bluuebunny/crossref_metadata_2025 huggingface dataset:
Current understanding of the mechanism of action of classic and newer antidepressant drugs
Authors: Brunello Nicoletta , Langer Salomon Z. , Perez Jorge , Racagni Giorgio
Published: November 2007

Until 1980, the two major classes of antidepressant drugs were the tricyclics (TCAs) and the monoamine oxidase inhibitors (MAOIs). During the 1980s several additional classes of drugs appeared. Among these, selective serotonin reuptake inhibitors (SSRIs) have a distinct and well‐characterized mechanism of action, and have become among the most widely prescribed antidepressant drugs.

A common factor in the action of antidepressants with different chemical structures is the ability to increase the synaptic availability of one or more neurotransmitters, as a result either of blockade of the reuptake process or inhibition of metabolic degradation. However, the delay in clinical response to antidepressants suggests that, even if the acute pharmacologic effects of antidepressants may be essential for efficacy, symptom resolution requires some adaptive changes in neurotransmission. More recent studies, therefore, have focused on the signal transduction process beyond the receptor level, and on the regulation of gene expression of specific proteins.

The side‐effect profiles of antidepressants are related to their acute mechanisms of action. TCAs lack specificity of their pharmacological action, and are associated with antimuscarinic, antihistaminic, and alpha‐adrenergic blocking actions, that account for many unwanted side effects but do not contribute to their therapeutic profile. The SSRIs, as a result of their selective action to inhibit serotonin reuptake, appear to have more tolerable side effects than TCAs and are less likely to be lethal when taken in overdose. SSRIs have little or no affinity for neurotransmitter receptors. The most common side effect is gastrointestinal discomfort. Depression 2:119–126 (1994/1995). © 1995 Wiley‐Liss, Inc.
Effect of pharmacotherapy on suicidal ideation and behavior
Authors: Judd Lewis L. , Rapaport Mark H.
Published: November 2007

Suicide has become an important public health issue. It is the eighth leading cause of death among adults and varies between the second and third leading cause of death for youth under the age of 24 years. Suicidal ideation is a common symptom of psychiatric disorders; over 55% of individuals with mental disorders report suicidal ideation at some point in their lives. Fully 25% of individuals with mental disorders make at least one lifetime suicide attempt and over 12% make multiple suicide attempts. Suicidal ideation and suicidal acts are most prevalent in individuals with mood disorders. Almost 17% of individuals with either major depression or dysthymia make at least one suicide attempt while over 28% of individuals with bipolar disorders attempt suicide. Intensification of suicidal thoughts and behavior can occur in depressed patients undergoing active treatment, including antidepressant pharmacotherapy, and the risk may persist until remission occurs. Within this context, it is likely that reports linking the SSRI fluoxetine (and other antidepressants) with intensification of suicidal ideation represent random occurrences rather than causation. Although it is possible that some type of aberration in CNS serotonergic function in rare individuals might be associated with an idiosyncratic response to serotonin‐specific medications, the retrospective meta‐analyses of a number of databases indicate there is no causal relationship between SSRI or other antidepressant medication treatment and the emergence of suicidal ideation or behavior. Rather, the available data support the conclusion that antidepressant pharmacotherapy diminishes suicidal ideation and acts. Depression 2:169–172 (1994/1995). © 1995 Wiley‐Liss, Inc.
Economics of depression and cost‐benefit comparisons of selective serotonin reuptake inhibitors and tricyclic antidepressants
Authors: Judd Lewis L. , Rapaport Mark H.
Published: November 2007

The social and economic impact of depression on society at large has only recently been elucidated. The U.S. National Institute of Mental Health (NIMH) Epidemiology Catchment Area (ECA) Program demonstrated that the 1 year prevalence of DSM‐III mood disorders was almost 10% in the adult population of the United States—or that in any year over 17 million adults suffer from a major mood disorder. Moreover, data gathered by the Cross‐National Collaborative Group suggest further that the incidence of depression is increasing, not only in the United States, but in many countries all over the world. And results from the Medical Outcomes Study, which assessed the level of disability associated with depression compared with other common medical disorders, suggested that patients with major depression and dysthymia suffer greater levels of impairment than patients with hypertension, diabetes, arthritis, lung disease, and GI disorders.

A number of recent investigations have sought to quantify the costs of depression in the United States and the United Kingdom, and found that depression has remarkably high direct and indirect economic costs, comparable to those associated with other major public health problems. This paper reviews depression within this larger framework and evaluates the impact of treatment advances on the costs of depression. Both pharmaceutical‐sponsored and non‐sponsored cost‐benefit analyses reveal that while the classical anti‐depressants cost less on a per‐pill basis, ultimately treatment may be less expensive with the newer SSRIs because of improved compliance leading to better outcomes. Depression 2:173–177 (1994/1995). © 1995 Wiley‐Liss, Inc.
Discrimination of recovery in the treatment of elderly patients with recurrent major depression: Limits of prediction
Authors: Reynolds Charles F. , Frank Ellen , Dew Mary Amanda , Perel James M. , Mazumdar Sati , Buysse Daniel J. , Begley Amy , Houck Patricia R. , Miller Mark D. , Cornes Cleon , Kupfer David J.
Published: November 2007

The aim of this work was to determine: (1) the temporal course of recovery in elderly patients with recurrent major nonpsychotic depression treated with combined pharmacotherapy and psychotherapy; (2) the point at which recovering patients can be reliably distinguished from those who will not recover; and (3) the limits of accuracy in predicting recovery. The study group consisted of 101 elderly patients: 82 recovered, 19 no recovered. The method used was random regression and discriminant junction analyses. Reliable and persistent differences between recovering and no recovering elderly patients in Hamilton depression ratings were detected by week 4 of treatment in a random regression model. Discrimination of final outcome, using Hamilton ratings, current age, episode duration, and personality pathology score (derived from the Personality Assessment Form) increased greatly between weeks 4 and 5 of treatment, reaching a ceiling of 75‐80%. The ability to predict eventual treatment outcome for major depressive episodes in late life rests upon changes in clinical condition during the first 4 to 5 weeks of treatment. Under highly standardized treatment conditions, 75‐80% of patients can be reliably discriminated during early treatment with respect to eventual treatment outcome. Depression 2:218–222 (1994/1995). © 1995 Wiley‐Liss, Inc.
Use of single case analyses in off‐on‐off‐on trials in affective illness: A demonstration of the efficacy of nimodipine
Authors: McDermut Wilson , Pazzaglia Peggy , Huggins Teresa , Mikalauskas Kirstin , Leverich Gabriele S. , Ketter Terrence A. , Bartko John , Post Robert M.
Published: November 2007

This paper 1) demonstrates the efficacy of nimodipine in the treatment of a patient with rapid‐cycling bipolar disorder using an intensive single subject design, and 2) evaluates three statistical techniques that are useful in the analysis of single case data. The patient is a 42‐year‐old bipolar II female refractory to multiple medication trials who underwent double‐blind treatment with placebo (B), nimodipine (A), and verapamil (C) in a B‐A‐B‐A‐C‐A design. The use of statistics in single subject studies has been the subject of controversy. One problem with single subject data is that data points are often correlated with data points from adjacent time periods (i.e., nonindependent), and therefore such data have been considered inappropriate for statistics that assume independence of error terms. One statistical technique we examined was a t‐test in the context of repeated on‐offdrug trials suggested by Gentile, Roden, and Klein (1972), in which all data points from treatment phases are aggregated and then compared to aggregated data from baseline or placebo phases. We compared this t‐test to a variant of meta‐analysis in which each phase is statistically compared to its adjacent phases and the t‐values from those comparisons are summed and converted to a z‐score. As illustrated with this patient, the t‐test method tended to be more conservative than the z‐score method in instances where there is an overall time trend for improvement or deterioration. The Chassen technique also provides an alternative for analysis of data with time trends. The 2 method was more conservative than the single aggregated t‐test if the direction of predicted change on a given measure (i.e., improvement during an active drug phase and deterioration during a placebo phase) did not occur as expected at each medication transition. These statistical techniques, in combination with the sequential off‐on‐off‐on clinical trial design, provide strong evidence for the mood‐stabilizing effect of nimodipine in this rapid‐cycling BP II female. Depression 2:259–271 (1994/1995). © 1995 Wiley‐Liss, Inc.
Fluoxetine in tricyclic refractory depression in adolescents
Authors: Ghaziuddin Neera , Naylor Michael W. , King Cheryl A.
Published: November 2007

In an open cross‐over trial, six hospitalized adolescents (15–18 years) with a DSM‐III‐R diagnosis of major depression, who had failed to respond to a trial of tricyclic antidepressant (TCA) with or without lithium augmentation, were treated with fluoxetine. Fluoxetine treatment (20–60 mg/day) was associated with a reduction in depression severity after 4 weeks, as measured by Hamilton Rating Scale for Depression. The Hamilton Rating Scale for Depression scores (HRSD) reduced significantly after 4 weeks, from 15.8 ± 2.3 to 8.1 ± 3.4 (Z = 2.2, P < 0.02; Wilcoxin signed rank test). Fluoxetine was well tolerated and no subject required discontinuation of medication. One patient became hypomanic on 60 mg/day but responded to dose reduction. Data suggest that, as in the adult age group, there may be a subgroup of TCA non‐responsive depressed adolescents who respond to fluoxetine. Shortcomings of the present report are a small number of subjects, open nature of study design, and absence of standardized treatment before commencing trial of fluoxetine. Findings of this report suggest that controlled trials using a placebo‐controlled design and involving a larger number of subjects are indicated. Depression 2:287–291 (1994/1995). © 1995 Wiley‐Liss, Inc.
Polysomnogram in major depressive and obsessive‐compulsive disorders: A preliminary study
Authors: Armitage Roseanne , Debus John , Kiger Bonnie , Trivedi Madhukar , Cain John , Roffwarg Howard P. , Rush A. John
Published: November 2007

The sleep macroarchitecture of 10 outpatients with obsessive‐compulsive disorder (OCD) was compared to a group of symptomatic, unmedicated outpatients with nonpsychotic major depressive disorder (MDD) (n = 10). No group main effects were observed. Gender by group interactions were observed on the amount of wakefulness and total sleep period. Male patients with MDD had the highest amount of wakefulness, whereas female patients with OCD showed the least amount of wakefulness. Of the REM sleep parameters, only the duration of the individual REM periods showed between‐group differences, interacting with gender. Gender main effects were also obtained on the amount of Stage 1 sleep, which was lower among females. REM latency did not differentiate the groups. These findings suggest that selected sleep EEG parameters may differentiate patients with MDD from those with OCD, but that these effects are moderated by gender. Depression 2:291–302 (1994/1995). © 1995 Wiley‐Liss, Inc.
Glucocorticoid cascade hypothesis revisited: Role of gonadal steroids
Authors: Young Elizabeth A.
Published: November 2007

Sex differences in HPA axis regulation have been documented in other species, particularly in rats, where estrogen regulates cortisosteroid binding globulin (CBG). Given that depression is more common in women, gonadal steroids may impact upon the HPA axis dysregulation often seen in depression. A number of our studies comparing HPA axis dysregulation in depressed men and women suggest that there are differences. We suggest that gonadal steroids may play a modulatory role in premenopansal depressed women. In particular, estrogen increases the level of CBG providing a greater buffering capacity against hypercortisolemia. In addition, progesterone can function as a glucocorticoid antagonist, thus blocking some of the negative sequellae of hypercortisolemia. Following menopause, the incidence of resistance to dexamethasone suppression increases to almost 100%, suggesting that loss of gonadal steroids is an important aspect of the age‐HPA axis interaction. Depression 3:20–27 (1995). © 1995 Wiley‐Liss, Inc.
Sex hormones, orcadian rhythms, and depressive vulnerability
Authors: Parry Barbara L.
Published: November 2007

The objective of this review is to delineate the chronobiologic studies of mood disorders linked to the reproductive cycle in women. The experimental designs range from baseline studies of sleep and melatonin circadian rhythms to challenge designs utilizing light therapy and sleep deprivation as experimental perturbations. In summary, melatonin profiles, the best marker for circadian rhythmicity in humans, are abnormally blunted in women with premenstrual dysphoric disorder (PMDD). Further, light therapy and sleep deprivation, chronobiologic interventions designed to correct underlying circadian rhythm disturbances, are effective in reducing particularly depressive symptoms in PMDD and may have benefit in other reproductive‐related depressions in women such as postpartum or menopausal depressions. Depression 3:43–48 (1995). © 1995 Wiley‐Liss, Inc.
Cognitive‐behavioral treatment of premenstrual syndrome and chronic gynecologic pain
Authors: Stout Anna L.
Published: November 2007

Mood disorders have been associated with reproductive events and gynecologic conditions which specifically affect women. Somatic therapies have dominated treatment for these disorders, possibly because of the commonly held belief that the accompanying mood changes are primarily related to physiological states. Some women, however, may receive inadequate symptom relief from currently available pharmacologic therapies, or find other treatment options, such as surgical or hormonal therapies, unacceptable because of the negative impact on their future reproductive or health status. Based on the documented effectiveness of cognitive‐behavioral therapies in the treatment of other mood disorders, exploratory studies of the efficacy of cognitive‐behavioral treatment strategies for gynecologically related mood disorders have been initiated. This review focuses on the problem areas of premenstrual syndrome and chronic pelvic pain.

A number of cognitive‐behavioral strategies for treating premenstrual mood symptoms have been reported in the literature; however, few have been subjected to controlled studies with well‐evaluated and well‐described subjects. Preliminary findings suggest that a combination of cognitive‐behavioral interventions and relaxation training, when administered in an adequate number of treatment sessions, may significantly improve premenstrual mood disorders and possibly maintain benefits for a longer period time than pharmacologic treatments. Few therapeutic modalities specific for pelvic pain beyond medical/ surgical approaches have been evaluated. Depending on the treatment setting, general pain management approaches may be applied to pelvic pain patients; however, there is some evidence that chronic pelvic pain patients may differ from other chronic pain conditions and may have special therapeutic needs. Reports of controlled trials of psychological interventions are quite limited; however, several studies report that combined multidisciplinary approaches result in improved levels of functioning. A proposed model for chronic pelvic pain and suggested intervention strategies are also discussed. Depression 3:60–65 (1995). © 1995 Wiley‐Liss, Inc.
Rapid onset of antidepressant activity with venlafaxine treatment
Authors: Rickels Karl , Derivan Albert , Entsuah Richard , Miska Susan , Rudolph Richard
Published: November 2007

A literature review indicates that many clinical reports of rapid onset of anti‐depressant action were not supported by later clinical trials or use. In addition, few of the authors or investigators had compared results on multiple depression scales or looked at depression factors. The purpose of this study was to evaluate response during the first week of clinical trials of the novel antidepressant, venlafaxine. A comprehensive evaluation was done by using efficacy data from two double‐blind placebo‐controlled studies of venlafaxine in which doses were rapidly adjusted. In one study, 323 depressed outpatients received placebo or one of three venlafaxine doses for 6 weeks; in the other study 93 depressed inpatients with melancholia received placebo or venlafaxine for 4 weeks. Venlafaxine was significantly superior to placebo in lowering total and factor scores on depression scales and increasing global improvement at 1 week. Venlafaxine‐treated patients whose doses are rapidly titrated to above 200 mg per day have improvement in depression as early as 1 week. This improvement could be important in severely depressed patients. Depression 3:146–153 (1995). © 1995 Wilsey‐Liss, Inc.
Bipolar II: Not so different when co‐morbidity excluded
Authors: Cooke Robert G. , Young L. Trevor , Levitt Anthony J. , Pearce Michelle M. , Joffe Russell T.
Published: November 2007

Subjects with unipolar depression and bipolar disorder types I and II who had been selected to be free of recent substance abuse and severe character pathology as part of their participation in two research studies, were compared on a number of clinical features. No significant differences were observed between bipolar I and II subjects on any of these measures. These results are consistent with the suggestion that previously reported differences between bipolar I and II might be attributable in part to the presence of character pathology and substance abuse in unselected bipolar II populations. Depression 3:154–156 (1995). © 1995 Wiley‐Liss, Inc.
Reactive mood and atypical depression in psychiatrically hospitalized depressed adolescents
Authors: Kaminski Kathleen M. , Naylor Michael W. , King Cheryl A. , Ghazuiddin Neera
Published: November 2007

We undertook this study to determine the frequency of atypical depression and associated features in a sample of adolescents hospitalized for depression. One hundred and twenty‐two consecutively admitted depressed adolescents were included in the study. Each adolescent was retrospectively assessed for the presence of atypical depression based on the DSM W Atypical Feature Specifier criteria (mood reactivity plus two of four associated symptoms: hypercharge, hypersomnia, leaden paralysis, and/or a pathological sensitivity to rejection). We found that 45% of the depressed adolescents displayed a reactive mood. Seven percent of our subjects met criteria for atypical depression. An additional 7% met criteria for probable atypical depression (reactive mood plus one associated feature). Subjects with atypical depression and probable atypical depression were significantly less depressed than those with nonreactive mood. Depression 3:176–181 (1995). © 1995 Wiley‐Liss, Inc.
Hypothesis linking the noradrenergic and dopaminergic systems in depression
Authors: Weiss Jay M. , Demetrikopoulos Melissa K. , West Charles H. K. , Bonsall Robert W.
Published: November 2007

A hypothesis is presented that attempts to describe the mechanism by which noradrenergic neurons in the brain influence dopaminergic neurons to produce behavioral changes seen in depression. The historical background pointing to a norepinephrine (NE)‐dopamine (DA) interaction in depression is described. This interaction is suggested by numerous observations indicating that whereas NE is important in therapy and pathogenesis of depression, basic research implicates DA in depression‐related behavioral responses (motor activity changes, hedonic response) much more so than NE. The hypothesized NE‐DA interaction is introduced in relation to an animal model (stress‐induced behavioral depression) that has traced depressive symptomatology to abnormal activity (hyperresponsivity) of locus coeruleus (LC) neurons. Based on recent data by Grenhoff et al. (1993; J Neural Transm 93:11–25), it is suggested that the augmented burst firing of LC neurons found in behavioral depression releases galanin from LC axon terminals, and this inhibits (hyper‐polarizes) DA neurons in the ventral tegmentum (VTA) to mediate depression‐related behavioral changes. Initial results showing that microinfusion of galanin into the VTA decreases spontaneous and swim‐test motor activity of animals are described. Depression 3:225–245 (1995/1996). © 1996 Wiley‐Liss, Inc.
Effects of electroconvulsive treatment on somatostattn, neuropeptide Y, endothelin, and neurokinin a concentrations in cerebrospinal fluid of depressed patients: A pilot study
Authors: Mathé A. A. , Rudorfer M. V. , Stenfors C. , Manji H. K. , Potter W. Z. , Theodorsson E.
Published: November 2007

Cerebrospinal fluid (CSF) was obtained from eight drug‐free depressed patients before and 5–10 days after completion of a series of electroconvulsive treatments (ECT). Somatostatin‐ (STS), neuropeptide Y‐ (NPY), endothelin‐(ET), and neurokinin A‐ (NKA) like immunoreactivity (LI), as well as MHPG, HVA, and 5‐HIAA concentrations were determined in CSF samples. In line with previous reports, HVA and 5‐HIAA CSF concentrations were correlated and increased following ECT. The new findings are that STS‐LI, NPY‐LI, and ET‐LI were significantly elevated after the treatment. Means ± SD, pmol/l were: STS‐LI 8.6 ± 4.8 to 15.4 ± 10.8, P < 0.05; NPY‐LI 44.5 ± 8.9 to 51.4 ± 12.1, P < 0.01; ET‐LI 0.91 ± 0.27 to 1.54 ± 0.39, P <0.01. The results raise the possibility that one of ECT's mechanisms of action, consistent with the well‐documented action of electroconvulsive stimuli (ECS) on peptides in distinct rat brain regions, involves alterations of synthesis, release or clearance of SS, NPY, and ET. As seven/eight subjects improved, the findings could also depend on changes in the patients' clinical condition rather than a cascade of biochemical alterations induced by ECT. Studies in patients receiving but not responding to ECT would be necessary to decide between these possibilities. Depression 3:250–256 (1995/1996). ± 1996 Wiley‐Liss, Inc.
Adverse events in 583 valproate‐treated patients
Authors: Calabrese Joseph R. , Goethe John W. , Kayser Allen , Marcotte David B. , Monagin John A. , Kimmel Susan E. , Brugger Andrew M. , Morris David , Fatemi S. Hossein
Published: November 2007

Double‐blind placebo‐controlled studies indicate that valproate is an effective therapy for bipolar mania. The objective of this research was to evaluate the profile of adverse events associated with the medical management of bipolar disorder when valproate was administered with routine adjunctive psychotropic agents. A structured retrospective chart review for adverse events was done in 583 valproate‐treated bipolar patients across five medical centers. Valproate was used for 3 months by 392 patients and >1 year in 168. For 961 patient‐years, 97% patients were treated concomitantly with other medications. Eighty‐three percent of patients were comorbid, with clinically significant medical illnesses. The average total daily dose of valproate was approximately 1400 mg and serum level was 82 μg/ml. Consistent with prior reports in epilepsy, adverse events associated with valproate included (in order of decreasing prevalence) tremor, nausea, somnolence, hair changes/thinning, asthenia, diarrhea, weight gain, dizziness, abdominal pain/stomach cramping, benign thrombocytopenia, headaches, and vomiting. These data suggest that when valproate is openly administered with a wide array of other psychiatric medications over relatively long periods, as is frequently the case in routine clinical practice, the profile of valproate‐related adverse events is similar to those already observed in the treatment of epilepsy. Depression 3:257–262 (1995/1996). © 1996 Wiley‐Liss, Inc.
Responsivity of allergic depressed subjects to antidepressant medication: A preliminary study
Authors: Kennedy Barbara L. , Morris Richard L. , Schwab John J.
Published: November 2007

The prevalence of allergies in 52 patients with major depression was higher than that reported in the general population. After 8 weeks of treatment with either one of two serotonin reuptake inhibitors (SSRIs) or the heterocyclic antidepressant that we used in the clinical trials, the non‐allergic depressed had a significantly greater response than the partial response of the allergic depressed as measured by decreases in HAM‐D scores from baseline to the end of 8 weeks. Also, all of the non‐allergic depressed responded to antidepressants whereas slightly fewer than one‐half of the allergic depressed did so. Moreover, after the 8 weeks there were no differences between the HAM‐D scores of the allergic depressed receiving active medication and those receiving placebos whereas the HAM‐D scores of the non‐allergic were significantly lower than those of the placebo group. Although the results are only preliminary observations, they have clinical implications. There is a need for investigators conducting clinical drug trials and for practitioners to obtain information about each depressed patient's allergy status. The discussion focuses on possible methodologic and other explanations for the lower responsivity of the depressed allergic than the non‐allergic to antidepressants and also on the need for additional studies to determine whether the results can be replicated. Depression 3:286–289 (1995/1996). © 1996 WIey‐Liss, Inc.
Lifestyle regularity and activity level as protective factors against bereavement‐related depression in late‐life
Authors: Prigerson Holly G. , Monk Timothy H. , Reynolds Charles F. , Begley Amy , Houck Patricia R. , Bierhals Andrew J. , Kupfer David J.
Published: November 2007

This study sought to determine whether high regularity in the timing of daily activities among the elderly soon after spousal death was protective against depressive symptomatology 1 and 2 years later, and the degree to which the depression‐buffering effects of high lifestyle regularity were contingent upon the level of activity performed. The regularity of daily activities was assessed at 3 months post‐loss among 41 spousally bereaved subjects aged 60 and above; depressive symptomatology was measured at 3, 12, and 24 months post‐loss. Multiple regression analyses revealed that greater lifestyle regularity at 3 months post‐loss predicted lower levels of depressive symptoms at 1 year post‐loss among those in the upper‐half level of activity. There was a trend, which suggested that greater lifestyle regularity at 3 months post‐loss was associated with lower levels of depressive symptoms at 24 months post‐loss among those in the upper‐third level of activity. These preliminary results suggest that for aged widows and widowers, lifestyle regularity may prevent long‐lasting depressive symptomatology secondary to spousal bereavement, provided an adequate number of activities are performed. Depression 3:297–302 (1995/1996). © 1996 Wiley‐Liss, Inc.
Manipulation of NK cytotoxicity by the IAP family member Livin
Authors: Nachmias Boaz , Mizrahi Sa'ar , Elmalech Meital , Lazar Itay , Ashhab Yaqoub , Gazit Roi , Markel Gal , Ben‐Yehuda Dina , Mandelboim Ofer
Published: November 2007

Natural killer (NK) cells are part of the innate immune system, capable of killing tumor and virally infected cells. NK cells induce apoptosis in the target cell by either granule‐ or receptor‐mediated pathways. A set of inhibitory and activation ligands governs NK cell activation. As transformed cells often attempt to evade NK cell killing, up‐regulation of a potential anti‐apoptotic factor should provide a survival advantage. The inhibitor of apoptosis protein (IAP) family can inhibit apoptosis induced by a variety of stimuli. We have previously described a new IAP family member, termed Livin, which has two splice variants (α and β) with differential anti‐apoptotic activities. In this study, we explore the ability of Livin to inhibit NK cell‐induced killing. We demonstrate that Livin β moderately protects against NK cell killing whereas Livin α augments killing. We show that Livin β inhibition in Jurkat cells is apparent upon concomitant activation of an inhibitory signal, suggesting that Livin augments an extrinsic inhibitory signal rather than functioning as an independent inhibitory mechanism. Finally, we demonstrate that detection of both Livin isoforms in melanoma cells correlates with a low killing rate. To date, this is the first evidence that directly demonstrates the ability of IAP to protect against NK cell‐induced apoptosis.
Selective silencing of DNA‐specific B lymphocytes delays lupus activity in MRL/lpr mice
Authors: Tchorbanov Andrey I. , Voynova Elisaveta N. , Mihaylova Nikolina M. , Todorov Todor A. , Nikolova Maria , Yomtova Vihra M. , Chiang Bor‐Luen , Vassilev Tchavdar L.
Published: November 2007

The pathological DNA‐specific B lymphocytes in lupus are logical targets for a selected therapeutic intervention. We have hypothesized that it should be possible to suppress selectively the activity of these B cells in lupus mice by administering to them an artificial molecule that cross‐links their surface immunoglobulins with the inhibitory FcγIIb surface receptors. A hybrid molecule was constructed by coupling the DNA‐mimicking DWEYSVWLSN peptide to a monoclonal anti‐mouse FcγRIIb antibody. This chimeric antibody was added to cultured spleen cells from sick MRL/lpr mice, immunized with diphtheria toxoid, resulting in reduction of the numbers of anti‐DNA but not of anti‐diphtheria IgG antibody‐producing cells. Intravenous infusions with the DNA‐peptide antibody chimera to 7‐wk‐old animals prevented the appearance of IgG anti‐DNA antibodies and of albuminuria in the next 2 months. The administration of the DNA‐peptide chimeric antibody to 18 wk‐old mice with full‐blown disease resulted in the maintenance of a flat level of IgG anti‐DNA antibodies and in delay of the aggravation of the lupus glomerulonephritis. The use of chimeric antibodies targeting inhibitory B lymphocyte receptors represents a novel approach for the selective suppression of autoreactive disease‐associated B cells in autoimmune diseases.
The activity of lipopeptide TLR2 agonists critically depends on the presence of solubilizers
Authors: Voss Söhnke , Ulmer Artur J. , Jung Günther , Wiesmüller Karl‐Heinz , Brock Roland
Published: November 2007

Lipoproteins activate cells of the innate immune system via heteromers of Toll‐like receptor (TLR) 2 with either TLR1 or TLR6. In spite of progress in understanding TLR‐dependent signal transduction and the pathophysiological relevance of TLR2, the molecular basis of ligand recognition by this receptor is poorly defined. Here, we show that the bioactivity of lipopeptides (LP) critically depends on the dilution protocol and especially the presence of proteins or detergents acting as solubilizers. Fluorescence correlation spectroscopy of fluorescently labeled analogs of synthetic LP revealed that the LP form aggregates in solution. Dilution into protein‐ and serum‐free buffers led to a complete loss of activity due to formation of large and highly heterogeneous aggregates. When dimethylsulfoxide stock solutions were diluted into BSA or serum‐containing buffers particles of strongly reduced size were obtained. For some LP, an intermediary dilution step either with tert.‐butyl alcohol/H2O (4:1) or with octyl‐β‐D‐glucopyranoside further increased activity. For a panel of LP exhibiting very different activities when diluted directly into protein‐containing solutions, introduction of this dilution step resulted in comparable bioactivities. These results demonstrate the significance of solubilizing agents for the bioactivity of LP and are highly relevant for analyzing structure‐activity relationships of LP‐dependent TLR2 activation.
Anti‐chromatin antibodies drive in vivo antigen‐specific activation and somatic hypermutation of rheumatoid factor B cells at extrafollicular sites
Authors: Herlands Robin A. , William Jacqueline , Hershberg Uri , Shlomchik Mark J.
Published: November 2007

A dominant type of spontaneous autoreactive B cell activation in murine lupus is the extrafollicular generation of plasmablasts. The factors governing such activation have been difficult to identify due to the stochastic onset and chronic nature of the response. Thus, the ability to induce a similar autoreactive B cell response with a known autoantigen in vivo would be a powerful tool in deciphering how autoimmune responses are initiated. We report here the establishment and characterization of a system to initiate autoreactive extrafollicular B cell responses, using IgG anti‐chromatin antibodies, that closely mirrors the spontaneous response. We demonstrate that exogenously administered anti‐chromatin antibody, presumably by forming immune complexes with released nuclear material, drives activation of rheumatoid factor B cells in AM14 Tg mice. Anti‐chromatin elicits autoreactive B cell activation and development into antibody‐forming cells at the T zone/red pulp border. Plasmablast generation occurs equally in BALB/c, MRL/+ and MRL/lpr mice, indicating that an autoimmune‐prone genetic background is not required for the induced response. Importantly, infused IgG anti‐chromatin induces somatic hypermutation in the absence of a GC response, thus proving the extrafollicular somatic hypermutation pathway. This system provides a window on the initiation of an autoantibody response and reveals authentic initiators of it.
Covariance estimation for multivariate conditionally Gaussian dynamic linear models
Authors: Triantafyllopoulos K.
Published: November 2007

In multivariate time series, estimation of the covariance matrix of observation innovations plays an important role in forecasting as it enables computation of standardized forecast error vectors as well as the computation of confidence bounds of forecasts. We develop an online, non‐iterative Bayesian algorithm for estimation and forecasting. It is empirically found that, for a range of simulated time series, the proposed covariance estimator has good performance converging to the true values of the unknown observation covariance matrix. Over a simulated time series, the new method approximates the correct estimates, produced by a non‐sequential Monte Carlo simulation procedure, which is used here as the gold standard. The special, but important, vector autoregressive (VAR) and time‐varying VAR models are illustrated by considering London metal exchange data consisting of spot prices of aluminium, copper, lead and zinc. Copyright © 2007 John Wiley & Sons, Ltd.
Hydrothermal catalytic conversion of biomass for lactic acid production
Authors: Kong Lingzhao , Li Guangming , Wang Hua , He Wenzhi , Ling Fang
Published: November 2007

The production of lactic acid has increased owing to growing polymer markets, increased demand in the chemical sector and many applications in the food industry. Biomass hydrothermal decomposition is potentially a method for lactic acid production. To obtain a higher yield of lactic acid, the influence of metal ions (Zn(II), Ni(II),Co(II) and Cr(III)) on biomass decomposition in sub‐critical water (T = 300 °C) was investigated and the catalyst function in the complex reaction network of biomass degradation was discussed. In comparison with a non‐catalytic process, the addition of 400 ppm Ni(II) catalyst increased the yield of lactic acid from 3.25% to 6.62% at 300 °C and 120 s for microcrystalline cellulose. The lactic acid yield for glucose was 9.51% for 400 ppm Co(II) catalyst at 300 °C and 120 s. In the case of Cr(III) and Ni(II), the conversion of maize straw, sawdust and rice husk first increased, and then decreased from 0 to 800 ppm. For catalyst Cr(III), Zn(II) and Ni(II), the conversion of wheat bran indicated a decreasing trend. Transition metal ions have a great influence on raw materials conversion to lactic acid. In the conversion of pyruvaldehyde to lactic acid, the ionic catalyzed Cannizzaro‐type reaction would take place. Copyright © 2007 Society of Chemical Industry
Reconstruction of winter climate variations during the 19th century in Japan
Authors: Hirano Junpei , Mikami Takehiko
Published: November 2007

An attempt was made to reconstruct winter climate conditions in Japan for the period 1810/1811 to 1858/1859 on the basis of daily weather records documented in old diaries. Daily weather maps for each winter were drawn using 19th century weather records collected by our research group. Maps were divided into five types by classifying daily snowfall and rainfall distributions and the occurrence frequencies of each weather pattern for the period 1810/1811 to 1858/1859 were analysed. It was found that the occurrence frequencies of winter monsoon weather patterns were high from the late 1820s to the early 1840s. This period almost coincided with a summer cold period in the 19th century. The result implies that strengthening of a cold air mass around Japan occurred in the late 1820s, not only in summer but also in winter. The frequencies of the typical winter monsoon patterns correspond with the freezing dates of Lake Suwa, which have been used as an indicator of winter coldness in previous studies. On the basis of the frequencies of the winter monsoon weather patterns, mean January temperatures for western Japan were estimated. In the time series of estimated temperatures, a cooling period from the late 1820s to the early 1830s was revealed. Copyright © 2007 Royal Meteorological Society
Application of multilayered particles formed by poly(3,4‐ethylenedioxythiophene) and poly(N‐methylpyrrole) as anti‐corrosive additives of conventional organic coatings
Authors: Aradilla D. , Ocampo C. , Armelin E. , Alemán C. , Oliver R. , Estrany F.
Published: November 2007

Multilayered systems containing 3 or 5 layers of poly(3,4‐ethylenedioxythiophene) and poly(N‐methylpyrrole) have been prepared using a layer‐by‐layer electrodeposition technique. These multilayered systems have been found to present very high electroactivities suggesting that their performance as anti‐corrosive additive of conventional organic coatings (paints) could be even better than that of single‐component conducting polymers. The performance of the prepared multilayered systems as anti‐corrosive additives of epoxy paints has been checked. For this purpose, accelerated corrosion tests were performed using an aggressive solution medium. Analysis of the corroded area indicates that the addition of a low concentration (0.2% w/w) of these multilayered systems to the paint formulation enhances significantly the corrosion protection imparted by the coating.
Hot corrosion of a plasma sprayed Ni3Al coating on a Ni‐base superalloy
Authors: Singh H. , Puri D. , Prakash S. , Ghosh T. K.
Published: November 2007

Ni3Al metallic powder was prepared by the mechanical mixing of pure nickel and aluminium powders and deposited on a Ni‐base superalloy namely Superni 75 by the shrouded plasma spray process. Hot corrosion behaviour of Ni3Al coated and uncoated superalloy specimens was evaluated in a simulated environment of fossil fuel boilers comprising of Na2SO4–60%V2O5by accelerated corrosion tests. The accelerated testing was done under cyclic conditions for 50 cycles, with each cycle consisting of 1 h heating in the silicon carbide furnace and cooling for 20 min in air. The coated superalloy was also subjected to air oxidation for 50 cycles to get an idea about its oxidation behaviour and adherence of the Ni3Al coating and its oxide scale with the substrate superalloy. The oxide scales were characterised by X‐ray diffraction (XRD), scanning electron microscopy/energy dispersive X‐ray (SEM/EDAX) analyses and electron probe microanalysis (EPMA). The uncoated superalloy suffered an accelerated corrosion in the form of spallation of its oxide scale, whereas the oxide scale formed on the Ni3Al coated specimen was intact during the air as well as the molten salt oxidation. Furthermore, the coating was found successful in preventing the internal oxidation of the substrate superalloy. The coating maintained its adherence to the substrate superalloy during the exposure to both the environments of the study. The XRD analysis revealed the presence of oxides like Al2O3, NiO and NiAl2O4in the oxide scale of the coated superalloy. The XRD results were further supported by the SEM/EDAX and EPMA analyses.
Selectively Dendronized Cellulose: Synthesis and Characterization
Authors: Pohl Matthias , Schaller Jens , Meister Frank , Heinze Thomas
Published: November 2007

Selectively dendronized cellulose at C‐6 was synthesized homogeneously (in DMSO) and heterogeneously (in methanol) by the conversion of 6‐azido‐6‐deoxy cellulose (degree of substitution, DS 0.75) with polyamidoamine (PAMAM) dendrons possessing an ethynyl focal moiety via the copper‐catalyzed Huisgen reaction (click reaction) under mild conditions. First to third generation of PAMAM‐triazolo cellulose derivatives with DS values of up to 0.69 could be prepared, which are soluble in organic solvents (DMSO, DMF) and in water. The novel biopolymer derivatives were characterized by elemental analysis, FTIR, and NMR spectroscopic methods, showing no impurities and no conversion at the secondary positions.

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First‐principles calculations of the mechanical properties of boron‐rich compounds B12N2X (X = Be, Zn, Cd)
Authors: Gou Huiyang , Hou Li , Zhang Jingwu , Sun Guifang , Gao Lihua , Gao Faming
Published: November 2007

Using first‐principles calculations, we have investigated the mechanical properties (bulk, shear, and Young's moduli, Poisson's ratio, and brittleness) of boron‐rich compounds B12N2X (X = Be, Zn, Cd) with the boron carbide‐type structure. The higher shear modulus, 221 GPa for B12N2Be, and the unusual ratio of shear modulus to bulk modulus suggest that the boron‐rich compound B12N2Be is a superhard material. The ionicity of B–X bonds increases with the introduction of metal atoms from Be to Zn to Cd. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Tribological interactions between DLC coatings and lubricants
Authors: Podgornik B. , Vizintin J. , Strnad S. , Stana‐Kleinschek K.
Published: November 2007

In the last couple of years a tremendous research work has been done in the field of development and characterization of hard coatings, mainly to boost their use in machine component applications working under normal and extreme operating conditions. Generally, hard coatings improve tribological properties of contact surfaces under dry sliding, while under lubricated conditions their inertness hinder the possibility of boundary film formation. The aim of this paper is to elaborate on the interactions between diamond‐like carbon (DLC) coatings and lubricants, and possible tribofilm formation in different tribological contacts. Therefore, relationships between surface properties (i.e. surface tension, surface free energy, contact angle) and tribological properties of the lubricated DLC coated contact, as well as the influence of oil additive type and concentration and contact conditions will be presented. It is believed that this type of knowledge will lead to further coatings modification in terms of improved tribological properties under boundary lubrication. Copyright © 2007 John Wiley & Sons, Ltd.
The estimation of a bivariate fitness function from two samples taken from a population
Authors: Manly B. F. J.
Published: November 2007

The fitness of animals subjected to natural selection can be defined as the probability of surviving selection for a given interval of time, or some convenient multiple of this. If the fitness is related to some measurable variablesX, Y, Z,… then the relationship is expressed mathematically in the fitness functionw(x, y, z,…)and this function can be estimated by comparing the joint distribution ofX, Y, Z,… in samples taken before and after selection.

In an earlier paper (Manly, 1975) the problems involved in estimating a fitness function of one variable were discussed. In the present paper various methods for estimating a bivariate fitness function are proposed and compared on some semiartificial sample data. It is concluded that either a generalized version ofO'Donald's(1968) method of moments or a weighted multiple regression method will be most satisfactory. Alternative methods involving assumptions of normality will need to be used with great care.
A further note on Kiritani and Nakasuji's model for stage‐frequency data including comments on the use of Tukey's jackknife technique for estimating variances
Authors: Manly B. F. J.
Published: November 2007

Some general equations for stage‐frequency estimation are presented and their applications discussed.Tukey's(1958) jackknife technique is suggested for the calculation of the approximate variances associated with estimators of population parameters.
A sequential estimation technique for capture‐recapture censuses
Authors: Kuno Eizi
Published: November 2007

A simple technique of sequential estimation was proposed for capture‐recapture census by thePetersenmethod. In theory this technique makes it possible to secure automatically a required precision level for the population estimate to be obtained, irrespective of the population size. Some problems about its practical application were discussed.
Maternal age as a source of variation in the ability of an aphid to produce dispersing forms
Authors: MacKay Patricia A. , Wellington W. G.
Published: November 2007

Apterous parthenogentic females of the pea aphid, Acyrthosiphon pisum (Harris), begin to produce alate offspring soon after they have been subjected to crowding. Females which were born early in their own parent's reproductive period respond most strongly to crowding, producing much larger numbers of alatae than their late‐born sisters.

In contrast, the early‐born daughters of most alate females do not produce winged offspring after being crowded. Some of their later‐born sisters may produce a few winged individuals, resembling in this respect the late‐born daughters of the apterous females.

Control of the production of alatae thus begins in the grandparental generation. Risk‐spreading by means of differential dispersal becomes a less uncertain venture when local populations can modify their responses to environmental changes by utilizing past as well as present signals from their surroundings.
Quantitative demography of copperheads, Agkistrodon contortrix (Serpentes: Viperidae)
Authors: Vial James L. , Berger Thomas L. , McWilliams William T.
Published: November 2007

A quantitative analysis of population characteristics is applied to a previously published descriptive natural history of the copperhead (Agkistrodon contortrix).

Mathematical applications have permitted an expanded interpretation of the original field data to a number of dynamic, age‐specific, parameters including life tables, survivorship curves, natality and mortality, rate of population increase, age distribution and reproductive value. Similar data available for other snake populations are meager and only limited comparisons can be made.

The results obtained from our procedures firmly establish the value of reexamining the existing herpetological literature for potential application of methods that will generate quantitative expressions of population dynamics.