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Dilantin (phenytoin) is a commonly used antiepileptic agent that is known to decrease conductance of sodium and calcium ions and delay outward potassium currents. Separate from its antiseizure activity, dilantin interferes with microtubule protein polymerization. It induces metaphase arrest and potentiates the effects of the antimitotics vincristine and vinblastine in cell culture. We show here by fluorescence binding studies that dilantin interacts directly with tubulin at a low affinity site [Ka = 3.5 (+/- 2.5) x 10(3) M(-1); Kd = 286 microM]. We quantitatively examined the effect of dilantin on bulk microtubule formation and found that the drug raises the critical concentration for microtubule polymerization in 2 M glycerol identically in the presence or absence of vinblastine. The change in free energy for microtubule polymerization attributable to 400 microM dilantin [deltadelta G = 117 (+/- 28) cal/mol] is additive with vinblastine effects. Under the same conditions, mean microtubule lengths are 7.7 +/- 4.3 microm (n = 558) and 7.4 +/- 4.0 microm (n = 477) in the presence or absence of dilantin, respectively. Dilantin has no effect on vinblastine-induced tubulin spiral formation, as measured by sedimentation velocity. Our data suggest that the mechanism for the antimicrotubule effects of dilantin involves sequestration of tubulin heterodimers in 1:1 drug:tubulin complexes that do not participate in tubulin polymerization. The dilantin binding site is distinct from the Vinca binding site, and these independent binding modes account for the additive effects in vitro. The sequestration of tubulin heterodimers could explain the combined drug synergy in cell cultures if it disrupted interactions with proteins that regulate microtubule dynamics and/or cell cycle events.

We present a comparison of the energetics of spiral formation for two vinca alkaloids: a novel difluorinated vinorelbine derivative 20',20'-difluoro-3',4'-dihydrovinorelbine (F12158, or vinflunine) and the parent compound, vinorelbine. Vinca alkaloids are antineoplastic agents that halt cell division at metaphase by inhibiting microtubule assembly and inducing tubulin self-association into spiral aggregates. The overall affinities for tubulin of vincristine, vinblastine, and vinorelbine seem to correlate with their clinical doses, where vincristine with the highest overall affinity is used at the lowest doses. Doses of chemotherapeutic agents, however, also are determined by toxicities. In the physicochemical study described here, we used sedimentation velocity to compare vinorelbine- and vinflunine-induced self-association of porcine brain tubulin in the presence of 50 micro M GDP or 50 micro M GTP. Vinflunine demonstrates 3-16-fold lower overall affinity for tubulin and induces smaller polymers compared with vinorelbine. Sedimentation velocity provides the only direct evidence to date that vinflunine is a tubulin-binding drug. Stopped-flow light scattering demonstrates the shortest relaxation times for polymer redistribution for vinflunine consistent with induction of the shortest spirals. Data collected at 5 degrees, 15 degrees, 25 degrees, and 37 degrees show increasing 20,w values with increasing temperature and are consistent with an entropically driven process. These data are entirely consistent with our hypothesis that vinflunine is likely to result in reduced clinical neurotoxicity relative to vinorelbine, vinblastine, and vincristine.

The life history of Epicauta lemniscata Fab. (order Coleoptera, family Meloidae) is given for southern Louisiana.

In experiments conducted in Southwestern Louisiana for the control of blister beetles on soybeans, calcium arsenate and Paris green were tried both as dusts and sprays with and without lime. These acted as repellents, giving no control. Dusting with sodium cyanide gave a very small percentage of control. Various contact insecticides were tried without success. Attraction to artificial light was small. In June 1925 applications of sodium fluosilicate (analyzed as sodium fluosilicate 97.90 to 98.10 by Bureau of Chemistry, U. S. D. A.) applied at the rate of 15 pounds per acre gave practically 100 per cent control. A mixture of equal parts by volume of sodium fluosilicate and hydrated lime gave practically the same results but did not kill so quickly as undiluted sodium fluosilicate.

Sugarcane is injured by the gnawing of the adult ( Euetheola rugiceps Lec.) into the underground stem of the young plant. Observations show that the number of sugarcane beetles in different places around a plantation varied from zero in woodlands to more than 100,000 per acre in pasture. Owing to the much greater number of early cane shoots produced by planting sugarcane in the summer rather than in the fall, the former practice affords a much better chance than the latter of producing a crop in the areas where the beetle is a serious problem.

The thirty-second annual meeting of the Cotton States Branch, E.H.A., was held in the Hotel Peabody, Memphis, Tennessee, on December 2, 3, 4, and 5, 1957. The meeting was heldin conjunction with the parent association of the Entomological Society of America. One hundred twenty-eight members and guests registered for the four-day meeting. Chairman Norman Allen opened the first of two branch business meetings promptly at 4:30 P.M. on December 2.

A survey of the sugar-cane fields of Louisiana showed the number of soil animals and root injury to be greatest on heavy soils. The most numerous of the injurious species in sugar-cane fields was Hanseniella unguiculata Bagnall, with Onychiurus armatus Tull., Japyx sp., Lepidocyrtus violentus Fols., and Zonitoides arboreus Say following in the order named. After extermination of soil animals normal numbers were reached again in two years.

Several insecticides were applied in a band along the drill at corn-planting time or soon after plants emerged for the control of the sugarcane beetle, Euetheola rugiceps (Lee.), in Mississippi. Aldrin and heptachlor granules and sprays at 1 pound per acre were the most effective and gave about equal control. Dieldrin was as effective as aldrin in a spray, but not in granules. Thiodan, Thimet, Guthion, Chlorthion, and Sevin were ineffective at the dosages used.

The current study was carried out to examine the possible relationships among personality/behavioral characteristics and anterior/posterior (A/P) functional cerebral asymmetry in children referred for learning problems. Two hundred nineteen children between 7 and 12 years of age were administered a battery of neuropsychological measures, and their parents completed the Child Behavior Checklist (CBC) and the Personality Inventory for Children-Revised (PIC). Anterior and posterior composite scores were obtained for each subject using scores on the neuropsychological measures. Out of this subject pool, 33 children had sufficient anterior/posterior (A/P) score differences (i.e., greater than one standard deviation difference) to permit their categorization into either an A (n = 19) or P (n = 14) group. The MANOVA results showed that the A group scored significantly higher than the P group on the CBC scales of social withdrawal, aggressiveness, hyperactivity and externalizing, while the P group scored higher, though not significantly, on the (PIC) scale of anxiety. Thus, it appeared that, by using neuropsychological measures along the A/P dimension to classify children with learning problems, significant differences could also be identified on personality/ behavioral variables for some children. In addition, in the current study, children with A type functional cerebral asymmetry exhibited a relatively greater number of behavioral problems.

Spectral irradiance in the near U.V. was measured for several welding operations at a large steel fabrication shop. The variations of spectral irradiance with time were measured and a brief study of the effects of amperage welding rod, and distance was performed. At the measurement distance used in this study the proposed standard for near U.V. was not exceeded.

The newly discovered injury to sugarcane by a small weevil, Anacentrus sp., is described. The character of damage is the destruction of the eyes of sugarcane and also killing of the young plants.

The case in question was that of a young man, aged 27, who, while employed as a railroad brakeman, was injured Nov. 6, 1906, by a collision of the locomotive, on which he was riding, with a carload of logs. I saw the patient Dec. 4, 1906, twenty-eight days after the injury was received. During this time the patient had been treated by the company physician, with occasional consultations with the family physician. He had been told that an amputation of the leg would be the only procedure. This was asked for by his physicians on several different occasions, but was refused by both the patient's father and the patient himself. After a careful examination I found that a compound comminuted fracture of both bones existed at about the junction of the lower with the middle third of the leg. The communication on the external side was from two and

Case 1. —Colored child, aged 7; previous history negative. History. —The child had been sick for three weeks when I was called. The father stated that the child had been treated for typhoid fever during the entire time, but without any appreciable change for the better. The history was misleading in many respects. The child complained of nausea, slight headache, loss of appetite, abdominal tenderness, pain through the small of the back, as the father put it, constipation, frequent and painful micturition. The temperature was less than 100 F., pulse was somewhat accelerated. The general appearance was that of one who had suffered long and patiently. Examination. —I suggested to the mother that a more thorough examination of the child be made, to which she readily consented. In the outward appearance of the vulva there was nothing to attract special attention, except that the tissues were slightly inflamed; on pressure