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Biomedical subjects

D A Clark

Publications and source records attributed to D A Clark.

At least 19 recordsLinked to original sources

No association between ADRA2A polymorphisms and schizophrenia.

There is evidence to suggest that the alpha(2A)-adrenergic receptor may be involved in schizophrenia. With attention directed at the upstream regulatory region of the gene which codes for this receptor (ADRA2A), we proposed that single nucleotide polymorphisms (SNPs) within this region influences susceptibility to schizophrenia by altering the expression of this receptor. We opted to test for an influence on susceptibility by association study using 112 schizophrenic/schizoaffective disorder patients and 159 controls. The region of interest was screened for SNPs using a combination of bioinformatic searches and sequencing. A total of nine SNPs were discovered, of which four (-5972-G/A, -2211-A/T, -1291-C/G and -261-G/A) were genotyped in the entire clinical sample. No associations were evident, suggesting no influence for these SNPs in susceptibility to schizophrenia.

Adult↗

A systems comparison of once- versus twice-daily milking of pastured dairy cows.

The objective of this study was to compare the effect of milking frequency (once vs. twice-daily milking) and breed (Holstein-Friesians vs. Jerseys) on milk and milk solids (MS; milk fat + milk protein), yield per cow, milk composition, somatic cell count and lactation length; cow body weight, body condition score, and reproductive performance over a 4-yr period. Total cow numbers in each herd were 30, 35, 36, and 42 for Holstein-Friesians milked once or twice daily, and Jerseys milked once or twice daily, respectively. Forty hectares of pasture were subdivided into 4 smaller pastures of 10 ha each. Stocking rates for the once-daily herds were 16.7% greater than the twice-daily herd in their respective breed. An increased stocking rate was chosen to achieve equal milk and MS per ha from the 2 milking frequencies. Annual milk, fat, protein, and lactose yields per cow were less for once-daily than for twice-daily milking. Interactions were detected between milking frequency and breed for annual milk, fat, protein, and lactose yields per cow, because Jerseys were relatively less affected by once-daily than by twice-daily milking than Holstein-Friesians. Holstein-Friesian cows milked once daily produced 31.2% less milk and 29.4% less MS per cow than their twice-daily counterparts. In contrast, Jersey cows milked once daily produced 22.1% less milk and 19.9% less MS per cow than their twice-daily counterparts. Milk per ha was 17.7 and 9% less for the once-daily Holstein-Friesians and once-daily Jersey herds, respectively, compared with their twice-daily counterparts, because the greater stocking rate for the once-daily herds did not fully compensate for the milk loss per cow. Milking once daily increased somatic cell count throughout the year in both breeds. Cows milked once daily conceived 3 d earlier, took 5 d less from calving to conception, and needed 11% fewer controlled internal drug release devices than those milked twice daily. Milking once daily is a viable milking option for New Zealand farmers who are prepared to trade-off loss of MS income for increased time to accomplish other non-milking activities.

Animals↗

Yields and persistency of lactation in Friesian and Jersey cows milked once daily.

Effects of milking cows once daily throughout lactation at high stocking rates (17% more cows/ha than for those milked twice daily) were studied in 2 Friesian and 2 Jersey herds during 3 lactations. Cows were allocated to 2 herds within breed and were milked either once or twice daily, based on age, genetic merit, and previous performance. Cows remained in their original herd and were milked at the same milking frequency during all lactations. Culled cows (20% per year) were replaced by 2-yr-old heifers. Yields of milk, lactose, protein, and fat were measured every 2 wk by commercial herd test. Cubic splines (5 knots) were used to approximate the lactation curve for each cow-yr to provide estimates of performance for each day of lactation. Yields of milk were greater for Friesian and Jersey cows milked twice daily (4,751 +/- 89 and 3,067 +/- 81 kg/cow) than for cows milked once daily (3,329 +/- 80 and 2,431 +/- 75 kg/cow), respectively. Cows milked once daily had lesser total and peak yields of milk, lactose, protein, and fat than cows milked twice daily. Friesians had greater total and peak yields than Jerseys. Peak production for all milk components occurred earlier in lactation for cows milked once daily than twice daily (d 24 to 39 vs. 32 to 44). Three measures of persistency of lactation were considered for each cow with 2 measures (Pers1 and Pers2) indicating that cows milked twice daily had better persistency than those milked once daily. Ranking of herds in persistency tended to match the ranking based on total yields. Measures of persistency (Pers1 and Pers2) were positively related to total yield in the Jerseys milked once daily and negatively related to peak yield in the Friesians. The third persistency measure (Pers3) ranked once-daily Jerseys first and twice-daily Friesians last, and was negatively correlated with total yield in the Friesian herds and negatively correlated with peak yield in all herds. For most performance measures, cows milked twice daily had better total yields and persistency than cows milked once daily.

Animals↗

The chemistry of exploding ants, Camponotus spp. (cylindricus complex).

A detailed comparative analysis of the exocrine chemistry of nine Bruneian Camponotus species in the cylindricus complex is reported. Workers of these species are known to have hypertrophied mandibular glands and release their glandular contents suicidally from the head by rupturing the intersegmental membrane of the gaster. All of the species produce mixtures of polyacetate-derived aromatics, including hydroxyacetophenones, which display pH-dependent color changes, and aliphatic hydrocarbons and alcohols. In addition, three species contained (6R)-2,6-dimethyl-(2E)-octen-1,8-dioic acid (9) or (3S)-8-hydroxycitro-nellic acid (10a), previously unreported from insects. These compounds were characterized from their spectral data, and confirmed by comparison with synthetic samples. The allomonal role of these compounds is based on numerous field observations, and their chemotaxonomic value is presented.

Acetates↗

Advances in pasture management for animal productivity and health.

A wide range of management techniques is available to enhance quantity and quality of forage supply to grazing animals throughout the annual production cycle. Within broad limits, dry matter (DM) production is relatively insensitive to management of defoliation frequency, severity and duration. However defoliation management has effects on feed quality which can be enhanced, in particular, by control of pasture growth in the spring through maintenance of relatively low average pasture masses. Treading damage can have significant immediate and ongoing effects on pasture production and farmers can use a range of management techniques to minimise these. Fertiliser application practices have a potent influence on pasture production and seasonality of that production. Available soil nitrogen is the primary nutrient deficiency limiting production in New Zealand's characteristically grass-dominant pastures. Nitrogen fertiliser usage has increased markedly in recent years, particularly to grow substantially greater amounts of forage during the cool season, and this trend looks set to continue. However, the use of nitrogen fertiliser has important environmental implications. Pasture renewal and forage crop use has also increased in recent years. Care needs to be taken in conducting cost-benefit analyses, selecting the options that best meet the needs, and in establishment and subsequent management practices. Ryegrass (perennial and hybrids) and white clover remain the primary choice for permanent pasture renewal, the availability of safe endophytes having largely alleviated effects of endophyte toxicosis. Special-purpose mixtures are used, especially in dry environments. Italian ryegrasses, brassicas and chicory are common choices for forage crops. A range of management techniques can be used to alleviate deleterious effects of some forages, including ryegrass endophyte toxicosis, facial eczema, and toxins associated with Fusarium fungi. Generally these techniques are not totally effective. More research is required to increase our understanding of these disorders, and in order to develop more effective and reliable management practices.

Journal Article↗

Feeding value of pastures for ruminants.

Perennial ryegrass is the primary forage component of ruminant diets in New Zealand. It is persistent and palatable, and immature ryegrass has a high nutritive value (NV). However, seedhead development substantially lowers its feeding value (FV) as fibre concentration increases, the rate and extent of digestibility decreases, and voluntary intake declines. Ryegrass pastures are susceptible to accumulation of endophytic and saprophytic fungi in dead material at the base of the sward, especially when mature and laxly grazed. Feeding forage legumes to ruminants grazing grass-dominant pastures will improve animal performance and lessen the reliance on a single species to meet all nutritional requirements. The FV of forage is a function of intake and NV, measured by chemical analyses and animal feeding trials. Performance of individual animals grazing forages is usually limited by energy intake because structural fibre can slow digestion and clearance from the rumen and because of competition between individuals for available feed. The use of metabolisable energy (ME) content of forage to signify FV can give a reasonable indication of animal performance, but it should be used in conjunction with chemical analyses to improve the accuracy of predictions. The relationship between FV, pasture production, animal performance and profitability is complex. The importance of skilled management to maintain pasture quality and optimise animal performance under inconsistent climatic conditions should not be underestimated. Acceptable animal performance with minimal veterinary intervention requires good nutrition, but the genetic potential of livestock in New Zealand cannot be met solely by grazing pasture, especially when a high utilisation of pasture is required to maintain quality and profitability. Producers are responding to industry demands to reduce the seasonality in supply of milk and meat by changing lambing and calving dates, and extending lactation length in dairy cows. Social changes include adoption of once-daily milking in the dairy industry. Some changes have necessitated increased use of supplements and others can be met by feeding forages with a higher FV than ryegrass, all of which require an improved knowledge of feed quality. This information is available through rapid and inexpensive near infrared spectroscopy (NIRS) analysis, enabling animal nutritional needs to be balanced by appropriate nutrient supply. It is essential that producers continue to improve animal welfare, limit excessive use of fertilisers and meet the demands of overseas consumers. Good nutrition, with an increased use of legumes and other forages to complement ryegrass pastures, will enable these objectives to be achieved.

Journal Article↗

Distribution and quantification of human herpesvirus 6 in multiple sclerosis and control brains.

Multiple sclerosis (MS) is thought to be precipitated by environmental factors, potentially including viruses, in genetically susceptible individuals and recently human herpesvirus 6 (HHV-6) has been associated with the disease. We have analysed post mortem brain for the presence, variant type and quantity of HHV-6 by PCR. A total of 124 samples from seven anatomically defined regions of brain were tested from MS cases and controls. HHV-6 DNA was detected in 41% and 44% of MS case and control samples. The median viral loads were 11 and 9 genome copies/microg DNA in cases and controls respectively and the viral load was not increased in lesions. Except in one instance, the HHV-6 DNA detected was variant B. There was no apparent difference in the distribution of HHV-6 DNA in the brains of MS cases versus controls, nor between normal appearing and lesional tissue in MS cases. Periventricular regions of the brain were more frequently positive for HHV-6 DNA in both MS cases and controls, although this difference was not statistically significant. These studies confirm the neurotropism of HHV-6 but do not demonstrate differences in the distribution, variant type or quantity of HHV-6 in brains from patients with MS versus controls.

Aged↗

[Challenges facing nurses' associations and unions: a global perspective].

Nurses are at the heart of every country's health care system. What sort of problems do they face at work? What are the coping strategies that they and their organizations pursue? Drawing on the findings of a unique global survey of nurses' associations and unions, the authors provide clear answers to these and related questions at a time when population ageing, epidemics, privatization and understaffing are putting heightened pressures on health care systems around the world. Interestingly, the priority concerns of nurses' organizations the world over have much in common despite the widely differing national contexts in which they operate.

Data Collection↗

Tropical rain forest tree growth and atmospheric carbon dynamics linked to interannual temperature variation during 1984-2000.

During 1984-2000, canopy tree growth in old-growth tropical rain forest at La Selva, Costa Rica, varied >2-fold among years. The trees' annual diameter increments in this 16-yr period were negatively correlated with annual means of daily minimum temperatures. The tree growth variations also negatively covaried with the net carbon exchange of the terrestrial tropics as a whole, as inferred from nearly pole-to-pole measurements of atmospheric carbon dioxide (CO(2)) interpreted by an inverse tracer-transport model. Strong reductions in tree growth and large inferred tropical releases of CO(2) to the atmosphere occurred during the record-hot 1997-1998 El Niño. These and other recent findings are consistent with decreased net primary production in tropical forests in the warmer years of the last two decades. As has been projected by recent process model studies, such a sensitivity of tropical forest productivity to on-going climate change would accelerate the rate of atmospheric CO(2) accumulation.

Atmosphere↗

The Meta-Cognitive Beliefs Questionnaire: development of a measure of obsessional beliefs.

A 67 item self-report questionnaire called the Meta-Cognitive Beliefs Questionnaire (MCBQ) was developed to assess endorsement of beliefs about the importance of control and negative consequences associated with unwanted, ego-dystonic intrusive thoughts, images and impulses. The MCBQ and a battery of questionnaires that assessed symptoms and cognitions of worry, obsessive-compulsive disorder, anxiety, and depression were administered to large samples of undergraduate students. Beliefs about control of intrusive thoughts and perceived negative consequences due to uncontrolled mental intrusions had a unique significant relationship with obsessions, and to a lesser extent, worry. These findings are consistent with current cognitive behavioral theories that suggest an important role for meta-cognitive beliefs in the pathogenesis of obsessions.

Adult↗

Farnesylamine from the ant Monomorium fieldi Forel.

(2E)- and (2Z)-Farnesylamine were detected in the extracts of the myrmicine ant Monomorium fieldi Forel from Australia. Their structures were established by direct comparison with synthetic (2E)- and (2Z)-farnesylamine. This finding of a sesquiterpene is unique in a genus known to produce unbranched fatty acid derived alkaloids and amines. Additionally, while farnesylamine has not been reported from natural sources, the synthetic material has been shown to have a variety of biological activities.

Alkaloids↗

Th1 cytokines and the prothrombinase fgl2 in stress-triggered and inflammatory abortion.

PROBLEM: The immune system contributes to the outcome of pregnancy by complex immunological interactions. Cytokines especially influence the immune milieu pro or contra pregnancy. T helper 1 (Th1) cytokines [tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma)] cause inflammation and together are thought to threaten the maintenance of pregnancy. It has been proposed that increased levels of these Th1 cytokines activate coagulation via up-regulating the novel prothrombinase, fgl2. This study further investigates the Th1 cytokine up-regulation of fgl2 expression in a pathophysiological, stress induced abortion model, and an inflammatory, interleukin-12 (IL-12) triggered abortion model. METHOD: The DBA/2J-mated CBA/J female mice were exposed to sonic sound stress or were injected with IL-12 during early gestation. On day 13.5 of pregnancy the uteri were removed and the resorption rate was calculated. We evaluated TNF-alpha, IFN-gamma, fgl2 as well as IL-12 messenger RNA (mRNA) expression in decidual samples of all mice by quantitative, real-time polymerase chain reaction (PCR). RESULTS: A similar resorption rate of 24% was detected in stressed mice, as well as in IL-12 injected mice compared with approximately 11% in non-stressed, non-injected control mice. In stressed mice compared with controls, we observed on day 13.5 up-regulated TNF-alpha, unchanged IFN-gamma down-regulated fgl2, and a slightly increased levels of IL-12. In the IL-12 triggered abortion model, we observed up-regulated levels of TNF-alpha, IFN-gamma and fgl2. CONCLUSION: These novel data suggest two distinct cytokine patterns leading to similar abortion rates. A physiological cascade associated with up-regulation of TNF-alpha, and an IL-12-triggered cascade characterized by persistent up-regulation of TNF-alpha and IFN-gamma as well as a persistent increase in fgl2.

Abortion, Spontaneous↗

Oliguric acute renal failure in mycosis fungoides with lymphomatous infiltrates in the kidneys.

OBJECTIVE: To present the clinical picture of acute renal failure in patients with mycosis fungoides (MF) and renal lymphomatous infiltrates. To analyze the pathogenesis of renal failure. METHODS: Correlation of clinical picture, urinary findings, imaging reports and autopsy findings in two patients with long-standing MF who died with renal failure. CASE SUMMARIES: Both subjects had sustained oliguria in the last 2 weeks. One patient had persistent hypotension, normal urinalysis, normal renal sonogram, and scarce interstitial lymphomatous infiltrates with preservation of renal parenchymal architecture. He was thought to have ischemic acute renal failure not directly linked to the lymphomatous infiltrates. The second patient developed hypertension one month prior to death, and had moderate proteinuria, hematuria, pyuria, grossly enlarged kidneys with hypoechoic masses, and extensive replacement of the renal parenchyma by lymphomatous infiltrates. This picture is typical of renal failure secondary to lymphomatous replacement of the kidneys. CONCLUSIONS: The development of oliguric renal failure in MF with renal lymphomatous infiltrates may have varying clinical and imaging manifestations and pathogeneses. Potentially reversible pathogenic mechanisms should be systematically investigated, particularly if the overall clinical picture is not characteristic of renal failure secondary to lymphomatous replacement of the parenchyma.

Acute Kidney Injury↗

Lung deposition of budesonide from the novel dry powder inhaler Airmax.

The deposition of budesonide at fast (60 l min(-1)) and slow (301 min(-1)) inspiratory flow rates from Airmax, a new multi-dose dry powder inhaler, was compared with that from Turbuhaler and a standard pressurized metered dose inhaler (pMDI). Twelve patients with mild to moderate asthma took part in a five-way randomized crossover study, and inhaled a single nominal dose of 200 microg budesonide, labelled with 99mTc, on each study day. Deposition was determined by gamma scintigraphy. At the fast flow rate, Airmax and Turbuhaler deposited 25.8+/-6.5% (mean +/- sD) and 29.8+/-6.9%, respectively of the delivered dose in the whole lung (P = 0.080). At the slow flow rate, Airmax deposited 28.3+/-5.6%, Turbuhaler 22.7+/-5.6% and pMDI 12.1+/-3.4%. Using data on emitted doses determined in vitro, it was estimated that Airmax deposited 53.1+/-13.3 microg and 43.6+/-8-6 microg budesonide in the lungs at 60 l min(-1) and 30 l min(-1) respectively whilst Turbuhaler deposited 48.3+/-11.2 microg at 60 l min -and 24.2+/-6.0 microg at 30 l min(-1). In conclusion, lung deposition of budesonide from Airmax was comparable to that of Turbuhaler at a high flow rate but was markedly superior to Turbuhaler and pMDI at a lower flow rate. Unlike Turbuhaler, Airmax performs with relative flow-rate independence.

Administration, Inhalation↗

Defining the roles of perforin, Fas/FasL, and tumour necrosis factor alpha in T cell induced mucosal damage in the mouse intestine.

BACKGROUND AND AIMS: Mucosal flattening and epithelial cell apoptosis are typical features of T cell induced inflammatory diseases of the bowel, such as coeliac disease and graft versus host disease. Mice injected with a T cell activating anti-CD3 antibody develop a severe diarrhoeal illness. We describe the histological features of this enteropathy and define the effector mechanisms involved in T cell induced mucosal injury in this in vivo model. METHODS: Wild-type and genetically modified mice were injected with the anti-CD3 antibody 3C11 (50 microg). Changes in the murine intestine were characterised by light microscopy analysis and terminal uridine nick-end labelling (TUNEL) assay. The role of perforin, Fas/Fas ligand (FasL), tumour necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma) in T cell induced mucosal damage was assessed using selected immunodeficient mouse strains. RESULTS: T cell activation caused severe damage, including small intestinal mucosal flattening and apoptosis of crypt epithelial cells. Mucosal damage was unaltered in anti-CD3 treated mice lacking IFN-gamma, Fas, or TNF-alpha receptors. In mice lacking TNF-alpha receptors and Fas (TNF-R1xR2 lpr/lpr strain), enterocyte apoptosis was diminished but there was no significant reduction in tissue damage. Apoptosis and mucosal injury were significantly reduced in perforin knockout mice. Abrogation of both FasL and perforin (perforin KOxgld mice) further significantly reduced tissue damage and apoptotic bodies. CONCLUSIONS: T cell induced mucosal injury is mediated by the combined effect of multiple pathways but predominantly by perforin. The redundancy of the mechanisms of tissue damage will have significant impact on therapeutic strategies aimed at specific and targeted inhibition of inflammatory processes.

Animals↗

Novel homozygous splice acceptor site GnRH receptor (GnRHR) mutation: human GnRHR "knockout".

Mutations in the GnRH receptor (GnRHR) have been shown to be responsible for a significant number of autosomic recessive and, less commonly, sporadic cases of idiopathic hypogonadotropic hypogonadism. We describe a woman with complete GnRH resistance secondary to a novel homozygous GnRHR gene mutation, transmitted as an autosomal recessive trait. The propositus presented with primary amenorrhea and absent thelarche and pubarche. Dynamic tests demonstrated absent spontaneous gonadotropin pulsatility, and no response to either exogenous pulsatile (10 microg/pulse at 90-min intervals over 6 h) or acute (100 microg) GnRH administration. However, she responded to exogenous gonadotropin administration, with a resulting normal pregnancy. Genomic DNA extracted from peripheral blood was PCR amplified using amplimers spanning intron-exon boundaries for the three exons of GnRHR and revealed a homozygous splice junction mutation (G to A transversion) at the intron 1-exon 2 boundary. Her unaffected sister, with a totally normal phenotype, was heterozygous for this mutation. After lymphocyte Epstein-Barr virus transformation, RNA was extracted and subjected to RT-PCR, using primers located in the first and third exons. Results showed a transcript lacking all of exon 2 (exon 2 skipping), with splicing of exon 1 to exon 3. This created a frame shift, generating a coding sequence for three new amino acids, followed by a stop codon. Although it is not clear whether the mutant receptor is actually expressed, the resultant mRNA sequence was presumed to produce a truncated receptor with no binding or signaling capacity.

Adolescent↗

Chemical image fusion. The synergy of FT-NIR and Raman mapping microscopy to enable a more complete visualization of pharmaceutical formulations.

The pharmaceutical industry uses successfully both FT-NIR and Raman microscopy to produce chemical images of solid dosage forms, typically in troubleshooting roles. However, due to the chemical composition of the formulations, it is not always possible to describe the entire chemical formulation by using a single spectroscopic method. As Raman and NIR spectroscopies are complementary in nature, their combined usage offers the opportunity to describe heterogeneous mixtures in more detail. A novel sample referencing approach has been developed that allows data to be acquired from exactly the same area of the sample using both Raman and FT-NIR microscopies. The optimum images for the components are then overlaid, which gives rise to a combined chemical image that visually describes the entire formulation. We have named this approach chemical image fusion (CIF). CIF has been applied to two examples. The first shows how a simple formulation was used to validate the CIF approach. In the second, CIF allowed an entire formulation to be visualized and the cause of tabletting problems determined. CIF provides increased confidence in the results generated by each individual technique and offers a more powerful method for the evaluation of pharmaceutical formulations.

Pharmaceutical Preparations↗