Aggressive behavior linked to corticotropin-reactive autoantibodies.

BACKGROUND: Altered stress response is characteristic for subjects with abnormal aggressive and antisocial behavior, but the underlying biological mechanisms are unclear. We hypothesized that autoantibodies (autoAbs) directed against several stress-related neurohormones may exist in aggressive subjects. METHODS: Using enzyme-linked immunosorbent assay, we studied whether autoAbs directed against corticotropin (ACTH), alpha-melanocyte-stimulating hormone (alpha-MSH), oxytocin, and vasopressin are present in serum of male subjects with conduct disorder and prisoners with history of violence. Healthy blood donors served as control subjects. RESULTS: Both conduct disorder and prisoners groups displayed strongly increased levels of ACTH-reactive immunoglobulin G (IgG) and immunoglobulin M (IgM) autoAbs compared with control subjects. Levels of oxytocin-reactive IgM autoAbs were slightly increased in both groups of aggressive subjects, whereas levels of vasopressin-reactive IgG and IgM autoAbs were lower only in conduct disorder. No differences in the levels of alpha-MSH-reactive autoAbs were found between aggressive and control subjects. CONCLUSIONS: High levels of ACTH-reactive autoAbs as well as altered levels of oxytocin- and vasopressin-reactive autoAbs found in aggressive subjects may interfere with the neuroendocrine mechanisms of stress and motivated behavior. Our data suggest a new biological mechanism of human aggressive behavior that involves autoAbs directed against several stress-related neurohormones.     

Intravenous cidofovir treatment for recalcitrant warts in the setting of a patient with myelodysplastic syndrome

Cidofovir is an acyclic nucleoside phosphonate with broad-spectrum activity against DNA viruses, including human papilloma virus (HPV). However, data on the efficacy of cidofovir in an immunosuppressive setting remain contradictory. We report for the first time on the promotion of the healing of recalcitrant warts in a patient with myelodysplastic syndrome with intravenous cidofovir treatment.     

Morphology of corticotectal cells in the primary visual cortex of hooded rats

In primary visual cortex of hooded rats, pyramidal cells in layer V may be classified as long, medium, or short, on the basis of the layer in which the apical dendrite terminates. The present study determines which of these types of pyramidal cells project to the superior colliculus. Two different strategies were used to label corticotectal cells with horseradish peroxidase (HRP). In the first set of experiments, a large number of corticotectal cells were labeled by retrograde transport following injection of HRP into the superior colliculus. In the second set of experiments, single unit recording was used to identify corticotectal cells physiologically by antidromic activation from the superior colliculus. These cells were then impaled and labeled by intracellular iontophoresis of HRP. The results from both techniques suggest that only long pyramidal cells send an axon to the superior colliculus. These cells are distinguished by an apical dendrite that extends into layer I. We conclude that in hooded rats corticotectal cells in primary visual cortex are the long pyramids in layer V.     

Glial cell line-derived neurotrophic factor-dependent recruitment of Ret into lipid rafts enhances signaling by partitioning Ret from proteasome-dependent degradation

The receptor tyrosine kinase (RTK) Ret is activated by the formation of a complex consisting of ligands such as glial cell line-derived neurotrophic factor (GDNF) and glycerophosphatidylinositol-anchored coreceptors termed GFRalphas. During activation, Ret translocates into lipid rafts, which is critical for functional responses to GDNF. We found that Ret was rapidly ubiquitinated and degraded in sympathetic neurons when activated with GDNF, but, unlike other RTKs that are trafficked to lysosomes for degradation, Ret was degraded predominantly by the proteasome. After GDNF stimulation, the majority of ubiquitinated Ret was located outside of lipid rafts and Ret was lost predominantly from nonraft membrane domains. Consistent with the predominance of Ret degradation outside of rafts, disruption of lipid rafts in neurons did not alter either the GDNF-dependent ubiquitination or degradation of Ret. GDNF-mediated survival of sympathetic neurons was inhibited by lipid raft depletion, and this inhibitory effect of raft disruption on GDNF-mediated survival was reversed if Ret degradation was blocked via proteasome inhibition. Therefore, lipid rafts sequester Ret away from the degradation machinery located in nonraft membrane domains, such as Cbl family E3 ligases, thereby sustaining Ret signaling.     

Late side-effects with cosmetic relevance following soft X-ray therapy of cutaneous neoplasias

Background Cosmetic changes are to be expected after radiotherapy for skin tumours. Objectives This study aimed to answer the questions: How frequent are cosmetic changes after soft X‐ray therapy? Do treatment parameters, tumour thickness, localization and size of the irradiated field have a major influence? Were patients irritated by the visual appearance of the irradiated field? Methods In total, 2474 examinations of 1149 irradiated fields were performed. Results Hypopigmentation was found in 64.7% of examinations more than 90 days after therapy, teleangiectases in 43.1%, erythema in 24.8%, and hyperpigmentation in 16.8%. The frequency of hypopigmentation, teleangiectases and hyperpigmentation increased with time from X‐ray exposure; more than 4 years after therapy hypopigmentation was diagnosed in 91.8% and teleangiectases in 82.2% of examinations. Total dose, the time–dose–fractionation factor (TDF), field size and dose per fraction were significantly related to the frequency of cosmetic changes. Incidence rates of cosmetic changes differed by less than 15% if different treatment conditions were compared: thicker vs. thinner tumours, larger vs. smaller fields, higher vs. lower total doses, doses per fraction, and TDF. Frequencies of hypopigmentation, teleangiectases, erythema and hyperpigmentation differed by more than 15% between some localizations on the head. Women reported irritation by the visual appearance of the irradiated field in 12.6% of 1116 interviews, and men in 4.4% of 1284 interviews. Conclusions Cosmetic changes after soft X‐ray therapy are relatively frequent. Treatment parameters, tumour thickness and field size have only a minor influence. Few patients, but more women than men, were irritated by the visual appearance of the irradiated field.     

HYPOKALEMIA IN THE ELDERLY: IS IT ALWAYS DIURETIC-INDUCED?

SUMMARY Serum potassium was measured within 24 hours in 156 patients (48 male, 108 female) with an average age of 81.9 years admitted to the unit with acute illness. Of the 156 patients, 88 (56.4%) were taking diuretics (none was on ACE inhibitors); 20 patients (12.8%) were also on digoxin therapy. In all, 24 patients (16%) had hypokalaemia and 3 (2%) hyperkalaemia. Hypokalaemia was seen in patients associated with acute illness. There was no significant difference between the diuretic and non-diuretic groups. Monitoring of serum potassium is not routinely indicated to detect hypokalaemia in patients on diuretic therapy except in those with severe hepatic or renal impairment or those on digoxin.     

Antigenicity of low molecular weight surfactant species.

The authors tested the antigenicity of human lung surfactant isolated from amniotic fluid. Mice and rabbits were immunized. Rabbit polyclonal antisera to these surfactant preparations were absorbed with normal human plasma proteins. Polyclonal antisera reacted with both high molecular weight (35 kd) surfactant apoprotein and to lower molecular weight species, both 18 kd and 9 kd. Mice were used to generate monoclonal antibodies to surfactant. Enzyme-linked immunosorbant assay was used to identify five monoclonal antibodies that reacted with surfactant. By Western blot analysis, all of these recognized a low molecular weight surfactant species (9 kd) that could be either SP-B or SP-C. One reacted with a 37 kd protein in the surfactant preparation, consistent with SP-A. One monoclonal antibody also recognized a higher molecular weight species (44 kd) of unknown origin. The ability of antisera and monoclonal antibodies to inhibit the functional activity of surfactant was assayed using a pulsating bubble surfactometer. Rabbit polyclonal antisera inhibited initial surface adsorption to equilibrium surface tension and increased the minimum surface tension after 1 and 5 minutes of initiation of pulsations. This inhibitory activity of the antisera was noted in divalent F(ab')2 fragments. Monovalent F(ab) fragments and control normal rabbit sera did not inhibit surfactant function in this assay. Of the anti-surfactant monoclonal antibodies that reacted with surfactant by ELISA and Western blot, three inhibited its capacity to lower surface tension on the pulsating bubble apparatus. The other two monoclonal antibodies showed no functional inhibitory activity. It is concluded that both the 35 kd SP-A and the 9 kd proteins of human surfactant are highly immunogenic and partially crossreactive. Resulting antibodies could alter the ability of surfactant to perform its physiologic function, ie, to lower surface tension.     

Homozygosity mapping of achromatopsia to chromosome 2 using DNA pooling

Achromatopsia is an autosomal recessive disease of the retina, characterized clinically by an inability to distinguish colors, impaired visual acuity, nystagmus and photophobia. A genome-wide search for linkage was performed using an inbred Jewish kindred from Iran. To facilitate the genome-wide search, we utilized a DNA pooling strategy which takes advantage of the likelihood that the disease in this inbred kindred is inherited by all affected individuals from a common founder. Equal molar amounts of DNA from all affected individuals were pooled and used as the PCR template for short tandem repeat polymorphic markers (STRPs). Pooled DNA from unaffected members of the kindred was used as a control. A reduction in the number of alleles in the affected versus control pool was observed at several loci. Upon genotyping of individual family members, significant linkage was established between the disease phenotype and markers localized on chromosome 2. The highest LOD score observed was 5.4 (theta = 0). When four additional small unrelated families were genotyped, the combined peak LOD score was 8.2. Analysis of recombinant chromosomes revealed that the disease gene lies within a 30 cM interval which spans the centromere. Additional fine-mapping studies identified a region of homozygosity in all affected individuals, narrowing the region to 14 cM. A candidate gene for achromatopsia was excluded from this disease interval by radiation hybrid mapping. Linkage of achromatopsia to chromosome 2 is an essential first step in the identification of the disease-causing gene.