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Biomedical subjects

M Rodgers

Publications and source records attributed to M Rodgers.

At least 19 recordsLinked to original sources
PubMed2026

Antimicrobial-resistant Staphylococcus aureus isolated from Australian wildlife admitted to a veterinary hospital.

Although antimicrobial resistance (AMR) is a growing One Health concern, little is known about AMR in Staphylococcus aureus from Australian wildlife. This study investigated the occurrence, phenotypic AMR profiles, and genetic characteristics of S. aureus from six representative Australian wildlife species admitted to a wildlife hospital in Western Australia, including the western grey kangaroo (Macropus fuliginosus), quenda (Isoodon fusciventer), pelican (Pelecanus conspicillatus), galah (Eolophus roseicapilla), shingleback skink (Tiliqua rugosa) and long-necked turtle (Chelodina colliei). Staphylococcus aureus was isolated from 11.7% (21/180, 95% CI: 7.4%-17.3%) of the animals on admission. Whole genome sequencing identified 13 multi-locus sequence types (STs) and various virulence factors, including the human-specific immune evasion cluster (IEC). Resistance to at least one antimicrobial class was observed in 63.6% of the isolates. The blaZ, erm(T), aac(6')-aph(2″), and tet(L) AMR genes were detected in 63.6%, 13.6%, 4.5%, and 4.5% of S. aureus, respectively. After 7 days of hospitalisation, S. aureus was isolated from 16.5% (16/97, 95% CI: 9.7%-25.4%) of the animals, including two methicillin-resistant S. aureus (MRSA) isolated from two pelicans. The two MRSA were identified as community-associated MRSA clones (mecA-positive ST1-IV and ST93-IV), suggesting direct or indirect transmission between humans and wildlife during hospitalisation may have occurred. This study highlighted Australian wildlife may be a potential reservoir for genetically diverse antimicrobial-resistant S. aureus. AMR surveillance including wildlife using a One Health approach may be required.

Animals↗
PubMed1997

Subcellular localization and purification of a p-hydroxyphenylpyruvate dioxygenase from cultured carrot cells and characterization of the corresponding cDNA.

p-Hydroxyphenylpyruvate dioxygenase catalyses the transformation of p-hydroxyphenylpyruvate into homogentisate. In plants this enzyme has a crucial role because homogentisate is the aromatic precursor of all prenylquinones. Furthermore this enzyme was recently identified as the molecular target for new families of potent herbicides. In this study we examine precisely the localization of p-hydroxyphenylpyruvate dioxygenase activity within carrot cells. Our results provide evidence that, in cultured carrot cells, p-hydroxyphenylpyruvate dioxygenase is associated with the cytosol. Purification and SDS/PAGE analysis of this enzyme revealed that its activity is associated with a polypeptide of 45-46 kDa. This protein specifically cross-reacts with an antiserum raised against the p-hydroxyphenylpyruvate dioxygenase of Pseudomonas fluorescens. Gel-filtration chromatography indicates that the enzyme behaves as a homodimer. We also report the isolation and nucleotide sequence of a cDNA encoding a carrot p-hydroxyphenylpyruvate dioxygenase. The nucleotide sequence (1684 bp) encodes a protein of 442 amino acid residues with a molecular mass of 48094 Da and shows specific C-terminal regions of similarity with other p-hydroxyphenylpyruvate dioxygenases. This cDNA encodes a functional p-hydroxyphenylpyruvate dioxygenase, as evidenced by expression studies with transformed Escherichia coli cells. Comparison of the N-terminal sequence of the 45-46 kDa polypeptide purified from carrot cells with the deduced peptide sequence of the cDNA confirms that this polypeptide supports p-hydroxyphenylpyruvate dioxygenase activity. Immunodetection studies of the native enzyme in carrot cellular extracts reveal that N-terminal proteolysis occurs during the process of purification. This proteolysis explains the difference in molecular masses between the purified protein and the deduced polypeptide.

4-Hydroxyphenylpyruvate Dioxygenase↗
PubMed1997

Adequacy of hormone replacement therapy for osteoporosis prevention assessed by serum oestradiol measurement, and the degree of association with menopausal symptoms.

BACKGROUND: Patients on hormone replacement therapy (HRT) for osteoporosis prevention rather than menopausal symptom control may be asymptomatic, despite inadequate replacement and low serum oestradiol (E2) levels. In the primary health care setting, therapeutic monitoring of HRT is not carried out routinely so that patients with serum E2 levels inadequate to protect bone may be missed. AIM: To determine the proportion of women on transdermal E2 preparations with serum E2 levels insufficient to protect bone and to assess the value of a questionnaire-derived menopausal symptom score (MSS) for detecting these patients. METHOD: A cross-sectional analysis of 45 patients aged 35-70 years using transdermal E2 preparations obtained from a computer register of 14500 patients in a suburban practice. One blood sample was obtained from each patient at the time the MSS questionnaire was completed. Serum E2 concentration was measured using a fluoroimmunoassay and compared with the MSS. Levels below 150 pmol/l were considered to be insufficient to protect bone. The diagnostic accuracy of the MSS in screening for levels below 150 pmol/l was determined using receiver operating characteristic (ROC) curve analysis. RESULTS: The median (95% CI) serum E2 was 147 pmol/l (126-198 pmol/l) and levels were below 150 pmol/l in 24 out of 45 patients. There was no difference in the MSS (median, 95% CI) between those with serum E2 < 150 pmol/l (8.5, 5.0-17) and > or = 150 pmol/l (9.0, 5.0-14; P = 0.477). The degree of association between the serum E2 and the MSS, using the Spearman rank correlation coefficient, rs (95% CI) was small and not significant (-0.04, -0.34 to 0.26; P = 0.398). ROC curve analysis revealed an area under the curve (95% CI) of 0.51 (0.33-0.68). CONCLUSIONS: More than half the women were inadequately replaced to protect against osteoporosis. Furthermore, the MSS was of no value in screening for those with low serum E2 levels. Serum E2 levels should be monitored in women on HRT for osteoporosis prevention and the E2 dosage adjusted accordingly.

Adult↗
PubMed1995

In-vitro biopotency and glycoform distribution of recombinant human follicle stimulating hormone (Org 32489), Metrodin and Metrodin-HP.

In this study the in-vitro biopotency and glycoform distribution of human recombinant follicle stimulating hormone (FSH, Org 32489) has been assessed. The biopotency of recombinant FSH was studied using animal (rat Sertoli) and human (granulosa-lutein) cell models. Recombinant FSH, as measured in the rat Sertoli cell assay, was more potent than the urinary preparations Metrodin, Metrodin-HP and IS 70/45 with half maximal stimulation (ED50; mean +/- SEM, n > 3) occurring at 2.2 +/- 0.5 IU/I (recombinant FSH), 4.7 +/- 1.1 IU/I (Metrodin), 13.2 +/- 0.7 IU/I (Metrodin-HP) and 6.4 +/- 0.3 IU/I (IS 70/45); the pituitary preparation IRP 83/575 had an ED50 of 10.4 +/- 0.1 IU/I. Using human granulosa-lutein cells, cultured for up to 4 days in the absence of exogenous steroid precursors, recombinant FSH was either without effect (three out of five patients) or inhibited both oestradiol and progesterone secretion. FSH (83/575) was without effect on oestradiol with preparations from any of the patients but slightly stimulated (134 +/- 8%; mean +/- SEM, P < 0.05) progesterone production at the highest dose (80 IU/I). The distribution of FSH isoforms, assessed by polyclonal radioimmunoassay, following chromatofocusing over the ranges pH < 3.5 and pH 3.5-7.0 respectively was recombinant FSH, 12.4 and 87.6%; Metrodin, 19.8 and 80.2%; Metrodin-HP, 50.2 and 49.8%; IS 70/45, 15.0 and 85.0%; IS 83/575, 70.9 and 29.1%. All glycoforms were pI < 7.0 for the five preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Variability in the immunoreactive and bioactive follicle stimulating hormone content of human urinary menopausal gonadotrophin preparations.

The within- and between-batch variation in the immunoreactive and in-vitro bioactive FSH content of Pergonal, Metrodin and Metrodin-HP was investigated. Three batches of Pergonal and Metrodin, consisting of three ampoules in each batch, and three batches of Metrodin-HP, consisting of between one and three ampoules per batch, were selected at random. The follicle stimulating hormone (FSH) content of Pergonal, Metrodin and Metrodin-HP was determined by radioimmunoassay (R-FSH) and the in-vitro rat Sertoli cell bioassay (B-FSH) using the international urinary standard 70/45. The variability in the FSH content of the preparations was evaluated within and between batches by analysis of variance. Within-batch variability of B-FSH was not observed in Pergonal or Metrodin-HP but was seen in two batches of Metrodin in which the potency varied by up to 2.4 fold (P = 0.03). The between-batch R-FSH potencies of Pergonal (P1-P3) varied, with P2 (59.8 +/- 0.6) and P3 (61.7 +/- 0.9) being higher than P1 (47.1 +/- 1.5 mean +/- SEM IU/ampoule, P < 0.01). A similar pattern of variability was observed for B-FSH. For Metrodin, each of the batch R-FSH potencies was dissimilar (P < 0.02), with estimates ranging from 34.9 +/- 1.2 to 64.3 +/- 1.8 IU/ampoule. Furthermore, the extensive within-batch B-FSH variation from two batches confounded any meaningful comparison of between-batch variability. For Metrodin-HP, there was no between-batch B-FSH variation (29.0 +/- 6.1 to 33.0 +/- 0.3 IU/ampoule) and the R-FSH content was also well controlled (41.2 +/- 0.5 to 46.9 +/- 1.1 IU/ampoule).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1994

Accumulation of human chorionic gonadotrophin in the serum of patients during in-vitro fertilization treatment cycles with Pergonal.

We examined the possible contribution of human chorionic gonadotrophin (HCG) in Pergonal to the serum luteinizing hormone (LH)-like bioactivity in 10 patients (median age 32 years, range 28-38) with tubal infertility who were undergoing in-vitro fertilization (IVF), together with 19 controls (median age 30 years, range 21-43). IVF patients were treated with clomiphene (50 mg twice daily) over days 2-6 and Pergonal (150 IU i.m.) daily from day 5 until at least day 10. Serum LH was measured by fluoro-immunometric assay (I-LH) and in-vitro Leydig cell bioassay (B-LH). Serum HCG was measured by fluoro-immunometric assay. The data were analysed by paired two-tailed t-test, following logarithmic transformation. From days 1-5, there was an increase in serum B-LH (mean, 95% confidence intervals given in parentheses) from 8.3 (6.8, 10.2) IU/l to 11.7 (9.8, 13.9) IU/l [P = 0.004], and in serum I-LH from 4.5 (3.7, 5.4) IU/l to 5.4 (4.6, 6.3) IU/l [P = 0.002]. From days 5-8, there was a rise in B-LH to 16.6 (12.6, 21.9) IU/l [P = 0.023]. The rise in I-LH to 6.3 (5.1, 7.8) IU/l [P = 0.081] failed to reach significance. Furthermore, serum HCG was < 0.75 IU/l until after Pergonal was administered on day 5, then rose to a plateau on day 8 at 1.2 (0.8, 1.6) IU/l. Serum HCG in the controls remained < 0.75 IU/l throughout.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Human chorionic gonadotrophin contributes to the bioactivity of Pergonal.

OBJECTIVE: We examined batch variation in the LH-like bioactive content of Pergonal and determined whether hCG contributes to this. DESIGN: Random selection of three batches of Pergonal, consisting of three ampoules in each batch. MEASUREMENTS: The LH content in each ampoule was determined by radioimmunoassay (R-LH), immunoradiometric assay (I-LH) and in vitro Leydig cell bioassay (B-LH) using the urinary hMG International Standard 70/45. Human chorionic gonadotrophin was determined by immunoradiometric assay (I-hCG) using the hCG IRP 75/537. The isohormone content of each batch was examined by chromatofocussing over the range pH 4.5-7.0 and the fractions collected were assayed for LH and hCG content. The variability in potency between batches was assessed by single factor analysis of variance. RESULTS: The gonadotrophin content of each batch (IU/ampoule, mean +/- SEM, n = 3 ampoules) was R-LH (40.9 +/- 0.5, 40.8 +/- 0.2, 39.3 +/- 0.7, P > 0.15), I-LH (39.0 +/- 1.5, 28.3 +/- 0.8, 36.9 +/- 3.3, P < 0.001), B-LH (27.3 +/- 0.3, 12.0 +/- 0.9, 19.3 +/- 0.9, P < 0.001) and I-hCG (16.4 +/- 0.7, 11.7 +/- 0.2, 10.5 +/- 0.5, P < 0.001). The chromatofocussing recoveries below pH 5.5 expressed as a percentage of the total amount of analyte eluted from the column and collated for all three batches of Pergonal were (mean % +/- SD, n = 3 batches) R-LH (58.4 +/- 4.0), I-LH (41.3 +/- 7.5), B-LH (81.4 +/- 2.8) and I-hCG (87.8 +/- 3.7). CONCLUSIONS: There was significant batch variation in the I-LH, B-LH and I-hCG (P < 0.001) but not the R-LH (P > 0.15) content of Pergonal. More than 80% of the total B-LH recovery chromatofocussed below pH 5.5 and corresponded to the region of highest I-hCG (> 87%) and lowest I-LH (< 42%) recovery. This was highly suggestive of hCG contributing to the LH-like bioactivity of Pergonal.

Chorionic Gonadotropin↗
PubMed1992

Multidrug resistance in Leishmania donovani is conferred by amplification of a gene homologous to the mammalian mdr1 gene.

Drug resistance is a major impediment to the effective treatment of parasitic diseases. The role of multidrug resistance (mdr) genes and their products in this drug resistance phenomenon, however, remains controversial. In order to determine whether mdr gene amplification and overexpression can be connected to a multidrug resistance phenotype in parasitic protozoa, a mutant strain of Leishmania donovani was generated by virtue of its ability to proliferate in medium containing increasing concentrations of vinblastine. The vinblastine-resistant strain, VINB1000, displayed a cross-resistance to puromycin and the anthracyclines, a growth phenotype that could be attributed to an impaired ability to accumulate the toxic drugs. By using the polymerase chain reaction, two different DNA fragments, LEMDR06 and LEMDRF2, were amplified from leishmanial genomic DNA, and each amplified fragment encoded a product that was significantly homologous to parts of the mammalian P-glycoprotein. In the VINB1000 strain, the mdr gene recognized by the LEMDR06 probe was amplified approximately 50-fold in copy number, whereas the mdr genes that hybridized to LEMDRF2 or to a fragment of the previously characterized ltpgpA gene were not amplified. Moreover, the VINB1000 cell line expressed a LEMDR06 gene transcript of 12.5 kb in size that was not detected in the parental wild-type strain. To furnish a functional test for mdr gene amplification and expression in L. donovani, the L. donovani gene recognized by the LEMDR06 polymerase chain reaction product, ldmdr1, was isolated from a genomic library, transfected into wild-type cells, and amplified over 500-fold by selection in 0.5 mg of G418 per ml. The resulting transfectants were resistant to all drugs to which VINB1000 cells were resistant and sensitive to all drugs to which VINB1000 cells were sensitive. These studies demonstrate that amplification of the ldmdr1 gene either by direct selection or subsequent to transfection can confer a drug-resistant phenotype in parasitic protozoa similar to that observed for MDR mammalian cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Leishmaniasis in a domestic goat in Kenya.

The pathological and electron-microscopic features of the first case of autochthonous leishmaniasis affecting a domestic goat in Kenya are described. They are similar to what have been described in man and other animals. Using a short amino-acid sequence common to all the species of leishmania as primers for kDNA synthesis, the intervening sequence of 120 bases was amplified in the goat's tissues by polymerase chain reaction (PCR). The leishmania kinetoplast DNA sequence was detected in all the different infected tissues of the goat examined. The sensitivity and specificity of this assay are discussed. The result of the assay used was consistent with the parasite being either L. major or L. aethiopica as the infecting agent. The isoenzyme studies were consistent with L. aethiopica as the strain responsible for this goat's infection. The control of leishmaniasis and its vector must take into account the potential role of animal reservoirs in the environment. Even though Kenya and other East African countries are endemic for kala-azar, the presence of kala-azar in goats is of considerable veterinary public health importance in Africa. Efforts must not be spared to identify and detect other possible animal reservoirs in the subregion. Using DNA amplification techniques, which are sensitive and specific, such as the one described in this paper, sera and other biological fluids and tissues from different animal species should be utilized for detecting additional reservoirs for leishmania parasites particularly in known endemic areas of the world.

Animals↗
PubMed1989

Three year hospital experience with control of major obesity by VLCD in medically compromised individuals.

A very low calorie formula diet (VLCD) with physician and dietitian support was used to achieve and maintain weight loss in 408 overweight patients, referred by consultants because of concurrent health problems. The patients had failed to lose weight on conventional diets, and their obesity was considered a significant risk factor in their health. Using 330 or 405 kcal formula diets, the mean rate of weight loss in men was 1.87 kg/week and in women 1.27 kg/week. Women sustained the dieting process over longer periods, with a time to maximum weight loss of 5-72 weeks (mean 24) compared to the achievement in men of 4-40 weeks (mean 12.5). Sixteen per cent of the patients dropped out in the first 3 weeks. Of the remaining 84 per cent, weight loss to within 80-100 per cent BMI 25 (target weight) was achieved by 53 per cent men and 46 per cent women who had completed more than 5 weeks dieting. Women were more complaint than men at weight maintenance follow-up and 58 per cent of the start group were observed for more than 50 weeks (50-164), only 10 per cent experiencing weight regain of 20-70 per cent. Physician support was required to adjust medication in patients attending. Complications of obesity were remarkably improved after weight loss.

Adolescent↗
PubMed1981

Serum lipids in a teenage population: geographic, seasonal and familial factors.

The lipid results of a cross-sectional study of cardiovascular disease risk factors in over 600 13-18 year olds drawn from general practices in contrasting areas are reported. Differences were noted between the 3 practices, including a significant variation in the blood group distribution. HDL cholesterol showed a marked variation between the 3 practices which was unlikely to be due solely to seasonal variation. Alcohol consumption though not an univariate correlate of HDL cholesterol was however a strong partial correlate, as were age, height, sexual maturation, adiposity and smoking. Using 6 factors in each sex, 13% of the interchild variance of HDL cholesterol in boys could be explained in a multiple linear regression analysis, and 8% in girls. Including the practice variation as a further independent variable increased the explanation in 18% in boys and 15% in girls. An intraclass correlation (sib-sib) of 0.36 was found for HDL cholesterol, suggesting a strong familial influence. The implications of these results are discussed, along with the difficulties of screening for hyperlipidaemia in this age group.

Adolescent↗
PubMed1980

Changes in blood lipids and blood pressure during adolescence.

A total of 625 adolescents from three general practices participated in a cross-sectional study of cardiovascular disease risk factors. The girls had higher serum total and high density lipoprotein (HDL) cholesterol concentrations than the boys, while the boys had higher serum triglyceride concentrations. Smoking (equally prevalent in both sexes) was associated with lower HDL cholesterol concentrations, particularly in boys, while in girls use of oral contraceptives was associated with higher total cholesterol and lower HDL cholesterol concentrations showed striking associations with age, height, and sexual maturation in boys, but not in girls. Triglyceride concentrations were associated with age in boys. Systolic blood pressure and serum urate concentrations were higher in boys and rose steeply with age, but no age association was seen for urate concentrations or systolic blood pressure in girls or for diastolic pressures in either sex. Girls, however, had higher diastolic pressures. There was a strong association between urate concentration and the other cardiovascular disease risk factors, especially HDL cholesterol. Adolescence is associated with considerable changes in cardiovascular disease risk factors, and there are striking sex differences in these changes.

Adolescent↗
PubMed1980

Two new non-barbiturate buffers for electrophoresis of serum proteins on cellulose acetate membranes.

Two new non-barbiturate buffers have been formulated for serum protein electrophoresis on cellulose acetate membranes. Both buffers give five distrinct fractions and are suitable for all systems, but have been primarily designed to meet the needs of the Gelman "Sepratek" system. One buffer is a tris(hydroxymethyl)aminomethane (Tris)/hippurate formulation; the other is composed of Tris/N-[tris(hydroxymethyl)methyl]glycine (Tricine)/sodium chloride/sodium salicylate. Both buffers allow reliable quantitation of protein fractions, giving results that correlated well with those obtained from barbiturate separations. The major advantage of these buffers is that they do not contain drugs of abuse.

Barbiturates↗