Uncoupling of stem cell inhibition from monocyte chemoattraction in MIP-1alpha by mutagenesis of the proteoglycan binding site

We have studied the role of proteoglycans in the function of Macrophage Inflammatory Protein-1 alpha (MIP-1alpha), a member of the proteoglycan binding chemokine family. Sequence and peptide analysis has identified a basic region within MIP-1alpha which appears to be the major determinant of proteoglycan binding and we have now produced a mutant of MIP-1alpha lacking the basic charges on two of the amino acids within this proteoglycan binding site. This mutant (Hep Mut) appears to have lost the ability to bind to proteoglycans. Bioassay of Hep Mut indicates that it has retained stem cell inhibitory properties but has a compromised activity as a monocyte chemoattractant, thus suggesting uncoupling of these two properties of MIP-1alpha. Receptor studies have indicated that the inactivity of Hep Mut on human monocytes correlates with its inability to bind to CCR1, a cloned human MIP-1alpha receptor. In addition, studies using proteoglycan deficient cells transfected with CCR1 have indicated that the proteoglycan binding site in MIP-1alpha is a site that is also involved in the docking of MIP-1alpha to the monocyte receptor. The site for interaction with the stem cell receptor must therefore be distinct, suggesting that MIP-1alpha utilizes different receptors for these two different biological processes.     

Fish oils lower rat plasma and hepatic, but not immune cell alpha-tocopherol concentration

These studies were designed to measure the impact of different fish oil sources of dietary (n-3) polyunsaturated fatty acid on the alpha-tocopherol content of rat immune cells. In the first experiment, rats were fed diets containing either lard, corn oil, menhaden fish oil or cod liver oil. In the second study, sardine fish oil replaced corn oil. Dietary fat source did not significantly influence body weights or the yield of immune cells in either study. In both studies, plasma and liver alpha-tocopherol concentrations were significantly lower in (n-3) polyunsaturated fatty acid-fed rats than in rats fed lard. In the first study, immune cell alpha-tocopherol concentrations followed those observed in the plasma and liver. These concentrations closely paralleled the amount of RRR-alpha-tocopheryl acetate added to diets and not the total vitamin E present, which was the same for all treatment groups. However, in the second study, alpha-tocopherol concentration of immune cells was not significantly different among rats fed lard, menhaden fish oil, and sardine fish oil. In that study both the amount and form of vitamin E were carefully balanced across dietary treatment groups. In conclusion, despite having similar amounts of (n-3) polyunsaturated fatty acids, two out of three fish oils tested did not lower immune cell alpha-tocopherol concentration even in the face of significantly reduced plasma and liver alpha-tocopherol concentrations.     

Effect of immunotherapy on sCD23 levels in patients allergic to Hymenoptera venom

BACKGROUND: sCD23 is the designation given to the low affinity IgE receptor. The soluble fragment of this receptor (sCD23) participates in the regulation of IgE synthesis. OBJECTIVE: The purpose of this study is to examine the effect of a venom immunotherapy regimen on sCD23 levels. METHODS: We measured sCD23 levels by ELISA in Hymenoptera venom-allergic patients (positive skin tests and a history of systemic reactions to Hymenoptera sting) in serial sera collected over a course of venom immunotherapy with a mean duration of 54 months. Mean pre-sCD23 and post-sCD23 levels were compared using a Student's two-tailed t test. RESULTS: sCD23 levels were found to be unchanged over the course of venom immunotherapy. CONCLUSIONS: This is the first longitudinal study that has been done. It suggests that while both immunotherapy and sCD23 are known to be involved in the regulations of IgE synthesis in the atopic patient, the immunomodulation seen in venom immunotherapy is not mediated through sCD23 in any simple regulatory manner.     

Postcatheterization retroperitoneal hematoma due to spontaneous lumbar arterial hemorrhage

Non-traumatic stereotyped postictal purpura is rare. A 25-year-old woman presented with right facial, cheek and periorbital purpuric eruptions that occurred after secondarily generalized tonic-clonic seizures. The stereotyped, invariably right-sided facial skin eruption, which resolved in 48 hours, falsely raised concerns of spousal abuse. Possible pathophysiological mechanisms include: (a) valsalva-induced capillary hypertension with secondary purpura, (b) ictal corticolimbic stimulation of the autonomic nervous innervation of facial vasomotor structures, and (c) trigeminal-mediated local release of vasoactive substances. Although rare, such stereotyped patterns of purpura should be recognized to avoid incorrect attribution of spousal abuse.     

Peptides and anxiety: a dose-response evaluation of pentagastrin in healthy volunteers

A large body of data suggest that brain cholecystokinin (CCK) systems are involved in the regulation of anxiety, and numerous studies have demonstrated that CCK-4, a CCKB agonist, reliably induces panic attacks in patients with panic disorder. Recently, pentagastrin, a commercially available CCKB agonist, has been reported to have similar anxiogenic properties. To further explore the utility of pentagastrin as a challenge agent and to determine whether its effects are dose-related, a dose-response study was conducted in ten healthy volunteers. Pentagastrin (0.2 microgram/kg, 0.6 microgram/kg and 1.0 microgram/kg) and inactive placebo were infused over one minute on four separate challenge days in a double-blind fashion. Subjects received pentagastrin while participating in a structured social interaction task. Repeated measures of anxiety, blood pressure, pulse, ACTH, and cortisol were taken at baseline and postinfusion. Pentagastrin administration led to increases in anxiety, pulse, ACTH, cortisol and physical symptoms of panic, in a dose-related manner. Participation in the social interaction task led to increases in measures of anxiety as well as increases in pulse and blood pressure. Few differences were found between the 0.2 microgram/kg dose of pentagastrin and placebo, or between the 0.6 microgram/kg and the 1.0 microgram/kg doses of pentagastrin. These findings support the notion that CCK systems are involved in the regulation of anxiety, and suggest that the 0.6 microgram/kg dose may be optimal for increasing symptoms of anxiety while minimizing unpleasant side effects. The powerful anxiogenic effects of the social interaction task underscore the importance of contextual variables in challenge studies.     

Lethal infection of newborn mice, caused by hepatitis C virus

Intracerebral infection of mice aged 2-3 days with hepatitis C virus (HCV) from chronically infected suckling mouse brain cultures and porcine embryo cells resulted in the death of animals after 12-14 days. Repeated passages of HCV in animals decreased the incubation period to just 3-4 days. Blood serum of surviving mice collected during the 4th week postinfection contained antiHCV antibodies detected by enzyme immunoassay and hemagglutination inhibition test. The results are proof of creation of a new in vivo model of experimental HCV infection.