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Biomedical subjects

R Johnson

Publications and source records attributed to R Johnson.

At least 55 records · Page 3Linked to original sources
PubMed2000

Does prolonged combined androgen blockade have survival benefits over short-term combined androgen blockade therapy?

OBJECTIVES: To explore whether less than 120 days of an antiandrogen plus a luteinizing hormone-releasing hormone agonist resulted in a different survival outcome than 120 days or more of combined treatment in patients with Stage D2 prostate cancer. METHODS: Survival data were available from a previously published controlled trial that had evaluated the efficacy and tolerability of two antiandrogens, bicalutamide and flutamide, each combined with a monthly depot preparation of leuprolide or goserelin, in 813 patients with Stage D2 prostate cancer. Cox's proportional hazards regression model assessed the relative effects of the length of combined androgen blockade (CAB) therapy on survival. This analysis was repeated in the subset of patients who lived at least 2 years beyond the date of randomization. Data were obtained at a median follow-up of 160 weeks. RESULTS: A survival benefit was demonstrated for patients receiving prolonged CAB therapy, with a hazard ratio of 0.275 (95% confidence interval 0.213 to 0.355, P = 0.0001) in favor of patients who received 120 days or more of CAB therapy (median survival 1035 days versus 302 days for less than 120 days of therapy). This result was confirmed in the patients who lived at least 2 years, in whom the median survival time was increased by 35%. The hazard ratio for 120 days or more of CAB therapy versus less than 120 days was 0.415 (95% confidence interval 0.246 to 0.702, P = 0.001). CONCLUSIONS: The results of the present exploratory analysis suggest that prolonged (120 days or more) antiandrogen treatment as part of CAB therapy may result in a better survival outcome.

Adult↗
PubMed2000

Cumulative effect of family environment on psychiatric symptomatology among multiethnic adolescents.

PURPOSE: To examine the influence of family adversity and support on levels of psychiatric symptomatology in Hawaiian and non-Hawaiian adolescents. METHOD: More than 4000 students from five high schools in Hawaii completed a survey during the 1992-1993 school year about their family environment and mental health. The response rate was approximately 60%. Logistic regression analyses were performed and responses for Hawaiians and non-Hawaiians were compared. RESULTS: Hawaiian adolescents experienced significantly more adversity than their non-Hawaiian counterparts. The cumulative effect of family adversity had a greater effect on psychiatric symptomatology than any single indicator. Family support reduced the risk for internalizing symptoms, particularly for Hawaiian adolescents. The influence of family support was less clear for externalizing symptoms, increasing the risk for some adolescents and decreasing the risk for others. CONCLUSION: We identified strong associations between family adversity and levels of psychiatric symptomatology. We found that Hawaiian adolescents are at increased risk for psychiatric symptomatology, given the presence of family adversity and the effect of reduced family support. However, risk was also substantial for non-Hawaiians. Clinicians need to assess the family environment routinely and implement family-oriented interventions.

Adolescent↗
PubMed2000

Improving the quality of care through routine teleradiology consultation.

RATIONALE AND OBJECTIVES: The hypotheses of this study were as follows: (a) University subspecialty radiologists can provide consultations effectively to general radiologists as part of routine clinical operations; (b) these consultations will improve the quality of the final radiologic report; and (c) the consultations will improve the care process and may save money, as well. MATERIALS AND METHODS: For 2,012 consecutive computed tomographic or magnetic resonance (MR) imaging studies, the initial interpretations provided by radiology generalists were subsequently reviewed by specialists, with a final consensus report available. "Truth" was established by final consensus reports. To control for potential bias, 150 adult MR imaging and 250 pediatric radiologic studies were interpreted initially by specialists and then by generalists. Again, truth was established by final consensus reports. RESULTS: There was disagreement between generalist and specialist radiologist interpretations in 427 (21.2%) of the cases reviewed. These disagreements were stratified further by independent specialists, who graded them as important, very important, or unimportant. Differences were considered important or very important in 99% of the cases reviewed. CONCLUSION: Consultations by subspecialty radiologists improved the quality of the radiology reports studied and, at least in some cases, improved the process of care by eliminating unnecessary procedures or suggesting more specific follow-up examinations. The consultation services can be provided cost-effectively from the payer's perspective and may save additional costs when unnecessary procedures can be eliminated.

Humans↗
PubMed2000

Sleeping with the enemy? A randomized controlled trial of a collaborative health authority/industry intervention to influence prescribing practice.

AIMS: To evaluate the effectiveness of a health authority/pharmaceutical company collaborative intervention to influence the choice of proton pump inhibitors METHODS: Randomized controlled trial, with general practices forming the unit of allocation and analysis. RESULTS: Constructive working relationships were achieved with five of six pharmaceutical companies involved. One hundred and two out of 140 practitioners in intervention group practices received at least one visit from an industry representative. There were no reports of representatives operating outside their agreed remit. Prescribing in both the intervention and control group moved towards that recommended by the guidelines but there was no difference between the groups in either the proportion of prescriptions in line with the guidelines or the overall cost. CONCLUSIONS: Health authorities can achieve professional working relationships with the pharmaceutical industry although no changes in practice attributable to the intervention are achieved. Further work is required to develop effective means to influence prescribing in line with independent guidelines especially in the context of the development of Primary Care Groups.

Drug Industry↗
PubMed2000

Induction of TGF-beta1 by the matricellular protein SPARC in a rat model of glomerulonephritis.

UNLABELLED: Induction of TGF-beta1 by the matricellular protein SPARC in a rat model of glomerulonephritis. BACKGROUND: SPARC has been implicated as a counteradhesive and antiproliferative protein associated with deposits of extracellular matrix in renal disease. METHOD: We have examined the effect of recombinant SPARC containing a C-terminal His tag (rSPARC) in an acute model of mesangial cell injury that is induced in the rat by an antibody against the Thy1 antigen on the mesangial cell membrane. The recombinant protein was administered 24 hours after the induction of nephritis and was infused through day 4. RESULTS: rSPARC was localized to the renal glomeruli of rats treated with anti-Thy1 antibody. Type I collagen and fibronectin, as well as transforming growth factor-beta1 (TGF-beta1), were increased at day 5 in rats treated with rSPARC (N = 4, P < 0.05 vs. delivery buffer), but only minimal effects were seen on mesangial cell and endothelial cell proliferation. In primary cultures of rat mesangial cells, infusion of rSPARC was associated with increases in TGF-beta1 mRNA and in total, secreted TGF-beta1 protein. CONCLUSIONS: rSPARC stimulates expression of TGF-beta1 both in vitro and in vivo. Given the closely regulated expression of SPARC, TGF-beta1, and type I collagen in several animal models of glomerulonephritis, we propose that SPARC could be one of the major mediators of the induction of TGF-beta1 in renal disease.

Animals↗
PubMed2000

Optic nerve sheath fenestration for a reversible optic neuropathy in radiation oncology.

To the authors' knowledge, there is a paucity of published accounts of management of radiation-induced optic neuropathy (RION) by optic nerve sheath fenestration (ONSF) in the conventional medical literature. With higher doses of radiation being given by using conformal techniques, more radiation-induced optic neuritis and neuropathy will be identified. We report here the successful use of ONSF to restore vision to three consecutive patients with pending anterior RION, and the importance of early identification and intervention in these potentially reversible cases.

Adult↗
PubMed2000

Evidence of Rab3A expression, regulation of vesicle trafficking, and cellular secretion in response to heregulin in mammary epithelial cells.

Heregulin beta1 (HRG), a combinatorial ligand for human growth factor receptors 3 and 4, is a regulatory polypeptide that promotes the differentiation of mammary epithelial cells into secretory lobuloalveoli. Emerging evidence suggests that the processes of secretory pathways, such as biogenesis and trafficking of vesicles in neurons and adipose cells, are regulated by the Rab family of low-molecular-weight GTPases. In this study, we identified Rab3A as a gene product induced by HRG. Full-length Rab3A was cloned from a mammary gland cDNA library. We demonstrated that HRG stimulation of human breast cancer cells and normal breast epithelial cells induces the expression of Rab3A protein and mRNA in a cycloheximide-independent manner. HRG-mediated induction of Rab3A expression was blocked by an inhibitor of phosphatidylinositol 3-kinase but not by inhibitors of mitogen-activated protein kinases p38(MAPK) and p42/44(MAPK). Human breast epithelial cells also express other components of regulated vesicular traffic, such as rabphilin 3A, Doc2, and syntaxin. Rab3A was predominantly localized in the cytosol, and HRG stimulation of the epithelial cells also raised the level of membrane-bound Rab3A. HRG treatment induced a profound alteration in the cell morphology in which cells displayed neuron-like membrane extensions that contained Rab3A-coated, vesicle-like structures. In addition, HRG also promoted the secretion of cellular proteins from the mammary epithelial cells. The ability of HRG to modify exocytosis was verified by using a growth hormone transient-transfection system. Analysis of mouse mammary gland development revealed the expression of Rab3A in mammary epithelial cells. Furthermore, expression of the HRG transgene in Harderian tumors in mice also enhanced the expression of Rab3A. These observations provide new evidence of the existence of a Rab3A pathway in mammary epithelial cells and suggest that it may play a role in vesicle trafficking and secretion of proteins from epithelial cells in response to stimulation by the HRG expressed within the mammary mesenchyma.

Animals↗
PubMed2000

International variations in youth drug use: the effect of individual behaviours, peer and family influences, and geographical location.

This international study investigates factors underlying international variations in rates of youth drug use among representative samples of 15-year-olds in five cities (Bremen, n = 871; Dublin, n = 983; Groningen, n = 487; Newcastle upon Tyne, n = 880; Rome, n = 666). It reveals a higher level of drug use in English-speaking compared to continental populations. Drug use was associated with peer, family and individual factors. Logistic regression showed that family structure and sport were associated with lower rates and delinquent behaviour with higher rates of drug use in all cities and among males and females. Among males, city of residence also independently predicted drug use. The effect of traditional families and studiousness in reducing drug use was most evident for male drug use in low-use cities: higher rates of use in English-speaking cities appear partially due to the drug use of low-risk males.

Adolescent↗
PubMed2000

Hypoxia-inducible factor-1 (HIF-1) up-regulates adrenomedullin expression in human tumor cell lines during oxygen deprivation: a possible promotion mechanism of carcinogenesis.

Little is known about the molecular mechanisms that control adrenomedullin (AM) production in human cancers. We demonstrate here that the expression of AM mRNA in a variety of human tumor cell lines is highly induced in a time-dependent manner by reduced oxygen tension (1% O2) or exposure to hypoxia mimetics such as desferrioxamine mesylate (DFX) or CoCl2. This AM expression seems to be under hypoxia-inducible factor-1 (HIF-1) transcriptional regulation, since HIF-1alpha and HIF-1beta knockout mouse cell lines had an ablated or greatly reduced hypoxia AM mRNA induction. Similarly, inhibition or enhancement of HIF-1 activity in human tumor cells showed an analogous modulation of AM mRNA. Under hypoxic conditions, immunohistochemical analysis of tumor cell lines revealed elevated levels of AM and HIF-1alpha as compared with normoxia, and we also found an increase of immunoreactive AM in the conditioned medium of tumor cells analyzed by RIA. AM mRNA stabilization was shown to be partially responsible for the hypoxic up-regulated expression of AM. In addition, we have identified several putative hypoxia response elements (HREs) in the human AM gene, and reporter studies with selected HREs were capable of enhancing luciferase expression after exposure to DFX. Furthermore, transient coexpression of HIF-1alpha resulted in an augmented transactivation of the reporter gene after DFX treatment. Given that most solid human tumors have focal hypoxic areas and that AM functions as a mitogen, angiogenic factor, and apoptosis-survival factor, our findings implicate the HIF-1/AM link as a possible promotion mechanism of carcinogenesis.

Adrenomedullin↗
PubMed2000

Myxoid liposarcoma of the supraclavicular fossa.

Liposarcomas generally originate most often in the extremities or retroperitoneum, less frequently in the head and neck, and rarely in the thorax. We describe a particularly rare presentation of myxoid liposarcoma originating in the supraclavicular fossa. The mass was resected and has not recurred. We searched our pathology database for other soft-tissue tumors of the supraclavicular fossa and found no other case of sarcoma originating in this site. In addition, we performed a literature review of thoracic and neck liposarcomas to identify similar cases and discuss their clinical course.

Aged↗
PubMed2000

Anterior cruciate injuries in the skeletally immature athlete: a review of treatment outcomes.

The documentation of anterior cruciate ligament (ACL) injuries in the skeletally immature athlete has significantly increased over the past decade, primarily due to increased awareness of these injuries within this younger athletic population. The evaluation of these injuries are similar to that in the adult population. Diagnostic studies such as plain radiographs, as well as magnetic resonance imaging, can delineate the location of the ACL failure. Physical presentation most commonly includes an acute haemarthrosis and ligamentous insufficiency. Several studies have demonstrated that the diagnostic reliability of the physical examination is poor in children, especially in patients less than 12 years old. The site of ACL failure in this adolescent population is most commonly at the tibial insertion. We recommend arthroscopic or arthroscopically assisted open reduction and internal fixation with nonabsorbable sutures for all displaced tibial eminence fractures. Mid-substance ACL failures also occur in this athletic age group. The association of meniscal injuries with these ACL failures appears to be greater than 50%. Historically, poor subjective and objective outcomes have been associated with primary and extra-articular repairs. Intra-articular reconstruction is the gold standard. The issue of placing the graft across open physeal plates is under investigation. Recent animal studies as well as human clinical series have demonstrated safety in placing soft tissue, i.e. hamstring grafts, across open growth plates without subsequent angular or leg length discrepancy. Historically, non-operatively treated ACL failures are associated with poor functional outcomes as well as a high incidence of meniscal re-injury. If the treatment of an adolescent athlete with an ACL failure is to be rehabilitation until skeletal maturity, close follow-up is essential to detect functional instability, which may prompt earlier surgical reconstruction.

Adolescent↗
PubMed2000

MMPI-A performance of African and Mexican American adolescent first-time offenders.

54 African and Mexican American adolescent first-time offenders were examined with the MMPI-A to evaluate ethnic differences. Multivariate analyses by ethnicity and MMPI-A scales (validity, clinical, content, and supplementary scales) were not significant; however, there was a significant univariate difference where African American adolescents scored significantly higher on the Repression scale than the Mexican American group. A greater percentage of within-normal-limits profiles were African American (50%) than Mexican American (25%). Research and clinical implications for using the MMPI-A with these groups are discussed.

Adolescent↗
PubMed2000

Use of a Shiga toxin (Stx)-enzyme-linked immunosorbent assay and immunoblot for detection and isolation of Stx-producing Escherichia coli from naturally contaminated beef.

The purpose of this study was to evaluate an enzyme-linked immunosorbent assay (ELISA) and an immunoblot procedure for detection and isolation of Shiga toxin-producing Escherichia coli (STEC) from beef, and to correlate the presence of STEC in beef with E. coli and total coliform counts. A total of 120 samples of boneless beef supplied to a meat processor in southern Ontario were tested for the presence of STEC, E. coli, and total coliforms. Following enrichment in modified tryptic soy broth, samples were screened for Shiga toxin (Stx) by a Stx-ELISA and a Vero cell assay (VCA). Samples that were positive in the Stx-ELISA were subjected to the Stx-immunoblot for STEC isolation. Overall, 33.3% of samples were positive in the VCA, and 34.2% were positive in the Stx-ELISA. There was almost complete agreement between the Stx-ELISA and the VCA results (kappa = 0.98). The sensitivity and specificity of the Stx-ELISA with respect to the VCA were 100% and 98.75%, respectively. STEC were isolated by the Stx-immunoblot from 87.8% of the samples that were positive in the Stx-ELISA. The STEC isolates belonged to 19 serotypes, with serotype O113:H21 accounting for 10 of 41 isolates. No STEC of serotype O157:H7 were isolated. There was a significant correlation between E. coli counts and total coliform counts (Spearman correlation coefficient = 0.68, P < 0.01). The E. coli count was positively correlated with detection of STEC by both the Stx-ELISA and the VCA (P < 0.01).

Animals↗
PubMed2000

Correlations among p53, Her-2/neu, and ras overexpression and aneuploidy by multiparameter flow cytometry in human breast cancer: evidence for a common phenotypic evolutionary pattern in infiltrating ductal carcinomas.

Human solid tumors develop multiple genetic abnormalities that accumulate progressively in individual cells during the course of tumor evolution. We sought to determine whether there are specific sequences of occurrence of these progressive evolutionary changes in human breast cancers by performing correlated cell-by-cell measurements of cell DNA content, p53 protein, Her-2/neu protein, and ras protein by multiparameter flow cytometry in 56 primary tumor samples obtained at surgery. In addition, p53 allelic loss and Her-2/neu gene amplification were determined by fluorescence in situ hybridization in cells from the same samples. We reasoned that if there is a specific order in which genetic changes occur, the same early changes would be found consistently in the cells with the fewest abnormalities. We reasoned further that late-developing abnormalities would not occur alone in individual cells but would almost always be found together with the early changes inherited by the same cells. By these criteria, abnormalities involving p53 generally occurred early in the course of development of invasive breast cancers, whereas ras protein overexpression was found to be a late-occurring phenomenon. Within individual tumors, cellular p53 overexpression was often observed alone in individual cells, whereas ras protein overexpression was rarely observed in the absence of p53 overexpression and/or Her-2/neu overexpression in the same cells. Furthermore, the intracellular level of each abnormally expressed protein was found to increase progressively as new abnormalities were acquired. Infiltrating ductal carcinomas exhibited characteristic phenotypic patterns in which p53 allelic loss and/or p53 protein overexpression, Her-2/neu amplification and/or overexpression, aneuploidy, and ras overexpression accumulated within individual cells. However, this pattern was not a prominent feature of lobular breast cancers. All six lobular breast cancers studied were diploid. p53 allelic loss and/or early p53 overexpression, and late ras cooverexpression in the same cells were less common in lobular breast cancers than in infiltrating ductal carcinomas. Although Her-21neu overexpression was a common finding in lobular breast cancers, Her-2/neu amplification was not observed in these tumors.

Aneuploidy↗
PubMed2000

Guidelines for using human event-related potentials to study cognition: recording standards and publication criteria.

Event-related potentials (ERPs) recorded from the human scalp can provide important information about how the human brain normally processes information and about how this processing may go awry in neurological or psychiatric disorders. Scientists using or studying ERPs must strive to overcome the many technical problems that can occur in the recording and analysis of these potentials. The methods and the results of these ERP studies must be published in a way that allows other scientists to understand exactly what was done so that they can, if necessary, replicate the experiments. The data must then be analyzed and presented in a way that allows different studies to be compared readily. This paper presents guidelines for recording ERPs and criteria for publishing the results.

Cognition↗