Variations in ventral root axon morphology and locomotor behavior components across different inbred strains of mice

Locomotion is a complex behavior affected by many different brain- and spinal cord systems, as well as by variations in the peripheral nervous system. Recently, we found increased gene expression for EphA4, a gene intricately involved in motor neuron development, between high-active parental strain C57BL/6J and the low-active chromosome substitution strain 1 (CSS1). CSS1 mice carry chromosome 1 from A/J mice in a C57BL/6J genetic background, allowing localization of quantitative trait loci (QTL) on chromosome 1. To find out whether differences in motor neuron anatomy, possibly related to the changes in EphA4 expression, are involved in the motor activity differences observed in these strains, motor performance in various behavioral paradigms and anatomical differences in the ventral roots were investigated. To correlate the behavioral profiles to the spinal motor neuron morphology, not only CSS1 and its parental strains C57BL/6J (host) and A/J (donor) were examined, but also a set of other mouse inbred strains (AKR/J, 129×1/SvJ and DBA/2J). Significant differences were found between inbred strains on home cage motor activity levels, the beam balance test, grip test performance, and on alternating versus synchronous hind limb movement (hind limb hopping). Also, considerable differences were found in spinal motor neuron morphology, with A/J and CSS1 showing smaller, possibly less developed, motor neuron axons compared to all other inbred strains. For CSS1 and C57BL/6J, only genetically different for chromosome 1, a correlation was found between motor activity levels, synchronous hind limb movement and neuro-anatomical differences in spinal motor neurons. Inclusion of the other inbred strains, however, did not show this direct correlation. These data verifies the complex nature of the mammalian motor system that may be further dissected using genetic mapping populations derived from these inbred strains.     

BAFF binding to T cell-expressed BAFF-R costimulates T cell proliferation and alloresponses

Binding of the TNF family member, B cell activating factor (BAFF), to its receptor (BAFF-R, TNFRSF13C) is required for generation and maintenance of mature B cells, but there are no data as to any role for the BAFF/BAFF-R pathway in T cell functions. We report that the binding of BAFF to BAFF-R expressed by a subset of primarily CD4(+) T cells costimulates T cell activation and allo-proliferation in vitro and in vivo, and that mice with a mutation in the BAFF-R, or with a targeted deletion of BAFF, show prolonged cardiac allograft survival as compared to wild-type or transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI)(-/-) controls. Taken together, these data indicate the BAFF/BAFF-R pathway contributes to both T and B cell responses and may be an attractive target for control of acute and chronic allograft rejection.     

The Changed Balance of Regulatory and Naive T Cells Promotes Tolerance after TLI and Anti‐T‐Cell Antibody Conditioning

The goal of the study was to determine how the changed balance of host naïve and regulatory T cells observed after conditioning with total lymphoid irradiation (TLI) and antithymocyte serum (ATS) promotes tolerance to combined organ and bone marrow transplants. Although previous studies showed that tolerance was dependent on host natural killer T (NKT) cells, this study shows that there is an additional dependence on host CD4⁺CD25⁺ Treg cells. Depletion of the latter cells before conditioning resulted in rapid rejection of bone marrow and organ allografts. The balance of T‐cell subsets changed after TLI and ATS with TLI favoring mainly NKT cells and ATS favoring mainly Treg cells. Combined modalities reduced the conventional naïve CD4⁺ T cells 2800‐fold. The host type Treg cells that persisted in the stable chimeras had the capacity to suppress alloreactivity to both donor and third party cells in the mixed leukocyte reaction. In conclusion, tolerance induction after conditioning in this model depends upon the ability of naturally occurring regulatory NKT and Treg cells to suppress the residual alloreactive T cells that are capable of rejecting grafts.     

Auditory brain-stem responses in guinea pigs following middle ear implantation of Ceravital

Summary The effects on auditory function caused by implantation of the bioactive glass ceramic Ceravital in the middle ear of guinea pigs was investigated. Auditory brain-stem responses (ABR) were used to measure hearing function. A threshold shift due to a conductive hearing loss was observed immediately post-operatively. This threshold shift increased towards the 20th post-operative day and improved thereafter. Surgical manipulation of the middle ear and biochemical reactions between the Ceravital granules and the middle ear wall may have contributed respectively to the immediate and late temporary ABR threshold shift recorded. However, cochlear function was not affected by middle ear implantation of Ceravital. These results correlate well with morphological studies of Ceravital implanted in the middle ear and give further support to the safe use of Ceravital as an implantation material in middle ear reconstructive surgery. Offprint requests to: D. Zikk, Department of Otorhinolaryngology, Tel Aviv Sourasky Medical Center, Ichilov Hospital, 6 Weizman St., Tel Aviv 64239, Israel     

可吸收、解剖型颈椎椎间融合器的临床应用初步报告

目的观察可吸收颈椎椎间融合器（ADFC）临床应用的疗效并分析其特点、优越性、适应证及并发症。方法对18例脊髓型颈椎病患者行前路减压ADFC植入术，术后随访11～18个月，平均14．3个月。结果18例患者末次随访时均获得骨性融合，融合率为100％；17例患者的疗效为优良，1例患者为良好，无疗效为满意或差的病例；无术中及术后并发症产生。结论ADFC具有早期的确实制动作用，有效维持颈椎的生理弧度和椎间隙的高度，提供初始及中间时期的稳定性以实现骨性融合，有效防止下沉，并稳定融合节段及便于判断融合的特点。     

钛网融合器配合钉板系统在颈椎前路重建中的应用

目的探讨颈椎问前路减压钛网联合钉板系统治疗颈椎疾患的临床疗效。方法对12例颈椎疾病患者行颈前路椎体次全切除同时采用钛网植骨融合联合带锁钢板内固定。结果平均随访11个月(6-24个月)，植骨均在6个月达到临床融合，无内固定松动、断裂等不良现象。术后疗效按JOA评分，术前5～13分，术后提高4-6分，脊髓功能平均改善率为82．4％。结论颈椎前路减压术同时采用钛网融合器植骨联合钉板系统内固定可使颈椎得到即刻稳定，重建颈椎正常解剖结构，有利于骨性融合。     

大段冷冻异体骨移植复合人工关节置换的保肢术

目的 研究分析大段冷冻异体骨移植复合人工关节置换修复股骨上下段肿瘤切除后骨缺损的疗效。方法 本组22例,行复合股骨上段的全髋关节置换8例,复合股骨下段全膝关节置换14例。按Enneking分期,广泛边缘性切除股骨上下段肿瘤,选用长柄人工关节将大小和形态合适的同种异体骨关节与宿主骨经骨水泥髓内固定,假体柄插入宿主骨髓内长度与异体骨轴心长度比≥0.8～1。术后均未用免疫抑制剂。结果 20例(除2例复合股骨下段患者外)患者随访6～64个月,平均46个月。3例分别于术后4、6和7个月局部软组织复发,经广泛切除后治愈;2例分别于术后9个月和15个月死亡;其余患者均无瘤生存。所有患者均无关节脱位、假体松动和断裂。5例异体股骨大转子区部分吸收。异体骨和宿主骨间均达骨性愈合,愈合时间5～12个月,平均8月。8例复合股骨上段的全髋关节置换者,髋关节活动度为76°～114°,平均87°。12例复合股骨下段全膝关节置换者,膝关节活动度为68°～104°,平均82°。按ISOLS骨肿瘤术后功能重建评分20～28分,平均25.2分。结论 人工关节通过现代骨水泥固定技术将异体骨与宿主骨有机地连接在一起,从而达到牢固的髓内固定。异体骨与宿主骨间的生物性连接,增加了人工关节的固定臂,从而降低了肿瘤人工关节下沉、松动或断裂的发生率。     

Blockade of Macrophage Migration Inhibitory Factor Does Not Prevent Acute Renal Allograft Rejection

Macrophage migration inhibitory factor (MIF) is a pro-inflammatory molecule involved in cell-mediated immunity and delayed-type hypersensitivity (DTH). We inhibited systemic and local MIF production to determine its contribution to acute rejection (AR). Skin DTH response and acute rejection of skin and kidney allografts were examined using MIF gene knockout (MIF -/-) and wild-type mice (MIF +/+) with anti-MIF or control antibody. MIF-Ab reduced skin DTH by 60% (p < 0.01), but absence of the MIF gene (MIF -/-) had no effect. Local absence of MIF had no effect on the survival of skin grafted onto BALB/c recipients. Similarly MIF +/+ and MIF -/- kidneys transplanted into BALB/c recipients showed a similar degree of histological rejection, graft dysfunction and cellular infiltrate suggesting that AR is not dependent on local MIF production. To investigate the influence of systemic MIF, BALB/c donor skin was grafted onto MIF +/+ and MIF -/- mice. The tempo of AR was not altered by systemic absence of MIF (MIF-Ab or MIF -/-). BALB/c kidneys transplanted into MIF +/+ (with or without MIF-Ab) and MIF -/- mice showed similar parameters of rejection. MIF blockade reduces the DTH response; however, neither local nor systemic MIF are required for the rejection of fully mismatched skin and renal allografts.     

Janus kinase-3 (JAK3) inhibition: a novel immunosuppressive option for allogeneic transplantation

Current immunosuppressive therapy in clinical organ transplantation is based on drugs that suppress various functions of immunocompetent cells but still affect cells and organ compartments other than the immune system. Hence, these drugs have considerable side effects which lead to increased morbidity and reduced life-quality of transplant recipients. A major step forward in the rationale design of clinical immunosuppression resides in the elucidation of molecular targets that play a critical role specifically within the immune system. Recently, Janus kinase 3 (JAK3) has been identified as such a molecule. Genetic absence or ablation of this tyrosine kinase is associated with defective T-cell immunity that results in severe combined immunodeficiency (SCID) without apparent changes in other organ systems. Furthermore, pharmacological inhibition has significantly prolonged allograft survival in several experimental models of organ transplantation. The present review provides an overview of the emerging role of JAK3 in the immune system and the development of JAK3-inhibiting drugs. The potential clinical application of JAK3 inhibitors in organ transplantations is discussed in the light of a recent series of successful kidney transplantations in non-human primates immunosuppressed solely with a novel JAK3 inhibitor.     

Radiolucent cage for cervical vertebral reconstruction: A prospective study of 17 cases with 2-year minimum follow-up

In cervical spondylotic myelopathy, extended anterior spinal cord decompression necessitates subsequent stable vertebral reconstruction. Reconstruction with an iliac crest graft and screw-plate fixation gives satisfactory clinical and radiological results, but they are often compromised by morbidity involving the bone harvest. The purpose of this study was to evaluate the contribution to cervical reconstruction of a biocompatible, radiolucent cage combined with screw-plate fixation, making use of bone harvested in situ. This prospective study was performed between July 2000 and March 2001 in eight women and nine men (mean age, 55 years) operated for cervical spondylotic myelopathy. Situated between levels C3 and C6, the cage was inserted after one corporectomy in ten patients, two corporectomies in five patients, and three corporectomies in two patients. The cage consisted of a polyester mesh impregnated with poly-L-lactic acid (PLLA) conferring temporary rigidity to the cage during bony fusion. Clinical and radiological follow-up (plain films, computed tomographic reconstruction in three cases) was performed at 2 months, 6 months, 12 months, 24 months and 36 months, postoperatively, with a mean follow-up of 30 months. Functional results were evaluated according to the Japanese Orthopaedic Associations scoring system. An independent surgeon assessed the radiological evidence of anterior cervical fusion using the grades proposed by Bridwell [6]. Every patient experienced neurological recovery. At last follow-up, radiological findings were consistent with grade I (complete fusion) in five cases, grade II (probable fusion) in ten cases, grade III (radiolucent halo in favor of non fusion) in one case, and grade IV (graft lysis) in one case with persistent neck pain. In three cases there was screw breakage (two grade II, one grade IV). None of these cases required surgical revision at latest follow-up. In extensive spinal cord decompression through an anterior approach, cervical reconstruction using the present type of cage can achieve clinical results comparable to conventional techniques. The rigidity of the cage meets biomechanical imperatives. Its radiolucency permits one to monitor the course of consolidation, contrary to metal cages. The cases of probable non-fusion and screw breakage were not accompanied by signs of instability on the flexion extension films. This cage meets the biologic and biomechanical imperatives of cervical reconstruction. It obviates complications involving bone harvest.