Biomedical subjects

K J Liu

Publications and source records attributed to K J Liu.

At least 55 records · Page 3Linked to original sources

PubMed1996

Measurement of PO2 in liver using EPR oximetry.

With the use of India ink and lithium phthalocyanine (LiPc) as electron paramagnetic resonance (EPR) oximetry probes, the PO2 of the liver was investigated in mice. Because India ink was taken up by the Kupffer cells of the liver, the EPR signal of the India ink reflected the average PO2 in phagocytic vesicles of these cells. The mean value of PO2 in the Kupffer cells measured by India ink was 15.3 +/- 4.4 Torr in unanesthetized animals. LiPc was administered as a macroscopic crystal and therefore reflected the PO2 of the overall liver. The PO2 measured by LiPc was 23.4 +/- 4.4 Torr, which is consistent with the median value of 23.5 Torr reported previously with the use of an oxygen electrode. Anesthesia (injection of 60 mg/kg ip pentobarbital sodium) decreased the average PO2 in both Kupffer cells and the overall liver. The effects of perturbing the blood flow were studied by reversible blockage of the portal vein and hepatic artery in anesthetized mice; the PO2 in both Kupffer cells (measured with India ink) and in overall liver (measured with LiPc) decreased with obstruction of the blood flow and returned toward normal with reperfusion. These results indicate that the PO2 in different locations in the liver can be significantly different under both normal conditions and after perturbation by either anesthesia or ischemia. These results also demonstrate that EPR oximetry can provide sensitive measurements of PO2 in the liver in vivo under various conditions.

Anesthesia↗

PubMed1996

Multicentric primary adenocarcinomas of the midgut: the first case report.

Multicentric adenocarcinomas of the midgut have not been described; even multiple adenocarcinomas limited to the small intestine are extremely uncommon, with only 14 cases reported in the literature. We report a case of multicentric synchronous involvement of the entire midgut with adenocarcinoma in a 52-yr-old Polish woman who had more than 30 lesions extending from duodenum to mid-transverse colon. There was no family history of cancer. Preoperative evaluation and intraoperative exploration were negative for primary malignancy of the lungs, breasts, ovaries, pancreas, and other parts of the gastrointestinal tract. Results of histopathological examination, immunohistochemical staining, and ras mutational analysis of the lesions uniformly support the diagnosis of multicentric poorly differentiated adenocarcinoma. The cause for this unusual presentation is unknown, although sporadic genetic alteration(s) of oncogene(s) might have been the precipitating event.

Adenocarcinoma↗

PubMed1995

Chromate-induced chromium(V) formation in live mice and its control by cellular antioxidants: an L-band electron paramagnetic resonance study.

A recent note from our laboratory reported that L-band (1.2 GHz) electron paramagnetic resonance spectroscopy can be utilized in detecting the formation of Cr(V) intermediates from chromate-treated whole mice. Since Cr(V) is thought to be one of the key species in the mechanism of chromate's toxicity, we carried out additional measurements with improved sensitivity. The new spectra show partially resolved hyperfine structure from protons that suggests that the Cr(V) ion is ligated to NAD(P)H moieties via oxygens. Using laboratory-synthesized Cr(V) (K3CrO8) as a standard, the yield of Cr(V) formation was estimated to be 153 +/- 12 nmol after intravenous injection of 100 microliters of 100 mM sodium dichromate into mice. Pretreatment of the mice with ascorbic acid and glutathione significantly reduced the Cr(V) formation yield in a dose-related manner, while pretreatment with NADH had the opposite effect. Injection of ascorbic acid also had the effect of enhancing the rate of Cr(V) disappearance in vivo. By comparing these results with in vitro results utilizing L-band as well as X-band (9.6 GHz) measurements, we conclude that L-band spectroscopy can indeed be effectively utilized for following the metabolism of Cr(V) in live mice and that Cr(V) formation can be controlled by utilizing cellular antioxidants in vivo.

Animals↗

PubMed1995

Assessment of cerebral pO2 by EPR oximetry in rodents: effects of anesthesia, ischemia, and breathing gas.

This report describes experiments designed to assess and illustrate the effectiveness of a new method for the measurement of cerebral interstitial pO2 in conscious rodents. It is based on the use of low frequency electron paramagnetic resonance (EPR) spectroscopy with lithium phthalocyanine as the oxygen sensitive probe. Magnetic resonance imaging was used to document placement of the probe in the brain, and to assess potential cerebral changes associated with the placement. The technique provided accurate and reproducible measurements of localized pO2 in the brains of conscious rodents under a variety of physiological conditions and for time periods of at least 2 weeks. Using this approach we quantitated the depressing effects on cerebral pO2 of three representative anesthetics, isoflurane, ketamine/xylazine, and sodium pentobarbital. The effects of changing the content of oxygen in the breathing gas was investigated and found to change the cerebral pO2. In experiments with gerbils, crystals of lithium phthalocyanine were implanted in each side of the brain and using a one-dimensional magnetic field gradient, simultaneous measurement of pO2 values from normal and ischemic (ischemia induced by unilateral ligation of a carotid artery) hemispheres of the brain were obtained. These results demonstrate that EPR oximetry with lithium phthalocyanine is a versatile and useful method in the measurement of cerebral pO2 under various physiological and pathophysiological conditions.

Anesthetics↗

PubMed1995

Detection of short-lived free radicals by low-frequency electron paramagnetic resonance spin trapping in whole living animals.

We report the direct observation of sulfur trioxide anion free radical (SO3.-) from the body of live mice by using a low-frequency (1.2 GHz, L-band) EPR spin trapping method. Intraperitoneal injection of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) (15 mmol/kg) used as trapping agent was followed by sequential iv injections of sodium sulfate (2-5 mmol/kg) and sodium dichromate (0.3 mmol/kg). The mouse was placed in an L-band loop gap resonator. The observed spectra consisted of two superposed components: DMPO/SO3.- (alpha N = 14.0, alpha H = 16.0) and Cr(V) (g = 1.9798). The time course for the generation and reduction of DMPO/SO3.- was followed. The signal intensity reached a maximum at about 7 min. In vitro experiments carried out at 9.15 GHz confirmed the production of SO3.- under the conditions used for in vivo studies; the hyperfine splittings of DMPO/SO3.- produced in the in vitro experiments were the same as those produced in the in vivo studies. The production of SO.-3 is supported by oxygen uptake studies, which show that the prior addition of 300 mM DMPO inhibits oxygen consumption by SO3.-.

Animals↗

PubMed1995

Changes of oxygen tension in experimental tumors after a single dose of X-ray irradiation.

Electron paramagnetic resonance oximetry was used to measure the partial pressure of oxygen (pO2) in two types of tumor in vivo in C3H/HeJ mice. The pO2 in MTG-B (high hypoxic fraction) and RIF-1 (low hypoxic fraction) tumors was monitored prior to and at several time points after a single dose of X-ray irradiation (up to 7 days after treatment). Initial values of pO2 in RIF-1 (8.7 +/- 1.1 mm Hg; n = 14) were higher than that of pO2 in MTG-B (3.3 +/- 0.5 mm Hg; n = 19). The pO2 in both types of unirradiated tumors decreased slowly with tumor growth. Irradiation of tumors had a two-phase effect on pO2: an initial sharp decrease in pO2, followed by slow reoxygenation. After a 20-Gy radiation dose, the pO2 was 2.2 +/- 0.5 mm Hg at 6 h [significantly lower (P < 0.0001) than in control] and 3.2 +/- 0.5 mm Hg at 48 h [significantly higher (P < 0.02) than in control] in MTG-B, and 5.4 +/- 1.2 mm Hg at 24 h and 8.2 +/- 1.0 mm Hg at 72 h in RIF-1. The time course for these changes in pO2 was found to be independent of the doses in use in this study (10, 20, and 40 Gy). The occurrence of radiation-induced changes in pO2 and the different time courses of these changes suggest that repeated monitoring of pO2 in tumors during treatment could be used to enhance the efficacy of clinical treatments.

Adenocarcinoma↗

PubMed1995

Hepatic glycerol metabolism in tumorous rats: a 13C nuclear magnetic resonance study.

Cancer cachexia contributes to the demise of a significant number of cancer patients, and severe loss of adipose tissue is a prominent component of this syndrome. One of the products of fat catabolism is glycerol, and its turnover is elevated in the cancerous state. Since glycerol is also one of the most important gluconeogenic substrates, its role in the augmented and abnormal gluconeogenesis of cancer hosts needs to be defined. In the present study, we examined hepatic glycerol metabolism in livers of Fischer 344 rats bearing s.c. nonmetastatic adenocarcinoma R3230AC. Five weeks after tumor inoculation, the liver was removed and perfused with 5 mM [2-13C]glycerol while 13C nuclear magnetic resonance spectroscopy was performed. In the livers of tumorous rats, we found: (a) lipogenesis from glycerol was augmented; (b) the rate of hepatic glycerol uptake was unchanged; (c) glucose production from glycerol was not altered; and (d) conversion of glycerol 3-phosphate to dihydroxyacetone phosphate remains the rate-limiting step. Therefore, it appears that, in cancer hosts, diminished glycerol clearance is not due to reduction in hepatic glycerol uptake or metabolism, and the abnormal gluconeogenesis involves the pathway prior to the entry of glycerol. The exaggerated lipolysis is probably used for the pathological hepatomegaly, and the availability of the cytosolic hydrogen acceptor remains the rate-limiting factor for glycerol metabolism.

Adenocarcinoma↗

PubMed1995

Low-frequency EPR study of chromium(V) formation from chromium(VI) in living plants.

The reduction of Cr(VI) by green algae and higher plants was investigated using a low-frequency EPR spectrometer equipped with an extended loop gap resonator. Incubation of algae (Spirogyra and Mougeotia) with Cr(VI) generated both Cr(V) and Cr(III). The maximum Cr(V) signal was observed in about 10 minutes. Incubation of Cr(VI) with oat, soybean, and garlic generated Cr(V). The maximum Cr(V) peak appeared after more than 10 hours of incubation, and Cr(V) was located predominantly in the roots. The Cr(V) peak exhibited hyperfine splittings of about 0.79 gauss, typical of the Cr(V) complexes with diol-containing molecules. The results suggest that the reduction of Cr(VI) to lower oxidation states by living plants may provide a detoxification pathway for Cr(VI) in ecological systems. The results also indicate that low-frequency EPR may be used to investigate the metabolism of paramagnetic metal ions in intact plants.

Chlorophyta↗

PubMed1995

In vivo oximetry using EPR and India ink.

Recent advances in electron paramagnetic resonance (EPR) oximetry have established the use of the particulate materials fusinite and lithium phthalocyanine (LiPc) as probes for measurement of oxygen tensions in tissues in vivo with a sensitivity and accuracy that is relevant for studying pathophysiological processes. India ink, another potentially very useful new probe for EPR oximetry, shares the critical properties of fusinite and LiPc and has the additional advantage of already having been widely used clinically with no apparent toxicity. The line width is particularly sensitive to changes in oxygen tension of less than 30 mmHg; in this range the line broadening/unit of pO2 is much greater than that of fusinite and LiPc. Over the range of biological conditions that can occur in vivo, the response of the EPR spectrum of India ink to pO2 is independent of pH, oxidants, reductants, and the nature of the medium. In this paper we describe the relevant properties of India ink and its use to measure pO2 in vivo in experimental animals and a human subject.

Adenocarcinoma↗

PubMed1995

The apparent diffusion constant measured by MRI correlates with pO2 in a RIF-1 tumor.

As tissue oxygen tension (pO2) is an important variable in cancer therapy, it would be of major clinical benefit to be able to measure pO2 noninvasively. Current methods for determining pO2 in clinical settings are limited to superficial tumors. The authors measured the apparent diffusion constant (ADC) in an implanted murine fibrosarcoma (RIF-1) using magnetic resonance imaging and correlated the ADC with tissue pO2 measured by electron paramagnetic resonance oximetry. The ADC correlates significantly with tissue pO2 in this tumor (r = 0.89; n = 14) and so may provide a noninvasive index of pO2 in tumors.

Animals↗

PubMed1995

An analysis of the effects of eddy currents on L-band EPR spectra.

Recently, impressive results have been obtained with EPR studies of living animals and perfused organs using low-frequency EPR. In many instances in such studies, however, there are apparent distortions of the spectra. The shapes of these spectra and theoretical considerations indicate that these effects are due to eddy currents in the moderately conductive biological materials. Therefore the effects of eddy currents produced in biological samples under typical conditions being employed for in vivo EPR studies have been systematically studied in order to determine the extent of these effects and to develop methods for compensating for these effects. The presence of eddy currents was found to decrease the Q factor and distort the shapes of the EPR spectra. The distortion of the spectra led to linewidth broadening, changes in peak heights, and shifts of the apparent center of the lines. These effects could be corrected instrumentally, but this was effective only when signals have a high S/N. The use of appropriate computer simulations, based on linear combinations of the expected absorption and dispersion signals, can effectively correct for the effects of eddy currents and provide accurate data on the parameters of EPR spectra that are needed for most or all of the analyses used in biological studies of animals and tissues at low frequencies.

Animals↗

PubMed1995

The pO2 in a murine tumor after irradiation: an in vivo electron paramagnetic resonance oximetry study.

Using electron paramagnetic resonance (EPR) oximetry with the oxygen-sensitive paramagnetic material, fusinite, we have measured the partial pressure of oxygen (pO2) in the mouse mammary adenocarcinoma MTG-B. The average pO2 in untreated tumors was low (about 5 mm Hg) and decreased with tumor growth. Magnetic resonance imaging and histological examination were used to localize the position of the fusinite with respect to tumor margins and vascularization. The pO2 was generally higher in the periphery than in the center of the tumors, but there was considerable variation among tumors both during normal growth and after radiation treatment. After a single 20-Gy dose, a characteristic pattern of change in tumor pO2 was observed. In irradiated tumors, there was an initial reduction in pO2 (minimum occurred 6 h postirradiation) which was followed by a transient increase in pO2 to levels higher than the preirradiation pO2 (maximum occurred 48 h postirradiation). This work demonstrates postirradiation changes in pO2 of potential radiobiological significance. Compared to other oxygen assessment techniques, EPR oximetry is very useful because it can assess pO2 in the same region of the tumor over the course of tumor growth and during response to treatment. Thus EPR could be used to identify potentially radioresistant tumors as well as to identify tumors with slow reoxygenation.

Adenocarcinoma↗

PubMed1995

Marked asymmetry of LES: important element of LES barrier in subsets of patients with reflux symptoms.

Computerized axial manometry (CAM) of the lower esophagus measures squeeze pressure at multiple points in each segment of the lower esophageal sphincter (LES), calculates several unique parameters of LES function, and constructs a 3-D display of the LES. Whether parameters derived from CAM, such as the radial mean pressure (LESrmp), Asymmetry (Asym), and Vector Volume (VV), have relevance to function of the LES remains undefined. This study compares the results of CAM in patients with gastroesophageal reflux disease (GERD) and controls. There were 54 patients with GERD and 21 volunteers; all underwent CAM as part of their evaluation; GERD was defined by clinical and endoscopic examinations, and all patients had abnormal 24-hour pH tests. Statistical evaluation was performed. The LESrmp and the Vector Volume were significantly correlated in both groups of patients and differed significantly in both. Asymmetry of the LES was a significant negative factor in LES strength as shown by VV and LESrmp. Asymmetry alone, however, did not show a strong correlation with reflux. Asymmetry is indirectly correlated with the major determinants of LES strength; in patients with low VV, asymmetry might be a critical factor. When a high VV is present, asymmetry has no particular relevance. CAM provides invaluable measurements of the LES.

Analysis of Variance↗

PubMed1994

Surface immunoglobulins mediate efficient transport of antigen to lysosomal compartments resulting in enhanced specific antigen presentation by B cells.

A BCL1 immunoglobulin (Ig) transfectant, expressing wild-type surface (s)IgM with the TEPC-15 idiotype (T15-Id) and anti-phosphorylcholine (PC) specificity, was previously shown to present PC-conjugated hen egg-white lysozyme (PC-HEL) to a HEL-specific T cell hybridoma at a lower antigen (Ag) concentration than that required for native HEL. Two variant Ig transfectants, expressing T15-Id sIgM with substitutions either in the entire spacer, transmembrane (TM) domain and cytoplasmic tail (B186 variant) or in the NH2-terminal third of TM domain only (TM2 variant), failed to display this sIgM-mediated, enhanced presentation of PC-HEL at low concentrations. However, prolonged treatment with anti-T15-Id monoclonal antibody (mAb) led to a reduction of surface expression of the T15-Id sIgM in the wild-type and TM2 variant, but not in the B186 variant sIgM transfectants. Treatment with anti-T15-Id mAb also resulted in an increased intracellular accumulation of T15-Id sIgM in the wild-type transfectant, but not in the B186 variant. Subcellular fractionation analysis revealed that the ligands bound to the T15-Id sIgM are not efficiently transported to the dense lysosomal compartments in both B186 and TM2 transfectants, as compared to the wild-type sIgM transfectant. A significant increase in tyrosine phosphorylation after cross-linking of the T15-Id sIgM was observed only in the wild-type sIgM transfectant. These results suggest that, while the NH2-terminal third of the TM region is not involved in the process responsible for the ligand-induced reduction of surface expression of sIgM, it appears to be essential for subsequent transport of sIgM/ligand complexes to the lysosomal compartments, as well as efficient activation of tyrosine kinases. These results strongly suggest that sIg-mediated enhancement of specific antigen presentation reflects the ability of sIg to efficiently transport antigen to the lysosomal compartments, and possibly the activation of protein tyrosine kinases.

Amino Acid Sequence↗

PubMed1994

In vivo and in vitro EPR oximetry with fusinite: a new coal-derived, particulate EPR probe.

The peak-to-peak line width (LW) of the first derivative electron spin resonance (EPR) spectrum of the coal maceral fusinite is reversibly broadened by O2. The extent of broadening per unit of partial pressure of oxygen (pO2) is unusually large, exceeding that of nitroxides by almost two orders of magnitude. This paramagnetic property of fusinite, combined with its very stable physicochemical properties and low toxicity, is shown to be of utility in the measurement of pO2 in vitro and in vivo. Fusinite particles are endocytosed by chinese hamster ovary (CHO) cells in vitro; this is useful for intracellular O2 measurements with commercially available EPR spectrometers operating at 9.1-9.3 GHz. For measurement of oxygen in vivo using low frequency EPR (1.1-1.3 GHz), fusinite provides a sensitive and persistent means to measure pO2 in tissues. Particles implanted into the gastrocnemius muscle of A/J mice remained interstitially in the same position for months with undiminished sensitivity to pO2 and no specific toxic effects.

Adsorption↗

PubMed1994

India ink: a potential clinically applicable EPR oximetry probe.

Using a material that already is in widespread use in humans, India ink, the first EPR measurements in a human have been made, using the India ink in a pre-existing tattoo. The EPR spectra of India ink are very sensitive to the partial pressure of oxygen (pO2), thereby making it feasible to use this approach to measure pO2 in tissues in patients. This potentially provides a means to measure this parameter directly with a sensitivity, accuracy, and repeatability that have not been available previously, and thereby to be able to individualize and guide treatment of diseases such as cancer and peripheral vascular insufficiency.

Animals↗

PubMed1994

Low-frequency EPR detection of chromium(V) formation by chromium(VI) reduction in whole live mice.

Measurements by direct low frequency EPR spectroscopy provide the first evidence that Cr(V) is generated in one-electron reduction of Cr(VI) in live mice. The Cr(V) yield reached a maximum about 10 min following Cr(VI) intravenous injection and then decayed slowly with a life time of approximately 37 min. The time for the Cr(V) EPR signal to reach maximum intensity increased with the dose of Cr(VI). A discernible EPR signal was still observable at a dose as low as 0.1 mmol/kg. The Cr(V) was found predominantly in the liver, with a small amount in the blood. No Cr(V) signal was detectable in heart, spleen, kidney, and lung. Pretreatment of the animals with metal ion chelators, ethylenediaminetetraacetic acid, diethylenetriaminepentaacetic acid, and 1,10-phenanthroline significantly reduced the intensity of the Cr(V) signal that was observed.

Animals↗

PubMed1994

Physical and instrumental considerations in the use of lithium phthalocyanine for measurements of the concentration of the oxygen.

The use of crystals of lithium phthalocyanine (LiPc) to measure the concentration of oxygen in vivo and in vitro by electron paramagnetic resonance leads to experimental constraints due to the very narrow EPR lines that may occur (as narrow as 11-13 mG in the absence of O2), distortions induced by the automatic frequency control system, anisotropy in the spectra (orientation-dependent linewidth is 11-17 mG in the absence of O2), microwave power saturation, and the effect of physiological motion. These constraints can be overcome if recognized. This article highlights the experimental and theoretical basis of these properties of the EPR signal of LiPc and suggests some technical solutions. It is most important to recognize that paramagnetic species such as LiPc present problems that are not commonly encountered in EPR spectroscopy.

Electron Spin Resonance Spectroscopy↗