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Biomedical subjects

K Bauer

Publications and source records attributed to K Bauer.

At least 127 records · Page 7Linked to original sources

Biosynthesis of carnosine and related peptides by skeletal muscle cells in primary culture.

Synthesis of carnosine (beta-alanyl-L-histidine) and related dipeptides could be demonstrated in primary muscle cell cultures derived from embryonic chick pectoral muscle. After incubation with radiolabeled beta-alanine or gamma-aminobutyric acid, the radiolabeled dipeptides were isolated from the cell extracts and also in small amounts from the culture medium. The kinetics of dipeptide formation indicated that anserine (beta-alanyl-1-methylhistidine) is not formed directly by these cells but as a secondary product via the methylation of carnosine. Coinciding with the morphological differentiation of the mononucleated myoblast to form multi-nucleated myotubes, a rapid increase in beta-alanine uptake and also in dipeptide synthesis could be observed. These results demonstrate that carnosine and related peptides are not merely deposited in skeletal muscles but that they are actively synthesized by muscle cells in culture.

Alanine↗

Osmotic release oral drug delivery system of metoprolol in hypertensive asthmatic patients. Pharmacodynamic effects on beta 2-adrenergic receptors.

This study investigated the effects of an osmotic release oral drug delivery system of metoprolol on the changes induced by cumulative doses of inhaled salbutamol on bronchomotor tone, skeletal muscle, and the circulatory system after single (day 1) and multiple (day 7) dosing in 18 hypertensive asthmatic patients (forced expiratory volume in 1 second > 50% predicted; diastolic blood pressure > 90 mm Hg). The patients were given 14/190 mg metoprolol, 100 mg atenolol, and placebo once daily for a 7-day period each in a randomized, double-blind, crossover design. At the estimated time of peak plasma concentrations, cumulative doses of salbutamol (12.5, 37.5, 112.5, 412.5, 812.5, and 1612.5 micrograms) were applied every 20 minutes. Specific airway conductance, finger tremor amplitude, heart rate, and blood pressure were registered at baseline and at each dose increment. The slopes of the salbutamol dose-response curves of specific airway conductance did not differ on day 1 (P > .05). On day 7, atenolol caused a shift of the dose-response curves of specific airway conductance to the right (P < .05), whereas metoprolol was indistinguishable from placebo (P > .05). The median cumulative salbutamol concentrations causing a 50% increase in specific airway conductance were 416 and 384 micrograms (days 1 and 7, respectively) for placebo, 594 and 444 micrograms for metoprolol, and 562 and 1419 micrograms for atenolol. The median cumulative salbutamol concentrations causing a 35% increase in tremor were 732 and 706 micrograms for placebo, 812 and 1213 micrograms for metoprolol, and 797 and 1323 micrograms for atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

[The value of sequential CD 34 measurement for carrying out stem cell pheresis].

The recent significant improvement in disease-free survival in patients with certain haematological malignancies is due to high-dose chemotherapy and subsequent autologous bone marrow and/or stem cell transplantation. The proliferation and egression of stem cells into the peripheral blood must first be stimulated by defined chemotherapy and/or by administration of cytokines. However, the increase of circulating stem cells in peripheral blood is limited to only a few days. By immunologically analysing white blood cells for the expression of the surface antigen CD 34 it is possible to calculate the numbers of haematopoietic progenitor cells. Thus, besides monitoring haematopoietic recovery, the estimation of CD34+ cells in the peripheral blood can be used to indicate the optimal time point for stem cell collection. Two to four stem cell pheresis (one per day) may then yield sufficient stem cells to enable the safe and rapid reconstitution of haematopoiesis following supralethal chemotherapy.

Antigens, CD↗

[Immunophenotyping of leukemia: overview].

Leukaemias that cannot be classified properly by morphological/cytochemical parameters may be diagnosed clearly by immunophenotyping. In this way, the neoplastic cells can be designated to either the myeloid or the lymphatic line of blood cells. Furthermore, myeloid leukaemias can be subtyped immunophenotypically in cases of type M0, M6, and M7, leukaemias, as well as in cases of mixed lineage or undifferentiated leukaemias. In patients with non-Hodgkin-lymphomas the cells can be characterized as being of B- or T-cell origin, and their activational or proliferative state can be assessed. Notably with acute lymphatic leukaemias, the prodigious therapeutical progress over the past years must be attributed to the refined definition of subtypes by immunophenotyping.

Antibodies, Monoclonal↗

Identification of the thyrotropin-releasing-hormone-degrading ectoenzyme as a metallopeptidase.

A time-dependent inhibition of the thyrotropin-releasing-hormone (TRH)-degrading ectoenzyme (EC 3.4.19.-) from rat brain by the metal-complexing agents imidazole, NaCN, EDTA and 1,10-phenanthroline could be demonstrated. In contrast, the inhibition by the non-chelating analogues 4,7- and 1,7-phenanthroline was not time-dependent. At a concentration of 100 microM EDTA the enzymic activity decreased by 50% only after pretreatment for 6 h. It could be restored by addition of Zn2+, Ni2+ and Co2+ but not by other transition metal ions and also not by Ca2+ and Mg2+. Without pretreatment, the enzyme was activated by Co2+ and inhibited by Cu2+, Cd2+ and Hg2+ in a time-dependent manner, but remained unaffected by Ni2+ and Mn2+, as well as by Ca2+ and Mg2+. Compatible with the His-Glu-Xaa-Xaa-His consensus sequence of most zinc-containing metallopeptidases, chemical modification studies with carbodiimide revealed the presence of an essential acidic amino acid residue, probably located at the active site of the enzyme. The catalytically active metal ion could be exchanged for 65Zn and the enzyme could be effectively inhibited by L-pyroglutamyl hydroxamic acid, the chelating derivative of the TRH cleavage product pyroglutamic acid. The TRH-degrading ectoenzyme thus classifies as a member of the zinc-dependent metallopeptidase family.

Aminopeptidases↗

[meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]- dichloroplatinum(II), a new drug not only parenterally but also orally active in the therapy of breast and prostate cancer.

The platinum complex [meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)- ethylenediamine]dichloroplatinum(II),K, was tested for its antitumor activity on hormone-sensitive tumor models under peroral administration. The resorption from the gastrointestinal tract was proved by determining the estrogenic effect of K in a dose/activity study using the immature-mouse uterine weight test. In comparison to the subcutaneous injection, a tenfold peroral dose was administered to achieve identical effects. By peroral treatment of the hormone-sensitive MXT(M3.2) mammary carcinoma of the mouse with K an almost complete inhibition of the tumor growth was obtained. This effect was superior to that of subcutaneously applied cisplatin and significantly better than that obtained by perorally administered ligand L at an equimolar dose, indicating that the antitumor effect is caused by the intact complex K and not by the liberated ligand L. The strong antitumor activity of perorally applied K was also demonstrated on the hormone-sensitive Noble Nb-R prostatic carcinoma of the rat. Histological examinations showed that the platinum complex K did not cause cisplatin-like kidney damage or irritations of gastric or intestinal mucosa when given perorally.

Administration, Oral↗

Effect of intrauterine growth retardation on postnatal weight change in preterm infants.

To investigate the cause or causes of early postnatal weight change, we measured total body water and fluid and energy balances in 14 preterm infants who were appropriate in size for gestational age (AGA) and in 5 weight-matched, preterm, small-for-gestational-age (SGA) infants. On the first day of life, AGA and SGA infants had the same weight and total body water content. At 6 +/- 2 days (mean +/- SD), AGA infants had had significant weight loss (94 +/- 45 gm) and body water loss (67 +/- 80 ml), whereas weight and total body water content in the SGA infants at the same age (5 +/- 1 days) did not differ from the values at birth. Loss of weight and total body water in AGA infants was accompanied by a greater diuresis than in SGA infants at the same amount of fluid intake. At the end of week 1, AGA and SGA infants had the same total energy expenditure (184 +/- 33 vs 171 +/- 17 kJ.kg-1 x day-1); energy intake, which had exceeded total energy expenditure from the third day of life and beyond, already provided 188 +/- 46 (AGA) or 209 +/- 109 kJ.kg-1 x day-1 (SGA), respectively, for energy storage. Nitrogen balance was positive. Subsequent weight gain occurred at the same rate in AGA and SGA infants; both total body water and solids increased. Energy intake, total energy expenditure, and the amount of energy stored (measured during stable weight gain on a regimen of full enteral feedings) had significantly increased compared with week 1, but both groups maintained similar energy storage.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Composition↗

Pharmacodynamic effects of inhaled dry powder formulations of fenoterol and colforsin in asthma.

The airway and tremor response and cardiovascular and hypokalemic effects of single doses of inhalative fenoterol dry powder capsules (0.4 mg) were compared with the fenoterol metered dose inhaler (0.4 mg) and colforsin (forskolin) dry powder capsules (10.0 mg), a direct activator of the adenylate cyclase system, in 16 patients with asthma. Subjects (FEV1 < or = 60% predicted) were investigated in a randomized, double-masked, placebo-controlled, four-period, crossover trial for a 120 minute period. All active drugs caused a significant increase in specific airway conductance (p < 0.05); the order of potency (mean +/- SEM maximum increase from baseline) was fenoterol metered dose inhaler (0.51 +/- 0.06 sec-1 x kPa-1), fenoterol dry powder capsules (0.49 +/- 0.07), and colforsin dry powder capsules (0.30 +/- 0.03). A marked increase in finger tremor amplitude resulted after fenoterol metered dose inhaler only (62.93% +/- 10.21%; p < 0.05) in contrast to fenoterol dry powder capsules (15.84% +/- 4.35%; p < 0.05) and colforsin dry powder capsules (12.87% +/- 10.44%; p > 0.05). A decrease in plasma potassium was found after fenoterol (metered dose inhaler > dry powder capsules; p < 0.05). In conclusion, fenoterol dry powder capsules caused less tremor response and hypokalemic effects than the metered dose inhaler, although the bronchodilator capacity was similar. Colforsin dry powder capsules resulted in a measurable bronchodilatation in patients with asthma.

Administration, Inhalation↗

Assessment of beta-adrenergic receptor blockade after isamoltane, a 5-HT1-receptor active compound, in healthy volunteers.

This study investigated the effects of isamoltane on the changes induced by cumulative doses of inhaled albuterol (salbutamol) on bronchomotor tone, skeletal muscle, circulatory system, and metabolism after single (day 1) and multiple dosing (day 7) in 15 healthy subjects. The volunteers were given placebo, 4 mg isamoltane, 10 mg isamoltane, or 20 mg propranolol over a 7-day period in a randomized, double-blind, crossover design. The greatest attenuation in albuterol-induced beta-adrenergic receptor responses occurred with propranolol. The median provocative dose of albuterol causing a 50% increase in specific airway conductance was 337 and 315 micrograms (day 1 and day 7, respectively) for placebo, 336 and 322 micrograms for 4 mg isamoltane, 344 and 389 micrograms for 10 mg isamoltane, and 667 and 652 micrograms for propranolol. The provocative dose of albuterol producing a 35% increase in tremor was 464 and 539 micrograms (day 1 and day 7, respectively) for placebo, 1122 and 1270 micrograms for 4 mg isamoltane, 1612 and > 1612 micrograms for 10 mg isamoltane, and > 1612 and > 1612 micrograms for propranolol. On day 5 of each period an exercise test was performed. Propranolol reduced exercise heart rate by 11% (compared with placebo), 10 mg isamoltane reduced heart rate by 5%, and 4 mg isamoltane reduced heart rate by 1%. In conclusion, low-dose isamoltane caused measurable systemic effects on both beta 2- and beta 1-adrenergic receptors, and the dose-dependent blockade on beta 2-receptors of skeletal muscle was more clear than the attenuation of exercise heart rate.

Adrenergic beta-Antagonists↗

Short-term effects of blood transfusion on blood volume and resting peripheral blood flow in preterm infants.

The effects of blood transfusion on cardiac output and blood pressure are variable, but resting peripheral blood flow (RPBF) may be a sensitive indicator of changes in blood volume. The purpose of this investigation was to study the effects of red cell transfusion on blood volume (Evans blue), blood pressure, RPBF in the leg (strain-gauge plethysmography) and blood viscosity (cone-plate viscometer) in preterm infants during the first week after birth. Fourteen infants with mean +/- SD birth weight of 1658 +/- 429 g, gestational age 33 +/- 3 weeks and postnatal age 64 +/- 40 h received 18 +/- 4 ml/kg of packed red cells (red cells 11 +/- 2 ml/kg, plasma 7 +/- 1 ml/kg) because their hematocrit was less than 0.45 l/1. Mean blood volume before transfusion was 88 +/- 15 ml/kg. The increase in blood volume (9 +/- 4 ml/kg) measured 4 to 6 h after transfusion was smaller than the transfused volume (18 +/- 4 ml/kg), due to a shift of plasma to the extravascular space. The plasma shift increased with increasing pretransfusion blood volume (r = 0.70; p = 0.007). Red cell transfusion caused an increase in RPBF by 25% (p < 0.01), whereas systolic blood pressure (BP) increased by only 12%. Peripheral resistance (R = BP/RPBF) decreased by 9% (p < 0.01). Blood viscosity (eta) increased by 21% (p < 0.001) and vascular hindrance (R/eta) decreased by 24% (p < 0.001), indicating vasodilatation of limb arteries. The increase in RPBF and the decrease in hindrance were particularly pronounced in infants with high pretransfusion blood volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

Systolic blood pressure and blood volume in preterm infants.

Blood volume and systolic blood pressure (SBP) were measured in 43 preterm infants. Mean (SD) blood volume was 83 (19) ml/kg (range 48-119) and SBP 50 (9) mm Hg (range 34-69), showing a significant overall relationship. Blood volume in infants with SBP > 60 mm Hg (110 (6) ml/kg) was significantly higher than in infants with SBP 40-60 mm Hg (78 (16) ml/kg) and in infants with SBP < 40 mm Hg (75 (10) ml/kg). In conclusion, SBP is of limited value in detecting hypovolaemia in very low birthweight infants.

Blood Pressure↗

Systemic T-cell lymphoma presenting with isolated neurological dysfunction and intraparenchymal brain lesions. Case report.

Secondary non-Hodgkin's lymphoma of the central nervous system is typically a late manifestation of systemic T-cell lymphoma, with a 2-month median survival time after the development of neurological disease. Of the reported patients with this late complication, only 1% manifest spread of the disease to the brain parenchyma. The authors report a patient with an unusual initial neurological presentation of systemic T-cell lymphoproliferative disorder and associated space-occupying lesions of the brain parenchyma. The diagnosis was supported by extensive molecular, immunological, and histopathological analysis. Neurological symptoms appeared early in the course of systemic disease and were characterized by spontaneous exacerbations and remissions. The patient has survived for more than 5 years since the onset of his neurological symptoms. Histopathological characterization including immunoperoxidase staining for T-cell markers, DNA content, and cell-cycle analysis of brain tissue obtained at stereotactic biopsy were compared to those of atypical lymphoid cells of peripheral blood, bone marrow, and liver. The neurological manifestations and possible etiologies of T-cell lymphoma are discussed.

Adult↗

[The control of bovine salmonellosis under field conditions using herd-specific vaccines].

Data were collected from 39 cattle herds in Northern Bavaria with confirmed outbreaks of salmonellosis and analysed regarding the use of herd-specific Salmonella vaccines in control of this infectious disease. The inactivated vaccine was applied intranasally three times at intervals of 1 week (each dose of 5 ml; concentration of antigen about 10(10) organisms/ml, inactivated by heat at 100 degrees C). Efficacy of vaccine was evaluated by comparing bacteriological examination of fecal shedding of Salmonellae before and after vaccination. The number of Salmonella-positive fecal samples was reduced within one week p. vacc. from 25% to less than 1% of all examined fecal samples. Two thirds (65.7%) of the herds were free of infection within 3 weeks p. vacc. Best results after vaccination were obtained when each animal, including the calves, was vaccinated. Further it could be determined that smaller farms with up to 70 cattle did better than larger farms, where often only a part of the herd was immunized (82.6% and 33.3%).

Administration, Intranasal↗

Primate phylogeny studied by comparative determinant analysis. A preliminary report.

In this preliminary report the divergence times for the major primate groups are given, calculated from a study by comparative determinant analysis of 69 proteins (equaling 0.1% of the whole genetic information). With an origin of the primate order set at 80 million years before present, the ages of the last common ancestors (LCAs) of man and the major primate groups obtained this way are as follows: Pan troglodytes 5.2; Gorilla gorilla 7.4; Pongo pygmaeus 19.2; Hylobates lar 20.3; Old World monkeys 31.4; Lagothrix lagotricha 46.0; Cebus albifrons 59.5; three lemur species 67.0, and Galago crassicaudatus 73.3 million years. The LCA results and the approach are shortly discussed. A full account of this extended investigation including results on nonprimate mammals and on the determinant structures and the immunologically derived evolutionary rates of the proteins analyzed will be published elsewhere.

Animals↗

The primitive metazoan Hydra expresses antistasin, a serine protease inhibitor of vertebrate blood coagulation: cDNA cloning, cellular localisation and developmental regulation.

We have isolated and characterized cDNAs from Hydra which encode antistasin, a potent inhibitor of factor Xa in the vertebrate blood clotting cascade. Hydra antistasin is expressed in gland cells and represents a major class of transcripts from Hydra's head. Sequence analysis revealed that Hydra antistasin contains 6 internal repeats of a 25-26 amino acid sequence with a highly conserved pattern of 6 cysteine and 2 glycine residues identical to that in leech antistasin. Conservation of antistasin in a lower metazoan provides a potential link between the vertebrate and invertebrate coagulation systems.

Amino Acid Sequence↗