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Biomedical subjects

K Moser

Publications and source records attributed to K Moser.

At least 91 records · Page 5Linked to original sources

Evidence for the separation of albumin- and apo A-I-dependent mechanisms of cholesterol efflux from cultured fibroblasts into human plasma.

The role of albumin has been studied in the plasma-mediated efflux of cholesterol from cultured fibroblasts. Immunoaffinity chromatography of plasma on immobilized anti-albumin antibody decreased by 25-50% total efflux catalyzed by plasma. The remainder of the efflux-promoting capacity of plasma was deleted by immunoaffinity chromatography on antibody to apolipoprotein A-I, the major apoprotein of high density lipoprotein. Both components of efflux were saturable with half-saturation at 0.5-1.0% (v/v) plasma. However, the net transport of sterol from cells to medium catalyzed by lecithin:cholesterol acyltransferase, was not reduced by the deletion of the albumin-catalyzed component of efflux. This finding was confirmed with congenitally analbuminemic plasma. These results indicate that efflux to albumin and to high density lipoprotein in plasma represent independent mechanisms; only the latter is coupled to net transport.

Apolipoprotein A-I↗

The value of prognostic parameters for the stratification of advanced breast cancer patients.

One hundred seventy-five patients with metastatic breast cancer, treated with a combination chemotherapy (Cooper regimen), were analyzed retrospectively to identify the value of the traditional prognostic parameters (disease-free interval; menopausal status; dominant site of metastatic lesion) for the stratification of patients before randomization. Response rate and survival time were not significantly affected by the disease-free interval and menopausal status. A significant difference was detected among the three categories of dominant disease (locoregional; osseous; visceral). However, an estimate of total extent of disease (according to Swenerton) was found to be the most important factor for predicting response and survival time after combination cytotoxic treatment. The differences between the dominant size of metastatic disease are mainly influenced by different size of metastatic spread. Therefore, there is found a significant correlation between the different types of dominant lesions and total extent of disease. In conclusion, the particular sites of metastatic spread seem to be of less importance than overall extent of disease in predicting the outcome. A critical evaluation of the three traditional stratification parameters and introduction of a semiquantitative estimation of total tumor burden as a new stratification parameter seems to be necessary when planning and comparing future trials.

Adult↗

Promotion of sterol efflux and net transport by apolipoprotein E in lecithin:cholesterol acyltransferase deficiency.

In the plasma of 4 subjects homozygous for deficiency of lecithin:cholesterol acyltransferase, the level of many apolipoproteins (apo A-I, apo A-II, apo B, apo D) was greatly relative to normal, while that of apo E is increased 5-fold. The lipoprotein complex containing lecithin:cholesterol acyltransferase with apo A-I and apo D in normal plasma is completely absent. The major part of apo E is unassociated with other apolipoproteins. The apoprotein-dependence of sterol efflux and net transport from human skin fibroblasts into plasma was determined by immunoaffinity chromatography. In normal plasma the major component of efflux of sterol radioactivity from labeled fibroblasts was dependent upon unassociated apo A-I. In LCAT-deficient plasma, apoprotein-dependent efflux was largely a function of unassociated apo E. When fibroblasts were incubated with fibrinogen-free unfractionated LCAT-deficient plasma, there was no spontaneous net transport of sterol either into or from the cells, indicating that efflux and influx rates were in balance. When apo E was removed by affinity chromatography, there was net transport from plasma to cells. These findings suggest a novel metabolic role for apo E in the promotion of sterol transport uncoupled to LCAT-activity.

Apolipoproteins↗

Plasmapheresis in patients with advanced malignant disease: a pilot study.

Plasmapheresis has been performed in 16 patients with advanced malignant disease (12 malignant melanoma, 2 breast cancer, 2 colon cancer). Up to 3,000 ml of plasma (range 1,650-3,000 ml) have been replaced by one single plasma exchange. Side effects observed in about 50% of the patients were mainly nausea and chills. Serum proteins including acute phase reactants were monitored before and 2, 4, and 7 days after plasma exchange. A transient change of these proteins was observed in the first days, but, later on, pretreatment values were always retained. Peripheral blood lymphocyte blastogenic response to mitogens was increased in 5 out of 9 patients 7 days after plasma exchange. In 7 out of 9 patients pretreatment serum was found inhibitory to autologous lymphocyte reactivity to mitogens. Furthermore, plasmapheresis was found to decrease significantly the blocking effect of patients' sera on normal donor lymphocyte reactivity. Plasmapheresis was found tolerable in all patients treated, but without any clinical efficacy. Further studies are warranted to establish the therapeutic value of plasma exchange in patients with advanced malignancies.

Blood Proteins↗

Postural changes in pulmonary blood flow in pulmonary hypertension: a noninvasive technique using ventilation-perfusion scans.

To determine whether postural changes in ratio of upper to lower (U:L) zone pulmonary blood flow reflect pulmonary arterial pressures, we used pulmonary perfusion photoscintigraphy to study 12 normal subjects and 10 patients with precapillary pulmonary hypertension (eight classified as "primary" and two as thromboembolic). All patients underwent right-heart catheterization and measurement of pulmonary arterial systolic, diastolic, mean and capillary (wedge) pressures. The distribution of perfusion was then assessed in the supine and erect positions after i.v. injection of technetium-99m-labeled, macroaggregated albumin. Perfusion distribution was corrected for lung volume by xenon-133 equilibrium ventilation scans. In normal subjects, the U:L lung zone perfusion ratio decreased by 70.7 +/- 12.2% with the change in position. The patient group differed (p less than 0.0001) from normal subjects in that there was only a 19 +/- 17.4% shift of U:L ratio with the postural change. The mean pulmonary arterial pressure in the patient groups was 50 +/- 24.2 mm Hg. The postural change in U:L zone ratio correlated significantly with the mean pulmonary arterial pressure (r = -0.84, p less than 0.01) pulmonary arterial systolic (r = -0.83, p less than 0.01) and diastolic pressures (r = -0.72, p less than 0.05) and with the pulmonary vascular resistance (r = -0.74, p less than 0.02). No correlation was found with other hemodynamic, spirometric or blood gas data. We conclude that the postural shift in U:L ratio warrants further exploration as a noninvasive approach for detecting and quantifying pulmonary hypertension.

Adult↗

[Human interferons -- features and chances (author's transl)].

Interferons are soluble cellular products secreted by vertebrate cells in response to a wide variety of inducers. They confer resistance against many different viruses, inhibit proliferation of normal and malignant cells, impede multiplication of intracellular parasites, enhance macrophage and granulocyte phagocytosis, augment natural killer cell activity, and show several other immunomodulatory functions. In viral infections, interferon controls the spread of viruses by inhibiting viral protein synthesis and/or nucleic acid replication and by activating cellular immune responses which effectively eliminate virus-infected cells. Immune interferon, produced in a cellular immune response as the result of an infection, tumour, or hypersensitivity reaction, governs the local immune response to the abrogation of that tumour or other injury by directly reducing cell multiplication and recruiting cytotoxic cells. Clinical trials have shown some effectiveness of interferon in the treatment of chronic viral infections as well as some possible antitumour effects. Because of the extreme scarcity of human interferon and the use of highly impure preparations, the results to date are not conclusive. Therapeutic effectiveness rather than prophylactic effects, has still to be proved by controlled clinical studies with purified interferon under economically feasible conditions.

Fibroblasts↗

Evaluation of left ventricular function in chronic pulmonary disease by exercise gated equilibrium radionuclide angiography.

To assess left ventricular (LV) response to supine bicycle exercise, we studied 10 normal (group 1). 10 patients with coronary artery disease (CAD) (group 2), 12 patients with severe obstructive lung disease (COPD) (group 3), and eight patients with both CAD and COPD (group 4) by gated equilibrium radionuclide angiography. Most individuals in all groups also had pulmonary catheter-obtained measurements of LV filling pressures during exercise. Normal individuals increased their ejection fraction (EF) during exercise by increasing stroke volume (SV) and reducing end-systolic volume (ESV) without changing end-diastolic volume (EDV); pulmonary artery (PAP) and wedge (PAW) pressures were unaltered. CAD patients (group 2) showed no change in EF with increased EDV, ESV, SV, and PAW. COPD patients (group 3) exhibited decreases in EDV, ESV, and SV, accounting for abnormal EF responses in 6 of 12; PAW was unchanged and the marked elevation of PAP correlated with reduced EDV. Group 4 patients (CAD plus COPD) had abnormal EF responses with increased EDV and ESV without change in SV. Thus an abnormal LV function response to exercise in COPD patients may be multifactorial, thereby indicating the possible need for therapeutic modalities in addition to those employed in alleviating pulmonary parenchymal disease.

Adult↗

Evidence of age-dependent activity increase of poly(C)-avid-serum ribonuclease in man.

The activity of ribonuclease (E 3.1.4.22) was estimated in sera of 401 normal subjects (normal renal function, no signs of catabolism), age ranging from 16 to 100 years (mean: 50.25 +/- 19.98) with Poly (C) as substrate. Further activity was measured with the substrates Poly (U), Poly (A) and Poly (G) in 10 sera from each age decade between 21-30 years and 81-90 years. Greatest activity was found with Poly (C) as substrate (mean: 15.88 kU/l +/- 9.57). Covariant analysis (age as covariant) revealed no sex-related activity distribution at any age, whereas the age-dependent activity increase was highly significant (p less than 0.001; 11-20 years: 9.48 kU/l +/- 3.07; 81-90 years: 34.72 kU/l +/- 5.88). Activity with the other substrates was very low and constant throughout all ages. It seems to be mandatory to consider the age of the patient when interpreting ribonuclease activity.

Adolescent↗

[Developments in the serological diagnosis of malignant diseases].

The present study gives an evaluation of carcinoembryonic antigen (CEA), macrophage electrophoretic mobility test (MEM), sialyltransferase, galactosyltransferase isoenzyme (SGT), ribonuclease and reverse transcriptase as diagnostic aids in malignant diseases. CEA and sialyltransferase are of certain value in the monitoring of cancer, as their values in the serum may rise before progression of disease or relapse. Both tests are not reliable parameters in the early diagnosis of malignancy. Our results with regard to the MEM test have not proved in any way useful in the diagnosis of cancer. Our preliminary results appear to indicate that, provided further simplification of the method can be achieved, SGT isoenzyme determination seems to be a better means of diagnosing cancer. In view of inherent-methodological difficulties reverse transcriptase has, at present, no clinical application in the diagnosis of cancer.

Carcinoembryonic Antigen↗

[Oestrogen receptors and prognosis in breast cancer].

The determination of oestrogen receptors seems to be of prognostic value in the radically-operated breast cancer patient. Patients with negative receptor values exhibit early recurrence in a significantly higher percentage of cases than those with positive values. The prognostic implications of oestrogen receptor determination seem to be even higher than an assessment of axillary lymph node involvement. In metastatic breast carcinoma a correlation exists between response to hormonal therapy and receptor assay. The clinical implications for therapeutic management are discussed.

Adult↗

Long-term experience with simultaneous movement of the upper and lower jaw.

A series of 25 extreme Angle class III cases who were operated on by a combined advancement of the maxilla after Le Fort I osteotomy and retropositioning of the mandible after sagittal splitting of the rami was evaluated clinically and radiologically (mean 4 years) after the osteotomies. A very limited number of early postoperative complications and problems were found. A late follow up 22 cases showed a good or even excellent aesthetic result. Occlusion had remained absolutely stable in 17 cases, while in 4 a partial relapse to an edge to edge position of the incisors had occurred. Cephalometric X-ray analysis showed that only in one case had the maxilla move slightly back-wards, while in 5 a small relapse of the mandibular movement was seen. It is therefore concluded from this study, that a combined osteotomy of upper and lower jaw is the treatment of choice for extreme Angle class III deformities. The low complication rate, the enormous aesthetic gain and the few problems and small partial relapses seen at late follow up lead us to recommend this procedure strongly.

Adolescent↗

Bioequivalence of subcutaneous calcium and sodium heparins.

The bioequivalence of subcutaneous porcine calcium and sodium heparins was studied in 48 normal male subjects randomly assigned to 1 of 4 study groups. Each subject received a single subcutaneous injection of 15,000 U of calcium heparin or 1 of 3 sodium heparins. Serial coagulation studies (Lee-White clotting time, activated partial thromboplastin time, thrombin calcium clotting time, and heparin level) were performed over 10 hr. There were no significant differences in anticoagulant effect between groups.

Adolescent↗

[Phase 2 study with cis-dichlorodiaminoplatinum (II) in advanced solid tumors].

cis-Dichlorodiammineplatinum(II) was administered in 23 patients with far advanced solid malignancies using a dose schedule of 50 mg/m2 every 3 weeks. All patients previously had progressive disease using conventional cytotoxic therapies. More than 50% of the patients had been pretreated with at least four different drugs, 9 patients had additionally been irradiated. IN 4 patients there was objective tumor regression (duration 1-4 months); in 7 patients tumor progression could be stopped for at least 1 month; 12 patients did not respond. By sufficient fluid administration combined with electrolyte substitution, furosemide and mannitol, no severe toxic side effects were encountered.

Breast Neoplasms↗

Sialyl transferase activity: a serum enzyme marker in the follow-up of cancer patients.

Clinical evaluation of serum sialyl transferase as a diagnostic tool in malignant disease has shown that there is a strong correlation between enzyme activity and extent of tumor tissue. Thus, patients with large tumor masses show higher enzyme activity than patients with small tumors or in remission. Furthermore, the surgical removal of tumor tissue results in a decrease of enzyme activity to the normal range. The values remain low until metastases recur; this is connected with a new increase in enzyme activity. It has also been shown that successful chemotherapy corresponding to tumor reduction is reflected in lower values. We are thus led to believe that sialyl transferase is a relevant diagnostic blood parameter in the follow-up of cancer patients.

Breast Neoplasms↗