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Biomedical subjects

C A Harrington

Publications and source records attributed to C A Harrington.

At least 19 recordsLinked to original sources
PubMed2002

Expression profiling of B cell chronic lymphocytic leukemia suggests deficient CD1-mediated immunity, polarized cytokine response, altered adhesion and increased intracellular protein transport and processing of leukemic cells.

We used oligonucleotide microarrays to profile the expression of chronic lymphocytic leukemia (CLL) B cells from eight patients compared with CD5-expressing normal B cells from four donors and with pooled normal circulating B cells. Of 6790 genes examined, we identified 87 genes that were differentially expressed at least two-fold between CLL and the normal B cells. CLL cells significantly down-regulated transcripts from CD1c and CD1d genes, which encode proteins known to present lipid antigen and mediate innate and adaptive immunity. The expression pattern was also consistent with reduced signaling by interferon gamma but increased response to interleukin 4 in leukemic cells. CLL cells increased the expression of several collagen-associated extracellular matrix and adhesion molecules, up-regulated many genes involved in intracellular protein transport and processing, while downregulating genes involved in proliferation and metabolism. Based on the expression pattern, we propose that CLL-B cells prolong their survival through increased interaction with survival factors such as IL-4, and through various mechanisms of evading the immune response, such as turning off the expression of CD1c and CD1d, reducing immunogenic response to interferon gamma, inactivating T cell in B-T interaction and increasing the expression of immunoglobulin receptors which neutralize antibody-dependent cell-mediated cytotoxicity.

Adult↗
PubMed2002

Analysis of high density expression microarrays with signed-rank call algorithms.

MOTIVATION: We consider the detection of expressed genes and the comparison of them in different experiments with the high-density oligonucleotide microarrays. The results are summarized as the detection calls and comparison calls, and they should be robust against data outliers over a wide target concentration range. It is also helpful to provide parameters that can be adjusted by the user to balance specificity and sensitivity under various experimental conditions. RESULTS: We present rank-based algorithms for making detection and comparison calls on expression microarrays. The detection call algorithm utilizes the discrimination scores. The comparison call algorithm utilizes intensity differences. Both algorithms are based on Wilcoxon's signed-rank test. Several parameters in the algorithms can be adjusted by the user to alter levels of specificity and sensitivity. The algorithms were developed and analyzed using spiked-in genes arrayed in a Latin square format. In the call process, p-values are calculated to give a confidence level for the pertinent hypotheses. For comparison calls made between two arrays, two primary normalization factors are defined. To overcome the difficulty that constant normalization factors do not fit all probe sets, we perturb these primary normalization factors and make increasing or decreasing calls only if all resulting p-values fall within a defined critical region. Our algorithms also automatically handle scanner saturation.

Algorithms↗
PubMed2001

Health and long-term care for people with Alzheimer's disease and related dementias: policy research issues.

Policy research into the service needs of persons with dementia had its origin looking at challenges confronting caregivers--extended hours of instrumental task assistance, social isolation, fatigue, depression--and how public policy might support informal care-giving while saving public expenditures from nursing home care. This paper, drawing on the experience of the Medicare Alzheimer's Disease Demonstration and other work, provides suggestions for extending care and financing considerations to include health care use and the medical management of chronic health conditions. Basic research is needed to document current use and risk factors, as is experimentation with clinical and other interventions designed to achieve desired quality of care and cost outcomes. This section of the paper will be of direct interest to both US and international readers. The second half of the paper reviews the US state role in regulating and financing nursing homes, home and community-based care, and residential care. All these sectors have high rates of staff turnover, staff shortages, and concerns with quality of care. The international community and US states provide naturally occurring opportunities for delivery system experimentation and innovation. Research taking advantage of these opportunities could greatly inform public policy.

Aged↗
PubMed2000

Analysis of mucosal gene expression in inflammatory bowel disease by parallel oligonucleotide arrays.

DNA arrays capable of simultaneously measuring expression of thousands of genes in clinical specimens from affected and normal individuals have the potential to provide information about disease pathogenesis not previously possible. Few studies have applied mRNA profiling to diseases involving complex tissues like the intestinal mucosa, reflecting the unique challenges inherent to this type of analysis. We report the analysis of mucosal gene expression in ulcerative colitis (UC) patients and inflamed and noninflamed control specimens. Genes can be used as markers for cell recruitment, activation, and mucosal synthesis of immunoregulatory molecules. Self-organizing maps were applied to cluster and analyze gene expression patterns and were paired with histopathological scores to identify genes associated with increased disease activity. Clustering was achieved on the basis of differences in expression levels across individual specimens. Several inflammatory mediators were identified as likely determinants of characteristic histological features of active UC. These results provide proof of principle for application of functional genomics to larger inflammatory bowel disease populations for gene discovery, to facilitate identification of disease subgroups on the basis of gene expression signatures, and for prediction of disease behavior or optimal therapeutic intervention.

Adolescent↗
PubMed2000

Monitoring gene expression using DNA microarrays.

The concurrent development of high-density array technologies and the complete sequencing of a number of microbial genomes is providing the opportunity to comprehensively and efficiently survey the transcription profile of microorganisms under different conditions and well-defined genotypes. Microarray-based studies are uncovering broad patterns of genetic activity, providing new understanding of gene functions and, in some cases, generating unexpected insight into transcriptional processes and biological mechanisms. One topic that has come to the forefront is how best to effectively manage and interpret the large data sets being generated. Although progress has been made, this remains a challenging opportunity for functional genomics research.

Gene Expression Regulation, Bacterial↗
PubMed2000

Germany's long-term-care insurance: putting a social insurance model into practice.

A growing population of elderly has intensified the demand for long-term care (LTC) services. In response to the mounting need, Germany put into effect a LTC Insurance Act in 1995 that introduced mandatory public or private LTC insurance for the entire population of 82 million. The program was based on the organizational principles that define the German social insurance system. Those individuals in the public system and their employers each pay contributions equal to 0.85 percent of each employee's gross wages or salary. Ten percent of the population with the highest incomes have chosen the option of purchasing private long term care insurance. Provisions were made for uniform eligibility criteria, benefits based on level of care needs, cost containment, and quality assurance. Over the first four years of its operation, the system has proved financially sound and has expanded access to organized LTC services. The German system thus may serve as an example for other countries that are planning to initiate social LTC insurance systems in other nations.

Aged↗
PubMed1998

Ribosomal RNA transcriptional activation and processing in hamster facial motoneurons: effects of axotomy with or without exposure to testosterone.

A key step in the ability of neurons to survive injury and successfully regenerate involves ribosomal RNA production. Testosterone propionate (TP), augments facial nerve regeneration in the adult hamster. TP modulates the nucleolar reaction in injured facial motoneurons, such that mature ribosome levels increase more rapidly and in greater magnitude than with injury only. In this study, molecular and electron microscopic stereologic approaches were used to determine the effects of axotomy and steroid treatment on ribosomal transcription and processing in facial motoneurons. Castrated adult male hamsters were subjected to right facial nerve transection at the stylomastoid foramen. Half the animals were subcutaneously implanted with one Silastic TP capsule, with the remainder sham implanted. For the in situ hybridization experiments, postoperative survival times were 0.5, 2, or 6 hours. In situ hybridization with a ribosomal DNA probe specific to the external transcribed spacer region located at the 5' end of the ribosomal gene was accomplished. Transcriptional activation of the rRNA gene occurred rapidly, within 2 hours, after injury only. Unexpectedly, TP treatment did not alter the time course or magnitude of rRNA transcriptional activity. For the electron microscope experiments, the postoperative time of 12 hours was selected. Stereologic analysis of 3 nucleolar subcomponents, fibrillar centers (site of rRNA transcription), nucleolonema (site of rRNA processing), and granular material (site of preribosome storage), was accomplished. TP decreased the nucleolonemal strands and the granular material, relative to injury only. These results suggest that, although rRNA transcription is rapidly activated by axotomy, rRNA processing is temporarily stalled. TP does not affect the early, axotomy-induced transcriptional activation of the ribosomal gene, but may, instead, prevent the subsequent disruption in rRNA processing. An hypothesis for the molecular mechanism by which steroids augment the regenerative capabilities of injured facial motoneurons is presented.

Animals↗
PubMed1996

Investigation of the effects of solution composition and container material type on the loss of 11-nor-delta 9-THC-9-carboxylic acid.

The loss of 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) from solution was studied using fluorescence polarization immunoassay (FPIA) technology and x-ray photoelectron spectroscopy (XPS). Several materials (glass, silylated glass, high density polyethylene, polypropylene, polystyrene, polymethylmethacrylate, Teflon, and Kynar) were studied along with three solvents (water, urine, and Abbott cannabinoids diluent). THC-COOH losses ranging from 0 to 9.7 ng/cm2 and concentration reductions to 46% of starting values were measured. XPS indicated the presence of fluorine-labeled THC-COOH at materials surfaces. A half-life of 10 min was calculated for THC-COOH loss from urine stored in high density polyethylene at room temperature. Sample handling losses during pipetting were determined and ranged from 1.1 to 7.9 ng per aliquot. The effects of sample volume and sample handling on the THC-COOH concentrations of controls were also investigated.

Dronabinol↗
PubMed1994

Nitric oxide formation does not underlie the memory deficits produced by ibotenate injections into the nucleus basalis of rats.

Basal forebrain (BF) injections of ibotenic (IBO) acid impair memory, whereas quisqualic (QUIS) acid injections do not. The authors investigated whether the cytotoxicity and differential behavioral effects of IBO and QUIS in rats depend on the generation of nitric oxide (NO). Injections of IBO or sodium nitroprusside (NP), but not QUIS, significantly increased BF NO formation, as determined by guanosine 3,5-cyclic monophosphate levels. IBO, alone or coinjected with methylene blue (MB), and QUIS, alone or coinjected with NP, decreased cortical choline acetyltransferase (ChAT) activity and the number of ChAT-positive BF neurons. The BF levels of galanin or neuropeptide Y were unchanged in all lesion groups. QUIS, but not IBO, dose-dependently destroyed NO-producing BF cells. Injections of IBO, with or without MB, impaired choice accuracy in a T-maze alternation task. The results suggest that the generation of NO in the BF does not underlie the spatial working memory deficit produced by IBO.

Animals↗
PubMed1994

Immunoassay reagents for psychoactive drugs. Part 4. Quantitative determination of amitriptyline and nortriptyline by fluorescence polarization immunoassay.

Methods for the quantitative determination of amitriptyline and nortriptyline by fluorescence polarization immunoassay (FPIA) is described. One immunoassay allows for the accurate quantification of amitriptyline in the presence of nortriptyline while the second immunoassay allows for the accurate quantification of nortriptyline in the presence of amitriptyline.

Amitriptyline↗
PubMed1994

Immunoassay reagents for psychoactive drugs. Part 5. Quantitative determination of imipramine and desipramine by fluorescence polarization immunoassay.

Two methods for the quantitative determination of imipramine (IMI) and desipramine (DMI) by fluorescence polarization immunoassay (FPIA) are described. One immunoassay allows for the accurate quantification of imipramine in the presence of desipramine, while the other allows for the accurate quantification of desipramine in the presence of imipramine.

Chromatography, High Pressure Liquid↗
PubMed1994

Etiopathogenesis and treatment of psychosis.

Psychotic illnesses (schizophrenia and schizoaffective and affective psychosis) have a lifetime prevalence of 2-3% and probably occur at a similar rate in all human societies. No etiologically significant environmental precipitants have been identified, and this suggests that these diseases are primarily genetic. Brain studies reveal that in schizophrenic patients, development of cerebral asymmetry is arrested, which may be associated with a small reduction in cortical mass. Episodes of illness can be ameliorated by dopamine (in particular D2) antagonists, drugs that are antipsychotic rather than merely antischizophrenic. The discovery of at least five dopamine receptor subtypes and their genes paves the way for new approaches to treatment. However, whether psychotic patients undergo a primary disturbance of dopaminergic transmission remains unclear.

Adult↗
PubMed1993

Immunoassay reagents for psychoactive drugs. Part 3. Removal of phenothiazine interferences in the quantification of tricyclic antidepressants.

Phenothiazines and their metabolites are known to interfere in the quantification of tricyclic antidepressants (TCAs). A method for selective chemical modification of phenothiazines by chloramine-T in the presence of TCAs is described. This method allows for accurate quantification of the TCA analyte in a serum sample without interference from the modified phenothiazine.

Antidepressive Agents, Tricyclic↗
PubMed1992

Basal forebrain neurons and memory: a biochemical, histological, and behavioral study of differential vulnerability to ibotenate and quisqualate.

The differential vulnerability of basal forebrain cells to ibotenate (IBO) or quisqualate (QUIS) was investigated in rats. IBO was also coinjected with cystine (CYS) or zinc (Zn). Cortical choline acetyltransferase (ChAT) and glutamate decarboxylase (GAD) activity, neurotensin receptors, and high-affinity choline uptake sites were quantified in conjunction with radioimmunoassays for neurotensin, substance P, and somatostatin; immunocytochemistry for neurotensin-, somatostatin-, Leu-enkephalin-, and ChAT-positive cells; and in situ hybridization histochemistry of somatostatin, substance P, and enkephalin mRNAs. Compared with the performance of controls, continuous alternation performance in a T maze of IBO+Zn or IBO+CYS rats was better than that of IBO rats, whereas the performance of QUIS rats was unimpaired. Of those neurotransmitter systems examined, only ChAT-immunoreactive cells were vulnerable to IBO or QUIS. However, cholinergic cell loss did not correlate with impaired performance.

Animals↗
PubMed1990

Steroid hormone regulation of ribosomal RNA in rat hypothalamus: early detection using in situ hybridization and precursor-product ribosomal DNA probes.

In the female rat, behavioral and endocrine aspects of reproduction are controlled, in part, by the action of the steroid hormone estradiol on several regions of the brain, including the ventrolateral portion of the ventromedial hypothalamus (VL-VMN) and the arcuate nucleus of the hypothalamus (ARC). Quantitative assessment of the effects of estradiol on the regulation of ribosomal RNA in rat hypothalamus was accomplished in this study by tandem in situ hybridization experiments with 2 ribosomal DNA probes specific to the initial transcript (precursor) or mature, stable (product) rRNA. This novel approach allowed the regulation of RNA processing by steroid hormones to be analyzed in the individual neuron, a particularly important concern in heterogeneous tissue such as the brain. Estradiol was administered subcutaneously to ovariectomized rats for 15 min, 30 min, or 2 hr, or a discontinuous schedule of 2 hr on/7 hr off/2 hr on. Levels of precursor and product rRNA were measured in VL-VMN and ARC neurons using a computerized image-analysis system. Significant increases in the levels of precursor rRNA were observed only in the VL-VMN as early as 30 min after hormone exposure, with a doubling in the amount of precursor rRNA occurring at 2 hr. No changes in product rRNA were observed in either brain region at these early times. These data, in conjunction with our previous findings of increases in product rRNA after longer hormone exposure times, lead us to conclude that rRNA gene transcription is activated in rat hypothalamic neurons within 30 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Tyrosine hydroxylase mRNA in the neurons of the tuberoinfundibular region and zona incerta examined after gonadal steroid hormone treatment.

The dopamine-producing neurons of the tuberoinfundibular region are known targets of estrogen and progesterone, and are of considerable neuroendocrine importance. To determine the anatomical distribution, and number of cells that contain tyrosine hydroxylase (TH) mRNA in the tuberoinfundibular region and other regions of the brain we carried out in situ hybridization on sections prepared from ovariectomized female rats given either oil vehicle, or estrogen, or estrogen plus progesterone. The intensity of label per cell was assessed to compare the relative amount of mRNA found per cell among TH-mRNA containing cells. [3H]cRNA probes to the rat TH sequence were used. Autoradiograms demonstrated the presence of TH-mRNA in the cytoplasm of cells in the arcuate and periventricular nuclei, zona incerta, substantia nigra, and the adrenal medulla. The number and anatomical distribution of cells that contained TH-mRNA was identical to the number and distribution of cells previously demonstrated by others to contain TH immunoreactivity. In the arcuate and periventricular nuclei, compared to treatment with estrogen alone, estrogen plus progesterone did lead to a statistically significant decrease in the number of TH mRNA-containing cells we could detect. No alteration in the mean number of grains per cell, among cells detected as containing TH-mRNA was found in any group. In contrast, these same hormone treatments had no effect on the number TH-mRNa producing cells we could detect in the zona incerta. Most of the cells in the zona incerta are found within the same tissue sections as arcuate/periventricular cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1988

Quantitation of thiothixene in plasma by high-performance thin-layer chromatography and fluorometric detection.

A specific and sensitive assay procedure to measure thiothixene (Navane) in plasma has been developed and used to measure plasma concentrations in patients receiving thiothixene. The procedure involves in situ fluorescent detection after separation by high-performance thin-layer chromatography. Fluorescent detection permits a limit of detectability of approximately 0.1 ng/ml in plasma and the coefficient of variation is less than 6% at 2 ng/ml. Thirty samples may be processed through the entire procedure in less than 6-h period and up to 60 samples may be simultaneously spotted and chromatographed with a larger-capacity spotter and plate. Plasma levels (n = 62) drawn 10-12 h after dosage ranged from 0 to 42 ng/ml from dosages of 4-100 mg/day.

Chromatography, Thin Layer↗