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PubMed2001

Immunostaining of calmodulin and aluminium in Alzheimer's disease-affected brains.

Previous in vitro studies have shown that Al(3+) binds to calmodulin, inducing alterations in its capability to interact with target proteins, accompanied by loss of immunological recognition by its conformational specific monoclonal antibody CAM1. In spite of the wealth of data of calmodulin action in vitro, little information is available on the possible involvement of this protein in the pathology typical of Alzheimer's disease. In the present study, we investigated calmodulin immunoreactivity in post-mortem human brains affected by Alzheimer's disease, compared with age-matched control brains. Conformational monoclonal antibodies raised against Ca(2+)-calmodulin, namely CAM1 and CAM4, were used in this study for the characterization of calmodulin. Calmodulin immunorecognition by monoclonal antibody CAM1 was found to be lost in cortical tissue sample from brains affected by Alzheimer's disease. This finding leads to the hypothesis of a new, possibly inactive, conformation of the molecule during the disease. On the other hand, CAM4 immunoreactivity was decreased in neurons of brains affected by Alzheimer's disease. Anti-Al(3+) monoclonal antibodies revealed instead more marked aluminium immunoreactivity in the affected brains compared to normal ones. The loss of CAM1 immunoreactivity and the occurrence of large amounts of aluminium suggest an alteration of the active conformation of calmodulin in disease-affected brains. These alterations could be involved in the development of Alzheimer's disease pathology.

Aged↗
PubMed1998

The comorbidity of alcohol dependence and affective disorders: treatment implications.

This paper reviews recent literature on the prevalence of alcohol dependence and affective disorders (major depression, dysthymia), the comorbidity of these conditions and the effects of comorbid affective disorders on the outcome of treatment for alcohol dependence. Alcohol dependence and affective disorders co-occur at significantly higher rates than would be expected by chance within the general population. This comorbidity is further elevated in samples of people seeking treatment for alcohol dependence, suggesting that the co-occurrence of affective disorders may be an important determinant of treatment seeking. The results of a number of recent placebo-controlled studies have suggested that pharmacological treatment with anti-depressants may enhance the efficacy of treatment for alcohol dependence in individuals with comorbid affective disorders.

Alcoholism↗
PubMed2000

Anatomic factors affecting microkeratome placement in laser in situ keratomileusis(2)(2).

PURPOSE: To identify the significant anatomic factors that affect placement of 2 microkeratomes and compare the ease of their placement. SETTING: The Laser Center, Houston, Texas, USA. METHODS: Anatomic factors affecting microkeratome placement were evaluated in 250 eyes of 137 myopic patients in a prospective consecutive-enrollment study. Anatomic factors measured included vertical orbital width, horizontal interpalpebral fissure (HPF), corneal diameter, and position of the corneal apex relative to the lateral orbital rim (PCL). Vertical orbital width and HPF were measured with a micrometer caliper (Mitutoyo); corneal diameter, with Orbscan topography (Bausch & Lomb Surgical); and PCL, with a Hertel exophthalmometer. Patients were randomly divided into 2 groups (125 eyes/group) to have surgery with the Automated Corneal Shaper((R)) (ACS) (Bausch & Lomb Surgical) or Hansatome (Bausch & Lomb Surgical) microkeratome. Microkeratome placement was graded by 1 surgeon as "easy" (grades 1, 2, and 3) or "difficult" (grades 4 and 5). Results were correlated with anatomic factors to evaluate possible anatomic influences on the difficulty of microkeratome placement. RESULTS: The PCL and vertical orbital width were statistically significant factors in predicting the difficulty of ACS microkeratome placement (P <.05). For the Hansatome microkeratome, since only 1 eye was graded as a difficult placement, the anatomic parameters affecting placement could not be evaluated. There were no statistically significant between-group differences in mean age and means of all anatomic factors measured (independent t test, P >.05). Difficult applanations were encountered in the ACS group (8/125 eyes, 6.4%) more than in the Hansatome group (1/125 eyes, 0.8%), which was a statistically significant difference by the Pearson chi-square test (P <.05). CONCLUSIONS: The PCL and vertical orbital width were significant anatomic factors affecting placement of the ACS microkeratome. The anatomic factors affecting Hansatome microkeratome placement could not be determined. The percentage of difficult placements was significantly lower with the Hansatome than with the ACS.

Adult↗
PubMed1998

Seasonal influences on admissions in schizophrenia and affective disorder in Ireland.

Although the seasonal patterns of admissions of affective disorder have been extensively studied, less attention has been given to the seasonal admission patterns of schizophrenia. The traditional method of aggregating the data over a study period, rather than analysing by year of admission may obscure potentially relevant fluctuations in the seasonal pattern. We examined the year-to-year variation in the admission patterns of schizophrenia and affective disorder in Ireland. Using the National Psychiatric Inpatient Reporting System (NPIRS), individuals admitted with an ICD-9/10 diagnosis of a first episode of schizophrenia or affective disorder during the 6-year period 1989-1994 were identified. Seasonal variations in their admission patterns were examined statistically and graphically. There was a significant seasonal variation in the monthly admission patterns of both schizophrenia and affective disorder. This pattern was more marked for individuals with affective disorder. However, the seasonal pattern was not constant from year to year, particularly for schizophrenia.

Humans↗
PubMed2002

Epidemiological study of suicide in the Republic of Croatia -- comparison of war and post-war periods and areas directly and indirectly affected by war.

We examined the differences in the suicide characteristics between areas directly and indirectly affected by war activities and in war and post-war periods according to the following variables: suicide rate, sex, age and method of suicide. Analysis was done on 5349 suicides committed in the period 1993-1998 (war and post-war years). The suicide rates in the Republic of Croatia oscillated in the pre-war, war and post-war periods (1985-2000) but without significant differences. In the areas directly affected by war, the suicide rate was significantly lower than in other areas during the study period 1993-1998 (chi-square = 10.3245; P = 0.0017). The number of suicides in both sexes declined in the areas directly affected by war-more in men than in women; the difference between sexes was statistically significant (chi-square = 3.6697; P = 0.055). Middle- and old-aged people were the population with high suicide risk in both areas (t = 1.76; P = 0.078). There were significant differences in the methods of suicides between war and non-war areas (chi-square = 108.8473; P = 0.001). Firearms or explosive devices were the methods used more significantly for suicides in the areas directly affected by war than in other areas, whereas hanging was more frequently used in the areas indirectly affected by war.

Adolescent↗
PubMed2003

Association analysis of the insertion/deletion polymorphism in serotonin transporter gene in patients with affective disorder.

A polymorphism of serotonin transporter was studied in 226 patients with affective disorders (n = 132 for bipolar, n = 94 for unipolar affective disorder) and in 213 healthy subjects. Consensus diagnosis by at least two psychiatrists, according to the ICD-10 and DSM-IV criteria was made for each patient using SCID (Structured Clinical Interview for DSM-IV Axis I Disorders). A functional polymorphism in the promoter region of serotonin transporter gene, where 44 bp are either inserted (long allele) or deleted (short allele) was analysed. Genotype s/s was significantly more frequent in patients comparing to the control group (P = 0.011 for bipolar and P = 0.003 for unipolar affective disorder)--the most marked association was found in males with bipolar and unipolar illness. The allele frequencies also differ significantly between patients and controls (P = 0.003 for bipolar and P = 0.001 for unipolar affective disorder). The frequency of the low activity (short) allele was higher in patients than in controls (51.1% in bipolar, and 54.3 in unipolar vs 39.4% in controls). We suggest that the presence of allele s may increase the susceptibility to occurrence of affective disorder.

Carrier Proteins↗
PubMed1999

Selected parameters affecting characterization of nebulized aqueous solutions by inertial impaction and comparison with phase-Doppler analysis.

The objective of this study was to evaluate selected parameters affecting the characterization of air-jet nebulized aqueous solutions by inertial impaction. Parameters affecting characterization of the droplet size distribution by inertial impaction were considered to be nebulizer T-piece connecting tube length, solute concentration, droplet charge accumulation, sample time and marker concentration. Parametric effects on nebulizer output characteristics were evaluated using a fractional factorial design. Response factors were defined as mass median aerodynamic diameter (MMAD), relative span factor (Delta), fine particle mass and delivery rate of solute. Connecting tube length, grounding the impaction stages and marker concentration did not significantly affect the response factors (0.05). Mass median aerodynamic diameter (MMAD) and delivery rate of solute were significantly affected by solute concentration (p<0.05). Fine particle mass was significantly affected by the interaction between solute concentration and sampling time. Droplets attained an equilibrium size with an MMAD=1.0 microm, Delta=2.12 (0.9% solute) and MMAD=1.7 microm, Delta=2.00 (9. 0% solute) before the exit of the nebulizer T-piece. The droplet size distributions obtained by inertial impaction were compared with data obtained by phase-Doppler analysis.

Aerosols↗
PubMed2004

Power calculations for the transmission/disequilibrium and affected sib pair tests using elementary probability methods.

The transmission/disequilibrium test (TDT) and the affected sib pair test (ASP) both test for the association of a marker allele with some conditions. Here, we present methods for calculating the probability of detecting the association (power) for a study examining a fixed number of families for suitability for the study and for calculating the number of such families to be examined. Both calculations use a genetic model for the association. The model considered posits a bi-allelic marker locus that is linked to a bi-allelic disease locus with a possibly nonzero recombination fraction between the loci. The penetrance of the disease is an increasing function of the number of disease alleles. The TDT tests whether the transmission by a heterozygous parent of a particular allele at a marker locus to an affected offspring occurs with probability greater than 0.5. The ASP tests whether transmission of the same allele to two affected sibs occurs with probability greater than 0.5. In either case, evidence that the probability is greater than 0.5 is evidence for association between the marker and the disease. Study inclusion criteria (IC) can greatly affect the necessary sample size of a TDT or ASP study. IC considered by us include a randomly selected parent at least one parent or both parents required to be heterozygous. It also allows a specified minimum number of affected offspring to be required (TDT only). We use elementary probability calculations rather than complex mathematical manipulations or asymptotic methods (large sample size approximations) to compute power and requisite sample size for a proposed study. The advantages of these methods are simplicity and generality.

Chromosome Mapping↗
PubMed1985

The psychopathology of affectivity: conceptual and historical aspects.

The disorders of affect have not contributed much to the diagnostic definition of mental disease, and their phenomenological description has never achieved the richness of the psychopathology of perception or cognition. This paper shows how the subordinate role played by affectivity in the Western concept of man led to the early and enduring view of mental illness as an exclusive disturbance of intellect. Attempts by nineteenth-century alienists to challenge this notion were only partially successful, due to the conceptual unmanageability of most forms of affective behaviour and the terminological redundancy that this engendered. These efforts were frustrated by the rebirth of Associationism, the rise of brain localization experiments, the peripheralist definition of the emotions and, finally, by the unfolding of Darwinism. As a result, no autonomous psychopathology of affectivity was ever developed. The eventual recognition of the so-called 'primary' disorders of mood has not led, however, to a refinement in the semiology of the experiences themselves. This has been impeded by the use of descriptive behavioural surrogates or by metapsychological accounts of affect as a form of energy or as a driving force. None of these developments has contributed to the clinical description of the mood disorders.

Emotions↗
PubMed2001

Verbal fluency in patients with schizophrenia and affective psychoses and their first-degree relatives.

BACKGROUND: Schizophrenic patients are known to have neuropsychological deficits including impaired verbal fluency, but it is not clear whether this latter deficit is: (a) a consequence of overall intellectual deficit; (b) shared with affective psychotic patients; or (c) shared by the relatives of schizophrenic patients; and (d) shared by the relatives of affective psychotic patients. METHODS: We administered Thurstone's Verbal Fluency Test to 45 schizophrenic patients and 72 of their relatives, and 30 affective psychotic patients and 53 of their relatives. Subjects were asked to generate as many words as possible beginning with the letters 'C' and 'S' and the total was taken as the dependent variable. Subjects also completed the National Adult Reading Test (NART) to provide a measure of (pre-morbid) IQ. RESULTS: Schizophrenic patients generated significantly fewer words than affective psychotic patients, however adjusting for NART this became non-significant. Schizophrenic (but not affective psychotic) patients generated significantly fewer words than their relatives; again adjusting for NART this became non-significant. Patients who had been exposed to obstetric complications (OC+) and those who had not (OC-) had similarly poor verbal fluency scores. Relatives of OC+ schizophrenic patients had superior verbal fluency than relatives of OC- schizophrenic patients and this remained significant after adjustment for NART. CONCLUSIONS: The results suggest that some families transmit impairment in verbal fluency as part of a pattern of lower overall IQ. However, in other families, relatives show largely normal neuropsychological function, and the poorer verbal performance of the schizophrenic member appears to have arisen secondary to his/her exposure to OCs.

Adult↗
PubMed2001

Dysphoria: self-devaluative and affective components in recovered depressed patients and never depressed controls.

BACKGROUND: The Interacting Cognitive Subsystems analysis of cognitive vulnerability to depression predicts that subjective experiences of dysphoria in recovered depressed patients will be qualitatively different from those of controls. This study tested this prediction using a new instrument, the Depressed States Checklist. METHODS: Twenty-three recovered recurrently depressed patients and 54 never depressed controls rated the affective and self-devaluative components of a dysphoric experience. RESULTS: Groups reported similar levels of affective component but recovered depressed patients reported higher self-devaluative dysphoric experience. At zero affective component of dysphoria neither group reported any self-devaluative feelings. With increasing affective component of dysphoria, the self-devaluative component increased significantly more in recovered patients than in controls. The ratio of self-devaluative to affective components of dysphoria significantly differentiated recovered depressed patients from controls. CONCLUSIONS: As predicted, dysphoria in recovered depressed patients is qualitatively different from controls in ways that increase vulnerability to major depression. The Depressed States Checklist is a new, brief, measure of cognitive vulnerability to depression that may be particularly useful in large, prospective, epidemiological studies.

Adolescent↗
PubMed2006

Cognitive function in unaffected twins discordant for affective disorder.

BACKGROUND: Patients may present with cognitive impairment in the euthymic phase of affective disorder, but it is unclear whether the impairment is prevalent before onset of the illness. The aim of the present study was to examine the hypothesis that genetic liability to affective disorder is associated with cognitive impairment. METHOD: In a cross-sectional high-risk case-control study, healthy monozygotic (MZ) and dizygotic (DZ) twins with (High-Risk twins) and without (the control group/Low-Risk twins) a co-twin history of affective disorder were identified through nationwide registers. Cognitive performance of 203 High-Risk and Low-Risk twins was compared. RESULTS: Healthy twins discordant for unipolar disorder showed lower performance on almost all measures of cognitive function: selective and sustained attention, executive function, language processing and working and declarative memory, and also after adjustment for demographic variables, subclinical symptoms and minor psychopathology. Healthy twins discordant for bipolar disorder showed lower performance on tests measuring episodic and working memory, also after adjustment for the above-mentioned covariables. The discrete cognitive impairment found seemed to be related to genetic liability, as the MZ High-Risk twins showed significant impairment on selective and sustained attention, executive function, language processing and working and declarative memory, whereas the DZ High-Risk twins presented with significantly lower scores only on language processing and episodic memory. CONCLUSIONS: The hypothesis that discrete cognitive impairment is present before the onset of the affective disorder and is genetically transmitted was supported. Thus, cognitive function may be a candidate endophenotype for affective disorders.

Adult↗
PubMed1996

1995 IPA/Bayer Research Awards in Psychogeriatrics. Late-life consequences of affective spectrum disorder.

Recent research suggests that affective disorder is associated with increased mortality and physical morbidity, but the reasons for this association remain uncertain. This report describes a 50-year prospective study of 240 men evaluated from the time they were university students in 1940-1942. A family history of mental illness was obtained and the men's habits, psychological adjustment, and marital and occupational satisfaction were followed every 2 years and their objective physical health was tracked every 5 years until age 70. Twenty-five men were identified as having affective spectrum disorder prior to age 53. Of the variables studied, the presence of affective spectrum disorder was the most powerful predictor of poor psychosocial outcome at age 65 and one of the most powerful predictors of poor physical health. Alcohol abuse and cigarette abuse accounted for the observed increased rates of heart disease and cancer. When alcohol abuse, smoking, and suicide were controlled for, affective disorder made a significant contribution to physical morbidity by age 70, but not to mortality from natural causes. Affective spectrum disorder, even in an educated population without antisocial trends, carries a profound negative risk to late-life physical and social adjustment.

Adaptation, Psychological↗
PubMedDate not supplied

Delusion formation and insight in the context of affective disturbance.

OBJECTIVE: Delusions and lack of insight have traditionally been viewed as the defining characteristics of insanity and in modern psychiatry continue to be central to the diagnosis of psychosis. Little is known about the mechanisms of delusion formation and much of the research into delusions and lack of insight has been focussed on schizophrenia, in spite of the fact that these symptoms are also prominent in other disorders e.g., affective psychosis. The objective of this paper is to review the literature on existing theories of delusions and insight with reference to the effects of affective disturbance on memory processes. METHOD: Narrative review supplemented by literature searches using Medline, PsycINFO and EMBASE databases for the period 1980 to present using terms "delusion", and "insight" and "affect". RESULTS: The role of affect on memory in normal psychology and delusions in psychopathology is being increasingly recognised. We sketch out a theory which gives weight to locating the formation and maintenance of mood congruent and mood incongruent delusional beliefs (and insight into such beliefs) within a model of normal memory processes. CONCLUSION: We conclude that delusional beliefs may represent false or biased memories of internal or external events modified and strengthened of by affective states. We propose that insight rests on an ability to identify these memories as internally generated or biased. In view of the growing body of knowledge accumulating from the study of memory, emotion and their neuropsychological correlates we would suggest using this as an evidence base for the further neuropsychiatric investigation of delusional beliefs.

Delusions↗
PubMed2003

Molecular genetics of affective disorders.

Family studies have provided evidence for familial transmission in suicide in major psychiatric disorders, and in particular affective disorders. Even though they may seem contradictory, linkage studies have suggested several genetic regions implicated in affective disorders. Association studies have mainly focused on genes related to serotonergic and monoaminergic pathways. Other genes involved in GABAergic and substance P pathways have also been studied in association studies. Another way to approach the genetics of affective disorders is the definition of more detailed phenotypes. Suicidal behaviour is one of the more largely studied subphenotypes within affective disorders. Tryptophan hydroxylase and serotonin transporter genes, related to the serotonergic pathway, have been found to be associated to suicidal behaviour, in particular violent suicidal behaviour but need to be replicated before definitive conclusion. Improved methodologies and updated tools in genetic studies will improve in the future our knowledge of affective disorders.

DNA↗
PubMed2004

A positive charge at position 33 of thioredoxin primarily affects its interaction with other proteins but not redox potential.

Oxidoreductases of the thioredoxin superfamily possess the C-X-X-C motif. The redox potentials vary over a wide range for these proteins. A crucial determinant of the redox potential has been attributed to the variation of the X-X dipeptide. Here, we substitute Lys for Gly at the first X of Escherichia coli thioredoxin to investigate how a positive charge would affect the redox potential. The substitution does not affect the protein's redox potential. The equilibrium constant obtained from pairwise reaction between the mutant and wild-type proteins equals 1.1, indicating that the replacement does not significantly affect the thiol-disulfide redox equilibrium. However, the catalytic efficiency of thioredoxin reductase on the G33K mutant decreases approximately 2.8 times compared to that of the wild type. The mutation mainly affects K(m), with little effect on k(cat). The mutation also inhibits thioredoxin's ability to reduce insulin disulfide by approximately one-half. Whether the mutant protein supports the growth of phages T3/7 and f1 was tested. The efficiency of plating (EOP) of T3/7 on the mutant strain decreases 5 times at 37 degrees C and 3 x 10(4) times at 42 degrees C relative to that of the wild-type strain, suggesting that interaction between phage gene 5 protein and thioredoxin is hindered. The mutation also reduces the EOP of phage f1 by 8-fold at 37 degrees C and 1.5-fold at 42 degrees C. The global structure of the mutant protein does not change when studied by CD and fluorescence spectra. Therefore, G33K does not significantly affect the overall structure or redox potential of thioredoxin, but primarily interferes with its interaction with other proteins. Together with the G33D mutation, the overall results show that a charged residue at the first X has a greater influence on the molecular interaction of the protein than the redox potential.

Amino Acid Substitution↗
PubMed2006

Do reaction conditions affect the stereoselectivity in the Staudinger reaction?

The stereochemistry is one of the critical issues in the Staudinger reaction. We have proposed the origin of the stereoselectivity recently. The effects of solvents, additives, and pathways of ketene generation on the stereoselectivity were investigated by using a clean Staudinger reaction, which is a sensitive reaction system to the stereoselectivity. The results indicate that the additives, usually existed and generated in the Staudinger reaction, and the pathways of the ketene generation do not generally affect the stereoselectivity. The solvent affects the stereoselectivity. The polar solvent is favorable to the formation of trans-beta-lactams. The addition orders of the reagents affect the stereoselectivity in the Staudinger reaction between acyl chlorides and imines. The addition of a tertiary amine into a solution of the acyl chloride and the imine generally decreases the stereoselectivity, which is affected by the interval between additions of the acyl chloride and the tertiary amine, and the imine substituents. Our current results provide further understanding on the stereochemistry of the Staudinger reaction between acyl chlorides and imines and on the factors affecting the stereochemistry and also provide a method to prepare beta-lactams with the desired relative configuration via rationally tuning the stereoselectivity-controlling factors in the Staudinger reaction.

Amines↗
PubMed2003

Fluoride inhibits root water transport and affects leaf expansion and gas exchange in aspen (Populus tremuloides) seedlings.

The effects of sodium fluoride (0.3, 5 and 10 mM NaF) on root hydraulic conductivity, and gas exchange processes were examined in aspen (Populus tremuloides Michx.) seedlings grown in solution culture. A long-term exposure of roots to NaF significantly decreased root hydraulic conductivity (Lp) and stomatal conductance ( gs). Root absorbed NaF significantly affected electrolyte leakage in leaf tissues and substantially restricted leaf expansion. NaF did not significantly affect leaf chlorophyll contents but decreased net photosynthesis (Pn). A short-term exposure of excised roots to 5 mM NaF and KF significantly decreased root water flow (Qv) with a concomitant decline in root respiration and reduced gs when applied through intact roots or excised stems. The same molar concentration of NaCl also decreased Qv and gs in intact seedlings, but to a lesser extent than NaF or KF, and did not significantly affect root respiration. The results suggest that fluoride metabolically inhibited Qv or Lp, probably by affecting water channel activity. We suggest that the metabolic inhibition of Lp by root-absorbed fluoride affected gas exchange and leaf expansion in aspen seedlings.

Journal Article↗