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Biomedical subjects

G Lund

Publications and source records attributed to G Lund.

At least 19 recordsLinked to original sources

Inhibition of rBet v 1-induced basophil histamine release with specific immunotherapy -induced serum immunoglobulin G: no evidence that FcgammaRIIB signalling is important.

BACKGROUND: Human basophils and mast cells express the low-affinity immunoglobulin (Ig)G receptor FcgammaRIIB. It has previously been shown in artificial model systems that cross-linking of the high-affinity IgE receptor FcepsilonRI and FcgammaRIIB leads to inhibition of FcepsilonRI signalling. OBJECTIVE: The aim of the present study was to investigate whether cross-linking of FcepsilonRI and FcgammaRIIB contributes to IgG-mediated inhibition of histamine release in human basophils in a system using the sera from specific immunotherapy (SIT) patients and the major allergen from birch pollen, Bet v 1. As IgG4 furthermore has been proposed to have special blocking properties, we investigated the significance of IgG subclass specificity for this inhibition. METHODS: Binding of recombinant Bet v 1-IgG complexes to FcgammaRII and IgG-binding activities in the sera from 25 birch pollen-allergic patients treated with SIT were measured using (125)I-rBet v 1. Inhibition of basophil histamine release was assessed by incubating washed leucocytes with complexes of rBet v 1-IgG with or without blocking of FcgammaRII. RESULTS: We observed low binding of rBet v 1-IgG complexes to FcgammaRII, which was negatively correlated with the relative IgG4-binding activities. Blocking of FcgammaRII did not reverse the SIT-IgG-induced inhibition of basophil histamine release. However, IgG-binding activities correlated significantly with the ability of the SIT sera to inhibit basophil histamine release. CONCLUSION: We suggest that at least in birch pollen SIT, the contribution of FcgammaRIIB-mediated inhibitory signalling to SIT-IgG-induced inhibition of human basophil histamine release is of minor importance. The main contributor to the inhibitory effect of SIT-induced IgG seems to be blocking of the allergen-IgE interaction.

Allergens↗

Magnetic resonance characterization of the peri-infarction zone of reperfused myocardial infarction with necrosis-specific and extracellular nonspecific contrast media.

BACKGROUND: Because ischemically injured myocardium is frequently composed of viable and nonviable portions, a method to discriminate the two is useful for clinical management. METHODS AND RESULTS: Ischemically injured myocardium was characterized with extracellular nonspecific (Gd-DTPA) and necrosis-specific (mesoporphyrin) MR contrast media in rats. Relaxation rates (R1) were measured on day 1 and day 2 by inversion-recovery echoplanar imaging. Spin-echo imaging was used to define contrast-enhanced regions and regional wall thickening. Gadolinium concentration, area at risk, and infarct size were measured at postmortem examination. DeltaR1 ratio (DeltaR1(myocardium)/DeltaR1(blood)) after administration of Gd-DTPA was greater in ischemically injured myocardium (1.20+/-0.15) than in normal myocardium (0.47+/-0.05, P<0.05), which was attributed to differences in gadolinium concentration and water content. The Gd-DTPA-enhanced region on day 2 was larger (32.8+/-0.9%) than true infarction as demonstrated by triphenyltetrazolium chloride (TTC) (24.6+/-1.4%, P<0.001, r=0.21). Bland-Altman analysis revealed that the Gd-DTPA-enhanced region overestimated true infarct size by 7.8+/-5.9%. On the other hand, the mesoporphyrin-enhanced region (26.9+/-1.8%, P=NS, r=0.87) and true infarct size were identical. The difference in the areas demarcated by the 2 agents is the peri-infarction. Systolic and diastolic MR images revealed no wall thickening in the mesoporphyrin-enhanced region (0.3+/-3.3%) but reduced thickening in the Gd-DTPA-enhanced rim (8.5+/-5.5%, P<0.05). CONCLUSIONS: The Gd-DTPA-enhanced region encompasses both viable and nonviable portions of the ischemically injured myocardium. The Gd-DTPA-enhanced area overestimated infarct size, but the mesoporphyrin-enhanced area matched true infarct size. The salvageable peri-infarction zone can be characterized with double-contrast-enhanced and functional MR imaging; the mismatched area of enhancement between the 2 agents shows residual wall thickening.

Animals↗

Accuracy of segmented MR velocity mapping to measure small vessel pulsatile flow in a phantom simulating cardiac motion.

The purpose of this study was to investigate the accuracy of conventional, segmented, and echo-shared MR velocity mapping sequences to measure pulsatile flow in small moving vessels using a phantom with simulated cardiac motion. The phantom moved either cyclically in-plane, through-plane, in- and through-plane, or was stationary. The mean error in average flow was -2% +/- 3% (mean +/- SD) for all sequences under all conditions, with or without background correction, as long as the region of interest (ROI) size was equal to the vessel cross-sectional size. Overestimation of flow as a result of an oversized ROI was less than 20%, and independent of field of view (FOV) and matrix, as long as the offset in angle between the imaging plane and flow direction was less than 10 degrees. Segmented velocity mapping sequences are surprisingly accurate in measuring average flow and render flow profiles in small moving vessels despite the blurring in the images due to vessel motion. J. Magn. Reson. Imaging 2001;13:722-728.

Blood Flow Velocity↗

Myocardial viability: magnetic resonance assessment of functional reserve and tissue characterization.

The determination of myocardial viability is crucial in patients with left ventricular dysfunction resulting from acute myocardial ischemia or chronic coronary artery disease. Viable myocardium will most likely benefit from revascularization procedures. However, the revascularization of scar tissue will not lead to improvement of ventricularfunction andfurthermore bears unnecessary riskfor the patient. Currently, echocardiographic and radionuclide techniques are the most established methods for the assessment of presence and extent of viable myocardium. Magnetic resonance imaging (MRI) also provides multiple approaches for determining viability of acute ischemically injured and hibernating myocardium. MRI can assess contractile reserve in a manner similar to echocardiography. Additionally, contrast-enhanced MRI can characterize myocardial ischemic injury, including the ability to discriminate viable from nonviable zones. Several new contrast media have been introduced for this purpose. This review addresses the progress toward the goal of defining myocardial viability based on MR techniques and focuses on the current and future role of MR in the assessment of viable myocardium.

Cell Membrane↗

Blocking antibodies induced by specific allergy vaccination prevent the activation of CD4+ T cells by inhibiting serum-IgE-facilitated allergen presentation.

Allergen-specific CD4+ T lymphocytes are activated at extremely low allergen concentrations in vivo as a result of serum-facilitated allergen presentation (S-FAP). It is not clear at present if specific allergy vaccination (SAV) has an effect on this mechanism. Here we show that birch allergen-specific serum-IgE facilitates the presentation of Bet v 1, the major birch pollen allergen, to Bet v 1-specific CD4+ T lymphocytes by a factor of >100. This process is CD23 mediated, could be detected in sera from the majority of birch-allergic patients, and was clearly dose dependent. S-FAP of Bet v 1 was inhibited in patients undergoing long-term birch SAV, but not by sera from patients undergoing grass SAV, indicating that birch-specific Abs are involved. This resulted in decreased proliferation and IL-4, IL-5, IL-10, and IFN-gamma production of Bet v 1-specific T cells. The inhibition was already noted after 3-9 mo of SAV and could not be solely explained by increased serum levels of birch-specific IgG4. When IgG- and IgA/IgM-containing fractions of long-term SAV sera were used to inhibit S-FAP, only IgG-containing fractions were shown to inhibit S-FAP. These results indicate that blocking IgG Abs induced by SAV inhibits the occurrence of S-FAP at very low allergen concentrations, resulting in significantly higher allergen threshold levels to obtain T cell proliferation and cytokine production and thus allergen-induced late-phase responses.

Allergens↗

Nonsurgical reconstruction of thoracic aortic dissection by stent-graft placement.

BACKGROUND: The treatment of thoracic aortic dissection is guided by prognostic and anatomical information. Proximal dissection requires surgery, but the appropriate treatment of distal thoracic aortic dissection has not been determined, because surgery has failed to improve the prognosis. METHODS: We prospectively evaluated the safety and efficacy of elective transluminal endovascular stent-graft insertion in 12 consecutive patients with descending (type B) aortic dissection and compared the results with surgery in 12 matched controls. In all 24 patients, aortic dissection was diagnosed by magnetic resonance angiography. In each group, the dissection involved the aortic arch in 3 patients and the descending thoracic aorta in all 12 patients. With the patient under general anesthesia, either surgical resection was undertaken or a custom-designed endovascular stent-graft was placed by unilateral arteriotomy. RESULTS: Stent-graft placement resulted in no morbidity or mortality, whereas surgery for type B dissection was associated with four deaths (33 percent, P=0.09) and five serious adverse events (42 percent, P=0.04) within 12 months. Transluminal placement of the stent-graft prosthesis was successful in all patients, with no leakage; full expansion of the stents was ensured by balloon inflation at 2 to 3 atm. Sealing of the entry tear was monitored during the procedure by transesophageal ultrasonography and angiography, and thrombosis of the false lumen was confirmed in all 12 patients after a mean of three months by magnetic resonance imaging. There were no deaths or instances of paraplegia, stroke, embolization, side-branch occlusion, or infection in the stent-graft group; nine patients had postimplantation syndrome, with transient elevation of C-reactive protein levels and body temperature plus mild leukocytosis. All the patients who received stent-grafts recovered, as did seven patients who underwent surgery for type B dissection (58 percent) (P=0.04). CONCLUSIONS: These preliminary observations suggest that elective, nonsurgical insertion of an endovascular stent-graft is safe and efficacious in selected patients who have thoracic aortic dissection and for whom surgery is indicated. Endoluminal repair may be useful for interventional reconstruction of thoracic aortic dissection.

Adult↗

Contrast-enhanced MRI for quantification of myocardial viability.

During the past 10 years substantial advances have taken place in magnetic resonance imaging (MRI) capabilities and in contrast media development. Furthermore, knowledge of in vivo contrast media interactions with surrounding water and distribution into tissue has increased, permitting regional quantification of concentration-time profiles in the myocardium. The combination of these advances has substantially improved the capability of contrast-enhanced MRI characterization of myocardial ischemic injury, including its ability to discriminate viable from nonviable zones. Discrimination of viable from nonviable myocardial subregions is important for patient management and for research applications. This review addresses recent progress toward the goal of defining viable and nonviable myocardium based on MRI detection of contrast media effects. J. Magn. Reson. Imaging 1999;10:694-702.

Animals↗

Growth and the distal tip of mouse chromosome 7.

This review concerns the general problem of understanding growth control in the whole organism, starting with a saltatory change in size generated by a chromosome translocation or a mutation in a single gene. In particular, changes in insulin-like growth factor-II levels, by genetic and embryological manipulation, have major effects on wet weight size, but the intermediary events that link these levels to this measure of growth are uncertain. Thus it is currently impossible to eliminate any of the intermediary candidate processes that have been observed in model systems, including changed rates of apoptosis, cell multiplication, protein synthesis, capillary permeability and fluid transport.

Animals↗

Endosperm-specific demethylation and activation of specific alleles of alpha-tubulin genes of Zea mays L.

We have investigated the methylation status of the alpha-tubulin genes, and the degree of accumulation of their mRNAs in endosperm, embryo and seedling tissues of Zea mays L. We have found that many of the alpha-tubulin genes are differentially demethylated in the endosperm relative to the embryo and seedling. However, only for tub alpha 2 and tub alpha 4 could a correlation between DNA demethylation and increased RNA accumulation be detected. By analyzing the inbred lines W64A and A69Y and their reciprocal crosses, we have also identified in the endosperm two alpha-tubulin genes, tub alpha 3 and tub alpha 4, that are differentially demethylated if transmitted by the maternal germline, but that remain hypermethylated when transmitted by the paternal germline.

Alleles↗

Maternal-specific demethylation and expression of specific alleles of zein genes in the endosperm of Zea mays L.

Zeins constitute 60-70% of maize endosperm protein. Zein genes are specifically transcribed in the endosperm, and a correlation has been established between tissue-specific expression and demethylation. Three inbred lines and their reciprocal crosses were analysed to assess for allele-specific differences in methylation, transcription and translation. DNAs from endosperm, embryo and seedling tissues analysed by cleavage with methylation-sensitive restriction enzymes and Southern blot hybridization with zein cDNA and genomic sequences show that specific demethylation of zein sequences occurs only in endosperm and is restricted to the maternal complements. Steady-state transcript accumulation of zein mRNA assessed by RNase protection assay reveals qualitative and quantitative differences among endosperm RNAs of the inbreds and of their reciprocal hybrids. Moreover, two-dimensional gel electrophoresis of zein proteins identified polypeptides that are maternally imprinted in reciprocal crosses. These results indicate that endosperm-specific expression of specific zein alleles may occur via parental imprinting and disclose a possible role of methylation in regulating the expression of genes differently contributed in the endosperm by the maternal and paternal genomes.

Alleles↗

Treatment of renal cell carcinoma in von Hippel-Lindau disease: a multicenter study.

A total of 65 patients with von Hippel-Lindau disease underwent surgery for renal cell carcinoma (54 bilaterally and 11 unilaterally) at 8 medical centers. Only 1 patient presented with metastatic disease. Radical nephrectomy and nephron sparing surgery were performed in 16 and 49 patients, respectively. Mean posttreatment followup was 68 months. The 5 and 10-year cancer-specific survival rates for all patients were 95% and 77%, respectively. The corresponding rates for patients treated with nephron sparing surgery were 100% and 81%, respectively. Of the latter patients 25 (51%) had postoperative local tumor recurrence but only 2 had concomitant metastatic disease. Survival free of local recurrence was 71% at 5 years but only 15% at 10 years. End stage renal failure occurred in 15 patients (23%): 6 underwent renal transplantation (5 are alive with satisfactory renal function and no evidence of malignancy) and 9 were treated with chronic dialysis (6 are free of tumor). Our results indicate that nephron sparing surgery can provide effective initial treatment for patients with renal cell carcinoma and von Hippel-Lindau disease. These patients must be followed closely, since most will eventually have locally recurrent renal cell carcinoma. When removal of all renal tissue is necessary to achieve control of malignancy, renal transplantation can provide satisfactory replacement therapy for end stage renal disease.

Adolescent↗

[Neuroradiological embolization].

The authors describe five years of experience of embolization in arteriovenous malformations and fistulas, aneurysms and tumours of the central nervous system and head and neck. Altogether 143 patients were embolized in 185 sessions. Polyvinyl alcohol particles and platinum fibre coils were used as embolic agents. Permanent complications were rare, e.g 5% in arteriovenous malformations of the brain. Embolizations were either complete or preoperatively incomplete and seemed to positively influence the final outcome for the patients. The authors advocate a policy which gives due consideration to the volume of patients who might benefit from this specialized neuroradiological activity.

Adult↗

Characterization of a rice gene coding for a lipid transfer protein.

The cloning and sequence analysis of a gene that encodes a lipid transfer protein (LTP) from rice is reported. A genomic DNA library from Oryza sativa was screened using a cDNA encoding a maize LTP. One genomic clone containing the gene (Ltp) was partially sequenced and analyzed. The open reading frame is interrupted by an 89-bp intron. From the results of Southern hybridizations, Ltp appears to be a member of a small multigenic family. Transcripts of the corresponding gene were detected in several tissues including coleoptile, leaf, endosperm, scutellum and root. The transcription start point was determined by primer extension. The deduced amino-acid sequence of the Ltp product is shown to be homologous to LTPs from other crops.

Amino Acid Sequence↗

[Synchronized coronary vein retroperfusion for identification of myocardium with chronic ischemic disorders of wall movement ("hibernating myocardium")].

UNLABELLED: ECG-synchronized retroperfusion (SRP) via the coronary sinus has been recently demonstrated to efficiently deliver arterial blood to ischemic myocardium in an experimental setting and during PTCA. To assess the potential of SRP for identifying hibernating myocardium by improved contractile function resulting from retrograde delivery of oxygen, 10 patients (M/F = 9/1; age 56 +/- 9 years) with ischemic wall motion abnormalities, but, according to ECG-criteria, no transmural infarction in the territory of a totally occluded LAD, underwent 30 min of SRP at a flow rate of 145-250 ml/min prior to mechanical recanalization. Serial digital ventriculograms were obtained before, after 30 min of SRP and, finally, after successful PTCA at follow-up of 28 +/- 4 days. RESULTS: Wall motion analysis revealed improved global and regional contractile function in seven of 10 patients, which was maintained after successful PTCA. Continuous SRP over 30 min resulted in an improvement of global and segmental systolic function. Left ventricular ejection fraction (LVEF) increased from 53 +/- 8% to 58 +/- 5% with 30 min of SRP (p < 0.03) and significant improvement in regional function was detected in the anterobasal, apical and inferior segment of the left ventricular circumference (p < 0.05). CONCLUSION: An improved contractile response to retrograde delivery of oxygen by SRP appears to document the reversibility of myocardial hibernation. Thus, ECG-synchronized SRP via the coronary sinus has the potential to unmask viable myocardium likely to completely recover from contractile dysfunction after successful antegrade recanalization. Moreover, continuous SRP procedure over 30 min was safe and had no hazardous side-effects.

Adult↗

Catheter-related thrombosis in patients with refractory lymphoma undergoing autologous stem cell transplantation.

Long-term indwelling central venous catheters have eased the administration of drugs, blood products, and hyperalimentation to patients with cancer. However, their use is associated with thrombotic complications. We report here on the thrombotic complications prospectively observed in 46 patients with refractory lymphoma (22 Hodgkin's disease, 24 non-Hodgkin's lymphoma) who had placement of one or more catheters in preparation for autologous stem cell transplantation (ASCT). Thrombosis of 26 catheters in 19 patients was observed. Specific abnormalities of hemostasis were equally common in patients who developed thrombosis and in those who did not. Thrombotic complications were more common in patients with Hodgkin's disease (13/22) than in patients with non-Hodgkin's lymphoma (6/24, p = 0.04). Although more patients with Hodgkin's disease had received prior splenectomy and/or irradiation to the area involved by thrombosis than patients with non-Hodgkin's lymphoma, the incidence of splenectomy and irradiation was similar for patients with Hodgkin's disease who developed thrombosis and those who did not. Therefore, although the etiology remains unexplained, patients with Hodgkin's disease undergoing intensive chemotherapy and ASCT appear to have a higher incidence of catheter-related thrombosis than patients with non-Hodgkin's lymphoma undergoing similar therapy.

Adult↗

Interhemispheric transfer in patients with incomplete section of the corpus callosum. Anatomic verification with magnetic resonance imaging.

Tests of interhemispheric disconnection including visual, somesthetic, kinesthetic, auditory, and complex motor functions were performed on seven patients with chronic epilepsy who had undergone partial surgical section of the corpus callosum, verified by magnetic resonance imaging. Two patients with only one third of the splenium remaining demonstrated disconnection syndromes involving all modalities except vision, which was completely intact. Five patients had lesions involving the rostrum and the anterior two thirds to four fifths of the body of the callosum, with the splenium spared. They demonstrated little evidence of disconnection in the modalities indicated, except for left ear suppression on a dichotic listening task and partial somatosensory disruption in some cases. These results emphasize the importance of the posterior corpus callosum for interhemispheric sensory and sensorimotor transfer, although some discrepancies between current behavioral data and previous anatomic findings remain.

Adolescent↗