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Biomedical subjects

K Wagner

Publications and source records attributed to K Wagner.

At least 253 records · Page 14Linked to original sources

Glucose uptake, lactate release, ketone body turnover, metabolic micromilieu, and pH distributions in human breast cancer xenografts in nude rats.

Glucose uptake, lactate release, ketone body utilization, spatial distribution of glucose, lactate, and ATP concentrations as well as tissue pH distributions were systematically investigated in s.c. and/or "tissue-isolated" human breast cancer xenografts in T-cell-deficient rnu/rnu rats. Large variations in all parameters were detected within and between tumors indicating a very nonuniform substrate turnover. Glucose was taken up by all xenografts. Glucose consumption rates increased with increasing glucose availabilities, implying that the glucose uptake is mainly determined by the efficiency of nutritive tumor blood flow. The average glucose uptake was 0.37 mumol/g/min in medullary and 0.26 mumol/g/min in squamous cell carcinomas of the breast. At wet weights below 5 g, medullary breast cancers consumed more glucose than squamous cell carcinomas (2P less than 0.05). Most tumors (97%) released lactate in an amount linearly related to glucose consumption. The lactate production of medullary (0.33 mumol/g/min) and squamous cell (0.31 mumol/g/min) breast cancers was similar. In general, the xenografts utilized ketone bodies. beta-Hydroxybutyrate was consumed by 82% and acetoacetate by 73% of the tumors, the uptake rates being linearly related to the respective availabilities. The mean uptake of beta-hydroxybutyrate was 3.48 nmol/g/min and that of acetoacetate 2.56 nmol/g/min. No significant differences were seen between medullary and squamous cell breast cancers. The beta-hydroxybutyrate/acetoacetate ratio in the tumor-venous blood rose with decreasing tumor blood flow indicating the development of hypoxia at advanced growth stages. Glucose, lactate, and ATP levels were all very heterogeneously distributed in medullary and squamous cell tumors as compared with normal tissue. No relationship was evident between the spatial distribution of concentrations of these three substrates. The xenografts were acidotic compared with pH values in normal subcutis. The mean tissue pH in medullary breast cancers was 6.81 +/- 0.25 (SD). Compared with these values, the tissue pH distribution in squamous cell breast cancers was shifted to significantly higher values. The mean pH of the latter tumors was 7.04 +/- 0.19 (2P less than 0.001). From the experimental data presented there is clear indication that the metabolism of the xenografts investigated was mainly determined by the efficiency of nutritive blood flow, i.e., by substrate availability, and not by the metabolic demand of the cancer cells.

Animals↗

Antibodies against acetylcholinesterase and low levels of cholinesterases in a patient with an atypical neuromuscular disorder.

Antibodies against acetylcholinesterase were found in the serum of a patient presenting dyspnea, generalized muscle paresis, diminished tendon reflexes, and fasciculations. Electrodiagnostic studies showed a decremental response, an incomplete interference pattern, and reduced motor nerve conduction velocity. Edrophonium administration resulted in extreme cholinergic crisis. Biopsies displayed muscle atrophy and nervous tissue degeneration. Recurrent acute respiratory failure ended in death. The patient's serum pseudocholinesterase and red blood cells acetylcholinesterase levels were generally very low, with periodical fluctuations. Minute quantities of the patient's serum inhibited the activity of cholinesterases from normal human serum and from various fetal tissues. Enzyme inhibition was abolished following preadsorption of the serum immunoglobulins with goat antihuman Fab, and radioiodinated acetylcholinesterase from human erythrocytes was precipitated by the patient's serum, confirming that anticholinesterase antibodies were present. Acetylcholinesterase extracted from fetal striated muscle with detergent and salt was inhibited to a larger extent than the enzymes similarly prepared from other fetal tissues and more efficiently than buffer-soluble muscle enzyme. These findings suggest that the patient's serum contained antibodies which interacted preferentially with the membrane-associated forms of muscle acetylcholinesterase and indicate that autoantibodies against acetylcholinesterase could play a role in the pathogenesis of the disease.

Acetylcholinesterase↗

The 24-hour posttransfusion survival and lifespan of autologous baboon red cells treated with inositol hexaphosphate-polyethylene glycol or inositol hexaphosphate-adenosine triphosphate-polyethylene glycol to decrease oxygen affinity.

Baboon red cells were treated to reduce oxygen affinity by an osmotic-pulse procedure using dimethyl-sulfoxide. Inositol hexaphosphate (IHP) alone or IHP and adenosine triphosphate (ATP) were incorporated into the red cells in the presence of polyethylene glycol (PEG). The procedure produced variable increases in the red cell P50 value, i.e., the partial pressure of oxygen at which 50% of the hemoglobin was saturated. The effect of treatment of autologous baboon red cells on the 24-hour posttransfusion survival value and lifespan T50 value was measured using a double-label procedure. The data demonstrate that the increase in the P50 value of treated red cells was negatively correlated with the 24-hour posttransfusion survival value; the higher the P50 value, the poorer the 24-hour posttransfusion survival value. The 24-hour posttransfusion survival value for nontreated baboon red cells was 90% and the T50 value was 14 days. The IHP-ATP-PEG-treated red cells had significantly higher red cell ATP levels than did IHP-PEG-treated red cells. The 24-hour posttransfusion survival value was 68% for the IHP-ATP-PEG treated red cells and 52% for the IHP-PEG-treated red cells when the increase in P50 ranged from 10 to 20 mm Hg; the lifespan T50 value for both the IHP-ATP-PEG-treated red cells and the IHP-PEG-treated red cells was 15 days. Osmotic pulse treatment produced significant red cell injury manifested by the 24-hour posttransfusion survival value. However, modification of the RBC with IHP-PEG or IHP-ATP-PEG to decrease hemoglobin affinity for oxygen did not affect their lifespan.

Adenosine Triphosphate↗

Peptide conformation. 48. Conformation and biological activity of proline containing cyclic retro-analogues of somatostatin.

Six cyclic retro-analogues of the peptide hormone somatostatin have been synthesized using the solid phase technique. The peptides cyclo(-Xaa1-Phe2-Thr3-Lys4-Ybb5-Phe6-) and cyclo(-Phe1-Xaa2-Thr3-Lys4-Ybb5-Phe6-) with Xaa = D- or L-Pro and Ybb = D- or L-Trp were cyclized via the azide method. The conformations of the cyclic hexapeptides in DMSO-d6 solution were determined by a number of homo- and heteronuclear two-dimensional n.m.r.-techniques including 2D rotating frame NOE-spectroscopy. Two-step coherence transfers, ROE and chemical exchange, are observed for the first time in ROESY spectra. The backbone conformation of the all-trans cyclopeptides consists of a beta-turn containing the Pro residue in the position i + 1. These retro-analogues of somatostatin exhibit a high activity in the inhibition of cholate and phalloidin uptake by liver cells (cytoprotective effect); however, the hormonal activities of the natural hormone are completely suppressed. The constitutional and conformational requirements for the cytoprotective activity are discussed.

Amino Acid Sequence↗

[Cysteine in parenteral nutrition: comparative study of N-acetyl-cysteine and N,N-diacetylcystine in the rat model].

In this study the question of whether N-N-diacetylcystine (DAC), which is more stable than N-acetylcysteine (AcCYS), may provide a useful cysteine source for parenteral nutrition was investigated. In in vitro studies the release of cysteine from DAC was measured. The Michaelis, constant and maximum velocity were compared with the corresponding results for AcCYS. In in vivo studies 3 groups of growing rats were maintained entirely by parenteral nutrition low in methionine for 15 days. Group I (n = 4) received a solution containing AcCYS, and group II (n = 6) was supplied with a corresponding amount of DAC. In the solution given to group III (n = 6) the CYS derivative was replaced by an isonitrogeneous amount of glycine. Utilization of the respective CYS derivatives was judged from weight gain, nitrogen balance, plasma amino acid pattern, and urinary excretion of free amino acids. The results from both the in vitro and in vivo studies indicate that DAC is not a suitable substitute for AcCYS in parenteral nutrition.

Acetylcysteine↗

[Effect of diltiazem on blood cyclosporin levels].

The simultaneous administration of the calcium channel blocker diltiazem and cyclosporin results in a significant increase of RIA cyclosporin blood levels. The HPLC cyclosporin levels are not influenced.

Acute Kidney Injury↗

[Problems of instituting insulin therapy in advanced age].

The population of diabetics of a district was analysed concerning the age structure, the proportion of the insulin-dependent patients as well as the insulin-dependent diabetics older than 60 years were analysed with regard to the degree of the realization of insulinisation. 13.8% of all diabetics with an age older than 60 years are insulin-dependent. In 71.5% of them the insulinisation is realized. Only in 43% of all insulin-dependent older diabetics an autoinjection of insulin is possible. The results are discussed and propositions for changing the situation are submitted.

Aged↗

[Incidence, diagnosis and therapy of acute respiratory tract diseases caused by influenza viruses, Mycoplasma, Legionella and Chlamydia].

Epidemiology, diagnostics and specific therapy of the infections of the respiratory organs by influenza viruses, mycoplasmas, legionellae and chlamydia are represented at the example of the so-called atypical pneumonias. Among our own hospitalized patients by means of bacteriological and serological methods the proportion of the pathogen agents mentioned in acute diseases of the respiratory tract was established. In more than 30% of the cases cared for, in pneumonias even in 50%, an etiologic clarification was possible. The results render probable that in adult patients who are hospitalized with acute infections of the respiratory system in the winter half-year in 25% is to be reckoned with an influenza virus infection, in 10% with an infection by mycoplasma pneumoniae and in 15% with a legionellosis.

Anti-Bacterial Agents↗

Pregnancy and delivery after bone marrow transplantation (BMT) for severe aplastic anemia (SAA). A case report.

A 23 years old multiple pretransfused female with severe aplastic anemia (SAA) underwent bone marrow transplantation (BMT). Cyclophosphamide (200 mg/kg) was used for conditioning, donor buffy coat cells were given as rejection prophylaxis. Seven months after BMT regular menses started in the absence of exogenous hormonal manipulation and 21 months after BMT the patient became pregnant. Pregnancy was complicated by mumps in the 14th week. It was terminated at term by cesarean section. The normally developed newborn girl (3,450 gm) presented with a "persistent fetal circulation syndrome". After surgical correction of the patent ductus arteriosus Botalli the girl baby recovered quickly.

Adult↗

Effect of the application of a mucin-based saliva substitute on the oral microflora of xerostomic patients.

A cross-sectional study among 46 xerostomic patients was carried out to determine the influence of a mucin-based artificial saliva on the microflora of standardized oral washings. Patient and non-xerostomic control groups were formed according to the use of saliva substitute (ad libitum or from an intraoral reservoir) and dentition (dentate, edentulous, full dentures). Only few differences were observed among the subgroups based on dentition within a specified salivary group. However, the total number of microorganisms and the proportions of veillonellae, actinomycetes, streptococci and S. salivarius were significantly reduced in xerostomic patients not using artificial saliva, whereas lactobacilli, Candida and S. mitior were significantly increased compared to the control groups. Ad libitum use of artificial saliva had little effect, but semi-continuous wetting of the oral cavity through an intra-oral reservoir reversed the xerostomia-induced shifts in the indigenous microflora. However, no significant effect was observed on the proportions of lactobacilli and yeasts, leaving a potentially acidogenic flora.

Aged↗