International Journal of Clinical and Laboratory Research

C4b-binding protein (C4b-BP) is a high molecular weight plasma protein which inhibits the activity of the classical complement pathway C3 convertase. In addition to multiple binding sites for C4b, C4b-BP possesses a single binding site for vitamin K-dependent protein S, an inhibitor of blood coagulation. As protein S bound to C4b-BP has no anticoagulant activity, C4b-BP participates in the regulation of both the complement and the coagulation pathways. We have produced and immunochemically characterized a series of murine monoclonal antibodies to human C4b-BP. A mixture of four monoclonal antibodies precipitating C4b-BP both in agarose gel and in solution was used to develop a highly reproducible radial immunodiffusion method for the measurement of C4b-BP in human serum. C4b-BP levels were measured in sera from 284 patients referred to our central laboratory. Samples from subjects with an increased erythrocyte sedimentation rate (ESR), a1-acid glycoprotein (a1-AGP) or C-reactive protein (CRP) had significantly higher C4b-BP levels (307 mg/l, 292–322 mg/l, geometric mean and 95% confidence limits of the mean) than those from subjects without elevation of the aforementioned established acute phase reactants (231 mg/l, 226–237 mg/l,P<0.00001). C4b-BP was significantly (P<0.001) correlated with ESR (r=0.715), a1-AGP (r=0.692) and CRP (r=0.567). There was no genderrelated difference in C4b-BP levels. In subjects with no increased acute phase reactants there was a significant correlation between C4b-BP levels and age (r=0.387,P<0.001). High C4b-BP might contribute to the increased thrombotic risk associated with inflammation and aging.

The use of tracers with high radioactivity in rapid dynamic quantitative studies (such as radioisotope angiocardiography), performed by the Anger-camera and data-processor, makes it possible to obtain a high counting rate. For correct interpretation of the results of the analysis of activity/time curves in regions of interest, the authors determined, under different working conditions, the deadtimes of two Anger-cameras (Pho-gamma HP and Radicamera II), both connected to a data-processing system (Med-II). The problems inherent in this determination are analyzed and discussed. A computer program for curve correction was written and some examples of applications of it are presented, including an experiment to test the accuracy of the correction.

Recenti ricerche hanno fornito i seguenti dati sull’amiloide: 1) esso ha natura proteica fibrillare, con catatteristico aspetto al microscopio elettronico e alla diffrazione ai raggi X; 2) esistono due tipi immunochimici principali delle proteine dell’amiloide: il primo è correlate con le catene leggere delle immunoglobuline, il secondo è una proteina finora non identificata. Il primo si riscontra nella forma primaria ed in quella associata al mieloma, mentre il secondo è la componente principale della forma secondaria ed in certi tipi di amiloidosi familiare; 3) le proteine correlate a queste forme sono presenti nel siero e possono essere utilizzate come precursori.

There is considerable experimental evidence that the RES is an important host defense system in critical illness. The role of fibronectin in the control of RES phagocytic function and the potential for fibronetin therapy to ameliorate or reverse multisystem organ failure in critically ill patients are less well documented. This documentation may be difficult to accrue in the clinical setting because of the multifactorial problems of individual critically ill patients and the heterogeneity of underlying diseases in such patients. More work needs to be done in animal models in which these variables can be controlled. Large scale production of pasteurized biologically active fibronection should be possible32 if the cryoprecipitate studies prove the clinical utility of fibronectin concentrates. Fibronectin will certainly not be a panacea for critically ill patients, but the addition of any useful substance to the now meager armamentarium would be most welcome.

The strong transplantation antigens (called histocompatibility or H antigens) in a number of species are determined by genes of a single genetic complex — the major histocompatibility complex. While there are other H antigens which, if different in two individuals, can lead to graft rejection, it is the antigens of the major histocompatibility complex which are of overwhelming importance. These antigens can be divided into two classes: first, the antigens initially detected by serological methods which are present on the surfaces of all lymphoid cells and essentially all other tissues; second, those differences between cells which lead to activation of lymphocytes in the Mixed Leukocyte Culture (MLC) test. These two components of the major histocompatibility complex have been referred to as the SD and LD components respectively. Since both these types of differences apparently lead to graft rejection, it is desirable to match donor and recipient optimally for both systems. This is best achieved by minimizing the number of SD antigens by which donor and recipient differ and by assuring the lowest degree of stimulation in the MLC test between donor and recipient. Gli antigeni forti del trapianto (denominati antigeni H o dell’istocompatibilitè) sono controllati, in talune specie, da geni di un singololocus genetico: illocus principale dell’istocompatibilitè. Sebbene esistano altri antigeni H che, se diversi in due individui, possono portare al rigetto del trapianto, gli antigeni dellocus principale dell’istocompatibilitè sono senz’altro i più importanti. Tali antigeni possono essere suddivisi in due classi: la prima comprende gli antigeni esplorati all’inizio mediante metodiche sierologiche, i quali sono presenti sulle superficie di tutte le cellule linfoidi e praticamente in tutti gli altri tessuti, e la seconda le differenze tra le cellule che provocano attivazione linfocitaria nel test di coltura mista leucocitaria (MLC). Queste due componenti dellocus principale dell’istocompatibilitè sono state denominate rispettivamente componente SD e LD. Poiché queste differenze sembrano condurre entrambe al rigetto del trapianto, è bene rendere compatibili in modo ottimale il donatore ed il ricevente ad entrambi i sistemi. Il modo migliore per ottenere questo risultato è la riduzione al massimo degli antigeni SD che differenziano il donatore ed il ricevente e l’induzione dlia più bassa stimolazione nel test MLC tra donatore e ricevente.

The envelope proteins of hepatitis B virus are highly conserved. They are involved in viral attachment to hepatocytes, virion assembly and secretion and induction of humoral and T-cell immune responses. The major neutralisation epitope is located within the S protein and is conformation dependent, probably due to the formation of disulphide bridges. Variation in the envelope proteins of hepatitis B virus has been described in vaccinees and in patients receiving monoclonal and polyclonal antibody therapy. Thes arise through point mutations in the surface gene and appear to be selected by the immune response. The emergence of such variants has clinical relevance, in particular with regard to vaccine failure and diagnostic difficulties.

The principal differences of the USA plasmapheresis collection system from most other countries are: it is conducted by the pharmaceutical industry rather than government, it uses remunerated donors, and it draws a larger volume of plasma than is permitted elsewhere. The implications of these features are reviewed in terms of the effects on donors and the effects on the plasma supply. Protein metabolism is reviewed, and the effects of plasmapheresis on overall nitrogen balance are presented.