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The length of survival of 149 patients harboring primary brain tumors was retrospectively correlated with the presence and location of lymphocytic infiltration. Mononuclear invasion of malignant gliomas confined to the perivascular spaces was the only histolgical finding that correlated significantly with survival. Patients with malignant gliomas containing perivascular infiltration live up to four months longer than those with no lymphocyte infiltration. The survival of patients with brain tumors who had lymphocyte invasion associated with areas of hemorrhage and necrosis beyond and separate from perivascular spaces was the same as far as for those with no lymphocyte involvement.

Calpain, a calcium-activated cysteine protease, is involved in modulating a variety of cell activities such as shape change, mobility, and apoptosis. The two ubiquitous isoforms of this protease, calpain I and II, are considered to be cytosolic proteins that can translocate to various sites in the cell. The activity of calpain is modulated by two regulatory proteins, calpastatin, the specific endogenous inhibitor of calpain, and the 28-kDa regulatory subunit. Using velocity gradient centrifugation, the results of this study confirm and greatly expand upon our previous finding that the calpain/calpastatin network is associated with the endoplasmic reticulum and Golgi apparatus in cells. Moreover, confocal microscopy demonstrates that calpain II colocalizes with specific proteins found in these organelles. Additional experiments reveal that hydrophobic rather than electrostatic interactions are responsible for the association of the calpain/calpastatin network with these organelles. Treatment of the organelles with Na 2 CO 3 or deoxycholate reveal that calpain I, 78-kDa calpain II, and the regulatory subunit are "embedded" within the organelle membranes similar to integral membrane proteins. Proteinase K treatment of the organelles shows that calpain I and II, calpastatin, and the regulatory subunit localize to the cytosolic surface of the organelle membranes, and a subset of calpain II and the regulatory subunit are also found within the lumen of these organelles. These results provide a new and novel explanation for how the calpain/calpastatin network is organized in the cell. Calpain (Cp)1 is a Ca 2ϩ -dependent neutral cysteine protease (1). The major isoforms of Cp, Cp I and Cp II, are heterodimers composed of an 80-kDa catalytic subunit and an identical 28-kDa regulatory subunit (Rs). The Cp I and Cp II isoforms differ not only in the amino acid sequence of the catalytic subunits but in their in vitro Ca 2ϩ requirements for activation. Thus, Cp I (-calpain) requires 3-50 M Ca 2ϩ , whereas 0.2-1.0 mM of Ca 2ϩ is required for activation of Cp II (m-calpain) (2-4). In general, these concentrations of Ca 2ϩ are far greater than can be achieved intracellularly (Ͻ1 M) (5), suggesting that additional factors, such as binding to phospholipids (6, 7) or activation proteins (8, 9), are required for in vivo activation of both isoforms. The specific endogenous inhibitor of Cp I and Cp II is calpastatin (Cs).The Cp/Cs network is ubiquitously expressed in all vertebrate cells (10 -12) and is involved in a number of important cellular processes, including cell adherence, shape change, migration, and apoptosis (13). Activation of Cp during these processes requires increases in intracellular calcium ([Ca 2ϩ ] i ) as a consequence of receptor-ligand binding or the addition of Ca 2ϩ ionophores (14 -20). These increases in [Ca 2ϩ ] i also induce translocation of Cp from the cytosol to the plasma membrane (PM) and focal adhesions, contacts, or clusters (3, 21-25), where it facilitates reorganization of the actin cytoskeleton...