Complement C6 and C2 Biosynthesis in Syngeneic PVG/c− and PVG/c+ Rat Strains

A PVG rat strain with total deficiency of C6 and partial deficiency of C2 (PVG/c⁻), and a syngeneic control strain (PVG/c⁺), were used to study the production of extrahepatically synthesized complement. Livers of complement deficient rats were transplanted in sufficient rats (Tx−L). The C6 and C2 levels in Tx−L rats declined within 2 days to 25% and 30%, respectively, and remained stable for more than 6 weeks. To investigate the contribution of C6 synthesis by the liver, C6 sufficient livers were grafted in deficient rats (Tx+l). After an initial increase, with maximum C6 levels of 119% at 10 days following transplantation, the C6 levels decreased gradually and C6 was no longer detectable 28 days after transplantation. This decline in C6 levels was dependent on antibody production against C6. No significant change in the C3, C4, factor H and factor B levels was observed. Expression of C6 mRNA in the grafted PVG/c⁺ sufficient liver was comparable to the expression of C6 mRNA in control PVG/c⁺ livers while C6 mRNA expression in the transplanted PVG/c⁻ liver and the control PVG/c⁻ liver was lower. In conclusion, it was demonstrated in vivo that not only C6 but also C2 is synthesized extrahepatically in PVG/c rats.     

The IgA-Binding Lectin Jacalin Induces Complement Activation by Inhibition of -Inactivator Function

Jacalin, a D-galactose-specific lectin from jackfruit, interacts with human IgA and one or two other serum proteins. Incubation of jacalin with fresh human serum was shown to result in activation of the complement system. Therefore the mechanism of complement activation by jacalin was studied. Jacalin was extracted from jackfruit seeds (crude preparation) and purified to homogeneity by affinity chromatography on IgA-Sepharose to yield a pure preparation of jacalin. Both crude and pure jacalin were able to activate complement, accompanied by conversion of C3. Consumption of C1, C4 and C-1-inactivator (C-1-In) indicated involvement of the classical pathway. Aggregated IgG (AIgG) caused partial (38%) and jacalin induced complete consumption of C1-In functional activity. It was found upon Ouchterlony analysis that jacalin forms a precipitation line with purified C-1-In. In addition binding of 125I-C-1-In to jacalin-Sepharose was observed, and this binding was inhibitable by either secretory IgA or D-galactose. Next to binding of jacalin to C-1-In, jacalin was also shown to inhibit the functional activity of C-1-In. These results indicate that jacalin induces complement activation by inhibition of C-1-In function and thereby facilitates the activation of precursor C1 in either the absence or presence of low amounts of C1 activators.     

Lowering of lipid composition in aorta of guinea pigs by Curcuma domestica

Background

A short-term study was carried out using guinea pigs to determine the effects of Curcuma domestica on lipid composition in the serum and aorta.

Methods

Animals were given food pellets containing 4% (w/w) powdered rhizome of C. domestica in order to determine its effect on cholesterol, triglyceride and phospholipid levels in the aorta and serum. The animals were fed either a cholesterol free diet or a high cholesterol diet (2% cholesterol, w/w, in food pellet) in order to induce hypercholesterolemia.. After five weeks of this diet treatment, blood and aorta were taken for biochemical analysis and histological studies.

Results

C. domestica in the diet showed no significant effect on the levels of cholesterol, triglyceride and phospholipid in the serum and aorta of the cholesterol free diet animals. However, addition of C. domestica to a high cholesterol diet counteracted increases in the levels of cholesterol, triglyceride and phospholipid in the aorta. Histology studies showed less cholesterol deposits in the aorta of high cholesterol diet animals given C. domestica compared to the high cholesterol diet animals not given C. domestica supplement. C. domestica also had a lowering effect on triglyceride level in the serum of high cholesterol diet animals but showed no effect on serum cholesterol and phospholipid levels.

Conclusion

This study has shown that dietary intake of C. domestica decreased all lipid composition levels in the aorta and also the serum triglyceride level. In addition, C. domestica also reduced cholesterol deposition in the aorta of high cholesterol diet animals.     

Activation of human complement by mouse and mouse/human chimeric monoclonal antibodies

The complement (C)-activating capabilities in human serum of 32 mouse and 10 mouse/human chimeric MoAbs of different isotypes, and their fragments, were tested in vitro. Activation of C via the classical pathway (CP) was performed in 1% factor D-deficient serum in gelatin containing Veronal buffer in the presence of calcium and magnesium (GVB⁺⁺), while activation of the alternative pathway of C (AP) was assessed in 10% Clq-depleted serum in the presence of 5 mm MgCl₂ in GVB⁺⁺. The C-activating ability of MoAbs was expressed relative to the degree of activation of complement by aggregated IgG for the CP and relative to mouse IgG 1 for the AP. All of seven mouse IgG2a MoAbs were potent activators of the CP. The results of CP activation by IgG1, IgG2b and IgG3 isotypes were different for individual MoAbs. Only three (two IgG 1 and one IgG3) of 32 mouse MoAbs were potent activators of the AP. IgG2a and IgG2b were relatively poor AP activators. There were a few MoAbs which activated both the AP and CP. Of 10 chimeric MoAbs, two IgG1, one IgG2 and one IgG4 were poor or non-activators of the CP. On the other hand, IgG2 and IgG4 were good AP activators. IgG3 was the most potent AP activator. Most of the F(ab')₂ fragments were activators of the AP and displayed no activation of the CP. Fc fragments only activated the CP. whereas Fab'did not activate the CP or the AP. These studies suggest that the route of complement activation by class and subclass MoAbs can not always be predicted in advance and based only on their subclass identity.     

Coexistence of diffuse plane normolipaemic xanthoma and amyloidosis in a patient with monoclonal gammopathy

Diffuse plane normolipaemic xanthomatosis (DPNX) is a well-defined clinicopathological entity that characteristically presents with yellow–orange plaques in the periorbital areas, the neck, the upper trunk and the flexural folds. DPNX has been reported in association with lymphoproliferative disorders and, occasionally, with miscellaneous, probably coincidental disorders. A case of DPNX in a patient with an IgGλ monoclonal gammopathy and systemic amyloidosis is reported. Clinical and histopathological findings revealed typical features of DPNX and amyloidosis coexisting in the cutaneous lesions. To our knowledge this is the first reported case showing coexistence of xanthoma and amyloidosis in cutaneous lesions in a patient with a monoclonal gammopathy.     

Phylogeography of the human mitochondrial haplogroup L3e: a snapshot of African prehistory and Atlantic slave trade

The mtDNA haplogroup L3e, which is identified by the restriction site +2349 Mbo I within the Afro-Eurasian superhaplogroup L3 (−3592 Hpa I), is omnipresent in Africa but virtually absent in Eurasia (except for neighbouring areas with limited genetic exchange). L3e was hitherto poorly characterised in terms of HVS-I motifs, as the ancestral HVS-I type of L3e cannot be distinguished from the putative HVS-I ancestor of the entire L3 (differing from the CRS by a transition at np 16223). An Mbo I screening at np 2349 of a large number of Brazilian and Caribbean mtDNAs (encompassing numerous mtDNAs of African ancestry), now reveals that L3e is subdivided into four principal clades, each characterised by a single mutation in HVS-I, with additional support coming from HVS-II and partial RFLP analysis. The apparently oldest of these clades (transition at np 16327) occurs mainly in central Africa and was probably carried to southern Africa with the Bantu expansion(s). The most frequent clade (transition at np 16320) testifies to a pronounced expansion event in the mid-Holocene and seems to be prominent in many Bantu groups from all of Africa. In contrast, one clade (transition at np 16264) is essentially restricted to Atlantic western Africa (including Cabo Verde). We propose a tentative L3e phylogeny that is based on 197 HVS-I sequences. We conclude that haplogroup L3e originated in central or eastern Africa about 46,000 (±14,000) years ago, and was a hitchhiker of much later dispersal and local expansion events, with the rise of food production and iron smelting. Enforced migration of African slaves to the Americas translocated L3e mitochondria, the descendants of which in Brazil and the Caribbean still reflect their different regional African ancestries.     

Epidemiology of paediatric trauma admissions at Queen Elizabeth Central Hospital,Blantyre

We conducted an audit of paediatric trauma admissions to QECH, Blantyre, in September 2003. There were 107 trauma cases representing 8.8% of all paediatric admissions and mean age was 6 years. The commonest cause of trauma was falls (42.9%) followed by burns (31.8%) and road traffic accidents (14.9%). Of the road traffic accidents, only one case was a passenger, the rest were pedestrians hit by moving vehicles. Fracture of limbs was the commonest injury sustained (44.9%) and burns the second commonest injury (31.8%). Most (52.6%) children were brought into hospital within 24 hours of injury while 26.3% came in between 24 hours and 48 hours and 21.1% after 48 hours or more. Death occurred in 7.5% of cases. The mean number of days in hospital was 8.9 days.