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M Haag

Publications and source records attributed to M Haag.

At least 37 records · Page 2Linked to original sources

Inhalation of toluene diisocyanate affects cytochrome P450 2B1 expression in rat lung.

In the lung the expression of xenobiotic-metabolizing enzymes such as cytochromes P450 (CYP) and glutathione S-transferases (GST) may be affected by inhaled pollutants. Toluene diisocyanate (TDI) is a highly volatile chemical compound known to induce a wide array of diseases in workers exposed to vapors or sprays, including respiratory allergy and asthma. We investigated the effect of inhaled TDI on expression of CYP 1A1, 2B1, 2E1, and 3A1 and of alpha-, mu-, and pi-GST in rat lung. Animals were exposed to targeted concentrations of 0.01, 0.1, or 1 ppm TDI vapors or to cleaned filtered air for 8 h. Expression of CYP and GST was analyzed 18 24 h after the end of exposure using western blotting, northern blotting, and immunohistochemistry. Constitutive levels of CYP 2B1 and 3A1 proteins were found in lung tissue from control rats, whereas CYP 1A1 and 2E1 proteins were not detectable. Animal exposure to TDI vapors neither modified CYP 3A1 protein expression, nor led to any detectable expression of CYP 1A1 or 2E1. In contrast, exposure to 1 ppm TDI induced a 40% reduction in CYP 2B1 protein levels. This decrease was associated with a 33% decrease in CYP 2B1 mRNA levels. Additionally, CYP 2B1 immunolabeling localized to ciliated epithelial cells, Clara cells, and type II alveolar cells in the lung tissue of control rats was markedly decreased in animals exposed to 1 ppm TDI. Constitutive levels of alpha-, mu-, and pi-GST proteins were found in lung tissue from control rats. Exposure to TDI had no effect on lung expression of either of the GST. In conclusion, this study clearly shows a selective decrease in CYP 2B1 expression by TDI vapors in rat lung. The contribution of CYP 2B1 to metabolize further xenobiotics is therefore altered.

Administration, Inhalation↗

Inhibition of duodenal enterocyte Mg2+-ATPase by arachidonic acid is not mediated by an effect on protein kinase C.

Active absorption processes in the duodenal enterocyte are driven by various ATPases. It is known that the activity of Na+,K+-ATPase, Ca2+-ATPase and Mg2+-ATPase can be modulated by polyunsaturated fatty acids of the n-6 series, for example by linoleic and gamma-linolenic acids. These effects may be achieved by protein phosphorylation via protein kinase C. The present study was undertaken to determine the effect of arachidonic acid on Mg2+-ATPase (measured colorimetrically) activity in basolateral membranes prepared from rat duodenum. It shows, for the first time, significant dose-dependent inhibition of Mg2+-ATPase (26-62%) by arachidonic acid (10-50 microg/ml) which already takes place after one minute of exposure, indicating involvement of a rapid signal transduction mechanism. Addition of the protein kinase C inhibitors bisimidolylmaleimide (2.5 microM) and calphostin (0.5 microM) did not influence the action of arachidonic acid on Mg2+-ATPase; protein kinase C involvement in this process is thus not indicated.

Animals↗

[Transforaminal endoscopic microdiscectomy. Indications and short-term to intermediate-term results].

101 patients with lumbar disc herniation were treated by transforaminal endoscopic microdiscectomy between 5/94 and 6/97. Caused by technical problems the procedure could not be successfully completed in 3 patients. They must be excluded from the presented study as 9 others, who were lost for follow up. So 89 patients were followed with a median follow-up time of 28 months (15-56 months). 69 patients (78%) were satisfied. 16 patients needed a second operation. In 11 of these 16 patients it was done by an open procedure, in 5 by transforaminal endoscopic microdiscectomy again. 4 of these 5 patients showed a good or satisfying result. As in open procedures the most important prognostic factor is a promptly disappearing radicular leg pain. Only 6 of 61 patients with a radicular leg pain disappearing within one week were reoperated, but 10 of 28, who showed a leg pain persisting longer than one week postoperatively.

Adolescent↗

Web-based training: a new paradigm in computer-assisted instruction in medicine.

Computer-assisted instruction (CAI) programs based on internet technologies, especially on the world wide web (WWW), provide new opportunities in medical education. The aim of this paper is to examine different aspects of such programs, which we call 'web-based training (WBT) programs', and to differentiate them from conventional CAI programs. First, we will distinguish five different interaction types: presentation; browsing; tutorial dialogue; drill and practice; and simulation. In contrast to conventional CAI, there are four architectural types of WBT programs: client-based; remote data and knowledge; distributed teaching; and server-based. We will discuss the implications of the different architectures for developing WBT software. WBT programs have to meet other requirements than conventional CAI programs. The most important tools and programming languages for developing WBT programs will be listed and assigned to the architecture types. For the future, we expect a trend from conventional CAI towards WBT programs.

Artificial Intelligence↗

Polyunsaturated fatty acids inhibit Mg2+ -ATPase in basolateral membranes from rat enterocytes.

It is known that certain polyunsaturated fatty acids of the n-6 family, for example linoleic and arachidonic acids, can activate both Na+, K+-ATPase and Ca2+-ATPase. These enzymes drive active absorption processes in the duodenal enterocyte. This study presents data which show a 30-50% inhibition of Mg2+-ATPase activity in enterocyte basolateral membrane preparations by linoleic and gamma-linolenic acids (also a member of the n-6 family.) Mg2+-ATPase activity has several possible roles in the enterocyte: involvement in Mg2+ and Ca2+ absorption (as part of Ca2+-ATPase and also myosin I activity) as well as control of phospholipid distribution in the membrane by a class of Mg2+-ATPases called 'flippases'. The action of linoleic and gamma-linolenic acids on basolateral membrane Mg2+-ATPase may thus modulate several cellular transport processes.

Animals↗

[Paralysis of the foot as the first symptom of a herniated thoracic disc].

Herniated thoracic discs are uncommon entities that are difficult to diagnose. They may be associated with a myriad of symptoms, which often delays diagnosis. In general dorsal pain that radiats around the chest or abdomen are found. In case of spinal cord compression signs of thoracal myelopathy are common. This paper describes a patient with a complete paralysis of the left foot as the first symptom of a herniated thoracic disc. After frustrated diagnostic of the lumbar spine, the exact neurological examination showed a sensible cut at the level of D6/7, the MR tomography diagnosed a herniated thoracic disc at the same level. Four months later he was presented again with a plegia of the left foot and a sensible cut at the level D5/6. The MR tomography showed a herniated disc at the level above the spondylodesis. The immediately performed transthoracic disc excision and fusion of D6/7 was followed by complete remission of the plegia and the sensible cut. Four months later we performed a rethoracotomy, disc excision and decompression with a spondylodesis D5/6. The procedure was again followed by complete remission. In case of paralysis of the lower extremities one has to consider a herniated thoracic disc.

Adult↗

Vasospasm in smooth coronary arteries as a cause of asystole and syncope.

In a patient with proven myocardial infarction, coronary artery disease was excluded angiographically. Four weeks later the patient experienced recurrent syncope of unknown cause. By means of Holter monitoring, ST-segment elevation with subsequent first-degree AV block progressing to asystole and resulting in loss of consciousness were documented. Treatment with gallopamil and a VVI-pacemaker led to complete relief of all symptoms. Hence, Prinzmetal's angina may be a rare cause of syncope even in smooth coronary arteries.

Angina Pectoris, Variant↗

[The first successful lung resection].

In 1883 Krönlein resected a sarcoma of the ribs in an 18 year old female. Six months later he reoperated the patient for a local recurrency. At the second operation which necessitated a wide exposure of the thoracic cavity he deliberately removed a pulmonary metastasis about the size of a walnut. Two years later a new recurrence had to be resected. The three interventions led to a survival of 7 years. The patient succumbed to a further recurrence in 1890. Krönleins operation opened two new chapters in surgery, pulmonary interventions in general and in particular surgery of pulmonary metastasis. Surgery of lungs was not a topic of that era, particularly since some incisions for abscesses and resections of pulmonary parenchyma had not been successful. By limiting the indication to patients with sufficient pulmonary function and by following the successful pneumonectomy experiments in animals Krönlein favored pulmonary resection. The success of this intervention confirmed these considerations especially since it lasted for years. It was followed in 1885 by a pulmonary resection by G. Ruggi in Bologna. Surgery of the lung, however, came in general use only 50 years later.

Germany↗

Effects of 17 beta-estradiol metabolites on cell cycle events in MCF-7 cells.

Different cell growth effects were observed in MCF-7 cells after six daily exposures to either 17 beta-estradiol (E2), 2-hydroxyestradiol (2-OHE2), or 2-methoxyestradiol (2-MeOE2) at 10 nM levels. 2-OHE2 enhanced cell growth significantly (P < 0.05) more than did the parent compound, whereas 2-MeOE2 inhibited cell growth. To identify the estrogen-affected cellular processes involved in cell cycle progression, hydroxy urea-synchronized MCF-7 cells were studied. No effects on DNA synthesis in mid-S-phase or on mitotic indices were observed after E2 or 2-OHE2 treatment. 2-MeOE2, however, significantly (P < 0.05) inhibited DNA synthesis and mitosis. Synchronized cells were exposed for 1 h to E2, 2-OHE2, or 2-MeOE2 before cAMP levels were determined in early S-phase and mid-S-phase, as well as during mitosis. E2 and 2-OHE2 had no effect, but 2-MeOE2 caused a significant (P < 0.05) increase in cAMP concentration in early S-phase and a decrease during mitosis. Phosphorylation of S-phase proteins was also studied. [32P]Pi incorporation was significantly (P < 0.05) enhanced in many proteins in 2-MeOE2-exposed cells. Small proteins (M(r) < 25,000), as well as large proteins (M(r) > 220,000), were most prominently affected. In comparison, E2 and 2-OHE2 had little effect. We suggest that the enhanced 2-MeOE2-induced protein phosphorylation during S-phase may affect S-phase events, which subsequently causes inhibition of mitosis. Protein synthesis during G2/M transition was unexpectedly enhanced by 2-OHE2 and was not enhanced by E2. [35S]Methionine incorporation into proteins in the order of M(r) 32,000-46,000, 47,000-50,000, 58,000-67,000, and 83,000-89,000 was significantly (P < 0.05) increased. 2-MeOE2 had no effect. The results of this study indicate that 2-OHE2 may be the more potent mitogen, whereas 2-MeOE2 acts as a cytostatin.

2-Methoxyestradiol↗

[In Africa as a nurse].

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Acquired Immunodeficiency Syndrome↗

Confocal microscopy of genome exposure in normal, cancer, and reverse-transformed cells.

Genome exposure studies were carried out on malignant CHO-K1 and C6 rat glioma cells and their respective, phenotypically normal counterparts (reverse-transformed CHO-K1, and both reverse-transformed C6 glioma and normal rat fibroblasts). Cells were subjected to the nick-translation technique previously developed to make visible the exposed (i.e., DNase I-sensitive) nuclear DNA, and examined by both epifluorescence and confocal microscopy. The confocal microscopy, by permitting examination of sections throughout the nucleus, made possible clearer identification of the regions of exposed and sequestered DNA in the cells studied. A peripheral shell of exposed DNA with some discontinuities was displayed in the great majority of the cells with normal phenotype, but in none of the cancer cells. Both types of cells displayed regions of exposed DNA in the nuclear interior, particularly surrounding the nucleoli. In accordance with previous theoretical proposals we postulate: the peripheral nuclear shell of exposed DNA contains differentiation-specific genes that include the specific growth-control genes and that are functional in normal cells but not in cancer; the exposed genes surrounding the nucleoli may represent housekeeping genes active in both normal and cancer cells; and the DNase I-resistant DNA in the interior of the nucleus we postulate to consist for the most part of genes specific to alternative differentiation states and to be sequestered and inactive. Previous differences in evaluation of roles of peripheral and internal DNA sensitivity to DNAse I hydrolysis appear to be reconciled by this formulation. Identification of exposed DNA may be useful in cancer diagnosis.

1-Methyl-3-isobutylxanthine↗

Effect of nifedipine on carbohydrate metabolism in the rat.

The potential role of an oral administration of nifedipine was investigated in the rat. Therefore, animals were fed on a nifedipine-containing or control diet for 12 days. Nifedipine caused a significant decrease of liver glycogen (47.9 +/- 4.9 vs 132.6 +/- 17.1 micrograms/mg protein), whereas liver glucose (213.1 +/- 15.3 vs 110.4 +/- 6.4 micrograms/mg) and lactate (44.8 +/- 4.1 vs 26.5 +/- 1.8 nmol/mg) concentrations increased. Various concentrations of nifedipine failed to influence glycogenolysis but stimulated gluconeogenesis in isolated rat hepatocytes. Blood lactate and pyruvate levels were significantly elevated in the nifedipine pretreated rats, whereas ketone bodies remained constant. Nifedipine pretreatment also increased the rates of excretion of various electrolytes and water followed by significantly lower plasma sodium, potassium, phosphate, and normal glucose values. We conclude that nifedipine-induced liver glycogenolysis may deteriorate glucose tolerance in patients with an already impaired carbohydrate metabolism.

Administration, Oral↗

Characterization of non-TCA-precipitable 'Lowry protein' in plasma of patients with acute renal failure.

An increase of 'Lowry protein' was observed in plasma supernatants obtained after TCA precipitation (final concentration 30.6 mmol/l) from patients with catabolic states. Therefore, a study was performed to evaluate whether this increase of 'Lowry protein' in plasma supernatants from post-traumatic ARF patients is caused by amino acids, peptides and low molecular weight proteins. Mixing different TCA concentrations with different proportions of plasma PTC-amino acids represent 16.0 +/- 4.9% to 42.2 +/- 5.9%) of 'Lowry protein' in ARF patients, whereas in controls a percentage between 35.4 +/- 4.6% and 74.6 +/- 10.6% was found. Therefore, we tried to find factors responsible for this difference. Urea, creatinine, uric acid, guanidines or dopamine are not responsible for this effect. Performing fast protein liquid chromatography and PTC-amino acid analyses of the peaks we could confirm that increased 'Lowry protein' observed in ARF patients is caused only in a small part by protein degradation products. Plasma free amino acid concentration showed no difference between ARF patients (2,054 +/- 162 mumol/l) and controls (2,503 +/- 105 mumol/l). Our data demonstrate that determination of 'Lowry protein' may be helpful in evaluation of catabolic state. However, this increase results mainly from non-protein related and until now not identified factors.

Acute Kidney Injury↗

Lithium response and the sequence of episode polarities: preliminary report on a Hamilton sample.

This is a preliminary report on a study which replicated the finding of a significant relationship between the response to long-term lithium stabilization and the sequence of episode polarities (depressive/manic) in bipolar and schizoaffective (bipolar) patients. The lithium response and the clinical course data were assessed independently, in a blind manner, utilizing a data collection which has been gathered in earlier studies. There was a significant association between lithium response (stability achieved on long-term lithium treatment) and the sequence of episode polarities. The main determinant of this association was a close link between lithium response and the MDI sequence of episode polarities. The observed association may be explained in several ways: as an artifact; due to the exclusively antimanic effect of lithium; due to true psychobiological differences between mania and depression; as a result of the differences between bipolar type one and type two patients; and finally due to bipolar heterogeneity. Considering the data available to date the explanation via bipolar heterogeneity appears to be the most likely one.

Bipolar Disorder↗