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Biomedical subjects

S Jansen

Publications and source records attributed to S Jansen.

At least 73 records · Page 4Linked to original sources
PubMed1995

Localisation of the Fanconi anaemia complementation group A gene to chromosome 16q24.3.

Fanconi anaemia (FA) is an autosomal recessive disorder associated with diverse developmental abnormalities, bone-marrow failure and predisposition to cancer. FA cells show increased chromosome breakage and hypersensitivity to DNA cross-linking agents such as diepoxybutane and mitomycin C. Somatic-cell hybridisation analysis of FA cell lines has demonstrated the existence of at least five complementation groups (FA-A to FA-E), the most common of which is FA-A. This genetic heterogeneity has been a major obstacle to the positional cloning of FA genes by classical linkage analysis. The FAC gene was cloned by functional complementation, and localised to chromosome 9q22.3 (ref. 2), but this approach has thus far failed to yield the genes for the other complementation groups. We have established a panel of families classified as FA-A by complementation analysis, and used them to search for the FAA gene by linkage analysis. We excluded the previous assignment by linkage of an FA gene to chromosome 20q, and obtained conclusive evidence for linkage of FAA to microsatellite markers on chromosome 16q24.3. Strong evidence of allelic association with the disease was detected with the marker D16S303 in the Afrikaner population of South Africa, indicating the presence of a founder effect.

Chromosome Mapping↗
PubMed1995

Analysis of polysulfate-binding domains in porcine proacrosin, a putative zona adhesion protein from mammalian spermatozoa.

Proacrosin is one of the major proteins found within the acrosomal vesicle of mammalian spermatozoa. Previous work has shown that it binds non-enzymatically and with high affinity to polysulfate groups on zona pellucida glycoproteins (ZPGPs) thereby leading to the hypothesis that at fertilization it functions as a secondary ligand molecule to retain acrosome-reacted spermatozoa on the surface of the egg. In the present work we have investigated the nature and extent of the polysulfate binding domain on boar sperm proacrosin using a combination of group-specific modifying reagents, fragmentation analysis, peptide synthesis and expression of deletion recombinants in E. coli bacteria. Taken overall, our results show that arginine, lysine and histidine residues located between Gly 93 and Ala 275, together with the participation of His 47 and Arg 50, are necessary for maximum polysulfate binding activity. The secondary and tertiary structure of this central peptide domain is also important to ensure correct alignment of basic residues with complementary sulfate groups on ZPGPs. Proacrosin, therefore, has many properties in common with other polysulfate binding proteins, such as antithrombin III and sea urchin sperm binding, in having a conformation-dependent domain containing basic amino acids that mediates specific protein-protein interactions. These observations strengthen the hypothesis that proacrosin is a multifunctional protein with a major role as a ligand molecule at fertilization.

Acrosin↗
PubMed1994

Rhenium-labeled somatostatin analog RC-160. 1H NMR and computer modeling conformational analysis.

The solution conformations of RC-160, cyclic D-Phe1-Cys2-Tyr3-D-Trp4-Lys5-Val6-Cys7+ ++-Trp8-NH2, an analog of the tumor antiproliferatory neuropeptide somatostatin, and RC-160 labeled with rhenium (Re-RC-160), have been determined by using two-dimensional 1H NMR spectroscopy (600 MHz) and restrained molecular dynamics simulations. Re-RC-160 yields the same average solution conformation as does the apo form with an antiparallel beta-sheet fold and a type II' beta-turn centered at D-Trp4-Lys5. These results indicate that the spatial topography of the side chains essential for somatostatin receptor binding is maintained in Re-RC-160.

Amino Acid Sequence↗
PubMed1994

Genetic mapping of the FACC gene and linkage analysis in Fanconi anaemia families.

Fanconi anaemia is an autosomal recessive disorder associated with increased chromosome breakage and progressive bone marrow failure. The gene for complementation group C (FACC) has been cloned and mapped to chromosome 9q22.3, but neither its genetic location nor the proportion of patients belonging to group C is known. We have used a polymorphism within the FACC gene to localise it within a 5 cM interval on chromosome 9q, bounded by D9S196/D9S197 and D9S176. The genes for Gorlin's syndrome and multiple self-healing squamous epitheliomata have also been mapped to this interval. Linkage analysis with the three highly informative microsatellite polymorphisms flanking FACC in 36 Fanconi anaemia families showed that only 8% of families were linked to this locus. This indicates that the genes for the other Fanconi anaemia complementation groups must map to one or more different chromosomal locations. The markers also allowed rapid exclusion of 56% of the families in our panel from complementation group C, thus substantially reducing the number of patients who need to be screened for FACC mutations.

Chromosome Mapping↗
PubMed1992

Experience with a provocative test of calcitonin release as a prospective screening for preclinical medullary thyroid carcinoma in MEN type 2A family members.

We report our experience with a provocative test of calcitonin (CT) release using a combined stimulus of intravenous 10% CaCl2 solution and pentagastrin on 34 normal adults (15 females: age 41 +/- 12.3 years and range 22-65 years; and 19 males: age 43 +/- 9.1 years and range 23-60 years) and in 44 family members of three proven multiple endocrine neoplasia type 2A syndrome (MEN 2A) patients. A commercial radioimmunoassay was used to determine the serum CT levels. Peak CT levels were reached within 2 to 5 minutes after administration of the stimulus in all subjects tested. In the group of normal subjects there was no significant difference in the mean basal CT levels between males (54.8 +/- 21.7 pg/ml) and females (56.5 +/- 34.8 pg/ml), whilst the mean peak response values for males was 146.3 +/- 120.6 pg/ml, which was significantly different from the mean value of females, namely 71.6 +/- 39.0 pg/ml. We did not find significant correlations between the basal CT level, peak CT response, and age. Of the 44 family members tested, 9 showed an exaggerated CT response to the combined stimulus and subsequently had a total thyroidectomy. Histological examination confirmed C-cell hyperplasia (CCH) in one and medullary thyroid carcinoma (MTC) in the other 8. Three of the 9 had high basal plasma CT levels. The 9 patients were retested postoperatively and all showed a flat response to the combined stimulus. Those family members with histological proof of MTC or CCH were screened for genetic linkage to the disease gene for MEN 2A using probe MCK2, and showed correlation in each instance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

In-vitro efficacy of a central venous catheter ('Hydrocath') loaded with teicoplanin to prevent bacterial colonization.

A technique is described by which a central venous catheter ('Hydrocath') is loaded with the glycopeptide teicoplanin for the prevention of catheter infection. Catheters are immersed in teicoplanin solution and, due to the hydrophilic surface coating of the 'Hydrocath' catheter, teicoplanin is absorbed by the surface layer. The catheter loading is influenced by the experimental conditions and is assessed by measuring teicoplanin elution from the catheter using a bioassay. Increasing the antibiotic concentration, incubation time and temperature leads to the binding of higher amounts of teicoplanin to the catheter, resulting in a higher teicoplanin release from the catheter. Experiments on in-vitro bacterial adherence to teicoplanin-loaded and unloaded catheters reveal that the initial bacterial adhesion is not prevented. However, in the case of the teicoplanin-loaded catheter initially adherent bacteria are eliminated from the catheter surface, thus preventing catheter colonization by bacteria for at least 48 h. Such loaded catheters could be suitable for inhibiting early-onset, catheter-related infections.

Bacterial Adhesion↗
PubMed1992

Adhesion of fimbriated and non-fimbriated Klebsiella strains to synthetic polymers.

Adherence of three fimbriated and non-fimbriated Klebsiella strains to polyetherurethane was investigated in order to assess the possible role of fimbriae in the adhesion of Klebsiella to synthetic polymers. Fimbriated strains with type 1 and type 1.3 fimbriae adhere significantly stronger to polyurethane than the same strains lacking fimbriae, whereas a strain with type 3 fimbriae shows no different adherence compared with the non-fimbriated variant. Analysis of adhesion kinetics and isotherms reveals that adherence of fimbriated Klebsiella strains is proceeded by the formation of multicellular bacterial layers on the polymer surface. Measurements of the relative hydrophobicity of the strains and adherence experiments under exclusion of unspecific interactions point out that fimbriae obviously play a more important role in adhesion than relative hydrophobicity. The demonstration of reduction of bacterial adherence to polyetherurethane by blocking fimbrial action with fimbriae-specific sugars supports this further.

Bacterial Adhesion↗
PubMed1992

In-vitro efficacy of a central venous catheter complexed with iodine to prevent bacterial colonization.

Infections of central venous lines are still a problem in daily medicine. Despite adequate antibiotic therapy, removal of an infected catheter often becomes necessary. A simple procedure has been developed by which a special hydrophilic central venous catheter (Secalon-Hydrocath) can be loaded with iodine. Iodine is complexed in the hydrophilic polyvinylpyrrolidone surface coating of the Hydrocath catheter and is released during contact with an aqueous medium. The amount of complexed iodine depends on the incubation time in Lugol's solution. Antimicrobial activity of the loaded catheters was assessed with Staphylococcus epidermidis, showing complete inhibition of bacterial adherence to the catheters for the duration of iodine release. Depending on the experimental conditions, iodine released from the catheter is also active on bacteria in the surrounding medium.

Bacterial Adhesion↗
PubMed1991

Multiple endocrine neoplasia type 2A (MEN 2A) syndrome in a South African family. Biochemistry and molecular genetics.

Multiple endocrine neoplasia type 2A (MEN 2A), an uncommon heritable disease, was investigated in an Afrikaner kindred. Serum calcitonin levels after combined pentagastrin and calcium chloride stimulation were measured to determine thyroid involvement, as were urinary metadrenalin levels to determine adrenal gland involvement. MEN 2A genotype status was determined using the DNA probe MCK2 (D10S15). The index patient, who showed both thyroid and adrenal gland involvement, died of phaeochromocytoma complications. Thirty-four of his 114 family members, in 4 generations, were investigated. Nine had positive histological and calcitonin tests and were predicted to be MEN 2A genotypes by DNA analysis. One asymptomatic individual had a positive calcitonin test after being predicted to be a MEN 2A genotype with the probe MCK2. In 3 DNA-positive cases calcitonin stimulation tests were negative. Preclinical detection of the heritable form of MEN 2A will be facilitated by utilising the DNA probe MCK2 to determine carrier status in this large South African family. It is also the first South African family in which biochemical and molecular genetic techniques were used to facilitate diagnosis.

Adolescent↗
PubMed1991

Early thyroidectomy for medullary thyroid carcinoma in children and young adults with the multiple endocrine neoplasia type 2A (MEN 2A) syndrome.

A South African family, at risk for the multiple endocrine neoplasia type 2A (MEN 2A) syndrome, was identified. The Bloemfontein MEN Study Group was founded, inter alia, to study the effects of early detection of medullary carcinoma of the thyroid (MTC) and treatment by total thyroidectomy in children and young adults with MEN 2A. Genotypes were identified by DNA probe and MTC diagnosed by basal and stimulated calcitonin levels. Between 1986 and 1989, 10 members of the family underwent total thyroidectomy and central lymph node dissection for MTC. There were 6 female and 4 male patients (mean age 22,0 years; range 10 - 35 years). Histological examination of the resected thyroid revealed MTC in all patients; 8 had bilateral disease and 2 unilateral. Lymph nodes were negative for MTC in all patients. None of the patients suffered injury to the recurrent nerve, while 1 experienced transient hypoparathyroidism postoperatively. Replacement therapy is maintaining thyroid hormone levels in all patients. Screening should probably begin at the age of 1 year, and total thyroidectomy should be performed when an elevated calcitonin level is observed.

Adolescent↗
PubMed1991

Turner/Down mosaicism. A case report.

A 45,X/47,XX, +21 mosaicism (80%:20%) in a young girl with clinical features of Down syndrome is reported. The proportion of 45,X:47,XX, +21 cells present in peripheral lymphocytes does not necessarily have a profound effect on the phenotype. A possible explanation for the occurrence of double aneuploidy is given.

Child↗
PubMed1990

Biological dose estimation in a radiation accident involving low-dose exposure.

Blood specimens were collected from 8 people 18 days after they had been accidentally exposed to a 947.2 GBq iridium-192 source during industrial application. The equivalent whole-body dose received at day 0 was estimated using a model based on quantitative and qualitative chromosome aberration analysis in lymphocytes. According to physical dose estimations, all 8 people were exposed to whole-body doses varying from 12 mGy to 61 mGy. Substantiated evidence to this effect was found in at least 3 cases using biological dosimetric criteria, proving the sensitivity of this cytogenetic model even at low doses.

Accidents, Occupational↗
PubMed1989

Plasma glutamate--a prognostic marker of cancer and of other immunodeficiency syndromes?

Elevated plasma levels of glutamate (GLU) have been reported to occur in patients with malignancies and other immunodeficiency syndromes (IDS). To evaluate, whether GLU is useful as prognostic indicator, the plasma concentrations were determined in patients with colorectal carcinoma (CRC), with breast cancer (BRC), and with HIV-infection (HIV). The results were correlated with the disease-stages, and compared with data obtained from patients with benign diseases of the same organ, as well as from sex-matched healthy volunteers. GLU concentrations (volunteers: 27.4 +/- 17.6 mumol/l) were elevated in all BRC patients (range of mean values: 53.5-83.2 mumol/l), in CRC patients with T2-T4-tumours (means: 46.8-85.9), and in HIV+ patients of stage WR 5, 6 (means: 53.9-69.7 mumol/l). All CRC- and BRC-patients with metastases showed highly significant elevations of GLU concentrations (p less than 0.001), but there were no direct correlations between disease stages and GLU levels. Pre-operative patients with benign diseases (diverticulitis, adenoma = GID; and mastopathy = MTP) showed increased GLU levels, which were comparable to those of the tumour patients. The glutamine/GLU ratios (volunteers: 19.3 +/- 15.0) were decreased only in HIV-WR 6 (7.6 +/- 2.1), and BRC-stage 4 (8.0 +/- 1.7). From these results we deduce that the plasma GLU concentrations do not allow a discrimination either between patients with malignancies and without, and between persons of different disease stages.

Aged↗
PubMed1988

Asparaginase-induced derangements of glutamine metabolism: the pathogenetic basis for some drug-related side-effects.

Several side-effects of asparaginase therapy have been said to be a consequence of the glutaminase activity of Escherichia coli asparaginase, especially the deleterious influence on the liver function. We report here the drug-induced impairments of asparagine and glutamine metabolism in correlation to concentrations changes of plasma proteins, synthesized in the liver, in patients with acute lymphatic leukaemia. One hour after asparaginase application, plasma glutamine decreased to 5% (0-39%: median, range) of the initial values, with a subsequent rise to concentrations slightly lower than those prior to therapy. During the 14 days of drug application the fasting plasma concentrations of glutamine fell to a median of 63% of the pre-therapeutic levels, indicating a depletion of the glutamine pools. Two days after the end of asparaginase application, in one patient the glutamine concentrations increased to the pre-therapeutic range. Plasma concentrations of fibrinogen and antithrombin III decreased to 46% and 56%, respectively, of the initial values, with a slight increase 2 days after the end of therapy. The changes of plasma protein concentrations followed the course of plasma glutamine and asparagine. From that we deduce that the hepatic synthesis of the plasma proteins might be influenced by asparagine and glutamine depletion as a consequence of the therapy with E. coli asparaginase.

Amino Acids↗