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Biomedical subjects

D Nash

Publications and source records attributed to D Nash.

At least 19 recordsLinked to original sources

Are temporal characteristics of fast repetitive oscillating movement invariant?

Validation of the proportional duration model was attempted using very fast single-joint repetitive horizontal abductive-adductive movements of the stretched upper extremity with minimal cognitive input. Participants drew oscillating horizontal lines during 20 sec. over relatively short distances as quickly as possible without visual feedback. Spatial, temporal, and kinetic parameters were analysed. The amplitude and the time spent accelerating, decelerating, and reversing in both directions of each experimental line were recorded and related to the centre of gravity of the upper extremity. The accelerations of the centre of mass of the upper extremity were calculated and used to calculate the forces involved. The ratios of durations were compared and intercorrelated for the two fastest, two average, and two slowest cycles from each participant. Results exhibited significant standard deviations and variability of temporal and kinetic parameters within individual trials. The number of significant coefficients of correlation within individual trials was small despite the controlling influence of the same generalised motor program. The proportional duration model did not hold for our data. Peripheral factors (probably the length-tension relationship rule for skeletal muscles and viscosity of muscle) may be important in this type of action.

Biomechanical Phenomena↗

Characterization of Peromyscus MHC class II beta sequences by ligation-anchored RT-PCR and denaturing gradient gel electrophoresis.

We characterized MHC class II beta sequences in deermice (genus Peromyscus), which are amongst the most common mammals in North America. We find evidence for two different families of class II beta loci, most closely related to either the A-type or E-type loci in Mus. Population studies suggest the presence of more than one A-type locus but only one E-type locus for the species investigated.

Amino Acid Sequence↗

Epidemic West Nile encephalitis, New York, 1999: results of a household-based seroepidemiological survey.

BACKGROUND: In the summer of 1999, West Nile virus was recognised in the western hemisphere for the first time when it caused an epidemic of encephalitis and meningitis in the metropolitan area of New York City, NY, USA. Intensive hospital-based surveillance identified 59 cases, including seven deaths in the region. We did a household-based seroepidemiological survey to assess more clearly the public-health impact of the epidemic, its range of illness, and risk factors associated with infection. METHODS: We used cluster sampling to select a representative sample of households in an area of about 7.3 km(2) at the outbreak epicentre. All individuals aged 5 years or older were eligible for interviews and phlebotomy. Serum samples were tested for IgM and IgG antibodies specific for West Nile virus. FINDINGS: 677 individuals from 459 households participated. 19 were seropositive (weighted seroprevalence 2.6% [95% CI 1.2-4.1). Six (32%) of the seropositive individuals reported a recent febrile illness compared with 70 of 648 (11%) seronegative participants (difference 21% [0-47]). A febrile syndrome with fatigue, headache, myalgia, and arthralgia was highly associated with seropositivity (prevalence ratio 7.4 [1.5-36.6]). By extrapolation from the 59 diagnosed meningoencephalitis cases, we conservatively estimated that the New York outbreak consisted of 8200 (range 3500-13000) West Nile viral infections, including about 1700 febrile infections. INTERPRETATION: During the 1999 West Nile virus outbreak, thousands of symptomless and symptomatic West Nile viral infections probably occurred, with fewer than 1% resulting in severe neurological disease.

Adolescent↗

The outbreak of West Nile virus infection in the New York City area in 1999.

BACKGROUND: In late August 1999, an unusual cluster of cases of meningoencephalitis associated with muscle weakness was reported to the New York City Department of Health. The initial epidemiologic and environmental investigations suggested an arboviral cause. METHODS: Active surveillance was implemented to identify patients hospitalized with viral encephalitis and meningitis. Cerebrospinal fluid, serum, and tissue specimens from patients with suspected cases underwent serologic and viral testing for evidence of arboviral infection. RESULTS: Outbreak surveillance identified 59 patients who were hospitalized with West Nile virus infection in the New York City area during August and September of 1999. The median age of these patients was 71 years (range, 5 to 95). The overall attack rate of clinical West Nile virus infection was at least 6.5 cases per million population, and it increased sharply with age. Most of the patients (63 percent) had clinical signs of encephalitis; seven patients died (12 percent). Muscle weakness was documented in 27 percent of the patients and flaccid paralysis in 10 percent; in all of the latter, nerve conduction studies indicated an axonal polyneuropathy in 14 percent. An age of 75 years or older was an independent risk factor for death (relative risk adjusted for the presence or absence of diabetes mellitus, 8.5; 95 percent confidence interval, 1.2 to 59.1), as was the presence of diabetes mellitus (age-adjusted relative risk, 5.1; 95 percent confidence interval, 1.5 to 17.3). CONCLUSIONS: This outbreak of West Nile meningoencephalitis in the New York City metropolitan area represents the first time this virus has been detected in the Western Hemisphere. Given the subsequent rapid spread of the virus, physicians along the eastern seaboard of the United States should consider West Nile virus infection in the differential diagnosis of encephalitis and viral meningitis during the summer months, especially in older patients and in those with muscle weakness.

Adolescent↗

Sampling design for total and filterable reactive phosphorus monitoring in a lowland stream: considerations of spatial variability, measurement uncertainty and statistical power.

An analysis for spatial variation of phosphorus (P) concentrations in the dissolved and particulate compartments of Latrobe River water in Victoria, Australia is described. Water sampling was based on a nested hierarchical design and variation was measured at different spatial scales. Total variance of the dissolved and particulate P compartments was partitioned using analysis of variance (ANOVA) to determine the spatial scale that requires most sampling effort. Statistical power analysis was used to determine the optimum sample size for the spatial scale. An uncertainty budget was estimated from sampling and analytical uncertainty. Ten and twelve samples, at the smallest spatial scale, required the greatest sampling effort, and led to the greatest required statistical power for the determination of dissolved and particulate P, respectively, in the Latrobe River catchment. The results emphasize the need for aquatic chemists to be aware of the ramifications of different types of uncertainty and variance in environmental studies.

Environmental Monitoring↗

MHC class II beta sequence diversity in the deer mouse (Peromyscus maniculatus): implications for models of balancing selection.

We studied population polymorphism at a major histocompatibility complex (MHC) class II beta gene in the deer mouse (Peromyscus maniculatus). We found that: (i) a single population of P. maniculatus has significantly higher levels of DNA and protein sequence diversity than worldwide samples from homologous genes in other taxa, including humans and mice; and (ii) the genealogy of allelic sequences in P. maniculatus deviates significantly from theoretical expectation under a model of symmetric balancing selection, in that alleles are relatively more divergent than expected. We suggest that the observation of high levels of pairwise allelic sequence divergence and deviation of the genealogy from theoretical expectation in P. maniculatus together provide support for a divergent allele advantage model for the maintenance of MHC polymorphism.

Alleles↗

Sinusitis.

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Acute Disease↗

Repeat victims of violence: report of a large concurrent case-control study.

HYPOTHESIS: Repeat victims of violence (violence victim recidivism) is a phenomenon known throughout the nation by those who work in hospital emergency departments. A level I trauma center in Baltimore, Md, conducted this study to investigate the postulated risk factors for repeat victims of violence, ie, unemployment, limited educational attainment, and involvement with illicit drug use or drug dealing. DESIGN: A case-control study identified 200 cases and 224 controls during a 16-month period. Cases were persons admitted with traumatic injury secondary to violent assault who had been previously hospitalized for a similar reason. Controls were a random selection of eligible age- and sex-matched patients admitted for reasons unrelated to violent injury. RESULTS: Prominent risk factors associated with recidivism were African American male, median age 31 years, unemployed, lacking medical insurance, annual income less than $10000, current drug user, past or present drug dealer, and a positive test for psychoactive substances on admission to the hospital. One hundred seventy-two (86%) of the cases felt that disrespect (called "dissing" in the local vernacular) was involved with their injury. CONCLUSIONS: The multiplicity of risk factors and the fact that they are interrelated mandate a comprehensive approach to the difficult problem of violence recidivism. Experiments in hospital-based intervention strategies are needed.

Adult↗

Differential effects of MK-801 on cerebrocortical neuronal injury in C57BL/6J, NSA, and ICR mice.

1. Antagonists of the N-methyl-D-aspartate (NMDA) glutamate (Glu) receptor, including [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate], dizocilpine maleate (MK-801), injure pyramidal neurons in the posterior cingulate/retrosplenial (PC/RS) cortex when administered systemically to adult rats and mice. 2. These results have, to our knowledge, only been reported previously in Harlan Sprague Dawley albino rats and International Cancer Research (ICR) mice, an outbred albino strain. 3. Male Non-Swiss Albino (NSA) mice, an albino outbred strain, and male C57BL/6J (B6) mice, a pigmented inbred strain, were injected systemically with 1 mg/kg of MK-801 in the first experiment. This dose of MK-801 reliably produces cytoplasmic vacuoles in neurons in layers III and IV of the PC/RS cortex in 100% of ICR mice treated 4. There was a significant difference in the number of vacuolated neurons in B6 and NSA mice, as assessed by ANOVA. The NSA were not significantly different than previously examined ICR mice, but the B6 had fewer vacuolated neurons than either of the two outbred strains. 5. In the second experiment, male NSA, ICR, and B6 mice were injected systemically with a high dose, 10 mg/kg, of MK-801. This dose has been demonstrated to result in necrosis in the same population of neurons injured by lower doses of MK-801. 6. An ANOVA indicated that there was a significant difference among the three strains of mice, and a Fisher's protected t revealed that the B6 mice were significantly different from both the NSA and ICR, but that, with our test, those two strains were indistinguishable. 7. Male ICR, NSA, and B6 mice were tested in the holeboard food search task 5 hours after 1 mg/kg of MK-801. There were significant differences between the strains in performance both pre and posttreatment. The effect of the drug was not statistically significant. 8. These results suggest that there may be a genetically mediated difference in the reaction to NMDA receptor antagonists, a finding which may be important given the NMDA receptor hypofunction hypothesis for the etiology of schizophrenic symptoms.

Animals↗

The Drosophila melanogaster ade5 gene encodes a bifunctional enzyme for two steps in the de novo purine synthesis pathway.

Steps 6 and 7 of de novo purine synthesis are performed by 5-aminoimidazole ribonucleotide carboxylase (AIRc) and 4-[(N-succinylamino)carbonyl]-5-aminoimidazole ribonucleotide synthetase (SAICARs), respectively. In vertebrates, a single gene encodes AIRc-SAICARs with domains homologous to Escherichia coli PurE and PurC. We have isolated an AIRc-SAICARs cDNA from Drosophila melanogaster via functional complementation with an E. coli purC purine auxotroph. This cDNA encodes AIRc yet is unable to complement an E. coli purE mutant, suggesting functional differences between Drosophila and E. coli AIRc. In vertebrates, the AIRc-SAICARs gene shares a promoter region with the gene encoding phosphoribosylamidotransferase, which performs the first step in de novo purine synthesis. In Drosophila, the AIRc-SAICARs gene maps to section 11B4-14 of the X chromosome, while the phosphoribosylamidotransferase gene (Prat) maps to chromosome 3; thus, the close linkage of these two genes is not conserved in flies. Three EMS-induced X-linked adenine auxotrophic mutations, ade4(1), ade5(1), and ade5(2), were isolated. Two gamma-radiation-induced (ade5(3) and ade5(4)) and three hybrid dysgenesis-induced (ade5(5), ade5(6), and ade5(8)) alleles were also isolated. Characterization of the auxotrophy and the finding that the hybrid dysgenesis-induced mutations all harbor P transposon sequences within the AIRc-SAICARs gene show that ade5 encodes AIRc-SAICARs.

Alleles↗

A new conceptual model of asymmetry in motor performance for bidimensional fast-oscillating movements in selected variants of performance.

Spatial characteristics and lateral differences between two upper extremities were investigated in unilateral graphical tasks involving fast oscillating movements in the vertical plane based on the model of restricted (less than 10 degrees) horizontal abduction adduction in the shoulder joint. The spatial locations of reversal points were used to identify two groups of motor performance: with big angles and gross vertical vectors (stretched accordion group), and small projectile angles with small vertical vectors (compressed accordion group). Both groups appeared in right and left arm performance. The former group had a strong pattern of distribution of big and small projectile angles which reflects a particular variant of execution with a significant difference between angles and intermittent big and small angles (BB). Two other variants of execution relating to specific angular patterns of performance were identified in the compressed accordion group: one (Bs) showed a big difference between big and small angles but without intermittance; the other (ss) had only small differences between magnitudes of angles. The Bs variant of execution was observed only in left-handed performance, whilst ss was typical of both extremities. The performances affiliated to the stretched accordion group with the BB variant of execution mostly operated with reciprocal cooperation between alterations of X and Y vectors for the right arm. Performance related to the same group with the Bs variant of execution used concurrent collaboration involving alteration of these vectors for the left arm. The compressed accordion group which deployed the ss variant of execution mostly displayed concurrent alteration of vectors irrespective of the side of performance. It is suggested that the spatial movement strategies might reflect several different schemes of motor control wherein coupling of oscillators controls vertical and horizontal movements. It is also proposed that specific subunits of the functional system of nervous elements responsible for the expression of spatial derivatives of motor programmes may exist at lower levels of the CNS and might be initiated by the left brain or by the cooperative activity of the left and right hemispheres.

Adult↗

stress sensitive B encodes an adenine nucleotide translocase in Drosophila melanogaster.

Adenine nucleotide translocases (ANT) are required for the exchange of ADP and ATP across the inner mitochondrial membrane. They are essential for life, and most eukaryotes have at least two different Ant genes. Only one gene had been described from Drosophila, and this had not been characterized genetically. We show that mutations in this gene correspond to the previously described loci, sesB and l(1)9Ed. Immediately adjacent to this gene is another encoding a second ANT protein, which has 78% identity to that encoded by sesB/l(1)9Ed. These two genes are transcribed from a common promoter, and their mRNAs are produced by differential splicing. Hutter and Karch suggested that the sesB ANT gene corresponded to Hmr, a gene identified by an allele that rescues otherwise inviable interspecific hybrids between Drosophila melanogaster and its sibling species. This hypothesis is not supported by our study of the ANT genes of D. melanogaster.

Amino Acid Sequence↗

The Guillain-Barré syndrome and the 1992-1993 and 1993-1994 influenza vaccines.

BACKGROUND: The number of reports of influenza-vaccine-associated Guillain-Barré syndrome to the national Vaccine Adverse Event Reporting System increased from 37 in 1992-1993 to 74 in 1993-1994, arousing concern about a possible increase in vaccine-associated risk. METHODS: Patients given a diagnosis of the Guillain-Barré syndrome in the 1992-1993 and 1993-1994 influenza-vaccination seasons were identified in the hospital-discharge data bases of four states. Vaccination histories were obtained by telephone interviews during 1995-1996 and were confirmed by the vaccine providers. Disease with an onset within six weeks after vaccination was defined as vaccine-associated. Vaccine coverage in the population was measured through a random-digit-dialing telephone survey. RESULTS: We interviewed 180 of 273 adults with the Guillain-Barré syndrome; 15 declined to participate, and the remaining 78 could not be contacted. The vaccine providers confirmed influenza vaccination in the six weeks before the onset of Guillain-Barré syndrome for 19 patients. The relative risk of the Guillain-Barré syndrome associated with vaccination, adjusted for age, sex, and vaccine season, was 1.7 (95 percent confidence interval, 1.0 to 2.8; P=0.04). The adjusted relative risks were 2.0 for the 1992-1993 season (95 percent confidence interval, 1.0 to 4.3) and 1.5 for the 1993-1994 season (95 percent confidence interval, 0.8 to 2.9). In 9 of the 19 vaccine-associated cases, the onset was in the second week after vaccination, all between day 9 and day 12. CONCLUSIONS: There was no increase in the risk of vaccine-associated Guillain-Barré syndrome from 1992-1993 to 1993-1994. For the two seasons combined, the adjusted relative risk of 1.7 suggests slightly more than one additional case of Guillain-Barré syndrome per million persons vaccinated against influenza.

Adolescent↗

High-resolution, high-pressure NMR studies of proteins.

Advanced high-resolution NMR spectroscopy, including two-dimensional NMR techniques, combined with high pressure capability, represents a powerful new tool in the study of proteins. This contribution is organized in the following way. First, the specialized instrumentation needed for high-pressure NMR experiments is discussed, with specific emphasis on the design features and performance characteristics of a high-sensitivity, high-resolution, variable-temperature NMR probe operating at 500 MHz and at pressures of up to 500 MPa. An overview of several recent studies using 1D and 2D high-resolution, high-pressure NMR spectroscopy to investigate the pressure-induced reversible unfolding and pressure-assisted cold denaturation of lysozyme, ribonuclease A, and ubiquitin is presented. Specifically, the relationship between the residual secondary structure of pressure-assisted, cold-denatured states and the structure of early folding intermediates is discussed.

Biophysical Phenomena↗