Lymphoid tissues induce NGF-dependent and NGF-independent neurite outgrowth from rat superior cervical ganglia explants in culture

Induction of neurite outgrowth from superior cervical ganglia (SCG) by rat lymphoid tissues was studied using a tissue culture model. Neonatal rat SCG were cultured with 6–12-week-old rat thymus, spleen, or mesenteric lymph node (MLN) explants in a Martrigel layer, in defined culture medium without exogenous nerve growth factor (NGF). SCG were also co-cultured with neonatal rat heart (as positive control) or spinal cord (SC; as negative control). To determine whether inflammation affects the ability of lymphoid tissues to induce neurite outgrowth, we also examined MLN at various times after infecting rats with Nippostrongylus brasiliensis (Nb-MLN). In one series of experiments, a single lymphoid tissue explant was surrounded by four SCG at a distance of 1 mm. The extent of neurite outgrowth was determinded by counting the number of neurites 0.5 mm away from each ganglion at several time points. Adult thymus and, to a lesser extent, spleen had strong stimulatory effects on neurite outgrowth from SCG after 12 hr or more in culture. For thymus tissue, this was similar to the positive control heart explants. MLN from normal rats had minimal effect on neurite outgrowth; however, Nb-MLN showed a time-dependent enhancement of the neurite outgrowth, maximal at 3 weeks after infection. The relative efficacy of neurite outgrowth induction (heart ≥ thymus ≥ Nb-MLN ≥ spleen ≥ MLN ≥ SC) was confirmed in a second series of experiments where one SCG was surrounded by three different tissue explants. We then examined the role of 2.5S NGF, a well-known trophic factor for sympathetic nerves, in the lymphoid tissue-induced neurite outgrowth. Anti-NGF treatment of co-cultures of SCG and heart almost completely blocked the neurite outgrowth. Anti-NGF also significantly inhibited thymus- and spleen-induced neurite outgrowth, but not as effectively as heart-induced neuritogenesis (93,80, and 77% inhibition at 24 hr; 86,70, and 68% inhibition at 48 hr for heart, thymus, and spleen, respectively). On the other hand, anti-NGF inhibited only 8% of neurite outgrowth induced by 3-week post-infection Nb-MLN at 24 hr, and 41% at 48 hr. These data show that several adult rat lymphoid tissues exert neurotrophic/tropic effects. The predominant growth factor in thymus and spleen is NGF, while Nb-MLN produces factor(s) which is (are) immunologically distinguishable from NGF. These neurotrophic/tropic factors are produced during the reactive lymphoid hyperplasia that forms part of the inflammatory response against the nematode, N. brasiliensis. This suggests the possibility that cytokines produced by lymphocytes or other inflammatory cells may stimulate sympathetic neurite outgrowth in vivo. © 1994 Wiley-Liss, Inc.     

Sulphanilic acid: divergent results in the guinea pig maximization test and the local lymph node assay

The guinea pig maximization test (GPMT) has proven to be a valuable tool for the identification of the skin sensitization potential of chemicals. The method identifies a hazard which can lead in the EC to compulsory labelling of that chemical. In the present study, data on sulphanilic acid derived from the GPMT has been compared with results from a second guinea pig assay (the cumulative contact enhancement test) and the murine local lymph node assay, both of which require only topical application of chemical. Except for the GPMT, no test identified any sensitizing activity associated with exposure to sulphanilic acid. These latter results are consistent with the experience gained from substantial human exposure in an occupational setting and from which no cases of allergic contact dermatitis to sulphanilic acid have arisen over a 20-year period. In consequence, it is questioned which test protocol in practice has given the more accurate identification of sensitization hazard relevant to man.     

Impact of lymph node metastasis on survival in patients with pathological T1 carcinoma of the ampulla of vater

To determine the prognostic factors for patients with pathological T1 (pT1) carcinoma of the ampulla of Vater, 36 consecutive patients with carcinoma of the ampulla of Vater who underwent surgery were retrospectively analyzed in terms of clinicopathological features. The overall 5-year Kaplan-Meier survival in all patients was 50.2%, and the median survival of all patients was 64.0 months. Factors favorably influencing a long-term outcome were the absence of lymph node metastasis (P<0.0001), the absence of ulcer formation of the tumor (P=0.0062), and the absence of tumor invasion into the duodenum (P = 0.0025) and the pancreas (P=0.0098). In a multivariate analysis, lymph node metastasis was the only predictor of survival (P=0.0023). In the pT1 stage patients, 20% of the patients had lymph node metastasis, and their survival was statistically poor compared to the pT1 patients without lymph node metastasis (P=0.017). As for survival after the operation, there was no significant difference between pancreatoduodenectomy and pylorus-preserving pancreatoduodenectomy.     

VEGF-C和VEGF-D蛋白表达在胰腺癌淋巴转移中的意义

目的探讨胰腺癌中VEGF-C、VEGF-D蛋白表达与淋巴结转移之间的相关关系,阐明癌周淋巴管增生在胰腺癌淋巴转移中的作用及意义。方法免疫组化检测30例胰腺癌组织中VEGF-C、VEGF-D的表达及其与临床病理、淋巴结转移的关系。结果胰腺癌VEGF-C、VEGF-D蛋白表达阳性率分别为73%(22/30)、57%(17/30),肿瘤周边部位显著高于肿瘤中心部位,其表达与肿瘤的部位、分化程度、组织学类型无关,与肿瘤的TNM分期有关,Ⅲ~Ⅳ期显著高于Ⅰ~Ⅱ期。在VEGF-C、VEGF-D蛋白阳性组,淋巴结转移均显著增多。结论VEGF-C和VEGF-D与诱导胰腺癌淋巴管生成,促进肿瘤细胞淋巴道转移有关。     

阈下刺激定位慢径消融靶点的临床应用研究

目的 :探讨利用阈下刺激 (STS)定位房室结折返性心动过速 (AVNRT)的慢径消融靶点的临床应用价值。方法 :选择AVNRT患者 6例 ,经常规电生理检查明确诊断后 ,将大头电极放在冠状窦口下缘与希氏束之间的中下区域进行标测 ,测定该点的起搏阈值后 ,诱发AVNRT ,然后发放STS终止AVNRT ,在终止位点处试消融 ,观察STS标测消融的有效性 ;在非终止位点处 ,结合局部心内电图判断是否进行试消融 ,如在非终止位点处试消融 ,观察STS标测的可靠性。同时观察STS标测定位的安全性。结果 :在 6例患者中 ,有 3例STS终止了持续性AVNRT ,且在终止位点处试消融并获得成功 ;有 5例共在 10个位点处发放了STS ,其中在 9个位点未终止心动过速 ,在这些非终止位点处试消融均未获得成功 ,非 1个位点出现了心房夺获。所有患者在STS标测过程中 ,未出现心房颤动、心动过速的加速或心室颤动等现象。结论 :STS终止AVNRT的位点是判断消融靶点的一个良好的电生理学指标。STS标测定位是安全、有效和可靠的一种方法 ,值得进一步地深入研究     

Use of laboratory data to identify risk factors of giant coronary aneurysms due to Kawasaki disease

BACKGROUND: Although some laboratory findings are known to be indicators of the risk of giant coronary aneurysm formation among Kawasaki disease patients, an appropriate cut-off point to predict aneurysm formation is not clear. METHODS: One hundred and five patients with giant coronary aneurysms were selected from the 15th and 16th nationwide surveys of Kawasaki disease in Japan. A total of 2936 patients without Kawasaki disease were recruited from a single hospital as a control group. Odds ratios were calculated for six laboratory data with specific values as cut-off points. Receiver operating characteristic (ROC) curves were observed to determine the most appropriate laboratory tests and cut-off points. RESULTS: Hematocrit, leukocyte count, neutrophil proportion, and hemoglobin had one or more peaks of odds ratio for specific cut-off points, but they did not have a clear cut-off point for the predictor according to the receiver operating characteristic curves. Alanine aminotransferase (ALT) increased the risk of giant coronary aneurysms continuously so no clearly appropriate cut-off point was identified. Serum sodium concentration of 135 mEq/L had a peak of odds ratio, and those with <135 mEq/L had the highest odds ratio (4.78). This value seemed appropriate with a sensitivity of 78% and specificity of 57%, although the predictive positive value was as small as 5%. CONCLUSION: The author's propose that a serum sodium concentration of <135 mEq/L at the patient's first visit to hospital may be a predictor of giant coronary aneurysms due to Kawasaki disease.     

乳腺癌前哨淋巴结活检的临床意义

目的 评价应用蓝染料示踪剂识别乳腺癌前哨淋巴结（sentinel lymph node,SLN)的可行性和SLN预测腋窝淋巴结（axillary lymph node,ALN)转移的准确性。方法 应用专利蓝对42例临床腋窝淋巴结阴性的乳腺癌患者进行SLN定位和活检术。结果 37例找到SLN，SLN检出率88.1%，SLN的成功定位与患者的年龄有关。SLN预测ALN状态的准确率为93.8%，假阴性2例。结论 蓝染料示踪法定位乳腺癌SLN是成功率较高的方法，且操作简单，花费少，SLN活检能够准确预测腋窝淋巴结的转移状况，在将来治疗腋淋巴结阴性的乳腺癌中，这一技术可以免除患者接受不必要的腋淋巴结清扫术。     

结直肠癌淋巴结转移与部分肿瘤分子标志物表达的相关性研究

目的 探讨部分肿瘤相关分子标志物免疫组织化学的表达与结直肠癌淋巴结转移的相关性.方法 应用免疫组织化学技术检测65例结直肠癌手术标本Ki-67、p53的表达情况,对照手术所见和手术标本的病理检查结果 ,研究这些肿瘤相关分子标志物与肿瘤的生物学特性如浸润和淋巴结转移等的关系.结果 65例结直肠癌手术标本Ki-67、p53免疫组织化学的表达与肿瘤肠壁浸润深度无明显相关性(P＞0.05).Ki-67的表达及Ki-67标记指数的表达与淋巴结转移及Dukes分期有明显的相关性(P＜0.01);p53标记指数的表达与淋巴结转移有相关性(P＜0.05),与Dukes分期有明显的相关性(P＜0.01).结论 作为反应细胞增殖活性的肿瘤相关分子标志物Ki-67,其免疫组织化学的表达程度可间接反映结直肠癌淋巴结转移状况,可能成为反映淋巴结转移的一个标志物.     

Detection of disseminated tumor cells in the lymph nodes of colorectal cancer patients using a real-time polymerase chain reaction assay

Introduction Postoperative treatment for colorectal cancer depends on tumor stage as defined by the International Union Against Cancer (UICC). Adjuvant chemotherapy is not recommended in patients without lymph node involvement (UICC stages I and II). As many as 20–30% of these patients, however, will develop recurrence. Aims and objectives We conducted this study to determine the presence of disseminated tumor cells in the lymph nodes by quantitative real-time polymerase chain reaction (QRT-PCR) for cytokeratin 20 (CK20) in an attempt to provide supplementary information compared to histopathological findings. Materials and methods Using a standard QRT-PCR assay, we examined primary tumors and 391 lymph nodes from 31 patients with completely resected colorectal cancer. Results Of the 31 primary tumors, 29 were positive for CK20 by QRT-PCR. Discussion An examination of the lymph nodes from the 29 patients with CK20-positive primary tumors revealed that 35 (92.1% sensitivity) of the 38 histopathologically positive lymph nodes and 54 (16.7%) of the 324 histopathologically negative lymph nodes were positive by molecular analysis. CK20 expression was detected in 10 (100%) of 10 patients with a histopathologically positive lymph node status (pN1). In 9 (47.4%) of 19 patients with negative histopathological results (pN0), we detected a CK20 mRNA signal in at least one lymph node. Whereas eight patients with histopathologically negative lymph nodes could be upstaged on the basis of the molecular findings, no patient would be downstaged. Conclusion Our results suggest that QRT-PCR for CK20 is a useful tool for the quantitative detection of micrometastases in the regional lymph nodes. We introduce a standardized procedure that integrates a molecular diagnostic technique in the clinical staging.     

The Cardiac Pacemaker Current if

Pacemaker Current if. Since the hyperpolarization-activated current, if, was originally associated with the diastolic depolarization phase of action potential in the sinoatrial (SA) node in 1979, its central role in the generation and control of pacemaker activity has become increasingly clear through a series of experimental findings, some of which have substantially modified the pre-existing theories of cardiac pacemaking and its modulation by the autonomic transmitters. Thus, the pacemaker current of Purkinje fibers, formerly described as a deactivating pure potassium (K) current, was found to be in fact, like the nodal if, inward and activating on hyperpolarization. Furthermore, in SA node cells, as well as mediating rhythm acceleration induced by catecholamines, if was found to underlie the slowing effect of low acetylcholine (ACh) concentrations, in contrast with the generally accepted hypothesis that activation of a K conductance is the main process responsible for cardiac slowing. A final, atypical property of if recently demonstrated concerns the activating action exerted on if by intracellular cAMP. Unlike that on other voltage-gated, cAMP-modulated cardiac channels, this action is independent of phosphorylation and involves a direct binding of cAMP to if channels. (J Cardiovasc Electrophysiol, Vol. 3, pp. 334–344, August 1992)