Antibody-mediated specific binding and cytotoxicity of liposome-entrapped doxorubicin to lung cancer cells in vitro.

Liposome entrapment of doxorubicin has been shown to reduce its cardiotoxicity in vivo and increase its therapeutic index. A further improvement in therapeutic index could be achieved through targeting of liposome-entrapped drug selectively to cancer cells. Monoclonal antibodies against the squamous lung cancer cell line KLN-205 have been ligated to the surface of long-circulating (Stealth) and conventional liposomes. The antibody-bearing liposomes showed specific, competitive uptake by KLN-205 cells as compared to liposomes bearing nonspecific isotype-matched antibodies or antibody-free liposomes. Doxorubicin-containing antibody-liposomes resulted in as much as a 15-fold decrease in the 50% inhibitory concentration for doxorubicin against KLN-205 cells as compared to free doxorubicin or doxorubicin entrapped in antibody-free liposomes.     

Alterations in the superoxide dismutase gene of an isoniazid-resistant strain of Mycobacterium tuberculosis.

Genetic analysis of a set of six Mycobacterium tuberculosis strains differing in virulence for the guinea pig revealed an altered restriction enzyme fragmentation pattern associated with the superoxide dismutase (SOD) gene in a low-virulence, isoniazid-resistant strain. In addition, it was found that the SOD enzyme produced by the isoniazid-resistant strain differed in its electrophoretic mobility from the SOD of other M. tuberculosis strains. Detailed analysis of these strain-specific differences showed that the restriction fragment length polymorphism resulted from the presence of a copy of a repetitive element 552 bp upstream of the SOD gene and that the anomalous electrophoretic mobility arose from a single nucleotide change, resulting in replacement of an aspartic acid residue by histidine in the SOD enzyme of the isoniazid-resistant strain. Possible relationships between genetic changes and strain-dependent differences in virulence are discussed.     

Abraham Lincoln and the insanity plea

A confederate civilian physician shot and killed a white Union officer who was drilling Negro troops in Norfolk, Virginia. With no question as to guilt, President Abraham Lincoln decided to have a medical expert conduct a professional sanity/insanity examination. Documentation indicates that legal and political factors may have influenced Lincoln's decision. As a lawyer, Lincoln prosecuted a case where the insanity plea was used as a defense. Two influential Cabinet members, William H. Seward and Edwin M. Stanton, also had legal experience involving the insanity plea. Politically, Lincoln faced serious issues such as the draft riots, the military necessity to recruit slaves into the army, the impact of Union Negro soldiers upon the border states, the morale and discipline of the army and the upcoming presidential election. Upon Seward's recommendation, Lincoln chose a physician who had a reputation for finding the accused sane and who did so in this case. As the southern physician was hanged, Lincoln's means achieved the desired legal and political ends.Partial research support from a Continuing Faculty Development Award from the New York State/United University Professions Professional Development and Quality of Working Life Committee. Thanks to the following who rendered assistance: U.S. Senator Alfonse M. D'Amato; John C. Brennan, Laurel, MD; Ruth E. Cook, The Lincoln Museum; Cullom Davis, Lincoln Legal Papers; Dr. Norman B. Ferris, Middle Tennessee State University History Dept.; Stephen G. Hague, Abraham Lincoln Museum; Dr. Mary C. Gillet, Army Center of Military History; Elizabeth M. Gushee, Virginia Historical Society; Peggy A. Haile, Norfolk City Libraries; U.S. Senator Frank R. Lautenberg; Dr. Frank R. Millikan, Arlington, VA; Herbert Mitgang,New York Times; Dr. James C. Mohr, University of Oregon History Dept.; U.S. Representative Major R. Owens; Gary R. Planck, Literary Editor,Lincoln Herald; Debra Randorf, Interlibrary Loan, SUNY Health Science Center at Brooklyn; Thomas F. Schwartz, Lincoln Collection, Illinois State Historical Library; Dr. Thomas R. Turner, Editor,Lincoln Herald; Dr. Morris F. Weiner, Lincoln Memorial University.     

Massive strychnine intoxication: serial blood levels in a fatal case.

A fatal case of strychnine intoxication is reported. The patient expired despite early aggressive management and prevention of metabolic complications. Serial blood levels are reported. In contrast to a previous report describing first order elimination kinetics, our data suggest that strychnine follows Michaelis-Menton elimination kinetics. The case illustrates the rapid, dramatic course of severe strychnine ingestions. A review of the toxicokinetics, mechanism of action and treatment of strychnine intoxication follows.     

Medical complications of prematurity

The improved survival of extremely premature infants has generated intense interest in the quality of life of the survivors. This review focuses on the major long-term complications of prematurity (developmental disability, retinopathy of prematurity, chronic lung disease) and concludes with an overview of the broader spectrum of morbidity. Severe impairment (cerebral palsy, mental retardation, retrolental fibroplasia, severe chronic lung disease) fortunately occurs in a small proportion of survivors. However, the prevalence of the lesser morbidities (minimal cerebral dysfunction/learning disability, poor growth, postneonatal illnesses, rehospitalization) is less clearly defined. These problems all have an impact on families, and on medical and educational services.     

Monoclonal antibodies to intermediate filament proteins: Diagnostic specificity in orbital pathology

Intermediate filaments derived from different cell types are antigenically distinct. Monoclonal antibodies to human intermediate filament proteins can, therefore, be used as tissue-specific reagents capable of distinguishing cell type in poorly differentiated neoplasms. We report a case demonstrating the specificity of antiintermediate filament protein antibodies in establishing a difficult orbital diagnosis of esthesioneuroblastoma.