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Biomedical subjects

J Turner

Publications and source records attributed to J Turner.

At least 109 records · Page 6Linked to original sources

Effects of psyllium on glucose and serum lipid responses in men with type 2 diabetes and hypercholesterolemia.

BACKGROUND: Water-soluble dietary fibers decrease postprandial glucose concentrations and decrease serum cholesterol concentrations. This study examined the effects of administering psyllium to men with type 2 diabetes. OBJECTIVE: The objective was to evaluate the safety and effectiveness of psyllium husk fiber used adjunctively to a traditional diet for diabetes in the treatment of men with type 2 diabetes and mild-to-moderate hypercholesterolemia. DESIGN: After a 2-wk dietary stabilization phase, 34 men with type 2 diabetes and mild-to-moderate hypercholesterolemia were randomly assigned to receive 5.1 g psyllium or cellulose placebo twice daily for 8 wk. Serum lipid and glycemic indexes were evaluated biweekly on an outpatient basis and at weeks 0 and 8 in a metabolic ward. RESULTS: In the metabolic ward, the psyllium group showed significant improvements in glucose and lipid values compared with the placebo group. Serum total and LDL-cholesterol concentrations were 8.9% (P < 0.05) and 13.0% (P = 0.07) lower, respectively, in the psyllium than in the placebo group. All-day and postlunch postprandial glucose concentrations were 11.0% (P < 0.05) and 19.2% (P < 0.01) lower in the psyllium than in the placebo group. Both products were well tolerated, with no serious adverse events related to treatment reported in either group. CONCLUSION: The addition of psyllium to a traditional diet for persons with diabetes is safe, is well tolerated, and improves glycemic and lipid control in men with type 2 diabetes and hypercholesterolemia.

Adult↗

Necrosis, apoptosis, cytostasis and DNA damage in human lymphocytes measured simultaneously within the cytokinesis-block micronucleus assay: description of the method and results for hydrogen peroxide.

A method is described for the inclusion of apoptotic and necrotic cells in the cell counts obtained in the cytokinesis-block micronucleus (CBMN) assay, which is conventionally used solely for the assessment of chromosome breakage, chromosome loss and frequency of dividing cells. The morphological criteria for the recognition and discrimination between necrotic, apoptotic and viable cells are described. Using this comprehensive method we have evaluated the cytotoxic and genotoxic effects of hydrogen peroxide (0-100 microM) in lymphocytes exposed in RPMI 1640 medium. The results obtained indicated significant (P < 0.05) correlations between hydrogen peroxide concentration and the frequency of micronucleated cells (r = 0.39), necrotic cells (r = 0.73), apoptotic cells (r = -0.26) and binucleated cells (r = -0.55). Almost similar results were obtained using the cytosine arabinoside modification of the CBMN assay, which enables excision-repaired sites to be converted to micronuclei. Some of the above end-points were significantly (P < 0.05) correlated with each other (necrosis and apoptosis, R = -0.39; necrosis and micronucleated cell frequency, R = 0.46; necrosis and binucleated cells, R = -0.78; apoptosis and binucleated cells, R = 0.32). It was therefore necessary to use multiple regression analysis to identify the main event induced by hydrogen peroxide, which was necrosis (beta = 0.57, P = 0.0001) and not micronucleus formation (beta = 0. 15, P = 0.1332). Using an ELISA assay we showed that hydrogen peroxide did not induce 8-hydroxydeoxyguanosine. Our data show that the proposed comprehensive test system may provide a better procedure for classifying potential toxic chemicals and enable discrimination between agents that primarily induce cytotoxic effects as opposed to genotoxic effects. The integration of apoptosis and necrosis into the micronucleus assay may also be of practical use in radiosensitivity studies.

Adult↗

A phase I trial of topical topitriol (calcitriol, 1,25-dihydroxyvitamin D3) to prevent chemotherapy-induced alopecia.

This study evaluated the toxicity and efficacy of topical topitriol (calcitriol, 1,25-dihydroxyvitamin D3) to prevent chemotherapy-induced alopecia (CIA). Patients with breast cancer scheduled to receive FAC chemotherapy (5-fluorouracil, adriamycin and cyclophosphamide) were eligible for the study. Initially, the first six patients were randomized in a double-blind fashion to have received topitriol or placebo with all subsequent patients being treated with topitriol. Topitriol cream (0.0025 or 0.005%; 25 and 50 microg/g concentration) was administered topically twice a day. Three different doses and schedules of administration were evaluated including: 500 and 1000 microg daily for 7 days prior to chemotherapy, and 2000 microg daily for 5 days prior and 5 days post-chemotherapy. Fourteen patients were treated (12 with topitriol and two with placebo) at three different dose levels. All patients developed grade 2 alopecia between day 20 and 30 after chemotherapy, demonstrating the lack of efficacy of topical topitriol on this schedule of administration to prevent CIA. Eight patients exposed to topitriol developed a toxic maculopapular dermatitis in areas exposed to the drug. In conclusion, topical topitriol at the doses and schedules evaluated in this trial was ineffective to prevent CIA and induced a local dermatitis in areas exposed to the drug.

Administration, Topical↗

A case of acute renal failure and compartment syndrome after an alcoholic binge.

A 25 year old man presented with anuria and bilateral leg pain two days after an alcoholic binge. He subsequently developed rhabdomyolysis causing acute renal failure, with compartment syndrome of both lower legs. This required urgent dialysis and fasciotomy respectively within six hours of admission. He remained dialysis dependent for three weeks and only after four months was he able to weight bear on both legs. Alcohol is a leading cause of rhabdomyolysis. Early recognition and prompt treatment is essential to prevent serious complications.

Acute Kidney Injury↗

Case managers' and clients' perspectives on a representative payee program.

OBJECTIVE: Clients with severe and persistent mental illnesses often require a representative payee to help manage benefit funds. This study compared the perceptions of clients and clinical case managers about the benefits of and problems with the representative payee relationship. METHODS: Fifty-four clients receiving assertive community treatment completed an interview that assessed satisfaction with their experience of having a representative payee and the resulting impact on their substance use, budgeting, and housing. The clients' clinical case managers completed a similar questionnaire. Analyses examined associations between providers' and clients' responses and clients' gender, race, diagnosis, previous experience with a representative payee, and duration of the current representative payeeship. RESULTS: Clients and case managers recognized benefits of the representative payeeship in the areas of housing, substance use, and budgeting. Although little evidence was found that the payeeship pervasively interfered with the therapeutic relationship, 44 percent of case managers reported incidents in which clients verbally abused them over management of their funds. Clients' satisfaction with the representative payeeship was initially low but grew over time. Longer duration of the current payeeship and clients' previous experience with representative payeeship were associated with greater satisfaction and fewer problems. Case managers overestimated clients' initial satisfaction and underestimated their current satisfaction. CONCLUSIONS: Findings suggest that both mental health professionals and clients value the representative payee process as helpful in improving outcomes, although the benefits of the arrangement may be more evident with time and experience.

Case Management↗

Performance of an algorithm to detect Pneumocystis carinii pneumonia in symptomatic HIV-infected persons. Pulmonary Complications of HIV Infection Study Group.

STUDY OBJECTIVES: To determine whether an algorithm consisting of a chest radiograph and the diffusing capacity of the lung for carbon monoxide (D(LCO)) is effective in detecting Pneumocystis carinii pneumonia (PCP) in symptomatic HIV-infected persons; and to establish a benchmark for future comparisons of alternative algorithms. DESIGN: Prospective, 64-month study. SETTING: Multicenter, ambulatory care. PATIENTS: 306 HIV-infected subjects enrolled in the Pulmonary Complications of HIV Infection Study who developed 467 episodes of new or worsening respiratory symptoms. MEASUREMENTS: Chest radiography followed by D(LCO) measurement, if the radiograph was normal or unchanged. RESULTS: An algorithm combining a chest radiograph followed by a D(LCO) measurement, if the radiograph was normal or unchanged, was effective and detected abnormalities that led to a diagnosis of PCP in 78 of 80 evaluable episodes (97.5%). The radiograph (specific parenchymal abnormality, number of lung zones involved) and the D(LCO) (degree of decrease, degree of decrease from baseline) also provided additional information on the probability of PCP. CONCLUSIONS: In symptomatic HIV-infected patients suspected of having PCP, the diagnostic evaluation should begin with a chest radiograph, followed by a D(LCO) measurement, if the radiograph is normal or unchanged. If both of these tests are normal, it may be reasonable to conclude the evaluation rather than to proceed on to additional testing. This algorithm can serve as a benchmark for future comparisons.

AIDS-Related Opportunistic Infections↗

Triton tumor.

Explore the source record for details and available documents.

Cerebellar Neoplasms↗

A feasibility study of gene gun mediated immunotherapy for renal cell carcinoma.

PURPOSE: Gene modified autologous tumor cell vaccines have demonstrated a protective and therapeutic effect in murine tumor model systems. The majority of trials to date have used viral methods of gene transfer for vaccine construction. An alternative approach to transfer genes into tumor cells is to use the gene gun, which is a physical method of gene transfection that produces high levels of gene expression without viral agents. We establish the feasibility of generating cytokine secreting autologous renal tumor cell vaccines for use in gene therapy for metastatic renal cell carcinoma. MATERIALS AND METHODS: We obtained 1 cm3 tumor tissue from 12 patients undergoing resection of primary or metastatic renal cell carcinoma. The tumor was disaggregated and placed in culture. The phenotype of the primary renal cell lines was established by microscopy and immunohistochemistry. The 1x10(7) lethally irradiated tumor cells were transfected with plasmid deoxyribonucleic acid containing the human (h) granulocyte-macrophage colony-stimulating factor (GM-CSF) gene under control of a cytomegalovirus promoter using the gene gun. The hGM-CSF production was assayed by enzyme-linked immunosorbent assay in the cell culture media 24 hours after transfection. RESULTS: Of 12 tumor samples 8 grew rapidly to produce a mean of 1.8x10(8) cells after 4 to 5 passages in culture, which was sufficient to produce between 24 and 32 vaccines. Immunocytochemistry confirmed that all cultures were almost exclusively renal tumor cells. Gene gun mediated transfection of lethally irradiated tumor cells resulted in high levels of hGM-CSF production (mean 330 ng./10(6) cells per 24 hours). CONCLUSIONS: We have demonstrated the feasibility of producing cytokine secreting tumor cell vaccines from primary and metastatic human renal tumors, and plan to use this approach in phase I clinical trials of gene therapy for metastatic renal cell carcinoma.

Biolistics↗

Cytokine transgene expression and promoter usage in primary CD34+ cells using particle-mediated gene delivery.

Induction or short-term transgenic expression of specific cytokines, growth factors, or other candidate therapeutic genes in hematopoietic progenitor or stem cells is potentially applicable to gene therapy for cancer. In this study, we explored the application of a gene gun technique, as an alternative to viral vectors, for ex vivo gene transfer into and transient gene expression in highly enriched CD34+ cells derived from human umbilical cord blood. Twenty-four hours posttransfection, 32.6 to 1500 pg/l x 10(6) CD34+ cells of transient gene expression was routinely obtained for specific cytokine and reporter genes. Transgene expression at the single-cell level was revealed by X-Gal staining of lacZ cDNA-transfected CD34+ cells. Expression of four candidate therapeutic genes, namely human granulocyte-macrophage colony-stimulating factor, tumor necrosis factor alpha, interleukin 2, and interferon gamma, was detectable for 4 to 7 days in CD34+ cells. A human elongation factor 1alpha promoter/intron 1 transcription unit was identified as a strong cellular promoter for CD34+ cells, exhibiting strength similar to that of the commonly employed cytomegalovirus immediate-early promoter. These results suggest that the nonviral, gene gun technique offers an efficient alternative approach for transient transgenic studies of hematopoietic cells and may provide new possibilities for certain cancer gene therapy strategies using CD34+ cells.

Antigens, CD34↗

Pre-steady state analysis of the assembly of wild type and mutant circular clamps of Escherichia coli DNA polymerase III onto DNA.

The beta protein, a dimeric ring-shaped clamp essential for processive DNA replication by Escherichia coli DNA polymerase III holoenzyme, is assembled onto DNA by the gamma complex. This study examines the clamp loading pathway in real time, using pre-steady state fluorescent depolarization measurements to investigate the loading reaction and ATP requirements for the assembly of beta onto DNA. Two beta dimer interface mutants, L273A and L108A, and a nonhydrolyzable ATP analog, adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS), have been used to show that ATP binding is required for gamma complex and beta to associate with DNA, but that a gamma complex-catalyzed ATP hydrolysis is required for gamma complex to release the beta.DNA complex and complete the reaction. In the presence of ATP and gamma complex, the beta mutants associate with DNA as efficiently as wild type beta. However, completion of the reaction is much slower with the beta mutants because of decreased ATP hydrolysis by the gamma complex, resulting in a much slower release of the mutants onto DNA. The effects of mutations in the dimer interface were similar to the effects of replacing ATP with ATPgammaS in reactions using wild type beta. Thus, the assembly of beta around DNA is coupled tightly to the ATPase activity of the gamma complex, and completion of the assembly process requires ATP hydrolysis for turnover of the catalytic clamp loader.

Adenosine Triphosphate↗

A mysterious dust clump in a disk around an evolved binary star system.

The discovery of planets in orbit around the pulsar PSR1257+12 shows that planets may form around post-main-sequence stars. Other evolved stars, such as HD44179 (an evolved star which is part of the binary system that has expelled the gas and dust that make the Red Rectangle nebula), possess gravitationally bound orbiting dust disks. It is possible that planets might form from gravitational collapse in such disks. Here we report high-angular-resolution observations at millimetre and submillimetre wavelengths of the dusk disk associated with the Red Rectangle. We find a dust clump with an estimated mass near that of Jupiter in the outer region of the disk. The clump is larger than our Solar System, and far beyond where planet formation would normally be expected, so its nature is at present unclear.

Astronomical Phenomena↗

Cloning and characterization of mCtBP2, a co-repressor that associates with basic Krüppel-like factor and other mammalian transcriptional regulators.

Basic Krüppel-like factor (BKLF) is a zinc finger protein that recognizes CACCC elements in DNA. It is expressed highly in erythroid tissues, the brain and other selected cell types. We have studied the activity of BKLF and found that it is capable of repressing transcription, and have mapped its repression domain to the N-terminus. We carried out a two-hybrid screen against BKLF and isolated a novel clone encoding murine C-terminal-binding protein 2 (mCtBP2). mCtBP2 is related to human CtBP, a cellular protein which binds to a Pro-X-Asp-Leu-Ser motif in the C-terminus of the adenoviral oncoprotein, E1a. We show that mCtBP2 recognizes a related motif in the minimal repression domain of BKLF, and the integrity of this motif is required for repression activity. Moreover, when tethered to a promoter by a heterologous DNA-binding domain, mCtBP2 functions as a potent repressor. Finally, we demonstrate that mCtBP2 also interacts with the mammalian transcripition factors Evi-1, AREB6, ZEB and FOG. These results establish a new member of the CtBP family, mCtBP2, as a mammalian co-repressor targeting diverse transcriptional regulators.

Alcohol Oxidoreductases↗

Biochemical basis of SOS-induced mutagenesis in Escherichia coli: reconstitution of in vitro lesion bypass dependent on the UmuD'2C mutagenic complex and RecA protein.

Damage-induced SOS mutagenesis requiring the UmuD'C proteins occurs as part of the cells' global response to DNA damage. In vitro studies on the biochemical basis of SOS mutagenesis have been hampered by difficulties in obtaining biologically active UmuC protein, which, when overproduced, is insoluble in aqueous solution. We have circumvented this problem by purifying the UmuD'2C complex in soluble form and have used it to reconstitute an SOS lesion bypass system in vitro. Stimulated bypass of a site-directed model abasic lesion occurs in the presence of UmuD'2C, activated RecA protein (RecA*), beta-sliding clamp, gamma-clamp loading complex, single-stranded binding protein (SSB), and either DNA polymerases III or II. Synthesis in the presence of UmuD'2C is nonprocessive on damaged and undamaged DNA. No lesion bypass is observed when wild-type RecA is replaced with RecA1730, a mutant that is specifically defective for Umu-dependent mutagenesis. Perhaps the most noteworthy property of UmuD'2C resides in its ability to stimulate both nucleotide misincorporation and mismatch extension at aberrant and normal template sites. These observations provide a biochemical basis for the role of the Umu complex in SOS-targeted and SOS-untargeted mutagenesis.

Bacterial Proteins↗

The TIR1 protein of Arabidopsis functions in auxin response and is related to human SKP2 and yeast grr1p.

Genetic analysis in Arabidopsis has led to the identification of several genes that are required for auxin response. One of these genes, AXR1, encodes a protein related to yeast Aos1p, a protein that functions to activate the ubiquitin-related protein Smt3p. Here we report the identification of a new gene called TRANSPORT INHIBITOR RESPONSE 1 (TIR1). The tir1 mutants are deficient in a variety of auxin-regulated growth processes including hypocotyl elongation and lateral root formation. These results indicate that TIR1 is also required for normal response to auxin. Further, mutations in TIR1 display a synergistic interaction with mutations in AXR1, suggesting that the two genes function in overlapping pathways. The TIR1 protein contains a series of leucine-rich repeats and a recently identified motif called an F box. Sequence comparisons indicate that TIR1 is related to the yeast protein Grr1p and the human protein SKP2. Because Grr1p and other F-box proteins have been implicated in ubiquitin-mediated processes, we speculate that auxin response depends on the modification of a key regulatory protein(s) by ubiquitin or a ubiquitin-related protein.

2,4-Dichlorophenoxyacetic Acid↗

The role of the psychologist in crisis/hostage negotiations.

Over the past three decades, there has been a noted increase in hostage and barricade incidents involving perpetrators with a variety of emotional, economic, and political motives. A hostage incident may be defined as an incident in which (a) perpetrator(s) hold(s) one or more persons against their will in a location known to police. A barricade incident, on the other hand, is an incident without hostages in which a perpetrator is barricaded, also in a location known to police and refusing to surrender. Approximately 25 years ago, a theory of crisis/hostage negotiations was developed which has been continuously refined in field applications. This article will define the goal of crisis/hostage negotiation, review the history of hostage taking from biblical times to the present, review the utilization of psychologists and other mental health consultants by police crisis/hostage negotiation teams, and discuss the four roles and related functions of psychologists on crisis/hostage negotiation teams.

Consultants↗

Cationic lipids (lipofectamine) and disturbance of cellular cholesterol and sphingomyelin distribution modulates gamma-secretase activity within amyloid precursor protein in vitro.

To study beta-amyloid protein generation we expressed different amyloid precursor protein (APP) isoforms in the human neuroblastoma cell line SY5Y (for details see (1)). Treatment with lipofectamine, an cationic lipid for eucaryotic cell transfection, inhibits gamma-secretase activity and stimulates the physiological APP cleavage by alpha-secretase activity. Beside the MDL inhibitor (2), this is the second agent that shows modulation of gamma-secretase activity in vitro. Further, we show that disturbance of cellular cholesterol and sphingomyelin distribution in transfected SY5Y cells results in an overproduction of beta-amyloid protein. This provides experimental evidence that membrane instability influenced the proteolytic activity of gamma-secretase within the APP molecule.

Amyloid Precursor Protein Secretases↗

Unusual lesions of the internal auditory canal.

Acoustic neuromata (AN) account for nearly 90 per cent of internal auditory canal (IAC) and cerebello-pontine angle (CPA) tumours. The second most common tumour is meningioma. Rare lesions include primary cholesteatoma, facial neuroma, lipoma, angioma and various cysts. Two cases of IAC tumour are presented, one of hamartoma in which smooth muscle was prominent and the other of lymphangioma. Of interest are the specific clinical and radiological features associated with these lesions.

Adolescent↗