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Biomedical subjects

S Frank

Publications and source records attributed to S Frank.

At least 127 records · Page 7Linked to original sources
PubMed1994

Quantitative trait locus analysis of susceptibility to diet-induced atherosclerosis in recombinant inbred mice.

Quantitative trait locus (QTL) analysis is a statistical method that can be applied to identify loci making a significant impact on a phenotype. For the phenotype of susceptibility to diet-induced atherosclerosis in the mouse, we have studied four quantitative traits: area of aortic fatty streaks and serum concentrations of high-density lipoprotein-bound cholesterol (HDL-cholesterol), apolipoprotein A-I, and apolipoprotein A-II (apo A-II). QTL analysis revealed a significant locus on chromosome 1 distal impacting serum apo A-II concentration on a high-fat diet and serum HDL-cholesterol concentration on a chow diet. This locus is presumably Apoa-2, the structural gene for apo A-II. QTL analysis of aortic fatty streaks failed to reveal a significant locus.

Animals↗
PubMed1994

Single-stage repair of distal aortic arch and thoracoabdominal dissecting aneurysms using aortic tailoring and circulatory arrest.

The adjuncts of profound hypothermic circulatory arrest and aortic tailoring are combined with standard graft replacement of the noncritical portions of the aorta. This combination permits single-stage replacement of the arch, thoracic, and abdominal aorta in patients with postdissection aneurysm. Reconstruction is begun with repair of the mid to distal aortic arch and Dacron graft replacement of the proximal descending thoracic aorta, usually under profound hypothermic circulatory arrest. The proximal graft is then cannulated and the patient partially warmed while the middle segment is "tailored." Aortic tailoring consists of longitudinal aortotomy and removal of the dissection membrane(s) from the distal third of the descending thoracic aorta to below the renal arteries. The aorta is then closed creating a single channel 2 to 3 cm in diameter and containing the origins of the important intercostal, lumbar, and visceral arteries. A Dacron graft is used to replace the infrarenal segment. Five patients have successfully undergone single-stage, total repair of the aorta including the arch, thoracic, and abdominal segments. All survival without paraplegia or significant visceral ischemia. Follow-up has not shown dilatation of the tailored segment. We believe that reduction in diameter of the tailored aortic segment and thus wall tension, growth of neointima on all luminal aortic surfaces, and active collagen deposition contribute to the success of this procedure.

Adult↗
PubMed1994

Psoralen-fatty acid cycloadducts activate protein kinase C (PKC) in human platelets.

The C4-photocycloadduct psoralen-linolenic acid activates protein kinase C (PKC), in human platelets, which in turn phosphorylates 47 kDa protein, representing its major substrate in these cells. This behaviour is similar to that shown by diacylglycerol, a main second messenger responsible of various biological effects, e.g. of melanogenesis.

Aspirin↗
PubMed1994

The role of lecithin: cholesterol acyltransferase for lipoprotein (a) assembly. Structural integrity of low density lipoproteins is a prerequisite for Lp(a) formation in human plasma.

The composition of lipoproteins in the plasma of patients with LCAT deficiency (LCAT-D) is grossly altered due to the lack of cholesteryl esters which form the core of normal lipoproteins. When plasma from LCAT-D patients and their relatives was examined we found that nine heterozygotes had plasma Lp(a) levels of 2-13 mg/dl whereas none of 11 affected homozygous individuals from different families contained detectable amounts of Lp(a) in their plasma. Therefore, the binding of apo(a) to LDL density particles was studied in vitro using LDL density fractions prepared from patients, and recombinant apo(a) [r-apo(a)], which was expressed and secreted by transfected COS-7 cells. The LDL from heterozygotes were chemically indistinguishable from normal LDL and homogeneous with regard to morphology, whereas the crude LDL floating fraction from homozygotes consisted of a heterogeneous mixture of large vesicles, and small spheres resembling normal LDL. The LDL density fraction from the LCAT-D patient lacked almost completely cholesteryl esters. Incubation of LCAT-D plasma with active LCAT caused a substantial augmentation of the original subfraction which morphologically resembled normal LDL. Using r-apo(a) and normal LDL or LDL of heterozygous individuals, apoB:r-apo(a) complexes were formed when incubated at 37 degrees C in vitro for 20 h. In contrast, the total LDL floating fraction from a homozygous LCAT-D patient failed to form apoB:r-apo(a) complexes. After treatment with active LCAT, a significant apoB:r-apo(a) association was observed with LCAT-D LDL-density particles. Our data emphasize the importance of the integrity of LDL structure and composition for the formation of Lp(a). In addition, we demonstrate that the absence of LCAT activity has a fundamental impact on the regulation of plasma Lp(a) levels.

Apolipoproteins A↗
PubMed1994

Pyrroloquinolinone methylderivatives, furocoumarin analogues: interaction with biomolecules and computer-aided studies.

Pyrroloquinolinones, furocoumarin analogues, contain a divinilbenzene moiety, suggesting possible photoreactivity. Quantum mechanics calculations indicate that the pyrrole-side double bond exhibits strong photoreactivity, while the pyridone-side double bond is only poorly photoreactive. Intercalation models obtained by molecular mechanics calculations suggest that, in the cis-syn intercalation arrangement, the pyridone-side double bond is well aligned with the nearby thymine, supporting possible C4-cycloaddition with the 5,6 double bond of thymine, while the pyrrole-side double bond assumes an unfavourable position for photobinding. These data suggest that photoreaction between the pyridone-side and thymine double bonds may takes place, although with very low yield. Experimental evidence concerning DNA-photobinding exhibited by 2,6-dimethyl-9-methoxy-4H-pyrroloquinolinone (Compound I) confirms theoretical predictions. The formation of C4-cycloadducts between the pyridone side double bond and thymine also takes place with very low yield. Compound I shows marked BSA photobinding, suggesting that pyrroloquinolinones may photoreact with proteins. The three pyrroloquinolinones examined show high yields of singlet oxygen generation, suggesting that photobiological effects may be obtained through this photodynamic pathway, rather than through DNA photobinding.

Base Sequence↗
PubMed1994

[Improvement of storage capability of blood by the use of biocompatible absorbents].

A new filtration method for leucocyte and chloride ion depletion of erythrocyte concentrates in one step by DEAE cellulose was developed. After passage of the packed red cells through this filter material a chloride depletion of 70-80% and a leucocyte depletion of 90% could be reached. The 25 degrees C storage of this in-line-filtered red cells characterized by metabolic parameters (ATP, 2,3-DPG) suggests the possibility of a long-term red blood cell storage.

Absorption↗
PubMed1993

Voltage-sensitive magnetic gels as magnetic resonance monitoring agents.

Many polymer gels undergo a volume phase transition in electric fields. We report here the synthesis of a polyelectrolyte gel that incorporates magnetic particles of iron oxide into the polymer network; these particles couple the gel volume transition to the NMR relaxation times of the surrounding water. We find that the water proton relaxation rates (T2(-1)) in aqueous suspensions of particles of the magnetic gel increase significantly in an electric field. Such changes can also be induced by the hyperpolarization of red blood cells in the suspension, presumably as a result of the electric fields at the cell membrane surfaces. These gels may play a part in magnetic resonance imaging analogous to that of voltage-sensitive dyes in optical imaging.

Animals↗
PubMed1993

Clinician assessment of psychiatric comorbidity and alcoholism severity in adult alcoholic inpatients.

Although psychiatric comorbidity and alcoholism severity are risk factors for poor outcomes in treating alcoholism, little is known about whether clinicians assess these conditions accurately. In this study we evaluated four clinicians' assessments of two indicators of alcoholism severity and three psychiatric co-morbidities in 78 inpatients in their third to seventh day of hospitalization in alcohol treatment programs. Clinicians overestimated the number of days drinking in 28% of subjects, and the number of drinks per drinking day in 37% of subjects. Clinicians underestimated alcohol consumption for patients with higher incomes. Clinicians correctly diagnosed 67% of 18 subjects with antisocial personality disorder, 65% of 26 with major depression, and 89% of 28 with drug abuse. These preliminary results need to be replicated in larger samples of clinicians to determine whether interventions are needed to improve the recognition of important prognostic factors in the treatment of alcoholic patients.

Adult↗
PubMed1992

Determination of the coding capacity of the BamHI DNA fragment B of apathogenic Herpes simplex virus type 1 strain HFEM by DNA nucleotide sequence analysis.

Herpes simplex virus type 1 (HSV-1) strain HFEM acquired an apathogenic phenotype due to a deletion within the DNA sequences of the BamHI DNA fragment B of the viral genome. In order to investigate the coding strategy of this particular region of the genome of HSV-1 strain HFEM the DNA nucleotide sequence of the BamHI DNA fragment B was determined. This analysis revealed that the BamHI DNA fragment B of HSV-1 strain HFEM comprises 6593 bp, corresponding to the nucleotide positions (np) 113322 to 117088 and np 120643 to 123465 of the genome of HSV-1 strain 17. According to these data the deletion of the genome of HSV-1 strain HFEM occurred between the np 117089 and 120642. The promoter region of the UL56 gene of HSV-1 strain HFEM is a part of the deleted DNA sequences. Therefore, this gene of HSV-1 strain HFEM is affected and cannot be expressed. The first 35 amino acid (AA) residues of the deduced amino acid sequence of the UL56 open reading frame (ORF) were found to be identical to the amino acid sequence of the UL56 genes of HSV-1 strains 17 and F. However, due to a deletion at np 3494 of the BamHI DNA fragment B of HSV-1 strain HFEM the amino acid composition of the predicted UL56 gene of HSV-1 strain HFEM is different from HSV-1 strain 17 between amino acid positions 36 and 233. In addition the deduced amino acid sequence of the IRL (inverted repeat of the long segment) copy of the IE110 gene of HSV-1 strain HFEM was found to be about 342 amino acids shorter than the amino acid sequence of IE110 gene of HSV-1 strain 17 (775 AA). This was based on a point mutation which was detected within the DNA sequences of Exon 3 of this copy of IE110 gene of HSV-1 strain HFEM.

Amino Acid Sequence↗
PubMed1991

Preventive medicine in primary care. Moving from theory to practice.

Primary care physicians are in a unique position to offer preventive services. They have access to patients when intervention may be most successful, and they see most patients over a long period, which allows for adequate follow-up. The challenges are choosing the most effective interventions and organizing records and office staff to facilitate delivery of preventive services. Preventive medicine may not be as dramatic or as immediately successful as curative medicine, but it can have a tremendous long-term impact on health and well-being.

Humans↗
PubMed1991

Inhibition of proteolysis protects hippocampal neurons from ischemia.

Intense proteolysis of cytoskeletal proteins occurs in brain within minutes of transient ischemia, possibly because of the activation of calcium-sensitive proteases (calpains). This proteolytic event precedes overt signs of neuronal degeneration, is most pronounced in regions of selective neuronal vulnerability, and could have significant consequences for the integrity of cellular function. The present studies demonstrate that (i) the early phase of enhanced proteolysis is a direct response to hypoxia rather than other actions of ischemia, (ii) it is possible to pharmacologically inhibit the in vivo proteolytic response to ischemia, (iii) inhibition of proteolysis is associated with a marked reduction in the extent of neuronal death, and (iv) protected neurons exhibit normal-appearing electrophysiological responses and retain their capacity for expressing long-term potentiation, a form of physiological plasticity thought to be involved in memory function. These observations indicate that calcium-activated proteolysis is an important component of the post-ischemic neurodegenerative response and that targeting this response may be a viable therapeutic strategy for preserving both the structure and function of vulnerable neurons.

Animals↗
PubMed1990

Localization and evolution of two human phospholipase A2 genes and two related genetic elements.

Mammals are now known to contain at least two distinct classes of phospholipases A2, the progenitors of which can be seen in the venoms of snakes. Mammalian "Type I" PLA2, synthesized primarily by the pancreas, is also present in smaller amounts in other tissues including lung, spleen, and kidney. Recently, a mammalian "Type II" PLA2 has been sequenced, and shown to occur in platelets, synovial cells and fluid, cells of inflammatory peritoneal exudate, liver, intestine, kidney, and placenta. This form, referred to here as Type IIA PLA2, could play a key role in arachidonate release in both normal and pathologic inflammation. The genes encoding both forms have also been recently cloned. Here, the sites of synthesis and respective roles of the two known enzymes are discussed, along with an analysis of the evolutionary conservation of Type IIA PLA2 gene sequence. In addition, two related genetic elements containing sequences homologous to a portion of Type II PLA2 are described, which map to the same chromosome as the Type IIA PLA2 gene (chromosome 1). Either or both of these could also encode a portion of additional mammalian PLA2s.

Amino Acid Sequence↗
PubMed1990

Effect of exercise on propranolol pharmacokinetics.

The effect of submaximal exercise on the pharmacokinetics of low dose intravenous propranolol was studied in 15 healthy human subjects. There was a wide individual variation in the results for each subject and a large difference in the degree of changes with exercise. The effect of exercise on the pharmacokinetics of propranolol, a flow limited drug, is marked but variable. This phenomenon may have profound effects on patients taking the drug regularly who exercise intermittently and drug doses may have to be adjusted.

Adult↗
PubMed1990

Detection of the trans activity of the plum pox virus NIa-like protease in infected plants.

The NIa-like protein of plum pox virus is a protease with high sequence specificity that is autocatalytically released from the viral polyprotein. In order to determine whether the protease is active in trans we constructed a fusion protein consisting of the C-terminal region of the plum pox virus polyprotein and the staphylococcal Protein A. The authentic protease recognition sequence Asn-Val-Val-Val-His-Gln-Ala occurs in the centre of this protein fusion. This protein was cleaved specifically by extracts of plum pox virus-infected plants due to the strong activity of the viral protease making it a useful tool for diagnostic purposes.

Amino Acid Sequence↗