Search PubMed⌕ Search

Biomedical subjects

D Hofmann

Publications and source records attributed to D Hofmann.

At least 37 records · Page 2Linked to original sources
PubMed1999

Expression of the thrombopoietin gene in human fetal and neonatal tissues.

Thrombopoietin (TPO) regulates megakaryopoiesis and platelet production. In the adult, TPO is mainly produced by the liver and the kidneys. This study focuses on fetal and neonatal TPO mRNA expression. In 26 human fetuses and preterm neonates, samples from liver, kidney, spleen, lung, and bone marrow were extracted for total RNA. We measured platelet counts, TPO serum concentrations by enzyme-linked immunosorbent assay, and TPO mRNA contents by reverse transcription/competitive polymerase chain reaction. TPO mRNA concentrations per microgram total RNA were similar in liver, spleen, and bone marrow, slightly lower in kidney, and significantly lower in lung. When related to gram tissue, TPO mRNA levels were highest in the liver. Considering the total amount of TPO mRNA produced in liver, kidney, and spleen, the liver accounted for 95.3%. No correlations between TPO mRNA expression and serum TPO concentration, blood platelet count, or gestational age were observed. In conclusion, the liver is the primary site of TPO gene expression in human fetuses and neonates. The spleen may contribute to TPO production during fetal life. Like in the adult, TPO mRNA is expressed in fetal bone marrow.

Adult↗
PubMed1999

Lipid-laden alveolar macrophages (LLAM): a useful marker of silent aspiration in children.

At present there is no test available which identifies children suffering from silent aspiration due to gastroesophageal reflux (GER). The purpose of this study was to determine whether lipid-laden alveolar macrophage (LLAM) scoring is a useful method to arrive at the diagnosis. We evaluated bronchoalveolar lavage fluid (BALF) from 68 children aged 6 months to 14 years (median 3.75 years) for the presence of lipid-laden alveolar macrophages. We compared children with chronic chest disease (CCD) and GER to healthy surgical controls without known lung disease, and to children with recurrent pneumonia without GER. By grading the amount of intracellular Sudan Red-positive material, we determined a semiquantitative lipid-laden macrophage (LLAM) score for each patient. Patients with chronic chest disease suspected to be caused by silent aspiration secondary to GER had a significantly higher LLAM score (median, 117; range, 10-956) than children with recurrent pneumonia due to other reasons (median, 29; range, 5-127; P < 0.01) and healthy controls (median, 37; range, 5-188; P < 0.01). We believe that simply observing lipid-laden macrophages is nonspecific, but quantitation of these cells is a useful method for diagnosing silent aspiration in children, especially when the score exceeds 200.

Adolescent↗
PubMed1999

Antireflux surgery in children suffering from reflux-associated respiratory diseases.

The aim of our study was to evaluate the success, complications, and morbidity following a modified Thal fundoplication in children with reflux-associated respiratory disease (RARD). We used a procedure consisting of retroesophageal hiatal plasty, wrapping the gastric fundus around the gastroesophageal junction 180 degrees, and fixation of the lesser curvature at the abdominal wall. Follow-up by questionnaire of 128 (77 male, 51 females) out of 196 antireflux procedures between 1992 and 1995 was achieved. Surgical therapy was considered justified whenever there was gastroesophageal reflux resulting in severe recurrent respiratory symptoms. Eleven percent of the children suffered from bronchiectasis. The diagnosis of RARD was based on a high index of suspicion, barium swallow with fluoroscopy, 24-hr two-level pH-monitoring, bronchoscopy, bronchoalveolar lavage and detection of lipid-laden alveolar macrophages, esophago-gastroscopy, and esophageal biopsy. Patients with bronchopulmonary diseases such as allergy, immunodeficiency, cystic fibrosis, primary ciliary dyskinesia, and malformation of the bronchial tree or vessels had been excluded. "Evident improvement" as a result of surgery was reported in 88%, "no change" in 10%, and a "change for the worse" in 2% of patients. Persistent mild difficulties in swallowing were observed in 11%. Paraesophageal hernia, gas-bloat syndrome, and dumping syndrome were not observed. Two children needed a second operation because of relapse. The use of emergency steroidal medication for acute respiratory distress decreased impressively (219 single doses/year before surgery vs. 30 single doses/year after surgery). The need for more than 4 times/year of antibiotic therapy before surgery was reduced from 52. 3% before to 14% after surgery. Most (90.6%) of the parents stated they would agree to have surgery done again if medically indicated. In conclusion, Thal fundoplication is sufficient, safe, and effective in the management of RARD. Complications of the procedure were minor and of little consequence to the patient.

Adolescent↗
PubMed1999

Therapeutic apheresis in myasthenia gravis patients: a six year follow-up.

Six years ago 4 patients suffering from myasthenia gravis (MG) types C and E according to Compston with failed drug therapy were initially treated 3 times (1 patient, a total of 11 times) by protein A immunoadsorption (Immunosorba, Excorim AB, Lund, Sweden). No further immunoadsorption treatments have been carried out. In addition, 3 patients were given a thymectomy. The present status of the patients was checked. We could see a beneficial effect in all MG patients. The patients are fit for work; each has an improved Besinger index. The patients were used as their own controls. A higher anti-AChRAb level 6 years after protein A immunoadsorption than at the beginning was seen in all patients, combined with less serious MG. In addition, their immunomodulation could be induced as seen in lymphocyte and inflammatory protein changes during the first 36 days after beginning immunoadsorption treatment. A larger population has to be investigated to verify these results.

Adult↗
PubMed1999

[Reference values of hemosiderin-laden alveolar macrophages in bronchoalveolar lavage in children].

Pulmonary haemosiderosis is a rare disease of unknown etiology, mainly affecting children and adolescents. Pulmonary haemosiderosis may occur in association with several respiratory or other disease (Lupus erythematosus, Goodpastures syndrome). Delay in diagnosing can lead to fatal complications. BAL appears to be the method of choice to detect haemosiderin-laden macrophages. No reference values are available for children to date. 64 bronchoalveolar lavages were performed to establish reference values of haemosiderin-laden macrophages in children. Less haemosiderin was found in children compared to adults, and hence a new haemosiderin score was established for paediatric patients. Compared to healthy children, no elevated haemosiderine levels were found in children with chronic pulmonary disease such as bronchiectasis or chronic aspiration caused by gastro-oesophageal reflux. Therefore even a mildly increased amount of haemosiderin-laden macrophages in children requires medical attention.

Adolescent↗
PubMed1999

[Severe interstitial lung disease from pathologic gastroesophageal reflux in children].

Interstitial lung diseases comprise a heterogeneous group of pulmonary conditions that cause restrictive lung disease of poor prognosis, especially if growth failure, pulmonary hypertension and fibrosis appears. We report on the case of a girl of 11 years of age who suffered from severe nonallergic asthma in early childhood and who developed severe interstitial pulmonary disease caused by gastro-oesophageal reflux at the age of 8 years. This diagnosis was established by lung biopsy, bronchoalveolar lavage and a high amount of lipid-laden alveolar macrophages, 2-level pH measurement and oesophageal biopsy. Because therapy with oral and inhaled steroids failed and Omeprazol showed benificial effects, hemifundoplication according to THAL was performed. At present the lung function is clearly normal and there is no need of any medicaments. Following the history, we can assume the pathological gastro-oesophageal reflux to be the cause of the disease. It is important to state that there were no typical symptoms at any time pointing to gastro-oesophageal reflux disease. The development of pulmonary disease by pathological reflux is very often caused by "silent aspiration". Very typically there are no symptoms such as vomiting, heartburn and pain but only signs of chronic lung disease.

Asthma↗
PubMed1998

Erythropoietin mRNA expression in human fetal and neonatal tissue.

Based on animal experiments, a switch of the erythropoietin (EPO) production site from the liver in the fetus to the kidneys in the adult has been postulated. To study the switch in humans, we have quantitated EPO mRNA expression in liver, kidney, spleen, and bone marrow of human fetuses and neonates by means of a competitive polymerase chain reaction (PCR). Tissue samples from 66 routine postmortem examinations were obtained. EPO mRNA was expressed in 97% of the tissue specimen derived from the liver (n = 66) and in 93% of those from the kidneys (17 weeks of gestation until 18 months after birth; n = 59). For the first time the EPO gene was found expressed in vivo in human spleen (96% of 64 samples) and in fetal and neonatal bone marrow (81% of 21 samples). EPO mRNA expression in the kidneys increased significantly beyond 30 weeks of gestation (P < .05). Although there was a slight decrease in EPO mRNA content per g liver tissue towards birth, the liver accounted for about 80% of the total body EPO mRNA. The contribution of the spleen and bone marrow were minor compared with liver and kidneys. Our results indicate that in humans the liver is the primary site of EPO gene expression not only in fetal, but also in neonatal life. A significant increase of renal EPO mRNA expression after 30 weeks of gestation might indicate the beginning switch.

Bone Marrow↗
PubMed1998

The subunit b of the F0F1-type ATPase of the bacterium Mycoplasma pneumoniae is a lipoprotein.

The DNA sequence analysis of the F0F1-ATPase operon of the bacterium Mycoplasma pneumoniae predicted that the subunit b, encoded by the gene atpF, is a lipoprotein of the murein lipoprotein type of Escherichia coli. Here we experimentally verify this prediction by metabolic labeling of subunit b with [14C]palmitic acid and by in vivo interfering with the processing of the prolipoprotein form of subunit b by the antibiotic globomycin, a specific inhibitor of the signal peptidase II. Our results suggest that the subunit b of the F0F1-ATPase of M. pneumoniae is anchored at the cytoplasmic membrane by an N-terminal lipid modification in addition to its transmembrane domain. The lipoprotein nature of subunit b and its proposed membrane topology seems to be characteristic for mycoplasmas, since among all sequenced bacterial atpF genes, only those from Mycoplasma gallisepticum and Mycoplasma genitalium code for a conserved lipoprotein consensus sequence.

Amino Acid Sequence↗
PubMed1998

Effects of mibefradil, a novel calcium channel blocking agent with T-type activity, in acute experimental myocardial ischemia: maintenance of ventricular fibrillation threshold without inotropic compromise.

OBJECTIVES: We tested whether mibefradil, a selective T-type calcium channel blocking agent, could differentially inhibit experimental ventricular arrhythmogenesis more than contractility during acute regional ischemia and reperfusion compared with that during L-channel blockade by verapamil. BACKGROUND: T-type calcium channels are found in nodal and conduction tissue and in vascular smooth muscle, but in much lower density in contractile myocardium. The potential role of mibefradil in ventricular arrhythmogenesis remains unclear. METHODS: Mibefradil (Ro 40-5967, 1 mg/kg body weight intravenously [i.v.]) was given as a bolus 30 min before anterior descending coronary artery ligation, followed by 2 mg/kg per h i.v. during 20 min of ischemia and 25 min of reperfusion in open chest pigs. In a second group, mibefradil was given in a dose twice as high. A third group received verapamil (0.3 mg/kg i.v.), followed by an infusion of 0.6 mg/kg per h. RESULTS: During the ischemic period, the low (clinically relevant) dose of mibefradil prevented the fall of the ventricular fibrillation threshold, without depressing the maximal rate of pressure development of the left ventricle (LVmax dP/dt). This low dose increased left ventricular blood flow, whereas peripheral arterial pressure remained unchanged. The higher dose of both mibefradil and verapamil was antiarrhythmic during ischemia, at the cost of depressed contractile activity. During reperfusion, only the higher dose of mibefradil and verapamil was antiarrhythmic but both depressed contractile activity. CONCLUSIONS: Mibefradil is antiarrhythmic, without inotropic compromise. Speculatively, both T-type and L-type calcium channel blockade are involved in these effects.

Animals↗
PubMed1998

15N investigation into the effect of a pollutant on the nitrogen metabolism of Tetrahymena pyriformis as a model for environmental medical research.

A pilot study was performed to examine the potential of stable isotope techniques for monitoring the impact of a harmful substance on the cellular nitrogen metabolism in the ciliate species Tetrahymena pyriformis. After identical cultivation periods of control cells and toluene-exposed cells in a defined culture medium enriched with [guanidino-15N2]l-arginine, a number of nitrogen-containing pools were analyzed: 1) quantity and 15N abundance of ammonia as the end product of nitrogen metabolism in the system; 2) pattern and 15N abundances of the protein-bound amino acids in the cells; 3) pattern and 15N abundances of free amino acids in the cells; and 4) pattern and 15N abundances of the amino acids in the culture medium. In addition to 15N emission spectrometry, a new gas chromatography/combustion interface-isotope ratio mass spectrometry/mass spectrometry analytical system was used. The production and 15N content of ammonia were higher in the toluene-exposed system by 30% and 43%, respectively, indicating higher deamination rates and greater arginine consumption. The toluene-exposed cells exhibited increased 15N abundances of protein-bound amino acids in alanine, aspartic acid, glutamic acid, and tyrosine. Furthermore, structural analyses revealed the presence of N[Omega]-acetylarginine and pyrrolidonecarboxylic acid--compounds that had not previously been detected in Tetrahymena pyriformis. Differences in the 15N-enrichment of free amino acids were also evident. This new effect-monitoring system designed to investigate the impact of a pollutant on protein metabolism by using a stable isotope-labeled cell culture is a powerful tool for environmental medical research.

Amino Acids↗
PubMed1997

Morphological analogies of fetal prostate stroma and stromal nodules in BPH.

BACKGROUND: A "reawakening" of ontogenetic processes in the development of BPH is still in debate. Therefore, morphological analogies of fetal prostate stroma and nodular stromal proliferates in BPH were investigated. METHODS: Fetal prostates (n = 30; weeks 12-40 of gestation) and stromal nodules of benign prostatic hyperplasia (n = 375 from autopsies, n = 100 from biopsies) were investigated by histo- and immunohistochemistry with special regard to cytoskeletal (alpha-actin, desmin, myosin, and vimentin), neuronal (S-100 protein), neuroendocrine (neuron-specific enolase), leukocytic (CD3, CD20, and CD68) and vascular (CD34, BMA-120, and factor VIII) antigens. RESULTS: The developing fetal prostate stroma consists of immature mesenchymal cells up to week 17 of gestation, followed by fibroblastic and fibromuscular stromal cells up to week 25 of gestation and predominantly smooth-muscular cells until the end of gestation. Stromal nodules occur as immature mesenchymal, fibroblastic, fibromuscular, and smooth-muscular, suggestive of a maturational process. The fetal prostate stroma and the stromal nodules present, with an increasing degree of maturation, a similar vascular pattern and a similar occurrence of CD3 (T-lymphocytes), CD20 (B-lymphocytes), CD68 (macrophages), S-100, and neuron-specific enolase-positive cells. CONCLUSIONS: The data suggest that ontogenetic processes are recapitulated in the development of stromal nodules in benign prostatic hyperplasia, supporting the idea of a "re-awakening" of fetal processes in BPH.

Adult↗
PubMed1997

Low molecular weight proteins secreted by peritoneal macrophages obtained from 2,3,7,8-tetrabromodibenzo-p-dioxin-treated NMRI mice.

The protein secretion patterns in a macrophage-like cell line (CBrD), established from the peritoneal cells of NMRI mice treated with the dioxin analog 2,3,7,8-tetrabromodibenzo-p-dioxin (TBrDD), were analyzed by high resolution two-dimensional gel electrophoresis (2-D PAGE), and compared to the pattern of proteins secreted by control macrophages which were intraperitoneally activated by bacterial lipopolysaccharide. The most striking alterations were observed in the low molecular range. The transformed cells encode a number of low molecular mass proteins (10-20 kDa) which were not detected in control cells under identical experimental conditions. The protein pattern with respect to isoelectric point, molecular weight, optical density (OD) and area of the spot (in mm2) has been depicted by computer analysis in relation to a standardized spot outline and the spot's background (in OD). It is concluded that the transformation of murine peritoneal macrophages by TBrDD leads to an upregulation of proteins, in particular of low-molecular-weight proteins.

Animals↗
PubMed1997

Anthropogenic impacts on natural nitrogen isotope variations in Pinus sylvestris stands in an industrially polluted area.

Natural variations of the nitrogen isotopes 15N/14N (delta15N values) and the N concentrations of one-year-old needles from 7-12-year-old pine trees (Pinus sylvestris L.) were determined on 27 sites in the heavily polluted Leipzig-Halle region (former GDR). At three selected sites measurements were repeated over a period of 2 years. N concentrations and delta15N values in different needle age classes were compared at the three sites. The delta15N values of the N in the humus layer and the potential plant available N in the A(h) horizon of the local soil were determined. The 15N/14N isotope ratios (delta15N values) of one-year-old pine needles in the region of Leipzig-Halle were found to vary depending on their specific location by a factor of up to one order of magnitude (-9.6 per thousand to + 0.4 per thousand ). N concentrations in one-year-old pine needles varied between 0.71 and 1.38 mmol eq N g dw(-1). Pine stands with positive or slightly negative delta15N values and high N concentrations in one-year-old needles were concentrated around the cities of Leipzig and Halle and in the industrial areas. More negative delta15N values and lower N concentrations in one-year-old pine needles were found on sites at greater distances from the industrial agglomerations, mainly in the NE forested part. Site specific differences in the delta15N values of the N in the humus layer from three selected sites were similar to those found for the needles. No site specific differences, however, were found for the delta15N values of the water soluble nitrogen fraction from the mineral soil horizons of the same sites.

Journal Article↗
PubMed1997

[The helium-3 MRT of pulmonary ventilation: the initial clinical applications].

PURPOSE: of the study is the visualisation of normal pulmonary ventilation in healthy volunteers and the evaluation of abnormalities in patients with different lung diseases using 3He magnetic resonance imaging (3He-MRI). MATERIAL AND METHODS: Hyperpolarized 3He gas (V = 300 ml, p = 3 x 10(5) Pa, polarised to 35-45% by optical pumping, provided in special glass cells) was inhaled by eight healthy volunteers and ten patients with different lung diseases. A 3D FLASH sequence (TR = 11.8 ms; TE = 5 ms; matrix 144 x 256, FOV 350 mm, section thickness 7-10 mm, coronal orientation) was performed in a single breath-hold (22-42 s). Clinical and radiological examinations were available for correlation. RESULTS: The studies were successfully carried out in 8/8 volunteers and in 8/10 patients. The central airways were constantly visualised with intermediate to high signal intensity. The lung parenchyma of volunteers with normal ventilatory function showed rather homogeneous intermediate to high signal, whereas patients with chronic obstructive lung disease and/or pneumonia presented severe signal inhomogeneities. Space-occupying lesions and pleural effusion caused large areas with little or no signal. The represented the lesion and adjacent ventilatory disturbances whose extent had not been presumed from chest x-ray or CT. The spatial resolution was higher than in ventilation scintigraphy. CONCLUSION: 3He MRI is a promising new modality for the assessment of pulmonary ventilation and its anomalies.

Administration, Inhalation↗