Gene structure of the goldfish agouti-signaling protein: a putative role in the dorsal-ventral pigment pattern of fish

One of the most successful chromatic adaptations in vertebrates is the dorsal-ventral pigment pattern in which the dorsal skin is darkly colored, whereas the ventrum is light. In fish, the latter pattern is achieved because a melanization inhibition factor inhibits melanoblast differentiation and supports iridophore proliferation in the ventrum. In rodents, the patterned pigmentation results from regional production of the agouti-signaling protein (ASP). This peptide controls the switch between production of eumelanin and pheomelanin by antagonizing alphaMSH effects on melanocortin receptor (MCR) 1 in the melanocytes. In addition, ASP inhibits the differentiation and proliferation of melanoblast. Thus, the mammalian ASP may be homologous to the poikilotherm melanization inhibition factor. By screening of a genomic library, we deduced the amino acid sequence of goldfish ASP. The ASP gene is a four-exon gene spanning 3097 bp that encodes a 125-amino acid precursor. Northern blot analysis identified two different ASP mRNAs in ventral skin of red- and black-pigmented and albino fish, but no expression levels were observed in the dorsal skin of the same fish. The dorsal-ventral expression polarity was also detected in both black dorsally pigmented fish and albino fish. Pharmacological studies demonstrate that goldfish ASP acts as a melanocortin antagonist at Fugu MC1R and goldfish MC4R. In addition, goldfish ASP inhibited Nle4, D-Phe7-MSH-stimulated pigment dispersion in medaka melanophores. Our studies support agouti signaling protein as the melanization inhibition factor, a key factor in the development of the dorsal-ventral pigment pattern in fish.     

Severe autoimmune neutropenia associated with acute autoimmune hepatitis

A 49-year-old previously healthy female presented with acute hepatitis and severe neutropenia. A diagnosis of type 1 autoimmune hepatitis was made based on the histological appearance of a liver core biopsy, positive anti-smooth muscle antibodies, and positive anti-neutrophil cytoplasmic antibody (atypical ANCA). Hemogram revealed mild leukopenia with severe neutropenia (absolute neutrophil count 256/mm³), normal hemoglobin and mild thrombocytopenia (115000/mm³). A bone marrow biopsy and aspirate had a normal karyotype, increase in granulopoiesis, prominence of promyelocytes (31%) and absence of mature granulocytes. Anti-neutrophil antibodies were detected in the patient’s blood. Therapy was directed at the underlying hepatitis with resolution of neutropenia without the use of colony-stimulating factors.     

Memory impairment induced by IL-1β is reversed by α-MSH through central melanocortin-4 receptors

Interleukin-1beta (IL-1β) significantly influences memory consolidation. Treatments that raise the level of IL-1β in the brain, given after training, impair contextual fear conditioning. The melanocortin α-MSH exerts potent anti-inflammatory actions by physiologically antagonizing the effect of pro-inflammatory cytokines. Five subtypes of melanocortin receptors (MC1R–MC5R) have been identified, with MC3R and MC4R predominating in the central nervous system. The present experiments show that injection of IL-1β (5 ng/0.25 μl) in dorsal hippocampus up to 15 min after training decreased freezing during the contextual fear test. The treatment with IL-1β (5 ng/0.25 μl) 12 h after conditioning cause amnesia when animals were tested 7 days post training. Thus, our results also demonstrated that IL-1β can influence persistence of long-term memory. We determined that animals previously injected with IL-1β can acquire a new contextual fear memory, demonstrating that the hippocampus was not damaged. Treatment with α-MSH (0.05 μg/0.25 μl) blocked the effect of IL-1β on contextual fear memory. Administration of the MC4 receptor antagonist HS014 (0.5 μg/0.25 μl) reversed the effect of α-MSH. However, treatment with γ-MSH (0.5 μg/0.25 μl), an MC3 agonist, did not affect IL-1β-induced impairment of memory consolidation. These results suggest that α-MSH, through central MC4R can inhibit the effect of IL-1β on memory consolidation.     

Cardiac involvement in hypertension. A non-invasive study of patients with previous malignant hypertension and ''benign'' hypertension

Non-invasive assessment of cardiac hypertrophy and functionwas made in 15 male patients with previous malignant hypertensionas well as in 15 matched patients with ‘benign’hypertension and 15 matched normotensive control subjects. Inthe group with previous malignant hypertension, echocardiographyrevealed increased (>1.3 cm) thickness of the interventricularseptum in all but one patient (93%) as compared to 67% in thegroup with ‘benign’ hypertension and 7% in the controlsubjects. Other indices of left ventricular hypertrophy, includingleft ventricular mass, were also more pronounced in the hypertensivegroups and significantly higher than in the control subjects. Conventional ECG appeared to be much less sensitive in detectingleft ventricular hypertrophy, in particular the traditional‘combined LVH criteria’ (high voltage+ST-T changes)which were positive in only 27% of the patients with previousmalignant hypertension as compared to 0% in the other two groups.With less stringent and less specific criteria the diagnosticyield could be increased to 60 and 40% in the two hypertensivegroups. Regarding left ventricular performance, an increased a/H ratio(15.4, 13.4 and 8.5%, respectively) and a lower E-F slope (67,94 and 114 mm/s, respectively) indicated abnormal diastolicfunction in the hypertensive groups. On the other hand, indicesof systolic function (ejection fraction and mean velocity ofcircumferential fiber shortening) were found to be normal inthe hypertensive groups. In the patients with previous malignanthypertension these indices appeared to be ‘supranormal’[i.e. significantly higher values were found (77 v. 70%, P <0.01and 1.31 v. 1.08 circ/s, P<0.01, respectively) than in thenormotensive control subjects].     

Ocular trauma. Observation in 105 patients

A report on 105 cases of ocular trauma hospitalized in St. Joseph's Hospital in Reykjavik during a 12-year period is presented. Of these patients 94 were males and 11 females. Thirty-nine patients were children, and only six patients were older than 50 years. Most common were occupational accidents (43 cases) and of these 29 were connected to industry. Other main causes were traffic accidents, sport and dangerous play by children. Of the total 105 cases, 70 had perforation of the bulb. All but nine underwent some kind of operation, and enucleation was performed in 10 patients. Nearly two thirds of the patients were hospitalized within six hours of the accident and 84% within 24 h.     

A genome-wide study of allelic imbalance in human testicular germ cell tumors using microsatellite markers

Testicular germ cell tumors (TGCT) arise by multistep carcinogenesis pathways involving selective losses and gains of chromosome material. To locate cancer genes underlying this selection, we performed a genome-wide study of allelic imbalance (AI) in 32 tumors, using 710 microsatellite markers. The highest prevalence of AI was found at 12p, in line with previous studies finding consistent gain of the region in TGCTs. High frequency of AI was also observed at chromosome arms 4p, 9q, 10p, 11q, 11p, 13q, 16q, 18p, and 22q. Within 39 candidate regions identified by mapping of smallest regions of overlap (SROs), the highest frequency of AI was at 12p11.21 approximately p11.22 (62%), 12p12.1 approximately p13.1 (53%), 12p13.1 approximately p13.2 (53%), 11q14.1 approximately q14.2 (53%), 11p13 approximately p14.3 (47%), 9q21.13 approximately q21.32 (47%), and 4p15.1 approximately p15.2 (44%). Two genes known to be involved in cancer reside in these regions, ETV6 at 12p13.2 (TEL oncogene) and WT1 at 11p13. We also found a significant association (P = 0.02) between AI at 10q21.1 approximately q22.2 and higher clinical stage. This study contributes to the ongoing search for genes involved in transformation of germ cells and provides a useful reference point to previous studies using cytogenetic techniques to map chromosome changes in TGCTs.     

A debate on current eating disorder diagnoses in light of neurobiological findings: is it time for a spectrum model?

ABSTRACT: BACKGROUND: Sixty percent of eating disorders do not meet criteria for anorexia- or bulimia nervosa, as defined by the Diagnostic and Statistical Manual version 4 (DSM-IV). Instead they are diagnosed as 'eating disorders not otherwise specified' (EDNOS). Discrepancies between criteria and clinical reality currently hampering eating disorder diagnoses in the DSM-IV will be addressed by the forthcoming DSM-V. However, future diagnoses for eating disorders will rely on current advances in the fields of neuroimaging and genetics for classification of symptoms that will ultimately improve treatment. DISCUSSION: Here we debate the classification issues, and discuss how brain imaging and genetic discoveries might be interwoven into a model of eating disorders to provide better classification and treatment. The debate concerns: a) current issues in the classification of eating disorders in the DSM-IV, b) changes proposed for DSM-V, c) neuroimaging eating disorder research and d) genetic eating disorder research. SUMMARY: We outline a novel evidence-based 'impulse control' spectrum model of eating disorders. A model of eating disorders is proposed that will aid future diagnosis of symptoms, coinciding with contemporary suggestions by clinicians and the proposed changes due to be published in the DSM-V.     

Current practice in Staphylococcus aureus screening and decolonization

We surveyed infectious disease physicians to determine their preoperative Staphylococcus aureus screening and decolonization practices. Sixty percent reported preoperative screening for S. aureus. However, specific screening and decolonization practices are highly variable, are focused almost exclusively on methicillin-resistant S. aureus, and do not include testing for mupirocin or chlorhexidine resistance.