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Biomedical subjects

S R Campbell

Publications and source records attributed to S R Campbell.

17 recordsLinked to original sources
PubMed2005

Chemical and enzymatic synthesis of 4'-thio-beta-D-arabinofuranosylcytosine monophosphate and triphosphate.

N4-Acetyl-1-(2, 3-di-O-acetyl-4-thio-beta-D-arabinofuranosyl) cytosine (2) was synthesized in three steps from 1-(4-thio-beta-D-arabinofuranosyl) cytosine (1). The reaction of this partially blocked 4'-thio-ara-C derivative 2 with 2-chloro-4H-1,3,2-benzodioxaphosphorin-4-one gave the 5-phosphitylate derivative 3, which on reaction with pyrophosphate gave the 5'-nucleosidylcyclotriphosphite 4. Product 4 was then oxidized with iodine/pyridine/water and deblocked with concentrated ammonium hydroxide to provide the desired 4'-thio-ara-C-5'-triphosphate 5. This triphosphate 5 was converted to 4'-thio-ara-C -5'-monophosphate 6 by treatment with snake venom phosphodiesterase I. The details of the synthesis, purification, and characterization of both nucleotides are described.

Ammonium Hydroxide↗
PubMed2001

Synchronization in relaxation oscillator networks with conduction delays.

We study locally coupled networks of relaxation oscillators with excitatory connections and conduction delays and propose a mechanism for achieving zero phase-lag synchrony. Our mechanism is based on the observation that different rates of motion along different nullclines of the system can lead to synchrony in the presence of conduction delays. We analyze the system of two coupled oscillators and derive phase compression rates. This analysis indicates how to choose nullclines for individual relaxation oscillators in order to induce rapid synchrony. The numerical simulations demonstrate that our analytical results extend to locally coupled networks with conduction delays and that these networks can attain rapid synchrony with appropriately chosen nullclines and initial conditions. The robustness of the proposed mechanism is verified with respect to different nullclines, variations in parameter values, and initial conditions.

Animals↗
PubMed1999

Synchrony and desynchrony in integrate-and-fire oscillators.

Due to many experimental reports of synchronous neural activity in the brain, there is much interest in understanding synchronization in networks of neural oscillators and its potential for computing perceptual organization. Contrary to Hopfield and Herz (1995), we find that networks of locally coupled integrate-and-fire oscillators can quickly synchronize. Furthermore, we examine the time needed to synchronize such networks. We observe that these networks synchronize at times proportional to the logarithm of their size, and we give the parameters used to control the rate of synchronization. Inspired by locally excitatory globally inhibitory oscillator network (LEGION) dynamics with relaxation oscillators (Terman & Wang, 1995), we find that global inhibition can play a similar role of desynchronization in a network of integrate-and-fire oscillators. We illustrate that a LEGION architecture with integrate-and-fire oscillators can be similarly used to address image analysis.

Algorithms↗
PubMed1994

Ixodes scapularis (Acari: Ixodidae) deer tick mesoscale populations in natural areas: effects of deer, area, and location.

Nymphal Ixodes scapularis Say deer ticks were collected at 22 parks or other natural areas on Long Island, New York, to examine the relationship between tick populations and geographic position, size of area, presence of white-tailed deer, Odocoileus virginianus (Zimmerman), and numbers of human Lyme disease cases in adjacent communities. Nymphal ticks were 93% less abundant when deer were absent and were also less common in smaller natural areas. Geographic position on Long Island was not important. Tick numbers were significantly correlated with human Lyme disease incidence in adjacent townships. A second survey of larval ticks from five areas where deer were absent and six where deer were present found larvae present at four of the five sites without deer, but at only 2% of the levels found where deer were present. These results suggest that populations of I. scapularis can occur and reproduce in the absence of white-tailed deer, so that eradication of all deer would greatly reduce, but not eliminate, all risk of Lyme disease.

Animals↗
PubMed1994

Landscape patterns of abundance of Ixodes scapularis (Acari: Ixodidae) on Shelter Island, New York.

Nymphal Ixodes scapularis Say, the vector of Lyme borreliosis, was most common in forested areas across Shelter Island, Suffolk County, New York, and least common in xeric habitats such as beach and grassland. At the scale of individual house yards, nymphs were most common at wooded edges of property and least common on lawns. The abundance of ticks at yard edges was positively correlated with numbers on lawns and in landscaping, suggesting that tick abundance in woods affects abundances in adjacent yards. Because 57% of all yard area is adjacent to woodlands on Shelter Island, public health efforts to reduce tick populations in wooded areas should supplement efforts by individual yard owners to decrease risk. Methods of tick control for woodlands should also be evaluated for their effect on tick populations in adjacent yard habitats.

Animals↗
PubMed1993

An unexpected result from burning vegetation to reduce Lyme disease transmission risks.

The risk for human infection with Lyme disease appears linked to the abundance of infected vector ticks, principally Ixodes dammini Spielman, Clifford, Piesman & Corwin, in the eastern United States. Habitat destruction by burning, although not well studied, has long been considered as an effective alternative to synthetic insecticides as a means of reducing tick populations. We evaluated the effect of a single spring burning of the woodland understory on the transmission risk of Lyme disease spirochetes (Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner) on Shelter Island, Long Island, NY. Following a burn in early April 1991, the abundance of nymphal I. dammini was 49% lower in the burned portion of a woodlot compared with the unburned portion. However, risk of encountering nymphs infected with B. burgdorferi remained similar in both burned and unburned woods. It is suggested that burning vegetation may disproportionately kill deer-derived rather than rodent-derived nymphs, significantly reducing tick abundance without affecting transmission risk.

Animals↗
PubMed1993

Unique phylogenetic position of Diplomonadida based on the complete small subunit ribosomal RNA sequence of Giardia ardeae, G. muris, G. duodenalis and Hexamita sp.

Complete small-subunit rRNA (SSU-rRNA) coding region sequences were determined for two species of the intestinal parasite Giardia: G. ardeae and G. muris, both belonging to the order Diplomonadida, and a free-living member of this order, Hexamita sp. These sequences were compared to published SSU-rDNA sequences from a third member of the genus Giardia, G. duodenalis (often called G. intestinalis or G. lamblia) and various representative organisms from other taxa. Of the three Giardia sequences analyzed, the SSU-rRNA from G. muris is the smallest (1432 bases as compared to 1435 and 1453 for G. ardeae and G. duodenalis, respectively) and has the lowest G+C content (58.9%). The Hexamita SSU-rRNA is the largest in this group, containing 1550 bases. Because the sizes of the SSU-rRNA are prokaryotic rather than typically eukaryotic, the secondary structures of the SSU-rRNAs were constructed. These structures show a number of typically eukaryotic signature sequences. Sequence alignments based on constraints imposed by secondary structure were used for construction of a phylogenetic tree for these four taxa. The results show that of the four diplomonads represented, the Giardia species form a distinct group. The other diplomonad Hexamita and the microsporidium Vairimorpha necatrix appear to be distinct from Giardia.

Animals↗
PubMed1992

The nucleotide sequence of the entire ribosomal DNA operon and the structure of the large subunit rRNA of Giardia muris.

The total nucleotide sequence of the rDNA of Giardia muris, an intestinal protozoan parasite of rodents, has been determined. The repeat unit is 7668 basepairs (bp) in size and consists of a spacer of 3314 bp, a small-subunit rRNA (SSU-rRNA) gene of 1429, and a large-subunit rRNA (LSU-rRNA) gene of 2698 bp. The spacer contains long direct repeats and is heterogeneous in size. The LSU-rRNA of G. muris was compared to that of the human intestinal parasite Giardia duodenalis, to the bird parasite Giardia ardeae, and to that of Escherichia coli. The LSU-rRNA has a size comparable to the 23S rRNA of E. coli but shows structural features typical for eukaryotes. Some variable regions are typically small and account for the overall smaller size of this rRNA. The structure of the G. muris LSU-rRNA is similar to that of the other Giardia rRNA, but each rRNA has characteristic features residing in a number of variable regions.

Animals↗
PubMed1991

Cloning and restriction enzyme mapping of ribosomal DNA of Giardia duodenalis, Giardia ardeae and Giardia muris.

In an attempt to study Giardia at the DNA sequence level, the rRNA genes of three species, Giardia duodenalis, Giardia ardeae and Giardia muris were cloned and restriction enzyme maps were constructed. The rDNA repeats of these Giardia show completely different restriction enzyme recognition patterns. The size of the rDNA repeat ranges from approximately 5.6 kb in G. duodenalis to 7.6 kb in both G. muris and G. ardeae. These size differences are mainly attributable to the variation in length of the spacer. Minor differences exist among these Giardia in the sizes of their small subunit rRNA and the internal transcribed spacer between small and large subunit rRNA. The genetic maps were constructed by sequence analysis of the DNA around the 5' and 3' ends of the mature rRNA genes and between the rRNA covering the 5.8S rRNA gene and internal transcribed spacer. Comparison of the 5.8S rDNA and 3' end of large subunit rDNA from these three Giardia species showed considerable sequence variation, but the rDNA sequences of G. duodenalis and G. ardeae appear more closely related to each other than to G. muris.

Amino Acid Sequence↗
PubMed1990

Giardia sp.: comparison of electrophoretic karyotypes.

Species in the genus Giardia have been named on the basis of host specificity, cell dimensions, and median body morphology. Despite these criteria, the species taxonomy of Giardia is still in question. To investigate Giardia taxonomy on a molecular level, Giardia chromosomal DNA was analyzed by orthogonal-field-alternation gel electrophoresis (OFAGE) and transverse alternating field electrophoresis (TAFE). Chromosomal DNA of G. duodenalis isolates (human, muskrat, sheep, dog, beaver), G. muris (mouse), and G. ardeae (great blue heron) were subjected to OFAGE and TAFE analyses. Comparable DNA patterns were obtained by both electrophoretic methods, but OFAGE required 8 days while TAFE required only 3 days. DNA patterns among all G. duodenalis isolates, although quite similar to each other, were distinctly different from those of G. muris and G. ardeae; G. muris and G. ardeae DNA patterns were distinctly different from each other. A G. duodenalis (Portland 1) total DNA probe hybridized to the DNA of all G. duodenalis isolates on Southern blots, but not detectably to G. muris and G. ardeae DNA. Similarly, G. muris and G. ardeae total DNA probes only hybridized detectably to their respective DNA. One probe that appears to hybridize to the DNA of all G. duodenalis and to G. ardeae DNA rather than G. muris DNA has been developed. Another probe that hybridizes only to G. muris and G. ardeae DNA has been developed. These data suggest that the differentiation of Giardia isolated from host and environmental samples may eventually be accomplished by DNA probes. Additionally, these techniques perhaps combined with other criteria may lead to the establishment of a sound taxonomic scheme for this genus.

Animals↗
PubMed1990

Axenic culture and characterization of Giardia ardeae from the great blue heron (Ardea herodias).

Trophozoites of Giardia ardeae were obtained from the great blue heron (Ardea herodias) and established in axenic culture using the TYI-S-33 medium. The generation time in culture for G. ardeae was 22-25 hr, which was 3-fold longer than for Giardia duodenalis (WB strain). A morphological comparison of trophozoites in the original intestinal isolate to those grown in culture revealed that they were identical for the following characteristics: a pyriform-shaped body, a ventral adhesive disc with a deep notch in the posterior border, teardrop-shaped nuclei, pleomorphism in median body structure ranging from a round-oval appearance (Giardia muris type) to that of a clawhammer (G. duodenalis type), and a single caudal flagellum on the right side (as viewed dorsally) with the left one being rudimentary. Analysis of the chromosomal migration patterns was performed by orthogonal-field-alternation gel electrophoresis and demonstrated that the pattern for G. ardeae was distinctly different from that for G. duodenalis (Portland 1-CCW strain). Bacterial symbionts were seen attached to trophozoites in the original isolate but could not be detected in cultured trophozoites using scanning electron microscopy, fluorescence light microscopy using the Hoechst 33258 dye for DNA localization, or by standard microbiological techniques using nonselective media for growing aerobic or anaerobic bacteria. This study demonstrated that avian-derived Giardia could be grown in axenic culture; based on morphological criteria and chromosomal migration patterns, that G. ardeae should be considered a distinct species; and that rationale for determining Giardia spp., based on median body structure alone, should no longer be considered adequate for classification at the species level.

Animals↗
PubMed1989

Aberrant guanosine triphosphate-beta-tubulin interaction in Alzheimer's disease.

Guanosine triphosphate (GTP) is an absolute requirement for tubulin polymerization in situ. The nucleotide photoaffinity probe 8-azidoguanosine 5'-triphosphate (8N3GTP) has been shown to be a biological mimic of GTP in this system and, also, an effective active site probe of the exchangeable GTP binding site. Using [32P]8N3GTP we demonstrate that the exchangeable GTP site of the beta subunit of tubulin is available to added guanine nucleotide in normal aged brain homogenates, whereas it is variably unavailable in Alzheimer's diseased brain. Inability of 8N3GTP to photolabel beta tubulin appears to be associated with neurofibrillary tangle density. These results support the hypothesis that microtubule formation is abnormal in brains affected by Alzheimer's disease.

Aged↗
PubMed1988

Aluminum intoxication and the victim of Alzheimer's disease: similarities and differences.

Aluminum (Al) has been implicated in the pathogenesis and may produce a model of senile dementia of the Alzheimer's type (SDAT). To better understand the effects of Al on the mammalian brain, Al was studied in rabbits and rats using several experimental approaches. Similar behavioral toxicity and site and degree of neurofibrillary tangle (NFT) development were obtained after intracerebroventricular (icv) or repeated sc Al, although a more protracted time course after the latter. SDAT victims demonstrate some similar behavioral signs but a different type of NFT. A classically conditioned, defensive reflex (nictitating membrane extension) was used to compare response acquisition, retention, and extinction in Al-exposed and control rabbits of various ages. Both increasing age and Al exposure attenuated these measures, suggesting that advanced age and Al intoxication provide behavioral models of SDAT. A deficit in acquisition of a classically conditioned response (eyeblink) in senile-demented patients has been reported. These cognitive deficits in rabbits occurred after a less than two-fold increase in brain Al. Brain Al in SDAT victims has been reported to be unchanged or slightly increased. Further similarity to SDAT was obtained with 4-aminopyridine (4-AP) which attenuated Al-induced behavioral deficits in rabbits and the Al inhibition of glutamate release from rat hippocampal slices. 4-Aminopyridine has been reported to attenuate behavioral deficits in SDAT patients. A tubulin, GTP binding site was blocked in SDAT victim brain but not in control or Al-intoxicated rabbit brain, indicating a biochemical dissimilarity. In summary, Al-intoxication produces a model of SDAT with many similarities but significant differences.

Aluminum↗