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C Keller

Publications and source records attributed to C Keller.

At least 19 recordsLinked to original sources
PubMed1995

Identification of the valine 408 to methionine mutation in the LDL receptor in a Greek patient with homozygous familial hypercholesterolemia.

We have identified the cytosine to thymine change in the codon for amino acid 408 which causes valine to be replaced by methionine in exon 9 of the LDL receptor gene in a 12-year-old Greek boy living in Germany, with homozygous familial hypercholesterolemia, by using polymerase chain reaction-amplified genomic DNA and subsequent restriction digestion. Homozygosity was confirmed by direct DNA sequencing. The mutation was present in both his parents, and his brother, grandmother, uncle and cousin. Six restriction fragment length polymorphisms of the LDL receptor gene were used to determine the haplotype of the defective allele. The haplotype was different from the one reported earlier in African Afrikaners and from Holland. We conclude that the mutation in the Greek boy probably occurred as an independent mutation. Because the parents are from different areas in Greece, this mutation may be common in Greeks.

Base Sequence↗
PubMed1995

Ten LDL receptor mutants explain one third of familial hypercholesterolemia in a German sample.

Mutational defects in the LDL receptor are responsible for familial hypercholesterolemia (FH); thus far more than 150 mutations have been described. Nevertheless, systematic searches among the Germans have not been conducted. We used single-strand conformational polymorphism and polymerase chain reaction to find mutations in 10 index patients and in 40 other individuals with heterozygous FH. Our screen in the 10 index patients revealed 7 hitherto undescribed mutations. A screen of the 40 additional FH patients disclosed 20 defective of 54 total alleles and allowed specific diagnoses in 88 family members. We also found two families in which the children were markedly affected by FH, but the expected parental expression of the trait was not manifest. This observation suggests a role for additional environmental and genetic influences. Our report represents the first comprehensive effort to identify FH mutations in Germany. We found 10 mutations and these mutations explain 37% of FH cases. Our data may have relevance to expected FH patterns in central Europe.

Adult↗
PubMed1992

Endotracheal tube safety during electrodissection tonsillectomy.

A case report of an endotracheal tube fire occurring during electrodissection tonsillectomy is presented. The authors believe that this incident occurred because a retrograde leak of ventilating gases around an uncuffed endotracheal tube during positive-pressure ventilation produced a high oxygen concentration in the mouth, allowing indirect ignition of the tube. In vitro testing supported this hypothesis. Ignition tests on polyvinylchloride endotracheal tubes using electrocautery in various oxygen concentrations were performed. As oxygen concentration increased, the endotracheal tube could be moved further from the cautery and still allow ignition of the tube. At 52% oxygen, with the cautery set at 25-W coagulation current, the endotracheal tube could not be ignited. Recommendations to prevent a recurrence of this incident are included.

Child↗
PubMed1992

Dichloro-[1-(hydroxyphenyl)-2-phenylethylenediamine]platinum(II) complexes: testing on the human ovarian cancer cell lines NIH: OVCAR3 and SK OV 3.

The diastereoisomeric dichloro-[1-(2-, 3- and 4-hydroxyphenyl)-2-phenylethylenediamine]platinum(II) complexes were tested on two human ovarian cancer cell lines NIH: OVCAR-3 and SK-OV-3, both resistant against cisplatin. Dichloro-[threo-1-(3-hydroxyphenyl)-2-phenylethylenediamine]platinum(II) (threo-5-PtCl2) proved to be the most active representative of the new series, producing cytocidal effects at a concentration range of 2.5 to 5.0 microM on the NIH: OVCAR-3 cell line. On the more resistant SK-OV-3 cell line, threo-5-PtCl2 was only moderately active, while in combination with BSO, a GSH level lowering compound, threo-5-PtCl2 showed a strong synergistic effect.

Adenocarcinoma↗
PubMed1992

Detection of transcriptionally active hepatitis B virus DNA in peripheral mononuclear blood cells after infection during immunosuppressive chemotherapy using the polymerase chain reaction.

Using PCR we have studied mononuclear peripheral blood leucocytes (PMBLs) from HBV-infected immunosuppressed patients in order to detect the presence of HBV genomes. Our results indicate that non-transient PMBL infection is common in immunotolerant carriers. In addition, the presence of pregenomic mRNA sequences suggests that virus replication may take place in PMBLs, possibly implicating the latter as a source of virus after replication has ceased in the liver.

Adolescent↗
PubMed1992

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↗
PubMed1992

[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↗
PubMed1992

[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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗