PEUTZ‐JEGHERS SYNDROME ASSOCIATED WITH RENAL AND GASTRIC CANCER THAT DEMONSTRATED AN STK11 MISSENSE MUTATION

A 75‐year‐old male was admitted to the gastroenterology unit of Nagoya City University Hospital due to epigastralgia after surgical treatment for right renal cancer. Endoscopy revealed advanced type 1 gastric cancer in the corpus of the stomach and multiple polypoid lesions in the stomach and duodenum. X‐ray examination of the small intestine using barium showed multiple polyps in the upper jejunum. Faint pigmentation on the palm was also detected. Peutz‐Jeghers syndrome (PJS) was diagnosed, despite a lack of family history. Total gastrectomy, resection of part of the upper jejunum and intraoperative endoscopic polypectomy of duodenal polyps was performed. This is the second reported case of PJS associated with renal cancer. We also detected a missense mutation in the tumor suppressor gene STK11 that, when mutated, is causative for PJS.     

新的高强度高选择性阿片μ受体激动剂[11C]-羟甲芬太尼的合成

羟甲芬太尼(I)是一个新的高强度高选择性阿片μ受体激动剂。本文用cis-A-N-[1-(2-羟基-2-苯乙基)-3-甲基-4-哌啶基]-苯胺(II)或cis-N-[1-(苯甲酰甲基)-3-甲基-4-哌啶基]-苯胺(III)作为前体合成了[¹¹C]-羟甲芬太尼,以便用正电子发射断层扫描(PET)来观察μ受体。通过水解cis-A-羟甲芬太尼(I)和cis-N-[1-(苯甲酰甲基)-3-甲基-4-哌啶]-N-苯基丙酰胺(cis-IV)的4-N-丙酰基分别获得II和III。溴乙烷的格氏试剂与回旋加速器产生的[¹¹C]-二氧化碳反应后继而直接加入邻苯二甲酸二酰氯和2,6-二叔丁基吡啶生成同位素标记中间体[¹¹C]-丙酰氯。[¹¹C]-丙酰氯与OH-前体(II)反应后再经HPLC分离纯化直接得[¹¹C]-羟甲芬太尼;[¹¹C]-丙酰氯与酮-前体(III)反应后,再用硼氢化钠甲醇溶液处理,然后进行HPLC分离纯化得[¹¹C]-羟甲芬太尼。两种方法均可获得ll.1～14.8GBq/μmol的特异性放射化学纯[¹¹C]-羟甲芬太尼。总共耗时为40～50min(EOB)。     

结核分枝杆菌Mtb8.4基因疫苗与人白细胞介素12表达质粒联合免疫的细胞免疫应答观察

目的 观察结核分枝杆菌Mtb8.4基因疫苗与人白细胞介素12(hIL-12)联合免疫小鼠所诱导的细胞免疫应答.方法 15只C57BL/6N小鼠随机分为Mtb8.4基因疫苗 hIL-12质粒组(联合免疫组)、Mtb8.4基因疫苗组、卡介苗(BCG)组、空载体组和PBS组,基因疫苗、空载体和PBS经肌内注射法免疫各组小鼠,每隔3周免疫1次,共免疫3次,BCG组经尾部皮下注射1×106 CFU BCG免疫1次.ELISA法检测小鼠脾细胞培养上清中细胞因子水平;乳酸脱氢酶(LDH)释放法检测免疫小鼠特异性细胞毒性T淋巴细胞(CTL)杀伤活性.结果 联合免疫组能诱导较强的抗原特异性Th1型细胞免疫应答,免疫小鼠脾细胞培养上清液IFN-γ和IL-2水平(分别为1 493.340±8.128pg/ml、747.489±48.676pg/ml)显著高于Mtb8.4基因疫苗组,与BCG组相当,IL-4分泌减少,特异性CTL杀伤活性增强.结论 hIL-12表达质粒能够增强Mtb8.4基因疫苗所诱导的细胞免疫应答.     

白介素-12家族与实验性自身免疫性脑脊髓炎的研究进展

实验性自身免疫性脑脊髓炎(EAE)是自身反应性CD4+T细胞,即辅助性T细胞(Th细胞)介导的自身免疫性中枢神经系统脱髓鞘性炎症,在EAE的发病中,Th细胞分泌的细胞因子起了重要的调节作用。白介素-12(IL-12)家族由IL-12和最近发现的白介素-23(IL-23)、白介素-27(IL-27)组成,是一类结构相似、具有共价结合的杂化双链的细胞因子,在细胞免疫尤其是Th1型炎症反应中,起重要的调节作用。本文综合论述了IL-12家族各成员与EAE的关系的研究,揭示了各因子在EAE发生发展中的作用。     

Monocyte adhesion molecule expression in interstitial inflammation in patients with renal failure.

BACKGROUND: Patients with renal failure have an increased susceptibility to infections. We therefore studied the recruitment of monocytes and their expression of adhesion molecules CD11b and CD62L at the site of interstitial inflammation in patients with renal failure. Furthermore, we studied if the capacity of monocytes to up-regulate CD11b in interstitial inflammation was determined by the interstitial concentration of chemotactic factors. METHODS: Three intensities of interstitial inflammation (0, intermediate and intense) were established in skin blister chambers. Leukocyte count, CD11b/CD62L expression, monocyte chemotactic protein-1 (MCP-1) and blister activity in terms of CD11b mobilization were determined. RESULTS: The CD62L expression on monocytes was lower in the peripheral circulation in patients with renal failure compared with healthy subjects (P<0.005 and P<0.001). At the site of interstitial inflammation patients had a higher expression of CD62L (intermediate, P<0.05; intense, P<0.005). Furthermore, monocytes from patients had an impaired capacity to mobilize CD11b both in the peripheral circulation (P<0.005) and at the intermediate and intense sites of interstitial inflammation (P<0.005 and P<0.001, respectively) compared with cells collected from healthy subjects. We incubated monocytes in blister exudates, in order to explore whether this phenomenon is caused by cellular factors and/or to the interstitial concentration of chemotactic mediators. The expression of CD11b on monocytes from healthy blood donors incubated in blister exudates from either patients or healthy subjects in vitro was similar. The interstitial concentration of MCP-1 at the site of intermediate inflammation was significantly lower in patients with renal failure compared with the corresponding blister exudate collected from healthy subjects (P<0.05), but no differences were observed at the site of intense inflammation. Furthermore, neutralizing the action of MCP-1 in blister exudates with monoclonal antibodies did not have any impact on monocyte CD11b expression following incubation in blister exudates. CONCLUSION: These studies indicate that the impaired capacity of monocytes to mobilize CD11b at the site of inflammation in patients with renal failure is more dependent on constitutive cellular factors than the concentration of CD11b mobilizing factors in the interstitium.     

Comparison of the use of bulk to micro culture of cell preparations for lymphokine-activated cytotoxicity assays.

Different assay systems have been used to quantitate lymphokine-induced natural cytotoxic activity as a measure of immune status. This study compares the effects of inducing cytotoxicity in a bulk culture system, where effector cells are transferred to a micro culture well for assay, to a micro culture system where the effector cells are not transferred. The effector/target ratio for both the bulk and micro culture systems was calculated using the number of viable effector cells present at the time of target cell addition. After overnight incubation with interleukin-2 (IL-2), the lytic activity of murine spleen cells to targets using a micro culture system was increased two-fold over the bulk culture method. This increase was amplified further after 5 days of activation with IL-2, in that the micro culture system resulted in a four-fold increase in cytotoxic activity. The loss of some adherent cells in the bulk culture system did not explain the overall decrease in recovered cytotoxicity. The difference appeared to be related to cell loss during centrifugation. Therefore, the E/T ratios are different in the two systems if not corrected for the number of viable cells.     

Positron emission tomography in oncology

Summary. The particular advantages of positron emission tomography (PET) technique are that it has higher sensitivity, higher resolution, and a higher quality of image than that found in conventional nuclear medicine. The possibility of quantification and the wide range of useful tracers have raised expectations of this new method. To date, most of the human PET cancer studies have been performed with [¹⁸F]fluorodeoxyglucose (FDG) or [¹¹CJmethionine. These are good imaging agents for tumours. However, more specific radiopharmaceuticals are required if other features of tumour metabolism are to be observed, f¹¹Thymidine may prove to be a good tracer for quantitative measurements of tumour proliferation and [¹⁸F]misonidazole has been suggested for imaging of hypoxia.     

The influence of anaesthetic techniques and type of delivery on peripartum serum interleukin-6 concentrations

Background: Interleukin-6 is a pleiotropic cytokine with a wide range of physiological activities. It plays an important role in the immuno-neuro-humoral axis during stress and surgery.
Methods: Serum interleukin-6 in parturients was measured on hospital admission, immediately after birth and 12 and 24 hours later. All parturients had uncomplicated pregnancies, and delivered vaginally without (n=31) or with (n=20) epidural analgesia, or underwent Caesarean section under epidural (n=20) or general (n=10) anaesthesia.
Results: Serum interleukin-6 assayed immediately following Caesarean section was low, but peaked 12 hours later, irrespective of the anaesthetic technique or other foetomaternal characteristics. Patients who delivered vaginally showed the highest interleukin-6 levels immediately after delivery. These were positively correlated with serum interleukin-6 on admission and duration of labour. Serum interleukin-6 was significantly higher in parturients who had epidural analgesia, and was significantly lower in those receiving intravaginal prostaglandins compared to those without prostaglandins.
Conclusion: The interleukin-6 response after Caesarean section can be explained by a generalized acute phase response to surgery, with no anaesthetic, maternal or neonatal interference. The rapid increase in peripartum serum interleukin-6 levels after vaginal delivery reflects, in part, cervical ripening or labour, their physiological triggers and psychological or physical stress. Regional anaesthesia, duration of labour and exogenous prostaglandin administration can modulate the peripartum interleukin-6 response and subsequently the physiological effects of this cytokine.     

Opioid binding in DYT1 primary torsion dystonia: an 11C-diprenorphine PET study.

The opioid transmitters enkephalin and dynorphin are known to regulate pallidal output and consequently cortical excitability. Indeed, abnormal basal ganglia opioid transmission has been reported in several involuntary movement disorders, including levodopa-induced dyskinesias in Parkinson's disease (PD), tardive dyskinesias/dystonia, Huntington's disease, and Tourette's syndrome. Moreover, a previous 11C-diprenorphine PET study investigating levodopa-induced dyskinesias found reduced opioid receptor availability in PD with but not without dyskinesias. We wished to investigate if a similar alteration in basal ganglia opioid binding was present in DYT1 primary torsion dystonia (PTD). Regional cerebral 11C-diprenorphine binding was investigated in 7 manifesting carriers of the DYT1 gene and 15 age-matched normal controls using a region-of-interest (ROI) approach and statistical parametric mapping (SPM). No difference in regional mean 11C-diprenorphine binding was found between DYT1-PTD and controls, and no correlation between the severity of dystonia and opioid binding was seen. We conclude that aberrant opioid transmission is unlikely to be present in DYT1-PTD and altered opioid transmission is not a common mechanism underlying all disorders of involuntary movement.     

IL-2激活的TIL对自体肿瘤细胞的杀伤活性及其与LAK细胞活性的比较

肿瘤浸润性淋巴细胞(TIL)经白细胞介素2(IL-2)体外培养后具有很强的体内外抗肿瘤作用,且有一定的靶细胞特异性,其抗肿瘤效果强于淋巴因子激活的杀伤细胞即LAK细胞(P<0.01)。从瘤体中新鲜分离到的TIL对自体肿瘤细胞的杀伤活性极低,经IL-2体外培养后,其杀伤活性逐渐增高,以培养至7～25d的杀伤活性最强,这与IL-2使TIL分泌3种抗癌淋巴因子包括IL-2、IFN-γ、淋巴毒素(LT)增加有关。体外培养25d后,TIL的抗肿瘤活性下降,实验表明这与培养过程中TIL的Lyt-2~+细胞(Tc)减少而L3T4~+细胞(T_H)增多有关。TIL经冻存复苏和IL-2体外培养后仍保持很强的抗肿瘤活性,冻存前后比较未见显著差异(P>0.05),这为间断地运用TIL治疗复发性、晚期肿瘤提供了一条可行的途径。