Synthesis of a new carrier for immunization: polytuftsin

Sequential poly(Arg-Thr-Lys-Pro) consisting mainly of the repeat of tuftsin Thr-Lys-Pro-Arg was synthesized by condensing the p-nitrophenyl ester of Arg(HCI)-Thr-Lys-(2-CI-Z)-Pro in the presence of HOBt . Two haptenic sequences of the Pre-S region of hepatitis B virus antigen (10–26 and 39–55) were prepared by solid phase and coupled to polytuftsin via glutaraldehyde. The peptides, either free or coupled to polytuftsin, were administrated to mice and the antisera were assayed by ELISA . Coupling the peptides to the polypeptide significantly improved the anti-peptide antibody titer in Freund complete adjuvant or in NaCI 0.9%. Cross-reaction between antibodies induced by the peptides and the native protein was also improved. Polytuftsin alone is very poorly immunogenic.     

Self-selection of enrollers at the creation of a managed care organization

Factors affecting choice between a managed care organization(MCO) and a fee-for-service insurance plan were examined whenthe University of Geneva health insurance plan was transformedinto an MCO, in October 1992. A case-control study using a mailedquestionnaire (response rate 84%) was conducted to compare formermembers who joined the MCO (joiners, n=421) to former memberswho opted out in order to keep fee-for-service coverage (non-joiners,n=222). Non-joiners were more likely to be women (odds ratio(OR) from multivariate model was 1.15, p=0.50), to be born inSwitzerland (OR=2.04, p<0.01), to have an annual income >75,000Swiss francs (OR=2.00, p<0.01), to have a personal physician(OR=1.96, p<0.01) and to have consulted a specialist (OR=1.69,p=0.02) or used unconventional medicine (OR=4.59, p<0.01)in the past year. During the previous year, non-joiners hadmore health care visits than joiners (14.6 versus 9.1, p=0.01).Non-joiners reported better mental health and fewer complainedof persistent fatigue (OR=2.18, p=0.03). The choice of healthplan was strongly influenced by socio-demographic characteristics,past patterns of health services utilization and health status.The self-selection process was paradoxical: MCO joiners hadused fewer health care visits than non-joiners, but their self-reportedhealth status was worse. The differences we have observed betweenself-selected populations have important implications for thefinancial performance of competing health care delivery systems.     

Inhibition of the Mixed Lymphocyte Culture Response by Antibody Following Successful Human Renal Transplantation

Immunoglobulin G, appearing after several months in the serum of a recipient of a successful kidney transplant from a closely matched sibling donor, was demonstrated to progressively inhibit unidirectional mixed lymphocyte cultures when donor lymphocytes were used either in responding or stimulating cell populations. The active recipient IgG had no effect in cultures in which donor cells were not used, nor did IgG obtained from other individuals show nonspecific inhibitory effects on cultures containing donor cells. It is suggested that the MLC inhibitory immunoglobulin may serve an immunoregulatory function after renal transplantation.     

Evaluation of Live Attenuated Varicella Vaccine (Oka-RIT Strain) and Combined Varicella and MMR Vaccination in 13–17-Month-Old Children

ABSTRACT. The Oka-RIT strain of live attenuated varicella vaccine at dose levels 5300 PFU (high titre) and 2000 PFU (low titre) was tested in 13–17-month-old children; 50% of the children received the varicella vaccine alone, and the other 50 % received it together with a measles-mumps-rubella (MMR) vaccine. The high titre and low titre varicella vaccines induced 96% and 92% seroconversion rates, respectively. Following combined vaccination with MMR, the corresponding seroconversion rates for varicella were significantly lower at 85% and 72% respectively. Seroconversion rates to measles, mumps and rubella were not affected by the combination of varicella vaccine plus MMR vaccination. Single varicella vaccine at both titre levels was found safe, although 10% of the children had minor skin reactions, possibly attributable to the vaccine. Reactions typically associated with MMR vaccination did not significantly increase after the combined varicella plus MMR vaccination. This study confirmed that the Oka-RIT strain varicella vaccine is safe and immunogenic in healthy young children, but failed to find a totally satisfactory combination for a varicella-MMR vaccine.     

Synthesis and biological activities of some cholecystokinin analogues substituted in position 29 by a β-alanine

Syntheses of analogues of the C-terminal heptapeptide of cholecystokinin are described. These analogues were obtained by replacing glycine 29 by a β-alanine. The C-terminal phenylalanine amide was in some cases substituted by 2-phenylethyl alcohol and/or residues of the C-terminal tetrapeptide by their d -enantiomers. These compounds were tested for their action on stimulation of amylase release from rat pancreatic acini and for their ability to inhibit binding of labeled CCK to rat pancreatic acini and guinea pig brain membranes. Some of these derivatives behaved as CCK receptor antagonists.     

Plasma vitamin D metabolites in a patient with sporadic hypophosphataemic osteomalacia (adult-onset type)

Sporadic hypophosphataemic osteomalacia (adult-onset type) was demonstrated in a 40-year-old man on the basis of severe osteomalacia, hypophosphataemia, hyperphosphaturia and glycinuria. Plasma immunoreactive parathyroid hormone (iPTH) concentration was 9.3 ng prot./ml (normal range: 4-8 ng prot./ml). Plasma 25-hydroxy-vitamin D and 24,25-dihydroxy-vitamin D concentrations were 11 and 2.4 ng/ml respectively. Basal 1 alpha,25-dihydroxy-vitamin D concentrations were slightly elevated (116 and 96 pg/ml) and increased to 240 pg/ml after 3 days on a low-phosphorus diet. The patient was put on oral treatment with 25-hydroxycholecalciferol (100 microgram per day) and phosphorus (1500 mg per day). On the 4th month on treatment, a clinical improvement was apparent. Plasma 25(OH)D was 44 ng/ml, plasma 1,25(OH)2D was 256 pg/ml. However, plasma phosphorus remained low (0.77 mmol/l). On the 9th month of treatment a radiological improvement was evident despite a persistent hypophosphataemia (0.68 mmol/l). These facts suggest in our patient the existence of a vitamin D-independent renal phosphorus leak.     

Magnesium Therapy in Ventricular Arrhythmias

Magnesium (Mg) is the known activator of 300 enzymes which govern energy utilization, cell permeability, and ionic membrane currents in the cardiac conducting cells. This may explain the antiarrhythmic efficacy of Mg in specific clinical settings, despite its only modest electrophysiological effects. This review summarizes the effect of Mg administration in four clinical conditions: in digitalis toxicity; in drug-induced torsade de pointes; in patients with chronic diuretic therapy; and in acute myocardial infarction. Mg effectively abolished ventricular tachyarrhythmias associated with digitalis intoxication. This effect of Mg is related to the activation of sodium-potassium ATP-ase, which is inhibited by digitalis. Drug-induced torsade de pointes was promptly abolished by Mg sulfate in the clinical setting. Experimental studies showed that Mg suppresses the early afterdepolarizations and the triggered activity responsible for occurrence of the arrhythmia. In diuretic-treated hypertensives, potassium depletion has been associated with increased ventricular ectopy and sudden death. Mg has been found to be an important adjuvant for intracellular repletion of potassium in these patients. Several randomized, double-blind studies in patients with acute infarction showed that Mg administered on admission improved survival or reduced the incidence of complex ventricular arrhythmias. Thus, Mg should be employed as first-line therapy in digitalis intoxication and drug-related torsade de pointes, and should be considered an important adjuvant therapy in hypertensives treated with diuretics and patients with acute myocardial infarction.     

Wallaby Serum Amyloid A Protein: cDNA Cloning, Sequence and Evolutionary Analysis

A serum amyloid A (SAA) clone was isolated from a Tammar wallaby cDNA library, the most distantly related mammalian species for which an SAA has been described to date. The clone predicts a premolecule of 127 amino acids with good homology to other mammalian SAAs, and consists of an 18 residue leader peptide and a mature protein of 109 amino acids. Evolutionary analysis at both the protein and nucleotide level indicate that the wallaby SAA clone clusters with the acute phase SAAs. However, as the SAA superfamily has undergone concerted evolution it is not possible to determine at this point which acute phase SAA it is most like. The grouping of wallaby SAA inside the acute phase SAA cluster demonstrates that at least some of the duplication events giving rise to multiple acute phase genes occured prior to the divergence of the eutherian and metatherian mammals.