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U Karbach

Publications and source records attributed to U Karbach.

At least 37 records · Page 2Linked to original sources
PubMed1992

Proliferation-associated oxygen consumption and morphology of tumor cells in monolayer and spheroid culture.

The oxygen consumption rate, proliferative activity, and morphology of EMT6/Ro mouse mammary sarcoma cells in monolayer and multicellular spheroid culture have been investigated in a comparative study. During the transition of monolayer cells from the exponential into the plateau growth phase, there is a distinct decrease in the cellular volume that is associated with a corresponding decrease in the proliferative and respiratory activity of the cells. The decline in cell volume is mainly due to a decrease in the content of cytoplasm, whereas the size of the nucleus is only slightly reduced. A concomitant decrease in the number of mitochondria per cell obviously accounts for the reduction in cellular oxygen uptake. Despite a continuous decrease of cell proliferation from the surface to interior regions of EMT6 spheroids reflected by a gradient in tritiated thymidine labeling, volume-related oxygen consumption is rather uniform in viable regions of these aggregates. The finding can be explained by the results of the morphometric evaluation showing a uniform volume density of mitochondria, i.e., of oxygen-consuming sites within these spheroids.

Animals↗
PubMed1992

Paracellular calcium transport across the small intestine.

Concentration and voltage dependence of unidirectional 45Ca transport measurements indicated that approximately 60-70% of the mucosa-to-serosa calcium flux measured across the short-circuited rat duodenum, jejunum and ileum is paracellular, with only 30-40% of the mucosa-to-serosa calcium transport cellular. The calcium flux from serosa to mucosa was purely paracellular in all segments. Duodenal calcium serosal-to-mucosal flux was of the same order of magnitude as the mucosal-to-serosal paracellular movement. However, the serosal-to-mucosal flux of jejunum and ileum was twice as high. Therefore, net calcium absorption occurs only in the duodenum, whereas calcium is secreted in the jejunum and ileum by a passive paracellular route, presumably involving an anomalous solvent drag effect. Administration of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) led to an increase in the transcellular mucosa-to-serosa flux in the duodenum only. It also led to a stimulation of paracellular calcium flux in both directions in all three intestinal segments, with no change in net paracellular calcium absorption. Thus, the only vitamin D-related increase in calcium absorption was due to the increase in duodenal transcellular absorption. The mechanism by which 1,25-(OH)2D3 increased paracellular flux is not known but may have resulted from an osmotic effect on the intercellular spaces.

Animals↗
PubMed1992

Enteric protein loss as a marker of intestinal inflammatory activity in Crohn's disease: comparability of enteric clearance and stool concentration of alpha-1-antitrypsin?

Intestinal alpha 1-antitrypsin (alpha 1-AT) clearance has been shown a reliable index of intestinal inflammatory activity in Crohn's disease (CD). For reasons of practicability, it has been repeatedly suggested to replace alpha 1-AT clearance by alpha 1-AT concentration in random stool samples. In 60 controls and in 70 patients with CD, in 21 patients before and after treatment, fecal alpha 1-AT concentration and the ratio of stool and serum alpha 1-AT concentration were compared with alpha 1-AT clearance. In 11 patients alpha 1-AT clearance, fecal concentration and stool/serum alpha 1-AT concentration ratio were compared with 51Cr-albumin clearance. alpha 1-AT clearance (104 +/- 14 vs. 17.5 +/- 2 ml/d, p < 0.0001) as well as fecal alpha 1-AT concentration (155 +/- 21 vs. 30 +/- 3 mg/100 ml, p < 0.0001) and stool/serum alpha 1-AT concentration ratio (45 +/- 6 vs. 12 +/- 1) were significantly higher in CD patients than in controls. alpha 1-AT clearance (60 +/- 9 vs. 37 +/- 4 ml/d, p < 0.01), fecal alpha 1-AT concentration (113 +/- 21 vs. 59 +/- 8 mg/100 ml, p < 0.01) and the stool/serum alpha 1-AT concentration ratio (27 +/- 4 vs. 18 +/- 2) decreased after treatment, but fecal alpha 1-AT concentration and the stool/serum alpha 1-AT concentration ratio failed to parallel the course of alpha 1-AT clearance in 33% and in 24% of patients, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Different mechanism of magnesium and calcium transport across rat duodenum.

Concentration and voltage dependence of Mg transport across the rat duodenum was measured in an Ussing chamber. Mucosa (m) to serosa (s) Mg flux exhibits a cellular fraction comparable to that found for Ca. Mg sm flux is purely diffusive and probably restricted to the paracellular pathway. At all concentrations between 0.5 and 5 mmol/liter, Mg is secreted. Diffuse sm Mg flux is 3.5 times higher than the diffusive component of ms Mg transport. This prevalence of diffusive sm Mg flux over that from mucosa to serosa, which may be explained by an "anomalous solvent drag effect," is responsible for the Mg secretion observed. Mg 5 mmol/liter decreases ms Ca flux and abolishes Ca absorption. The voltage clamp experiments reveal that Mg has no effect on the cellular transport but only decreases diffusive ms Ca flux. 1 alpha,25-dihydroxyvitamin D3 has only a small effect on cellular Mg transport but remarkably stimulates ms Ca flux and increases Ca absorption by about 85%. Dexamethasone increases ms Mg flux but decreases ms Ca transport and hereby abolished Mg secretion or Ca absorption. In conclusion, Mg is secreted across the short-circuited duodenum whereas Ca is absorbed. There is evidence that both earth alkalines are transported by distinct cellular mechanisms. The data also demonstrate that diffusive movement across the paracellular pathway plays an important role on net Mg transport.

Animals↗
PubMed1991

Segmental heterogeneity of cellular and paracellular calcium transport across the rat duodenum and jejunum.

Concentration- and voltage-dependent 45Ca transport was measured across the rat duodenum and jejunum. Mucosa-to-serosa calcium transport across the short-circuited tissue exhibits a saturable component, whereas serosa-to-mucosa calcium flux in both segments is linear to the calcium concentration between 0.125 mmol/L and 10 mmol/L. Calcium is absorbed in the duodenum at concentrations between 0.125 mmol/L and 2.5 mmol/L but is secreted in the jejunum at all concentrations. The simultaneously measured paracellular marker [3H]mannitol at all calcium concentrations is secreted in both segments. The study across clamped preparations shows that (a) only mucosa-to-serosa calcium flux has a voltage-independent cellular component; (b) serosa-to-mucosa calcium flux is totally voltage dependent, i.e., diffusive and probably restricted to the paracellular pathway; (c) diffusive calcium flux in the duodeum is equal in both directions; and (d) diffusive serosa-to-mucosa flux in the jejunum is higher than the corresponding flux in the opposite direction, suggesting that calcium passively is secreted in the jejunum as the consequence of a preference of the paracellular serosa-to-mucosa calcium movement caused by "anomalous solvent drag effect." 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] stimulates serosa-to-mucosa and more pronounced mucosa-to-serosa calcium flux and increases calcium absorption in the duodenum and abolishes calcium secretion in the jejunum. 1,25(OH)2D3 stimulates cellular mucosa-to-serosa calcium flux in the duodenum only but has no effect on cellular calcium in the jejunum. However, the vitamin increases bidirectional diffusive calcium fluxes across both segments. Tissue resistance is decreased and the flux of the paracellular marker mannitol in both directions is increased, suggesting that 1,25(OH)2D3 stimulates diffusive calcium flux across both segments by increasing the paracellular permeability. Dexamethasone inhibits cellular mucosa-to-serosa calcium flux and abolishes calcium absorption in the duodenum only but has no effect on cellular calcium flux in the jejunum. The glucosteroid has no influence on diffusive calcium flux in the duodenum but increases voltage-dependent bidirectional calcium flux across the jejunum. Simultaneously, the flux of the paracellular probe mannitol in both directions across the jejunum is increased, whereas mannitol flux in the duodenum is unresponsive to dexamethasone.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Pathophysiological approaches to identifying tumor hypoxia in patients.

The present report summarizes observations of the authors on tumor oxygenation and on techniques for characterizing tumor hypoxia in patients. Cryospectrophotometric measurements of HbO2 saturations in tumor microvessels allow for estimates of the proportion of well oxygenated tissue regions. Labeling of tissue areas at oxygen (O2) tensions (pO2) less than 10 mm Hg with misonidazole may be used for a general characterization of the oxygenation status in patient tumors rather than for the determination of the radiobiologically hypoxic cell fraction. Quantitative bioluminescence and single photon imaging make it possible to determine ATP concentrations in absolute terms with a spatial resolution at the cellular level. It is shown that the ATP distribution reflects the efficiency of the O2 supply to tumors. Since all these techniques rely on biopsy material, the measured values can be assessed in relation to the histological structure and vascular pattern of the tumors. Such a direct interrelationship is not obtained when using polarographic microelectrodes in tumor tissue. However, a novel technology, the "computerized pO2 histography" has enabled direct polarographic measurements of pO2 values in patients, in extended and systematic clinical trials. Preliminary results in cervix and breast cancers demonstrate that pO2 values are lower in tumors than in adjacent normal tissues, and that great intra- and intertumoral differences occur even among tumors of the same clinical stages and histological grades, illustrating the necessity of such a pathophysiological approach to an "individualization" of tumor therapy.

Cell Hypoxia↗
PubMed1991

New clinical and experimental aspects of intestinal magnesium transport.

Mg transport across various segments of the rat small and large bowel was measured in the absence of electrochemical gradients and using the voltage clamp technique. In the mucosa-to-serosa (ms) Mg flux across the duodenum, ileum, and colon a cellular part is involved, amounting to 40-70% of the total ms Mg flux measured across the short-circuited tissue. However, serosa-to-mucosa (sm) Mg flux is purely passive, suggesting that net Mg transport is largely determined by convectively driven Mg flux across the paracellular pathway. Mg is absorbed across the colon and ileum but in the duodenum paracellularly it is secreted due to an 'anomalous solvent drag effect'. Mg in the caecum decreases cellular ms Ca transport but in the other segments only passive ms Ca flux is reduced by a decrease of the paracellular permeability for Ca, or by a Mg-induced decrease in water absorption. Mg transport across all segments is insensitive to 1,25(OH)2D3. Dexamethasone abolishes cellular Ca transport but stimulates paracellular ms Mg flux in the duodenum. It is concluded that in the rat (a) Mg and Ca are transported by distinct cellular and paracellular mechanisms; (b) Mg transport is largely confined to the paracellular pathway; (c) the ileum and the colon are the major sites for the gut regulation of Mg homeostasis.

Animals↗
PubMed1990

Cellular and paracellular magnesium transport across the terminal ileum of the rat and its interaction with the calcium transport.

Concentration and voltage dependence of unidirectional magnesium fluxes across the stripped mucosa of the rat terminal ileum were measured in an Ussing chamber. The mucosa-to-serosa magnesium flux exhibited a curvilinear concentration dependence, whereas serosa-to-mucosa flux of magnesium was linearly related to magnesium concentration between 0.25 and 5 mM. At low concentrations magnesium was absorbed, whereas at the magnesium concentration of 5 mM the serosa-to-mucosa magnesium flux was higher than the mucosa-to-serosa flux, resulting in magnesium secretion. Only the mucosa-to-serosa flux of magnesium had a voltage-independent (i.e., nondiffusive) cellular component. Due to the high capacity of this cellular mucosa-to-serosa transport of magnesium, which was about 7.5 times greater than that of calcium, absorption of magnesium was performed in the terminal ileum in contrast to calcium, which was secreted under the same conditions. However, magnesium serosa-to-mucosa flux was totally voltage dependent (i.e., diffusive) and probably restricted to the paracellular pathway. The diffusive serosa-to-mucosa flux of magnesium was about two times greater than the diffusive fraction of the mucosa-to-serosa transport of magnesium. The prevalence of the diffusive serosa-to-mucosa flux of magnesium over that from mucosa to serosa, responsible for magnesium secretion observed at the magnesium concentration of 5 mM, may be explained by an "anomalous solvent drag effect." Voltage clamp experiments showed that magnesium had no effect on the cellular mucosa-to-serosa transport of calcium. However, it decreased the diffusive calcium flux in this direction. 1 alpha,25-dihydroxyvitamin D3 did not influence the unidirectional or net magnesium transport but increased the calcium flux in both directions to the same degree. In conclusion, magnesium is absorbed in the terminal ileum at least partially by a cellular, vitamin D3-insensitive process that is different from the calcium transport mechanism.

Animals↗
PubMed1989

Interrelationship among morphology, metabolism, and proliferation of tumor cells in monolayer and spheroid culture.

The proliferative activity of tumor cells is positively correlated with the cellular respiration rate. Thus, a decrease in the proliferative fraction during monolayer growth of EMT6 cells is associated with a decrease in the oxygen consumption rate both per cell and per cellular volume. These changes are paralleled by variations in the morphology of the tumor cells. The cellular volume, the cytoplasmic volume, the number and volume of mitochondria is decreased, whereas the volume of the nucleus remains relatively constant during the transition of cells from the exponential to the plateau growth phase. Similar observations have been made in outer, highly proliferative and inner non-proliferating cells in EMT6 spheroids. However, the local oxygen consumption in this three dimensional, tissue-like assemblage of cells is obviously modified by the cellular packing density leading to a rather uniform oxygen uptake in the proliferating and non-proliferating cell areas.

Animals↗
PubMed1989

Magnesium transport across colon ascendens of the rat.

Concentration and voltage dependence of unidirectional Mg fluxes across the rat colon ascendens were measured in a modified Ussing chamber. Mucosa (M) to serosa (S) Mg flux exhibits a cellular component, whereas SM flux is totally diffusive. At all the concentrations between 0.125 and 8 mmol/liter MS Mg transport is higher than the flux in the opposite direction, resulting in Mg absorption. In contrast to Mg, in Ca transport a cellular component is involved in both directions across the tissue, 1 alpha, 25-Dihydroxyvitamin D3 has no influence on the Mg transport. Mg (5 mmol/liter) remarkably decreases MS Ca flux and reduces Ca absorption by 70%. The parallel decrease in MS Ca flux with that of the simultaneously measured paracellular marker mannitol and the voltage clamp experiments reveal that Mg has no influence on cellular Ca transport but only reduces diffusive MS Ca flux, possibly by decreasing transepithelial fluid absorption. The experiments demonstrate that the colon ascendens of the rat is capable of absorbing Mg at rates comparable to that found for Ca. There is evidence that Mg and Ca are transported by separate cellular mechanisms. Diffusive movement across the paracellular route plays an important role on net transport of both earth alkali ions.

Animals↗
PubMed1989

Cellular-mediated and diffusive magnesium transport across the descending colon of the rat.

Concentration and voltage dependence of unidirectional magnesium fluxes across the rat descending colon were measured in a modified Ussing-chamber. Mucosa to serosa (ms) magnesium flux exhibits a saturable component, whereas serosa to mucosa (sm) flux is linearly related to the magnesium concentration from 0.125 to 8 mmol/L. At all the concentrations used, ms magnesium transport is higher than the flux in the opposite direction, resulting in net magnesium absorption. Only ms magnesium transport has a voltage-independent, i.e., cellular-mediated component. Magnesium flux from serosa to mucosa, however, is totally voltage-dependent, i.e., purely diffusive and probably constrained to the paracellular pathway. The cellular-mediated fraction of ms magnesium transport is comparable to that found for calcium. Calcium (5 mmol/L) has no influence on ms flux or on the magnesium flux in the opposite direction. Magnesium (5 mmol/L) has no influence on the sm calcium flux but abolishes calcium absorption by decreasing ms calcium flux. The voltage clamp experiments reveal that magnesium has no influence on the cellular-mediated ms calcium transport but exclusively decreases diffusive calcium flux in this direction. Pretreatment with 1 alpha,25-dihydroxyvitamin D3 (250 ng/kg s.c. daily given for 4 days) has no effect on ms magnesium flux but it remarkably stimulates ms calcium transport. These findings suggest that both earth alkaline ions in the descending colon are transported by separate cellular-mediated mechanisms. On the other hand, the similarity of the kinetic parameters as well as the similarity of the voltage-independent ms fluxes would support the assumption that both ions are absorbed by the same mechanism. Hence, the question of whether both ions are absorbed by the same or by distinct transport processes cannot be answered by the present experiments. Diffusive movement across the paracellular route plays an important role in net transport of both ions. Diffusive magnesium flux is equal in both directions. In contrast, for calcium an asymmetry in the paracellular fluxes with a prevalence of the diffusive sm flux over the diffusive fraction of the flux from mucosa to serosa has been reported. The different behavior with respect to the paracellular movement can be explained by the radius of the hydrated magnesium ion, which is smaller than calcium with its hydration shells.

Animals↗
PubMed1989

Enteric protein loss in various gastrointestinal diseases determined by intestinal alpha 1-antitrypsin clearance.

Intestinal protein loss was measured by means of faecal alpha 1-antitrypsin clearance (alpha 1 ATC) in patients with various gastrointestinal diseases. In healthy controls and in patients with various gastrointestinal diseases there is a remarkable intraindividual fluctuation of the faecal protein loss from day to day. Alpha 1 AT clearance calculated from a three-day stool collection is usually sufficient to indicate enteric protein loss in Crohn's disease, ulcerative colitis, celiac sprue, and Whipple's disease. However, in two patients with intermittent diarrhea coinciding with edema and hypalbuminemia excessive enteric protein loss was observed on one day during a two week stool sampling period only. In one of these patients suction biopsies showed histologically intestinal lymphangiectasia of a 10 cm segment of the upper jejunum. The alpha 1 ATC is a suitable and cheap method to determine enteric protein loss without the use of radioactive tracers and therefore can be used in clinics without departments of nuclear medicine. In contrast to the conventional Gordon test the use of the endogenous marker alpha 1 AT facilitates the determination of faecal protein loss over long time periods, which might be of value in the diagnosis of intermittent occurring enteric protein loss. Furthermore, the endogenous marker alpha 1 AT is of use in following the course of illness and in monitoring the efficacy of therapy in patients with enteric protein loss.

Adult↗
PubMed1989

Comparison of maximal postprandial serum cholylglycine concentration with the retention of 75Se-homotaurocholic acid in ileal dysfunction.

The retention of 75Se-homotaurocholic acid (75SeHCAT) was measured in 12 healthy controls and in 21 patients with Crohn's disease and compared with the maximum postprandial rise in the serum concentration of cholylglycine (CG) in order to detect bile acid malabsorption. The retention of 75SeHCAT was lowered in all patients with inflammation or resection of the terminal ileum over a length more than 20 cm. In 64% of these patients bile acid malabsorption could also be detected by the absence of a significant rise of the postprandial CG serum level but only if the loss of the ileal function exceeded 30 cm. Although less sensitive than the 75SeHCAT retention, the CG method is simpler to apply in terms of laboratory technology and does not involve exposure to radioactivity. The CG method appears to be of use to detect bile acid malabsorption in certain cases. In the case of negatively if still bile acid malabsorption is suspected more sensitive tests such as 75SeHCAT retention should be carried out to further evaluate bile acid malabsorption.

Adolescent↗