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W Negendank

Publications and source records attributed to W Negendank.

At least 19 recordsLinked to original sources
PubMed1997

Proton-decoupled 19F spectroscopy of 5-FU catabolites in human liver.

An RF network and a dual-tuned surface coil are described for obtaining proton-decoupled, NOE enhanced 19F spectra from a whole body clinical imager operating at 1.5 Tesia. The network removes 19F frequency noise from the decoupler transmitter, and prevents preamplifier saturation from high-level decoupling signals. Proton decoupling of 19F spectra was optimized using a sample of urine containing 5-fluorouracil (5-FU) and its catabolite fluoro-beta-alanine (FBAL). Proton-decoupled 19F spectroscopy in vivo is demonstrated by obtaining both nonlocalized spectra and spectra localized with three-dimensional chemical shift imaging from the liver of patients undergoing 5-FU chemotherapy.

Fluorouracil↗
PubMed1993

Magnetic resonance imaging in patients with bone marrow disorders.

Magnetic resonance imaging (MRI) provides a non-invasive means to evaluate a large fraction of marrow in less than one hour. Marrow disorders produce non-specific changes in marrow signal intensities which primarily reflect changes in proportions of fat and cellular elements. The pattern of these signal changes narrows the differential diagnosis, and the combination of these features with the clinical context allows interpretations which are clinically useful in many ways. These include: 1) the diagnosis of avascular necrosis (and its distinction from other causes of joint pain), 2) detection of osteomyelitis, 3) differential diagnosis of hypoplastic disorders, 4) staging of lymphomas and myeloma, 5) selection of patients for autologous bone marrow transplant, 6) objective measures of marrow response to therapy, 7) detection of leukemic transformation, and 8) improved detection of marrow disease (primary or secondary) in patients with otherwise unexplained bone pain.

Adult↗
PubMed1992

Treatment of cerebral ischemia with Dextran-40 or Fluosol DA 20%.

A cat stroke model was used to evaluate the efficacy of Dextran-40 (DEX) or Fluosol-DA 20% (FDA) in the treatment of focal cerebral ischemia. The animals were assigned randomly to one of three treatment groups: control, isovolemic hemodilution with DEX or isovolemic hemodilution with FDA. The oxidation state of cytochrome aa3 was measured in-vivo using near infrared reflectance spectrophotometry. The cerebral edema was measured by magnetic resonance imaging (MRI). The MRI edema indices for the three groups revealed that the FDA group had less edema (p less than 0.05), approaching that of non-stroke controls. The relative oxidation state of aa3 for the DEX group declined both during and after hemodilution. At the ninth hour post stroke the FDA group was better (aa3 more oxidized. p less than 0.025). Changes in blood and plasma components were reflective of the extent of hemodilution. Whole blood viscosity analysis revealed a difference (p less than 0.05) at the lower shear rates comparing DEX to FDA with FDA being higher than DEX. Two animals in each of the groups were allowed to awaken at the end of the procedure for functional assessment. These observations suggest that hemodilution with FDA following stroke significantly reduces early post-ischemic cerebral edema, improves oxidation in the peri-infarct area and appears to minimize functional deficits.

Animals↗
PubMed1991

Evidence for clonal disease by magnetic resonance imaging in patients with hypoplastic marrow disorders.

Some patients with hypoplastic marrow disorders, including aplastic anemia (AA), are at risk for clonal evolution to myelodysplastic syndromes (MDS) and leukemia. Magnetic resonance imaging (MRI) of marrow of the spine, pelvis, and femurs was performed in 24 patients with hypoplastic marrow disorders. In 12 patients (three AA, nine MDS) MRI was compatible with the clinical and biopsy diagnoses and served to define the spectrum of marrow patterns in these disorders. In eight patients with hypocellular marrow biopsies and a clinical diagnosis of AA, MRI showed an unexpected inhomogeneous or diffuse cellular pattern. Concurrent or subsequent marrow or cytogenetic studies have led to diagnoses of hypoplastic MDS in seven of these patients. In four patients with prolonged hypoplasia after bone marrow transplantation for lymphoma, a speckled pattern superimposed on a fatty background appeared in serial MRI studies. One case evolved to AML, two developed megaloblastic foci, and one remains hypoplastic at 19 months. This study suggests that MRI is able to detect early clonal disease in patients with AA, and can distinguish AA from hypoplastic MDS.

Adult↗
PubMed1991

Evidence for a contribution of paramagnetic ions to water proton spin-lattice relaxation in normal and malignant mouse tissues.

Paramagnetic ions complexed to proteins may lose, retain, or enhance solvent paramagnetic relaxation (SPR) relative to free solution. We measured T1 and T2 of three mouse cancers, their normal counterparts, and six additional tissues. Long T1 of cancers was not caused by necrosis or by different contents of water, fat, or blood. Dissociable (TCA-extractable) and nondissociable (ashed) Mn, Cu, and Fe were measured by AA. Cancers had less Mn, Cu, and Fe than did normal counterparts. All 12 tissues had inverse correlations between T1 and dissociable Mn and Cu. For Mn alone to account for reduced T1, the extent to which SPR of the Mn-protein complexes would be enhanced is by factors of 0.6 to 13, below the maximum observed in Mn-enzymes. Different amounts of paramagnetic ion-protein complexes may account for part of the differences in T1 of water protons in different tissues, and the longer T1 of cancer cell water may be caused in part by reduced amounts of such complexes.

Animals↗
PubMed1991

Beneficial effects of isovolemic hemodilution using a perfluorocarbon emulsion in a stroke model.

In a clinically applicable cat stroke model, 16 purpose-bred adult animals were used to evaluate the beneficial effects of two treatment regimens: isovolemic hemodilution with either a perfluorocarbon emulsion or dextran 40 (a glucose polymer). Animals that received these treatment regimens were then compared with a control group of untreated animals. Focal cerebral infarctions were produced by transorbital ligation of the left middle cerebral artery. The randomly allocated treatment arms of the study were instituted 3 hours after ligation of the middle cerebral artery, thereby simulating a human clinical situation. In vivo mitochondrial metabolic activity of the peri-infarct cerebral tissue was continually assessed by means of a multiwavelength near-infrared spectrophotometer. This allowed measurement of cellular oxygenation at the cytochrome aa3 level, the terminal member of the cytochrome chain. Sequential proton-based magnetic resonance imaging was used to measure intracerebral water in vivo. Cardiac output, oxygen consumption/delivery, chemical, histologic, and rheologic parameters were also assessed. The data collected were analyzed by group means and standard statistical analyses, which revealed that the group treated with the perfluorocarbon emulsion had both less brain edema in the early post-infarct period (p less than 0.05), as well as a higher level of oxidation of cytochrome aa3 (p less than or equal to 0.025). This evidence supports the premise that isovolemic hemodilution with an oxygen-carrying hemodiluent may be beneficial in the treatment of ischemic strokes.

Animals↗
PubMed1991

Periorbital necrobiotic xanthogranuloma and stage I multiple myeloma. Ultrastructure and response to pulsed dexamethasone documented by magnetic resonance imaging.

We observed a 40-year-old woman with necrobiotic xanthogranuloma from the inception of indurated eyelid and periorbital infiltrates and concurrent stage I multiple myeloma to resolution of infiltrates in skin and bone marrow after pulsed high-dose oral dexamethasone therapy. Ultrastructural studies revealed lipid vacuoles in epidermal keratinocytes, in dermal histiocytic macrophages, and in vascular and lymphatic endothelial cells. The presence of lipid vacuoles in epidermal keratinocytes has not been reported previously in xanthogranuloma.

Adult↗
PubMed1989

Bladder lymphoma: diagnosis and documentation of response by magnetic resonance imaging.

Invasion of the bladder by lymphoma rarely is encountered clinically. The characteristics on magnetic resonance imaging have not been described. We report a case of secondary nonHodgkin's lymphoma of the bladder in which we show the ability of magnetic resonance imaging to visualize the lymphomatous invasion and to monitor the response to chemotherapy.

Female↗
PubMed1989

The physical state of potassium in the human lymphocyte: a review.

Studies of the effects of chemical potential, temperature, and metabolic perturbation on static ion contents, kinetics of the approach to equilibrium, and kinetics of ionic self-exchange in human lymphocytes are reviewed. The results contradict the classical concept of cell ion and water physiology, the membrane-osmotic, pump-leak theory, and are re-interpreted by an adsorption model of the cell. In this model, most of cell water exists in a physical state sufficiently ordered to reduce the partition function of dissolved ions, and most of cell potassium is associated with fixed charges on macromolecules. Competing adsorption of potassium and sodium is cooperative and has a critical temperature dependence. The kinetics of the approach to equilibrium are described by a time dependent Ising model. High rates of isotopic self-exchanges of potassium and sodium near the transition point are postulated to result from an increased rate of fluctuations within the ensemble of ion-adsorbing proteins.

Adsorption↗
PubMed1988

A cooperative transition theory applied to the kinetics of ionic exchanges in cells.

Manifestations of a cooperative interaction between ion-adsorbing sites in cells include steep, sigmoidal equilibrium adsorption isotherms of K+ and Na+, critical temperature transitions of net exchanges of Na+ for K+, and the allosteric nature of the effects of ligands on cellular K+ and Na+. Cooperative ionic adsorption is described by a one-dimensional Ising model. The experimentally-determined equilibrium parameters permit prediction of the kinetics of exchange of K+ for Na+ (the approach to equilibrium) by stochastic or hydrodynamic solutions of a time-dependent Ising model. Studies of the rates of self-exchange of adsorbed ions reveal properties of the cooperatively interacting adsorption sites and their dependence on temperature and chemical potential. High rates of isotopic exchanges of K+ and Na+ occur near the transition point. This is explained by the hypothesis of an increase in susceptibility of the ensemble to slight variations of microK or microNA near the phase transition, which leads to an increase in microscopic fluctuations within the ensemble. It is suggested that the isotopic ion exchange experiment may be a means to explore the microscopic states of the ensemble and their transition probabilities.

Animals↗
PubMed1988

Overview of physical studies of bulk water in biopolymers.

The Symposium of which this paper is a part, "The State Of Water In The Cell", examines evidence which indicates that the bulk water of the cell has physical properties that are different from those of free water in a dilute aqueous solution. The heterogeneity of environments of water within cells makes direct application of physical studies difficult. However, the major physiologic effect of an ordered state of bulk cell water is solute exclusion, and this is also demonstrated by simple polymer solutions. Such systems have provided an opportunity to show that such water has motional correlation times within an order of magnitude of those of free water, and to model other unique properties of bulk cell water.

Biopolymers↗
PubMed1984

The permeability of human lymphocytes to chloride.

The normal amount of Cl in human lymphocytes is 82 mmoles/kg wet weight. Half of this undergoes rapid self-exchange with a half-time of 3 minutes, while the remainder exchanges slowly with a half-time of 180 minutes. The fast fraction of self-exchange of Cl also undergoes a rapid net loss into medium with a low concentration of Cl. Thus, exchange of Cl in lymphocytes has properties like that of K and Na with permeability constants on the order of 10(-6) cm/sec. The results are compatible with a simple model in which the fast fractions are dissolved within ordered cellular water at concentrations less than in the external medium and the slow fractions are adsorbed onto intracellular macromolecules.

Adult↗
PubMed1984

Alterations in oxygen transport following WR-2721.

The toxicity of radiation and alkylating agent chemotherapy is in part related to free radical formation in DNA and associated proteins, which is enhanced by oxygen and other electron affinic compounds. During the Phase I clinical trials of WR-2721 and alkylating agent chemotherapy, venous blood samples were obtained prior to and immediately following the WR-2721 infusion. We have observed a marked increase in the oxygen saturation of venous blood following WR-2721 (430-910 mg/m2 at a rate of 15 mg/m2/minute). The mean venous PO2 (PvO2) rose from a baseline of 34.0 +/- 13.54 torr to a mean value of 54.60 +/- 12.47 torr (p less than 0.001). The percent venous oxygen saturation increased from 54.52 +/- 21.38% to 82.73 +/- 7.66%. The highest values generally occurred within the first 2 hours after the completion of the WR-2721 infusion. No significant differences were found between the pre and post WR-2721 values for either the venous pH, CO2, or bicarbonate levels. Despite increased PvO2, the patients' heart rates, blood pressures, or respiratory rates did not change pre and post WR-2721. No apparent differences were noted in the effects of WR-2721 or PvO2 when given at doses of 740 or 910 mg/m2. However, when WR-2721 (418-1100 mg/m2) was administered over 15 minutes, the PvO2 increased in only 8/13 courses. We postulated that the marked increase in venous blood oxygen concentration was secondary to one of the following mechanisms: 1) Increased affinity of hemoglobin for oxygen, 2) microcirculatory shunting, or 3) decreased tissue requirements for oxygen. In 12 patients oxygen-hemoglobin dissociation curves and intracellular red cell pH's were obtained before and after 740-910 mg/m2 of WR-2721. Despite the significant increase in oxygenation of venous blood after WR-2721, there were no changes in either oxygen-hemoglobin dissociation or intracellular red cell pH to account for this increase. The oxygen consumption of peripheral blood granulocytes was measured prior to and following 15 courses of WR-2721. A marked decrease in granulocyte oxygen consumption was observed in 6/8 patients who had a significant increase in PvO2 and only 1/7 patients who had either a decrease or no change in PvO2 after WR-2721. Our preliminary investigations suggest that the increased venous blood oxygen content may be secondary to a reduction in normal tissue oxygen consumption. WR-2721 may afford protection by both decreasing oxygen consumption and delivery to normal tissues and increasing intracellular sulfhydryls.

Amifostine↗
PubMed1984

Self-exchange of sodium in human lymphocytes.

Self-exchanges of Na and K in human lymphocytes were measured by isotopic efflux techniques. In washed cells, K exchanged in a single slow exponential fraction, but the Na exchange had a marked curvature. It was shown that the curvature was not caused by simple bulk-phase diffusion, and it was resolved into three major fractions: fast (F) (half-time, t1/2 = 2-4 min), intermediate (I) (t1/2 = 12 min), and slow (S) (t1/2 = 125 min). Each of these appeared to follow an exponential function. The I fraction contained approximately 10 mmol Na/kg cells (25-30% of normal cellular Na), was not affected by manipulations that cause lymphocytes to gain Na, and had little or no temperature dependence. The S fraction of Na in normal cells (S1) contained approximately 10 mmol Na/kg cells, had only a slight temperature dependence, and the amount and rate of S1 were independent of external K concentration (Kex). Another slow fraction (S2) appeared when the cells underwent a net gain of Na in exchange for K, and was characterized by a steep temperature dependence and a peak rate around the transition point (the point at which half of cellular K is replaced by Na) at 0.4 mM Kex. The results are discussed within context of a theory that assigns the exchange of the major part of K in its slow exponential fraction and the Na exchange in S2 to interactions of these ions with fixed anionic sites, on intracellular macromolecules, which have been shown previously to interact cooperatively in their association with K and Na.

Adsorption↗
PubMed1984

Potassium efflux from frog oocytes: effects of temperature, preincubation and injection of a gelatin bead.

42K efflux was studied in frog oocytes. 17 of 43 cells had only a single slow exponential exchange of 42K, while the remainder had a curvature of 42K exchange with one or more fast fractions preceding the slow exponential one. This variability in the characteristic of 42K efflux is not associated with evident damage, occurs at both 5 degrees and 25 degrees C., is independent of the method of preincubation, and occurs whether or not the cells are injected with a gelatin bead. Most of the fast-exchange fraction of K is not caused by follicle cells or other extraoocytic sources. These results may help explain some of the apparently conflicting results reported in studies of K exchange in amphibian oocytes.

Animals↗
PubMed1984

Ionic distributions and volume maintenance in human lymphocytes.

The equilibrium water contents and distributions of Na, K, Cl, Mg, Ca, and inorganic phosphate were studied under a variety of conditions that included 0 degrees C., low external K, ouabain and ATP-depletion. Net exclusion of Na was fully inhibited as manifested by a gain of cellular Na to a level greater than or equal to that in the environment. In none of these conditions did the cells swell in a manner expected in the classical pump-leak, double-Donnan concept of volume maintenance. Moreover, Na, K, Cl, and Mg fail to follow consistently a Donnan equilibrium in cells no longer able to exclude ions. Postulated volume-regulating mechanisms other than outwardly directed Na pumps, such as hydrostatic pressure, a Cl pump, altered charge or osmotic coefficient of proteins, and shrunken and swollen compartments did not explain the results. Therefore, we evaluated the data from the standpoint of a theory of cellular physiology in which cellular ions are adsorbed onto macromolecules. From these concepts and the data presented, a new theory of the maintenance and regulation of cellular volume, in which macromolecular salt-linkages provide a cohesive force, is discussed.

Adenosine Triphosphate↗
PubMed1983

Initial assessment of the performance of an 0.3 T permanent magnet in whole body NMR imaging.

An 0.3 Tesla permanent magnet was constructed and incorporated into a complete whole body NMR imager. Axial, sagittal and coronal images from human subjects were obtained using a two-dimensional Fourier Transform analysis of selected planes 8 mm thick, combined with an efficient multislice technique that produces sections centered 12 mm apart. Images were obtained based on inversion recovery and spin echo modes. The permanent magnetic field is uniform to 10 ppm over 38 cm. The magnet requires no special maintenance and has an extremely small fringe field. The magnet design, with its field vertical to the long axis of the subject, permits use of a solenoidal radiofrequency receiving coil for optimal signal-to-noise ratio. Images were shown that are of high quality and produced under conditions simulating those necessary for efficient patient throughout in a clinical setting. Many of the unique features of NMR imaging, such as ability to directly obtain axial, sagittal and coronal projections, the variety of imaging modes, the natural sources of contrast, and the ability to visualize clearly medium and large blood vessels, were demonstrated.

Adipose Tissue↗