Ionic Flash NanoPrecipitation (iFNP) for the facile, one-step synthesis of inorganic-organic hybrid nanoparticles in water.

Ionic Flash NanoPrecipitation (iFNP) was evaluated as a novel method for the synthesis of inorganic-organic hybrid nanomaterials and proved to be remarkably effective, fast and practical. To prove the potential of iFNP, various nanostructured GdPO4-based materials of biomedical imaging relevance were easily prepared in a one-step, tunable and highly controlled manner using only water as solvent.

Axonal tau mRNA localization coincides with tau protein in living neuronal cells and depends on axonal targeting signal.

Subcellular mRNA localization, a fundamental mechanism for regulating gene expression, leads to local protein translation that results in the generation of neuronal cell polarity. In this study, we have used P19 embryonic carcinoma cells, which are amenable to transfection, and selection of clonal stable cell lines that are not overexpressing the constructs. We identified the 3' untranslated region (3'UTR) tau axonal localization signal and examined its effect on tau protein localization in nondifferentiated and neuronally differentiated P19 cells. Using GFP-tagged tau constructs combined with in situ hybridization analysis, we demonstrated colocalization of the targeted tau mRNA and its translated protein in the axon and growth cone. Absence of or mutation in the 3'UTR axonal targeting region of tau mRNA resulted in suppression of tau mRNA localization, and both tau mRNA and tau protein remained in the cell body. Swapping between the 3'UTR tau mRNA axonal localization signal and the 3'UTR MAP2 mRNA dendritic targeting signal proved that the localization of the proteins into the axon or dendrites depends on the specific 3'UTR targeting signals. Moreover, the identification of ribosomal proteins in the axon lends further support to the presence of protein synthetic machinery in the axons, a prerequisite for local translation. It is suggested therefore that the P19 cell system can be used to analyze mutations that affect mRNA transport and local translation and that it has the potential of being used to examine the onset of the neuronal differentiation process.

Social work with adult cancer patients: a vote-count review of intervention research.

The meaning of a cancer diagnosis has changed in the past decades, bringing with it a myriad of psychosocial interventions to improve the psychological or functional status of those coping with the disease. Today, social workers in oncology need to be current with research in order to integrate empirical and practical knowledge. In an effort to assist in this process, we reviewed empirical studies to address the following questions: (1) When are patients likely to be willing to accept help? (2) Is there sufficient evidence to show that some types of psychosocial treatment are effective in improving psychological or physical functioning? (3) Are certain treatments preferable for some cancer patients depending on the type of cancer and stage of disease? Using a vote-count review of 40 intervention studies in psychosocial oncology, 36 documented some positive outcomes from treatments, 4 studies exhibited null findings, and no studies were found to have clearly negative results. Studies revealed the most positive results from interventions during the treatment phase, next from interventions at diagnosis, and lastly from interventions during the terminal stage. Individual and group formats showed a comparable level of efficacy. Interventions that included cognitive behavioral methods had the most consistently positive results. Those intervention studies where social workers were involved in the research were less successful at demonstrating efficacy. This difference was due primarily to the fact that social workers often did not include cognitive behavioral interventions in their research. Based on the results of this study, social workers might want to reevaluate their intervention strategies.

Embryonic lethal abnormal vision-like RNA-binding proteins regulate neurite outgrowth and tau expression in PC12 cells.

The embryonic lethal abnormal vision (ELAV)-like proteins are mRNA-binding proteins that regulate mRNA stability. The neuronal members of this family are required for neuronal differentiation. We identified the binding region of purified HuD protein to a target neuronal mRNA encoding for the tau microtubule-associated protein and demonstrated an in vivo interaction between the ELAV-like protein and its target tau mRNA. We show that treatment of neuronal cells with antisense oligodeoxynucleotides directed against HuD blocks the induction of neurite outgrowth and decreases the levels of tau mRNAs, indicating that the ELAV-like proteins are required for neuronal differentiation.

Organizing social work services with adult cancer patients: integrating empirical research.

Today only half of those diagnosed with cancer will die of the disease, leaving enormous room for psychosocial interventions to improve the psychological or functional status of those coping with the disease. Therefore, social workers in oncology must be current with empirical research. In an effort to integrate current research into social work practice, we reviewed empirical studies with sound research designs to answer the following questions: (1) What portion of cancer patients are likely to need social work services? (2) What types of services do social workers provide to meet these needs? and (3) Who is likely to be (or not to be) the recipient of these services. Does intervention research include diverse (non-traditional, non-white and non-middle class) clients? The results show about one third of patients will be judged at high-risk for psychosocial problems but that only 15-25% of those who are diagnosed with cancer will eventually use psychosocial oncology services. Some have mainly instrumental, concrete needs, and others will use psychosocial counseling. A review of the inclusion of minorities and non-traditional, non-middle-class groups, shows that they are not adequately represented in current intervention research in psychosocial oncology. Methods for enlarging their access and participation are suggested.

Application of a first-pass effect model to characterize the pharmacokinetic disposition of venlafaxine after oral administration to human subjects.

Venlafaxine (VEN), a drug used in the treatment of depression, undergoes significant first-pass metabolism after oral dosing to O-desmethylvenlafaxine (ODV), a metabolite with comparable therapeutic activity to that of parent drug. The pharmacokinetic disposition of VEN was characterized using a "first-pass" model that incorporates a presystemic compartment (liver) to account for the first-pass metabolism of VEN to ODV. A series of differential equations were simultaneously fitted to plasma concentrations of parent and metabolite. A good fit of the model to observed data was demonstrated, generating estimates for the following parameters: ka (1.31 +/- 0.009 hr-1), VVEN (252 +/- 87.6 liters), CLint (65.8 +/- 39.7 liters/hr), RL (liver:plasma partition coefficient, 29.6 +/- 18. 3), VODV (181 +/- 84.1 liters), and CLODV (23.5 +/- 12.5 liters/hr). Parameter estimates correlated closely with those obtained through noncompartmental methods. These results indicate that the time-course disposition of a compound undergoing first-pass hepatic metabolism after oral dosing can be successfully modeled.

Calcium channel blockers: association with myocardial infarction, mortality, and cancer.

The purpose of this study was to review the results of trials assessing the association between the use of calcium channel blockers (CCBs) and mortality, myocardial infarction (MI), and cancer. Possible mechanisms of such relationships are discussed and recommendations regarding the use of CCBs made. Since 1995, 10 controversial studies have been published that associate the use of CCBs with an increased risk of mortality, MI, and cancer; these findings have caused widespread anxiety and frustration among patients and physicians. For health care professionals to properly advise patients, the facts surrounding this controversy should be reviewed. To do this, we reviewed and assessed English-language clinical studies, abstracts, editorials, and review articles pertaining to the use of CCBs and mortality, MI, and cancer in humans. The designs of ongoing prospective, randomized studies are discussed. Based on current published studies, the US Food and Drug Administration has agreed to a label warning against off-label use of short-acting nifedipine in patients with hypertension, acute MI, or nonvasospastic unstable angina. Practitioners should exercise caution when prescribing CCBs, especially to high-risk patients (e.g., those with congestive heart failure or clinical or subclinical coronary artery disease). When possible, long-acting CCBs should be used.

Exogenous tau RNA is localized in oocytes: possible evidence for evolutionary conservation of localization mechanisms.

The multistep pathway leading to intracellular RNA localization is known to involve cis-acting signals in targeted mRNAs, which are presumably recognized by specific RNA-binding proteins and interact with a functional cytoskeleton. Tau RNA is localized to the proximal hillock of rat axons, and this movement requires intact microtubules. Because Xenopus oocytes demonstrate a clear polarity involving microtubule-mediated RNA localization, we have studied the distribution of tau RNA injected into oocytes. We find that a fragment from the 3'-untranslated region of tau RNA is localized to the vegetal cortex of stage III/IV oocytes in a distribution indistinguishable from Vg1 RNA, a vegetally localized oocyte mRNA. A fragment from the tau RNA coding region, however, is homogeneously distributed in oocytes. Tau RNA contains a functional binding site for Vg1 RBP, a Xenopus microtubule-associated protein that binds vegetally localized oocyte RNAs with high affinity, and this binding correlates with vegetal localization ability. The present studies demonstrate, for the first time, localization of heterologous RNA in oocytes. Given the role of Vg1 RBP as a mediator of specific RNA-microtubule interactions, these results are strong evidence that Vg1 RBP is involved in the vegetal localization of RNAs in oocytes and raise the intriguing possibility of the existence of proteins with similar function in neurons.

Activation of m1 muscarinic acetylcholine receptor regulates tau phosphorylation in transfected PC12 cells.

Hyperphosphorylated tau proteins are the principal fibrous component of the neurofibrillary tangle pathology in Alzheimer's disease. The possibility that tau phosphorylation is controlled by cell surface neurotransmitter receptors was examined in PC12 cells transfected with the gene for the rat m1 muscarinic acetylcholine receptor. Stimulation of m1 receptor in these cells with two acetylcholine agonists, carbachol and AF102B, decreased tau phosphorylation, as indicated by specific tau monoclonal antibodies that recognize phosphorylation-dependent epitopes and by alkaline phosphatase treatment. The muscarinic effect was both time and dose dependent. In addition, a synergistic effect on tau phosphorylation was found between treatments with muscarinic agonists and nerve growth factor. These studies provide the first evidence for a link between the cholinergic signal transduction system and the neuronal cytoskeleton that can be mediated by regulated phosphorylation of tau microtubule-associated protein.

Does ischemia occur with panic attacks?

OBJECTIVE: The authors examined ambulatory ECG changes during panic attacks in patients with panic disorder. METHOD: Ten otherwise healthy women with panic disorder and complaints of chest pain during panic attacks underwent a symptom-limited exercise test on a treadmill and then wore an ambulatory ECG monitor with software designed to detect and record ischemic events and used a hand-held computer for up to 6 days. RESULTS: Eight of the women had panic attacks while using the hand-held computer and the ECG monitor. No ischemic events occurred during any of the exercise tests. Twelve tachycardiac events occurred during panic attacks and 84 tachycardiac events occurred that were not associated with panic attacks. Panic attacks were associated with significantly more symptoms than were tachycardiac episodes. CONCLUSIONS: In this group of otherwise healthy women with panic disorder and chest pain, ambulatory ischemic changes were not recorded during panic attacks.

cis-acting signals and trans-acting proteins are involved in tau mRNA targeting into neurites of differentiating neuronal cells.

Tau microtubule-associated protein is a neuron specific protein found primarily in axons and is developmentally regulated. The function of tau is in stabilization of microtubules, which is important in establishing and maintaining neuronal morphology. Axonal localization of tau involves a multistep process which is studied in differentiating primary neuronal culture. The initial step involves sorting and subcellular localization of its encoding mRNA into the proximal portion of the axon. Using the transfection assay into neuronal cells, we have demonstrated that sequences located in the 3'-untranslated region include a cis-acting signal which is involved in tau mRNA targeting. In addition, using ultraviolet cross-linking assay, two RNA-binding proteins of 43 and 38 kDa were identified, that exhibit specific binding to a minimal sequence of 91 nucleotides located within the same functional region, which is involved in targeting. The 43 and 38-kDa RNA-binding proteins are present in cytoplasmic extracts, prepared from neuronal cells, and in isolated microtubule preparations. Our results support a novel model in which cis-acting signals, together with RNA-binding proteins are involved in the targeting of tau mRNA, that may ultimately lead to its axonal localization.

Child and adolescent psychiatric emergencies: referral and discharge patterns.

Records were reviewed for 358 children and adolescents treated on 410 visits to a psychiatric emergency room in Newark. The study supports the need for more specialized emergency psychiatric services. Guidelines for the allocation of resources for children need to be developed.

Complete sequence of 3'-untranslated region of Tau from rat central nervous system. Implications for mRNA heterogeneity.

Tau is a family of microtubule associated proteins, heterogeneous in molecular weights, which are expressed specifically in neurons. Tau is encoded by a single gene, while its transcript undergoes a complex and regulated alternative splicing, giving rise to several mRNA species that migrate on Northern blots at approximately 6 and 2 kb. In this report we characterize a full size transcript of tau mRNA from rat brain and demonstrate that it contains 5203 nucleotides (not including exon 2 and 3), which correlates well with the exact size of the transcript as analyzed by Northern blot using RNA standard size markers. The full length of the 3'-untranslated region contains 3848 bp and includes two polyadenylation signals which may yield the two size transcripts in the central nervous system. The first polyadenylation signal is located in the retained intron 13/14 and the second polyadenylation signal is 19 nucleotides before the poly(A) tail. Unspliced intron 13/14 was detected in all RNA preparations tested, including RNA from different ages and different regions of rat brain, RNA from dorsal root ganglia and from undifferentiated and differentiated PC12 cells. In none of the above tissues and cells was a spliced transcript lacking intron 13/14 detected.

Financing mental health services for children and adolescents.

Proponents of extended hospitalization for the most seriously disturbed children and adolescents face increasing difficulty in obtaining funds for such expensive care. The author advocates a continuum-of-care system that will provide a spectrum of treatment modalities, and she notes that when costs are averaged for all children treated at various points on the continuum, the cost per child drops dramatically. She challenges mental health care professionals to justify their treatment effectiveness to payers (1) by developing creative treatment programs that will reduce costs and (2) by compiling research data to demonstrate the cost-effectiveness of extended hospitalization for seriously disturbed children and adolescents.

Differential localization of microtubules in cerebellar cells.

The distribution and subcellular localization of microtubules in rat brain cerebellum was analyzed by immunohistochemistry with antibodies prepared against 3 synthetic peptides corresponding to the C-terminal region of beta-tubulin. The peptides used correspond to amino acid positions 416-425 (peptide 1), 416-431 (peptide 2), and 426-445 (peptide 4). The antibodies thus obtained displayed a remarkable specificity in reacting with different cell types in the rat cerebellum. Antibodies directed against peptide 1 primarily stained Purkinje cells and their dendrites and axons. Peptide 2 antibodies preferentially stained the glomeruli, while antibodies directed against peptide 4 preferentially stained Bergmann glial fibers. These results are discussed in terms of dissimilarities in microtubule organization and masking of epitopes by microtubule-associated proteins (MAPs) in individual cerebellar cells, which may be related to specific functional properties.

Regulation of three beta-tubulin mRNAs during rat brain development.

The nucleotide sequence of a complete rat brain beta-tubulin T beta 15 has been determined from three overlapping cDNA clones. The overall length of the T beta 15 sequence is 1589 bp and shows between 84.5% and 88.6% homology within the coding region as compared with chick and human beta-tubulin sequences. On the other hand, the 3'-non-coding region is highly divergent. Comparison of the derived amino acid sequences from different species demonstrates that the amino acid changes are not randomly distributed, but rather there are several conserved and two highly variable regions common to beta-tubulin polypeptides from various sources. The T beta 15 sequence encodes a dominant neuronal 1.8-kb beta-tubulin mRNA species. Two other minor beta-tubulin mRNA species of 2.6 and 2.9 kb are present in rat brain. By using two synthetic oligonucleotide probes complementary to the carboxyl-terminal divergent region and to the amino-terminal conserved region, we have shown that the three mRNAs are distinct species, which are developmentally regulated. The level of the 1.8-kb mRNA species increases till the age of 12 days thereafter its level decreases. The 2.9-kb mRNA is an early neuronal mRNA species, while the 2.6-kb mRNA is a late neuronal species which is detected at 30 days of rat brain development. The data illustrate that there is a differential expression of the beta-tubulin multigene family during rat brain development which may suggest different functions for the various beta-tubulin isotopes.

Modulation of mRNA for microtubule-associated proteins during brain development.

The heterogeneity of tau microtubule-associated proteins from rat brain is developmentally determined. Newborn rat brain contains two tau polypeptides (tau 0) with somewhat different molecular weights than the five tau components associated with microtubules from 12-day-old brain (tau 12). tau 0 and tau 12 are immunologically related and crossreact with antibodies against tau 12 proteins. Enrichment of the tau mRNA was achieved by prior hybridization of unfractionated poly(A)-containing mRNA to cDNA preparations containing tubulin and actin sequences. The remaining unhybridized mRNA was further fractionated by electrophoresis on methylmercury hydroxide agarose gels. Experiments involving cell-free translation of mRNA indicated that the major differences in the composition of tau proteins from newborn and developing brain are controlled at the mRNA level. The mRNA from newborn rat brain directed the synthesis of five tau proteins, two of which are specific for newborn brain, whereas the other three forms are characteristic of the developing brain. Thus, the appearance in newborn brain of mRNA species specific for three tau 12 forms precedes the phase of the synthesis of these proteins in the cell. By contrast, mRNA from 12-day brain directed the synthesis of four tau proteins specific for the developing brain, one of which is not synthesized by mRNA from newborn brain. None of the newborn tau 0 forms were synthesized with mRNA isolated from 12-day brain.