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M Loda

Publications and source records attributed to M Loda.

95 records · Page 6Linked to original sources
PubMed1984

Encephalopathy, oxygen consumption, visceral amino acid clearance, and mortality in cirrhotic surgical patients.

To assess the relationship of the high mortality of coma in cirrhotic surgical patients to defects in energy metabolism, reduced utilization of amino acids by the liver and other visceral tissues, oxygen consumption, central plasma clearance rate of amino acids (CPCR of amino acids), and the plasma concentrations of plasma inducing factors were measured in a series of 59 cirrhotic patients. They were classed as alert, encephalopathic, and comatose (Groups A, E, and C, respectively). The comatose group was set apart from the other two by a significantly higher mortality of 83 percent (p less than 0.005) combined with a lower whole body oxygen consumption of 103 +/- 6.8 ml/min per m2 compared with 135 +/- 10 ml/min per m2 in alert patients and 159 +/- 12 ml/min per m2 in the encephalopathic patients (p less than 0.01) and CPCR of amino acids of only 120 +/- 20 ml of plasma/min per m2 compared with 240 +/- 30 ml of plasma/min per m2 in the alert patients and 300 +/- 50 in the encephalopathic patients (p less than 0.01). An inverse correlation of tyrosine and phenylalanine concentrations existed with both whole body oxygen consumption (r = -0.56, p less than 0.01) and also with total amino acid clearance (r = -0.61, p less than 0.01). Tyrosine and phenylalanine concentrations also correlated directly with the octopamine concentration (r = 0.64, p less than 0.01). Thus, we conclude that coma is a symptom of hyperaminoacidemia, but that death is the result of impaired oxidative energy production and a deficiency of amino acid clearance for synthesis of proteins required for survival.

Adult↗
PubMed1984

Amino acid clearance and prognosis in surgical patients with cirrhosis.

To measure the effects of cirrhosis on amino acid (AA) flux and to assess the value of the central plasma clearance rate of amino acids (CPCR-AA) as a hepatocyte function test, 35 patients with cirrhosis were studied before and after operation. Fourteen of these patients died after the operation. CPCR-AA measures the number of milliliters of plasma cleared of AA per minute by the liver and other visceral tissues. It is the ratio of AA entry rate into plasma (from peripheral tissues plus infusion) to the arterial AA plasma concentration. Preoperative CPCR-AA measurements in 21 fasted patients with cirrhosis who were not infected revealed a pattern of AA plasma concentration and exchange similar to that previously observed in patients with sepsis with normal liver function. Whereas the concentration of AA in both groups was slightly lower than normal, the CPCR-AA of each was more than four times that of normal postabsorptive people (p less than 0.01). However, preoperative values of CPCR-AA in patients with cirrhosis who survived was 220 +/- 26 ml/M2/min while that in those who died was 97 +/- 16 ml/M2/min (p less than 0.001). Postoperative measurements remained relatively unchanged: survivors 212 +/- 24 ml/M2/min and those who died 89 ml/M2/min (p less than 0.0005). Measurements in vitro of the hepatic protein synthetic rate in liver biopsy specimens taken at operation correlated well with CPCR-AA values obtained immediately before operation in 10 patients (r = 0.73; p less than 0.01). Thus in patients with cirrhosis visceral amino acid uptake and hepatic protein synthesis are maximally stimulated. Nevertheless, if the preoperative CPCR-AA does not approach the value of 284 +/- 76 ml/M2/min previously observed in patients with sepsis who recover, the patient with cirrhosis is prone postoperatively to die of overwhelming infection and multisystem failure.

Amino Acids↗
PubMed1984

Induction of hepatic protein synthesis by a peptide in blood plasma of patients with sepsis and trauma.

Accelerated release of amino acids from muscle and their uptake for protein synthesis by liver and other visceral tissues are characteristic of trauma or sepsis. Experimentally, this response is induced by interleukin-1 (IL-1) generated by activated macrophages in vitro. However, IL-1 has not been demonstrated in human blood. A small 4000-dalton peptide recently isolated from plasma of patients with sepsis and trauma induces muscle proteolysis and is called "proteolysis-inducing factor" (PIF). To test whether this agent has the ability also to induce hepatic protein synthesis, a series of animal experiments and clinical observations were undertaken. The structural and secretory (acute-phase reactants) in vitro protein synthesis in livers of normal rats injected intraperitoneally with IL-1 or PIF was significantly greater than that of normal rats or those injected with Ringer's lactate (p less than 0.01). In patients with sepsis and trauma the central plasma clearance rate of amino acids, a measure of visceral (principally hepatic) amino acid uptake, was elevated and correlated with the rates of protein synthesis in incubated liver slices obtained by biopsy at operation from the same patients (p less than 0.05). Both in vivo measured central plasma clearance rate of amino acids and in vitro measured hepatic protein synthesis correlated with plasma levels of PIF in the same patients (p less than 0.01 and p less than 0.05, respectively). We conclude that since PIF, and not IL-1, is present in human plasma and both are produced by activated macrophages, PIF seems to be the stable circulating cleavage product of IL-1, which induces not only muscle proteolysis but also hepatic protein synthesis, principally in the form of acute-phase reactants during infection and other states in which inflammation is present.

Amino Acids↗
PubMedDate not supplied

Role of p27 in prostate carcinogenesis.

The cyclin dependent kinase inhibitor p27 binds to and inhibits preferentially S-phase kinases thereby halting cell cycle progression. Loss of p27 expression has been shown to be associated with aggressive behavior in a variety of human epithelial tumors including prostate cancer. In this review, the role of p27 in cell cycle progression as well as its regulation by the ubiquitin-proteasome pathway are discussed. The experimental evidence pointing to the role of p27 as a tumor suppressor gene is outlined. The data generated to date on the prognostic significance of loss of p27 protein expression in human prostate cancers are summarized. Finally, the implications of the changes in p27 expression which occur as a result of androgen ablation in normal and neoplastic prostate are discussed.

Androgens↗