潍坊市区人群麻疹抗体水平及麻疹疫苗强化免疫血清学效果监测

为了解潍坊市麻疹疫苗(MV)强化免疫的效果和人群麻疹抗体水平,在2个区随机抽取767名0-39岁健康人,应用酶联免疫吸附试验检测麻疹IgG抗体。结果:767人中抗体阳性595人,阳性率77.57%,几何平均滴度(GMT)1:783。以1-12岁儿童抗体阳性率高(85.71%-98.44%),GMT则从6岁开始下降至中低等水平,抗体阳性率有随年龄增长而下降的趋势。观察MV初种8-12月龄儿童94人,免疫成功率为96.81%;MV复种5-7岁儿童93人,免疫成功率61.29%;免疫后抗体GMT分别比免疫前提高28.4倍和3.1倍。不论是初种或复种,免疫前抗体处于中低等水平者其免疫成功率显著高于免疫前高抗体水平者。     

单项低水平抗—HBs阳性者对接种乙肝疫苗的免疫应答

血清单项低水平抗-HBs阳性者,仅有15%的人对接种乙肝疫苗后出现了回忆反应。其余大部份人,抗-HBs持续时间及接种疫苗后的免疫反应与HBV标志全阴性组相比无显著差别;从低水平安慰剂组出现乙肝感染情况来看,可能仍是易感者。在制定接种乙肝疫苗方案时,应对这部份人足够重视。     

The Measles Outbreak in Chikuhou District, Fukuoka, Japan, 1990: Correlation between Herd Immunity Level and Outbreak Size

A measles outbreak occurred in the Chikuhou district of Fukuoka, Japan from May to October 1990, during which 71 patients were cared for at the Itoda Public Hospital. Hospital records revealed a large outbreak in the adjacent town of Kanada. In order to characterize the outbreak, questionnaires were sent to all preschool-age children in Itoda (73% effective response) and in Kanada (76% effective response) requesting information about their vaccination and/or history of measles. The number of patients was 22 (4%) in Itoda and 63 (14%) in Kanada, most of these being preschoolers, while the vaccination rate was 61% and 44%, respectively. The herd immunity levels in age-specific groups were compared between the two towns. Before the epidemic, the immunity level of 1 year old children in Kanada, who showed the higher attack rate, was lower (18%) than that in Itoda (39%), while after the epidemic it rose above 60% in both towns. When we studied the correlation between the attack rate and the vaccination rate, or the number of children susceptible to measles (susceptibility rate) in each preschool, the attack rate correlated negatively with the vaccination rate (correlation coefficient [CC] = - 0.818; P < 0.01), and positively with the susceptibility rate (CC 0.860; P < 0.01). The regressed equation on the correlation indicated that the immunity level should be more than 70% to keep the attack rate under 5% in preschoois. After the epidemic, the immunity levels of all preschoolers reached above 70%. Early vaccination should be given to at least 70% of young preschoolers in order to prevent a large outbreak of measles under the present vaccination program in Japan.     

The impact of technical adjuncts in the surgical management of cerebral hemispheric low-grade gliomas of childhood

Pediatric brain tumors occur within a frequency of 24 to 27 cases/year within a cohort of 1 million children. Nearly 25% of these lesions will involve the cerebral hemisphere, with the low-grade glioma representing the most common group of tumors in this location. Pilocytic and fibrillary astrocytomas are the most frequently encountered glioma, although other variants, such as the ganglioglioma, pleomorphic xanthoastrocytoma, astroblastoma, ependymoma, and oligodendroglioma, must also be considered in the differential diagnosis. The etiology of these tumors remains obscure, although may be linked to therapeutic radiotherapy, previous history of hematopoietic malignancy, and maternal exposure to nitrosamine-laden foods. An associated link to a phakomatosis, e.g., neurofibromatosis, tuberous sclerosis, has also been documented to exist with astrocytomas, in particular. The goals of surgery include a complete removal, in most circumstances, with an attempt to alleviate an associated seizure disorder when intractable. This is possible in nearly every type of hemispheric glioma with the aid of intraoperative navigational systems, i.e., frameless stereotaxy, neurophsyiological based stimulation mapping, and electrocorticography. In the setting where a complete removal is possible, no further therapy is warranted. For those lesions that are incompletely resected, conservative management with routine diagnostic imaging follow-up is appropriate. Reoperation is necessary if recurrence is documented and radiotherapy is utilized for those lesions that are incompletely resected following recurrence.     

Neonatal poliomyelitis

A case of neonatal, poliomyelitis is discussed. The clinical, electromyographic and serologic studies confirmed the diagnosis of paralytic poliomyelitis, thus illustrating the risk of disease in neonates born of non-immune mothers, into an environment where infection is very common.     

恶性淋巴瘤mdr1和MRP mRNA及 P-gp表达水平与化疗疗效的相关研究

目的探讨恶性淋巴瘤mdr1、MRP mRNA和P-gp表达水平与化疗疗效的相关性.方法应用半定量逆转录多聚酶链反应(RT-PCR)技术和流式细胞术(FCM)方法,以8例人正常淋巴结为正常对照,对46例淋巴瘤患者[23例初治(HD1例,NHL22例)及23例复发(HD5例,NHL18例)]的mdr1 mRNA、MRP mRNA和P-gp表达水平与化疗疗效间的关系进行了前瞻性研究.结果复发患者mdr1基因和P-gp表达水平及阳性率均高于初治患者(P<0.001),而MRP基因表达水平及阳性率在复发与初治患者间差异无显著意义(P>0.05).mdr1基因及P-gp表达阳性患者的化疗有效(CR+PR)率(33.33%和26.67%)明显低于mdr1基因及P-gp表达阴性患者(85.71%和83.87%,P<0.001),而MRP基因表达阳性患者与阴性患者的化疗有效率差异无显著意义(P>0.05).相关分析显示,mdr1基因和P-gp表达水平之间有明显相关性(r=0.296 3,P<0.05),而mdr1和MRP之间、MRP与P-gp之间均无明显相关性(r=0.072 3,P>0.05;r=0.081 8,P>0.05).结论 mdr1基因及P-gp表达是恶性淋巴瘤患者多药耐药的主要机制,而MRP基因不是产生耐药的主要机制.mdr1基因及P-gp表达水平的高低与恶性淋巴瘤化疗疗效密切相关,而MRP基因的表达与化疗疗效未见相关.     

Toll样受体与固有免疫的进化

固有免疫是在进化中形成的免疫机制,在对抗微生物的入侵方面,固有免疫的策略是通过模式识别受体(PRR)识别微生物的病原相关分子模式(PAMP)。Toll样受体是近年来在多种生物体内发现的一类介导固有免疫的细胞膜受体家族,它通过活化一系列与免疫相关的基因表达而发挥作用,在进化中表现高度的保守性,但其功能却随着动物进化中免疫机能的复杂化而多样化。对Toll样受体研究的深入可以加深我们对固有免疫的发生与进化的认识。     

Detection of free-circulating tumor-associated DNA in plasma of colorectal cancer patients and its association with prognosis

Tumor cells are characterized by specific genetic alterations. When such genetic alterations are identified in body fluid including plasma, regardless of the presence of detectable tumor cells, it shows the existence of free-circulating tumor-associated DNA. The objective of our study was to assess the prognostic value of free-circulating tumor-associated DNA in colorectal cancer patients' plasma. The first step of our work was to find common genetic alterations in tumors that would subsequently be used for plasma DNA screening. We focused on KRAS2 mutations in codons 12 and 13 by the mutant allele-specific amplification (MASA) method and p16 hypermethylation by the methylation-specific polymerase chain reaction (MSP) method. Patients with a tumor presenting either alteration were selected for plasma screening; 58 tumors were analyzed for KRAS2 mutations and tested for p16 gene promoter methylation. Survival and recurrence rates were assessed in patients with and without free-circulating tumor-associated DNA alterations in plasma. Of the 58 tumors analyzed, 39 (67%) demonstrated either one or both of the studied genetic alterations. Twenty-two (38%) were mutated at KRAS2, and an identical alteration was detected in 10 (45%) of the 22 corresponding plasma samples. Thirty-one (53%) had p16 gene promoter hypermethylation that could also be detected in the plasma in 21 cases (68%). Among the 39 patients who had one or the other alteration in tumor DNA, 37 had at least one reliable plasma test. In 26 (70%) of the 37 patients, free-circulating tumor-associated DNA was detected in plasma. The 2-year overall survival rate was 48% in the group where free-circulating tumor-associated DNA was detected in plasma and 100% in the one where free-circulating tumor-associated DNA was not detected in plasma (p < 0.03). Among these 37 patients, 25 patients had a stage I, II or III disease. In this subgroup of patients, the 2-year recurrence-free survival rate for the 17 patients with free-circulating tumor-associated DNA detected in plasma was 66%, compared to 100% for the 8 patients without free-circulating tumor-associated DNA detected in plasma (p = 0.044). The presence of free-circulating tumor-associated DNA in plasma seems to be a relevant prognostic marker for patients with colorectal cancer and may be used to identify patients with a high risk of recurrence.     

Lovastatin is a Potent Inhibitor of Meningioma Cell Proliferation: Evidence for Inhibition of a Mitogen Associated Protein Kinase

Lovastatin inhibits 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase the rate limiting enzyme for synthesis of mevalonic acid, a precursor for cholesterol, farnesyl and geranylgeranyl pyrophosphate isoprenoids. Recent studies suggest it also has growth inhibitory properties. Posttranslational farnesyl or geranylgeranylation of low molecular weight GTP-binding proteins such as RAS and RHO are thought to be an essential step in activation of phosphorylation cascades such as the RAS–RAF-1–MEK-1–MAPK/ERK pathway which stimulate cell proliferation. In this study, we evaluated lovastatin effects on meningioma cell proliferation and activation of the MEK-1–MAPK/ERK pathway.The effect of lovastatin on cell proliferation was assessed in eight human meningioma cell cultures stimulated by platelet derived growth factor (PDGF)-BB, cerebrospinal fluid (CSF), and fetal bovine serum (FBS). Concomitant lovastatin effects on phosphorylation/activation of mitogen-activated protein kinase/extracellular signal regulated kinase (MAPK/ERK) kinase (MEK-1) and MAPK/ERK were assessed by Western blot. Whether lovastatin acts via a mevalonate-dependent mechanism was also evaluated.Coadministration of lovastatin completely blocked PDGF-BB, CSF, and FBS stimulation of [³H]-thymidine incorporation and cell proliferation. Lovastatin inhibited PDGF-BB's stimulatory effect in a dose dependent manner. Concomitant with its growth inhibitory effects, lovastatin reduced phosphorylation/activation of MEK-1/2 in five meningiomas and MAPK/ERK in seven. Coadministration of mevalonate with lovastatin partially restored PDGF's mitogenic effect.Lovastatin is a potent inhibitor of meningioma cell proliferation which may act in part by reducing activation of MEK-1–MAPK/ERK pathway. Additional studies are warranted to assess whether lovastatin and similar HMG-CoA reductase inhibitors represent a new adjunctive chemotherapy for recurrent meningiomas.     

Developmental timing of hair follicle and dorsal skin innervation in mice

The innervation of hair follicles offers an intriguing, yet hardly studied model for the dissection of the stepwise innervation during cutaneous morphogenesis. We have used immunofluorescence and a panel of neuronal markers to characterize the developmental choreography of C57BL/6 mouse backskin innervation. The development of murine skin innervation occurs in successive waves. The first cutaneous nerve fibers appeared before any morphological evidence of hair follicle development at embryonic day 15 (E15). Stage 1 and 2 developing hair follicles were already associated with nerve fibers at E16. These fibers approached a location where later in development the follicular (neural) network A (FNA) is located on fully developed pelage hair follicles. Prior to birth (E18), some nerve fibers had penetrated the epidermis, and an additional set of perifollicular nerve fibers arranged itself around the isthmus and bulge region of stage 5 hair follicles, to develop into the follicular (neural) network B (FNB). By the day of birth (P1), the neuropeptides substance P and calcitonin gene-related peptide became detectable in subcutaneous and dermal nerve fibers first. Newly formed hair follicles on E18 and P1 displayed the same innervation pattern seen in the first wave of hair follicle development. Just prior to epidermal penetration of hair shafts (P5), peptide histidine methionine-IR nerve fibers became detectable and epidermal innervation peaked; such innervation decreased after penetration (P7- P17). Last, tyrosine hydroxylase-IR and neuropeptide Y-IR became readily detectable. This sequence of developing innervation consistently correlates with hair follicle development, indicating a close interdependence of neuronal and epithelial morphogenesis.