Publications

The ligand-gated ion channel, TRPV4, functions as a transducer of hypotonic stimuli in primary afferent nociceptive neurons and contributes to inflammatory and neuropathic pain. Hypertonic saline also stimulates primary afferent nociceptors and the injection of mild hypertonic saline (2-5%) is widely used as an experimental model of pain in humans. Therefore, we tested whether TRPV4 participates in the transduction of hypertonic stimuli. Intradermal injection of 2% (607 mOsm) or 10% (3,250 mOsm) saline solution in the hind paw of rats induced a concentration-dependent pain-related behavior, flinching. Sensitization with prostaglandin E(2) (PGE(2)) caused a 7-fold increase in the number of flinches induced by 2% saline but failed to increase those caused by 10% saline. Spinal administration of antisense oligodeoxynucleotides to TRPV4 caused a 46% decrease in the number of flinches induced by 2% saline, but there was no change in flinching induced by 10% saline. Similarly, only the nociceptive behavior caused by 2% saline was reduced in TRPV4(-/-) knockout mice. The TRPV4-mediated nociceptive behaviors induced by hyper- and hypotonic stimuli were dependent on Src tyrosine kinase. We suggest TRPV4 is a transducer in primary afferents that mediates nociceptive behavior induced by small increases or decreases in osmolarity. Such changes in osmolarity might contribute to pain in inflammatory and neuropathic states.

T cell immunoglobulin-domain and mucin-domain (TIM) proteins constitute a receptor family that was identified first on kidney and liver cells; recently it was also shown to be expressed on T cells. TIM-1 and -3 receptors denote different subsets of T cells and have distinct regulatory effects on T cell function. Ferritin is a spherical protein complex that is formed by 24 subunits of H- and L-ferritin. Ferritin stores iron atoms intracellularly, but it also circulates. H-ferritin, but not L-ferritin, shows saturable binding to subsets of human T and B cells, and its expression is increased in response to inflammation. We demonstrate that mouse TIM-2 is expressed on all splenic B cells, with increased levels on germinal center B cells. TIM-2 also is expressed in the liver, especially in bile duct epithelial cells, and in renal tubule cells. We further demonstrate that TIM-2 is a receptor for H-ferritin, but not for L-ferritin, and expression of TIM-2 permits the cellular uptake of H-ferritin into endosomes. This is the first identification of a receptor for ferritin and reveals a new role for TIM-2.

BACKGROUND

Ventricular assist devices (VADs) are approved for destination therapy because they improve survival in end-stage heart failure (HF). VADs are powered pneumatically or electrically. Pneumatic and electric left ventricular assist devices (LVADs) and biventricular assist devices (BiVADs) provide excellent hemodynamic support at rest, but differences in their effects on exercise tolerance are unclear. We sought to evaluate the effect of devices with varying operating parameters on exercise capacity.

METHODS

Exercise physiology data obtained during maximal exercise with on-line gas-exchange analysis were collected for 38 consecutive VAD-implanted HF patients referred for exercise testing.

RESULTS

Electric LVADs were implanted in 18 patients, and pneumatic LVADs in 10 patients. Percent of predicted peak exercise oxygen consumption (VO2%) was significantly greater in pneumatic LVAD patients (52.1 +/- 11.1% vs 38.2 +/- 11.3%, p < 0.05). The 10 patients implanted with a pneumatically powered LVAD were compared to 10 patients implanted with a pneumatically powered BiVAD. LVAD-supported patients had a higher VO2% (52.1 +/- 11.1% vs 36.5 +/- 17.7%, p < 0.05).

CONCLUSIONS

HF patients supported with a pneumatic LVAD appear to have better exercise tolerance than those receiving an electric LVAD. Patients on LVAD support have better exercise tolerance than BiVAD-supported patients. This highlights the importance of right ventricular function to exercise tolerance in HF patients, and may have implications for future VAD design.

BACKGROUND

Primary pulmonary lymphoma is a rare disease. The clinical characteristics, methods of treatment, and outcomes are not well elucidated.

METHODS

A retrospective review of primary pulmonary lymphoma cases at a single institution from 1990 to 2002 was performed.

RESULTS

Eighteen patients were included, with a mean follow-up of 2.9 years. Fourteen patients had mucosa-associated lymphoid tissue (MALT) lymphoma, 2 had large cell transformation of sheet cells in MALT lymphoma, and 1 each had Hodgkin's disease and follicular lymphoma. Computed tomography-guided biopsy was diagnostic in only two of eight attempts. Eleven patients had disease confined to the pulmonary parenchyma, and 7 had parenchymal disease as well as mediastinal lymphadenopathy. Treatment methods included observation only (n = 1), surgery only (n = 6), surgery plus chemotherapy (n = 8), surgery plus radiotherapy (n = 1), and surgery plus chemotherapy plus radiotherapy (n = 2). Kaplan-Meier estimate of median time to disease recurrence or death was 6 years. Only 1 patient died of disease-related causes. Patients who had bilateral disease were more likely to have recurrent disease or death (p = 0.03).

CONCLUSIONS

A wide range of treatments were used for patients with generally MALT lymphoma, resulting in good outcomes, and recurrent disease was well controlled.