicity. In contrast, the Facb antibody fragment, which lacks the Cγ3 domains, was nearly ineffective in activating the effector cells, whereas intact antibody activity was demonstrated by its ability to inhibit the cytotoxicity induced by unsplit IgG. Similarly, partial reduction and alkylation of the IgG antibodies, under conditions affecting the interchain disulphide bonds only, greatly diminished their ability to induce cytotoxicity, although they effectively inhibited the cytotoxicity induced by untreated IgG. On the basis of these results and previous data, we suggest that the reaction of the Fc region of IgG with the effector cell depends on the integrity of the Cγ² domain in the native, divalent state or on the interaction between the Cγ² and Cγ³ domains.