Mass spectrometry screening of combinatorial mixtures, correlation of measured and predicted electrospray ionization spectra

Methodology was developed to afford rapid characterization of multicomponent mixtures of small organic molecules prepared by split-and-mix combinatorial synthesis. This methodology involved the use of liquid chromatography mass spectrometry (LC/MS) combined with correlation analysis of measured versus predicted electrospray ionization mass spectra. Low-resolution mass spectra of complex mixtures revealed predictable patterns that confirm library products, assisted in identifying chemical synthesis errors, and assessed overall library integrity. In general, equal signal intensities were observed for most combinatorial mixture components, indicating that differences in electrospray ionization efficiency was not a major limitation to this approach. High-throughput data processing programs and informatics tools were used to speed data analysis and to simplify the presentation of the library characterization results. This approach has been used to characterize combinatorial libraries that were synthesized for a variety of drug-discovery programs. Examples are shown for library formats of 1, 40, 66, 280, and 400 component(s)/well. The applicability of this approach to large combinatorial mixtures should allow direct characterization of massive combinatorial libraries.     

Effects of self-esteem manipulation on arousal and reactions to sad models in depressed and nondepressed college students.

24 depressed and 24 nondepressed college students were given spurious feedback, either positive or negative, about the results of personality tests. They then watched a film of an intensive encounter group. Psychophysiological reactions to both feedback and observation of sad film models were recorded. Depressed Ss showed greater arousal than nondepressed Ss only after negative feedback. Depressed Ss reacted emotionally to the sad models after negative feedback; nondepressed Ss, after positive feedback. Arousal results indicate that depressed Ss were particularly reactive to a "loss" of self-esteem. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Commentary.

Comments on the articles of J. J. Furedy (see record 199801996-002), O. E. Favreau (see record 199801996-003), C. Stark (see record 199801996-005), D. Kimura (see record 199801996-006), and K. S. Dobson (see record 199801996-007), on the multifaceted topics surrounding political correctness in academia, including academic freedom, and women's issues. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Food yeast growth on peanut protein waste liquors

Summary Peanut protein waste liquor supplemented only with an ammonium salt was found to be an excellent medium for the propagation of the food yeast,Torulopsis utilis, in batch and continuous processes. When nitrogen was provided to give a carbon/nitrogen ratio of 8/1, 100 grams of sugar yielded 48 grams of a high-protein yeast that was comparable in food value and vitamin content to food yeasts from other sources. One of the laboratories of the Bureau of Agricultural and Industrial Chemistry, Agricultural Research Administration, U. S. Department of Agriculture.     

The activation state of p38 mitogen-activated protein kinase determines the efficiency of ATP competition for pyridinylimidazole inhibitor binding

The serine/threonine kinase p38 is a ubiquitous, highly conserved, stress responsive, signal-transducing enzyme. It regulates the production of proinflammatory mediators and is the target of the cytokine synthesis inhibitory pyridinylimidazoles. We have expressed human p38 in Drosophila S2 cells and characterized preparations of mixed unphosphorylated/monophosphorylated (inactive) and homogeneously diphosphorylated (active) forms of the enzyme. We observed that only the active preparation of the enzyme has significant kinase activity when assayed using an ATF2-GST fusion protein as the substrate. We determined that the value of KM[ATP] in this reaction is 25 microM and that the pyridinylimidazole inhibitor of p38 kinase activity, SB203580, competes with ATP. We have found that a tritiated pyridinylimidazole, SB202190, has an equal affinity for both the active and inactive forms of the enzyme and that SB203580 competes with it equally well for binding to either form of the enzyme. However, ATP can compete with the tritiated inhibitor for binding to only the active form of the enzyme. Further, we demonstrate in vivo that at concentrations consistent with its IC50 as a cytokine inhibitor, SB203580 can inhibit stimulus-induced phosphorylation of p38 at the Thr-Gly-Tyr activation motif. Our observations suggest that pyridinylimidazoles may block the biological activity of p38 kinase by binding to the inactive form of p38 and reducing its rate of activation. Under these conditions, ATP would not effectively compete with the inhibitors in vivo.     

Evolving trends revealed by autopsies of patients with the acquired immunodeficiency syndrome. 565 autopsies in adults with the acquired immunodeficiency syndrome, Los Angeles, Calif, 1982-1993 [corrected

OBJECTIVE: To determine changes in causes of death, survival, and organ system distribution of major opportunistic infections and neoplasms in adults dying with the acquired immunodeficiency syndrome (AIDS) following the widespread use of antiretroviral therapy and prophylaxis for opportunistic infections since 1988. DESIGN: A retrospective review of autopsy records with gross and microscopic pathologic findings, laboratory data, and clinical histories in cases of AIDS, comparing findings from 1982 through 1988 with those from 1989 through May 1993. SETTING: All autopsies were performed on persons dying in the metropolitan Los Angeles, Calif, area from January 1982 through May 1993. RESULTS: In 565 adult cases of AIDS at autopsy, Pneumocystis carinii pneumonia (PCP) remained the most common cause of death, but both the frequency of and number of deaths of PCP declined over time. Deaths from bacterial sepsis, cytomegalovirus infection, Mycobacterium avium complex infection, and toxoplasmosis also declined during this period, but mortality from fungal infections, tuberculosis, encephalopathy, and causes unrelated to AIDS increased. The death rate from malignant lymphoma remained high. Kaposi's sarcoma (KS) continued to occur more frequently in patients whose risk factor for human immunodeficiency virus infection (HIV) was homosexuality or bisexuality, but the death rate from KS was greatest for patients with a risk factor of blood exposure to HIV. Survival was shorter and deaths from tuberculosis more common in patients with a history of intravenous drug use. Overall survival of patients in other AIDS risk groups increased over time, particularly in those treated with antiretroviral therapy. The organ system distribution of major opportunistic infections and neoplasms was similar throughout the years of the study. The lung was the most frequent organ involved by AIDS-associated diseases leading to death, followed by the gastrointestinal tract and the central nervous system. CONCLUSIONS: The causes of death in AIDS have evolved since 1988 following the widespread use of prophylactic and antiretroviral therapies in patients with HIV infection. This has occurred primarily from changes in overall frequency and death rates from infections. Organ system involvement by AIDS-associated diseases has not changed significantly over time.     

Retrorectal herniation of the sigmoid colon: report of a case

A rare retrorectal hernia of the sigmoid colon associated with diverticulitis and a presacral abscess is reported. The anatomy of the retrorectal space is reviewed. The value of routine lateral fluoroscopy and overhead films is emphasized.