10. tbl. 96.árg. 2010
Inherited deficiency of the initiator molecules of the lectin-complement pathway
Arfgengur skortur í ræsisameindum lektínferils komplímentvirkjunar
Introduction: Information about the education, training and future employment prospects of Icelandic surgeons has not been available.
Materials and methods: The study included all Icelandic surgeons, in all subspecialties, educated at the Faculty of Medicine at the University of Iceland. Information on specialty training, higher academic degrees and in which country these were obtained was collected. Future employment prospects were analysed by calculating supply and demand until the year 2025. Approximations, such as sustained demand for surgeons per capita, were used.
Results: Out of 237 licensed surgeons, two thirds were living in Iceland and 36 were retired. Majority (69.2%) had been trained in Sweden and orthopaedic (26.9%) and general surgery (23.9%) were the most common subspecialties. The average age of surgeons in Iceland was 52 years and 44 years for surgeons abroad. Females were 8% of surgeons in Iceland while being 17.4% among 36 doctors in surgical training overseas. Over 19% had received a PhD degree. Predictions suggest that supply and demand for surgeons in Iceland will be equal in the year 2025, not taking into account the prospects for the working market outside Iceland.
Conclusion: A third of Icelandic surgeons live outside Iceland. The proportion of female surgeons is low but it is increasing. Our predictions indicate a balanced work market for surgeons in Iceland for the next 15 years. However, there are many uncertainty factors in the calculations and they do not predict the prospects for individual subspecialties.
Figure 1. Three pathways to compliment activation.
a. The classical pathway is initiated by the binding of C1q (structural homolog to MBL and ficolins) to the Fc portion of immunoglobulins bound to antigens on bacterial surface. Binding results in autoactivation of the serine protease C1r. Clr then cleaves and activates C1s, which translates the activation of the C1 complex into complement activation through cleavage of C4 and C2 to form a C4bC2a enzyme complex. C4bC2a acts as a C3 convertase and cleaves C3, which results in products (C3b or opsonins) that bind to and cause destruction of invading bacteria. The final product is MAC (membrane attack complex) (not shown in this figure) which causes membrane lysis of bacteria or viruses.
b. The lectin pathway is immunoglobulin independant. MBL or ficolins (1-3) bind carbohydrate patterns on the microorganisnms' surface and upon binding the associated enzyme MASP-2 is activated and the complement cascade starts as in the classical pathway.
c.The alternative pathway is initiated by hydrolysed C3. Reprint with permission from © Nature Publishing Group 200256.
Figure 2. Functions of MBL.
a. Opsonophagocytosis. MBL bound to microbial surfaces is able to promote opsonophagocytosis by two mechanisms. (i) By activation of the complement system through MASP-2 generating C3b fragments (opsonins). Such fragments are recognised by the CR1 (CD35) receptor of the phagocyte. (ii) By direct uptake of MBL by phagocytes but the putative collectin receptor involved has not yet been identified. MBL is also able to promote inflammation by a dose-dependant modulation of cytokine release from monocytes.
b. Clearance of apoptopic cells. MBL binds to apoptopic T cells and polymorphonuclear neutrophils through the globular CRD region. Uptake by mononuclear phagocytes requires recognition of the CRD domain by cC1qR in association with CD91. Reprint with permission from © Elsevier 200357.
Figure 3. Structure of the human MBL-2 gene and its protein product. Location and name of genetic polymorphism is indicated under the boxes. The protein is illustrated as three subunits or as a trimer. Reprint with permission from © Nature Publishing Group 200256
Figure 4. The relationship between MBL serum levels and genotypes. A is the wild-type allele in exon 1 and B, C and D (O) are single nucleotide polymorphisms in exon 1 (see figure 3). Population size 1183. Median, interquartile and 90% interval and range are indicated. Reprint with permission from © Elsevier 200319.