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Biomedical subjects

D L Johnson

Publications and source records attributed to D L Johnson.

At least 109 records · Page 6Linked to original sources
PubMed1997

Biomechanical comparison between BioScrew and titanium alloy interference screws for bone-patellar tendon-bone graft fixation in anterior cruciate ligament reconstruction.

This investigation compared the maximum load at failure of BioScrew (Linvatec Corp, Largo, FL) and titanium alloy interference screw femoral fixation using a human cadaveric model that approximated the anatomical orientation and physiological strain rate of in vivo bone-patellar tendon-bone (BPTB) graft loading following anterior cruciate ligament reconstruction. Eighteen fresh-frozen human BPTB allografts (10-mm wide, 10-mm thick, 25-mm long bone plugs) with either BioScrew or titanium alloy (Ti 6A14V) screw (7 x 25 mm) fixation were compared for maximum load at failure at a strain rate of 20 mm/minute. Nine cadaver femurs with bone mineral densities of 0.88 +/- 0.18 g/cm2 (anterior/posterior) and 1.3 +/- 0.24 g/cm2 (lateral) received the allografts. No statistical differences were observed in maximum load at failure (P = .95) or failure mode (P = .11) between specimens fixed with either screw type. When biomechanically tested with anatomic orientation and at functionally relevant strain rates, the BioScrew provided maximum load at failure equal to a titanium alloy screw.

Absorption↗
PubMed1997

Amino-terminal dimerization of an erythropoietin mimetic peptide results in increased erythropoietic activity.

BACKGROUND: Erythropoietin (EPO), the hormone involved in red blood cell production, activates its receptor by binding to the receptor's extracellular domain and presumably dimerizing two receptor monomers to initiate signal transduction. EPO-mimetic peptides, such as EMP1, also bind and activate the receptor by dimerization. These mimetic peptides are not as potent as EPO, however. The crystal structure of the EPO receptor (EBP) bound to EMP1 reveals the formation of a complex consisting of two peptides bound to two receptors, so we sought to improve the biological activity of EPO-mimetic peptides by constructing covalent dimers of EMP1 and other peptide mimetics linked by polyethylene glycol (PEG). RESULTS: The potency of the PEG-dimerized EPO peptide mimetics both in vitro and in vivo was improved up to 1,000-fold compared to the corresponding peptide monomers. The dimers were constructed using peptide monomers which have only one reactive amine per molecule, allowing us to conclude that the increase in potency can be attributed to a structure in which two peptides are linked through their respective amino termini to the difunctional PEG molecule. In addition, an inactive peptide was converted into a weak agonist by PEG-induced dimerization. CONCLUSIONS: The potency of previously isolated peptides that are modest agonists of the EPO receptor was dramatically increased by PEG-induced dimerization. The EPO receptor is thought to be dimerized during activation, so our results are consistent with the proposed 2:2 receptor : peptide stoichiometry. The conversion of an inactive peptide into an agonist further supports the idea that dimerization can mediate receptor activation.

Animals↗
PubMed1997

Disposition of aerosolized liposomal amphotericin B.

Amphotericin B (AmB) is an important drug for the treatment of fungal infection, but toxicity limits the lung tissue doses which may be achieved through intravenous administration. Although incorporation of AmB in liposomes reduces these effects and increases the therapeutic index for intravenous administration, targeted delivery to lung tissues via inhaled liposomal AmB aerosol may be a more effective approach. Aerosolization of liposomal amphotericin B targets the lungs, the organs first infested by many fungi. Development of optimal aerosolized liposomal AmB therapies requires a better understanding of the effect that liposome surface charge has on lung clearance kinetics. In this work we evaluated the clearance kinetics and organ distribution of inhaled liposomal AmB in male Balb/C mice. Mice were exposed via nose only to AmB-containing liposomal aerosols having positive, negative, or neutral surface charge characteristics. The formulations were aerosolized using a Collison nebulizer. Groups of animals were euthanized at predetermined times and the lungs and other organs were analyzed for AmB. AmB was not detected in serum and other organs such as kidneys, liver, and brain. The disposition of neutral and positive liposomal amphotericin B in lungs followed biexponential kinetics. The alpha and beta phase half-lives for positive liposomes were 1.3 and 15.1 days, respectively, and 2.3 and 22 days for neutral liposomes. AmB delivered via negative liposomes exhibited monoexponential clearance with a half-life of 4.5 days. These results suggest that toxic side effects in nontarget tissues are minimal and may indicate a potential for long term protection against fungal infections.

Aerosols↗
PubMed1997

Pharmacokinetics of allopurinol in Dalmatian dogs.

The pharmacokinetics of allopurinol were studied in Dalmatian dogs. Eight dogs were given allopurinol orally at a dose of 10 mg/kg for seven doses prior to sample collection. After a period of at least two weeks, four of these dogs and four additional Dalmatians were later given a single intravenous (i.v.) dose of allopurinol (6 mg/kg) prior to sample collection. Allopurinol was found to follow first-order absorption and elimination kinetics. In the i.v. kinetic study, the elimination constant (Kel) = 0.31 +/- 0.03 per h, the half-life (t1/2) = 2.22 +/- 0.20 h, the initial concentration (C0) = 5.26 +/- 0.34 micrograms/mL and the specific volume (Vd) = 1.14 +/- 0.07 L/kg. Clearance of allopurinol was estimated to be 0.36 +/- 0.03 L/kg.h. In the oral kinetic study, the absorption rate constant (Kab) = 1.06 +/- 0.13 per h, the elimination rate constant (Kel) = 0.26 +/- 0.01 per h, the absorption half-life (t1/2ab) = 0.66 +/- 0.06 h, and the elimination half-life (t1/2el) = 2.69 +/- 0.14 h. Peak plasma concentrations (Cmax) = 6.43 +/- 0.18 micrograms/mL were obtained within 1 to 3 h (mean time of maximum concentration (Tmax) = 1.9 +/- 0.1 h). The volume of distribution corrected by the fraction of dose absorbed (Vd/F) was estimated to be 1.17 +/- 0.07 L/kg. Good agreement was obtained between mean kinetic parameters in the oral and i.v. studies. There was little variation between individual dogs in the i.v. study, whereas the rate of absorption and elimination of orally administered allopurinol was more varied among individual dogs. Because of this, and the fact that the magnitude of hyperuricosuria varies among Dalmatians, it is not possible to specify an exact dose of allopurinol that will effectively lower the urinary uric acid concentration to acceptable values in all Dalmatians with hyperuricosuria; rather, the dose must be titrated to the needs of each dog.

Administration, Oral↗
PubMed1997

Comparison of temporal order memory in early and middle stage Alzheimer's disease.

Four tests, each including a new learning and a prior learning component were developed to investigate temporal order memory in subjects with early and middle stage Alzheimer's disease (AD). For newly learned information, both AD groups performed worse than controls but did not differ from each other. For previously learned information, the subjects with AD performed worse than controls. The early AD group performed better than the middle AD group. It appears then, that progression of the disease is associated with decreased access to knowledge systems.

Aged↗
PubMed1997

Lost airway during anesthesia induction: alternatives for management.

Pediatric and adult patients with upper airway obstruction pose several challenges to the anesthesiologist and otolaryngologist--head and neck surgeon. The initiation of general anesthesia and endotracheal intubation may progress to complete life-threatening respiratory decompensation with failure to achieve endotracheal intubation or mask ventilation. Hurried invasive maneuvers such as large-bore needle tracheal entry and cricothyrotomy are recognized salvage techniques, but other modes of extratracheal ventilation are now possible before surgical airway procedures are required. The laryngeal mask airway and esophagotracheal Combitube (Kendall Sheridan Health Care Products Co., Argyle, NY) are described, with examples of their clinical application. The combined technique of anterior commissure laryngoscopy and intubation with the gum elastic bougie is the preferred alternative for achieving tracheal entry when extratracheal ventilation cannot be accomplished. An algorithm for joint management of the problem airway by anesthesiologist and otolaryngologist--head and neck surgeon is illustrated.

Adult↗
PubMed1997

Evaluation of stresses and forces in selected I-bars using the finite element method.

PURPOSE: Three-dimensional models of half-round, tapered and full-round, untapered I-bar clasps of varying configurations and material properties were constructed. The purpose of this study was to examine the stresses and reaction forces produced within each model upon deflection to 0.01 in (0.254 mm), 0.02 in (0.508 mm), and 0.03 in (0.762 mm) at 1 mm from the tip using the finite element method. MATERIALS AND METHODS: Three-dimensional computer models of half-round and full-round clasps were constructed using solid eight-node brick elements. The half-round, tapered I-bar clasp model was 2.4 and 1.4 mm in diameter at the base and tip, respectively. The full-round, untapered I-bar clasp model was 1 mm in diameter. Three design groups were created for each clasp form. Group A had 25% of the total length in the straight anchor end of the I-bar clasp, B had 35%, and C had 50%. All models were 31 mm in length and had a radius of curvature of 5 mm. Different material properties were incorporated into the models. Each model was deflected at a point 1 mm from the tip to 0.01 in (0.254 mm), 0.02 in (0.508 mm), and 0.03 in (0.762 mm). RESULTS: The stresses and forces produced as a result of the deflection applied to each clasp were viewed and displayed graphically. The maximum von Mises stresses in megapascals and the reaction force in newtons (N) were recorded. Stresses varied in each clasp in the range of 0 to 154.3 MPa for the half-round, tapered I-bar clasp models, and 0 to 100.9 MPa for the full-round I-bar clasp models at 0.01-in deflection. Reaction force measured near the tip of the clasp models was between 1.60 N and 6.31 N for the half-round, and between 0.22 N to 2.13 N for the full-round I-bar clasp models. For all clasps studied, as the deflection increased, the location of stress within each group remained the same regardless of the material properties; however, the stress and force values increased linearly. CONCLUSIONS: The location of maximum stress varied with the length of the anchor portion of the clasps studied. Maximum stresses were located on the flat side of the half-round, tapered I-bar clasp model.

Color↗
PubMed1997

Hepatitis B virus X protein induces RNA polymerase III-dependent gene transcription and increases cellular TATA-binding protein by activating the Ras signaling pathway.

Our previous studies have shown that the hepatitis B virus protein, X, activates all three classes of RNA polymerase III (pol III)-dependent promoters by increasing the cellular level of TATA-binding protein (TBP) (H.-D. Wang et al., Mol. Cell. Biol. 15:6720-6728, 1995), a limiting transcription component (A. Trivedi et al., Mol. Cell. Biol. 16:6909-6916, 1996). We have investigated whether these X-mediated events are dependent on the activation of the Ras/Raf-1 signaling pathway. Transient expression of a dominant-negative mutant Ras gene (Ras-ala15) in a Drosophila S-2 stable cell line expressing X (X-S2), or incubation of the cells with a Ras farnesylation inhibitor, specifically blocked both the X-dependent activation of a cotransfected tRNA gene and the increase in cellular TBP levels. Transient expression of a constitutively activated form of Ras (Ras-val12) in control S2 cells produced both an increase in tRNA gene transcription and an increase in cellular TBP levels. These events are not cell type specific since X-mediated gene induction was also shown to be dependent on Ras activation in a stable rat 1A cell line expressing X. Furthermore, increases in RNA pol III-dependent gene activity and TBP levels could be restored in X-S2 cells expressing Ras-ala15 by coexpressing a constitutively activated form of Raf-1. These events are serum dependent, and when the cells are serum deprived, the X-mediated effects are augmented. Together, these results demonstrate that the X-mediated induction of RNA pol III-dependent genes and increase in TBP are both dependent on the activation of the Ras/Raf-1 signaling cascade. In addition, these studies define two new and important consequences mediated by the activation of the Ras signal transduction pathway: an increase in the central transcription factor, TBP, and the induction of RNA pol III-dependent gene activity.

Animals↗
PubMed1997

Weight loss for women: studies of smokers and nonsmokers using hypnosis and multicomponent treatments with and without overt aversion.

Study 1 compared overweight adult women smokers (n = 50) and nonsmokers (n = 50) in an hypnosis-based, weight-loss program. Smokers and nonsmokers achieved significant weight losses and decreases in Body Mass Index. Study 2 treated 100 women either in an hypnosis only (n = 50) or an overt aversion and hypnosis (n = 50) program. This multicomponent follow-up study replicated significant weight losses and declines in Body Mass Index. The overt aversion and hypnosis program yielded significantly lower posttreatment weights and a greater average number of pounds lost.

Adult↗
PubMed1997

The effect of artificial insemination once versus twice per day.

The objective of this study was to determine the effect of inseminating Jersey cows and heifers once per day or according to the a.m.-p.m. rule. A total of 337 artificial inseminations (AI) were completed by three technicians at the University of Tennessee Dairy Experiment Station at Lewisburg for 6 mo. Cows and heifers were inseminated at estrus using the a.m.-p.m. rule on even days of the month. On odd days of the month, AI were once daily between 0800 and 1200 h. Estrus detection was conducted two to three times daily. Pregnancy was confirmed by rectal palpation 60 to 80 d after AI. Herd DHIA averages were a 12.2-mo calving interval, 76 d to first AI, 83% observed estruses, and a 50% conception rate during the trial. Pregnancy data were analyzed with a model including treatment, AI, lactation number, parity, technician, and group. This study grouped cows and heifers according to when they were in estrus and inseminated (a.m.-a.m., a.m.-p.m., or p.m.-a.m.); means were 43.7, 57.9, and 59.0%, respectively. The a.m.-p.m. AI versus once per day AI yielded a pregnancy rate of 55.6% versus 51.3%. These results show no difference among Jersey cows or heifers that were inseminated artificially once daily in the a.m. However, those cows and heifers inseminated in the a.m. of first estrus detection had a lower pregnancy rate.

Animals↗
PubMed1997

Optimizing Medical reimbursement for out-of-state providers.

The federal law pertaining to the creation of the Medical program, USC 42, recognizes the Medicaid beneficiaries sometimes receive healthcare services at facilities outside of their home states. This law, therefore, requires that Medicaid plan provide for the inclusion of out-of-state providers in their programs. The regulation promulgated to implement this law, 42 CFR section 341.52, states the Medicaid plans must provide a mechanism for paying out-of-state healthcare providers that treat the plan's beneficiaries. The law says that a state must "pay for services furnished in another state to the same extent that it would pay for services furnished within its boundaries..." However, many providers that render service to Medicaid patients from other states often do not receive the reimbursement they are entitled to because they do not carefully monitor this segment of their patient population. Healthcare providers can take steps to ensure they receive payment for the services they provide to out-of-state Medicaid patients. These steps include billing for such services properly, investigating additional sources of reimbursement, appealing reimbursement decisions, and participating in bordering states' Medicaid programs as contract providers.

Catchment Area, Health↗
PubMed1997

The potential role of fecal carbonic anhydrase II in screening for colorectal cancer.

Several studies have demonstrated a relationship between mucosal carbonic anhydrase (CA) isoenzymes, particularly CA II, and cancer of the large intestine. Recent work has suggested the potential usefulness of fecal CA assay for colorectal cancer screening. This clinical study examined the accuracy of fecal CA II as a marker of adenocarcinoma of the colon and rectum. An enzyme-linked immunosorbent assay was used to measure CA II in urine, serum, and stool samples from 31 colorectal cancer patients and 26 control subjects. An immunochemical fecal occult blood test was also performed in all study participants. Urine and serum CA II were similar in the two study groups. However, both the prevalence and the mean level of fecal CA II in the cancer patients were significantly higher than those in the control group. The detection rate for CA II in the stool was 65 per cent for the cancer patients versus 4 per cent for the control population. The fecal CA II test was similar in sensitivity and specificity to the immunochemical fecal occult blood test (65 vs 48%; 96 vs 100%). Measurement of fecal CA II might be useful in screening for colorectal cancer.

Biomarkers, Tumor↗
PubMed1996

Small peptides as potent mimetics of the protein hormone erythropoietin.

Random phage display peptide libraries and affinity selective methods were used to isolate small peptides that bind to and activate the receptor for the cytokine erythropoietin (EPO). In a panel of in vitro biological assays, the peptides act as full agonists and they can also stimulate erythropoiesis in mice. These agonists are represented by a 14- amino acid disulfide-bonded, cyclic peptide with the minimum consensus sequence YXCXXGPXTWXCXP, where X represents positions allowing occupation by several amino acids. The amino acid sequences of these peptides are not found in the primary sequence of EPO. The signaling pathways activated by these peptides appear to be identical to those induced by the natural ligand. This discovery may form the basis for the design of small molecule mimetics of EPO.

Amino Acid Sequence↗
PubMed1996

Functional mimicry of a protein hormone by a peptide agonist: the EPO receptor complex at 2.8 A.

The functional mimicry of a protein by an unrelated small molecule has been a formidable challenge. Now, however, the biological activity of a 166-residue hematopoietic growth hormone, erythropoietin (EPO), with its class 1 cytokine receptor has been mimicked by a 20-residue cyclic peptide unrelated in sequence to the natural ligand. The crystal structure at 2.8 A resolution of a complex of this agonist peptide with the extracellular domain of EPO receptor reveals that a peptide dimer induces an almost perfect twofold dimerization of the receptor. The dimer assembly differs from that of the human growth hormone (hGH) receptor complex and suggests that more than one mode of dimerization may be able to induce signal transduction and cell proliferation. The EPO receptor binding site, defined by peptide interaction, corresponds to the smaller functional epitope identified for hGH receptor. Similarly, the EPO mimetic peptide ligand can be considered as a minimal hormone, and suggests the design of nonpeptidic small molecule mimetics for EPO and other cytokines may indeed be achievable.

Amino Acid Sequence↗
PubMed1996

The form and bioavailability of non-ionic organic chemicals in sewage sludge-amended agricultural soils.

The application of sewage sludges to agricultural land may increase the concentrations of many toxic organic chemicals in soils which could have adverse effects on wildlife and human health if these compounds enter foodchains. Chlorobenzenes (CBs), polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) are amongst those compounds currently receiving most attention. The "form' in which these, and other organic chemicals, are present in soils and their potential to be lost by various processes including leaching, volatilisation and (bio)degradation is shown to be dependent on the physicochemical characteristics of the soil and sewage sludge, environmental conditions and the properties of the chemicals themselves. The distinction is made between those compounds that are labile, reversibly sorbed and irreversibly sorbed by sewage sludge-amended soils. The implications of the form in which the chemicals are present in soil for their "availability' to transfer from the soil to bacteria, fungi, earthworms, grazing livestock and food crops followed by the potential for further transfers, metabolism or bioaccumulation are discussed. The importance of the timing and method of sewage sludge application to soil on "form' and "availability' are also considered.

Agriculture↗
PubMed1996

Identification of a critical ligand binding determinant of the human erythropoietin receptor. Evidence for common ligand binding motifs in the cytokine receptor family.

The erythropoietin receptor (EPOR) is a member of a family of cytokine and growth factor receptors that share conserved features in their extracellular and cytoplasmic domains. We have used site-specific mutagenesis within the extracellular domain of the EPOR to search for amino acid residues involved in erythropoietin (EPO) binding. Mutant proteins were expressed in bacteria as soluble EPO binding proteins (EBP) and characterized for EPO binding activity in a number of different assays. Substitution of phenylalanine at position 93 (Phe93) with alanine (F93A mutation) resulted in a drastic reduction in EPO binding in the EBP. More conservative tyrosine or tryptophan substitutions at Phe93 resulted in much less dramatic effects on EPO binding. Biophysical studies indicated that the F93A mutation does not result in gross structural alterations in the EBP. Furthermore, the F93A mutation in full-length EPOR expressed in COS cells abolished detectable EPO binding. This was not a result of processing or transport defects, since mutant receptor was present on the surface of the cells. Mutations in the region immediately around Phe93 and in residues homologous to other reported ligand binding determinants of the cytokine receptor family had small to moderate effects on EPO binding. These data indicate that Phe93 is a critical EPO binding determinant of the EPOR. Furthermore, since Phe93 aligns with critical ligand binding determinants in other receptors of the cytokine receptor family, these data suggest that receptors of this family may use common structural motifs to bind their cognate ligands.

Alanine↗
PubMed1996

GRIP1, a novel mouse protein that serves as a transcriptional coactivator in yeast for the hormone binding domains of steroid receptors.

The yeast two-hybrid system was used to isolate a clone from a 17-day-old mouse embryo cDNA library that codes for a novel 812-aa long protein fragment, glucocorticoid receptor-interacting protein 1 (GRIP1), that can interact with the hormone binding domain (HBD) of the glucocorticoid receptor. In the yeast two-hybrid system and in vitro, GRIP1 interacted with the HBDs of the glucocorticoid, estrogen, and androgen receptors in a hormone-regulated manner. When fused to the DNA binding domain of a heterologous protein, the GRIP1 fragment activated a reporter gene containing a suitable enhancer site in yeast cells and in mammalian cells, indicating that GRIP1 contains a transcriptional activation domain. Overexpression of the GRIP1 fragment in mammalian cells interfered with hormone-regulated expression of mouse mammary tumor virus-chloramphenicol acetyltransferase gene and constitutive expression of cytomegalovirus-beta-galactosidase reporter gene, but not constitutive expression from a tRNA gene promoter. This selective squelching activity suggests that GRIM can interact with an essential component of the RNA polymerase II transcription machinery. Finally, while a steroid receptor HBD fused with a GAL4 DNA binding domain did not, by itself, activate transcription of a reporter gene in yeast, coexpression of this fusion protein with GRIP1 strongly activated the reporter gene. Thus, in yeast, GRIP1 can serve as a coactivator, potentiating the transactivation functions in steroid receptor HBDs, possibly by acting as a bridge between HBDs of the receptors and the basal transcription machinery.

Amino Acid Sequence↗