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Biomedical subjects

A Beckmann

Publications and source records attributed to A Beckmann.

At least 19 recordsLinked to original sources
PubMed2000

Length and loss of heterozygosity of an intron 1 polymorphic sequence of egfr is related to cytogenetic alterations and epithelial growth factor receptor expression.

Overexpression of epithelial growth factor receptor (EGFR) is correlated with a poor prognosis and reduced steroid receptor expression. Recently, it was demonstrated that the length of a CA repeat in the intron 1 of EGFR correlated with the expression of EGFR in vitro. We investigated 112 cases of cancerous and noncancerous breast tumor samples for loss of heterozygosity (LOH) in intron 1 of the egfr gene and determined the intratumoral EGFR content and genetic alterations by comparative genomic hybridization. Heterozygous tumors with short CA repeats showed elevated EGFR expression in contrast to tumors with longer CA repeats. Tumors with LOH in intron 1 of egfr revealed higher EGFR expression when the longer allele was lost compared with loss of the shorter allele. Additionally, tumors with a loss of the long allele showed more chromosomal alterations, especially a higher frequency of amplifications. We conclude that the CA repeat status in intron 1 of the egfr gene also modulates the intratumoral EGFR content in vivo. Furthermore, LOH at the CA repeat is associated with genetically advanced tumors. Therefore, allele-specific gene expression due to LOH of the CA repeat could be assumed to be an important event in invasive breast cancer development.

Alleles↗
PubMed2000

Simultaneous carotid endarterectomy and coronary artery bypass grafting in 313 patients.

The coincidence of coronary and carotid artery disease (uni- or bilateral, with or without involvement of the supra-aortic branch) is still a problem with regards to surgical strategy. Since the opening of the Heart Centre Duisburg in 1989 the authors have favoured a simultaneous approach to lesions in both arterial systems in order to avoid myocardial infarction or stroke. The aim of this retrospective study was to review the early and late results of the combined procedures for the endpoints of death, myocardial infarction and stroke. During a 7-year period (1990-1997) a total of 18,050 patients underwent cardiac surgery and extracorporeal circulation. Simultaneous intervention in both arterial systems was performed in 313 patients (1.73%). All patients underwent preoperative ultrasonic diagnostics, digital subtraction angiography, neurological examination and cardiac catheterization. The principal indication was the need for myocardial revascularization, and symptomatic or asymptomatic carotid stenosis of 80% diameter reduction or more (with or without contralateral disease). The mean age was 66.4 +/- 6.9 years; 240 patients (76.7%) were male, 73 patients (23.3%) female; 243 patients (77.6%) had triple-vessel disease, 82 patients (26.2%) had left main stenosis and 94 patients (43.5%) had a reduced ejection fraction. A total of 171 patients (54.6%) had a previous myocardial infarction, 54 patients (17.3%) presented with unstable angina and nine patients (2.9%) had prior coronary artery bypass grafts. Eighty-seven patients (27.8%) had an internal carotid artery stenosis on the right side, 75 patients (24%) on the left side and 151 patients (48.2%) lesions in both carotid arteries. Prior carotid endarterectomy was performed in 14 patients (4.5%), and the contralateral carotid was occluded in 24 patients (7.7%). Fifty patients had a previous stroke (16%) and 185 patients (59.1%) were asymptomatic. During surgery, the the carotid artery was first exposed, followed by median sternotomy, systemic heparinization, cannulation and cardiopulmonary bypass. After achieving mild hypothermia (30 degrees C), endarterectomy was performed with a venous patch closure. An occluded contralateral carotid artery was always an indication for shunting. Coronary artery bypass grafting was carried out with intermittent cross-clamping under moderate hypothermia (22-27 degrees C). Ten patients suffered a myocardial infarction (3.2%), seven patients (2.2%) had an apoplectic insult perioperatively ( < 30 days) and one patient (0.3%) had an event during long-term follow-up. Early overall mortality was 28 (8.9%), of which 13 were cardiac related (4.2%). Overall late mortality was eight (2.6%), of which six were cardiac related (1.9%). Mean survival time was 6.18 years. Simultaneous carotid endarterectomy and myocardial revascularization can be justified as a routine surgical management of severe lesions in both arterial systems. The risk of myocardial infarction, apoplectic stroke or mortality was not significantly different than isolated procedures.

Aged↗
PubMed2000

Evidence for a melatonin receptor within pancreatic islets of neonate rats: functional, autoradiographic, and molecular investigations.

In a recent perifusion investigation, we showed that the pineal secretory product melatonin reduces insulin secretion from isolated pancreatic islets of neonate rats stimulated with potassium chloride (KCl), glucose, and forskolin. This effect of melatonin was reproduced with doses ranging from 200 pmol/L to 5 micromol/L. Because it is generally accepted that melatonin exerts some of its biological effects through specific, high-affinity pertussis-toxin-sensitive G-protein-coupled receptors, we blocked the putative melatonin receptor of pancreatic islets using both the non-hydrolyzable guanosine triphosphate analog guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS, 30 micromol/L) and the melatonin antagonist luzindole (10 micromol/L). Both GTPgammaS and luzindole caused a near normalization of the melatonin-induced inhibition of the forskolin-stimulated insulin secretion. To localize putative melatonin receptors within the pancreatic islets autoradiographic studies were additionally carried out. These investigations showed specific binding of 2-[125I]iodomelatonin, which were in exact correspondence with the localization of the islets. In addition, gray-level analysis showed that unlabeled melatonin was able to reduce the binding of 2-[125I]iodomelatonin in a dose-dependent manner. Concentrations of unlabeled melatonin of 10(-9) mol/L produced a 50% reduction in specific binding, whereas concentrations of 10(-6) mol/L displaced the binding completely. Likewise, the results of molecular investigations showed that the rat pancreas contains a melatonin receptor, since reverse transcription polymerase chain reaction (RT-PCR) experiments, using specific primers for the rat melatonin receptor Mel1a, showed that mRNA for this melatonin receptor type is expressed in pancreatic tissue of newborn rats. In summary, it may be said that our functional. autoradiographic, and molecular results indicate that the Mel1a receptor is located on the pancreatic islets, possibly in the beta cells.

Animals↗
PubMed1998

Randomized, controlled phase II trial of subcutaneous interleukin-2 in combination with highly active antiretroviral therapy (HAART) in HIV patients.

OBJECTIVE: To determine the immunological, virological and clinical effects of subcutaneous IL-2 in 44 HIV-patients in conjunction with pre-existing tri-therapy (zidovudine, 3TC, saquinavir). DESIGN: Partially randomized, controlled, prospective trial. SETTING: Single center study at tertiary care center. PATIENTS: Sixty four patients (CD4 count 200-500 x 10(6)/l). INTERVENTION: Fourty four patients were randomized to receive 5-day cycles of IL-2 (9 Mio IU/d) every 6 weeks (Group A) or whenever the CD4 cell count dropped below the 1.25-fold of baseline (Group B), whereas 20 control patients received the same HAART without IL-2. OUTCOME MEASURES: The optimal individual treatment interval and the immunological and virological effects of subcutaneously administered IL-2 were analysed. Importantly, the level of cellular in vivo immunity and the frequency of dermatological marker diseases and infectious complications were assessed. RESULTS: IL-2 was well tolerated although fever, influenza-like symptoms and indurated injection sites were commonly encountered. After 1 year of IL-2, there was a median increase of more than 100 x 10(6)/l CD4 cells in both IL-2 groups in contrast to the controls (P < 0.01, 0.01 and not significant). The median HIV load did not increase either in plasma or in lymph nodes. Lymphocyte activation decreased as assessed by MHC class II (P < 0.001), CD25 (P < 0.001) and CD38 expression (P < 0.005). Although delayed type hypersensitivity against common recall antigens increased in both IL-2 groups, it did not reach statistical significance. However, it is of note, that in 7 of 11 (63.6%) patients delayed type hypersensitivity against recombinant HIV antigens improved significantly. Whereas there was no opportunistic infection in either IL-2 group, three cases of Kaposi's sarcoma occurred in the controls. Dermatological indicator diseases (thrush, condyloma, herpes simplex) were found to occur more frequently in the control group. CONCLUSIONS: Subcutaneous IL-2 in addition to HAART was safe and led to sustained qualitative and quantitative immunological improvements in the majority of patients. Individualisation of therapy intervals further improved the efficacy and tolerance of IL-2.

Adult↗
PubMed1998

Direct quantification of polymerase chain reaction fragments using field-amplified sample injection in capillary zone electrophoresis for gene dosage estimation.

To assess gene dosages for clinical application, especially for prognostication of cancer, we developed a direct quantification method for polymerase chain reaction products. We report on an application of field amplified sample injection (FASI) to capillary zone electrophoresis which allows the quantification of PCR products without sample preparation. Using an external standard and UV detection for the quantification of DNA, a low coefficient of variation has been obtained. Overall, the described method provides a fast and easy tool for PCR product quantification in clinical laboratories.

DNA↗
PubMed1997

Translational research studies of erbB oncogenes: selection strategies for breast cancer treatment.

Specific gene families, e.g. encoding members of signal transduction pathways, show a gene dosage sensitivity. We report on the determination of the gene dosages of egfr and c-erbB-2 in relation to the intratumoral concentration of the tyrosine kinase receptor protein EGFR and p185c-erbB-2 and the clinical outcome of breast cancer patients in a retrospective study. Prognostic unfavorable subgroups were determined in a life-table analysis by (a) an average gene copy number of egfr of less than 0.4 and greater than 1.6 and an intratumoral EGFR concentration of more than 56 fmol/mg, (b) an intratumoral p185c-erbB-2 concentration above 26 HNU/mg and (c) a quotient of egfr and c-erbB-2 average gene copy numbers of less than 0.15 and greater than 4.35.

Breast Neoplasms↗
PubMed1997

Immediate early gene expression and delayed cell death in limbic areas of the rat brain after kainic acid treatment and recovery in the cold.

Systemic injection of kainic acid (KA) results in characteristic behaviors and programmed cell death in some regions of the rat brain. We used KA followed by recovery at 4 degrees C to restrict damage to limbic structures and compared patterns of immediate early gene (IEG) expression and associated DNA binding activity in these damaged areas with that in spared brain regions. Male Wistar rats were injected with KA (12 mg/kg, i.p.) and kept at 4 degrees C for 5 h. This treatment reduced the severity of behaviors and restricted damage (observed by Nissl staining) to the CA1 and CA3 regions of the hippocampus and an area including the entorhinal cortex. DNA laddering, characteristic of apoptosis, was first evident in the hippocampus and the entorhinal cortex 18 and 22 h after KA, respectively. The pattern of IEG mRNA induction fell into three classes: IEGs that were induced in both damaged and spared areas (c-fos, fos B, jun B, and egr-1), IEGs that were induced specifically in the damaged areas (fra-2 and c-jun), and an IEG that was significantly induced by saline injection and/or the cold treatment (jun D). The pattern of immunoreactivity closely followed that of mRNA expression. Binding to the AP-1 and EGR DNA consensus sequences increased in all three regions studied. This study describes a unique modification of the animal model of KA-induced neurotoxicity which may prove a useful tool for dissecting the molecular cascade that ultimately results in programmed cell death.

Animals↗
PubMed1994

Gene expression during ethanol withdrawal.

The expression of the proteins (C-FOS and C-JUN) encoded by the immediate early genes c-fos and c-jun was investigated in the brains of rats undergoing ethanol withdrawal. Both proteins were induced in the cerebral cortex, the piriform cortex, the olfactory bulb, the inferior colliculus, the granular cell layer of the cerebellum and in the brain stem, but only C-JUN was induced in the hippocampus of animals undergoing withdrawal without overt seizures. C-FOS was detected in the hippocampus only in animals with overt seizures. Maximal C-FOS expression occurred 15 hr after withdrawal while C-JUN was maximal at 24 hr. Gel-shift assays indicated the formation of AP-1 binding factors in nuclear extracts of the cerebral cortex, hippocampus and cerebellum 15 and 17 hr after withdrawal. These data reveal a complex pattern of immediate early gene expression during ethanol withdrawal, which may be associated with changes in neuronal plasticity underlying phenomena such as withdrawal kindling.

Animals↗
PubMed1993

Heterogeneous lipoprotein (a) size isoforms differ by their interaction with the low density lipoprotein receptor and the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor.

Lipoprotein (a) (Lp(a)) is a complex of low density lipoprotein (LDL) with apolipoprotein (apo) (a). To examine the size distribution of Lp(a), plasma was separated by fast flow gel filtration and Lp(a):B complexes were determined in the eluate by enzyme immunoassays, in which detection was performed with monoclonal antibodies specific for apoB. Lp(a):B particles displayed apparent molecular masses (M(r)) of 2 x 10(6) to at least 10 x 10(6). Lp(a) size isoforms differed by the expression of apoB epitopes and their interaction with cultured human skin fibroblasts. LDL was more effective in inhibiting binding, uptake, and degradation of low M(r) Lp(a) than of high M(r) Lp(a). In contrast, Glu-plasminogen, alpha 2-macroglobulin and tissue-type plasminogen activator were more effective in competing for the cellular degradation of high M(r) Lp(a) than of low M(r) Lp(a). Ligand blotting revealed that Lp(a) bound to the low density lipoprotein receptor, the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP) and to two other endosomal membrane proteins. We propose that the LDL receptor preferentially internalizes low M(r) Lp(a), whereas LRP may have a role in the clearance of high M(r) Lp(a).

Cells, Cultured↗
PubMed1993

Wound care.

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Bandages↗
PubMed1991

Subclinical manifestations of vulvar human papillomavirus infection.

We studied the presence of human papillomavirus (HPV) DNA by in situ hybridization in 74 colposcopically defined subclinical vulvar lesions obtained from 51 patients (mean age 25 years, range 18-42 years) referred for atypical Papanicolaou smears to the Colposcopy Clinic. Serial sections of formalin-fixed, paraffin-embedded biopsy tissue were stained by routine hematoxylin and eosin stain or were separately hybridized with biotin-labeled probes of HPV types 6, 11, 16, and 18 at high stringency and with mixed HPV probes at low stringency. Histologic evidence of HPV infection (koilocytosis or dysplasia) was found in eight lesions. Overall, 10 lesions were positive by in situ hybridization with HPV DNA. Although certain colposcopic features were more strongly associated with HPV DNA than others were, we were unable to demonstrate any consistent correlation between HPV DNA positivity or specific HPV DNA types and colposcopic categories. There was little correlation between HPV DNA positivity and the histopathologic incidence of HPV infection and dysplasia. Three of the 10 hybridization-positive lesions were severely dysplastic as compared with 0 of 64 nonhybridizing lesions. In spite of this association between HPV DNA and dysplasia, HPV DNA hybridization added no additional clinically relevant information to the histopathologic findings. We emphasize the significance of careful colposcopic examination of the vulva with directed biopsies.

Adult↗
PubMed1985

Wound fluid angiogenesis factor stimulates the directed migration of capillary endothelial cells.

During wound healing, new capillaries grow into the wound site. An angiogenesis factor isolated from wound fluid stimulates the movement of capillary endothelial cells in a filter migration assay. Experiments were carried out to determine whether the movement seen in the assay was chemokinetic or chemotactic. Capillary endothelial cells were plated onto a collagen-coated coverslip and inverted over a visualization apparatus. Cells exposed to a constant concentration of wound fluid angiogenesis factor (WAF) were more mobile than cells not exposed to WAF, and this movement was chemokinetic. When exposed to a gradient of WAF, the cells translocated toward the higher concentration; this directional movement was chemotactic. Cells in a gradient of WAF morphologically aligned with the gradient. These data support the idea that wound healing angiogenesis is regulated by the chemotaxis of capillary endothelial cells.

Angiogenesis Inducing Agents↗
PubMed1985

[Intracranial forms of malignant lymphoma manifestations].

Approximately 10% of patients with malignant lymphoma will show neurological symptoms at some time during the course of their illness. In non-Hodgkin lymphoma, CNS involvement is more frequent than in Hodgkin's disease. Diffuse histiocytic and poorly differentiated lymphomas, bone marrow involvement, advanced tumor stage and hematogenous spread are particular risk factors. Invasion of the spinal canal is the most common type of CNS involvement. Intracranial lesions, which are comparatively rare, may present as intracerebral metastases, epi- or subdural masses or focal or diffuse leptomeningeal disease. Lymphomatous leptomeningitis usually cannot be demonstrated by CT. On the other hand, dural and cerebral parenchymal lesions are sometimes highly characteristic of lymphoma as a result of their features and location.

Adolescent↗
PubMed1983

Activation of chemotactic factors in serum and wound fluid by dextranomer.

Dextranomer (Debrisan), a frequently used wound-cleansing agent, was shown to cause activation of chemotactic factors in human serum and wound fluid. These factors attracted both polymorphonuclear leukocytes (PMNs) and mononuclear leukocytes (MNs) in an agarose migration assay. When Debrisan-activated sera were used as the chemotactic stimulus, migration scores for PMNs and MNs were respectively 50% and 70% of the values obtained with zymosan-activated sera. Differential chelation studies demonstrated that Debrisan causes activation of the alternate complement pathway, and the factors produced cause receptor-mediated leukotaxis of both PMNs and MNs. Formation of chemotactic factors at the wound surface is a mechanism whereby Debrisan could conceivably augment wound healing and the inflammatory response to infection.

Chemotactic Factors↗
PubMed1980

Production of acute pulmonary injury by leukocytes and activated complement.

The adult respiratory distress syndrome (ARDS) frequently occurs after sepsis and major trauma. Since both sepsis and trauma may cause activation of the complement system, we have infused rabbits with complement-activated plasma (AP) and have studied the effects on leukocyte counts, respiratory rate, PaO2, and lung morphology. Sustained AP infusion caused: (1) early granulocytopenia, (2) progressive hypoxemia and tachypnea, and (3) pulmonary vascular plugging by aggregates of degenerating granulocytes with interstital edema and endothelial injury. These changes were not observed in control animals infused with unactivated plasma or in animals rendered leukopenic with nitrogen mustard. Complement activation in patients with sepsis and trauma may be an etiologic factor in the development of ARDS.

Agranulocytosis↗