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Biomedical subjects

C R Johnson

Publications and source records attributed to C R Johnson.

At least 19 recordsLinked to original sources

A randomised controlled trial of the reciprocating syringe in arthrocentesis.

OBJECTIVE: To evaluate the outcomes of arthrocentesis with the new highly controllable, one handed reciprocating procedure syringe compared with a conventional syringe. METHODS: 100 arthrocentesis procedures were randomised between the reciprocating syringe and the conventional syringe. Outcome measures included patient pain, procedure duration, operator satisfaction, synovial fluid volume, cell counts, and complications. RESULTS: 50 arthrocentesis procedures with the conventional syringe resulted in a mean (SD) procedure time of 3.39 (1.88) minutes, a mean VAPS (patient pain) score of 5.35 (3.15), and a mean VASS (operator satisfaction) score of 4.88 (1.92); 30 of the 50 subjects experienced moderate to severe pain (VAPS score 5 or greater) during arthrocentesis. In contrast, the reciprocating syringe resulted in a reduced procedure time of 1.94 (1.14) minutes (p<0.001), a reduced VAPS (patient pain) score of 2.54 (1.60) (p<0.001), and an increased VASS (operator satisfaction) score of 8.91 (0.79) (p<0.001). Only five of the 50 of subjects experienced moderate to severe pain with the reciprocating syringe. Synovial cell counts were similar between the two syringes (p>0.05), but there was a trend toward greater volume (greater synovial fluid yield) and fewer red blood cells with the reciprocating syringe. CONCLUSIONS: Arthrocentesis with a conventional syringe results in moderate to severe pain in 60% of subjects. The reciprocating syringe prevents significant pain, reduces procedure time, and improves physician performance of arthrocentesis. The reciprocating syringe is superior to the conventional syringe in arthrocentesis.

Adult↗

Caspase-9 regulation: an update.

The complex sequence of events leading to apoptotic cell death is governed by an elaborate regulatory scheme involving the actions of both initiator and executioner proteases. Among the most intensively studied of the initiator caspases is caspase-9, an essential throughput element in the so-called intrinsic or mitochondrially gated pathway of apoptosis. Previous reviews have described the proteolytic processing and activation of this protease in much detail; here we provide an update on caspase-9 regulation. A comprehensive description of the intra- and intermolecular events involved in modulating protein expression and activity are presented. Particular emphasis is placed on the role alternative splicing plays in the expression of functionally divergent protein isoforms, as well as, the participation of specific post-translational events in regulating caspase-9 activity. Such discrete modulation in reported activity characterizes, not only the pivotal role of this protease in the final commitment process itself, but also emphasizes the more general interplay that exists between mutually opposing cytotoxic and cytoprotective influences in maintaining cellular homeostasis.

Alternative Splicing↗

Requirement for SAPK-JNK signaling in the induction of apoptosis by ribosomal stress in REH lymphoid leukemia cells.

The present studies examined performance of SAPK cascades and apoptotic commitment following ribosomal trauma in REH lymphoid leukemia cells. Ribostatic insults included disruption of ribosomal activity by mechanistically dissimilar agents such as blasticidin-S (BCS) (which binds 28S-rRNA to block peptidyl bond formation), kasugamycin (KSM) (which binds 18S-rRNA to prevent translational initiation), and cycloheximide (CHX) (which blocks A-site to P-site translocation of peptidyl-tRNA). Exposure of REH cells to BCS elicited DNA degradation and apoptotic cytolysis. BCS stimulated JNK1/JNK2 and p38, and their shared targets c-Jun and ATF2. Inhibition of JNK1/JNK2 (but not of p38) antagonized blasticidin-induced apoptosis, whereas targeting alternative ribosomal sites with KSM or CHX limited translation, but failed to activate the SAPK cascade or initiate apoptosis. Our findings indicate that interference with 28S-rRNA by BCS initiates apoptosis in REH cells through recruitment of SAPK-JNK signaling. Disparities between the lethal actions of BCS, KSM, and CHX appear to reflect established differences in the subribosomal targets of these agents. We propose that the SAPK cascade comprises an essential mechanism for the transduction of specific lethal stress signals emanating from active ribosomes, and that interference with the 28S-rRNA, rather than the peptidyl transfer center of the large subunit, is critical to apoptotic commitment.

Apoptosis↗

Influence of milk production potential on forage dry matter intake by multiparous and primiparous Brangus females.

Brangus cows (n = 29) were used in three experiments to evaluate the effects of parity (multiparous vs. primiparous) and potential genetic merit for milk production (high vs. low) on forage intake during late gestation, early lactation, and late lactation. Cows were selected for milk production based on their sire's EPD for milk production (MEPD). Cows had ad libitum access to (130% of previous 2-d average intake) low-quality hay (5.3% CP and 76% NDF), and cottonseed meal was supplemented to ensure adequate degradable intake protein. All females were adapted to diets for at least 7 d, and individual intake data were collected for 9 d. During the lactation trials, actual milk production was determined using a portable milking machine following a 12-h separation from calves. During late gestation, multiparous cows consumed 24% more (P = 0.01) forage DM (kg/d) than primiparous cows; however, parity class did not influence forage intake when intake was expressed relative to BW. Furthermore, MEPD did not influence forage intake during late gestation. During early lactation, multiparous cows produced 66% more (P < 0.001) milk than primiparous cows, and high MEPD tended (P = 0.10) to produce more milk than low MEPD. Multiparous cows consumed 19% more (P < 0.0001) forage DM than did primiparous cows when expressed on an absolute basis, but not when expressed on a BW basis. High-MEPD cows consumed 8% more (P < 0.05) forage DM than did low-MEPD cows. During late lactation, multiparous cows produced 84% more milk than primiparous cows, although MEPD did not influence (P = 0.40) milk yield. In addition, multiparous cows consumed 17% more (P < 0.01) forage DM per day than primiparous cows, but when intake was expressed relative to BW, neither parity nor MEPD influenced forage DMI during late lactation. Milk yield and BW explained significant proportions of the variation in forage DMI during early and late lactation. Each kilogram increase in milk yield was associated with a 0.33- and 0.37-kg increase in forage DMI for early and late lactation, respectively. Results suggest that multiand primiparous cows consume similar amounts of low-quality forage DM, expressed per unit of BW, during late gestation and lactation. Selecting beef cows for increased genetic merit for milk production increases forage DMI during early lactation.

Animal Feed↗

An efficient synthesis of 3-hetero-13,14-dihydro prostaglandin F1alpha analogues.

[structure: see text]. A new class of 3-hetero-13,14-dihydro prostaglandin F(1)(alpha) analogues was synthesized from a common intermediate. The latter was constructed via a two-step, three-component process. The lower chain, containing the 15-(phenoxymethyl) group, was synthesized in enantiopure form using Jacobsen's (salen)Co-catalyzed kinetic resolution of a terminal epoxide with phenol.

Animals↗

Vagus nerve stimulation (VNS) for treatment-resistant depression: efficacy, side effects, and predictors of outcome.

This open pilot study of vagus nerve stimulation (VNS) in 60 patients with treatment-resistant major depressive episodes (MDEs) aimed to: 1) define the response rate; 2) determine the profile of side effects; and, most importantly; 3) establish predictors of clinical outcome. Participants were outpatients with nonatypical, nonpsychotic, major depressive or bipolar disorder who had not responded to at least two medication trials from different antidepressant classes in the current MDE. While on stable medication regimens, the patients completed a baseline period followed by device implantation. A 2-week, single blind, recovery period (no stimulation) was followed by 10 weeks of VNS. Of 59 completers (one patient improved during the recovery period), the response rate was 30.5% for the primary HRSD(28) measure, 34.0% for the Montgomery-Asberg Depression Rating Scale (MADRAS), and 37.3% for the Clinical Global Impression-Improvement Score (CGI-I of 1 or 2). The most common side effect was voice alteration or hoarseness, 55.0% (33/60), which was generally mild and related to output current intensity. History of treatment resistance was predictive of VNS outcome. Patients who had never received ECT (lifetime) were 3.9 times more likely to respond. Of the 13 patients who had not responded to more than seven adequate antidepressant trials in the current MDE, none responded, compared to 39.1% of the remaining 46 patients (p =.0057). Thus, VNS appears to be most effective in patients with low to moderate, but not extreme, antidepressant resistance. Evidence concerning VNS' long-term therapeutic benefits and tolerability will be critical in determining its role in treatment-resistant depression.

Adolescent↗

Attentional processes in autism.

Attentional processes in individuals with high-functioning autism were compared with a matched control group. Participants for the study were 103 children and adults with autism and 103 control subjects. Measures administered corresponded to Mirsky et al.'s (1991) factor analysis of tests of attention. Diminished performance was noted on measures that loaded on the Focus-Execute and Shift factors, but not on the Sustain and Encode factors. For tests in which psychomotor speed was used as the score, and the difference between groups was significant, covariance analyses were performed, using tests of basic motor functions as covariates. This procedure led to attenuation to the point of nonsignificant differences in the case of some of the attention tests. Thus, this comprehensive analysis of attention in individuals with high-functioning autism only found differences on measures in which the task placed demands on cognitive flexibility or psychomotor speed. Thus, purported attention deficits in autism may actually be primary deficits in complex decision making or psychomotor abilities.

Adolescent↗

Generation and characterization of a PhoP homologue mutant of Neisseria meningitidis.

Two-component regulatory systems are important regulators of virulence genes in a number of bacteria. Genes encoding a two-component regulator system, with homology to the phoP/phoQ system in salmonella, were identified in the meningococcal genome. Allele replacement was used to generate a meningococcal knock-out mutant of the regulator component of this system, and its phenotype was examined. The mutant displayed many differences in protein profiles compared with wild type, consistent with it being a gene-regulatory mutation. Many of the growth characteristics of the mutant were similar to those of phoP mutants of salmonella: it was unable to grow at low concentrations of magnesium and was sensitive to defensins and other environmental stresses. Magnesium-regulated differences in protein expression were abrogated in the mutant, indicating that the meningococcal PhoP/PhoQ system may, as in salmonella, respond to changes in environmental magnesium levels. These results are consistent with the PhoP homologue playing a similar role in the meningococcus to PhoP in salmonella and suggest that it may similarly be involved in the regulation of virulence genes in response to environmental stimuli in the meningococcus. In support of this conclusion, we found the mutant grew was unable to grow in mouse serum and was attenuated in its ability to traverse through a layer of human epithelial cells. Identification of those genes regulated by the meningococcal PhoP may provide a route towards the identification of virulence genes in the meningococcus.

Alleles↗

Effects of nitrogen fertilization and harvest date on yield, digestibility, fiber, and protein fractions of tropical grasses.

To evaluate the response of three tropical forage species to varying rates of nitrogen (N) fertilization [0, 39, 78, 118, 157 kg of N/(ha x cutting)] and five summer harvests, forage DM mass and nutritive value were evaluated in a randomized complete block design with a split-split plot arrangement of treatments. Plots (n = 60) were established in 1996, and five harvests were conducted every 28 d from June through September in 1997 and 1998, with fertilizer applications occuring after each harvest. Fertilization with 78 kg of N/(ha x cutting) increased forage mass in these grasses by 129% (P < 0.01) compared with no N fertilization. Additional N did not result in further increases of forage mass. Bermudagrass (Cynodon dactylon) produced more forage DM [P < 0.01; 1,536 +/- 43 kg/(ha x cutting)] than stargrass [Cynodon nlemfuensis; 1,403 +/- 43 kg/(ha x cutting)] or bahiagrass [Paspalum notatum; 1,297 +/- 43 kg/(ha x cutting)]. Peak forage mass for all species occurred in late June and July. In vitro organic matter digestibility (IVOMD) of stargrass increased (P < 0.01) linearly with fertilization. A quadratic response to N fertilization (P < 0.01) was noted in IVOMD of bermudagrass, whereas bahiagrass was not affected. Bermudagrass was more (P < 0.01) digestible (57.5 +/- 0.4) than stargrass (54.6 +/- 0.4) and bahiagrass (51.9 +/- 0.4%). As fertilization level increased, NDF decreased linearly (P < 0.01) in all three forages. Total N concentration increased (P < 0.01) linearly as N fertilization increased in all forages. Total N concentration was highest (P < 0.01) in stargrass (2.4%, DM basis) compared with bermudagrass (2.2%) and bahiagrass (2.0%). Total N concentration was depressed in all forages for late June and July harvests (P < 0.01). Fertilization increased (P < 0.05) the concentration (% of DM) of all protein fractions. In July and August, nonprotein N was reduced 11.8% (P < 0.01), whereas ADIN increased in July (P < 0.01). Bahiagrass had less N in cell contents than did bermudagrass and stargrass but had a greater concentration of N associated with the cell wall. Managerial factors, including rates of N fertilization and harvest dates, can have profound effects on the nutritional value of forage. An increased understanding of these effects is imperative to improve supplementation programs for ruminants.

Animal Feed↗

Poliovirus induces an early impairment of mitochondrial function by inhibiting succinate dehydrogenase activity.

Poliovirus infection of COS-1 and T47D cells caused a rapid decrease in total cell respiration, and this was attributed to an inhibition of mitochondrial respiration. The stimulation of mitochondrial respiration by pyruvate plus malate or succinate was impaired in saponin-permeabilised cells. However, this inhibition could be overcome by the addition of N,N,N',N'-tetramethyl-1, 4-phenylenediamine and ascorbate. The activity of succinate dehydrogenase was impaired in parallel with the inhibition of mitochondrial respiration during poliovirus infection. This shows that mitochondrial function is profoundly altered during poliovirus infection and that this occurs primarily through inhibition of electron flow at complex II of the mitochondrial respiratory chain.

Animals↗

Synthesis of unnatural amino acids via Suzuki cross-coupling of enantiopure vinyloxazolidine derivatives.

[formula: see text] (R and S)-alpha-Amino alcohols and alpha-amino acids, including 4-methoxyhomophenylalanine, with a variety of unnatural side chains have been synthesized via palladium-catalyzed cross-coupling Suzuki reactions. The key building blocks 1 and 2, synthesized from the common achiral precursor 2-butene-1,4-diol, were made enantiopure utilizing a Pseudomonas cepacia lipase-catalyzed kinetic resolution. The optimal conditions for the Suzuki cross-coupling and the subsequent oxidations of the resultant alpha-amino alcohols are described.

Amino Acids↗

Long-bone fractures in llamas: six cases (1993-1998).

OBJECTIVE: To determine clinical and radiographic findings, treatment, and outcome for llamas with long-bone fractures. DESIGN: Retrospective study. ANIMALS: 6 llamas. PROCEDURE: Medical records of llamas admitted between 1993 and 1998 because of long-bone fractures were reviewed. Data collected included age, sex, type of fracture, method of fracture repair, and postoperative complications. The Fisher exact test was used to compare age and sex of the llamas with long-bone fractures with those of the hospital population of llamas. All owners were contacted by telephone to determine perceived postoperative problems and whether the llamas were able to perform as expected. RESULTS: Mean age was 160.8 days (range, 23 to 365 days). There was 1 male and 5 females. Fractures were more likely to occur in young llamas (< or = 1 year old) than in adults. Five of the fractures were attributed to traumatic episodes. Long bones affected included the tibia (n = 2), radius (2), femur (1), and humerus (1). Internal fixation with lag screws, plating, or both was performed on fractures of all llamas except 1; that llama was treated by use of confinement to a stall. None of the llamas had intraoperative complications, but postoperative complications were reported in 2 llamas. All fractures healed eventually, and clients were pleased with outcomes. CONCLUSIONS AND CLINICAL RELEVANCE: Long-bone fractures in llamas are uncommon. Several types of long bone fractures can be successfully repaired by use of internal fixation, resulting in few complications and minimal convalescent time.

Age Factors↗

Efficacy of methylphenidate among children with autism and symptoms of attention-deficit hyperactivity disorder.

Thirteen children (ages 5.6 to 11.2 years) with autism and symptoms of attention-deficit hyperactivity disorder (ADHD) participated in a double-blind, placebo-controlled crossover study of methylphenidate (0.3 and 0.6 mg/kg per dose). Eight subjects responded positively, based upon a minimum 50% decrease on the Conners Hyperactivity Index. Ratings of stereotypy and inappropriate speech, which are often associated with autistic core features, also decreased. However, no changes were found on the Child Autism Rating Scale, a global assessment of autistic symptomotology. Significant adverse side effects occurred in some children including social withdrawal and irritability, especially at the 0.6 mg/kg dose. Results suggest that methylphenidate can be efficacious for children with autism and ADHD symptoms. However, this group of children seems to be particularly susceptible to adverse side effects.

Attention Deficit Disorder with Hyperactivity↗

Advances in radiotherapy for carcinoma of the head and neck.

Increasingly, progress in the radiotherapy of carcinomas of the head and neck is being driven by principles of radiobiology. This article discusses some of the major advances in head and neck radiotherapy, including altered fractionation, concomitant chemotherapy, and intensity-modulated radiotherapy, in the context of radiobiologic rationale, potential impact on tumor control, and normal tissue complications.

Carcinoma↗

Induction of apoptosis in U937 human leukemia cells by suberoylanilide hydroxamic acid (SAHA) proceeds through pathways that are regulated by Bcl-2/Bcl-XL, c-Jun, and p21CIP1, but independent of p53.

Determinants of differentiation and apoptosis in myelomonocytic leukemia cells (U937) exposed to the novel hybrid polar compound SAHA (suberoylanilide hydroxamic acid) have been examined. In contrast to hexamethylenbisacetamide (HMBA), SAHA-related maturation was limited and accompanied by marked cytoxicity. SAHA-mediated apoptosis occurred within the G0G1 and S phase populations, and was associated with decreased mitochondrial membrane potential, caspase-3 activation, PARP degradation, hypophosphorylation/cleavage of pRB, and down-regulation of c-Myc, c-Myb, and B-Myb. Enforced expression of Bcl-2 or Bcl-XL inhibited SAHA-induced apoptosis, but only modestly potentiated differentiation. While SAHA induced the cyclin-dependent kinase inhibitor p21CIP1, antisense ablation of this CDKI increased, rather than decreased, SAHA-related lethality. In contrast, conditional expression of wild-type p53 failed to modify SAHA actions, but markedly potentiated HMBA-induced apoptosis. Finally, SAHA modestly increased expression/activation of the stress-activated protein kinase (SAPK/JNK); moreover, SAHA-related lethality was partially attenuated by a dominant-negative c-Jun mutant protein (TAM67). SAHA did not stimulate mitogen-activated protein kinase (MAPK), nor was lethality diminished by the specific MEK/MAPK inhibitor PD98059. These findings indicate that SAHA potently induces apoptosis in human leukemia cells via a pathway that is p53-independent but at least partially regulated by Bcl-2/Bcl-XL, p21CIP1, and the c-Jun/AP-1 signaling cascade.

Apoptosis↗

Effect of nitrogen and phosphorus addition on phenanthrene biodegradation in four soils.

Phenanthrene mineralization rates were found to vary widely among four soils; differences in soil nutrient levels was one hypothesis to explain this variation. To test this hypothesis, phenanthrene mineralization rates were measured in these soils with, and without, added nitrogen and phosphorus. Mineralization rates either remained unchanged or were depressed by the addition of nitrogen and phosphorus. Phenanthrene degradation rates remained unchanged in the soil which had the highest indigenous levels of nitrogen and phosphorus and which showed the largest increase in phosphorus levels after nutrients were added. The soils in which degradation rates were depressed had lower initial phosphorus concentrations and showed much smaller or no measurable increase in phosphorus levels after nutrients were added to the soils. To understand the response of phenanthrene degradation rates to added nitrogen and phosphorus, it may be necessary to consider the bioavailability of added nutrients and nutrient induced changes in microbial metabolism and ecology.

Biodegradation, Environmental↗

Exercise programs for fitness and health for geriatrics.

"As a consequence of diminished exercise tolerance, a large and increasing number of elderly people will be living below, at, or just above 'thresholds' of physical ability, needing only minor intercurrent illness to render them completely dependent" (Astrand, 1992, p. 1231S). The NP can play a crucial role in educating motivating, and encouraging geriatric clients to continue or initiate a fitness program. The exercise program that is prescribed by NPs for their patients "depends on their needs, goals, physical and health status, personal preference, and available time, equipment, and facilities" (Pollack et al., 1994, p. 588). Fitness is a goal for all geriatric patients, that they might remain healthy and physically fit longer, and therefore continue to lead active, fulfilling lives.

Aged↗

Evidence that the apoptotic actions of etoposide are independent of c-Jun/activating protein-1-mediated transregulation.

We recently demonstrated that physiological induction of apoptosis by cytotoxic sphingolipid messengers proceeds via activating protein-1 (AP1)-dependent and AP1-independent mechanisms in U937 human monoblastic leukemia cells. Here we examine involvement of the stress-activated protein kinase (SAPK) cascade and AP1 in the initiation of apoptosis in U937 cells by podophyllotoxin-derived inhibitors of topoisomerase II. Induction of apoptotic cell death and DNA damage by treatment of U937 cells with etoposide (100 microM) was associated with phosphorylation and activation of the c-Jun NH(2)-terminal kinase (JNK1) SAPK enzymes p46 and p54-JNK2 and transient increases in expression of the transcription factor c-Jun, a primary JNK substrate. These responses were accompanied by a modest, but sustained, recruitment of the mitogen-activated protein kinases p42-extracellular signal receptor-activated kinase (ERK)1 and p44-extracellular signal receptor-activated kinase 2. The capacity of etoposide to promote double-stranded DNA degradation and cell death was unaffected by manipulations that interfere with SAPK signaling outflow through c-Jun/AP1, including: 1) pharmacological inhibition of AP1 activity by diferuloylmethane and 2) molecular ablation of normal c-Jun function by the Jun dominant-negative mutant TAM-67. Cytotoxicity of the structurally related compound teniposide was similarly unaffected. In parallel trials, the lethal actions of ceramide (but not of sphingosine) were markedly diminished by pretreatment with diferuloylmethane or expression of TAM-67, confirming the effectiveness of these interventions in suppression of SAPK/AP1-dependent apoptosis. The involvement of AP1 in the proapoptotic actions of other inhibitors of topoisomerase II activity was also evaluated. Induction of cell death by the anthracyclines daunorubicin, daunorubicin, and idarubicin was found to be insensitive to pretreatment with diferuloylmethane or expression of TAM-67. Collectively, the present data indicate that induction of apoptosis by etoposide and related inhibitors of topoisomerase II is mediated through a cell death pathway that does not require SAPK-dependent recruitment of AP1. These findings additionally suggest that activation of the SAPK represents a consequence, rather than an underlying cause, of etoposide-induced apoptosis in myeloid leukemia cells.

Antibiotics, Antineoplastic↗