Biomedical subjects

J L Johnson

Publications and source records attributed to J L Johnson.

At least 91 records · Page 5Linked to original sources

PubMed2000

Primate cytomegaloviruses encode and express an IL-10-like protein.

An open reading frame (ORF) with homology to interleukin-10 (IL-10) has been identified in rhesus cytomegalovirus (RhCMV). The IL-10-like protein is generated from a multispliced, polyadenylated early gene transcript encompassing part of the corresponding UL111A ORF of human CMV (HCMV). Immunological analyses confirm expression of the IL-10-like protein both in tissue culture and in RhCMV-infected rhesus macaques. Conserved ORFs were subsequently identified in human, baboon, and African green monkey CMV, and a fully processed transcript has been mapped in fibroblasts infected with the Towne strain of HCMV. The conservation of this previously unrecognized ORF suggests that the protein may play an essential role in primate CMV persistence and pathogenesis.

Amino Acid Sequence↗

PubMed2000

Analysis of prognosis and disease progression after local recurrence of melanoma.

BACKGROUND: Local recurrence of melanoma is associated with a grave prognosis. However, the characteristics and the mode of disease progression for patients with local recurrence have not been adequately addressed in the literature. METHODS: A retrospective analysis of patients treated at a single institution revealed a subset of patients (n = 648) with local recurrence of melanoma as a first event. Patient characteristics, histologic determinants, and disease free interval were variables used to identify prognostic factors. RESULTS: In this group of patients, male gender (P = 0. 0163), increasing age (P = 0.0001), head and neck primaries (P = 0. 0001), thicker Breslow depths (P = 0.0022), deeper Clark levels (P = 0.0010), and ulceration of the primary tumor (P = 0.0348) suggested a shorter time until local recurrence. Breslow depth (P = 0.0004), Clark level (P = 0.0043), and ulceration (P = 0.0001) still factored into the survival prognosis after recurrence. Truncal primaries (P = 0.0005) and shorter disease free intervals (P = 0.0098) were also associated with poorer outcomes after recurrence. Of the 648 patients, 124 showed no progression, 196 developed another local recurrence, 178 developed in-transit/lymph node metastases, and 150 had systemic recurrences. Survival was only 33.6% for patients with further metastases, compared with 77.4% for patients with no progression of disease after a median follow-up of 38.9 months. CONCLUSIONS: There was a 48.5% mortality rate at 5 years of follow-up after local recurrence. Long term survival (> 10 years) was estimated to be 34.9%. The patterns of failure after local recurrence suggest that patients may benefit from aggressive locoregional therapy.

Aged↗

PubMed2000

Maximal human neutrophil priming for superoxide production and elastase release requires p38 mitogen-activated protein kinase activation.

HYPOTHESIS: Neutrophil priming has been implicated in the development of multiple organ failure, although the precise intracellular mechanisms that regulate neutrophil priming remain unclear. Our previous work characterized platelet-activating factor (PAF) priming of human neutrophils for concordant superoxide anion (O2-) generation and elastase degranulation. The p38 mitogen-activated protein kinase (MAPK) is activated by PAF stimulation. We hypothesized that PAF-induced human neutrophil priming for O2- and elastase release is mediated via the p38 MAPK pathway. DESIGN: Isolated neutrophils from 6 human donors were preincubated with the specific p38 MAPK inhibitor SB 203580 (1 micromol/L) or buffer (control) for 30 minutes. Cells were then primed with PAF (200 nmol/L), followed by receptor-dependent (N-formyl-methionyl-leucyl-phenylalanine, 1 micromol/L) or receptor-independent phorbol myristate acetate (PMA, 100 ng/mL) activation. SETTING: Urban trauma research laboratory. PATIENTS: Healthy volunteer donors of neutrophils. MAIN OUTCOME MEASURES: Maximal rate of O2- generation was measured by superoxide dismutase-inhibitable reduction of cytochrome c and elastase release by the cleavage of N-methoxysuccinyl-Ala-Ala-Pro-Val-p-nitroanilide. RESULTS: SB 203580 significantly attenuated the generation of O2- and release of elastase from neutrophils activated with N-formyl-methionyl-leucyl-phenylalanine but not with PMA. Independent of the activator receptor status, SB 203580 almost completely blocked the exaggerated neutrophil cytotoxic response due to PAF priming. CONCLUSIONS: The p38 MAPK pathway is required for maximal PAF-induced neutrophil priming for O2- production and elastase degranulation. Therefore, the MAPK signaling cascade may offer a potential therapeutic strategy to preempt global neutrophil hyperactivity rather than attempt to nullify the end products independently.

Enzyme Activation↗

PubMed2000

Narratives of smoking relapse: the stories of postpartum women.

Many women who stop smoking during pregnancy relapse soon after the birth of their infants. Using narrative research, experiences of smoking relapse were explored using interviews with 27 postpartum women. The stories of relapse were analyzed to identify important components, paying attention to commonalities, differences, and areas of emphasis. Five general story lines were identified: (1) controlling one's smoking (starting with a "puff" and consciously restricting the amount smoked); (2) being vulnerable to smoking(relapsing because of an inability to resist cigarettes); (3) nostalgia for one's former self(relapsing to recapture feelings of freedom and happier times); (4) smoking for relief(relapsing to manage emotions and stress); and (5) never really having quit (relapsing because they did not quit for themselves). The findings of this study provide support for the claim that the experiences of smoking cessation and relapse among postpartum women may be unique and, consequently, may require specialized intervention.

Adaptation, Psychological↗

PubMed2000

Enhanced proliferation and differentiation of human articular chondrocytes when seeded at low cell densities in alginate in vitro.

Dedifferentiated human articular chondrocytes exhibited a wide variation in their capacity to proliferate and redifferentiate in an alginate suspension culture system. The greatest extent of proliferation and redifferentiation was seen to be dependent on the formation of clonal populations of chondrocytes and correlated inversely with the initial cell seeding density. Redifferentiating chondrocytes seeded at low density (1 x 10(4) cells/ml alginate) compared with chondrocytes that were seeded at high density (1 x 10(6) cells/ml alginate) showed a nearly 3-fold higher median increase in cell number. a 19-fold greater level of type-II collagen mRNA expression, a 4-fold greater level of aggrecan mRNA expression, and a 6-fold greater level of sulfated glycosaminoglycan deposition at 4 weeks of culture. Matrix molecules from low-density cultures were assembled into chondrocyte-encapsulated, spherical extracellular matrices that were readily visualized in sections from 12-week cultures stained with antibodies against types I and II collagen and aggrecan. Ultrastructural analysis of 12-week low-density cultures confirmed the presence of thin collagen fibrils throughout the matrix.

Adult↗

PubMed2000

Demonstrations of the influence of the eating environment on food acceptance.

In two independent demonstrations, pre-prepared food was served in different environments: first, identical prepared meals were served in both a training restaurant and in a student cafeteria; second, a prepared main dish was served in a food science laboratory class, and as part of an entire meal in two student cafeterias and in a training restaurant. In the training restaurants and in the student cafeterias, people selected and paid for their meals. The acceptability ratings of the food served varied across the three different environments in the following order: restaurant>laboratory>cafeteria. Differences in acceptance were attributed to contextual effects and the expectations they produce, actual product differences, and a number of possible covariates. Ratings of sensory attributes tended to mirror the acceptability effects. The difficulty of comparing contexts within actual food service systems is discussed.

Eating↗

PubMed2000

Reactions of Azotobacter vinelandii nitrogenase using Ti(III) as reductant.

Nitrogenase-catalyzed reactions using Ti(III) were examined under a wide variety of conditions to determine the suitability of Ti(III) to serve as a general nitrogenase reductant. Solutions prepared from H2-reduced TiCl3, aluminum-reduced TiCl3, TiCl2, evaporated TiCl3 from an HCl, solution, and TiF3 were evaluated as reductants. Three general types of reactivity were observed. The first showed that, below Ti(III) concentrations of about 0.50 mM, nitrogenase catalysis utilized Ti(III) in a first-order reaction. The second showed that, above 0.50 mM, the rate of nitrogenase catalysis was zero order in Ti(III), indicating the enzyme was saturated with this reductant. Above 2.0-5.0 mM, nitrogenase catalysis was inhibited by Ti(III) depending on the titanium source used for solution preparation. This inhibition was investigated and found to be independent of the buffer type and pH, while high salt and citrate concentrations caused moderate inhibition. [Ti(IV)] above 2.0-3.0 mM and [Ti(III)] above about 5.0 mM were inhibitory. ATP/2e values were 4-5 for [Ti(III)] at or below 1.0-2.0 mM, 2.0 from 5.0 to 7.0 mM Ti(III) where nitrogenase is not inhibited, and 2.0 above 7.0 mM Ti(III) where severe inhibition occurs. For nitrogenase-catalyzed reactions using Ti(III) as reductant, the potential of the solution changes with time as the Ti(III)/Ti(IV) ratio changes. From the change in the rate of product formation (Ti(III) disappearance) with change in solution potential, the rate of nitrogenase catalysis was determined as a function of solution potential. From such experiments, a midpoint turnover potential of -480 mV was determined for nitrogenase catalysis with an associated n = 2 value.

Adenosine Triphosphate↗

PubMed2000

The association of platelet-derived growth factor receptor expression, plaque morphology and histological features with symptoms in carotid atherosclerosis.

Platelet-derived growth factor may influence smooth muscle cell migration and proliferation and, therefore, carotid plaque composition and stenosis. Platelet-derived growth factor receptor expression and histological features were compared in carotid plaques from symptomatic and asymptomatic patients. Immunocytochemistry and histology determined platelet-derived growth factor-alpha and -beta receptor expression, white blood cell infiltration, smooth muscle cell, elastin, cholesterol, collagen and intraplaque haemorrhage in carotid artery plaques removed at surgery or the post-mortem. Plaques with > 70% stenosis from asymptomatic (n = 10) and symptomatic patients (n = 27) had higher expression of platelet-derived growth factor and beta receptors and higher scores for macrophages and intraplaque haemorrhage than plaques with < 70% stenosis from asymptomatic patients (n = 33). Plaques with > 70% stenosis from symptomatic patients had significantly lower alpha receptor expression than plaques with > 70% stenosis from asymptomatic patients. The reduction of alpha receptor expression, which may inhibit smooth muscle cell migration, suggests that differential expression of platelet-derived growth factor receptor subunits in plaques may be related to symptoms.

Aged↗

PubMed2000

Phase II study of infusional chemotherapy with doxorubicin, vincristine and etoposide plus cyclophosphamide and prednisone (I-CHOPE) in resistant diffuse aggressive non-Hodgkin's lymphoma: CALGB 9255. Cancer and Leukemia Group B.

BACKGROUND: Patients with resistant diffuse aggressive non-Hodgkin's lymphoma (DA-NHL) have a poor prognosis. Studies have suggested infusional therapy may be beneficial. PATIENTS AND METHODS: This trial used an infusional regimen called I-CHOPE in resistant patients who had previously received only bolus CHOPE or CHOP regimen. Resistance was defined as: a) primary refractory disease, b) progression on therapy, c) partial response, d) complete remission lasting less than one year. Eligibility criteria included a diagnosis of DA-NHL (IWF E-H), no prior irradiation and adequate organ function. RESULTS: Thirty-seven patients were entered and twenty-nine were eligible. Reasons for ineligibility were incorrect histology (5) and other (3). The median age was 57 years (range 29-81) with 21 males. The performance status scores were: 0 (12 patients); 1 (9 patients); 2 (8 patients). Prior therapy consisted of standard CHOP (26 patients), bolus CHOPE (2 patients), high dose CHOP (1 patient). Therapy consisted of a 120 hour continuous intravenous infusion of doxorubicin 10 mg/m2/day, vincristine 0.28 mg/m2/day (maximum 0.4 mg/day), and etoposide 48 mg/m2/day. Cyclophosphamide 750 mg/m2 was given as an i.v. bolus day 6 and prednisone was given at 100 mg/day p.o. on days 1-5. G-CSF was allowed for myelosuppression. The overall response rate was 48% (CR 17%; PR 31%). Freedom from progression was 24% at six months and 8% at one year. Survival was 69% at six months and 40% at one year. In an exploratory analysis a prior CR or PR predicted response to I-CHOPE. Twelve of sixteen patients who had a CR/PR on previous therapy responded while two of thirteen who had no prior response, responded to I-CHOPE (P = 0.003). The toxicity was tolerable with grade 3-4 hematologic toxicity being leucopenia 94% and thrombocytopenia 41%. The grade 3-4 non-hematologic toxicities were infection in 28%, phlebitis in 11%, and stomatitis in 15%. CONCLUSIONS: I-CHOPE can induce responses in this group of patients with a poor prognosis, but most were seen in those who had previously had a response to bolus chemotherapy.

Adult↗

PubMed2000

Positive and negative patterning in human causal learning.

Investigations of patterning discriminations by nonhuman animals have generally found that positive patterning is easier to learn than negative patterning. Studies of patterning discriminations in human causal learning tasks have failed to document any differences between positive and negative patterning. In the present study, human participants predicted an outcome on trials involving either a compound cue or its elements. Positive and negative patterning problems were successfully solved in a within-subjects design; negative patterning problems proved to be more difficult when an additional, 50% contingent cue was included (Experiment 2), but not when it was excluded (Experiment 1). Possible reasons for these results are discussed. The discussion concludes with an analysis of exemplar models (e.g., Pearce, 1994) of human causal learning and considers the conditions under which these models do and do not anticipate our results.

Adult↗

PubMed2000

Four earplugs in search of a rating system.

OBJECTIVE: The performance of four insert earplugs was evaluated by determining the Noise Reduction Rating (NRR) and the Subject-Fit Noise Reduction Rating [NRR(SF)]. The NRR and NRR(SF) were calculated from real-ear attenuation at threshold (REAT) data collected using the experimenter-fit protocol described in the now-rescinded ANSI S3.19-1974 (American National Standards Institute, 1974) and the subject-fit protocol of the recently revised ANSI S12.6-1997 (American National Standards Institute, 1997) standards for REAT measurement. DESIGN: A comparison of the experimenter-fit and subject-fit REAT performance was conducted using four pools of subjects, one pool per protector. Each device was tested with at least 20 subjects, the minimum size necessary to estimate the NRR(SF) for an earplug. The REAT was measured with third-octave narrowband noise stimuli for center frequencies at 0.125, 0.25,0.5, 1, 2, 3.15, 4, 6.3, and 8 kHz. The REAT means and standard deviations were compared with the manufacturer data. RESULTS: This study showed that the NRR(SF) is typically lower than the NRR and that the NRR(SF) is not well-predicted by the NRR derating schemes recommended by the National Institute for Occupational Safety and Health and required by the Occupational Safety and Health Administration. CONCLUSION: The difference between the present NRR on hearing protector labels and the NRR(SF) is sufficiently large and unpredictable enough to render the application of derating schemes meaningless even though these schemes attempt to account for the difference between the laboratory and real-world outcomes. The only way to provide a protector noise rating that is predictive of a real-world outcome is to retest the protector according to the subject-fit method of ANSI S12.6-1997 (American National Standards Institute, 1997).

Auditory Threshold↗

PubMed2000

Uncertainty and expectations: taking care of a cardiac surgery patient at home.

Family members of postsurgical patients are, by necessity, taking on the caregiving role sooner without any specified resources to help them. The input of these caregivers is essential so nurses can understand their concerns, needs, and struggles and develop strategies to support the caregivers in their caregiving role. This study was designed to increase nursing knowledge regarding the experiences of being a caregiver of a cardiac surgery patient during the immediate postdischarge period. The qualitative research method of Interpretative Description, first described by Thorne, Kirkham, and MacDonald-Emes in 1997 guided the study. In-depth interviews were held with eight spousal caregivers. Findings revealed that the experience was molded by caregivers' past participation as a caregiver, as well as caregivers' and care recipients' outlook on life, their interpersonal relationship, and their expectations. Caregivers engaged in the process of caregiving that involved being vigilant and monitoring the care recipient's recovery, implementing strategies to assist the recovery process, and taking on a role to provide care and seek help as required. The encounter with caregiving affected all realms of caregivers' lives, and they experienced feelings of stress, vulnerability, and having to put their lives on hold; these feelings were often compounded by uncertainty.

Aged↗

PubMed2000

Hypertonic saline resuscitation abrogates neutrophil priming by mesenteric lymph.

OBJECTIVE: Neutrophil (PMN) priming after hemorrhagic shock is predictive of the subsequent development of multiple organ failure, but the mechanism remains unknown. Recently, we and others have demonstrated that mesenteric lymph from shock animals resuscitated with lactated Ringer's solution (LR) is not only a potent PMN priming agent but also causes lung injury. Work by others has shown that resuscitation with hypertonic saline (HTS) protects animals from lung injury after hemorrhagic shock. Therefore, we hypothesize that resuscitation with HTS will abolish PMN priming by postshock mesenteric lymph. METHODS: After mesenteric lymph duct catheterization, male rats underwent hemorrhagic shock (mean arterial pressure of 40 mm Hg for 90 minutes) and resuscitation with shed blood plus either LR (2x volume of shed blood) or 4 mL/kg of 7% HTS (isonatremic). Priming for superoxide by PMN was measured after fMLP (1 microM) activation. RESULTS: Shock significantly decreased mesenteric lymph flow from preshock levels in both groups. LR resuscitation produced significantly more mesenteric lymph than HTS resuscitation. Mesenteric lymph from LR animals primed PMN for superoxide production, whereas, HTS eliminated this priming. CONCLUSION: HTS not only decreases postshock mesenteric lymph production, it eliminates PMN priming by mesenteric lymph, suggesting a mechanism for the beneficial effects of HTS resuscitation.

Animals↗

PubMed2000

Abdominal perfusion pressure: a superior parameter in the assessment of intra-abdominal hypertension.

OBJECTIVE: To assess the clinical utility of abdominal perfusion pressure (mean arterial pressure minus intra-abdominal pressure) as both a resuscitative endpoint and predictor of survival in patients with intra-abdominal hypertension. METHODS: 144 surgical patients treated for intra-abdominal hypertension between May 1997 and June 1999 were retrospectively reviewed. Multivariate logistic regression and receiver operating characteristic curve analysis of common physiologic variables and resuscitation endpoints were performed to determine the decision thresholds for each variable that predict patient survival. RESULTS: Abdominal perfusion pressure was statistically superior to both mean arterial pressure and intravesicular pressure in predicting patient survival from intra-abdominal hypertension and abdominal compartment syndrome. Multiple regression analysis demonstrated that abdominal perfusion pressure was also superior to other common resuscitation endpoints, including arterial pH, base deficit, arterial lactate, and hourly urinary output. CONCLUSION: Abdominal perfusion pressure appears to be a clinically useful resuscitation endpoint and predictor of patient survival during treatment for intra-abdominal hypertension and abdominal compartment syndrome.

Abdominal Injuries↗

PubMed2000

Adult tuberculosis overview: African versus Western perspectives.

Tuberculosis is currently an enormous global health problem. In industrialized countries in Western Europe and North America, tuberculosis case rates are low and an increasing proportion of cases now occur in foreign-born individuals and in marginalized populations, including the homeless, prisoners, drug users, and persons with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS). In contrast, the burden of tuberculosis in sub-Saharan Africa continues to grow, largely fueled by the HIV pandemic and poor public health infrastructure. Use of the World Health Organization's (WHO) directly observed therapy, short course (DOTS) strategy has been successful in improving outcomes and preventing the emergence of acquired drug resistance in several African countries; however, case rates are increasing throughout most of the region. It is clear that control of tuberculosis in Africa is closely linked to control of HIV and AIDS. Substantial external donor support and innovative approaches to enhance interactions between HIV/AIDS prevention and treatment efforts and tuberculosis control programs will be needed to improve the current tuberculosis situation in Africa. The purpose of this review is to provide a synopsis of recent developments in these areas and to serve as a reference source for interested readers.

AIDS-Related Opportunistic Infections↗

PubMed2000

A comparative In vitro surveillance study of gemifloxacin activities against 2,632 recent Streptococcus pneumoniae isolates from across Europe, North America, and South America. The Gemifloxacin Surveillance Study Research Group.

From 1997 to 1999, 94 study centers in 15 European, 3 North American, and 2 South American countries contributed 2,632 isolates of Streptococcus pneumoniae to an international antimicrobial susceptibility testing study. Only 62.0% of isolates were susceptible to penicillin, while 22.3% were penicillin intermediate and 15.6% were penicillin resistant. Resistance to trimethoprim-sulfamethoxazole (24.4%), azithromycin (26.0%), and clarithromycin (27.1%) was also highly prevalent. For the penicillin-resistant isolates (n = 411), the MICs at which 90% of isolates are inhibited (MIC(90)s) for gemifloxacin, levofloxacin, ofloxacin, clarithromycin, and azithromycin were 0.03, 1, 2, >16, and >64 microgram/ml, respectively. Similarly, for isolates resistant to both azithromycin and clarithromycin (n = 649), gemifloxacin, levofloxacin, ofloxacin, and penicillin MIC(90)s were 0.03, 1, 2, and 4 microgram/ml, respectively. Overall rates of resistance to trovafloxacin (0.3%), levofloxacin (0.3%), grepafloxacin (0.6%), and ofloxacin (0.7%) were low. For ofloxacin-intermediate and -resistant isolates (n = 142), gemifloxacin had the lowest MIC(90) (0.12 microgram/ml) compared to the MIC(90)s of trovafloxacin (0.5 microgram/ml), grepafloxacin (1 microgram/ml), and levofloxacin (2 microgram/ml). For all S. pneumoniae isolates tested, gemifloxacin MICs were </=0.5 microgram/ml, suggesting that gemifloxacin has the potential to be used as a treatment for pneumococcal infections, including those arising from isolates resistant to beta-lactams and macrolides.

Adolescent↗

PubMed2000

A role for the Hsp40 Ydj1 in repression of basal steroid receptor activity in yeast.

In addition to its roles in translocation of preproteins across membranes, Ydj1 facilitates the maturation of Hsp90 substrates, including mammalian steroid receptors, which activate transcription in yeast in a hormone-dependent manner. To better understand Ydj1's function, we have constructed and analyzed an array of Ydj1 mutants in vivo. Both the glucocorticoid receptor and the estrogen receptor exhibited elevated activity in the absence of hormone in all ydj1 mutant strains, indicating a strict requirement for Ydj1 activity in hormonal control. Glucocorticoid receptor containing a mutation in the carboxy-terminal transcriptional activation domain, AF-2, retained elevated basal activity, while mutation of the amino-terminal transactivation domain, AF-1, eliminated the elevated basal activity observed in ydj1 mutant strains. This result indicates that the source of activity is AF-1, which is normally repressed by the carboxy-terminal hormone binding domain in the absence of hormone. Chimeric proteins containing the hormone binding domain of the estrogen or glucocorticoid receptor fused to heterologous activation and DNA binding domains also exhibited elevated activity in the absence of hormone. Thus, Ydj1 mutants appear to increase basal receptor activity by altering the ability of the hormone binding domain of the receptor to repress nearby activation domains. We propose that Ydj1 functions to present steroid receptors to the Hsp90 pathway for folding and hormonal control. In the presence of Ydj1 mutants that fail to bind substrate efficiently, some receptor escapes the Hsp90 pathway, resulting in constitutive activity.

Electrophoresis, Polyacrylamide Gel↗

PubMed2000

Predicting the outcome of therapy for pulmonary tuberculosis.

Patients vary considerably in their response to treatment of pulmonary tuberculosis. Although several studies have indicated that adverse outcomes are more likely in those patients with delayed sputum sterilization, few tools are available to identify those patients prospectively. In this study, multivariate models were developed to predict the response to therapy in a prospectively recruited cohort of 42 HIV-uninfected subjects with drug-sensitive tuberculosis. The cohort included 2 subjects whose initial response was followed by drug-sensitive relapse. The total duration of culture positivity was best predicted by a model that included sputum M. tuberculosis antigen 85 concentration on Day 14 of therapy, days-to-positive in BACTEC on Day 30, and the baseline radiographic extent of disease (R = 0.63). A model in which quantitative AFB microscopy replaced BACTEC also performed adequately (R = 0.58). Both models predicted delayed clearance of bacilli in both relapses (> 85th percentile of all subjects) using information collected during the first month of therapy. Stratification of patients according to anticipated response to therapy may allow TB treatment to be individualized, potentially offering superior outcomes and greater efficiency in resource utilization, and aiding in the conduct of clinical trials.

Antitubercular Agents↗