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Biomedical subjects

M M Müller

Publications and source records attributed to M M Müller.

At least 145 records · Page 8Linked to original sources

Early prediction of deep sternal wound infection after heart operations by alpha-1 acid glycoprotein and C-reactive protein measurements.

Serum C-reactive protein (CRP) and alpha 1-acid glycoprotein (AAG) levels were studied in 188 patients undergoing heart operations with cardiopulmonary bypass. Mediastinitis or osteomyelitis of the sternum or both developed in 10 patients on postoperative day 4 to 13 (median, day 9). The mean CRP levels on day 2 were lower in patients with later deep sternal wound infection (9.1 +/- 1.5 mg/dl [mean +/- standard error]) compared with patients without major infections (14.0 +/- 0.8 mg/dl; p = 0.103 [univariate logistic regression]). AAG levels on day 2 reacted in a similar manner, yielding 78.2 +/- 5.5 mg/dl and 100.9 +/- 2.7 mg/dl, respectively (p = 0.0004). No correlation was found between CRP or AAG and duration of cardiopulmonary bypass, number of blood transfusions, or total protein levels on day 2. The white blood cell count (WBC) on day 2 was 13.1 +/- 1.7 X 10(3)/microliter for patients with infection and 9.7 +/- 0.3 for those without infection. Multivariate logistic regression analysis revealed that AAG, WBC, and CRP on day 2 were significant risk factors sufficiently predicting the probability of a deep sternal infection. After adjustment for these three variables, other variables (age, sex, total protein on day 2, diabetes mellitus, type of operation, duration of cardiopulmonary bypass, length of operation, repeat thoracotomy for bleeding, number of blood transfusions on the day of operation, intraaortic balloon pumping, reoperation, emergency operation, and surgeon's professional status) were not of additional significance. The goodness of fit of the statistical model was confirmed by a high correspondence between predicted and observed cases of deep sternal infection.(ABSTRACT TRUNCATED AT 250 WORDS)

C-Reactive Protein↗

Assessment of the sensitivity of leukaemic cells to cytotoxic drugs by bioluminescence measurement of ATP in cultured cells.

A short-term test in vitro is described, which can be used to detect resistance to cytostatic agents in leukaemic cells. Leukaemic cell suspensions were incubated with cytostatic agents and the resulting intracellular ATP concentrations were measured by a bioluminescence ATP assay. There was a clear dose-effect relationship in acute leukaemia and chronic lymphocytic leukaemia cells for drugs used in the treatment of leukaemias. A good correlation was found between the ATP content of leukaemic cells and cell viability as determined by the trypan blue dye exclusion test. Preliminary individual clinical correlations suggest a correlation between the chemosensitivity in vitro and the response patterns in vivo in leukaemia patients. This simple, fast and sensitive method may have application for determination of drug-induced cytotoxicity in leukaemic cells in vitro.

Acute Disease↗

Neopterin and interferon gamma serum levels in patients with heart and kidney transplants.

The main problem in the follow-up of patients receiving organ allografts is the early differential diagnosis of rejection episodes and infections. Serum levels of interferon gamma, a marker of T-lymphocyte activity, were determined with an immunoradiometric assay, specific for biologically active interferon gamma and sufficiently sensitive (20 U/l) for the determination of circulating interferon gamma. Neopterin, a pteridine released from stimulated macrophages, was determined by radioimmunoassay. Both rejection crises and infections are accompanied by distinct increases of serum neopterin (median values 124 and 128 nmol/l; N = 98). Interferon gamma levels are elevated for a short period one or two days earlier, the maximal values during infections (median 430 U/l, range 120-1220 U/l, N = 25) being higher than those during rejection episodes (median 120 U/l, range less than 20-330 U/l, N = 73). Each rise of interferon gamma was followed by an increase of neopterin, but not every neopterin increase was preceded by a interferon gamma peak. Neither of these parameters showed an increase during deterioration of kidney function due to cyclosporin toxicity. The determination of interferon gamma, a lymphokine involved in the activation of alloreactivity, reflecting T-cell stimulation, and the measurement of neopterin, a secretory product of activated macrophages, allows the simple, quick and reliable monitoring of the immune status of transplant recipients.

Adolescent↗

The use of bioluminescence to evaluate the influence of chemotherapeutic drugs on ATP-levels of malignant cell lines.

Influence of various cytostatic agents on intracellular ATP concentrations of malignant cell lines was studied. The HL-60 promyelocytic cell line, the SW-480 cell line, derived from an adenocarcinoma of the colon and the SW-620 cell line, derived from a lymphonodal metastasis of the colon carcinoma, were investigated. Cell lines were incubated with cytostatic agents and changes in intracellular ATP concentrations were measured after various incubation times by means of bioluminescence. A marked fall in intracellular ATP concentrations was observed, when HL-60 cells were incubated with drugs used in clinical protocols for treatment of acute leukaemia (daunorubicin, vinblastine, vincristine), whereas only a slight decrease of ATP concentrations was measured after incubation with bleomycin, dacarbazin and prednisolone. The decrease in intracellular ATP concentrations of SW-480 and SW-620 cells was much less pronounced after incubation with cytostatic agents compared to the HL-60 cells. This is in accordance with the clinical experience of the known resistance of colon carcinoma against cytostatic agents. Dose-response curves were obtained for the single cytostatic agents. Comparison of intracellular ATP concentrations and cell viability as determined by the trypan blue and eosin dye exclusion test showed that the trypan blue dye exclusion test underestimated cell kill compared to the eosin dye exclusion test and the bioluminescence assay.

Adenosine Triphosphate↗

A homeo-box-containing gene expressed during oogenesis in Xenopus.

We report the isolation of a second Xenopus gene containing a homeo domain homologous to those of Drosophila. Out of 60 amino acids, 59 are conserved with Antennapedia, and 54 with a previously isolated frog gene. The predicted carboxy-terminus of this homeotic-like protein is 21 amino acids downstream from the conserved domain, ending with six glutamic acids in a row. The main interest of this gene lies in the fact that it is abundantly transcribed in large Xenopus oocytes, where it might be translated into proteins potentially involved in the early determination of embryonic cell types.

Amino Acid Sequence↗

Increased angiotensin-converting enzyme activities in diabetes mellitus: analysis of diabetes type, state of metabolic control and occurrence of diabetic vascular disease.

Serum angiotensin-converting enzyme activities were measured in 41 type 1 diabetics (16.4 +/- 4.0 U/ml), in 40 type 2 diabetics (15.0 +/- 5.2 U/ml) and in 52 controls (13.0 +/- 2.7 U/ml, mean +/- SD). Twenty six (32%) of 81 patients presented with serum angiotensin-converting enzyme activities above the normal range. No relation between serum angiotensin-converting enzyme activities and the presence or lack of diabetic vascular diseases in type 1 and type 2 diabetics could be detected. No significant differences in serum angiotensin-converting enzyme activities were found when comparing various types of diabetic vascular disease (retinopathy, neuropathy, renal failure, arterial vascular disease, diabetic vascular disease, coronary artery disease). However, mean serum angiotensin-converting enzyme activities were significantly increased in diabetics with retinopathy when compared with controls (p less than 0.0005). Correlation between metabolic long term control as determined by measuring glycohaemoglobin (HbA1) concentrations and serum angiotensin-converting enzyme activities could not be established. Serum angiotensin-converting enzyme activities did not show any correlations with duration of diabetes, age or sex of patients. A representative number of diabetics (32%) showed elevated serum angiotensin-converting enzyme activities, but a correlation with diabetic vascular disease, metabolic control or type of disease could not be established.

Adult↗

[Serum plasminogen levels and timing of ovulation].

During diagnosis and treatment of female sterility, plasminogen and fibrinogen degraduation products were measured from patient's vein blood in the cycle of menstruation on the days round menstruation. On the days round ovulation and also before beginning of menstrual bleeding an elevated plasminogen level by unchanged fibrin(ogen) degraduation products was found. Therefore the plasminogen modulation as a causal factor for the rupture of follicles is discussed.

Anovulation↗

Regulation of purine uptake in normal and neoplastic cells.

Purine bases and purine nucleosides pass the cell membrane by facilitated diffusion. For purine bases two different carrier proteins seem to exist. Purine bases are trapped intracellularly immediately after passage of the cell membrane by the action of purine phosphoribosyltransferases (PRTs). Comparison of kinetic data of transport and intracellular enzyme reactions shows that intracellular metabolism is rate limiting for the whole uptake process. Since phosphate stimulates the uptake of bases, limited availability of phosphoribosylpyrophosphate (PRPP) might play a regulatory role. Purine nucleosides apparently enter cells via a common carrier. Of the nucleosides under investigation, only adenosine was taken up in significant amounts. Uptake of adenosine is mainly determined by the ratio of adenosine deaminase (ADA) and adenosine kinase (AK) activities. For uptake of purine nucleotides sequential action of ecto-5'-nucleotidase (ecto-5'-NT), nucleoside carrier and intracellular metabolism is necessary. Cells without ecto-5'-NT activity did not accumulate radioactivity from nucleotides. Proliferating neoplastic cells (K 562 and HL 60 cells) showed enhanced uptake of purine bases and nucleosides, when compared to quiescent cells (erythrocytes and granulocytes). From initial rates of uptake and intracellular enzyme activities it could be concluded that this enhanced uptake was due to alterations of enzyme pattern in the neoplastic cells.

5'-Nucleotidase↗

Enzymological aspects of disorders in purine metabolism.

Congenital enzyme defects of purine synthesis de novo and the salvage pathway are responsible for excessive uric acid production and are often associated with hyperuricemia and gout. On the other hand, defects of enzymes essential for the purine nucleotide cycles are the biochemical basis of dysfunction of the immune system. The influence of several congenital enzyme deficiencies on the regulation of biosynthesis de novo, on the regulation of purine nucleotide concentrations, and on adenosine concentration, as well as the effect on purine transport through cell membranes are discussed. The determination of enzymes involved in purine metabolism in noncongenital diseases seems to be of diagnostic importance. As examples, enzyme activities in lymphocytes of leukemic patients, and the determination of serum guanase activity in patients with liver dysfunction are described.

Adenosine↗

[Laboratory findings in the "Vienna Health Study 79" (author's transl)].

In the course of a health study carried out 1979 in Vienna on more than 2,500 persons at the age of 25, 40 and 60 years respectively, the following blood parameters were investigated: erythrocytes, hemoglobin, hematocrit, serum iron, OGTT, HbA1, uric acid, cholesterol, HDL-cholesterol, SGOT, SGPT, AP, creatinine, BUN; furthermore the usual clinical urine findings. Results are exposed and discussed.

Adult↗

[High-density-lipoprotein and renal insufficiency (author's transl)].

Disturbances in lipid metabolism and accelerated atherosclerosis are well-known phenomena of chronic renal insufficiency. The disturbance in lipid metabolism has been repeatedly described as secondary type IV hyperlipoproteinemia according to the classification of Fredrickson. The classification of Fredrickson, however, does not take into account the role of the alpha-lipoproteins (the HDL lipoproteins and HDL cholesterol). Hence, HDL cholesterol was determined and correlated to other routine parameters of lipid metabolism in 66 patients with different degrees of renal insufficiency. Furthermore, an intravenous fat tolerance test was performed in 14 patients with terminal renal insufficiency. Beside the well-known hypertriglyceridemia with cholesterol values near the upper limits of normal, a significant reduction in HDL cholesterol was found, showing a significant inverse correlation to plasma creatinine values. Patients with advanced or terminal renal insufficiency additionally showed a significant inverse correlation between HDL cholesterol and plasma triglycerides. The disappearance rate of intravenously administered fat emulsion (which corresponds to the clearance rate of chylomicrons and VLDL) was diminished in azotaemic patients, showing a significant inverse correlation between HDL cholesterol and disappearance rate in the intravenous FTT. Beside hypertriglyceridemia, the diminished HDL cholesterol values represent an additional risk factor for the genesis of accelerated atherosclerosis. The diminished k value demonstrates a diminished activity of lipoprotein lipase as cause of hypertriglyceridemia, whereby the positive correlation between the k value and HDL cholesterol and the inverse correlation between HDL cholesterol and triglycerides suggest a causal relationship between the decreased activity of lipoprotein lipase and diminished HDL cholesterol levels.

Arteriosclerosis↗

[Angiotensin-converting enzyme (ACE). Increased serum activities in patients with dermatological diseases (author's transl)].

Serum activities of ACE were investigated in 40 patients with dermatological disease and in nine patients with sarcoidosis. The method of Cushman and Cheung, modified according to Lieberman, was used. Both sarcoidosis patients and patients with dermatological diseases showed marked elevations of ACE-activity. The increase in ACE-activity might result from inflammation and immunological events.

Humans↗