Search PubMed⌕ Search

Biomedical subjects

M Linden

Publications and source records attributed to M Linden.

At least 163 records · Page 9Linked to original sources
PubMed1990

Expression of tyrosinase in vegetative cultures of Neurospora crassa transformed with a metallothionein promoter/protyrosinase fusion gene.

Wild-type Neurospora crassa, strain Singapore, was transformed with a N. crassa metallothionein promoter/protyrosinase fusion gene. Transformants produced tyrosinase during vegetative growth, as determined by Western analyses and activity assays. This is in sharp contrast to wild-type strains, where this enzyme is only expressed in situations of starvation or sexual differentiation. Complete integration of a 400 bp metallothionein promoter-fragment leads to constitutive expression of protyrosinase, whereas a 3.6 kb promoter-fragment conferred copper inducibility on the reporter gene in four transformants. A transformant with high constitutive tyrosinase levels was able to produce melanin on complete medium agar plates supplemented with 1 mg/ml L-tyrosine.

Cloning, Molecular↗
PubMed1990

Myeloperoxidase in human lung lavage. I. A marker of local neutrophil activity.

The origin of myeloperoxidase (MPO) in bronchoalveolar lavage (BAL) was investigated in the first part of the study. Radioimmunoassay of the cellular and supernatant MPO content as well as the peroxidase-antiperoxidase (PAP) technique were employed to determine the cellular source of MPO. The concentrations of MPO were measured in serum and BAL in the second part of the study. The aim was to determine whether the capillary bed was also a source of MPO. Neutrophil numbers in BALs obtained from 20 healthy subjects correlated significantly to the concentrations of MPO in cell-free BAL supernatants (r = 0.643, P less than or equal to 0.01). The cellular content of MPO in mixed BAL cells was significantly correlated to the number of neutrophils in the mixture (r = 0.536, P less than 0.05), but not to the number of any other cells. Moreover, the PAP-technique identified MPO in lung tissue neutrophils in resection specimens obtained from three patients undergoing surgery. This technique also revealed strong MPO activity in all BAL neutrophils and a weak activity in merely 4% of the alveolar macrophages in cytospin preparations obtained from seven BALs. High BAL/serum ratio of MPO concentrations suggests that MPO is of local origin, rather than passively diffused from the circulating pool. We therefore conclude that strong evidence suggests that MPO in BAL originates from lung neutrophils and that BAL MPO content may be used to estimate the neutrophil presence or activation in epithelium lining fluid.

Adult↗
PubMed1990

Myeloperoxidase in human lung lavage. II. Internalization of myeloperoxidase by alveolar macrophages.

Bronchial wash and bronchoalveolar lavage were performed in 12 healthy subjects (five smokers), in order to elucidate whether or not material of neutrophil origin may be phagocytized by lung macrophages in vivo. Cells from different levels in the bronchial tree were obtained by sequential injection and subsequent aspiration of either four 50-ml or five 10-ml aliquots. Each aliquot was used for the determination of total and differential cell counts. The proportion of myeloperoxidase-positive alveolar macrophages was determined by specific immune histochemical staining. The percentage of myeloperoxidase-positive macrophages was highest (median 94.8%, range 37-98.5%) in the 10-ml aliquots and lowest in the last three 50-ml aliquots (median values 1-2.5%) (P less than 0.001). A significant correlation was obtained between the fraction of myeloperoxidase-positive macrophages and the percentage count of bronchoalveolar lavage neutrophils (r = 0.466, P less than 0.05). Furthermore, the cellular myeloperoxidase showed a significant inverse correlation (r = -0.46, P less than 0.05) to the viability of the bronchoalveolar lavage cells. Our findings are compatible with previous demonstrations in animals of neutrophil phagocytosis by lung macrophages and show that this phenomenon in particular occurs in the more proximal airways. The internalization of neutrophils or neutrophil components by airway macrophages may be an important scavenger mechanism for protection of the lung from the deleterious effects of activated neutrophils.

Adult↗
PubMed1990

Depressive syndromes in schizophrenic patients after discharge from hospital. ANI Study Group Berlin, Düsseldorf, Göttingen, Munich.

A total of 364 schizophrenic outpatients who were stabilized for 3 months on continuous neuroleptic therapy after discharge from the hospital were rated according to three different scales for depressive syndromes (Brief Psychiatric Rating Scale anxious depression factor, AMDP/depression, and the self-rating PD-S depression scale). Between 19.5% and 27.5% of the patients were rated as depressed, or 35.7%-42.8%, when mild depressive syndromes were included. There were low, but significant correlations between demographic or life-event data and depression scores on the self-rating scale, whereas fewer correlations were found on the observer ratings. No associations were found between social adjustment and depression. Moderate correlations were found between measures of the apathetic syndrome and depression ratings, while observer ratings showed higher correlations than the self-rating. High depression scores, especially in the observer ratings, correlated with scales for global psychopathological assessment (CGI, GAS). There were significant correlations between extrapyramidal rigidity and observer rating depression scores, whereas the total amount of neuroleptics given had no influence. These results are interpreted on the basis of hypotheses about depressive syndromes in schizophrenia.

Antipsychotic Agents↗
PubMed1990

Effects of an inhaled corticosteroid, budesonide, on alveolar macrophage function in smokers.

Selected functions of alveolar macrophages obtained by bronchoalveolar lavage of 12 healthy smokers were examined before and after eight weeks' treatment with an inhaled glucocorticosteroid, budesonide (400 micrograms twice daily). After budesonide treatment spontaneous as well as opsonised zymosan triggered prostaglandin E2 (PGE2) secretion from harvested cells was reduced; no such reduction in opsonised zymosan triggered leukotriene B4 (LTB4) production was observed. Neither the capacity to phagocytose opsonised yeast particles nor the superoxide radical generation triggered by the calcium ionophore A23187, 4 beta-phorbol 12-myristate 13-acetate (PMA), or opsonised zymosan ex vivo were more than marginally affected by the glucocorticosteroid treatment in vivo. Lavage fluid concentrations of angiotensin converting enzyme (ACE), however, after treatment were twice those before treatment and concentrations of fibronectin were reduced to half. Albumin concentrations in lavage fluid were not affected by the glucocorticosteroid treatment. In separate experiments treatment of alveolar macrophages with 10(-7) or 10(-6) M budesonide overnight in vitro did not affect their superoxide radical or PGE2 generation but significantly blocked LTB4 release. These data indicate that inhaled gluco-corticosteroid treatment may affect synthesis or release (or both) of ACE and fibronectin by alveolar macrophages from healthy smokers whereas other functions of these cells, such as the generation of reactive oxygen derived products ex vivo, are only marginally affected.

Administration, Inhalation↗
PubMed1990

Transfer of 99mTc DTPA and bronchoalveolar lavage findings in patients with asymptomatic extrinsic allergic alveolitis.

An investigation was performed to determine whether symptom free patients with previously diagnosed extrinsic allergic alveolitis had signs of inflammation in the lung. Pulmonary clearance of inhaled technetium-99m labelled diethylene triamine penta-acetic acid (DTPA) was measured in seven patients with a history of extrinsic allergic alveolitis but with no symptoms at the time of the study and in 12 control subjects. Monoexponential clearance curves were obtained in all 12 control subjects. In contrast, lung clearance was abnormal in five of the seven patients: biexponential clearance curves were noted in four and an abnormally rapid monoexponential curve in one. Bronchoalveolar lavage was performed in all patients. Fluid from the second and third aliquots showed increased concentrations of albumin and urea in fluids from the patients, suggesting increased plasma leakage through the alveolocapillary membranes. More eosinophils and more eosinophil cationic protein were also found in the lavage fluid from the patients. The trend towards increased numbers of eosinophils in patients with abnormal lung clearance of DTPA suggests that this may be due to a continuing inflammatory reaction. Lung inflammation was also suggested by the fact that less leukotriene B4 was secreted by cultured alveolar macrophages obtained from patients than by control macrophages. It is concluded that symptom free patients with previous extrinsic allergic alveolitis have continuing alveolar disease as shown by lung clearance and lavage findings.

Adult↗
PubMed1990

Inflammatory cells and eosinophilic activity in asthmatics investigated by bronchoalveolar lavage. The effects of antiasthmatic treatment with budesonide or terbutaline.

We investigated the constituents of bronchoalveolar lavage (BAL) regarding cell profiles and released eosinophilic cationic protein (ECP) in 11 patients treated occasionally with inhaled bronchodilators (Group A) and 11 patients treated regularly with inhaled corticosteroids (Group B). A normal, healthy control group of 12 subjects was also recruited. Compared with Group A, Group B had a reduced recovery percentage of infused volume (p less than 0.05) and total cell number (p less than 0.01). Compared with the control group, there was a significant increase in the percentage of eosinophils (p less than 0.05) in both groups of asthmatics. In Group A there was also a significant increase in mast cells (p less than 0.05), serum-ECP (p less than 0.05), and BAL-ECP (p less than 0.001). No correlations between any of the cell variables and the level of airway responsiveness measured as PC20 histamine were found in any group. Group A patients were investigated twice--before and after 4 wk of randomly allocated treatment with either a regular beta-2-receptor agonist (terbutaline 250 micrograms, two puffs four times a day) or a regularly inhaled corticosteroid (budesonide 200 micrograms twice a day). The BAL differential cell counts were similar and not significantly affected by either treatment. However, BAL-ECP levels were decreased by budesonide treatment (p less than 0.05). ECP levels in serum and BAL were significantly correlated (p less than 0.05 to 0.001). The eosinophilic cell involvement in asthma is further emphasized by this study but the increase in numbers of eosinophils seems less important than their activity, here measured as release of one degranulation product, ECP. To suppress disease activity, repeated long-term treatment is important, but clear preference for either treatment cannot be given on the basis of our present results.

Adult↗
PubMed1990

Veno-venous bypass in experimental liver transplantation: portal-jugular versus caval-portal-jugular.

This study was undertaken to compare the changes in physiologic variables caused by the use of two different types of pump-assisted veno-venous bypass during experimental liver transplantation. The experiments, performed on female pigs weighing 30 +/- 2 kg, were divided into two groups depending on the bypass used. During the anhepatic phase a pump-assisted portal-jugular (PJ) bypass was used in Group 1 (n = 8) at a flow rate of 15 ml kg-1-min-1, while a pump-assisted caval-portal-jugular (CPJ) bypass was used in Group 2 (n = 8) at a flow rate of 20 ml kg-1-min-1. Intraoperative haemodynamics, pulmonary gas exchange, haematological and serum biochemical parameters were evaluated. Postoperative animal survival rate and complications associated with the bypass used were evaluated. Mean pulmonary artery pressure (Ppa) and pulmonary vascular resistance (Pvr) showed significantly different behaviour in the two groups, whereas the remaining parameters all showed the same trend. Thus an earlier and more substantial increase in Ppa and Pvr values was found in Group 1 when compared to Group 2 during the anhepatic phase. The different behaviour shown by Group 1 may depend on the release of circulating vasoactive substances generated following pelvic venous congestion caused by the temporary clamping of the inferior vena cava. In conclusion, this study indicates that the pump-assisted CPJ bypass is more suitable than the pump-assisted PJ bypass. Furthermore, in order to obtain better results it should be used routinely in porcine liver transplantation.

Anesthesia, General↗
PubMed1989

Rapid partial degradation of DDT by a cytochrome P-450 model system.

Heme compounds, in combination with a reducing agent and oxygen, can express various activities of cytochrome P-450 enzymes. In the present study it was found that a mixture of hemin and excess cysteine was able to degrade the insecticide DDT partially. The major products were three water-soluble, non-toxic conjugates of DDT metabolites with cysteine which had lost two or three of the five chlorine atoms of DDT per molecule and whose structures were elucidated by gas chromatography/mass spectrometry. In 0.05 M NH4HCO3, pH 7.7/ethanol (5:6, by vol.), the degradation reaction catalyzed by the hemin-cysteine model system was at least 8 x 10(4) times faster than the uncatalyzed reaction. In the presence of a designed 24-residues polypeptide or beta-casein, two DDT-binding proteins, an additional fourfold increase in the rate of DDT degradation was observed. Although the concentrations of DDT and cysteine occurring in an organism would be expected to be lower than those in the experiments described, the formation of water-soluble conjugates of DDT metabolites with cysteine (and other amino acids) could also play a role in metabolism and excretion of DDT in vivo.

Binding Sites↗
PubMed1989

Glutathione in bronchoalveolar lavage fluid from smokers is related to humoral markers of inflammatory cell activity.

Cigarette smoking results in variable degrees of inflammation in the lower respiratory tract. Furthermore, smoking produces oxidant-mediated changes in the lung, important to the pathogenesis of emphysema. Since glutathione can neutralize reactive oxygen species and prevent peroxidation of unsaturated lipids, it may constitute an important component of the lung's defense against oxidant and inflammatory injury. In the present study, broncholaveolar lavage (BAL) was performed in 27 smokers, and the concentrations of total glutathione as well as the cellular and humoral markers of inflammatory activity were studied. There were significant correlations between total glutathione and neutrophils; two neutrophil granule components, myeloperoxidase and elastase; and chemotactic activity for neutrophils. Moreover, the total glutathione correlated with the eosinophil cationic protein (ECP), a granule constituent of the eosinophil, with two locally produced antiproteases, secretory leukocyte protease inhibitor (SLPI) and antichymotrypsin (ACHY), but not with an alpha 1-protease inhibitor and albumin. These data suggest that the total glutathione levels in BAL fluid may reflect a degree of oxidative and inflammatory stress caused by cigarette smoke, and they are therefore likely to contribute to the protection against this stress.

Biomarkers↗
PubMed1989

Benzodiazepine prescriptions and therapist non-compliance.

In an investigation of benzodiazepine (BDZ) prescription patterns, psychiatrists in private practice were found to exhibit "therapist non-compliance" with regard to general medical recommendations for BDZ use. The findings indicate that BDZ prescriptions in general (53% among patients treated with psychotropics) as well as long-term treatment of patients (37%) are quite common among private practice psychiatrists. BDZ treatment is not restricted to "minor psychiatric disorders", and contrary to the guidelines, even patients with substance dependence are not excluded. A positive association was found for BDZ use and patients' self-reported symptoms and health complaints, the number of other medications prescribed and age. In a discussion of therapist non-compliance it is proposed that this may be a consequence of a symptom-based treatment model, individual health concepts, the doctor-patient relationship and physician's cost-benefit analysis. Thus, psychiatrists' non-compliance may reflect to some extent a case-oriented treatment rationale.

Anti-Anxiety Agents↗
PubMed1989

The antagonistic effect of oxytocin and relaxin on rat uterine segment contractility.

To test the interaction of various hormones on the myometrium, the following experiments were done studying in vitro contractile activity of uterine segments from immature rats. The rats were divided into two groups: group 1 animals were treated with estrogen (n = 9) and group 2 animals were treated with both estrogen and progesterone (n = 11). Uteri from animals in each group were removed and segments were maintained in a temperature- and pH-controlled organ bath. After baseline contractions were established, uterine segments were treated with either oxytocin and then relaxin, or relaxin and then oxytocin. The dose of relaxin used, 20 ng/ml, was previously shown to be effective in inhibiting uterine contractions of animals treated with either estrogen or estrogen plus progesterone. The dose of oxytocin, 2.5 mlU/ml, was the maximal effective dose shown not to produce prolonged tetany. Estrogen plus progesterone treatment increased the frequency of contractions and resulted in contractions of greater duration of the maximal contractile force, as compared with treatment with estrogen alone. Oxytocin caused a stimulation of contractions in relaxin-inhibited uterine strips. Relaxin decreased the hypertonic contractions produced by oxytocin treatment, resulting in contractions similar to baseline. These data demonstrate that oxytocin and relaxin are directly antagonistic in their effects on uterine contractility. This suggests that labor may occur as a result of increased sensitivity to oxytocin or a decreased sensitivity to relaxin.

Animals↗
PubMed1989

[Psychopathology-oriented ergotherapy. An example of the treatment of negative schizophrenic symptoms using the batik technic].

Ergotherapy or occupational therapy is an indispensable part of psychiatric treatment, and which has an exceptionally long history of use ergotherapy focuses on psychopathology. Treatment of schizophrenic patients with batic-work exemplifies how product oriented creative work, with concrete materials, can be used to regain capabilities which have been lost during an illness and/or to foster healthy coping strategies in a compensatory manner. Ergotherapy can be viewed as a "mediator therapy" and as such, is always part of a complex, general treatment plan. Physicians referring patients for ergotherapy have a responsibility to clarify indications as well as to specify treatment demands.

Adaptation, Psychological↗