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Biomedical subjects

S Saxena

Publications and source records attributed to S Saxena.

At least 37 records · Page 2Linked to original sources
PubMed2001

Brain metabolic changes associated with symptom factor improvement in major depressive disorder.

BACKGROUND: Symptoms of major depressive disorder (MDD) have been linked to regional brain function through imaging studies of symptom provocation in normal control subjects and baseline studies of subjects with MDD. We examined associations between change in depressive symptom factors and change in regional brain metabolism from before to after treatment of MDD. METHODS: Thirty-nine outpatients with MDD underwent 18F-fluorodeoxyglucose positron emission tomography scanning before and after treatment with either paroxetine or interpersonal psychotherapy. Associations were determined between changes in regional brain metabolism and changes in four Hamilton Depression Rating Scale factors (anxiety/somatization [ANX], psychomotor retardation [PR], cognitive disturbance [COGN], and sleep disturbance) and two corresponding Profile of Mood States subscales (tension [TENS] and fatigue [FATIG]). RESULTS: Improvement in ANX, PR, TENS, and FATIG factors was associated with decreasing ventral frontal lobe metabolism. Improvement in ANX and TENS was also associated with decreasing ventral anterior cingulate gyrus (AC) and anterior insula activity, whereas improvement in PR was associated with increasing dorsal AC activity. COGN improvement was associated with increasing dorsolateral prefrontal cortex metabolism. CONCLUSIONS: Brain regions that show significant relationships with symptom provocation in normal control subjects have similar relationships with MDD symptoms as they improve with treatment.

Major Depressive Disorder↗
PubMed2001

Cerebral metabolism in major depression and obsessive-compulsive disorder occurring separately and concurrently.

BACKGROUND: The frequent comorbidity of major depressive disorder (MDD) and obsessive-compulsive disorder (OCD) suggests a fundamental relationship between them. We sought to determine whether MDD and OCD have unique cerebral metabolic patterns that remain the same when they coexist as when they occur independently. METHODS: [18F]-fluorodeoxyglucose positron emission tomography (PET) brain scans were obtained on 27 subjects with OCD alone, 27 with MDD alone, 17 with concurrent OCD+MDD, and 17 normal control subjects, all in the untreated state. Regional cerebral glucose metabolism was compared between groups. RESULTS: Left hippocampal metabolism was significantly lower in subjects with MDD alone and in subjects with concurrent OCD+MDD than in control subjects or subjects with OCD alone. Hippocampal metabolism was negatively correlated with depression severity across all subjects. Thalamic metabolism was significantly elevated in OCD alone and in MDD alone. Subjects with concurrent OCD+MDD had significantly lower metabolism in thalamus, caudate, and hippocampus than subjects with OCD alone. CONCLUSIONS: Left hippocampal dysfunction was associated with major depressive episodes, regardless of primary diagnosis. Other cerebral metabolic abnormalities found in OCD and MDD occurring separately were not seen when the disorders coexisted. Depressive episodes occurring in OCD patients may be mediated by different basal ganglia-thalamic abnormalities than in primary MDD patients.

Adult↗
PubMed2001

Targeting of the c-Abl tyrosine kinase to mitochondria in the necrotic cell death response to oxidative stress.

The ubiquitously expressed c-Abl tyrosine kinase is activated in the response of cells to genotoxic and oxidative stress. The present study demonstrates that reactive oxygen species (ROS) induce targeting of c-Abl to mitochondria. We show that ROS-induced localization of c-Abl to mitochondria is dependent on activation of protein kinase C (PKC)delta and the c-Abl kinase function. Targeting of c-Abl to mitochondria is associated with ROS-induced loss of mitochondrial transmembrane potential. The results also demonstrate that c-Abl is necessary for ROS-induced depletion of ATP and the activation of a necrosis-like cell death. These findings indicate that the c-Abl kinase targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death.

Animals↗
PubMed2001

J-domain protein, Jac1p, of yeast mitochondria required for iron homeostasis and activity of Fe-S cluster proteins.

J-proteins are molecular chaperones with a characteristic domain predicted to mediate interaction with Hsp70 proteins. We have previously isolated yeast mutants of the mitochondrial Hsp70, Ssq1p, in a genetic screen for mutants with altered iron homeostasis. Here we describe the isolation of mutants of the J-domain protein, Jac1p, using the same screen. Mutant jac1 alleles predicted to encode severely truncated proteins (lacking 70 or 152 amino acids) were associated with phenotypes strikingly similar to the phenotypes of ssq1 mutants. These phenotypes include activation of the high affinity cellular iron uptake system and iron accumulation in mitochondria. In contrast to iron accumulation, Fe-S proteins of mitochondria were specifically deficient. In jac1 mutants, like in ssq1 mutants, processing of the Yfh1p precursor protein from intermediate to mature forms was delayed. In the genetic backgrounds used in this study, jac1 null mutants were found to be viable, permitting analysis of genetic interactions. The Deltajac1 Deltassq1 double mutant was more severely compromised for growth than either single mutant, suggesting a synthetic or additive effect of these mutations. Overexpression of Jac1p partially suppressed ssq1 slow growth and vice versa. Similar mitochondrial localization and similar mutant phenotypes suggest that Ssq1p and Jac1p are functional partners in iron homeostasis.

Aconitate Hydratase↗
PubMed2001

Adrenodoxin reductase homolog (Arh1p) of yeast mitochondria required for iron homeostasis.

Arh1p is an essential mitochondrial protein of yeast with reductase activity. Here we show that this protein is involved in iron metabolism. A yeast strain was constructed in which the open reading frame was placed under the control of a galactose-regulated promoter. Protein expression was induced by galactose and repressed to undetectable levels in the absence of galactose, although cells grew quite well in the absence of inducer. Under noninducing conditions, cellular iron uptake was dysregulated, exhibiting a failure to repress in response to medium iron. Iron trafficking within the cell was also disturbed. Exposure of Arh1p-depleted cells to increasing iron concentrations during growth led to drastic increases in mitochondrial iron, indicating a loss of homeostatic control. Activity of aconitase, a prototype Fe-S protein, was deficient at all concentrations of mitochondrial iron, although the protein level was unaltered. Heme protein deficiencies were exacerbated in the iron-loaded mitochondria, suggesting a toxic side effect of accumulated iron. Finally, a time course correlated the cellular depletion of Arh1p with the coordinated appearance of various mutant phenotypes including dysregulated cellular iron uptake, deficiency of Fe-S protein activities in mitochondria and cytoplasm, and deficiency of hemoproteins. Thus, Arh1p is required for control of cellular and mitochondrial iron levels and for the activities of Fe-S cluster proteins.

Aconitate Hydratase↗
PubMed2001

Regional brain metabolic changes in patients with major depression treated with either paroxetine or interpersonal therapy: preliminary findings.

BACKGROUND: In functional brain imaging studies of major depressive disorder (MDD), regional abnormalities have been most commonly found in prefrontal cortex, anterior cingulate gyrus, and temporal lobe. We examined baseline regional metabolic abnormalities and metabolic changes from pretreatment to posttreatment in subjects with MDD. We also performed a preliminary comparison of regional changes with 2 distinct forms of treatment (paroxetine and interpersonal psychotherapy). METHODS: Twenty-four subjects with unipolar MDD and 16 normal control subjects underwent resting F 18 ((18)F) fluorodeoxyglucose positron emission tomography scanning before and after 12 weeks. Between scans, subjects with MDD were treated with either paroxetine or interpersonal psychotherapy (based on patient preference), while controls underwent no treatment. RESULTS: At baseline, subjects with MDD had higher normalized metabolism than controls in the prefrontal cortex (and caudate and thalamus), and lower metabolism in the temporal lobe. With treatment, subjects with MDD had metabolic changes in the direction of normalization in these regions. After treatment, paroxetine-treated subjects had a greater mean decrease in Hamilton Depression Rating Scale score (61.4%) than did subjects treated with interpersonal psychotherapy (38.0%), but both subgroups showed decreases in normalized prefrontal cortex (paroxetine-treated bilaterally and interpersonal psychotherapy-treated on the right) and left anterior cingulate gyrus metabolism, and increases in normalized left temporal lobe metabolism. CONCLUSIONS: Subjects with MDD had regional brain metabolic abnormalities at baseline that tended to normalize with treatment. Regional metabolic changes appeared similar with the 2 forms of treatment. These results should be interpreted with caution because of study limitations (small sample size, lack of random assignment to treatment groups, and differential treatment response between treatment subgroups).

Adult↗
PubMed2001

Social functioning and quality of life comparisons between obsessive-compulsive and schizophrenic disorders.

Treatment of obsessive-compulsive disorder has focused almost exclusively on symptom reduction; however, deficits in social functioning and quality of life of individuals with this disorder may contribute more to their "burden," suffering, and disability. To gauge the significance of social dysfunction and quality of life of persons with obsessive-compulsive disorder (OCD), we made comparisons with a group of persons with schizophrenia matched for age and gender. Thirty-one patients with OCD participating in a partial hospital treatment program were compared with 68 schizophrenic outpatients participating in a day rehabilitation program. The Independent Living Skills Survey (ILSS) and Lehman Quality of Life Scale (QOL) were administered before and after treatment for both cohorts. QOL scores were significantly lower for the OCD patients both before and after treatment, but improved significantly during treatment. OCD and schizophrenic patients had similar scores on almost every domain of the ILSS at pretreatment. The OCD patients improved significantly on many of the domains of social and independent living skills as a result of treatment and acquired significantly greater skills by post-treatment than did their counterparts with schizophrenia; however, the performance of social and independent living skills by OCD patients remained less than satisfactory even in domains where they improved. In the areas of job and leisure skills, there were significant group-by-time interactions. We concluded that patients with severe OCD and patients with schizophrenia are equally socially impaired. However, OCD patients experience greater significant functional improvement with multimodal treatment.

Activities of Daily Living↗
PubMed2001

Memory self-appraisal and depressive symptoms in people at genetic risk for Alzheimer's disease.

OBJECTIVES: A previous study found that subjective memory loss in middle-aged and older persons is associated with the major genetic risk for Alzheimer's disease, the apolipoprotein E-4 (APOE-4) allele. No previous study has focused on subjective memory complaints and depressive symptoms in the same subject population at genetic risk for Alzheimer's disease. METHOD: Sixty-six persons (mean age = 64 years, range = 43 to 82 years) without major depression or dementia but with mild age-related memory complaints were rated for severity of depressive symptoms, using the Hamilton Depression Rating Scale, and assessed for the presence of the APOE-4 allele. Severity of subjective memory loss was assessed using the Memory Functioning Questionnaire, which measures four memory domains: frequency of forgetting, seriousness of forgetting, retrospective functioning, and mnemonics usage. RESULTS: Depressive symptoms were significantly associated with subjective memory loss in subjects without the APOE-4 allele, for retrospective functioning (perceived change in memory) and mnemonics usage, but not in APOE-4 carriers. The same significant associations were found when the analysis was limited to the 44 subjects in the mid-age range (55-74 years), wherein APOE-4 confers its greatest effects on risk for Alzheimer's disease. CONCLUSION: These results confirm that mild depressive symptoms are related to subjective memory loss, but for some forms of memory complaint, the relationship holds true only for people without the major known genetic risk for Alzheimer's disease.

Adult↗
PubMed2001

Human retinal S-antigen: T cell epitope mapping in posterior uveitis patients.

Uveitis, an intraocular inflammatory disease which affects the uveal tract and the retina of the eye in humans, is one of the major causes of visual impairment. Posterior uveitis is often associated with inflammation of the retina and vitreous. Unfortunately, etiological diagnosis of the disease is not possible in the majority of patients. It is generally felt that an autoimmune mechanism may be involved in so-called idiopathic cases. The role of retinal S-antigen, its 20 linear peptides spanning the entire sequence, and 2 additional peptides, known to be uveitopathogenic in experimental animals, was studied in 26 patients with uveitis. Lymphocyte proliferative response was tested in vitro to identify the epitopes of S-antigen involved and to establish their role in the pathogenesis of uveitis. Of 26 uveitis patients tested, 11 showed a significant T cell proliferative response in vitro to at least 1 antigen used. None among the controls showed any response to the peptides or native S-antigen used in this study. We have found that uveitis patients respond most frequently to peptide 4 (61--80), peptide 5 (81--100), peptide 8 (141--160), peptide 9 (161--180), peptide 12 (221--240), and peptide 13 (241--260) of the human S-antigen. These results further confirm that autoimmunity to retinal S-antigen may play a role in the etiopathogenesis of a subset of patients with idiopathic uveitis.

Adolescent↗
PubMed2001

Microbial metabolites as eco-friendly agrochemicals for the next millennium.

As a result of the increasing environmental and health-related problems caused by the synthetic agrochemicals currently used, suitable and non-hazardous innovative alternatives are being sought. Antagonism and allelopathy, both in nature and in agro-ecosystems, have attracted these researchers' attention, with the main goal of using these phenomena in the biological control of weeds. This article presents a review on the use and efficacy of microbial secondary metabolites which have potential as natural herbicides, either directly or as templates for bio-rational eco-friendly agrochemicals (allelochemicals). Their merits as alternatives to synthetic chemicals and biological control agents have been highlighted for an holistic approach in integrated pest/weed management.

Actinomycetales↗
PubMed2001

The WHO quality of life assessment instrument (WHOQOL-Bref): the importance of its items for cross-cultural research.

One of the fundamental issues in the area of assessment of quality of life is to determine what is important to the individuals' quality of life. This is even more crucial when the instrument is for use in diverse cultural settings. This paper reports on the importance ratings on WHOQOL-Bref items obtained as a part of WHOQOL pilot field trial on 4804 respondents from 15 centres from 14 developed and developing countries using 12 languages. All items were rated as moderately or more important, but this was expected because the items were selected by extensive qualitative research for their salience across the centres. Significant differences on mean importance ratings were found between centres, but rank orders of item for their importance showed highly significant correlations between centres. This was especially true for items in the top and the bottom thirds of the item list arranged by overall importance. Most items were rated as more important by women compared to men and by younger compared to older persons. The results are discussed for their relevance in cross-cultural research on quality of life assessment.

Adolescent↗
PubMed2001

Mitochondrial targeting of JNK/SAPK in the phorbol ester response of myeloid leukemia cells.

Treatment of human U-937 myeloid leukemia cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) is associated with activation of the stress-activated protein kinase (SAPK) and induction of terminal monocytic differentiation. The present studies demonstrate that TPA targets SAPK to mitochondria by a mechanism dependent on activation of protein kinase C (PKC) beta. Translocation of SAPK to mitochondria in response to TPA is associated with release of cytochrome c, caspase-3 activation and induction of apoptosis. The results show that TPA induces the association of SAPK with the mitochondrial anti-apoptotic Bcl-x(L) protein. Overexpression of Bcl-x(L) attenuated the apoptotic response to TPA treatment. Moreover, expression of Bcl-x(L) mutated at sites of SAPK phosphorylation (Thr-47, -115) was more effective than wild-type Bcl-x(L) in abrogating TPA-induced cytochrome c release and apoptosis. By contrast, expression of Bcl-x(L) had little effect on induction of the monocytic phenotype. These findings indicate that myeloid leukemia cells respond to TPA with targeting of SAPK to mitochondria and that this response contributes to terminal differentiation through the release of cytochrome c and induction of apoptosis.

Apoptosis↗
PubMed2001

Monitoring for underutilization of RBC components and platelets.

BACKGROUND: Monitoring blood transfusion for overutilization is standard practice at most institutions. STUDY DESIGN AND METHODS: This study monitored for underutilization of blood transfusion over a 14-month period, by evaluating patients who had Hb levels that were reported to be <5 g per dL or platelet counts <10 x 10(9) per L and who did not receive an RBC or platelet transfusion within 24 hours of the reported results. RESULTS: During the study period, 24,004 units of RBCs and 3,967 units of apheresis platelets were transfused. There were 148 patients who had a Hb level that was reported to be <5 g per dL or a platelet count reported to be <10 x 10(9) per L and who did not receive a transfusion during the 24 hours after the reporting of these results. In 5 cases, the patients died before the reporting of the low Hb or platelet counts, which precluded the low Hb or low platelet count reports from triggering transfusion therapy. In 8 cases, an underutilization review investigation could not be done, because of the unavailability of patient charts. Of the remaining 135 cases, investigation revealed justifiable reasons for withholding transfusion in 133. In 2 cases, the withholding of transfusion was deemed by peer review to be inappropriate, as the patients should have received a transfusion. Overall, there was one documented underutilization of RBC transfusion therapy during a period when 24,004 units were transfused and one underutilization of platelet transfusion therapy during a period when 3,967 units of apheresis platelets were transfused. CONCLUSION: Monitoring for underutilization of transfusion therapy fulfills the requirements of the Joint Commission on the Accreditation of Healthcare Organizations: While the underutilization of transfusion therapy did not appear to be a significant problem at this medical center, determining the reasons for withholding transfusions shed light on important patient care-related issues, including preexisting causes of falsely low platelet counts and Hb levels, delays in investigating critical laboratory values, and the need for policies for the treatment of patients who refuse transfusion for personal or religious reasons.

Erythrocyte Transfusion↗
PubMed2001

Brain-behavior relationships in obsessive-compulsive disorder.

Advances in neuroimaging have led to a greater understanding of brain-behavior relationships in obsessive-compulsive disorder (OCD). This article provides an updated review and analysis of the structural and functional neuroimaging studies in OCD published to date and discusses how evidence from various types of neuroimaging studies has been synthesized to generate and test hypotheses regarding these relationships. We also review the basic science literature on the functional neuroanatomy of cortico-basal ganglia-thalamo-cortical circuits and integrate this information with neuroimaging data in OCD, to present a theoretical model of brain mediation of OCD symptoms and response to treatment. Taken together, neuroimaging studies indicate that OCD symptoms are mediated by hyperactivity in orbitofrontal-subcortical circuits, which may be attributable to an imbalance of tone between direct and indirect striato-pallidal pathways. Serotonergic drugs may ameliorate OCD symptoms by changing the relative balance of tone through the indirect versus direct orbitofrontal-subcortical pathways, thereby decreasing activity in the overall circuit that exists in the symptomatic state.

Brain↗
PubMed2001

Prefrontal-subcortical and limbic circuit mediation of major depressive disorder.

Substantial progress has been made in elucidating the pathophysiology of major depressive disorder (MDD) using functional and structural brain imaging. In functional imaging studies comparing MDD subjects to normal controls at baseline, dorsolateral prefrontal cortex (DLPFC) activity has been found to be decreased and ventrolateral prefrontal cortex (VLPFC) activity has been found to be increased in MDD. Other regions found abnormal in baseline studies include the anterior cingulate gyrus (AC), temporal lobe, and basal ganglia. Studies examining mood state change (using sleep deprivation, sadness-induction, and tryptophan depletion) and changes from pre- to posttreatment have generally shown improvement of these abnormalities with improved MDD symptoms and worsening of these abnormalities with worsening symptoms. In structural imaging studies, decreased frontal lobe, hippocampal, and basal ganglia volumes are the most commonly reported findings. Several associations can be made between clinical features of MDD and brain function: (1) active sad thoughts/sadness with both decreased DLPFC and dorsal AC activity and increased VLPFC and ventral AC activity (2) psychomotor retardation with decreased left prefrontal activity (3) anxiety with increased left AC activity (4) impaired episodic memory with left prefrontal and medial temporal dysfunction and (5) impaired sustained attention with right prefrontal and parietal dysfunction.

Affect↗
PubMed2001

Detoxification of aqueous zinc using fluorapatite--bearing lean grade rock phosphate.

Detoxification of aqueous zinc was studied using the adsorption technique by application of fluorapatite bearing low grade phosphate as a sorbent. The effects of particle size of adsorbent, contact time, initial concentration of zinc and temperature on the adsorption process were studied. Initial rate of adsorption of zinc increases with time up to 30 min and thereafter it reaches equilibrium. Percent adsorption is adversely affected by increase in initial concentration of zinc and increase in particle size of sorbent. Adsorption processes follow first order kinetics and are found to be exothermic.

Absorption↗