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Biomedical subjects

M M Anderson

Publications and source records attributed to M M Anderson.

At least 37 records · Page 2Linked to original sources

Ki-1 anaplastic large cell lymphoma with a prominent leukemic phase.

Patients with Ki-1 (CD30)-positive anaplastic large cell lymphoma (ALCL) occasionally have rare circulating lymphoma cells. We report a case of ALCL with a prominent leukemic phase. A 36-year-old man presented with widespread ALCL involving lymph nodes, spleen, pleural fluid, cerebrospinal fluid, and bone marrow. His white blood cell count was 106,000/mm3 with 20% lymphoma cells. The circulating neoplastic cells were large, and had irregular nuclei with multiple small nucleoli, ample cytoplasm, and multiple clear cytoplasmic vacuoles. This case illustrates that ALCL may have a marked leukemic phase composed of large anaplastic cells.

Adult↗

Remote clinic/patient monitoring for multicenter trials. Optic Neuritis Study Group.

Clinic monitoring is essential for the quality control of multicenter clinical trials. In studies of eye diseases, certification of visual function testers is integral to such monitoring. Routine site visits, while useful for evaluating clinic performance and certifying visual function testers, are expensive and not suitable for every study. As part of the Longitudinal Optic Neuritis Study (LONS), a follow-up study of the patients entered into the Optic Neuritis Treatment Trial (ONTT), we established a central system for clinic monitoring and visual function tester certification in lieu of performing site visits. We also established a centralized and well-defined system for maintaining patient contact in an attempt to enhance follow-up visit compliance. Both have been used over the first three years of the LONS. Coordinators at two of the participating clinical centers were selected to serve as regional coordinators; each was responsible for overseeing seven or eight clinics and 200 patients. Annually by phone these coordinators perform certification of each technician's visual function testing. Clinic monitoring is performed by monthly phone calls. Conference calls involving each clinic's personnel, the regional coordinator, and Data Coordinating Center personnel are held one or two times per year. Patient phone contact at four-month intervals between annual patient exams is done to evaluate visual and general health status, to review study information, and to coordinate and encourage annual protocol exams at the respective centers. This system has helped achieve a visit completion rate of over 90% for active study patients. Patient phone contact by the regional coordinators has been well received. Telephone certification of visual function technicians by the regional coordinators appears to be as effective as on-site certification. Clinic performance appears to be continuing at the same high level as during the period of annual site visits. Although site visits are valuable for clinical trials, if routine site visits are not feasible the methods we have implemented for remote monitoring may be useful.

Appointments and Schedules↗

Risk-taking behavior among Native American adolescents in Minnesota public schools: comparisons with black and white adolescents.

OBJECTIVES: To examine rates of risk-taking behavior among native American adolescents in comparison with blacks and whites, and then to compare our off-reservation native American sample to available national statistics on reservation youth. METHODS: A secondary data analysis of a Minnesota public school health survey. Contingency table analyses were performed on a 10% random sample of over 6000 young people focussing on three categories of behavioral risk: antisocial behavior, sexual behavior and substance use. Comparisons were then made to a national convenience sample from reservations and adjacent rural areas. RESULTS: In general, native American adolescents have a significantly higher prevalence of risk behaviors across all indices of antisocial behavior and substance use relative to white and black peers. Native American females presented the most troubling picture. Comparisons to a national convenience sample from reservation lands indicated that native American adolescents in the sample often exceeded national rates of risk behavior. CONCLUSIONS: Residence and attendance at public schools outside reservation lands may make native American adolescents more likely to engage in risky behaviors which endanger their health.

Adolescent↗

Activation of the human thymidine kinase (TK) promoter by simian virus 40 large T antigen requires both the T antigen pRb family-binding domain and TK promoter sequences resembling E2F-binding sites.

Infection of quiescent cells with the DNA tumor virus simian virus 40 induces expression of the cellular thymidine kinase (TK) gene a minimum of 10- to 20-fold, and this induction depends upon the viral protein large T antigen (T-Ag). To define both human TK promoter elements and T-Ag functional domains required for transcriptional induction, we have established a system in which stable Rat-1 transfectants harboring TK promoter-luciferase hybrid genes are infected with recombinant adenoviruses expressing either wild-type or mutant forms of T-Ag and luciferase expression is measured as an indicator of promoter activity. The results show that (i) a 135-bp TK promoter fragment is activated 10- to 15-fold by viral infection; (ii) this activation is the result of both T-Ag-dependent and -independent mechanisms; (iii) the T-Ag pRb family-binding domain, but not the p53-binding, helicase, or ATPase domain, is required for activation; and (iv) activation is severely diminished with a TK promoter fragment in which E2F-like-binding sites have been removed. These data demonstrate a requirement for both an E2F-related factor and a pRb family member in activation of the TK promoter by T-Ag. This contrasts with the promiscuous activation of many cellular and viral genes by T-Ag, which is independent of its ability to bind pRb.

Animals↗

Molecular basis of human mitochondrial very-long-chain acyl-CoA dehydrogenase deficiency causing cardiomyopathy and sudden death in childhood.

beta-Oxidation of long-chain fatty acids provides the major source of energy in the heart. Defects in enzymes of the beta-oxidation pathway cause sudden, unexplained death in childhood, acute hepatic encephalopathy or liver failure, skeletal myopathy, and cardiomyopathy. Very-long-chain acyl-CoA dehydrogenase [VLCAD; very-long-chain-acyl-CoA:(acceptor) 2,3-oxidoreductase, EC 1.3.99.13] catalyzes the first step in beta-oxidation. We have isolated the human VLCAD cDNA and gene and determined the complete nucleotide sequences. Polymerase chain reaction amplification of VLCAD mRNA and genomic exons defined the molecular defects in two patients with VLCAD deficiency who presented with unexplained cardiac arrest and cardiomyopathy. In one, a homozygous mutation in the consensus dinucleotide of the donor splice site (g+1-->a) was associated with universal skipping of the prior exon (exon 11). The second patient was a compound heterozygote, with a missense mutation, C1837-->T, changing the arginine at residue 613 to tryptophan on one allele and a single base deletion at the intron-exon 6 boundary as the second mutation. This initial delineation of human mutations in VLCAD suggests that VLCAD deficiency reduces myocardial fatty acid beta-oxidation and energy production and is associated with cardiomyopathy and sudden death in childhood.

Acyl-CoA Dehydrogenase, Long-Chain↗

Studying the effect of clinical uncertainty on physicians' decision-making using ILIAD.

The influence of uncertainty on physicians' practice behavior is not well understood. In this research, ILIAD, a diagnostic expert system, has been used to study physicians' responses to uncertainty and how their responses affected clinical performance. The simulation mode of ILIAD was used to standardize the presentation and scoring of two cases to 46 residents in emergency medicine, internal medicine, family practice and transitional medicine at Methodist Hospital of Indiana. A questionnaire was used to collect additional data on how physicians respond to clinical uncertainty. A structural equation model was developed, estimated, and tested. The results indicate that stress that physicians experience in dealing with clinical uncertainty has a negative effect on their clinical performance. Moreover, the way that physicians respond to uncertainty has positive and negative effects on their performance. Open discussions with patients about clinical decisions and the use of practice guidelines improves performance. However, when the physician's clinical decisions are influenced by patient demands or their peers, their performance scores decline.

Clinical Competence↗

In vitro antiplasmodial, antiamoebic, and cytotoxic activities of a series of bisbenzylisoquinoline alkaloids.

Twenty-four bisbenzylisoquinoline alkaloids were screened for antiplasmoidal, antiamoebic, and cytotoxic activities by use of in vitro microtests. Eight of the alkaloids had antiplasmodial activity, with a 50% inhibitory concentration (IC50) of less than 1 microM against a multidrug-resistant strain of Plasmodium falciparum (chloroquine had an IC50 of 0.2 microM). The three alkaloids most active against Entamoeba histolytica, aromoline, isotrilobine, and insularine, had IC50s of 5 to 11.1 microM (metronidazole had an IC50 of 1.87 microM). None of the 24 bisbenzylisoquinoline alkaloids exhibited significant cytotoxicity against the KB cell line, the most toxic being berbamine, with an IC50 of 17.8 microM (the IC50 of podophyllotoxin was 0.008 microM). Bisbenzylisoquinoline alkaloids merit further investigation as potential novel antimalarial agents.

Alkaloids↗

NMR lipid profiles of cells, tissues, and body fluids: proton NMR analysis of human erythrocyte lipids.

One- and two-dimensional high resolution NMR spectroscopy was applied to determine quantitatively and qualitatively the lipids extracted from human erythrocyte membranes. The relative amounts of the major lipids were determined from the spectra of unfractionated lipid extracts. After HPLC fractionation of the lipid extracts and NMR analysis of the fractions, it was possible to determine the features of the component lipids of each lipid class and to compare, especially, the fatty acid types and composition of the individual major glycerophospholipids. The results of this proton NMR analysis were compared to those obtained elsewhere using classical lipid analytical techniques and found to be in substantial agreement.

Cholesterol↗

Proton NMR lipid profile of Leishmania donovani promastigotes.

The proton nuclear magnetic resonance (NMR) lipid profile of Leishmania donovani was obtained in the one-dimensional and two-dimensional modes. Partial assignments of lipid classes and individual lipids were obtained purely from the proton NMR spectrum of the mixture. A more complete assignment and quantitative analysis was achieved by prior separation of the lipids by high pressure liquid chromatography (HPLC) followed by proton NMR analysis of the fractions. This work showed that proton NMR spectroscopy could facilitate lipid analysis and classification of various parasitic protozoa and serve as a basis for rapid studies of comparative lipid metabolism in parasites.

Animals↗

Design, methods, and conduct of the Optic Neuritis Treatment Trial.

The Optic Neuritis Treatment Trial (ONTT) was an investigator-initiated, multi-centered, randomized, controlled clinical trial supported by cooperative agreements and grants. It was designed to evaluate the efficacy and safety of oral prednisone or intravenous methylprednisolone followed by oral prednisone as compared with oral placebo. The primary outcome measures were contrast sensitivity and visual field; secondary measures were visual acuity and color vision. Four hundred fifty-seven patients were followed for a minimum of 6 months and a maximum of 3 years. This article describes the design and the methods used to implement the ONTT.

Adolescent↗

A microwell cytotoxicity assay using Artemia salina (brine shrimp).

A new microplate assay for cytotoxicity testing using A. salina has been developed and shown to give results comparable to a previously published test-tube method. The assay reliably detected all of the compounds toxic to KB cells in a series of 21 pharmacologically active agents, except for two which require metabolic activation in man. Four quassinoids with cytotoxic and antiplasmodial activity were also toxic to the brine shrimp while quassin itself was inactive in all three systems. It is proposed that this assay provides a convenient means by which the presence of cytotoxic quassinoids may be detected during the fractionation of plant extracts.

Animals↗