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Biomedical subjects

C Murphy

Publications and source records attributed to C Murphy.

At least 145 records · Page 8Linked to original sources
PubMed1996

Further analysis of the relationship between self-injury and self-restraint.

It has been suggested that self-restraint, a phenomenon often correlated with self-injurious behavior (SIB), may be maintained by negative reinforcement in the form of escape from the aversive properties of SIB (e.g., pain). We examined the effects of blocking SIB (and presumably removing any aversive effects) on the self-restraint of a 19-year-old male with severe mental retardation. Consistent with the negative reinforcement hypothesis, blocking SIB resulted in near-zero levels of SIB and moderate reductions in self-restraint.

Adult↗
PubMed1996

Development of major depressive disorder during smoking-cessation treatment.

BACKGROUND: Several studies have shown an association between smoking and major depressive disorder (MDD), but few have prospectively examined subjects who develop MDD after quitting smoking. This descriptive study evaluated the development of MDD after smoking cessation, as assessed by a structured clinical interview at both baseline and the end of treatment. METHOD: Nondepressed participants (N = 114) in a trial investigating the effect of fluoxetine on smoking cessation were administered the Structured Clinical Interview for DSM-III-R at baseline and posttreatment to evaluate the impact of quitting smoking on the development of MDD. Depressive symptoms were additionally assessed with the Beck Depression Inventory and the Hamilton Rating Scale for Depression. RESULTS: At baseline, 32% of the subjects reported a history of MDD. Sixty-nine subjects completed the SCID at baseline and posttreatment. At posttreatment, 5 subjects (7%) met threshold criteria for MDD; none were taking the highest dose of fluoxetine (60 mg), 4 were taking 30 mg, and 1 was taking placebo. All 5 had a history of MDD; 3 were women. Four had a history of substance abuse and attained at least 3 consecutive biochemically verified weeks of smoking abstinence. Those who developed MDD after treatment scored significantly higher on measures of depressed mood at baseline than those who did not develop MDD after smoking-cessation treatment. CONCLUSION: The results from this descriptive study suggest that a subset of smokers may be at risk for developing MDD after smoking cessation.

Behavior Therapy↗
PubMed1996

The Sm binding site targets U7 snRNA to coiled bodies (spheres) of amphibian oocytes.

Using cytoplasmic and nuclear injection assays, we show that U7 snRNA constructs are targeted rapidly and specifically to the coiled bodies (spheres) in the germinal vesicle (GV) of the amphibian oocyte, including those coiled bodies attached to the lampbrush chromosomes at the histone gene loci. Because the U7 snRNP is required for removing the 3' end of histone pre-mRNA, we suggest that a major function of coiled bodies is to recruit U7 snRNPs to the histone gene loci, before they associate with the pre-mRNA. Targeting to coiled bodies requires the specific U7 Sm binding site; replacement of the U7 Sm site by that of U2 snRNA reduces this targeting dramatically. No other part of the molecule is required, and the U7 Sm binding site alone is sufficient to direct nuclear import of an unrelated RNA sequence and its specific targeting to coiled bodies. Injected U7 constructs displace the endogenous U7 in the coiled bodies, the amount of injected U7 that ends up in coiled bodies being roughly equal to the amount of endogenous U7 snRNA.

Amphibians↗
PubMed1996

Expression and activation of protein kinase C isoforms in a human megakaryocytic cell line.

Megakaryocytes undergo a unique differentiation program, becoming polyploid through repeated cycles of DNA synthesis without concomitant cell division. We have shown previously that phorbol 12-myristate 13-acetate (PMA) induces the Dami human megakaryocytic cell line to become polyploid and to express platelet-specific proteins, including von Willebrand factor (vWF) and glycoprotein Ib (GpIb). Phorbol esters are thought to regulate gene expression principally through the activation of protein kinase C (PKC), a family of structurally related kinases with potentially unique activation requirements and substrate specificities. A survey of PKC isoforms in Dami cells revealed that, by both Western and Northern analyses, PKC isoforms alpha, beta, delta, epsilon, eta, theta, and zeta were reproducibly detected. PKC-gamma was not detected. In order to define the role of individual PKC isoforms in megakaryocytic maturation, PMA and 2-deoxyphorbol 13-phenylacetate 20-acetate (dPPA), a putative selective activator of the PKC-beta 1 isotype, were compared for their effects on Dami cell maturation. Treatment with either dPPA or PMA caused Dami cells to cease proliferating, to become polyploid, and to express vWF. We also examined dPPA and PMA for their ability to activate and to downregulate expression of different PKC isoforms. Fifteen-minute treatment with PMA resulted in the translocation of PKC isoforms alpha, epsilon, and theta from the cytosolic to the membrane fraction; twenty-four hour treatment resulted in the downregulation of these isoforms. In contrast, dPPA was found to be a potent activator of PKC-epsilon alone and exhibited weaker effects on alpha and theta. These data suggest that PKC isoforms beta, delta, eta, and zeta, which appear not to be activated by either phorbol ester, are unlikely to be primarily involved in megakaryocytic maturation in response to these agents. The isoforms that are translocated by both phorbol esters-PKC isoforms alpha and theta, and particularly epsilon-are more likely to transduce the signals that stimulate Dami cell differentiation.

Cell Differentiation↗
PubMed1995

Effect of adrenaline and phorbol myristate acetate or bacterial lipopolysaccharide on stimulation of pathways of macrophage glucose, glutamine and O2 metabolism. Evidence for cyclic AMP-dependent protein kinase mediated inhibition of glucose-6-phosphate dehydrogenase and activation of NADP+-dependent 'malic' enzyme.

Adrenaline has recently been shown to stimulate both glucose metabolism and H2O2 release by macrophages but the activity of the key pentose phosphate pathway enzyme, glucose-6-phosphate dehydrogenase (which generates the NADPH crucial for the reduction of molecular oxygen), was reduced under these conditions [Costa Rosa, Safi, Cury and Curi (1992) Biochem. Pharmacol. 44, 2235-2241]. We report here that adrenaline activates another NADPH-producing enzyme, NADP(+)-dependent 'malic' enzyme, while also inhibiting glucose-6-phosphate dehydrogenase, via cyclic AMP-dependent protein kinase (PKA) activation. Regulation of glucose-6-phosphate dehydrogenase activity by PKA has not been reported elsewhere. The sparing of some glucose from pentose phosphate pathway consumption may be important in the provision of glycerol 3-phosphate which in the macrophage may be required for new phospholipid synthesis. Glutamine oxidation was also stimulated by adrenaline thus providing increased substrate (malate) for NADP(+)-dependent 'malic' enzyme and therefore shifting some of the burden of NADPH production from glucose to glutamine metabolism. We also report a novel synergistic effect of adrenaline and some bacterial products and/or gamma-interferon in stimulating secretory and metabolic pathways in macrophages which may be a part of a larger network of signals that lead to enhanced macrophage activity.

Animals↗
PubMed1995

Regulation of the human C-reactive protein gene in transgenic mice.

Human C-reactive protein (hCRP) is a major acute-phase reactant in man. The regulation of the hCRP gene in transgenic mice is similar to that in humans. To map DNA regions required for the correct regulation of the hCRP gene, several constructs have been generated, and their expression in transgenic mice has been analyzed. Constructs lacking DNA regions surrounding the poly(A) site of the gene are not expressed either before or after induction in transgenic mice. Minimal regions 540 base pairs upstream and 1.2 kilobases downstream of the hCRP gene are sufficient for liver-specific expression. Extended 5'- and 3'-flanking regions are required to silence the expression prior to induction. Our findings demonstrate that regulatory sequences shown to confer inducible expression of the hCRP gene in hepatoma cell lines are insufficient in transgenic mice.

Animals↗
PubMed1995

Is the sphere organelle/coiled body a universal nuclear component?

We present evidence for the essential homology of four nuclear organelles that have previously been described under four different names: coiled bodies in mammalian somatic nuclei, prenucleolar bodies in nuclei assembled in vitro in Xenopus egg extract, sphere organelles in amphibian germinal vesicles (GVs), and Binnenkörper in insect GVs. Each of these organelles contains coilin or a coilin-related protein plus a variety of small nuclear ribonucleoproteins. We suggest that the sphere organelle/coiled body is a "universal" nuclear component in the sense that it is involved in common nuclear processes and hence will be found in one form or another in most eukaryotic cells. We postulate that it functions in the assembly and sorting of snRNP complexes for three RNA processing pathways: pre-mRNA splicing, rRNA processing, and histone pre-mRNA 3' end formation. Specifically, the sphere organelle/coiled body may be the initial site for assembly of processing complexes, which are then sorted to other places in the nucleus, where the actual RNA processing takes place.

Animals↗
PubMed1995

Recombinant immunoglobulin variable domains generated from synthetic genes provide a system for in vitro characterization of light-chain amyloid proteins.

The primary structural features that render human monoclonal light chains amyloidogenic are presently unknown. To gain further insight into the physical and biochemical factors that result in the pathologic deposition of these proteins as amyloid fibrils, we have selected for detailed study three closely homologous protein products of the light-chain variable-region single-gene family VkIV. Two of these proteins, REC and SMA, formed amyloid fibrils in vivo. The third protein, LEN, was excreted by the patient at levels of 50 g/day with no indication of amyloid deposits. Sequences of amyloidogenic proteins REC and SMA differed from the sequence of the nonpathogenic protein LEN at 14 and 8 amino acid positions, respectively, and these amino acid differences have been analyzed in terms of the three-dimensional structure of the LEN dimer. To provide a replenishable source of these human proteins, we constructed synthetic genes coding for the REC, SMA, and LEN variable domains and expressed these genes in Escherichia coli. Immunochemical and biophysical comparisons demonstrated that the recombinant VkIV products have tertiary structural features comparable to those of the patient-derived proteins. This well-defined set of three clinically characterized human kIV light chains, together with the capability to produce these kIV proteins recombinantly, provide a system for biophysical and structural comparisons of two different amyloidogenic light-chain proteins and a nonamyloidogenic protein of the same subgroup. This work lays the foundation for future investigations of the structural basis of light-chain amyloidogenicity.

Amino Acid Sequence↗
PubMed1995

Sensory- and memory-mediated olfactory dysfunction in Huntington's disease.

Neuropathology in Huntington's disease (HD) known to project to areas that process olfactory information raises the questions of which olfactory function, if any, is most affected in HD, and how to explain such dysfunction in terms of olfactory sensitivity and cognition. These questions were studied by comparing HD patients and controls (matched for age, gender, and education) on absolute detection, intensity discrimination, quality discrimination, short-term recognition memory, and lexical- and picture-based identification for odor. Taste or vision were used as comparison modalities. The results suggest that whereas odor-recognition memory is not affected in patients with HD, these patients have impaired olfactory functioning with respect to absolute detection, intensity discrimination, quality discrimination, and identification. The three latter impairments were significantly explained by poor detection sensitivity. Odor identification was the function most affected.

Adult↗
PubMed1995

Odor identification as an early marker for Alzheimer's disease: impact of lexical functioning and detection sensitivity.

The impact of lexical functioning and detection sensitivity on the deficit of odor identification in Alzheimer's disease (AD) was studied in persons diagnosed with probable and questionable AD. Tests consisted of lexical-based odor identification, lexical-based picture identification, picture-based odor identification, and odor-detection threshold. Results suggest (1) that odor identification is poorer than picture identification in probable and questionable AD, (2) that odor identification continues to be poor even when lexical demands are eliminated, (3) that odor detection does contribute to the odor-identification deficit, but does not account for it completely, and (4) that odor identification tests have a correct classification rate of 83-100%. Odor identification tests can be very useful tools in diagnosing AD and should be considered an important addition to existing diagnostic test batteries.

Aged↗
PubMed1995

Reliability and validity of electrogustometry and its application to young and elderly persons.

Electrogustometric-threshold assessment demonstrated excellent test-retest reliability, good bilateral correspondence and age-related differences. Tactile and stimulus-related descriptors of the sensation elicited at detection threshold, as well as a lack of correlation between whole-mouth chemical thresholds and anterior tongue electrogustometric thresholds, raise questions for future research.

Adult↗
PubMed1995

Unawareness of smell loss in normal aging and Alzheimer's disease: discrepancy between self-reported and diagnosed smell sensitivity.

Awareness of loss in smell sensitivity was assessed in 80 normal elderly subjects, 80 patients with probable Alzheimer's disease (AD), and 80 patients with sinusitis by comparing measured smell sensitivity to questionnaire-based, self-reported sensitivity. Both AD patients and sinusitis patients had significantly poorer diagnosed smell sensitivity than the normal elderly. Both patient groups had thresholds which on average were about nine times more concentrated than those of the normal elderly. However, 74% of the AD patients and 77% of the normal elderly with smell loss reported normal smell sensitivity. In contrast, only 8% of the sinusitis patients with loss reported normal smell sensitivity.

Adolescent↗
PubMed1995

Perinatal nurse practitioners and health care reform.

Health care delivery for pregnant women at high risk is changing in response to the nation's need to contain costs and improve care. Perinatal nurse practitioners can provide specialized care to women at high risk in a wide variety of settings. They provide quality, cost-effective care and can improve access to prenatal care for families at risk for untoward pregnancy outcomes.

Curriculum↗
PubMed1995

Photic headshaking in the horse: 7 cases.

Seven horses with headshaking are described. No physical abnormalities were detected in any of the cases. Six of these horses had onset of clinical signs in the spring. The role of light was assessed by application of a blindfold or dark grey lens to the eyes, covering the eyes with a face mask and observing the horse in total darkness outdoors. Cessation of headshaking was observed with blindfolding (5/5 horses), night darkness outdoors (4/4 horses) and use of grey lenses (2/3 horses). Outdoor behaviour suggested efforts to avoid light in 4/4 cases. The photic sneeze in man is suggested as a putative mechanism for equine headshaking. Five of 7 horses had improvement with cyproheptadine treatment (0.3 mg/kg bwt b.i.d.). Headshaking developed within 2 calendar weeks of the same date for 3 consecutive years in one horse. Neuropharmacological alterations associated with photoperiod mechanisms leading to optic trigeminal summation are suggested as possible reasons for spring onset of headshaking.

Animals↗
PubMed1995

Stress-associated reductions of cytotoxic T lymphocytes and natural killer cells in asymptomatic HIV infection.

OBJECTIVE: Previous research has documented a possible relation of stress and depression to cell-mediated immunity. The authors examined how stressful events and depression may affect key parameters of cellular immunity in subjects with and without HIV infection. METHOD: Data were collected on 99 asymptomatic HIV-positive and 65 HIV-negative homosexual men as part of an ongoing, longitudinal study. Criticisms of previous studies of psychoimmunity were addressed by 1) using a comprehensive, semistructured interview to measure the objective context of stressful events, 2) double labeling of lymphocytes with monoclonal antibodies to measure subsets of cytotoxic/suppressor T lymphocytes and natural killer (NK) cells, and 3) controlling for circadian effects and methodological factors. RESULTS: In the HIV-positive men, severe stress was significantly associated with reductions in NK cell populations and a subset of T cells thought to represent cytotoxic T effector cells, particularly the CD8+ T cells expressing the CD57 antigen. In the HIV-negative men, no clear and consistent relation between stress and immune system measures was found. Depression was not correlated with any variables in either of the groups, perhaps due to the low levels of depressive symptoms. CONCLUSIONS: The findings suggest that stress is associated with reductions in killer lymphocytes (decreased NK cell and cytotoxic T lymphocyte phenotypes). The data provide evidence that stress may alter cell populations that provide cytotoxic defense against infection in HIV-positive men and indicate that the clinical significance of stress-related changes in cytotoxic T lymphocytes and NK cells in HIV infection warrants further study.

Adaptation, Psychological↗