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Biomedical subjects

M E Johnson

Publications and source records attributed to M E Johnson.

At least 91 records · Page 5Linked to original sources
PubMed1996

Assessing reading level of drug users for HIV and AIDS prevention purposes.

Using the short form of the Woodcock Reading Mastery Test-Revised and the reading subtest of the Wide Range Achievement Test-Revised, the reading abilities of 284 male and 128 female drug users from five sites across the United States were evaluated. All subjects were participants in a National Institute on Drug Abuse HIV/AIDS prevention project aimed at intravenous drug users and cocaine smokers. Results revealed differences in reading abilities among ethnic groups with Native and white subjects having significantly higher reading levels than Hispanic and black subjects. Significant site differences were revealed, with mean grade equivalent scores ranging from 2.7 to 10.1 grades. Across all subjects, the average grade equivalent reading level was 5.8 to 7.7, indicating that the subjects read below the level of 81.5% to 93% of the general population. We provide implications for development of educational materials that are accessible for this population.

Adult↗
PubMed1995

Proposed cation-pi mediated binding by factor Xa: a novel enzymatic mechanism for molecular recognition.

Factor Xa (FXa) is an important serine protease in the blood coagulation cascade. Small synthetic competitive inhibitors of FXa are under development as potential anticoagulants. To better understand FXa structural features and molecular recognition mechanisms, we have constructed three dimensional models of FXa-inhibitor complex structures via a new search approach that samples conformational space and binding space simultaneously for DABE and DX-9065a, two bis amidinoaryl derivatives that are among the most potent and selective FXa inhibitors reported to date. We find the most probable binding modes for the two inhibitors to be a folded conformation, with one distal amidino group extending into the S1 pocket, forming a salt-bridge with FXa Asp-189, and the other positively charged group fitting into the S4 subsite, and stabilized by a cation-pi interaction. We propose as a hypothesis that the cavity-like S4 subsite formed by the three pi-faces of the aromatic residues Tyr-99, Phe-174 and Trp-215 is sufficiently rich in pi electrons that it is not only a hydrophobic pocket, but also forms a cation recognition site. This proposed cation-pi binding mechanism is one of the first proposed for enzymatic molecular recognition, and for which experimental verification can be obtained without any complicating charge compensation mechanism. Our models provide plausible explanations of the structure-activity relationships observed for these inhibitors, and suggest that cation-pi interactions may provide a novel mechanism for molecular recognition.

Amino Acid Sequence↗
PubMed1995

Photoaffinity labelling of cyanomethaemoglobin with derivatives of tryptophan and 5-bromotryptophan.

Tryptophan and 5-bromotryptophan (5-BrTrp) are relatively potent inhibitors of sickle-haemoglobin polymerization. The binding sites of these compounds to normal and sickle haemoglobin (HBA and HBS) have been suggested, but not firmly established, through the use of spin-labelled derivatives and/or computer modeling. In the present study we approached the problem by utilizing the technique of photoaffinity labelling. The cyanomet forms of HBA and HBS were subjected to photoaffinity labelling with N alpha-(4-azidotetrafluorobenzoyl)tryptophan and N alpha-(1-ethyl-2-diazomalonyl)-5-bromotryptophan respectively. Both irradiated samples of HBA and HBS were denatured, digested with trypsin, and then separated by reversed-phase HPLC. A labelled tryptic peptide was isolated from the photolabelling of HBS with N alpha-(1-ethyl-2-diazomalonyl)-5-bromotryptophan. The peptide was identified to be Val1(alpha)-Lys7(alpha), with the label attached to Val1(alpha), by virtue of amino acid analysis and sequencing, in conjunction with fast-atom-bombardment MS. The binding mode of N alpha-(1-ethyl-2-diazomalonyl)-5-bromotryptophan is proposed and its relevance to the potency of the 5-BrTrp-based anti-sickling agents is discussed.

Affinity Labels↗
PubMed1995

Permeation of steroids through human skin.

The permeabilities of many steroids through human skin have been previously measured and reported in the literature. Analysis of these data reveals that significant discrepancies exist between the measurements of Scheuplein et al. and those of other groups. Six of the 14 steroids which were examined by Scheuplein et al., aldosterone, corticosterone, estradiol, hydrocortisone, progesterone, and testosterone, have also been examined by other groups. For each of these steroids, the permeability measurements of Scheuplein et al. are lower than those reported by other groups by factors of between 5.0 and 77. Eight independent measurements of the permeability of estradiol are in good agreement with one another, but are greater than the value reported by Scheuplein et al. by factors of between 11 and 20. Several possible sources of experimental error, including the variability of the skin samples, the differences in the experimental temperature, the establishment of steady-state conditions, the use of radiolabeled drugs, and the skin preparation technique, have been considered and do not appear to account for the magnitude of the observed discrepancies nor for the fact that the data of Scheuplein et al. are consistently lower than those reported by other groups.

Humans↗
PubMed1995

Dapiprazole's effect upon accommodative recovery: is it due entirely to changes in depth of field?

We conducted a study to evaluate the ability of dapiprazole 0.5% ophthalmic solution to reverse accommodative loss brought about by mydriatic drugs having mild cycloplegic effects. To accomplish this, we analyzed data from several earlier randomized, masked clinical studies. Our composite data include over 90 subjects dilated with tropicamide. Tropicamide was used alone in 1% concentration, as well as in combination with phenylephrine, 2.5% and in the proprietary preparation, Paremyd (Allergan Pharmaceuticals). Accommodative amplitude and pupillary diameter were measured before instilling dilating drops and then again one-half hour later, immediately before instilling either dapiprazole or a placebo. Accommodative amplitude and pupil diameter measurements were then repeated four more times, on both the treatment and control eyes and at 30, 60, 120, and 180 min after instillation of the last drop of dapiprazole or placebo. We found accelerated "accommodative" recovery with dapiprazole for each of the three tropicamide-containing drugs used in our study. This is not surprising because some recovery of accommodative amplitude after dapiprazole's administration is expected. This is because dapiprazole accelerates pupillary recovery and a narrowing of the pupil gives rise to an increase in ocular depth of field. Rate of accommodative recovery with dapiprazole was found not to be significantly different for all three tropicamide-containing preparations tested (p > 0.05). Does dapiprazole produce improvement in amplitude of accommodation beyond that attributable to increased depth of field?(ABSTRACT TRUNCATED AT 250 WORDS)

Accommodation, Ocular↗
PubMed1995

Reading abilities of drug users in Anchorage, Alaska.

Evaluated the reading abilities of 122 male and fifty-nine female intravenous and other drug users in Anchorage, Alaska. Reading abilities were assessed through the Reading subtest of the Wide Range Achievement Test-Revised and the short Form of the Woodcock Reading Mastery Test-Revised. Results indicated that men and Black subjects reported the highest levels of schooling completed. However, no differences were revealed across gender and ethnicity in actual reading levels. Among all subjects, the average reading ability was between 8.5 and 8.7 grade level. These scores place the average subject reading at a level lower than approximately 76 percent of the general population. Implications are provided for development of educational materials accessible for this population.

Adolescent↗
PubMed1995

Evidence for autocrine basis of transformation in NIH-3T3 cells transfected with met/HGF receptor gene.

NIH-3T3 cells transformed with met/HGF receptor gene proliferate in the absence of serum and growth factors. Immunocytochemical staining with anti-HGF antibody revealed intense HGF staining in the transfected cells. Additionally, these cells secrete bioactive HGF as evidenced by the ability of the conditioned media to stimulate met/HGF receptor phosphorylation in epithelial cells, and to promote migration of bovine adrenal capillary endothelial cells in a modified Boyden chamber assay. The migration of endothelial cells could be specifically inhibited by anti-HGF antibody but not by an irrelevant antibody. Suramin, a drug known to disrupt ligand-receptor interactions, inhibits the serum and growth-factor free proliferation, and the endogenous phosphorylation of met/HGF receptor in the transformed cells. Taken together, our data suggests an autocrine mode of transformation in NIH-3T3 cells transfected with met/HGF receptor gene.

3T3 Cells↗
PubMed1995

Comparison of values of Alaska Native and non-Native alcoholics and counselors.

Values of 42 Alaska Native clients, 30 Alaska Native counselors, and 19 non-Native counselors at seven Indian Health Service inpatient alcoholism treatment programs in Alaska are compared. Using the Rokeach Value Survey, differences were revealed on six instrumental values and six terminal values. The primary value disparities were between the Alaska Native groups and non-Native counselors. Specifically, both Alaska Native groups placed greater importance on values that were other-focused while the non-Native counselors placed more importance on values that were self-focused. Minor differences were noted also between clients and both groups of counselors. Therapeutic implications of such values disparities are discussed as are possible avenues to remediate the problem.

Adolescent↗
PubMed1995

Seven days and counting: how inpatient nurses might adjust their practice to brief hospitalization.

1. Inpatient nurses can help create a seamless health care system by designing groups and specific interventions that begin at the time of admission and continue after discharge. 2. Inpatient nurses must clearly articulate how they intervene for the benefit of patients and how they engineer the coordinated staff effort that maintains the basic safety and structure of the environment. 3. Nurses should learn how to organize and report observations so they formulate a concise assessment summary while also collecting data that are useful to the unit's outcome evaluation.

Continuity of Patient Care↗
PubMed1995

Surgical management of primary bone sarcomas.

Effective chemotherapy regimens have changed the nature and scope of surgical management of primary sarcomas of bone. Limb-salvage surgical procedures are performed in the majority of patients without a significantly increased risk of local tumor relapse. Advances in technology have expanded the options available for skeletal reconstruction. End-result analyses have helped refine the application of this technology to maximize function. Further advances are necessary to maintain function in the long term.

Adolescent↗
PubMed1995

DNA sequence assembly and genetic algorithms new results and puzzling insights.

Applying genetic algorithms to DNA sequence assembly is not a straightforward process. Significantly improved results in terms of performance, quality of results, and the scaling of applicability have been realized through non-standard and even counter-intuitive parameter settings. Specifically, the solution time for a 10kb data set was reduced by an order of magnitude, and a 20kb data set that was previously unsolved by the genetic algorithm was solved in a time that represents only a linear increase from the 10kb data set. Additionally, significant progress has been made on a 35kb data set representing real biological data. A single contig solution was found for a 752 fragment subset of the data set, and a 15 contig solution was found for the full data set. This paper discusses the new results, the modifications to the previous genetic algorithm used in this study, the experimental design process by which the new results were obtained, the questions raised by these results, and some preliminary attempts to explain these results.

Algorithms↗
PubMed1994

[D-TRP32]neuropeptide Y: a competitive antagonist of NPY in rat hypothalamus.

Neuropeptide Y (NPY) is a potent orexigenic peptide. Structure-activity studies have revealed that nearly the entire sequence of NPY is required to elicit feeding responses. Therefore, in order to develop antagonistic peptides for NPY-induced feeding, we synthesized full-length analogs of NPY, substituting D-Trp in the C-terminal receptor binding region, and screened their activity in rat hypothalamus. Although [D-Trp36]NPY and [D-Trp34]NPY inhibited isoproterenol-stimulated hypothalamic membrane adenylate cyclase activity, [D-Trp32]NPY exhibited no intrinsic activity. Furthermore, [D-Trp32]NPY inhibited [125I]NPY binding to rat hypothalamic membranes with a potency comparable to that of NPY. The presence of 30 and 300 nM concentrations of [D-Trp32]NPY shifted the inhibitory dose-response curve of NPY on isoproterenol-stimulated hypothalamic membrane adenylate cyclase activity parallel to the right with comparable KB values. Moreover, in vivo experiments in rats revealed that [D-Trp32]NPY (10 micrograms) significantly attenuated the 1-h feeding response induced by NPY (1 microgram). Several other substitutions at position 32 including 2-D-Nal resulted in agonist activity, suggesting that there are strict structural requirements to induce the antagonistic property in NPY. These findings confirm that [D-Trp32]NPY is a competitive antagonist of NPY in both in vitro and in vivo systems. Analogs based on [D-Trp32]NPY may have potential clinical application, since NPY has been implicated in the pathophysiology of a number of feeding disorders including obesity, anorexia, and bulimia.

Adenylyl Cyclase Inhibitors↗
PubMed1994

Conformational rearrangements required of the V3 loop of HIV-1 gp120 for proteolytic cleavage and infection.

HIV gp120 is specifically cleaved at a single site in the V3 loop between Arg315 and Ala316 by thrombin. Previous observations by others have indicated that binding to CD4 enhances the rate of V3 loop cleavage, and that this cleavage is a prerequisite for HIV infection. Other observations also suggest that the cleavage site is in a type II beta-turn centered at Pro313-Gly314. However, our docking experiments indicate that this conformation cannot dock to thrombin and other trypsin-like serine proteases. Thus, based on the thrombin-bound conformation of peptide substrates, we propose that CD4 binding, at a site remote from the V3 loop, induces and stabilizes a trans to cis isomerization of the highly conserved residue Pro313, and that this conformational shift is a prerequisite for cleavage by a 'thrombin-like' cellular protease and subsequent infection.

Binding Sites↗
PubMed1994

Mitochondrial dysfunction during anoxia/reoxygenation injury of liver sinusoidal endothelial cells.

Sinusoidal endothelial cell injury plays a pivotal role in anoxia/reoxygenation liver damage. However, the mechanisms culminating in anoxia/reoxygenation endothelial cell injury remain unclear. Our aims were to determine whether anoxia/reoxygenation injury of sinusoidal endothelial cells causes mitochondrial dysfunction. In cultured rat liver sinusoidal endothelial cells, the mitochondrial membrane potential, cytosolic free calcium and cytosolic pH were quantitated by means of fluorescent probes and multiparameter digitized video microscopy. Cell viability was measured on the basis of lactate dehydrogenase release, and ATP was quantitated with a luciferin/luciferase assay. Mitochondrial membrane potential was stable during 90 min of aerobic perfusion. After 60 and 90 min of anoxia, mitochondrial membrane potential decreased gradually to 97% +/- 6% and 79% +/- 7% of the basal value, respectively. However, mitochondrial membrane potential decreased abruptly with reoxygenation after 60 min of anoxia to 45% +/- 12% of the basal value and did not recover over 30 min of aerobic perifusion. Loss of mitochondrial membrane potential could not be attributed to changes of cytosolic free calcium, cytosolic pH, nitric oxide generation or activity of poly(ADP-ribose) polymerase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗