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Biomedical subjects

S Jansen

Publications and source records attributed to S Jansen.

At least 19 recordsLinked to original sources
PubMed2001

Molecular and genealogical evidence for a founder effect in Fanconi anemia families of the Afrikaner population of South Africa.

Fanconi anemia (FA) is a rare, genetically heterogeneous autosomal recessive disorder associated with progressive aplastic anemia, congenital abnormalities, and cancer. FA has a very high incidence in the Afrikaner population of South Africa, possibly due to a founder effect. Previously we observed allelic association between polymorphic markers flanking the FA group A gene (FANCA) and disease chromosomes in Afrikaners. We genotyped 26 FA families with microsatellite and single nucleotide polymorphic markers and detected five FANCA haplotypes. Mutation scanning of the FANCA gene revealed association of these haplotypes with four different mutations. The most common was an intragenic deletion of exons 12-31, accounting for 60% of FA chromosomes in 46 unrelated Afrikaner FA patients, while two other mutations accounted for an additional 20%. Screening for these mutations in the European populations ancestral to the Afrikaners detected one patient from the Western Ruhr region of Germany who was heterozygous for the major deletion. The mutation was associated with the same unique FANCA haplotype as in Afrikaner patients. Genealogical investigation of 12 Afrikaner families with FA revealed that all were descended from a French Huguenot couple who arrived at the Cape on June 5, 1688, whereas mutation analysis showed that the carriers of the major mutation were descendants of this same couple. The molecular and genealogical evidence is consistent with transmission of the major mutation to Western Germany and the Cape near the end of the 17th century, confirming the existence of a founder effect for FA in South Africa.

Base Sequence↗
PubMed2001

Fanconi anemia. a statistical evaluation of cytogenetic results obtained from South African families.

Fanconi anemia (FA) is a rare autosomal recessive genetic disorder showing progressive bone marrow failure, and various phenotypic abnormalities. The lymphocytes show an increased sensitivity to the clastogenic agents diepoxybutane (DEB) or mytomycin C (MMC), measured as chromosomal aberrations. Statistical analysis of chromosome aberration yield showed that: (i) differentiation between obligate carriers and the control group was not possible; (ii) homozygotes were clearly distinguishable from heterozygotes as well as from controls by analyzing only 20 metaphase spreads per person; (iii) most of the FA patients had only one cell line present as measured by distribution of chromosomal damage among cells analyzed; (iv) and when the DEB sensitivity of a patient was high, the amount of cells without damage was low.

Case-Control Studies↗
PubMed2001

Nickel speciation and complexation kinetics in freshwater by ligand exchange and DPCSV.

A technique of ligand exchange with DMG (dimethylglyoxime) and DPCSV was applied to determine Ni speciation in lake, river, and groundwater samples. The working conditions related to ligand-exchange equilibrium were optimized, and the ligand-exchange kinetics were examined. The observed pseudo-first-order rate, kobsd, was about 3 x 10(-5) (s-1) for Ni(DMG)2 complex formation with an excess of DMG (microM) over Ni (nM) at pH 7.1-7.7. The second-order exchange kinetic constants, kexch, were between 1.2 x 10(2) and 5.7 x 10(3) s-1 M-1 for ligand exchange of NiEDTA with DMG and between 5 x 10(2) and 7 x 10(3) s-1 M-1 for exchange of natural ligands with DMG in the freshwater samples under similar conditions. Ni ligand exchange between natural ligands and DMG occurred over days with half-lifes of 5-95 h. Total dissolved Ni concentrations in samples from various freshwater systems in Switzerland ranged from 4 nM in an oligotrophic lake to 30 nM in a small river affected by inputs from sewage effluents and agriculture. Free ionic Ni2+ concentrations were determined in the range of 10(-13)-10(-15) M (pNi = 12.2-14.7), indicating that more than 99.9% of dissolved Ni was bound by organic ligands with strong affinity (log K 12.1-14.9) and low concentrations (13-100 nM) at pH 7.2-8.2. Because of slow ligand-exchange kinetics, Ni speciation in natural waters may in many cases not reach equilibrium.

Kinetics↗
PubMed2001

Study of pyoverdine type and production by Pseudomonas aeruginosa isolated from cystic fibrosis patients: prevalence of type II pyoverdine isolates and accumulation of pyoverdine-negative mutations.

The lungs of cystic fibrosis patients are frequently colonized by Pseudomonas aeruginosa, which produces high-affinity fluorescent peptidic siderophores, pyoverdines. Three pyoverdines which differ in their peptide chain and are easily differentiated by isoelectric focusing exist, only one being produced by a given strain. P. aeruginosa isolates from cystic fibrosis patients of a German hospital were analyzed by sequential, pulse-field gel electrophoresis (PFGE) and for pyoverdine production and type. Only producers of type I and type II pyoverdine were found. There was a perfect correlation between the type of pyoverdine produced and the clonality determined by PFGE. PFGE clone C, the most prevalent among cystic fibrosis patients, and found in an aquatic environment, produced type II pyoverdine. Pyoverdine-negative mutants seemed to increase as a function of the lung colonization time, but retained the capacity to take up pyoverdines. Most isolates that took up type II pyoverdine were also able to utilize type I pyoverdine as judged by growth stimulation experiments. No correlation was observed between the loss of pyoverdine production and mucoidy.

Cystic Fibrosis↗
PubMed2001

Aerosolized prostacyclin in acute respiratory distress syndrome caused by Chlamydiaceae spp. pneumonia.

Management of respiratory failure in acute respiratory distress syndrome (ARDS) typically requires ventilatory assistance. If traditional approaches to mechanical ventilation and adjunctive measures fail to succeed in achieving adequate oxygenation, alternative measures should be considered. We describe an ARDS patient with respiratory failure caused by a severe Chlamydiaceae species community-acquired pneumonia (CAP). Aerosolized prostacyclin (PGI(2)) treatment was successfully instituted for refractory hypoxemia.

Administration, Inhalation↗
PubMed2001

Energy yield of respiration on chloroaromatic compounds in Desulfitobacterium dehalogenans.

The amount of energy that can be conserved via halorespiration by Desulfitobacterium dehalogenans JW/IU-DC1 was determined by comparison of the growth yields of cells grown with 3-chloro-4-hydroxyphenyl acetate (Cl-OHPA) and different electron donors. Cultures that were grown with lactate, pyruvate, formate, or hydrogen as an electron donor and Cl-OHPA as an electron acceptor yielded 3.1, 6.6, 1.6, and 1.6 g (dry weight) per mol of reduction equivalents, respectively. Fermentative growth on pyruvate yielded 14 g (dry weight) per mol of pyruvate oxidized. Pyruvate was not fermented stoichiometrically to acetate and lactate, but an excess of acetate was produced. Experiments with 13C-labeled bicarbonate showed that during pyruvate fermentation, approximately 9% of the acetate was formed from the reduction of CO2. Comparison of the growth yields suggests that 1 mol of ATP is produced per mol of acetate produced by substrate-level phosphorylation and that there is no contribution of electron transport phosphorylation when D. dehalogenans grows on lactate plus Cl-OHPA or pyruvate plus Cl-OHPA. Furthermore, the growth yields indicate that approximately 1/3 mol of ATP is conserved per mol of Cl-OHPA reduced in cultures grown in formate plus Cl-OHPA and hydrogen plus Cl-OHPA. Because neither formate nor hydrogen nor Cl-OHPA supports substrate-level phosphorylation, energy must be conserved through the establishment of a proton motive force. Pyruvate ferredoxin oxidoreductase, lactate dehydrogenase, formate dehydrogenase, and hydrogenase were localized by in vitro assays with membrane-impermeable electron acceptors and donors. The orientation of chlorophenol-reductive dehalogenase in the cytoplasmic membrane, however, could not be determined. A model is proposed, which may explain the topology analyses as well as the results obtained in the yield study.

Bacteria, Anaerobic↗
PubMed2001

Sperm adhesion molecules: structure and function.

Fertilisation is a unique event in which the morphologically disparate gametes recognise, bind and fuse with each other. This event follows a highly regulated schedule of biochemical interactions, in which molecules are involved that mediate cell adhesion, signal transduction and the initiation of metabolic pathways. A plethora of molecules has been found on the male gamete and with regard to the different protein structures it is almost impossible to overlook the structures involved. Even more, carbohydrate structures cause an additional diversity with regard to the generation of surface structures. In this communication we try to elucidate the structures of proteins that have been known so far. We have focussed on spermadhesins, the zonadhesin, proacrosin and the PH-20 antigen. The variety of structures and also the common features among them as well as the presence of redundant systems are attributable to the evolutionary force of intraspecific sperm competition. This evolutionary force is assumed to be also responsible for the species selectivity observed in these adhesion molecules, which explains the preferential binding of gametes in a homologous system.

Animals↗
PubMed2000

Association of complementation group and mutation type with clinical outcome in fanconi anemia. European Fanconi Anemia Research Group.

Fanconi anemia (FA) is a clinically and genetically heterogeneous disorder. Clinical care is complicated by variable age at onset and severity of hematologic symptoms. Recent advances in the molecular biology of FA have allowed us to investigate the relationship between FA genotype and the nature and severity of the clinical phenotype. Two hundred forty-five patients from all 7 known complementation groups (FA-A to FA-G) were studied. Mutations were detected in one of the cloned FANC genes in 169 patients; in the remainder the complementation group was assigned by cell fusion or Western blotting. A range of qualitative and quantitative clinical parameters was compared for each complementation group and for different classes of mutation. Significant phenotypic differences were found. FA-G patients had more severe cytopenia and a higher incidence of leukemia. Somatic abnormalities were less prevalent in FA-C, but more common in the rare groups FA-D, FA-E, and FA-F. In FA-A, patients homozygous for null mutations had an earlier onset of anemia and a higher incidence of leukemia than those with mutations producing an altered protein. In FA-C, there was a later age of onset of aplastic anemia and fewer somatic abnormalities in patients with the 322delG mutation, but there were more somatic abnormalities in patients with IVS4 + 4A --> T. This study indicates that FA patients with mutations in the FANCG gene and patients homozygous for null mutations in FANCA are high-risk groups with a poor hematologic outcome and should be considered as candidates both for frequent monitoring and early therapeutic intervention. (Blood. 2000;96:4064-4070)

Abnormalities, Multiple↗
PubMed2000

[Frequency of HFE gene mutations and genotype-phenotype correlations in patients with hereditary hemochromatosis in Switzerland].

Hereditary haemochromatosis is one of the most common genetic disorders affecting populations of European ancestry. Isolation of a strong candidate gene, the HFE gene, allows genetic diagnosis in a large number of cases. However, different mutation frequencies have been reported in hereditary haemochromatosis patient populations from various geographic regions. Such data and phenotype-genotype correlations from Swiss patients with hereditary haemochromatosis are lacking. The objective of our study was to determine the frequency of HFE gene mutations in Swiss patients with hereditary haemochromatosis and to describe the clinical phenotype of patients with either a homozygous C282Y mutation or compound heterozygotes. 71 patients with a clinical diagnosis of hereditary haemochromatosis were identified through a questionnaire sent to physicians caring for hereditary haemochromatosis patients. Pertinent clinical data, in particular those reflecting iron body stores, were collected. Genotyping for the C282Y and H63D mutation of the HFE gene was performed. In 90% of the cases a mutation of the HFE gene was found. 86% of the patients were homozygous for the C282Y mutation, 4% were compound heterozygotes for the C282Y and the H63D mutation. Patients with the homozygous C282Y mutation showed a broad phenotypic spectrum that could not be accounted for by age or sex differences only. Our results demonstrate that within the Swiss population genetic testing can also identify the vast majority of patients with hereditary haemochromatosis. However, the diagnosis is not ruled out by a negative genetic test. Furthermore, a broad phenotypic spectrum is associated with the homozygous C282Y mutation in Swiss hereditary haemochromatosis patients. The implications of these findings for planning of widespread genetic screening for hereditary haemochromatosis in the general population are discussed.

Adult↗
PubMed2000

Chemical-warfare techniques for insect control: insect 'pests' in Germany before and after World War I.

During World War I, chemical-warfare practices were introduced into economic entomology in Germany. Fritz Haber, 'the father of chemical warfare', realized that Germany could not win the war and thus looked for 'civilian' uses for his chemical arsenal. Before the war, there was a rhetoric of dangerous 'masses' of insects but the large-scale techniques needed to deal with them had not been developed. The gap between rhetoric and practices enabled entomology to integrate chemical weapons into its working methods. This article traces transformations in the ways of seeing insects and their control from the mid-nineteenth century to after World War I.

Animals↗
PubMed2000

Increased high-density lipoprotein-3 binding to leukocytes following weight loss and improved glycemic control in type 2 diabetic patients.

This study evaluates the effect on high-density lipoprotein (HDL) binding activity in cultured granulocytes before and after metabolic control of non-insulin-dependent diabetes mellitus ([NIDDM] type 2 diabetes) patients. In 20 type 2 diabetic patients, diabetic control was accomplished by administration of oral antidiabetic agents and dietary restrictions. Adequate metabolic control was reflected by a decrease in the fasting glucose, glycosylated hemoglobin (HbA1c), mean insulin, and body mass index (BMI). After control of the diabetes, the mean HDL3 cholesterol was increased from 0.918 +/- 0.05 to 1.008 +/- 0.05 mmol/L (P < .05) and apolipoprotein AI (apo AI) was increased from 103 +/- 5.8 to 115 +/- 5.1 mg/dL (P < .01). The HDL3 maximum specific binding was higher after versus before diabetic control, 77 +/- 6 versus 122 +/- 8 ng/mg cell protein (P < .01). This increase was related to an increase in maximum binding ([Bmax] from 4.97 x 10(-10) to 8.3 x 10(-10) mol/L, P < .001), and no significant changes were observed in the Kd (from 1.47 x 10(-7) v 2.04 x 10(-7) mol/L). These results suggest that the metabolic control of type 2 diabetes increases HDL3 binding activity.

Adult↗
PubMed2000

Low-fat and high-monounsaturated fatty acid diets decrease plasma cholesterol ester transfer protein concentrations in young, healthy, normolipemic men.

BACKGROUND: Cholesterol ester transfer protein (CETP) mediates the transfer of cholesteryl esters from HDL to apolipoprotein (apo) B-containing lipoproteins. The possible atherogenic role of this protein is controversial. Diet may influence plasma CETP concentrations. OBJECTIVE: The objective was to determine whether the changes in plasma lipids observed after consumption of 2 lipid-lowering diets are associated with changes in plasma CETP concentrations. DESIGN: : We studied 41 healthy, normolipidemic men over 3 consecutive 4-wk dietary periods: a saturated fatty acid-rich diet (SFA diet: 38% fat, 20% saturated fat), a National Cholesterol Education Program Step I diet (NCEP Step I diet: 28% fat, 10% saturated fat), and a monounsaturated fatty acid-rich diet (MUFA diet: 38% fat, 22% monounsaturated fat). Cholesterol content (27.5 mg/MJ) was kept constant during the 3 periods. Plasma concentrations of total, LDL, and HDL cholesterol; triacylglycerol; apo A-I and B; and CETP were measured at the end of each dietary period. RESULTS: Compared with the SFA diet, both lipid-lowering diets significantly decreased plasma total and LDL cholesterol, apo B, and CETP. Only the NCEP Step I diet lowered plasma HDL cholesterol. Positive, significant correlations were found between plasma CETP and total (r = 0.3868, P < 0.0001) and LDL (r = 0.4454, P < 0.0001) cholesterol and also between changes in CETP concentrations and those of total (r = 0.4543, P < 0.0001) and LDL (r = 0.4554, P < 0.0001) cholesterol. CONCLUSIONS: The isoenergetic substitution of a high-saturated fatty acid diet with an NCEP Step I or a high-monounsaturated fatty acid diet decreases plasma CETP concentrations.

Adult↗
PubMed2000

Wood anatomy of Elaeagnaceae, with comments on vestured pits, helical thickenings, and systematic relationships.

The secondary xylem of Elaeagnus, Hippophae, and Shepherdia is described and illustrated in detail. Shrubs and small trees of Elaeagnaceae have ring-porous or semi-ring-porous wood with simple perforation plates, vascular tracheids, fiber-tracheids, diffuse or rarely paratracheal axial parenchyma, and uni- or biseriate rays in Hippophae and Shepherdia, but wider rays in Elaeagnus. Walls of vessel elements, especially narrow ones, tracheids, or fiber-tracheids sometimes show helical thickenings; in a few instances these intergrade with small bud-like protrusions associated with pits. Scanning electron microscopy illustrates that small to vestigial vestures are present in all species studied, although nonvestured pits are also common. The analogous nature of vestures and helical thickenings is considered. Comparative wood anatomy suggests a rather isolated position of the family Elaeagnaceae; affinities with Rhamnaceae, Proteaceae, and Thymelaeaceae are discussed.

Journal Article↗
PubMed1999

[The diet rich in monounsaturated fat modifies in a beneficial way carbohydrate metabolism and arterial pressure].

OBJECTIVE: Two dietary regimens recommended for the reduction of coronary risk, by way of their effects on lipid profile, are the diet low in saturated fat and a diet rich in monounsaturated fats (MUFA). However the effects of these diets on carbohydrate metabolism in healthy subjects are not well known. The objective of this study was to compare the effect of both diets on various parameters of carbohydrate metabolism. METHODS: 41 healthy young males were submitted to 3 consecutive diets, each for a duration of 4 weeks. The first diet was rich in saturated fat (SAT) (38% fat, 20% saturated). The second was rich in carbohydrates following the recommendations of the NCEP-I (National Cholesterol Education Program type I) (28% fat, 47% carbohydrates). The last one was a diet rich in monounsaturated fatty acids (38% fat, 22% MUFA). At the end of each dietary period, blood pressure (BP) and blood levels of glucose, insulin and free fatty acids were determined. 29 subjects were also submitted to an oral glucose tolerance test (OGTT) at the end of each diet. RESULTS: The SAT diet induced the highest levels of insulin after the OGTT. The consumption of the MUFA diet determined the lowest levels of fasting blood glucose (-0.60 mmol/l [13%], p < 0.0002), insulin (-9 microUl/ml [47%], p < 0.0002) and free fatty acids (-0.11 mmol/l [24%], p = 0.006), compared to the NCEP-I diet. Systolic and diastolic blood pressure were higher in the NCEP-I diet than during the other periods (SBP: +6 mmHg compare with SAT [5%], p = 0.0001; and +5 mmHg compare with MUFA [4%], p = 0.0001; DBP: +20 mmHg compare with MUFA [27%], p = 0.0001) and +6 mmHg compared with SAT [8%], p = 0.0001). CONCLUSION: Of the diets most commonly used for the treatment and prevention of arteriosclerosis, a diet rich in monounsaturated fats is the most beneficial for the healthy population from the point of view of carbohydrate metabolism and blood pressure.

Adult↗
PubMed1999

[The Mediterranean diet improves the profile of male smokers compared with the diet recommended by the American Cholesterol Program (NCEP-I)].

BACKGROUND: A study of the effect of smokers' diets on their atherogenic lipidic profile. SUBJECTS AND METHODS: 41 healthy males (32 non-smokers and 9 smokers) consumed consecutively a diet low in fat and rich in carbohydrates (28% total fat content < 10% saturated fats, and 57% carbohydrates), and a diet rich in monounsaturated fatty acids (38% total fat content with 22% monounsaturated fats). At the end of each dietary period, adhesion was confirmed by quantification of LDL cholesterol esters, plasma lipids and insulin levels. RESULTS: There were no significant differences between the age or the body mass of the groups of smokers or non-smokers. After both diets tobacco was found to have a significant effect on triglyceride levels (p < 0.0007), HDLc (p < 0.007), apo A-I (p < 0.02) and the LDLc/HDLc ratio (p < 0.005), revealing an interaction between diet and both HDLc levels (p < 0.004) and LDLc/HDLc ratios (p < 0.003). With the low fat and high monounsaturated fatty acid content diets smokers presented higher triglyceride levels (both with p < 0.0002) and LDLc/HDLc ratios (p < 0.0002 and p < 0.05, respectively) and lower levels of apo A-I (p < 0.002 and p < 0.004, respectively). However, in smokers the HDLc levels were only reduced after the low fat diet (p < 0.0003) and after the diet with a high monounsaturated fat content there was a rise in HDLc levels (p < 0.02) and a drop in the LDLc/HDLc ratio (p < 0.005) compared to the group of non-smokers. There were no significant differences in the insulin levels between groups. CONCLUSION: The atherogenic lipidic profile of smokers is due to an effect of tobacco on the lipidic metabolism. This atherogenic profile is accentuated with a low fat diet rich in carbohydrates and can be rectified to some degree with a diet with a high monounsaturated fatty acid content.

Adult↗
PubMed1999

Cardiopulmonary bypass reduces pulmonary surfactant activity in infants.

OBJECTIVE: Infants younger than 1 year of age undergoing cardiopulmonary bypass surgery often have severe lung injury necessitating increased postoperative respiratory mechanical support. Inasmuch as the mechanisms may involve an impairment of the pulmonary surfactant system, our aim was to determine whether changes of surfactant occur in such infants. METHODS: From the day of the operation to day 7 after the operation, serial tracheobronchial small-volume lavages of 19 infants (aged 166 +/- 29 days) were fractionated into a small and a large surfactant aggregate fraction and compared with those of 13 infants without lung disease (aged 203 +/- 33 days). RESULTS: After cardiac operations with cardiopulmonary bypass surgery, total protein in lavages was increased 3-fold to 4-fold and decreased linearly with time. Surfactant protein A was increased on day 1 and day 2 and then decreased, whereas surfactant protein B and total phospholipids were increased on day 1. The ratio of phospholipids in small and large surfactant fractions was unchanged, but the surface activity of the large-aggregate surfactant was impaired on days 1 to 3. CONCLUSIONS: Lung injury in infants after cardiopulmonary bypass surgery involves significant biochemical and functional disturbances of the pulmonary surfactant system. Inasmuch as substitution with natural surfactant might correct these deficiencies, the potential of this approach to reduce postoperative morbidity needs to be investigated.

Biomarkers↗
PubMed1998

Site-directed mutagenesis of boar proacrosin reveals residues involved in binding of zona pellucida glycoproteins.

Proacrosin, the zymogen form of the serine protease beta-acrosin, is thought to function as a secondary binding molecule between mammalian gametes during fertilization (Jansen et al., 1995: Int J Dev Biol 39, 501-510). The interaction involves strong ionic bonds between positively charged amino acids on proacrosin and negatively charged polysulphate groups on zona pellucida glycoproteins. In this investigation, we identified the basic residues on proacrosin that are important for this binding. Site-directed mutagenesis shows that two groups of amino acids comprising His47, Arg50, and Arg51 together with Arg250, Lys252, and Arg253 are crucial because their deletion or replacement severely reduces affinity for zona glycoproteins. Molecular models of proacrosin reveal that these residues are located along one face of the protein on two exposed surface loops that project over and around the catalytic site. These findings support the hypothesis that polysulphate binding sites on proacrosin are formed by a restricted number of basic amino acids on the surface of the protein, presenting a specific orientation that is complementary to negatively charged sulphate groups on zona glycoproteins. Identification and elucidation of the stereochemistry of these charged moieties will aid design of new kinds of nonsteroidal antifertility agents.

Acrosin↗