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Biomedical subjects

Linda Johnson

Publications and source records attributed to Linda Johnson.

16 recordsLinked to original sources
PubMed2006

Positron emission tomography and leiomyomas: clinicopathologic analysis of 3 cases of PET scan-positive leiomyomas and literature review.

INTRODUCTION: Studies have suggested that PET scans can differentiate between leiomyomas and leiomyosarcomas. Our experience, however, shows that PET scan-positive smooth muscle tumors are not necessarily malignant. CASE REPORTS: Three patients with cancer underwent PET imaging. In all three, the most worrisome finding was a PET scan-positive uterine tumor. After surgical extirpation, all three uterine tumors were found to be benign smooth muscle neoplasms. DISCUSSION: To explore the potential reason these tumors were positive on PET imaging, we performed a detailed histopathologic and immunohistochemical study of all specimens. Pathologic evaluation revealed a leiomyoma, a cellular leiomyoma, and a stromomyoma. There was no association between an increased Ki67 (proliferative) index and positivity on PET imaging. Increased vascularity, however, appeared to be a feature common to the leiomyomas that were PET-positive.

Female↗
PubMed2006

Context conditioning and behavioral avoidance in a virtual reality environment: effect of predictability.

BACKGROUND: Sustained anxiety can be modeled using context conditioning, which can be studied in a virtual reality environment. Unpredictable stressors increase context conditioning in animals. This study examined context conditioning to predictable and unpredictable shocks in humans using behavioral avoidance, potentiated startle, and subjective reports of anxiety. METHODS: Subjects were guided through three virtual rooms (no-shock, predictable, unpredictable contexts). Eight-sec duration colored lights served as conditioned stimuli (CS). During acquisition, no shock was administered in the no-shock context. Shocks were paired with the CS in the predictable context and were administered randomly in the unpredictable context. No shock was administered during extinction. Startle stimuli were delivered during CS and between CS to assess cued and context conditioning, respectively. To assess avoidance, subjects freely navigated into two of the three contexts to retrieve money. RESULTS: Startle between CS was potentiated in the unpredictable context compared to the two other contexts. Following acquisition, subjects showed a strong preference for the no-shock context and avoidance of the unpredictable context. CONCLUSIONS: Consistent with animal data, context conditioning is increased by unpredictability. These data support virtual reality as a tool to extend research on physiological and behavioral signs of fear and anxiety in humans.

Adult↗
PubMed2006

Low-dose Mycobacterium bovis infection in cattle results in pathology indistinguishable from that of high-dose infection.

To understand the relevance of aerogenic transmission for bovine tuberculosis, it is important to study cattle experimentally infected with low doses of Mycobacterium bovis that result in pathology of the lower respiratory tract resembling that of most naturally infected cattle. In this study, we have compared and contrasted granuloma distribution and formation from cattle infected with low doses (1-1000 colony-forming units (cfu)) of M. bovis over 24 weeks. We also studied the expression of the cytokine IFN-gamma in lymph nodes by immunohistochemistry (IHC) as well as by ELISA from in vitro-stimulated peripheral blood cells. Our results confirmed that 50% of cattle infected with only 1cfu of field strain (AF2122/97) M. bovis developed advanced granulomas in thoracic lymph nodes. The degree of lesion advancement and granuloma distribution was similar between the lowest dose group (1cfu) and the highest of the 4 groups (1000cfu). The number of acid-fast bacilli identified within the granulomas was also similar among all groups. IFN-gamma expression was not significantly correlated with the infective dosage in either granuloma IHC or ante-mortem ELISA. These studies confirm that within the same time period, the smallest possible infective dose, properly administered, can produce pathology indistinguishable from a dose 1000-fold greater.

Animals↗
PubMed2006

Immunohistochemical markers augment evaluation of vaccine efficacy and disease severity in bacillus Calmette-Guerin (BCG) vaccinated cattle challenged with Mycobacterium bovis.

Development of necrotic granulomas in response to Mycobacterium bovis infection in cattle is pathognomonic for bovine tuberculosis. Previously our laboratory reported on M. bovis granuloma classification by stage of lesion advancement within bovine lymph nodes and developed immunohistochemical markers to further characterize these granulomas. In this study of bovine lymph node granulomas we applied this classification system to assess the dynamics of vaccination challenge. Lymph nodes collected from cattle vaccinated with M. bovis bacillus Calmette-Guerin (BCG) and subsequently challenged with virulent M. bovis were compared to lymph nodes from unvaccinated, challenged cattle. Expression of interferon-gamma (IFN-gamma), transforming growth factor-beta (TGF-beta), type I procollagen and cell marker identification of T cells, B cells, macrophages and WC1(+)gammadelta TCR+ cells were assessed. Granulomas formed in vaccinated cattle were greatly reduced in number, area, degree of necrosis and peripheral fibrosis and contained fewer Langhans' giant cells, acid fast bacilli, WC1(+)gammadelta TCR+ cells and less TGF-beta expression in comparison to controls. B cells clustered intensely along the outer granuloma margins within vaccinated calves, with significantly more IFN-gamma producing cells identified in the medullary regions of lymph nodes from BCG-vaccinated animals compared to unvaccinated controls. This may be indicative of immune activation and surveillance in regions not directly associated with ongoing disease. Lymph node evaluation using light microscopy and immunohistochemical markers is useful to assess the immune response and discriminate granulomas to determine vaccine efficacy and disease severity.

Animals↗
PubMed2006

Leptin enhances lung maturity in the fetal rat.

Pulmonary alveolar type II cells synthesize and secrete phospholipids and surfactant proteins. In most mammalian species, the synthesis of phospholipids and proteins of lung surfactant increases with fetal lung maturation, which occurs late in gestation. Factors that may promote lung maturation and surfactant production include the placental hormone, leptin, whose expression increases with advancing gestational age. We demonstrate that physiologic concentrations of leptin (1 and 10 ng/mL) increase the levels of surfactant proteins (SP) A, B, and C mRNA as well as SP-A and SP-B protein in d-17 fetal rat lung explants in vitro. To determine whether leptin exerts similar effects in vivo, we administered leptin antenatally to pregnant rats and compared its effects to that of dexamethasone, a known mediator of fetal lung development. Antenatal treatment with leptin for 2 d significantly increased the average weight of the fetal lungs in relation to their body weight. Histologic analysis revealed that the increase in fetal lung weight was accompanied by an increase in the number and maturation of type II alveolar cells and the expression of surfactant proteins B and C in these cells. Collectively, these results suggest that leptin is a cytokine regulator of rat fetal lung maturity.

Animals↗
PubMed2006

Assessment of individual and combined toxicities of four non-essential metals (As, Cd, Hg and Pb) in the microtox assay.

Although most researches with non-essential metals (NEMs) have been done with single or individual metals, in reality, organisms are often exposed to multiple contaminants at the same time through the air, food and water. In this study, we tested the toxicity of four NEMs, As, Cd, Pb, and Hg, individually and as a composite mixture using the microtox bioassay. This assay uses the reduction of bioluminescence of the bacterium Vibrio fischeri as a measure of toxicity. The concentrations of each chemical in the mixture were based on multiples of their maximum contaminant levels (MCLs) set by the U.S. EPA. The highest concentration of exposure was 20 times the MCL, which translated into 200, 100, 40 and 300 ppb for As, Cd, Hg and Pb, respectively. The ratio for the mixture from these concentrations was 10:5:2:15 for As, Cd, Hg and Pb, respectively. Among the individual metals tested, the ranking of toxicity was Hg>Pb>Cd>As based on the EC50 values of 109, 455, 508 and 768 ppb for Hg, Pb, Cd and As, respectively. The EC50 for the composite mixture was 495% MCL which translated into nominal concentrations of 49, 25, 10 and 74 ppb for As, Cd, Hg, and Pb, respectively. Overall, the EC50 value of each NEM within the mixture was lower than the EC50 of the individual chemical; an evidence of synergism for the mixture. The individual toxic units (TU) were 0.06, 0.05, 0.09, and 0.16 for As, Cd Hg, and Pb, respectively and the summed toxic unit (TU) was 0.37 (less than 1). This study provides needed scientific data necessary for carrying out complete risk assessment of As, Cd, Hg, and Pb mixtures of some priority compounds.

Aliivibrio fischeri↗
PubMed2005

Anticipation of public speaking in virtual reality reveals a relationship between trait social anxiety and startle reactivity.

BACKGROUND: Startle reflex modification has become valuable to the study of fear and anxiety, but few studies have explored startle reactivity in socially threatening situations. METHODS: Healthy participants ranging in trait social anxiety entered virtual reality (VR) that simulates standing center-stage in front of an audience to anticipate giving a speech and count backward. We measured startle and autonomic reactivity during anticipation of both tasks inside VR after a single baseline recording outside VR. RESULTS: Trait social anxiety, but not general trait anxiety, was positively correlated with startle before entering VR and most clearly during speech anticipation inside VR. Speech anticipation inside VR also elicited stronger physiologic responses relative to anticipation of counting. CONCLUSIONS: Under social-evaluative threat, startle reactivity showed robust relationships with fear of negative evaluation, a central aspect of social anxiety and clinical social phobia. Context-specific startle modification may be an endophenotype for subtypes of pathological anxiety.

Adult↗
PubMed2005

Cardiac and CNS defects in a mouse with targeted disruption of suppressor of fused.

The hedgehog (Hh) pathway is conserved from Drosophila to humans and plays a key role in embryonic development. In addition, activation of the pathway in somatic cells contributes to cancer development in several tissues. Suppressor of fused is a negative regulator of Hh signaling. Targeted disruption of the murine suppressor of fused gene (Sufu) led to a phenotype that included neural tube defects and lethality at mid-gestation (9.0-10.5 dpc). This phenotype resembled that caused by loss of patched (Ptch1), another negative regulator of the Hh pathway. Consistent with this finding, Ptch1 and Sufu mutants displayed excess Hh signaling and resultant altered dorsoventral patterning of the neural tube. Sufu mutants also had abnormal cardiac looping, indicating a defect in the determination of left-right asymmetry. Marked expansion of nodal expression in 7.5 dpc embryos and variable degrees of node dysmorphology in 7.75 dpc embryos suggested that the pathogenesis of the cardiac developmental abnormalities was related to node development. Other mutants of the Hh pathway, such as Shh, Smo and Shh/Ihh compound mutants, also have laterality defects. In contrast to Ptch1 heterozygous mice, Sufu heterozygotes had no developmental defects and no apparent tumor predisposition. The resemblance of Sufu homozygotes to Ptch1 homozygotes is consistent with mouse Sufu being a conserved negative modulator of Hh signaling.

Animals↗
PubMed2004

Partial analysis of the genomes of two nontypeable Haemophilus influenzae otitis media isolates.

In 1995, The Institute for Genomic Research completed the genomic sequence of a rough derivative of Haemophilus influenzae serotype d, strain KW20. This sequence, though extremely useful in understanding the basic biology of H. influenzae, has yet to provide significant insight into our understanding of disease caused by nontypeable H. influenzae (NTHI), because serotype d strains are not generally pathogens. In contrast, NTHI strains are frequently mucosal pathogens and are the primary pathogens of chronic otitis media as well as a significant cause of acute otitis media in children. Thus, it is of great importance to further understand their biology. We used a DNA-based microarray approach to identify genes present in a clinical isolate of NTHI that were absent from strain Rd. We also sequenced the genome of a second NTHI isolate from a child with chronic otitis media to threefold coverage and then used an array of bioinformatics tools to identify genes present in this NTHI strain but absent from strain Rd. These methods were complementary in approach and results. We identified, in both strains, homologues of H. influenzae lav, an autotransported protein of unknown function; tnaA, which encodes tryptophanase; as well as a homologue of Pasteurella multocida tsaA, which encodes an alkyl peroxidase that may play a role in protection against reactive oxygen species. We also identified a number of putative restriction-modification systems, bacteriophage genes and transposon-related genes. These data provide new insight that complements and extends our ongoing analysis of NTHI virulence determinants.

Bacterial Proteins↗
PubMed2003

Expression of the F-box protein SKP2 induces hyperplasia, dysplasia, and low-grade carcinoma in the mouse prostate.

Low or absent expression of the cyclin-dependent kinase inhibitor p27(Kip1) serves as an excellent malignant marker for prostate and other human cancers. The level of p27(Kip1) is regulated primarily by the ubiquitin E3 ligase SCF(SKP2) through ubiquitin-dependent proteolysis. Expression of the F-box protein SKP2 is inversely correlated with p27 in many cancers. To determine the role of SCF(SKP2) in proliferation and tumorigenesis, we established transgenic mouse lines that specifically expressed SKP2 in the prostate gland. Unscheduled expression of SKP2 promoted marked overproliferation, resulting in hyperplasia, dysplasia, and low-grade carcinoma in the prostate gland. Consistent with its critical role in p27 proteolysis, SKP2 expression caused significant down-regulation of p27 in prostate glands from transgenic animals. Immunohistological staining indicated that SKP2 expression is restricted to the hyperplastic/dysplastic regions and that there is an inverse relationship between SKP2 and p27 expression in the ductal epithelium in transgenic animals. The prostate glands from transgenic mice also exhibited high levels of proliferative and mitotic markers such as Ki67 and cyclin B1. Our data suggest that SKP2 acts as an oncoprotein in the mouse prostate gland, probably through its function as a limiting factor for ubiquitin-dependent degradation of p27.

Animals↗
PubMed2003

Effect of an implantable cardioverter defibrillator with atrial detection and shock therapies on patient-perceived, health-related quality of life.

BACKGROUND: This study used a device (DDD implantable cardioverter defibrillator [ICD]) capable of delivering pacing and shock therapies to restore normal sinus rhythm in patients with atrial tachycardias or atrial fibrillation (AF). The purpose of this study was to assess the effect of the device on patient-perceived, health-related quality of life (QOL). METHODS: The DDD ICD was implanted in 267 patients with drug refractory, symptomatic AF from 45 centers across Europe, the United States, and Canada. Patients completed self-reported, validated QOL assessments at baseline and at 3- and 6-month follow-up visits (The Medical Outcomes Short Form 36 [SF-36] and the Symptom Checklist [SCL]). RESULTS: The mean age of the study group was 62 +/- 12 years, and 73% of the patients were male. A total of 150 patients completed SF-36 assessments, and 138 patients completed SCL assessments at all 3 times. Baseline scores were more impaired (P <.05) on most SF-36 scales compared with norms for a general population, but were similar to a comparison group of patients with AF who were referred to tertiary care centers. The role-physical, physical functioning, vitality, mental health, and social functioning scales all improved significantly with time (all P <.04). Similarly, symptom frequency and severity (SCL) also improved significantly from baseline to 6 months (both P <.01). Shock therapy was delivered in 86 of the 150 patients (57%) with complete SF-36 evaluations. There was no evidence that receiving shocks decreased the relative improvement in QOL associated with implantation of the device. CONCLUSIONS: In a 6-month period, QOL improves after implantation of a DDD ICD with atrial shock and pacing therapies. These improvements were not attenuated by receipt of shocks.

Atrial Fibrillation↗
PubMed2003

Early markers of late-onset sepsis in premature neonates: clinical, hematological and cytokine profile.

BACKGROUND: Late-onset sepsis in the NICU is a major problem associated with high morbidity and mortality. OBJECTIVE: To determine if clinical characteristics, hematological parameters and serial measurements of serum IL-6 and IL-8 can detect late-onset sepsis in premature neonates prior to positive blood cultures. DESIGN: The study was done in 2 phases. The first phase (S1) was a retrospective evaluation of clinical signs and timing of blood culture positivity in all neonates with late-onset cultures proven sepsis from 1991-1998. The second phase (S2) was a prospective study that enrolled infants > or = 72 hours old, suspected of sepsis based on the presence of criteria identified in S1. At that time (day 0), blood was drawn for a CBC with differential, blood culture, IL-6 and IL-8 levels; cytokine levels were repeated on day 1. Infants with positive cultures were diagnosed as confirmed sepsis; those with negative cultures, as no sepsis. RESULTS: S1: Of the 48 episodes of culture proven, late-onset sepsis, 54% of the blood cultures were positive by 24 hours and 90% by 48 hours. The most common presenting signs were desaturations (50%) and increased gastric residuals (33%); I/T ratio > 0.16 differentiated between gram-positive, negative and fungal infections (p = 0.007). S2: 27 infants were enrolled. Eight (mean [SEM] gestational age of 28.2 [0.94] weeks; birth weight of 1.15 [0.11] kg) had positive blood cultures; 19 (gestational age of 27.7 [0.9] weeks; birth weight of 1.06 [0.13] kg) had no sepsis. Infants with sepsis were more likely to have apnea/bradycardia (p = 0.002); no differences in hematological profile, as compared to those with no sepsis. Seven (88%) infants had positive blood cultures by 48 hours. Median values of IL-6 (pg/ml) were higher in infants with sepsis vs. those with no sepsis on days 0 [40 vs. 13] (p = 0.03) and 1 [24 vs. 9] (p < 0.001). IL-8 levels were not significantly different. CONCLUSIONS: In both S1 and S2, a majority of the blood cultures were positive by 48 hours. IL-6 levels on days 0 and 1 were significantly higher in infants with confirmed sepsis, prior to the blood culture being positive. IL-6 levels may be useful in the initiation as well as early termination of antibiotic therapy in late-onset neonatal sepsis.

Biomarkers↗
PubMedDate not supplied

Understanding the arousal of anger: a patient-centred approach.

The aim of this article is to enable reflection on practice by exploring a nurse-patient scenario and identifying what factors trigger anger and aggressive behaviour. It recommends strategies that can be used to tackle anger among patients, and emphasises the importance of the therapeutic relationship. Anger management, which usually refers to cognitive behavioural therapy designed to enable people to manage anger, is not explored.

Anger↗