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Biomedical subjects

E M Copeland

Publications and source records attributed to E M Copeland.

At least 19 recordsLinked to original sources
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

Growth hormone regulates amino acid transport in human and rat liver.

Human growth hormone (GH) has been shown to improve nitrogen balance in surgical patients and to decrease urea production. This has been thought to be due primarily to an increase in protein synthesis in skeletal muscle. Little attention has focused on the liver as a possible site where GH may modulate amino acid uptake and thereby divert nitrogen away from urea-genesis. The authors hypothesized that GH regulates amino acid transport in hepatocytes at the plasma membrane level. They studied hepatic amino acid transport in 20 healthy surgical patients that received saline, low-dose GH (0.1 mg/kg/day), or high-dose (0.2 mg/kg/day) GH for 3 days before operation. At operation, a 5- to 10-g wedge biopsy of the liver was obtained, and hepatocyte plasma membrane vesicles were prepared by Percoll density gradient centrifugation. Vesicle transport of [3H]-MeAIB, a highly selective system A substrate, and [3H]-glutamine, a selective system N substrate, was measured, employing a rapid mixing/filtration technique. Hepatocyte plasma membrane vesicles were also prepared from 14 rats treated with saline or one of three different GH treatment regimens: (A) 12 hours after chronic GH treatment (6 mg/kg every 12 hours x 4 doses); (B) 4 hours after acute (1 dose) GH treatment; and (C) 4 hours after chronic GH treatment. In human liver vesicles, low-dose GH resulted in a 13% decrease in system A activity (p = not significant), whereas high-dose GH caused a marked 79% decrease (6.7 +/- 1.7 pmol/mg protein/10 seconds in control patients versus 1.4 +/- 0.7 in GH, p less than 0.05). System N was unaffected. Kinetic analysis of MeAIB transport by vesicles from high-dose GH patients showed the reduction in transport to be due to a 63% decrease in the Vmax (maximal transport velocity) with no alteration in the transport Km (carrier affinity). Vesicles from rats treated chronically with GH using a protocol similar to that used for human subjects exhibited decreased system A transport activity (10.4 +/- 0.4 pmol/mg pro/10 seconds in controls versus 7.5 +/- 0.2 in GH, p less than 0.05) secondary to a 59% reduction in the transport Vmax. Chronic growth hormone treatment decreases the activity of system A in both human and rat hepatocytes. This may be one mechanism by which GH diminishes hepatic urea-genesis and spares amino acids for peripheral protein synthesis.

5'-Nucleotidase↗
PubMed1979

Evaluation of nutritional indices as prognostic indicators in the cancer patient.

The nutritional and immunological status of 140 malnourished cancer patients who were to receive intravenous hyperalimentation (IVH) were evaluated prior to treatment with IVH and chemotherapy (CMX), surgery or radiation therapy (XRT). Subsequently, these indices were correlated with responses to treatment. Cell-mediated immunocompetent (CMI+) patients (41%) had lost an average weight of 10 +/- 2.2 lbs., while cell-mediated immunoincompetent (CMI-) patients (59%) had lost an average weight of 31 +/- 2.5 lbs. (p less that 0.05). Total lymphocyte count (TLC) averaged 1290 +/- 250 cells/mm3 in CMI+ patients and 900 +/- 140 cells/mm" in CMI- patients (p less than 0.05). Serum albumin concentration (SA) was 3.6 +/- 0.06 g/dl in CMI+ patients and 3.3 +/- 0.05 g/dl in CMI- patients (p less than 0.05). In the CMI+ group, 49% had a positive response to CMX, whereas only 27% of the CMI-group responded to CMX (p less than 0.01). In the surgery group, 88% of the CMI+ patients, but only 65% of CMI- patients, had uncomplicated postoperative recovery periods. Although nutritional repletion with IVH was undertaken in all patients, those patients with initial CMI- responses had greater body weight loss, lower SA and TLC and either a decreased response to CMX or an increase in postoperative morbidity and mortality when compared with patients who initially had CMI+ responses.

Adolescent↗
PubMed1979

Nutrition, cancer, and intravenous hyperalimentation.

In over 1000 cancer patients treated with intravenous hyperalimentation (IVH), tumor growth has not been identified and catheter-related sepsis has been minimal. Studies in rats demonstrated that the host benefits more than the tumor during nutritional repletion, and any stimulation of tumor growth in the rat-tumor model could be manipulated with DNA specific drugs to benefit the host. A study of 65 malnourished cancer patients undergoing oncologic therapy and treated with IVH indicated that much of the immune suppression in these patients was the result of malnutrition coincident with or secondary to oncologic treatment. Conclusions reached in this study were that nutritional repletion resulted in a return of skin test reactivity, proper wound healing in the surgical patient, and possibly an increase in response to chemotherapy. Certainly, the use of IVH allowed specific oncologic therapy to be administered to a group of malnourished patients who otherwise might not have been acceptable candidates for intensive antineoplastic therapy.

Animals↗
PubMed1979

Enteral and parenteral feeding to evaluate malabsorption in intestinal parasitism.

General evidence of malnutrition such as loss in body weight associated with intestinal parasitism has been attributed to decreased food intake, to intestinal malabsorption, and to change in host basal metabolism. To establish the relative importance of these factors in this regard, rats with trichinosis were studied. The weights of infected and uninfected animals were followed after being placed on one of three feeding regimens for 1 week--stock diet ad libitum, intraduodenal nutrition, and intravenous nutrition. Infected rats on a stock diet lost weight whereas those on the other two regimens maintained the same weight pattern as uninfected counterparts. The maintainance of body weight occurred despite alterations at the level of the intestinal brush border as indicated by a depression of intestinal disaccharidase activities (sucrase and lactase) and by reduction of monosaccharide absorption (measured as accumulation of beta-methyl glucoside) in the proximal, heavily infected region of the small intestine. There was no compensatory increase in enzyme activity nor in the absorptive capacity in the distal gut. Results support the conclusion that inadequate oral food intake rather than changes in basal metabolism or intestinal pathophysiology accounts for weight loss during the intestinal phase of infection.

Animals↗
PubMed1979

The effects of nutrition and treatment of cancer on host immunocompetence.

Conventional approaches to therapy for cancer, such as chemotherapy, operative therapy and radiation therapy, can produce profound changes in host immunity. The effects of chemotherapy upon immune responses are related both to the dosage and duration of therapy and are readily reversible. Operative therapy likewise suppresses both humoral and cell-mediated immunity for two to three weeks, as manifested by in vitro and in vivo tests of these functions. Radiation therapy, however, seems to decrease host immune responses for more prolonged periods of time, up to ten years. Nutritional status may also affect both limbs of the immune system, and malnutrition is being recognized with increasing frequency as a clinical problem in patients with advanced primary malignant or metastatic disease, especially during antineoplastic therapy. Intravenous hyperalimentation is a safe and effective method for correcting nutritional deficits in patients with cancer; moreover, immunocompetence may be enhanced during adequate nutritional rehabilitation.

Animals↗
PubMed1978

Inguinal node metastases.

Twenty-two hundred and thirty-two patients with inguinal node metastases were reviewed. The primary site of malignancy was determined in 2210 (99%) of these patients and was, in order of frequency, skin of the lower extremities, cervix, vulva, skin of the trunk, rectum and anus, ovary and penis. The determinant three-year survival rate for the remaining 22 patients with metastatic disease from an unknown primary site was 50%. The source of the primary (stomach) was discovered in only one of the 22 patients; however, the treatment of choice was superficial groin dissection, and if surgical excision was adequate, radiation therapy did not appear to be necessary to obtain local control.

Adolescent↗
PubMed1978

Effects of protein depletion and repletion on cell-mediated immunity in experimental animals.

Protein-calorie malnutrition leads to depression of host cell-mediated immunity. Nutritional repletion initially results in rapid weight gain followed by a more gradual return of immunocompetence. Administration of a synthetic amino acid diet to normal animals did not preserve body weight or cell-mediated immunity any better than did a high carbohydrate, protein-free diet. Administration of a synthetic amino acid diet to malnourished animals maintained body weight, but did not restore immunocompetence. Proper nutritional repletion should provide both adequate protein and nonprotein calories if a return of immunocompetence is to be anticipated.

Amino Acids↗
PubMed1978

The effects of a 10% soybean oil emulsion on lymphocyte transformation.

Free essential fatty acids (EFA) are reported to suppress cell-mediated immunity. Because Intralipid contains a high concentration of esterified EFA, the effects of this emulsion on in vitro lymphocyte transformation were studied. Intralipid concentrations of 11.5, 115, and 230 mg% in lymphocyte cultures increased phytohemagglutinin (PHA) stimulation by an average of 8.2% (not significant [NS]), 18.1% (p < 0.01), and 11.8% (NS), respectively. These same concentrations also increased Varidase stimulation in lymphocyte cultures by an average of 11.3 (p < 0.02), 18.9 (p < 0.02), and 4.4% (NS), respectively. Control wells did not demonstrate allergic reactions to Intralipid. These data demonstrate that Intralipid can significantly increase the mitogenic response of human thymic lymphocytes and the antigenic response of human lymphocytes, in vitro.

Antigens↗
PubMed1978

Effects of intravenous nutrition on tumor growth and host immunocompetence in malnourished animals.

To evaluate the effects of oral and intravenous nutritional repletion on tumor growth and host immunocompetence in malnourished animals, 60 adult purified protein derivative (PPD) positive Buffalo rats were inoculated with Morris hepatoma 5123 and were fed a regular diet for 14 days. All animals then were switched to a high carbohydrate, protein-free diet for the next 14 days, at which time only 30% of the animals remained PPD positive. Rats then were divided into three groups: group I underwent superior vena cava catheterization and received a constant infusion of 25% dextrose--4.25% amino acid solution; group II was switched to the regular protein diet orally ad libitum; and group III remained on the oral protein-free diet. PPD reactivities were measured prior to death 7 days later. Group I animals gained an average of 14 gm of body weight, and 91% of the animals were PPD positive. Group II animals lost an average of 17 gm of body weight, but 78% of the animals were PPD positive. Group III animals lost an average of 23 gm of body weight, and only 12% of the animals remained PPD positive. Absolute tumor weight and tumor weight: body weight ratios were not significantly different among the three groups of animals. Provision of adequate nutrition intravenously to malnourished tumor-bearing animals restores body weight and host immunocompetence without adversely stimulating tumor growth out of proportion to growth of the host.

Animals↗
PubMed1978

Regional chemotherapy by isolation-perfusion.

For 20 years, regional chemotherapy by isolation-perfusion has been employed for limb and selected pelvic lesions using high doses of drugs without systemic side effects. When used prophylactically, it is combined with local excision of the lesion and primary closure reducing the number of skin grafts and recurrence rate for local or intransit disease. Overall survival rate is better than for patients treated by surgery, and perfusion patients also do better with secondary therapy. For advanced melanoma patients with intransit metastasis, a 50% five-year survival may be less than expected. For patients with soft tissue sarcomas < 5 cm in diameter, the five-year survival is just under 80% and just over 40% for those > 5 cm. Complications may occur in 10% of patients treated by prophylactic perfusion, and the rate increases as the dosage and number of drugs are increased, up to a 37% complication rate for patients with advanced disease in a limb.

Antineoplastic Agents↗