Temperature/magnetization-induced distortions in the local structure of substituted LaMnO3.
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Journal Article↗
Biomedical subjects
M Anderson
Publications and source records attributed to M Anderson.
Transforming growth factor beta receptors in verrucous and squamous cell carcinoma.
OBJECTIVES: To study the intracellular location of transforming growth factor beta type II receptors (TbetaR-II) in verrucous carcinoma (VC) and squamous cell carcinoma (SqCC), and to evaluate their role in the biological behavior of both neoplasias. DESIGN: Ten VC and 10 well-differentiated SqCC specimens were analyzed by immunohistochemistry and in situ hybridization for the expression and intracellular location of TbetaR-II. Receptor expression was evaluated in areas of invasion and in areas of transformation of VC into SqCC. TbetaR-II expression was compared with expression of the type I receptor (TbetaR-I). SUBJECTS: Formalin-fixed, paraffin-embedded tissue sections from VCs and well-differentiated SqCCs, operated on at the H. L. Moffitt Cancer Center and Research Institute from May 1987 to January 1998, were selected for the study. INTERVENTIONS: None. RESULTS: While in all VCs TbetaR-II was found to be located along the membrane of the neoplastic keratinocytes, TbetaR-II expression in SqCC was observed predominantly in a cytoplasmic location. This cytoplasmic location of TbetaR-II was also seen in areas of transition from VC to SqCC. Expression of TbetaR-I was found in a cytoplasmic location in both tumor types. CONCLUSIONS: The membranous location of TbetaR-II in VC exposes the receptor to the growth inhibitory control of TGF-beta and may explain why VC tumors are less aggressive clinically. The marked reduction of membranous TbetaR-II and their predominant cytoplasmic location diminishes TGF-beta growth inhibition and may contribute to the transformation of VC into the more aggressive SqCC.
Activin Receptors, Type I↗
Persistent effects of doxorubicin on cardiac gene expression.
During administration of the anthracycline antitumour agents, their cardiotoxicity can progress from cardiac dysfunction to heart failure. Cardiomyopathy can also develop years after receiving anthracyclines. To determine if persistent and/or progressive anthracycline effect(s) are referable to anthracycline effects on cardiac gene expression, steady-state mRNA levels were determined 4 days (n=8), 4 weeks (n=7) and 10 weeks (n=7) after doxorubicin (DOX; 2 mg/kg IV) in a well-characterized rabbit model. Levels of mRNA for alpha -actin, beta -myosin heavy chain and the calcium pump of the sarcoplasmic reticulum (SERCA2a) in the left ventricle (LV) were determined by Northern blot hybridization and expressed relative to an 18S constitutive marker. The mRNA levels for the high molecular weight subunit (cardiac isoform) of the ryanodine receptor (RyR2), sarcolemmal calcium channel (dihydropyridine receptor; DHPR), angiotensin-converting enzyme (ACE), angiotensin II receptor (ATR) and atrial naturetic peptide prohormone (ANP) were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot analysis, and expressed relative to GAPDH, a constitutive marker. Histopathologic evidence for anthracycline-induced myocardial cell injury was absent (score <1) in all hearts examined except one (score=1.1; 4 weeks post-DOX), which was considered separately. Relative mRNA levels for beta -myosin heavy chain 4 days after DOX increased 1.9-fold compared to the vehicle-treated group, but by 4 weeks levels had returned to baseline. Relative mRNA levels for DHPR were increased 1.2-fold 4 days after DOX and were persistently increased 1.9- and 2.2-fold 4 and 10 weeks after DOX, respectively. The mRNA levels for ANP were first decreased (4.5-fold) 4 days after DOX. Four weeks after DOX, ANP message levels approached Control in seven out of eight rabbits. The one rabbit with early LV histopathology 4 weeks post-DOX had increased mRNA for DHPR (2.7-fold) and ANP (80-fold). Between 4 and 10 weeks after DOX, mRNA levels for ANP increased C 16-fold: evidence for late progression. In situ hybridization with specific riboprobes localized the persistent increase in DHPR and the progressive increase in ANP to myocytes. Thus, DOX alters steady-state mRNA levels in LV that are referable to both persistent and progressive anthracycline effects on myocellular gene expression.
Animals↗
Refolding, purification, and characterization of a loop deletion mutant of human Bcl-2 from bacterial inclusion bodies.
This report describes the cloning of recombinant human Bcl-2, in which the putative disordered loop region has been replaced with a flexible linker and the hydrophobic C-terminus has been replaced with a 6xHis tag (Bcl-2(6-32)-AAAA-Bcl-2(86-206)-HHHHHH, abbreviation rhBcl-2; amino acid numbering excludes the initiating methionine). This protein was expressed in Escherichia coli where it accumulated in insoluble form in inclusion bodies. After lysis the washed inclusion bodies were solubilized and an l-arginine assisted protein refolding route was employed to obtain biologically active protein. rhBcl-2 was purified further by nickel chelate chromatography to give protein of >95% purity, with an overall yield of 5 mg per g of E. coli cell paste. Edman sequencing showed that approximately 90% of the rhBcl-2 retained the initiating methionine residue. Analytical size exclusion chromatography suggested that the refolded and purified rhBcl-2 was monomeric in nondenaturing solution. Purified protein had an affinity for a Bax BH3 domain peptide comparable to that for in vivo folded recombinant human Bcl-2 and suppressed caspase activation in a cell-free assay for apoptosis. 1H NMR spectroscopy of rhBcl-2, both free and complexed with the Bax BH3 domain peptide, provided further evidence for the structural and functional integrity of the refolded protein. These findings parallel and extend those of Muchmore et al., who found that a loop deletion mutant of human Bcl-XL retained anti-apoptotic function.
Amino Acid Sequence↗
Use of the 6-methylsalicylic-acid-synthase gene as a discriminating marker between Aspergillus terreus and Aspergillus flavipes.
In nineteen pathogenic and saprophytic isolates denoted as Aspergillus terreus the presence and restriction pattern of the gene pksM (6-methylsalicylic acid synthase) was determined. Five patterns (A-E) were found and in three isolates the gene was missing. The RAPD (Random Amplified Polymorphic DNA) patterns with three primers were analyzed. The strains with pksM pattern possibly derived from the most common pattern A by single mutation (patterns B-D) were also related by RAPD. Among them, three clades were found. The first one contained saprophytes from Asia, the other two clades contained both European and American pathogens and each of them one saprophyte. The sequences of rDNA region containing 5.8S rDNA and spacers ITS1 and ITS2 were established for representatives of each group and the strains missing the pksM gene. The isolates possessing pksM (although with different restriction patterns) grouped as A. terreus group, whereas the isolates lacking this gene were close to Fennellia flavipes.
Acyltransferases↗
Disorientation combined with bilateral parietal cortex lesions causes path integration deficits in the water maze.
The navigational abilities of rats were examined using the water maze after disorientation induced by rotation and/or swimming in darkness. Control and light-disoriented groups performed similarly, whereas the dark group and the dark-disoriented groups were initially much slower but improved to control levels. After receiving bilateral parietal lesions, multiple start position tests showed that both rotation groups were severely impaired in finding the hidden platform. The effects of disorientation induced by darkness and by rotation are therefore separable.
Analysis of Variance↗
The use of research in local health service agencies.
A critical and often overlooked component of the use and transfer of research in the health care system is the local health and social service delivery agency. There is also very little understanding of the extent to which local community-based agencies conduct research internally to improve their operational capacity. More than ever, these local service organizations require research to guide activity in a rapidly changing health care environment which is characterized by diminishing health and social service budgets, de-institutionalization and concomitant increases and metamorphoses in service demands. This study interviewed 25 executive directors and held a focus group with a group of other directors to examine the use and transfer of research in these organizations. A number of central issues were identified by the directors that affect the contribution of research to the delivery of their programs and services. A conceptual model for developing 'locally-based research transfer' was subsequently outlined that could serve as the basis for enhanced research use and research transfer in other local area contexts.
Community Health Services↗
Ruptured abdominal aortic aneurysm, a "two-hit" ischemia/reperfusion injury: evidence from an analysis of oxidative products.
PURPOSE: Ruptured abdominal aortic aneurysm (RAAA) remains a lethal condition despite improvements in perioperative care. The consequences of RAAA are hypothesized to result from a combination of two ischemia/reperfusion events: hemorrhagic shock and lower torso ischemia. Ischemia/reperfusion results in tissue injury by diverse mechanisms, which include oxygen free radical-mediated injury produced from activated neutrophils, xanthine oxidase, and mitochondria. Oxygen-free radicals attack membrane lipids, resulting in membrane and subsequently cellular dysfunction that contributes to postoperative organ injury/failure. The purpose of this investigation was to quantify the oxidative injury that occurs as a result of the ischemia/reperfusion events in RAAAs and elective AAAs. METHODS: Blood samples were taken from 22 patients for elective AAA repair and from 14 patients for RAAA repair during the perioperative period. Plasma F(2)-isoprostanes were extracted, purified, and measured with an enzyme immunoassay. Aldehydes and acyloins were purified and quantified. Neutrophil oxidative burst was measured in response to a receptor independent stimulus (phorbol 12-myristate 13-acetate) with luminol-based chemiluminescence. RESULTS: Plasma from patients with RAAAs showed significantly elevated F(2)-isoprostane levels on arrival at hospital and were significantly elevated as compared with the levels of patients for elective repair throughout the perioperative period (two-way analysis of variance, P <.0001). Multiple regression showed a significant relationship between the phagocyte oxidative activity and F(2)-isoprostane levels (P <.013). Total acyloin levels were significantly higher in patients with RAAAs as compared with the levels in elective cases. CONCLUSION: The F(2)-isoprostane levels, specific markers of lipid peroxidation, showed that patients with RAAAs had two phases of oxidative injury: before arrival at hospital and after surgery. The significant relationship between the postoperative increases in F(2)-isoprostane levels and the neutrophil oxidant production implicates neutrophils in the oxidative injury that occurs after RAAA. New therapeutic interventions that attenuate neutrophil-mediated oxidant injury during reperfusion may decrease organ failure and ultimately mortality in patients with RAAAs.
Aldehydes↗
Genome-wide mapping with biallelic markers in Arabidopsis thaliana.
Single-nucleotide polymorphisms, as well as small insertions and deletions (here referred to collectively as simple nucleotide polymorphisms, or SNPs), comprise the largest set of sequence variants in most organisms. Positional cloning based on SNPs may accelerate the identification of human disease traits and a range of biologically informative mutations. The recent application of high-density oligonucleotide arrays to allele identification has made it feasible to genotype thousands of biallelic SNPs in a single experiment. It has yet to be established, however, whether SNP detection using oligonucleotide arrays can be used to accelerate the mapping of traits in diploid genomes. The cruciferous weed Arabidopsis thaliana is an attractive model system for the construction and use of biallelic SNP maps. Although important biological processes ranging from fertilization and cell fate determination to disease resistance have been modelled in A. thaliana, identifying mutations in this organism has been impeded by the lack of a high-density genetic map consisting of easily genotyped DNA markers. We report here the construction of a biallelic genetic map in A. thaliana with a resolution of 3.5 cM and its use in mapping Eds16, a gene involved in the defence response to the fungal pathogen Erysiphe orontii. Mapping of this trait involved the high-throughput generation of meiotic maps of F2 individuals using high-density oligonucleotide probe array-based genotyping. We developed a software package called InterMap and used it to automatically delimit Eds16 to a 7-cM interval on chromosome 1. These results are the first demonstration of biallelic mapping in diploid genomes and establish means for generalizing SNP-based maps to virtually any genetic organism.
Arabidopsis↗
Waiting for harm: deliberate self-harm and suicide in young people--a review of the literature.
Mental health professionals, particularly nurses, practicing in child and adolescent psychiatry are key players in the continued development of expertise, awareness and understanding of deliberate self-harm (DSH) and suicide in young people. Enhancing this knowledge and the associated skills will contribute to effective, therapeutic relationships with individuals and their families. The purpose of this paper is to review the current literature surrounding the issue of deliberate self-harm and suicide in young people. The paper will address national and international studies selected from a variety of child and adolescent and general psychiatric literature. The research presented highlights important issues to be addressed in practice. In particular, the evidence supports the influence of mental illness in DSH and suicide, particularly depression and substance abuse. However, a clearly important factor is an individual's experience of family and social life. The literature is considered in the light of relevant governmental policy documents relating to DSH and suicide. The future role of the mental health nurse in child and adolescent psychiatry in the United Kingdom (UK) is discussed in the contexts of family work and assessment.
Adolescent↗
Human tracheobronchial deposition and effect of a cholinergic aerosol inhaled by extremely slow inhalations.
Ten subjects inhaled the same amounts of cholinergic aerosol of a mass median diameter (MMD) of 7.7 microns in a normal provocation test and in a test with extremely slow inhalations (ESI). This new technique using ESI and large droplets/particles gives a high degree of deposition in small ciliated airways which cannot be obtained by using small particles. The purpose was to compare measured effects with calculated doses of the aerosol in large and small ciliated airways. The effect on large airways was measured by airway resistance (R(aw)), and the effect on small airways was measured by the phase III slope of single breath nitrogen test (N2-delta). Mouth and throat deposition was calculated from human experimental data, and deposition of the cholinergic aerosol into large and small airways was calculated, using a computerized lung model. The study showed that the extremely slow inhalation caused a larger effect on R(aw) and tendency to a larger effect on N2-delta compared to the effect in the normal provocation. Deposited dose in the large airways, in percent of inhaled dose, was calculated to be 25-33% for normal inhalation and 20-24% for ESI. Calculated deposited dose in the small airways (bronchioles; generations 12-16) was 1.8-3.4% for normal inhalation and 18-25% for ESI. For large airways a stronger effect was induced by ESI, perhaps by the more uniform distribution of particles within each generation, compared to normal inhalations when particles deposit near the bifurcations. Concerning the small airways, N2-delta did not differ significantly between normal and ESI provocations, indicating that they did not react much on cholinergic exposure. We believe that our approach using ESI for small airway deposition of a nebulized aerosol can be of value for estimating the effects of various substances on large and small airways.
Administration, Inhalation↗
Select 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors vary in their ability to reduce egg yolk cholesterol levels in laying hens through alteration of hepatic cholesterol biosynthesis and plasma VLDL composition.
The inability to markedly attenuate cholesterol levels in chicken eggs has led to speculation that cholesterol is essential for yolk formation and that egg production would cease when yolk cholesterol deposition was inadequate for embryonic survival. However, this critical level hypothesis remains unproven. Here, we determine the relative responsiveness of laying hens to three select inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR), the rate-limiting enzyme of cholesterol biosynthesis. A control diet, either alone or supplemented with one of two dietary levels (0.03 or 0.06%) of atorvastatin, lovastatin, or simvastatin, was fed to White Leghorn hens for 5 wk. Liver cholesterol concentrations (mg/g tissue) were decreased (P </= 0.05) by each HMGR inhibitor; however, total liver cholesterol (mg) did not differ among treatments. Microsomal hepatic HMGR activities were increased one- to twofold in all HMGR inhibitor-treated groups, while HMGR mRNA levels were unaffected. Diameters of plasma VLDL particles, the main cholesterol-carrying yolk precursor macromolecules, were reduced (P </= 0.05) only in hens fed 0.06% atorvastatin, and the particles contained 38% less total cholesterol (P </= 0.05) than controls. Plasma total cholesterol concentrations were lowered (P </= 0.05) by both doses of atorvastatin (-56, -63%) and simvastatin (-36,-45%). Egg cholesterol contents were maximally reduced by 46% (P </= 0.05), 7% (P > 0.05), and 22% (P </= 0.05) in hens fed the 0.06% level of atorvastatin, lovastatin, and simvastatin, respectively, while overall egg production [-19% (P </= 0.05), +4% (P > 0.05), and -3% (P > 0.05)], was much less affected. We concluded that cholesterol per se may not be an obligatory component for yolk formation in chickens and, as such, may be amenable to further pharmacological manipulation
Animals↗
Fixation, polyethylene wear, and pelvic osteolysis in primary total hip replacement.
A multicenter retrospective review was performed analyzing 1081 primary total hip replacements in 944 patients using the Harris Galante-I cementless acetabular component with screw fixation. All patients were followed up for a minimum of 5 years with a mean followup of 81 months. Linear polyethylene wear averaged 0.11 mm/year (range, 0-0.86 mm/year). Pelvic osteolysis was seen in 25 patients (2.3%). Migration of the acetabular component was seen in four hips. A subgroup of patients was reanalyzed at a minimum followup of 10 years. The mean linear polyethylene wear rate remained 0.11 mm/year. In this group, only one socket had migrated. There was an association between wear rate and age. On average, younger patients had higher wear rates. The risk for having pelvic osteolysis develop and the need for revision surgery also was age-related. Twenty-two percent of hip replacements (15 hips) in patients younger than 50 years of age at the time of their index operation had pelvic osteolysis develop. In contrast, for patients older than 50 years of age at the time of surgery only 7.8% (eight hips) had osteolysis of the pelvis develop. For patients older than 70 years of age at the time of primary total hip replacement, none had pelvic osteolysis develop.
Adolescent↗
Human T-cell leukemia virus type 2 Rex protein increases stability and promotes nuclear to cytoplasmic transport of gag/pol and env RNAs.
The human T-cell leukemia virus (HTLV) Rex protein is essential for efficient expression of the viral structural and enzymatic gene products. In this study, we assessed the role of the HTLV-2 rex gene in viral RNA expression and Gag protein production. Following transfection of human JM4 T cells with wild-type and rex mutant full-length proviral constructs, PCR was used for semiquantitative analysis of specific viral RNA transcripts. In the presence of Rex, the total amount of steady-state viral RNA was increased fourfold. Rex significantly up-regulated the level of incompletely spliced RNAs by increasing RNA stability and was associated with a twofold down-regulation of the completely spliced tax/rex RNA. PCR analysis of subcellular RNA fractions, isolated from transfected cells, indicated that the level of gag/pol and env cytoplasmic RNAs were increased 7- to 9-fold in the presence of Rex, whereas Gag protein production was increased 130-fold. These data indicate that HTLV-2 Rex increases the stability and promotes nucleus-to-cytoplasm transport of the incompletely spliced viral RNAs, ultimately resulting in increased structural protein production. Moreover, this model system provides a sensitive approach to further characterize HTLV gene expression from full-length proviral clones following transfection of human T cells.
B-Lymphocytes↗
Differential expression of keratins 10, 17, and 19 in normal cervical epithelium, cervical intraepithelial neoplasia, and cervical carcinoma.
AIM: To examine the value of immunohistochemistry in defining a keratin profile to aid cervical histopathological diagnosis. METHODS: Immunohistochemical localisation of keratins 17, 10, and 19 was studied in 268 cervical biopsies from 216 women including normal epithelia (with and without human papilloma virus), low and high grade cervical intraepithelial neoplasia, and invasive carcinoma. The percentage of positive immunostaining was scored using a Kontron MOP videoplan image analyser. RESULTS: All major categories of cervical epithelia expressed these keratins to varying degrees. The median percentage of immunostaining for keratin 10 was 40% in normal tissue compared with just 1% in invasive carcinoma (p < 0.0001). The medians for keratin 17 were 0% in the normal group and 80% in carcinomas (p < 0.0001). By contrast, there was no significant difference in staining for keratin 19. Using a combination of the keratin 10 and 17 percentages, it was possible to separate the carcinomas from the benign conditions with a sensitivity of 100% and a specificity of 93%. Further analyses within the groups revealed more extensive staining for keratins 10 and 19 in reserve cell hyperplasia, immature squamous metaplasia, and congenital transformation zone. CONCLUSIONS: The morphological variety within the cervix is reflected, in part, by distinct keratin patterns. There are striking differences in the patterns of keratins 10 and 17 between infiltrating squamous carcinoma and normal cervical epithelia.
Biomarkers, Tumor↗
Prevalence and associations of MRI-demonstrated brain infarcts in elderly subjects with a history of transient ischemic attack. The Cardiovascular Health Study.
BACKGROUND AND PURPOSE: MRI is more sensitive than CT, but the significance of brain abnormalities seen on MR images obtained in older subjects with transient ischemic attack (TIA) is not clear. We studied the prevalence and risk factors associated with MRI-demonstrated infarcts in elderly subjects with a history of TIA. METHODS: Participants of the Cardiovascular Health Study, aged 65 years or more and without prior stroke, were studied with brain MRI (n=3456). The prevalence of brain infarcts (>/=3 mm) on MRI was determined in subjects with and without TIA. The cardiovascular risk factors and clinical and subclinical cardiovascular disease associated with MRI infarcts were studied in subjects with TIA. RESULTS: Subjects with TIA (n=100) had a higher prevalence of MRI infarcts than subjects without TIA (46% versus 28%; P<0.001). The unadjusted odds ratio for having MRI infarcts in subjects with TIA was 2.20 (95% CI, 1.47 to 3.30) and remained significantly elevated after adjustments for risk factors and cerebrovascular disease (odds ratio, 1.86; 95% CI, 1.23 to 2.83). In subjects with TIA, diastolic blood pressure (P=0.01) and internal carotid artery intima-media thickness (P=0.01) were the only factors predictive of the presence of MRI infarcts by stepwise logistic regression analysis. CONCLUSIONS: MRI infarcts are imaging manifestations of clinically important cerebrovascular disease in subjects with a history of TIA, given their increased prevalence and positive association with increased diastolic blood pressure and internal carotid artery intima-media thickness.
Aged↗
Tecatas: an ethnotheoretical look at Mexican American female injecting drug users.
Ethnotheory is suggested as a way to study the roles Mexican American female injecting drug users play. It is suggested that ethnotheory extends present theoretical models used to explain and modify female IDUs' behavior; provide insights on female IDUs' roles useful for the development of effective intervention strategies; and suggests a type of ethnographic data collection that uncovers the subject's view of reality. Three detailed ethnographic excerpts from Mexican American female IDUs illustrate how female IDUs manage the array of roles they play and how information gained through ethnotheory is useful in the design of culturally relevant interventions.
Adult↗
Observations on the effects of low frequency electromagnetic fields on cellular transcription in Drosophila larvae reared in field-free conditions.
Drosophila larvae reared inside a micro-metal box with an internal field strength 0.004 microT, were treated with a magnetic field of 50 Hz, 8 microT. for 20 min. Control experienced 0.004 microT. Cellular transcript levels were assessed using slot blots and quantified using a Phosphorimager. Blots were hybridised using probes against HSP 70a, Histone 1.9, and Copia. The low frequency EMFs very significantly decreased transcript levels, indicating that experimental responses may be influenced by previous exposure or lack of previous exposure.
Analysis of Variance↗