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Biomedical subjects

N Müller

Publications and source records attributed to N Müller.

At least 289 records · Page 16Linked to original sources

Tissue culture methods for the investigation of anti-inflammatory drugs.

Tissue culture methods are used increasingly in the investigation of anti-inflammatory drugs. Compared to in vivo experiments they offer the advantages of a) relative reproducibility, b) reduced cost, and c) simplified interpretation of results. Moreover, tissue culture methods can be applied without major ethical concern. The disadvantage of cell culture techniques is the need to re-check in vivo the medical relevance of all data obtained. A few applications of cell culture methods are exemplified by results obtained in our laboratory from experiments using macrophages, endothelial cells and chondrocytes.

Anti-Inflammatory Agents↗

The diagnosis of emphysema. A computed tomographic-pathologic correlation.

To assess the accuracy of computed tomography (CT) in the diagnosis of emphysema, we performed CT on 32 patients prior to surgery for removal of suspected tumors. The CT scans were assessed visually for emphysema by 2 independent radiologists and 1 chest physician. Intraobserver and interobserver variation were assessed. Pathologic emphysema was graded on the resected lung specimens. These grades were correlated with the CT scores and with pulmonary function tests obtained prior to surgery. Significant correlation was found between the pathologic grade on resected lung specimens and the preoperative CT score of both the resected lobe (r greater than or equal to 0.57, p less than 0.001) and the whole lung (r greater than or equal to 0.63, p less than 0.001). Compared with pulmonary function tests, CT was a better predictor of emphysema and distinguished patients with moderate emphysema from patients with normal lungs. We conclude that CT is a useful adjunct in assessing the presence and severity of emphysema.

Adult↗

In vivo human tracheal pressure-area curves using computerized tomographic scans. Correlation with maximal expiratory flow rates.

In order to develop a simple technique to measure in vivo pressure-area (P-A) curves of the extrathoracic trachea in humans, we studied 14 normal male subjects. Valsalva and Mueller maneuvers were performed at FRC, and tracheal cross-sectional area (TXSA) was measured using computed tomography. Extrathoracic tracheal transmural pressure (TMP) was obtained as airway opening minus atmospheric pressure (Pat). Tracheal "compliance" (TC) was measured on the "inflation" limb of the P-A curve. Tracheal compliance was not a significant predictor of maximal expiratory flow rates, and TXSA at zero TMP was a significant predictor of peak expiratory flow rate but not of FEV1 or Vmax50. P-A curves showed an unexpected configuration characterized by a plateau or an increase in TXSA with TMP lower than -15 cm H2O. P-A curves obtained in 5 subjects using extrathoracic esophageal pressure as tracheal external pressure instead of atmospheric pressure did not show a plateau or an increase in TXSA with Mueller maneuvers. In these 5 subjects, TC using esophageal pressure rather than Pat did not aid in the prediction of flow. We conclude that extrathoracic tracheal external pressure is not Pat because this pressure is probably affected by transmission of pleural pressure to the cervical interstitial tissue as well as by the contraction of cervical accessory inspiratory muscles. Therefore, true tracheal compliance cannot be simply measured since it requires placement of an esophageal balloon.

Adult↗

Drug design: nitrosoureas.

Attempts to develop more effective and less toxic antineoplastic nitrosoureas are summarized. Previous research resulted in the synthesis and extensive preclinical testing of new, short-chain, water-soluble, but lipophilic compounds--1-(2-chloroethyl)-1-nitroso-3-(2-hydroxyethyl)urea (HECNU) and 1-(2-chloroethyl)-1-nitroso-3-(methylene carboxamido)urea. Molecular mechanisms of reactions with biomolecules are discussed with regard to DNA alkylation and cross-linking, carbamoylation of glutathione and glutathione reductase inhibition. Results of a clinical phase-II study show that HECNU, as predicted from preclinical tests, exhibits outstanding activity in brain tumours. Future development concentrates on the use of carrier molecules for nitrosoureas. Results of an extensive structure-activity study with oestradiol-linked analogues show that an oestradiol-17 ester derivative is much more active than other analogues.

Alkylating Agents↗

Phagocytosis of erythrocyte membranes (white ghosts) from different species by the isolated perfused rat liver.

Autologous and heterologous erythrocyte membranes (white ghosts) - suspended in a perfusion medium free of immunoglobulins, proteins and hemoglobin - were offered for phagocytosis to isolated perfused livers of different rat strains. The mononuclear phagocyte system of the liver was able to phagocytize these membranes without opsonization. An immunological reaction between Kupffer cells and red cell membranes cannot be excluded, since autologous cell membranes are phagocytized at a higher rate than heterologous cell membranes.

3-Hydroxybutyric Acid↗

Trazodone in endogenous depressed patients: a negative report and a critical evaluation of the pertaining literature.

The antidepressant efficacy of trazodone has been studied during three weeks in 13 endogenously depressed patients, using a fixed dosage of 5/10 mg/kg bodyweight per day. Psychopathological assessments were documented by means of observer rating (HDRS, AMP) and selfratings (Bf-S, EWL-K). Most variables assessed during course of treatment did not reveal amelioration of statistical significance or clinical relevance. If the most frequently applied response criteria of a 50% reduction of the initial HDRS-score was taken, only three patient improved. Those results were surprising in view of the previous and subsequent response to antidepressant therapy of the patient group studied. Plasmalevels of trazodone were monitored once weekly; they showed a nine-fold interindividual variation and did not correlate to the fixed dosage steps. A critical review of the pertaining literature led the authors assume, that the main indication of this drug is within non-endogenous-depression.

Adult↗

Temperature-sensitive catabolite activator protein in Escherichia coli BUG6.

BUG6 is a temperature-sensitive cell division mutant which forms filaments at the nonpermissive temperature. Synthesis of the maltose- and galactose-binding protein-dependent transport systems is also temperature sensitive in BUG6. Using operon and protein fusions of the maltose transport genes to lacZ, we observed that the temperature-sensitive control of the maltose transport system in BUG6 occurs at the transcriptional level. By P1-mediated transductions, we found that BUG6 contains two independent temperature-sensitive mutations. One maps between 2 and 3 min on the Escherichia coli linkage map, in close proximity to the fts-envA region. This mutation is responsible for temperature-sensitive cell division. The other mutation maps at 73 min in crp, the structural gene of the catabolite activator protein. The latter could be complemented by a hybrid plasmid carrying the wild-type crp as the only gene on a 0.9-kilobase HindIII-AluI restriction fragment. The mutation in crp alone was found to be responsible for the temperature-sensitive synthesis of the maltose transport system. Although it causes a complete block of transcription of the maltose transport genes at 41 degrees C, this mutation had only a marginal effect on the transcription of the lac operon.

ATP-Binding Cassette Transporters↗

Characterization of the Salmonella typhimurium mgl operon and its gene products.

In Salmonella typhimurium and Escherichia coli the high-affinity galactose transport system, which contains a periplasmic galactose-binding protein as an essential component, is encoded by the mgl genes. The entire mgl region of S. typhimurium is contained on a 6.3-kilobase EcoRI restriction fragment, which has been cloned into plasmid vectors. We determined the extent of the mgl region on this fragment by Tn5 mutagenesis, examination of lacZ fusions to mgl genes, and subcloning smaller restriction fragments. Polyacrylamide gel electrophoresis of protein preparations derived from strains carrying different plasmids was used to identify the mgl gene products. We conclude that the mgl operon consists of four genes that form a single transcription unit: mglB, mglA, mglE, and mglC. The mglB gene codes for galactose-binding protein (33,000 daltons), mglA codes for a membrane-bound protein of 51,000 daltons, and mglC codes for a 29,000-dalton membrane protein. The mglE product was less well characterized. Its existence was inferred from a mglE-lacZ protein fusion located between mglA and mglC. In addition, the coupled transcription-translation in vitro system indicated that mglE codes for a 21,000-dalton protein.

Bacterial Proteins↗

Needle aspiration biopsy in cystic papillary carcinoma of the thyroid.

The records of 11 patients with cystic papillary carcinoma of the thyroid who had undergone preoperative sonography and fine-needle aspiration biopsy were retrospectively reviewed. The lesions varied from 1.5 to 5 cm in diameter. In only six (55%) of the 11 patients was the correct diagnosis made preoperatively. In the other 45%, the lesion was initially misdiagnosed as a benign or hemorrhagic cyst. These data indicate that needle aspiration often yields false-negative results in patients with cystic papillary carcinoma. All patients diagnosed on sonography and fine-needle aspiration as having benign cysts should have continued clinical follow-up. If lesions do not disappear either clinically or by sonography, a more aggressive approach should be taken.

Adult↗

Popliteal artery entrapment demonstrated by CT.

The computed tomographic (CT) findings in a young man with bilateral popliteal entrapment are presented. CT may be the procedure of choice in young adults with intermittent claudication.

Adult↗

Ultrasonic refraction by the rectus abdominis muscles: the double image artifact.

Using a real-time mechanical sector scanner in a transverse plane of section, the authors noticed that a double image of an intrauterine gestational sac or an intrauterine contraceptive device can be obtained when the transducer is passed over the midline of the abdomen. It was suggested that this is caused by refraction of the sound passing through the medial edges of both rectus abdominis muscles. The authors were able to reproduce this artifact in vitro using isolated human cadaver rectus muscles and imaging a single object in a water bath.

Abdominal Muscles↗

Long-term cytapheresis in the treatment of Sézary-syndrome.

Lymphocytaphereses using the Fenwal CS 3000 cell separator were performed in three patients with far advanced disease of Sézary-syndrome that was refractory to standard form of therapy. Patients underwent cytapheresis two to three times per week until the WBCs counts were regressed. Thereafter, one pheresis per week was performed for a total of 29 (Pat. A), 18 (Pat. B) to 70 (Pat. C) procedures during periods of 13 (A), 4 (B) to 19 (C) months. During each pheresis the volume of blood processed was 6-7000 mls. The cytaphereses resulted in an average WBCs reduction of 25 to 35% and of 35-56% of the original peripheral blood Sézary-cell counts. Lymphocytes counts dropped by 47 +/- 12% and 87 to 95% of the collected cells were lymphocytes. In addition to the fall in absolute numbers of circulating lymphocytes a change in the relative portions of lymphocytes subpopulations was observed. T-cells were reduced and concurrently B-cells increased. Significant side effects did not occurred during or following cytaphereses. Long-term pheresis can effectively treat symptmoms also in older patients resulting in preferential loss of T-cells and Sézary-cells without exposing the patients to dangerously large shifts in fluid volume. The results suggest also that there may be selected patients for whom lymphocytapheresis is an useful therapy, but no in vitro test can reliably separate responders from non-responders, and some patients become refractory to further cytapheresis-therapy after initial clinical remission.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Occurrence and characterization of different types of cytotoxic antibodies in pregnant women in relation to parity and gestational age.

Lymphocytotoxic antibodies in sera from 55 pregnant women (of whom 23 were in their first, 21 were in their second, and 11 were in their third pregnancy), as detected by four different microcytotoxicity tests, were predominantly cold reactive and of the IgM class. During pregnancy, there is an increase in lymphocytotoxic antibody formation which is most pronounced after delivery. It is impressive that during first and second pregnancies antibody frequency is similar in the first and second trimesters, whereas in a third pregnancy there is a decrease intermittently. The behavior of antibody frequency in the second trimester may suggest a possible absorption by fetal and/or placental structures. The antibodies seem to be part of a natural immunization process and may play a protective role in pregnancy.

Antilymphocyte Serum↗

[Use of chromogenic substrate in cerebrospinal fluid diagnosis].

Amidolytic assays with chromogenic substrates exhibit great sensitivity, easy management, and good reproducibility. Consequently, they can be used with advantage in the analysis of cerebrospinal fluid (CSF). CSF levels of alpha 2-macroglobulin, alpha 1-antitrypsin, and plasminogen can thus be determined without a concentration step prior to analysis--lowered alpha 1-antitrypsin levels included. Serum/CSF concentration ratios obtained with these assays agree well with data calculated from immunochemical procedures. Moreover, there was a good correlation between amidolytic and immunochemical procedures. These reflections make it apparent that they can be adapted for routine evaluation of the above mentioned parameters.

Cerebrospinal Fluid Proteins↗