Excitons in poly(para-phenylenevinylene).
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Biomedical subjects
Publications and source records attributed to S Mazumdar.
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By changing Met64 into a glutamate by means of site-directed mutagenesis a negative charge was introduced into the hydrophobic patch of azurin from Pseudomonas aeruginosa. The three-dimensional structure of the protein and the structure of the metal site in particular, appear unaffected by the mutation. The observed change of the midpoint potential of the mutant of 28 mV is ascribed to the deprotonation of Glu64. The electron-self-exchange rate constant equals that of the wild-type protein at pH 4.5 but decreases by almost two orders of magnitude at high pH. Electron transfer is inhibited only when both of the reacting azurin molecules have an ionized glutamate at position 64 in their hydrophobic patch. Electron transfer at a graphite electrode is slowed down by the presence of the negative charge in the hydrophobic patch. The results demonstrate once again that the Cu-ligand His117 in the hydrophobic patch is the likely entry and exit point for electrons. This observation holds both for the (homogeneous) electron-self-exchange reaction in solution as well as for the (heterogenous) reaction at an electrode.
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Quality control should be maintained in all disease registries by appropriate statistical procedures to assure complete, accurate, reliable, and timely morbidity and mortality data. Shewhart control charts are recommended for evaluating item completeness. Accuracy and reliability can be evaluated with stringent diagnostic criteria, re-abstraction of records, and statistical measures such as the kappa statistic. Discrepancies between observed and expected data in various time periods can be used to evaluate whether data entering a registry meet timeliness criteria. The reporting delay distribution can be used to examine timeliness of reported data and to adjust incidence rates for potential lack of timeliness in reporting. An application of these quality control procedures is demonstrated using two variables selected from a hospital-based study consisting of 119 breast cancer records collected from the Division of Medical Records, Dr Soetomo Hospital, Surabaya, Indonesia. The results indicate that the variable LASTNAME met the selected criteria for completeness and reliability. The variable ADDRESS met the reliability but not the completeness criterion. All reported cases met the timeliness criterion. The demonstration confirmed the need for registries to establish formal quality control procedures.
OBJECTIVE: The purpose of this study was to determine treatment outcome in elderly patients with consecutively treated episodes of recurrent unipolar major depression. METHOD: Subjects were 32 "young" elderly patients with recurrent unipolar depression (mean age = 66.8 years, SD = 5.1) and with two consecutively treated episodes of major depression. Both index and subsequent episodes of major depression were treated in open trial with combined nortriptyline and interpersonal psychotherapy. Rates of remission in index and subsequent episodes were compared by using nonparametric statistics and survival analysis with proportional hazards modeling. RESULTS: Of 30 patients who completed treatment of the subsequent episode, 27 (90%) achieved stable remission of symptoms in both consecutively treated episodes, whereas three patients (10%) did not. Twenty-two (81%) of 27 patients who responded to treatment had a shorter time to remission in treatment of the subsequent episode than in the index episode. Survival analysis with proportional hazards modeling detected a significant difference in time to remission of the index and subsequent episodes (32 paired observations). CONCLUSIONS: In this research study group, recurrent episodes of unipolar major depression in the young elderly were successfully treated to remission in over 80% of patients by using combined pharmacotherapy and psychotherapy similar to that employed in treatment of the index episode. Remission rate and time to remission in consecutively treated episodes were comparable to those in a group of midlife patients with recurrent depression reported by Kupfer et al. in 1989. Thus, recurrent depressive disorder appears to be as treatable in the young elderly as it is in midlife patients.
Time-resolved study of fluorescence decay of the tryptophan residue in bovine cytochrome c oxidase in phospholipid vesicles is reported for the first time. The effect of the redox state of the protein on its conformation has been investigated using time-resolved decay of tryptophan fluorescence in the oxidised and reduced protein. The fluorescence decay was best fitted using a discrete three exponential model. Amplitude distribution of lifetimes also showed three distinct regions in the analysis of decay profiles by the maximum entropy method (MEM). Results of the time resolved studies showed that the amplitudes as well as the lifetimes of the tryptophan fluorescence remain the same for the oxidised and the reduced states of cytochrome c oxidase, indicating that the environment around tryptophan residues remains more or less unaltered on reduction of the protein. The results suggest that there is no global conformational change in the protein on electron transfer and support the possibility of the existence of local fluctuations in the protein during the redox cycle.
AIM: In this study, we compared repeated measures of electroencephalographic (EEG) sleep and subjective sleep quality in nondepressed, spousally bereaved elders and a healthy control group, in order to search for possible psychobiological correlates of bereavement not confounded by concurrent major depression. METHOD: Laboratory-based EEG sleep studies and measures of subjective sleep quality (Pittsburgh Sleep Quality Index [PSQI]) were repeated at 3, 6, 11, 18, and 23 months after spousal bereavement in a study group of 27 elderly volunteers. Data were compared with similar measures from a control group of 27 nonbereaved subjects recorded on three occasions 1 year apart. Repeated-measures analysis of variance (ANOVA), using age as a covariate, examined effects due to time on selected variables in the bereaved group, as well as effects due to group, time, and group-by-time interactions in the experimental and control subjects. RESULTS: Bereaved and control groups showed consistent differences over time in the phasic measures of rapid eye movement (REM) sleep (higher in bereaved subjects during the first and third REM sleep periods), but were similar on all other EEG sleep measures over the 2 years of observation. The bereaved showed a small decline in the percentage of slow-wave sleep over 2 years, but measures of sleep efficiency, REM latency, and delta sleep ratio were stable and did not differ from values seen in control subjects. Bereaved and control subjects were also similar on subjective sleep quality. CONCLUSION: During successful adaptation to the loss of a spouse, and in the absence of major depression, spousal bereavement is associated with elevation in the phasic measures of REM sleep but does not appear to be associated with other physiologic sleep changes typical of major depression when studied at 3 to 23 months after the event. Although this observation does not preclude the possibility of significant sleep disturbance nearer the time of the event, it suggests that preservation of normal sleep following a major negative life event may be an important correlate of the resilience seen in successful aging. The elevation in REM density may provide a psychobiological correlate of bereavement not confounded by concurrent major depression.
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The present investigation was undertaken to assess the binding characteristics of eight different lectins to normal oral mucosa (11 cases), leukoplakia with varying degrees of dysplasia (five cases), and oral mucosal squamous cell carcinoma (12 cases) by the use of biotinylated lectins and avidin biotin peroxidase complexes. The lectins employed were soybean (SBA), peanut (PNA), Dolichos biflorus (DBA), concanavalin A (Con A), wheat germ (WGA), Ulex europaeus (UEA), Ricinus communis (RCA), and Lotus tetragonolobus (LTA). It was observed that SBA, DBA, WGA, UEA, RCA, and LTA showed very strong to strong binding in healthy oral mucosa but no or very weak binding in squamous cell carcinoma. On the contrary, PNA showed weak binding to normal mucosal epithelial cells but showed strong binding to malignant cells. The dysplastic mucosa had an intermediate binding pattern. The lectin Con A was not bound at all or seen in very low concentration in the malignant cells and dysplastic epithelium, but it showed weak binding in the normal mucosa. Hence, we conclude that lectins may be utilized as probes to determine the dysplastic and malignant status of the oral mucosal epithelium.
The aim of this double-blind placebo-controlled study was to assess the effects of clinical state on electroencephalographic (EEG) sleep measures in elderly patients with recurrent major depression. We hypothesized that rapid-eye movement (REM) latency and delta sleep ratio would remain stable between actively depressed and remitted states (i.e., show state independence), and measures of sleep continuity would improve with remission (i.e., show state dependence). Fifteen elderly outpatients (mean age 65.3 years) had sleep evaluations while ill and after remission, an average of 38 weeks later. All patients were in a double-blind placebo-maintenance condition at the time of follow-up studies. The major findings were: 1) no significant change in either REM latency or delta sleep ratio; 2) reduction in early morning awakening; and 3) improvement in subjective sleep quality despite the stability of most polysomnographic measures. We conclude that REM latency and delta sleep ratio are state-independent in patients with late-life depression, and that early morning awakening and sleep quality improve with remission of symptoms. These findings suggest that EEG sleep changes may have significance for understanding the longitudinal course of depression in late life.
Although spousal bereavement in late life is common and frequently leads to major depression, the boundary between bereavement without a depressive syndrome and bereavement-related depression has been insufficiently studied from a physiological perspective. Because other forms of depression are associated with physiological changes, including sleep, we have attempted to clarify the relationship of bereavement and bereavement-related depression by investigating electroencephalographic (EEG) sleep in 31 elderly volunteers with recent spousal bereavement, stratified by the presence (n = 15) or the absence (n = 16) of major depression (Research Diagnostic Criteria). Entry into the study was limited to volunteers without a personal history of psychiatric disorder. As hypothesized, bereaved subjects with major depression had significantly lower sleep efficiency, more early morning awakening, shorter rapid eye movement (REM) latency, greater REM sleep percent, and lower rates of delta wave generation in the first nonREM (NREM) period, compared with bereaved subjects without depression. Furthermore, the sleep of bereaved subjects with single-episode major depression resembled that of elderly patients with recurrent unipolar major depression (n = 15) on measures noted above. Sleep in bereavement without depression was similar to that of 15 healthy control subjects (neither bereaved nor depressed). These findings suggest that the current DSM-III-R concept of uncomplicated bereavement is not confirmed, as the sleep patterns of subjects who develop a depressive syndrome in the context of bereavement, many of whom might be considered to have "uncomplicated bereavement" by DSM-III-R standards, are identical to sleep patterns found in major depressive episodes. To our knowledge, this is the first study of EEG sleep in spousal bereavement with and without major depression.
Reliable quantitative ratings of chronic medical illness burden have proved to be difficult in geropsychiatric practice and research. Thus, the purpose of the study was to demonstrate the feasibility and reliability of a modified version of the Cumulative Illness Rating Scale (CIRS; Linn et al., 1968) in providing quantitative ratings of chronic illness burden. The modified CIRS was operationalized with a manual of guidelines geared toward the geriatric patient and for clarity was designated the CIRS(G). A total of 141 elderly outpatient subjects (two medical clinic groups of 20 each, 45 recurrent depressed subjects, 21 spousally bereaved subjects, and 35 healthy controls) received comprehensive physical examinations, reviews of symptoms, and laboratory testing. These data were then used by nurse practitioners, physician's assistants, and geriatric psychiatrists to compute CIRS(G) ratings of chronic illness burden. As hypothesized, analysis of variance demonstrated significant differences among groups with respect to total medical illness burden, which was highest among medical clinic patients and lowest in control subjects. Good interrater reliability (i.e., intraclass correlations of 0.78 and 0.88 in a subsample of 10 outpatients and a separate group of 10 inpatients, respectively) was achieved for CIRS(G) total scores. Among medical clinic patients, a significant correlation was found, as expected, between CIRS(G) chronic illness burden and capability as quantified by the Older Americans Activities of Daily Living Scale; and between CIRS(G) scores and physicians' global estimates of medical burden. Finally, with repeated measures of illness burden approximately 1 year from symptom baseline, significant rises were detected, as expected. The current data suggest that the CIRS(G) can be successfully applied in medically and psychiatrically impaired elderly subjects, with good interrater reliability and face validity (credibility).
OBJECTIVE: The authors examined the rate of response to the combination of nortriptyline and interpersonal psychotherapy for acute and continuation treatment of elderly patients with recurrent major depression. METHOD: The subjects were 73 elderly patients, 61 of whom completed treatment. Nortriptyline steady-state blood levels were maintained at 80-120 ng/ml, and interpersonal psychotherapy was administered weekly for 9.1 weeks (medium) of acute therapy and was decreased from biweekly to triweekly during 16 weeks of continuation therapy. During acute treatment nonresponding patients also received brief adjunctive pharmacotherapy with lithium or perphenazine. RESULTS: Of the 61 subjects given adequate trials of nortriptyline and interpersonal psychotherapy, 48 (78.7%) achieved full remission (Hamilton depression rating of 10 or lower over 16 weeks of continuation therapy), 10 patients (16.4%) did not respond (Hamilton rating never below 15), and three achieved only partial remission (Hamilton rating of 11-14). Early versus late onset was not associated with a difference in response rate. During the placebo-controlled, double-blind transition to maintenance therapy, 19 (76.0%) of the 25 patients randomly assigned to placebo maintenance conditions showed continued recovery and six relapsed. None of the 24 patients assigned to nortriptyline conditions relapsed. CONCLUSIONS: Use of nortriptyline plus interpersonal psychotherapy for 9.1 weeks (median) of acute and 16 weeks of continuation therapy appears to be associated with good response and relatively low attrition but about a 25% chance of relapse during double-blind discontinuation of nortriptyline. These data require confirmation in a controlled clinical trial of acute and continuation therapy.
Neuropeptides form a part of the brain-gut axis which may regulate gastrointestinal functions, including immune regulation. Various changes in the neuropeptides--most important, vasoactive intestinal peptide and substances P (VIP and SP)--have been described in inflammatory bowel disease. We employed a sensitive immunoperoxidase (avidin-biotin-peroxidase complex) technique, using anti-VIP and anti-SP antibodies to localize and compare the distribution of VIP and SP in the colon. Colon specimens from 19 normal subjects, eight patients with ulcerative colitis (UC), and eight with Crohn's disease (CD) were used. In the normal colon, VIP and SP immunoreactivity (IR) were localized in the muscularis mucosa, circular muscles, walls of blood vessels, nerve fibers, and some distinct cells, probably enterochromaffin cells. SP-IR was also present in the epithelial cells, mainly along the basolateral domain. VIP-IR was considerably diminished at all locations in patients with UC and CD. However, the SP-IR was increased in UC in the colonic epithelial cells along the basolateral areas. The SP-IR was intense in patients with CD, in the epithelium, the granulomas, cells lining the mucosal fissure, and in the muscle layers. In contrast to normals, SP-IR in patients with CD was observed both in the longitudinal and circular muscles. We conclude that VIP-IR and SP-IR are distributed widely in the mucosa, submucosa, and in the circular muscle in normal colon. VIP-IR is decreased in UC and CD, whereas SP-IR is increased in both, but more so in CD.
Weight change in pounds and body mass index was documented in 29 geriatric patients with recurrent depression successfully treated with nortriptyline over a 30-week period of acute and continuation therapy (925 patient-weeks of nortriptyline treatment). Weight before index episode as documented by physician records, and weight at three points (beginning of treatment, end of acute therapy, and end of continuation therapy) were recorded. Weight changes over the interval between these times and net weight change over the entire interval were then calculated. Only five patients (17.2%) gained a clinically significant (greater than 10 lb) amount of weight during treatment, ranging from 10 to 43 lb above premorbid weights. Seven of 29 patients (24.1%) showed a net weight loss below premorbid levels (maximum loss 12.5 lb), and 6 patients (20.7%) showed no weight change. The pattern of weight gain was variable; no correlations were found between initially high body mass index and weight gain over the entire interval. These data suggest that nortriptyline is apparently not a potent weight promoter in this group.
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