Inflammation Causes Resistance to Anti-CD20-Mediated B Cell Depletion.

B cells play a central role in antibody-mediated rejection and certain autoimmune diseases. However, B cell-targeted therapy such as anti-CD20 B cell-depleting antibody (aCD20) has yielded mixed results in improving outcomes. In this study, we investigated whether an accelerated B cell reconstitution leading to aCD20 depletion resistance could account for these discrepancies. Using a transplantation model, we found that antigen-independent inflammation, likely through toll-like receptor (TLR) signaling, was sufficient to mitigate B cell depletion. Secondary lymphoid organs had a quicker recovery of B cells when compared to peripheral blood. Inflammation altered the pharmacokinetics (PK) and pharmacodynamics (PD) of aCD20 therapy by shortening drug half-life and accelerating the reconstitution of the peripheral B cell pool by bone marrow-derived B cell precursors. IVIG (intravenous immunoglobulin) coadministration also shortened aCD20 drug half-life and led to accelerated B cell recovery. Repeated aCD20 dosing restored B cell depletion and delayed allograft rejection, especially B cell-dependent, antibody-independent allograft rejection. These data demonstrate the importance of further clinical studies of the PK/PD of monoclonal antibody treatment in inflammatory conditions. The data also highlight the disconnect between B cell depletion on peripheral blood compared to secondary lymphoid organs, the deleterious effect of IVIG when given with aCD20 and the relevance of redosing of aCD20 for effective B cell depletion in alloimmunity.

Bacteriological aspects of the disposal of manure from beef cattle.

Manure, collected from cattle housed in yards, was spread on experimental plots at the rate of 120 tonnes per hectare per annum. The manure was applied to 2 plots at 6-monthly intervals while a further 2 plots received monthly applications. Samples of manure soil, run-off and ground waters were examined for their counts of total aerobic bacteria, coliforms, faecal coliforms and for the presence of salmonellae. Comparison of the bacterial counts from samples from the test plots to those of the control plots showed that no change occurred in the levels of coliforms or faecal coliforms over the 3 years of manure application. One hundred and fifty-seven isolations of salmonella were made from the soil and water samples, but only 51 could be attributed to the manure. No difference was observed in the effects of different application frequencies.

An analysis of leg abnormalities of boars in the Queensland performance testing station.

An analysis was made of the results of leg inspections of boars in the Queensland boar testing station at the start and end of their performance tests. The frequency among boars of 12 specific faults ranged from zero to 90% at the start and 7% to 73% and the end of testing. Of the 362 boars examined, 20% suffered from leg weakness. 11% of these had to be slaughtered and 9% recovered after return to the farm. The only faults significantly associated with leg weakness were: "up on toes" of the front feet and excessive flexion of the front knees ("over at knee"). The sire, breed and herd of origin of a boar had little effect on its having any one of the 12 faults. However, herds were found to differ in the total number of faults per boar and Large White had more front leg faults than Landrace. The correlation between number of leg faults and growth rate of a boar during test was + 0.12. Although lef weakness was an important cause of boar wastage, neither it nor leg faults were significant sources of error in evaluating the performance of boars which completed testing.

The efficacy of protein supplementation in overcoming urea toxicity in sheep.

1. In the first experiment sheep taken from pasture were given a low-protein diet for six weeks in individual pens. Then, for 1 week, groups were given a supplement of lucerne chaff, safflower meal or lucerne chaff plus safflower meal. In the second experiment eighteen sheep maintained on lucerne chaff rather than pasture were then depleted of protein to a greater extent by feeding on a restricted low-protein diet. Six of the sheep received a supplement of molasses throughout the period of protein depletion while six of the sheep on the basal ration received a supplement of safflower meal after 6 weeks on the low-protein diet. 2. The urea tolerance of the sheep, is indicated by blood ammonia levels after oral dosing with aqueous solutions of urea, was determined after the period of supplementation. "Arginine synthetase" activity (combined activities of argininosuccinate synthetase (EC 6.3.4.5) and argininosuccinate lyase (EC 4.3.2.1) was determined in liver samples obtained by biopsy at various intervals during the experiment. 3. Supplementation for 7 d with 73 g crude protein (nitrogen X 6-25)/d increased the tolerance to urea as indicated by reduced blood NH3 levels, and also increased "arginine synthetase" activity. 4. Giving supplements of molasses delayed the onset of urea toxicity but not the extent of toxicity. 5. It is suggested that short-term feeding of protein concentrates to sheep before giving urea supplements can increase their tolerance to urea.