Biomedical subjects

D Siebert

Publications and source records attributed to D Siebert.

At least 19 recordsLinked to original sources

PubMed2001

Binuclear complexes as building blocks for polynuclear complexes with high-spin ground states: synthesis and structure of a tetranuclear nickel complex with an S = 4 ground state.

The coordinatively unsaturated dinickel(II) complex [(L2)Ni2](BPh4)2 (2), where (L2)2- represents the dianionic form of the 'N4S2' ligand N,N'-bis(2-thio-3-aminomethyl-5-tert-butylbenzyl)propane-1,3-diamine), has been investigated with respect to its ability to function as a building block for the preparation of polynuclear nickel complexes with a high-spin ground state. Treatment of 2 with pyridazine (pydz) followed by addition of two equivalents of NH4SCN afforded the dinuclear mupyridazine complex [(L2)Ni2(mu-pydz)(NCS)2] (4). The reaction of 2 with pyridazine and NaN3 in a 1:1:1 molar ratio gave the tetranuclear nickel(II) complex [[(L2)Ni2(mu-pydz)(N3)]2](BPh4)2 (5). Both complexes have been characterized by X-ray crystallography and variable-temperature magnetic susceptibility studies. In complex 4 two fac(SCN)N2Ni(II) units are linked by two thiophenolate sulfur atoms and a mu-pydz ligand to give a (SCN)N2Ni(mu-S)2(mu-pydz)NiN2(NCS) core structure with a pseudoconfacial bioctahedral geometry. The two NCS- groups occupy opposite coordination sites, each is in a cis position to the pydz bridge. Analyses of the susceptibility data indicate the presence of an intramolecular ferromagnetic exchange interaction between the two Ni(II) (S = 1) ions. Complex 5 is composed of two binuclear [(L2)Ni2(mu-pydz)]2+ subunits which are linked by two azide ions to give a rectangular array of four six-coordinate Ni(II) ions. The binuclear [(L2)Ni2(mu-pydz)]2+ fragments in 4 and 5 are isostructural. Analyses of the susceptibility data of 5 reveal ferromagnetic exchange interactions between the Ni(II) ions of the binuclear subunit as well as for the mu(1,3)N3-bridged Ni(II) ions. Thus, compound 4 has an S = 2 ground state, whereas in 5 it is S = 4.

Journal Article↗

PubMed2001

Seroprevalence of varicella zoster virus, parvovirus B19 and Toxoplasma gondii in a Melbourne obstetric population: implications for management.

At an antenatal clinic at a Melbourne obstetric hospital, 308 women were questioned about a known past history of infection with varicella zoster virus (VZV), human parvovirus B19 and Toxoplasma gondii. Immunoglobulin G (IgG) concentrations were determined for the 3 infectious agents and a recalled history of infection was compared with the presence of specific antibody. Exactly 66% of women recalled being infected with chickenpox (VZV) and 94% showed serological evidence of past exposure. Although 64% of women had parvovirus specific IgG, only one gave a definite history of past parvovirus infection. None of the 23% of women with evidence of previous exposure to Toxoplasma gondii recalled a past infection. The proportion of antenatal women at risk in this study was used to estimate the potential burden of disease from congenital infections in Australia and to examine implications for management of pregnancies complicated by these 3 infections.

Adolescent↗

PubMed2001

Telepathology.

The development of a Queensland-wide videoconferencing network provided an opportunity to develop telepathology. In 1999, weekly videoconferences began with remote laboratories and clinical staff in four peripheral hospitals and the Royal Brisbane Hospital and in 2000 biweekly videoconference pathology grand rounds started across Queensland with up to six sites, from Cairns to the Gold Coast, joining in or presenting. The average number of sites connected was 3.0 in 1998, 3.5 in 1999, 4.4 in 2000 and 4.5 in 2001. Problems included the complexity of the system, timing and need for bookings, coordination of presenters and presentations, and the time needed to organize sessions, set up linkages, advertise sessions and attend the telepathology conference. Successful meetings have been associated with well prepared cases, time for discussion, attendance by all sites, timeliness of cases and responses, and the presence of experts to respond to questions, as well as effective linkages and trouble-free hardware. Future needs include better infrastructure and trained staff to coordinate the linkages and presentations. Telepathology has an important part to play in the provision of cost-effective medical care in Queensland.

Computer Terminals↗

PubMed2000

The age-specific prevalence of human parvovirus immunity in Victoria, Australia compared with other parts of the world.

The age-specific immunity to human parvovirus infection was estimated in Victoria, Australia using prospectively collected samples from the Royal Children's Hospital, the Royal Women's Hospital and the Australian Red Cross Blood Service and from sera stored at the Victorian Infectious Diseases Reference Laboratory (VIDRL). All testing was performed at VIDRL using a commercial enzyme-linked immunosorbent assay (Biotrin). Of the 824 sera tested, 28% of those drawn from people aged 0-9 years contained protective antibodies to human parvovirus. This rose to 51% in the next decade of life. There was then a slow rise to about 78% immunity over 50 years of age. An analysis of all requests for parvovirus serology at VIDRL from 1992 to 1998 suggested that parvovirus tended to occur in 4-year cycles, with 2 epidemic years followed by 2 endemic years. A review of published reports of parvovirus immunity suggested that parvovirus infection may be more common, with a correspondingly higher proportion of the community immune, in temperate as opposed to tropical countries.

Adolescent↗

PubMed1999

Virtual 3D cutting for bone segment extraction in maxillofacial surgery planning.

An important step toward our main goal of a completely computer-based maxillofacial surgical planning system is the availability of tools for the surgeon to define bone segments from skull and jaw bones. We have developed an easy-to-handle user interface that employs visual and force-feedback devices to define subvolumes of a patient's volume dataset. This interface is a main component of our maxillofacial surgical planning tool MeVisTo-Jaw [1]. The defined subvolumes together with their spatial arrangements lead to an operation plan.

Humans↗

PubMed1996

MoaA of Arthrobacter nicotinovorans pAO1 involved in Mo-pterin cofactor synthesis is an Fe-S protein.

MoaA, involved in an early step in the biosynthesis of the molybdopterin cofactor (MoCo), has not yet been characterized biochemically and the reaction it catalyzes is unknown. We overexpressed MoaA from pAO1 of Arthrobacter nicotinovorans in Escherichia coli as a N-terminal fusion with either glutathione-S-transferase or a 6-histidine tag. The pAO1 encoded MoaA as well as the fusion proteins functionally complement E. coli moaA mutants. Here we show that purified MoaA contains approximately 4 microM Fe and approximately 3 microM acid-labile S/microM protein. EPR spectroscopy revealed a predominant signal at g(av) = 2.01, indicative of a [3Fe-xS] cluster.

Amino Acid Sequence↗

PubMed1990

Determination of endogenous concentrations of N1-methylnicotinamide in human plasma and urine by high-performance liquid chromatography.

A high-performance liquid chromatographic assay for the determination of endogenous plasma and urine concentrations of N1-methylnicotinamide was developed. N1-Methylnicotinamide and N1-ethylnicotinamide (internal standard) are reacted with acetophenone in a strong base at 0 degree C, formic acid is added, and the reaction mixture is heated in a boiling water bath, resulting in the formation of fluorescent derivatives. These derivatives were chromatographed on a C18 reverse-phase column using a mobile phase of acetonitrile-triethylamine and 0.01 M heptanesulfonic acid adjusted to pH 3.2. Fluorescent detection was achieved using 366-nm excitation and 418-nm emission filters. Precision and accuracy were generally greater than 90%, interfering peaks did not cochromatograph, and the limit of quantification was 2 ng/ml in plasma using a 0.2-ml sample. The method was used to examine the concentrations of endogenous N1-methylnicotinamide in the plasma of 36 subjects with various pathology. The mean concentration was 18 ng/ml and the range was 6.2 to 116.7 ng/ml. The assay represents a marked improvement on previous methods and is suitable for routine clinical monitoring.

Acetophenones↗

PubMed1987

Dipyridamole: pharmacokinetics and effects on aspects of platelet function in man.

1. The effect of dipyridamole on platelet function was measured in twelve normal subjects given 150 or 200 mg tablets as single and multiple doses, and in six subjects given single doses of 25, 50 and 100 mg and multiple doses of 50 mg 8 hourly. 2. Platelet aggregation was measured in response to ADP and collagen. In the subjects given 150/200 mg, the platelets were assayed for content of cyclic AMP and for formation of thromboxane after addition of collagen. The responses to ADP and collagen and the cyclic AMP content were assessed in both the presence and absence of added PGE1. The pharmacokinetics of dipyridamole were studied in all subjects. 3. One hour after 150/200 mg single doses of dipyridamole there was significant inhibition of platelet aggregation in response to both collagen and ADP. There was no detectable effect on aggregation at other time points or with lower doses of dipyridamole. The addition of PGE1 to platelets prior to testing did not enhance the effect of dipyridamole on platelet aggregation. 4. In multiple doses, dipyridamole (150/200 mg twice daily for 11 days) had no detectable effect on platelet aggregation. 5. Dipyridamole did not have any effect on platelet cyclic AMP content, whether or not PGE1 was added prior to assay. 6. Dipyridamole did not affect platelet thromboxane formation. 7. Plasma dipyridamole concentrations were maximal 1-2 h after ingestion, at the same time that inhibition of platelet aggregation was detected. The concentrations declined in a biexponential fashion, with a terminal half life of 24.1 +/- 1.9 h (mean +/- s.e. mean). In six of the 17 subjects, the mean steady state plasma concentration was less than 75% of the value predicted from the single dose data.

Adolescent↗

PubMed1984

Testing of chemicals for genetic activity with Saccharomyces cerevisiae: a report of the U.S. Environmental Protection Agency Gene-Tox Program.

The yeast Saccharomyces cerevisiae is a unicellular fungus that can be cultured as a stable haploid or a stable diploid . Diploid cultures can be induced to undergo meiosis in a synchronous fashion under well-defined conditions. Consequently, yeasts can be used to study genetic effects both in mitotic and in meiotic cells. Haploid strains have been used to study the induction of point mutations. In addition to point mutation induction, diploid strains have been used for studying mitotic recombination, which is the expression of the cellular repair activities induced by inflicted damage. Chromosomal malsegregation in mitotic and meiotic cells can also be studied in appropriately marked strains. Yeast has a considerable potential for endogenous activation, provided the tests are performed with appropriate cells. Exogenous activation has been achieved with S9 rodent liver in test tubes as well as in the host-mediated assay, where cells are injected into rodents. Yeast cells can be recovered from various organs and tested for induced genetic effects. The most commonly used genetic end point has been mitotic recombination either as mitotic crossing-over or mitotic gene conversion. A number of different strains are used by different authors. This also applies to haploid strains used for monitoring induction of point mutations. Mitotic chromosome malsegregation has been studied mainly with strain D6 and meiotic malsegregation with strain DIS13 . Data were available on tests with 492 chemicals, of which 249 were positive, as reported in 173 articles or reports. The genetic test/carcinogenicity accuracy was 0.74, based on the carcinogen listing established in the Gene-Tox Program. The yeast tests supplement the bacterial tests for detecting agents that act via radical formation, antibacterial drugs, and other chemicals interfering with chromosome segregation and recombination processes.

Aneuploidy↗

PubMed1981

Polycyclic aromatic hydrocarbons and possible metabolites: convertogenic activity in yeast and tumor initiating activity in mouse skin.

The diploid respiratory-deficient strain of yeast D4-RDII was used to assay PAH and urethane as well as some oxygenated derivatives of PAH and the (aliphatic) epoxide hydrolase inhibitor TCPO for convertogenic (mutagenic) activity. As a positive control, the convertogenic ultimate rat liver carcinogen NOAcAAF was used. PAH and urethane were found inactive as convertogens, TCPO was weakly active, whereas oxygenated electrophilic derivatives of PAH, such as K-region oxides, were found strong convertogens. For comparison, some convertogenic key compounds were assayed for their tumor-initiating activity in mouse skin in the standardized system using TPA as a promotor. PAH were stronger initiators than all oxygenated derivatives of PAH tested. TCPO alone exhibited very weak, if any, initiating activity. It was unable to modify initiation to any significant extent, if administered 5 min prior to administration of an initiator. In the absence of correlation between convertogenic and initiating activity the question of the chemical nature of "ultimate initiators" of mouse skin carcinogenesis awaits further investigation.

Animals↗

PubMed1979

The application of mitotic gene conversion in Saccharomyces cerevisiae in a pattern of four assays, in vitro and in vivo, for mutagenicity testing.

The induction of mitotic gene conversion of the nitrofuran derivatives nitrofurantoin (N-(5-nitro-2-furfuryliden)-1-aminohydantoin), nifurprazinum (1-(5-nitro-2-furyl)-2-(6-amino-3-pyridazyl)-ethylenehydrochloride) and FANFT (2-formylamino-4-(5-nitro-2-furyl)thiazole) was investigated in the D4-RDII strain of Saccharomyces cerevisiae (heteroallelic at the gene loci ade2 and trp5, respiration-deficient). A battery of tests was applied: direct action of the substance to yeasts, the liver microsome test in vitro, the host-mediated assay and the urinary assay. From the various combinations of positive and negative results, additional pharmacokinetic conclusions were drawn. The three nitrofuran derivatives gave positive results by direct action and in the urine of rats. The additon of liver microsomes of mice in the test in vitro reduced the number of induced convertants. In the first hours, a great deal of nitrofurantoin given orally to rats was excreted in the urine, as shown by a high genetic activity. Nifurprazinum and FANFT were excreted to a lesser extent or more slowly. Addition of glucuronidase/arylsulfatase reduced the genetic activity in the urine in the case of nitrofurantoin, had an increasing effect with nifurprazinum and was without any effect in the case of FANFT. In the host-mediated assay, only nitrofurantoin gave positive results. These results seem to be a consequence of the quick but different excretion of the nitrofuran derivatives.

Animals↗

PubMed1977

Genetic effects of some new bifunctional and water-soluble analogs of the anti-cancer agent 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in Saccharomyces cerevisiae.

A series of 1,1'-polymethylenebis-3-(2-chloroethyl)-3-nitrosoureas, 1-(omega-hydroxyalkyl)-3-(2-chloroethyl)-3-nitrosoureas, 1,1'(4-methyl-m-phenylenebis)-3-(2-chloroethyl)-3-nitrosourea, 2-[3-(2-chloroethyl)]-3-nitrosoureido-2-deoxy-D-glycopyranose (chlorozotocin and 1-(2-methanesulfonyloxyethyl)-3-(2-chloroethyl)-3-nitrosurea were examined for their genetic activities. BCNU was simultaneously tested as an established, clinically used reference compound. A diploid strain of Saccharomyces cerevisiae, heteroallelic at the gene loci ade2 and trp5, was used as a test system for the induction of mitotic gene conversion (intragenic recombination). All compounds showed strong genetic effects. In the series of aliphatic bifunctional nitrosoureas, 1,1'-ethylenebis-3-(2-chloroethyl)-3-nitrosourea (1) was the most active compound. The water-soluble derivatives, including chlorozotocin, displayed all genetic effects of the same order of magnitude. There was no correlation between genetic activity and chemotherapeutic potential of the test compounds.

Carmustine↗

PubMed1975

Host-mediated assay with yeast and rats using probenecid (Benemid) to block the renal tubular excretion of cyclophosphamide metabolites.

The genetic activity of cyclophosphamide (Cy) was tested in the host-mediated assay (injection of yeasts into the peritoneal cavity of rats) modified by the use of probenecid (Pro) (Benemid) to block the renal tubular excretion of the genetically active metabolites. The genetic test system used was the induction of mitotic gene conversion in two unliked loci of a diploid strain of Saccharomyces cerevisiae. By this method the genetic effect of By was doubled in comparison with the case of administering Cy alone. Compared with the animals which received only Pro, increases of conversion frequencies of 20 times in the ade2 locus and of 15 times in the trp5 locus were found.

Animals↗

PubMed1974