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Biomedical subjects

M Johnson

Publications and source records attributed to M Johnson.

At least 217 records · Page 12Linked to original sources
PubMed1999

CCR7 (EBI1) receptor down-regulation in asthma: differential gene expression in human CD4+ T lymphocytes.

Asthma is an inflammatory disorder, and the CD4+ T lymphocyte plays a key role in mediating the inflammatory response. We used a high-density grid, hybridization-based, differential gene expression technology to analyse molecular mechanisms underlying in vivo CD4+ T-cell activation in both steroid-resistant asthma (SRA) and steroid-sensitive asthma (SSA). Hybridization of radioactively-labelled first-strand cDNAs prepared from different biological samples, to identical high-density gridded arrays of PCR amplicons derived from cDNA clone inserts immobilized on nylon membranes, was compared by phosphorimaging. Hybridization data were captured and processed using image analysis software that can identify the location and signal intensity of each hybridized cDNA. This produces a hierarchy of signals of differing intensities between the two grids, representing differential gene expression in the two different RNA samples. CCR7 (EBI1), a lymphocyte-specific G-protein-coupled receptor, was down-regulated in the CD4+ T cells of SRA and SSA non-atopic, compared to non-asthmatic non-atopic individuals. This observation is intriguing given that CCR7 and its ligand EBI1-Ligand Chemokine (ELC), may play a role in the migration and homing of normal lymphocytes. Also, TNFR2 is up-regulated in both SSA non-atopic and SRA atopic as compared to non-asthmatic controls. LAMR1 is down-regulated in CD4+ T cells of SRA compared to non-asthmatic individuals, irrespective of their atopic status. These could be general phenomena resulting from cytokine release.

Adult↗
PubMed1999

Evaluation of clinical practice guidelines on outcome of infection in patients in the surgical intensive care unit.

OBJECTIVE: In this study, clinical practice guidelines were developed by a multidisciplinary team for patients with infections admitted to a surgical intensive care unit (ICU). DESIGN: A 51-day baseline audit period (Phase I) in a 20-bed (private rooms) surgical ICU was compared with a 34-day period in the same unit after implementation of the guidelines (Phase II). PATIENTS: Phase I included 182 patients (670 patient days), and Phase II included 139 patients (427 patient days). RESULTS: There was no significant difference between patients in the Phase I and Phase II groups regarding age (65.4/19-95 vs. 64.8/18-90 yrs), gender (56% male vs. 55% male), severity of illness (mean Acute Physiology and Chronic Health Evaluation III, 38 vs. 39.1), total infections (respiratory, 8% vs. 4%; urinary tract, 15% vs. 4%; wound, 4% vs. 3%; skin/soft tissue, 3% vs. 7%; sepsis, 5% vs. 3%; intra-abdominal, 9% vs. 17%), and no infection (64% vs. 67%). Clinical outcomes of patients with infections in the Phase I group compared with those in the Phase II group were as follows: clinical improvement or cure, 64% vs. 76%; persistent infection, 17% vs. 11%; clinical failure, 0 vs. 2%; and death, 18% vs. 7% (p = NS). When patients with infections were compared, death rates were 20% in the Phase I group and 5.6% in the Phase II group (p = .02). After implementation of the clinical pathways, antibiotic costs were reduced from $676.54 per patient to $157.88 per patient (p = .001). Length of stay in the ICU was 3.7 days in the Phase I trial and a mean of 3 days in the Phase II trial (p = NS). Specimens of Escherichia coli demonstrated a trend toward a decreased resistance to all antibiotics and Pseudomonas aeruginosa to ciprofloxacin and aminoglycosides (p = NS). CONCLUSIONS: In this study, the use of clinical practice guidelines for patients who were admitted to the surgical ICU was shown to reduce costs, without adversely affecting patients' outcomes. This study has important implications for the use of clinical practice guidelines for the management of patients with infections who are admitted to surgical ICUs.

Aged↗
PubMed1999

The effects of cisplatinum and vincristine on peripheral nerve regeneration.

Current treatment modalities for extremity sarcoma often include tumor extirpation plus neoadjuvant therapy. Limb-sparing surgery may require reconstruction of critical nerve defects. Neurotoxic side effects from adjuvant chemotherapy have been reported and raise concerns regarding the effects of chemotherapy on nerve regeneration. In an attempt to define the effects of adjuvant chemotherapy on peripheral nerve regeneration, cisplatin and vincristine were administered to rats following isografting of the posterior tibial nerve. Parameters used to assess peripheral nerve regeneration included walking track analysis and histomorphology. Sixty 250-g Sprague-Dawley rats were randomly allocated into one of three treatment groups. Each animal underwent a 15-mm reversed interposition nerve isograft from 30 donor rats into the right posterior tibial nerve. Ten animals served as control. The remaining animals were divided into two groups of 25 animals each. One group received cisplatin (75 mg/m2) and the other group received vincristine (1 mg/m2). Chemotherapy was administered at 4-week cycles for a total of six cycles (24 weeks). Walking track analysis was performed monthly. Nerve specimens were harvested from the grafted segment and the distal posterior tibial nerve for histomorphology. Walking track analysis demonstrated no statistical difference in print length between the control and chemotherapeutic groups at the conclusion of the study. The number of axons per square millimeter and nerve fiber density were not statistically different between control and chemotherapeutic groups. In the rodent posterior tibial nerve model, postoperative adjuvant therapy does not significantly alter functional outcome in peripheral nerve regeneration. The practice of immediate nerve grafting after tumor extirpation, despite planned postoperative chemotherapy, is supported.

Animals↗
PubMed1999

Pigmented schwannoma of the ventral spinal cord.

Pigmented schwannomas of the spinal canal are rare entities. We present a case of such in an unusual, ventral intradural, extramedullary location in a 27-year-old man. Imaging and histopathologic findings, including electron microscopy, showed an intradural, extramedullary pigmented schwannoma, densely adherent to the leptomeninges of the anterior median septum. This lesion is demonstrative of the neuroectodermal origin of these lesions and represents a rare location of these tumors.

Adult↗
PubMed1999

Biophysical characterization and modeling of lung surfactant components.

The present study characterizes the dynamic interfacial properties of calf lung surfactant (CLS) and samples reconstituted in a stepwise fashion from phospholipid (PL), hydrophobic apoprotein (HA), surfactant apoprotein A (SP-A), and neutral lipid fractions. Dipalmitoylphosphatidylcholine (DPPC), the major PL component of surfactant, was examined for comparison. Surface tension was measured over a range of oscillation frequencies (1-100 cycles/min) and bulk phase concentrations (0.01-1 mg/ml) by using a pulsating bubble surfactometer. Distinct differences in behavior were seen between samples. These differences were interpreted by using a previously validated model of surfactant adsorption kinetics that describes function in terms of 1) adsorption rate coefficient (k1), 2) desorption rate coefficient (k2), 3) minimum equilibrium surface tension (gamma*), 4) minimum surface tension at film collapse (gammamin), and 5) change in surface tension with interfacial area for gamma < gamma* (m2). Results show that DPPC and PL have k1 and k2 values several orders of magnitude lower than CLS. PL had a gammamin of 19-20 dyn/cm, significantly greater than CLS (nearly zero). Addition of the HA to PL restored dynamic interfacial behavior to nearly that of CLS. However, m2 remained at a reduced level. Addition of the SP-A to PL + HA restored m2 to a level similar to that of CLS. No further improvement in function occurred with the addition of the neutral lipid. These results support prior studies that show addition of HA to the PL markedly increases adsorption and film stability. However, SP-A is required to completely normalize dynamic behavior.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1999

Hearing conservation: an industry-school partnership.

An informal observation of hearing test results of employees in hearing conservation programs noted hearing losses among younger workers. As part of a community service project for the Arizona Valle del Sol Association of Occupational Health Nurses, a pilot hearing conservation program was implemented in two junior high schools in Mesa, Arizona. Occupational health nurses conducted sound level measurements in band rooms and industrial technology (shop) classes. Members of the professional association then taught classes of seventh, eighth, and ninth graders about the effects of noise on hearing; how to protect their hearing and use hearing protection; and how to keep their ears clean. Pre- and post-tests were distributed. Sound levels ranged from about 80 to 110 decibels in band rooms and 95-110 decibels in shop rooms. The post-tests revealed increases in knowledge regarding the effects of noise on hearing, ways to determine if noise is damaging to hearing, and safe measures to clean ears. Students also indicated a willingness to wear hearing protection when exposed to noise. The success of this pilot program supports the expansion of a partnership between industry and schools with the goal of hearing conservation.

Adolescent↗
PubMed1999

Mutations of CTSK result in pycnodysostosis via a reduction in cathepsin K protein.

Pycnodyostosis, an autosomal recessive osteosclerosing skeletal disorder, has recently been shown to result from mutations in the cathepsin K gene. Cathepsin K, a lysosomal cysteine protease with an abundant expression in osteoclasts, has been implicated in osteoclast-mediated bone resorption and remodeling. DNA sequence analysis of the cathepsin K gene in a nonconsanguineous family demonstrated compound heterozygozity for mutations in two affected siblings. We have identified a missense mutation with a single base G-->A transition at cDNA nucleotide 236, resulting in conversion of a conserved glycine to a glutamine residue (G79E). The other mutation is an A-->T transition at nucleotide 154, leading to the substitution of a lysine residue by a STOP codon (K52X) predicting premature termination of the precursor cathepsin K polypeptide. Sequencing of genomic and cDNAs from the parents demonstrated that the missense mutation was inherited from the father and the nonsense mutation from the mother. Protein expression in both affected children was virtually absent, while in the parents was reduced by 50-80% compared with controls. The protein studies demonstrate that even significantly reduced cathepsin K levels do not have any phenotypic effect, whereas absent cathepsin K results in pycnodysostosis.

Cathepsin K↗
PubMed1999

Fluticasone alone or in combination with salmeterol vs triamcinolone in asthma.

OBJECTIVES: To compare the efficacies of medium-dose fluticasone propionate (FP), medium-dose triamcinolone acetonide (TAA), and combined low-dose FP plus salmeterol (SL). DESIGN: Randomized, double-blind, triple-dummy, multicenter, 12-week clinical trial. SETTING: Allergy/respiratory care clinics. PATIENTS: Six hundred eighty patients with asthma previously uncontrolled with low-dose inhaled corticosteroids. INTERVENTIONS: FP, 220 microg bid; TAA, 600 microg bid; or FP, 88 microg plus SL, 42 microg bid. MEASUREMENTS AND RESULTS: Outcome measures included FEV1, peak expiratory flow (PEF), supplemental albuterol use, nighttime awakenings, asthma symptoms, and physician global assessment. Compared with TAA, 600 microg bid, treatment with FP 220, microg bid, significantly increased FEV1, morning and evening PEF, and percent symptom-free days, and significantly reduced rescue albuterol use, number of nighttime awakenings, and overall asthma symptom scores (p < or = 0.035). Improvements with low-dose FP, 88 microg, plus SL, 42 microg bid, were significantly (p < or = 0.004) greater than TAA, 600 microg bid, in all the aforementioned efficacy measures as well as percent of rescue-free days. Combined low-dose FP, 88 microg, plus SL, 42 microg bid, also significantly increased FEV1 and percent of rescue-free days, and significantly reduced albuterol use compared with medium-dose FP, 220 microg bid (p < or = 0.018). At endpoint, both FP, 220 microg bid, and FP, 88 microg, plus SL, 42 microg bid, significantly increased FEV1 by 0.48 L and 0.58 L, respectively, compared with 0.34 L with TAA, 600 microg bid. CONCLUSION: In patients who are symptomatic while taking low-dose inhaled corticosteroids, medium-dose FP (440 microg/d) and combination treatment with low-dose FP (176 microg/d) plus SL (84 microg/d) are both more effective than medium-dose TAA (1200 microg/d) in improving pulmonary function and asthma symptom control.

Administration, Inhalation↗
PubMed1999

Temporal stability of ambulatory blood pressure and heart rate in youths.

BACKGROUND: The use of ambulatory blood pressure monitoring for pediatric populations is increasing. OBJECTIVE: ; To determine the 2-year stability of ambulatory blood pressure in youths. METHODS: We evaluated 2-year stabilities of resting and ambulatory blood pressures in 197 youths (aged 13.9+/-2.3 years at initial evaluation). Readings were taken every 20 min during the daytime (0800-2200 h) and every 30 min at night (0000-0600 h). RESULTS: Daytime and night-time systolic blood pressure increased (P < 0.01 for both) as did resting systolic blood pressure (P < 0.05). Measures of diastolic blood pressure did not change. Changes in systolic blood pressure were related to changes in body size. Estimates of stability for resting and ambulatory measurements were similar, ranging from 0.65 to 0.75. In addition, correlation coefficients for relationships between first and second readings for resting and ambulatory measurements were similar ranging from 0.43 and for resting heart rate to 0.72 for 24h systolic blood pressure (P < 0. 001 for each). The only significant correlation between change scores for resting and ambulatory values was that between resting and night-time diastolic blood pressures (r = 0.33, P < 0.001). CONCLUSION: Measures of blood pressure derived from ambulatory blood pressure monitoring reflect changes in blood pressure in youths at least as well as do changes in resting blood pressure despite the high degree of variability in levels of physical activity and affective states of the children during the ambulatory recordings.

Adolescent↗
PubMed1999

Promoting breastfeeding in the neonatal intensive care unit.

The technology and separation of the mother and baby in the neonatal unit make bonding difficult and create barriers to breastfeeding. This pilot study aimed to define those nursing interventions that promote breastfeeding. The neonatal nurse plays a vital role in the influence of the breastfeeding outcome. Forty-one preterm babies had their breastfeeding activities, (including kangaroo care), recorded daily. The specific phases in preterm infants of 32 weeks or more were identified as 1. stabilisation and assessing ability, 2. controlled challenge, 3. progression and regression and 4. stability of feeding activity. This study has increased the awareness among the neonatal nurses involved as to the nursing practices that promote breastfeeding and has provided a basis from which nurses can promote breastfeeding to mothers of preterm babies.

Adult↗
PubMed1999

[Standards for neonatal intensive care nursing: unit directed management standards].

The neonate has the right to quality nursing care and the Neonatal Intensive nursing care practitioner is professionally-ethically and personally liable for quality nursing care. The process of quality improvement is a structured, planned and purposeful action were standards are set and the nursing care is evaluated after which remedial steps are taken to improve quality nursing care. In this study the focus is on the first step in the quality assurance cycle:the setting of standards. The purpose of the study is to describe and formulate standards for Neonatal Intensive nursing care which can be utilised as an accreditation instrument for institutional selfevaluation to improve quality nursing care. Standards for Neonatal Intensive nursing care were developed and validated by utilising a three-phase research method. In phase one subjects for standards were identified by a panel of experts. The identification was done by means of a critical debate, after which a preliminary conceptual framework was formulated. During the second phase a literature control was done to refine the conceptual framework. It consisted of a conceptual framework pertaining to unitmanagement (article 1) and an conceptual framework pertaining to high incidency, high risk interactions in the Neonatal Intensive Care Unit. The conceptual framework pertaining to the high incidency, high risk interactions in the Neonatal Intensive Care Unit consisted of: assessment of the neonate preparedness for neonatal resuscitation mechanical ventilation humidification during ventilation physiotherapy and suctioning of the ventilated neonate weaning during mechanical ventilation ecstubation During the third phase, the standards were validated by means of a consencus debate. An accreditation instrument was developed for institutional selfevaluation to improve quality nursing care in the Neonatal Intensive Care Unit. The standards that were formulated consisted of standards for unitmanagement (article 1) and standards directed at high incidency, high risk interactions in the Neonatal Intensive Care Unit which is published in the second article in this series.

Accreditation↗
PubMed1998

GABA(B) receptors function as a heteromeric assembly of the subunits GABA(B)R1 and GABA(B)R2.

The principal inhibitory neurotransmitter GABA (gamma-aminobutyric acid) exerts its effects through two ligand-gated channels, GABA(A) and GABA(C) receptors, and a third receptor, GABA(B) , which acts through G proteins to regulate potassium and calcium channels. Cells heterologously expressing the cloned DNA encoding the GABA(B)R1 protein exhibit high-affinity antagonist-binding sites, but they produce little of the functional activity expected from studies of endogenous GABA(B) receptors in the brain. Here we describe a new member of the GABA(B) polypeptide family, GABA(B)R2, that shows sequence homology to GABA(B)R1. Neither GABA(B)R1 nor GABA(B)R2, when expressed individually, activates GIRK-type potassium channels; however, the combination of GABA(B)R1 and GABA(B)R2 confers robust stimulation of channel activity. Both genes are co-expressed in individual neurons, and both proteins co-localize in transfected cells. Moreover, immunoprecipitation experiments indicate that the two polypeptides associate with each other, probably as heterodimers. Several G-protein-coupled receptors (GPCRs) exist as high-molecular-weight species, consistent with the formation of dimers by these receptors, but the relevance of these species for the functioning of GPCRs has not been established. We have now shown that co-expression of two GPCR structures, GABA(B)R1 and GABA(B)R2, belonging to the same subfamily is essential for signal transduction by GABA(B) receptors.

Amino Acid Sequence↗
PubMed1998

Altered p53 is associated with aggressive behavior of chondrosarcoma: a long term follow-up study.

BACKGROUND: p53 is a major tumor suppressor gene that has been implicated in the biology of a variety of human neoplasms, including some that affect the skeleton. Recent studies based on small numbers of cases have shown that overexpression or alteration of the p53 gene is frequently present in high grade, clinically aggressive chondrosarcomas of bone. In this study, the authors addressed the relation between overexpression and alteration of the p53 gene and the clinical aggressiveness of chondrosarcoma in a large series of patients for whom long term follow-up data were available. METHODS: The authors analyzed the expression and/or alteration of the p53 gene in 158 cases of chondrosarcoma of bone using immunohistochemistry, single-strand conformation polymorphism, and direct sequencing. They then related the findings to various clinicopathologic parameters and long term follow-up data. RESULTS: The presence of overexpression and/or structural alterations of the p53 gene was documented in 38.1% of chondrosarcomas of bone. A statistically significant correlation was observed between overexpression or alteration of the p53 gene and both the histologic grade of the tumor and the presence of metastasis. The probability of local recurrence free, metastasis free, and overall survival was significantly higher for patients with no overexpression or alteration of p53 than for patients with p53 overexpression or alteration. CONCLUSIONS: Overexpression or alteration of the p53 gene is an important predictor of aggressive clinical behavior in chondrosarcoma of bone.

Adolescent↗
PubMed1998

Human serum attenuates the activity of protease inhibitors toward wild-type and mutant human immunodeficiency virus.

The potency of therapeutic regimens containing human immunodeficiency virus (HIV) protease inhibitors is related to the ability to maintain concentrations of drug in the plasma of patients that are sufficient for blocking viral replication. The estimation of concentrations required for in vivo activity using in vitro assays is complicated by the fact that extensive binding of many protease inhibitors to serum proteins attenuates their antiviral potency. To provide insight into the relative in vivo potency of current protease inhibitors, we assayed their in vitro activity against wild-type and mutant HIV in the presence of human serum (HS). Using this assay, ABT-378, a new protease inhibitor with trough levels in humans far in excess of the EC50 in the presence of 50% HS, was identified. The antiviral activity of ABT-378 was only modestly attenuated by HS, in contrast to ritonavir, saquinavir, and nelfinavir. Examination of the effect of individual serum components suggested that the activity of ABT-378 is affected predominantly by binding to alpha1-acid glycoprotein (AGP) while the activity of ritonavir is modulated by both AGP and albumin. The method described here may provide insight into the in vivo potency of protease inhibitors and be useful for the preclinical evaluation and selection of new protease inhibitors for clinical studies.

Blood Proteins↗
PubMed1998

Nigrostriatal dopaminergic activities in dementia with Lewy bodies in relation to neuroleptic sensitivity: comparisons with Parkinson's disease.

BACKGROUND: In dementia with Lewy bodies (DLB) mild extrapyramidal symptoms are associated with moderate reductions in substantia nigra neuron density and concentration of striatal dopamine. Many DLB patients treated with typical neuroleptics suffer severe adverse reactions, which result in decreased survival. METHODS: In a series of DLB cases, with and without neuroleptic sensitivity, substantia nigra neuron densities, striatal dopamine and homovanillic acid concentrations, and autoradiographic [3H]mazindol and [3H]raclopride binding (to the dopamine transporter and D2 receptor, respectively) were analyzed and compared to control and idiopathic Parkinson's disease cases. RESULTS: D2 receptors were up-regulated in neuroleptictolerant DLB and Parkinson's disease compared to DLB without neuroleptic exposure and controls. D2 receptors were not up-regulated in DLB cases with severe neuroleptic reactions. Dopamine uptake sites were reduced concomitantly with substantia nigra neuron density in Parkinson's disease compared to controls, but there was no significant correlation between substantia nigra neuron density and [3H]mazindol binding in DLB groups. There was no significant difference in substantia nigra neuron density, [3H]mazindol binding, and dopamine or homovanillic acid concentration between neuroleptic-tolerant and -sensitive groups. CONCLUSIONS: Failure to up-regulate D2 receptors in response to neuroleptic blockade or reduced dopaminergic innervation may be the critical factor responsible for neuroleptic sensitivity.

Adult↗