News & Views in 2000

Kaposi sarcoma-associated herpesvirus (KSHV) is linked to the development of Kaposi sarcoma and certain lymphoproliferative malignancies. The main immunogenic latent nuclear antigen of KSHV can form a complex with retinoblastoma tumor suppressor protein and transform cells, indicating that the oncogenic activities of KSHV are mechanistically related to the transforming functions of the small DNA tumor viruses (pages 1121–1127).

Investigation into the ability of anti-retroviral therapy and therapeutic immunization in primary simian immunodeficiency virus infection of macaques demonstrates the importance of anti-retroviral treatment in early infection. The findings also indicate that it may be possible to boost the virus-specific immune response through immunization (pages 1140–1146).

The T-cell co-receptor CD4 is required for T-cell activation, and it may be involved in stabilization of the T-cell receptor and class II major histocompatibility complexes during antigen presentation. However, video microscopic analyses of the interactions between T cells and antigen-presenting cells indicate otherwise.

A naturally occurring metabolite of ceramide, sphingosine-1-phosphate, reportedly protects mouse oocytes from chemotherapy and radiation-induced apoptosis. What is the potential for using ceramide analogs to prevent human infertility? (pages 1109–1114)

Retinoids have a wide variety of biological functions and have been recently shown to regulate cholesterol transport, bile acid synthesis and cholesterol absorption. These findings indicate a new line of mechanisms to control cholesterol homeostasis.

Expression of the uncoupling protein Ucp in skeletal muscle prevents diet-induced obesity and insulin resistance. Similar effects are seen in response to increased physical exercise, indicating that pharmacological strategies designed to manipulate energy expenditure can be used to treat obesity and diabetes. (pages 1115–1120)

The hair follicle is a major repository for epidermal stem cells. Learning more about the processes that regulate the differentiation of these cells will improve the prospects for skin replacement and treatments for skin cancers.

Two clinical trials testing an altered peptide ligand (APL) in multiple sclerosis report seemingly contradictory results. Immunologic analysis shows that the biological effects of APLs extend far beyond what was initially envisioned, raising important issues for the development of this type of therapy (pages 1167–1175 & 1176–1182).

The finding that unregulated, continuous delivery of vascular endothelial growth factor to the myocardium causes the formation of hemangiomas and death in mice indicates that more research is required on this potent molecule before clinical trials can proceed.

Estrogen derivatives have been found to inhibit superoxide dismutase and selectively kill human leukemia cells in vitro. But is SOD a realistic target for human cancer therapy?

Statins, commonly prescribed cholesterol-lowering drugs, have also been identified as anti-oxidants, anti-inflammatories and now, as angiogenic agents. Elucidation of the statin signal transduction pathway should reveal how one class of drugs can have so many activities (pages 1004–1010).

Disruption of the Sp1-related transcription factor HF-1b leads to alterations in the cardiac conduction system that result in ventricular arrhythmias and sudden death. What does this tell us about how ventricular cardiomyocytes differentiate into the specialized cells that form the heart's conductance system?

A collection of clinical and animal studies suggest that exposure to pain during the neonatal period leads to long-term changes in neural circuitry and behavior, contradicting the theory that infants don't ‘remember’ painful experiences.

Combination therapies involving inhibitors of the epidermal growth factor and cyclooxygenase signaling prevent colorectal adenomas in mice. This synergistic effect may be due to the convergance of these two signaling pathways (pages 1024–1028).

Although several excellent drugs are available to treat tuberculosis, their mechanisms are not well understood. Identification of the target of the tuberculosis drug pyrazinamide underscores the role that lipids play in disease pathogenesis, and reveals new avenues for drug design (pages 1043–1047).

The use of dendritic cells to immunize against tumor antigens is improving the prospects for cancer vaccines. However, caution must be taken to avoid activating autoimmunity against normal cells (pages 1011–1017).

Overexpression of two members of the AP-1 transcription factor family has dramatic effects on bone development, raising the question: why are there so many molecules that affect bone remodeling (pages 980–984 and 985–990)

Mounting evidence suggests that non-steroidal anti-inflammatory drugs may be useful in reducing the risk of Alzheimer disease. After much study, the mechanism by which these drugs reduce the amyloid deposition associated with the disease is still open to speculation.

Correlational data and mathematical modeling suggest that increased division rate of naïve T cells, not reduced thymic output, lowers the frequency of original thymic emigration among these cells in HIV infected individuals. But are there alternate explanations for these data? (pages 1036–1042)