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Biomedical subjects

A Lenz

Publications and source records attributed to A Lenz.

At least 19 recordsLinked to original sources
PubMed2005

Platelet-leukocyte interaction and platelet activation in acute stroke with and without preceding infection.

OBJECTIVE: Acute coronary syndromes and ischemic cerebral stroke share similarities regarding elevated platelet activation. In coronary syndromes, the importance of inflammation with platelet-leukocyte interaction has been demonstrated. Recent infection is an established risk factor for ischemic stroke; the role of platelet-leukocyte interaction in these patients had not been investigated. METHODS AND RESULTS: Using a flow cytometric assay we investigated 58 stroke patients, 21 with and 37 without infection 1 week before acute cerebral ischemia, and compared them to 58 controls with regard to platelet-leukocyte aggregation and platelet activation on admission and on day 7. Patients with previous infection were significantly up-regulated with regard to platelet activation and platelet-leukocyte aggregation compared with patients without infection. On day 7, these increases in the postinfective group had drawn level with the lower values of the other patients. As reported previously, recent infection was associated with a more severe postischemic deficit. CONCLUSIONS: These results suggest an important role of intercellular platelet-leukocyte interaction in the pathophysiology of acute cerebral ischemia which may also contribute to the increased incidence and clinical severity of ischemic stroke following infection. This may lead to therapeutic considerations of blocking intercellular adhesion molecules like P-selectin or the P-selectin glycoprotein ligand.

Acute Disease↗
PubMed2003

Pulsatile perfusion and cardiomyocyte viability in a solid three-dimensional matrix.

BACKGROUND: The manufacture of full thickness three-dimensional myocardial grafts by means of tissue engineering is limited by the impeded cellular viability in unperfused in vitro systems. We introduce a novel concept of pulsatile tissue culture perfusion to promote ubiquitous cellular viability and metabolism. METHODS: In a novel bioreactor we established pulsatile flow through the embedded three-dimensional tissue culture. Fibrin glue served as the ground matrix wherein neonatal rat cardiomyocytes were inoculated. Fluor-Deoxy-Glucose-Positron-Emission-Tomography (FDG-PET) and life/dead assays were employed for comparative studies of glucose uptake resp. cell viability. RESULTS: A solid 8 mm thick structure resulted. Cellular viability significantly increased in the perfused chambers. We observed centripetal migration of the embedded cardiomyocytes to the site of the core vessel. However, cellular viability was high in the periphery of the tissue block too. FDG-PET revealed enhanced metabolic activity in perfused chambers. CONCLUSIONS: The present concept is highly effective in enhancing cellular viability and metabolism in a three-dimensional tissue culture environment. It could be utilized for various co-culture systems and the generation of viable tissue grafts.

Animals↗
PubMed2003

Carboxyfluorescein diacetate succinimidyl ester facilitates cell tracing and colocalization studies in bioartificial organ engineering.

BACKGROUND: We demonstrate a method that includes colocalization studies to analyze cell suspensions after isolation and to characterize 3-dimensional grafts consisting of cells and matrix in vitro and in vivo. MATERIALS AND METHODS: Neonatal rat cardiomyocytes were labelled by CFDA-SE after harvest. Cells in the isolated cell suspension, the embodied cells in the seeded scaffolds were characterized measuring features such as viability and distribution of the cell types. RESULTS: Selective cell count revealed high yields of viable cardiomyocytes. After seeding cells in collagen matrix, viability of the cells decreased gradually in the time process in vitro. Histology of implanted bioartificial myocardial tissue detected viable cardiomyocytes within the graft. CONCLUSION: Using colocalization histology we could label and track cells within the bioartificial myocardial tissue graft in vitro and post implant and assess viability and distribution.

Animals↗
PubMed2001

[Local tumor control and cosmetic outcome following breast-conserving surgery and radiation up to a total dose of 56 Gy without boost in breast cancer].

PURPOSE: To evaluate overall survival, local tumor control and cosmetic outcome after breast-conserving surgery followed by radiotherapy without boost irradiation. PATIENTS AND METHODS: In a retrospective study 270 breast cancer patients were treated with breast conserving surgery combined with a homogenous radiation of the tumor bearing breast up to a total dose of 56 Gy without local boost irradiation. Mean follow-up was 48 months. Local tumor control, side effects, cosmetic results and contentment with treatment were assessed using physical examinations and interviews based on a standardized questionnaire. RESULTS: Cause-specific survival at 5 years after treatment was 88.3%, actuarial disease-free survival at 5 years was 76.1%. Within 23 to 78 months after treatment 12 patients suffered from ipsilateral breast recurrence. The actuarial freedom from local recurrence (single tumor manifestation) was 96.8% at 5 years after treatment, 89% at 10 years. The occurrence of local failures was not significantly correlated to tumor size, margins, grading, nodal status, age or lymphangiosis. 15.6% of the patients developed distant metastases. In all patients treatment was performed without interruption. Side effects were predominantly of mild degree, no severe side effects were detected. 73% of physicians and 81% of patients scored their cosmetic outcome as excellent or good. 93% of patients would again decide in favor of this procedure. Whereas use of adjuvant chemotherapy as well as subcutaneous reconstruction of breast tissue did not significantly affect breast cosmesis, analysis demonstrated impaired cosmetic results related to a larger breast size. CONCLUSION: The data of this study show that tumor control achieved by breast conserving surgery in combination with a radiation technique up to a total dose of 56 Gy which omits boost irradiation is within the range of literature data. Side effects of the therapy were tolerable. The treatment displayed a good compatibility with tolerable side effects and good cosmetic results.

Actuarial Analysis↗
PubMed2001

Nitrogen and phosphorus budget in rewetted fens.

A former dewatered fen was flooded for a multi-purpose landuse system including cattail production, fen protection, and water purification. These research plants with an area of 6 ha consist of three constructed surface-flow wetlands. The inflowing water is polluted by non-point sources due to intensive agriculture. The focus of this paper is the estimation of the potential of rewetted fens to reduce phosphorus and nitrogen. The dominating forms of nitrogen in the inflow are organic nitrogen and nitrate. The reduction rate is higher for nitrate than for organic nitrogen, although the nitrate reductions occur only during the summer season. If no nitrate is available for denitrification, there is a release of ammonia from the peat into the water. The main form of phosphorus in the in- and outflow is ortho-phosphate. In contrast to the values of nitrate, the concentrations of phosphorus are very regular with no significant seasonal pattern. When nitrate isn't available in the water any more, the release of phosphorus begins and the rewetted fens change from a sink for phosphorus to a source of it. Rewetted fens can be a sink for phosphorus and nitrogen with nitrate as the limiting factor. Only if denitrification can occur, can the release of ammonia and phosphorus from the peat layer be prevented.

Ammonia↗
PubMed2000

[Where are the children in family counseling? Results of an explorative study].

Since the late seventies the family setting has become a normal model in counseling, not least because of the systemic change in psychotherapy. The lack of methodologically well-founded considerations on how to involve the children in the family talk is therefore even more surprising. In the present study 40 counselors were interviewed how they propose to fill the special gap in their practical work, what strategies they have developed to involve children and how important for them children are in the family talk. The result was that the majority of the counselors are adult oriented in their activities and rarely include the children actively in the interactive proceedings. Nevertheless all those interviewed regarded their presence as necessary because they provide helpful diagnostic assistance in uncovering and recognizing parental problems and relational conflicts.

Adolescent↗
PubMed1999

Effect of filgrastim treatment on inflammatory cytokines and lymphocyte functions.

Twenty-four healthy male volunteers received either placebo or 75, 150, or 300 microg filgrastim (recombinant methionyl human granulocyte colony-stimulating factor) for 12 days to study effects on monocytes and lymphocytes. In all filgrastim-treated groups, tumor necrosis factor alpha (TNF-alpha), interleukin-12 (IL-12), and interferon gamma (IFN-gamma) release by whole blood in response to endotoxin (lipopolysaccharide) was reduced. IL-12 added in vitro to lipopolysaccharide-stimulated blood of filgrastim-treated donors restored IFN-gamma and TNF-alpha release, suggesting that the anti-inflammatory effect of granulocyte colony-stimulating factor is exercised through IL-12 suppression. Phytohemagglutinin- or anti-CD3 antibody-induced lymphocyte proliferation ex vivo was reduced by 60% from day 5 to day 15, after a 50% increase at day 2 with concomitant doubled IL-2 release. In vivo, filgrastim induced doubling of all T-cell populations by day 8. Filgrastim decreased proinflammatory cytokine production and lymphocyte proliferation ex vivo throughout prolonged treatment at all doses. This indicates that endogenous granulocyte colony-stimulating factor may counterregulate the inflammatory cytokine cascade and implies a potential indication for filgrastim in chronic inflammatory conditions.

Adult↗
PubMed1999

Health effects of sulfur-related environmental air pollution. II. Cellular and molecular parameters of injury.

Recently, concern has been raised about effects related to environmental sulfur and/or acidic aerosols. To assess long-term effects on nonrespiratory lung function, 8 beagle dogs were exposed over a period of 13 mo for 16.5 h/day to a neutral sulfite aerosol at a sulfur(IV) concentration of 0.32 mg m(-3) and for 6 h/day to an acidic sulfate aerosol providing a hydrogen concentration of 15.2 micromol m(-3) for inhalation. Prior to exposure the dogs were kept under clean air conditions for 16 mo to establish physiological baseline values for each animal. A second group of eight dogs (control) was kept for the entire study under clean air conditions. No clinical symptoms were identified that could be related to the combined exposure. Biochemical and cellular parameters were analyzed in sequential bronchoalveolar lavage (BAL) fluids. The permeability of the alveolo-capillary membrane and diethylenetriaminepentaacetic acid (DTPA) clearance was not affected. Similarly, oxidant burden of the epithelial lining fluid evaluated by levels of oxidation products in the BAL fluid protein fraction remained unchanged. Both the lysosomal enzyme beta-N-acetylglucosaminidase and the alpha-1-AT were increased (p <.05). In contrast, the cytoplasmic marker lactate dehydrogenase remained unchanged, indicating the absence of severe damages to epithelial cells or phagocytes. Various surfactant functions were not altered during exposure. Three animals showed elevated levels of the type II cell-associated alkaline phosphatase (AP), indicating a nonuniform response of type II cells. Significant correlations were found between AP and total BAL protein, but not between AP and lactate dehydrogenase, suggesting proliferation of alveolar type II cells. Absolute and relative cell counts in the BAL fluid were not influenced by exposure. Alveolar macrophages showed no alterations with regard to their respiratory burst upon stimulation with opsonized zymosan. The percentage of alveolar macrophages capable of phagocytozing latex particles was significantly decreased (p<.05), while the phagocytosis index was not altered. In view of the results of this and previous studies, we conclude that there is no synergism of effects of these two air pollutants on nonrespiratory lung functions. It is hypothesized that antagonistic effects of these air pollutants on phospholipase A2-dependent pathways account for compensatory physiological mechanisms. The results emphasize the complexity of health effects on lung functions in response to the complex mixture of air pollutants and disclose the precariousness in the risk assessment of air pollutants for humans.

Aerosols↗
PubMed1998

Expression of maturation-/migration-related molecules on human dendritic cells from blood and skin.

Progress in dendritic cell research has been overwhelming in the past few years. This was made possible by the recent development of simple methods to generate large numbers of dendritic cells. These methods use as starting populations for culture either CD34+ progenitor cells from cord blood or bone marrow, or monocytes from peripheral blood. The latter approach is critically dependent on the combination of GM-CSF and interleukin 4. Such "priming cultures" yield populations of immature dendritic cells (CD83-/CD86 +/- /CD115+/antigen uptake high/antigen processing high/T cell sensitization low). In order to generate mature dendritic cells a subsequent "differentiation culture" has to be added whereby monocyte-conditioned medium appears to be the optimal stimulus for maturation. This results in terminally mature dendritic cells (CD83+/CD86++/CD115-/antigen uptake low/antigen processing low/T cell sensitization high). We investigated the expression of some molecules involved in maturation and migration on human monocyte-derived dendritic cells from blood in comparison with dermal dendritic cells and epidermal Langerhans cells. We present a method to highly enrich epidermal Langerhans cells. Survival of purified Langerhans cells in culture is dependent on the presence of GM-CSF and TNF-alpha. During maturation a substantial part of the Langerhans cells loses expression of the cutaneous lymphocyte antigen (CLA); mature dendritic cells from the dermis are completely devoid of CLA. Similarly, CLA as well as CD15s (Sialyl Lewis x) and CD31 (PECAM-1) that can be readily detected on immature monocyte-derived dendritic cells are down-regulated upon maturation. CD68 expression is very low in cutaneous dendritic cells; in monocyte-derived dendritic cells this molecule is abundantly present. Subsets of monocyte-derived dendritic cells express E-cadherin; CD87 (urokinase plasminogen activator receptor) is weakly expressed on both immature and mature monocyte-derived dendritic cells. Taken together, these data suggest that the phenotype of monocyte-derived dendritic cells (E-cadherin low to negative, CD68++) is not indicative for a cutaneous destiny. Furthermore, the downregulation upon maturation of molecules involved in migration through vessel walls (CD31, CLA, CD15s) indicates that the entry of mature dendritic cells into lymphatic vessels may not be as rigidly regulated by adhesion molecules as the process of extravasation from blood vessels.

Antigens, CD↗
PubMed1997

[Deciding criteria for vaginal delivery from breech presentation--effect on neonatal early and late morbidity].

In the past 20 years, breech presentation obstetrics has been characterised mainly by the work of Kubli (1975): "The safest and most simple way to prevent the foetal obstetric risk of breech presentation is the systematic Caesarean section." In the past, this resulted in judicial decisions in which due to vaginal delivery a child has been damaged and the doctor has been reproached for not performing a Caesarean section. In the report of the "Standardkommission BEL" (1983) as well as in the Guidelines for the Management of Breech Delivery (FIGO 1993), subtile criteria of decision were demanded for the vaginal delivery method. To an increasing extent clinics lack the necessary training for vaginal-operative delivery for breech presentation, followed by economic obligations and, as a result, in 1994 the frequency of Caesarean sections in cases of breech presentation was 86.9% in Bavaria. Investigations should be made as to whether it is actually necessary, for the benefit of the child, to subject a mother of a breech baby to such high-risk operations. From 1988 to 1995, 1116 breech babies were born in the Gynaecological Clinic Nürnberg, Dept. of Obstetrics. The case history of 650 children with a period of gestation > 32 weeks of pregnancy were evaluated: parity, period of gestation, method of delivery, condition after Caesarean section, premature rupture of the foetal membranes, position of legs, weight of child, Apgar score, umbilical artery pH, base excess in umbilical artery mval/l, transfer ratio to paediatric clinic, reason of transfer to paediatric clinic, rate and duration of intubation, cranial sonogram and electroencephalogram.

Acid-Base Equilibrium↗
PubMed1994

Proliferating dendritic cell progenitors in human blood.

CD34+ cells in human cord blood and marrow are known to give rise to dendritic cells (DC), as well as to other myeloid lineages. CD34+ cells are rare in adult blood, however, making it difficult to use CD34+ cells to ascertain if DC progenitors are present in the circulation and if blood can be a starting point to obtain large numbers of these immunostimulatory antigen-presenting cells for clinical studies. A systematic search for DC progenitors was therefore carried out in several contexts. In each case, we looked initially for the distinctive proliferating aggregates that were described previously in mice. In cord blood, it was only necessary to deplete erythroid progenitors, and add granulocyte/macrophage colony-stimulating factor (GM-CSF) together with tumor necrosis factor (TNF), to observe many aggregates and the production of typical DC progeny. In adult blood from patients receiving CSFs after chemotherapy for malignancy, GM-CSF and TNF likewise generated characteristic DCs from HLA-DR negative precursors. However, in adult blood from healthy donors, the above approaches only generated small DC aggregates which then seemed to become monocytes. When interleukin 4 was used to suppress monocyte development (Jansen, J. H., G.-J. H. M. Wientjens, W. E. Fibbe, R. Willemze, and H. C. Kluin-Nelemans. 1989. J. Exp. Med. 170:577.), the addition of GM-CSF led to the formation of large proliferating DC aggregates and within 5-7 d, many nonproliferating progeny, about 3-8 million cells per 40 ml of blood. The progeny had a characteristic morphology and surface composition (e.g., abundant HLA-DR and accessory molecules for cell-mediated immunity) and were potent stimulators of quiescent T cells. Therefore, large numbers of DCs can be mobilized by specific cytokines from progenitors in the blood stream. These relatively large numbers of DC progeny should facilitate future studies of their Fc epsilon RI and CD4 receptors, and their use in stimulating T cell-mediated resistance to viruses and tumors.

Animals↗
PubMed1994

Coincidence of familial platelet glycoprotein Ib/IX deficiency (Bernard-Soulier syndrome), idiopathic autoantibody against platelet glycoprotein Ib/IX, familial appearance of antiphospholipid antibodies, and familial factor XII deficiency.

The case of an 8-year-old boy with apparently homozygous Bernard-Soulier syndrome (platelet GP Ib/IX complex deficiency) and a transient idiopathic autoantibody against GP Ib/IX is described. He had been diagnosed with chronic autoimmune thrombocytopenia (due to the detection of antiplatelet autoantibodies) before Bernard-Soulier syndrome was proven. Both parents and his brother displayed intermediate deficiency of GP Ib/IX, thus indicating a heterozygote state for Bernard-Soulier syndrome. Alloimmunization as an explanation for the appearance of GP Ib/IX antiplatelet antibodies in the propositus can be excluded. A so-called pseudo Bernard-Soulier syndrome due to selective antibodies was also excluded. Flow cytometric analysis revealed residual expression of 2% GP Ib and 13% GP IX on the propositus' platelets. It seems that the propositus showed an idiopathic autoantibody against a platelet glycoprotein in which he is genetically deficient (but which is not completely lacking). Thus, in patients with untypical behavior upon therapy of "autoimmune thrombocytopenia", other differential diagnoses should also be considered even if antiplatelet antibodies are detected. In addition, all family members displayed elevated concentrations of antiphospholipid antibodies. These findings raise the question of a genetic predisposition for the development of autoantibodies. Moreover, an F. XII deficiency was found in all family members except the mother.

Adult↗
PubMed1993

Three-dimensional structure of the ternary complex between ribonuclease T1, guanosine 3',5'-bisphosphate and inorganic phosphate at 0.19 nm resolution.

The ternary complex formed between RNase T1, guanosine 3',5'-bisphosphate (3',5'-pGp) and Pi crystallizes in the cubic space group I23 with a = 8.706(1) nm. In a previous publication [Lenz, A., Heinemann, U., Maslowska, M. & Saenger, W. (1991) Acta Crystallogr. B47, 521-527], the structure of the complex (in which Pi was not located) was described at a resolution of 0.32 nm. This is now extended to 0.19 nm with newly grown, larger crystals. Refinement with restrained least-squares converged at R = 17.8% for 8027 reflections with [Fo[ > or = 1 sigma ([Fo[); the final model comprises 120 water molecules. 3',5'-pGp is bound to RNase T1 in the anti form, with guanine in the specific recognition site; the 3'-phosphate protrudes into the solvent, and the 5'-phosphate hydrogen bonds with Lys41 O and Asn43 N4. A tetrahedral anion assigned as Pi occupies the catalytic site and hydrogen bonds to the side chains of Tyr38, Glu58, Arg77 and His92. The overall polypeptide fold of RNase T1 in the cubic space group does not differ significantly from that in the orthorhombic space group P2(1)2(1)2(1) except for changes < or = 0.2 nm in loop regions 69-72 and 95-98.

Guanosine Diphosphate↗
PubMed1993

On the appearance of islet associated autoimmunity in offspring of diabetic mothers: a prospective study from birth.

For the first time the incidence of insulin autoantibodies and islet cell antibodies were evaluated in a prospective study from birth. Consecutive neonates (168) from mothers with Type 1 (insulin-dependent) diabetes mellitus (n = 113) and gestational diabetes (n = 55) were included at birth. To date, follow-up sera were obtained from 90 of 168 mother-child-pairs 9 months postpartum and from 39 of 168, 2 years postpartum. At birth, there was a strong correlation between the presence of antibodies in the cord blood of neonates and in maternal circulation [Type 1 diabetic mothers: 20% islet cell antibodies > or = 20 JDF-U (detection threshold of our islet cell antibody assay), 74% insulin antibodies > 49 nU/ml (upper limit of normal range in sera of healthy control subjects aged 0.5 to 46 years); neonates: 21% islet cell antibodies > or = 20 JDF-U, 76% insulin antibodies > 49 nU/ml; gestational diabetic mothers: 11% islet cell antibodies > or = 20 JDF-U, 18% insulin antibodies > 49 nU/ml; neonates: 13% islet cell antibodies > or = 20 JDF-U, 55% insulin antibodies > 49 nU/ml]. This supports transplacental passage of insulin antibodies and islet cell antibodies from diabetic mothers to their offspring. During follow-up, the majority of children lost antibody-positivity after birth. A few offspring, however, exhibited or developed antibodies consistently, whereby insulin autoantibodies preceded islet cell antibodies in each case (antibody-positivity: 9 months: 0% islet cell antibody positive, 3.3% insulin autoantibody positive; 2 years: 2.6% islet cell antibody positive, 7.7% insulin autoantibody positive).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Human and murine dermis contain dendritic cells. Isolation by means of a novel method and phenotypical and functional characterization.

Dendritic cells (DC) comprise a system of cells in lymphoid and nonlymphoid organs that are specialized to present antigens and to initiate primary T cell responses. The Langerhans cell of the epidermis is used as a prototype for studies of DC in the skin. We have characterized a population of DC in human dermis, one of the first examples of these cells in nonlymphoid organs other than epidermis. To identify their distinct functions and phenotype, we relied upon the preparation of enriched populations that emigrate from organ explants of dermis. The dermal cells have the following key features of mature DC: (a) sheet-like processes, or veils, that are constantly moving; (b) very high levels of surface MHC products; (c) absence of markers for macrophages, lymphocytes, and endothelium; (d) substantial expression of adhesion/costimulatory molecules such as CD11/CD18, CD54 (ICAM-1), B7/BB1, CD40; and (e) powerful stimulatory function for resting T cells. Dermal DC are fully comparable to epidermis-derived DC, except for the lack of Birbeck granules, lower levels of CD1a, and higher levels of CD36. DC were also detected in explants of mouse dermis. We conclude that cutaneous DC include both epidermal and dermal components, and suggest that other human nonlymphoid tissues may also serve as sources of typical immunostimulatory DC.

Animals↗
PubMed1992

[The integration of thoracic epidural anesthesia into anesthesia for intra-abdominal surgery].

Upper abdominal and thoracic surgeries require efficient pain management. The complications of postoperative analgesia include respiratory depression and--when choosing the epidural route--possible damage to the spinal cord by infection, trauma, or bleeding. Therefore, thoracic epidural analgesia may appear to be too risky and is frequently cancelled although many studies have shown its excellent efficacy. Controlled studies comparing thoracic epidural analgesia to lumbar epidural analgesia or intravenous analgetic regimens with special regard to the patient's outcome are contradictory. To make the preoperative decision on the method of pain control more rational, we studied catheter-related complications from 2056 thoracic epidural catheters used for intra- and postoperative analgesia retrospectively (n = 1002) and prospectively (n = 1054) over a 5 1/2-year period. In all patients the thoracic epidural catheter was inserted preoperatively using local anaesthesia, in most cases by the paramedian approach between level T 5/6 and T 8/9. During the clinical course of all patients there were no clinical signs of any epidural bleeding or infection. Neurological complications caused by the epidural catheter did not occur. Seven patients (0.035%) experienced radicular pain that disappeared after removal of the catheter or interruption of the puncture, respectively. A primary perforation of the dura mater was noticed in 0.5% of cases retrospectively and 1.23% prospectively. Respiratory depression following epidural application of 0.3 mg buprenorphine was seen in 1 patient (0.05%). Continuous analgesia with local anaesthetics and/or opioids applied epidurally by a thoracic catheter was performed on the peripheral ward (n = 829, 40%) if close monitoring of the neurological status as well as rapid diagnosis of any painful paraesthesia or paraplegia was possible.

Abdomen↗