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Biomedical subjects

J A Taylor

Publications and source records attributed to J A Taylor.

At least 19 recordsLinked to original sources

Optical transmission through double-layer metallic subwavelength slit arrays.

We present measurements of transmission of infrared radiation through double-layer metallic grating structures. Each metal layer contains an array of subwavelength slits and supports transmission resonance in the absence of the other layer. The two metal layers are fabricated in close proximity to allow coupling of the evanescent field on individual layers. The transmission of the double layer is found to be surprisingly large at particular wavelengths, even when no direct line of sight exists through the structure as a result of the lateral shifts between the two layers. We perform numerical simulations using rigorous coupled wave analysis to explain the strong dependence of the peak transmission on the lateral shift between the metal layers.

Journal Article↗

Lead exposure as a risk factor for amyotrophic lateral sclerosis.

BACKGROUND: The etiology of amyotrophic lateral sclerosis (ALS) likely involves an environmental component. We qualitatively assessed literature on ALS and lead exposure. Problems of study design make case reports and studies of lead in blood or tissues difficult to interpret. Most previous case-control studies found an association of ALS with self-reported occupational exposure to lead, with increased risks of 2- to >4-fold. However, these results may have been affected by recall bias. OBJECTIVE: To address inconsistencies among published reports, we used both lead biomarkers and interview data to assess lead exposure, and we evaluated the role of genetic susceptibility to lead. METHODS: We conducted a case-control study in New England in 1993-1996 with 109 ALS cases and 256 population-based controls. We measured blood and bone lead levels, the latter using X-ray fluorescence, and interviewed participants regarding sources of lead exposure. RESULTS: In our study, ALS was associated with self-reported occupational lead exposure, with a dose response for cumulative days of exposure. ALS was also associated with blood and bone lead levels, with a 1.9-fold increase in risk for each mug/dl increment in blood lead and a 2.3- to 3.6-fold increase for each doubling of bone lead. A polymorphism in the delta-aminolevulinic acid dehydratase gene was associated with a 1.9-fold increase in ALS risk. CONCLUSION: These results, together with previous studies, suggest that lead exposure plays a role in the etiology of ALS. An increase in mobilization of lead from bone into blood may play a role in the acute onset of disease.

Amyotrophic Lateral Sclerosis↗

Are a minimum number of concordant matches needed to establish identity in forensic odontology?

Forensic odontology plays an important role in the identification of human remains. While numerous studies have proven conclusively the uniqueness of the human dentition, forensic odontologists worldwide remain divided about the need for a minimum number of concordant points to confirm dental identification. This study reviewed 690 cases from the archives of the Forensic Odontology Unit, The University of Adelaide, to determine the validity of using a minimum number of concordant points to positively identify human remains. It was found that positive identification had been established using a varying number of concordant points. Although the incidence of positive identification was more frequent with a minimum of 12 concordant points, there were numerous cases where 12 or more concordant points failed to achieve a positive identification. Identities were also confirmed in some cases using less than 12 points of correspondence. There appears to be no basis for defining a minimum number of concordant points necessary before a positive identification can be made on dental evidence. Rather, the findings of this study reinforce the view that each case has its own individuality and should be treated as such.

Dental Records↗

Sexually differentiated regulation of gnRH release by gonadal steroid hormones in sheep.

Exposure of the sheep fetus to testosterone from day 30 to day 90 of a 147 day gestation causes the neurones that control GnRH secretion, the GnRH neuronal network, to become organized in a sex-specific manner. After androgen exposure in utero, GnRH neurones are activated in a sexually differentiated pattern by gonadal steroid hormones. Specifically, follicular phase concentrations of oestrogen trigger a GnRH 'surge' in ewes, but not in rams or females treated with androgen during fetal life. Furthermore, progesterone is a less potent inhibitor of GnRH release in rams or females treated with androgen during fetal life. The reasons for the sexual differentiation of these steroid feedback mechanisms probably reside in a dimorphism in steroid-sensitive neural inputs to GnRH neurones. The density of neurones containing oestrogen receptor alpha is sexually differentiated in areas of the ovine brain that are known to be involved in the steroidal regulation of GnRH. Furthermore, neurones in these regions are activated in a gender-specific pattern. A determination of the neural phenotype of these steroid-sensitive cells will form a basis for understanding the mechanisms by which the GnRH neuronal network is organized and activated in a sexually differentiated manner.

Animals↗

The effects of outcome imagery on golf-putting performance.

The aim of this study was to determine the effects of positive and negative outcome imagery on golf-putting performance. Players of both high and low ability performed a golf-putting task in three imagery conditions: (a) a positive outcome imagery condition, (b) a negative outcome imagery condition and (c) a no-imagery control condition. The task was conducted in a competitive setting, reducing the possibility of demand characteristics. We found that negative outcome imagery was detrimental to putting performance; however, performance in the positive outcome imagery condition was no better than performance in the control condition. There was also evidence to suggest that outcome imagery operated through the mechanism of confidence, as negative outcome imagery was detrimental to both confidence and performance. The results of the present study suggest that golfers should avoid visualizing negative images, as this could damage both confidence and performance.

Adolescent↗

A radiographic assessment of the prevalence of pulp stones in Australians.

BACKGROUND: Pulp stones are discrete calcified bodies found in the dental pulp. The aims of this study were to calculate the prevalence of pulp stones in young Australian adults using radiographs, and to report any associations between occurrence of pulp stones and sex, tooth type, dental arch, side and dental status. METHODS: From 217 undergraduate dental students, comprising 123 males and 94 females aged between 17-35 years, 3296 teeth were examined under 2x magnification on bitewing radiographs. Pulp stones were scored as present or absent, and associations with sex, tooth type, dental arch, side and dental status noted. RESULTS: Pulp stones were found in 100 (46.1 per cent) of the subjects and 333 (10.1 per cent) of the teeth examined. Occurrences were rare in premolars (0.4 per cent) but significantly higher in molars (19.7 per cent). Pulp stones were significantly more common in first molars than in second molars, and in maxillary first molars than in mandibular first molars. Carious and/or restored maxillary right first molars and maxillary left second molars displayed higher prevalences of pulp stones than unrestored and intact molars. CONCLUSION: Pulp stones may provide useful forensic information when examining dental records to identify deceased persons.

Adolescent↗

Tooth development standards for South Australia.

BACKGROUND: Chronological age, as recorded by registration of birth date, is referred to throughout an individual's life. This information is relevant in medical and dental practice for evaluating developmental progress, for educational purposes, and in legal matters, particularly in the application of criminal law. The absence of birth date information raises particular concerns, and estimates of chronological age are often required. Standards of dental maturation may be used to estimate age, but they have been shown to be gender and population sensitive. METHODS: The revised Demirjian' system of dental age estimation was applied to a sample of 615 South Australian children in order to assess its accuracy. RESULTS: The results of our study have shown that the Demirjian system is of limited accuracy when used to estimate the age of South Australian children. CONCLUSIONS: Generation of new standard curves, specific to the Australian population, is indicated.

Adolescent↗

A case of bitten Bettongs.

Australia has a unique collection of native fauna, which is often threatened by physical harm or the destruction of its habitat and conservation of endangered species is a primary concern. Investigation of the recent deaths of Bettongs in Lincoln National Park, South Australia was undertaken by the Forensic Odontology Unit, Adelaide University to determine the likely perpetrator. Feral domestic cats were deemed to be responsible, as indicated by bitemarks on the radiotransmitter collars.

Animals↗

Treatment of a granuloma caused by Halicephalobus gingivalis in a horse.

A 12-year-old Arabian gelding with a granuloma caused by the nematode Halicephalobus gingivalis caudal and dorsal to the left orbit was examined. There was no evidence of dissemination of the nematode to the kidneys or the CNS, and the horse was treated with ivermectin (1.2 mg/kg [0.55 mg/lb] of body weight, p.o., every 2 weeks for 3 treatments). The granuloma was surgically debulked 2 days after the first dose of ivermectin. The granuloma resolved with no evidence of nematode infection after 18 months. Halicephalobus gingivalis is a ubiquitous saprophytic nematode that has been reported to infect humans and horses. The nematode may form granulomas in the integument or may disseminate to various organs with a tropism for the CNS and kidneys. Once clinical signs of CNS involvement develop, the disease is rapidly fatal.

Animals↗

Preparation of vinylogous 2-sulfonylindolines by the palladium-catalyzed heteroannulation of o-iodoanilines with dienyl sulfones and their further transformation to indoles and carbazoles.

The palladium-catalyzed heteroannulation of o-iodoanilines with dienyl sulfones provides a convenient route to vinylogous 2-sulfonylindolines 3. The reaction proceeds in DMF/water in the presence of potassium carbonate and catalytic palladium(II) acetate and is compatible with both electron-donating and -withdrawing substituents in the para position of the aniline, and with an alkyl substituent at C-2 of the dienyl sulfone. The indolines underwent oxidation with DDQ to afford the corresponding indoles 4. The latter were then employed as dienes in Diels-Alder reactions with dimethyl acetylenedicarboxylate (DMAD), methyl propiolate, or methyl acrylate. In the case of the latter two dienophiles, the cycloadditions were highly regioselective, affording the corresponding 1,3-products (with respect to the relative positions of the sulfone and ester groups), exclusively. The cycloadducts from acetylenic dienophiles were converted to the corresponding carbazoles by elimination of the sulfone moiety with DBU, and that from methyl acrylate was subjected to reductive desulfonylation and oxidation to the corresponding carbazole with DDQ. The method thus provides access to carbazoles with various substituents at the 3-, 4-, and 6-positions.

Journal Article↗

Kinetics of leukocyte and myeloid cell traffic in the murine corneal allograft response.

BACKGROUND: Little information exists on the trafficking of myeloid and lymphoid cells between the transplanted cornea and the secondary lymphoid tissue. This study reports on changes in the cornea and the draining lymph node (DLN) from the time of graft emplacement. METHODS: Using a mouse corneal graft model (C57BL/10Sn to BALB/c), eyes and submandibular DLN were examined by immunohistochemistry and three-color flow cytometry for evidence of T cell activation and dendritic cell (DC) conditioning (up-regulation of costimulatory molecules) at various times (15 min to 24 days; n=4 for each time). RESULTS: In the DLN, early (2 hr) DC conditioning was sustained throughout allograft rejection whereas a remarkable drop in percentage of activated CD4+ and CD8+ T cells (P <0.001) was followed by a biphasic rise in activated CD4+ and, to a lesser extent, CD8+ T cells (24 hr, P <0.001 and 6 days, P <0.01). CD11b+ and MOMA-2+ macrophages, MHC Class II+ cells, CD86+ DC, and neutrophils were the earliest cells infiltrating the cornea (at 24 hr), whereas T cells appeared after 2 days, with CD4+ T cells being confined largely to the graft recipient border. CONCLUSIONS: Immediate and rapid changes in T cell and DC populations in the DLN correlate with the type of cellular infiltration in the corneal graft. The data are consistent with a model in which CD4+ T cell help for CD8+ cytotoxic T cells could be provided by sequential two-way activation of T cells and DC in the DLN. The majority of cells infiltrating the graft were macrophages and neutrophils, with fewer DC and T cells.

Animals↗

A model for the genesis of arterial pressure Mayer waves from heart rate and sympathetic activity.

Both theoretic models and cross-spectral analyses suggest that an oscillating sympathetic nervous outflow generates the low-frequency arterial pressure fluctuations termed Mayer waves. Fluctuations in heart rate also have been suggested to relate closely to Mayer waves, but empiric models have not assessed the joint causative influences of heart rate and sympathetic activity. Therefore, we constructed a model based simply upon the hemodynamic equation derived from Ohm's Law. With this model, we determined time relations and relative contributions of heart rate and sympathetic activity to the genesis of arterial pressure Mayer waves. We assessed data from eight healthy young volunteers in the basal state and in a high sympathetic state known to produce concurrent increases in sympathetic nervous outflow and Mayer wave amplitude. We fit the Mayer waves (0.05-0.20 Hz) in mean arterial pressure by the weighted sum of leading oscillations in heart rate and sympathetic nerve activity. This model of our data showed heart rate oscillations leading by 2-3.75 s were responsible for almost half of the variance in arterial pressure (basal R2 = 0.435 +/- 0.140, high sympathetic R2= 0.438 +/- 0.180). Surprisingly, sympathetic activity (lead 0-5 s) contributed only modestly to the explained variance in Mayer waves during either sympathetic state (basal: delta R2 = 0.046 +/- 0.026; heightened: delta R2 = 0.085 +/- 0.036). Thus, it appears that heart rate oscillations contribute to Mayer waves in a simple linear fashion, whereas sympathetic fluctuations contribute little to Mayer waves in this way. Although these results do not exclude an important vascular sympathetic role, they do suggest that additional factors, such as sympathetic transduction into vascular resistance, modulate its influence.

Adult↗

Estrogen replacement therapy improves baroreflex regulation of vascular sympathetic outflow in postmenopausal women.

BACKGROUND: Menopausal estrogen loss has been associated with increased cardiovascular disease in postmenopausal women. However, the link between estrogen and cardiovascular disease remains unclear. Some data suggest estrogen mediates its effect through changes in arterial pressure and its regulation. However, the data available in older women are equivocal regarding estrogen's ability to reduce resting arterial pressure or to improve its regulation. METHODS AND RESULTS: We studied 11 healthy, postmenopausal women before and after 6 months of estrogen administration. Arterial pressure was measured by brachial auscultation and finger photoplethysmography. Vascular sympathetic nerve activity was measured in the peroneal nerve by microneurography, and the slope of the relations between changes in heart period, sympathetic activity, and arterial pressure caused by bolus infusions of nitroprusside and phenylephrine were used as an index of baroreflex gain. Estrogen therapy did not change systolic pressure (128+/-2 versus 123+/-2 mm Hg) or cardiac-vagal baroreflex gain (6.6+/-0.9 versus 6.7+/-0.7 ms/mm Hg). However, vascular sympathetic baroreflex gain was increased (-4.6+/-0.6 versus -7.4+/-1.0 arbitrary integrated units/mm Hg; P=0.02). CONCLUSION: These findings suggest long-term estrogen replacement therapy has effects on cardiovascular regulation that may not be reflected in resting arterial pressures.

Administration, Oral↗

The role of estrogen and estrogen receptor-alpha in male adipose tissue.

Males and females both express estrogen receptor (ER) in white adipose tissue (WAT), and estrogens appear to play an important role in regulating WAT in females. However, the role of ER in male WAT was unclear. In this review, we describe our work, which used wild type (WT) and ERalpha-knockout (alphaERKO) male and female mice to determine the role of ERalpha in regulating WAT and brown adipose tissue (BAT). There were progressive increases in WAT with advancing age in alphaERKO compared with WT males; weights of various WAT depots in alphaERKO males were increased by more than 100% compared with WT controls during adulthood. Conversely, BAT weight was similar in alphaERKO and WT males at all ages. Adipocyte areas and numbers were also increased in WAT from alphaERKO compared with WT males. Compared with WT controls, alphaERKO females also had increases in WAT. The alphaERKO mice also had insulin resistance and impaired glucose tolerance, similar to humans lacking ERalpha or aromatase. The obesity in alphaERKO males appeared to involve decreased energy expenditure rather than hyperphagia. In summary, ERalpha absence causes adipocyte hyperplasia and hypertrophy in WAT, but not BAT, and is accompanied by insulin resistance and glucose intolerance in both males and females. These results are the first evidence that the estrogen/ERalpha signaling system is critical in female and male WAT deposition, and may have clinical implications.

Adipose Tissue↗

Implementation and uses of automated de novo peptide sequencing by tandem mass spectrometry.

There are several computer programs that can match peptide tandem mass spectrometry data to their exactly corresponding database sequences, and in most protein identification projects, these programs are utilized in the early stages of data interpretation. However, situations frequently arise where tandem mass spectral data cannot be correlated with any database sequences. In these cases, the unmatched data could be due to peptides derived from novel proteins, allelic or species-derived variants of known proteins, or posttranslational or chemical modifications. Two additional problems are frequently encountered in high-throughput protein identification. First, it is difficult to quickly sift through large amounts of data to identify those spectra that, due to poor signal or contaminants, can be ignored. Second, it is important to find incorrect database matches (false positives). We have chosen to address these difficulties by performing automatic de novo sequencing using a computer program called Lutefisk. Sequence candidates obtained are used as input in a homology-based database search program called CIDentify to identify variants of known proteins. Comparison of database-derived sequences with de novo sequences allows for electronic validation of database matches even if the latter are not completely correct. Modifications to the original Lutefisk program have been implemented to handle data obtained from triple quadrupole, ion trap, and quadrupole/time-of-flight hybrid (Qtof) mass spectrometers. For example, the linearity of mass errors due to temperature-dependent expansion of the flight tube in a Qtof was exploited such that isobaric amino acids (glutamine/lysine and oxidized methionine/ phenylalanine) can be differentiated without careful attention to mass calibration.

Amino Acid Sequence↗

Does reduced vascular stiffening fully explain preserved cardiovagal baroreflex function in older, physically active men?

BACKGROUND: We measured cardiovagal baroreflex gain and its vascular mechanical and neural components during dynamic baroreflex engagement in 10 young untrained men, 6 older untrained men, and 12 older, physically active men. METHODS AND RESULTS: Our newly developed assessment of beat-to-beat carotid diameters during baroreflex engagement estimates the mechanical transduction of pressure into barosensory stretch (diameter/pressure), the neural transduction of stretch into vagal outflow (R-R interval/diameter), and conventional integrated cardiovagal baroreflex gain (R-R interval/pressure). Integrated gain was lower in older untrained men than in young untrained men (6.8+/-1.2 versus 15.7+/-1.8 ms/mm Hg) due to both lower mechanical (9.1+/-1.0 versus 17.1+/-2.4 mm Hg/microm) and lower neural (0.57+/-0.10 versus 0.90+/-0.10 ms/microm) transduction. Integrated gain in older active men (13.3+/-2.7 ms/mm Hg) was comparable to that in young untrained men. This was achieved through mechanical transduction (12.1+/-1.4 mm Hg/microm) that was modestly higher than that in older untrained men and neural transduction (1.00+/-0.20 ms/microm) comparable to that in young untrained men. Across groups, both mechanical and neural components were related to integrated gain; however, the neural component carried greater predictive weight (beta=0.789 versus 0.588). CONCLUSIONS: Both vascular and neural deficits contribute to age-related declines in cardiovagal baroreflex gain; however, long-term physical activity attenuates this decline by maintaining neural vagal control.

Adult↗

A novel host cell reactivation assay to assess homologous recombination capacity in human cancer cell lines.

Repair of DNA double-strand breaks (DSB) is essential for cell viability and genome stability. Homologous recombination repair plays an important role in DSB repair and impairment of this repair mechanism may lead to loss of genomic integrity, which is one of the hallmarks of cancer. Recent research has shown that the tumor suppressor genes p53 and BRCA1 and -2 are involved in the proper control of homologous recombination, suggesting a role of this type of repair in human cancer. We developed a novel assay based on recombination between two Green Fluorescent Protein (GFP) sequences in transiently transfected plasmid DNA. The plasmid construct contains an intact, emission-shifted, "blue" variant of GFP (BFP), with a 300 nucleotide stretch of homology to a nonfunctional copy of GFP. In the absence of homologous recombination only BFP is present, but homologous recombination can create a functional GFP. The homologous regions in the plasmid were constructed in both the direct and the inverted orientation of transcription to detect possible differences in the recombination mechanisms involved. A panel of human tumor cell lines was chosen on the basis of genetic background and chromosome integrity and tested for homologous recombination using this assay. The panel included cell lines with varying levels of karyotypic abnormalities, isogenic cell lines with normal and mutant p53, isogenic cell lines with or without DNA mismatch repair, BRCA1 and -2 mutant cell lines, and the lymphoma cell line DT40. With this assay, the observed differences between cell lines with the lowest and highest levels of recombination were about 100-fold. Increased levels of recombination were associated with mutant p53, whereas a low level of recombination was found in the BRCA1 mutant cell line. In the cell line HT1080TG, a mutagenized derivative of HT1080 with two mutant alleles of p53, high levels of recombination were found with the direct orientation but not with the inverted orientation plasmid. No difference in recombination was detected between two isogenic cell lines that only differed in DNA mismatch repair capability. We conclude that this assay can detect differences in homologous recombination capacity in cultured cell lines and that these differences follow the patterns that would be expected from the different genotypes of these cell lines. Future application in normal cells may be useful to identify genetic determinants controlling genomic integrity or to detect differences in DNA repair capacity in individuals.

Base Pair Mismatch↗

Melanocortin receptor-mediated mobilization of intracellular free calcium in HEK293 cells.

Mouse melanocortin receptors, MC1-R, MC3-R, MC4-R, and MC5-R, when expressed in HEK293 cells and stimulated with either alpha-melanocyte-stimulating hormone (alpha-MSH) or desacetyl-alpha-MSH, mediate increases in intracellular free calcium concentration ([Ca(2+)](i)) with EC(50) values between 0.3 and 4.3 nM. The increase in [Ca(2+)](i) is cholera toxin sensitive and pertussis toxin insensitive. The mechanism involves calcium mobilization from intracellular stores without a transient rise in inositol trisphosphate. Mouse agouti protein (55 nM) is a competitive antagonist of alpha-MSH (6-fold) and desacetyl-alpha-MSH (8-fold), coupling the mMC1-R to increased [Ca(2+)](i). Agouti protein (55 nM) significantly increased the EC(50) for alpha-MSH (3-fold), and 550 nM agouti protein significantly increased the EC(50) for desacetyl-alpha-MSH (4-fold), coupling the mMC4-R to a rise in [Ca(2+)](i). However, agouti protein antagonism of the MC4-R may not be competitive since there was a trend for the maximum response to also increase. There was no significant antagonism of the MC3-R and MC5-R by agouti protein (55 nM). Understanding the physiological relevance of the transduction of a calcium signal by melanocortin peptides may be important for future development of therapeutic targeting of the melanocortin receptors.

Agouti Signaling Protein↗