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Biomedical subjects

A Jordan

Publications and source records attributed to A Jordan.

At least 37 records · Page 2Linked to original sources

Objectivity and reliability in qualitative analysis: realist, contextualist and radical constructionist epistemologies.

The effect of the individual analyst on research findings can create a credibility problem for qualitative approaches from the perspective of evaluative criteria utilized in quantitative psychology. This paper explicates the ways in which objectivity and reliability are understood in qualitative analysis conducted from within three distinct epistemological frameworks: realism, contextual constructionism, and radical constructionism. It is argued that quality criteria utilized in quantitative psychology are appropriate to the evaluation of qualitative analysis only to the extent that it is conducted within a naive or scientific realist framework. The discussion is illustrated with reference to the comparison of two independent grounded theory analyses of identical material. An implication of this illustration is to identify the potential to develop a radical constructionist strand of grounded theory.

Humans↗

Hsp70 plasma membrane expression on primary tumor biopsy material and bone marrow of leukemic patients.

A tumor-selective cell surface localization of heat shock protein 70 (Hsp70), the major heat-inducible member of the Hsp70 group, correlates with an increased sensitivity to lysis mediated by human natural killer (NK) cells and, therefore, might be of clinical relevance. With the exception of mammary carcinomas, an Hsp70 plasma membrane expression was found on freshly isolated human biopsy material of colorectal, lung, neuronal, and pancreas carcinomas, liver metastases, and leukemic blasts of patients with acute myelogenous leukemia. Since normal tissues and bone marrow of healthy human individuals do not express Hsp70 on the cell surface, Hsp70 can be considered as a tumor-selective structure in vivo. Furthermore, we demonstrate that autologous, Hsp70-positive leukemic blasts can be killed by NK cells stimulated with low doses of interleukin 2 plus recombinant Hsp70 protein.

Adenocarcinoma↗

A new model of thermal inactivation and its application to clonogenic survival data for WiDr human colonic adenocarcinoma cells.

Based on the analysis of clonogenic survival data for human colonic adenocarcinoma cells (WiDr) after a single heating, a new model is proposed to describe cell survival after hyperthermia quantitatively. The effects of heat are explained as heat-induced cell damage assuming a first-order (single-hit) and a second-order (cumulative damage) process. Thus cell survival at a specified temperature can be described by the linear-quadratic (LQ) model. The proposed model is based on an alternative definition of the (single) thermal dose, given as the (normalized) product of heating time and a specified nonlinear function of the increase in temperature (relative to a threshold temperature) to be interpreted as the thermal dose rate. In further analogy to the modeling of the effects of low-dose-rate radiation, an inherent capacity of the cells to repair sublethal damage is assumed, and these effects are quantified by the usual g factor measuring incomplete repair effects. The model defines thermal dose-response and isoeffect dose relationships, enabling a direct (i. e. single-step) analysis of the available thermal response data. Additionally, the analysis of our data based on heating times in the range from 0 to 360 min and temperatures from 41 to 46 degrees C and covering a broad spectrum of different densities of cells seeded for colony formation did not yield any evidence of the existence of a breaking point usually derived from Arrhenius plots based on the single-hit, multitarget model and the Arrhenius equation. The model includes no specific assumptions describing the development of thermotolerance, which can be assumed to be negligible under our experimental conditions. The proposed thermal dose-response model correlates satisfactorily with the in vitro survival data for WiDr adenocarcinoma cells.

Adenocarcinoma↗

Maximal isometric strength of the cervical musculature in 100 healthy volunteers.

STUDY DESIGN: A descriptive study involving maximal isometric strength measurements of the cervical musculature. OBJECTIVES: To determine the maximal isometric strength of the flexors and extensors and of the cervical musculature in 100 healthy volunteers (50 men and 50 women). SUMMARY OF BACKGROUND DATA: The literature contains only a few descriptive studies pertaining to strength levels of the cervical musculature. These studies include small subject populations, and measurement methods have demonstrated weak reliability. METHODS: Testing was carried out using strain-gauge technology on a neck muscle training apparatus. RESULTS: A reliability study demonstrated acceptable intraday and day-to-day values. Maximal isometric strength was approximately 20% to 25% higher in male subjects than female subjects in both flexion and extension from the third to the sixth decades. In the seventh decade, the women's strength levels surpassed values for men in both flexion and extension. Extension-flexion ratios were approximately 1.7 to 1 in both the men and women participants. The men demonstrated a significant decrease in maximal isometric strength with increasing age in both flexion and extension, whereas the women were able to maintain strength values in the ages tested. CONCLUSIONS: Men and women demonstrate impressive levels of muscular strength in the flexors and extensors of the cervical spine and can maintain these values until the seventh decade of life. Successful rehabilitation of the cervical musculature will require considerable resistance for sufficient stimulation of the cervical musculature.

Adult↗

Allosteric control of three B12-dependent (class II) ribonucleotide reductases. Implications for the evolution of ribonucleotide reduction.

Three separate classes of ribonucleotide reductases are known, each with a distinct protein structure. One common feature of all enzymes is that a single protein generates each of the four deoxyribonucleotides. Class I and III enzymes contain an allosteric substrate specificity site capable of binding effectors (ATP or various deoxyribonucleoside triphosphates) that direct enzyme specificity. Some (but not all) enzymes contain a second allosteric site that binds only ATP or dATP. Binding of dATP to this site inhibits the activity of these enzymes. X-ray crystallography has localized the two sites within the structure of the Escherichia coli class I enzyme and identified effector-binding amino acids. Here, we have studied the regulation of three class II enzymes, one from the archaebacterium Thermoplasma acidophilum and two from eubacteria (Lactobacillus leichmannii and Thermotoga maritima). Each enzyme has an allosteric site that binds ATP or various deoxyribonucleoside triphosphates and that regulates its substrate specificity according to the same rules as for class I and III enzymes. dATP does not inhibit enzyme activity, suggesting the absence of a second active allosteric site. For the L. leichmannii and T. maritima enzymes, binding experiments also indicate the presence of only one allosteric site. Their primary sequences suggest that these enzymes lack the structural requirements for a second site. In contrast, the T. acidophilum enzyme binds dATP at two separate sites, and its sequence contains putative effector-binding amino acids for a second site. The presence of a second site without apparent physiological function leads to the hypothesis that a functional site was present early during the evolution of ribonucleotide reductases, but that its function was lost from the T. acidophilum enzyme. The other two B12 enzymes lost not only the function, but also the structural basis for the site. Also a large subgroup (Ib) of class I enzymes, but none of the investigated class III enzymes, has lost this site. This is further indirect evidence that class II and I enzymes may have arisen by divergent evolution from class III enzymes.

Allosteric Regulation↗

[Tube feeding in malnutrition].

Malnutrition is known to be very common in geriatric patients. The incidence is ranging from 30 to 60% of all patients. Therefore, indication for nutritional support via nasogastric or percutaneous tubes is frequently given. Since percutaneous endoscopic gastrostomy (PEG) has several advantages over nasogastric tube feeding including reduced risk of tube displacement and blockage, and higher patient acceptance, it has become the method of choice in enteral tube feeding. Complication rates are low provided that guidelines for enteral tube feeding are considered. Early home enteral nutrition contributes to patients quality of life.

Aged↗

Empowerment evaluation as a social work strategy.

This article explores the application of empowerment strategies to program evaluation within a community health setting and presents a case study to examine the policy, direct practice, and research issues associated with the plan to evaluate a community-based HIV-prevention program. Empowerment evaluation strategies were used to develop an innovative street outreach intervention that can be measured and evaluated, to transfer evaluation knowledge from the researcher-expert to the program stakeholders, and to help overcome evaluation implementation obstacles. The article addresses the benefits and risks inherent in an empowerment approach to the evaluative research process.

Community Health Services↗

Visualization and registration of three-dimensional E-field distributions in annual-phased-array applicators.

A testing system is presented allowing registration, digitization, and evaluation of three-dimensional power distributions rendered by annular-phased-array applicators in homogeneous liquid media. The system is based on a lamp phantom originally developed to visualize power distributions. Now the brightness distribution is registered via a charge-coupled device camera and transferred to a PC-based evaluation system outside the shielding room. An appropriate mechanical coupling of camera and sensor matrix probing the phantom was built in order to keep optical image conditions constant under movement. For visualization and evaluation commercially customized software was employed. The evaluation of the system shows the linearity between sensor signal and power density magnitude to be sufficient for evaluation and graphical representation of three-dimensional data sets. In a first practical application the testing system was employed to evaluate dependencies of power distributions as a function of frequency and phase settings on temperatures and, subsequently, the relevance of those results for clinical hyperthermia in a SIGMA-60 applicator (BSD-2000 system). Now, the system is ready to evaluate more complex multiantenna array applicators like the SIGMA-Eye applicator. The measuring system is particularly suitable for a fast comparison of APA applicators applied for a homogeneous medium. Implications for heterogeneous structures (like in patients) are then possible via modeling calculations.

Calibration↗

Ribonucleotide reduction in Pseudomonas species: simultaneous presence of active enzymes from different classes.

Three separate classes of ribonucleotide reductases exist in nature. They differ widely in protein structure. Class I enzymes are found in aerobic bacteria and eukaryotes; class II enzymes are found in aerobic and anaerobic bacteria; class III enzymes are found in strict and facultative anaerobic bacteria. Usually, but not always, one organism contains only one or two (in facultative anaerobes) classes. Surprisingly, the genomic sequence of Pseudomonas aeruginosa contains sequences for each of the three classes. Here, we show by DNA hybridization that other species of Pseudomonas also contain the genes for three classes. Extracts from P. aeruginosa and P. stutzeri grown aerobically or microaerobically contain active class I and II enzymes, whereas we could not demonstrate class III activity. Unexpectedly, class I activity increased greatly during microaerobic conditions. The enzymes were separated, and the large proteins of the class I enzymes were obtained in close to homogeneous form. The catalytic properties of all enzymes are similar to those of other bacterial reductases. However, the Pseudomonas class I reductases required the continuous presence of oxygen during catalysis, unlike the corresponding Escherichia coli enzyme but similar to the mouse enzyme. In similarity searches, the amino acid sequence of the class I enzyme of P. aeruginosa was more related to that of eukaryotes than to that of E. coli or other proteobacteria, with the large protein showing 42% identity to that of the mouse, suggesting the possibility of a horizontal transfer of the gene. The results raise many questions concerning the physiological function and evolution of the three classes in Pseudomonas species.

Aerobiosis↗

Depression in Europe. Geographical distribution among older people.

BACKGROUND: This is the first report of results from the EURODEP Programme. AIMS: To assess the prevalence of depression judged suitable for intervention in randomised samples of those aged > or = 65 in nine European centres. METHOD: The GMS-AGECAT package. RESULTS: Differences in prevalence are apparent, 8.8% (Iceland) to 236% (Munich). When sub-cases and cases are added together, five high- and four low-scoring centres emerge. Women predominated over men. Proportions of sub-cases to cases revealed striking differences but did not explain prevalence. There was no constant association between prevalence and age. A meta-analysis (n = 13,808) gave an overall prevalence of 12.3%, 14.1% for women and 8.6% for men. CONCLUSIONS: Considerable variation occurs in the levels of depression across Europe, the cause for which is not immediately obvious. Case and sub-case levels taken together show greater variability, suggesting that it is not a matter of case/sub-case selection criteria, which were standardised by computer. Substantial levels of depression are shown but 62-82% of persons had no depressive level. Opportunities for treatment exist.

Age Distribution↗

Cross-cultural comparison of depressive symptoms in Europe does not support stereotypes of ageing.

BACKGROUND: Stereotypes of older people suggest that they are depressed. AIMS: To examine depression symptoms among people aged > or = 65 in the general population and to ask the following questions. Are there high proportions of depressive symptoms among otherwise well people? Do these levels reflect the prevalence of depression? Do key symptoms vary with age and do they confirm stereotypes? METHOD: Nine centres contributed data from community-based random samples, using standardised methods (GMS-AGECAT package). RESULTS: Proportions of depressive symptoms varied between centres. Some often associated with ageing were rare. Many were more common in women. Low-prevalence centres tended to have fewer symptoms among 'well' people, but there were inconsistencies. Low levels of symptoms among the well population of a centre did not necessarily predict lower levels in the depressed. CONCLUSIONS: Variations in the prevalence of depressive symptoms occurred between centres, not always related to levels of illness. There was no consistent relationship between proportions of symptoms in well persons and cases for all centres. Few symptoms were present in > 60% of the older population--stereotypes of old age were not upheld.

Age Factors↗

Structure of Salmonella typhimurium nrdF ribonucleotide reductase in its oxidized and reduced forms.

The first class Ib ribonucleotide reductase R2 structure, from Salmonella typhimurium, has been determined at 2.0 A resolution. The overall structure is similar to the Escherichia coli class Ia enzyme despite only 23% sequence identity. The most spectacular difference is the absence of the pleated sheet and adjacent parts present in the E. coli R2 structure; the heart-shaped structure loses its tip. From sequence comparisons, it appears that this feature is shared with all other class Ib enzymes and, in this respect, is more like the mammalian class Ia enzymes. Both the oxidized and reduced iron forms have been investigated. In the ferric iron center, both iron ions are octahedrally coordinated and bridged by one carboxylate and one oxide ion. The ferrous form has lost the bridging oxide ion but is bridged by two carboxylates. Accompanying the change in redox state, helix E changes its conformation from one covering the metal center in the oxidized form to a more open reduced form. A narrow channel is opened which may permit easier access of oxygen to the ferrous iron site and to efficiently generate the tyrosyl radical.

Amino Acid Sequence↗

The manganese-containing ribonucleotide reductase of Corynebacterium ammoniagenes is a class Ib enzyme.

Ribonucleotide reductases (RNRs) are key enzymes in living cells that provide the precursors of DNA synthesis. The three characterized classes of RNRs differ by their metal cofactor and their stable organic radical. We have purified to near homogeneity the enzymatically active Mn-containing RNR of Corynebacterium ammoniagenes, previously claimed to represent a fourth RNR class. N-terminal and internal peptide sequence analyses clearly indicate that the C. ammoniagenes RNR is a class Ib enzyme. In parallel, we have cloned a 10-kilobase pair fragment from C. ammoniagenes genomic DNA, using primers specific for the known class Ib RNR. The cloned class Ib locus contains the nrdHIEF genes typical for class Ib RNR operon. The deduced amino acid sequences of the nrdE and nrdF genes matched the peptides from the active enzyme, demonstrating that C. ammoniagenes RNR is composed of R1E and R2F components typical of class Ib. We also show that the Mn-containing RNR has a specificity for the NrdH-redoxin and a response to allosteric effectors that are typical of class Ib RNRs. Electron paramagnetic resonance and atomic absorption analyses confirm the presence of Mn as a cofactor and show, for the first time, insignificant amounts of iron and cobalt found in the other classes of RNR. Our discovery that C. ammoniagenes RNR is a class Ib enzyme and possesses all the highly conserved amino acid side chains that are known to ligate two ferric ions in other class I RNRs evokes new, challenging questions about the control of the metal site specificity in RNR. The cloning of the entire NrdHIEF locus of C. ammoniagenes will facilitate further studies along these lines.

Amino Acid Sequence↗

Intensive training, physiotherapy, or manipulation for patients with chronic neck pain. A prospective, single-blinded, randomized clinical trial.

STUDY DESIGN: A randomized, prospective clinical study was conducted that included 119 patients with chronic neck pain of greater than 3 months' duration. OBJECTIVES: To compare the relative effectiveness of intensive training of the cervical musculature, a physiotherapy treatment regimen, and chiropractic treatment on this patient group. SUMMARY OF BACKGROUND DATA: There are only a few studies involving chronic neck pain patients representative of those seeking care in primary health care centers. Mobilization techniques and intensive training have been shown to be useful, but cervical manipulation has not been assessed. Clinical results involving these commonly used therapies have not been compared. METHODS: A total of 167 consecutive patients were screened. One hundred nineteen patients were admitted to the study and were randomized according to Taves' minimization principles. Primary outcome measures included self-reported pain, disability, medication use, patients' perceived effect, and physician's global assessment. Patients were assessed at enrollment and at completion of the study. Postal questionnaires were used to carry out 4- and 12-month follow-up assessments. Secondary outcome measures included active range of motion of the cervical spine as well as strength and endurance measurements of the cervical musculature. These measurements were carried out at enrollment and completion of the study. RESULTS: A total of 88% of the patients completed the study. Of these, 97% completed the 4-month questionnaire and 93% the 12-month questionnaire. Patients from all three groups demonstrated significant improvements regarding self-reported pain and disability on completion of the study. Improvements were maintained throughout the follow-up period. Medication use was also significantly reduced in all groups. There was, however, no significant difference between groups at any assessment period. Physician's and patients' assessments were also positive, and again group scores were essentially equal. Patients who underwent intensive training demonstrated significantly greater endurance levels at the completion of treatment. CONCLUSIONS: There was no clinical difference between the three treatments. All three treatment interventions demonstrated meaningful improvement in all primary effect parameters. Improvements were maintained at 4- and 12-month follow-up. However, whether this was a result of the treatments or simply a result of time is unknown. Future studies will be necessary to delineate ideal treatment strategies.

Adult↗

Tubulin as a target for anticancer drugs: agents which interact with the mitotic spindle.

Tubulin is the biochemical target for several clinically used anticancer drugs, including paclitaxel and the vinca alkaloids vincristine and vinblastine. This review describes both the natural and synthetic agents which are known to interact with tubulin. Syntheses of the more complex agents are referenced and the potential clinical use of the compounds is discussed. This review describes the biochemistry of tubulin, microtubules, and the mitotic spindle. The agents are discussed in relation to the type of binding site on the protein with which they interact. These are the colchicine, vinca alkaloid, rhizoxin/maytansine, and tubulin sulfhydryl binding sites. Also included are the agents which either bind at other sites or unknown sites on tubulin. The literature is reviewed up to October 1997.

Antibiotics, Antineoplastic↗

Ribonucleotide reductases.

Ribonucleotide reductases provide the building blocks for DNA replication in all living cells. Three different classes of enzymes use protein free radicals to activate the substrate. Aerobic class I enzymes generate a tyrosyl radical with an iron-oxygen center and dioxygen, class II enzymes employ adenosylcobalamin, and the anaerobic class III enzymes generate a glycyl radical from S-adenosylmethionine and an iron-sulfur cluster. The X-ray structure of the class I Escherichia coli enzyme, including forms that bind substrate and allosteric effectors, confirms previous models of catalytic and allosteric mechanisms. This structure suggests considerable mobility of the protein during catalysis and, together with experiments involving site-directed mutants, suggests a mechanism for radical transfer from one subunit to the other. Despite large differences between the classes, common catalytic and allosteric mechanisms, as well as retention of critical residues in the protein sequence, suggest a similar tertiary structure and a common origin during evolution. One puzzling aspect is that some organisms contain the genes for several different reductases.

Allosteric Regulation↗

Intensive dynamic training for females with chronic neck/shoulder pain. A randomized controlled trial.

OBJECTIVES: To compare the clinical effectiveness of an intensive three-month training programme with a less intensive programme on females suffering from chronic neck/shoulder pain. STUDY DESIGN: A prospective observer-blinded clinical trial including 12-month pretreatment follow-up. SETTING: Patients were referred to the Departments of Rheumatology and Physical Medicine at Hvidovre Hospital by their general practitioners. Training was undertaken at a satellite clinic for physiotherapy of Hvidovre Hospital. SUBJECTS: Female patients aged 18-65 years suffering from chronic neck/shoulder pain for a minimum of six months. INTERVENTION: Patients were examined by a physician in order to exclude serious diseases. They were then randomized to either an intensive neck/shoulder training programme or a programme of lesser intensity but of similar duration. MAIN OUTCOME MEASURES: Scales measuring pain and activities of daily living (ADL) were used, and strength and endurance measurements of the cervical and shoulder muscles were carried out at baseline and completion of the study. Follow-up measurements were carried out by postal questionnaire at 6 and 12 months after inclusion, and included pain, ADL and treatment satisfaction measurements. RESULTS: Seventy-seven patients were included in the trial, of whom 27 (69%) completed the intensive programme and 25 (61%) the lighter programme. Forty-one (>80%) completed the follow-up questionnaires. The patients in the two groups did not differ with regard to age, pain, ADL scores and physical measurements prior to training. Patients in both groups that completed the trial demonstrated statistically significant improvements in nearly all of the outcome measurements at completion. ADL scores maintained statistical significance at 12 months in both groups, but pain scores were only significantly improved in the intensive group at 12 months follow-up. There was no statistically significant difference between groups regarding pain or ADL, but overall 50% of all patients showed improvement. CONCLUSIONS: The type of low-tech dynamic training used in either of our two programmes resulted in both subjective and objective improvements in patients suffering from chronic neck/shoulder pain, but there were no statistically significant differences in outcome between the two approaches. The subjective improvements were maintained throughout the follow-up period.

Activities of Daily Living↗