Search PubMed⌕ Search

Biomedical subjects

S Taylor

Publications and source records attributed to S Taylor.

At least 253 records · Page 14Linked to original sources

A refractory phase in cyclic AMP-responsive transcription requires down regulation of protein kinase A.

Cyclic AMP (cAMP) stimulates the expression of numerous genes through the protein kinase A (PK-A)-mediated phosphorylation of the nuclear factor CREB at Ser-133 (G. A. Gonzalez and M. R. Montminy, Cell 59:675-680, 1989). Like other signal transduction pathways, cAMP induces gene expression with burst-attenuation kinetics; cAMP-dependent transcription and CREB phosphorylation peak within 30 min and decline steadily over the next 4 to 6 h via the protein phosphatase 1-mediated dephosphorylation of CREB (M. Hagiwara, A. Alberts, P. Brindle, J. Meinkoth, J. Feramisco, T. Deng, M. Karin, S. Shenolikar, and M. Montminy, Cell 70:105-113, 1992). Here we characterize a third phase in cAMP-responsive transcription--a refractory period during which hormone-treated cells become transcriptionally unresponsive to subsequent stimulation by cAMP. This refractory period begins 6 to 8 h after stimulation and lasts 3 to 5 days after the removal of hormone. In contrast to the earlier attenuation phase, transcription of cAMP-responsive genes during the refractory period is not restored by inhibitors of protein phosphatase 1 activity. Rather, the establishment and maintenance of this phase rely on a marked reduction in PK-A catalytic subunit expression at the translational level. As overexpression of C-subunit protein can reactive transcription of cAMP-responsive genes during the refractory period, our results suggest that hormone-responsive cells may stimulate, attenuate, and then silence signal-dependent genes through distinct regulatory mechanisms.

Animals↗

Overexpression of human apolipoprotein B-100 in transgenic rabbits results in increased levels of LDL and decreased levels of HDL.

In this study, and 80-kb human genomic DNA fragment spanning the human apoB gene was used to generate transgenic New Zealand White rabbits that expressed human apoB-100. The concentration of human apoB in the plasma of the transgenic rabbits ranged between 5 and 100 mg/dL. The transgenic rabbits had nearly threefold elevations in the plasma levels of triglycerides and cholesterol compared with nontransgenic controls. Nearly all the cholesterol and human apoB in the plasma was in the LDL fraction. Pronounced triglyceride enrichment of the LDL fraction was a striking feature of human apoB overexpression in the transgenic rabbits, in which the LDL fraction contained more than 75% of the plasma triglycerides. The triglyceride-enriched LDL particles were smaller and more dense than the native rabbit LDL and contained markedly increased amounts of apoE and apoC-III. In the nontransgenic control animals most of the triglycerides were in the VLDL, and most of the apoE and apoC-III were in the VLDL and HDL fractions. In addition to increased LDL levels, overexpression of human apoB in rabbits resulted in lower plasma levels of HDL cholesterol and apoA-I. In our prior studies on transgenic mice expressing human apoB, we documented triglyceride-rich LDL and reduced levels of HDL cholesterol. These prior findings in mice, together with the present findings in transgenic rabbits, suggest that triglyceride-rich LDL and lowered levels of HDL cholesterol may be hallmark features of apoB overexpression.

Animals↗

Sneddon's syndrome with granulomatous leptomeningeal infiltration.

BACKGROUND: There is limited neuropathologic information available from cases of Sneddon's syndrome in which strokes are associated with livedo reticularis. Pathogenesis of the syndrome is controversial, although current opinion favors a coagulopathy, often with antiphospholipid antibodies. We describe a case lacking antiphospholipid antibodies but having a granulomatous infiltration of the leptomeninges. CASE DESCRIPTION: The patient presented at age 29 with stroke, livedo reticularis, essential hypertension, and Raynaud's phenomenon. Assessment uncovered no underlying disease, including absent antiphospholipid antibodies. A leptomeningeal biopsy showed granulomatous infiltration. CONCLUSIONS: The findings suggest that an inflammatory process plays a role in at least some cases of Sneddon's syndrome.

Adult↗

Expression of human apolipoprotein B90 in transgenic mice. Demonstration that apolipoprotein B90 lacks the structural requirements to form lipoprotein.

Lipoprotein(a) (Lp(a)) is a lipoprotein formed by the disulfide linkage of apolipoprotein(a) (apo(a)) to the apoB100 of a low density lipoprotein particle. Earlier site-directed mutagenesis studies of apo(a) demonstrated that apo(a) cysteine 4057 is required for the disulfide linkage; however, the cysteine residue within apoB100 that is involved in the disulfide bond has not been identified. We previously demonstrated that the apoB100 produced by human apoB transgenic mice binds to apo(a) and forms Lp(a) (Linton, M.F., Farese, R. V., Jr., Chiesa, G., Grass, D. S., Chin, P., Hammer, R. E., Hobbs, H.H., and Young, S.G. (1993) J. Clin. Invest. 92, 3029-3037). To further explore the structural features of human apoB that are required for the formation of Lp(a), we used a transposon-interrupted human apoB gene clone to develop transgenic mice that express high levels of a truncated form of human apoB, apoB90, which contains the amino-terminal 4084 amino acids of apoB. In vitro incubation of apo(a) with the plasma of human apoB90 transgenic mice did not yield Lp(a), as judged by Western blots of SDS-polyacrylamide gels or by a monoclonal antibody-based radioimmunoassay. In contrast, incubation of apo(a) with the plasma of a mouse that expressed an equivalent amount of the full-length apoB100 did yield Lp(a). In addition to these in vitro incubation studies, no Lp(a) could be detected in the plasma of a "double transgenic" mouse expressing both human apoB90 and apo(a). These data indicate that the carboxyl-terminal 10% of apoB100 contains amino acid sequences that are essential for the formation of Lp(a).

Animals↗

Acute-phase hepatocytes regulate liver sinusoidal cell mediator production.

BACKGROUND: Overproduction of liver sinusoidal cell (LCS) mediators in response to endotoxemia or gram-negative infection that follows tissue injury may contribute to hepatic dysfunction. OBJECTIVE: To better define the role of hepatocyte-derived acute-phase reactants in the regulation of sinusoidal cell mediator production following sequential insults, we tested the hypothesis that interleukin-6 (IL-6) prestimulation alters hepatocyte regulation of lipopolysaccharide (LPS)-stimulated sinusoidal cell tumor necrosis factor (TNF), IL-6, and nitric oxide production. METHODS: Hepatocytes and LSCs were isolated from Wistar rats, and in vitro responses were compared between LSCs alone and hepatocyte-LSC cocultures. Cocultures and LSCs alone were sequentially stimulated with IL-6 (5000 U/mL) then LPS (dose-response), and culture supernatants were analyzed for TNF (L929 cytolysis), IL-6 (7TD1 proliferation), and nitric oxide (Griess reaction). Induction of acute-phase protein synthesis by the stimulation of hepatocytes with IL-6 and dexamethasone (0.1 mumol/L) was assayed by methionine radiolabeling and SDS-PAGE (sodium dodecyl sulfate-polyacrylamide gel electrophoresis). Coculture levels of messenger RNA for TNF-alpha and IL-6 were examined by RNA extraction and reverse transcriptase polymerase chain reaction with specific primers. RESULTS: Interleukin-6 and dexamethasone signal hepatocyte acute-phase protein synthesis. Prestimulation of cocultures, but not of LSCs alone, with IL-6 inhibits LPS-stimulated IL-6 and nitric oxide production significantly. Bioactivity of TNF is reduced to a lesser extent. Polymerase chain reaction analysis demonstrated similar levels of TNF and IL-6 message following sequential stimulation. CONCLUSIONS: Interleukin-6-stimulated acute-phase hepatocytes limit LPS-stimulated coculture cytokine bioactivity and nitric oxide production. This hepatocyte response may provide a local counterregulatory mechanism to limit LSC-mediated injury.

Acute-Phase Proteins↗

Tibial hemimelia syndrome: prenatal diagnosis by real-time ultrasound.

The tibial hemimelia syndrome is a rare autosomal dominant condition associated with limb deficiencies. We recently diagnosed this condition in a pregnancy at 16.5 weeks' gestation by ultrasound and a positive family history. To our knowledge, this represents the first case to be detected prenatally.

Adult↗

Phase II study of intravenous melphalan (NSC-8806) in the treatment of patients with advanced squamous carcinoma of the head and neck.

The Illinois Cancer Center entered 25 patients on a phase II trial of intravenous melphalan treating patients with recurrent, metastatic or locally advanced and inoperable squamous cell carcinoma of the head and neck. All patients had bi-dimensionally measurable disease, at least a sixty day life expectancy, and adequate performance status (ECOG scale < or = 2). All patients except one had received prior radiotherapy, chemotherapy or both. Melphalan dosage was 30 mg/m2 every three weeks. Twenty-four patients were evaluable for response. One patient with laryngeal carcinoma had a clinical complete response of a nodal metastasis. Four patients had stabilization of disease for one to three months. There was formidable toxicity, including neutropenia (ANC < 1000/microliters 36%), and thrombocytopenia (< 50,000/microliter 32%). There were no drug-related deaths. Melphalan administered intravenously does not appear to be efficacious therapy in patients with previously treated advanced head and neck squamous carcinomas.

Adult↗

A follow-up of a media-based, worksite smoking cessation program.

Described an examination of data collected 2 years following the onset of a media-based, worksite smoking cessation intervention. Thirty-eight companies in Chicago were randomly assigned to one of two experimental conditions. In the initial 3-week phase, all participants in both conditions received self-help manuals and were instructed to watch a 20-day televised series designed to accompany the manual. In addition, participants in the group (G) condition received six sessions emphasizing quitting techniques and social support. In the second phase, which continued for 12 months, employees in G participated in monthly peer-led support groups and received incentives, while participants in the nongroup (NG) condition received no further treatment. Twenty-four months after pretest, 30% of employees in G were abstinent compared to only 19.5% in NG. This study is one of the few experimentally controlled worksite smoking cessation interventions to demonstrate significant program differences 2 years following the initial intervention.

Employment↗

A stimulus control technique for improving the efficacy of an established toilet training program.

Standard toilet training regimens used with children with developmental disabilities have demonstrated effectiveness at achieving bladder and bowel continence. However, in some clinical applications in everyday practice, success has not been achieved, necessitating research into possible modifications of the current approaches. A widely used toilet training program was modified to reduce toileting accidents of a referred child. The modification involved the assessment of the discriminative stimulus for eliminating, namely, his undergarments. By removing the undergarments when an elimination became imminent, an "errorless" learning paradigm was established that allowed for more rapid and enduring acquisition of toileting skills than seen in previous training attempts. The results indicate the present procedure could expedite training for individuals who are difficult to teach appropriate toileting skills through an analysis of the controlling antecedent stimulus for accidents and subsequent manipulation of such stimuli.

Autistic Disorder↗

Role of selective recall in the overprediction of fear.

Overprediction of fear is a bias in which phobic individuals tend to overestimate the amount of fear they will experience in a subjectively threatening situation. The selective recall model states that this bias arises because memories of highly fearful experiences are more easily retrieved than memories of nonfearful experiences. The model predicts that phobics should show a greater magnitude of overprediction if they receive fear-relevant priming compared with fear-irrelevant priming. A study of 100 spider-fearful Ss found that the magnitude of overprediction was smallest after fear-relevant priming, thus refuting the model. Alternative models are considered, and directions for further investigation are set out.

Adult↗

The overprediction of fear: is it a form of regression toward the mean?

Fearful people tend to overpredict the amount of fear they will experience in subjectively threatening situations. Little is known about the determinants of overprediction bias, although it has been suggested that it is a form of regression toward the mean. In this article I argue that the regression effect is a description (phenomenon) rather than explanation, and so the regression toward the mean cannot "explain" the overprediction bias. Regression may be due to psychologically meaningful factors, and should not be dismissed as a statistical artifact. However, there are present several reasons why the overprediction of bias is unlikely to be a form of regression. This conclusion is supported by reanalyses of two recent studies.

Fear↗

Correlation between the activities of five ribosome-inactivating proteins in depurination of tobacco ribosomes and inhibition of tobacco mosaic virus infection.

The rRNA depurination activities of five ribosome-inactivating proteins (RIPs) were compared in vitro using yeast and tobacco leaf ribosomes as substrates. All of the RIPs (pokeweed antiviral protein (PAP), dianthin 32, tritin, barley RIP and ricin A-chain) were active on yeast ribosomes. PAP and dianthin 32 were highly active and ricin A-chain weakly active on tobacco ribosomes, whereas tritin and barley RIP were inactive. PAP and dianthin 32 were highly effective in inhibiting the formation of local lesions caused by tobacco mosaic virus (TMV) on tobacco leaves, whereas tritin, barley RIP and ricin A-chain were ineffective. The apparent anomaly between the in vitro rRNA depurination activity, but lack of antiviral activity of ricin A-chain was further investigated by assaying for rRNA depurination in situ following the topical application of the RIP to leaves. No activity was detected, a finding consistent with the apparent lack of antiviral activity of this RIP. Thus, it is concluded that there is a positive correlation between RIP-catalysed depurination of tobacco ribosomes and antiviral activity which gives strong support to the hypothesis that the antiviral activity of RIPs works through ribosome inactivation.

Aniline Compounds↗

Imagery and craving in alcohol dependent persons.

There is limited evidence supporting the effectiveness of imagery techniques in exposure-based treatments for alcohol dependence. Changes in craving for alcohol following imagery instruction, measured by cognitive and physiological indices, have not been demonstrated. Furthermore, the influence of different imagery script content has not been investigated. This study compared levels of craving elicited, measured by self-report and salivation, under control and imagery conditions, in subjects receiving treatment for alcohol dependence. Imagery script content was varied across three levels. Participants generally reported forming good quality images with strong affective components. Significant effects of imagery treatment were found for changes in self-reported craving levels, but not for the salivation measure. Significant decay in levels of self-reported craving was also observed. No differences in effectiveness between the three script types were discovered. Implications of the results for therapy approaches such as cue exposure are considered.

Journal Article↗

Class I major histocompatibility complex-restricted cytotoxic T lymphocytes are not necessary for heterotypic immunity to influenza.

Mice transgenic for beta 2-microglobulin deletion (beta 2M-/-) were immunized intranasally with either a recombinant vaccinia virus that expressed both nucleoprotein and interleukin-2 or by infection with H3N2 influenza virus; 3-4 weeks later they were challenged with H1N1 influenza virus. The immunized beta 2M-/- mice had increased survival and enhanced clearance of virus relative to nonimmune controls. This protection correlated with the development of class II major histocompatibility complex-restricted pulmonary cytotoxic T lymphocyte activity and nasal IgA anti-nucleoprotein antibody. Heterotypic immunity can therefore be generated by a mechanism that does not involve class I major histocompatibility complex-restricted T cells.

Animals↗

Pressure and volume control for local drug-delivery catheters: development of a new microprocessor-controlled system.

BACKGROUND: Local drug delivery is a potential solution to postintervention restenosis. Most catheters developed for local delivery depend upon control of pressure and of delivered volume for optimal performance. The present study was designed to assess the accuracy of current methods for inflation of local delivery catheters compared with a new microprocessor-controlled system specifically designed for this application. METHODS: An in vitro gravimetric testing system was constructed to record developed pressure and delivered volume using a variety of inflation devices and a microporous infusion catheter. Experienced catheterization laboratory personnel were given commercial angioplasty indeflators and a pressure-driven syringe and asked to quickly apply 5 atm and deliver 2.0 ml. A new microprocessor-controlled system was then tested using the same protocol. RESULTS: The time required to reach a plateau pressure was lowest with the pressure-driven syringe (0.164 +/- 0.017 s) and much higher with standard indeflators (2.94 +/- 2.54, 4.64 +/- 2.98, 7.69 +/- 4.89, 8.28 +/- 6.31 s). The corresponding microprocessor-controlled value was much lower than that of the manual systems (0.84 +/- 0.37 s). The variability of plateau pressure, as measured by the standard deviation, was lowest with the pressure-driven syringe (0.029 +/- 0.014 atm) and highest with the manual systems (0.37 +/- 0.26, 0.40 +/- 0.18, 0.44 +/- 0.31, 0.32 +/- 0.10 atm). The microprocessor-controlled system also produced very little variability in pressure (0.08 +/- 0.004 atm). The volume delivered varied significantly with all manual devices (1.77 +/- 0.64, 1.74 +/- 0.66, 1.36 +/- 0.45, 1.80 +/- 0.33 ml) as well as with the pressure-driven syringe (1.86 +/- 0.32 ml), but the volume delivered by the microprocessor-controlled system was highly accurate (1.99 +/- 0.06 ml). CONCLUSIONS: Manual inflation devices do not allow precise control of pressure or volume when used with local delivery catheters. Use of a pressure-driven syringe minimizes pressure error, but does not deliver an accurate volume. The microprocessor-controlled system minimizes pressure and volume error and should maximize transfer efficiency for local delivery catheter systems.

Angioplasty, Balloon, Coronary↗