Inhibition of sucrose intake by continuous celiac, superior mesenteric, and intravenous CCK-8 infusions.

Two experiments compared the potency of continuous infusions of cholecystokinin octapeptide (CCK-8) for reducing sucrose intake when administered into abdominal arteries or the jugular vein. Adult, male Sprague-Dawley rats received 22-min infusions of saline or several doses of CCK-8. Sucrose was available for 20 min, beginning 2 min after onset of infusions. In the first experiment, intraceliac CCK-8 in doses of 50, 125, and 312 ng produced significant reductions in intake, but no dose affected intake when administered into the jugular vein. In experiment 2, only the highest dose, 312 ng, suppressed intake when infused into the superior mesenteric artery, and jugular infusions were again ineffective. Behavioral observations indicated that intra-arterial CCK-8 had no affect on feeding within the first several minutes of test meals but accelerated the subsequent decline in incidence of feeding. These results suggest that receptors involved in cholecystokinin satiety are widely distributed within the gastrointestinal tract.

Irradiances of spectral lines in mercury pencil lamps.

The irradiancesof 37 spectral lines emitted bymercury pencil-type lamps were measuredby comparison with calibrated continuum sources. The lines span the region 230-590 nm. For the 14 most prominent lines the absolute irradiances should be useful for radiometric calibrations at an uncertainty level of ~15% 195% confidence2. The ratios of the irradiances for this same group of lines are significantly more reproducible; they should be useful at an uncertainty level of ~10%.

Structure-function relationships of the erythropoietin molecule.

The tertiary structure of erythropoietin (EPO) remains to be elucidated by X-ray crystallography. Although the amino acid sequence of EPO is known, the specific features that confer its biological activity are not well understood. In order to study the structure-function relationships of EPO by in vitro mutagenesis, we have used the vector pGEX-2T to express human and murine EPO fused to the carboxyl terminus of glutathione S-transferase (GST) in E. coli. The fusion proteins were the predicted size (46 kDa) by SDS-PAGE. GST-huEPO eluted from glutathione-agarose using reduced glutathione (GSH) was tested by radioimmunoassay and in a mouse spleen cell assay (MSCA). Dose-response curves parallel to recombinant human EPO (rHuEPO) were obtained in both assays. The ratio of immuno- to bioactivity was 4.7:1. Thus the presence of the 26 kDa GST protein at the end terminus of EPO does not abrogate biological activity. GST-mEPO also gave dose-response curves parallel to rHuEPO in the MSCA but not in the RIA. The wild-type murine and three mutant GST-EPO fusion proteins (166 Des-Arg, Glu 159-->Val, and Arg 163-->Glu) were tested in the MSCA and assayed for GST activity. The ratio of bioactivity to enzyme activity for the Arg 163-->Glu mutant was approximately one third of the value obtained for each of the other fusion proteins, indicating that arginine at 163 is functionally important for EPO activity. The availability of these human and murine gene constructs in pGEX should facilitate site-directed mutagenesis and permit detailed studies of the structure-function relationships for the two erythropoietins.

Granulocyte and granulocyte-macrophage colony-stimulating factors in cord and maternal serum at delivery.

Impaired neutrophil responses contribute to the neonate's increased susceptibility to infection. Because granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) enhance granulocyte and macrophage number and function, their use in the management of neonatal sepsis may be beneficial. Little is known about the endogenous levels of G-CSF and GM-CSF. In adults, raised values for G-CSF, but not GM-CSF, have been demonstrated in patients with infection, and conflicting data has emerged regarding CSF levels in neonates. We have used an ELISA to measure maternal and cord serum G-CSF and GM-CSF at the time of delivery, with gestational age between 25 and 42 wk. In mothers, an inverse linear relationship between gestational age and GM-CSF levels (p = 0.049) was found, but no association with G-CSF levels was observed. In neonates, a quadratic association was found between GM-CSF levels and gestational age (p = 0.019), whereas G-CSF levels showed an inverse linear association (p = 0.015). In addition, an association was found between maternal and cord GM-CSF (p = 0.007) but not G-CSF levels in paired samples. The effect of gestational age on the cytokine levels could not be explained by the white cell count, the absolute neutrophil count, pregnancy-induced hypertension, or the presence of infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Informal carers: a Marxist analysis of social, political, and economic forces underpinning the role.

Increasingly, families are being called to provide care to their elderly family members. Nursing has an important role to play in enabling families to assume such responsibilities. In this article, however, it is argued that nursing needs to examine its goals for nursing care and approaches to care delivery in their broader social, political, and economic context. Marxist theory is introduced and used to raise questions about taken-for-granted aspects of nursing practice and trends in health policy as they relate to family carers for the elderly. The article specifically examines assumptions about family, women, and household economies that are inherent in traditional nursing theory. It is argued that nursing needs to move its focus of action beyond work at the individual and family level to include work at system and policy levels. To do so, nursing must examine theoretical perspectives that enable such an inquiry into practice.

Hypobaric hypoxia: a method for testing bioreductive drugs in vivo.

Hypobaric hypoxia has been used to induce tumor hypoxia for in vivo comparison of the anti-tumor effects of the bioreductive agents SR 4233 (3-amino-1,2,4-benzotriazine-1,4-dioxide), RSU 1069 (1(2-nitro-1-imidazolyl)-3-aziridino-2-propanol), and Nitromin (methylbis(2-chloroethyl)amine N-oxide). BDF mice bearing the T50/80 mammary carcinoma were treated with these agents over a range of doses under normobaric (oxic) and hypobaric (hypoxic) conditions. The time taken for the tumor to double treatment volume (volume doubling time) was used as a measure of anti-tumor effect. Volume doubling time was plotted against log dose and dose response curves were fitted. A dose enhancement ratio (the ratio of drug doses required to give an equivalent anti-tumor effect under oxic and hypoxic conditions) was determined. The dose enhancement ratios for SR 4233 and RSU 1069 were 8.8 and 8.5, respectively, showing that these agents had an equivalent and substantial enhancement of their cytotoxicity when combined with hypobaric hypoxia. For Nitromin, no significant dose response effect was obtained under oxic conditions precluding the calculation of the dose enhancement ratio. SR 4233 was found to have increased systemic toxicity when combined with hypobaric hypoxia, suggesting that it is more readily activated than the other drugs tested. This in vivo test system will allow determination of the dose enhancement ratio for novel bioreductive agents and facilitate their comparison.

Normal unstimulated lymphocytes produce granulopoietic inhibitory activity.

Normal unstimulated lymphocytes cocultured with normal bone marrow will inhibit day-7 colony- forming units in culture. We have shown that this phenomenon has a molecular basis and attempted to characterize it further. Using specific assays and neutralizing monoclonal antibodies we have found that this granulopoietic inhibitory activity (GIA) is not due to alpha- or gamma-interferon, tumor necrosis factor, or acidic or basic isoferritins. Biochemical studies suggest that it is a glycoprotein with a molecular weight greater than 100,000 daltons. It appears to act on cells in S phase, although it may not be S-phase specific. GIA represents a novel inhibitor that merits further investigation.

The proliferative activity of B-chronic lymphocytic leukaemia lymphocytes prior to and after stimulation with TPA and PHA.

The proliferative activity of B-CLL lymphocytes from 10 patients was investigated both prior to and after stimulation with TPA and PHA. The analysis of cell cycle-associated features such as BrdU incorporation and the expression of the nuclear proliferation-associated antigen, Ki-67, together with the phenotypic profile of the cells, was performed using double colour immunofluorescent methods. The unstimulated B-CLL cells represented a homogeneous population with the same cell cycle position (G0) as resting peripheral blood lymphocytes. After TPA stimulation 22.7% of the lymphocytes were found in G1, 9.4% in S + G2/M and 13.4% in post-M. PHA stimulation induced a greater proportion of cells in G1, i.e. 35% and 17.8% into S + G2/M and 13.4% into post-M. Double colour immunofluorescence was able to demonstrate that in TPA cultures the majority of the stimulated lymphocytes originated from the malignant clone. Evidence of B-CLL lymphocyte proliferation using double colour labelling with BrdU and Ig kappa and/or Ig lambda showed that a small minority of B-CLL lymphocytes were stimulated into S + G2/M phases of the cell cycle. PHA was also capable of inducing a small proportion of B-CLL cells into mitosis although this proportion of cells was smaller compared to the TPA-stimulated lymphocytes.

Effect of recombinant human erythropoietin on anemia caused by a murine mammary carcinoma.

CA NT is a transplantable murine mammary carcinoma that causes progressive anemia accompanied by granulocytosis and splenomegaly. Serum erythropoietin (Epo) levels, as measured by RIA, did not become elevated in anemic tumor-bearing mice; there was no correlation between hematocrit and serum Epo levels. Treatment with recombinant human (rHu) Epo prevented anemia in tumor-bearing mice when given in large doses, commencing on days 3-5 of tumor growth. Recombinant human Epo-treated mice had smaller spleens than controls. When treatment commenced on day 7, the development of anemia was retarded but not completely prevented. Treatment commenced on day 14 was less effective. This study demonstrates that treatment with rHu Epo can markedly influence the course of tumor-induced anemia.

Literature review on the images of the nurse and nursing in the media.

This study concentrates on the images of the nurse and nursing seen most commonly in the media and attempts to trace the images back to their origins and to explain their continued use, despite the rapidly changing role of the nurse in today's world. The images have been derived mostly from the historical roots of nursing and sometimes as a reaction to the increasing influence of the feminist movement. The author takes a look at the four main images of the nurse seen in the media, which are the ministering angel, the battleaxe, the naughty nurse and the doctor's handmaiden and then goes on to take a brief look at the other images commonly perpetuated by the media. The author summarizes the probable effects of the media stereotypes on nurses themselves and the service they provide and also takes a look at attempts to dispel these stereotypes.

Erythropoietin production in kidney tubular cells.

The erythropoietin gene has been cloned in three mammalian species including man and recombinant erythropoietin is now used to treat the anaemia of chronic renal failure. Despite the isolation of the gene the precise cellular location of erythropoietin synthesis remains controversial. We present studies which demonstrate erythropoietin production by kidney tubular cells. Erythropoietin gene expression (messenger RNA) was detected by in situ hybridization using an oligonucleotide gene probe and the translated protein product by immunohistochemistry employing antibodies raised to pure recombinant DNA derived erythropoietin.

The metabolism of erythropoietin in the normal and uraemic rabbit.

The metabolism of recombinant human erythropoietin (rHuEpo) labelled with 125I has been investigated in five normal and nine 5/6-nephrectomised rabbits. The plasma erythropoietin half-life was significantly prolonged at 5.1 +/- 1.2 h (mean +/- SD) in the 5/6-nephrectomised rabbits, compared to 3.0 +/- 0.4 h in sham-operated controls (P less than 0.001). The disappearance of 125I-labelled rHuEpo is biphasic. Examination of serum by fast protein liquid chromatography (FPLC) following administration of 125I-labelled rHuEpo by FPLC showed a single peak of radioactivity in all rabbits except two of the nephrectomised group. In serum from both of these animals a second labelled peak was found, corresponding to material of MW 200,000-250,000 D. We conclude that the 5/6-nephrectomised rabbit provides a stable model for the study of hormonal metabolism in chronic renal failure.

The effect of hypobaric hypoxia on misonidazole binding in normal and tumour-bearing mice.

The effect of hypobaric hypoxia on the in vivo binding of misonidazole was investigated in normal mice and mice bearing T50/80 or CA NT mammary carcinomas. After the intraperitoneal injection of radiolabelled misonidazole, mice were randomised to breathe either room air or air at 0.5 atmospheres. The distribution of misonidazole in liver, kidney, heart, spleen and tumour tissue, 24 h later, was studied by scintillation counting and by autoradiography. Significantly higher misonidazole binding occurred in the livers (x2.5), kidneys (x2.4), spleens (x2.9) and hearts (x1.8) of hypoxic mice compared to controls. Hypobaric hypoxia was associated with a greater than four-fold increase in misonidazole binding within T50/80 tumours. However, significantly higher binding was not demonstrated within CA NT tumours after exposure of tumour-bearing animals to hypoxic conditions. In autoradiographs of hypoxic liver, labelling was intense in regions near to hepatic veins but sparse in areas surrounding portal tracts. This pattern was striking and consistent. In hypoxic kidney, labelling was most intense over tubular cells, less intense over glomeruli and sparse in the renal medulla. It is likely that the hepatic and renal cortical distributions of misonidazole binding reflect local oxygen gradients.

Serum erythropoietic activity in acute anemia--an animal model.

Serum erythropoietic activity and reticulocyte response to anemia were investigated using a rabbit model. In hemolytic anemia, induced by injections of phenylhydrazine on Day 0 the hemoglobin reached a nadir (mean, 6.23 g/dl) on Day 4 when SEA was maximal (mean, 765 mU/ml). In animals venesected on Day 0 and Day 1 to produce anemia of equal severity, the SEA was maximal (mean 235 mU/ml) on Day 2. In both groups the reticulocyte response peaked on Day 7--at 34% for the hemolytic group and 21% for the venesected group. The 2,3-diphosphoglycerate, measured on Day 4, was significantly reduced in the PHZ-treated group. In the venesected group the 2,3-DPG increased between Day 0 and Day 4. There were no concurrent changes in acid-base balance. These results imply that the degree of anemia is only one of the factors which influence the level of circulating SEA.

The initiation of erythropoiesis following renal transplantation.

Erythropoiesis has been examined in relation to kidney function in 38 patients during the 3-month period following successful renal transplantation, using serial determinations of erythropoietin, haemoglobin, and creatinine. Two peaks of serum erythropoietin were observed: an early peak that occurred within 2 days of transplantation and was observed in ten patients, and a late one between 8 and 30 days, observed in 28 patients. The early peak did not produce an increase in haemoglobin and occurred only in the presence of delayed onset of graft excretory function when serum creatinine was greater than 1000 mumols/l. The ineffectiveness of the early peak may be due to the uraemic environment, which is probably a sequel of the tubular damage associated with postoperative acute tubular necrosis. The late peak followed a decrease in serum creatinine to less than 200 mumols/l and was associated with an increase in haemoglobin of 3-4 g/dl during the next 2-6 weeks.

Comparison of the mouse spleen cell assay and a radioimmunoassay for the measurement of serum erythropoietin.

The mouse spleen cell assay (MSCA) has been compared with a radioimmunoassay for the measurement of serum erythropoietin (Ep). In 20 normal subjects the serum values ranged from 15 to 73 mU/ml for the MSCA compared with 5-30 mU/ml for the RIA. For normal sera there was no correlation between the results of the two assays. In 37 patients with anaemias of differing aetiologies and at various stages of treatment values ranged from 10 to 3645 mU/ml for the MSCA and 13-10,000 mU/ml for the RIA. Although patient values from the two assays were highly correlated (r = 0.98, P less than 0.001), the MSCA results were generally lower. These discrepancies can be largely accounted for by two factors. Firstly the MSCA is sensitive to non-specific matrix effects. Secondly, heat inactivation of serum, a prerequisite for the MSCA, but not for the RIA, destroys a variable and unpredictable proportion of the Ep in the test sera leading to an underestimation of Ep in the MSCA. We conclude that the RIA is more reliable than the MSCA which, in its present form, cannot be recommended for the accurate measurement of serum erythropoietin.