Search PubMed⌕ Search

Biomedical subjects

R Schulz

Publications and source records attributed to R Schulz.

At least 307 records · Page 17Linked to original sources
PubMed1996

Status and transcriptional activity of a bovine-papillomavirus-I-based expression vector in a recombinant production cell line.

We have analysed the status and transcriptional activity of the bovine papillomavirus-I (complete BPV-I genome)-based expression vector pCES in CI27i-cell-line-derived 3TI cells used for the industrial production of recombinant human erythropoietin (rhuEpo). Complete tandem head-to-tail integration of about 600 vector copies at a single site of the cellular genome was observed. Deletions, insertions or rearrangements of pCES-specific sequences or extrachromosomal copies of vector sequences were not detected. Transcriptional analyses demonstrated that rhuEpo was abundantly expressed. BPV-I early transcription was detected, as expected from a BPV-I-transformed cell line; however, compared with the mouse metallothionein-I-promoter-driven rhuEpo-specific transcription, it was very weak. Late BPV-I transcription was also not detected in 3TI cells under conditions of large-scale rhuEpo production. Therefore this expression system proved to be safe and suitable for the production of rhuEpo.

Animals↗
PubMed1996

Prevalence of obstructive sleep apnoea in patients with coronary artery disease.

BACKGROUND: Obstructive sleep apnoea (OSA) is characterized by recurring upper airway collapse with continual respiratory effort during sleep, causing apnoea, a fall in arterial oxygen saturation, arousal and excessive daytime sleepiness. It is a common disorder, with an estimated prevalence of about 1-5% in the adult population. OSA is related to arterial hypertension, an essential risk factor for the development of coronary artery disease (CAD). Furthermore, a high dietary intake is a common risk factor for OSA as well as for CAD. OBJECTIVE: To investigate the prevalence of OSA in CAD patients. METHODS: A random sample of 50 patients (aged 61 +/- 6 years, body mass index 26.8 +/- 3.8 kg/m2) diagnosed to have CAD by coronary angiography was investigated prospectively. Respiration and nocturnal oxygen saturation were registered during one night. Snoring and daytime sleepiness were evaluated by a questionnaire. RESULTS: In 25 patients the apnoea index was > 10/h sleep. Excessive daytime sleepiness was exhibited by eight of these patients. Nineteen of the patients with an apnoea index > 10/h participated in a full night polysomnography. The apnoea index was 17.0 +/- 10.9/h and the apnoea-hypopnoea index was 32.4 +/- 16.5/h sleep. The mean nadir oxygen saturation was 87.3 +/- 1.6% and the minimal oxygen saturation was 75.5 +/- 10.6%. For seven patients the apnoea index was > 20/h. CONCLUSION: CAD patients have a high prevalence of OSA. Since obstructive apnoeas may trigger severe cardiac events such as myocardial ischaemia or ventricular tachycardias in CAD patients, the presence of OSA in these patients should be considered.

Aged↗
PubMed1996

Prothipendyl: detection and elimination in the horse--a case report.

The azaphenothiazine neuroleptic prothipendyl (Dominal) is suspected to be administered illegally at low doses to race-horses to improve their performance. Since for this species pharmacokinetic data of the drug are missing we studied its elimination from blood and urine in a standard-bred mare. At a low (subtherapeutic) dose (i.v., 0.24 mg/kg) the horse is described to be less excited while locomotor activity and attention remain unaffected. In contrast, sedation and ataxia are brought about at 1 mg/kg (therapeutic dose). Identification of prothipendyl given i.v. at subtherapeutic doses was achieved in blood only by means of gas chromatography-mass spectrometry (GC-MS), while the neuroleptic was found both in blood and urine upon 1 mg/kg. Quantification of the neuroleptic was carried out by virtue of triflupromazine as internal standard with the MS operating in the selected ion monitoring (SIM) mode. Under these conditions, the detection limit was 10 ng/ml body fluid. Disappearance of prothipendyl from blood was determined in the horse studied from terminal elimination process, yielding a t1/2 of 2.4 h. The results suggest that for detection of prothipendyl in the horse--in contrast to phenothiazine neuroleptics--screening of blood is preferred over urine as the drug was not recovered in urine after administration of subtherapeutic doses.

Animals↗
PubMed1996

[Detection of doping compounds in the racing pigeon].

To overcome the doping problems in racing pigeons it requires reliable methods to detect illegally medicated drugs. Difficulties applying specifically to pigeons caused the present investigation, since urine and blood commonly analyzed cannot be gathered from pigeons. Drug detection is complicated by those compounds exhibiting an extremely high potency such as the anabolic boldenone, the glucocorticoid prednisolone, and the bronchodilator clenbuterol. The material for analysis selected was faeces of pigeons treated with the doping substances under investigation. The freeze-dried material was subjected to liquid/liquid extraction (Extrelut), and the extracts were submitted to high performance liquid chromatography. Identification of drugs present in the fractions was carried out by specific antibodies (ELISA), and their relative chromatographic retentions were calculated by means of internal standards. The results obtained provide an overall information about elimination kinetics of the three drugs examined. Thus, boldenone, prednisolone, and clenbuterol were detected in the faeces up to 7 weeks, 2 and 1 day, respectively (limits of detection amounted to 0.1-4 ng per g of the freeze-dried faeces.) The detection periods correspond to the periods of pharmacological action of the individual compounds. The results reported here exemplify the proof of doping by examination of faeces from pigeons treated with very potent drugs. High performance liquid chromatography combined with ELISA turned out to be a suitable technique to detect illegal medication in racing pigeons.

Anabolic Agents↗
PubMed1996

[Hibernating myocardium: no involvement of endogenous adenosine].

During moderate but nevertheless prolonged myocardial ischemia, the myocardium is dysfunctional but can remain viable. In such ischemic and dysfunctional myocardium, contractile function is reduced in proportion to the reduction in regional myocardial blood flow; i.e. a state of "perfusion-contraction matching" exists. The metabolic status of such myocardium improves over the first few hours, as myocardial lactate production is attenuated and creatine phosphate, after an initial reduction, returns towards control values. Ischemic myocardium, characterized by perfusion-contraction matching, metabolic recovery and lack of necrosis, has been termed "short-term hibernating myocardium". Short-term hibernating myocardium can respond to an inotropic stimulation with increased contractile function, however, at the expense of a renewed worsening of the metabolic status. This situation of an increased regional contractile function at the expense of metabolic recovery during inotropic stimulation can be used to identify short-term hibernating myocardium. A role for endogenous adenosine in the development of hibernation has been excluded, since neither contractile function nor metabolic parameters nor viability are altered by increased catabolism of endogenous adenosine by infusion of adenosine deaminase. Whereas short-term hibernation is well characterized in animal experiments, the existence of hibernation over weeks or months (long-term hibernation) can only be inferred from clinical studies. Hibernation, as defined by Rahimtoola, is a state of chronic contractile dysfunction in patients with coronary artery disease which is fully reversible upon reperfusion.

Adenosine↗
PubMed1995

[Sleep-related breathing disorders in patients with coronary heart disease].

INTRODUCTION AND AIM OF STUDY: Obstructive sleep apnoea (OSA) favours the development of arterial hypertension independently of body-weight and may thus have an effect on coronary heart disease (CHD). This study was undertaken to determine the prevalence of OSA in patients with CHD. PATIENTS AND METHODS: From among all patients in whom left heart catheterization with coronary angiography had provided the diagnosis of coronary heart disease 50 were randomly chosen (47 men, 3 women; mean age 61 +/- 6 years) for further investigations. During the night airway flow, heart rate, body position and arterial oxygen saturation were recorded. The patients also had to fill in a questionnaire concerning tiredness during the day and any snoring. Polysomnography was performed in all those whose apnoea index (AI) was > 10/h. RESULTS: 25 patients had an apnoea index of > 10/h. Eight of them also had increased tiredness during the day. The patients with an AI > 10/h were significantly older than those in whom it was < or = 10/h (63.1 +/- 3.5 vs 58.4 +/- 7.2 years; P < 0.002) and also had a higher body-mass index (27.8 +/- 4.2 vs 25.7 +/- 3.0 kg/m2; P < 0.05). Polysomnography, done in the sleep laboratory, in 19 of the 25 patients with an AI > 10/h registered an average AI of 17.0 +/- 10.9 per hour sleep; in seven patients it was > 20/h. CONCLUSIONS: The prevalence of obstructive sleep apnoea (OSA) is higher in patients with coronary heart disease (CHD) than in the healthy population. As OSA associated with a marked fall in nocturnal blood oxygen saturation and a rise in blood pressure may cause myocardial ischaemia, OSA should also always be considered when CHD is diagnosed.

Anthropometry↗
PubMed1995

[Doppler echocardiographic analysis of diastolic function in dilatative cardiomyopathy for the evaluation of its progression and prognosis].

The relationship between left-ventricular diastolic function and the course of the disease was investigated in a prospective study of 61 patients (44 men, 17 women; median age 51 [26-74] years) with dilated cardiomyopathy. The diastolic function was measured by recording the transmitral Doppler flow profile. During a follow-up period of 33 +/- 23 months, 15 patients died (twelve of progressive heart failure, three suddenly without previous heart failure). Cardiac transplantation was performed in four patients. The overall 1-year mortality rate was 14%. A "restrictive" Doppler echocardiographic filling pattern with a steep early-diastolic maximum and a small atrial filling component predominated in the patients who died from progressive heart failure or had a cardiac transplantation because of it. The deceleration of the early diastolic velocity maximum was clearly shorter than in the survivors (111 +/- 32 ms vs 194 +/- 62 ms; P < 0.001). In a Cox proportional hazard model the deceleration time was the best prognosticator, followed by the end diastolic left-ventricular diameter (LVD). The group of patients with a short deceleration time (< or = 140 ms) had a significantly higher 1-year mortality rate (28% [confidence interval 9-47%]) than those in whom it was longer (3% [0-11%]; P < 0.0001). Taking into account LVD it proved possible to identify a prognostically especially unfavourable group with a 1-year mortality rate of 53% (26-80%), characterized by a LVD > 70 mm and a deceleration time < or = 140 ms. Repeated echocardiography in 26 survivors and nine patients who died later or had been operated on showed that the deceleration time did not change significantly in the course of the disease. On the other hand, the systolic function, as measured by the echocardiographically determined shortening fraction, improved in the survivors (from 0.18 +/- 0.07 to 0.22 +/- 0.08; P < 0.05), but not in those who later on died.

Adult↗
PubMed1995

Detection of minimal residual disease by polymerase chain reaction in B cell malignancies.

It was the aim of this study to examine the prognostic value of the detection of minimal residual disease (MRD), with the help of the polymerase chain reaction (PCR), in patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM) who underwent sequential high-dose therapy with peripheral blood progenitor cell (PBPC) support, and in patients with acute myeloid leukemia (AML) of the subclass M4Eo who underwent high-dose consolidation therapy. Basis for the application of a PCR assay in these disease entities are the following specific gene rearrangements: the t(14;18) translocation in a high percentage of NHL, the clonal rearrangement of the Ig heavy chain locus resulting in a unique complementary determining region 3 (CDR3) for MM region and the inversion 16 characteristic for the M4Eo subclass of AML. Before the G-CSF-supported cytotoxic chemotherapy was given, 65% of the 52 patients with low- and intermediate-grade NHL enrolled into the study had PCR+ bone marrow (BM) and/or peripheral blood (PB) samples. The majority of patients (29 of 52) were autografted with a PCR+ transplant. The proportion of harvests containing t(14;18)+ cells was two-fold less in patients mobilized in first remission than in those with a history of previous treatment failure. This was also reflected when examining the B cell contents of the harvests measured as CD19+ cells with a 3.3-fold smaller proportion of CD19+ cells in leukapheresis (LP) products of patients mobilized in first remission. Patients who received a PCR- transplant are in remission and remained PCR- in BM and PB samples post-transplantation. Conversion to PCR-negativity in BM and PB samples post-transplantation was observed in 11 of 19 patients who were also in remission. In contrast, 6 of 29 patients who were autografted with PCR+ products relapsed, while 4 of them presented with PCR- samples on several occasions post-transplantation. In patients with MM, the assessment of MRD in PBPC harvests was based on the CDR3 regions of the Ig heavy chain locus as a marker for clonality. The great majority of LP products (17 out of 19) contained tumor cells. To prove positive enrichment procedures for the elimination of tumor cells, CD34+ and CD19+ cell fractions obtained from LP samples in an experimental setting via preparative flow cytometry were analyzed for MRD resulting in PCR-negativity for all CD34+ fractions. The results of the four patients with AML M4Eo and inversion 16 are preliminary, with a tendency of persistence of PCR-positivity after finishing the high-dose consolidation therapy. In one case, recurrence of disease was accompanied by an increase of the signal strength in the PCR assay. Longer follow-up periods are necessary to determine the prognostic value of these PCR findings in the different disease entities.

Acute Disease↗
PubMed1995

Involvement of endogenous adenosine in ischaemic preconditioning in swine.

Adenosine release and the subsequent activation of adenosine receptors are involved in ischaemic preconditioning in dogs and rabbits. In the present study, we investigated whether adenosine also mediates ischaemic preconditioning in swine. Swine were used since, due to the lack of an innate collateral circulation, infarct development in this species most closely resembles that observed in humans. In 36 enflurane-anaesthetized swine the impact of increased adenosine breakdown with exogenous porcine adenosine deaminase (5 IU/ml blood/min) on global and regional myocardial function (sonomicrometry), subendocardial blood flow (ENDO, microspheres) and infarct size (IS, triphenyl tetrazolium chloride staining following 90 min ischaemia and 120 min reperfusion) were analysed. Low-flow ischaemia for 90 min at an ENDO of 0.09 +/- 0.04 (mean +/- SD) ml/min/g caused an IS of 13.2 +/- 9.7% (n = 8) of the area at risk. Ischaemic preconditioning by a cycle of 10 min low-flow ischaemia followed by 15 min reperfusion prior to the 90-min ischaemic period (ENDO = 0.06 +/- 0.03 ml/min/g) reduced IS to 2.6 +/- 3.0% (n = 11, P < 0.05). The interstitial adenosine concentration (microdialysis) increased from 1.60 +/- 0.87 nmol/ml to above 10 microM during ischaemia; with intracoronary adenosine deaminase, the interstitial adenosine concentration fell from 1.65 +/- 0.23 to 0.12 +/- 0.07 nmol/ml and did not increase during ischaemia. Adenosine deaminase per se did not alter IS after 90 min ischaemia (n = 7, ENDO = 0.08 +/- 0.04 ml/min/g, IS = 12.1 +/- 6.9%) but abolished the beneficial effect of ischaemic preconditioning (n = 10, ENDO = 0.06 +/- 0.03 ml/min/g, IS = 8.8 +/- 5.8%). For any given ENDO, IS was significantly reduced in the ischaemic preconditioned group compared with the other three groups. Global and regional myocardial function were comparable among all groups of swine. We conclude that endogenous adenosine mediates ischaemic preconditioning also in swine.

Adenosine↗
PubMed1995

Atrial natriuretic peptide inhibits nitric oxide synthesis in mouse macrophages.

The atrial natriuretic peptide (ANP) affects cardiovascular physiology, and, as has been suggested more recently, exerts immunomodulatory activities. In this context, we examined the effect of ANP on nitric oxide (NO) synthesis in murine bone marrow derived macrophages as well as in peritoneal macrophages. Cultured macrophages were stimulated with lipopolysaccharides (LPS 0.1-10 micrograms/ml) and NO synthesis was monitored by measuring increased concentrations of NO2 in the medium. In initial experiments employment of NG-monomethyl-L-arginine (L-NMMA) and dexamethasone, two specific inhibitors of nitric oxide synthase (NOS), confirmed the presence of inducible NOS activity in the cells. Exposure of cells to rat ANP99-126 in the range of 10(-8) to 10(-6) M significantly decreased LPS induced NO synthesis over 24 hours of incubation. Thus, ANP may alter macrophage function by affecting their nitric oxide synthesizing pathway.

Animals↗
PubMed1995

Co-expression of the natriuretic peptides (ANP, BNP, CNP) and their receptors in normal and acutely involuted rat thymus.

The natriuretic peptides (NP) ANP, BNP and CNP constitute circulating hormones as well as neuropeptides. The present investigation reveals that these peptides are also constituents of the immune system. BNP and CNP, in addition to ANP as previously communicated, are synthesized in the rat thymus. The NP seem to be produced by different types of thymic cells. Moreover, expression of NP is differentially affected by acute involution of the organ caused by dexamethasone (DEX). The concentration of BNP and CNP mRNA was not changed in gradually involuted thymi (i.e. at day 2, 3 and 4 after DEX administration). ANP mRNA was increased in parallel with the degree of involution (2-, 5- and 40-fold, respectively). The concentration of immunoreactive CNP (CNP-IR) was not affected by acute involution of the thymus (4th day after DEX); BNP-IR, however, was increased 2-fold and for comparison, ANP-IR as previously shown, was found 10-fold elevated. Our studies also revealed the presence of the specific mRNAs coding for the A-, B-, and C-type NP receptor in the thymus. The thymic NP system may be involved in the communication between the immune and neuroendocrine system.

Animals↗
PubMed1995

A mixed-ligand iron-sulfur cluster (C556SPaB or C565SPsaB) in the Fx-binding site leads to a decreased quantum efficiency of electron transfer in photosystem I.

The proposed structure of Photosystem I depicts two cysteines on the PsaA polypeptide and two cysteines on the PsaB polypeptide in a symmetrical environment, each providing ligands for the interpolypeptide Fx cluster. We studied the role of Fx in electron transfer by substituting serine for cysteine (C565SPsaB and C556SPsaB), thereby introducing the first example of a genetically engineered, mixed-ligand [4Fe-4S] cluster into a protein. Optical kinetic spectroscopy shows that after a single-turnover flash at 298 K, the contribution of A1- (lifetime of 10 microseconds, 40% of total and lifetime of 100 microseconds, 20% of total) and Fx- (lifetime of 500-800 microseconds, 10-15% of total) to the overall P700+ back reaction have increased in C565SPsaB and C556SPsaB at the expense of the back reaction from [FA/FB]-. The electron paramagnetic resonance spectrum of Fx shows g-values of 2.04, 1.94, and 1.81 in both mutants and a similarly decreased amount of FA and FB reduced at 15 K after a single-turnover flash. These results indicate that the mixed-ligand (3 cysteines, 1 serine) Fx cluster is an inefficient electron carrier, but that a small leak through Fx still permits FA and FB to be reduced quantitatively when the samples are frozen during continuous illumination. The data confirm that Fx is a necessary intermediate in the electron transfer pathway from A1 to FA and FB in Photosystem I.

Binding Sites↗
PubMed1995

Activity restriction mediates the association between pain and depressed affect: a study of younger and older adult cancer patients.

Associations are reported frequently among pain, functional disability, and symptoms of depression. The purpose of this longitudinal study was to further clarify relations among these variables. In 268 younger (ages 30-64) and older (ages 65-90) cancer outpatients, cross-sectional analyses replicated previous findings showing that effects of pain on symptoms of depression are mediated by functional disability. Longitudinal analyses revealed that as pain increased over time, so did activity restriction, which in turn predicted increases in depressed affect. Comparative analyses indicate that restriction of routine activities that are due to illness and pain may be more distressing to individuals less than 65 years of age than to those 65 years of age or older. The results suggest that older persons are less distressed by restricted activities because of lower expectations about functional status and more experience with illness and disability.

Activities of Daily Living↗
PubMed1995

A life-span theory of control.

A life-span theory of development is presented that is based on the concepts of primary and secondary control. Primary control refers to behaviors directed at the external environment and involves attempts to change the world to fit the needs and desires of the individual. Secondary control is targeted at internal processes and serves to minimize losses in, maintain, and expand existing levels of primary control. Secondary control helps the individual to cope with failure and fosters primary control by channeling motivational resources toward selected action goals throughout the life course. Primary control has functional primacy over secondary control. An analysis of extensive and diverse literatures spanning infancy through old age shows that trade-offs between primary and secondary control undergo systematic shifts across the life course in response to the opportunities and constraints encountered.

Adolescent↗
PubMed1995

Chronic activation of inhibitory delta-opioid receptors cross-regulates the stimulatory adenylate cyclase-coupled prostaglandin E1 receptor system in neuroblastoma x glioma (NG108-15) hybrid cells.

The present article investigates chronic opioid regulation of the stimulatory adenylate cyclase-coupled prostaglandin E1 (PGE1) receptor system in neuroblastoma x glioma (NG108-15) hybrid cells. Persistent activation of delta-opioid receptors by morphine (10 mumol/L; 3 days) substantially down-regulates the number of PGE1 binding sites by approximately 30%, without affecting their affinity. Radioligand binding studies performed in the presence of GTP gamma S (100 mumol/L) further revealed that the remaining PGE1 binding sites are still capable of interacting functionally with their associated stimulatory G proteins, Gs. On the postreceptor level, neither changes in the abundance nor in the intrinsic activity of the alpha subunit of Gs (Gs alpha) were found during the state of opioid dependence, as has been verified by western blot and S49 cyc- reconstitution experiments, respectively. Evaluation of the functional interaction between PGE1 receptors and Gs by means of receptor-stimulated, cholera toxin-catalyzed ADP-ribosylation of Gs alpha revealed a significant increase in the ability of PGE1 receptors to activate Gs alpha (3.3-fold increase in EC50; p < 0.05) in cells chronically exposed to morphine. This effect was completely blocked by coincubation of the cells together with the opiate antagonist naloxone (100 mumol/L; 3 days), whereas precipitation of morphine withdrawal by naloxone (100 mumol/L) had no further effect on sensitization in PGE1 receptor/Gs coupling. These findings provide evidence that the stimulatory adenylate cyclase-coupled PGE1 receptor system represents a potential target of chronic delta-opioid receptor activation in NG108-15 hybrid cells. They further suggest that sensitization in stimulatory signal transduction plays a critical role in the generation of opioid dependence.

Adenosine Diphosphate Ribose↗
PubMed1995

Characterization of hibernating and stunned myocardium.

Both the hibernating and the stunned myocardium are characterized by reversible contractile dysfunction. In hibernating myocardium, perfusion is still reduced, whereas in stunned myocardium blood flow is fully or almost fully restored. Both the hibernating and the stunned myocardium retain an inotropic reserve. In hibernating myocardium the increase in contractile function is at the expense of metabolic recovery, whereas in the stunned myocardium no metabolic deterioration occurs during inotropic stimulation. Therefore, inotropic stimulation in combination with metabolic imaging may help not only to identify viable, dysfunctional myocardium but also to distinguish hibernating and stunned myocardium. The therapy of hibernating myocardium is to restore blood flow to the hypoperfused tissue. Myocardial stunning per se requires no therapy at all, since, by definition, blood flow is normal and contractile function will recover spontaneously. If, however, myocardial stunning is severe, and it involves large parts of the LV and thus impairs global LV function, it can be reversed with inotropic agents and procedures. In the experimental setting, anti-oxidant agents, calcium antagonists and ACE inhibitors attenuate stunning, but most effectively when administered before ischaemia.

Animals↗
PubMed1995

Psychiatric and physical morbidity effects of dementia caregiving: prevalence, correlates, and causes.

The dementia caregiving literature is reviewed with the goals of (a) assessing the prevalence and magnitude of psychiatric and physical morbidity effects among caregivers, (b) identifying individual and contextual correlates of reported health effects and their underlying causes, and (c) examining the policy relevance of observed findings. Virtually all studies report elevated levels of depressive symptomatology among caregivers, and those using diagnostic interviews report high rates of clinical depression and anxiety. The evidence is more equivocal and generally weaker for the association between caregiving and physical morbidity, such as self-rated health, number of illnesses, symptomatology, health care utilization, preventive health behaviors, and cardiovascular functioning. Across studies, psychiatric morbidity in caregivers was linked to patient problem behaviors, income, self-rated health, perceived stress, and life satisfaction. Physical morbidity was associated with patient problem behaviors and cognitive impairment, and with caregiver depression, anxiety, and perceived social support. Possible causes of reported effects and policy implications are discussed.

Activities of Daily Living↗