The relation between glycemic control and HDL-C in type 2 diabetes: a preliminary step forward?

Low high-density lipoprotein cholesterol (HDL-C) levels are associated with cardiovascular (CV) disease in type 2 diabetes (T2D). Unfortunately available drugs to increase HDL-C have failed to demonstrate a reduction in CV risk. We assessed the effect of improving glycemic control on HDL-C levels. A 6-month intervention resulted in significant improvement in HbA1c but not in HDL-C levels. However, when considering the subgroup of subjects with low levels of HDL-C at baseline, we found a significant and inverse relation between improvement in HbA1c and HDL-C levels.

Polymerase chain reaction analysis of T-cell receptor gamma gene rearrangements in cutaneous B-cell lymphomas.

PCR analyses of T-cell receptor (TCR) gamma gene rearrangements in B-lymphoid neoplasms have shown lineage infidelity and double rearrangements involving both immunoglobulin heavy chain (igH) and TCRgamma genes. In order to investigate if this event is also a feature of cutaneous B-cell malignancies, we tested for clonal TCRgamma rearrangements a panel of immunophenotypically and genotypically well characterized cutaneous B cell lymphomas (CBCL). Fifteen samples of frozen CBCL biopsies were selected for the study. Diagnoses were established by routine histology and immunohistochemistry. Each of these cases displayed clonal igH gene rearrangement. Polymerase chain reaction (PCR) analysis of the TCRgamma rearrangements followed by high-resolution polyacrylamide gel electrophoresis was utilized for detection of clonal TCRgamma rearrangements. In our investigation, none of the cases of CBCL investigated by PCR showed the presence of clonal TCRgamma gene rearrangements. These data indicate that double rearrangements involving both igH and TCRgamma genes are not a feature of CBCL and confirm the B cell lineage specificity of this group of cutaneous lymphoid neoplasms.

Release of the aspartyl protease cathepsin D is associated with and facilitates human breast cancer cell invasion.

Data concerning the hormone sensitivity of the release and role of the aspartyl protease cathepsin D in tumor proliferative and invasive processes have been contradictory. To clarify the mechanisms of its release and role we first studied the contribution of estradiol and stripped serum to the time course and kinetics of cathepsin D release, proliferation, and invasion in parallel in the MCF-7 in vitro breast cancer cell culture model. Both estradiol and stripped serum independently stimulated both proliferation and cathepsin D release. However, the dose-response of estradiol and stripped serum-dependent stimulated release were similar to those for invasion and differed from those for proliferation: cathepsin D release and invasion were first stimulated at a stripped serum concentration more than 10-fold lower than that which initiated proliferation and had half stimulation constants almost 10-fold lower than those for proliferation. These results demonstrate that cathepsin D release is not related in any direct way to proliferation. The effect of the reduction of cathepsin D activity or release on in vitro invasion was also measured: both the inhibition of secreted cathepsin D activity by a specific inhibitor, diazoacetyl-DL-Nle-OMe, and the reduction of cathepsin D release by antisense oligonucleotides against its translation start site reduced cellular in vitro invasion without affecting proliferation. Cathepsin D release and activity are concluded to be directly involved in the process of invasion.

Analysis of clonal antigen receptor gene rearrangements in T-cells involved with Kaposi's sarcoma.

Kaposi's sarcoma (KS) is a multifocal neoplasm of unknown origin. All forms of KS are composed of spindle-shaped cells with elongated nuclei and sheets of endothelial-like cells. The proliferation of spindle cells is accompanied by the presence of an inflammatory infiltrate composed predominantly of T-cells. It has been suggested that this infiltrate might consist of a virally stimulated clonal population of T-lymphocytes which can produce growth factors initiating and substaining the proliferation of spindle-shaped cells. In this study we analyzed for clonal T-cell receptor gama gene rearrangements the T-cell populations present in the cutaneous infiltrate of seven cases of classical Kaposi's sarcoma using a polymerase chain reaction-based approach. Our data demonstrate the lack of a significant clonal population of T-cells in the cutaneous infiltrates of KS. This finding is indicative of a reactive polyclonal response of T-cells to the spindle-shaped cells and supports the contention that spindle-shaped cells are pathogenetically the central cell type in the disease. Our data also indicate that the anti-KS T-cell response, being polyclonal in nature, does not result from clonal expansion of T-cells targeting tumor-associated antigenic peptides.