BACKGROUND & AIMS: The World Bank in its document under the title 'Investing in Health' (1993) states that the health status of the population, including the working population, and working conditions in individual countries depend essentially on the value of gross national product per capita. The attitudes towards the role and objectives of occupational medicine have changed significantly over the last three decades. A high priority given to primary prevention reflects the mainstream of a new approach to preventive measures. Advancements in technology, production and services, common use of computers and flattening of work organisation structures have brought about the need for workers' active participation in planning of activities and shaping working conditions in own enterprise. At the same time, workers are required to possess much higher qualifications facilitating their participation in applying new technologies and using new information systems, which resulted in a fierce competition on the labour market. In the countries in the political, social and economic transition, the conditions for introducing a new system of sustained development, described by Gustavsen at the 25th International Congress on Occupational Health have not as yet been established. A procedure-based system involving negotiations between employers and workers' representatives failed to be successful in improving working conditions as the roles of the state, employers and trade unions had not been defined precisely. It is expected that further health promotion at the worksites in these countries will depend mainly on the economic progress and the reformed system of education.

背景与目标： 世界银行在其题为“投资卫生”（1993年）的文件中指出，人口的健康状况，包括劳动人口，以及各个国家的劳动条件，基本上取决于人均国民生产总值。在过去的三十年中，人们对职业医学的作用和目标的态度发生了巨大变化。对初级预防的高度重视反映了预防措施新方法的主流。技术，生产和服务的进步，计算机的普遍使用以及工作组织结构的扁平化带来了工人积极参与活动计划和塑造本企业工作条件的需求。同时，要求工人具有更高的资格，以促进他们参与应用新技术和使用新信息系统，从而导致劳动力市场上的激烈竞争。在政治，社会和经济转型国家中，古斯塔夫森在第25届国际职业卫生大会上描述的引入新的可持续发展系统的条件尚未建立。涉及雇主和工人代表之间的谈判的基于程序的系统未能成功改善工作条件，因为国家，雇主和工会的角色尚未得到准确界定。预计这些国家在工作场所进一步促进健康将主要取决于经济进步和教育体制的改革。

BACKGROUND & AIMS: :We report an unusual case in which a patient presented with a large posterior mediastinal goiter that extended to the level of the aorta. The goiter was resected through a standard Kocher neck incision with mediastinoscopic assistance. The large goiter was completely excised without the need for a sternotomy.

背景与目标： ：我们报告了一个不寻常的病例，其中患者出现了一个较大的后纵隔甲状腺肿，延伸至主动脉水平。甲状腺肿通过标准的Kocher颈部切口在纵隔镜下切除。大甲状腺肿完全切除，不需要胸骨切开术。

BACKGROUND & AIMS: :The hypoxic environment in tumor is reported to play an important role in pancreatic cancer progression. The interaction between stromal and cancer cells also contributes to the malignant behavior of pancreatic cancer. In the present study, we investigated whether hypoxic stimulation affects stromal as well as pancreatic cancer cells. Our findings demonstrated that hypoxia remarkably elevated the HIF-1alpha expression in both pancreatic cancer (PK8) and fibroblast cells (MRC5). Hypoxic stimulation accelerated the invasive activity of PK8 cells, and invasiveness was thus further accelerated when the hypoxic PK8 cells were cultured with conditioned medium prepared from hypoxic MRC5 cells (hypoxic conditioned medium). MMP-2, MMP-7, MT1-MMP and c-Met expressions were increased in PK8 cells under hypoxia. Hypoxic stimulation also increased the hepatocyte growth factor (HGF) secretion from MRC5 cells, which led to an elevation of c-Met phosphorylation in PK8 cells. Conversely, the elevated cancer invasion, MMP activity and c-Met phosphorylation of PK8 cells were reduced by the removal of HGF from hypoxic conditioned medium. In immunohistochemical study, the HIF-1alpha expression was observed in surrounding stromal as well as pancreatic cancer cells, thus indicating hypoxia exists in both of cancer and stromal cells. Moreover, the stromal HGF expression was found to significantly correlate with not only the stromal HIF-1alpha expression but also the c-Met expression in cancer cells. These results indicate that the hypoxic environment within stromal as well as cancer cells activates the HGF/c-Met system, thereby contributing to the aggressive invasive features of pancreatic cancer.

背景与目标： ：据报道肿瘤中的低氧环境在胰腺癌的进展中起重要作用。基质细胞与癌细胞之间的相互作用也有助于胰腺癌的恶性行为。在本研究中，我们调查了低氧刺激是否影响基质以及胰腺癌细胞。我们的发现表明，低氧显着提高了胰腺癌（PK8）和成纤维细胞（MRC5）中HIF-1alpha的表达。低氧刺激加速了PK8细胞的侵袭活性，因此，当用由低氧MRC5细胞制备的条件培养基（低氧条件培养基）培养低氧PK8细胞时，侵袭性进一步加快。在缺氧条件下，PK8细胞中的MMP-2，MMP-7，MT1-MMP和c-Met表达增加。缺氧刺激还增加了MRC5细胞的肝细胞生长因子（HGF）分泌，从而导致PK8细胞中c-Met磷酸化的升高。相反，通过从低氧条件培养基中去除HGF，可以降低PK8细胞的癌浸润，MMP活性和c-Met磷酸化水平的升高。在免疫组织化学研究中，在周围的基质细胞和胰腺癌细胞中均观察到了HIF-1alpha的表达，因此表明在癌细胞和基质细胞中均存在缺氧。此外，发现基质HGF表达不仅与癌细胞中的基质HIF-1α表达而且与c-Met表达显着相关。这些结果表明基质以及癌细胞内的低氧环境激活了HGF / c-Met系统，从而促进了胰腺癌的侵袭性侵袭性。

BACKGROUND & AIMS: :Through an endoscopic transvesico-transurethral approach, we closed a vesicovaginal fistula that occurred after hysterectomy in a patient with uterine leiomyoma. The 3-mm fistula, located in the midportion of retrotrigone, was resected transurethrally and sutured in two layers through two 5-mm suprapubic trocars placed into the bladder and the urethral route under pneumobladder. The patient had no urine leakage from the vagina after surgery.

背景与目标： ：通过内窥镜经膀胱-经尿道入路，我们关闭了子宫平滑肌瘤患者子宫切除术后发生的膀胱阴道瘘。将3毫米瘘管（位于逆行三角骨的中部）经尿道切开，并通过两根5毫米耻骨上套管针将其缝合在两层中，然后将其插入膀胱和在气囊下的尿道。病人术后没有尿液从阴道漏出。

BACKGROUND & AIMS: :The Clostridium perfringens alpha-toxin has previously been implicated as the major virulence factor in necrotic enteritis in chickens, although definitive proof has not been reported. In this study an alpha-toxin mutant was constructed in a virulent chicken isolate and shown to retain full virulence in a chicken disease model. These results demonstrated that alpha-toxin is not an essential virulence factor in the pathogenesis of necrotic enteritis in chickens.

背景与目标： 产气荚膜梭菌α毒素以前被认为是鸡坏死性肠炎的主要毒力因子，尽管尚未有确切的证据报道。在这项研究中，在有毒的鸡隔离株中构建了α-毒素突变体，并显示在鸡疾病模型中保留了全部毒力。这些结果表明，α-毒素不是鸡坏死性肠炎发病机理中必不可少的毒力因子。

BACKGROUND & AIMS: :Surgery for thyroid disease requires skin incisions that can result in postsurgical problems such as prominent scars, adhesions, hypesthesia, and paresthesia in the neck. To overcome these problems we performed gasless endoscopic thyroidectomy via an axillary approach. Between May 2004 and April 2005, 30 patients underwent gasless endoscopic thyroidectomy via an axillary approach. The mean operating time was 126.8+/-32.4 minutes, and the mean length of hospital stay was 4.3+/-1.1 days. No cases required conversion to open surgery and none involved significant intraoperative complications. Three patients (10.0%) complained of slight hypesthesia or paresthesia in the anterior chest wall, and only 2 patients (6.7%) complained of discomfort while swallowing 4 months after surgery. All patients were satisfied with the cosmetic results. Gasless endoscopic thyroidectomy via an axillary approach is feasible and safe and provides excellent cosmetic results with a minimal degree of postoperative complaints.

背景与目标： ：甲状腺疾病的手术需要皮肤切口，这可能导致术后问题，例如明显的疤痕，粘连，感觉异常和颈部感觉异常。为了克服这些问题，我们通过腋窝入路进行了无气内镜甲状腺切除术。在2004年5月至2005年4月之间，有30例患者通过腋窝入路行无气内镜甲状腺切除术。平均手术时间为126.8 /-32.4分钟，平均住院时间为4.3 /-1.1天。没有病例需要转换为开放手术，也没有涉及重大的术中并发症。 3例患者（10.0％）抱怨前胸壁轻度感觉异常或感觉异常，而只有2例患者（6.7％）吞咽术后4个月吞咽不适。所有患者对美容效果均满意。通过腋窝入路的无气内镜甲状腺切除术是可行且安全的，并能以极少的术后不适程度提供出色的美容效果。

BACKGROUND & AIMS: :Diabetes is associated with augmentation of prothrombogenic von Willebrand factor (vWF) content in plasma. Earlier, the author and colleagues have shown that high glucose and insulin do not appreciably influence deposition of vWF into the subendothelial extracellular matrix (SECM) produced by cultured human umbilical vein endothelial cells (HUVECs). In the present work, the author used this model to test the effects of nonenzymatically glycated albumin (Glyc-HSA) and two lectins, concanavalin A (ConA) and wheat germ agglutinin (WGA), on vWF deposition into the SECM. First-passage HUVECs were seeded into gelatin-coated 96-well plates and cultured for 6 to 7 days. HSA or Glyc-HSA (at concentrations 25, 50, and 100 microg/mL), and WGA or ConA (4, 8, and 16 microg/mL) were added 3 h after seeding. Cell viability was tested by the MTT method. To determine vWF contents in the SECM, HUVECs were detached by treatment with NH4OH and the residual material was used as a solid phase in an enzyme-linked immunosorbent assay (ELISA)-like assay with primary (anti-vWF) and secondary (peroxidase-conjugated) antibodies. Addition of Glyc-HSA did not essentially influence VWF contents in the SECM (A490 was 0.226 versus 0.268 at 0 and 100 microg/mL, respectively; p > .05, n = 16). Cultivation in the presence of WGA led to the deterioration of cell viability, which was accompanied by a significant decrease of vWF in the SECM (0.248 versus 0.128 at 0 and 16 microg/mL, respectively; p < .001, n = 16). ConA did not influence viability of HUVECs, but this lectin at all concentrations consistently increased the deposition of vWF (up to 164% relative to control, p <.001; n = 16). These data indicate that endothelial carbohydrate determinants and corresponding ligands (namely, mannose-specific lectins) may be involved in the regulation of production and deposition of vWF.

背景与目标： 糖尿病与血浆中促血栓性血管性血友病因子（vWF）含量的增加有关。早前，作者和同事已经表明，高葡萄糖和胰岛素不会明显影响vWF在培养的人脐静脉内皮细胞（HUVEC）产生的内皮下细胞外基质（SECM）中的沉积。在目前的工作中，作者使用该模型测试了非酶促糖基化白蛋白（Glyc-HSA）和两种凝集素，伴刀豆球蛋白A（ConA）和小麦胚芽凝集素（WGA）对vWF沉积到SECM中的影响。将第一代HUVEC接种到明胶包被的96孔板中，并培养6至7天。播种后3小时，添加HSA或Glyc-HSA（浓度分别为25、50和100微克/毫升）和WGA或ConA（4、8和16微克/毫升）。细胞存活力通过MTT方法测试。为了确定SECM中的vWF含量，通过用NH4OH处理将HUVEC分离，并将残留的物质作为固相用于类似酶联免疫吸附测定（ELISA）的类似测定中，该测定具有一级（抗vWF）和二级（过氧化物酶-偶联的）抗体。添加Glyc-HSA基本上不影响SECM中的VWF含量（0和100 microg / mL时A490分别为0.226和0.268； p> .05，n = 16）。在存在WGA的情况下进行培养会导致细胞活力下降，并伴有SECM中的vWF显着下降（0和16 microg / mL分别为0.248和0.128； p <.001，n = 16）。 ConA不会影响HUVEC的生存力，但是该凝集素在所有浓度下均会持续增加vWF的沉积（相对于对照，高达164％，p <.001； n = 16）。这些数据表明内皮糖决定簇和相应的配体（即，甘露糖特异性凝集素）可能参与vWF的产生和沉积的调节。

BACKGROUND & AIMS: :Attention-deficit hyperactivity disorder (ADHD) is a common childhood psychiatric disorder. Despite intensive research efforts, the aetiology of ADHD remains unknown. Current evidence suggests that the aetiology of ADHD is heterogeneous, comprising of multiple factors. Recently, it has been proposed that brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, may be implicated in the pathogenesis of ADHD. This hypothesis is supported by recent genetic studies in ADHD. Drawing on findings from studies into the drugs for ADHD relating to central BDNF expression, hyperactivity in BDNF knockout mice, BDNF effects in midbrain dopaminergic function and the close association between BDNF and the dopamine transporter (an important molecule for ADHD pathogenesis), it is proposed here that decreased central BDNF, particularly in the midbrain region, may play an important role in the pathogenesis ADHD. This hypothesis may have some implications for clinical findings in ADHD (for example, the co-morbidity between ADHD and major depression), and provide a new direction for the development of medication for ADHD treatment.

背景与目标： 注意缺陷多动障碍（ADHD）是儿童期常见的精神病。尽管进行了深入的研究，但多动症的病因仍然未知。当前证据表明，ADHD的病因是异质的，由多种因素组成。最近，已经提出，脑源性神经营养因子（BDNF），神经营养因子家族的成员，可能与ADHD的发病有关。这一假说得到了多动症最近的遗传学研究的支持。根据对ADHD药物的研究发现，该药物与中枢BDNF表达，BDNF基因敲除小鼠的过度活跃，BDNF对中脑多巴胺能功能的影响以及BDNF与多巴胺转运蛋白（ADHD发病机理的重要分子）之间的紧密联系有关，因此提出了这一建议。在这里，中央BDNF的降低，特别是在中脑区域，可能在ADHD的发病中起重要作用。该假设可能对ADHD的临床发现有一定的影响（例如，ADHD与严重抑郁症的合并症），并为ADHD治疗药物的开发提供了新的方向。

BACKGROUND & AIMS: :A novel procaryotic transcriptional regulatory element, AlgP, with a histone H1-like carboxy-terminal domain was identified in Pseudomonas aeruginosa. AlgP is required for transcription of the key biosynthetic gene algD, which is necessary for production of the exopolysaccharide alginate causing mucoidy in P. aeruginosa. Mucoidy is a critical virulence determinant of P. aeruginosa invariably associated with the respiratory infections causing high mortality in cystic fibrosis. Here we show that AlgP and histones H1 both have repeated units of the Lys-Pro-Ala-Ala motif (KPAA) and its variations within their long (over 100 amino acids) carboxy-terminal domains. This region of histone H1 tails has been shown to bind to the linker DNA in eucaryotic chromatin fibers. A synthetic 50-mer peptide consisting of repeats from the AlgP carboxy-terminal domain was found to bind DNA in a mobility shift DNA-binding assay. AlgP is encoded by a gene that contains multiple direct repeats organized as tandem, head-to-tail, 12-base-pair (bp) units overlapping with six highly conserved 75-bp units. The repetitive structure of the algP gene appears to participate in the processes underlying the metastable character of mucoidy in P. aeruginosa. Relatively large DNA rearrangements spanning the region with tandem direct repeats encoding the carboxy-terminal histone H1-like structure of AlgP were detected in several strains upon conversion from the mucoid to the nonmucoid phenotype. The frequency of the detectable algP rearrangements associated with the transition into the nonmucoid state varied from strain to strain and ranged from 0 to 50%. The nonmucoid derivatives with the clearly rearranged chromosomal copy of algP were complemented to mucoidy with plasmids containing algP from P. aeruginosa PAO. When a random collection of mucoid strains, isolated from different cystic fibrosis patients, was analyzed by using polymerase chain reaction, an additional level of strain-dependent sequence variation in algP was observed. Variations in the number of the 12-bp repeats were found; however, they did not appear to influence the mucoid status of the strains examined. Thus, the repeated region of algP appears to be a hot spot for DNA rearrangements and strain-dependent variability.

背景与目标： ：在铜绿假单胞菌中鉴定了具有组蛋白H1样羧基末端结构域的新型原核转录调控元件AlgP。 AlgP是关键生物合成基因algD转录所必需的，而agD是产生铜绿假单胞菌黏液状的胞外多糖藻酸盐所必需的。粘液性蛋白是铜绿假单胞菌的关键毒力决定因素，总是与引起囊性纤维化高死亡率的呼吸道感染相关。在这里，我们显示AlgP和组蛋白H1都具有Lys-Pro-Ala-Ala基序（KPAA）的重复单元及其在其长（超过100个氨基酸）羧基末端域内的变异。组蛋白H1尾巴的该区域已显示与真核染色质纤维中的接头DNA结合。在迁移率转移DNA结合试验中，发现由来自AlgP羧基末端结构域的重复序列组成的合成的50-mer肽与DNA结合。 AlgP由一个基因编码，该基因包含多个直接重复序列，这些重复序列被组织为串联的，首尾相接的12个碱基对（bp）单元，与六个高度保守的75 bp单元重叠。 algP基因的重复结构似乎参与了铜绿假单胞菌黏液状亚稳特性的潜在过程。从粘液样转变为非粘液表型后，在多个菌株中检测到了较大的DNA重排，该区域跨越了串联的直接重复序列，该重复序列编码AlgP的羧基末端组蛋白H1样结构。与转变为非粘液态相关的可检测到的algP重排的频率因菌株而异，范围为0％至50％。用含铜绿假单胞菌PAO的algP质粒将具有明显重排的algP染色体拷贝的非粘液衍生物与粘液互补。当使用聚合酶链反应分析从不同囊性纤维化患者中分离出的粘液样菌株的随机收集时，在algP中观察到了另一水平的菌株依赖性序列变异。发现12bp重复的数目有变化。但是，它们似乎没有影响所检查菌株的粘液状态。因此，algP的重复区域似乎是DNA重排和菌株依赖性变异的热点。

BACKGROUND & AIMS: Genetic studies have recently revealed a role for transforming growth factor-beta-1 (TGF-beta 1) and its receptors (TGF-beta Rs I and II as well as endoglin) in embryonic vascular assembly and in the establishment and maintenance of vessel wall integrity. The purpose of this review is threefoldfirst, to reassess previous studies on TGF-beta and endothelium in the light of these recent findings; second, to describe some of the well-established as well as controversial issues concerning TGF-beta and its regulatory role in angiogenesis; and third, to explore the notion of "context' with respect to TGF-beta and endothelial cell function. Although the focus of this review will be on the endothelium, other vascular wall cells are also likely to be important in the pathogenesis of the vascular lesions revealed by genetic studies.

背景与目标： 遗传研究最近揭示了在胚胎血管组装以及血管壁的建立和维持中转化生长因子-β-1（TGF-β1）及其受体（TGF-βRs I和II以及内皮糖蛋白）的作用。正直。这篇综述的目的是三重的，以根据这些最新发现重新评估先前对TGF-β和内皮的研究。其次，描述有关TGF-beta及其在血管生成中的调控作用的一些公认的和有争议的问题；第三，探讨有关TGF-β和内皮细胞功能的“背景”概念，尽管本综述的重点是内皮，但其他血管壁细胞也可能在血管的发病机理中起重要作用。通过遗传学研究发现病变。

BACKGROUND & AIMS: The expression and localization of hepatocyte growth factor/scatter factor (HGF/SF) were examined immunohistochemically in 59 human coronary artery lesions retrieved by directional coronary atherectomy and compared with the localization of transforming growth factor beta isoforms (TGF-beta 1, -beta 2, and -beta 3). In 21 of the 59 specimens (35.6%) HGF-like immunoreactivity (HGF-IR) was revealed. The HGF immunopositivity rate of 45% (14/31) in thrombotic tissue was significantly (P < 0.05) higher than the rates of 7.3% (4/55), 7.1% (3/42), and 0% (0/14) in fibrous tissue, neointimal hyperplasia and atheromatous gruel, respectively. Immunoreactivity for HGF was much weaker than that for TGF-beta isoforms in these components except in thrombotic tissue. These cells exhibiting strong HGF-IR were inflammatory cells such as monocytes/macrophages in thrombotic tissue, in tissue lesions adjacent to a thrombus, and outside the capillary walls in a portion of the neovascularized lesions. Smooth muscle cells (SMCs) hardly demonstrated HGF-IR. In contrast, in control coronary arteries obtained at autopsy, the HGF-IR was strongly expressed in SMCs. These findings suggest that HGF produced by macrophages play a part in the process of coronary plaque formation attributable to thrombus in man.

背景与目标： 免疫组织化学方法检测了定向冠状动脉粥样斑块切除术取回的59例人类冠状动脉病变中肝细胞生长因子/分散因子（HGF / SF）的表达和定位，并与转化生长因子β同工型（TGF-beta 1，-beta 2和-beta 3）。在59个样本中的21个（35.6％）中发现了类似HGF的免疫反应性（HGF-IR）。血栓形成组织中HGF免疫阳性率为45％（14/31）显着（P <0.05）分别高于7.3％（4/55），7.1％（3/42）和0％（0/14） ）分别在纤维组织，新内膜增生和粥样粥样硬化中。除了血栓形成组织外，在这些组件中，HGF的免疫反应性比TGF-β亚型的免疫反应性弱得多。这些表现出强HGF-IR的细胞是炎性细胞，例如血栓形成组织中，与血栓相邻的组织病变中，以及在部分新血管形成的病变中的毛细血管壁之外的单核细胞/巨噬细胞。平滑肌细胞（SMCs）几乎没有表现出HGF-IR。相反，在尸检时获得的对照冠状动脉中，HGF-IR在SMC中强烈表达。这些发现表明，巨噬细胞产生的HGF在可归因于人类血栓的冠状斑块形成过程中起作用。

BACKGROUND & AIMS: MyristoylCoA:protein N-myristoyltransferase (NMT) catalyzes the cotranslational covalent attachment of a rare cellular fatty acid, myristate, to the N-terminal Gly residue of a variety of eukaryotic proteins. The myristoyl moiety is often essential for expression of the biological functions for these proteins.

Attachment of C14:0 alone provides barely enough hydrophobicity to allow stable association with membranes. The partitioning of N-myrisotylproteins is therefore often modulated by "switches" that function through additional covalent or noncovalent modifications. Candida albicans, the principal cause of systemic fungal infection in immunocompromised humans, contains a single NMT gene that is essential for its viability. The functional properties of the acylCoA binding site of human and C. albicans NMT are very similar. However, there are distinct differences in their peptide binding sites. An ADP ribosylation factor (Arf) is included among the few cellular protein substrates of the fungal enzyme. Alanine scanning mutagenesis of an octapeptide derived from an N-terminal Arf sequence (GLYASKLS-NH2) disclosed that Gly1, Ser5, and Lys6 play predominant roles in binding. ALYASKLS-NH2 is an inhibitor competitive for peptide [Ki(app) = 15.3 +/- 6.4 microM] and noncompetitive for myristoylCoA. Remarkably, replacement of the N-terminal tetrapeptide with an 11-aminoundecanoyl group results in a competitive inhibitor (11-aminoundecanoyl-SKLS-NH2) that is approximately 40-fold more potent [Ki(app) = 0.40 +/- 0.03 microM] than the starting octapeptide. Removal of Leu-Ser from the C-terminus generates a competitive dipeptide inhibitor (11-aminoundecanoyl-SK-NH2) with a Ki(app) of 11.7 +/- 0.4 microM, equivalent to that of the starting octapeptide. A derivative dipeptide inhibitor containing a C-terminal N-cyclohexylethyl lysinamide moiety has the advantage of being more potent (IC50 = 0.11 +/- 0.03 microM) and resistant to digestion by cellular carboxypeptidases. Rigidifying the flexible aminoundecanoyl chain results in very potent general NMT inhibitors (IC50 = 40-50 nM). Substituting a 2-methylimidazole for the N-terminal amine and adding a benzylic alpha-methyl group with R stereochemistry to the rigidifying element produces even more potent inhibitors (IC50 = 20-50 nM) that are up to 500-fold selective for the fungal compared to human enzyme. A related less potent member of this series of compounds is fungistatic. Its growth inhibitory effects are associated with a reduction in cellular protein N-myristoylation, judged using cellular Arf as a reporter. These studies establish that NMT is a new antifungal target.

背景与目标： MyristoylCoA ：蛋白N-肉豆蔻酰基转移酶（NMT）催化稀有细胞脂肪酸肉豆蔻酸酯与多种真核蛋白N-末端Gly残基的共翻译共价连接。肉豆蔻酰基部分通常对于表达这些蛋白质的生物学功能是必不可少的。

C14 ：0的附着本身仅提供了不足以使与膜稳定结合的疏水性。因此，N-肉豆蔻酰蛋白的分区通常由通过附加的共价或非共价修饰起作用的“开关”调节。白色念珠菌是免疫功能低下的人体内全身真菌感染的主要原因，它含有一个对其生存能力至关重要的单个NMT基因。人和白色念珠菌NMT的酰基辅酶A结合位点的功能特性非常相似。但是，它们的肽结合位点存在明显差异。 ADP核糖基化因子（Arf）包括在真菌酶的几种细胞蛋白底物中。来自N末端Arf序列（GLYASKLS-NH2）的八肽的丙氨酸扫描诱变显示，Gly1，Ser5和Lys6在结合中起主要作用。 ALYASKLS-NH2是一种对肽[Ki（app）= 15.3 /-6.4 microM]具有竞争性的抑制剂，对肉豆蔻酰辅酶A不具有竞争性。值得注意的是，用11-氨基十一烷酰基取代N末端四肽会产生竞争性抑制剂（11-氨基十一烷酰基-SKLS-NH2），其效力比[Ki（app）= 0.40 /-0.03 microM]高40倍左右。起始八肽。从C末端去除Leu-Ser会产生竞争性的二肽抑制剂（11-氨基十一烷酰基-SK-NH2），Ki（app）为11.7 /-0.4 microM，与起始八肽相当。含有C-末端N-环己基乙基赖氨酰胺部分的衍生物二肽抑制剂具有更有效的优势（IC 50 ＝ 0.11 /0.03μM），并且对细胞羧肽酶的消化具有抵抗力。刚性化柔性氨基十一烷酰基链会产生非常有效的常规NMT抑制剂（IC50 = 40-50 nM）。用2-甲基咪唑取代N端胺，并在刚性元素中添加具有R立体化学的苄基α-甲基，可产生更强效的抑制剂（IC50 = 20-50 nM），对真菌的选择性高达500倍与人类酶相比。该系列化合物的一个相关的效力较弱的成员是抑真菌的。使用细胞Arf作为报告基因判断，其生长抑制作用与细胞蛋白N-肉豆蔻酰化的减少有关。这些研究确定NMT是一种新的抗真菌靶标。