In situ expression of mononuclear cell markers and interleukin-2 receptor in renal allograft biopsies of acute rejection and borderline cases

The correct diagnosis of renal allograft rejection may be difficult using only clinical and/or histopathological criteria. Immunological assays should be considered in order to evaluate the phenotype of inflammatory infiltrate in renal allograft biopsies. Immunohistochemical studies were performed to detect mononuclear cells, CD4 and CD8 T lymphocytes, B lymphocytes, macrophages, null cells, and positive cells for interleukin-2 receptors. A total of 41 allograft biopsies classified into three groups were studied: acute cellular rejection (28 biopsies/22 patients), borderline (7 biopsies/5 patients) and control (6 biopsies/6 patients). In the rejection group (RG), increased cellularity was found mainly at the tubulo-interstitial level. Expression of CD8 positive cells was higher in RG when compared to borderline (BG) and control (CG) groups, respectively (0.9 vs. 0.0 vs. 0.35 cells/mm2; p < 0.001). Expression of macrophages was not statistically significant among the three groups (RG = 0.6 vs. BG = 0.2 vs. CG = 0.0 cells/mm2; p < 0.02). In the BG, CD4 + cells predominated (BG = 0.2 vs. RG = 0.05 vs. CG = 0.0 cells/mm2; p < 0.05). Clinically these patients were treated as cases of acute rejection. The numbers and different types of infiltrating cells did not correlate with patient's clinical outcome. Copyright © Informa Healthcare.

LPS Induces Greater Bone and PDL Loss in SPARC-null Mice

Individuals with periodontal disease have increased risk of tooth loss, particularly in cases with associated loss of alveolar bone and periodontal ligament (PDL). Current treatments do not predictably regenerate damaged PDL. Collagen I is the primary component of bone and PDL extracellular matrix. SPARC/Osteonectin (SP/ON) is implicated in the regulation of collagen content in healthy PDL. In this study, periodontal disease was induced by injections of lipopolysaccharide (LPS) from Aggregatibacter actinomycetemcomitans in wild-type (WT) and SP/ON-null C57/B16 mice. A 20-mu g quantity of LPS was injected between the first and second molars 3 times a week for 4 weeks, whereas PBS control was injected into the contralateral maxilla. LPS injection resulted in a significant decrease in bone volume fraction in both genotypes; however, significantly greater bone loss was detected in SP/ON-null maxilla. SP/ON-null PDL exhibited more extensive degradation of connective tissue in the gingival tissues. Although total cell numbers in the PDL of SP/ON-null were not different from those in WT, the inflammatory infiltrate was reduced in SP/ON-null PDL. Histology of collagen fibers revealed marked reductions in collagen volume fraction and in thick collagen volume fraction in the PDL of SP/ON-null mice. SP/ON protects collagen content in PDL and in alveolar bone in experimental periodontal disease.

CYP1A2*1C, CYP2E1*5B, and GSTM1 polymorphisms are predictors of risk and poor outcome in head and neck squamous cell carcinoma patients

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of mutations in acetate metabolism on high-cell-density growth of Escherichia coli

To study the role played by acetate metabolism during high-cell-density growth of Escherichia coli cells, we constructed isogenic null mutants of strain W3100 deficient for several genes involved either in acetate metabolism or the transition to stationary phase. We grew these strains under identical fed-batch conditions to the highest cell densities achievable in 8 h using a predictive-plus-feedback-controlled computer algorithm that maintained glucose at a set-point of 0.5 g/l, as previously described. Wild-type strains, as well as mutants lacking the sigma(s) subunit of RNA polymerase (rpoS), grew reproducibly to high cell densities (44-50 g/l dry cell weights, DCWs). In contrast, a strain lacking acetate kinase (ackA) failed to reach densities greater than 8 g/l. Strains lacking other acetate metabolism genes (pta, acs, poxB, iciR, and fadR) achieved only medium cell densities (15-21 g/l DCWs). Complementation of either the acs or the ackA mutant restored wild-type high-cell-density growth, on a dry weight basis, poxB and fadR strains produced approximately threefold more acetate than did the wild-type strain. In contrast, the pta, acs, or rpoS strains produced significantly less acetate per cell dry weight than did the wild-type strain. Our results show that acetate metabolism plays a critical role during growth of E. coli cultures to high cell densities. They also demonstrate that cells do not require the sigma(s) regulon to grow to high cell densities, at least not under the conditions tested.