Evidence for murine macrophage nitric oxide synthesis in the absence of exogenous L-arginine.
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Animals↗
Biomedical subjects
C Murphy
Publications and source records attributed to C Murphy.
Prevalence and assessment of qualitative olfactory dysfunction in different age groups.
The prevalence of parosmia and phantosmia among 363 chemosensory and nasal/sinus patients was studied, as was the accuracy with which our clinical questionnaire could assess these dysfunctions. We then investigated whether patients with parosmia or phantosmia, matched for odor intensity, perform poorer on odor identification than do patients with no dysosmia. More than 40% of the study group evidenced either parosmia (18.7%) and/or phantosmia (25.6%), a finding that suggests that more attention should be paid by the medical practitioner in addressing qualitative olfactory dysfunction. Furthermore, it appears that assessment of these dysfunctions may aid in differential diagnosis, and that questionnaires can be used with reasonable validity irrespective of the patient's age. Finally, the results imply that parosmia may be reflected in a discrepancy between odor identification and detection.
Adult↗
Linear growth of very young asthmatic children treated with high-dose nebulized budesonide.
The aim of this open study was to observe linear growth in young children with asthma treated with nebulized budesonide. Infants and young children (< 3 years old) with severe uncontrolled asthma were studied. They were treated with nebulized budesonide (1-4 mg day-1) and treated for at least 6 months. Height standard deviation scores (HtSDS) were measured before ("pre-measurements") immediately prior to commencing nebulized budesonide therapy (baseline) and after at least 6 months of therapy ("post-measurements"). The mean HtSDS score at pretreatment was -0.21 and at baseline had fallen further to -0.46. The mean HtSDS increased to -0.17 when the post-measurements were made (p = 0.035) after at least 6 months of nebulized budesonide therapy. Treatment with nebulized budesonide for longer than 6 months in very young children with severe asthma was not associated with reduced linear growth.
Administration, Inhalation↗
Comparison of facial form in primary alveolar bone-grafted and nongrafted unilateral cleft lip and palate patients: intercenter retrospective study.
The purpose of this study was to describe and compare posttreatment craniofacial morphology in samples of complete unilateral cleft lip and palate (CUCLP) patients treated at two leading clinics: The Children's Memorial Hospital Cleft Palate Clinic, Chicago, Illinois, and the Lancaster Cleft Palate Clinic, Lancaster, Pennsylvania. These centers have well-defined treatment protocols that allow the long-term effects on craniofacial form of the following treatment regimes to be contrasted: (1) Chicago--primary alveolar bone grafting, with definitive lip repair at age 4 to 6 months and hard and soft palate repair at 6 to 12 months; and (2) Lancaster--definitive triangular-flap lip repair at 3 months of age, followed by staged surgeries of the hard and soft palates, both completed by 18 months of age, but without primary alveolar bone grafting. Although the Lancaster center now performs secondary alveolar bone grafting, the majority of the patients studied here were treated before this procedure became part of their protocol. Patients were eligible for inclusion if they had no other congenital anomalies and no previous orthodontic treatment. A sample of 43 (24 male, 19 female) CUCLP patients was obtained from the Chicago Center, each of which was then matched to a nongrafted Lancaster CUCLP patient. The matching criteria were age, sex, and sella-nasion distance (to control, at least in part, for size differences). Lateral cephalometric radiographs of these 86 CUCLP patients were traced, digitized, and analyzed. Additionally, all linear data were adjusted to a standard magnification of 8% because the cephalograms from each center featured different enlargements. The Chicago and Lancaster samples had mean posttreatment ages of 10.32 years (SD = 1.96) and 10.40 years (SD = 2.18), respectively. The grafted Chicago group had faces that were on average less maxillary protrusive compared with the nongrafted Lancaster sample; it appeared, however, that the mandible compensated for the maxillary position by downward and backward rotation. As a result, a similar maxillomandibular relationship was noted in both groups, although, in the Chicago group, the lower anterior facial height increased.
Alveolar Process↗
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↗
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↗
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↗
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↗
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↗
A molecular model for self-assembly of amyloid fibrils: immunoglobulin light chains.
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Alzheimer Disease↗
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↗
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↗
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↗
Expression of Rab proteins during mouse embryonic development.
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Amino Acid Sequence↗
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↗
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↗
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↗
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↗