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Three independent autopsy samples of brains without apparent neuropathology were studied to ascertain whether there was sexual dimorphism in the human corpus callosum (CC). Using planimetric measurements on midsagittal brain sections, several morphometric features of the CC were studied: total callosal area, maximum dorsoventral splenial width, the posterior one fifth of the total area of the CC (mostly splenium), and brain weight. Ratio data correcting for brain size were also studied. In all samples, absolute brain size was larger in males, and significantly so. Measurements of splenial dorsoventral width were higher in females than males, but not significantly, except in the Australian sample. Total callosal area was absolutely higher in the Australian female sample than in males, and almost equal in the two American samples, without statistically significant differences. The posterior one-fifth area (splenium) was larger for females in each of the samples. The variables which were corrected for brain size were usually significantly larger in females, although this pattern varied in each sample. The statistical pattern of sexual dimorphism for the human CC differs from that found in most other neural structures, such as the amygdaloid nucleus, cerebellum, hippocampus, and thalamus. The absolute sizes of these structures are always significantly larger in males. When corrected for brain size, the relative sizes are not significantly larger. The CC is the only structure to show a larger set of relative measures in females.

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3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase catalyzes the formation of mevalonate, an essential precursor for isoprenoid compounds in mammalian cells. Recent studies have shown that mevinolin, a competitive inhibitor of the reductase, inhibits cell proliferation and induces differentiation in cultured C1300 (Neuro-2A) murine neuroblastoma cells. We now report that mevinolin can inhibit neuroblastoma growth in vivo. The specific activity of HMG-CoA reductase in subcutaneous neuroblastomas increased more than 20-fold between the fifth and eighth days after tumor inoculation, and remained elevated for the remainder of the tumor lifetime in mice. The increase in reductase activity was correlated with a marked increase in tumor DNA content and exponential increase in tumor weight. Using an in vitro assay to monitor the ability of mouse serum to suppress sterol synthesis, we determined that mevinolin was inactivated or cleared from the circulation within 3-6 h after a single subcutaneous injection. However, by using subcutaneous osmotic pumps to deliver a constant infusion of mevinolin, we were able to maintain adequate blood levels of the drug for 7 d. Mevinolin (5 mg/kg per h) suppressed tumor growth (wet weight) significantly when treatment was carried out between day 1 and day 8 or between day 5 and day 12 after tumor inoculation. Histopathological examination of tumors from mevinolin-treated mice revealed few or no mitotic figures and marked cellular degeneration. Measurements of incorporation of (3H)acetate into neuroblastoma sterols and ubiquinones 24 h after implantation of osmotic pumps showed that mevinolin produced a marked inhibition of isoprenoid synthesis in the tumors in vivo. The data suggest that, in addition to their demonstrated utility as cholesterol-lowering drugs, competitive inhibitors of HMG-CoA reductase may have considerable potential as novel antineoplastic agents.

By use of the indirect peroxidase-antiperoxidase complex immunocytochemical technique, antibody to purified human renal renin was applied to formalin-fixed paraffin sections of human cadaver brain. Immune reaction products were observed in most nerve cells in all areas of the ran examined; staining was limited to the soma and proximal dendrites. These experiments have confirmed the presence of a renin-like substance in central nervous tissue and suggest a more generalized function for "brain renin" than was previously anticipated.Controversy regarding the existence of a functional brain renin-angiotensin system prompted this investigation. Reninlike enzymatic activity has been demonstrated in low concentration in brain homogenates (1-3), and isolation of each of the components of the renin-angiotensin system from brain (4) suggested that the system might be functional there. Inability to distinguish renin enzymatic activity from that of cathepsin D, however, has generated much confusion (5-7). Hirose et al. (8) MATERIALS AND METHODS Human renal renin was purified by published methods, except that affinity chromatography was used as the final (seventh) step with purified immunoglobulin fraction of antisera raised against pure renin as the ligand (9). The product of elution represented a 500,000-fold purification and had a final specific activity of 1000 Goldblatt units/mg of protein. No contaminant bands were seen on NaDodSO4/polyacrylamide or polyacrylamide disc-gel electrophoresis. The potency of immune rabbit antisera was determined by inhibition of the enzymatic activity of 0.5 X 10-4 Goldblatt unit of Haas human renal renin standard (no. 216, gift of Erwin Haas) compared to autologous preimmune serum and expressed as the dilution producing 50% inhibition-1:20,000 dilution for the antisera used in these experiments. Antibody diffusion in Ouchterlony plates (36 hr at room temperature) produced single precipitation lines with smooth fusion against pure (step 7) or partially pure (steps 6 and 5) renin. There was no precipitation with bovine spleen ca-

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