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Biomedical subjects

L Taylor

Publications and source records attributed to L Taylor.

At least 109 records · Page 6Linked to original sources

Report from the 1995 Core Indicators for Peritoneal Dialysis Study Group.

The 1995 Peritoneal Dialysis Core Indicators Study was conducted by the Health Care Financing Administration to ascertain standard practices and outcomes in chronic peritoneal dialysis patients. Data from 1,202 patients who did not receive hemodialysis but who were on chronic ambulatory peritoneal dialysis (CAPD) for at least part of the 6-month period between November 1, 1994, and April 30, 1995, are reported. The mean serum albumin level for this cohort was 3.5 g/dL by the bromcresol green method and 3.2 g/dL by the bromcresol purple method. Data sufficient to calculate a weekly Kt/V(urea) or weekly creatinine clearance were available for only 34% of patient submissions. In these patients, the median weekly Kt/V(urea) was 1.7 using a fixed value for V of 0.58 x body weight and was 2.0 using the Watson equation to calculate V; the median weekly creatinine clearance was 60.7 L/wk/1.73 m2. The mean hematocrit for this cohort was 32% and the average weekly recombinant human erythropoietin (rHmEPO) dose was 115 u/kg. Hematocrit values < or = 30% were found in 50% of black patients and 31% of white patients. The average blood pressure among peritoneal dialysis patients was 139/80 mm Hg, with 29% of patients having a systolic blood pressure exceeding 150 mm Hg and 18% a diastolic blood pressure greater than 90 mm Hg. In summary, serum albumin levels were significantly lower in peritoneal dialysis patients than in hemodialysis patients. Approximately one third of peritoneal dialysis patients did not have an adequacy measure obtained during the 6-month observation period. A significant minority of patients had either inadequately treated anemia of chronic renal disease or hypertension. There is an opportunity to substantially improve the medical care provided to chronic peritoneal dialysis patients.

Adolescent↗

Kinetics of radiolabeled adrenocorticotropin hormone in infant and weanling rats.

Unlike the adult animal, the developing rat has a diminished ability to activate and inhibit the hypothalamic pituitary adrenal axis. In general, a gradual ACTH and corticosterone response to stressors appear after postnatal day 10 and is well established to adult level by weaning age. Although at this age the peak ACTH level is comparable to that of the adult, ACTH levels remain elevated for a longer period of time. The purpose of this study was to investigate the possibility that ACTH metabolism can, in part, explain this prolonged ACTH elevation after a challenge. The plasma half life of disappearance (t1/2, the apparent volume of distribution and metabolic clearance rate (MCR) were determined after injection of a tracer dose of 3-I125-Iodotyrosyl23 ACTH1-39 in rats at 14 and 25 days of age. An adult animal group (65 days old) was used for comparison. The t1/2 for ACTH decreases with age (14 day old = 7.47 +/- 0.9 min; 25 day old = 6.48 +/- 0.4 min; adult = 4.46 +/- 0.2 min) while the volume of distribution remains constant. The MCR is also decreased in the young animals (14 day old = 1.5 +/- 0.19 min; 25 day old = 1.6 +/- 0.18 min; adult = 3.0 +/- 0.56 min). For the first time, it is established that the young animals require longer to clear ACTH from an equivalent volume of blood when compared to the adult. Thus, the kinetic properties of ACTH are different in the developing animal and this partly explains the prolonged ACTH elevation observed after stress challenges.

Adrenocorticotropic Hormone↗

An audit of long-term octreotide therapy for acromegaly.

BACKGROUND: Octreotide has been successfully used for the treatment of acromegaly, but little long-term data are available. AIMS: To determine the long-term efficacy and safety of octreotide in the treatment of acromegaly. METHODS: Twenty-seven patients with acromegaly were treated with octreotide in a non randomised study. Six patients had not had previous surgery or radiotherapy, and were treated with octreotide alone. Symptoms of acromegaly, IGF-I levels, growth hormone suppression by glucose, pituitary tumour size, and side effects were monitored. The median duration of treatment was 44 months (range six-102). RESULTS: Symptom control was excellent. Twenty (74%) patients had a reduction of IGF-I into the normal range. IGF-I levels fell after one year from 94.2 +/- 6.1 nmol/L (mean +/- SEM) to 50.0 +/- 2.7 nmol/L (p < 0.0001). Ten of 13 (77%) patients had normal IGF-I levels after four years. These reductions have persisted for up to nine years of octreotide therapy. The GH response to glucose was normalised in 14 of 16 (88%) subjects. Eleven of 25 (44%) patients had a reduction in pituitary gland height. Side effects were common, but usually of a minor nature. Cholelithiasis occurred in 39% of patients. Two patients ceased octreotide because of side effects. CONCLUSIONS: We conclude that octreotide is an effective and safe long-term treatment for acromegaly. It is a useful adjunct to surgery, and may be offered as sole therapy for patients with smaller adenomas.

Acromegaly↗

Comparative analysis of biotin intranuclear inclusions of gestational endometrium using the APAAP, ABC and the PAP immunodetection systems.

AIMS/BACKGROUND: Intranuclear inclusions have been observed in gestational endometrial glands. Although resembling Herpes simplex virus infected cells, these nuclei have been shown to contain endogenous biotin. Hence, immunohistochemical systems using the avidin-biotin complex will result in cross reaction and false positivity. This study investigates a series of 10 gestational endometria (formalin fixed and paraffin wax embedded) with intranuclear inclusions using three different immunodetection systems with primary anti-biotin. RESULTS: Both the alkaline phosphatase anti-alkaline phosphatase (APAAP) and peroxidase anti-peroxidase (PAP) systems confirmed that the intranuclear inclusions were endogenous biotin. The streptavidin biotin complex (StreptABC) system produced a positive reaction in both test sections and controls (omitting primary anti-biotin) in the presence of prior blocking with free avidin and biotin. In addition, aberrant immunoreactivity was observed in adjacent nuclei/cytoplasm of endometrial glands and decidualised stroma in the negative control of the PAP system. This was subsequently eliminated using microwave pretreatment prior to immunohistochemistry. CONCLUSION: The use of either the APAAP or PAP immunodetection systems (the latter with microwave pretreatment) is recommended for any immunohistochemical or non-isotopic in situ hybridisation investigation undertaken on gestational endometria.

Biotin↗

Human papillomavirus and schistosomiasis associated bladder cancer.

AIMS: To determine the human papillomavirus DNA status of schistosomal associated squamous cell carcinoma of the urinary bladder in South Africa. METHODS: Twenty five archival samples of bladder squamous cell carcinoma associated with Schistosoma haematobium were subjected to non-isotopic in situ hybridisation and the polymerase chain reaction for the detection of human papillomavirus 6, 11, 16, 18, 31, and 33 genotypes. RESULTS: Using these two techniques, none of the 25 cases was shown to harbour human papillomavirus DNA. CONCLUSIONS: This study abrogates the role of human papillomavirus in schistosoma associated bladder carcinoma in South Africa. It is suggested that other factors including nitrosamine exposure, p53 mutation, and additional unknown chromosomal events play a major role in the development of this parasite associated neoplasm.

Carcinoma, Squamous Cell↗

Mental health in schools: expanded opportunities for school nurses.

Emerging trends are reshaping the work of school nurses and other school service personnel. With respect to direct service and consultation, school nurses increasingly are called upon to deal with psychosocial and mental health problems. Beyond that, school nurses must continue to actuate their roles as advocates, catalysts, brokers, and facilitators of the type of reforms that can effectively address barriers to student learning and promote healthy development. Continuing education is seen as key to enabling school nurses to build capacity for such roles and functions. The newly formed Center for Mental Health in Schools at the University of California, Los Angeles (UCLA) hopes to be of assistance in this respect. This presentation highlights the Center's orientation to mental health in schools and offers a draft outline for related continuing education.

Community Mental Health Services↗

A new mtDNA mutation showing accumulation with time and restriction to skeletal muscle.

We have identified a new mutation in mtDNA, involving tRNALeu(CUN) in a patient manifesting an isolated skeletal myopathy. This heteroplasmic A-->G transition at position 12320 affects the T psi C loop at a conserved site and was not found in 120 controls. Analysis of cultured fibroblasts, white blood cells/platelets, and skeletal muscle showed that only skeletal muscle contained the mutation and that only this tissue demonstrated a biochemical defect of respiratory-chain activity. In a series of four muscle-biopsy specimens taken over a 12-year period, there was a gradual increase, from 70% to 90%, in the overall level of mutation, as well as a marked clinical deterioration. Single-fiber PCR confirmed that the proportion of mutant mtDNA was highest in cytochrome c oxidase-negative fibers. This study, which reports a mutation involving tRNALeu(CUN), demonstrates clearly that mtDNA point mutations can accumulate over time and may be restricted in their tissue distribution. Furthermore, clinical deterioration seemed to follow the increase in the level of mutation, although, interestingly, the appearance of fibers deficient in respiratory-chain activity showed a lag period.

Base Sequence↗

Evaluation of outcome following lumbar discectomy.

AIM: To assess the outcome of patients who underwent lumbar discectomy for sciatica as determined by return to work, residual functional disability and self reported pain measures. METHODS: Ninety seven patients who had undergone L4-5 or L5-S1 discectomies for sciatica were reviewed 20 months after surgery. Variables assessed were: gender; length of preoperative time off work and compensation claims for treatment. Outcome was determined by current earning capacity, residual pain level and the Oswestry disability questionnaire. RESULTS: The length of preoperative sick leave had a significant effect on all outcome measures of function, pain, ability to return to full time work and current compensation status. Those patients who had more than 6 months sick leave prior to operation were less likely to have a favourable outcome. CONCLUSION: While chronicity of symptoms does not negate the indications for discectomy, the results suggest that the duration of preoperative leave needs to be considered prior to operation.

Analysis of Variance↗

Mapping the receptor domains critical for the binding selectivity of delta-opioid receptor ligands.

While a good deal has been learned about determinants of high affinity ligand/receptor interactions in G-protein-coupled receptors, less is known about mechanisms of ligand selectivity. The opioid receptors offer an excellent opportunity to study the mechanisms whereby structurally very similar receptors discriminate between different but structurally highly related ligands. In the current study, we use a series of chimeric constructs between the delta-opioid receptor and either the mu- or the kappa-opioid receptors to investigate the structural basis of binding selectivity of multiple classes of delta-opioid receptor selective ligands. Our results demonstrate that a region containing the sixth transmembrane domain (TM6) and the third extracellular loop (EL3) in the delta-opioid receptor is absolutely critical for delta-opioid receptor selectivity. The introduction of this region into the kappa-opioid receptor is sufficient to impart a delta profile for delta-opioid receptor selective alkaloids such as naltrindole and naltriben. In order to locate the amino acid residues that may be involved in ligand selectivity in TM6 and EL3 of the delta-opioid receptor, several mutations were introduced into that region. These mutations showed differential effects on peptide and alkaloid ligands. In addition, none of the individual mutations alone could account for the changes exhibited by the chimeric receptors. We conclude that the selectivity of most delta-opioid ligands is achieved through their interaction with many different residues in the TM6/EL3 region. Our results also support a view that the extracellular domains of peptide receptors may provide the basis of a sorting mechanism for ligand selectivity.

Binding, Competitive↗

Regulation of lysyl oxidase and cyclooxygenase expression in human lung fibroblasts: interactions among TGF-beta, IL-1 beta, and prostaglandin E.

Prostaglandin E2, transforming growth factor-beta, and interleukin-1 beta variably regulate the expression of cyclooxygenase 1, cyclooxygenase 2, and lysyl oxidase in IMR90, human embryo lung fibroblasts. Prostaglandin E2 at 100 nM upregulates cyclooxygenase 1 mRNA by approximately three-fold while it downregulates lysyl oxidase mRNA levels. Notably, prostaglandin E2 suppresses the enhancing effect of TGF-beta on basal levels of lysyl oxidase mRNA. These changes in steady state mRNA levels reflect transcriptional level control, at least in part. Corresponding changes are seen in the protein levels of lysyl oxidase, cyclooxygenase 1 and cyclooxygenase 2 and catalytic activities of these enzymes, including net prostaglandin E2 synthesis. Cyclooxygenase 2 mRNA(t1/2, 30 min) is considerably less stable than that of cyclooxygenase 1 (t1/2, 4 h) while lysyl oxidase mRNA is unusually stable (t1/2 > 14 h). Taken together with the differing kinetics with which these genes respond to perturbation by these cytokines, the present results suggest a coordinated, autocrine-like mechanism of regulation of cyclooxygenase 1 and cyclooxygenase 2 and further point to the potential of their metabolic product, prostaglandin E2, to suppress the expression of lysyl oxidase in the inflammatory response to injury.

Cyclooxygenase 1↗

Overexpression of the transcription factor UBF1 is sufficient to increase ribosomal DNA transcription in neonatal cardiomyocytes: implications for cardiac hypertrophy.

The accelerated protein accumulation characteristic of cardiomyocyte hypertrophy results from increased cellular protein synthetic capacity (elevated ribosome content). The rate limiting step in ribosome accumulation is transcription of the rRNA genes. During neonatal cardiomyocyte hypertrophy induced by norepinephrine or spontaneous contraction, changes in the expression of a ribosomal DNA transcription factor, UBF, correlated with increased rates of ribosome biogenesis. We hypothesized that elevated expression of UBF was part of the mechanism by which these hypertrophic stimuli effected increases in the rate of transcription from the rDNA promoter. In this study, we have examined directly the effect of overexpressing UBF on rDNA transcription in neonatal cardiomyocytes in culture. In control experiments, a novel reporter construct for rDNA transcription (pSMECAT) showed similar increases in activity in response to hypertrophic stimuli (10(-4) M phenylephrine, 10(-7) M endothelin, and spontaneous contraction) as did the endogenous rRNA genes. When contraction-arrested cardiomyocytes were cotransfected with pSMECAT and increasing amounts of a UBF1 expression vector; a dose-dependent (3-5 fold) increase in rDNA transcription was observed. Western blot analysis confirmed that the overexpressed, FLAG-tagged UBF accumulated in the cardiomyocyte nuclei. The observation that overexpression of UBF1 is sufficient to increase rDNA transcription in neonatal cardiomyocytes provides evidence in support of the hypothesis that the regulation of UBF is a key component of the increased ribosome biogenesis and protein accumulation associated with cardiomyocyte hypertrophy.

Animals↗

Structure of recombinant rat UBF by electron image analysis and homology modelling.

We have studied the structure of recombinant rat UBF (rrUBF), an RNA polymerase I transcription factor, by electron microscopy and image analysis of single particles contrasted with methylamine tungstate. Recombinant rat UBF appeared to be a flat, U-shaped protein with a central region of low density. In the dominant projections, 2-fold mirror symmetry was seen, consistent with the dimerization properties of this molecule, and of dimensions in agreement with the length of DNA that rat UBF protects in footprinting studies. Electron microscopy of various rrUBF-DNA complexes confirmed that our recombinant protein was fully able to bind the 45S rDNA promoter, and that it caused substantial bends in the DNA. Upon extended incubation in a droplet covered by a lipid monolayer at the liquid-air interface, rrUBF formed long filamentous arrays with a railway track appearance. This structure was interpreted to consist of overlapping rrUBF dimers 3.5 nm apart, which value would represent the thickness of the protein. Our results show rrUBF to interact with and bend the promoter DNA into a roughly 10 nm diameter superhelix. Based on all these electron microscopical results, an atomic structure was predicted by homology modelling of the HMG fingers, and connected by energy minimized intervening segments.

Animals↗