PubMed Health⌕ Search

Biomedical subjects

M K Chen

Publications and source records attributed to M K Chen.

At least 19 recordsLinked to original sources
PubMed1992

Cytokine regulation of intestinal glutamine utilization.

The effects of cytokines on intestinal glutamine metabolism were studied to gain further insight into the regulation of altered glutamine metabolism that occurs during severe infection. One hundred thirteen adult rats were given a single dose of interleukin-1 (IL-1, 50 micrograms/kg), tumor necrosis factor (TNF, 50 micrograms/kg or 150 micrograms/kg), or saline (controls), and flux studies were performed 4 or 12 hours later. Intestinal blood flow was not different between control and cytokine-treated animals at either time point. At the 4-hour time point, arterial glutamine fell by 16% to 21% in the cytokine-treated animals (p less than 0.05); at the 12-hour time point, the arterial glutamine concentration had returned to normal. Intestinal glutamine extraction decreased in the animals treated with IL-1 at both time points (4 hours: 13% +/- 1.3% in IL-1 versus 20% +/- 1.6% in controls, p less than 0.05; and 12 hours: 9% +/- 2% in IL-1 versus 17% +/- 2% in controls, p less than 0.05). Consequently, net intestinal glutamine uptake fell in the animals treated with IL-1 at both time points (p less than 0.05). Similarly, the activity of mucosal glutaminase, the principal enzyme of glutamine hydrolysis in the gut, fell by 50% in the 4-hour study (6.1 +/- 0.6 mumol/h/mg protein in IL-1 versus 9.6 +/- 0.8 mumol/h/mg protein in controls, p less than 0.01) and by 40% in the 12-hour study (5.4 +/- 0.5 mumol/h/mg protein in IL-1 versus 8.8 +/- 0.4 mumol/h/mg protein in controls, p less than 0.05). Concomitant with the aforementioned decrease in gut glutamine metabolism was a 25% incidence of positive blood cultures for gram-negative organisms in IL-1 treated rats studied at the 12-hour time point (p = 0.05 versus controls). In the doses administered and at the time points studied, TNF had no effects on the parameters of gut glutamine metabolism examined. The results indicate that IL-1 is a potential mediator of the alterations in gut glutamine metabolism observed in sepsis and endotoxemia.

Animals↗
PubMed1992

Mechanisms of accelerated hepatic glutamine efflux in the tumour-bearing rat.

The mechanisms potentially controlling the net release of glutamine by the liver that occurs in tumour-bearing rats were investigated. Studies were undertaken when the tumour comprised approximately 7% (15 +/- 2 g) of total body weight. Hepatic glutamine gradient ratios were calculated by dividing hepatic glutamine content by arterial blood glutamine concentration. Both sodium-dependent and sodium-independent hepatocyte carrier-mediated glutamine transport were evaluated employing hepatic plasma membrane vesicles (HPMVs). In TBR the hepatic glutamine gradient ratio doubled (P < 0.001) secondary to a 52% increase in hepatic content (P < 0.005) and a 16% decrease in circulating glutamine (P < 0.001). Sodium-dependent glutamine transport was increased in HPMVs from TBR secondary to a 24 +/- 4% increase in the maximal velocity of transport (Vmax; P < 0.01) without alteration in apparent transporter affinity (Km). Saturable sodium-independent carrier-mediated glutamine transport was increased in HPMVs from TBR over CONT to a much greater relative degree owing to a 2.7-fold increase in transport Vmax (P < 0.05) without a change in transport Km. The accelerated hepatic efflux of glutamine which characterizes malignant growth appears to be the result of both mass-action gradient phenomena and alterations at the level of hepatocyte membrane transport activity.

Animals↗
PubMed1992

Adaptive regulation in skeletal muscle glutamine metabolism in endotoxin-treated rats.

The effects of a single dose of endotoxin (7.5 mg/kg BW) on skeletal muscle glutamine metabolism were studied in vivo in rats to gain further understanding of the altered glutamine metabolism that characterizes sepsis and other catabolic diseases. In endotoxin-treated animals the arterial glutamine concentration fell early initially and then increased compared with control values. Twelve hours after treatment, the arteriovenous concentration difference for glutamine across the hindquarter doubled, resulting in a significant increase in net muscle glutamine release in endotoxin-treated rats. As a consequence, the muscle glutamine concentration fell in the endotoxin-treated animals by 25%-40%, an event that was apparent as early as two hours after endotoxin treatment. Skeletal muscle glutaminase activity, the major enzyme of glutamine breakdown, was unchanged by endotoxemia, but expression of glutamine synthetase mRNA and glutamine synthetase specific activity increased in a time-dependent fashion. The glutamine depletion that develops in skeletal muscle during endotoxemia is caused by accelerated muscle glutamine release rather than an increase in intracellular degradation or a fall in intracellular biosynthesis. The adaptive increase in glutamine synthetase expression that occurs requires de novo RNA and protein synthesis and may be designed to prevent complete depletion of the intracellular glutamine pool.

Adaptation, Physiological↗
PubMed1991

Endotoxin and renal glutamine metabolism.

The effect of endotoxin on renal glutamine metabolism and ammoniagenesis was investigated in vivo in the rat to gain further insight into the altered glutamine flow that characterizes critical illness. Studies were done 15 hours following a single dose of Escherichia coli lipopolysaccharide (10 mg/kg). Renal blood flow and arterial glutamine concentration were similar in control and study rats, but the kidney switched from an organ of slight glutamine uptake in controls (129 +/- 52 nmol/100 g of body weight per minute) to net release in the endotoxin-treated animals (-273 +/- 170 nmol/100 g of body weight per minute). Simultaneously, the specific activity of renal glutamine synthetase increased by almost 50% (374 +/- 40 nmol/mg of protein per hour in rats given endotoxin vs 253 +/- 12 nmol/mg of protein per hour in controls), while glutaminase was unchanged. Urinary ammonia excretion was reduced by 35% in the endotoxin-treated animals (47 +/- 6 mumol/12 h in endotoxin-treated animals vs 70 +/- 8 mumol/12 h in controls) despite a 10% fall in the arterial bicarbonate value. Endotoxin alters the net flux of glutamine across the kidney which appears to be partially regulated enzymatically. This may impair the kidneys' ability to maintain acid/base homeostasis.

Ammonia↗
PubMed1991

The effects of endotoxin on the splanchnic metabolism of glutamine and related substrates.

The effects of endotoxemia on glutamine metabolism by the splanchnic bed was studied in vivo in adult rats 12 hours following administration of E. coli LPS. Glutamine uptake by the portal-drained viscera fell in the endotoxin-treated animals while glucose uptake doubled. Simultaneously, hepatic glutamine uptake increased ten-fold owing to both an increase in hepatic blood flow and glutamine extraction from the bloodstream. Hepatic alanine uptake, oxygen consumption, and glucose release were also accelerated in endotoxemic rats. The increase in liver glutamine utilization was associated with increases in parenchymal DNA and glutathione levels and an increase in glutathione and urea release into the systemic circulation. This marked increase in metabolic activity occurred in animals with chemical evidence of hepatocellular injury and histologic evidence of hepatocyte necrosis. During endotoxemia the liver becomes the major organ of glutamine consumption. This accelerated utilization provides carbons for energy and gluconeogenesis, nitrogen for ureagenesis, and substrate for nucleotide and glutathione biosynthesis in order to support cell repair and detoxification reactions.

Alanine↗
PubMed1991

Glutamine metabolism by the endotoxin-injured lung.

The alterations in lung glutamine (GLN) metabolism that occurs in the endotoxin-injured lung were studied in rats and subsequently correlated with flux changes that occur in patients with the adult respiratory distress syndrome (ARDS). Measurements in animals were made at various time-points following the administration of endotoxin, while studies in surgical patients were done in a group of healthy controls, in patients with "early" sepsis who had normal chest x-ray films, and in patients with radiographic and physiologic evidence of ARDS. In healthy control rats, net amounts of GLN are released by the lungs into the systemic circulation. This release rate doubled 30 minutes after intravenous endotoxin (1,580 +/- 320 nmol GLN/100 g BW/min vs. 736 +/- 179 in controls, p less than 0.01) but glutamine synthetase activity was unchanged, suggesting an outpouring of cellular glutamine stores. Two hours after endotoxin treatment, this accelerated fractional release of glutamine by the lungs was no longer detected. By the 12-hour time-point, the lungs reversed to an organ of net glutamine balance (234 +/- 248 nmol/100 g BW/min, p less than 0.05 vs. controls and ENDO30 min) despite a more than two-fold increase in glutamine synthetase activity (p less than 0.01). Simultaneously, lung weights were increased by 21% (p less than 0.01) and histologic examination showed an interstitial infiltrate and pulmonary edema. Similar observations were made in humans; patients with "early" sepsis exhibited a marked increase in lung glutamine release, while patients with ARDS demonstrated glutamine balance across the lungs (4,030 +/- 910 nmol GLN/kg BW/min vs. 637 +/- 496 in ARDS, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1979

A quantitative index for evaluating patient care with longitudinal data.

This paper describes a patient-outcome based index of the quality of health care useful to health services researchers and planners. This index is applicable in any health care situation where longitudinal data are available from patients who can be classified into mutually exclusive stages of severity by functional status, psychological well-being or diagnosis and followed over a period of time. The rationale of the index is presented, along with an illustrative example based on a study on long-term care. The procedure for generating weights for the index is briefly described.

Data Collection↗
PubMed1979

Measuring need for health services: a proposed model.

Despite the emphasis of the National Health Planning and Resources Development Act of 1974 on need assessment as the basis of health planning, no valid measures of need for health services are currently available. In this paper a need measurement model is presented for the use of health services planners and researchers following a brief critique of two existing models. Data requirements for the model and in hypothesis-testing situations are described.

Health Planning↗
PubMed1978

A study of the health status of the black population in Alameda County, California.

The purpose of this paper is to compare the overall health status of blacks with whites in Alameda County, California, using an index based on the mortality and disability experiences of the two population groups. It is demonstrated that this index, which requires disease-specific mortality and disability data, can be easily adapted to make use of existing data files containing data on mortality and any indicator of morbidity or disability. It was found that in the year 1974, the blacks lost approximately 10,000 productive years unnecessarily through higher mortality and disability rates than those of the white population. This disparity between the two populations may be underestimated because Chicano/Mexican Americans, who are known to enjoy a lower health status than whites, were included as part of the white population. The implications of the findings are discussed.

Black or African American↗
PubMed1976

The K index: a proxy measure of health care quality.

An index of health care quality is described that requires data on "sentinel health events"--unnecessary death and disability caused by specific ICDA-coded conditions on which medical agreement can be reached about avoidability of negative outcomes. The proposed index combines measures of incidence, severity, and concentration of sentinel health events in communities and compares the measures with mean values for a group of normative communities, to arrive at index values that are distributed as X2 for a group of communities with regard to the mean health conditions experienced by the normative communities. Calculation of the index is illustrated with hypothetical data, and problems of selecting normative communities are discussed.

Activities of Daily Living↗
PubMed1975

Aggregated physiological measures of individual and group health status.

Two health status indices applicable to individuals and groups are presented for research and health programme evaluation purposes. Both indices are functions of distances from cultural or group norms of the healthy state on a number of physiological dimensions that are theoretically or empirically related to health. Ways of deriving group norms are briefly discussed.

Health Status Indicators↗
PubMedDate not supplied

Tumor regulation of hepatic glutamine metabolism.

Fast-growing tumors are major glutamine consumers and may alter host glutamine metabolism to benefit the tumor. Previous studies from our laboratory have demonstrated that the liver switches from an organ of glutamine balance to one of glutamine release with progressive malignant growth. However, the regulation of this change is unclear. This study examined tumor modulation of hepatic glutamine metabolism by determining the activities of glutaminase, the principle enzyme of glutamine degradation, and glutamine synthetase, the principal enzyme of glutamine synthesis. Hepatic glutamine content was also determined. Rats with a fast-growing subcutaneous fibrosarcoma (TBR) and pair-fed controls were studied at 2 and 3 weeks after tumor or sham implantation, when the tumors comprised approximately 5% and 20% of total body weight. Arterial glutamine fell with progressive tumor growth (608 +/- 26 mumol/L in controls vs 494 +/- 15 in TBR, p less than 0.005) and was not attributable to a diminished food intake. Hepatic glutamine content was increased 45% (p less than 0.01) in tumor rats at 2 weeks due in part to a 35% fall in liver glutaminase activity. At 3 weeks, glutamine synthetase activity increased by 43% (0.58 +/- 0.07 mumol/mg of protein/hr in controls vs 0.83 +/- 0.04 in TBR, p less than 0.01) whereas glutaminase remained depressed (2.68 +/- 0.12 mumol/mg of protein/hr in controls vs 2.22 +/- 0.15 in TBR, p less than 0.05) and glutamine content fell compared to 2 week tumor-bearing rats, consistent with accelerated hepatic glutamine release. Tumors may alter liver glutamine metabolism by modulating hepatic enzyme activity in order to provide circulating glutamine for the growing malignancy.

Ammonia↗