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Biomedical subjects

H Schuster

Publications and source records attributed to H Schuster.

At least 127 records · Page 7Linked to original sources
PubMed1990

Genetic evidence from 7 families that the apolipoprotein B gene is not involved in familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCHL) is the most common genetic form of hyperlipidemia in which affected individuals manifest multiple lipoprotein phenotypes. Although the molecular defect is still unknown, several kinetic studies have demonstrated increased turnover rates of apolipoprotein B (apo B) in patients with FCHL, irrespective of their lipoprotein phenotype. Using 3 restriction fragment length polymorphisms (RFLPs) of the apo B gene (XbaI, MspI and EcoRI) we have investigated 33 families which fulfill the diagnostic criteria of FCHL. No significant difference in allele frequency was found between 33 unrelated individuals with FCHL and 107 normolipidemic controls. 3-RFLP haplotypes were constructed in each pedigree. A co-segregation analysis was performed in 7 informative families. In no family was co-segregation observed between the haplotype of the apo B gene and the phenotype of FCHL. These data are not compatible with the hypothesis that FCHL is caused by mutations of the apo B gene acting as a simple mendelian trait.

Adult↗
PubMed1990

Association of DNA-haplotypes in the human LDL-receptor gene with normal serum cholesterol levels.

For the low density lipoprotein receptor (LDLR), many mutations have been characterized which identify this gene as one with an important role in lipid metabolism in patients with familial hypercholesterolemia (FH). Genetic heterogeneity at this locus raises the possibility that the LDLR may also contribute to variation in cholesterol levels in the normocholesterolemic population. We have determined genotypes at the LDLR locus using restriction fragment length polymorphisms (RFLPs) detected with the enzymes StuI, ApalI, PvuII and NcoI in 324 normocholesterolemic individuals from Germany. A significant association (p less than 0.01) was detected between the cutting site for the PvuII RFLP and lower cholesterol levels, and variation associated with this polymorphism explains 3% of the sample variance in cholesterol levels. In family studies we have determined four-RFLP haplotypes of 148 independent LDLR genes and have observed 9 haplotypes in the population. Three of these haplotypes containing the cutting site for PvuII are associated with a reduction in plasma LDL-cholesterol levels. Phylogenetic analysis indicates that these three haplotypes are related by evolutionary history, and this suggests that a single functionally important sequence change in the LDLR explains our observations. Our data confirm other reports and strongly suggest that the LDLR locus may be one of those genes involved in determining serum cholesterol levels in the normal population.

Adult↗
PubMed1990

Color-coded Doppler imaging of normal vertebral arteries.

Using color-coded Doppler sonography, we studied the vertebral arteries of 42 persons without history or physical signs of vertebrobasilar disease. The intertransverse portion of the vertebral artery was visualized in all persons on both sides. Its origin was visualized in 37 persons (88.1%) on the right side and in 28 (66.7%) on the left; the atlas loop was visualized in 32 persons (76.2%) on the right side and in 36 (85.7%) on the left. Four vertebral arteries were hypoplastic. Peak systolic blood velocity ranged from 19 to 98 (mean 56) cm/sec and peak diastolic blood velocity ranged from 6 to 30 (mean 17) cm/sec. Resistive indices ranged from 0.62 to 0.75 (mean 0.69). Thus, color-coded Doppler sonography seems to be a promising noninvasive method for the evaluation of hemodynamics in the extracranial portion of the vertebral arteries.

Blood Flow Velocity↗
PubMed1989

Organization of the immunity region immI of bacteriophage P1 and synthesis of the P1 antirepressor.

The immI region of bacteriophage P1 includes the ant/reb gene, which encodes the antirepressor protein, and the c4 gene, which encodes a repressor molecule that negatively regulates antirepressor synthesis. The antirepressor interferes with the activity of the P1 repressor of lytic function, the product of the c1 gene. We have determined the DNA sequences of the immI region of P1 wild-type and the mutants virs, ant16, ant17, and reb22. Using suitable P1 immI DNA subfragments cloned into a vector of the T7 bacteriophage RNA polymerase expression system the antirepressor protein(s) was overproduced. On the basis of positions of immI mutations and the sizes of ant gene products, the following organizational feature of the P1 immI region is suggested: (1) the genes c4 and ant are cotranscribed in that order from the same promoter in the clockwise direction of the P1 genetic map; (2) an open reading frame for an unknown gene is located in between c4 and ant; (3) the site at which the c4 repressor acts is located within the c4 structural gene; (4) two antirepressor proteins of molecular weights 42,000 and 32,000 are encoded by a single open reading frame, with the smaller protein initiating at an in-frame start codon; (5) transcription of immI is regulated via a c1-controlled operator, Op51, indicating a communication between the immunity systems immC and immI.

Base Sequence↗
PubMed1989

The c1 repressor of bacteriophage P1 operator-repressor interaction of wild-type and mutant repressor proteins.

The c1 repressor gene of bacteriophage P1 and the temperature-sensitive mutants P1c1.100 and P1c1.162 was cloned into an expression vector and the repressor proteins were overproduced. A rapid purification procedure was required for the isolation of the thermolabile repressor proteins. Identification of the highly purified protein of an apparent molecular weight of 33,000 as the product of the c1 gene was verified by (i) the coincidence of partial amino acid sequences determined experimentally to that deduced from the c1 DNA sequence, and (ii) the temperature-sensitive binding to the operator DNA of the thermolabile repressor proteins. Analysis of the products of c1-c1.100 recombinant DNAs relates the thermolability to an unknown alteration in the C-terminal half of the c1.100 repressor. Binding to the operator DNA of c1 repressor is sensitive to N-ethylmaleimide. Since the only three cysteine residues are located in the C-terminal half of the repressor it is suggested that this part of the molecule is important for the binding to the operator DNA. This assumption is supported by the findings that a 14-kDa C-terminal repressor fragment obtained by cyanogen bromide cleavage retains DNA binding properties.

Amino Acid Sequence↗
PubMed1989

Three additional operators, Op21, Op68, and Op88, of bacteriophage P1. Evidence for control of the P1 dam methylase by Op68.

The repressor of bacteriophage P1, encoded by the c1 gene, is responsible for maintaining the P1 prophage in the lysogenic state. Previously, 11 c1 repressor binding sites or operators scattered over the whole genome of P1 have been found. From sequence analysis an asymmetric, 17-base pair consensus sequence, ATTGCTCTAATAAATTT, was derived. Using a synthetic 15-base-long oligodeoxyribonucleotide as operator probe, we have identified three additional operators. We have mapped the operators at the positions 21,68, and 88 of the P1 genome and determined their sequence. These operators are controlled by c1 because corresponding P1 DNA fragments (i) require c1 repressor in vivo in order to be clonable in multicopy plasmids, (ii) exhibit a c1-repressible promoter activity, (iii) are retarded by c1 repressor protein during electrophoresis, and (iv) contain the 17-base pair consensus sequence with one mismatch base each. Furthermore, we suggest that expression of the DNA adenine methylase (dam) encoded by P1 is controlled via Op68.

Bacteriophages↗
PubMed1989

ban operon of bacteriophage P1. Mutational analysis of the c1 repressor-controlled operator.

The repressor of bacteriophage P1, encoded by the c1 gene, represses the phage lytic functions and is responsible for maintaining the P1 prophage in the lysogenic state. The c1 repressor interacts with at least 11 binding sites or operators widely scattered over the P1 genome. From these operators, a 17 base-pair asymmetric consensus sequence, ATTGCTCTAATAAATTT, was derived. Here, we show that the operator, Op72 of the P1ban operon consists of two overlapping 17 base-pair sequences a and b forming an incomplete palindrome. Op72a matches the consensus sequence, whereas Op72b contains two mismatches. The evidence is based on the sequence analysis of 27 operator mutants constitutive for ban expression. They were identified as single-base substitutions at positions 2 to 10 of Op72a (26 mutants) and at position 8 of Op72b (one mutant). We conclude from gel retardation and footprinting studies that two repressor molecules bind to the operator and that positions 4, 5 and 7 to 10 of the operator play an essential role in repressor recognition.

Bacteriophages↗
PubMed1989

Four DNA polymorphisms in the LDL-receptor gene and their use in diagnosis of familial hypercholesterolemia.

To examine the potential usefulness of restriction fragment length polymorphisms (RFLPs) for diagnosis of familial hypercholesterolemia (FH), we determined the genotype of FH patients and their relatives for the Apa1I, NcoI, PvuII and StuI RFLP of the LDL-receptor gene in a sample of German patients attending the Lipid Clinic in Munich. There was no significant difference in the relative allele frequency between the group of FH patients and controls for any of the four polymorphisms. Using linkage analysis, we could determine the four-RFLP haplotypes of 39 defective and 90 normal LDL-receptor genes in 38 FH families. In our sample, defective LDL-receptor genes occur on 6 different chromosomes determined by the four RFLPs. This suggests that at least 6 different genetic defects may cause FH in this sample. RFLPs of the LDL-receptor gene cannot be used to detect FH in individuals; however, appropriate diagnosis can be carried out in more than 90% of families using linkage analysis and these RFLPs.

Gene Frequency↗
PubMed1989

Experience with radical surgical treatment of maxillofacial tumours invading the base of the skull. Long term results.

A review of patient data of maxillofacial tumours invading the base of the skull shows a relatively high fatality rate as a result of surgical intervention but also an unexpectedly high life expectancy. Surgical intervention seems to be the right choice whenever clinical examination suggest tumour removal is possible even if a tumour cannot be extirpated in one operation and a further operation from a second access is needed.

Carcinoma, Squamous Cell↗
PubMed1988

[Extra- and intracranial Doppler ultrasound. Evaluation of patients with surgical anastomosis of the arteria temporalis superficialis superficialis and arteria cerebri media].

During a mean postoperative period of 16 months, 51 patients who had received an extracranial-intracranial (EC-IC) arterial bypass were examined by means of transcranial and extracranial Doppler ultrasound, with the following results: the flow velocities of the middle cerebral artery (MCA) are postoperatively significantly lower than in normal control subjects. No differences were seen if the MCA was supplied via the EC-IC bypass or via any "natural" collateral vessels. In 32 cases, blood supply of the MCA artery was provided via the EC-IC bypass. In another 13 cases the MCA was supplied via the contralateral carotid artery and in six further cases via other collateral vessels. In the extracranial area, an internalisation of the flow pattern of the superficial temporal artery was found if the bloodstream from the anastomosis passed through the MCA. Similar changes at the external carotid artery were mainly due to the changed haemodynamics resulting from the extracranial occlusion of the internal carotid artery. No correlation was found between the clinical neurological course and haemodynamic data. The only indication for the EC-IC bypass, as we see it at the moment, is prophylactic surgery, such as, for example, treatment of giant aneurysms and definitely insufficient crossflow. All other indications that have been suggested after the publication of the results of the EC-IC Bypass Study Group will have to be confirmed by further study.

Aged↗
PubMed1988

The c1 repressor of bacteriophage P1. Isolation and characterization of the repressor protein.

The c1 repressor gene of bacteriophage P1 is located on P1 DNA EcoRI fragment 7 (Sternberg, N. (1979) Virology 96, 129-142). Subfragments of P1 DNA EcoRI fragment 7 were cloned into expression vectors, and the c1 repressor protein from P1 wild-type phage and a revertant of a temperature-sensitive repressor mutant were overproduced in Escherichia coli and purified to near-homogeneity. The decreased electrophoretic mobility of P1 DNA BamHI fragment 9 in the presence of appropriate protein fractions was used as an assay for the repressor protein. Highly purified repressor migrates as a single polypeptide on denaturing sodium dodecyl sulfate-polyacrylamide gels, corresponding to a molecular weight of about 33,000. A molecular weight of about 63,000 for the native repressor molecule was calculated from determinations of the sedimentation coefficient, which was 2.6 s, and the Stokes radius, which was 55 A. Cross-linking the protein with glutaraldehyde yielded two bands. These data and a high frictional coefficient (2.1) suggest that the native repressor exists in solution as an asymmetric dimer molecule.

Bacteriophages↗
PubMed1988

Atherosclerosis of the carotid arteries in young patients with familial hypercholesterolemia.

Patients with heterozygous and homozygous Familial Hypercholesterolemia exhibit a high incidence of premature coronary heart disease, presumably due to atheromatous plaque-formation in the coronary arteries. Clinical symptoms develop when the disease has progressed to more severe stages of atherosclerosis. Aim of our study was to visualize and document early atheromatous lesions in the carotid arteries of asymptomatic patients with familial hypercholesterolemia under 30 years of age by Duplex-scan. Of 44 patients, 70% had detectable carotid plaques, while only 12% of the controls were affected. All patients with severe carotid disease had serum cholesterol levels above 350 mg/dl. In the age group 2-20 years, 66% of the patients exhibited plaques. Only 6% of the FH patients 21-30 years had normal carotid arteries. We conclude that the process of atheromatous plaque formation in patients with FH starts early in life, severity of atherosclerosis being a function of both extent and duration of hypercholesterolemia. Duplex-scan examination of the carotid arteries is efficient and precise non-invasive method suitable to visualize this process and, by measuring regression, monitor the efficacy of therapeutic measures.

Adolescent↗
PubMed1988

[Fatal re-infarct in pregnancy].

We report on the third pregnancy of a 41-year-old patient with familial hypercholesterolemia. After preceding angina pectoris symptoms she had her first myocardial infarction at an age of 37. Thereafter she had no complaints under medicinal and dietary treatment. During her third pregnancy angina pectoris symptoms occurred again and finally a myocardial re-infarction caused her death. Our case report shows, that the hemodynamic alterations in pregnancy can aggravate the patient's situation even in prepartally uncomplicated coronary diseases.

Adult↗
PubMed1987

The ban operon of bacteriophage P1. Localization of the promoter controlled by P1 repressor.

Repression of a strong promoter localized 5' to the P1 ban gene is a prerequisite for cloning the ban operon in the multicopy plasmid pBR325. Repression is brought about by the binding of P1 repressor to the operator of the ban operon (Heisig, A., Severin, I., Seefluth, A. K., and Schuster, H. (1987) Mol. Gen. Genet. 206, 368-376). Binding of RNA polymerase in vitro overlaps with the operator and is inhibited by P1 repressor as shown by electron microscopy. The mutant P1 bac, which renders ban expression constitutive, contains a single base pair exchange within the operator. As a consequence, more repressor is required (i) for the inhibition of binding of RNA polymerase, and (ii) for the electrophoretic retardation of a P1 bac DNA fragment when compared to the corresponding bac+ fragment. A P1 ban recombinant plasmid containing a 4-base pair deletion close to the operator still allows binding of repressor but not of RNA polymerase. By that means, a repressible promoter is located at the P1 map position 72 in a distance of about 2.5 kilobase pairs to the beginning of the ban gene.

Bacteriophages↗
PubMed1987

A dnaB-like protein of Pseudomonas aeruginosa.

A dnaB-like protein from P. aeruginosa was purified to near homogeneity using as an assay the immunoprecipitation by E. coli dnaB antiserum in a solid-phase. In the chromatographic characteristics including the affinity to immobilized ATP the dnaB-like protein of P. aeruginosa is similar to the dnaB protein of E. coli with the exception that it does not bind to heparin-Sepharose. The dnaB-like protein has a native molecular weight of about 320,000 as determined by glycerol gradient sedimentation. It consists of several identical subunits of molecular weight of 56,000 as measured in a denaturing SDS gel. Associated with the enzyme is a DNA-dependent ATPase- and helicase activity. The dnaB-like protein is similar to the E. coli dnaB protein with regard to the binding of ATP gamma S and the formation of a ternary complex consisting of the enzyme, ATP gamma S, and phi X174 DNA. However, the enzyme of P. aeruginosa is inactive in a phi X174 DNA-dependent in vitro dnaB complementation assay using an E. coli dnaBts extract.

Adenosine Triphosphate↗
PubMed1987

Regulation of the ban gene containing operon of prophage P1.

A physical map of the ban gene of P1 and sites relevant to its regulation has been deduced from cloning of the appropriate regions of P1 wild-type and of P1 ban regulatory mutants. The cloning required the presence of P1 repressor in the cell confirming the existence of a repressible ban operon (Austin et al. 1978). Evidence for additional member(s) of that operon is presented. Of particular interest for understanding the regulation of ban are the relative positions of a binding site for the P1 repressor and of the regulatory mutations bac and crr that render ban expression constitutive. The results reveal a repressible operon-like structure of about 4 kb within the P1 EcoRI-3 fragment that comprises a c1 repressor binding site/bac - additional gene(s) - crr/ban in the clockwise direction of the circular map of P1.

Bacterial Proteins↗
PubMed1987

Multiple repressor binding sites in the genome of bacteriophage P1.

After digestion of bacteriophage P1 DNA with EcoRI in the presence of P1 repressor, 6 repressor binding sites were identified in 5 of 26 EcoRI fragments. Binding sites were localized by the decreased mobility of DNA fragment-repressor complexes during electrophoresis and by DNase protection ("footprinting") analysis. The repressor binding sites, or operators, comprise a 17-base-pair-long consensus sequence lacking symmetrical elements. Three operators can be related to known genes, whereas the function of the others is still unknown. The mutant P1 bac, rendering ban expression constitutive, is identified as an operator-constitutive mutation of the ban operon.

Bacteriophages↗