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Biomedical subjects

K Becker

Publications and source records attributed to K Becker.

At least 127 records · Page 7Linked to original sources
PubMed1993

Binding of tissue-specific forms of alpha A-CRYBP1 to their regulatory sequence in the mouse alpha A-crystallin-encoding gene: double-label immunoblotting of UV-crosslinked complexes.

The alpha A-CRYBP1 regulatory sequence (alpha A-CRYBP1RS), at nucleotides -66 to -57 of the mouse alpha A-crystallin-encoding gene (alpha A-CRY) promoter, is an important control element involved in the regulation of mouse alpha A-CRY expression. The gene encoding a protein (alpha A-CRYBP1) that specifically binds to the alpha A-CRYBP1RS sequence has been cloned from a cultured mouse lens cell line. In the present study, we have used an antibody (specific to the alpha A-CRYBP1 protein and made against a synthetic peptide) to directly identify UV-crosslinked protein-DNA complexes via a double-label immunoblotting technique. Multiple alpha A-CRYB1 antigenically related proteins interacted with alpha A-CRYBP1RS in nuclear extracts from both a cloned mouse lens cell line (alpha TN4-1) that expresses alpha A-CRY and a mouse fibroblast line (L929) that does not express the gene. Two sizes (50 kDa and 90 kDa) of proteins reacting with the alpha A-CRYBP1-specific Ab were detected in both cell lines and, in addition, a > 200-kDa protein reacting with the Ab was unique to the fibroblast line. Thus, alpha A-CRYBP1 antigenically related proteins interact with alpha A-CRYBP1RS regardless of alpha A-CRY expression. Moreover, differential processing of the alpha A-CRYBP1 protein and/or alternative splicing of the alpha A-CRY transcript may affect expression of alpha A-CRY.

Alternative Splicing↗
PubMed1993

Physiological response of Zebu and taurine oxen to draught work.

Four Zebu and four Simmental oxen were submitted to continuous and to graded draught work. Venous blood samples were taken before, during, and after exercise at intervals of 2-5 min. Anaerobic threshold was reached at a draught power of 1.6 +/- 0.06 kW for Zebu and 0.7 +/- 0.07 kW for Simmental. Corresponding plasma lactate concentrations were 1.7 +/- 0.2 mmol/liter and 1.6 +/- 0.3 mmol/liter, respectively. Partial pressure of oxygen (pvO2), carbon dioxide (pvCO2), and plasma free fatty acids (FFA) during and after work differed between breeds (P approximately .001) and individuals (P approximately .05). After work, an up to 8-fold increase in FFA was found. Highest plasma lactate concentrations during continuous maximal draught were 3.75 +/- 1.76 (Zebu) and 6.01 +/- 0.88 mmol/liter (Simmental). Acid-base-state during and after exhaustive work remained stable. Heart rate in both breeds did not exceed 190 min-1. It is concluded that 1) even during heavy draught work, anaerobic energy formation plays a minor role for cattle, 2) fatigue in working oxen may be related to cardiovascular limitations, and 3) the physical fitness of European beef-breed oxen is lower compared to multipurpose African Zebu oxen.

Acid-Base Equilibrium↗
PubMed1993

Importance of secondary TXA2 release in mediating of endothelin-1 induced bronchoconstriction and vasopressin in the guinea-pig.

The i.v. bolus application of 1 nmol/kg endothelin-1 (ET-1) in anaesthetized and ventilated guinea-pigs caused an increase in mean arterial blood pressure (BP) and a bronchoconstriction. Both have been reduced or abolished by COX inhibition (ASA) or substances specifically reducing the thromboxane A2 (TXA2) generation (HOE 944) or receptor binding (BM 13177). The significant increase in TXB2 concentrations in plasma and bronchoalveolar lavage (BAL) after ET-1 challenge (15-fold and 4-fold, respectively) have been reduced or abolished by ASA as well as HOE 944 and not altered by BM 13177.

Animals↗
PubMed1993

PAF-induced death in NMRI mice--a suitable shock model for testing new PAF receptor antagonists. Correlation with eicosanoid related substances.

The effects of PAF antagonists, of substances which influence the arachidonic acid metabolism, and of dexamethasone and ketotifen were evaluated in an acute PAF-induced mortality model in female NMRI mice. We established a dependence of sensitivity to PAF on strain (AB mice showed no dose dependence) and on sex of the animals as well as on the PAF charges used in our experiments. PAF produced resistance in surviving animals against the PAF-induced death on repeated application. The PAF antagonists, WEB 2170 and WEB 2086, provided the best dose-dependent protection against PAF toxicity, followed by dexamethasone, by the COX/LOX synthetase inhibitor X 86 (a BW 755 C-analogue) and by the PAF receptor antagonist BN 52021. Particularly remarkable was the excellent prevention by aspirin. Aspirin may not only inhibit the cyclooxygenase pathway but also endogenous PAF synthesis. Other drugs, i.e. indomethacin, the thromboxane receptor antagonist, BM 13177, the thromboxane synthetase inhibitor, HOE 944, as well as the lipoxygenase inhibitors (NDGA, esculetin, SHAM and phenidone) exerted a dose-dependent protection only at high doses.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1993

Detection of fat in a renal cell carcinoma mimicking angiomyolipoma.

The authors report a case of renal cell carcinoma in which computed tomography (CT) revealed fatty tissue and calcification within a solid renal mass. The detection of a mass with negative CT numbers at CT and increased echogenicity at ultrasound led to the incorrect diagnosis of angiomyolipoma (renal hamartoma). The presence of intratumoral calcification should have prompted further evaluation because angiomyolipomas usually do not calcify. The authors do not believe that the nonsurgical approach to angiomyolipomas should be abandoned.

Adipose Tissue↗
PubMed1993

Flavin adenine dinucleotide levels in erythrocytes of very low birthweight infants under vitamin supplementation.

Despite the potential dangers of over- and undersupplementation with riboflavin (vitamin B2), little is known about status, requirements and metabolism of this vitamin in very low birthweight (VLBW) infants. As reported here, it is possible to calculate the intraerythrocytic concentration of free flavin adenine dinucleotide (FAD), the predominant coenzyme form of riboflavin, on the basis of the erythrocyte glutathione reductase activation coefficient (EGRAC). This parameter was determined in 9 VLBW infants (median of birthweight 634 g, median of gestational age 24 weeks + 3 days) at intervals over a period of 6 weeks. All infants received riboflavin supplementation, either in milk (average intake: 175 micrograms/kg/day) and a multivitamin preparation (200 micrograms/day) or via total parenteral nutrition (TPN; 720 micrograms/kg/day). The average EGRAC was 1.07 (1.00-1.24) during enteral nutrition and 1.05 (1.00-1.18) during TPN. These values correspond to free FAD levels of 757 and 1,060 nM, which is 4 to 5 times higher than in cord blood or in breast-fed infants. EGRAC values between 1.15 and 1.35, representing free intracellular FAD levels of 350-150 nM, should be adequate in VLBW infants in order to minimize the hazards of flavin-induced radical reactions.

Enteral Nutrition↗
PubMed1993

High-dose versus intermediate dose cytosine arabinoside combined with mitoxantrone for the treatment of relapsed and refractory acute myeloid leukemia: results of an age adjusted randomized comparison.

193 patients with relapsed or refractory acute myeloid leukemia (AML) were entered into a prospective randomized comparison of high-dose versus intermediate dose cytosine arabinoside (AraC) both combined with mitoxantrone (mitox) according to the previously established sequential HD-AraC/mitox regimen (S-HAM). AraC was administered by 3 hr inf. q 12 hrs on days 1, 2, and 8, 9 at randomly assigned doses of either 3.0 versus 1.0 g/m2 in pts. < 60 years of age or 1.0 versus 0.5 g/m2 in older pts. Mitox was given to all cases at a dose of 10 mg/m2/d on days 3, 4, and 10, 11. Randomization was stratified for primary refractoriness against induction therapy and the length of first remission in relapsed cases (< 6 mths., 6-18 mths., > 18 mths.). From 151 presently evaluable cases 72 pts (48%) achieved a complete remission (CR), 38 cases (25%) were non-responders (NR) and 41 pts. (27%) died within the first 6 weeks after the start of treatment (early death = ED). No significant differences were found in CR rates being 52% and 44% for the 3.0 versus 1.0 g/m2 AraC regimens in pts. < 60 years and 48% and 45% after 1.0 versus 0.5 g/m2 AraC in older pts. No differences between the respective regimens emerged either for the time to CR (median 46 days) nor remission duration (median 4.5 mths). Analysis of treatment failures, however, demonstrated a significantly higher rate of NR after the lower dose regimens in both age groups of 41% and 32% versus 11% and 14% in pts. receiving AraC at higher doses (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Deficient synthesis of cysteinyl leukotrienes in glutathione synthetase deficiency.

Glutathione synthetase deficiency (GSD) is an inborn error of glutathione (GSH) metabolism. As a consequence of the block in the gamma-glutamyl cycle, the enzyme defect leads to a generalized intracellular GSH deficiency. The cysteinyl leukotrienes (LTs), LTC4, LTD4 and LTE4, are potent lipid mediators generated in the 5-lipoxygenase pathway. LTC4 is derived from the unstable epoxide LTA4 by conjugation with GSH, and therefore GSH is required for LTC4 synthesis. In the circulation LTC4 is rapidly metabolized to LTE4 which is excreted in the urine. In the present study, LT metabolites were separated in a patient with biochemically established GSD and intracellular GSH deficiency (0.5 mM in erythrocytes, normal range 2.0-2.5 mM) by reversed-phase high-performance liquid chromatography, and quantified by enzyme immunoassays. Our results revealed that in GSD LTC4 synthesis is significantly decreased in calcium ionophore A23187-activated monocytes as well as in neutrophils (11-14% and 7-10%, respectively, of the levels detected in the parents or healthy controls). Additionally, urinary LTE4 was also found to be abnormally decreased in GSD (0.4 nmol/mol creatinine as compared to 15-46 nmol/mol creatinine in parents and controls). GSD represents the first described disorder with decreased synthesis of cysteinyl LTs and may serve as a unique model for the linkage between LT synthesis and GSH metabolism in vivo. Moreover the impaired synthesis of cysteinyl LTs might be involved in the pathophysiology of GSD.

Cysteine↗
PubMed1992

A novel hypothalamic-dispersed pituitary co-perifusion model for the study of growth hormone secretion.

This study presents a novel, in vitro, hypothalamic-dispersed pituitary co-perifusion system (HPPS) developed to examine the influence of the hypothalamus on pituitary growth hormone (GH) secretion in a controlled environment. In this perifusion system, dispersed rat pituitary cells were loaded onto Biogel P-2 (P-2) beads in a 0.5-ml plexiglas chamber and were submerged in a 37 degrees C water bath. After stabilization, two hypothalami were placed into each chamber on a thin layer of P-2 beads and the chamber was re-equilibrated. To test the system, pituitary cells were stimulated either directly with growth hormone-releasing factor (GRF) or indirectly via the hypothalamus, with clonidine, an alpha 2-adrenergic (alpha 2) receptor agonist. Perifusion of HPPS or pituitary cells with GRF (40 ng/ml) induced a substantial endogenous GH surge. Clonidine (2 x 10(-8) M) treatment stimulated a GH surge in HPPS chambers, but not in chambers containing only pituitary cells. Thus, somatotrophs respond to hypothalamic factors released in response to clonidine and not directly to alpha 2 stimulation. To determine if the components involved in GH feedback are present in the perifusion system, HPPS chambers were sequentially perifused with hGH, clonidine, and GRF. hGH pretreatment suppressed the clonidine but not the GRF-induced GH surge(s) observed in chambers perifused with clonidine and GRF only. In chambers only containing pituitary cells, GH was only increased in response to GRF when sequentially perifused with all three substances. This study demonstrates the dynamic interaction between the hypothalamus and pituitary in the regulation of GH secretion in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Targeting of a chemically pure preprotein to mitochondria does not require the addition of a cytosolic signal recognition factor.

To analyze the role of cytosolic cofactors in mitochondrial protein targeting, we prepared a chemically pure mitochondrial preprotein. When diluted out of 7 M urea, this precursor protein was efficiently imported into mitochondria without the addition of cytosolic cofactors. Extensive prewashing of mitochondria (up to 2 M KCl) did not reduce its import. Import of the purified precursor showed the characteristics of authentic mitochondrial import including use of the receptor MOM19, requirement for a membrane potential, and proteolytic processing. When the precursor was preincubated at a low concentration of urea, cytosolic cofactors were needed to preserve its import competence. We conclude that targeting of this preprotein via the mitochondrial master receptor MOM19 does not require a cytosolic signal recognition factor; cytosolic cofactors apparently have chaperone-like functions in mitochondrial protein uptake. Moreover, we found that a cleavable presequence was sufficient to direct protein import via MOM19. Together with the cofactor-independent function of MOM19, it is thus conceivable that MOM19 functions as mitochondrial presequence receptor.

Animals↗
PubMed1992

Idiopathic portal hypertension in a renal transplant patient after long-term azathioprine therapy.

We report the case of a patient with renal insufficiency who was admitted for the evaluation of splenomegaly. He had received a kidney allograft 6 1/2 years ago. Treatment with azathioprine and prednisolone for immunosuppression had been discontinued 1 year before admission. The underlying cause of the splenomegaly appeared to be an idiopathic portal hypertension. Until now, this disease has been described in only 13 kidney transplant patients receiving long-term immunosuppressive therapy with azathioprine. For the first time we demonstrate that azathioprine can cause this chronic liver disease even if the drug has been withdrawn some time before. Therefore, the indication for azathioprine must be considered very carefully.

Angiography↗
PubMed1992

The role of osteonectin in human tooth development: an immunohistological study.

We investigated immunohistologically 160 teeth and dental germs in various stages of tooth development taken from human individuals (13th week of pregnancy to the 24th year of life) to study the osteonectin expression in dental hard tissue. In the course of dentinogenesis, the predentin, the odontoblasts, and their cell processes show a positive osteonectin staining reaction. During cementogenesis, osteonectin is synthesized by cement-producing fibroblasts, cementoblasts, and cementocytes. The expression of osteonectin during dentinogenesis and cementogenesis is closely related to the development of the respective calcified tissue. All cells of the inner and outer enamel epithelium, the cells of the stratum reticulare and stratum intermedium, the ameloblasts, and the enamel substance are osteonectin negative, just as dentin and cement are. The results of this study indicate one important physiological role of osteonectin as a protein associated with the formation of collagen containing mineralizing tissues like human bone, as well as human dentin and cement.

Adolescent↗
PubMed1992

Blood parameters in draught oxen during work: relationship to physical fitness.

1. Four Zebu and four Simmental oxen were submitted to moderate and exhaustive work. Venous blood samples were taken before, immediately after and 30 min after work and assayed for several blood parameters. 2. Draught work led to a decrease in carbon dioxide (pvCO2) and increases in pH, oxygen (pvO2), triglycerides, free fatty acids (FFA) and lactate. 3. Zebu oxen had higher pvCO2 and FFA and lower pH, pvO2 and lactate in response to exercise. 4. Ratios of individual draught power output and values of pvO2 and lactate after work enable the identification of fit and/or weak individuals.

Animals↗
PubMed1992

Clinical value of measuring the interferon-induced enzyme 2'-5'-oligoadenylate synthetase in children.

2'-5'-oligoadenylate synthetase, an interferon-induced enzyme and a sensitive indicator of the presence of interferon, was measured in peripheral blood mononuclear cells in children with inflammatory disorders of known and unknown origin in order to assess the value of such a test in patient management. Differences in median 2'-5'-oligoadenylate synthetase values in groups of children with viral or bacterial diseases or healthy children were observed. Considerable overlap of the 2'-5'-oligoadenylate synthetase range in the three groups was observed. All children with acute viral infections had increased levels early in their disease and a low value clearly argued against an acute viral infection. However, as more than one-third of children with bacterial diseases displayed elevated 2'-5'-oligoadenylate synthetase concentrations, distinction between a viral and bacterial cause of disease by measuring this enzyme was difficult. Estimation of 2'-5'-oligoadenylate synthetase concentrations in patients with inflammatory diseases of unknown origin, including juvenile rheumatoid arthritis, systemic lupus erythematosus, idiopathic uveitis and glomerulonephritis did not contribute to establishing a diagnosis or measuring disease activity.

2',5'-Oligoadenylate Synthetase↗