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K J Lackner

Publications and source records attributed to K J Lackner.

64 records · Page 4Linked to original sources
PubMed1985

Isoforms of apolipoprotein A-II in human plasma and thoracic duct lymph. Identification of proapolipoprotein A-II and sialic acid-containing isoforms.

Proapolipoprotein (apo-) A-II and several isoforms of apo-A-II including sialylated isoforms were identified in human plasma and thoracic duct lymph. Proapo-A-II secreted by HepG2 cells was identified by a combination of immunoblots and [14C]arginine incorporation. Proapo-A-II which contains 2 arginine residues could be readily differentiated from mature apo-A-II which contains no arginine. The pI of proapo-A-II is 6.79, whereas the pI of the major apo-A-II isoform in plasma and lymph is 4.90. Minor apo-A-II isoforms have pI values of 5.17, 4.68, 4.42, and 4.20, respectively. Sialoisoforms of apo-A-II were identified, which had a higher apparent molecular weight on sodium dodecyl sulfate-gel electrophoresis than the major isoform and disappeared following neuraminidase treatment. The relative quantity of proapo-A-II was relatively constant in lymph very low density lipoproteins, lymph high density lipoproteins, and plasma high density lipoproteins, whereas the sialoforms and the other minor isoforms of apo-A-II were greater in lymph very low density lipoproteins and the lowest in plasma high density lipoproteins.

Apolipoprotein A-II↗
PubMed1985

Human apolipoprotein B-100: cloning, analysis of liver mRNA, and assignment of the gene to chromosome 2.

Human apolipoprotein B-100 (apo B-100) is the major apolipoprotein of low density lipoproteins and the principal ligand for interaction with the low density lipoprotein receptor. The human apo B-100 gene has been inserted into a lambda gt-11 expression vector, and the apo B-100 cDNA clones have been identified by screening with a monospecific apo B-100 antiserum, by screening with synthetic oligonucleotides based on the amino acid sequence of peptides isolated from apo B-100, and by immunoblot analysis of the expressed protein with a monoclonal antibody to apo B-100. The complete nucleotide and derived-amino acid sequence of a 1.7-kilobase cDNA clone of apo B-100 was determined. The 560-amino acid residues of apo B-100 contain no unique linear or repeating sequences of amino acids. The computer-predicted conformation of the apo B-100 protein contains segments of helical structure; however, a large portion of the protein is organized into beta-structure. The beta-structure may be important in lipid-apo B-100 interactions in low density lipoprotein and may contribute to the insolubility of delipidated apo B-100 in aqueous buffers. RNA blot hybridization analysis of liver mRNA utilizing a Nco I/HindIII apo B-100 cDNA probe revealed that the apo B-100 mRNA is 15-18 kilobases long, which is of sufficient size to code for a 250-387 kDa apolipoprotein, the proposed molecular size of delipidated plasma apo B-100. The gene for human apo B-100 has been localized to chromosome 2 by filter hybridization of human-mouse somatic cell hybrids utilizing a 400-base-pair Nco I/HindIII apo B-100 cDNA probe. This location is in contrast to the low density lipoprotein receptor that has been localized to chromosome 19. The cloning of human apo B-100 has provided new insights into the structure and physicochemical properties of apo B-100 and will facilitate studies on the factors modulating apo B-100 biosynthesis and the expression of the apo B-100 gene in patients with dyslipoproteinemias.

Amino Acid Sequence↗
PubMed1984

Human apolipoprotein A-II: complete nucleic acid sequence of preproapo A-II.

The complete cDNA nucleic acid sequence of preproapolipoprotein (apo) A-II, a major protein constituent of high density lipoproteins, has been determined on clones from a human liver ds-cDNA library. Clones containing ds-cDNA for apoA-II were identified in the human liver ds-cDNA library using synthetic oligonucleotides as probes. Of 3200 clones screened, 4 reacted with the oligonucleotide probes. The DNA sequence coding for amino acids -17 to +17 of apoA-II were determined by Maxam-Gilbert sequence analysis of restriction fragments isolated from one of these clones, pMDB2049. The remainder of the cDNA sequence was established by sequence analysis of a primer extension product synthesized utilizing a restriction fragment near the 5'-end of clone pMDB2049 as primer with total liver mRNA. The apoA-II mRNA encodes for a 100 amino acid protein, preproapoA-II that has an 18 amino acid prepeptide and a 5 amino acid propeptide terminating with a basic dipeptide (Arg-Arg) at the cleavage site to mature apoA-II.

Adult↗
PubMed1984

The human apolipoprotein A-II gene is located on chromosome 1.

Apolipoprotein (apo) A-II is a major constituent of high density lipoproteins (HDL). The gene for apoA-II has been localized to the p21----qter region of chromosome 1 in man by Southern blot hybridization analysis of DNA from human-mouse cell hybrids using a cloned human apoA-II cDNA probe. The regional assignment was established using two hybrids carrying a reciprocal translocation involving chromosomes 1 and 2. Comparison with previously established gene loci on chromosomes 1 suggests that apoA-II may reside in a conserved linkage group with renin and peptidase C. On the other hand, apoA-II is not linked to the apoA-I gene, which has been localized previously to chromosome 11.

Animals↗
PubMed1980

[Percutaneous puncture of renal cysts for diagnostic and therapeutic purposes (author's transl)].

Percutaneous needle puncture of space-occupying lesions is an innocuous procedure in the differential diagnosis of renal masses. In conjunction with intravenous urography, ultrasonography and CT-scan it is a method of considerable diagnostic value, which will lead to a nearly complete accurate diagnosis. In this study we will report our experiences with diagnostic and therapeutic puncture of renal cysts. The instillation of Lipiodol has been given up, since a follow-up study became impossible due to radiological problems. The diagnostic procedure to differentiate expanding lesions of the kidney and the technique of percutaneous needle puncture are described as well as indications for surgical exploration.

Adult↗
PubMedDate not supplied

Mevalonate is essential for growth of porcine and human vascular smooth muscle cells in vitro.

The effects of mevalonate depletion on growth and cell cycle kinetics of porcine and human vascular smooth muscle cells (SMC) were studied by growth curves and flow cytometric determination of cell cycle distribution. Porcine and human SMC were growth arrested by serum depletion for 48 h. Subsequently, they were stimulated to maximal growth and DNA synthesis by addition of serum. There was a concentration dependent decrease in the proliferation of human and porcine SMC, when cells were incubated in the presence of fluvastatin, a new, fully synthetic HMGCoA-reductase inhibitor. The reduction of cell number was significant with 10(-5) M and 10(-4)M fluvastatin. The highest concentration induced cell loss after prolonged incubation (> 4 days). The G/S-phase transition of human and porcine vascular SMC was reduced to 50% of controls by 10(-4) M fluvastatin as revealed by cell cycle analysis. The effects of fluvastatin on growth kinetics and cell cycle distribution could be completely reversed by the addition of 1 mM mevalonolactone. This indicates that the inhibitory effect of fluvastatin is caused by the inhibition of HMGCoA-reductase and depletion of mevalonate rather than being unspecific. Addition of LDL to supply cholesterol failed to support cell growth and transition of smooth muscle cells from G(zero)/G1-phase to S-phase, even though LDL was taken up by the cells as shown by confocal fluorescence microscopy. Neither did the addition of squalene or cholesterol to the culture medium normalize cell growth. It is concluded that nonsterol products that are synthesized from mevalonate are necessary for growth of smooth muscle cells. HMGCoA-reductase inhibitors like fluvastatin block the synthesis of these nonsterol precursors in human and porcine vascular SMC in vitro and are therefore growth inhibitory.

Animals↗
PubMedDate not supplied

Results of a multicenter study of the retrievable Tulip Vena Cava Filter: early clinical experience.

PURPOSE: To evaluate clinically a new, retrievable vena caval filter in a multicenter study. METHODS: The Tulip filter is a stainless steel half-basket that is suitable for antegrade or retrograde insertion via an 8.5 Fr introducer sheath. The filter can be retrieved via the jugular approach using an 11 Fr coaxial retrieval system. Forty-eight filters were implanted via the femoral approach and 38 via the jugular approach in 83 patients. Follow-up examinations (plain films, colorcoded duplex sonography) were performed up to 3 years after filter insertion (mean 136 days) in 75 patients. Twenty-seven patients were screened by colorcoded duplex sonography for insertion site thrombosis. RESULTS: An appropriate filter position was achieved in all cases. Insertion problems occurred in 3 cases; these were not due to the filter design but to an imperfect prototype insertion mechanism that has now been modified (n = 2) or a manipulation error (n = 1). In 2 of these cases the filters were replaced percutaneously; 1 patient required venotomy for filter removal. No further complications due to filter insertion occurred. Two filters were used as temporary devices and were successfully removed after 6 and 11 days, respectively. There was 1 fatal recurrent pulmonary embolism (PE) and 2 non-fatal PE, 5 complete and 3 partial caval occlusions, and 3 caudal migrations of the filter. Insertion site venous thrombosis was not seen in the 27 patients monitored for this complication. CONCLUSION: Precise placement of the Tulip filter is feasible by either access route and the device appears mechanically stable. Further observations are needed to confirm that safe filter removal is practical up to 10 days after its insertion.

Adult↗
PubMedDate not supplied

Monitoring of peripheral blood cytotoxic T-cells under fluvastatin treatment in renal transplant recipients.

Flow cytometric T-cell analysis is capable of adding valuable information for balancing immunosuppression in transplant recipients as it can take into account individual effects of immunosuppressive drugs on each patient as well as effects of other drugs which may modify the overall immunosuppression. Studies suggest that HMG-CoA-reductase-inhibitors (statins) reduce the frequency of organ rejection, although the precise mechanism of this effect is unknown. We therefore evaluated the effect of fluvastatin on size and activation of T-cell subpopulations and NK-cell activity in renal transplant recipients. At baseline, the population size of activated (HLA-DR+) T-cells was negatively correlated to serum HDL cholesterol suggesting an increased T-cell activation at low HDL levels. Fluvastatin treatment of a hypercholesterolemic group of patients for two months significantly decreased the LDL cholesterol. A longitudinal analysis revealed a relative increase in non-MHC restricted cytotoxic T-cells (CD3+/CD16+ or CD56+) over time which was significantly attenuated in fluvastatin treated patients but not in normocholesterolemic controls. Moreover, a relative decrease of activated MHC class I-restricted cytotoxic CD8+ T-cells was only observed upon fluvastatin treatment. NK-cell number and activity did not differ between groups. In summary, fluvastatin treatment of hypercholesterolemic renal transplant recipients is associated with a specific modulation of T-cells exerting cytotoxic effector functions.

Adult↗