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Biomedical subjects

K J Liu

Publications and source records attributed to K J Liu.

At least 73 records · Page 4Linked to original sources

In vivo measurement of oxygen concentration using sonochemically synthesized microspheres.

Proteinaceous microspheres filled with nitroxides dissolved in an organic liquid have been synthesized for the first time using high intensity ultrasound; these were used to measure oxygen concentrations in living biological systems. The microspheres have an average size of 2.5 microns, and the proteinaceous shell is permeable to oxygen. Encapsulation of the nitroxides into the microsphere greatly increased the sensitivity of the electron paramagnetic resonance signal line width to oxygen because of the higher solubility of oxygen in organic solvents. The encapsulation also protected the nitroxide from bioreduction. No decrease in intensity of the electron paramagnetic resonance signal was observed during 70 min after intravenous injection of the microspheres into a mouse. Measurement of the changes in oxygen concentration in vivo by means of restriction of blood flow, anesthesia, and change of oxygen content in the respired gas were made using these microspheres.

Anesthetics, General↗

Cellular environment in the liver of tumor-bearing rats: a 13C NMR study.

Although hepatic metabolism is known to be altered in the presence of a remote tumor, it is unclear whether the alterations are brought on by changes in cellular conditions or dysfunction of enzymes. Chemical shifts of 13C NMR spectral peaks are known to vary depending on the physical conditions within the molecular environment, such as pH, electrolyte concentrations and temperature. In the present study, we examined the responsiveness of 13C NMR peak positions to different experimental conditions by comparing chemical shifts of metabolite peaks in perfused and extracted livers. The sensitivity of the technique was confirmed by observing chemical shift differences between these two experimental conditions of the amino carbons (C-2's) of glutamate, glutamine, N-carbamoylaspartate and aspartate. Subsequently, 13C NMR spectroscopy was employed to detect changes in the cellular environment in the livers of tumor-bearing rats. Minimal alterations in peak locations for intracellular metabolites were found in the presence of a distant tumor. This indicates that the overall cellular environment is not significantly altered by the presence of a distant tumor. Therefore, the known alterations in hepatic metabolism of tumor hosts are probably brought on by enzymatic abnormalities rather than changes in the cellular milieu. In addition, comparison of peak positions with other published reports were made, and the extent of unexplained chemical shift variations between biological studies is discussed.

Amino Acids↗

Esophagocardiomyotomy--floppy Nissen fundoplication effectively treats achalasia without causing esophageal obstruction.

BACKGROUND: Effective surgical treatments for achalasia of the esophagus facilitate swallowing by division of muscles that fail to relax normally during swallowing. If esophagocardiomyotomy is performed, a complementary antireflux procedure is mandatory to prevent postoperative gastroesophageal reflux. We evaluated patients who had undergone a circumferential antireflux procedure after esophagocardiomyotomy to determine the effects of this procedure in patients with an aperistaltic esophagus. METHODS: During the past 15 years we treated 94 patients with achalasia by use of pneumatic dilation (66), esophageal myotomy (19), or esophagocardiomyotomy with floppy Nissen fundoplication (24). Achalasia was defined by radiographic and manometric criteria until 1986 when computerized axial manometry of the esophagus was initiated, providing information about the three-dimensional contour and "volume" of the lower esophageal sphincter in addition to the usual manometric data. RESULTS: Dysphagia was effectively relieved in all, and neither postoperative reflux nor esophageal obstruction was observed after esophagocardiomyotomy followed by floppy Nissen fundoplication. The measured lower esophageal sphincter pressures and sphincter volume were markedly reduced. CONCLUSIONS: Esophagocardiomyotomy with floppy Nissen fundoplication is an effective treatment for achalasia; clinical evidence of obstruction of the esophagus was not seen, and manometric data were typical of a weakened sphincter.

Cardia↗

[Extended superselective vagotomy. Experimental bases and application in the surgical treatment of duodenal ulcer].

There is a sound basis for performing EHSV with reference to the "areas of vagotomy" as described and for wider application of EHSV. Most patients with complications of duodenal ulcer disease can be treated successfully by EHSV, with a small incidence of recurrent ulcers. The liberal use of pyloroplasty or drainage procedures is justified, since the potential problems of perioperative infection and postoperative alkaline reflux are not clinically significant. Post-gastrectomy syndromes can be largely avoided if gastric resection is reserved only for the few patients with deep ulcers of the lesser curvature. Intraoperative testing for completeness of vagotomy is a useful adjunct in the performance of EHSV, especially by those who are learning the technique. If the principles of EHSV are followed, routine use of intraoperative testing is superflous.

Drainage↗

Role of the B cell antigen receptor in antigen processing and presentation. Involvement of the transmembrane region in intracellular trafficking of receptor/ligand complexes.

To study the role of the B cell Ag receptor (membrane-bound Ig [mIg]) in Ag processing and presentation, we have generated several Ig transfectants that express transfected TEPC-15 idiotype (T15-Id) mIgM with phosphorylcholine (PC)-binding specificity. The wild-type Ig transfectant is able to present a specific Ag (e.g., PC-conjugated hen egg-white lysozyme [PC-HEL]) more efficiently than a nonspecific Ag (HEL) to a T cell hybridoma recognizing an epitope on the HEL molecule. A substitution in the entire spacer, transmembrane, and cytoplasmic region of mIg with an equivalent region of I-A alpha chain completely abolishes this mIg-enhanced Ag presentation. Experiments with the wild-type and substituted variant Ig transfectants suggest that this substitution may interfere with normal intracellular trafficking of mIg after cross-linking with specific Ag or antibodies specific for the mIg (anti-T15-Id mAb). Prolonged treatment of the wild-type Ig transfectants with specific Ag or anti-T15-Id mAb reduces the surface expression of T15-Id mIgM and leads to an accumulation of T15-Id mIgM inside the cells. The reduced surface expression and the elevated cytoplasmic accumulation of T15-Id mIgM are not observed in the variant Ig transfectant. Despite the ability of the variant to endocytose ligands similarly to the wild-type Ig transfectant, this variant displays a higher rate of recycling of the mIg/ligand complexes back to the cell surface and a lower rate of degradation of the ligands. These abnormalities may be responsible for the deficiency in mIg-mediated enhancement of Ag presentation in the variant Ig transfectant. Therefore, our results suggest that the transmembrane region of mIg is involved in intracellular trafficking of receptor/ligand complexes and that proper delivery and handling of internalized Ag are required for the enhanced presentation of specific Ag by B cells.

Amino Acid Sequence↗

Lithium phthalocyanine: a probe for electron paramagnetic resonance oximetry in viable biological systems.

Lithium phthalocyanine (LiPc) is a prototype of another generation of synthetic, metallic-organic, paramagnetic crystallites that appear very useful for in vitro and in vivo electron paramagnetic resonance oximetry. The peak-to-peak line width of the electron paramagnetic resonance spectrum of LiPc is a linear function of the partial pressure of oxygen (pO2); this linear relation is independent of the medium surrounding the LiPc. It has an extremely exchange-narrowed spectrum (peak-to-peak line width = 14 mG in the absence of O2). Physicochemically LiPc is very stable; its response to pO2 does not change with conditions and environments (e.g., pH, temperature, redox conditions) likely to occur in viable biological systems. These characteristics provide the sensitivity, accuracy, and range to measure physiologically and pathologically pertinent O2 tensions (0.1-50 mmHg; 1 mmHg = 133 Pa). The application of LiPc in biological systems is demonstrated in measurements of pO2 in vivo in the heart, brain, and kidney of rats.

Animals↗

Oxygen tension in a murine tumor: a combined EPR and MRI study.

The effects of fusinite, a new agent for the measurement of the concentration of oxygen in vivo by EPR, on MRI images have been studied. There was little effect on spin-echo T1-weighted images, but the fusinite resulted in large effects on T2-weighted images. Especially large effects could be observed when using spoiled gradient echo sequences (SPGR). The observed measurements of oxygen by EPR corresponded to the relative vascularity at the site of the fusinite both histologically and by MRI studies of vascularity using Gd-DTPA as a contrast agent. We conclude that by using the effects of fusinite on magnetic susceptibility, it can be located accurately and noninvasively with MRI and thereby the value of the use of fusinite to measure concentration of oxygen in vivo is enhanced.

Animals↗

Experimental basis and clinical application of extended highly selective vagotomy for duodenal ulcer.

An ideal operation for a benign disease, such as duodenal ulcer, must be effective, relatively free of serious postoperative complications and standardized for effective performance. Highly selective vagotomy, an operation known to have few side effects, has not been adopted by many surgeons because of the concerns about postoperative recurrent ulcers, as well as by concerns about the technical performance of the operation. Recurrent ulcers may be the result of incomplete denervation of the parietal cell mass; based upon the results of intraoperative testing, we suspected that previously unrecognized sites supplied preganglionic vagus nerves to the parietal cell mass. Nerve tracing studies identified four areas in the stomach that are not adequately denervated in the "standard" highly selective vagotomy. Based on these data, we defined and performed "extended highly selective vagotomy" upon 180 patients with ulcers. Herein, the results of follow-up examinations of 113 patients for a mean of at least 4.5 years postoperatively are reported. Recurrent duodenal ulcers occurred in 2.9 percent (two of 69) after extended vagotomy alone, and in none of 44 in whom a drainage procedure was used; the overall recurrence rate was 1.8 percent. Serious postoperative complaints were found in one patient in each group. The use of extended highly selective vagotomy for duodenal ulcer has a rational experimental basis and acceptable clinical results. Pyloroplasty, in conjunction with extended highly selective vagotomy, does not increase the incidence of serious postoperative side effects.

Duodenal Ulcer↗

Differential structure-function requirements of the transmembranal domain of the B cell antigen receptor.

By generating phosphorylcholine (PC)-specific, wild-type (mu), and chimeric (mu-I-A alpha) antigen receptor transfectants of mature B cells, we have shown that the COOH terminus of the mu heavy chain is essential for three major functions: immediate signal transduction (measured as changes in intracellular Ca2+), antigen presentation, and induction of immunoglobulin M secretion. A more detailed analysis of structural requirements of the COOH-terminal domains contributing to these functions was achieved by systematically replacing the spacer, cytoplasmic, and transmembranal domains of the mu-I-A alpha chimeric chain with those of mu. Using this rescue approach, we show that the carboxyl two-thirds of the transmembranal domain (proximal to the cytoplasmic domain) is required for induction of intracellular Ca2+, whereas the complete transmembranal domain is required for the function of antigen presentation but is dispensable for induction of antibody secretion.

Amino Acid Sequence↗

13C NMR study of hepatic pyruvate carboxylase activity in tumor rats.

Alanine and lactate, as major gluconeogenic substrates, must be converted into oxaloacetate by way of pyruvate carboxylase before their entry into gluconeogenesis. Although it is well known that hepatic gluconeogenesis from these substrates is increased in tumor hosts, the involvement of pyruvate carboxylase has not been demonstrated. In the present study, we examined pyruvate carboxylase activity in the perfused livers of tumor rats using 13C NMR spectroscopy with [3-13C]-alanine as the gluconeogenic substrate. A substantial increase in hepatic [3-13C]-aspartate production was found in the tumor rats. Since aspartate accumulation directly reflects fluxes of alanine through pyruvate carboxylase, the observed increase in hepatic production of [3-13C]-aspartate in tumor rats indicates that pyruvate carboxylase activity is significantly enhanced.

Alanine↗

Measurements of pertinent concentrations of oxygen in vivo.

A new method able to measure the concentration of oxygen in complex biological systems, including in vivo, has been developed using low-frequency EPR and newly characterized free radicals that are very sensitive to the concentration of oxygen. The free radicals (fusinite and lithium phthalocyanine) are very stable in tissues (for at least 150 days), apparently nontoxic, and can reflect oxygen concentrations that are less than the Km of cytochrome oxidase (0.1 microM or lower). Their biological stability is indicated by the fact that repeated measurements with fusinite of the concentration of oxygen in skeletal muscle have been made in the same animal for more than 150 days without any change in sensitivity or signs of toxicity.

Animals↗

Gluconeogenesis in the liver of tumor rats.

Altered gluconeogenesis is frequently observed in cancerous hosts. To define its derangements in the liver, we studied glucose and glycogen production in the perfused livers of tumor-bearing rats using 13C NMR spectroscopy. Nine Fischer 344 rats were inoculated with mammary adenocarcinoma. After 5 weeks, the livers were removed and perfused with Krebs buffer containing 8 mM L-[3-13C]alanine, and 13C NMR spectroscopy was performed. Nine pair-fed rats were studied as controls. The peak heights of glucose and glycogen in the 13C NMR spectra of the perfused livers and final perfusates of the two groups of rats were compared. We found comparable amounts of C1-labeled glucose and glycogen in the two groups, but C2- to C5-labeled and C6-labeled glucose and glycogen, as well as total 13C-labeled glucose and glycogen, appeared in smaller quantities in the tumor rats than in the pair-fed rats. These findings suggest that appreciable amounts of unlabeled glycerol were utilized by both groups, but less so by the tumor rats than the pair-fed rats. In addition, there was decreased production of oxaloacetate through pyruvate dehydrogenase and the Krebs cycle in the livers of the tumor rats, where the overall metabolism of alanine into glucose and glycogen was also reduced.

Adenocarcinoma↗

Left ventricular wall motion: its dynamic transmural characteristics.

Cardiac wall motion has been studied extensively. It is usually determined by indirect two-dimensional measurements for the true three-dimensional (3D) motion with its specific speed and direction. Errors are also introduced by using internally fixed reference systems and by the inability to identify precise points on the heart wall during the cardiac cycle. Because of these limitations, the endocardial and epicardial wall motion and their relationship are still unclear. This study was designed to assess endocardial and epicardial wall motion by measuring the direction and speed of implanted markers in an externally fixed 3D coordinate system. Fifty-seven pairs of endocardial and epicardial metallic markers were placed at anterior, lateral, posterior, basal, and apical regions of the left ventricles of 14 normal mongrel dogs. Biplane cineradiographs were performed at 50 frames/sec, and the 3D motions of the markers were analyzed using a specially designed computer system. It was found that the speeds, directions, displacements, and phases of the movements of corresponding endocardial and epicardial points were highly correlated. The correlation coefficients were 0.77 to 0.95 for the mean directions, 0.61 to 0.96 for the mean speeds, and 0.59 to 0.96 for the mean displacements at various regions of the heart, and the periodic movements of the endocardium and epicardium were always in phase. The mean epicardial speeds and displacements are fixed proportions (approximately 70%) of the mean endocardial speeds and displacements despite the differences in absolute values between regions in the same dog and the same regions in different dogs. The correlation coefficients for endocardial and epicardial instantaneous speeds, directions, and velocities ranged from 0.68 to 0.83, 0.81 to 0.88, and 0.77 to 0.86, respectively, for different regions of the heart. The correlation coefficients were significant for both the mean values and the instantaneous values. Thus, when only fixed epicardial points are accessible for wall motion measurements in clinical situations, it is possible to infer the endocardial motion from the epicardial motion.

Animals↗

Improving survival in patients with prostate cancer regionally spread at the time of diagnosis.

In the United States, cancer of the prostate ranks first among malignant neoplasms in elderly men. During the 20-year period 1960-1979, 5178 men with prostate cancer were registered at the Cancer Data Service of the University of Kansas. This study concerns 985 of these men in whom the cancer was regionally spread at the time of diagnosis. Survival differences were examined for four periods, i.e., 1960-1964, 1965-69, 1970-74, and 1975-79. Highly significant increases were observed in one-year and three-year survival (P less than 0.003) between the dosage of estrogen as standard therapy. Another noteworthy finding was that the initial use of radiotherapy (alone or combined) increased from 4.5 per cent in 1960-64 to 36.5 per cent in 1975-79, a period when survival had also increased significantly. In this subset of men with prostatic cancer, survival is approaching that for an age-matched male population as determined by U.S. Life Tables.

Actuarial Analysis↗