A critical function for type I interferons in cancer immunoediting

'Cancer immunoediting' is a process wherein the immune system protects hosts against tumor development and facilitates outgrowth of tumors with reduced immunogenicity. Although interferon-gamma (IFN-gamma) is known to be involved in this process, the involvement of type I interferons (IFN-alpha/beta) has not been elucidated. We now show that, like IFN-gamma, endogenously produced IFN-alpha/beta was required for the prevention of the growth of primary carcinogen-induced and transplantable tumors. Although tumor cells are important IFN-gamma targets, they are not functionally relevant sites of the actions of the type I interferons. Instead, host hematopoietic cells are critical IFN-alpha/beta targets during development of protective antitumor responses. Therefore, type I interferons are important components of the cancer immunoediting process and function in a way that does not completely overlap the functions of IFN-gamma.     

Choline acetyltransferase activity and cognitive domain scores of Alzheimer's patients

Choline acetyltransferase activity and cognitive domain scores of Alzheimer's patients. Item scores from the Mattis Dementia Rating Scale (MDRS) and the Mini-Mental State Examination (MMSE) from 389 patients with probable Alzheimer's disease were submitted to principal component analysis with orthogonal rotation. The optimal solution identified four factors that reflected the cognitive domains of attention/registration, verbal fluency/reasoning, graphomotor/praxis and recent memory. A subgroup of patients was identified for whom both the MDRS and the MMSE had been administered within the 12 months before death. Scores were assigned to these patients for the four factors. These cognitive-domain scores were then correlated with postmortem choline acetyltransferase (ChAT) activity in the medial frontal cortex, inferior parietal cortex, and hippocampus. ChAT activity in both the medial frontal and the inferior parietal cortex significantly correlated with scores on the graphomotor/praxis factor. Medial frontal ChAT also correlated significantly with the attention/registration scores. Hippocampal ChAT correlated significantly only with recent memory scores. These results are consistent with current animal research regarding the effect of selective cholinergic lesions on behavior.     

严重急性呼吸综合征患者尸解肺标本的病理改变和致病机制研究

目的研究严重急性呼吸综合征（SARS）患者尸解肺标本的病理改变和致病机制。方法观察了2003年4-7月期间死于SARS的6例患者的肺标本,并采用光镜、电镜、Masson三色染色和免疫组织化学染色方法（EnVision法）进行研究。结果肺标本的病理形态改变：（1）6例的双肺均可见到弥漫性实变病灶,肺重量明显增加;（2）6例均可见到弥漫性肺泡损伤,包括透明膜形成、肺泡腔内水肿／出血、纤维素沉积和肺泡上皮细胞脱屑,AE1／AE3免疫组织化学染色显示肺泡上皮细胞的完整性明显破坏;（3）Ⅱ型肺泡上皮细胞轻度增生,有一定异型性,细胞体积增大,胞质呈双染性和颗粒状,胞质内可见小脂肪空泡聚集（5／6）;（4）6例中有5例可见巨细胞在肺泡内浸润,巨细胞大多AEl／AE3阳性（5／6）,少数CD68阳性（2／6）;（5）组织学形态和免疫组织化学染色证实肺泡腔内和肺泡间隔内有多量巨噬细胞浸润（6／6）;（6）6例中有5例可见巨噬细胞噬红细胞象;（7）6例中有5例可见肺纤维化,包括肺泡间隔和肺间质增宽（5／6）、肺泡腔内渗出物机化（6／6）和胸膜增厚（4／6）。Masson三色染色证实胶原纤维明显增生,免疫组织化学染色显示大多数为Ⅲ型胶原。光镜和免疫组织化学染色显示5例有明显的成纤维细胞／肌纤维母细胞增生灶;（8）5例可见支气管黏膜鳞状上皮化生;（9）6例患者均可见血栓;（10）2例同时合并其他感染,1例合并细菌感染,另1例合并真菌感染。此外,电镜发现在肺泡上皮细胞和肺血管内皮细胞的胞质内有冠状病毒样颗粒。结论SARS冠状病毒直接损伤肺泡上皮细胞、巨噬细胞明显浸润和成纤维细胞／肌纤维母细胞显著增生在SARS的致病机制中起重要作用。     

Primary hepatic leiomyosarcoma in a child with the acquired immunodeficiency syndrome.

We report the first case of acquired immunodeficiency syndrome (AIDS)-related primary hepatic leiomyosarcoma in a 9-year-old girl. The pathologic diagnosis was made on a partial hepatectomy specimen and was confirmed by immunohistochemistry and electron microscopy. No human immunodeficiency virus-related nucleic acid was identified in tumor cells by in situ hybridization. Review of the AIDS-related literature reveals a rising incidence of tumors of smooth muscle origin in human immunodeficiency virus-infected patients. This case study details the eighth pediatric AIDS patient with a tumor of smooth muscle origin and represents the 20th and the youngest patient with primary hepatic leiomyosarcoma to be reported in the world literature.     

Simulation of laser tomoscopy in a heterogeneous biological medium

A Monte Carlo model has been developed to study the propagation of an ultrashort light pulse through a heterogeneous thick biological specimen. A circular blood vessel is moved within a tissular slab to simulate biological specimen scanning using a picosecond laser source and a collimated ultrafast multichannel opticl shutter. Features of the transmitted light are computed for each position of the blood vessel. The computer program gives an account of the transmitted photons, the flight time which does not exceed straightforward crossing time plus time gate of known duration. A small blood vessel (radius R=2 mm) placed in a 40 mm thick slab is easily located when a time gate of 10 ps duration is employed. Such a time gate also allows the detection of a middle-sized vessel (R=4 mm) embedded in a thicker sample (80 mm). The contrast computed for the transmittance profile is greatly improved when a time gate is used. In addition, shifting of the blood vessel towards the unilluminated side of the sample decreases the contrast. We demonstrate that the time selection process may provide a substantial improvement to the laser tomoscopy technique when used for imaging biological media.     

Fertility in myotonic dystrophy in Saguenay-Lac-St-Jean: a historical perspective

Myotonic dystrophy (MD) is an autosomal dominant disorder that has a high prevalence in Saguenay-Lac-St-Jean. A case-control study, based on a population register, of 373 MD patients who married in this region between 1855 and 1971 was conducted to determine whether their fertility was affected by the disorder. Six demographic parameters, that is the number of children, the age at marriage, the ages at the time of birth of the first and the last child, the interval between the marriage and the birth of the first child, and the interval between consecutive births, were analyzed. The mean number of children born to MD and control individuals was not different (P > 0.05). However, MD males had more children than MD females although they have started delaying their marriage since 1921. Fertility fell significantly in both the MD and control groups during the period of observation. This change reflects the decline in fertility of French Canadians in general during this period, but mainly after 1940.     

纤溶酶-α2抗纤溶酶复合物单克隆抗体的制备及鉴定

目的 :制备纤溶酶 α2 抗纤溶酶复合物 (PAP)的单克隆抗体(mAb)。方法 :以从血浆中纯化的PAP免疫BALB/c小鼠。按常规方法融合 ,以固相等分子浓度的纤溶酶原、α2 抗纤溶酶(α2 AP)及PAP为抗原 ,建立间接ELISA筛选杂交瘤细胞培养上清 ,并对杂交瘤细胞分泌的mAb的特异性和亲和力进行鉴定。结果 :共获得 2 4株可稳定分泌特异性mAb的杂交瘤细胞。其中 ,针对PAP分子中纤溶酶结构的mAb 16株 ,针对α2 AP结构的mAb 1株 ,针对新抗原 (PAP分子中新出现的不同于前体分子纤溶酶原及α2 AP的抗原决定簇 )结构的mAb 7株。这些腹水中抗PAPmAb的滴度为 2× 10 -4～ 1× 10 -8,其中 4株mAb的亲和常数为 5 .6 2× 10 -9～ 3.5 8× 10 -11mol/L之间。结论 :成功地制备针对PAP新抗原的具有高亲和力的mAb ,为建立不受其前体分子干扰的PAP特异性检测方法 ,研究纤溶系统的激活状态提供了工具。     

Significance of cytogenetic and fluorescence in situ hybridization analysis in evaluating antichronic myeloid leukemia efficacy of different immune effector cells

We report on the antileukemia effect of interleukin 2 (IL2) on different immune cells from 22 patients with chronic myeloid leukemia (CML). Bone marrow cells from these patients were first cultured in modified long-term bone marrow culture medium for several days, then separately cultured with lymphokine activated killer cells (LAK), cytokine-induced killer cells (CIK), and dendritic cell cocultured CIK (DC-CIK) for another 1-2 days. They were then detected for presence of the Philadelphia chromosome (Ph) by cytogenetic analysis and fluorescence in situ hybridization (FISH). The percentage of Ph-chromosome-positive cells in the bone marrow mononuclear cells after culturing with CIK and DC-CIK was significantly lower than that after culturing with IL2 or LAK. Our results demonstrate that cytogenetics and FISH are useful techniques for the evaluation of the anti-CML effect of immune cells and that CIK or DC-CIK can be appropriate candidates for adoptive immune cell therapy in vivo or for leukemia cell purging ex vivo.