Separation of plasma lipoproteins with a tabletop ultracentrifuge.
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Carbon Radioisotopes↗
Biomedical subjects
V Schulz
Publications and source records attributed to V Schulz.
Lipoprotein-mediated distribution of N-aspartyl chlorin-E6 in the mouse.
The localization of many photosensitizing agents has been attributed to distribution of low density lipoprotein (LDL)-bound drug as a function of the relative numbers of LDL receptors in different tissues. While the chlorin derivative NPe6 is a potent photosensitizing agent in the mouse, it binds mainly to mouse plasma high density lipoproteins (HDL) and albumin, with only 1% bound to LDL. This pattern suggests only a minor role for the LDL-receptor pathway with regard to N-aspartyl chlorin e6 (NPe6) biodistribution. Moreover, patterns of accumulation of radioactive NPe6, LDL and HDL in murine tissues are consistent with the suggestion that distribution of NPe6 to different tissues cannot be explained on the basis of an LDL-mediated mechanism.
Animals↗
[Risk-benefit assessment and value of beta-2-sympathomimetic drugs in asthma therapy].
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Administration, Inhalation↗
[Aortopulmonary fistula formation after operation of aortic isthmus stenosis as a rare cause of recurrent hemoptysis].
An aneurysm of the aorta with aortobronchial fistula formation was seen in a 33 year old patient as a rare cause of recurring hemoptysis. 18 years previously he had undergone surgery of coarctation of the aorta. By means of different imaging methods the diagnosis was established in time and the aneurysm resected, so that the patient survived this mostly fatal incident.
Adult↗
[Q fever endemic in the Palatinate].
In 1989 investigations revealed a small scale outbreak of Q fever in the area of Vorderpfalz several kilometers west of the city of Ludwigshafen/Rhein. In 16 cases the diagnosis of Q fever has been serologically confirmed by complement fixation test (CF), the estimated number of unknown cases, however, may be considerable. A flock of sheep was determined as the source of infection. Due to the prevalence of the tick species Dermacentor marginatus, one of the main vectors of the infection, the area is considered one of the natural foci of Q fever. Epidemiological aspects as well as case reports are shown.
Adolescent↗
High cell density fermentation of recombinant Escherichia coli with computer-controlled optimal growth rate.
In recent years recombinant DNA technology has enabled us to produce various proteins of therapeutic importance with microorganisms. As an appropriate host organism, E. coli plays a dominant role. Yields of E. coli dry cell mass in shaker flask culture range from 1-2 g/L, whereas in fermentors up to 10 g dry cells/L can be achieved. ZIMET and GBF have developed a high cell density fermentation process that produces E. coli (on a glucose/mineral salt medium) up to more than 100 g dry cells/L in a special fed-batch mode. This cultivation strategy prevents oxygen limitation and hence the accumulation of acetate and other metabolic byproducts. The specific growth rate can be adjusted so that product formation reaches its optimum value. An example of the production of alpha1-interferon is presented. The high cell density fermentations were realized in 30- and 450-L Chemap fermentors (ZIMET) and in a three-stage bioreactor scale-up system (72, 300, and 1,500 L) developed in cooperation with GBF and B. Braun Melsungen AG. Multiloop controllers were used to control the process variables.
Biotechnology↗
Characterization of multidrug resistance by fluorescent dyes.
Fluorimetric techniques were used to examine accumulation of fluorescent probes by the P388 murine leukemia and an anthracycline-resistant subline, P388/Adriamycin(ADR), which expresses the multidrug-resistant phenotype. P388 could be differentiated from P388/ADR on the basis of fluorescence intensity measurements using 3 classes of cationic dyes that are sensitive to membrane potential differences: rhodamine esters, cyanines, and styrylpyridinium dyes. But fluorescence intensity differences were also observed with potential-insensitive dyes: zwitterionic rhodamines and an acridine orange derivative. In all cases, fluorescence intensity differences were caused by impaired dye accumulation, and could be eliminated by treatment of P388/ADR cells with verapamil. Moreover, fluorescence signals from 2 anionic potential-sensitive dyes, merocyanine 540 and a bis-oxonol, were identical in P388 and P388/ADR. None of these dyes could be used to delineate CCRF-CEM, a lymphoblastic leukemia of human origin from the CEM/VM-1 subline that exhibits a markedly atypical drug resistance pattern not based on an enhanced outward transport. But accumulation of both neutral and cationic dyes was impaired in CEM/VLB100, a subline of CCRF-CEM expressing mdr. These studies show that many cationic and neutral fluorescent probes are substrates for the enhanced outward drug transport system associated with P388/ADR cells, and cannot be used to probe membrane-potential differences in cells expressing the mdr phenotype. With several dyes, differences in fluorescence intensity were sufficient so that flow cytometry could be used to delineate P388 from P388/ADR and CCRF-CEM from CEM-VLB100. The latter technique may be useful for identifying malignant cell populations expressing multidrug resistance in patients with neoplastic disease.
Animals↗
High cell density cultivation of Escherichia coli at controlled specific growth rate.
A high cell density cultivation (HCDC) for growth of Escherichia coli in an especially designed glucose/mineral salt medium is proposed. The HCDC essentially starts as a batch process which is followed by a two-phase fed-batch cultivation. After unlimited growth at mu max = 0.45 h-1 in the batch part, growth was controlled at a reduced specific growth rate (mu = 0.11 h-1 less than mu max) over a period of 3 doubling times in which the biomass concentration increased from 12 to 95 g 1(-1) (phase 1 of fed-batch cultivation). Control of growth (mu) was realized by a PO2 control loop (by variation of glucose feeding) and a mu control loop (by variation of agitation speed N) while the actual mu was calculated from the off-gas composition. If the agitation rate cannot be increased anymore the mu controller is switched off (end of phase 1). In the following phase 2, mu declines, however, the still acting pO2 (glucose) controller guarantees sufficient O2 supply till the end of the cultivation with a biomass concentration of 110 g 1(-1) (dry mass). The proposed HCDC suppresses generation of inhibitory by-products and the high yield coefficients indicate the economy of the process.
Bacteriological Techniques↗
[Limits of hyposensitization in bronchial asthma].
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Asthma↗
[Rapid diagnosis of tuberculosis by the polymerase chain reaction (PCR)].
The polymerase chain reaction (PCR) was used for the detection of Mycobacterium tuberculosis DNA. More than 2000 different clinical specimens were analyzed by this assay. The efficiency of two different methods for processing the DNA from biological material was analyzed. DNA amplification was done according to standard protocols by amplifying a segment of 402 bp of the 65 kD mycobacterial gene, electrophoretic separation of the amplification product followed by Southern transfer and hybridization with a Mycobacterium tuberculosis-specific probe or by a semi-nested amplification procedure in which the initial amplification product was reamplified by a second round with a Mycobacterium tuberculosis-specific primer. The specificity of primers and probe for mycobacterial DNA was proven by testing 70 of class-I microorganisms, as well as 20 different strains and own isolates of Mycobacterium tuberculosis and 67 strains of 25 different MOTTs. Some of the amplification products were sequenced. The clinical relevance of the results and the sensitivity of the PCR method were confirmed by simultaneous quantitative bacterial culture from the same clinical specimens. The results of conventional culture method received after 8 to 10 weeks culture time correlated with the results from PCR obtained within 12 hours in 95.4% in the semi-nested amplification procedure. The discrepancy of 4.6% was caused by positive results of PCR and negative cultures which might be due to the higher sensitivity of PCR compared to culture technique. The results show that PCR may be used for detection of Mycobacterium tuberculosis in clinical specimens. The specificity can be regarded as largely proven, advantages are velocity and sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)
Base Sequence↗
Classification of lung cancer: first experiences with the new TNM classification (4th edition).
In January 1987, the 4th edition of the TNM classification for malignant lung tumours by the International Union Cancer (UICC) came into effect. Thus, for the first time, a uniform worldwide staging system for lung cancer became available. In order to validate the new TNM definitions for lung cancer the data of 3,000 patients were analysed prospectively. Several items were examined: 1) the agreement between clinically (TNM) and pathologically (pTNM) confirmed classification; 2) the value of the various diagnostic techniques estimating the pathologically confirmed classification; 3) the influence of the TNM definitions on separating distinct prognostic groups. With regard to the primary tumour (T), clinical and pathological classifications were identical in 64%; for lymph node involvement (N) the agreement was 48%; for distant metastases it was 90% and for the stages it was 55%. As for the primary tumour (T) the accuracy of radiography (59%) was nearly identical to computed tomography (58%). Both techniques were less precise in determining the extent of lymph node involvement (computed tomography 50%, radiography 43%, correct assessments). The statistically significant differences in prognosis for the various T-, N- and M-categories as well as for the stages could be confirmed. By the new 1987 TNM definitions (4th edition) for lung cancer international conformity became feasible as well as practical, and the improvement in its prognostic relevance provided, therefore, a more reliable basis for establishing guidelines for individual oncological concepts of therapy.
Carcinoma, Bronchogenic↗
[Studies on the influence of releasing hormones TRH and CRH on respiratory regulation].
Patterns of neuroanatomical distribution of Thyrotropin-releasing hormone (TRH) and Corticotropin-releasing hormone (CRH) and of their receptors in brain areas of humans and of animals suppose a regulating function of both peptides on regulation of respiration. In experimental animals TRH induces rhythmical and synchronous firing of defined neurons of nucleus tractus solitarii. In fetal sheep, endogenous and exogenous CRH promotes maturation of breathing rhythm genesis. In own human studies we demonstrated a modulation of respiration in healthy test-subjects - predominantly a stimulation of respiration - by systemic TRH and CRH. This effect persists also during hypercapnia, as we showed in patients and in 12 healthy test subjects while re-breathing CO2: when compared to placebo, CRH i.v. (200 micrograms. Bissendorf, Hannover, FRG) induces a significant (p less than 0.0001) shift of the ventilatory response curve to the left (petCO2 vs minute volume). Stimulation of respiration by CRH is independent of activation of the pituitary-adrenal axis. At present two analogues of CRH are available for application in humans (as a diagnostic of endocrinological disorders): human CRH and ovine CRH. Both analogues are comparably effective in stimulation of ventilation although sequence of effects is different in both analogues. We also evaluated the effect of CRH in 10 aged patients who were under prolonged respirator therapy after major abdominal surgery; both human and ovine CRH (100-200 micrograms i.v.) induced a profound and long lasting stimulation of ventilation under assisted respirator therapy. Vigilance was also markedly increased in all patients and thus was of therapeutic value. CRH also has a potential to alter sleep architecture in healthy and in diseased persons.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
High cell density fermentation of recombinant Escherichia coli expressing human interferon alpha 1.
A defined medium was developed which, by means of a specific fed-batch mode, allows growth of the recombinant Escherichia coli strain TG1 (pBB210) up to a cell density of 60 g dry weight/l. Apart from glucose and aqueous ammonia fed as carbon and nitrogen sources, it was necessary to supply other nutrients or O2-enriched air. Aqueous ammonia also served for pH control. The pO2 level was kept at 20% saturation via closed-loop controls operating the two output variables of stirrer speed and glucose feeding rate. This fed-batch method prevented significant accumulation of acetate and other metabolic by-products. The recombinant E. coli expressed interferon alpha 1 more efficiently at a lower specific growth rate (muPr approximately 0.15 h-1) than at the maximum specific growth rate (mu max = 0.45 h-1). Therefore, fermentation in the batch phase at mu max was only allowed to continue up to a medium cell density. In the succeeding fed-batch phase, the specific growth rate was reduced to muPr by increasing the stirrer speed according to an empirically developed time scale.
Ammonia↗
Sites of photosensitization by protoporphyrin and tin protoporphyrin in leukemia L1210 cells.
Studies with protoporphyrin (PP) and tin protoporphyrin (SnPP) were carried out to assess the effects of tin insertion on the sites of dye localization. Fluorescence emission spectra and studies on the sites of photodamage were consistent with a concentration of PP at membrane loci. In contrast, SnPP photodamage involved an intracellular site.
Animals↗
[Clinical aspects, results of diagnostic pulmonary function tests and biochemical parameters in children with homozygote alpha-1-antitrypsin deficiency].
The clinical course and pulmonary function tests of individuals with severe Alpha-1-Antitrypsin (Alpha-1-AT) deficiency reveal a marked interindividual variability. 4 patients with PI type ZZ and 2 patients with PI type SZ had been identified by neonatal cholestasis. None had pulmonary symptoms at a mean age of 13 (range 9-16) years. Lung function tests disclosed signs of incipient pulmonary emphysema in one girl. Bronchial hyperreactivity had led to the diagnosis of Alpha-1 AT-deficiency (PI type ZZ) in another girl at the age of 7 years. The biochemical analysis of the serum of three children (two PI ZZ and one PI SZ) revealed additional protease inhibitors that may be effective as compensatory mechanisms. The lack of those protective factors as well as the presence of environmental hazards may contribute to the increased risk of emphysema in individual patients.
Adolescent↗
[Bronchiolitis obliterans following nitrogen dioxide (NO2) inhalation: clinical-roentgenologic-histologic study].
A case of bronchiolitis obliterans after prior inhalation of NO2 is described. The diagnosis was confirmed histologically following diagnostic thoracotomy and biopsy by means of pulmonary wedge resection. The clinical course of the case was compatible with the typical phases described in the literature, and the condition underwent complete remission following treatment with corticoids.
Air Pollutants, Occupational↗
[Trypsin and pancreatic elastase-inhibitory capacity of serum and bronchoalveolar lavage fluid of smokers, ex-smokers and nonsmokers].
Smoking habits have no differentiating effect on the functional activity of protease inhibitor (alpha 1PI) in the serum and bronchoalveolar lavage fluid (BALF). In the BALF, the trypsin-inhibitory capacity TIC/alpha 1PI ratio is significantly greater in patients with emphysema than in non-emphysematous subjects. PIC/alpha 1PI ratios that are greater than 1 demonstrate the existence of additional antiproteases in the lower respiratory tract.
Bronchoalveolar Lavage Fluid↗
[Fading of the provocation effect following inhaled provocation with carbachol].
The results of the present study aimed at establishing the subsidence of the effect of inhalative provocation with carbachol show that no ceiling activity is reached. Rather, following a maximum effect that is achieved after approximately 2 minutes, spontaneous subsidence of the provocation-related changes occurs. The average duration of this subsidence to below the level of change that is considered significant for the respective measured parameter was between 20 and 25 minutes.
Adult↗