Biomedical subjects

A Brandt

Publications and source records attributed to A Brandt.

At least 19 recordsLinked to original sources

PubMed2000

The cost-effectiveness of different management strategies for type I diabetes: a Swiss perspective.

AIMS/HYPOTHESIS: A computer model was developed to determine the health outcomes and economic consequences of different combinations of diabetes interventions in newly diagnosed patients with Type I (insulin-dependent) diabetes in Switzerland. METHODS: We modelled seven complications of diabetes: hypoglycaemia, ketoacidosis, acute myocardial infarction, stroke, lower extremity amputation, nephropathy, and retinopathy. Transition probabilities and costs were taken from published literature. The Swiss health insurance payer perspective was taken. Various combinations of diabetes management strategies, including intensive or conventional insulin therapy and screening and treatment strategies for renal and eye disease were defined. Life expectancy, cumulative incidences of complications, and mean expected total lifetime costs per patient were calculated under six different management strategies. Incremental cost-effectiveness ratios were calculated in terms of costs per life-year gained compared with conventional insulin therapy alone. RESULTS: The addition of screening for microalbuminuria and retinopathy followed by appropriate treatment, if detected, were cost saving, with reduction in cumulative incidence of end stage renal disease and blindness respectively, and, in the case of microalbulminuria screening and treatment, an improvement in life expectancy. Intensive therapy improved life expectancy but increased total lifetime costs. CONCLUSION/INTERPRETATION: Optimal management of Type I diabetic patients, including secondary and tertiary prevention, leads to reduced complications and improved life expectancy, with the increased costs of prevention offset to varying degrees by cost savings due to complications avoided.

Albuminuria↗

PubMed2000

Active osmoregulatory ion uptake across the pleopods of the isopod Idotea baltica (Pallas): electrophysiological measurements on isolated split endo- and exopodites mounted in a micro-ussing chamber.

The mechanism of active, osmoregulatory ion uptake was investigated in the pleopods of the marine isopod Idotea baltica (Pallas). Using isolated split half-podites of isopods acclimated to brackish water (20 salinity) mounted in a micro-Ussing chamber and symmetrically superfused with identical haemolymph-like salines, a mean short-circuit current I(sc) of -445 microA cm(-)(2) was measured in endopodites 3-5, corresponding to an inwardly directed transcellular movement of negative charge. Application of ouabain (5 mmol l(-)(1)) to the basolateral superfusate resulted in the almost total abolition of the I(sc) (reduced from -531 to -47 microA cm(-)(2)), suggesting that the Na(+)/K(+)-ATPase is the driving force for active, electrogenic uptake of NaCl. In contrast, mean I(sc) values close to zero were found in preparations of all exopodites and in endopodites 1 and 2. The specific activities of Na(+)/K(+)-ATPase corresponded with these results. Specific activities were highest in posterior endopodites 3-5 and depended on ambient salinity. In all other rami, the activities were much lower and independent of ambient salinity. Activities in posterior endopodites 3-5 were lowest in isopods acclimated to 30 salinity (2-4 micromol P(i )mg(-)(1 )protein h(-)(1)), increased in individuals kept in 20 salinity (8.4 micromol P(i )mg(-)(1 )protein h(-)(1)) and were highest in isopods acclimated to 15 salinity (18.2 micromol P(i )mg(-)(1 )protein h(-)(1)). When specimens were transferred from 30 to 40 salinity, Na(+)/K(+)-ATPase activity increased in the posterior endopodites. The electrophysiological and Na(+)/K(+)-ATPase activity measurements show that active electrogenic ion transport in this species occurs almost exclusively in posterior endopodites 3-5. The endopodite of the fifth pleopod of I. baltica exhibited a microscopic structure remarkably similar to that described for the lamellae of the phyllobranchiae of brachyurans. It is composed of two opposed epithelial monolayers of ionocytes, each covered by cuticle. Bundles of pillar cells are located within the ionocyte layers, which are separated by a fenestrated lamellar septum of connective tissue. The results obtained in this study indicate that endopodites 3-5 play the main role in osmoregulatory ion uptake of the isopod I. baltica. Moreover, the Na(+)/K(+)-ATPase is the only driving force behind active electrogenic ion uptake across the epithelial cells.

Animals↗

PubMed1999

Sequence and analysis of chromosome 4 of the plant Arabidopsis thaliana.

The higher plant Arabidopsis thaliana (Arabidopsis) is an important model for identifying plant genes and determining their function. To assist biological investigations and to define chromosome structure, a coordinated effort to sequence the Arabidopsis genome was initiated in late 1996. Here we report one of the first milestones of this project, the sequence of chromosome 4. Analysis of 17.38 megabases of unique sequence, representing about 17% of the genome, reveals 3,744 protein coding genes, 81 transfer RNAs and numerous repeat elements. Heterochromatic regions surrounding the putative centromere, which has not yet been completely sequenced, are characterized by an increased frequency of a variety of repeats, new repeats, reduced recombination, lowered gene density and lowered gene expression. Roughly 60% of the predicted protein-coding genes have been functionally characterized on the basis of their homology to known genes. Many genes encode predicted proteins that are homologous to human and Caenorhabditis elegans proteins.

Animals↗

PubMed1999

Neuropeptide FF and modulation of pain.

Neuropeptide FF (NPFF) and the related longer peptide neuropeptide AF (NPAF) derive from a single gene in several mammalian species. The gene product is expressed mainly in the CNS, where the posterior pituitary and dorsal spinal cord contain the highest concentrations. Evidence from biochemical and immunohistochemical studies combined with in situ hybridization using NPFF gene-specific probes suggest that all NPFF-like peptides may not derive from the characterized NPFF gene, but that other genes can exist which give rise to related peptides. Intraventricular NPFF exerts antiopioid effects, but intrathecal NPFF potentiates the analgesic effects of morphine. NPFF mRNA expression is upregulated in the dorsal horn of the spinal cord after carrageenan-induced inflammation in the hind paw of the rat, but not in the neuropathic pain model induced by ligation of the spinal roots. NPFF produces a submodality-selective potentiation of the antinociceptive effect induced by brain stem stimulation in the spinal cord during inflammation, and this effect is independent of naloxone-sensitive opioid receptors. In neuropathic animals, NPFF injected into the periaqueductal grey produces a significant attenuation of tactile allodynia, which is not modulated by naloxone. NPFF thus modulates pain sensation and morphine analgesia under normal and pathological conditions through both spinal and brain mechanisms.

Animals↗

PubMed1999

Determination of silymarine in the extract from the dried silybum marianum fruits by high performance liquid chromatography and capillary electrophoresis.

Silybine (SBN), isosilybine (ISBN), silycristine (SCN), silydianine (SDN), and taxifoline (TXF) are the main active flavanoids, generally found in the dried fruits of silybum marianum. The concentrations of these compounds, excepted TXF, are all together usually expressed as silymarine content. In this paper the determination of the silymarine titre was made by high performance liquid chromatography (HPLC), and high performance capillary electrophoresis (HPCE). Two reversed stationary phases, RP-18 and RP-8, were observed comparing the resolutions of all considered flavanoids with each stationary phases. The HPCE was carried out considering the possible improvement in the resolution of SBN, CN, SDN and TXF using, 8-cyclodextrines or organic modifier. The qualitative and quantitative data obtained by HPLC and HPCE were compared.

Chromatography, High Pressure Liquid↗

PubMed1999

Screening of the ryanodine receptor gene in 105 malignant hyperthermia families: novel mutations and concordance with the in vitro contracture test.

Malignant hyperthermia (MH) in man is an autosomal dominant disorder of skeletal muscle Ca(2+)-regulation. During anesthesia in predisposed individuals, it is triggered by volatile anesthetics and depolarizing muscle relaxants. In >50% of the families, MH susceptibility is linked to the gene encoding the skeletal muscle ryanodine receptor (RYR1), the calcium release channel of the sarcoplasmic reticulum, on chromosome 19q12-13.2. To date, 21 RYR1 mutations have been identified in a number of pedigrees. Four of them are also associated with central core disease (CCD), a congenital myopathy. Screening for these 21 mutations in 105 MH families including 10 CCD families phenotyped by the in vitro contracture test (IVCT) according to the European protocol revealed the following approximate distribution: 9% Arg-614-Cys, 1% Arg-614-Leu, 1% Arg-2163-Cys, 1% Val-2168-Met, 3% Thr-2206-Met and 7% Gly-2434-Arg. In one CCD family, the disease was caused by a recently reported MH mutation, Arg-2454-His. Two novel mutations, Thr-2206-Arg and Arg-2454-Cys were detected, each in a single pedigree. In the 109 individuals of the 25 families with RYR1 mutations cosegregation between genetic result and IVCT was almost perfect, only three genotypes were discordant with the IVCT phenotypes, suggesting a true sensitivity of 98.5% and a specificity of minimally 81.8% for this test. Screening of the transmembraneous region of RYR1 did not yield a new mutation confirming the cytosolic portion of the protein to be of main functional importance for disease pathogenesis.

Adult↗

PubMed1998

Two jasmonate-inducible myrosinase-binding proteins from Brassica napus L. seedlings with homology to jacalin.

Two homologous but different cDNAs encoding a 97-kDa and a 70-kDa protein from Brassica napus L. seedlings have been characterized. Both proteins contain sequence motifs with high homology to the IgA binding lectin, jacalin, and the deduced 97-kDa protein contains the peptide sequences of myrosinase-binding protein. The 70-kDa and the 97-kDa protein can both be isolated as a complex containing myrosinase, indicating they indeed are myrosinase-binding proteins. We provide evidence that the 70-kDa protein binds IgA in vitro, and therefore classify the protein as a jacalin-type lectin. Both the 97-kDa and the 70-kDa proteins are encoded by a small number of genes in the Brassica genome. The mRNA for the 97-kDa protein is detected in both light- and dark-grown seedlings, whereas the mRNA for the 70-kDa protein is mainly detected in etiolated seedlings. The transcript levels for both proteins are transient and are rapidly increased by methyl jasmonate. The 70-kDa protein is synthesized de novo during germination and accumulates mainly in the hypocotyl and in the root. By immunogold labeling we show that a few cells scattered in the cotyledons of young seedlings (approx. 5% of total cells), contain protein-body-like structures with the 70-kDa protein. These bodies are present in a 10,000 g pellet from which the 70-kDa protein can be extracted by sodium carbonate. In addition, the 70-kDa protein is detected in the amorphous structures of the vacuole in a few cells of the cotyledon, the hypocotyl and the root.

Amino Acid Sequence↗

PubMed1997

Functional cooperation of the mitochondrial processing peptidase subunits.

Domains important for the activity of the heterodimeric mitochondrial processing peptidase (MPP) were investigated, by inserting one alanine residue at ten positions along the polypeptide chain of the beta-subunit (beta-MPP). An alanine residue inserted after Glu70, Ser114, Lys215 and Ser314 respectively, abolished the cleavage activity of MPP. When the alpha-subunit (alpha-MPP) was co-expressed with N-terminal hexa-histidine tagged beta-MPP, alpha-MPP was co-eluted from a nickel-derivatized affinity resin, with a 1:1 stochiometry, both with wild-type beta-MPP and with the mutants with alanine inserted after Ser114 and Ser314. The mutants with alanine inserted after Glu70 and Lys215 did not associate with alpha-MPP. The mutagenesis studies indicate that: (1) the whole HXXEHX76H region of beta-MPP is important for the proper conformation of the active site of MPP and may also be in contact with alpha-MPP; (2) the non-conserved central region surrounding Lys215 is involved in the interaction with alpha-MPP; and (3) the carboxy-terminal region of beta-MPP surrounding Ser314 is also of importance for the catalysis. Cross-linking studies indicated that purified alpha-MPP bound a precursor protein in the absence of any beta-MPP. Furthermore, the interaction of MPP and its subunits with a peptide substrate, as analyzed by surface plasmon resonance, showed that alpha-MPP bound a peptide substrate as efficiently as MPP. The data suggest that the alpha-subunit is responsible for the binding of mitochondrial presequences prior their presentation to the catalytic site of MPP.

Alanine↗

PubMed1997

The glyoxysomal 3-ketoacyl-CoA thiolase precursor from Brassica napus has enzymatic activity when synthesized in Escherichia coli.

Glyoxysomal 3-ketoacyl-CoA thiolase is the last enzyme in the beta-oxidation of fatty acids in plant glyoxysomes. A full-length cDNA of the glyoxysomal 3-ketoacyl-CoA thiolase from Brassica napus and a truncated version, lacking the N-terminal targeting signal were cloned in a T7 promoter-based vector. Both recombinant proteins were expressed in Escherichia coli and activity was measured. Full-length and truncated 3-ketoacyl-CoA thiolase have comparable activity in E. coli. Moreover, full-length 3-ketoacyl-CoA thiolase was purified from E. coli and N-terminal sequencing of the protein confirmed that the precursor form indeed is enzymatically active.

Acetyl-CoA C-Acyltransferase↗

PubMed1997

Retinal capillary hemangioma: von Hippel (-Lindau) disease.

The clinical manifestations of von Hippel and von Hippel-Lindau's disease are illustrated. Four cases are presented with special emphasis on the angiographic characteristics, the evolution and the complications of the retinal capillary hemangiomas. Special attention is given to fundoscopy, fluorescein and indocyanine green angiography and to the systemic manifestations. We summarize new molecular genetic insights. The importance of systemic and familial evaluation is stressed. Retinal angiomatosis is a clinical diagnosis but the angiography has an adjuvant value.

Adult↗

PubMed1997

The Hermansky-Pudlak syndrome.

The Hermansky-Pudlak syndrome (HPS) associates oculocutaneous albinism with a haemorrhagic diathesis and the accumulation of ceroid-like material in different tissues. HPS is not an uncommon type of albinism as it was diagnosed in 13.5% (8/59) of our autosomal recessive albinos. These eight patients were evaluated ophthalmologically and haematologically. Apart from the symptoms caused by the albinism, accompanying signs vary from ecchymoses to life threatening haemorrhages and death by associated restrictive lung disease. Recognition of this syndrome by the ophthalmologist can be of major importance in this serious and eventually fatal disorder.

Adolescent↗

PubMed1996