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W Jelkmann

Publications and source records attributed to W Jelkmann.

155 records · Page 9Linked to original sources
PubMed1978

High pyruvate kinase activity causes low concentration of 2,3-diphosphoglycerate in fetal rabbit red cells.

1. The high oxygen affinity of fetal blood in rabbits is due to a very low concentration of 2,3-diphosphoglycerate (2,3-DPG) in the red cells. In order to gather informations on the factors responsible for this characteristic we have studied synthesis and break-down of 2,3-DPG in fetal and adult rabbit red cells in vitro and examined possible regulative pathways which may lead to the low 2,3-DPG concentration in vivo. 2. Under conditions where 2,3-DPG and 3-phosphoglycerate (3-PGA) accumulate in adult erythrocytes, i.e. in a solution containing inosine, pyruvate and inorganic phosphate, the amount of 2,3-DPG synthetized in fetal red cells was only 40% of the adult value and 3-PGA was not measurable. Upon inhibition of enolase by NaF, however, both 2,3-DPG and 3-PGA increased to a similar extent in fetal and adult red cells. These findings point towards differences in the pyruvate kinase (PK) reaction which is one of the rate limiting steps of glycolysis. Direct measurements revealed an over tenfold higher PK activity in fetal compared to adult red cells. This higher activity of PK will lead to a decreased concentration of 3-PGA with a consecutive fall in 2,3-DPG concentration. 3. Other factors, like a decreased glucose utilization, a decreased activity of 2,3-DPG mutase or an increased 2,3-DPG phosphatase activity could be excluded as a cause for the low 2,3-DPG concentration in fetal red blood cells. The same holds for extraerythrocytic factors like glucose concentration or pH value in fetal blood. 4. During the postnatal development of rabbits the PK activity decreased. 50 days after birth, PK activity was 20% of the fetal value but still somewhat higher than in adult erythrocytes. This change is paralleled by an increase in 2,3-DPG concentration and half saturation oxygen pressure. With respect to the synthesis of 2,3-DPG and ATP, the fetal rabbit red cell is comparable to hereditary high PK activity in human erythrocytes.

Animals↗
PubMed1978

Net charge and oxygen affinity of human hemoglobin are independent of hemoglobin concentration.

The dependence of net charge and oxygen affinity of human hemoglobin upon hemoglobin concentration was reinvestigated. In contrast to earlier reports from various laboratories, both functional properties of hemoglobin were found to be independent of hemoglobin concentration. Two findings indicate a concentration-independent net charge of carbonmonoxy hemoglobin at pH 6.6: (A) The pH value of a given carbonmonoty hemoglobin solution remains constant at 6.6 when the hemoglobin concentration is raised from 10 to 40 g/dl, indicating that there is no change in protonation of titratable groups of hemoglobin: (b) the net charge of carbonmonoxy hemoglobin as estimated from the Donnan distribution of 22Na+ shows no dependence on hemoglobin concentration in this concentration range. The oxygen affinity of human hemoglobin was determined from measurements of oxygen concentrations in equilibrated samples using a Lex-O2-Con apparatus (Lexington Instruments, Waltham, Mass.). P50 averaged 11.4 mm Hg at 37 degrees C, pH = 7.2, and ionic strength approximately 0.15. Neither P50 nor Hill's n showed any variation with hemoglobin concentrations increasing from 10 to 40 g/dl.

Electrophysiology↗
PubMedDate not supplied

Dynamic changes in serum erythropoietin levels in solid tumour patients undergoing 41.8 degrees C whole body hyperthermia and/or chemotherapy.

Whole Body Hyperthermia (WBH) has been shown to have physiological effects on myeloid and megakaryocytic haematopoietic tissue via both cytokine induction, as well as hormonal changes. In order to extend this knowledge base to the erythroid cells, endogenous erythropoietin (EPO) levels were studied in 17 cancer patients receiving 41.8 degrees C WBH and/or chemotherapy, as well as in 53 anaemic and non-anaemic control patients. Pre-treatment EPO levels showed a 'blunted' EPO response in cancer patients compared to the control patients. Post-treatment data demonstrated a significant chemotherapy induced increase in EPO levels with a peak at 36 to 48 hours (independent of changes in haemoglobin) and 10 to 13 days post chemotherapy (simultaneously with a drop in haemoglobin levels). The early change in EPO levels was not influenced by the addition of 41.8 degrees C (x 60 min) WBH to the same chemotherapy regimen, i.e., ifosfamide, carboplatin, and etoposide. Taken collectively, our data show that endogenous EPO levels in cancer patients can be effected by chemotherapy (independent of changes in haemoglobin). This EPO response to chemotherapy is not impacted on by 41.8 degrees C WBH. A relevant secondary conclusion can also be derived from this investigation, i.e., caution should be exercised as to the use of EPO levels during chemotherapy as predictors of exogenous EPO efficacy.

Adult↗
PubMedDate not supplied

Biotransformation enzymes in two renal epithelial cell lines (LLC-PK1 and RK-L).

The activities of smooth endoplasmic reticulum (SER) and cytosolic xenobiotic-metabolizing enzymes were studied in two established renal tubular cell lines, LLC-PK1 and RK-L (rat kidney, Lübeck). The glutathione content in both cell lines was about 20-fold higher than in rat kidney homogenates; this is explained by a 20- to 50-fold lower activity of gamma-glutamyl transpeptidase in the cell lines. Among SER enzymes, the cytochrome P-450-dependent dimethylhydrazine demethylase was in the same range in both cell lines as compared with rat kidney S9 fraction. Pretreatment with phenobarbital (0.1 mM in the culture medium for 3 d) did not induce SER or cytosolic enzyme activities. The glutathione content in both epithelial cell lines can be modified by an inhibitor of GSH synthesis (buthionine sulfoximine, BSO), whereas inhibition of gamma-glutamyl transpeptidase (acivicin) did not significantly increase the GSH-concentration. Despite these biochemical characteristics, the utility of the new RK-L-line needs to be evaluated in experimental studies on renal transport processes and metabolism as well as cytotoxicity and genotoxicity of xenobiotics.

Animals↗
PubMedDate not supplied

Serum erythropoietin and creatinine concentrations as predictive factors for response to recombinant human erythropoietin treatment in anaemic tumour patients on chemotherapy.

Recent studies have shown that recombinant human erythropoietin (rHuEPO) is effective in correcting anaemia in about 50% of tumour patients. Predictive parameters for the response to rHuEPO still need to be established. In the present prospective study, rHuEPO therapy was scheduled in 22 patients with solid tumours for 12 weeks (3x10,000 U rHuEPO/week s.c.). If response was not achieved within 4 weeks, the dose was increased to 3x20,000 U rHuEPO/week. All patients received combined chemotherapy (ifosfamide, carboplatin, etoposide) before and during rHuEPO therapy. 10 of the 22 patients responded to rHuEPO and did no longer need blood transfusions. In 8 of the 10 responders and in 2 of the 12 non-responders serum creatinine concentration was increased before rHuEPO therapy was started. In addition, the endogenous serum EPO concentrations were significantly lower in the responders versus the non-responders. We conclude that rHuEPO is primarily effective in patients with chemotherapy-induced renal impairment. The rate of the response to rHuEPO is high when the baseline serum EPO level is <75 U/l and the serum creatinine concentration is greater than normal (or the estimated creatinine clearance <60 ml/min).

Adult↗