Lymphocyte transformation induced by autologous cells.

Human peripheral blood T lymphocytes are stimulated to proliferate when cultured with autologous B-lymphoblastoid cell lines, autologous mitogen-induced lymphoblasts, or autologous non-T blood lymphocytes. This reaction, the autologous mixed lymphocyte reaction, has attributes of an immune response possessing both memory and specificity. The capacity to stimulate autologous T lymphocyte proliferation depends on the lineage of the lymphoid cell and not on its establishment in continuous culture or carriage of the EB viral genome. The determinant on non-T lymphocytes which stimulates the autologous mixed lymphocyte reaction appears to be an Ia determinant. Thus, allogeneic graft rejection and the allogenic mixed lymphocyte reaction are very likely extensions of an immune response expressed within the host.     

Peptide screening.

Since late 1990, there have been several advances in preparing and screening large numbers of various peptides. Developments have continued in methods of peptide screening based on peptides exposition on coat proteins, produced via fusion coliphage constructs. Further developments have been made in increasing the multitude of peptides produced by the chemical synthetic strategy, including light-directed, spatially addressable chemical synthesis, single-bead, single-peptide synthesis, as well as iterative peptide selection and synthesis.     

Homocitrate production by a lysine-requiring pichia guilliermondii mutant

Mutants of Pichia guilliermondii were isolated that lacked homoaconitate hydratase (lys4), homoisocitrate dehydrogenase (lys10) or α-aminoadipate reductase (lys2) and were able to excrete homocitrate into the culture medium. The effects of incubation time and lysine concentration in the medium on the excretion of homocitrate were examined. In the presence of 600 mg of L-lysine/1 in a minimum salt medium P. guilliermondii G75 (lys2) produced about 280 mg homocitrate/1 during 48 h of growth. A simple procedure to isolate homocitrate from the medium is described.     

Studies on a leukocyte elastase inhibitor present in the culture medium of inflamed synovial tissue

The spent medium of cultured inflamed synovial tissue contains a potent inhibitor of leukocyte elastase. This leukocyte elastase inhibitor has no effect on leukocyte cathepsin G and pancreatic elastase is only marginally affected. The inhibitor is a glycoprotein, stable to heat, acid and reductive alkylation. Pretreatment of the inhibitor with either trypsin or chymotrypsin results in its inactivation.     

mTORC1 Down-Regulates Cyclin-Dependent Kinase 8 (CDK8) and Cyclin C (CycC)

In non-alcoholic fatty liver disease (NAFLD) and insulin resistance, hepatic de novo lipogenesis is often elevated, but the underlying mechanisms remain poorly understood. Recently, we show that CDK8 functions to suppress de novo lipogenesis. Here, we identify the mammalian target of rapamycin complex 1 (mTORC1) as a critical regulator of CDK8 and its activating partner CycC. Using pharmacologic and genetic approaches, we show that increased mTORC1 activation causes the reduction of the CDK8-CycC complex in vitro and in mouse liver in vivo. In addition, mTORC1 is more active in three mouse models of NAFLD, correlated with the lower abundance of the CDK8-CycC complex. Consistent with the inhibitory role of CDK8 on de novo lipogenesis, nuclear SREBP-1c proteins and lipogenic enzymes are accumulated in NAFLD models. Thus, our results suggest that mTORC1 activation in NAFLD and insulin resistance results in down-regulation of the CDK8-CycC complex and elevation of lipogenic protein expression.