Platelet-melanoma cell interaction is mediated by the glycoprotein IIb- IIIa complex

A human malignant melanoma cell line (M3Dau) was observed by electron microscopy to interact directly with human platelets and induced platelet aggregation. Fab fragments of a monoclonal antibody MoAb (LYP18), directed against the platelet glycoprotein (GP) IIb-IIIa complex, inhibited platelet-melanoma interactions and platelet-platelet aggregation. M3Dau melanoma cells bind LYP 18 and synthesize IIb-IIIa- like GPs. When the melanoma cells were preincubated with LYP 18, tumor- platelet interaction did not occur, suggesting that the interaction may be mediated by the IIb-IIIa-like GPs present on the melanoma cell surface. Glanzmann's thrombasthenic platelets, lacking GPIIb and IIIa, did not interact with melanoma cells, indicating that the platelet GPIIb-IIIa complex is also necessary for the platelet-melanoma cell interaction. This work demonstrates the importance of the IIb-IIIa-like GPs, present on M3Dau melanoma cells, in mediating tumor-platelet interactions.     

Metabolic activity of phagocytosing granulocytes in chronic granulocytic leukemia: ultrastructural observation of a degranulation defect

The functional capacities of granulocytes in patients with chronic granulocytic leukemia are still a subject of controversy, probably due to the heterogeneity of the abnormalities observed from patient to patient. For a better definition of these abnormalities, 14 patients with untreated chronic granulocytic leukemia were studied. The patients were divided into three groups on the basis of the functional activities of their phagocytosing granulocytes. In four patients (group I), the granulocytes were normal in respect to particle ingestion, nitroblue tetrazolium (NBT)-stimulated reduction, cyanide-insensitive oxygen (O2) consumption, superoxide anion (O2-)-stimulated production, hydrogen peroxide (H2O2) production, and iodination. They also had a normal myeloperoxidase (MPO) content. In four patients (group III), the granulocytes were significantly defective in all of these activities. In the six remaining patients (group II), all the initial metabolic steps of the phagocytosing granulocytes (ingestion, NBT reduction, O2 consumption, O2-production, H2O2 production) were normal, as were the MPO content of the granulocytes, while iodination was strikingly decreased. These metabolic features suggested a degranulation defect which was observed ultrastructurally in the only patient studied among these six. The phagocytosing granulocytes of this patient did not degranulate and no deposits of MPO activity were seen in the phagosomes.     

TCR gamma delta bearing lymphocyte clones with lymphokine-activated killer activity against autologous leukemic cells

Activated T lymphocytes with the T-cell receptor (TCR) gamma delta (CD3+ and TCR delta 1+) exhibit strong cytotoxic activity against the standard natural killer (NK) and lymphokine-activated killer (LAK) sensitive target cells. In order to test the cytotoxic activity of gamma delta T lymphocytes against autologous leukemic cells, 84 clones of gamma delta T lymphocytes were obtained from the peripheral blood of three acute lymphoblastic leukemia (ALL) patients. Forty-four of these T-cell clones were active against an LAK-sensitive cell line and the other 40 were active against K562, an NK target cell line. In each of the three patients, cytotoxic clones against autologous leukemic cells were obtained. Among the 84 clones, ten were able to kill autologous tumor cells, including eight that lyse the LAK-sensitive target and two with NK activity. The clones were highly cytotoxic, stable, and easily expanded in large quantity.     

Does skin-to-skin contact reduce stress during diaper change in preterm infants?

Background

Skin-to-skin contact reduces pain response in preterm infants subjected to minor painful procedures, such as heel lance. Diaper change is a procedure performed several times daily in hospitalized preterm infants. Routine care giving tasks such as diaper change may be stressful for the infant.

Aims

The purpose of this study was to investigate whether diaper change induces stress and if skin-to-skin contact could reduce such stress, measured by changes in skin conductance.

Study design

This was a randomized crossover pilot study in 19 preterm infants with gestational age between 28 and 34 weeks. The diaper change procedure was done twice in each infant, once during skin-to-skin contact, and once in incubator or bed with the mother present.

Outcome measures

During diaper change heart rate (HR), peripheral oxygen saturation (SpO₂), and changes in skin conductance (SC) peaks per sec, using the Skin Conductance Algesimeter (SCA), were registered.

Results

The mean SC peaks/sec increased/decreased significantly under/after change of diapers which thereby underpins that this is a stressful procedure for the preterm infant.Skin-to-skin contact (SSC) entails significantly lower stress levels (p < 0.05) compared to diaper changed in an incubator/bed measured by the SCA.

Conclusions

Diaper change is a stressful procedure for preterm infants and may be ameliorated by skin-to-skin contact.     

The effects of short-term, high-dose treatment with prednisone on the nuclear uptake of 1,25-dihydroxyvitamin D3 in monocytes from normal human subjects

Animal and cell culture studies indicate glucocorticoid regulation of 1,25-dihydroxyvitamin D3 receptors and interference with cellular effects of vitamin D. These investigations prompted us to examine the effects of prednisone on the nuclear uptake of 1,25-dihydroxyvitamin D3 in freshly isolated human monocytes. Eighteen normal subjects were studied in a randomized, double-blind, placebo-controlled study. Analysis of receptor kinetics revealed that the maximal nuclear uptake (Bmax) of (3H)-1,25-dihydroxyvitamin D3 in monocytes decreased 40% (P less than .001) after prednisone treatment. In the group treated with prednisone (40 mg/d for 5 days) s-1,25-dihydroxyvitamin D increased 46% (P less than .01). S-25-Hydroxyvitamin D, S-phosphat, S-calcium, and S-iPTH remained unchanged. Osteoblastic production of the matrix protein, bone gla protein (BGP) is stimulated by 1,25-dihydroxyvitamin D3. However, despite increased serum levels of 1,25-dihydroxyvitamin D3, the prednisone-treated group revealed a 75% reduction in s-BGP. The present data indicate that corticosteroids decrease the nuclear uptake of 1,25-dihydroxyvitamin D3 in human monocytes. Further investigations are necessary, however, to elucidate the biologic mechanism for this observation and whether the mechanism is operative in other human tissues including bone.     

Weak diagnostic performance of troponin,creatine kinase and creatine kinase-MB to diagnose or exclude myocardial infarction after successful resuscitation

Background

The aim of this study is to evaluate the diagnostic accuracy of the cardiac injury markers troponin (TNT), creatine kinase (CK) and creatine kinase-MB (CK-MB) to diagnose or exclude acute myocardial infarction after cardiac arrest.

Methods

226 patients who underwent diagnostic coronary angiography after sudden cardiac arrest were analyzed retrospectively. Levels of TNT, CK and CK-MB on admission and 6 h, 24 h and 36 h later were retrieved from the files and compared with the results of coronary angiography.

Results

Acute myocardial infarction (AMI) as well as non-AMI patients showed increasing levels of TNT and CK after resuscitation, although the AMI group showed significantly higher TNT and CK levels. Receiver operator curves were calculated to determine the diagnostic precision of TNT, CK and CK-MB to differentiate AMI and non-AMI patients. All analyzed markers yielded mediocre diagnostic precision with an area under the ROC curve of 0.7020, 0.6802 and 0.6508 for 6 h TNT, CK and CK-MB, respectively. Applying a modified cut-off of 1 μg/l the 6 h TNT measurement had a sensitivity of 70.9% and specificity of 61.2% to diagnose AMI after cardiac arrest. Using CK 800 U/l as cut-off level resulted in a sensitivity of 62.5% and specificity of 73.7%, CK-MB levels higher than 100 U/l yielded a sensitivity of 58.8% and specificity of 72.7%.

Conclusion

Cardiac injury markers cannot be used to reliably diagnose or rule out AMI after resuscitation. Consequently we propose that indication for coronary angiography should be extended to all patients without a certain alternative diagnosis explaining the occurrence of cardiac arrest.