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Biomedical subjects

C Murphy

Publications and source records attributed to C Murphy.

At least 73 records · Page 4Linked to original sources
PubMed1999

Neuropsychological performance and cognitive olfactory event-related brain potentials in young and elderly adults.

The P3 event-related brain potential (ERP) reflects neuroelectric activity related to the speed of cognitive processing and allocation of attentional resources. The objective of the present study was to assess the relationship between the P3 and Slow Wave components of the olfactory event-related potential (OERP) with neuropsychological performance in young (n = 16) and elderly (n = 16) adults. OERPs were recorded monopolarly from midline electrode sites while subjects estimated the odor magnitude of each stimulus, eliciting highly reproducible P3s. Results showed that the late cognitive components (P3 amplitude, P3 latency and Slow Wave area) decline with age and that this decreased neuronal efficiency is associated with reductions in the neuropsychological performance indexed by the Trail Making Test and the California Verbal Learning Test.

Adult↗
PubMed1999

A test of odor fluency in patients with Alzheimer's and Huntington's disease.

In the present study, an olfactory analog to the verbal fluency test was designed and administered to 40 patients with Alzheimer's disease (AD) and 11 patients with Huntington's disease (HD). Because onset of AD is typically in the sixties while onset of HD is typically in the mid-thirties, the patient groups had their own control group, an older (ONC) and younger (YNC) control group, respectively. Both control groups included 40 participants who were age- and education-matched to their respective patient group. Odor threshold, odor identification, and odor fluency measures were administered to each participant. Results of the study indicate that patients with dementia perform more poorly on all three measures of olfactory functioning. Our results suggest that tests of odor memory show differential performance in healthy and demented patients, leading to the suggestion that tests of olfactory functioning may be useful in detection and diagnosis of neurodegenerative disease.

Adult↗
PubMed1999

Assembly of the nuclear transcription and processing machinery: Cajal bodies (coiled bodies) and transcriptosomes.

We have examined the distribution of RNA transcription and processing factors in the amphibian oocyte nucleus or germinal vesicle. RNA polymerase I (pol I), pol II, and pol III occur in the Cajal bodies (coiled bodies) along with various components required for transcription and processing of the three classes of nuclear transcripts: mRNA, rRNA, and pol III transcripts. Among these components are transcription factor IIF (TFIIF), TFIIS, splicing factors, the U7 small nuclear ribonucleoprotein particle, the stem-loop binding protein, SR proteins, cleavage and polyadenylation factors, small nucleolar RNAs, nucleolar proteins that are probably involved in pre-rRNA processing, and TFIIIA. Earlier studies and data presented here show that several of these components are first targeted to Cajal bodies when injected into the oocyte and only subsequently appear in the chromosomes or nucleoli, where transcription itself occurs. We suggest that pol I, pol II, and pol III transcription and processing components are preassembled in Cajal bodies before transport to the chromosomes and nucleoli. Most components of the pol II transcription and processing pathway that occur in Cajal bodies are also found in the many hundreds of B-snurposomes in the germinal vesicle. Electron microscopic images show that B-snurposomes consist primarily, if not exclusively, of 20- to 30-nm particles, which closely resemble the interchromatin granules described from sections of somatic nuclei. We suggest the name pol II transcriptosome for these particles to emphasize their content of factors involved in synthesis and processing of mRNA transcripts. We present a model in which pol I, pol II, and pol III transcriptosomes are assembled in the Cajal bodies before export to the nucleolus (pol I), to the B-snurposomes and eventually to the chromosomes (pol II), and directly to the chromosomes (pol III). The key feature of this model is the preassembly of the transcription and processing machinery into unitary particles. An analogy can be made between ribosomes and transcriptosomes, ribosomes being unitary particles involved in translation and transcriptosomes being unitary particles for transcription and processing of RNA.

Animals↗
PubMed1999

Olfactory event-related potentials in young and elderly adults: evaluation of tracking task versus eyes open/closed recording.

The purpose of the present study was to evaluate olfactory event-related potentials (OERPs) elicited by amyl acetate from subjects performing a visuomotor tracking task compared with the no-task conditions of eyes open and eyes closed. Task condition did not produce any reliable effects for any amplitude measure. Task type weakly influenced only P2 latency. Elder adults evinced smaller P2 and N1/P2 amplitudes and longer N1 and P2 latencies than young adults. The results suggest that tracking task performance is not necessary to obtain robust OERPs from normal subjects of a wide age range.

Adult↗
PubMed1999

Pronuclear location before the first cell division determines ploidy of polyspermic pig embryos.

Polyspermy occurs frequently in the fertilization of mammalian eggs, but little is known about whether polyspermic eggs have developmental ability in vitro or in vivo. We previously reported that poly-pronuclear (PPN; 3 or more pronuclei) pig eggs developed normally to the blastocyst stage despite having fewer inner cell mass cell numbers as compared to blastocysts derived from two-pronuclear (2PN) eggs. Here it is shown that most PPN pig eggs have abnormal cleavage patterns (having 3 or more cells) in the first cell division and retarded development of pronuclei prior to syngamy as compared to 2PN eggs. Most blastocysts (14 of 18) that developed from PPN eggs showed abnormal ploidy (were haploid, triploid, and tetraploid) whereas 20 of 22 blastocysts derived from 2PN embryos were diploid. The size and morphology of most Day 40 fetuses that developed from PPN eggs appeared to be normal. Of 8 Day 40 fetuses analyzed, 1 was triploid (XXY) and another was a mosaic with both diploid (XX) and tetraploid cells (frequency of less than 10%, XXXX), and the others were diploid. Anomalies of chromosomal composition were not detected in these fetuses. Five live piglets and one dead piglet were born from two recipients of PPN eggs. It is proposed that not all pronuclei of PPN pig eggs participate in syngamy, resulting in diploid cells in the conceptus. Our data suggest that there are two types of pronuclei location in polyspermic pig eggs and that the resulting ploidy is determined at the zygote stage before the first cell division according to pronuclear location.

Actins↗
PubMed1999

Traumatic brain injury assessed with olfactory event-related brain potentials.

Olfactory event-related potentials (OERPs) were evaluated to develop an objective, quantitative assessment of sensory and cognitive olfactory loss following traumatic brain injury (TBI). Subjects included 25 TBI patients and 25 age/gender-matched healthy controls. Following standard clinical evaluation of smell function, TBI patients were divided into three groups: 12 anosmics (loss of smell), 6 hyposmics (reduced smell), and 7 normosmics (normal smell). Cognitive ability was assessed using the Trail Making Test (A and B). OERPs were recorded monopolarly from midline electrode sites using an amyl acetate stimulus with a 60-second interstimulus interval; subjects estimated the magnitude of each odor stimulus. Anosmic TBI patients were also tested with OERPs using ammonia to ensure trigeminal nerve function. Amyl acetate OERPs demonstrated that the sensory N1 and P2 amplitudes and the cognitive P3 amplitudes were absent in the anosmic TBI patients and greatly reduced in the hyposmic and normosmic TBI patients compared to healthy controls. The trigeminal OERPs from the anosmic TBI patients were within normal limits, indicating that the primary olfactory deficits were objectively measured with OERPs. The relationship between the OERPs and neuropsychologic test performance supports the cognitive loss associated with TBI. The present study lends support to the utility of OERPs as an objective tool for measuring sensory and cognitive loss after traumatic brain injury.

Adult↗
PubMed1999

Cloning and expression of a DNA sequence encoding a 41-kilodalton Cryptosporidium parvum oocyst wall protein.

This study was conducted to produce a recombinant species-specific oocyst wall protein of Cryptosporidium parvum. Antigens unique to C. parvum were identified by gradient sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting of oocyst proteins from several different Cryptosporidium species. Antiserum was then prepared against a 41-kDa antigen unique to C. parvum and used to identify a recombinant DNA clone, designated rCP41. Expression of CP41 mRNA in C. parvum oocysts was confirmed by reverse transcriptase PCR (RT-PCR). Although the CP41 sequence was shown by PCR to be present in the genome of C. baileyi, CP41 mRNA was not detected in this species by RT-PCR. Immunofluorescence staining with antiserum against recombinant CP41 detected native CP41 antigen on the surface of C. parvum oocysts but failed to detect CP41 on C. baileyi oocysts. Immunoelectron microscopy demonstrated that native CP41 was distributed unevenly on the C. parvum oocyst surface and was associated with amorphous oocyst wall material. In an enzyme-linked immunosorbent assay, purified rCP41 performed as well as native C. parvum oocyst protein in measuring the serological responses of young calves and adult cows to experimental and natural C. parvum infections. These results indicate that recombinant CP41 antigen may have potential in the immunodiagnosis of cryptosporidiosis.

Amino Acid Sequence↗
PubMed1999

Upstream stimulatory factor regulates major histocompatibility complex class I gene expression: the U2DeltaE4 splice variant abrogates E-box activity.

The tissue-specific expression of major histocompatibility complex class I genes is determined by a series of upstream regulatory elements, many of which remain ill defined. We now report that a distal E-box element, located between bp -309 and -314 upstream of transcription initiation, acts as a cell type-specific enhancer of class I promoter activity. The class I E box is very active in a neuroblastoma cell line, CHP-126, but is relatively inactive in the HeLa epithelial cell line. The basic helix-loop-helix leucine zipper proteins upstream stimulatory factor 1 (USF1) and USF2 were shown to specifically recognize the class I E box, resulting in the activation of the downstream promoter. Fine mapping of USF1 and USF2 amino-terminal functional domains revealed differences in their abilities to activate the class I E box. Whereas USF1 contained only an extended activation domain, USF2 contained both an activation domain and a negative regulatory region. Surprisingly, the naturally occurring splice variant of USF2 lacking the exon 4 domain, U2DeltaE4, acted as a dominant-negative regulator of USF-mediated activation of the class I promoter. This latter activity is in sharp contrast to the known ability of U2DeltaE4 to activate the adenovirus major late promoter. Class I E-box function is correlated with the relative amount of U2DeltaE4 in a cell, leading to the proposal that U2DeltaE4 modulates class I E-box activity and may represent one mechanism to fine-tune class I expression in various tissues.

Alternative Splicing↗
PubMed1999

Familial amyloidosis in cats: Siamese and Abyssinian AA proteins differ in primary sequence and pattern of deposition.

Familial AA amyloidosis is a hereditary trait in Abyssinian cats, with the kidney as the main target organ. The amino acid sequence of the amyloid A protein of the Abyssinian cat has been described earlier. Recently, familial amyloidosis has been found in Siamese cats, with the liver as the main target organ. In the present paper, we describe the complete amino amid sequence of the major constituent protein, of two Siamese cats. Siamese hepatic protein AA showed homology with, but was different from all feline SAA and AA sequences hitherto reported. Two substitutions (46Q-R and 52A-V) from the Abyssinian protein sequence were identified, one of which (46Q-R) is a non-homologous substitution not found in mammalian SAA, but is present in two bird AA amyloid proteins. This shows the presence of an unique amyloidogenic SAA isotype in Siamese cats. Both the Siamese and the Abyssinian sequence are amyloidogenic, thus making identification of amyloidogenic residues difficult. Apart from the apparent inherent amyloidogenicity of SAA, it can not be excluded that certain amino acid substitutions could enhance its amyloidogenicity but also could contribute to tissue predilection in amyloidosis.

Amino Acid Sequence↗
PubMed1999

Evidence of a central role for p38 map kinase induction of tumor necrosis factor alpha in pancreatitis-associated pulmonary injury.

BACKGROUND: Tumor necrosis factor alpha (TNF alpha) has been implicated as an important mediator in acute pancreatitis-associated adult respiratory distress syndrome, but the precise pathogenesis remains unclear. The purpose of this work was to clarify the role of TNF alpha that is produced within the lung parenchyma in the inducement of pancreatitis-related pulmonary injury and to examine 1 of the potential pathways leading to the production of pulmonary TNF alpha. METHODS: Bile salt pancreatitis was induced in rats (n = 40) that were randomized to receive a p38 mitogen-activated protein (MAP) kinase inhibitor or vehicle. A separate group (n = 16) underwent sham operation. Pulmonary capillary permeability was determined with fluorescein isothiocyanate-labeled albumin and Evans blue dye, and lung histologic analysis was performed. TNF alpha protein was measured in bronchoalveolar lavage fluid, and p38 MAP kinase was activity determined by Western blot analysis. RESULTS: The induction of pancreatitis resulted in increased pulmonary capillary leakage and worsened histologic condition (P < .01 vs sham). Effective inhibition of p38 MAP kinase-induced TNF alpha production completely prevented pancreatitis-associated pulmonary injury (P < .01 vs vehicle). CONCLUSIONS: p38 MAP kinase-induced TNF alpha production plays a central role in the development of pulmonary dysfunction, which accompanies severe acute pancreatitis in this rodent model.

Acute Disease↗
PubMed1999

Macrophage-mediated lysis of a beta-cell line, tumour necrosis factor-alpha release from bacillus Calmette-Guérin (BCG)-activated murine macrophages and interleukin-8 release from human monocytes are dependent on extracellular glutamine concentration and glutamine metabolism.

Macrophages and monocytes are cells with a large capacity for cytokine production. Cytokines produced by these cells are not preformed and released upon stimulation, but must be transcribed and translated. Although much is known concerning the regulation of the latter processes at the molecular level, the role of exogenous amino acids in the secretory process has not been actively investigated. Glutamine is utilized by macrophages at a much faster rate than any other amino acid. The role for high rates of glutamine utilization in macrophages or monocytes is not fully understood. We demonstrate here that the rates of lipopolysaccharide-stimulated tumour necrosis factor-alpha secretion from bacillus Calmette-Guérin (BCG)-activated murine peritoneal macrophages and lipopolysaccharide-stimulated interleukin-8 production from human monocytes are dependent upon extracellular glutamine concentration. We also demonstrate that potent inhibition of cytokine production can be achieved by incubating macrophages or monocytes in the presence of the glutaminase inhibitor 6-diazo-5-oxo-norleucine. On co-culture of BCG-activated macrophages and the clonal pancreatic beta-cell line BRIN-BD11, macrophage-specific beta-cell death was significantly reduced on prior exposure of macrophages to 6-diazo-5-oxo-norleucine. Thus glutamine metabolism may be essential for generation of cytotoxic products from macrophages, including tumour necrosis factor-alpha.

Animals↗
PubMed1998

Age effects on central nervous system activity reflected in the olfactory event-related potential. Evidence for decline in middle age.

A series of studies in this laboratory using the olfactory event-related potential (OERP) have examined the underlying central nervous system activity associated with age-related changes in olfactory functioning. Early (sensory) components of the OERP showed reduced amplitude and longer latency in elderly subjects, with larger effects in males. Amplitudes are already decreased in middle age. The late cognitive component, P3, showed a longer latency as well as a decreased amplitude in the elderly, with effect sizes for age significantly larger for the late component than for the early components. We report here the significantly longer latency, particularly for the P3, in middle-aged persons, suggesting age-related slowing of olfactory information processing as early as the 50s. Results suggest that the elderly brain, and indeed, the middle-aged brain shows smaller responses to odors, is less able to allocate attentional resources and slows in its olfactory cognitive processing. The OERP is a potent reflection of these changes.

Adult↗
PubMed1998

Developmental effects on odor learning and memory in children.

The child version of the California Odor Learning Test (COLT) was designed to assess cognitive functioning in impaired and healthy children. The COLT's rationale was based on two assumptions. First, measures of cognitive functioning are a good index of severity or extent of brain damage if compared between normal and clinical populations. Second, the cognitive-mediated tasks of verbal odor recall, recognition and identification were suitable to evaluate cognitive functioning. The focus of this study was to determine the COLT's ability to detect developmental differences in odor learning and memory. The participants were 51 healthy children who were twice administered the COLT with a weekly delay between tests. They were ascribed to two age-groups (7-10 and 11-15 years old) according to levels of cognitive development. The COLT employed 22 common odors and included two sessions. In the first session, children learned two sets of six odors. The first set was presented three times, the second one once, during a single learning episode. Following learning, children recalled the odors of the first set by name at free recall and category-cued recall. The second session included the following tasks: long-term free odor recall and category-cued odor recall, odor recognition-memory and verbal odor identification. A series of analyses of variance (ANOVAs, p < 0.05) with age as between-subject variable and repeated measurements on recall revealed significant differences between the two groups on the number of odors correctly recalled by name both at free recall, category-cued recall, recognition and identification. There were differences in false alarms at odor recognition between the two groups. Children from both groups benefited from a learning effect over odor trials. A gender effect was found for odor free recall at retest. These results suggest that the COLT has the potential to serve as a useful tool in the assessment of cognitive functioning in children.

Adolescent↗
PubMed1998

Abnormality of semantic network in patients with Alzheimer's disease. Evidence from verbal, perceptual, and olfactory domains.

A series of studies was initiated to model the organization of semantic memory in Alzheimer's disease (AD) patients using multidimensional scaling (MDS) and Pathfinder analyses. The resulting models (cognitive maps or semantic networks) embed studied stimuli in a coordinate space or network where distances between points are assumed to reflect psychological proximity between items. The organization of semantic networks in verbal and sensory domains were modeled based upon the frequency of the subject's choice of two concepts as most alike. Results suggested that while the organization of concepts in the semantic networks of AD patients was primarily based upon a concrete perceptual dimension in both verbal and olfactory domains, those of normal controls subjects were predominantly organized by an abstract conceptual attribute. Also, networks of AD patients were more complex and chaotic than normal, that is, they consisted of more unnecessary connections and of atypical strengths of association between concepts.

Alzheimer Disease↗
PubMed1998

Odor memory in normal aging and Alzheimer's disease.

The ability in normal elderly to verbally recall previously presented odors and to learn this task across trials was studied by applying a design which compared performance on the California Verbal Learning Test (CVLT) with an analogous odor test. Results suggest that both immediate and delayed recall of odors, both free and cued, as well as the ability to learn across trials is impaired in normal aging, perhaps more so for olfaction than for audition, which can be referred to poor use of semantic-clustering strategies and poor identification. Olfactory decline in memory in normal aging is, however, far from as affected as in Alzheimer's disease (AD). Two studies of persons with questionable AD demonstrated significant deficits in both recognition memory and identification of odors. Although further research is required, the findings from these 'pre-clinical' cases imply that performance on olfactory-mediated tasks may contribute to early diagnosis of AD.

Aged↗
PubMed1998

Very early changes in olfactory functioning due to Alzheimer's disease and the role of apolipoprotein E in olfaction.

Alzheimer's disease (AD) is a progressive neurodegenerative illness marked by memory loss and at least one other cognitive disturbance. Early diagnosis of the disease has proved difficult and has therefore been the focus of much research. Apolipoprotein E (ApoE), a protein manufactured and distributed throughout the body, has shown specificity of binding to the beta A4 peptide, the primary component in the senile plaques of AD. Furthermore, the ApoE, epsilon 4 (epsilon 4) allele, is overrepresented in AD. These two lines of evidence suggest that ApoE, specifically the epsilon 4 allele, plays an important role in the development of AD. Further support for this hypothesis appears in neuropsychological data showing cognitive decrements in ostensibly nondemented individuals with the epsilon 4 allele, compared to those without the allele. It is also well known that olfaction is compromised in AD. Thus, the purpose of this study was twofold: (1) to examine very early changes in olfactory functioning due to AD and (2) to examine the role of ApoE in olfactory functioning in people at risk for AD by virtue of early cognitive decline. Results demonstrated changes in olfactory threshold the year immediately preceding change in diagnosis from normal control to AD. Also, in individuals with mild cognitive impairment, those with the ApoE epsilon 4 allele show poorer thresholds than those without the epsilon 4 allele.

Aged↗