A transient lesion in splenium of the corpus callosum in a patient with childhood-onset anorexia nervosa

OBJECTIVE: Although a transient lesion in the splenium of the corpus callosum (SCC) has been reported predominantly regarding patients with epilepsia, it is of rare occurrence, and its underlying biological basis remains unknown. This is a report of an SCC lesion in a patient with anorexia nervosa (AN). METHOD: The patient was a 15-year-old girl with childhood-onset (11 years) and a protracted course of AN. On admission, the patient showed no apparent neurological abnormalities. Magnetic resonance imaging (MRI) scans revealed a circumscribed lesion in the SCC. We treated her with nutritional rehabilitation supplemented with B vitamins. RESULTS: One month later, the lesion completely disappeared, but her weight was not restored. CONCLUSION: Treatment with B-vitamin supplementation may be beneficial for the treatment of patients with AN, in cases in which the disorder develops at an early age before brain maturation (i.e., childhood-onset cases), along with an enduring course of malnutrition.     

Genetic Alterations in Thyroid Tumor Progression: Association with p53 Gene Mutations

To identify the genetic events that must be involved in thyroid tumor progression, we initially investigated p53 gene alterations in 10 papillary adenocarcinomas, 4 follicular adenocarcinomas, and 8 undifferentiated carcinomas. Base substitutional mutations in exons 5 to 8 and loss of heterozygosity (LOH) of the p53 gene were not detected in papillary or follicular adenocarcinomas. However, 7 of 8 undifferentiated carcinomas were carrying base substitutional mutations, and LOH was detected in 3 of 5 informative cases. Furthermore, to verify that the p53 gene alterations are truly involved in tumor progression, DNA from individual foci of the four undifferentiated carcinomas coexisting with a differentiated focus and from one follicular adenocarcinoma with an undifferentiated focus was analyzed by direct sequencing and polymerase-chain-reaction-restriction-fragment-length polymorphism (PCR-RFLP). Base substitutional mutations in the p53 gene from exons 5 to 8 were identified exclusively in the undifferentiated foci, but not in the differentiated foci. LOH was observed in 3 of 4 informative undifferentiated foci. In one of these positive cases, LOH was observed in both papillary adenocarcinoma and undifferentiated carcinoma. However, a p53 gene mutation at codon 248 was detected in the undifferentiated carcinoma but not in the papillary adenocarcinoma. The results imply that LOH occurs first in papillary adenocarcinoma followed by a p53 mutation during the transition from papillary adenocarcinoma to undifferentiated carcinoma. Maintenance of LOH during tumor progression excludes the possibility that these different histological foci are derived from different origins and represents molecular evidence that undifferentiated carcinoma is very likely derived from preexisting papillary adenocarcinoma. Furthermore, these results strongly suggest that the mutated p53 gene plays a crucial role in de-differentiation during the progression of thyroid tumors.     

Mortality risk factors in chronic haemodialysis patients with infective endocarditis.

BACKGROUND: It is well documented that infective endocarditis (IE) is strongly associated with morbidity and mortality in haemodialysis (HD) patients. Less clear are the mortality risk factors for IE, particularly in an urban African-American dialysis population. METHODS: IE patients were identified from the medical records for the period from January 1999 to February 2004 and confirmed by Duke criteria. The patients were classified as 'survivors' and 'non-survivors' depending on in-hospital mortality, and risk factors for IE mortality were determined by comparing the two cohorts. Survivors were followed as out-patients with death as the endpoint. RESULTS: A total of 52 patients with 54 episodes of IE were identified. A catheter was the HD access in 40 patients (74%). Mitral valve (50%) was the commonest valve involved, and Gram-positive infections accounted for 87% of IE. In-hospital mortality was high (37%) and valve replacement was required for 13 IE episodes (24%). On logistic regression analyses, mitral valve disease [P = 0.002; odds ratio (OR) = 15.04; 95% confidence interval (CI) = 2.70-83.61] and septic embolism (P = 0.0099; OR = 9.56; 95% CI = 1.72-53.21) were significantly associated with in-hospital mortality. Using the Cox proportional hazards model, mitral valve involvement (P = 0.0008; hazard ratio 4.05; 95% CI = 1.78-9.21) and IE related to drug-resistant organisms such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus sp. (P = 0.016; hazard ratio 2.43; 95% CI = 1.18-5.00) were associated with poor outcome after hospital discharge. CONCLUSIONS: IE was associated with high mortality in our predominantly African-American dialysis population, when the mitral valve was involved, or septic emboli occurred and if MRSA or VRE were the causal organisms.     

Brachyury downstream notochord differentiation in the ascidian embryo

The ascidian tadpole represents the most simplified chordate body plan. It contains a notochord composed of just 40 cells, but as in vertebrates Brachyury is essential for notochord differentiation. Here, we show that the misexpression of the Brachyury gene (Ci-Bra) of Ciona intestinalis is sufficient to transform endoderm into notochord. Subtractive hybridization screens were conducted to identify potential Brachyury target genes that are induced upon Ci-Bra misexpression. Of 501 independent cDNA clones that were surveyed, 38 were specifically expressed in notochord cells. These potential Ci-Bra downstream genes appear to encode a broad spectrum of divergent proteins associated with notochord formation.     

Further genetic evidence for three psoriasis-risk genes: ADAM33, CDKAL1, and PTPN22

Predisposition to psoriasis is known to be affected by genetic variation in HLA-C, IL12B, and IL23R, and although other psoriasis-associated variants have been identified, incontrovertible statistical evidence for these markers has not yet been obtained. To help resolve this issue, we tested 15 single-nucleotide polymorphisms (SNPs) from 7 putative psoriasis-risk genes in 1,448 psoriasis patients and 1,385 control subjects; 3 SNPs, rs597980 in ADAM33, rs6908425 in CDKAL1 and rs3789604 in PTPN22, were significant with the same risk allele as in prior reports (one-sided P<0.05, false discovery rate<0.15). These three markers were tested in a fourth sample set (599 cases and 299 controls); one marker, rs597980, replicated (one-sided P<0.05) and the other two had odds ratios with the same directionality as in the original sample sets. Mantel-Haenszel meta-analyses of all available case-control data, including those published by other groups, showed that these three markers were highly significant (rs597980: P=0.0057 (2,025 cases and 1,597 controls), rs6908425: P=1.57 x 10(-5) (3,206 cases and 4,529 controls), and rs3789604: P=3.45 x 10(-5) (2,823 cases and 4,066 controls)). These data increase the likelihood that ADAM33, CDKAL1, and PTPN22 are true psoriasis-risk genes.     

Increased levels of serum soluble L-selectin in unmedicated patients with schizophrenia

OBJECTIVE: Numerous studies have linked schizophrenia with altered immune function. The selectin family of adhesion molecules plays a prominent role in immune/inflammatory responses. To further study the immunological processes in the pathophysiology of schizophrenia, we determined the serum levels of selectins in patients with schizophrenia. For specificity, we also investigated selectin levels in patients with major depression. METHOD: We studied 23 unmedicated patients with schizophrenia, 17 unmedicated patients with major depression, and 36 healthy subjects. The serum levels of three types of soluble-form selectin (sE-, sL- and sP-selectin) were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum sL-selectin levels were significantly higher in patients with schizophrenia than in either control subjects (p=0.005) or patients with major depression (p=0.02). No significant difference was found with regard to the level of either serum sE-selectin or sP-selectin. CONCLUSION: Elevated sL-selectin levels in patients with schizophrenia may represent immune system dysfunction and may be involved in the pathogenesis of the illness.     

Disruption of reelin signaling attenuates methamphetamine-induced hyperlocomotion

To clarify whether reelin signaling is involved in dopaminergic neurotransmission in the adult mouse brain, we investigated dopamine function in mice lacking reelin (reeler). We found that methamphetamine-induced locomotor activity is significantly attenuated in reeler mice. To elucidate the mechanism of this phenomenon, we first investigated presynaptic dopamine release; however, there were no significant differences in wildtype, heterozygous reeler and homozygous reeler mice. Next, we examined the locomotor response to intra-accumbens injection of dopamine D1 and D2 receptor agonists, and found that lack of reelin signaling results in decreases in both D1 and D2 receptor-mediated dopaminergic functions. In addition, we measured dopamine receptor binding in the striatum, and found that both D1 and D2 classes of dopamine receptors are reduced in reeler mice. Furthermore, we found that the phosphorylation levels of DARPP-32 are also changed by lack of reelin signaling. Finally, to distinguish between a developmental role of reelin or an acute role of reelin in adult mouse, we intraventricularly infused CR-50, a monoclonal antibody against reelin. Interestingly, infusion of CR-50 also significantly reduced methamphetamine-induced hyperlocomotion in wildtype mice, showing that reelin has an acute role in the dopaminergic system. These results indicate that reelin signaling plays a pivotal role in the dopaminergic system in adult mice, especially in postsynaptic levels.     

An association study between catechol-O-methyl transferase gene polymorphism and methamphetamine psychotic disorder

OBJECTIVE: A series of methamphetamine psychosis reveals two kinds of clinical courses of methamphetamine psychosis: transient type and prolonged type. Furthermore, paranoid psychosis sometimes recurs without methamphetamine reuse, referred to as spontaneous relapse. Dysfunction of central dopaminergic neurotransmission has been implicated in the pathogenesis of these psychiatric states. Catechol-O-methyl transferase appears to play a unique role in regulating synaptic dopaminergic activity. This study aimed to investigate whether a functional polymorphism of the catechol-O-methyl transferase gene would be involved in the development of these psychiatric states. BASIC METHODS: We examined the functional polymorphism of val 158 met (catechol-O-methyl transferase) in 143 patients with methamphetamine psychosis and 200 healthy controls in Japan. The patients were divided into subgroups by several characteristic clinical features. MAIN RESULTS: We found a significant difference in the catechol-O-methyl transferase allele frequency between patients with spontaneous relapse and the controls (P=0.018, odds ratio=1.67). Odds ratio implied that the patients with spontaneous relapse had a nearly 1.7-fold higher rate of the low activity alleles (met) than the controls. CONCLUSIONS: Our results indicate that the met allele frequency of the catechol-O-methyl transferase is associated with patients who experienced methamphetamine psychosis and spontaneous relapse, suggesting that patients with a met allele appear to be at increased risk of an adverse response to methamphetamine.     

Endocrine tumors of the ileum: factors correlated with survival

AIM: To evaluate the most important factors correlated with survival in patients with endocrine tumors of the ileum, both at the time of diagnosis and during the follow-up period. METHODS: Fifty-nine patients with ileal endocrine tumors diagnosed in our institution between 1990 and 2004 were studied. RESULTS: The study included 36 men (61%) and 23 women (39%). The median age of the patients at the time of diagnosis was 61.4 (range 18-83) years. The median follow-up period was 71.9 (range 5-287) months. Forty patients (67.8%) were still alive at the end of the study; the median survival time was 172 months, and the 5-year survival rate was 78.9%. By univariate analysis, the survival rate was significantly related to female sex (p = 0.024) and flushing alone (p = 0.028) and associated with diarrhea at diagnosis (p = 0.015), weight loss at diagnosis (p = 0.038), Ki-67 level (p = 0.025), stage of disease at diagnosis (p = 0.012), presence of liver metastases at follow-up (p = 0.005), presence of diffuse metastases at diagnosis (p = 0.005) and at follow-up (p = 0.007), and type of surgical approach (overall: p = 0.018; not operated vs. radical surgery: p = 0.008; not operated vs. palliative surgery: p = 0.045). Using multivariate analysis, only female gender (p = 0.012) and the presence of liver metastases at follow-up (p = 0.004) were significantly related to survival. CONCLUSION: In the present study, female gender and the appearance of liver metastases at follow-up seem to be the main conditions which determine the poor prognosis of patients with ileal endocrine tumors.     

Caprylic acid infusion acts in the liver to decrease food intake in rats

Hepatic portal vein (HPV) infusion of the medium chain fatty acid caprylic acid (CA; 2.3 mg/min, 40 microl/min) for 90 min beginning at dark onset in 18-h food-deprived male rats reduced the size of the first nocturnal meal about 40% (P < 0.01) and reduced 24-h food intake by about 15% (P < 0.001). Identical infusions into the vena cava affected neither initial meal size nor food intake. HPV CA infusion attenuated the postprandial decreases in plasma free fatty acids (P < 0.01) and beta-hydroxybutyrate (P < 0.01). HPV CA infusions did not significantly reduce nocturnal saccharine intake in a two-bottle conditioned taste aversion test, and there was no association between the saccharine intake on the test day and the feeding-inhibitory effect of CA on the conditioning day. HPV CA infusion did not affect plasma concentrations of corticosterone or of the pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha. HPV CA infusion did not increase plasma concentration of the liver enzyme alanine aminotransferase, but did increase plasma concentration of gamma-glutamyl transferase, although not into the pathophysiological range. These data indicate that CA acts in the liver to produce a signal that inhibits feeding and that this inhibitory effect may be related to increases in hepatic fatty acid oxidation rather than be the result of aversion or toxicity.