Hepatitis C

Hepatitis C virus infection is responsible for significant morbidity and mortality worldwide. Advances in detection and monitoring of hepatitis C virus infection, as well as treatment protocols, have contributed to the medical focus on this high profile disease. Presence of risk factors should increase the clinicians index of suspicion for this symptomatically nonspecific disease.     

FLUID PHASE DESTRUCTION OF C2hu BY C1hu : II. UNMASKING BY C4ihuOF C1hu SPECIFICITY FOR C2hu

It has been demonstrated that C1 isolated in the unactivated form fails to inactivate C4 or C2 in the fluid phase, while the activated molecule, C1 rapidly converts C4 to hemolytically inactive C4i, but does not efficiently inactivate C2. The production and presence of C4i now confers on C1 the ability to rapidly inactivate C2. After heating at 56°C, so as to destroy the hemolytic activity, heat inactivated C1 is still capable of inactivating C4 but the presence of C4i no longer confers an ability to inactivate C2. Studies with the subunits of C1–C1q, C1r, C1s, indicate that the action of C1s on C2 can be inhibited by C1r and that this inhibition is reversed by the presence of homologous C4. These studies indicate that the interaction of C4i with a heat labile receptor conformation in C1 uncovers a masked specificity for C2.     

Hepatitis C

Hepatitis C virus (HCV) infection is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma worldwide. Here, we briefly review the virology, diagnosis and therapy of hepatitis C. Standard therapy with pegylated interferon-alpha and ribavirin results in a sustained virological response in 40-50% of genotype 1- and in about 80% of genotype 2- or 3-infected patients. Recent progress has allowed the identification of novel antiviral targets and therapeutic strategies. These will likely complement existing therapeutic modalities in the near future.     

C2 and C3 pain dermatomes in man

This report defines the C2 and C3 pain dermatomes by the distribution of: the hypalgesia clearing after surgical root decompression; the dysaesthesias produced by electrical root stimulation; and the hypalgesia produced by anaesthetic root block. The C2 pain dermatome, so defined, consists of an occipital parietal area 6-8 cm wide, ascending paramedially from the subocciput to the vertex. The C3 pain dermatome is a craniofacial area including the scalp around the ear, the pinna, the lateral cheek over the angle of the jaw, the submental region and the lateral and anterior aspects of the upper neck. These C2 and C3 pain dermatomes do not overlap and are smaller than the C2 and C3 tactile dermatomes described in the literature.     

C5 deficiency and C5a or C5aR blockade protects against cerebral malaria

Experimental infection of mice with Plasmodium berghei ANKA (PbA) provides a powerful model to define genetic determinants that regulate the development of cerebral malaria (CM). Based on the hypothesis that excessive activation of the complement system may confer susceptibility to CM, we investigated the role of C5/C5a in the development of CM. We show a spectrum of susceptibility to PbA in a panel of inbred mice; all CM-susceptible mice examined were found to be C5 sufficient, whereas all C5-deficient strains were resistant to CM. Transfer of the C5-defective allele from an A/J (CM resistant) onto a C57BL/6 (CM-susceptible) genetic background in a congenic strain conferred increased resistance to CM; conversely, transfer of the C5-sufficient allele from the C57BL/6 onto the A/J background recapitulated the CM-susceptible phenotype. The role of C5 was further explored in B10.D2 mice, which are identical for all loci other than C5. C5-deficient B10.D2 mice were protected from CM, whereas C5-sufficient B10.D2 mice were susceptible. Antibody blockade of C5a or C5a receptor (C5aR) rescued susceptible mice from CM. In vitro studies showed that C5a-potentiated cytokine secretion induced by the malaria product P. falciparum glycosylphosphatidylinositol and C5aR blockade abrogated these amplified responses. These data provide evidence implicating C5/C5a in the pathogenesis of CM.