First International Workshop on Familial Defective apo B-100, Munich, November 1991.
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Apolipoprotein B-100↗
Biomedical subjects
C Keller
Publications and source records attributed to C Keller.
Familial defective apolipoprotein B-100: a common cause of primary hypercholesterolemia.
Familial defective apolipoprotein B-100 (FDB) is a recently identified dominantly inherited genetic disorder characterized by a decreased binding of low density lipoprotein (LDL) to the LDL receptor due to defective apo B-100. FDB is caused by a G to A mutation at nucleotide 10,708 in exon 26 of the apo B gene creating a substitution of glutamine for arginine in the codon for amino acid 3500. The arginine (3500)----glutamine mutation has been observed in several populations in North America and Europe with a similar frequency of approximately 1/500 to 1/700. Haplotype analysis has demonstrated that the arginine(3500)----glutamine mutation occurs on the same chromosomal background. The fact that all individuals with FDB are of Caucasian extraction implies that the mutation has its origin in this population. The arginine(3500)----glutamine mutation has a profound impact of varying strength on the plasma LDL cholesterol level, leading to heterogeneous clinical expression comparable to "classic" familial hypercholesterolemia (FH) caused by a defective LDL receptor: tendon xanthoma, premature atherosclerosis and arcus lipoides. The present data suggest that the combination of these clinical features is no longer appropriate for the diagnosis of LDL-receptor-defective FH, but may be a common feature of a defective LDL receptor pathway originating either from defective LDL receptors or from malfunctioning ligand apo B-100.
Apolipoprotein B-100↗
Detection of a hepatitis B virus variant with a truncated X gene and enhancer II.
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Amino Acid Sequence↗
[1,2-Bis(2-hydroxyphenyl)ethylenediamine]dichloroplatinum(II), a new compound for the therapy of ovarian cancer. II. Synthesis and preliminary testing of the enantiomeric complexes.
The enantiomeric [1,2-bis(2-hydroxyphenyl)-ethylenediamine]dichloroplatinum(II) complexes were synthesized and their configuration assessed. A preliminary test in the cisplatin-resistant human NIH:OVCAR-3 ovarian cancer cell line, which was previously characterized by its sensitivity against several therapeutically used drugs, showed that both enantiomers produce cytocidal effects in a concentration of 2.5 microM. A difference between the enantiomers became evident from the faster onset of cytocidal activity of the S,S-configurated compound.
Adenocarcinoma↗
[1,2-Bis(2-hydroxyphenyl)ethylenediamine]dichloroplatinum(II), a new compound for the therapy of ovarian cancer. III. Detailed evaluation of the antitumor activity of the enantiomeric complexes on the human NIH:OVCAR-3 ovarian cancer cell line.
The stereoisomeric [1,2-bis(2-hydroxyphenyl)ethylenediamine]dichloroplatinum(II) complexes were thoroughly tested on the cisplatin-resistant human NIH:OVCAR-3 ovarian cancer cell line. The racemate and its enantiomers produced cytocidal effects at a concentration of 2.5 microM (incubation time 256 h). The meso form, however, was merely cytostatically active. Differences between the enantiomers became evident after a short drug incubation time (1 h) followed by an incubation in drug-free medium (243 h). The S,S-configurated enantiomer (-)-3-PtCl2 proved to be the most active compound. To achieve cytocidal effects concentrations of 2.5-5.0 microM and incubation times of about 3 h were necessary for (-)-3-PtCl2. This compound is also sufficiently stable under test conditions as shown by the preincubation in cell-free medium for 3 h. These results and the augmentation of its antitumor activity by buthionine sulfoximine recommend the further preclinical development of (-)-3-PtCl2 for clinical use.
Antineoplastic Agents↗
Frequency and DNA sequence of tal-1 rearrangement in children with T-cell acute lymphoblastic leukemia.
Using nested polymerase chain reaction (PCR) a gene rearrangement named tal-1 deletion was found in five of 56 leukemic bone marrow samples from children with T-cell acute lymphoblastic leukemia (ALL). The DNA sequences of the PCR fragments consisted of the known conserved germline sequences in addition to short DNA insertions at the breakpoint region, which were different in each patient. Moreover, one patient was examined at diagnosis and at relapse 11 months later, revealing identical DNA sequences at the rearrangement site. The recombination site of the tal rearrangement therefore may be used as a genetic marker for detecting minimal residual disease in about 10% of T-cell ALL in childhood.
Base Sequence↗
Allele-specific and asymmetric polymerase chain reaction amplification in combination: a one step polymerase chain reaction protocol for rapid diagnosis of familial defective apolipoprotein B-100.
We have combined the asymmetric polymerase chain reaction (PCR) with allele-specific PCR to detect a single point mutation. A set of two priming oligonucleotides and a third allele-specific primer were used to identify heterozygotes for a G to A mutation at nucleotide 10,708 in the apolipoprotein B (apo B) gene. The system requires neither restriction enzyme digestion nor allele-specific oligonucleotides as conventionally applied for allele-specific hybridization of slot blots. This method clearly allows for the detection of the mutant allele by inspection, after agarose gel electrophoresis of a single PCR reaction. DNA from 40 patients with familial defective apo B-100 due to the G to A mutation at nucleotide 10,708 in the apo B gene and their normal relatives was analyzed. Complete agreement with allele-specific hybridization of slot blots confirms supposition that the system is effective to screen a larger population.
Alleles↗
Familial defective apolipoprotein B100: clinical characteristics of 54 cases.
Familial defective apolipoprotein B100 (FDB) is a recently identified dominantly inherited genetic disorder, which is characterized by a decreased affinity of low density lipoprotein (LDL) for the LDL receptor. FDB is caused by a G to A mutation at nucleotide 10 708 in exon 26 of the apo B gene creating a substitution of glutamine for arginine in the codon for amino acid 3500. To determine the consequences of the arginine(3500)----glutamine mutation on plasma lipid levels and other clinical features, we have investigated 54 FDB heterozygotes from Germany (24 men, 30 women, mean age 37.2 (4-73) years). The average total cholesterol level in plasma was 308 mg/dl (average LDL-cholesterol 242 mg/dl), which was 116 mg/dl (120 mg/dl) above the 50th percentile of the age and sex-matched controls reported in the LRC population studies (Lipid Research Clinics' Program 1980). Tendon xanthoma and arcus lipoides were present in 25.9% and 22.2% of the patients, respectively. Plaques in the carotid arteries, determined by duplex scanning, were present in 38.9%, and coronary artery disease was present in 22.2%. This study shows that the combination of tendon xanthoma, arcus lipoides and premature atherosclerosis is no longer totally appropriate for the diagnosis of familial hypercholesterolemia (FH). It rather seems that these features are characteristic of a defective LDL receptor pathway, which could be caused by a defective LDL receptor or a defective ligand apo B100. The distinction between FH and FDB may have therapeutic implications, because certain lipid lowering drugs act by stimulation of the LDL receptor, which has a normal function in FDB.
Adolescent↗
Narcolepsy: pathogenesis and nursing care.
Narcolepsy is a chronic, incurable disorder affecting at least a quarter of a million Americans. It is characterized by a tetrad of symptoms, which include excessive daytime sleepiness, cataplexy, sleep paralysis and hypnogogic hallucinations. Individuals may experience severe negative psychosocial consequences associated with these symptoms. The neuropathology of narcolepsy is largely unknown. Current work implicates decreased production or utilization of norepinephrine, dopamine and serotonin in the brain, and excessively numerous or hypersensitive cholinergic receptors in the brain. Medical management includes the use of separate drug therapies to control sleep attacks and cataplectic episodes. Nursing management requires comprehensive assessment of the interplay between the patient and environment and assistance with long-term coping.
Amphetamines↗
Diagnosis of familial hypercholesterolemia using DNA haplotype analysis in three large families with two hyperlipidemic parents.
Since the cloning of the human LDL receptor (LDLR) gene, familial hypercholesterolemia (FH) can be diagnosed by recombinant DNA technology either using restriction enzyme mapping to detect major rearrangements of the gene or using restriction fragment length polymorphisms (RFLPs) and linkage analysis in family studies. Genotypes and haplotypes of four RFLPs (StuI, ApaII 5', PvuII, NcoI) were used to study the inheritance of the detective LDLR gene in three families. Diagnosis of FH based on the lipid levels alone was not possible because in these kindreds both parents exhibit elevated lipid levels. However, in two families using haplotype analysis, elevated cholesterol levels in certain relatives could be attributed to the inheritance of a defective LDRL gene and thereby distinguished from hypercholesterolemia due to familial combined hyperlipidemia. In the third family where both hypercholesterolemic parents carried a defective LDLR gene, a case of homozygous FH could be excluded in a child by demonstrating the inheritance of a normal LDLR gene.
Adult↗
Fiberoptic bronchoplasty. Description of a simple adjunct technique for the management of bronchial stenosis following lung transplantation.
Bronchostenosis is a well-recognized complication of pulmonary transplantation occurring at the site of the anastomosis and occasionally spreading distally from the original site of obstruction. The management of these airway complications has relied heavily on stent placement that usually involves the use of a rigid bronchoscope and is a relatively complicated procedure in the patient requiring mechanical ventilation. Another has been the use of laser therapy in selected patients. We report three cases of postoperative bronchostenosis managed with bronchoscopically directed balloon dilatation. This relatively simple procedure performed under local anesthesia using a fiberoptic bronchoscope and a modification of the Seldinger technique for balloon placement permitted accurate and atraumatic dilatation of significant posttransplant stenosis. This technique may have potential for emergency and/or palliative management of postoperative, posttraumatic, or malignant airway obstruction.
Adult↗
[Primary hyperlipoproteinemias--pathophysiology, clinical aspects and genetics].
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Heterozygote↗
Drug-induced myocardial ischemia and acute myocardial infarction.
Myocardial infarction generally occurs in the presence of known risk factors and identifiable coronary artery disease. Atypical presentations due to therapeutic and illicit drug use are documented, however, and lead to the consideration of alternative pathophysiologic rationales for myocardial infarction. This article discusses central nervous system stimulants and other drugs that have the potential for myocardial damage and their nursing implications.
Amphetamines↗
Relationships among health beliefs, self-efficacy, and exercise adherence in patients with coronary artery disease.
Management of the pathologic progression of coronary artery disease requires life-style changes in patients, but the level of compliance with medical recommendations is low. Critical care nurses have a unique opportunity to encourage patients to assume responsibility for their health care and life-style behavior. In this study we developed a model to identify the relationships among variables that explained adherence to a recommended exercise regimen. The variables studied included self-efficacy, perceived severity, barriers, benefits, and cues to action.
Adult↗
Identification of a 76-year-old patient with compound heterozygous familial hypercholesterolemia by haplotype analysis of the LDL receptor gene.
In a large family with clinical characteristics of heterozygous familial hypercholesterolemia (FH) seven restriction fragment length polymorphisms (RFLP) were used to determine low-density-lipoprotein receptor (LDLR) gene haplotypes. Following the inheritance of the LDL receptor genes characterized by their seven RFLP haplotypes, two different alleles were found to cosegregate with elevated cholesterol levels within this family. In a 76-year-old man both alleles identified as defective were present, thus classifying this individual as heterozygous compound for FH. In five heterozygous family members one allele was associated with 38% higher cholesterol levels when compared to the other mutant allele in two heterozygous family members. Cosegregation of hypercholesterolemia with the apolipoprotein B (apoB) gene and apolipoprotein E (apoE) gene was excluded by genotyping all individuals for the apoB XbaI RFLP and apoE polymorphisms. These findings are consistent with variable phenotypic expression of the mutant LDLR gene alleles.
Aged↗
Identification of a silent point mutation in the LDL-receptor gene by direct DNA sequencing.
To study the allelic variation at the human LDL-receptor gene locus in a number of individuals with familial hypercholesterolemia, a protocol was applied for direct sequence analysis of genomic DNA. The asymmetric polymerase chain reaction (PCR) was used to synthesize single-stranded DNA. Sequencing was carried out with modified T7 DNA polymerase (Sequenase version 2.0, United States Biochemical) after purification of the amplification product with a glass powder adhesion method. The method is sensitive enough to identify the heterozygous state of allelic variation and bypasses cumbersome cloning and subcloning procedures. Here we report the occurrence of a guaninine-to-adenine change in the codon for amino acid 655. However, the glycine residue is not replaced by the base change at this position, and the mutation observed here does not represent the underlying genetic defect of the LDL-receptor defect in this individual. Preliminary data suggest that this mutation represents a rare genetic variation.
Amino Acid Sequence↗
Identification of a heterozygous compound individual with familial hypercholesterolemia and familial defective apolipoprotein B-100.
Familial defective apolipoprotein B-100 (FDB) is a recently identified dominantly inherited genetic disorder, which leads to increased serum levels of low density lipoprotein (LDL) cholesterol with reduced affinity for the LDL receptor. This genetic disorder is characterized by defective binding of the apolipoprotein B-100 (apo B-100), which is virtually the sole protein constituent of LDL, to the LDL receptor. The defective binding results from a G to A mutation at amino acid 10,708 in exon 26 of the apolipoprotein B (apo B) gene creating a substitution of glutamine for arginine in the codon for amino acid 3500. It is postulated that FDB can exhibit the same clinical features as familial hypercholesterolemia (FH) caused by a defective LDL receptor. The purpose of this paper is to report on an individual with a defective LDL and a defective LDL receptor. The clinical features of this individual were the same as in the family members with either defective LDL or a defective LDL receptor: premature arcus lipoides, tendon xanthomata, and premature atherosclerosis. Although the clinical features were present to the same degree as in individuals with either defect the prognosis and treatment of such an individual could be different.
Adolescent↗
Seeking normalcy: the experience of coronary artery bypass surgery.
The aim of this study was to describe the experience of coronary artery bypass surgery (CAB) from the patient's perspective. A grounded theory method was used to explore the postoperative experiences of eight men and one woman following CAB surgery. The major process individuals engaged in following CAB surgery was seeking normalcy which involved three conceptual stages: surviving, restoring, and being fixed. Some individuals sought other explanations for the symptoms accompanying heart disease. An understanding of patient experiences regarding the nature of cardiovascular disease through the experience of surgery regimens may contribute to the assessment and intervention strategies used by health care providers in the postoperative care of these patients.
Adaptation, Psychological↗