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Biomedical subjects

C Schaefer

Publications and source records attributed to C Schaefer.

At least 19 recordsLinked to original sources

Acute effects of tumor necrosis factor alpha or lymphotoxin on global blood flow, laser Doppler flux, and bioenergetic status of subcutaneous rodent tumors.

Global blood flow (TBF), tumor vascular resistance, laser Doppler flow in superficial tumor areas, and mean arterial blood pressure were evaluated in rats bearing s.c. DS sarcomas. Measurements were performed before and after i.v. administration of rhTNF-alpha 2 or recombinant human lymphotoxin (rhLT) (1 mg/kg). Upon application of the cytokines a significant drop in TBF was found at t greater than or equal to 90 min with a stronger action following rhLT than rhTNF-alpha. At relatively constant mean arterial blood pressure values following the cytokine injection, the microcirculatory function in the tumor periphery was found to be impaired somewhat earlier than TBF, indicating that the cytokines do not preferentially act on the poorly perfused tumor center in the model chosen. This finding is inconsistent with previous histological studies on murine tumors. Acute flow changes encompassed only substantial reductions (i.e., hypoperfusion) rather than a complete ischemia. TBF was slightly increased during the first hour following rhLT whereas after rhTNF-alpha a continuous drop was observed. This differential response could not be observed during laser Doppler flowmetry. Tumor vascular resistance changes largely reflected alterations in TBF. 31P-Nuclear magnetic resonance spectroscopy on murine Meth-A fibrosarcomas revealed dose- and time-dependent decreases of ATP/Pi and phosphocreatine/Pi ratios following i.v. administration of rhTNF-alpha. From comparisons of dose-response curves rhLT appears to be more detrimental than rhTNF-alpha with respect to the bioenergetic status. The observed changes in tumor energy metabolism are similar to those described for TBF. It may therefore be concluded that most of the cytokine effects on the bioenergetic status are secondary to the inhibition of the microcirculatory function. As a major causative factor for the latter, an arterial hypotension can be excluded in the tumor model chosen.

Adenosine Triphosphate

Mutations in the DnaA binding sites of the replication origin of Escherichia coli.

Mutations (base changes) were introduced into the four DnaA binding sites (DnaA boxes) of the Escherichia coli replication origin, oriC. Mutations in a single DnaA box did not impair the ability of these origins to replicate in vivo and in vitro. A combination of mutations in two DnaA boxes, R1 and R4, resulted in slower growth of the oriC plasmid-bearing host cells. DnaA protein interaction with mutant and wild-type DnaA boxes was analyzed by DNase I footprinting. Binding of DnaA protein to a mutated DnaA box R1 was not affected by a mutation in DnaA box R4 and vice versa. Mutations in DnaA boxes R1 and R4 did not modify the ability of the DnaA protein to bind to other DnaA boxes in oriC.

Bacterial Proteins

Intrauterine diethyltoluamide exposure and fetal outcome.

The CNS toxicity of the insect repellent, diethyltoluamide (DEET), has been documented by several publications on severely affected adults and children. We report a 4-year-old boy with mental retardation, impaired sensorimotor coordination, and craniofacial dysmorphology, whose mother applied DEET daily throughout her whole pregnancy in addition to the prophylactic use of chloroquine.

Abnormalities, Drug-Induced

[The visibility of a central venous catheter using digital luminescence radiography in intensive care radiology].

The aim of the following study was to assess the impact of dose alterations on the detection of catheters. We compared the performance of well-exposed conventional and digital portable chest radiographs in the detection of thin catheters and tested the influences of dose alterations. Portable chest radiographs of 20 patients were obtained with conventional film/screen (FR) and with storage phosphors at 50% (SRL), 100% (SRN), and 250% (SRH) of the conventionally required exposure dose. The region of the mediastinum was subdivided into an average of 18 fields, 50% of which were superimposed with thin catheter segments. ROC analysis of 11,600 observations by 8 readers found only SRH equivalent to FR in catheter visualisation. Performance decreased significantly with SRN and SRL. Detection of low contrast catheters was found to be significantly decreased in storage phosphor radiographs obtained with standard exposure dose. A dose reduction is not feasible with current equipment if performance equivalent to conventional radiography is to be achieved.

Catheterization, Central Venous

[Chemoembolization of hepatocellular carcinoma in cases of isolated liver involvement].

Chemoembolization is an effective treatment for hepatocellular carcinoma, giving results equally as good as surgical therapy for T2 tumours. Survival can be prolonged and side-effects can be reduced by combining Lipiodol and Gelfoam for chemoembolization, employing a modified technique, with repeated procedures, and using appropriate follow-up treatment. The toxicity of the procedure is acceptable, but it requires supportive therapy necessitating an intense interdisciplinary co-operation.

Aged

[Differences in the non-invasive assessment of left ventricular filling in patients with dilated cardiomyopathy using Doppler echocardiography and radionuclide angiography].

Doppler echocardiography and radionuclide angiography were shown to provide valuable tools with comparable functional parameters for the noninvasive assessment of left ventricular (LV) diastolic function in patients with coronary artery disease or LV hypertrophy. In order to examine the influence of an impaired systolic function on both methods, we studied LV filling simultaneously by Doppler echocardiography and radionuclide angiography in 47 patients with idiopathic dilated cardiomyopathy and stable sinus rhythm. The Doppler echocardiographic peak velocities (VE, VA) and radionuclide angiographic peak filling rates (PFRFF, PFRA) normalized to either left ventricular enddiastolic volume or stroke volume were measured and systolic function was assessed by obtaining the ejection fraction (EF) with the radionuclide angiography. Patients were divided into two groups with moderately (group 1: EF > or = 35%) or severely impaired (group 2: EF < 35%) systolic function. In group 2 the PFRFF (1.8 +/- 0.5 vs. 3.3 +/- 0.8 SV/s; p < 0.01) and PFRA (1.2 +/- 0.6 vs. 2.5 +/- 1.0 SV/s; p < 0.01) were both lower than in group 1, as was the Doppler echocardiographic VA (0.44 +/- 0.20 vs. 0.63 +/- 0.17 m/s; p < 0.01). However, VE was increased with reduced systolic function (0.75 +/- 0.20 vs. 0.53 +/- 0.16 m/s; p < 0.01). No relation was found between PFRFF and VE and only a weak relation between the atrial filling parameters of Doppler echocardiography and radionuclide angiography. The peak filling rates were closely correlated with the systolic function (PFRFF:r = 0.86; p < 0.001) and were reduced with an impaired systolic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Flow Velocity

DnaA protein/DNA interaction. Modulation of the recognition sequence.

In the active orientation the DnaA protein/dnaA box complex blocks transcribing RNA polymerase. The extent of transcription termination at different dnaA boxes was used to determine in vivo their various affinities to the DnaA protein. The rate of transcription distal to the respective dnaA box was monitored by the expression of the reporter gene galK. The dnaA boxes (5'-TTATACACA and 5'-TTATCCAAA), present in oriC, showed the strongest binding affinity. The dnaA box 5'-TTTTCCACA was mutated at eight positions such that the boxes differed from the consensus sequence, 5'-TT(A/T)T(A/C)CA(A/C)A, defined so far. Based on the different properties of the dnaA boxes, a new consensus sequence was derived: 5'-(T/C)(T/C)(A/T/C)T(A/C)C(A/G)(A/C/T(A/C).

Bacterial Proteins

Acute changes of systemic parameters in tumour-bearing rats, and of tumour glucose, lactate, and ATP levels upon local hyperthermia and/or hyperglycaemia.

Arterial blood pressure and relevant parameters of the arterial blood (O2 and CO2 tensions, pH, haematocrit, serum electrolytes and osmolality) were determined in tumour-bearing rats upon local hyperthermia (HT) and/or hyperglycaemia (HG). Tumour heating was performed in a saline bath (44 degrees C) for 120 min; hyperglycaemia was induced by i.v. infusion of 40% glucose solution for 150 min [blood glucose levels: 35-40 mM during heating; total amount of glucose: 1.19 g/100 g body wt.; infusion rates: 0.31 ml (100 g body wt.)-1 min-1 for 2 min, 0.02 ml (100 g body wt.)-1 min-1 for 88 min, and 0.01 ml (100 g body wt.)-1 min-1 for 60 min]. Immediately after treatment, glucose, lactate and ATP levels were determined in tumour and muscle specimens and compared to these values under normothermic (NT) and/or normoglycaemic (NG) conditions. In all groups (NT/NG, NT/HG, HT/NG, HT/HG) there were only minor but characteristic changes in blood parameters, which were mainly due to the volume and type of the infused fluids (glucose solution, saline). During hyperglycaemia, tumour glucose levels rose 13- to 17-fold, whereas muscle glucose concentrations exhibited only a 3- to 5-fold increase; lactate levels were 1.9-2.5 times higher in tumours than in muscle, indicating an increase in the metabolic differences between normal and malignant tissues. Despite an increased glucose availability, tumours did not show an improved energy status and, thus, would not be expected to develop a decrease in thermal sensitivity or stimulation in growth rate. The good systemic tolerability of the combined treatment (HT/HG) and the differential changes in malignant and normal tissue occurring under these conditions, support further attempts to manipulate tumour metabolic environment by glucose in order to achieve better therapeutic results.

Adenosine Triphosphate

[Digital projection radiography].

Several hundred storage phosphor digital projection radiography (DR) systems are in operation in many parts of the world in experimental and clinical settings. They are used clinically for almost all projection radiographic studies except mammography. An overview is given of the experimental and clinical results achieved so far. Image post-processing has yet to meet the initial expectations. The average image quality will certainly improve with automatic brightness control. Edge enhancement should be performed in selected applications only. A true increase in diagnostic information probably cannot be expected except with dual energy techniques. Dose reductions are possible only in those studies in which the specific imaging task permits a decrease in signal-to-noise ratio.

Humans

Assessment of tumor energy and oxygenation status by bioluminescence, nuclear magnetic resonance spectroscopy, and cryospectrophotometry.

The energy and oxygenation status of tumors from two murine sarcoma lines (KHT, RIF-1) and two human ovarian carcinoma xenograft lines (MLS, OWI) were assessed using three independent techniques. Tumor energy metabolism was investigated in vivo by 31P nuclear magnetic resonance spectroscopy. After nuclear magnetic resonance measurements, tumors were frozen in liquid nitrogen to determine the tissue ATP concentration by imaging bioluminescence and to register the intracapillary oxyhemoglobin (HbO2) saturation using the cryospectrophotometric method. There was a positive correlation between the nucleoside triphosphate beta/total resonance ratio or a negative correlation between the Pi/total resonance ratio and the model ATP concentration obtained by bioluminescence, respectively. This was true for small tumors with no extended necrosis irrespective of tumor type. Moreover, a positive correlation was obtained between the HbO2 saturations and the ATP concentration measured with bioluminescence. The results demonstrate the potential of combined studies using noninvasive, integrating methods and high-resolution imaging techniques for characterizing the metabolic milieu in tumors.

Adenosine Triphosphate

Self-concepts of creative girls: a twenty-five year follow-up.

The 25-yr. follow-up study of the self-concepts of a highly creative group of 10 adolescent girls showed both stability and change. In mid-life the group continued to describe themselves as both creative and intelligent; however, they also changed in that they now regard themselves as having a greater social interest.

Adolescent

[Drug-induced changes in the lungs].

There is a growing number of drugs with lung toxicity, and radiologists are increasingly confronted with nonspecific patterns of possibly drug-induced lung disease. The present article reviews clinical symptoms, pathological findings and radiographic features associated with drugs causing lung disease. Roentgen-morphological categorization is based on the predominant pattern and distinguishes five groups of drugs that cause interstitial opacities, air space consolidation, mixed interstitial and consolidating opacities, pulmonary edema and alterations associated with pulmonary vessels. Clinical, pathological and radiological findings are nonspecific in the majority of cases, and clinicians and radiologists can only hope to assess the probability of drug-induced lung disease by correlating radiographic and clinical data. Useful clinical data include respiratory symptoms, results of respiratory function tests, dose and schedule of drug administration, and information concerning concomitant or previous administration of drugs or radiation therapy. Useful radiographic data include the distribution of densities seen on the chest radiograph, the presence or absence of thoracic adenopathy and pleural effusion. Drug-induced lung disease frequently simulates disseminated opportunistic infections (particularly pneumocystis carinii) and must be differentiated from these because the treatment is completely different. Since early recognition and withdrawal of the noxious agent constitute the best treatment for drug-induced disease, the physician's alertness to drug toxicity is most important.

Drug-Related Side Effects and Adverse Reactions

Concentration and physicochemical characterisation of unsaturated cobalamin binding proteins in amniotic fluid.

Indirect evidence for the presence of intrinsic factor in amniotic fluid has been provided recently, using either a radioisotope binding assay or a radioimmunoassay. We have determined the unsaturated cobalamin binding capacity and the physicochemical properties of the 3 cobalamin binding proteins in 59 amniotic fluids using radioisotope binding assay, gel filtration and isoelectrofocussing. A good correlation with gestational age was found for the total unsaturated Cbl binding capacity (r = 0.735) and for the concentration of unsaturated haptocorrin (r = 0.746), but not for the concentration of unsaturated intrinsic factor (r = 0.003). When their binding capacities were expressed as a percentage of the total unsaturated Cbl binding capacity, the percentage of intrinsic factor, transcobalamin II and transcobalamin III (the less acidic fraction of haptocorrin) decreased and the percentage of haptocorrin increased in function of gestational age. The physicochemical properties of intrinsic factor in amniotic fluid were close to those in gastric juice: the molecular mass was estimated to 49,200 +/- 4,900 Da (n = 24) in Sephacryl S 300 gel filtration, the cobalamin-protein complex was resolved in 2-6 isoproteins isoelectric at a pH range of 4.6-5.8 and with a mean isoelectric point of 5.18 +/- 0.16 (n = 5) in isoelectrofocusing and it crossreacted with anti-intrinsic factor autoantibodies (from a Biermer anaemia serum). Amniotic fluid collected at 13 wk of gestational age was found to contain intrinsic factor and haptocorrin with less acidic isoproteins than those usually observed in gastric juice and serum. This could indicate that sialic acid is less involved in the composition of the carbohydrate core of cobalamin binding glycoproteins in this period of the gestational age than later on and that cobalamin binding proteins have mainly a foetal origin.

Amniotic Fluid