Dissimilarities between benzodiazepine-binding sites and adenosine uptake sites in astrocytes and neurons in primary cultures

The question whether the benzodiazepine receptor site in astrocytes or in neurons might be identical to the adenosine uptake site was studied by determining pharmacological profiles, inhibition types, and the effects of benzodiazepine antagonsts in primary cultures of either astrocytes or neurons. Fourteen different benzodiazepines and five different adenosine uptake inhibitors displaced [³H] diazepam and inhibited adenosine uptake in both astrocytes and neurons. However, the rank orders (determined as IC₅₀ values) with which these two parameters were affected were profoundly different, indicating dissimilarities between these two sites. For several of the compounds a difference in inhibition type (competitive vs. noncompetitive) was observed between the benzodiazepine-binding site and the adenosine uptake site in astrocytes and/or neurons, which further corroborated the conclusion of a difference between the benzodiazepine-binding site and the adenosine uptake site. Finally, the neuronal benzodiazepine antagonists RO 15-1788 and CGS-8216 and the astrocytic benzodiazepine antagonist PK 11195, which reverse the action of benzodiazepines, were not able to reverse inhibition of adenosine uptake by diazepam but exerted an inhibitory effect of their own.     

Methodenrelevanz in der Nachsorge des Mammakarzinoms

Ohne Zusammenfassung     

A novel method for synchronizing a B cell lymphoma.

Certain sub-lines of the murine B cell lymphoma BCL1 can be maintained in vitro and respond to cytokines including IL-2 and IL-5. BCL1 cells, as well as other B lymphomas, are difficult to synchronize using conventional techniques such as thymidine block or DNA synthesis inhibition. We have found that BCL1 cells maintained in Dulbecco's minimum essential medium (DMEM) with non-essential amino acids (NEAA) can be readily synchronized by culture in DMEM lacking NEAA. Within 10-18 h of medium replacement, 98% of BCL1 cells are 2 N in DNA content, suggesting that these cells are arrested in G0/G1. This population of BCL1 cells is viable and can be stimulated to enter S phase by culture in media containing NEAA; however, arrested cells did not appear to return synchronously into the cell cycle on addition of NEAA. A transient increase in levels of c-fos and c-myc mRNA was not detected after arrested BCL1 cells were stimulated to enter S phase, suggesting that arrested cells are in the G1 phase of the cell cycle, rather than G0. This technique for obtaining G1 arrested B lymphoma cells may prove useful in the analysis of molecular events that occur in B cells as a function of cell cycle position.     

Acute peripheral arterial and graft occlusion: treatment with selective infusion of urokinase and lysyl plasminogen

Thirty-five patients hospitalized for recent angiographically documented arterial occlusion in the legs (27 femoropopliteal arteries and eight grafts) benefited from local fibrinolytic therapy delivered at the site of the occlusion with a 4- or 5-F catheter. This therapy combined a continuous urokinase (UK) infusion of 1,000 U/kg/hour and a lysyl plasminogen (LYS-PLG) infusion of 15 microkatals every 30 minutes. Angiographically confirmed lysis was obtained in 85% of the cases. Only 3% of the patients had major and 6% had minor groin hematomas. Only two patients had concentrations of fibrinogen as low as 100 mg/dl. Intravascular infusion of UK-LYS-PLG is as effective as streptokinase. Its excellent tolerance makes it a good alternative in the treatment of acute ischemia in the lower limbs.     

Antigenic structure of bovine growth hormone: location of a growth enhancing region.

Site-directed antisera generated by peptide immunization have been used to study the antigenicity of bovine growth hormone (bGH). Prediction of sequential antigenic sites has been performed using secondary structure information derived from the 'Protean' prediction routine. The structures predicted by this programme agree closely with the corresponding structure of GH recently derived from crystallographic studies. We have previously shown that the binding of monoclonal antibodies of particular epitope specificity to human or bovine GH results in significant enhancement of hormonal activity in vivo; however, the sites recognized by these antibodies were not known. Here we identify a sequence region, corresponding to a loop structure joining helices 3 and 4, which, is associated with the growth enhancement phenomenon. Antisera raised to either of two overlapping peptides (residues 120-140 and 134-154) significantly increase the biological activity of GH in vivo. Antisera directed to other regions on the GH molecule failed to demonstrate this property. Coincidentally, the sites recognized by the growth-enhancing anti-peptide antisera overlap with the site on GH which is highly susceptible to proteolytic cleavage; such cleavage has been shown in some cases to result in hormone enhancement.     

A preliminary study of PDA-based dietary self-monitoring in hemodialysis patients

OBJECTIVE: The purpose of this study was to pilot test an intervention to enhance the adherence of study participants to the hemodialysis dietary regimen. DESIGN: A single case study design was used to examine the potential effectiveness of the intervention over a 4-month period of time. SETTING: A dialysis center in southwestern Pennsylvania. PATIENTS: Of the five individuals entered into the study, one was male and four were female, four were black, and one was white. Participants were 63 to 70 years of age, and had been receiving dialysis for a median of 36 months (range, 18 to 84 months). INTERVENTION: The intervention included counseling to enhance self-efficacy, by a renal dietitian, paired with personal digital assistant-based dietary self-monitoring. Participants met twice per week with interventionists during the first 6 weeks, weekly during the second 6-week period, and biweekly in the final 4-week period. MAIN OUTCOME MEASURES: Monthly laboratory data regarding serum albumin, potassium, and phosphorus levels; Kt/V; and data on average monthly interdialytic weight gain were abstracted from the participants' medical records. C-reactive protein level was determined at baseline and at 4 months. RESULTS: Four of five study participants had an increase in serum albumin level from baseline to their final measurement, and one participant maintained a stable albumin level. Four of five participants also experienced a small increase in serum phosphorus level. Mixed results were obtained with regard to serum potassium and average monthly interdialytic weight gain. CONCLUSIONS: Because of the small sample and single case study design, caution must be used in drawing firm conclusions from this study. Data suggest that the intervention may result in improved dietary intake and improved serum albumin levels. With increased dietary intake, serum phosphorus levels may increase. Additional research is needed to determine the potential efficacy and cost-effectiveness of this intervention for improving dietary adherence.