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Biomedical subjects

A Jones

Publications and source records attributed to A Jones.

At least 145 records · Page 8Linked to original sources
PubMed2001

An examination of the MMPI-2 Wiener-Harmon Subtle subscales for D and Hy: implications for parent scale and neurotic triad interpretation.

This research explores the scale development process for the MMPI-2 Wiener and Harmon (1946) Subtle subscales for Depression (D) and Hysteria (Hy) to provide insight into why certain items were included on these scales and were subsequently but inappropriately assumed to be subtle indicators of the same pathology that the Obvious items measure. In this research, I also explore what the Subtle scales on D and Hy measure and their potential utility for the interpretation of their parent scales and the "neurotic triad." It was hypothesized that the D and Hy Subtle subscales are related to denial, repression, or both and this hypothesis was supported. In a sample of 1,240 inpatient and outpatient psychiatric patients at a large Army medical center, it was found that these subscales had strong positive correlations with othe scales on the Minnesota Multiphasic Personality Inventory-2 (MMPI-2; Butcher, Dahlstrom. Graham, Tellegen, & Kaemmer, 1989) related to denial, repression, or both. It was also found that they had strong negative correlations with scales on the MMPI-2 and Millon Clinical Multiaxial Inventory (MCMI-II; Millon, 1987) that are related to symptom endorsement, which can be considered the opposite of denial or repression. In addition, ratings of the Subtle items on D and Hy by clinical psychology residents were consistent with the hypothesis that these items reflect a denial of psychological or physical dysfunction.

Defense Mechanisms↗
PubMed2001

Role of radionuclide imaging in hyperthyroid patients with no clinical suspicion of nodules.

The purpose of the study was to assess the role of radionuclide imaging of hyperthyroid patients with no suspicion of nodules. (99)Tc(m) radionuclide scans performed on all 190 patients referred over a 2-year period with symptoms and thyroid function tests compatible with thyrotoxicosis were retrospectively reviewed. 73% of patients were referred by a hospital clinician and 27% were referred direct from the general practitioner. Referral letters and, where applicable, the clinical notes were reviewed and patients with suspected thyroid nodules were excluded. The results of (99)Tc(m) thyroid scans of the 190 patients (age range 23-93 years, mean 48 years) were reviewed. 152 (80%) patients had Graves' disease, 10 (5.3%) had Graves' disease with nodules, 6 (3.2%) had Graves' disease with non-functioning nodules, 5 (2.6%) had viral thyroiditis, 5 (2.6%) had autonomously functioning nodules and 12 (6.3%) were normal studies. Therefore, 20% of patients had a diagnosis other than solely Graves' disease. These diagnoses are important with respect to clinical management. In conclusion, routine radionuclide imaging is worthwhile, as a significant proportion of patients with clinical "Graves' disease" in this study would have received incorrect treatment without the result of this scan.

Adult↗
PubMed2001

Error in radiology.

The level of error in radiology has been tabulated from articles on error and on "double reporting" or "double reading". The level of error varies depending on the radiological investigation, but the range is 2-20% for clinically significant or major error. The greatest reduction in error rates will come from changes in systems.

Magnetic Resonance Imaging↗
PubMed2001

Monensin toxicosis in 2 sheep flocks.

Several lambs in 2 sheep flocks died suddenly and others were examined for generalized weakness and dyspnea. Postmortem findings were suggestive of degenerative myocardial and skeletal muscle myopathy, which was confirmed histologically. Feed analysis revealed toxic levels of monensin and ionophore toxicosis was diagnosed.

Animal Feed↗
PubMed2001

Relation of vascular endothelial growth factor production to expression and regulation of hypoxia-inducible factor-1 alpha and hypoxia-inducible factor-2 alpha in human bladder tumors and cell lines.

Hypoxia is an important regulator of vascular endothelial growth factor (VEGF) expression, and VEGF is associated with poor prognosis in bladder cancer. To investigate further the mechanisms of VEGF regulation, we examined VEGF expression by mRNA and protein analysis in four human bladder cancer cell lines, showing a progression from well to poorly differentiated phenotypes under varying conditions of confluence and hypoxia (0.1% O(2)) and with chemical mimics of hypoxia. Hypoxia significantly increased VEGF protein expression in all cell lines, although this effect was dependent on the degree of confluence. The superficial bladder cancer cell line RT4 lost hypoxia inducibility at confluence, whereas inducibility was maintained in the invasive cell lines 253J and EJ28. This pattern of VEGF expression in the invasive cell lines correlated with the expression of the transcription factor hypoxia inducible factor-1 alpha (HIF-1 alpha) and with hypoxia-inducible factor-2 alpha (HIF-2 alpha) and in RT4 correlated with a marked reduction in HIF-1 alpha inducibility at confluence. Using the phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor LY 294002, we show that this VEGF hypoxia-inducible pathway regulated by HIF-1 alpha is distinct from a PI 3-kinase-dependent pathway, which regulates basal amounts of VEGF, but does not affect inducibility. Both HIF-1 alpha and HIF-2 alpha protein and mRNA were up-regulated in primary human bladder tumors (n = 12) compared with normal bladder specimens (n = 4), with significant intertumor variation. These results suggest that components of the hypoxia response pathway, including HIF-1 alpha and HIF-2 alpha, are important cofactors in the regulation of VEGF in bladder cancer and are therapeutic targets in this disease.

Basic Helix-Loop-Helix Proteins↗
PubMed2001

Phase II study of direct intralesional gene transfer of allovectin-7, an HLA-B7/beta2-microglobulin DNA-liposome complex, in patients with metastatic melanoma.

Cutaneous melanoma is one of the most rapidly increasing cancers in the United States. Because of the lack of effective treatment options and toxicities of most chemotherapeutic and radiation regimes, immunotherapies such as vaccination therapy represent an attractive approach for patients with advanced melanoma. The purpose of this study was to evaluate the response rate, time to progression, and survival of patients with metastatic melanoma treated by direct intratumoral injection with Allovectin-7 (a plasmid DNA encoding the genes HLA-B7 and beta2-microglobulin complexed with a cationic lipid mixture, DMRIE/DOPE. Fifty-two patients with metastatic melanoma were enrolled in this Phase II study. Therapy consisted of six intratumoral injections of 10 microg of Allovectin-7 over a 9-week period. Treatment was well tolerated. Treatment-related adverse events were mild to moderate, the most frequent of which were ecchymosis, pruritus (and/or discomfort at the injection site), and pneumothoraces. Regression of the injected lesion was observed in 18% of patients, including one complete response, three partial responses, and five minor responses. An overall response rate of 4% (two partial responses) was documented, and nine patients (18%) maintained stable disease for at least 11 weeks. Six patients remained alive 25.1 to 39.4 months from their first injection, including two patients with local (injected tumor) responses and one patient with an overall disease partial response. This study demonstrates that intratumoral administration of Allovectin-7 in metastatic melanoma is safe and can produce both responses in injected lesions and in overall disease. Clinical trials optimizing patient selection and combining Allovectin-7 with other modalities of therapy are currently ongoing in an effort to improve response rates.

Adult↗
PubMed2001

Students' conceptual model of a good community attachment.

BACKGROUND: In 1994, Manchester University Medical School introduced a new integrated curriculum using problem-based learning and which places an increased emphasis on community-based education. AIMS: Students commonly use a particular label ("a good GP" (general practitioner)) to describe a positive experience in the community. The purpose of the study was to explore what students mean by "a good GP" and how this relates to their perceptions of the value of the community aspect of the course. METHOD: Three single-year focus groups were run with year 3, 4 and 5 students. A model was then derived which was explored and checked against the views of a cross-year focus group. RESULTS: A theoretical model based on student conceptualization of "a good GP" was developed. "A good GP" was found to consist of the GP as a teacher, as a role model and as an indicator of a positive learning environment. With regard to "good teacher", students felt that the GP's enthusiasm about teaching and involving the student in an active learning process was important. For "good role model", students emphasized communication skills and non-judgmental attitudes. With regard to "good learning environment", a friendly atmosphere, variety of activities, and flexibility shown by the staff of the health centre were important. CONCLUSIONS: Students hold a complex conceptual model of "a good GP" which the label does not convey. We suggest that for evaluations of student experiences it is important to explore in depth what students mean by particular terms or labels.

Attitude of Health Personnel↗
PubMed2001

Mechanistic studies on the reversible metabolism of rofecoxib to 5-hydroxyrofecoxib in the rat: evidence for transient ring opening of a substituted 2-furanone derivative using stable isotope-labeling techniques.

Rofecoxib is a potent and highly selective cyclooxygenase-2 inhibitor used for the treatment of osteoarthritis and pain. Following administration of [4-(14)C]rofecoxib to intact rats, the plasma C(max) (at approximately 1 h) was followed by a secondary C(max) (at approximately 10 h), which was not observed in bile duct-cannulated rats. Following administration of [4-(14)C]5-hydroxyrofecoxib to intact or bile duct-cannulated rats, radiolabeled rofecoxib was detected in plasma, and once again a secondary C(max) for rofecoxib was observed (at approximately 10 h), which occurred only in the intact animals. These results indicate that reversible metabolism of rofecoxib to 5-hydroxyrofecoxib occurs in the rat and that the process is dependent upon an uninterrupted bile flow. Studies on the contents of the gastrointestinal tract of rats showed that conversion of 5-hydroxyrofecoxib to parent compound occurs largely in the lower intestine. Treatment of rats with [5-(18)O]5-hydroxyrofecoxib, followed by liquid chromatography-tandem mass spectrometry analyses of plasma samples, confirmed that 5-hydroxyrofecoxib undergoes metabolism to the parent drug, yielding [1-(18)O]rofecoxib, [2-(18)O]rofecoxib, and unlabeled rofecoxib. Similarly, treatment with [1,2-(18)O(2)]rofecoxib afforded the same three isotopic variants of rofecoxib. These findings are consistent with a metabolic sequence involving 5-hydroxylation of rofecoxib, biliary elimination of the corresponding glucuronide, and deconjugation of the glucuronide in the lower gastrointestinal tract. Reduction of the 5-hydroxyrofecoxib thus liberated yields a hydroxyacid that cyclizes spontaneously to regenerate rofecoxib, which is reabsorbed and enters the systemic circulation. This sequence represents a novel form of enterohepatic recycling and reflects the susceptibility of 5-hydroxyrofecoxib, as well as rofecoxib itself, to reversible 2-furanone ring opening under in vivo conditions.

Animals↗
PubMed2000

Qualitative study of views of health professionals and patients on guided self management plans for asthma.

OBJECTIVES: To explore the views held by general practitioners, practice nurses, and patients about the role of guided self management plans in asthma care. DESIGN: Qualitative study using nine focus groups that each met on two occasions. SETTING: South Wales. SUBJECTS: 13 asthma nurses, 11 general practitioners (six with an interest in asthma), and 32 patients (13 adults compliant with treatment, 12 non-compliant adults, and seven teenagers). RESULTS: Neither health professionals nor patients were enthusiastic about guided self management plans, and, although for different reasons, almost all participants were ambivalent about their usefulness or relevance. Most professionals opposed their use. Few patients reported sustained use, and most felt that plans were largely irrelevant to them. The attitudes associated with these views reflect the gulf between the professionals' concept of the "responsible asthma patient" and the patients' view. CONCLUSIONS: Attempts to introduce self guided management plans in primary care are unlikely to be successful. A more patient centred, patient negotiated plan is needed for asthma care in the community.

Adolescent↗
PubMed2000

Thymidine phosphorylase induces carcinoma cell oxidative stress and promotes secretion of angiogenic factors.

Thymidine phosphorylase (TP) (E.C. 2.4.2.4), also known as platelet-derived endothelial cell growth factor, is a potent angiogenic factor. The expression of TP correlates with poor prognosis in a range of tumor types. 2-Deoxy-D-ribose-1-phosphate, a product of thymidine catabolism by TP, is a strongly reducing sugar that generates oxygen radical species during the early stages of protein glycation. We show that thymidine induces oxidative stress in TP-overexpressing carcinoma cells, promoting secretion of the stress-induced angiogenic factors vascular endothelial growth factor and interleukin-8, and inducing matrix metalloproteinase-1. Our findings outline a putative mechanism for TP-induced angiogenesis and identify novel targets for intervention.

Carcinoma↗
PubMed2000

Novel omega-conotoxins from Conus catus discriminate among neuronal calcium channel subtypes.

omega-Conotoxins selective for N-type calcium channels are useful in the management of severe pain. In an attempt to expand the therapeutic potential of this class, four new omega-conotoxins (CVIA-D) have been discovered in the venom of the piscivorous cone snail, Conus catus, using assay-guided fractionation and gene cloning. Compared with other omega-conotoxins, CVID has a novel loop 4 sequence and the highest selectivity for N-type over P/Q-type calcium channels in radioligand binding assays. CVIA-D also inhibited contractions of electrically stimulated rat vas deferens. In electrophysiological studies, omega-conotoxins CVID and MVIIA had similar potencies to inhibit current through central (alpha(1B-d)) and peripheral (alpha(1B-b)) splice variants of the rat N-type calcium channels when coexpressed with rat beta(3) in Xenopus oocytes. However, the potency of CVID and MVIIA increased when alpha(1B-d) and alpha(1B-b) were expressed in the absence of rat beta(3), an effect most pronounced for CVID at alpha(1B-d) (up to 540-fold) and least pronounced for MVIIA at alpha(1B-d) (3-fold). The novel selectivity of CVID may have therapeutic implications. (1)H NMR studies reveal that CVID possesses a combination of unique structural features, including two hydrogen bonds that stabilize loop 2 and place loop 2 proximal to loop 4, creating a globular surface that is rigid and well defined.

Alternative Splicing↗
PubMed2000

Longitudinal analysis of symptoms reported by patients with chronic fatigue syndrome.

PURPOSE: To determine the effect of chronic fatigue syndrome (CFS) illness duration and onset type on the likelihood of reporting a symptom during successive follow-up periods.METHODS: In 1997, a two-phase RDD survey in Wichita, Kansas, was conducted to estimate the prevalence of CFS. Phase I identified 56,154 respondents 18-69 years of age and screened for severe fatigue, extreme tiredness or exhaustion lasting for 1 month or longer. In phase II an equal number of fatigued (n = 7,176) and randomly selected non-fatigued subjects were asked about 8 CFS and 13 non-CFS symptoms, as well as the presence of specific medical and psychiatric conditions. Eligible respondents were clinically evaluated to establish CFS diagnosis. Phase II respondents were re-contacted at 12- (n = 4,331) and 24-months (n = 4,266) for additional follow-up and diagnosis. In this study we considered symptoms reported as being present most of the time during each successive observation period. Generalized estimating equations were used to model symptoms over time and to address study questions. Such a model accounts for correlations among repeated symptoms for each subject. We used an auto-regressive structure for the correlation matrix, assuming the correlations between each pair of repeated symptoms should decrease as the time between symptoms increased.RESULTS: There were 74 CFS patients who had been ill for 1 to 20 years (median = 6.3 years). Among these, 46 reported gradual and 28 reported sudden onset. Symptoms fluctuated over the course of illness. However, only stomach pain (non-CFS symptom) was more likely to be reported as duration of illness increased (p < 0.05). There was no association between onset type and the likelihood of reporting a symptom during an interview, except that chills and severe headaches were more likely to be reported by sudden cases.CONCLUSIONS: The likelihood of expressing CFS and non-CFS symptom "most of the time" is the same across years of illness. More analyses are warranted to consider expression of symptoms for >/=6 months and severe symptoms.

Journal Article↗
PubMed2000

Nonmyeloablative stem cell transplantation for congenital immunodeficiencies.

The optimal approach for stem cell transplantation in children with immunodeficiency has yet to be determined. Conditioning therapy is necessary for reliable engraftment and full immune reconstitution; however, the beneficial effect of cytoreductive conditioning is counterbalanced by increased short- and long-term treatment-related toxicity. Whether bone marrow transplantation with a nonmyeloablative preparative regimen was sufficient for the establishment of donor immune reconstitution, with the resultant correction of disease phenotype, was investigated. Eight patients with severe immunodeficiency states underwent T-cell replete bone marrow transplantation from a human leukocyte antigen-matched unrelated (n = 6) or sibling (n = 2) donor with nonmyeloablative conditioning using a fludarabine-melphalan-anti-lymphocyte globulin-based regimen. All patients had severe organ dysfunction that precluded transplantation with conventional conditioning. All patients were engrafted with predominantly donor hematopoiesis, and the duration of neutropenia was brief. Significant acute graft-versus-host disease (GVHD) did not develop, but one patient had limited chronic GVHD. One patient died of disease recurrence, and 3 have stable, mixed chimerism. At a median follow-up of 1 year, all patients have had good recovery of CD3(+) T-cell numbers, and 6 of 7 evaluable patients have normal phytohemagglutinin stimulation indices. The rate of immune reconstitution is comparable with that of historical controls undergoing standard myeloablative protocols. Two patients with CD40 ligand deficiency now show significant expression, and a patient with adenosine deaminase deficiency has improved deoxy adenosine triphosphate metabolites. In summary, it has been demonstrated that nonmyeloablative stem cell transplantation permits rapid engraftment from both sibling and unrelated donors with minimal toxicity even in the presence of severe organ dysfunction. If long-term immune reconstitution of patients treated with this protocol is demonstrated, it is believed this approach might offer significant advantages compared with standard protocols by combining adequate immune reconstitution with reduced short- and long-term toxicity. (Blood. 2000;96:1239-1246)

Child↗
PubMed2000

DNA sequence and functional characterization of the human and rat epidermal growth factor promoter: regulation by cell growth.

Epidermal growth factor (EGF) regulates cell growth and differentiation through intracellular transduction networks activated by its tyrosine kinase receptor, EGFR. In this report we describe the structure and DNA sequence of transcriptional control regions from both human and Wistar-rat single copy EGF genes and their functional analysis in epithelial cell cultures. By sequence comparison we show these proximal gene regions have remained conserved in evolution to -640 (relative to the rodent mRNA initiation site), where similarity is interrupted by a rodent interspersed-repeat element (SINE). Transcript mapping reveals complexity in EGF initiation site selection: whereas a single rat liver initiation site (+1) appears 30bp 3' to the TTTAA element, an additional upstream site is detected in kidney RNA at -14. In contrast, in human RNA a single initiation is observed, which is displaced 12bp 3' to the rodent RNA terminus. Both promoters were defined in transient expression assays. Our results show the human promoter to be at least 20-fold more active than the equivalent rodent sequence, although both are activated during cell proliferation and negatively regulated in contact inhibited and quiescent cultures. The results indicate EGF gene expression and cell division are temporally linked, suggesting its promoter comprises a growth responsive regulatory domain.

3T3 Cells↗