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Biomedical subjects

B Jorgensen

Publications and source records attributed to B Jorgensen.

At least 19 recordsLinked to original sources
PubMed2000

Relationship between novel isoforms, functionally important domains, and subcellular distribution of CD164/endolyn.

Functional analyses have indicated that the human CD164 sialomucin may play a key role in hematopoiesis by facilitating the adhesion of human CD34(+) cells to the stroma and by negatively regulating CD34(+)CD38(lo/-) cell proliferation. We have identified three novel human CD164 variants derived by alternative splicing of bona fide exons from a single genomic transcription unit. The predominant CD164(E1-6) isoform, encoded by six exons, is a type I transmembrane protein containing two extracellular mucin domains (I and II) interrupted by a cysteine-rich non-mucin domain. The 103B2/9E10 and 105A5 epitopes, which specify ligand binding characteristics, are located on the exon 1-encoded mucin domain I. Three human CD164(E1-6) mRNA species, exhibiting differential polyadenylation site usage, are differentially expressed in hematopoietic and non-hematopoietic tissues. This study provides additional evidence that human CD164(E1-6) represents the ortholog of murine MGC-24v and rat endolyn. Comparative analysis of murine MGC-24v/CD164(E1-6) with human CD164(E1-6) revealed two potential splice variants and a similar genomic structure. Whereas the human CD164 gene is located on chromosome 6q21, the mouse gene occurs in a syntenic region on chromosome 10B1-B2. By confocal microscopy, human CD164 in CD34(+)CD38(+) hematopoietic progenitor (KG1B) and epithelial cell lines appears to be localized primarily in endosomes and lysosomes, with low concentrations at the cell surface. However, in a minority of KG1B cells, CD164 is more prominently expressed at the plasma membrane and in the recycling endosomes, suggesting that its distribution is regulated in cells of hematopoietic origin.

Amino Acid Sequence↗
PubMed2000

Postexercise ischemia is associated with increased neuropeptide Y in patients with coronary artery disease.

BACKGROUND: Neurohormones may influence vascular tone both during and after exercise. Neuropeptide Y (NPY), which is costored and released with norepinephrine (NE) during sympathetic activity, is a potent vasoconstrictor with a relatively long half-life. We therefore examined its possible association with the ischemic response to exercise in patients with coronary artery disease. METHODS AND RESULTS: Twenty-nine male patients with effort-induced angina pectoris underwent a symptom-limited exercise test. In addition to conventional ST-segment analysis, we examined ischemia on the basis of heart rate (HR)-adjusted ST-segment changes through calculation of the ST/HR slope during the final 4 minutes of exercise and of the ST/HR recovery loop after exercise. Blood samples were taken before, during, and after exercise for an analysis of several neurohormones. Mean ST-segment depression was -223+/-20.2 microV (P:<0.0001) just before the termination of exercise, followed by a gradual normalization, but it remained significant after 10 minutes (-49+/-8.9 microV, P:<0.0001). At the end of exercise, the ST/HR slope, which reflects myocardial ischemia, was -6.0+/-0.77 microV/HR. In most patients, ST-segment levels at a given HR were lower during recovery than during exercise, here referred to as ST "deficit." Exercise increased the plasma levels of NPY, NE, epinephrine, and N-terminal proatrial natriuretic peptide, but big endothelin remained unchanged. Although NE and epinephrine peaked at maximal exercise, the highest levels of NPY and N-terminal proatrial natriuretic peptide were observed 4 minutes after exercise. The maximal increase in the NPY correlated significantly with ST-segment depression at 3 minutes after exercise (r=-0.61, P:= 0.0005), the ST deficit at the corresponding time point (r=-0.66, P:= 0.0001), and the duration of ST-segment depression after exercise (r= 0.42, P:=0.02). In contrast, no such correlations were found for NE. CONCLUSIONS: The present study has for the first time demonstrated a correlation between plasma NPY levels and the degree and duration of ST-segment depression after exercise in patients with coronary artery disease, which suggests that NPY may contribute to myocardial ischemia in these patients.

Analysis of Variance↗
PubMed2000

DEMS - a second generation diabetes electronic management system.

Diabetes electronic management system (DEMS) is a component-based client/server application, written in Visual C++ and Visual Basic, with the database server running Sybase System 11. DEMS is built entirely with a combination of dynamic link libraries (DLLs) and ActiveX components - the only exception is the DEMS.exe. DEMS is a chronic disease management system for patients with diabetes. It is used at the point of care by all members of the diabetes team including physicians, nurses, dieticians, clinical assistants and educators. The system is designed for maximum clinical efficiency and facilitates appropriately supervised delegation of care. Dispersed clinical sites may be supervised from a central location. The system is designed for ease of navigation; immediate provision of many types of automatically generated reports; quality audits; aids to compliance with good care guidelines; and alerts, advisories, prompts, and warnings that guide the care provider. The system now contains data on over 34000 patients and is in daily use at multiple sites.

Diabetes Mellitus↗
PubMed2000

Results and clinical implications of the CAPARES trial.

The Coronary AngioPlasty Amlodipine REStenosis Study (CAPARES) is a multicentre, double-blind, placebo controlled restenosis trial investigating the effect of amlodipine on angiographic and clinical endpoints in patients undergoing routine percutaneous transluminal coronary angioplasty (PTCA) for stable angina pectoris. A total of 635 patients were randomized to amlodipine or placebo two weeks before PTCA and were followed for four months after PTCA. There were 451 nonstented patients who completed the study with angiographic follow-up. Quantitative coronary angiography revealed that the loss in minimal luminal diameter from immediately after PTCA to the four-month follow-up was unaffected by amlodipine treatment. However, the incidence of repeat PTCA and composite clinical events were significantly lower in patients treated with amlodipine.

Amlodipine↗
PubMed1999

Luminal loss and restenosis after coronary angioplasty. The role of lipoproteins and lipids.

AIMS: Lipoproteins and lipids, especially lipoprotein(a), have been studied as risk factors for restenosis after coronary angioplasty with conflicting results. We investigated the association between serum levels of lipoprotein(a) apolipoprotein A-1, apolipoprotein B-100, total-cholesterol, high density lipoprotein-cholesterol, triglycerides, and coronary luminal loss and restenosis after angioplasty. METHODS: The lipoproteins and lipids were measured in 305 consecutive patients who underwent successful angioplasty and reangiography 20+/-3 weeks after angioplasty. Single-vessel dilatation was performed in 251 patients. Luminal loss was defined as minimal luminal diameter post-angioplasty minus minimal luminal diameter at follow-up, divided by the interpolated reference diameter of the vessel. Restenosis was defined according to three dichotomous categorical criteria: (1) >50% diameter stenosis at follow-up (2) loss of >50% of the gain achieved by angioplasty, (3) the need for target vessel revascularization. RESULTS: There was no significant association between the serum levels of lipoproteins and lipids and luminal loss. Univariate analysis did not show any significant difference in the serum levels of any of the lipoproteins and lipids between the restenosis and no-restenosis groups. Multivariate analysis revealed that only the angiographic variables (luminal gain and post-angioplasty minimal luminal diameter) were associated with luminal loss and restenosis after angioplasty. CONCLUSION: Lipoproteins and lipids were neither associated with luminal loss nor independent risk factors for restenosis after angioplasty.

Amlodipine↗
PubMed1999

Bone densitometry should be included in the evaluation of candidates for lung transplantation.

Bone loss and fractures are common complications of heart and liver transplantation, and are likely related to high-dose immunosuppressive therapy. We have previously demonstrated that many patients with end-stage lung disease already have osteoporosis and may be at even greater risk for fracture after lung transplantation. The purpose of this study is to determine the incidence of fracture in lung transplant recipients on osteoporosis prevention regimens, the relationship of fracture to pretransplant bone mineral density, and the impact of fracture on quality of life after lung transplantation. Twenty-one lung transplant candidates were prospectively evaluated with spine radiographs and bone mineral densitometry. Bone density was expressed as T scores, the number of standard deviations from the mean bone density of a young normal population of the same gender. Of 21 patients, 8 (38%) fractured during the first year. The mean pretransplant lumbar spine T score was significantly lower in the fracture patients (P = .03). Four of the 7 surviving fracture patients and 1 of the 10 patients who survived without fracture believed that chronic pain diminished their quality of life (X2 = 4.408; P = .04). These findings suggest that bone mineral density should be routinely included in the evaluation of lung transplant candidates. Patients with extremely low bone density or osteoporotic fracture should be counseled about the increased risk of fracture after transplantation.

Absorptiometry, Photon↗
PubMed1998

Preliminary experience with mycophenolate mofetil used after lung transplantation.

This study reports our preliminary experience with mycophenolate mofetil (MMF)-based immune suppression after lung transplantation. Thirteen patients (group 1) received MMF as primary therapy immediately after transplantation. Use of MMF was associated with a linearized rate of 0.85 episodes of acute rejection per 100 patient days during the first 3 months after transplantation, as compared with rates of 1.49 and 1.38, observed in two groups of historical control subjects (p = .094 and p = .053, respectively). Rejection rates after the first 3 months were not lower than in historical control subjects. Nine additional patients were switched from azathioprine to MMF because of recurrent episodes of high-grade acute rejection (group 2). In this group, the linearized rate of acute rejection episodes declined significantly (p = .004) after initiation of MMF therapy. These data suggest a potential role for MMF in reducing the rate of acute rejection episodes after lung transplantation.

Azathioprine↗
PubMed1995

Activation of src-related tyrosine kinases by IL-3.

The activation of src-related tyrosine kinases following IL-3 stimulation was examined in 32Dcl3 cells. Three src-related tyrosine kinases were activated following IL-3 stimulation: fyn, hck, and lyn. 32Dcl3 cells were transfected with retroviral vectors expressing each of these kinases and independent clones overexpressing each kinase were isolated. In cells overexpressing either fyn or hck, IL-3 stimulated a rapid increase in catalytic activity, which remained elevated longer compared with the kinetics observed in parental 32Dcl3 cells. An increase in the number of tyrosine-phosphorylated proteins in the presence and absence of IL-3 stimulation was observed in cells overexpressing fyn or hck. Transfection of 32Dcl3 cells with a retroviral vector encoding lyn also resulted in an elevated level of kinase activity, although the increase was not as dramatic as that observed with fyn or hck. Consistent with observations in parental 32Dcl3 cells, a high basal level of lyn kinase activity was observed in unstimulated lyn-transfected cells and IL-3 stimulation resulted in an approximate threefold increase in kinase activity. Overexpression of c-src in 32Dcl3 did not result in IL-3-stimulated activation of c-src, indicating specificity for fyn, hck, and lyn. While the overexpression of fyn, hck, or lyn in 32Dcl3 cells resulted in increased kinase activity and IL-3 stimulated tyrosine phosphorylation, it did not render the cells more sensitive to IL-3. These results suggests that in addition to the JAK2 tyrosine kinase, src-related kinases may play a significant role in signal transduction by cytokine receptors.

Animals↗
PubMed1995

Differential stability of HLA-DR alleles independent of endogenous peptides.

Purified HLA DRB1*0101 was shown to be inherently more stable to dissociation than DRB1*0401. The residues responsible for the differential stability were defined by constructing hybrid molecules, which contained a small number of residues from DRB1*0101 substituted into the framework of DRB1*0401. One of the hybrid molecules, containing six substituted amino acids, was as stable as DRB1*0101, but exhibited the binding specificity of DRB1*0401. This result indicated that the differential stability between the alleles arose from structural differences, and was not due solely to varying populations of endogenous peptides.

Alleles↗
PubMed1994

Role of the polymorphic residues in HLA-DR molecules in allele-specific binding of peptide ligands.

Analysis of peptide binding to a set of HLA-DR alleles has allowed the proteins to be segregated into functional subsets, depending on the amino acids at positions 57 and 86 of the beta-chain. DR proteins with glycine at 86 beta and aspartic acid at 57 beta bound a simplified peptide with significantly lower IC50 values than alleles that did not have this combination of amino acids. The size of the amino acid at 86 beta seemed to modify the steric requirements for the single most important side chain of the peptide. Within each of the four subgroups, other polymorphic amino acids define allele-specific binding requirements. These were explored by analyzing the ability of eight different DR alleles to bind 13 known T cell determinants. The side chains in the peptides that seemed to be responsible for allele specificity were determined by correlating their common structural features with complementary polymorphic residues in the binding site. The importance of these residues was tested by incorporating them into a polyalanine backbone, and was confirmed by the ability of these residues to transfer allele specificity to these simplified analogues. Even though polymorphic contacts affected peptide affinity, the majority of the free energy of binding in all cases arose from interactions with the peptide backbone and the single hydrophobic amino acid at the third position. These constraints seem to orient all peptides in a similar location, forcing them to adopt a closely related conformation in the binding site. The corresponding side chain in each peptide contacts the same pocket in the binding site, regardless of the allele. This apparent similarity should allow any DR allele to be analyzed by extrapolation from the DR1 crystal structure.

Alleles↗
PubMed1994

Exploration of requirements for peptide binding to HLA DRB1*0101 and DRB1*0401.

The individual amino acid contacts responsible for peptide binding to DRB1*0101 and/or DRB1*0401 were defined using a quantitative binding assay. The differential contribution of each amino acid in two well studied T cell determinants, HA307-319 and RMBP 90-102, was delineated by comparing the IC50 values of analogues of varying length. This analysis confirmed the importance of a hydrophobic amino acid located near the amino-terminus for binding to both alleles and revealed that the contribution of the carboxyl-terminal amino acids differed between DRB1*0101 and DRB1*0401. Taking advantage of previous experiments demonstrating that all of the residues could be replaced with alanine, with the exception of the key hydrophobic amino acid, simplified analogues composed of polyalanines were used to prove 1) optimal binding depended on the position of the hydrophobic side chain relative to the amino- and carboxyl-termini; 2) aromatic amino acids were superior to aliphatic side chains at this position; and 3) a significant amount of free energy of binding arises from hydrogen bonding between the class II binding site and the amide bonds of the ligand. The role of each carbonyl and amide nitrogen was measured by assaying analogues containing reduced peptide bonds or N-methyl amino acids. Serine, but not glycine, could be used as a framework amino acid for peptide ligands, indicating that the beneficial aspects of these simplified structures was the combination of retaining the correct orientation of the peptide bonds, the restriction of the conformational freedom by limiting the possible phi/psi angles of the peptide, and avoidance of deleterious side-chain contacts. Collectively, these data were consistent with the peptide binding in a nonrepeating conformation with the vast majority of the free energy of binding arising from hydrogen bonds with the peptide backbone and a single, key hydrophobic side chain interacting in a conserved pocket in both DRB1*0101 and DRB1*0401.

Amino Acid Sequence↗
PubMed1977

The 600 gram CO2 absorption canister: an experimental study.

Model investigations were performed on a canister containing 600 g of Sodasorb indicator soda lime in a transparent lime compartment used in the Hafnia circle. The CO2 input was 300 ml per min. Carbon dioxide will be efficiently eliminated from the gas mixture conveyed to the patient connection in this system for at least 4 h, irrespective of the rate of fresh gas flow. There was proportionality between the fresh gas inflow and the duration of effective CO2 elimination. The relative efficacy of the CO2 absorption was investigated at different levels in the canister. The temperature in the axis of the lime compartment was 43-52 degrees C, and the temperature of the gas mixture conveyed to the patient attachment 30-35 degrees C. The colour shift in the lime charge was a reliable indicator of the efficiency of CO2 elimination. The canister should be replaced when the colour shift has progressed to 2/3 of the lime charge. The canister contains no disposable parts except for the lime charge. All the components of the circle system should be taken apart and cleaned after each anaesthesia.

Absorption↗