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Biomedical subjects

G S Zubenko

Publications and source records attributed to G S Zubenko.

At least 55 records · Page 3Linked to original sources
PubMed1993

Lack of variation in the nucleotide sequence corresponding to the transmembrane domain of the beta-amyloid precursor protein in Alzheimer's disease.

The nucleotide sequence corresponding to the APP transmembrane domain and flanking regions of charged amino acids was determined for 91 patients with histologically confirmed Alzheimer's disease, 9 patients with dementias of other etiologies, and 14 controls who had no identifiable brain disease. Twenty-eight of the AD patients had a first-degree relative with dementia. No mutations were detected among the 100 demented patients. However, one of the 14 controls exhibited a change in the 3' base of codon 716 which would not be expected to result in an amino acid substitution at this position.

Alzheimer Disease↗
PubMed1993

Schizophrenia in late life: elderly patients admitted to an acute care psychiatric hospital.

Although a considerable body of biological and clinical data has been accumulated on the mood disorders and organic disorders of late life, only a handful of studies have focused on aging schizophrenia patients. Using the results of a comprehensive evaluation of all elderly patients admitted over a 30-month period to a 26-bed acute care geriatric unit, we compared the demographic, social, and clinical characteristics of schizophrenia patients, patients with recurrent major depression with and without psychotic features, and patients with primary degenerative dementia of the Alzheimer's type with and without delusions. The main findings of this study are that elderly schizophrenia patients were younger, more often African-American, more often single, and poorer than the other groups. A concomitant history of substance abuse and institutionalization as an outcome were more frequent among schizophrenia patients. Like the older depressed and demented patients, schizophrenia patients were predominantly female and commonly presented with several medical disorders. The potential significance of these findings is discussed in the context of the literature on the long-term outcome of schizophrenia.

Aged↗
PubMed1993

Reliability and applicability of movement disorder rating scales in the elderly.

Geriatric research clinicians were readily trained to use three scales initially developed for rating neuroleptic-induced movement disorders in mixed-age patients: the Abnormal Involuntary Movements Scale (AIMS), Simpson Extra Pyramidal Side Effect Scale (SEPSE), and Barnes Akathisia Scale (BAS). Interrater reliability, calculated by intraclass correlation coefficients, ranged from 0.79 to 0.93. Of elderly psychiatric inpatients tested, 97% were able to complete the examination, despite significant psychiatric, cognitive, and physical disabilities. AIMS, SEPSE, and BAS are reliable instruments for assessment of movement disorders in the elderly, representing an important first step in standardized evaluation of dyskinesia, parkinsonism, and akathisia in elderly psychiatric populations.

Aged↗
PubMed1992

Clinically-silent mutation in the putative iron-responsive element in exon 17 of the beta-amyloid precursor protein gene.

Three missense mutations in exon 17 of the beta-amyloid precursor protein (APP) gene have been reported to cosegregate in families with early onset Alzheimer's disease (AD). All three mutations result in amino acid substitutions at codon 717 and may produce AD by altering the structure of the transmembrane domain of APP. Alternatively, the mutations may destabilize the stem of a putative iron-responsive element (IRE) in which they lie and confer pathogenicity by inactivating this negative regulatory element. We have detected a clinically-silent mutation in codon 716 that would also be expected to disrupt the putative IRE but results in no amino acid substitution. This result strongly suggests that the missense mutations at codon 717 produce AD by altering the amino acid sequence of APP rather than the IRE. Furthermore, the identification of a clinically-silent mutation among four point mutations that span only three nucleotides of exon 17 suggests that this region may be a mutational "hot" spot.

Alzheimer Disease↗
PubMed1992

Impact of psychiatric hospitalization on behavioral complications of Alzheimer's disease.

OBJECTIVE: The authors conducted a prospective study of the clinical utility of the four DSM-III-R subtypes of primary degenerative dementia of the Alzheimer type (with delirium, with delusions, with depression, or uncomplicated) and acute psychiatric hospitalization for treatment of these subtypes. METHOD: The subjects were 120 consecutive inpatients with Alzheimer's disease, most of whom had behavioral abnormalities. Each subject received detailed physical, neurological, psychiatric, and mental status examinations. The presence or absence of specific behavioral problems was also documented. Patients were treated with medication, psychotherapy, and behavioral techniques. RESULTS: While all patients could be assigned to one of the four DSM-III-R behavioral subtypes, the uncomplicated subtype did not accurately reflect the burden of behavioral symptoms in the patients who did not have delirium, delusions, or depression. Each behavioral subtype responded in a characteristic way to inpatient treatment, as reflected by changes in scores on four psychometric scales used to assess cognitive impairment, psychiatric symptoms severity, and level of functioning at admission and at discharge, as well as by changes in residential setting following hospitalization. Half of all patients admitted from their homes and two-thirds of those with depression were able to go home following discharge. CONCLUSIONS: Behavioral syndromes in Alzheimer's disease should not be overlooked, because they have both clinical and prognostic significance. Short-term psychiatric hospitalization is effective and efficient for achieving the goal of returning patients to their homes and for safely implementing specific treatments in this frail population, and it may reduce the need for institutionalization.

Aged↗
PubMed1992

Correlates of persistent depressive symptoms in widows.

OBJECTIVE: Delineation of factors that predict depressive symptom severity 6 or more months after the loss of a spouse may help identify individuals at risk for persistent depressive symptoms. In this study, sociodemographic and clinical correlates of depressive symptom severity were examined among widows 6 to 16 months after the deaths of their husbands. METHOD: The 50 subjects were identified from the Allegheny County, Penn., death records and were interviewed by telephone. The authors examined the relationship of depressive symptoms to sociodemographic variables, perceptions of sex role and quality of social supports, level of support sought for bereavement, and premorbid personal and family psychiatric history. RESULTS: Widows with persistent depressive symptoms were less likely to have worked outside the home, had less favorable perceptions of their interpersonal support systems, were more likely to have had previous psychiatric disorders, and were likely to have sought professional help in response to their bereavement. In a multivariate model, only premorbid psychiatric history and the perception of interpersonal support system made independent contributions to the prediction of Beck Depression Inventory scores above the normal range. CONCLUSIONS: These results suggest several factors that may identify women at risk of protracted psychiatric morbidity after their husbands' deaths. They also suggest that the persistence of depressive symptoms an average of 1 year after the loss of a spouse may reflect a pathological condition rather than normal grieving.

Aged↗
PubMed1992

Biological correlates of clinical heterogeneity in primary dementia.

While there is considerable variation in the clinical expression of Alzheimer's disease (AD), the determinants of this clinical heterogeneity remain unclear. Platelet membrane fluidity (PMF) identifies a subgroup of patients with AD with distinct clinical features that appear to be genetically determined. Results from an integrated series of studies suggest a cellular substrate for the increase in PMF associated with this clinical subgroup, and a model for the participation of the PMF locus in the pathophysiology of AD is proposed. In addition to this approach, studies of the neuropathologic and neurochemical determinants of major depression and psychosis in the context of primary dementia are presented. The results may explain the different prognoses associated with these behavioral syndromes in patients with AD, as well as the symptoms of the syndromes themselves.

Alzheimer Disease↗
PubMed1991

Emergence of psychosis and depression in the longitudinal evaluation of Alzheimer's disease.

Prospective psychiatric evaluations were performed as part of a longitudinal study of 32 demented patients who met criteria for the histopathological diagnosis of Alzheimer's disease at the time of death. Psychosis and major depressive disorder emerged in 15 (47%) and 7 (22%) patients, respectively, none of whom had a history of either behavioral disorder prior to the onset of dementia. The prevalence of psychosis increased with increasing dementia severity, was associated with more rapid cognitive decline, and once present was often persistent. In this regard, the emergence of psychosis in the context of Alzheimer's disease appears to be a poor prognostic sign. In contrast to its relationship to cognitive impairment, psychosis was not associated with an increased mortality rate.

Aged↗
PubMed1991

Neuropathologic and neurochemical correlates of psychosis in primary dementia.

Neuropathologic and neurochemical correlates of psychosis were determined using brain tissue from 27 autopsy-confirmed cases of Alzheimer's disease. The densities of senile plaques and neurofibrillary tangles were determined in the middle frontal and superior temporal cortex, the prosubiculum, and the entorhinal cortex of the hippocampus. The concentrations of norepinephrine, dopamine, and serotonin, the metabolites of these biogenic amines, and the specific activity of choline acetyltransferase were also determined in these four cortical regions as well as in the substantia nigra, thalamus, amygdala, and caudate nucleus. Psychosis was associated with significantly increased densities of senile plaques and neurofibrillary tangles in the prosubiculum and middle frontal cortex, respectively, with trends toward increased densities of these lesions in the other areas examined. This finding is consistent with the increased rate of cognitive decline that accompanies this behavioral disorder. Psychosis was also associated with the relative preservation of norepinephrine in the substantia nigra, with trends in this direction for five of the remaining seven brain regions examined, and a significant reduction of serotonin in the prosubiculum that was accompanied by trends toward reduced levels of serotonin and 5 hydroxyindoleacetic acid in the remaining regions. The profile of neuropathologic and neurochemical changes associated with psychosis is distinct from that previously reported for major depression in the context of primary dementia.

Aged↗
PubMed1991

Risk factors for stroke as predictors of platelet membrane fluidity in Alzheimer's disease.

We have previously reported that increased platelet membrane fluidity identifies a subgroup of patients with Alzheimer's disease who have distinct clinical features including an earlier age of symptomatic onset, a more rapidly progressive cognitive decline, and a decreased prevalence of focal electroencephalographic findings. In the current study, these patients also exhibited a decreased prevalence of risk factors for stroke compared with patients who had normal platelet membrane fluidity. Our findings suggest that the platelet membrane abnormality describes a clinical subgroup of patients with Alzheimer's disease who are less likely to have coexisting cerebrovascular disease than the remaining patients who meet clinical consensus criteria for probable Alzheimer's disease.

Aged↗
PubMed1990

Evidence against close linkage of unipolar affective illness to human chromosome 11p markers HRAS1 and INS and chromosome Xq marker DXS52.

The genetic basis of various subtypes of the affective disorders has been investigated by family, twin, and adoption studies, as well as by segregation and linkage analysis. Linkage analyses of bipolar disorder with the chromosome 11p15 DNA markers HRAS1 and INS, and the chromosome Xq28 markers for color blindness and G6PD have been reported. We have used restriction fragment length polymorphisms as markers to examine linkage in three extended families with unipolar affective illness, ascertained through probands with either recurrent unipolar or bipolar II illness. Using an inclusive definition of the affected phenotype, linkage could be excluded up to 28cM around the HRAS1-INS linkage group on chromosome 11p15, and up to 5 cM around the DNA marker DXS52 on Xq28. Negative linkage results were also obtained for two more restrictive definitions of affective illness. Thus, we find no evidence for the involvement of the chromosomal regions 11p15 and Xq28 with unipolar affective disorder in these three families.

Bipolar Disorder↗
PubMed1990

Neurochemical correlates of major depression in primary dementia.

Biogenic amine neurotransmitters and metabolites as well as choline acetyltransferase activity were quantified in eight brain regions from 37 demented patients, with or without major depression, and 10 controls with no history of dementia or depression. The middle frontal and temporal cortex, prosubiculum and entorhinal cortex of the hippocampus, substantia nigra, thalamus, amygdala, and caudate were examined. Demented patients with major depression exhibited a 10-fold to 20-fold reduction in the level of norepinephrine in the cortex, along with relative preservation of choline acetyltransferase activity in subcortical regions, compared with demented patients who were not depressed. Serotonin levels were reduced in all eight brain regions, but the reduction did not reach statistical significance in any region examined. A para-doxical increase in dopamine levels was observed in the entorhinal cortex of depressed, demented patients, although no consistent pattern of change in the level of this neurotransmitter emerged across brain regions. Our results indicate that the development of major depression in primary dementia is associated with a profile of concurrent neurochemical changes that is largely consistent with existing neurochemical hypotheses of idiopathic affective disorders, and qualitatively distinct from that associated with primary dementia.

Brain↗
PubMed1990

Brain imaging abnormalities in mental disorders of late life.

Psychiatric inpatients with dementia (N = 61) or depression (N = 67) in late life were 2.6 times more likely to manifest magnetic resonance imaging abnormalities of the brain than were elderly controls (N = 44). Controlling for the effects of age and gender, demented patients were distinguishable from controls by an increased prevalence of cortical atrophy and infarction, while depressed patients exhibited an increased prevalence of cortical infarctions and leukoencephalopathy. Patients with dementia were distinguishable from those with major depression by an increased prevalence of cortical atrophy. These results indicate that major depression in late life, like dementia, is associated with a remarkable increase in overt pathologic changes in the brain.

Adolescent↗
PubMed1990

Brain regional analysis of NADH-cytochrome C reductase activity in Alzheimer's disease.

The specific activity of antimycin A-insensitive nicotinamide adenine dinucleotide (NADH)-dependent cytochrome C reductase, an enzyme associated with endoplasmic reticulum, was determined in the superior temporal, entorhinal, and cerebellar cortex of 16 patients who died with Alzheimer's disease and eight nondemented controls. The specific activity of choline acetyltransferase was also measured to provide an index of presynaptic cholinergic dysfunction. Our results revealed reciprocal changes in these activities that were of similar magnitude across the three regions examined. Furthermore, cytochrome C reductase activity was positively correlated with the density of neurofibrillary tangles, especially in the superior temporal cortex. These results support the hypothesis that Alzheimer's disease may be associated with an alteration of endoplasmic reticulum and the functions related to this intracellular membrane system, including the post-translational modification and localization of essential proteins.

Alzheimer Disease↗
PubMed1990

The antidepressant potential of oral S-adenosyl-l-methionine.

S-adenosyl-l-methionine (SAMe), a naturally occurring brain metabolite, has previously been found to be effective and tolerated well in parenteral form as a treatment of major depression. To explore the antidepressant potential of oral SAMe, we conducted an open trial in 20 outpatients with major depression, including those with (n = 9) and without (n = 11) prior history of antidepressant nonresponse. The group as a whole significantly improved with oral SAMe: 7 of 11 non-treatment-resistant and 2 of 9 treatment-resistant patients experienced full antidepressant response. Side effects were mild and transient.

Administration, Oral↗