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Biomedical subjects

M M Anderson

Publications and source records attributed to M M Anderson.

At least 55 records · Page 3Linked to original sources

Frequency of ultraviolet radiation-induced mutation at the hprt locus in repair-proficient murine fibroblasts transfected with the denV gene of bacteriophage T4.

The frequency of spontaneous and ultraviolet radiation (UVR)-induced mutation at the hprt locus was determined in control and denV-transfected, repair-proficient murine fibroblasts. Control cells removed an average of 25% of pyrimidine dimers induced by exposure to 150 J/m2 UVR from an FS40 sunlamp within 24 h; under the same conditions of induction and repair, denV-transfected cells removed an average of 71% of pyrimidine dimers. Control cells were somewhat more resistant than denV-transfected cells to killing by UVR. The average frequency of spontaneous mutation at the hprt locus for control and denV-transfected cells was 3 and 15 6-thioguanine (6-TG)-resistant colonies per 10(6) surviving cells, respectively; there was no statistically significant difference between control and denV-transfected cells. However, after exposure to 75 or 150 J/m2 UVR, denV-transfected cells had a significantly lower frequency of mutation to 6-TG resistance. After exposure to a fluence of 75 J/m2, the average frequency of UVR-induced mutation at the hprt locus was 166 mutant colonies per 10(6) surviving cells for control cells and 92 mutant colonies for denV-transfected cells; after 150 J/m2, control cells had 205 6-TG-resistant colonies per 10(6) cells, while denV-transfected cells had 61 mutant colonies. These results demonstrate that UVR-induced pyrimidine dimers are mutagenic photoproducts in mammalian cells.

Animals↗

Regulation of the cellular thymidine kinase gene promoter in simian virus 40-infected cells.

We examined the regulation of the cellular thymidine kinase (TK) gene promoter in simian virus 40 (SV40)-infected simian CV1 cells. Nuclear run-on transcription assays demonstrated a three- to fourfold increase in the rate of transcription of the endogenous gene at 14 to 16 h following viral infection. In addition, hybrid genes containing the human TK promoter linked to the bacterial neomycin resistance gene were induced by SV40 in stably transfected cells, indicating that promoter sequences are sufficient to confer viral regulation. Analysis of human TK promoter deletion mutants indicated that sequences localized between -67 and +30 bp relative to the transcriptional initiation site are sufficient to confer regulation on SV40-infected cells. These sequence elements are distinct from those required for serum induction, which were previously localized to the region between -135 and -67. These results suggest that SV40 activates novel cellular pathways that are not activated by serum stimulation of quiescent cells.

Animals↗

HIV and adolescents.

Human immunodeficiency virus has entered the adolescent population, and pediatricians will be caring for youngsters who are HIV positive or at risk of being infected. We should remember that it is risky sexual behavior and injection drug use that places a teen at risk for HIV infection, not their sexual orientation, ethnicity, or gender. Parents and their teenagers desire and expect their pediatricians to provide care and guidance for the diseases and problems that adolescents face. A screening psychosocial assessment of teenagers can identify those who need more in-depth counseling. Although the subjects of sex and drug use initially may be uncomfortable for a physician, practice using the HEADSS assessment will rapidly lead to comfort in discussing these important subjects. An understanding of HIV testing and pre- and post-test counseling will prepare the physician for the inevitable patient who wishes testing or who is HIV positive. Much of the treatment of HIV-positive adolescents involves patience and support while the adolescent grapples with the serious implications of being HIV positive. The initial history and physical exam establishes baselines regarding previous infections and illnesses that may bear on HIV infection, as well as determining which symptoms and signs of HIV infection are present. The initial laboratory tests further define the patient's current clinical state and will determine what therapies are immediately needed. Human immunodeficiency virus continues to evolve toward a manageable chronic illness that responds most favorably to early intervention.

Adolescent↗

A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The Optic Neuritis Study Group.

BACKGROUND AND METHODS: The use of corticosteroids to treat optic neuritis is controversial. At 15 clinical centers, we randomly assigned 457 patients with acute optic neuritis to receive oral prednisone (1 mg per kilogram of body weight per day) for 14 days; intravenous methylprednisolone (1 g per day) for 3 days, followed by oral prednisone (1 mg per kilogram per day) for 11 days; or oral placebo for 14 days. Visual function was assessed over a six-month follow-up period. RESULTS: Visual function recovered faster in the group receiving intravenous methylprednisolone than in the placebo group; this was particularly true for the reversal of visual-field defects (P = 0.0001). Although the differences between the groups decreased with time, at six months the group that received intravenous methylprednisolone still had slightly better visual fields (P = 0.054), contrast sensitivity (P = 0.026), and color vision (P = 0.033) but not better visual acuity (P = 0.66). The outcome in the oral-prednisone group did not differ from that in the placebo group. In addition, the rate of new episodes of optic neuritis in either eye was higher in the group receiving oral prednisone, but not the group receiving intravenous methylprednisolone, than in the placebo group (relative risk for oral prednisone vs. placebo, 1.79; 95 percent confidence interval, 1.08 to 2.95). CONCLUSIONS: Intravenous methylprednisolone followed by oral prednisone speeds the recovery of visual loss due to optic neuritis and results in slightly better vision at six months. Oral prednisone alone, as prescribed in this study, is an ineffective treatment and increases the risk of new episodes of optic neuritis.

Acute Disease↗

Isolation and characterization of bovine gingival proteoglycans versican and decorin.

1. We have isolated, chemically and immunologically characterized versican and decorin from bovine gingiva. 2. Versican was of large molecular weight and the molecular size of the core protein was estimated to be greater than 200 kDa. 3. The glycosaminoglycan chains were susceptible to chondroitinase ABC and N-linked oligosaccharides were present on the protein core of the molecule. 4. Immunological studies provided evidence that a hyaluronic acid binding region was present in the core protein of versican. 5. The overall structure was similar to that of versican isolated from bovine sclera. 6. Decorin had a molecular weight of 102 kDa and its glycosaminoglycan chain was completely digested by specific glycosidases. 7. The partially deglycosylated core protein had a molecular weight of 55 kDa and N-linked oligosaccharides were present on the molecule.

Amino Acids↗

Methods, statistical features, and baseline results of a standardized, multicentered ophthalmologic surgical trial: the Silicone Study.

This article describes the trial design and baseline results for the Silicone Study, a multicenter, randomized surgical trial designed to compare the effectiveness of silicone fluid versus long-acting gas in the treatment of proliferative vitreoretinopathy (PVR). Design features include (1) standardization of the surgical protocol to reduce intersurgeon variability, (2) formulation of a PVR clinical classification system relevant to modern vitreoretinal surgery, and (3) creation of a photographic protocol to document PVR pathology. Statistical issues affecting the analysis of the outcome data include (1) the addition of a second group of patients with more severely diseased eyes after the trial began, (2) the change to a different long-acting gas during the course of the trial, and (3) recurrent retinal detachments that require reoperations with the randomized treatment, and, in some instances, a crossover from the randomized to the alternate treatment. Demographic and baseline ocular characteristics are presented for the two groups under study.

Adult↗

In vitro cytotoxicity of a series of quassinoids from Brucea javanica fruits against KB cells.

A microdilution technique was developed for the assessment of in vitro cytotoxicity against KB cells derived from a human epidermoid carcinoma of the nasopharynx. The test was used to determine the cytotoxicity of a series of quassinoids, isolated from Brucea javanica, and which have previously been shown to demonstrate activity against Plasmodium falciparum. The 50% effective dose (ED50) for 7 quassinoids tested against KB ranged from 0.008 microgram/ml for bruceantin, the most cytotoxic of the compounds tested to greater than 5 micrograms/ml for bruceolide, the least toxic tested. The activities of the quassinoids against KB did not parallel the known activities of the quassinoids against Plasmodium falciparum suggesting that the quassinoid mode of antimalarial action is not a simple cytotoxic effect and lends support to further investigation of the structure activity relationships within this group of compounds.

Antimalarials↗

Plasmodium falciparum: effects of phaeanthine, a naturally-occurring bisbenzylisoquinoline alkaloid, on chloroquine-resistant and -sensitive parasites in vitro, and its influence on chloroquine activity.

Phaeanthine, a bisbenzylisoquinoline alkaloid which occurs naturally in Triclisia species, was extracted from Triclisia patens (Menispermaceae) obtained from Sierra Leone (West Africa). In vitro, phaeanthine was found to be twice as potent against a chloroquine-resistant Plasmodium falciparum strain (K1), as against a chloroquine-sensitive clone (T9-96), with 50% inhibitory concentrations of 365.85 (+/- 11.41) nM and 704.87 (+/- 81.48) nM respectively. At a sub-inhibitory concentration of 80.35 nM, chloroquine resistance was not reversed by phaeanthine. Isobolograms constructed from experiments with chloroquine/phaeanthine combinations showed antagonism in T9-96 and an additive effect in K1. In a 48-hour microtest, phaeanthine at antimalarial concentrations showed no cytotoxicity to mammalian (KB) cells in vitro.

Animals↗

Refractive changes from use of silicone oil in vitreous surgery.

When silicone oil fills the vitreous cavity of the phakic eye or the entire aphakic eye, the refractive correction can be expected to change by 5-9 diopters and sometimes as much as 14 diopters. Aphakic eyes become less hyperopic when filled with silicone oil, whereas phakic eyes become more hyperopic when the vitreous cavity is filled with silicone oil. Previously emmetropic aphakic eyes that are filled with silicone oil have only 4-6 diopters of hyperopia, whereas the same eyes have 10-12 diopters of hyperopia before insertion or after removal of silicone oil. Phakic eyes develop 5-7 diopters of hyperopia when the vitreous cavity is filled with silicone oil, and this puts them in the same range as the silicone oil filled aphakic eyes. High myopia, incomplete silicone oil filling, and several other factors influence the final optical outcome. The vitreoretinal surgeon must anticipate significant changes in refractive error when silicone is introduced into an eye or removed from the eye. Careful retinoscopy and refraction is essential for obtaining optimal vision in these patients.

Adult↗

Informal communication networks and change in physicians' practice behavior.

This study used influential physicians to disseminate information concerning the advantages of developing and using computer-stored personal order sets with a hospital information system. The results indicate that continuing medical education delivered through influential physicians is an effective way of changing physicians' practice behavior.

Communication↗

Physician utilization of computers in medical practice: policy implications based on a structural model.

The development of policies regarding computer-based medical technology is hampered by a lack of knowledge about the process by which such applications are adopted and utilized by physicians. This study was designed to test a model of the process by which physicians change their practice behavior by utilizing a computer-based hospital information system (HIS). A structural model was developed, estimated, and tested using data from 270 members of the medical staff of a 1160 bed, private teaching hospital. The overall model consists of a measurement model which assumes that the observed variables are generated by a smaller number of unobserved variables or factors; and a structural equation model that relates exogenous and endogenous variables. The model indicates that consultation with other physicians on a hospital service leads to greater exposure to potential computer applications resulting in less concern about the potential impact of computers on medical practice. Physicians who are more knowledgeable about computers are far more likely to tailor the system to their individual practice by developing their own personal order sets for use on the HIS. All of these factors result in increased use of the HIS by physicians. A number of policy implications related to the introduction of new computer-based technology into medical practice settings are discussed.

Attitude to Computers↗

Why doctors don't use computers: some empirical findings.

The attitudes of 148 medical students, 141 residents, and 644 practising physicians towards computer applications in medicine were studied. The results indicate that physicians recognize the potential of computers to improve patient care, but are concerned about the possibility of increased governmental and hospital control, threats to privacy, and legal and ethical problems. In general, all three groups are uncertain as to the potential effects of computers on their traditional professional role and on the organization of practice. Practising physicians, however, express more concern about these potential effects of computers than do medical students and residents. While attitudes appear to be somewhat independent of prior computer experience, they significantly affect the extent to which physicians use a computer-based hospital information system. This may be a major reason for the slow introduction of clinical computer systems.

Attitude of Health Personnel↗

Abnormal vaginal bleeding in adolescents.

The evaluation and management of abnormal vaginal bleeding should be tailored to the individual case. Pediatricians caring for adolescents need to be skilled in the evaluation and management of this common adolescent problem. Physicians who do not feel comfortable with their skills in the performance of a pelvic exam should obtain consultation from an adolescent specialist or a gynecologist who has experience with adolescents.

Blood Coagulation Disorders↗

Hepatic microsomal metabolism and macromolecular binding of the antioxidant, N-phenyl-2-naphthylamine.

1. The hepatic microsomal metabolism of N-phenyl-2-naphthylamine (P2NA), an industrial antioxidant and suspected carcinogen, was studied in seven mammalian species to determine if N-dephenylation, reported to occur in vivo, could be demonstrated in vitro and if macromolecular binding occurs without an obligatory N-dephenylation. 2. The rate of hepatic microsomal metabolism decreased in the order: hamster much greater than mouse greater than rat congruent to monkey congruent to dog greater than human congruent to pig. Metabolism was increased by pretreatment with 3-methycholanthrene or phenobarbital and decreased by carbon monoxide or 2-[2,4-dichloro-6-phenyl)phenoxy]-ethylamine, which indicated the involvement of cytochrome P-450 rather than the flavoprotein mixed-function oxidase. 3. All seven species produced two major metabolites identified as 6-hydroxy-P2NA and 4-'hydroxy-P2NA. The carcinogen 2-naphthylamine was not detected in the microsomal incubations. 4. Incubations in the presence of 18O2 indicated that the oxygen incorporated in the products came from molecular oxygen. 5. There was a time-dependent linear increase in covalent binding of P2NA to microsomal protein and the extent of binding approximately paralleled the rate of metabolism. Thus, macromolecular binding of this aromatic amine appears to occur without an obligatory N-dephenylation and may be due to the metabolic formation of epoxides.

2-Naphthylamine↗

Spherophakia: a case report.

A case of spherophakia with unilateral traumatic phacometecesis is presented and the treatment of the postextraction sequelae by contact-lens therapy is described.

Adolescent↗