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Research was conducted to describe the structure of the gene for human protein Z. The protein's structure was compared with those of other vitamin K-dependent proteins, including protein C, factors VII, X and IX. The genomic clones were determined using a cDNA coding for human protein Z while the DNA sequence of an insert was obtained by the dideoxynucleotide technique. Results showed that the genomic clones were characterized by a SacI fragment that differed in size.

Familial Mediterranean fever (FMF) can be classified into typical and incomplete/atypical types. While accompanying severe abdominal pain by serositis is characteristic of typical FMF, periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis syndrome (PFAPA)-like symptoms have been observed in atypical FMF harbouring P369S-R408Q mutations in exon 3 of MEFV gene (i.e. exon 3 variants), treatment of which is often difficult. This study describes the clinical findings of a patient with FMF exon 3 variants and the effectiveness of tocilizumab therapy. We also surveyed the literature to identify the characteristics and treatments of MEFV exon 3 variants. An 8-year-old boy with FMF experiencing recurrent fever accompanied by strong abdominal pain and PFAPA-like symptoms was found to possess heterozygous alterations involving E148Q/P369S/R408Q. Corticosteroids produced a partial response, colchicine was largely ineffective, and a persistent cure was not obtained by tonsillectomy. However, further attacks were completely prevented by monthly administration of tocilizumab. We believe this to be a rare case of paediatric FMF exon 3 variants that showed a complete response to tocilizumab. A comprehensive review of 23 reported cases of FMF carrying P369S-R408Q alterations revealed that patients displayed various manifestations, such as abdominal pain, uveitis, osteomyelitis, and renal failure with amyloidosis, in addition to PFAPA-like symptoms. A wide range of responses was seen for colchicine, infliximab, etanercept, adalimumab, anakinra and another adult case of tocilizumab treatment. Tocilizumab therapy for FMF exon 3 variants may prevent the development of amyloidosis, and improve patient quality of life from recurrent fever attacks. [ABSTRACT FROM AUTHOR]

Only a few studies have examined the relationships between affective symptoms, cognitive function (e.g. verbal fluency), quality of life (QOL), and brain activation in a nonclinical population. The aim of the present study was to assess these relationships and examine the underlying cortical mechanisms in a nonclinical population. Fifty-two healthy male volunteers were assessed for depressive symp- toms using the Zung Self-Rating Depression Scale (SDS), for apathy using the Apathy Scale, and QOL using the Medical Outcomes Study short-form 36-item questionnaire (SF36). The volunteers also performed a verbal fluency test (VFT) while hemoglobin concentration changes were assessed on the surface of the frontal cortex using 24-channel near-in-frared spectroscopy (NIRS).The SDS and Apathy Scale scores showed significant negative correlations with the scores of most of the SF36 subscales. Frontal activation had a significant negative correlation with the SDS scores and the Apathy Scale. These results suggest that the degree of affective symptoms is associated with a lower QOL in a nonclinical population, and that cortical hypoactivation during a VFT measured by NIRS may objectively identify individuals with a high degree of affective symptoms. [ABSTRACT FROM AUTHOR]

Background: Several reports on patients with chronic schizophrenia suggest that atypical versus typical antipsychotics are expected to lead to better quality of life (QOL) and cognitive function. Our aim was to examine the association of chronic treatment with typical or atypical antipsychotics with cognitive function, psychiatric symptoms, QOL, and drug-induced extrapyramidal symptoms in long-hospitalized patients with schizophrenia. Methodology and Principal Findings: The Hasegawa Dementia Scale-Revised (HDS-R), Brief Psychiatric Rating Scale (BPRS), the Schizophrenia Quality of Life Scale, translated into Japanese (JSQLS), and the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) were used to evaluate cognitive function, psychiatric symptoms, QOL, and drug-induced extrapyramidal symptoms. We examined the correlation between the dose of antipsychotics and each measure derived from these psychometric tests. The student t-test was used to compare scores obtained from psychometric tests between patients receiving typical and atypical antipsychotics. Results showed significant correlations between chlorpromazine (CPZ)- equivalent doses of typical antipsychotics and atypical antipsychotics, and the total BPRS score and BPRS subscale scores for positive symptoms. CPZ-equivalent doses of typical antipsychotics were correlated with the JSQLS subscale score for dysfunction of psycho-social activity and DIEPSS score. Furthermore, the total BPRS scores, BPRS subscale score for positive symptoms, the JSQLS subscale score for dysfunction of psycho-social activity, and the DIEPSS score were significantly higher in patients receiving typical antipsychotics than atypical antipsychotics. Conclusion and Significance: These findings suggest that long-term administration of typical antipsychotics has an unfavorable association with feelings of difficulties mixing in social situations in patients with chronic schizophrenia. [ABSTRACT FROM AUTHOR]

The therapeutic use of interferon-alpha (IFN-α), a proinflammatory cytokine, is known to cause various neuropsychiatric adverse effects. In particular, depression occurs in 30–45% of patients, frequently interrupting treatment. IFN-α-treated animals also show depression-like behaviors. However, mechanisms underlying the depression caused by IFN-α remain to be defined. Recently, a decrease in adult hippocampal neurogenesis was revealed as a possible neuropathological mechanism of depression. Therefore, we investigated the effect of subchronic IFN-α treatment on neurogenesis in the adult rat dentate gyrus (DG). Immediately after the administration of IFN-α for 1 week, a decrease in the number of 5-bromo-deoxyuridine-labeled proliferating cells was observed in the DG; however, no effect was detected on the expression of mature neuronal phenotype in the newly formed cells 3 weeks later. Also, an increase in the level of interleukin-1beta (IL-1β), a major proinflammatory cytokine, was observed in the hippocampus following the administration of IFN-α. Furthermore, coadministration of an IL-1 receptor antagonist completely blocked the IFN-α-induced suppression of the cell-proliferative activity in the DG. Our results indicate that IFN-α suppresses neurogenesis in the DG, and that IL-1β plays an essential role in the suppression. The decreased cell proliferation caused by IFN-α-induced IL-1β may be responsible, at least in part, for IFN-α-induced depression.Neuropsychopharmacology (2006) 31, 2619–2626. doi:10.1038/sj.npp.1301137; published online 5 July 2006 [ABSTRACT FROM AUTHOR]

The article analyzes phenothiazines in human body fluids through the use of disk solid-phase extraction and liquid chromatography. Perazine, perphenazine, prochlorperazine, propericiazine, thioproperazine, trifluoperazine and flupentixol were found to be extractable from human plasma and urine samples. Disk solid-phase extraction was used. Drugs were eluted with chloroform-acetonitrile. Regression equations for the phenothiazine derivatives showed excellent linearity.

Lithium has long been one of the primary drugs used to treat bipolar mood disorder. However, neither the etiology of this disease nor the therapeutic mechanism(s) of this drug is well understood. Several lines of clinical evidence suggest that lithium has neurotrophic actions. For example chronic lithium treatment increases the volume of gray matter and the content of N-acetyl-aspartate, a cell survival marker, in bipolar mood disorder patients (Moore et al., 2000). Moreover, treatment with this mood-stabilizer suppresses the decrease in the volume of the subgenual pre-frontal cortex found in bipolar patients (Drevets, 2001). To elucidate molecular mechanisms underlying the neuroprotective and neurotrophic actions of lithium, we employed a preparation of cultured cortical neurons prepared form embryonic rats. We found that treatment with therapeutic doses (0.2-1.2 mM) of lithium robustly protects cortical neurons from multiple insults, notably glutamate-induced excitotoxicity. The neuroprotection against glutamate excitotoxicity is time-dependent, requiring treatment for 5-6 days for maximal effect, and is associated with a reduction in NMDA receptor-mediated Ca2+ influx. The latter is correlated with a decrease in Tyrosine 1472 phosphorylation levels in the NR2B subunit of NMDA receptors and a loss of Src kinase activity which is involved in NR2B tyrosine phosphorylation. Neither the activity of total tyrosine protein kinase nor that of tyrosine protein phosphatase is affected by this drug, indicating the selectivity of the modulation. Lithium neuroprotection against excitotoxicity is inhibited by a BDNF-neutralizing antibody and K252a, a Trk antagonist. Lithium treatment time-dependently increases the intracellular level of BDNF in cortical neurons and activates its receptor, TrkB. The neuroprotection can be completely blocked by either heterozygous or homozygous knockout of the BDNF gene. These results suggest a central role of BDNF and TrkB in mediating the neuroprotective effects of this mood-stabilizer. Finally, long-term lithium treatment of cortical neurons stimulates the proliferation of their progenitor cells detected by co-labeling with BrdU and nestin. Lithium pretreatment also blocks the decrease in progenitor proliferation induced by glutamate, glucocorticoids and haloperidol, suggesting a role in CNS neuroplasticity. We used animal models to investigate further therapeutic potentials for lithium. In the MCAO/reperfusion model of stroke, we found that post-insult treatment with lithium robustly reduced infarct volume and neurological deficits. These beneficial effects were evident when therapeutic concentrations of lithium were injected at least up to 3 h after ischemic onset. The neuroprotection was associated with activation of heat-shock factor-1 and induction of heat-shock protein-70, a cytoprotective protein. In a rat excitotoxic model of Huntington's disease, the excitotoxin-induced loss of striatal medium-sized neurons was markedly reduced by lithium. This lithium protection was correlated with up-regulation of cytoprotective Bcl-2 and down-regulation of apoptotic proteins p53 and Bax, and neurons showing DNA damage and caspase-3 activation. Taken together, our results provide a new insight into the molecular mechanisms involved in lithium neuroprotection against glutamate excitotoxicity. Moreover, these novel molecular and cellular actions might contribute to the neurotrophic and neuroprotective actions of this mood-stabilizer in patients, and could be related to its clinical efficacy for treating mood disorder patients. Clearly, mood-stabilizers may have expanded use for treating excitotoxin-related neurodegenerative diseases.