Molecular genetic diagnosis of a primary central nervous system T cell lymphoma.

Primary central nervous system T cell lymphomas are rare tumors. Histologically, they may be indistinguishable from other entities like inflammatory processes. In such cases, molecular genetic verification of clonal T cell receptor (TCR) gene rearrangements is an indispensable diagnostic tool. Here we present a case where identification of TCR beta and gamma gene rearrangements by polymerase chain reaction was used to differentiate between a vasculitis and a primary CNS T cell lymphoma, which has profound consequences for therapy management and outcome.

Cerebroretinal vasculopathy mimicking a brain tumor: a case of a rare hereditary syndrome.

We report a 35-year-old man with hereditary cerebroretinal vasculopathy (CRV) characterized by retinal microvascular changes and a right frontal intracerebral mass lesion that suggested a brain tumor. Histopathologic analysis of the patient's brain lesion as well as reviewed specimens of the patient's mother, who had reportedly died of a brain tumor, showed no neoplasia but did show cerebral microvasculopathy. CRV should be considered as a differential diagnosis for patients with intracerebral mass lesions, retinal vascular changes, and a positive family history of "brain tumors."

Formation and functional importance of endothelium-derived relaxing factor (EDRF) and prostaglandins in the microcirculation.

Vasodilation mediated by endothelium-derived relaxing factor (EDRF) has been demonstrated in large conduit arteries in vitro. Experiments were undertaken to investigate whether EDRF can also be produced in the microcirculation and thus could participate in the regulation of peripheral resistance. In a first series of experiments we studied a peripheral vascular bed, the hindlimb of the rabbit. The right femoral artery of anaesthetized rabbits was cannulated and blood was supplied through a shunt from the carotid artery. Blood flow through the hindlimb was measured in the shunt. Systemic pressure was measured in the abdominal aorta. Vascular resistance in the hindlimb was calculated from the two parameters. The haemodynamic effects of endothelium-dependent and -independent vasodilators (infused into the shunt) were measured before and after selective treatment of the vascular bed with gossypol, an irreversible inhibitor of the production or release of EDRF. The endothelium-dependent vasodilators acetylcholine and substance P, and the endothelium-independent vasodilators prostaglandin E1 and glyceryl trinitrate induced dose-dependent decreases in vascular resistance. Gossypol almost abolished the effects of acetylcholine and substance P on vascular resistance, but had no significant effect on the responses to prostaglandin E1 and glyceryl trinitrate. Also the decrease in peripheral resistance produced by hydralazine was not affected by gossypol although in the same rabbits the response to acetylcholine was inhibited by more than 70%. In bioassay experiments the production of EDRF was measured from cultured human microvascular (omentum) and macrovascular (umbilical vein) endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Gossypol attenuates selectively the blood pressure lowering effect of endothelium-dependent vasodilators in the rabbit in vivo.

The in vivo blood pressure lowering effect of three vasodilators whose in vitro effects are endothelium-dependent (acetylcholine, substance P and adenosine triphosphate) was reduced by 40-60% after systemic treatment of the animals with gossypol. In vitro, gossypol is an inhibitor of the production and/or release of endothelium-derived relaxing factor. Systemically administered gossypol had no effect on blood pressure decreases produced by the endothelium-independent agents prostaglandin E1 (alprostadil) and glyceryl trinitrate. These results suggest that endothelium-mediated vasodilator mechanisms could participate in blood pressure regulation.

Endothelium-derived relaxing factor is likely to modulate the tone of resistance arteries in rabbit hindlimb in vivo.

Vasodilation mediated by endothelium-derived relaxing factor (EDRF) has been demonstrated in large conduit arteries in vitro. In the present study we investigated whether the EDRF mechanism is also present in resistance arteries of a peripheral vascular bed, namely the hindlimb of the rabbit. The right femoral artery of anesthetized rabbits was cannulated and blood was supplied through a shunt from the carotid artery. Femoral arterial blood flow and pressure were measured in the shunt. Systemic pressure was measured in the abdominal aorta. The hemodynamic effects of endothelium-dependent and -independent vasodilators (infused into the shunt) were measured before and after treatment of the vascular bed with gossypol or p-bromophenacyl bromide (p-BPB). Gossypol, a polyphenolic antioxidant, is a selective and irreversible inhibitor of the EDRF-mediated vasodilation in isolated arteries; p-BPB is an alkylating agent and also produces irreversible inhibition of endothelium-mediated relaxations in vitro. During inhibitor treatment the hindlimb was temporarily isolated from the blood circulation and perfused with a cell-free medium; the venous effluent was drained off so that only minimal amounts of inhibitor reached the systemic circulation. The endothelium-dependent vasodilators acetylcholine (ACh) and substance P, and the endothelium-independent vasodilators prostaglandin E1 (PGE1) and glyceryl trinitrate (GTN) induced concentration-dependent increases in femoral arterial flow (and decreases in vascular resistance). Gossypol treatment had no direct effect on systemic blood pressure or femoral arterial flow. However, after gossypol, the effects of ACh and substance P on vascular resistance were almost abolished, but there was no significant effect on the responses to PGE1 and GTN.(ABSTRACT TRUNCATED AT 250 WORDS)

Selective inhibition by gossypol of endothelium-dependent relaxations augments relaxations to glyceryl trinitrate in rabbit coeliac artery.

1 Acetylcholine, substance P, prostaglandin E1 and the nitrovasodilator glyceryl trinitrate induced concentration-dependent relaxations of endothelium-intact strips of rabbit coeliac artery precontracted with noradrenaline. 2 Endothelium-denuded strip preparations contracted to acetylcholine and showed no response to substance P. The relaxant response to prostaglandin E1 was unimpaired after removal of endothelium, whereas the response to glyceryl trinitrate was increased. 3 A 20 min exposure of endothelium-intact strips to gossypol, an irreversible inhibitor of the production and/or release of endothelium-derived relaxing factor, abolished vasodilatation in response to the endothelium-dependent agents acetylcholine and substance P, did not change relaxations to prostaglandin E1, but significantly enhanced relaxations in response to glyceryl trinitrate. 4 In view of the assumed common mechanism of action of endothelium-derived relaxing factor and nitrovasodilators, these results suggest an interference of the two active principles at the level of the vascular smooth muscle cell.