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Biomedical subjects

B L Smith

Publications and source records attributed to B L Smith.

At least 19 recordsLinked to original sources
PubMed2005

Pithomycotoxicosis (facial eczema) in ruminants in the Azores, Portugal.

Outbreaks of pithomycotoxicosis (facial eczema), a hepatogenous photosensitisation caused by the mycotoxin sporidesmin, have affected ruminants in the Azores Islands of Portugal after warm, humid periods during late summer and autumn. Twenty-two outbreaks were recorded in cattle between 1999 and 2001, affecting 11.4 per cent of the animals in the affected herds, and in 2000 there was an outbreak in one sheep flock in which more than 20 per cent of the sheep died. The clinical signs included decreases in milk production, weight loss, photosensitisation and its sequelae, including death. The animals had high activities of gamma glutamyltransferase in their serum, and icterus and severe liver disease, including biliary hyperplasia and fibrosis, were found postmortem. The characteristic spores of the toxigenic saprophytic fungus Pithomyces chartarum were found on grass; all 381 isolates of the fungus were toxigenic for sporidesmin by elisa, and the results were confirmed by high-performance liquid chromatography analysis. Cattle from farms at greatest risk of pithomycotoxicosis were protected by supplementing their concentrate feed with zinc oxide, or using a slow-release intraruminal zinc bolus.

Animals↗
PubMed2005

Significantly increased recovery of intestinal parasites on routine stool specimen evaluation.

Three hundred thirty-six stool samples from October 2001 through October 2002 were analyzed for the presence of intestinal parasites. Fifty-six of these (16.7%) were positive for a total of 66 parasites; 65/66 (98.5%) were detected by iodine and dimethyl sulfoxide-modified acid-fast (DMSO-mAFB) stained smears of fresh and formalin-ethylacetate sedimentation concentrated samples. Saline, iodine, and DMSO-mAFB stained smears of fresh stool samples alone detected significantly fewer parasites, finding only 50/66 (75.8%) (p < 0.05). Stool samples analyzed by trichrome stained specimens preserved in Zinc sulfate polyvinyl alcohol (Zinc PVA) detected only 41/ 66 (62.2%) of the parasites. In our study population, it was necessary to perform the National Committee for Clinical Laboratory Standard (NCCLS) recommended to accurately detect intestinal parasites. The concentration technique is simple and significantly increased the detection of intestinal parasites.

Azo Compounds↗
PubMed2004

The efficacy of Herceptin therapies is influenced by the expression of other erbB receptors, their ligands and the activation of downstream signalling proteins.

ErbB2 and EGFR are attractive oncology therapeutic targets as their overexpression in tumors predicts a poorer clinical outcome in a variety of epithelial malignancies. However, clinical results with therapeutic compounds targeting these receptors have been mixed. Therefore, there is a need for improved predictive biomarkers for these targeted therapeutics. In this study we analysed tissue microarrays of patients treated with combination chemotherapy and Herceptin for expression or phosphorylation of signalling proteins associated with erbB receptors to identify protein biomarkers that are predictive of breast cancer patient response. A comparison of expression or phosphorylation of these markers with patient outcome revealed that response to Herceptin depended not only on expression levels of erbB2 but also on expression of EGFR, expression of erbB ligands, expression of other receptors and phosphorylation of downstream proteins. Elucidating the biological effects of EGFR/erbB2 targeted therapeutics will enable patient tumor profiling to identify likely responders and the determination of biologically effective doses that allows chronic administration of these agents in order to maximise efficacy.

Antibodies, Monoclonal↗
PubMed2004

Inheritance of resistance to facial eczema: a review of research findings from sheep and cattle in New Zealand.

Facial eczema (FE) is a costly problem to New Zealand pastoral agriculture, and has a detrimental impact on animal wellbeing. Incidence and severity of the disease can be reduced by grazing management and zinc prophylaxis. An additional strategy is to breed animals that are genetically resistant to intoxication with sporidesmin, the causative mycotoxin. This review summarises research findings on the inheritance of resistance of animals to FE, including evidence of among- and within-breed genetic variation, direct and correlated responses to selection, and identification of genetic markers and candidate genes for FE resistance.

Journal Article↗
PubMed2004

Gene encoding the group B streptococcal protein R4, its presence in clinical reference laboratory isolates & R4 protein pepsin sensitivity.

BACKGROUND & OBJECTIVES: R proteins were first identified by Lancefield in group B Streptococcus (GBS) as resistant to trypsin at pH8 and sensitive to pepsin at pH2. The R4 protein found predominantly in type III and some type II and V invasive isolates conforms to these criteria. The Rib protein, although structurally and epidemiologically similar to R4, was reported as resistant to both proteases. We report here the gene encoding the R4 protein from a type III group B streptococcal isolate (76-043) well characterized in our laboratory. METHODS: Trypsin extracted GBS proteins were assayed for protease sensitivities by double-diffusion Ouchterlony using varying conditions for the enzyme pepsin. Standard haemoglobin assay was used to examine pepsin enzymatic activity. Thirty clinical isolates of varying protein profiles identified by double-diffusion from our reference strain laboratory were screened by PCR and Southern technique. SDS-PAGE gel purified R4 amino acid sequences were determined and used to design oligonucleotide primers for screening a 76-043 genomic library. RESULTS: R4 was sensitive to pepsin at pH2 but appeared resistant at pH4, the reported pH used for Rib. By standard haemoglobin assay and trypsin extract studies of R4 protein, pepsin was shown to be active at pH2, yet easily inactivated; assays of GBS surface proteins are critical at pH2. Of the amino acids initially sequenced from R4, 88 per cent (61/69) showed identity to Rib; the r4 nucleotide sequence was identical to that of rib. All isolates with strong positive protein reactions for R4 were positive in both PCR and Southern technique, whereas isolates expressing alpha, beta, R1/R4, and R5 (BPS) protein profiles were not. INTERPRETATION & CONCLUSION: Sequenced PCR products aligned with identity to the R4 and Rib nucleotide sequences and confirmed the identity of these proteins and their molecular sequences.

Amino Acid Sequence↗
PubMed2003

Tremorgenic mycotoxins increase gastric smooth muscle activity of sheep reticulum and rumen in vitro.

Reticulum and rumen strips (consisting of both muscle layers and the myenteric plexus) were superfused with Tyrode Ringer and their contractions recorded isometrically. The strips were subjected to exogenous acetylcholine and electrical field stimulation (EFS) resulting in contractions that could be blocked by atropine. Responses to the tremorgenic mycotoxin penitrem A and others thought to be involved in ryegrass staggers, paxilline and lolitrem B (10(-10)-10(-6)M), were compared with those of control vehicle (0.1% DMSO). The tremorgens were without effect on quiescent preparations. Penitrem A and paxilline enhanced spontaneously active preparations and the amplitude of contractions in response to EFS. Responses to paxilline had a shorter latency than to penitrem A. Responses of spontaneously active preparations were resistant to atropine. Penitrem A, but not paxilline, increased responses to exogenous acetylcholine. Lolitrem B (10(-6)M) increased responses to EFS, but many responses were equivocal, possibly due to the lower solubility of lolitrem B in aqueous solutions compared to the other tremorgens. The results show that these mycotoxins have peripheral excitatory effects on the reticulorumen and it is suggested that such activity in vivo may reflexly affect centrally derived cyclical contractions.

Animals↗
PubMed2003

Spectrofluorometric analysis of phylloerythrin (phytoporphyrin) in plasma and tissues from sheep suffering from facial eczema.

AIMS: To study the increase in phylloerythrin concentration in plasma and the disposition of phylloerythrin in skin and other tissues of sheep in which the hepatogenous photosensitisation,facial eczema, had been experimentally induced by dosing with the mycotoxin, sporidesmin. Spectroscopic differences between plasma and skin measurements of animals kept inside and outside after dosing were also studied in order to establish whether phylloerythrin undergoes photodegradation when exposed to sunlight. METHODS: Twenty-six Romney x Polled Dorset (25-30 kg)weaned female lambs were purchased from a commercial flock in the Waikato region, New Zealand. Twenty-two of these lambs were dosed with 0.25 mg sporidesmin/kg liveweight on each of two consecutive days (Days -1 and 0); the remaining four lambs served as controls. Both sporidesmin-dosed lambs and controls were randomly divided into two penned groups, one group housed inside in a darkened room and the others outside, exposed to natural sunlight. The lambs were fed green lucerne pellets and lucerne chaff ad libitum for 10 days prior to dosing and until Day 12 after the first dose; thereafter, all the lambs were fed fresh, cut grass (mainly ryegrass) ad libitum, until the end of the experimental period on Day 26. Plasma samples collected on Days -2, 7, 10, 12, 14, 17, 20 and 25were analysed for gamma glutamyltransferase (GGT) activity, bilirubin concentration, and the fluorescence spectrum of phylloerythrin. Spectrofluorometric analysis of phylloerythrin in skin was performed in vivo on the same days, using an external fiber-optic probe. RESULTS: Eight of 11 lambs (73%) kept outside after sporidesmin dosing became photosensitised during the experimental period. None of the sporidesmin-dosed animals kept inside showed clinical signs of photosensitisation. The GGT activity in plasma increased exponentially during the experimental period in all sporidesmin-dosed animals until it reached a plateau. All plasma obtained from sporidesmin-dosed sheep had spectral characteristics similar to those of phylloerythrin, namely a peak in the excitation spectrum at 422 nm and strong emission band at 650 (SE 1) and 709 (SE 1) nm. The fluorescence under excitation at 422 nm of phylloerythrin added to plasma from control lambs had identical peaks. Emission spectra obtained from plasma from healthy sheep without addition of phylloerythrin showed either no fluorescence or minor fluorescence at around 671 nm. Fluorescence in skin of sporidesmin-dosed animals had similar spectra to that in plasma. The appearance of the phylloerythrin-like spectra occurred 2-3 days later in the skin than in plasma, and phylloerythrin in sunlight-exposed skin did not suffer photodegradation during the course of the study. CONCLUSION: Plasma concentrations of phylloerythrin in healthy sheep were <0.1 micromol/l, and clinical signs of photosensitisation were not evident until concentrations exceeded 0.3 micromol/l. Plasma concentrations of phylloerythrin rose as high as 4.9 micromol/l in some animals. The concentration of phylloerythrin in skin began increasing 2-3 days later than that in blood. Hepatogenous photosensitisation can be diagnosed by analysis of plasma phylloerythrin concentrations using a spectroscopic method.

Journal Article↗
PubMed2002

Relationship between sporidesmin-induced liver injury and serum activity of gamma-glutamyltransferase in Romney lambs sired by facial eczema-resistant or control rams.

AIM: To test whether long-term selection for resistance to facial eczema (FE) influences the relationship between liver injury score (LIS) and serum activity of gamma-glutamyltransferase (GGT) in sporidesmin-dosed sheep. METHODS: Two groups of Romney lambs were generated for this study in 1999, out of an unselected group of ewes and sired by either selected FE-resistant (R) line (n=74 lambs) or unselected Control (C) line (n=119 lambs) rams from the Ruakura Research Centre long-term FE-selection experiment. The lambs were given a single oral dose of sporidesmin, sampled for determination of serum GGT activity 3 weeks later, and lambs that had serum GGT activity >55 IU/l (reactors) were humanely killed and assessed for LIS post mortem, 6 weeks after dosing. A second round of dosing was applied to the nonreactors, followed as above by analysis of serum GGT activity and assessment of LIS post mortem (both reactors and nonreactors). RESULTS: There was a significant linear relationship between LIS and logeGGT, which did not differ between the 2 sire lines (LIS= -2.96 (SE 0.38) + 0.89 (SE 0.07) x loge GGT, R2=0.54, p<0.001). CONCLUSIONS: Serum GGT is a valid indicator of LIS in lambs by sires selected for different levels of susceptibility to FE. The logeGGT-LIS relationship has not changed as a result of genetic selection for resistance to FE.

Journal Article↗
PubMed2002

Mycotoxicoses of grazing animals in New Zealand.

Mycotoxicoses are some of the most important diseases of animals grazing pastures in New Zealand, especially in northern areas where the disease, facial eczema, occurs. New Zealand scientists have led the world in research on facial eczema and endophyte-related diseases associated with tremoring. Facial eczema (pithomycotoxicosis) was one of the first mycotoxicoses to be studied systematically and successful methods for its control now exist. Toxicity is caused by the concentration of sporidesmin in the biliary system and its redox cycling which leads to the formation of toxic free-radicals. Zinc salts are capable of preventing facial eczema. Their efficacy and safety for farm use has been demonstrated and intraruminal boluses containing zinc have been developed for use in sheep and cattle. Endophyte-related diseases have received special attention over the last 15 years. It is now recognised that Neotyphodium spp and grasses (especially ryegrass and fescue) are an essential symbiosis, making control of these diseases in grazing animals difficult. New Zealand research has demonstrated inhibitory effects of zearalenone, from Fusarium spp growing on pasture litter, on sheep fertility.

Journal Article↗
PubMed2001

Deaths: preliminary data for 2000.

OBJECTIVES: This report presents preliminary data on deaths for the year 2000 in the United States. U.S. data on deaths are shown by age, sex, race, and Hispanic origin. Data on life expectancy, leading causes of death, and infant mortality are also presented. METHODS: Data in this report are based on a large number of deaths comprising more than 94 percent of the demographic file and 85 percent of the medical file for all deaths in the United States in 2000. The records are weighted to independent control counts of infant deaths, and deaths 1 year and over received in State vital statistics offices for 2000. Unless otherwise indicated, comparisons are made with final data for 1999. For certain causes of death, preliminary data differ from final data because of the truncated nature of the preliminary file. These are, in particular, accidents, homicides, suicides, and respiratory diseases. RESULTS: The age-adjusted death rate in 2000 for the United States decreased slightly from 1999 to a record low in 2000. For causes of death, declines in age-adjusted rates occurred for heart disease, stroke, Chronic liver disease and cirrhosis, diabetes, and cancer. Age-adjusted rates for drug-induced deaths, alcohol-induced deaths, and firearm injuries also decreased during 2000. Declines also occurred for homicides, suicides, unintentional injuries, and Chronic lower respiratory diseases although the extent of the declines cannot be precisely assessed based on the preliminary data. Age-adjusted death rates increased between 1999 and 2000 for the following causes: Pneumonitis from solids and liquids, Alzheimer's disease, kidney disease, hypertension, Influenza and pneumonia, and Septicemia. The infant mortality rate for the black population was 4 percent lower, while the rate for the white population decreased (nonsignificantly) by 2 percent. Life expectancy at birth rose by 0.2 years to a record high of 76.9 years.

Adolescent↗
PubMed2001

Deaths: final data for 1999.

OBJECTIVES: This report presents final 1999 data on U.S. deaths and death rates according to demographic and medical characteristics. Trends and patterns in general mortality, life expectancy, and infant and maternal mortality are also described. A previous report presented preliminary mortality data for 1999. METHODS: In 1999 a total of 2,391,399 deaths were reported in the United States. This report presents tabulations of information reported on the death certificates completed by funeral directors, attending physicians, medical examiners, and coroners. Original records are filed in the State registration offices. Statistical information is compiled into a national data base through the Vital Statistics Cooperative Program of the National Center for Health Statistics (NCHS), Centers for Disease Control and Prevention. For the first time in a final mortality data report, age-adjusted death rates are based upon the year 2000 population and causes of death are processed in accordance with the Tenth Revision of the International Classification of Diseases (ICD-10). RESULTS: The 1999 age-adjusted death rate for the United States was 881.9 deaths per 100,000 standard population, a 0.7 percent increase from the 1998 rate, and life expectancy at birth remained the same at 76.7 years. For all causes of death, age-specific death rates rose for those 45-54 years, 75-84 years, and 85 years and over and declined for a number of age groups including those 5-14 years, 55-64 years, and 65-74 years. Aortic aneurysm and dissection made its debut in the list of leading causes of death and atherosclerosis exited from the list. Heart disease and cancer continued to be the leading and second leading causes of death. The age-adjusted death rate for firearm injuries decreased for the sixth consecutive year, declining 6.2 percent between 1998 and 1999. The infant mortality rate, 7.1 infant deaths per 1,000 live births, was not statistically different from the rate in 1998. CONCLUSIONS: Generally, mortality continued long-term trends. Life expectancy in 1999 was unchanged from 1998 despite a slight increase in the age-adjusted death rate from the record low achieved in 1998. Although statistically unchanged from 1998, the trend in infant mortality has been of a steady but slowing decline. Some mortality measures for women and persons 85 years and over worsened between 1998 and 1999.

Adolescent↗
PubMed2001

External quality assessment of laboratory performance in analysis of toxicological cases.

A mean of 44 members of the United Kingdom national external quality assessment scheme (UKNEQAS) for toxicology reported analytical findings on 10 toxicological cases circulated between December 1995 and February 2000. Material distributed usually consisted of a 5ml blood and a 20ml urine sample simulated by quantitative addition of drugs and their metabolites to material donated by volunteers and patients. The samples were accompanied by a brief outline of the circumstances surrounding the case. Laboratories were requested to report their analytical findings, list methods of analysis, and provide interpretation of their findings. The mean overall success rate for identification of drugs or their pharmacological group was 76%, failure being largely by laboratories providing an immunoassay-based screening service for a fixed range of drug groups. The latter laboratories indicated that cases would be referred to regional toxicology centres for further investigation or confirmation. The coefficient of variation of measurements was <7% for routine analytes, such as ethanol and paracetamol, but 26-44% for tricyclics and opiates. There were 3% false positive reports. The quantity and content of interpretative comment provided by the laboratories was very variable. A number provide nothing in addition to the analytical result.

Adolescent↗
PubMed2001

Deaths: preliminary data for 1999.

OBJECTIVES: This report presents preliminary data for 1999 on deaths in the United States. U.S. data on deaths are shown by age, sex, race, and Hispanic origin. Data on life expectancy, leading causes of death, and infant mortality are also presented. METHODS: Data in this report are based on a sample of deaths comprising more than 99 percent of the total deaths in the United States for 1999. The records are weighted to independent control counts of infant deaths, and deaths 1 year and over received in State vital statistics offices for 1999. Unless indicated, comparisons are made with final data for 1998. Effective with this report, all age-adjusted death rates for 1999 and earlier years are standardized to the year 2000 population. Also, effective with mortality data for 1999, causes of death are coded and classified according to the Tenth Revision of the International Classification of Diseases (ICD-10) replacing ICD-9 used in the United States for deaths occurring during 1979-98. RESULTS: In 1999 the age-adjusted death rate for the United States increased slightly, compared with 1998. For causes of death, declines in age-adjusted rates occurred for homicide (6 percent) and suicide (6 percent), while rates for Septicemia and hypertension increased 6.6 percent and 5.0 percent, respectively. Mortality also decreased for drug-induced deaths and deaths from injury by firearms. The infant mortality rate for the white population was down 3 percent, while the rate for the black population increased by 2 percent, but the increase was not statistically significant. Life expectancy remained the same at 76.7 years.

Adolescent↗
PubMed2001

New ages for the last Australian megafauna: continent-wide extinction about 46,000 years ago.

All Australian land mammals, reptiles, and birds weighing more than 100 kilograms, and six of the seven genera with a body mass of 45 to 100 kilograms, perished in the late Quaternary. The timing and causes of these extinctions remain uncertain. We report burial ages for megafauna from 28 sites and infer extinction across the continent around 46,400 years ago (95% confidence interval, 51,200 to 39,800 years ago). Our results rule out extreme aridity at the Last Glacial Maximum as the cause of extinction, but not other climatic impacts; a "blitzkrieg" model of human-induced extinction; or an extended period of anthropogenic ecosystem disruption.

Animals↗
PubMed2001

A survey of extraction techniques for drugs of abuse in urine.

Sixty nine participants in the United Kingdom national external quality assessment scheme for drugs of abuse in urine reported details of their sample extraction technique by questionnaire. Laboratories were categorised by differences in technique and their analytical test results compared for samples containing D-amfetamine 0.4 (4) and 0.8 (3) mg/l, morphine 0.4 (4) and 0.8 (4)mg/l, and benzoylecgonine 0.15/0.2 (2) and 0.45/0.5 (4) mg/l. Values in parentheses are numbers of samples. For amfetamine, there was no significant difference in the frequency of true positive results between liquid-liquid or solid phase extraction and the Toxi-Lab A system at 0.8 mg/l. Toxi-Lab A gave significantly fewer positives when operating below its specified threshold at 0.4 mg/l. Paradoxically, laboratories using >5 ml urine volume performed less well. Acidification of the extract before volume reduction gave significantly more true positives. For extraction of morphine, solid phase systems significantly outperformed both liquid-liquid and the Toxi-Lab A system at both 0.8 and 0.4 mg/l. No significant differences between extraction techniques were demonstrated for analysis of benzoylecgonine.

Amphetamines↗
PubMed2001

Effects of modulation of tissue activities of DT-diaphorase on the toxicity of 2,3-dimethyl-1,4-naphthoquinone to rats.

The enzyme DT-diaphorase mediates the two-electron reduction of quinones to hydroquinones. It has previously been shown that the toxicity of 2-methyl-1,4-naphthoquinone to rats is decreased by pre-treatment of the animals with compounds that increase tissue levels of this enzyme. In contrast, the severity of the haemolytic anaemia induced in rats by 2-hydroxy-1,4-naphthoquinone was increased in animals with high levels of DT-diaphorase. In the present experiments, the effect of alterations in tissue diaphorase activities on the toxicity of a third naphthoquinone derivative, 2,3-dimethyl-1,4-naphthoquinone, has been investigated. This compound induced severe haemolysis and slight renal tubular necrosis in control rats. Pre-treatment of the animals with BHA, a potent inducer of DT-diaphorase, diminished the severity of the haemolysis induced by this compound and abolished its nephrotoxicity. Pre-treatment with dicoumarol, an inhibitor of this enzyme, caused only a slight increase in the haemolysis induced by 2,3-dimethyl-1,4-naphthoquinone, but provoked a massive increase in its nephrotoxicity. Modulation of DT-diaphorase activity in animals may therefore not only alter the severity of naphthoquinone toxicity, but also cause pronounced changes in the site of toxic action of these substances. The factors that may control whether induction of DT-diaphorase in animals will decrease or increase naphthoquinone toxicity are discussed.

Administration, Oral↗
PubMed2001

Micromechanical and structural properties of a pennate diatom investigated by atomic force microscopy.

The mechanisms behind natural nanofabrication of highly structured silicas are increasingly being investigated. We have explored the use of a standard Nanoscope III Multimode atomic force microscope (AFM) to study the silica shell of diatoms. The delicate structures of the shell surface of the diatom Navicula pelliculosa (Bréb.) Hilse were imaged and the shell's micromechanical properties were measured semi-quantitatively with a resolution down to approximately 10 nm. The technique to measure elasticity and hardness with the AFM was demonstrated to be useable even on these hard glass-like surfaces. Different experimental configurations and evaluation methods were tested. They gave a consistent result of the shell micromechanical properties. The first results showed that the diatom shell's overall hardness and elasticity was similar to that of known silicas. However, regions with different mechanical properties were distinguished. The elastic modulus varied from 7 to 20 GPa, from 20 to 100 GPa and from 30 to hundreds of GPa depending on the location. In general, the hardness measurements showed similar spatial differences. The hardness values ranged from 1 to 12 GPa but one specific part of the shell was even harder. Hence, certain localized regions of the shell were significantly harder or more elastic. These regions coincide with known characteristic features and mechanisms appearing at the different stages of the shell's growth. These results show that this method serves as a complementary tool in the study of silica biomineralization, and can detect eventual crystalline phases.

Diatoms↗