News & Views in 2002

The neurotransmitter dopamine underlies most addictive processes—but its faint response to ethanol has puzzled researchers. New research suggests that ethanol interacts synergistically with adenosine and dopamine signaling to amplify the effect of drinking.

Murine antibodies that block cell-surface antigens have been engineered (humanized) to successfully elicit human immune-effector mechanisms. Now, a fully human antibody produced entirely in vitro kills tumor cells directly through signal transduction and shows promise against lymphoma in animal studies (pages 801–807).

A new anti-obesity drug that targets brain pathways controlling energy balance in rats also works against depression and anxiety (pages 825–830).

A newly discovered interplay between two human genes controlling the immune response to HIV has implications for antiretroviral drug therapy and the development of preventive vaccines.

There are currently no effective means to treat acute spinal cord injury, except for glucocorticoids, which produce moderate benefits at best. A new study suggests erythropoietin, now recognized as a potent neuroprotective cytokine, as a potential treatment for spinal cord injury.

Evasion of the immune system is an all too common feature of cancer. A new study suggests one evasion mechanism: induction of T-cell apoptosis through B7-H1, a molecule expressed on the surface of many tumor cells (pages 793–800).

Before leaving the body, cholesterol is converted to bile acids. Two studies implicate the nuclear receptor SHP as a major player in bile-acid production—but not the only one.

Efforts to control vessel growth have focused on vascular endothelial growth factor (VEGF) and its primary receptor VEGFR-2. New data could shift that focus to other members of the VEGF family and the receptor VEGFR-1, particularly in inflammatory diseases (pages 831–840 & 841–849).

Nitric oxide (NO) is a potent vasodilator that is produced in endothelial cells and has been assumed to act exclusively at its site of synthesis. New evidence suggests that red blood cells distribute NO bioactivity, matching blood flow to tissue oxygen demands and endowing NO with features of a hormone (pages 711–717).

Breast cancer patients who respond to tamoxifen and other estrogen-antagonizing drugs can succumb to disease when cancer growth becomes independent of the hormone. One protein, Efp, that might have a role in estrogen independence has now been linked to proteolytic events in the cell cycle.

RNA interference first gained notoriety in invertebrates and plants as a means to target genes for deactivation. Now, in vitro studies suggest that in human cells, this process can inhibit HIV-1 replication and potentially act as a novel and potent anti-retroviral therapy (pages 683–688).

The tumor-killing capacity and the systemic toxicity of the cytokine tumor necrosis factor (TNF) have appeared inseparable. Now a study shows that TNF loses its toxicity but still kills tumors in heat-treated mice.

Niemann–Pick type C (NPC) disease is a fatal lipid-storage disorder caused by a 'lipid traffic jam' in late endosomes and lysosomes. A recent study indicates that overexpression of the vesicular transport proteins Rab7 or Rab9 increases the flow of traffic, allowing accumulated lipids to leave the endosomes and reach the Golgi apparatus and endoplasmic reticulum.

Many premature infants have deficient pulmonary surfactant, which is required to reduce surface tension and prevent lungs from collapsing. A recent study may provide a new avenue for therapy by showing that vascular endothelial growth factor (VEGF) helps to regulate surfactant production. When given to premature mice near birth, VEGF can reduce symptoms of surfactant deficiency and relieve respiratory distress (pages 702–710).

Immunologists are just beginning to understand the early signals required to recruit memory T cells to sites of antigen-specific inflammation. Now it seems that activation of κ light chain–sensitized mast cells by antigen-specific recognition initiates local immune responses (pages 694–701).