Granulocyte-macrophage colony-stimulating factor augmentation of T-cell receptor-dependent and T-cell receptor-independent thymocyte proliferation

The effects of granulocyte-macrophage colony-stimulating factor (GM- CSF) are not confined to cells of the myeloid lineage. GM-CSF has been shown to have effects on mature T cells and both mature and immature T- cell lines. We therefore examined the GM-CSF responsiveness of murine thymocytes to investigate whether GM-CSF also affected normal immature T lymphocytes. The studies presented here indicate that GM-CSF augments accessory cell (AC)-dependent T-cell receptor (TCR)-mediated proliferation of unseparated thymocyte populations. To identify the GM- CSF responsive cell type, thymic AC and T cells were examined for GM- CSF responsiveness. We found that GM-CSF augmentation of TCR-induced thymocyte proliferation appears to be mediated via augmentation of AC function, and not via direct effects on mature single-positive (SP) thymocytes. Enriched double-negative (DN) thymocytes were also tested for GM-CSF responsiveness. GM-CSF induced the proliferation of adult and fetal DN thymocytes in an AC-independent and TCR-independent single- cell assay. Thus, in contrast to the SP thymocytes, a DN thymocyte population was directly responsive to GM-CSF. GM-CSF therefore may play a direct role in the expansion of DN thymocytes and an indirect role in the expansion of SP thymocytes.     

Quantification of the breakpoint cluster region rearrangement for clinical monitoring in Philadelphia chromosome-positive chronic myeloid leukemia

The purpose of this report was to evaluate scintigraphy analysis of Southern blot hybridization as a method to quantify the breakpoint cluster region (BCR) rearrangement of Philadelphia chromosome (Ph)+ chronic myelogenous leukemia (CML). Cytogenetic and molecular studies performed simultaneously on 474 bone marrow and/or blood samples from 300 patients treated with alpha-interferon-based therapy were compared. Molecular results were expressed as the percentage of rearranged BCR bands versus the total scintigraphic signal. The percentage of Ph+ metaphases was calculated on 25 metaphases. The results of molecular studies obtained on both peripheral blood and bone marrow samples were identical. The rank correlation between the BCR quantification and the percentage of Ph positivity in 465 samples was excellent (r = .78). However, of 99 samples with a normal karyotype, 24% had a BCR rearrangement. Of 86 samples with no BCR rearrangement, 13% showed a Ph chromosome. Of 49 samples with partial cytogenetic remission (Ph+ metaphases, 1% to 34%), 23% had no BCR rearrangement. In samples with a minor or no cytogenetic response (Ph+ metaphases, > 34%), BCR analysis overestimated the degree of response in 73 of 326 samples (22%). Nevertheless, survival analysis by BCR quantification level showed statistically better outcome for patients in complete or partial molecular response (P < .01). Molecular quantification of BCR was useful in monitoring the course of Ph+ CML. This method, which can be used on peripheral blood, detected residual disease not shown by cytogenetic analysis and was prognostically relevant as a measure of disease suppression.     

Effects of monoclonal antibody therapy in patients with chronic lymphocytic leukemia

A phase I clinical trial was initiated to treat patients with stage IV B-derived chronic lymphocytic leukemia (CLL) with the IgG2a murine monoclonal antibody T101. This antibody binds to a 65,000-mol wt (T65) antigen found on normal T lymphocytes, malignant T lymphocytes, and B- derived CLL cells. All of the patients had a histologically confirmed diagnosis of advanced B-derived CLL and were refractory to standard therapy, and more than 50% of their leukemia cells reacted with the T101 antibody in vitro. The patients received T101 antibody two times per week, over two to 50 hours by intravenous administration in 100 mL of normal saline containing 5% human albumin. Twelve patients were treated with a fixed dosage of 1, 10, 50, or 100 mg, and one patient was treated with 140 mg of antibody. It was demonstrated that patients given two-hour infusions of 50 mg developed pulmonary toxicity, with shortness of breath and chest tightness. This toxicity was eliminated when infusions of 50 or 100 mg of T101 were prolonged to 50 hours. All dose levels caused a rapid but transient decrease in circulating leukemia cell counts. In vivo binding to circulating and bone marrow leukemia cells was demonstrated at all dose levels with increased binding at higher dosages. Antimurine antibody responses were not demonstrated in any patients at any time during treatment. Circulating free murine antibody was demonstrated in the serum of only the two patients treated with 100 mg of antibody as a 50-hour infusion and the patient treated with 140 mg of antibody over 30 hours. Antigenic modulation was demonstrated in patients treated at all dose levels but was particularly apparent in patients treated with prolonged infusions of 50 and 100 mg of antibody. We were also able to demonstrate antigenic modulation in lymph node cells, which strongly suggests in vivo labeling of these cells. Overall, T101 antibody alone appears to have a very limited therapeutic value for patients with CLL. The observations of in vivo labeling of tumor cells, antigenic modulation, antibody pharmacokinetics, toxicity, and antimurine antibody formation may be used in the future for more effective therapy when drugs or toxins are conjugated to the antibody.     

乳腺浸润性导管癌超声影像特征分析

 目的 分析超声各特征性影像表现在乳腺浸润性导管癌中的诊断价值。方法 选取解放军总医院第六医学中心 2018-01至2019-12两年内收治的 135例乳腺浸润性导管癌患者纳入本研究,分析乳腺浸润性导管癌的超声影像特征、体检自检发现率以及淋巴结转移与病变大小、位置的相关性。结果 (1)单因素分析显示:形态不规则(91.11%)、边界不清楚(64.44％)、血流信号(44.44％)、微钙化(37.78%)、纵横比＞1(17.78％)、后方回声衰减(15.56％)超声诊断指标,与浸润性导管癌的诊断具有相关性;(2)与其他三个象限相比较,内上象限浸润性导管癌更容易被患者自检发现,占自检发现病例的34.93%;(3)内上象限及外上象限的浸润性导管癌更容易发生淋巴结转移(转移率为:内上:25.53%,内下:0.00%,外上:64.70%,外下:11.76%);(4)对＜3 cm的浸润性导管癌,其大小与腋窝淋巴结的转移没有相关性。结论 超声表现以形态不规则在乳腺浸润性导管癌中的发生率最高,且在早期病变中即表现出来;乳腺病变的自检检出率、乳腺癌淋巴转移率均与乳腺病变的大小和位置密切相关。     

The use of bisphosphonates in children: review of the literature and guidelines for dental management

Bisphosphonates are inhibitors of osteoclastic bone resorption with therapeutic benefit in a variety of bone disorders in both adults and children. While these agents have been routinely used in adults for the past three decades, their more recent introduction into paediatric medicine means there is a paucity of data on long‐term safety and effects on dental development. There is uncertainty regarding the dental management of children treated with bisphosphonates, particularly when invasive dental procedures, such as extractions and oral surgical procedures, are required. There are limited data with which to make recommendations about the dental management of patients treated with bisphosphonates, and there are no published recommendations that specifically address paediatric patients. This paper aims to outline paediatric uses and adverse effects of bisphosphonates and present recommendations on the dental management of children receiving bisphosphonates.     

基于层次分析法（AHP）的保健食品原料评价体系构建及分析

目的建立保健食品原料评价体系(Functional Food Crude Materials Evaluation System,FUFMES),为保健食品原料目录排名提供科学依据与技术保障。方法首先,利用文献调研和多轮专家访谈方法筛选FUFMES的指标并确定其层级关系;第二,使用层次分析法(Analytic Hierarchy Process,AHP)计算指标权重,具体方法是依据专家打分构建判断矩阵,利用R语言进行一致性检验与最大特征根检验,得出各级指标权重;第三,使用极值法计算原料的单个指标值;第四,利用线性加权综合法得到每种原料的评价指数并据此进行排名;最后,将获得的分析结果与专家评价结果进行比较。结果 FUFMES包括6个一级指标、39个二级指标、11个三级指标。利用FUFMES对9种保健食品原料进行评价,获得的评价指数依次是:西洋参(0.49)、人参(0.48)、银杏叶(0.21)、灵芝孢子粉(0.08)、鱼油(0.06)、螺旋藻(0.03)、辅酶Q10(0.02)、褪黑素(0.01)、大蒜油(-0.03)。基于该评价指数的排名结果与专家评价结果显示了较高一致性。结论构建了科学、完整的FUFMES,FUFMES将成为保健食品原料目录评价与排名的有力工具,为推进保健食品原料备案制提供科学依据与技术保障。     

Cardiorespiratory fitness and body mass index values in 9-year-old rural Norwegian children

Aim: To describe cardiorespiratory fitness and body mass index (BMI) values in a representative population of 9-year-old Norwegian children in two rural communities and compare present values with previous findings.
Methods: Two hundred and fifty-nine 9-year-old children were invited, and 256 participated in this study. Maximal oxygen uptake was directly measured during a continuous progressive treadmill protocol. Body mass and height were also measured.
Results: The mean ± SD relative maximal oxygen uptake was 52.8 ± 6.5 for boys and 46.9 ± 7.2 mL/kg/min for girls. Eight percent of the boys and 16.8% of the girls were classified as overweight, and 1.6% of the boys and 6.9% of the girls as obese. Mean age, body mass, height and Ponderal index were not significantly different between sexes. Girls had a higher BMI than boys (p = 0.05).
Conclusion: Compared to earlier Norwegian studies, children's BMI values seem to have increased substantially. This increase is most pronounced in girls. When assessing these differences using the PI, this increase is less marked. Comparing maximal oxygen uptake data with that in earlier Nordic studies, there is no evidence that fitness has declined among 9-year olds. However, the limitations of the few earlier studies make reliable comparisons difficult.     

Usefulness of muscle denervation as an MRI sign of peripheral nerve pathology

Peripheral nerve disorders may be classified into compressive or entrapment neuropathies and non‐compressive neuropathies. Muscle denervation recognized on MRI may be a useful sign in the diagnosis of peripheral nerve disorders. Acute or subacute denervation results in prolonged T2 relaxation time, producing increased signal in skeletal muscle on short tau inversion‐recovery and fat‐suppressed T2‐weighted images. Chronic denervation produces fatty atrophy of skeletal muscles, resulting in increased muscle signal on T1‐weighted images. This review will outline and illustrate the various ways that muscle denervation as seen on MRI may assist in the diagnosis and localization of peripheral nerve disorders.