bluuebunny/crossref_metadata_2025 huggingface dataset:
Drug Interventions Programme: clinical profile of service users v. attendees of standard services
Authors: Kouimtsidis Christos , Edwards Jo , Wallis Christine , Drabble Karen
Published: June 2008

Aims and Method

We conducted a retrospective survey of all cases referred to the Drug Interventions Programme in Hertfordshire for the first 9 months in order to compare them with those referred to one of the community drug and alcohol teams.

Results

The Drugs Interventions Programme had significantly more White British clients and clients who had dropped out from previous treatment. Compared with community team clients, the Programme had a higher percentage of clients with an opioid problem (92%), of whom a high percentage also misused other substances (78%) and injected drugs (30%, half of whom shared needles).

Clinical Implications

More chaotic clients who had failed previous treatment have entered treatment with the Drug Interventions Programme.
Routine measurement of mental health service outcomes: Health of the Nation Outcome Scales in Nova Scotia
Authors: Kisely Stephen , Campbell Leslie Anne , Robertson Heather , Crossman Doug , Martin Karen , Campbell John
Published: June 2008

Aims and Method

Although the Health of the Nation Outcome Scales (HoNOS) were designed for routine clinical use, completion rates in clinical settings rarely exceed 60%. We evaluated two initiatives to increase completion rates: timely feedback to clinicians, useful at individual, team and service levels, and improved supporting materials (tabulated glossaries for all versions covering the life-span).

Results

Clinicians in South Shore Health district provided ratings on all outpatient referrals over 12 months as part of routine care. Data were captured using the Nova Scotia routine administrative data system. Completion rates rose from 61% to 86% (n=1190). Clinicians' ratings of the instrument's ease of use were significantly improved.

Clinical Implications

Use of a tabulated glossary and enhanced feedback of clinically useful information improved clinician support for the routine measurement of health outcomes with HoNOS.
Safety at work: national survey of psychiatrists in basic training in Ireland
Authors: Rush Gavin , Reidy Julianne , Wright Brenda , Campbell Fiona , Ryan Maria , Molyneux Guy , Ambikapathy Anita , Leonard Peter
Published: June 2008

Aims and Methods

To investigate the experiences of Irish psychiatric trainees in relation to safety at work and the related training issues. A questionnaire was posted to 243 psychiatric trainees throughout Ireland.

Results

We obtained 113 responses (46.5%). Results indicated that tutors appear to consider safety at work as an important component of training. The availability of breakaway or similar training is much bigger than previously reported in Ireland. The standard of induction courses appears to be high. However, problems in working environments were revealed: 16% of trainees had been physically assaulted and 72% have felt threatened in the workplace.

Clinical Implications

Despite improvements in training in Ireland, workplaces remain largely unsafe, putting staff and patients at risk.
Valproate as prophylaxis for clozapine-induced seizures: survey of practice
Authors: Sparshatt Anna , Whiskey Eromona , Taylor David
Published: June 2008

Aims and Method

To evaluate the prescribing of valproate in clozapine-treated individuals who may be at risk of seizure. We collected point-prevalent clinical characteristics and demographics of all in-patients prescribed clozapine in an acute mental health trust. Data were collected from case notes, electronic records and drug charts, and analysed against a set audit standard.

Results

Data were collected for 81 in-patients. Of all deemed to be at risk of seizure (n=37) only 24% were prescribed valproate at a therapeutic plasma level.

Clinical Implications

The majority of patients prescribed clozapine at risk of seizures were not adequately protected from this risk. Clear guidelines are required.
James Bernard Walsh: Formerly Consultant Psychiatrist, Craigavon Area Hospital & St Lukes Hospital, Armagh, Northern Ireland
Authors: Egan Sean
Published: June 2008

James (Jim) Walsh was born on 25 August 1932 at Belleek on the Fermanagh–Donegal border. He showed early academic promise by winning a scholarship at St Columb's College, Derry, where he had commenced studies in 1945. By 1950 he had begun to study medicine at the Queen's University of Belfast, graduating in 1956, and completing his intern year at the Mater Infirmorum Hospital in Belfast.
John Gwilym Howells: Formerly Director of Family Psychiatry, Ipswich Hospital, Suffolk, and who played an important part in the foundation of the RCPsych
Authors: Freeman Hugh
Published: June 2008

John Gwilym was born in 1918 and was brought up in Holyhead, Anglesey, within the characteristic culture of North Wales, which in his boyhood was still relatively unaffected by modernisation. His father introduced him to country sports, but his mother diverted him towards more intellectual interests; however, she died when Gwilym was 15, which affected him deeply. At his grammar school, where he was captain of cricket, he received a good grounding in science subjects but was uncertain about his future direction.
Sleep Deprivation and Vigilant Attention
Authors: Lim Julian , Dinges David F.
Published: June 2008

Sleep deprivation severely compromises the ability of human beings to respond to stimuli in a timely fashion. These deficits have been attributed in large part to failures of vigilant attention, which many theorists believe forms the bedrock of the other more complex components of cognition. One of the leading paradigms used as an assay of vigilant attention is the psychomotor vigilance test (PVT), a high signal‐load reaction‐time test that is extremely sensitive to sleep deprivation. Over the last twenty years, four dominant findings have emerged from the use of this paradigm. First, sleep deprivation results in an overall slowing of responses. Second, sleep deprivation increases the propensity of individuals to lapse for lengthy periods (>500 ms), as well as make errors of commission. Third, sleep deprivation enhances the time‐on‐task effect within each test bout. Finally, PVT results during extended periods of wakefulness reveal the presence of interacting circadian and homeostatic sleep drives. A theme that links these findings is the interplay of “top‐down” and “bottom‐up” attention in producing the unstable and unpredictable patterns of behavior that are the hallmark of the sleep‐deprived state.
Neuronal Mechanisms Underlying Attention Deficit Hyperactivity Disorder
Authors: Brennan Avis R. , Arnsten Amy F.T.
Published: June 2008

Neuropsychological and imaging studies indicate that attention deficit hyperactivity disorder (ADHD) is associated with alterations in prefrontal cortex (PFC) and its connections to striatum and cerebellum. Research in animals, in combination with observations of patients with cortical lesions, has shown that the PFC is critical for the regulation of behavior, attention, and affect using representational knowledge. The PFC is important for sustaining attention over a delay, inhibiting distraction, and dividing attention, while more posterior cortical areas are essential for perception and the allocation of attentional resources. The PFC in the right hemisphere is especially important for behavioral inhibition. Lesions to the PFC produce a profile of distractibility, forgetfulness, impulsivity, poor planning, and locomotor hyperactivity. The PFC is very sensitive to its neurochemical environment, and either too little (drowsiness) or too much (stress) catecholamine release in PFC weakens cognitive control of behavior and attention. Recent electrophysiological studies in animals suggest that norepinephrine enhances “signals” through postsynaptic α2A adrenoceptors in PFC, while dopamine decreases “noise” through modest levels of D1 receptor stimulation. α2A‐Adrenoceptor stimulation strengthens the functional connectivity of PFC networks, while blockade of α2 receptors in the monkey PFC recreates the symptoms of ADHD, resulting in impaired working memory, increased impulsivity, and locomotor hyperactivity. Genetic alterations in catecholamine pathways may contribute to dysregulation of PFC circuits in this disorder. Medications may have many of their therapeutic effects by optimizing stimulation of α2A adrenoceptors and D1 receptors in the PFC, thus strengthening PFC regulation of behavior and attention.
Insights into the Pharmacological Potential of Estrogens and Phytoestrogens on Catecholamine Signaling
Authors: Yanagihara Nobuyuki , Toyohira Yumiko , Shinohara Yuko
Published: June 2008

We report here the effects of estrogens and phytoestrogens on catecholamine signaling in cultured bovine adrenal medullary cells used as a model of catecholaminergic neurons in the brain. Treatment of the cells for 20 min with 17β‐estradiol (E2) (0.3–100 nM) or phytoestrogens such as daidzein (0.01–1.0 μM), a soy isoflavone, and resveratrol (0.1–1.0 μM), a grape polyphenol, stimulated14C‐catecholamine synthesis from [14C]tyrosine, which was associated with the activation of tyrosine hydroxylase. The stimulatory effect of E2and phytoestrogens was not inhibited by ICI182,780, a nuclear estrogen receptor inhibitor, but abolished by U0126, an inhibitor of extracellular signal‐regulated kinase1/2 (ERK1/2) kinase. E2enhanced the phosphorylation of ERK1/2. The plasma membrane isolated from the adrenal medulla showed two classes of specific binding sites of [3H]E2. Resveratrol and daidzein at high concentrations (≥1.0 μM) inhibited catecholamine secretion induced by various secretagogues. The present findings suggest that estrogens and phytoestrogens most likely stimulate catecholamine synthesis via estrogen receptors in the plasma membrane, but in high concentrations phytoestrogens inhibit catecholamine secretion induced by secretagogues in adrenal medullary cells, and probably in brain neurons.
Neural Substrates for Sexual Preference and Motivation in the Female and Male Rat
Authors: Sakuma Yasuo
Published: June 2008

Rodents identify a mating partner by using olfactory cues. Female rats in estrus spend a longer time sniffing odors of sexually active males when physical contacts are hampered. Sexually active males are attracted by odors of receptive females. The preference in either sex disappears when the subjects are gonadectomized, an effect reversible by supplement with estrogen or testosterone. Thus, circulating sex steroids determine the odor preference in both sexes. In both sexes, olfactory cues get to the basal forebrain; this area includes the preoptic area (POA), substantia innominata and accumbens, structures with estrogen receptor–positive neurons. In estrous females, neurons in the POA are activated during precopulatory motivational behavior. Lesion in this area practically eliminates sexual preference and diminishes the motivation. An increase in locomotion in females in estrus, which apparently depends on estrogen‐sensitive POA projections to the midbrain locomotor region, has been considered to embody enhanced sexual motivation.
Motivational Influences on the Degree and Direction of Sexual Attraction
Authors: Hernández‐González Marisela , Guevara Miguel Angel , Ågmo Anders
Published: June 2008

Motivation can be defined as a class of central nervous processes determining the likelihood of display of a behavior and the intensity of the behavior if displayed. All behavior is, according to this definition, caused and controlled by motivation. Although the concept of motivation eventually could be replaced by an entirely mechanistic explanation of the causes of behavior, in terms of neural events, such explanations would be overly complex for everyday use. This is particularly the case with regard to the momentaneous fluctuations in the intensity of a behavior, like those occurring during copulation in rats. Thus, the concept of motivation will remain useful even when mechanistic explanations become available. Even though the propensity to perform sexual responses is determined by sexual motivation, another element is required for the execution of such responses. This other element is an appropriate stimulus, a sexual incentive. For a male rat, an appropriate incentive could be a sexually receptive female. For a human, it could be a mental representation of a sexual partner. The incentive activates approach behaviors, and the intensity of these behaviors will be determined by motivation and by the quality of the incentive stimulus, its attractivity. Much work has been done with the purpose of identifying the nature of the incentive stimulus or stimuli emitted by rats and other mammals. While visual stimuli seem to be of limited importance, auditory and particularly olfactory stimuli have been found to have incentive properties. Soluble chemicals may be important for some aspects of copulation, but copulatory motor patterns are basically under the control of tactile stimuli. The processing of sexual incentives in the rat brain has been studied with electroencephalographic techniques, and data show that the prefrontal cortex (PFC) participates in the identification of sexual incentives. Furthermore, there are important differences between the medial and orbital frontal cortices. The medial PFC, as well as the ventral tegmental area, also seem to participate in the generation of pelvic thrusting.
Intrinsic Brain Activity in Altered States of Consciousness
Authors: Boly M. , Phillips C. , Tshibanda L. , Vanhaudenhuyse A. , Schabus M. , Dang‐Vu T.T. , Moonen G. , Hustinx R. , Maquet P. , Laureys S.
Published: June 2008

Spontaneous brain activity has recently received increasing interest in the neuroimaging community. However, the value of resting‐state studies to a better understanding of brain–behavior relationships has been challenged. That altered states of consciousness are a privileged way to study the relationships between spontaneous brain activity and behavior is proposed, and common resting‐state brain activity features observed in various states of altered consciousness are reviewed. Early positron emission tomography studies showed that states of extremely low or high brain activity are often associated with unconsciousness. However, this relationship is not absolute, and the precise link between global brain metabolism and awareness remains yet difficult to assert. In contrast, voxel‐based analyses identified a systematic impairment of associative frontoparieto–cingulate areas in altered states of consciousness, such as sleep, anesthesia, coma, vegetative state, epileptic loss of consciousness, and somnambulism. In parallel, recent functional magnetic resonance imaging studies have identified structured patterns of slow neuronal oscillations in the resting human brain. Similar coherent blood oxygen level–dependent (BOLD) systemwide patterns can also be found, in particular in the default‐mode network, in several states of unconsciousness, such as coma, anesthesia, and slow‐wave sleep. The latter results suggest that slow coherent spontaneous BOLD fluctuations cannot be exclusively a reflection of conscious mental activity, but may reflect default brain connectivity shaping brain areas of most likely interactions in a way that transcends levels of consciousness, and whose functional significance remains largely in the dark.
Detecting Awareness in the Vegetative State
Authors: Owen Adrian M. , Coleman Martin R.
Published: June 2008

The assessment of residual brain function in the vegetative state, is extremely difficult and depends frequently on subjective interpretations of observed spontaneous and volitional behaviors. For those patients who retain peripheral motor function, rigorous behavioral assessment supported by structural imaging and electrophysiology is usually sufficient to establish a patient's level of wakefulness and awareness. However, it is becoming increasingly apparent that, in some patients, damage to the peripheral motor system may prevent overt responses to command, even though the cognitive ability to perceive and understand such commands may remain intact. Advances in functional neuroimaging suggest a novel solution to this problem; in several recent cases, so‐called “activation” studies have been used to identify residual cognitive function and even conscious awareness in patients who are assumed to be vegetative, yet retain cognitive abilities that have evaded detection using standard clinical methods.
Concepts and Mechanisms of Generalized Central Nervous System Arousal
Authors: Pfaff Donald , Ribeiro Ana , Matthews James , Kow Lee‐Ming
Published: June 2008

A concept of generalized arousal of the CNS is presented and given an operational definition that leads to quantitative physical measures. Because this primitive arousal function underlies all motivated behavioral responses, cognitive functions, and emotional expression, disorders of generalized arousal can be associated with a large number of problems in medicine and public health, including vegetative states, attentional disorders, depression, occupational hazards, and problems with sleep and anesthesia. Some of its known mechanisms are briefly reviewed, at the levels of neuroanatomy, neurophysiology, and functional genomics. Generalized arousal contributes to the excitement and the activation of behaviors during specific arousal states. Data are summarized for four genomic/neurochemical systems through which changes in generalized arousal could affect sexual arousal, two of which heighten, and the other two of which reduce arousal.
Functional Gene Variation in the Human Norepinephrine Transporter
Authors: Kim Chun‐Hyung , Waldman Irwin D. , Blakely Randy D. , Kim Kwang‐Soo
Published: June 2008

The norepinephrine (NE) transporter (NET) is responsible for the re‐uptake of NE into presynaptic nerve terminals, thus critically regulating noradrenergic signaling and homeostasis. Since NE signaling contributes to diverse brain functions, we hypothesize that promoter variation within the human NET gene (solute carrier family 6, member 2; SLC6A2) may impact risk for NE‐related disorders, including depression, attention deficit hyperactive disorder (ADHD), and autonomic dysfunction. In support of this, we recently found a functional polymorphism at −3081 position upstream of the transcription initiation site. This polymorphism displayed differential promoter function, which we showed could arise from recruitment of a transcriptional repressor. Further analyses identified Slug and Scratch as candidates involved in repression of SLC6A2 transcription generated by the −3081(T) allele. Moreover, we observed a significant association of the −3081(T) variant with ADHD. Altered transcription of SLC6A2 may therefore represent a novel risk factor for the development of ADHD.
Hypothalamic Regulation of Sleep and Arousal
Authors: Szymusiak Ronald , McGinty Dennis
Published: June 2008

Normal waking is associated with neuronal activity in several chemically defined ascending arousal systems. These include monoaminergic neurons in the brainstem and posterior hypothalamus, cholinergic neurons in the brainstem and basal forebrain, and hypocretin (orexin) neurons in the lateral hypothalamus. Collectively, these systems impart tonic activation to their neuronal targets in the diencephalon and neocortex that is reflected in the low‐voltage fast‐frequency electroencephalogram patterns of wakefulness. Neuronal discharge in these arousal systems declines rapidly at sleep onset. Transitions from waking to sleep, therefore, involve coordinated inhibition of multiple arousal systems. An important source of sleep‐related inhibition of arousal arises from neurons located in the preoptic hypothalamus. These preoptic neurons are strongly activated during sleep, exhibiting sleep/waking state‐dependent discharge patterns that are the reciprocal of that observed in the arousal systems. The majority of preoptic sleep regulatory neurons synthesize the inhibitory neurotransmitter GABA. Anatomical and functional evidence supports the hypothesis that GABAergic neurons in the median preoptic nucleus (MnPN) and ventrolateral preoptic area (VLPO) exert inhibitory control over the monoaminergic systems and the hypocretin system during sleep. Recent findings indicate that MnPN and VLPO neurons integrate homeostatic aspects of sleep regulation and are important targets for endogenous sleep factors, such as adenosine and growth hormone releasing hormone.
Associations between Sleep Loss and Increased Risk of Obesity and Diabetes
Authors: Knutson Kristen L. , Van Cauter Eve
Published: June 2008

During the past few decades, sleep curtailment has become a very common in industrialized countries. This trend for shorter sleep duration has developed over the same time period as the dramatic increase in the prevalence of obesity and diabetes. Evidence is rapidly accumulating to indicate that chronic partial sleep loss may increase the risk of obesity and diabetes. Laboratory studies in healthy volunteers have shown that experimental sleep restriction is associated with an adverse impact on glucose homeostasis. Insulin sensitivity decreases rapidly and markedly without adequate compensation in beta cell function, resulting in an elevated risk of diabetes. Prospective epidemiologic studies in both children and adults are consistent with a causative role of short sleep in the increased risk of diabetes. Sleep curtailment is also associated with a dysregulation of the neuroendocrine control of appetite, with a reduction of the satiety factor, leptin, and an increase in the hunger‐promoting hormone, ghrelin. Thus, sleep loss may alter the ability of leptin and ghrelin to accurately signal caloric need, acting in concert to produce an internal misperception of insufficient energy availability. The adverse impact of sleep deprivation on appetite regulation is likely to be driven by increased activity in neuronal populations expressing the excitatory peptides orexins that promote both waking and feeding. Consistent with the laboratory evidence, multiple epidemiologic studies have shown an association between short sleep and higher body mass index after controlling for a variety of possible confounders.
Fluorescent DNA Base Modifications and Substitutes: Multiple Fluorophore Labeling and the DETEQ Concept
Authors: Wagenknecht Hans‐Achim
Published: July 2008

There is an increasing need for fluorescent nucleic acid probes that are able to sense genetic variations without the application of enzymes. The incorporation of organic fluorophores either as DNA base modifications or as DNA base substitutions represents a powerful and versatile method for such new fluorescent DNA assays. Multiple labeling of oligonucleotides using several adjacent chromophore‐modified DNA bases yields fluorescence enhancement and modulation that are sensitive to single‐base mismatches in the complementary oligonucleotide. Charge transfer processes that cause fluorescence quenching are DNA‐base mediated and occur over several base pairs distance. Our “DETEQ” setup, consisting of a fluorescence DNA base substitution and the charge acceptor as a second modification two base pairs away, allows the homogeneous detection of single‐base mutations simply by fluorescence readout. This could lead to new DNA microarrays which are based on charge transfer processes and can be analyzed by commonly used fluorescence readout techniques.
Probing of Cosolvents in Polymer Latex Materials by Using Solvatochromic Fluorescence
Authors: Brouwer Albert M. , Raja Tanzeela N. , Biemans Koen , Nabuurs Tijs , Tennebroek Ronald
Published: July 2008

The process of film formation is of great importance for the application of organic coatings. In waterborne coatings, organic cosolvents are still indispensable, but regulations force the industry to reduce their amounts. Here we describe a method that uses the solvatochromic fluorescence of a probe molecule copolymerized in an emulsion polymerization process with different monomers to shed light on the partitioning of cosolvents in polymer latex materials. The formulation of the latex with organic cosolvents that are not very water soluble leads to a quantifiable redshift of the emission of the probe. The transfer of the cosolvent upon mixing of cosolvent‐containing and cosolvent‐free compartments can also be monitored.
Red/Near‐infrared Boron–Dipyrromethene Dyes as Strongly Emitting Fluorophores
Authors: Descalzo Ana B. , Xu Hai‐Jun , Shen Zhen , Rurack Knut
Published: July 2008

We present an overview of the state of the art in long‐wavelength boron–dipyrromethene (BODIPY) fluorophores, focusing on strategies to shift the absorption and emission bands into the red/near‐infrared (NIR) range of the spectrum. This report also discusses chemical modifications of the chromophoric core to obtain analyte‐responsive fluorophores, including examples of pH and metal ion indicators. Finally, we present a new series of phenanthrene‐fused BODIPY dyes, emitting with high efficiency in the red/NIR region of the spectrum, as well as discussing potential applications thereof as probes.
Dextrin‐Microencapsulated Porphyrin: Luminescent Properties
Authors: Luz Priscilla Paiva , Neri Cláudio Roberto , Serra Osvaldo Antonio
Published: July 2008

Photophysical properties of porphyrins in aqueous solutions are strongly affected by aggregation. One possible solution to this problem is to encapsulate the porphyrin into polymeric spheres, to provide an environment where the photosensitizer can be administered in its monomeric form in such treatments as photodynamic therapy. Here we report the microencapsulation of the meso‐tetrakis(4‐sulphonatophenyl) porphyrin (TPPS4) photosensitizer by the ultrasonic spray‐drying technique. The encapsulated TPPS4 was morphologically characterized by scanning electron microscopy, and its photophysical properties were studied and compared with those of a physical blend of dextrin and TPPS4. We successfully encapsulated TPPS4 into dextrin microspheres, and the encapsulated photosensitizer displays higher luminescence intensity than that of the prepared physical blends.
Stability and Fluorescence Quantum Yield of CdSe–ZnS Quantum Dots—Influence of the Thickness of the ZnS Shell
Authors: Grabolle Markus , Ziegler Jan , Merkulov Alexei , Nann Thomas , Resch‐Genger Ute
Published: July 2008

We investigated the correlation between the thickness of the ZnS shell of CdSe–ZnS quantum dots (QDs), the stability of the particles, and the fluorescence quantum yield. As a measure for stability, a new shell quality test was developed. This test is based on the reaction of the QDs with photochemically formed thiophenol radicals and communicates an imperfect ZnS shell by a rapid and complete loss of fluorescence. The quantum yield increases from less than 5% for unshelled CdSe up to 50%, with an increase in ZnS shell thickness up to 0.6–0.8 nm. At the same time, the particles become significantly more stable, as revealed by the shell test.
Toward Improved Biochips Based on Rolling Circle Amplification—Influences of the Microenvironment on the Fluorescence Properties of Labeled DNA Oligonucleotides
Authors: Mayer‐Enthart Elke , Sialelli Julien , Rurack Knut , Resch‐Genger Ute , Köster Daniela , Seitz Harald
Published: July 2008

Microarrays have become an increasingly important tool for biotechnology and molecular diagnostics. Despite many advantages, their sensitivity is still insufficient for such tasks as the analysis of small sample quantities and for the detection of alterations in gene expression of low‐abundance genes. Accordingly, amplification strategies are necessary. Approaches to amplify the signal intensity include the increase of the number of dye molecules per target through either particle labels or rolling circle amplification, as used for this study.
Frequency Domain Fluorometry with Pulsed Light‐Emitting Diodes
Authors: Herman Petr , Vecer Jaroslav
Published: July 2008

We present a simple way to extend the time resolution of a standard frequency domain (FD) fluorometer by use of pulsed light‐emitting diodes (LEDs) as an excitation source. High temporal resolution of the multifrequency FD method requires the excitation light to be modulated up to the highest possible frequencies with high modulation depth. We used harmonic content of subnanosecond‐pulsed LEDs for generation of modulated excitation light. By a replacement of the light source, the upper frequency limit increased to 500–600 MHz, which is almost triple the frequency limit of the standard FD fluorometer equipped with an ordinary photomultiplier tube and an electro‐optical modulator. Besides the increased time resolution, this approach allowed for elimination of a light modulator with an associated synthesizer and radio frequency power amplifier that are normally required for FD measurements with continuous wave light sources. Performance of the instrument with pulsed LED excitation is demonstrated on several examples of ultraviolet‐excited fluorescence decays. We show that pulsed LEDs can serve as an inexpensive alternative to pulsed laser sources for FD fluorescence spectroscopy.
Effect of pH on Aqueous Phenylalanine Studied Using a 265‐nm Pulsed Light‐emitting Diode
Authors: Macmillan Alexander M. , McGuinness Colin D. , Sagoo Kulwinder , McLoskey David , Pickup John C. , Birch David J. S.
Published: July 2008

Recently, we described the characteristics and application of a 265‐nm AlGaN light‐emitting diode (LED) operated at 1‐MHz repetition rate, 1.2‐ns pulse duration, 1.32‐μW average power, 2.3‐mW peak power, and approximately 12‐nm bandwidth. The LED enables the fluorescence decay of weakly emitting phenylalanine to be measured routinely in the condensed phase, even in dilute solution. For a pH range of 1–11, we find evidence for a biexponential rather than a monoexponential decay, whereas at pH 13, only a monoexponential decay is present. These results provide direct evidence for the dominance of two phenylalanine rotamers in solution with a photophysics closer to the other two fluorescent amino acids, tyrosine and tryptophan, than has previously been reported. Although phenylalanine fluorescence is difficult to detect in most proteins because of its low quantum yield and resonance energy transfer from phenylalanine to tyrosine and tryptophan, the convenience of the 265‐nm LED may well take protein photophysics in new directions, for example, by making use of this resonance energy transfer or by observing phenylalanine fluorescence directly in specific proteins where resonance energy transfer is inefficient.
Phenotypic and Functional Analysis of Dendritic Cells and Clinical Outcome in Patients With High-Risk Melanoma Treated With Adjuvant Granulocyte Macrophage Colony-Stimulating Factor
Authors: Daud Adil I. , Mirza Noweeda , Lenox Brianna , Andrews Stephanie , Urbas Patricia , Gao Gui X. , Lee Ji-Hyun , Sondak Vernon K. , Riker Adam I. , DeConti Ronald C. , Gabrilovich Dmitry
Published: June 2008

Purpose

Granulocyte macrophage colony-stimulating factor (GM-CSF) can induce differentiation of dendritic cells (DCs) in preclinical models. We hypothesized that GM-CSF–stimulated DC differentiation may result in clinical benefit in patients with high-risk melanoma.

Patients and Methods

We conducted a prospective trial in patients with high-risk (stage III B/C, IV), resected melanoma, with GM-CSF 125 μg/m2/d administered for 14 days every 28 days. Patients underwent clinical restaging every four cycles, with DC analysis performed at baseline and at 2, 4, 8, and 12 weeks.

Results

Of 42 patients enrolled, 39 were assessable for clinical outcome and DC analysis. Median overall survival was 65 months (95% CI, 43 to 67 months) and recurrence-free survival was 5.6 months (95% CI, 3 to 11 months). GM-CSF treatment caused an increase in mature DCs, first identified after 2 weeks of treatment, normalizing by 4 weeks. Patients with decreased DCs at baseline had significant increases in DC number and function compared with those with “normal” parameters at baseline. No change was observed in the number of myeloid-derived suppressor cells (MDSCs). Early recurrence (< 90 days) correlated with a decreased effect of GM-CSF on host DCs, compared with late or no (evidence of) recurrence.

Conclusion

GM-CSF treatment was associated with a transient increase in mature DCs, but not MDSCs. Greater increase of DCs was associated with remission or delayed recurrence. The prolonged overall survival observed warrants further exploration.
Relationship of Circulating Tumor Cells to Tumor Response, Progression-Free Survival, and Overall Survival in Patients With Metastatic Colorectal Cancer
Authors: Cohen Steven J. , Punt Cornelis J.A. , Iannotti Nicholas , Saidman Bruce H. , Sabbath Kert D. , Gabrail Nashat Y. , Picus Joel , Morse Michael , Mitchell Edith , Miller M. Craig , Doyle Gerald V. , Tissing Henk , Terstappen Leon W.M.M. , Meropol Neal J.
Published: June 2008

Purpose

As treatment options expand for metastatic colorectal cancer (mCRC), a blood marker with a prognostic and predictive role could guide treatment. We tested the hypothesis that circulating tumor cells (CTCs) could predict clinical outcome in patients with mCRC.

Patients and Methods

In a prospective multicenter study, CTCs were enumerated in the peripheral blood of 430 patients with mCRC at baseline and after starting first-, second-, or third-line therapy. CTCs were measured using an immunomagnetic separation technique.

Results

Patients were stratified into unfavorable and favorable prognostic groups based on CTC levels of three or more or less than three CTCs/7.5 mL, respectively. Patients with unfavorable compared with favorable baseline CTCs had shorter median progression-free survival (PFS; 4.5 v 7.9 months; P = .0002) and overall survival (OS; 9.4 v 18.5 months; P < .0001). Differences persisted at 1 to 2, 3 to 5, 6 to 12, and 13 to 20 weeks after therapy. Conversion of baseline unfavorable CTCs to favorable at 3 to 5 weeks was associated with significantly longer PFS and OS compared with patients with unfavorable CTCs at both time points (PFS, 6.2 v 1.6 months; P = .02; OS, 11.0 v 3.7 months; P = .0002). Among nonprogressing patients, favorable compared with unfavorable CTCs within 1 month of imaging was associated with longer survival (18.8 v 7.1 months; P < .0001). Baseline and follow-up CTC levels remained strong predictors of PFS and OS after adjustment for clinically significant factors.

Conclusion

The number of CTCs before and during treatment is an independent predictor of PFS and OS in patients with metastatic colorectal cancer. CTCs provide prognostic information in addition to that of imaging studies.
Prediagnostic Plasma Folate and the Risk of Death in Patients With Colorectal Cancer
Authors: Wolpin Brian M. , Wei Esther K. , Ng Kimmie , Meyerhardt Jeffrey A. , Chan Jennifer A. , Selhub Jacob , Giovannucci Edward L. , Fuchs Charles S.
Published: June 2008

Purpose

Although previous studies have demonstrated an inverse relationship between folate intake and colorectal cancer risk, a recent trial suggests that supplemental folic acid may accelerate tumorigenesis among patients with a history of colorectal adenoma. Therefore, high priority has been given to research investigating the influence of folate on cancer progression in patients with colorectal cancer.

Patients and Methods

To investigate whether prediagnostic levels of plasma folate are associated with colorectal cancer–specific and overall mortality, we performed a prospective, nested observational study within two large US cohorts: the Nurses' Health Study and Health Professionals Follow-Up Study. We measured folate levels among 301 participants who developed colorectal cancer 2 or more years after their plasma was collected and compared participants using Cox proportional hazards models by quintile of plasma folate.

Results

Higher levels of plasma folate were not associated with an increased risk of colorectal cancer–specific or overall mortality. Compared with participants in the lowest quintile of plasma folate, those in the highest quintile experienced a multivariable-adjusted hazard ratio for colorectal cancer–specific mortality of 0.42 (95% CI, 0.20 0.88) and overall mortality of 0.46 (95% CI, 0.24 0.88). When the analysis was limited to participants whose plasma was collected within 5 years of cancer diagnosis, no detrimental effect of high plasma folate was noted. In subgroup analyses, no subgroup demonstrated worse survival among participants with higher plasma folate levels.

Conclusion

In two large prospective cohorts, higher prediagnostic levels of plasma folate were not associated with an increased risk of colorectal cancer–specific or overall mortality.
Metal Ion-coupled Electron-transfer Reduction of Dioxygen
Authors: Fukuzumi Shunichi
Published: June 2008

Metal ion-coupled and proton-coupled electron-transfer reactions of dioxygen is described for one-electron, two-electron, and four-electron reduction of dioxygen by one-electron reductants such as ferrocene derivatives as well as by two-electron reductants such as NADH analogs. The catalytic mechanism of the four-electron reduction of dioxygen with cofacial dicobalt porphyrins has been clarified based on the detailed kinetic study and the detection of the intermediate.
Formation of ε-Fe2O3 Nanocrystals through Segregation in Mesoporous Silica Particles
Authors: Mori Kazumi , Oaki Yuya , Suda Masayuki , Einaga Yasuaki , Imai Hiroaki
Published: June 2008

Nanosized ε-Fe2O3 crystals with a diameter below 20 nm were successfully prepared at 600 °C in a mesoporous silica matrix. The formation of the metastable iron oxide occurred through nanoscale segregation in an immiscible SiO2–Fe2O3 system having a mesoporous structure. The nanocrystals incorporated into ca. 50 nm-size particles of the mesoporous silica exhibited a coercive field up to 8 kOe.
Prominent Inhibitory Effect of 2-Hydroxybutyl-β-cyclodextrin on Solution-mediated Polymorphic Transition of Chlorpropamide
Authors: Ishiguro Takako , Hirayama Fumitoshi , Iohara Daisuke , Uekama Kaneto
Published: June 2008

The effects of cyclodextrins on crystallization of chlorpropamide from aqueous solutions were investigated. Parent α-, β-, and γ-cyclodextrins and 2-hydroxypropyl-α-, and -β-cyclodextrins and glucose did not change the crystallization of the drug, providing the stable Form A crystal. On the other hand, 2-hydroxybutyl-β-cyclodextrin inhibited the solution-mediated polymorphic transition of the drug, providing the metastable Form II at higher cyclodextrin concentrations and Form III at lower cyclodextrin concentrations. The results suggested that 2-hydoxybutyl-β-cyclodextrin is useful for preparing metastable crystals during crystallization according to the Ostwald rule.
Pulsed-laser Irradiation to Suspended Carbon Particles in Aqueous Silver Nitrate Solution
Authors: Miura Yoshiko , Yui Kazuko , Uchida Hiroshi , Itatani Kiyoshi , Koda Seiichiro
Published: June 2008

When carbon suspended in water was irradiated repetitively by pulsed laser at 532 nm, the carbon particles were gradually consumed, being accompanied with morphology change. Transmission electron microscopy (TEM) showed formation of seemingly entangled long fibrils and/or thin shells from the particles. In the copresence of silver ions, characteristic plasmon absorption peak appeared and formation of nanosized silver particles was evidenced by TEM. Under the typical fluence of 125 mJ·cm−2·pulse−1, the quantum yield of silver reduction was 10−3.
A Traceless Solid-phase Synthesis of 1,4-Diazepan-2-ones
Authors: Saruta Kunio , Ogiku Tsuyoshi
Published: June 2008

A novel synthesis of 1,4-diazepan-2-ones using a traceless solid-phase approach is described, in which many kinds of 1,4-diazepan-2-one have been efficiently obtained in high purity. The strategy is based on intramolecular alkylation of tertiary amines, followed by elimination of the desired tertiary amines from the generated quarternary ammonium salts.
Site- and Stereoselectivity in the Photochemical Oxetane Formation Reaction (Paternò–Büchi Reaction) of Tetrahydrobenzofuranols with Benzophenone: Hydroxy-directed Diastereoselectivity?
Authors: Yabuno Youhei , Hiraga Yoshikazu , Abe Manabu
Published: June 2008

The Paternò–Büchi reactions of tetrahydrobenzofuranols with benzophenone were investigated to reveal site- and stereoselectivity in oxetane formation reactions. Both selectivities were found to be largely dependent on the reaction temperature. The trans selectivity increased with a decrease in temperature, and the more-substituted oxetanes were selectively formed at high temperature.
Surface-sulfonated Diamond Powder for Solid Acid
Authors: Kondo Takeshi , Kameshima Takashi , Kawai Takeshi
Published: June 2008

The surface of diamond powder (DP) was sulfonated via a covalent modification method using 1,3-propanesultone, for the fabrication of a new class of solid acid material. X-ray photoelectron spectroscopy (XPS) and diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy studies confirmed successful introduction of sulfo groups on the DP surface. The optimal condition for the preparation of sulfonated DP (S-DP) was investigated in terms of acid amount on the surface. The S-DP exhibited solid Brønsted acid properties in pure water and catalytic activity toward the formation of ethyl acetate.
Why determine only the total prostate-specific antigen, if the free-to-total ratio contains the information?
Authors: Eekers Daniëlle Berty Petra , Laschet Andrea , de Groot Monique , Roelofs Erik , Kester Arnold , Delaere Karl , Lambin Philippe , van Gils Francis , Nap Marius , ten Kate Joop
Published: June 2008

Background

Total prostate-specific antigen (tPSA) is the best available test for the detection of prostate cancer but it lacks specificity. The free-to-total ratio (F/T ratio) is used to increase specificity in the range of tPSA of 4–10 µg/L.

Materials and methods

Four hundred and seven biopsy results and quantitative tPSA and F/T ratio data were combined. Using the histological determination, normal/hyperplasia versus malignant as a gold standard, receiver operating characteristic (ROC) curves as well as the areas under the curve (AUC) for tPSA and F/T ratio were determined. The differences between the two AUCs were considered for various tPSA ranges and specificities of F/T ratio and tPSA were calculated.

Results

In the total group, there was a gain of specificity of 11% (from 23% to 34%) when the sensitivity was 92% (using a cut-off >0.28 for the F/T ratio and a cut-off >4 µg/L for tPSA). When considering the group of patients for which the F/T ratio is currently used (4–10 µg/L), the gain of specificity was 27% (from 2% to 29%). This implicates that the number of unnecessary biopsies taken will be reduced by 27%. Moreover, the AUC of the F/T ratio was significantly higher at an even broader range of tPSA, i.e. up to 40 µg/L.

Conclusions

This study demonstrates that the F/T ratio has better diagnostic performance than tPSA, not only in the grey zone of tPSA, but also outside the grey zone, i.e. up to 40 µg/L.
A case of aspartate aminotransferase macroenzyme
Authors: Cabrera-Abreu J , Jain R , Robinson P , Edees S , Staughton T
Published: June 2008

Aspartate aminotransferase (AST) macroenzyme can result in elevated AST activity in patients with no disease. This case report describes a six-year-old boy who presented to his family doctor with a history of chronic constipation and lower back pain. Routine blood tests showed normal creatine kinase activity (CK), normal alanine aminotransferase activity (ALT) but raised AST. The patient was referred to a hospital paediatrician for further investigation of the abnormal AST and back pain. The raised AST was confirmed as the only biochemical abnormality. Further investigation with polyethylene glycol, followed by measurement of AST in the supernatant, showed undetectable enzyme activity. The sample was sent to a specialist laboratory where it was analysed by Sephacryl S300 gel filtration. This procedure confirmed the presence of a high molecular mass form of AST. AST macroenzyme should be considered as a cause of isolated AST increase, which may avoid further costly investigations.
Biochemical diagnosis of placental infarction/damage: acutely rising alkaline phosphatase
Authors: Ranganath L , Taylor W , John L , Alfirevic Z
Published: June 2008

There are currently no simple tests in clinical use to detect acute placental damage. A case is described to demonstrate that a routinely used measurement such as alkaline phosphatase (ALP) can be employed to detect acute damage to the placenta. Seventeen serial blood samples, three pre-delivery, were collected from a 22-year-old primigravida who delivered a stillborn baby. Retrospectively, blood samples were analysed for total and heat-stable ALP as well as human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP) as a measure of placental function when an unusual pattern of change in ALP was noticed. Histological examination of the placenta revealed new and old placental infarcts. Total and heat-stable ALPs as well as AFP peaked by more than eight-, 19- and two-fold, respectively over 16 h. Plasma hCG fell sharply even before delivery of placenta by five-fold over 16 h before further falling slowly to baseline. The fall in hCG is also consistent with the placental damage being acute and critical. As far as we are aware this is the first description of changes in circulating proteins reflecting placental damage.
Isolation, identification and quantification of differentially expressed proteins from cancerous and normal breast tissues
Authors: Othman Mohd Izani , Majid M I A , Singh Manjit , Man Che Nin , Lay-Harn Gam
Published: June 2008

Background

Infiltrating ductal carcinoma (IDCA) is the most common type of breast cancer accounting for 85% of all invasive breast cancers.

Methods

Forty tissue specimens comprising 20 pairs of normal and cancerous tissues were analysed. The tissues were homogenized and proteins were extracted using phosphate buffer. The protein extracts from each pair of cancerous and normal tissue were separated using sodium dodecyl sulphate-polyacrylamide gel electrophoresis in the same gel. The protein profiles of both the tissues were compared, and the differentially expressed proteins that were detected at >70% in one or both of the tissue types were selected for protein identification analysis. Target proteins were excised and digested in situ with trypsin prior to liquid chromatography/tandem mass spectrometry (LC/MS/MS) analysis. A protein that was present in both tissue types was further quantified using extracted ions chromatogram.

Results

The proteins were grouped as down-regulated, up-regulated and unique proteins. Twenty-two proteins were identified and eight of the proteins were found unique to cancer. These proteins belong to various molecular classes, i.e. structural protein, hypothetical protein, cytoskeletal protein, enzyme, calcium binding protein and extracellular matrix protein. One extracellular matrix protein, namely collagen α-1(I) chain precursor was found unique to cancer. By virtue of its location on the cell surface and its function in cancer growth, this protein may be a biomarker candidate for breast cancer.

Conclusions

The proteins identified in this study were present in at least 70% of the tissues tested; therefore they should have significant roles in the development of IDCA.