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S F Lowry

Publications and source records attributed to S F Lowry.

191 records · Page 11Linked to original sources
PubMedDate not supplied

Interleukin-1 alpha (IL-1 alpha) and tumor necrosis factor alpha (TNF alpha) regulate insulin-like growth factor binding protein-1 (IGFBP-1) levels and mRNA abundance in vivo and in vitro.

TNF alpha and IL-1 alpha are thought to contribute to impaired anabolism in a variety of clinical states, including sepsis, cancer cachexia and the AIDS wasting syndrome. We asked whether cytokines exert direct effects on hepatic production of IGFBP-1, an important modulator of IGF bioavailability. C57BL/6 mice were treated with 100 micrograms/kg of recombinant IL-1 alpha or TNF alpha by intraperitoneal injection. Western ligand blotting and immunoprecipitation with specific antisera revealed that serum levels of IGFBP-1 (but not IGFBP-2, -3, -4, -5 or -6) are increased approximately 4 fold 2 h after treatment and then decline. Northern blotting confirms that hepatic IGFBP-1 mRNA abundance also is increased acutely in both IL-1 alpha- and TNF alpha-treated animals. Similar results obtained in adrenalectomized mice indicate that adrenal activation is not required for this effect. Cell culture studies show that cytokines exert direct effects on the production of IGFBP-1 by HepG2 hepatoma cells, increasing IGFBP-1 levels in conditioned medium and the abundance of IGFBP-1 mRNA approximately 3-fold. In contrast, transient transfection studies with IGFBP-1 promoter/luciferase reporter gene constructs show that IGFBP-1 promoter activity is reduced after 18 hr cytokine treatment. We conclude that IL-1 alpha and TNF alpha increase circulating levels of IGFBP-1, reflecting direct effects on hepatic IGFBP-1 mRNA abundance. Stimulation of hepatic IGFBP-1 production may contribute to alterations in IGF bioactivity and impaired anabolism in clinical conditions where cytokine production is high. Additional studies are required to identify specific mechanisms mediating effects of cytokines on hepatic production of IGFBP-1.

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PubMedDate not supplied

The response of fibronectin to differing parenteral caloric sources in normal man.

The relationship between circulating fibronectin concentration and nutritional status was examined in eight healthy male (31 +/- 1 yr old) volunteers in three nutritional states: the postabsorptive state, after 10 days of protein-caloric starvation, and during the 10th day of refeeding by total parenteral nutrition. Plasma fibronectin was significantly decreased from 330 +/- 22 to 154 +/- 11 micrograms/ml (p less than 0.001) from the postabsorptive to starved state which was accompanied by appropriate changes in body weight, anthropometric measurements, and nitrogen balance. Plasma fibronectin levels were restored to 402 +/- 39 micrograms/ml following 10 days of total parenteral nutrition. The plasma fibronectin response was greater (p less than 0.05) during total parenteral nutrition with dextrose as the nonprotein calorie source as compared to a 50% dextrose/50% lipid regimen. These results suggest that the calorie source must be considered during interpretation of plasma fibronectin levels in patients undergoing parenteral nutrition.

Adult↗
PubMedDate not supplied

Effect of starvation and total parenteral nutrition on electrolyte homeostasis in normal man.

Elemental balances, and skeletal muscle membrane potential (Em) and biopsy were utilized to evaluate electrolyte homeostasis and body composition in 11 healthy adult volunteers after 10 days of starvation. This controlled, acute malnutrition was followed by refeeding for 10 days with two different, commonly used, total parenteral nutrition (TPN) solutions. Six subjects were refed with crystalline amino acids and dextrose (dextrose group), while five subjects received amino acids, dextrose, and lipid (lipid group). During starvation, negative balances for potassium, phosphorous, magnesium, and nitrogen were observed in both groups. When compared to starvation, total parenteral nutrition produced statistically significant (p less than 0.05) equilibrium or positive electrolyte and nitrogen balances for both, the dextrose and lipid groups. During TPN, there was a significantly (p less than 0.001) positive chloride balance in the lipid group when compared to the dextrose group. At the conclusion of the 10-day period of TPN, there was a decrease (p less than 0.05) in skeletal muscle Em. This change, in concert with the electrolyte balance data obtained during parenteral repletion, lead us to postulate that restoration of lean tissue protein and cellular function does not occur at a rate which might be inferred from the positive nitrogen balance observed in this model. A persistent defect in cellular function which was evident after starvation, suggests that a brief period of TPN is insufficient to restore skeletal muscle integrity.

Adult↗
PubMedDate not supplied

Effect of total parenteral nutrition on whole body protein kinetics in cachectic patients with benign or malignant disease.

The metabolic effects of total parenteral nutrition on malnourished cancer and noncancer patients were investigated by determining whole-body protein metabolism before and during intravenous nutritional support. The results were compared to similar studies reported in normal subjects. Primed-continuous infusion of 15N glycine was used and the isotopic enrichments in urinary urea and ammonia were measured. The end product average values were used in the calculation of whole body protein turnover. After 10 days of nutritional support in cancer and noncancer patients whole body protein breakdown decreased by 50% (p = 0.01), and 59% (p = 0.001), whereas protein synthesis decreased by 21% (p = 0.005) and 33% (p = 0.025), respectively. Protein turnover did not change in noncancer patients but increased by 15% (p = 0.005) in cancer patients. The efficiency of utilization of the endogenous supply of amino acids from the breakdown of body proteins for synthetic purposes was 77% in this group of subjects. The utilization efficiency of the intravenously infused amino acids for synthesis of body protein was 39% in cancer and noncancer patients but 51% (p less than 0.05) in normals. The data suggest that depleted patients synthesize proteins from intravenous amino acids less well than normals.

Aged↗
PubMedDate not supplied

Low plasma carnitine in patients on prolonged total parenteral nutrition: association with low plasma lysine.

Plasma carnitine levels were determined in 17 patients maintained on long-term total parenteral nutrition (TPN) for a mean (+/- SEM) period of 69 +/- 11 months (range 12-196). All had severe malabsorption and were dependent on intravenous feeding. Plasma carnitine was determined by a modified Cederblad enzymatic method. Mean plasma carnitine was significantly below the mean normal for females (p less than 0.02) and borderline low for males (p = 0.07). In six patients the levels were below the low normal range, and in five others they were at the lowest levels of normal. Of the six patients with normal levels, three had elevated serum creatinine, indicating renal dysfunction which may by itself elevate plasma carnitine. In 10 patients the plasma levels of lysine (a carnitine precursor) were determined and found to be lower than normal (p less than 0.05). Plasma carnitine levels correlated positively with serum albumin (r = 0.62, p less than 0.05), and negatively with serum alkaline phosphatase (r = -0.64, p less than 0.05). Thus, patients maintained on long-term TPN may have low plasma carnitine, which could represent carnitine deficiency. The low plasma carnitine may be related to a deficiency of the carnitine precursor lysine. Further studies are required to determine the significance of the low plasma carnitine and whether carnitine supplementation should be required in long-term TPN.

Adult↗
PubMedDate not supplied

Harry M. Vars award. Glutamine or fiber supplementation of a defined formula diet: impact on bacterial translocation, tissue composition, and response to endotoxin.

Despite provision of adequate calories, defined formula diets in rats lead to bacterial translocation (BT), fatty infiltration of the liver, and an increased susceptibility to endotoxin. These deleterious effects may be due in part to a loss of intestinal barrier integrity resulting from bowel atrophy. Defined formula diets lack both glutamine and fiber, substances which may help maintain intestinal mass. To determine whether supplementation of defined formula diets with either glutamine or fiber might prevent bowel atrophy and, thus, BT, hepatic steatosis, and the altered response to endotoxin, Wistar rats were fed (1) defined formula diet ad libitum (DFD), (2) (DFD + 2% (w/v) glutamine, (GLUT), or (3) DFD + 2% (w/v) psyllium (FIBER). Rats given standard food isocalorically pair-fed to DFD were used as controls. Nutritional status was assessed by daily weight gain, as well as the ability to maintain serum albumin, hematocrit and white blood counts. After 2 weeks of these feeding regimens, animals were sacrificed, and organ weights and composition were determined, with rates of bacterial translocation determined by mesenteric lymph node, abdominal viscera, and cecal cultures. Additional animals receiving the same experimental diets were subsequently challenged with endotoxin and observed for mortality with rates of post-endotoxin BT and the responses of acute phase proteins and cytokines measured. All dietary regimens resulted in equivalent weight gain and other nutritional parameters. Both glutamine and fiber supplementation maintained small bowel mass, but only GLUT preserved normal jejunal mucosal architecture. Neither fiber nor glutamine supplementation prevented cecal bacterial overgrowth or BT, resulting from the DFD.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMedDate not supplied

Experimental and clinical applications of molecular cell biology in nutrition and metabolism.

Rapid advances in molecular biology have yielded important new techniques for understanding the cellular mechanisms of normal homeostasis and disease. In particular, molecular laboratory methodologies have become important investigative tools for nutritional studies. Detection techniques for specific DNAs, RNAs, and proteins allow direct examination of cellular regulation of protein expression in health and illness. Construction of transgeneic models by recent techniques of inserting foreign genes into experimental animals has provided novel models for studies of cellular metabolism. In addition, molecular biology has had impact on clinical nutrition and therapy. Molecular techniques not only allow for early diagnosis of many inborn genetic errors of metabolism, recombinant technology has also provided for large-scale production of proteins and hormones of potential therapeutic value. The possibility for direct gene therapies is also nearing reality. Hence, understanding the language of molecular biology and the recent developments in this field is not only of research interest, but is also of clinical relevance.

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PubMedDate not supplied

The role of cytokines in cancer cachexia.

There is, at present, considerable interest in the possible role for the proinflammatory cytokines, tumor necrosis factor-alpha, interleukin-1, interleukin-6, and interferon-gamma in the pathogenesis of cancer cachexia. Indirect evidence for such a role is based on the observation that chronic administration of many of these cytokines, either alone or in combination, can reproduce the myriad of host responses seen in experimental and human cancer cachexia. Elevated plasma levels of tumor necrosis factor-alpha, interleukin-2, and interferon-gamma have rarely been detected in patients or experimental animals with cancer, although interleukin-6 levels appear to correlate with tumor progression in animal models. The strongest evidence for a causal role for cytokines has come from rodent studies in which tumor-bearing animals have been passively immunized with antibodies directed against individual cytokines. Several groups have shown modest but significant improvements in food intake and lean tissue retention with antibodies directed against tumor necrosis factor-alpha, interleukin-1, interleukin-6, and interferon-gamma. However, there has been no consistent finding that one cytokine is universally involved in cancer cachexia in histologically distinct tumor models. One ominous finding in several tumor models has been that the endogenous production of cytokines appears to support tumor growth. Such findings raise the intriguing possibility that these cytokines, although contributors to tissue wasting and anorexia, may also serve the tumor as either direct or indirect cell growth factors.(ABSTRACT TRUNCATED AT 250 WORDS)

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