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Biomedical subjects

R Zimmermann

Publications and source records attributed to R Zimmermann.

At least 127 records · Page 7Linked to original sources
PubMed2000

Cytomegalovirus infection of vascular cells induces expression of pro-inflammatory adhesion molecules by paracrine action of secreted interleukin-1beta.

BACKGROUND: Infection with human cytomegalovirus (HCMV) has been associated with vascular disease processes such as vascular allograft rejection, transplantation vasculopathy, restenosis after angioplasty, and native atherosclerosis. To elucidate underlying pathomechanisms, the effect of acute HCMV infection on the expression of pro-inflammatory adhesion molecules on human umbilical vein endothelial cells (HUVEC) and human vascular smooth muscle cells (hvSMC) was examined. METHODS AND RESULTS: Cells were infected in vitro with clinical strains of HCMV and the resulting changes in adhesion molecule expression were quantified by histology and flow cytometric analysis. On HUVEC, surface expression of vascular cell adhesion molecule-1 and E-selectin was induced de novo on HCMV infection and intercellular adhesion molecule-1 expression was increased by >200%. On hvSMC, intercellular adhesion molecule-1 surface expression induced de novo, although vascular cell adhesion molecule-1 and E-selectin were not changed. Expression of major histocompatibility complex (MHC) class II, lymphocyte-function associated antigen 3 (LFA-3; CD58), and CD40 was not altered by HCMV infection in either cell type. In partially infected cultures, up-regulation of surface molecules also occurred on noninfected cells, suggesting a paracrine mechanism via a soluble factor. Expression of surface molecules could be enhanced in noninfected HUVEC and hvSMC by incubation with virus-free conditioned supernatant from HCMV-infected cells or by coincubation in transwells with infected cells. The responsible agent could be identified as IL- interleukin- (IL) 1beta by detection of de novo secretion of IL-1beta by HCMV-infected cells and by prevention of adhesion molecule up-regulation after addition of an IL-1-converting enzyme inhibitor or IL-1 receptor antagonist. Surface molecule up-regulation could be suppressed by UV inactivation of virus, but not by treatment of cell cultures with inhibitors of viral replication (ganciclovir). CONCLUSION: We propose that HCMV infection induces IL-1beta release and subsequent up-regulation of pro-inflammatory adhesion molecules on noninfected neighboring cells through a paracrine mechanism. This may lead to local potentiation of the inflammatory effects of HCMV infection, not amenable to current therapeutic antiviral strategies.

Cell Adhesion Molecules↗
PubMed2000

Apoptosis is initiated by myocardial ischemia and executed during reperfusion.

Ischemia/reperfusion leading to myocyte cell death has been reported as either necrotic or apoptotic or a combination of both. The importance of necrosis is well established but the role of apoptosis and the time of initiation are still unknown. Normothermic global ischemia of either 45 or 90 min duration followed by 6 h of reperfusion were induced in isolated canine hearts. After 45 min of ischemia, left ventricular function and adenine nucleotide (AN) content had recovered during reperfusion indicating reversible injury. DNA fragmentation determined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) was absent as was the 85 kDa fragment of poly-(ADP-ribose) polymerase (PARP). After 90 min of ischemia, electron microscopy indicated necrotic cell death in 90% of myocytes. Recovery of function and AN content during reperfusion was minimal. At the end of ischemia, caspase-3 was activated in 30% of all myocytes and PARP 85 kDa fragments were present by Western blot, indicating initiation of the apoptotic cascade. Lamin-B(1)labeling was significantly reduced from 90% in myocytes in control and ischemia to 30% in early reperfusion. Completion of apoptosis seen by TUNEL was evident in late reperfusion (7.6% of myocytes and 8.3% of non-myocytes). Experiments with 6 h ischemia without reperfusion showed absence of DNA fragmentation. We conclude that apoptotic cell death is initiated by ischemia but that reperfusion is needed for completion of the apoptotic cascade. Furthermore, it is concluded that cell death in acute global ischemia followed by reperfusion occurs predominantly by necrosis and that apoptosis is of minor importance in this pathophysiological situation.

Adenine Nucleotides↗
PubMed2000

Direct observation of the formation of aromatic pollutants in waste incineration flue gases by on-line REMPI-TOFMS laser mass spectrometry.

On-line REMPI-TOFMS laser mass spectrometry (Resonance Enhanced Multi-Photon Ionization-Time-Of-Flight Mass Spectrometry) was used to monitor combustion and pyrolysis byproducts from industrial combustion processes, including polycyclic aromatic hydrocarbons (PAH) and monochlorobenzene in the flue gas of an industrial 22 MW hazardous waste incineration plant. Sampling at different places in the flue gas stream revealed the complexity of the processes responsible for the formation of the different chemical species, while time resolved measurements depicted the emission dynamics.

Air Pollutants↗
PubMed2000

In vitro characteristics of red blood cell concentrates prepared from under- and overcollected units of whole blood and from a paediatric blood bag system.

The problem of how to deal with red blood cell concentrates (RBCs) prepared from under- or overcollected units of whole blood (WB) and how to collect blood from underweight persons arises in the context of autologous predeposit. To determine the quality of RBCs stored in PAGGS-M additive solution prepared from under- and overcollected units of whole blood and of PAGGS-M RBCs prepared from a paediatric 250-mL top outlet blood bag system we measured blood picture, haemolysis, K+, pH, ATP and 2,3-DPG on days 0, 10, 20, 30, 40 and 49 of storage. The volume of WB collected ranged from 150 to 600 mL in 50-mL increments (4 units per volume). Haemolysis was under 0.8% on day 49 in all RBCs prepared from WB donations between 200 mL and 600 mL. However, the day 49 haemolysis level of standard RBCs prepared from 450 mL of WB (0.15 +/- 0.03%) was reached earlier in RBCs from under- and overcollected units of whole blood. 2,3-DPG levels decreased rapidly between days 10 and 20 in all RBCs studied. RBCs from 450-mL donations showed acceptable ATP maintenance after 49 days (70.4% of day 0 value), while all other RBC ATP levels were below 50% of the day 0 level on day 49. In vitro quality data of RBCs prepared from a 250-mL donation in the paediatric blood bag system after storage for about 25 days were comparable to those after 49 days of storage of standard RBCs. Our results suggest that it is feasible to transfuse PAGGS-M RBCs prepared from under- as well as overcollected units of WB in the autologous setting. However, we strongly recommend shortening the storage period of such RBCs to maintain the quality level of standard RBCs.

Blood Donors↗
PubMed2000

Assembly of heterodimeric luciferase after de novo synthesis of subunits in rabbit reticulocyte lysate involves hsc70 and hsp40 at a post-translational stage.

Heterodimeric luciferase from Vibrio harveyi had been established as a unique model enzyme for direct measurements of the effects of molecular chaperones and folding catalysts on protein folding and subunit assembly after de novo synthesis of subunits in rabbit reticulocyte lysate. It was observed that luciferase assembly can be separated in time from synthesis of the two subunits and that under these post-translational conditions assembly was inhibited by either ATP depletion or inhibition of peptidylprolyl cis/trans isomerases, that is, by addition of cyclosporin A or FK506. Furthermore, it was observed that the inhibitory effect of FK506 on luciferase assembly can be suppressed by addition of purified cyclophilin, thereby providing the first direct evidence for the involvement of peptidylprolyl cis/trans isomerases in protein biogenesis in the eukaryotic cytosol. Here the ATP requirement in luciferase assembly has been characterized. Depletion of either Hsp90 or CCT from reticulocyte lysate did not interfere with luciferase assembly. However, addition of purified Hsc70 stimulated luciferase assembly. While addition of purified Hsp40 did not have any effect on luciferase assembly, the stimulatory effect of Hsc70 was further increased by Hsp40. Thus, after synthesis of the two subunits in reticulocyte lysate assembly of heterodimeric luciferase involves Hsc70 and its co-chaperone Hsp40. Therefore, Hsc70 aids protein biogenesis in the eukaryotic cytosol not only at the levels of nascent polypeptide chains and precursor proteins that have to be kept competent for transport into cell organelles, but also at the level of subunits that have to be kept competent for assembly.

Adenosine Triphosphate↗
PubMed2000

[Monteggia injuries in childhood].

The Monteggia-fracture dislocation is a characteristic combined injury of the forearm with fracture of the ulna and dislocation of the head of the radius. Monteggia- and equivalent injuries are rare. In the present study, we attempt to clarify the concept of therapy and observe the influence of this injury on the growth of the forearm bones. Between 1977 and 1996, 27 patients (three to thirteen years) with a Monteggia or a Monteggia-equivalent injury were treated. We present clinical and radiological long-term results of 20 patients, two to 21 years following the injury. Group I includes 12 patients with a classic Monteggia injury, five patients were treated conservatively, seven patients surgically. Ten patients were free of pain and had no loss of motion. In one patient there was a loss of pronation following an accompanying injury of the distal radius. Primary paresis of the radial nerve has a good prognosis. One patient presents a persisting dislocation of the radius head with a loss of flexion in the elbow joint, and a secondary persisting paraesthesia of the median nerve. Group II includes eight patients with a Monteggia-equivalent injury; all of them were treated surgically. The results in this group showed more loss of motion in elbow function, forearm rotation, and dislocation of the axis in the elbow joint. Monteggia and Monteggia-equivalent injuries in childhood have good functional results if correct reduction of the fracture of the ulna and the head of the radius is performed. If this is not possible conservatively, patients need open reduction and internal fixation.

Adolescent↗
PubMed2000

[Late sequelae of fractures of the distal third of the forearm during the growth period].

Fractures to the distal third of the forearm are the most common fractures of the upper extremity, with the majority occurring between the age of ten and 14 years. With the exception of the rare epiphyseal fractures, they have a favourable prognosis. The present study investigates the frequency and extent of potential clinical and radiological late sequelae of fractures in the distal third of the forearm during growth. Of the patients treated at the Innsbruck University Department of Traumatology from 1980 to 1992, 220 patients of a growing age with 232 closed fractures in the distal third of the forearm were followed up. The radius alone was affected in 60% of these cases; the radius and the ulna in 40%. Fractures of the ulna alone were not present. The mean age of the patients at the time of injury was nine years (range one to 16 years) and the mean time of follow-up ten years (range five to 16 years). In addition to the patient's subjective assessment, the right and left sides were compared with regard to mobility of the wrist and rotational movement of the forearm. Based on standard X-rays, the frontal (radio-ulnar) and lateral (dorso-palmar) radial joint angle as well as the difference in the radio-ulnar plane were compared with the contralateral side. Clinical and radiological findings were summarised into an overall result. 19% of the patients reported pain in the injured wrist. Mobility of the wrist in the sagittal and/or frontal plane was limited in 5% of patients and rotation of the forearm was limited in 16% of patients. A statistically significant accumulation of limited rotation was seen after physeal fractures of the ulna ("one-way" ANOVA-test, p = 0.0033). A difference between the left and right side in regard to the frontal radial joint angle was seen in 6% of patients and a difference in the lateral radial joint angle was registered in 2% of patients. A difference in the radio-ulnar plane was observed in 37% of patients. In the presence of relative ulna-plus variance, 75% of patients complained of pain in the ulnocarpal compartment of the wrist. In these patients, dynamic magnetic resonance tomography revealed a compression of the ulnocarpal disk between the proximal carpal bones and the head of the ulna, as well as degeneration in the central portion of the disk. The overall outcome was very good in 72%, good in 19%, moderate in 6% and poor in 3% of patients. The younger the children had been at the time of injury, the more favourable were the results (chi-square test, p = 0.009). Children older than ten years of age with an angulatory deformity of more than 20 degrees and/or fragment dislocation over half of the breadth of the shaft at fracture consolidation showed the poorest results. Further factors having a negative influence on the outcome were repeated reduction manoeuvres and an additional fracture of the ulna.

Adolescent↗
PubMed2000

[Prenatal ultrasonography in Switzerland--a repersentative national survey] .

BACKGROUND: The cost-effectiveness ratio of routine ultrasound during pregnancy has been debated for years. However, there is a lack of population based data concerning both costs and benefit. AIM: Population based survey of ultrasound examinations (US) during pregnancy in Switzerland with respect to quantity, indications and results; estimation of total costs, the proportion paid by health insurance and the costs for routine US. METHOD: During a representative week all certified physicians and obstetrical out-patient departments in Switzerland were asked to participate in an anonymous questionnaire based national survey on the use of ultrasound during pregnancy. RESULTS: With 62.9% of the physicians and 90.6% of the out-patient departments participating a total of 6455 questionnaires were returned. On average, 4.6 US were done per pregnancy or about 520,000 scans per year. At a mean price of $ 50 per scan total costs equalied $ 26 million a year. $ 19.5 million were covered by health insurance and the rest was not billed by the physicians. The indication for the scan was a medical problem in 48%, a routine scan in 36.9% of cases a first and a second trimester scan is paid for and in 15.1% reassurance of either the women or the physician. Abnormal results were found in 40.7% of medical indications, in 15% of routine scans and in 12.6% of reassurance cases. CONCLUSION: The considerable number of scans done for reasons of reassurance and not changed for does support our hypothesis that ultrasound during pregnancy has become a tool to routinely check the general state of the fetus comparable to the stethoscope of the general practitioner. One in seven US yielded a pathological result. Maximal cost savings for the health insurance amount to about 9 million a year. This amount has to be balanced by the health benefit, respectively if routine US were abolished.

Cost-Benefit Analysis↗
PubMed2000

Anal verrucous carcinoma and penile condylomata acuminata.

A 50-year-old man presented with recurrent tumorous lesions on the penis and the anal region. The anal lesion was histologically diagnosed as verrucous carcinoma (VC) and the penile lesions were in line with condylomata acuminata. Samples taken from tumors of both sites were human papillomavirus (HPV) DNA positive. Two of them taken from the penis and the perianal region scored HPV DNA 6 positive by using polymerase chain reaction and the Southern blot method. Treatment of both VC and condylomata acuminata consisted in surgery and adjuvant immune therapy. Neither tumor recurrence nor metastases occurred up until 6 months after therapy.

Anus Neoplasms↗
PubMed2000

[Psychological aspects of ultrasound examinations during pregnancy].

The acceptability of ultrasound examinations during pregnancy has been documented in many studies. Yet there is little empirical evidence for the postulated psychological benefits of ultrasound examinations. Although seeing the baby is most often rated as a moving experience, there are no proven long-term effects of ultrasound visualization on bonding with the fetus or on pregnant women's health-related maternal behaviour. There is evidence to support the notion that attenuated anxiety and stress immediately following the examination are likely artefactual - a reflection of increased anxiety before real-time scan. Review of the literature indicates no evidence as to whether antenatal detection of fetal abnormalities leads to improvement in coping or only prolongs the phase of psychological stress and mourning. This articles provides an overview of current research on psychological effects of prenatal ultrasound examination.

Adaptation, Psychological↗
PubMed2000

Role of macrophage-derived lipoprotein lipase in lipoprotein metabolism and atherosclerosis.

Lipoprotein lipase (LPL) synthesis by macrophages is upregulated in early atherogenesis, implicating the possible involvement of LPL in plaque formation. However, it is still unclear whether macrophage-derived LPL displays a proatherosclerotic or an antiatherosclerotic role in atherosclerotic lesion development. In this study, the role of macrophage-derived LPL on lipid metabolism and atherosclerosis was assessed in vivo by transplantation of LPL-deficient (LPL-/-) and wild-type (LPL+/+) bone marrow into C57BL/6 mice. Eight weeks after bone marrow transplantation (BMT), serum cholesterol levels in LPL-/--->C57BL/6 mice were reduced by 8% compared with those in LPL+/+-->C57BL/6 mice (P:<0.05, n=16), whereas triglycerides were increased by 33% (P:<0.05, n=16). Feeding the mice a high-cholesterol diet increased serum cholesterol levels in LPL-/--->C57BL/6 and LPL+/+-->C57BL/6 mice 5-fold and 9-fold, respectively, resulting in a difference of approximately 50% (P:<0. 01) after 3 months on the diet. No effects on triglyceride levels were observed under these conditions. Furthermore, serum apolipoprotein E levels were reduced by 50% in the LPL-/--->C57BL/6 mice compared with controls under both dietary conditions. After 3 months on a high-cholesterol diet, the atherosclerotic lesion area in LPL-/--->C57BL/6 mice was reduced by 52% compared with controls. It can be concluded that macrophage-derived LPL plays a significant role in the regulation of serum cholesterol, apolipoprotein E, and atherogenesis, suggesting that specific blockade of macrophage LPL production may be beneficial for decreasing atherosclerotic lesion development.

Animals↗
PubMed2000

Von Willebrand Disease type 2M "Vicenza" in Italian and German patients: identification of the first candidate mutation (G3864A; R1205H) in 8 families.

Von Willebrand disease type 2M "Vicenza" (VWD 2M V) is characterised by autosomal dominant inheritance, low von Willebrand factor (VWF) and the presence of "supranormal" multimers in plasma. This specific phenotype has been described in Italian and recently also in German patients. The molecular defect is linked to the VWF gene. However, no specific mutations have been identified until now. We analysed the complete coding region and adjacent intron sequences of the VWF gene in Italian families in comparison to German families with VWD 2M V by a PCR-based mutation screening, combined with SSC- and heteroduplex-analysis of exons 2 through 52, followed by direct sequencing. We identified the first heterozygous candidate mutation (G3864A; R1205H) in all affected members of the 7 Italian families and in 1 German patient but not in the unaffected family members nor on 100 chromosomes of normal subjects, suggesting a causal relationship between the mutation and the phenotype. Haplotype identity, with minor deviations in one Italian family, suggests a common but not very recent genetic origin of R1205H.

Female↗
PubMed2000

[Value of panendoscopy in assessment of mouth cavity, pharyngeal and laryngeal cancers].

The concept of multiple squamous cell carcinoma in the region of the upper aerodigestive tract was first described over 100 years ago by Billroth. The aim of our study was to assess the incidence of synchronous and metachronous second primary tumours and refine the role of panendoscopy in diagnosing them. The charts of 358 patients presenting for initial treatment of primary squamous cell carcinoma of the upper aerodigestive tract between January 1990 and December 1995 were reviewed. The incidence of second primary tumours was 16.2%, 6.4% being synchronous and 9.8% metachronous. In only 3.1% of all patients was a synchronous tumour clinically silent and only revealed by panendoscopy. Synchronous tumours were most likely to be located in the oral cavity, pharynx or larynx (61%), whereas metachronous second primary tumours were most likely to be located in the lung (57%). Though the incidence of synchronous second primary tumours revealed by routine panendoscopy is low (3%), we still recommend this investigation because it is often necessary for exact assessment of the first primary tumour. Further, it is ideal for training in the use of rigid endoscopy. In our opinion panendoscopy involves minimal time, cost and morbidity.

Carcinoma, Squamous Cell↗
PubMed1999

Endogenously produced lipoprotein lipase enhances the binding and cell association of native, mildly oxidized and moderately oxidized low-density lipoprotein in mouse peritoneal macrophages.

It has been well established that purified lipoprotein lipase (LPL) can facilitate the cellular uptake of various native and modified lipoproteins when added exogenously to macrophages. Because activated macrophages express LPL endogenously, it was the aim of this study to investigate the effect of macrophage-produced LPL on the uptake of native low-density lipoprotein (LDL) and LDL that has been modified to various degrees by Cu(2+)-mediated oxidation. Cell binding and uptake of Eu(3+)-labelled native and oxidized LDL was determined in mouse peritoneal macrophages (MPM) from normal mice and induced mutant mice that lack LPL expression in MPM. We found that LPL expressed by MPM was able to increase cell binding and association of native LDL (by 121% and 101% respectively), mildly oxidized LDL (by 47% and 43%) and moderately oxidized LDL (by 30% and 22%). With increased levels of lipoprotein oxidation, the relative proportion of LPL-mediated LDL uptake decreased. This decrease was not due to weakened binding of LPL to oxidized LDL. The drastically increased uptake of highly oxidized LDL in MPM by scavenger-receptor-mediated pathways might dominate the simultaneous exogenous or endogenous LPL-mediated uptake of this lipoprotein. Competition experiments with positively charged poly(amino acids) furthermore suggested that histidine, arginine and lysine residues in LPL are important for the interaction between LDL and LPL. Our results imply that physiological levels of LPL produced by macrophages facilitate the uptake of native LDL as well as mildly and moderately oxidized LDL. This process might, in the micro-environment of arteries, contribute to the accumulation of macrophage lipids and the formation of foam cells.

Amino Acids↗
PubMed1999

Prostaglandin-H-synthase isozyme expression in normal and neoplastic human skin.

Expression of prostaglandin-H-synthase (PGHS) isozymes was analyzed in 50 biopsies of normal human skin and of pre-malignant and malignant skin lesions, by means of quantitative RT-PCR, immunoprecipitation and Western blotting, as well as immunohistochemistry. Normal skin constitutively expressed PGHS-1 in all cell layers of the epidermis, in endothelial cells of small blood vessels and in sweat-gland epithelium. PGHS-2 expression was very low and restricted to a few keratinocytes of the interfollicular and follicular epidermis. Steady-state concentrations of PGHS-1 and PGHS-2 mRNA were similar in normal skin and in basal-cell carcinomas, but PGHS-1 mRNA was reduced and PGHS-2 mRNA was elevated in actinic keratoses, squamous-cell carcinomas and keratoacanthomas. PGHS-1 protein was detected in all tumor biopsies, being occasionally increased in basal-cell carcinomas. High amounts of PGHS-2 protein were found in actinic keratoses, squamous-cell carcinomas and keratoacanthomas, but not in basal-cell carcinomas. Four malignant melanomas included in this study contained PGHS-1 but no PGHS-2 protein. Immunohistochemical analysis of the biopsies identified keratinocytes, in addition to cells of inflammatory infiltrates and of dendritic morphology, as the major PGHS-expressing cell types. PGHS-2-specific signals were spread throughout the epidermal part of actinic keratoses and squamous-cell carcinomas. These data suggest that constitutive up-regulation of PGHS-2 expression is a consistent pre-malignant event in squamous-cell cancer development in man, as it is in animal models of skin carcinogenesis. Thus, pre-cancerous lesions such as actinic keratoses present a likely target for chemoprevention of skin cancer by selective PGHS-2 inhibitors.

Aged↗