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Biomedical subjects

James McCarthy

Publications and source records attributed to James McCarthy.

At least 19 recordsLinked to original sources
PubMed2007

Gait initiation in children with cerebral palsy.

The task of gait initiation (GI), or taking a first step from a static standing position requires the development of forward momentum while maintaining dynamic balance as the body's center of mass (COM) moves forward and outside the base of support. The dynamics of GI in children (aged 7-12 years) with hemiplegic cerebral palsy (CP), diplegic CP and children with typical development (TD) were compared to characterize the mechanics and control of this task. Ground reaction forces (GRFs) and muscle activity were collected during GI at three different self-selected speeds (slow, moderate and fast). Movement of a sacral marker was also tracked to estimate downward shifting of the body during the GI task. Results demonstrate the presence of a motor sequence characterized by increased forward momentum development with increased GI speed for all groups of children. Anticipatory movements of children with CP were different when compared to children with TD. Children with hemiplegic CP demonstrated decreased lateral shifting while children with diplegic CP demonstrated a trend of decreased downward shifting of the body compared to children of TD. Analysis of the GI motor sequence in children provides a means to characterize coordination and motor control of a functional ambulatory task in children with CP compared to children with TD.

Analysis of Variance↗
PubMed2006

A time-frequency based electromyographic analysis technique for use in cerebral palsy.

Surface electromyography (sEMG) is part of an instrumented gait assessment, however, the interpretation of the data in a clinically meaningful manner is often limited to the extraction of individual sEMG characteristics. The purpose of this study was to develop an assessment methodology using sEMG time and frequency characteristics extracted using wavelet analyses to provide clinically relevant information in children with cerebral palsy (CP). A retrospective study was conducted with 37 children (16 children with typical development (TD) and 21 children with spastic CP). sEMG signals were examined from selected musculature of the lower extremities during level ground walking. Wavelet analysis techniques, along with functional principal component analyses, were employed to calculate a sEMG index. The data indicated a grouping in the EMG index based on the level of motor impairment and the clinical diagnosis of spastic hemiplegia or diplegia. Further analyses of the index exhibited moderate to high (r=-0.43 to -0.74 and r=0.62-0.65) correlations with the existing gait kinetics, kinematics, and clinical measures of motor impairment, and was sensitive to walking ability according to the Gross Motor Functional Classification Scale (GMFCS). Overall, this methodology may have the potential to provide additional insight into the outcome of a clinical intervention that was not available previously, and may find use as a predictive tool that can be utilized for clinical decision making.

Adolescent↗
PubMed2006

Membrane ganglioside enrichment lowers the threshold for vascular endothelial cell angiogenic signaling.

Malignant tumor progression depends on angiogenesis, requiring vascular endothelial cell migration, and proliferation, triggered by tumor-derived vascular endothelial cell growth factor (VEGF). We show that gangliosides, which are actively shed by tumor cells and bind to normal cells in the tumor microenvironment, have the potential to sensitize vascular endothelial cells to respond to subthreshold levels of VEGF: Ganglioside enrichment of human umbilical vein vascular endothelial cells (HUVEC) caused very low, normally barely stimulatory, VEGF concentrations to trigger robust VEGF receptor dimerization and autophosphorylation, as well as activation of downstream signaling pathways, and cell proliferation and migration. Thus, by dramatically lowering the threshold for growth factor activation of contiguous normal stromal cells, shed tumor gangliosides may promote tumor progression by causing these normal cells to become increasingly autonomous from growth factor requirements by a process that we term tumor-induced progression of the microenvironment.

Cell Movement↗
PubMed2006

Assessing the genetic diversity of the aldolase genes of Plasmodium falciparum and Plasmodium vivax and its potential effect on performance of aldolase-detecting rapid diagnostic tests.

Malaria-specific rapid diagnostic tests (RDTs) targeting aldolase show highly variable sensitivities. We assessed diversity in Plasmodium falciparum and P. vivax aldolases by sequencing the coding genes from parasites of various origins. The results show that aldolases are highly conserved, indicating that antigenic diversity is not a cause of variable RDT sensitivity.

Aldehyde-Lyases↗
PubMed2006

Isolation and characterization of cDNA encoding three dehydrins expressed during Coffea canephora (Robusta) grain development.

BACKGROUND AND AIMS: Dehydrins, or group 2 late embryogenic abundant proteins (LEA), are hydrophilic Gly-rich proteins that are induced in vegetative tissues in response to dehydration, elevated salt, and low temperature, in addition to being expressed during the late stages of seed maturation. With the aim of characterizing and studying genes involved in osmotic stress tolerance in coffee, several full-length cDNA-encoding dehydrins (CcDH1, CcDH2 and CcDH3) and an LEA protein (CcLEA1) from Coffea canephora (robusta) were isolated and characterized. METHODS: The protein sequences deduced from the full-length cDNA were analysed to classify each dehydrin/LEA gene product and RT-PCR was used to determine the expression pattern of all four genes during pericarp and grain development, and in several other tissues of C. arabica and C. canephora. Primer-assisted genome walking was used to isolate the promoter region of the grain specific dehydrin gene (CcDH2). KEY RESULTS: The CcDH1 and CcDH2 genes encode Y(3)SK(2) dehydrins and the CcDH3 gene encodes an SK(3) dehydrin. CcDH1 and CcDH2 are expressed during the final stages of arabica and robusta grain development, but only the CcDH1 transcripts are clearly detected in other tissues such as pericarp, leaves and flowers. CcDH3 transcripts are also found in developing arabica and robusta grain, in addition to being detected in pericarp, stem, leaves and flowers. CcLEA1 transcripts were only detected during a brief period of grain development. Finally, over 1 kb of genomic sequence potentially encoding the entire grain-specific promoter region of the CcDH2 gene was isolated and characterized. CONCLUSIONS: cDNA sequences for three dehydrins and one LEA protein have been obtained and the expression of the associated genes has been determined in various tissues of arabica and robusta coffees. Because induction of dehydrin gene expression is associated with osmotic stress in other plants, the dehydrin sequences presented here will facilitate future studies on the induction and control of the osmotic stress response in coffee. The unique expression pattern observed for CcLEA1, and the expression of a related gene in other plants, suggests that this gene may play an important role in the development of grain endosperm tissue. Genomic DNA containing the grain-specific CcDH2 promoter region has been cloned. Sequence analysis indicates that this promoter contains several putative regulatory sites implicated in the control of both seed- and osmotic stress-specific gene expression. Thus, the CcDH2 promoter is likely to be a useful tool for basic studies on the control of gene expression during both grain maturation and osmotic stress in coffee.

Amino Acid Sequence↗
PubMed2006

Oleosin gene family of Coffea canephora: quantitative expression analysis of five oleosin genes in developing and germinating coffee grain.

Coffee grains have an oil content between 10% and 16%, with these values associated with Coffea canephora (robusta) and C. arabica (arabica), respectively. As the majority of the oil stored in oil seeds is contained in specific structures called oil bodies, we were interested in determining whether there are any differences in the expression of the main oil body proteins, the oleosins, between the robusta and arabica varieties. Here, we present the isolation, characterization and quantitative expression analysis of six cDNAs representing five genes of the coffee oleosin family (CcOLE-1 to CcOLE-5) and one gene of the steroleosin family (CcSTO-1). Each coffee oleosin cDNA encodes for the signature structure for oleosins, a long hydrophobic central sequence containing a proline KNOT motif. Sequence analysis also indicates that the C-terminal domain of CcOLE-1, CcOLE-3 and CcOLE-5 contain an 18-residue sequence typical of H-form oleosins. Quantitative RT-PCR showed that the transcripts of all five oleosins were predominantly expressed during grain maturation in robusta and arabica grain, with CcOLE-1 and CcOLE-2 being more highly expressed. While the relative expression levels of the five oleosins were similar for robusta and arabica, significant differences in the absolute levels of expression were found between the two species. Quantitative analysis of oleosin transcripts in germinating arabica grain generally showed that the levels of these transcripts were lower in the grain after drying, and then further decreased during germination, except for a small spike of expression for CcOLE-2 early in germination. In contrast, the levels of CcSTO-1 transcripts remained relatively constant during germination, in agreement with suggestions that this protein is actively involved in the process of oil body turnover. Finally, we discuss the implications of the coffee oleosin expression data presented relative to the predicted roles for the different coffee oleosins during development and germination.

Amino Acid Sequence↗
PubMed2006

Effect of sequence variation in Plasmodium falciparum histidine- rich protein 2 on binding of specific monoclonal antibodies: Implications for rapid diagnostic tests for malaria.

The ability to accurately diagnose malaria infections, particularly in settings where laboratory facilities are not well developed, is of key importance in the control of this disease. Rapid diagnostic tests (RDTs) offer great potential to address this need. Reports of significant variation in the field performance of RDTs based on the detection of Plasmodium falciparum histidine-rich protein 2 (HRP2) (PfHRP2) and of significant sequence polymorphism in PfHRP2 led us to evaluate the binding of four HRP2-specific monoclonal antibodies (MABs) to parasite proteins from geographically distinct P. falciparum isolates, define the epitopes recognized by these MABs, and relate the copy number of the epitopes to MAB reactivity. We observed a significant difference in the reactivity of the same MAB to different isolates and between different MABs tested with single isolates. When the target epitopes of three of the MABs were determined and mapped onto the peptide sequences of the field isolates, significant variability in the frequency of these epitopes was observed. These findings support the role of sequence variation as an explanation for variations in the performance of HRP2-based RDTs and point toward possible approaches to improve their diagnostic sensitivities.

Animals↗
PubMed2006

PCR-based assay to survey for knockdown resistance to pyrethroid acaricides in human scabies mites (Sarcoptes scabiei var hominis).

Permethrin, in the form of a topical cream, is being increasingly used for community-based programs to control endemic scabies. The development of resistance has reduced the use of pyrethroids for the control of many arthropods of economic and health importance. The best recognized form of pyrethroid resistance, known as knockdown resistance or kdr, has been linked to specific mutations in the target of these agents, the para-homologous voltage-sensitive sodium channel gene (Vssc). To develop tools to study resistance to pyrethroid acaricides, we cloned 3711 and 6151 bp, respectively, of cDNA and genomic fragments of the Vssc gene from scabies mite, Sarcoptes scabiei. The sequence encompasses the major polymorphic amino acid residues associated with pyrethroid resistance. A polymerase chain reaction-based strategy has been developed that enables genotyping individual scabies mites. This will facilitate early detection and monitoring of pyrethroid resistance in scabies mite populations under drug selection pressure.

Amino Acid Sequence↗
PubMed2005

Design and synthesis of tricyclic corticotropin-releasing factor-1 antagonists.

Antagonists of the corticotropin-releasing factor (CRF) neuropeptide should prove to be effective in treating stress and anxiety-related disorders. In an effort to identify antagonists with improved physicochemical properties, new tricyclic CRF(1) antagonists were designed, synthesized, and tested for biological activity. As a result of studies aimed at establishing a relationship between structure and CRF(1) binding affinity, NBI 35965 (12a) was identified as a high-affinity antagonist with a pK(i) value of 8.5. Compound 12a proved to be a functional CRF(1) antagonist with pIC(50) values of 7.1 and 6.9 in the in vitro CRF-stimulated cAMP accumulation and ACTH production assays, respectively, and 12a also reduced CRF or stress induced ACTH production in vivo.

Acenaphthenes↗
PubMed2005

Genetic diversity of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) and its effect on the performance of PfHRP2-based rapid diagnostic tests.

Rising costs of antimalarial agents are increasing the demand for accurate diagnosis of malaria. Rapid diagnostic tests (RDTs) offer great potential to improve the diagnosis of malaria, particularly in remote areas. Many RDTs are based on the detection of Plasmodium falciparum histidine-rich protein (PfHRP) 2, but reports from field tests have questioned their sensitivity and reliability. We hypothesize that the variability in the results of PfHRP2-based RDTs is related to the variability in the target antigen. We tested this hypothesis by examining the genetic diversity of PfHRP2, which includes numerous amino acid repeats, in 75 P. falciparum lines and isolates originating from 19 countries and testing a subset of parasites by use of 2 PfHRP2-based RDTs. We observed extensive diversity in PfHRP2 sequences, both within and between countries. Logistic regression analysis indicated that 2 types of repeats were predictive of RDT detection sensitivity (87.5% accuracy), with predictions suggesting that only 84% of P. falciparum parasites in the Asia-Pacific region are likely to be detected at densities < or = 250 parasites/microL. Our data also indicated that PfHRP3 may play a role in the performance of PfHRP2-based RDTs. These findings provide an alternative explanation for the variable sensitivity in field tests of malaria RDTs that is not due to the quality of the RDTs.

Amino Acid Sequence↗
PubMed2005

Strongyloidiasis: a review of the evidence for Australian practitioners.

OBJECTIVE: To summarise the available evidence concerning the prevalence, clinical manifestations, diagnosis and management of strongyloidiasis in Northern Australia. METHODS: We searched Medline, Clinical Evidence and the Cochrane Library using MeSH terms and text words 'strongyloides OR strongyloidiasis'. For Australian studies we included text words '(parasite* OR parasitic OR helminth*) AND Australia*'. We examined references contained in retrieved studies or identified from direct contact with researchers. Studies consistent with our objective that described their methods were eligible for inclusion. RESULTS: The prevalence in some tropical Aboriginal communities is high. Infection can be asymptomatic, cause a range of clinical syndromes or death. It may become chronic. Infected patients are at risk of developing severe disseminated disease particularly with immune compromise. There is little information about the relative frequency of different clinical outcomes. Available diagnostic tools are imperfect. Stool examination has a low sensitivity. Serology may have a low specificity in high prevalence populations and has not been evaluated in Aboriginal populations. Antihelmintic drugs are relatively safe and effective. Community programs based on treatment of stool-positive cases have been associated with a reduced prevalence of strongyloidiasis. We found no studies examining alternative public health interventions. CONCLUSION: There is a high prevalence in many Aboriginal communities. Strongyloides infection should be excluded prior to commencing immunosuppressive therapies in patients from endemic areas. Further studies examining the public health impact of strongyloidiasis, the role of the enzyme-linked immuno-sorbent assay serological test and population-based approaches to management of the disease in endemically infected Australian populations are needed.

Albendazole↗
PubMed2005

Sustained attention, visual processing speed, and IQ in children and adolescents with Schizophrenia Spectrum disorder and Psychosis Not Otherwise Specified.

To investigate the cognitive functioning of children and adolescents with Schizophrenia Spectrum disorders and Psychosis Not Otherwise Specified, 22 child and adolescent psychiatric inpatients and day-hospital patients at a state psychiatric hospital with Schizophrenia Spectrum disorders, 30 with Psychosis Not Otherwise Specified, and 130 with other psychiatric disorders, ages 8 to 17 years, were administered the Wechsler Intelligence Scale for Children-III for psychological assessment at admission. The Performance IQs of the ADHD and the Conduct Disorder and Oppositional Defiant Disorder groups were significantly higher than those of the Schizophrenia Spectrum and the Psychosis Not Otherwise Specified groups, and the Full Scale IQs of the Conduct Disorder and Oppositional Defiant Disorder group were significantly higher than those of the Schizophrenia Spectrum group and the Psychosis Not Otherwise Specified group. The Coding scores of the ADHD group were significantly higher than those of the Schizophrenia Spectrum, the Psychosis Not Otherwise Specified, and the Bipolar Disorder groups. There was a significant negative correlation between age and Digit Span for the Schizophrenia Spectrum disorders group.

Adolescent↗
PubMed2004

Phe*-Ala-based pentapeptide mimetics are BACE inhibitors: P2 and P3 SAR.

We describe herein the syntheses and evaluation of a series of C-termini pyridyl containing Phe*-Ala-based BACE inhibitors (5-19). In conjunction with four fixed residues at the P1 (Phe), P1' (Ala), P2' (Val), and P2' cap (Pyr.), rather detailed SAR modifications at P2 and P3 positions were pursued. The promising inhibitors emerging from this SAR investigation, 12 and 17 demonstrated very good enzyme potency (IC(50)=45 nM) and cellular activity (IC(50)=0.4 microM).

Amyloid Precursor Protein Secretases↗
PubMed2004

P3 cap modified Phe*-Ala series BACE inhibitors.

With the aim of reducing molecular weight and adjusting log D value of BACE inhibitors to more favorable range for BBB penetration and better bioavailability, we synthesized and evaluated several series of P3 cap modified BACE inhibitors obtained via replacement of the P3NHBoc moiety as seen in 3 with other polar functional groups such as amino, hydroxyl and fluorine. Several promising inhibitors emerging from this P3 cap SAR study (e.g., 15 and 19) demonstrated good enzyme inhibitory potencies (BACE-1 IC(50) <50 nM) and whole cell activities (IC(50) approximately 1 microM).

Amyloid Precursor Protein Secretases↗
PubMed2004

The larval specific lymphatic filarial ALT-2: induction of protection using protein or DNA vaccination.

Genes from the infective stage of lymphatic filarial parasites expressed at the time of host invasion have been identified as potential vaccine candidates. By screening an L3 cDNA library with sera from uninfected longstanding residents of an area endemic for onchocerciasis, so-called "endemic normals" (EN), we have cloned and characterized one such gene termed the abundant larval transcript two (ALT-2). The stage specificity of ALT-2 gene transcription and protein synthesis was confirmed by PCR using genespecific primers, and by western blot analysis of protein extracts from various stages of the parasite life cycle using specific antisera. Significant differences in antibody response to the recombinant ALT-2 were observed in endemic populations with differing clinical manifestations of lymphatic filariasis with an antibody response present in sera from 18 of 25 (72%) EN subjects compared to 9 of 25 (36%) with subclinical microfilaracmia (MF) and 14 of 25 (52%) of those with chronic lymphatic obstruction (CP) (P=0.01 for comparison of EN to CP or to MF). This differential responsiveness suggests that the protective immunity postulated to account for their uninfected status might be associated with a response to this protein. When the utility of ALT-2 as a vaccine candidate was tested in a murine model using either recombinant protein or a DNA vaccine construct, statistically significant protection was observed when compared to a control filarial gene product expressed across all stages of the parasite lifecycle (SXP-1; P=0.02 for protein and P=0.01 for the DNA vaccine) or compared to adjuvant alone. This level of protection indicates that this vaccine is a promising candidate for further development.

Adult↗
PubMed2004

Sustained attention and visual processing speed in children and adolescents with bipolar disorder and other psychiatric disorders.

To investigate the cognitive functioning of children and adolescents with bipolar illness, 112 child and adolescent psychiatric inpatients and day-hospital patients at a state psychiatric hospital were administered the Wechsler Intelligence Scale for Children-III (WISC-III) as part of an admission psychological assessment. There were 22 patients with Bipolar Disorder and 90 with other psychiatric disorders; all were between 8 and 17 years of age. The patients with Bipolar Disorder had a mean age of 14 yr., a mean Verbal IQ of 78, a mean Performance IQ of 76, and a mean Full Scale IQ of 75. When their WISC-III scores were compared with those who had Schizophrenia Spectrum disorders (Schizophrenia and Schizoaffective Disorder), Psychosis Not Otherwise Specified, Attention Deficit Hyperactivity Disorder, and Conduct Disorder and Oppositional Defiant Disorder, there were no significant between-group mean differences for Verbal IQ, but patients with Bipolar Disorder had a significantly lower mean Performance IQ than those with ADHD and those with Conduct Disorder and Oppositional Defiant Disorder. Contrary to the expectation that the patients with Bipolar Disorder might have better sustained attention (higher Digit Span scores) than those with Schizophrenia Spectrum disorders and worse visual processing speed (lower Coding scores) than the other diagnostic groups, the bipolar patients' Digit Span and Coding scores did not differ significantly from those of the other groups. The patients with Psychosis, Not Otherwise Specified had significantly lower mean Performance IQ, Full Scale IQ, and Coding than the ADHD and the Conduct Disorder and Oppositional Disorder groups.

Adolescent↗
PubMed2003

Evaluation of bizarre-idiosyncratic thinking scale as a measure of thought disorder in children and adolescents with severe psychiatric disorders.

To investigate the prevalence of thought disorder and the possible appropriateness of the Bizarre-Idiosyncratic Thinking Scale for children and adolescents with severe psychiatric disorders, 96 child and adolescent inpatients and day hospital patients, ages 6 to 18 years, at a state psychiatric hospital were rated by review of retrospective records using Marengo and Harrow's 1986 Evaluation of Bizarre-Idiosyncratic Thinking Scale for the presence of thought disorder in the Thematic Apperception Test and Rorschach Inkblot Test responses. Although the Evaluation of Bizarre-Idiosyncratic Thinking Scale had not been previously used with children and adolescents, the analysis suggested possible indications of thought disorder in several diagnostic groups. No significant differences were found on the Rorschach between patients with Schizophrenia and Psychosis, Not Otherwise Specified and those with Attention Deficit Hyperactivity Disorder, Major Depression, and Conduct Disorder. On the basis of the Thinking Scale ratings, the Thematic Apperception Test responses showed significantly higher ratings of thought disorder for patients with Schizophrenia and Psychosis, Not Otherwise Specified. There was no general relation between thought disorder and age or IQ, but schizophrenic patients, aged 13 and older, had more thought disorder than schizophrenic patients who were younger than 13.

Adolescent↗