Policy recommendations for family caregiver support.
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Aged↗
Biomedical subjects
K M Robinson
Publications and source records attributed to K M Robinson.
Respite care--volunteers as providers.
1. Although many studies examine the impact of respite care on caregivers, few studies have examined the impact of such programs on the volunteer respite provider. Results of such formative evaluation studies must be antecedent to the question of whether respite care "works." 2. Fear of persons with Alzheimer's Disease (AD) was a consistent theme verbalized in this study. Educational programs must therefore include more exposure to actual persons with AD. 3. Caregivers with some past experience composed the majority of volunteers in this group (n = 78%). Recruiting former caregivers of deceased persons with AD may be fruitful future areas of study.
Adult↗
Chromatin, TAFs, and a novel multiprotein coactivator are required for synergistic activation by Sp1 and SREBP-1a in vitro.
The promoter selectivity factor Sp1 often cooperates with other enhancer-binding proteins to activate transcription. To study the molecular underpinnings of these regulatory events, we have reconstituted in vitro the synergy observed in vivo between Sp1 and the sterol-regulated factor SREBP-1a at the low density lipoprotein receptor (LDLR) promoter. Using a highly purified human transcription system, we found that chromatin, TAFs, and a novel SREBP-binding coactivator activity, which includes CBP, are all required to mediate full synergistic activation by Sp1 and SREBP-1a. The SREBP-binding domain of CBP inhibits activation by SREBP-1a and Sp1 in a dominant-negative fashion that is both chromatin- and activator-specific. Whereas recombinant CBP alone is not sufficient to mediate activation, a human cellular fraction containing CBP can support high levels of chromatin-dependent synergistic activation. Purification of this activity to near homogeneity resulted in the identification of a multiprotein coactivator, including CBP, that selectively binds to the SREBP-1a activation domain and is capable of mediating high levels of synergistic activation by SREBP/Sp1 on chromatin templates. The development of a reconstituted chromatin transcription system has allowed us to isolate a novel coactivator that is recruited by the SREBP-1a activation domain and that functions in concert with TFIID to coordinate the action of multiple activators at complex promoters in the context of chromatin.
Animals↗
The use of chromatin templates to recreate transcriptional regulatory phenomena in vitro.
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Chromatin↗
The COQ5 gene encodes a yeast mitochondrial protein necessary for ubiquinone biosynthesis and the assembly of the respiratory chain.
Saccharomyces cerevisiae is a facultative anaerobe capable of meeting its energy requirements by fermentation and is thus an ideal system for studying the biogenesis of respiring mitochondria. We have isolated a respiration-deficient mutant exhibiting a pleiotropic loss of the mitochondrial electron transport chain. The corresponding wild-type gene, COQ5, was cloned, sequenced, and able to restore respiratory growth. Deletion of the chromosomal COQ5 gene results in a respiration deficiency and reduced levels of respiratory protein components. Exogenously added decylubiquinone can partially restore electron transport chain function to mitochondrial membranes from the deletion mutant. The COQ5 nucleotide sequence predicts a polypeptide of 307 amino acids containing a mitochondrial targeting signal. COQ5p is 43% identical to the polypeptide predicted by the Escherichia coli open reading frame, o251 (1). The COQ5 gene, when introduced into E. coli, complements the respiratory deficiency of an ubiE mutant that maps near o251, suggesting that it is the yeast homolog of the ubiE gene product. We conclude that the COQ5 gene encodes the mitochondria-localized 2-hexaprenyl-6-methoxy-1,4-benzoquinone methyltransferase of the yeast ubiquinone biosynthetic pathway.
Amino Acid Sequence↗
Lexical acquisition in probable Alzheimer's disease.
Patients with probable Alzheimer's disease (pAD) were exposed to a new verb in a naturalistic fashion. We probed their knowledge of the word's semantic and grammatical characteristics for several minutes following this exposure, and compared this with their performance on parallel measures assessing known words. Significant differences were seen between pAD patients and controls in the acquisition of the new verb's semantic meaning and its argument structure, but pAD patients did not differ from controls in the acquisition of the new word's grammatical form class. Individual patient analyses demonstrated parallel deficits restricted to the semantic meaning and argument structure of the new word and known words in several pAD patients, suggesting that a selective language impairment contributed to their word learning deficit. This pattern is consistent with an intimate relationship between semantic meaning and argument structure in semantic memory. Other pAD patients had difficulty learning about all aspects of the new word, despite good performance with known words, suggesting that compromised memory may have limited their lexical acquisition.
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The family's role in long-term care.
Long-term care provided by family members is the central care of our current health care system. The purpose of this article is to review the family's role in long-term care. Issues such as cost containment and inequities in our current social policy are reviewed. Suggestions for future directions in social policy are presented.
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Covalent attachment of FAD to the yeast succinate dehydrogenase flavoprotein requires import into mitochondria, presequence removal, and folding.
Succinate dehydrogenase (EC 1.3.99.1) in the yeast Saccharomyces cerevisiae is a mitochondrial respiratory chain enzyme that utilizes the cofactor, FAD, to catalyze the oxidation of succinate and the reduction of ubiqinone. The succinate dehydrogenase enzyme is a heterotetramer composed of a flavoprotein, an iron-sulfur protein, and two hydrophobic subunits. The FAD is covalently attached to a histidine residue near the amino terminus of the flavoprotein. In this study, we have investigated the attachment of the FAD cofactor with the use of an antiserum that specifically recognizes FAD and hence, can discriminate between apo- and holoflavoproteins. Cofactor attachment, both in vivo and in vitro, occurs within the mitochondrial matrix once the presequence has been cleaved. FAD attachment is stimulated by, but not dependent upon, the presence of the iron-sulfur subunit and citric acid cycle intermediates such as succinate, malate, or fumarate. Furthermore, this modification does not occur with C-terminally truncated flavoprotein subunits that are fully competent for import. Taken together, these data suggest that cofactor addition occurs to an imported protein that has folded sufficiently to recognize both FAD and its substrate.
Citric Acid Cycle↗
A requirement for matrix processing peptidase but not for mitochondrial chaperonin in the covalent attachment of FAD to the yeast succinate dehydrogenase flavoprotein.
Succinate dehydrogenase (EC 1.3.99.1) in the yeast Saccharomyces cerevisiae is a mitochondrial heterotetramer containing a flavoprotein subunit with an 8alpha-N(3)-histidyl-linked FAD cofactor. The covalent linkage of the FAD is necessary for activity. We have developed an in vitro assay that measures the flavinylation of the flavoprotein precursor in mitochondrial matrix fractions. Flavoprotein modification does not depend on translocation across a membrane, but it does require proteolytic processing by the mitochondrial processing peptidase prior to flavin attachment. Since ATP depletion, N-ethylmaleimide, or proteinase treatments of matrix fractions inhibit flavoprotein modification, at least one additional matrix protein component appears to be required. Having previously suggested that the flavoprotein begins folding before FAD attachment occurs, we tested whether the mitochondrial chaperonin, heat shock protein 60, might be necessary. Co-immunoprecipitation of the flavoprotein and the chaperonin demonstrate that the proteins do indeed interact. However, immunodepletion of the chaperonin from matrix fractions does not inhibit FAD attachment. Nonprotein components are also required for flavoprotein modification. In addition to ATP, effector molecules such as succinate, fumarate, or malate also stimulate modification. Together, these results suggest that FAD addition is an early event in succinate dehydrogenase assembly.
Adenosine Triphosphate↗
Anomaly judgments of subject-predicate relations in Alzheimer's disease.
Claims that patients with probable Alzheimer's disease (AD) have semantic memory difficulty have received equivocal support. A common assumption has been that defining or core information determines the truth value of word meaning on measures requiring semantic memory such as category membership judgments or confrontation naming, but this assumption may not be valid. In the present study, we assessed the comprehension of subject-predicate sentences independent of their truth value by asking AD patients to judge the coherence of statements such as "The tulip is tall" or "*The tulip is jealous." We found that AD patients are significantly more impaired than controls at judging the coherence of these simple subject-predicate sentences. Moreover, AD patients were more successful at judging the coherence of statements that contain attributes with a narrow scope of reference compared to attributes with a broad scope of reference. These findings support the hypothesis that AD patients have a semantic memory impairment and suggest a specific deficit processing the network of semantic relations underlying word meaning in semantic memory.
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Freehand drawing impairments in probable Alzheimer's disease.
We evaluated freehand picture production of familiar objects in patients with probable Alzheimer's disease. The overall recognizability of their drawings was significantly compromised. Error analyses revealed the production of category violations and the frequent inclusion of incorrect features in a picture that were borrowed from semantically related objects, suggesting difficulty distinguishing between items with overlapping features sets in semantic memory. Analyses of individual patient drawing profiles also revealed that some patients are disproportionately compromised in expressing a particular perceptual feature, implicating difficulty at the level of perceptual processing. Regression analyses demonstrated the contribution of limited visual attentional resources. We conclude that impaired freehand drawing in probable Alzheimer's disease is multifactorial in nature.
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Category-specific difficulty naming with verbs in Alzheimer's disease.
We studied 20 patients with Alzheimer's disease (AD) on a picture-naming task consisting of frequency-matched pairs of nouns and verbs that were homophonic and homographic (e.g., paint). Intragroup comparisons revealed that verb naming is significantly more difficult for patients with AD than noun naming. An error analysis demonstrated that patients with AD produce significantly more semantic and descriptive errors for verbs than nouns. We correlated verb naming and noun naming with measures of grammatical comprehension, lexical retrieval, and visuoperceptual processing, but there were no selective effects for verbs compared with nouns. Differences in the mental representation of concepts underlying verbs and nouns may account, in part, for the relative difficulty naming with verbs in AD.
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Language comprehension profiles in Alzheimer's disease, multi-infarct dementia, and frontotemporal degeneration.
We assessed language functioning in 116 age-, education-, and severity-matched patients with the clinical diagnosis of Alzheimer's disease (AD), multi-infarct dementia (MID) due to small-vessel ischemic disease, or a frontotemporal form of degeneration (FD). Assessments of comprehension revealed that patients with AD are significantly impaired in their judgments of single word and picture meaning, whereas patients with FD had sentence comprehension difficulty due to impaired processing of grammatical phrase structure. Patients with MID did not differ from control subjects in their comprehension performance. Traditional aphasiologic measures did not distinguish between AD, MID, and FD. Selective patterns of comprehension difficulty in patients with different forms of dementia emphasize that language deficits cannot be explained entirely by the compromised memory associated with a progressive neurodegenerative illness.
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Flavinylation of succinate: ubiquinone oxidoreductase from Saccharomyces cerevisiae.
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Cell Fractionation↗
The relationship between health and social support in caregiving wives as perceived by significant others.
This study explored the relationship between health and social support in wives who care for husbands with dementia. In order to understand how significant others begin mobilizing help for caregivers, the significant others' views of the carers' health and social support were analysed. Subjects comprised 75 significant others identified as being familiar with the caregiving situation of a like number of caregiving wives. Hypotheses, which were rejected, predicted that wife caregivers perceived as ill by the significant other would be seen as needing and receiving more social support as reported by the significant other. Findings indicated that healthy caregivers were perceived to have significantly more people in their social network.
Adult↗
Sentence comprehension in multiple sclerosis.
INTRODUCTION: Explanations of sentence processing difficulty in aphasia have implicated slowed information processing speed. We tested this hypothesis by evaluating sentence comprehension in multiple sclerosis (MS), and relating comprehension performance to measures of information processing speed. MATERIAL & METHODS: Twenty right-handed, high school-educated, non-demented, native English speakers with clinically definite MS and 16 age- and education-matched control subjects were examined on 3 different sentence comprehension measures that stress grammatical appreciation. Performance was related to quantitative assessments of mental information processing speed. RESULTS: Group-wide analyses demonstrated a trend toward sentence comprehension difficulty in MS. Analyses of individual patient profiles identified a subgroup of MS patients who were consistently impaired to a significant extent across all sentence comprehension tasks. Their sentence comprehension difficulty was associated with selectively compromised mental information processing speed. CONCLUSION: Sentence comprehension difficulty in MS is associated with slowed information processing speed. This finding supports the claim that information processing speed contributes to sentence processing.
Adult↗
Phonologic processing deficits in Alzheimer's disease.
We investigated phonologic production in patients with mild to moderate Alzheimer's disease (AD) on a repetition task. AD patients produced significantly more speech errors than age-matched controls. AD patients' errors, unlike those of controls, resulted in the transformation of real words into pseudowords, occurred disproportionately in word-initial positions, and were not influenced by the phonologic environment. This pattern of errors suggests a lexical phonologic retrieval deficit in AD.
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The covalent attachment of FAD to the flavoprotein of Saccharomyces cerevisiae succinate dehydrogenase is not necessary for import and assembly into mitochondria.
Succinate dehydrogenase of the bacterial or inner mitochondrial membrane catalyses the oxidation of succinate to fumarate and directs reducing equivalents into the electron-transport chain. The enzyme is also able to catalyse the reverse reaction, the reduction of fumarate to succinate. The enzyme is composed of four subunits. These subunits include a catalytic dimer composed of a flavoprotein subunit with a covalently bound FAD, and an iron-sulfur protein subunit with three different iron-sulfur centres, which is anchored to the membrane by two smaller integral membrane proteins. The FAD moiety is attached to the flavoprotein subunit by an 8 alpha-[N(3)-histidyl]FAD linkage at a conserved histidine residue, His90 of the Saccharomyces cerevisiae succinate dehydrogenase. By mutating His90 to a serine residue, we have constructed a flavoprotein subunit that is unable to covalently bind FAD. The mutant flavoprotein is targeted to mitochondria, translocated across the mitochondrial membranes, and is assembled with the other subunits where it binds FAD non-covalently. The resulting holoenzyme has no succinate-dehydrogenase activity but retains fumarate reductase activity. The covalent attachment of FAD is therefore necessary for succinate oxidation but is dispensable for both fumarate reduction and for the import and assembly of the flavoprotein subunit.
Binding Sites↗