Search

"Viable motheaten" mice are severely immunodeficient and develop autoantibodies early in life. The thymus appears normal for the first 3-4 weeks, after which there is depletion of cortical thymocytes and a diminution in the size of the organ until it is atrophic. The present study utilized an in vitro migration assay, in which bone marrow cells from viable motheaten mice were found to have a greatly diminished capacity to migrate in response to normal thymus supernatant when compared to normal bone marrow cells. It was also determined that thymus supernatant prepared from newborn viable motheaten mice was chemoattractive to normal bone marrow but not to viable motheaten bone marrow. The results of in vivo reconstitution of lethally irradiated viable motheaten mice with normal bone marrow cells also show that the thymus of the mutant is normal in its ability to attract and be repopulated by normal donor bone marrow. Therefore, the premature thymic involution of viable motheaten mice is related to the inability of bone marrow cells from these mice to migrate or respond to signals from the thymus.

6,7-Dimethoxyphthalazine was obtained in four steps from veratric acid and converted to its Reissert compound. Alkylation of this Reissert compound with 3,4-dimethoxybenzyl chloride followed by hydrolysis gave 3-azapapaverine.

Publisher Summary This chapter reviews developments in the field of isatin from 1944 to late 1974. The most frequently used synthesis of isatins is the Sandmeyer procedure, which involves the formation of an isonitrosoacetanilide from an aniline, chloral hydrate, and hydroxylamine. The isonitrosoacetanilide is converted into the isatin on treatment with sulfuric acid, or less frequently polyphosphoric. The Sandmeyer method has been used with di- and trisubstituted aniline to prepare di- and tri-substituted isatins. Isatin sodium or potassium salts react with dimethyl and dieth sulfate, a variety of alkyl halides, acyl halides, and anhydrides to give N-alkyl and N-acylisatins. N-substitutcd isatins have also been prepared by reactions of some of the compounds that were described earlier. A number of reactions that do not reasonably fit in other categories are included in this chapter. A number of complexes of isatin and metal salts have been reported. Extensive studies have been reported on infrared vibrational frequency correlations of isatin and a variety of substituted isatin. A number of studies of the ultraviolet absorption spectra of isatins have appeared. The most frequently reported oxidation reaction of isatins is the oxidation with alkaline hydrogen peroxide to give anthranilic acids. This procedure has been both as a proof of structure of isatins and as a method of synthesis of anthranilic acids. A wide variety of substituted isatins has reacted with hydroxylamine to give isatin-3-oximes. The cyclizations of certain 2-substituted isatin derivatives were studied so as to compare them with the above cyclizations. The chapter closes with a discussion on polymers.

Substituted isatins were condensed with acetone and other ketones to give analogs of 3-hydroxy-3-acetonyloxindole. Some of these alcohols were dehydrated. Several compounds with anticonvulsant activity were obtained.

The General Instrument multibeam sonar system offers the scientific and hydrographic community a system for real-time charting in depths from 3-620 meters. The major advantage of the multibeam sonar system is complete swath coverage of the surveyed area, with the capability to overlay adjacent swaths for increased area coverage. General Instrument is presently in the initial stages of improving its shallow water mapping system by integrating the latest electronic hardware and software technology into an upgraded system design. The improved system will provide the user with greater flexibility in meeting their shallow water mapping needs.

A number of 3-alkyl-1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-2H-benzo[a]2-quinolizinones and 2-substituted 3-ethyl-1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-2H-benzo[a]quinolizines were prepared and submitted for antineoplastic and anticonvulsant screening.

Although the intensity increase of the 5.9 nm layer-line (5.9 L.L.) on activation can potentially be informative, systematic investigation is left to be done. The present study is aimed to assign the cause of the intensity increase. Using the synchrotron radiation, X-ray diffraction patterns were recorded from live sartorius or semitendinosus muscle of the frog (mostly at a temperature of 3-4 degrees C) either on the "Imaging Plates", a newly developed X-ray image recording system, or with the fast linear detector. The Imaging Plates enabled us to measure the disorientation of the thin filaments in the contracting muscle, so that the intensity profiles of the layer-lines were corrected for the disorientation. After the correction, a slight inward shift of the intensity peak of 5.9 L.L. was measured which is associated with the intensity increase on activation at 4 degrees C. At higher temperatures, 5.9 L.L. increases less. The extent of the intensity increase is linearly related to the sarcomere overlap, whereas the outer part of the 2nd actin layer-line (2nd L.L.) is as high as 60% at 10% overlap. The rise of the intensity of 5.9 L.L. is as fast as that of 2nd L.L., but much faster than the changes of the equatorial reflexions and the tension rise. Although these results do not let us assign the cause, some properties are elucidated of the structural change which causes the intensity increase.

A number of spiro[1,3-dioxolane-2,3'-indolin]-2'-ones were synthesized and tested for anticonvulsant activity in the maximal electroshock seizure (MES) and pentylenetetrazole seizure threshold (sc-Met) tests. 5'-Chlorospiro[1,3-dioxolane-2,3'-indolin]-2'-one was the most active compound in the MES test and had ED50 = 27.97 mg/kg. Structural analogues spiro[1,3-dioxane-2,3'-indolin]-2'-one, spiro[1,3-dithiolane-2,3'-indolin]-2'-one, spiro[indoline-3,2'-[1,3]-oxathiolan]-2-one, and 3,3-dimethoxyindolin-2-one were also evaluated for anticonvulsant activity. Almost all compounds submitted for screening exhibited the ability to protect mice against electrically and chemically induced seizures. The ED50 and TD50 values for some of the title compounds are reported. Anticonvulsant screenings were carried out through NINCDS, NIH.

Substituted isatins and substituted acetophenones were condensed to give analogs of 3-hydroxy-3-phenacyloxindole. These alcohols were dehydrated, and the alkene was reduced. None of the products had the level of anticonvulsant activity exhibited by the parent compound.

A number of spiro[indoline-3,2′-thiazolidine]-2,4′-diones have been prepared via the cyclocondensation of isatin-3-imines with α-mercaptoacids. 1-Benzyl-5′,5′-dimethylspiro[indoline-3,2′-thiazolidine]-2,4′-diones were prepared by simultaneously refluxing 1-benzylisatin, α-mercaptoisobutyric acid and various anilines in toluene. 3′-(4-Chlorophenyl)-5,5′-dimethylspiro[indoline-3,2′-thiazolidine]-2,4′-dione was active in the P388 and the L1210 leukemia screen tests. A number of analogs of the active spiro compound have been prepared and submitted for antileukemic screening. Anticonvulsant screening results of related compounds are also included.

A number of 3-alkyl-1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-2H-benzo[a]2-quinolizinones and 2-substituted 3-ethyl-1,3,4,6,7,11b-hexahydro-9,10-dimethoxy-2H-benzo[a]quinolizines were prepared and submitted for antineoplastic and anticonvulsant screening.

The title compounds have been prepared by the cyclocondensation of mercaptosuccinic acid with isatin-3-imines. The 1-benzyl derivatives have been synthesized by simultaneously reacting 1-benzylisatin, substituted anilines and mercaptosuccinic acid. The structure of the products has been confirmed by X-ray diffraction measurements.