Active immunization of murine allogeneic bone marrow transplant donors with B-cell tumor-derived idiotype: a strategy for enhancing the specific antitumor effect of marrow grafts

Persistence of the underlying malignancy remains the major obstacle limiting the success of high-dose chemoradiotherapy with allogeneic bone marrow transplantation (BMT) for lymphomas and multiple myeloma. We used the C3H 38C13 murine B-cell lymphoma, which expresses and secretes clonally derived Ig, the idiotype of which can serve as a tumor-specific antigen, to test the principle of transfer of tumor idiotype-specific immunity with BM. BALB/c marrow donors were twice immunized with 38C13-derived Ig, or with an isotype-matched control Ig, conjugated to keyhole limpet hemocyanin. Lethally irradiated C3H recipients reconstituted with marrow from idiotype immune, but not nonspecifically immune, donors demonstrated protection against subsequent lethal tumor challenge. The immunoprotective effect of immune allogeneic marrow was abrogated by T-cell depletion of the marrow graft before infusion. Low levels of serum anti-idiotypic antibody remained unaltered in recipients of T-cell-depleted immune marrow, consistent with a primary role for T-cell immunity in the cellular mechanism of this phenomenon. A modest therapeutic effect of immune allogeneic marrow was observed against 10 day, 1 cm established subcutaneous tumors, but only in combination with a booster immunization of the recipient post-BMT. These results provide the rationale for a novel strategy for enhancing the specific antitumor effect of allogeneic marrow grafts.     

Response to 2'-deoxycoformycin after failure of interferon-alpha in nonsplenectomized patients with hairy cell leukemia

Two patients with hairy cell leukemia with massive splenomegaly and severe pancytopenia were treated with recombinant alpha-A interferon (IFN-alpha-2a). There was no significant response to a trial of IFN- alpha-2a (11 and 20 weeks) with respect to blood counts or spleen size. Subsequent treatment with 2'-deoxycoformycin (dCF) for 8 consecutive weeks (4 mg/m2/wk) resulted in normalization of spleen size and a normalization of peripheral blood counts and bone marrow in one patient. The second patient demonstrated a reduction in spleen size and improved blood counts following 9 weeks of dCF therapy but eventually became refractory. This demonstrates that dCF is non-cross-resistant with interferon and confirms the efficacy of dCF in nonsplenectomized patients.     

【特刊综述】雄激素对骨骼肌的作用：对乏力的发展和治疗的意义

雄激素对骨骼肌合成有明显影响,随着年龄增大,雄激素的下降常伴随肌量和肌力的下降。这种肌量和肌功能的下降,被称为少肌症或肌体老化,是老年人体质弱化（男性化减退）进展的关键事项。也是导致快速机能衰退及其不良后果的关键。雄激素水平下降对老年男性体质弱化（男性化减退）的潜在影响和对躯体功能的促进治疗作用无疑已经引起了相当的关注。本综述概述了近期关于肌肉老化、少肌症、老年体质弱化的概念、定义,并评估了关于雄激素和老年体质弱化的研究进展。近期源于观测性和介入性研究的证据强烈支持雄激素对老年男性肌量的作用,但雄激素对肌力和特有的躯体功能的效用并不明确。研究显示,雄激素治疗在老年男性中通常有良好的耐受性,而近期的研究则关注于雄激素的高剂量治疗和对于心血管风险较高人群的治疗。雄激素受体调节剂（SARMs）的初期试验研究显示传统雄激素治疗对于老年患者在肌量和肌功能方面有相同的效用。将来的重要研究方向包括利用这类雄激素治疗并结合适用于不同老年患者群体促进躯体功能的运动训练,同时将更多地关注近期关于激素水平、身体成分及躯体功能间关系的观测性（回顾性）研究。     

The effect of a basic home stimulation programme on the development of young children infected with HIV

Aims The human immunodeficiency virus (HIV) potentially causes a significant encephalopathy and resultant developmental delay in infected children. The aim of this study was to determine whether a home‐based intervention programme could have an impact on the neurodevelopmental status of children infected with HIV. Method A longitudinal, randomized, controlled trial was conducted. A total of 122 children aged less than 2 years 6 months were assigned to either a comparison or an experimental group. Children in the experimental group were given a home stimulation programme that was updated every 3 months. The home programme included activities to promote motor, cognitive, and speech and language development. Children in the comparison group received no developmental intervention. Children were assessed by a blinded assessor at baseline, 6 months, and 12 months using the Bayley Scales of Infant Development, 2nd edition. Results The children in this study came from poor socioeconomic backgrounds and their nutritional status was suboptimal. The experimental group included 60 children (30 males, 30 females) with a mean age of 18 months (SD 8.1mo). The comparison group included 62 children (32 males, 30 females) with a mean age 19 months (SD 8.2mo). Cognitive and motor development were severely affected at baseline, with 52% of the children having severe cognitive delay and 72% having severe motor delay at baseline. Children in the experimental group showed significantly greater improvement in cognitive (p=0.010) and motor (p=0.020) development over time than children in the comparison group. Interpretation A home stimulation programme taught to the caregiver can significantly improve cognitive and motor development in young children infected with HIV.     

Prophylactic immune tolerance induced by changing the ratio of antigen-specific effector to regulatory T cells

Summary.  Background : Gene and protein replacement therapies for inherited protein deficiencies such as hemophilia or lysosomal storage disorders are limited by deleterious immune responses directed against their respective therapeutic proteins. Therefore, the development of protocols preventing such responses is key to providing successful long-term therapy. Objectives : We sought to develop a protocol, utilizing a drug/peptide cocktail, that would effectively shift the antigen-specific CD4+ T-cell population, tipping the balance from effector T cells (Teffs) towards regulatory T cells (Tregs). Methods : Treg-deficient (DO11.10-tg Rag2^−/−) BALB/c mice were used to screen for an optimal protocol addressing the aforementioned goal and to study the mechanisms underlying in vivo changes in T-cell populations. Muscle-directed gene transfer to hemophilia B mice was also performed in order to test the optimal protocol in a therapeutically relevant setting. Results: Specific antigen administration (4-week repeated dosing) combined with rapamycin and interleukin-10 led to substantial reductions in Teffs, via activation-induced cell death, and induced CD4+CD25+FoxP3+ Tregs to a large extent in multiple organs. The proportion of apoptotic T cells also increased over time, whereas Teffs and Tregs were differentially affected. When applied to a model of protein deficiency (gene therapy for hemophilia B), the protocol successfully prevented inhibitor formation, whereas non-specific immunosuppression was only marginally effective. Conclusions : It is feasible to provide a short-term, prophylactic protocol allowing for the induction of immune tolerance. This protocol may provide a marked advance in efforts seeking to improve clinical outcomes in disorders involving therapeutic protein replacement.     

Uteroplacental Doppler flow velocity waveforms in the second trimester. A complex circulation

Summary. Continuous wave Doppler ultrasound was used to examine the Uteroplacental circulation of an unselected group of 993 women between 16 and 24 weeks gestation. Reference ranges for resistance index (RI) were determined and throughout this gestation range there was a significant fall in RI with increasing gestation. The RI was lower from placental than non-placental sites and from distal 'arcuate' than proximal 'uterine' sites. There is a need to define fixed standardized sites for sampling and for normal ranges to account for variables such as placental site.     

颅内动脉瘤栓塞后并发脑缺血的原因分析

1 临床资料我们总结2004-02/2004-06在第四军医大学唐都医院神经外科住院行栓塞治疗颅内动脉瘤患者27(男12,女15)例,年龄32～72岁.     

Unusual presentation of perirenal lung metastases

Lung cancer is not commonly known to metastasise to the perirenal space, with only five such cases previously published. We present an unusual case of perirenal lung metastases manifesting as diffuse perinephric stranding which to our knowledge has not been described before.     

High prevalence of HIV infection among homeless and street-involved Aboriginal youth in a Canadian setting

Aboriginal people experience a disproportionate burden of HIV infection among the adult population in Canada; however, less is known regarding the prevalence and characteristics of HIV positivity among drug-using and street-involved Aboriginal youth. We examined HIV seroprevalence and risk factors among a cohort of 529 street-involved youth in Vancouver, Canada. At baseline, 15 (2.8%) were HIV positive, of whom 7 (46.7%) were Aboriginal. Aboriginal ethnicity was a significant correlate of HIV infection (odds ratio = 2.87, 95%CI: 1.02 – 8.09). Of the HIV positive participants, 2 (28.6%) Aboriginals and 6 (75.0%) non-Aboriginals reported injection drug use; furthermore, hepatitis C co-infection was significantly less common among Aboriginal participants (p = 0.041). These findings suggest that factors other than injection drug use may promote HIV transmission among street-involved Aboriginal youth, and provide further evidence that culturally appropriate and evidence-based interventions for HIV prevention among Aboriginal young people are urgently required.     

Accuracy of passive ankle joint positioning during quiet stance in young and elderly subjects

Age-related postural deficits elicit compensatory mechanisms such as ankle dorsiflexion in the elderly. To gain further insight into this problem, the ability to match an ankle angle during quiet stance was studied in 12 elderly and 12 young subjects. Following an initial single limb angular perturbation presented in the ±4° range, a subject had to return a tilt platform to level, as determined by the nonperturbed limb. Elderly subjects exhibited significant positive (0.9°) over-shoot of the level position, in contrast to young subjects who matched ankle angle with a mean error of −0.1°. The elderly group also exhibited an increase in positioning error for angular displacements in the range between −1 and +1°. The results document age-related postural changes in ankle positioning which might affect postural stability in older adults.