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J C Morris

Publications and source records attributed to J C Morris.

At least 163 records · Page 9Linked to original sources
PubMed1996

Estimating the validity of the clinical Dementia Rating Scale: the CERAD experience. Consortium to Establish a Registry for Alzheimer's Disease.

The Clinical Dementia Rating (CDR) scale is broadly accepted by clinicians as a staging measure for Alzheimer's disease (AD). Extensive assessment of its validity is, however, lacking. We examined the concurrent and predictive validity of both summary CDR scores (global CDR, Sum of Boxes [sum of scores on the individual components]) and scores on two (Memory and Orientation) of the CDR's six components (the other four components are judgement and problem-solving, community affairs, home and hobbies, personal care) using cross-sectional, longitudinal and survival information on 434 community-resident probable AD patients. Cross-sectionally the Orientation box score correlated substantially with an independent neuropsychology measure of orientation, but the Memory box score correlated more poorly with an independent measure of memory than with any other neuropsychology measure. The relationship of the global CDR score and the Sum of Boxes score to scores on neuropsychology measures was comparable to that of the Orientation and Memory box scores. Longitudinally, Memory box score a year later was predicted equally well by the other box scores (personal care excepted). The individual components were comparable to both summary CDR scores in predicting time to death. The CDR has content and criterion validity. However, since intentionally all components measure aspects of cognitive functioning, they are closely related. Nevertheless, sufficient distinctions remain that assessment in each area is still warranted.

Aged↗
PubMed1996

Dementia and response to pain in the elderly.

To investigate the effect of dementia on response to pain, 51 community-dwelling, generally healthy, cognitively intact individuals > or = 65 years old and 44 community- or nursing home-dwelling persons > or = 65 years old with varying severity of dementia were studied. Cognitive status was assessed by standardized clinical evaluation and psychometric test performance. The following responses were measured before, during and after a standard venipuncture procedure: heart rate, the amplitude of respiratory sinus arrhythmia (RSA), self-reported anxiety and pain, and videotaped facial expressions. Although RSA did not differentiate procedural phases, in both samples, mean heart rate increased in the preparatory phase and decreased in the venipuncture phase. Independent of age, increasing severity of dementia was associated with blunting of physiologic response as measured by diminished heart rate increase in the preparatory phase and heart rate increase with venipuncture. Dementia significantly interfered with the subjects' ability to respond to direct questions about anxiety and pain. Those who were able to respond were relatively accurate self-assessors: higher anxiety was associated with greater magnitude heart rate responses. Facial expression was increased in demented individuals but it could not be classified by specific emotions. We conclude that dementia influences both the experience and reporting of pain in elderly individuals.

Aged↗
PubMed1996

In vitro assessment of variables affecting the efficiency and efficacy of adenovirus-mediated gene transfer to cystic fibrosis airway epithelia.

Primary cultures of airway epithelia were used to evaluate variables pertinent to adenovirus (Ad)-mediated gene transfer efficiency and efficacy including: (i) Ad-vectors with different promoters, (ii) the duration of vector incubation with cells, (iii) the concentration and depth of vector-containing medium at constant multiplicity of infection (moi) (10(3)), and (iv) the relative sensitivity of reverse transcription polymerase chain reaction (RT-PCR) versus functional analysis for the detection of transduced cystic fibrosis transmembrane conductance regulator (CFTR). An Ad5-lacZ vector with a cytomegalovirus (CMV) enhancer/promoter transduced the greatest amount of beta-galactosidase (beta-Gal) activity, while an Ad2-lacZ vector with an E1a enhancer/promoter transduced the least. Ad5-lacZ vectors with the Rous sarcoma virus (RSV), E1a/RSV, or CMV enhancer/beta-actin (CB) promoters transduced intermediate levels of beta-Gal. Optimal gene transfer efficiency was detected with a 4-8 hr incubation of Ad5-CMVlacZ with cells, although optimal CFTR Cl-transport function was detectable after only a 30 min incubation of Ad5-CBCFTR with cells, consistent with correction of > or = 6-10% of cells in the epithelial sheet. Ad5-CBCFTR transduction of CF airway epithelial cells (moi = 10(3)) was optimal when higher concentrations, lower volumes, or smaller depths of vector-containing medium were utilized. RT-PCR was at least 100-fold more sensitive for the detection of transduced CFTR than functional analysis, and could detect as few as 0.001% Ad5-CBCFTR-infected CF cells admixed with uninfected CF cells. In summary, the variables studied clearly affect the efficiency of Ad-mediated gene transfer in vitro and potentially in vivo. They also suggest that RT-PCR is a poor marker of gene transfer efficiency and efficacy.

Adenoviruses, Human↗
PubMed1996

Classification of dementia and Alzheimer's disease.

Classification of dementia involves the recognition of its presence, followed by the differential diagnosis of its cause. Informant-based methods for dementia detection can be highly sensitive, even when cognitive impairment is mild. Alzheimer's disease (AD) is by far the leading cause of dementia; standardized clinical criteria result in high diagnostic accuracy rates. Classification of other dementing disorders is less satisfactory, particularly because there is frequent clinical and pathological overlap with AD. After AD, the most common causes of dementia are vascular dementia and dementia in persons with Parkinson's disease. Less common dementias include progressive supranuclear palsy, Huntington's disease, Pick's disease, Creutzfeldt-Jakob disease, and inherited metabolic disorders, most of which are extremely rare. Identifying the cause of dementia is important because some forms can be treated with currently available therapies. In instances involving genetically transmitted disease, genetic testing and counseling of family members may be advisable.

Alzheimer Disease↗
PubMed1996

Clinical evaluation of global change in Alzheimer's disease: identifying consensus.

It is important that clinicians who rate global change as part of Alzheimer's disease (AD) clinical drug trials agree on a relevant set of behaviors and information to be considered in formulating their rating. Yet, consensus among raters has been difficult to establish, and inter-rater reliability of clinical global impression of change (CGIC) ratings has been low. In preparation for the development of a new CGIC scale to be used in AD clinical trials, the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC), we surveyed clinicians at sites comprising the National Institute on Aging-sponsored ADCS participating centers to identify whether or not consensus regarding CGICs exists. Overall, respondents reported that a CGIC should include an assessment of the patient's function and mental status, a care giver interview, and a standardized set of questions, and it should take approximately 20 minutes per interview. Depending on a patient's level of impairment, raters consider different areas of behavior in formulating a CGIC rating. These findings demonstrate the considerable consensus regarding the CGIC rating process, and were integrated into the design of the ADCS-CGIC, currently in use.

Alzheimer Disease↗
PubMed1996

Thyrotropin (TSH) receptor antibodies (TSHrAb) can inhibit TSH-mediated cyclic adenosine 3',5'- monophosphate production in thyroid cells by either blocking TSH binding or affecting a step subsequent to TSH binding.

In the present study, rabbit antibodies that possess thyroid stimulation-blocking activity were used to investigate potential mechanisms by which TSH receptor antibodies can inhibit thyroid cell function. The antibodies were produced against two synthetic peptides corresponding to amino acids 357-372 (p357) and 367-386 (p367) of the human TSHr (hTSHr). By enzyme-linked immunosorbent assay, both antisera (alpha 357 and alpha 367) had high titers ( > 1:100,000) of IgG against their respective peptides and recombinant extracellular TSHr protein (ETSHr); alpha 357 had a low IgG titer to p367 (1:800), and alpha 367 had a low IgG titer to p357 ( < 1:200). Based on competitive inhibition studies, alpha 357 and alpha 367 displayed similar relative binding affinities for their respective peptides and for recombinant ETSHr. When tested by commercial RRA, alpha 357 did not block (TSH binding inhibition index, -3.7%), whereas alpha 367 blocked TSH binding to TSHr (TSH binding inhibition index, 53.9%). The blocking effect of alpha 367 could be reversed by incubating the antiserum with p367 before assay. When applied alone to FRTL-5 cells, IgG from alpha 357 inhibited [compared to normal rabbit IgG (NRI); P < 0.01] based cAMP production by the cells, whereas IgG from alpha 367 did not. IgG from both alpha 357 and alpha 367, however, were able to inhibit (P < 0.001) TSH-mediated cAMP production by FRTL-5 cells [bovine (b) TSH, 2.5 x 10(-10) M; cAMP (mean +/- SD; picomoles per ml): NRI, 62.5 +/- 6.1; alpha 357, 12.2 +/- 2.4; alpha 367, 36.2 +/- 3.5]. Alpha 357 continued to inhibit (P < 0.05) cAMP production by FRTL-5 cells in 10(-8) M bTSH, whereas alpha 367 no longer inhibited cAMP production at bTSH concentrations above 5 x 10(-10) M. Compared to NRI, both alpha 357 and alpha 367 were also able to inhibit (P < 0.001) Graves' IgG-mediated cAMP production by FRTL-5 cells. When IgG were tested on FRTL-5 cells in the presence of 10(-7) M forskolin, only alpha 357 inhibited (P < 0.001) cAMP production (NRI, 75.1 +/- 4.8; alpha 357, 52.3 +/- 4.5; alpha 367, 77.2 +/- 1.4). To determine whether the inhibitory effect of alpha 357 on forskolin-mediated stimulation was thyroid cell dependent, IgG were tested on Chinese hamster ovary (CHO) cells transfected with the complementary DNA of the hTSHr (CHO-R). Again, alpha 357 inhibited (P < 0.005) cAMP production mediated by forskolin (at 10(-7) M; NRI, 68.7 +/- 4.4; alpha 357, 36.8 +/- 5.7; alpha 367, 64.6 +/- 8.5). alpha 357 did not inhibit forskolin-mediated cAMP production by untransfected CHO cells (CHO-N), indicating that the inhibitory effect of alpha 357 on forskolin stimulation was TSHr dependent. In addition, alpha 357 inhibited (P < 0.01) basal cAMP production by CHO-R cells, but not by CHO-N cells. alpha 367 had no effect on the basal cAMP production in either CHO-R or CHO-N cells. Neither alpha 357 nor alpha 367 inhibited cholera toxin-mediated cAMP production in FRTL-5 cells. In all relevant bioassays, the inhibitory effects of alpha 357 and alpha 367 could be reversed by preincubating the IgG with the respective peptides. From these data, we conclude that 1) alpha 367 binds to the ETSHr and blocks TSH-mediated cAMP production by inhibiting TSH from binding to its receptor; 2) alpha 357 binds to the TSHr and, without blocking TSH binding, inhibits TSH-mediated cAMP production at a step(s) subsequent to ligand binding that affects adenylate cyclase activity; and 3) forskolin-mediated cAMP production by thyroid cells can be inhibited by IgG that bind directly to the TSHr.

Animals↗
PubMed1996

Clinical and neuropsychological differences between patients with earlier and later onset of Alzheimer's disease: A CERAD analysis, Part XII.

To determine whether the age of the onset of Alzheimer's disease (AD) is related to the expression and rate of decline of this disorder, we examined the clinical and neuropsychological performance of 421 patients entered into the Consortium to Establish a Registry for Alzheimer's Disease and followed annually for up to 4 years. Statistical analyses were based on multivariable logistic regression analysis for dichotomous clinical measures and multivariable linear regression analysis for psychometric measures. All analyses examined the effect of age after controlling for gender, education, and stage of dementia. Clinical information obtained on entry into the study indicated that younger patients performed more poorly on measures of language and concentration, and older patients performed more poorly on measures of memory and orientation. On neuropsychological measures at entry, younger patients, performed more poorly on praxis and had significantly higher scores of confrontation naming. Younger age predicted a significantly faster rate of progression for all neuropsychological measures. These findings support the concept of age-related clinical subtypes of AD.

Age of Onset↗
PubMed1996

The consortium to establish a registry for Alzheimer's Disease (CERAD). Part XIII. Obtaining autopsy in Alzheimer's disease.

Although autopsy rates in the United States have been decreasing steadily, the necessity for brain autopsy to confirm Alzheimer's disease (AD) remains. Of 308 consecutively deceased AD patients at 24 CERAD (Consortium to Establish a Registry for Alzheimer's Disease) sites, 167 (54%) were autopsied; 141 (46%) were not. The autopsied and nonautopsied groups were comparable in gender (men, 57.5% versus 49.7%), marital status (married, 69.3% versus 67.1%), age at entry (73 versus 74 years), age at death (76 versus 77 years), and stage of disease at entry (mild, 46% versus 43%). However, the autopsied patients were significantly more likely to be white (94.5% versus 82.1%), to be better educated (13.1 versus 11.3 years), to have been in the study longer (mean, 3.3 versus 2.6 years), and to have had longer total duration of AD (8.1 versus 6.7 years). Of the 24 CERAD sites, 13 stressed the importance of autopsy by dedicating a staff member to seek autopsy and by providing free autopsy and transportation; 11 did not. Logistic regression analysis showed that white race (odds ratio [OR] = 2.74; 95% confidence interval [CI] = 1.10-6.83), increased education (OR = 1.12; 95% CI = 1.04-1.21), and emphasis on autopsy (OR = 4.69; 95% CI = 2.67-8.25) were the only significant factors. Although race and education were important, autopsy was more likely to be obtained when sites dedicated resources to this endeavor.

Aged↗
PubMed1996

Cerebral amyloid deposition and diffuse plaques in "normal" aging: Evidence for presymptomatic and very mild Alzheimer's disease.

The presence of senile plaques in the neocortex of apparently nondemented elderly persons often is accepted as part of "normal" aging. Alternatively, because cerebral deposition of beta-amyloid may be a key mechanism in the development of Alzheimer's disease (AD), the presence of beta-amyloid-containing plaques may represent very early AD. To examine the relationships of cognitively normal aging, very mild dementia of the Alzheimer type, and the presence of neocortical senile plaques, we performed clinicopathologic correlation in 21 longitudinally studied healthy elderly subjects (84.5 +/- 6.6 years old at death). Nine subjects had strikingly high plaque densities in the neocortex; two of these subjects died of head injury before which there was no evidence of cognitive impairment. The other seven subjects with high plaque densities had clinical evidence for very mild cognitive impairment (Clinical Dementia Rating score of 0.5) at some time during their course and mildly impaired psychometric performance at last assessment before death. The remaining 12 subjects had no clinical or psychometric impairment and had few or no neocortical AD lesions. These results suggest that senile plaques may not be part of normal aging but instead represent presymptomatic or unrecognized early symptomatic AD. The high density of senile plaques (predominately of the diffuse subtype) in the cortex of subjects just at the threshold of detectable dementia is consistent with the hypothesis that beta-amyloid deposition is an initial pathogenetic event in the development of AD.

Aged↗
PubMed1996

Cerebral amyloid angiopathy in the brains of patients with Alzheimer's disease: the CERAD experience, Part XV.

We studied the frequency, severity, and clinical correlations of cerebral amyloid angiopathy (CAA) in 117 CERAD subjects with autopsy-confirmed AD. Eighty-three percent showed at least a mild degree of amyloid angiopathy. Thirty of 117 brains (25.6%) showed moderate to severe CAA affecting the cerebral vessels in one or more cortical regions. These brains also showed a significantly higher frequency of hemorrhages or ischemic lesions than those of subjects with little or no amyloid angiopathy (43.3% versus 23.0%; odds ratio = 2.6, 95% CI = 1.1 to 6.2) High CAA scores also correlated with the presence of cerebral arteriosclerosis and with older age at onset of dementia. Our findings suggest that factors contributing to non-AD-related vascular pathology (e.g., atherosclerosis) may play a role in amyloid deposition in cerebral vessels in AD.

Aged↗
PubMed1996

CSF excitatory amino acids and severity of illness in Alzheimer's disease.

Researchers have proposed that increased release of excitatory amino acids (EAAs) is involved in the pathogenesis of dementia of the Alzheimer type (DAT), and CSF EAA concentrations have been measured to obtain evidence in support of this hypothesis. However, previous comparisons of CSF EAA concentrations in patients with DAT and in controls have yielded inconsistent results, perhaps because patient samples have been heterogeneous as to dementia severity. To determine whether there are changes in CSF concentrations of EAAs related to severity of illness in patients with DAT, we measured CSF concentrations of glutamate, aspartate, and taurine in 32 subjects with DAT, in whom we also assessed the severity of illness using clinical and neuropsychological measures, and 11 age-matched controls. The results suggested that increased CSF aspartate and glutamate concentrations, as well as decreased taurine concentrations, may occur in some persons with more advanced symptoms of DAT.

Aged↗
PubMed1996

Increased risk of dementia in mothers of Alzheimer's disease cases: evidence for maternal inheritance.

This study tests the hypothesis of maternal inheritance of AD in families of 118 subjects with this disorder enrolled in The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). The parental generation included 24 subjects with dementia. Using the Cox proportional hazards model, we found the age-adjusted mother-to-father relative risk to be 2.8 (95% CI, 1.1 to 7.7). Among a subset of 10 families with one affected parent and at least two affected siblings, the ratio of affected mothers-to-fathers was 9:1. These findings support recent studies that found a high mother-to-father ratio among affected parents of subjects with AD. Together, these results suggest maternal inheritance of AD and are consistent with several hypotheses regarding the genetic nature of AD.

Aged↗
PubMed1996

Cross-national interrater reliability of dementia diagnosis in the elderly and factors associated with disagreement.

Thirteen researchers from five centers in Australia, Germany, the Netherlands, United Kingdom, and United States applied DSM-III-R and Clinical Dementia Rating (CDR) syndrome-level dementia criteria to written vignettes of 100 elderly people identified in clinics or community surveys. Subjects ranged in type from cognitively intact to severely demented and many were also frail, partially sighted, or deaf. This paper concerns reliability within and between centers, and the relationship between reliability and factors such as diagnostic criteria, dementia severity, and respondents' clinical characteristics. Within-center interrater reliability was high, more so for "yes-no" DSM-III-R diagnoses than the multi-level CDR. Between-center rates were lower but still moderate to good. Concordance was lower for intermediate dementia levels than for no dementia and severe dementia. Physical disability made an additional contribution to uncertainty but deafness, poor vision, anxiety, and depression had no discernible effects. Reliability levels are likely to be lower in representative aged populations than in carefully selected clinical groups.

Aged↗
PubMed1996

Thallium-201 and iodine-131 scintigraphy in differentiated thyroid carcinoma.

UNLABELLED: The purpose of this study was to determine the concordance and discordance between diagnostic 131I and 201TI whole-body scintigraphy in patients with differentiated carcinoma of the thyroid. METHODS: Following thyroidectomy for differentiated thyroid carcinoma, 50 patients underwent whole-body 131I and 201TI scanning (60 pairs of scans in total). Fifteen pairs of studies were obtained before ablative therapy, 30 pairs after ablative therapy and 15 pairs after 131I therapy for metastatic disease. Serum thyroglobulin levels were concurrently determined by radioimmunoassay. RESULTS: Thirty-six 131I whole-body scans (in 34 patients) showed residual uptake in the neck, but only six (17%) of the corresponding whole-body thallium studies had detectable uptake in the neck. Fourteen 131I scans (in nine patients) identified multiple metastatic lesions, whereas the thallium scans were interpreted as either negative, nonspecific or showing fewer lesions. In four study pairs, the thallium scans showed solitary lesions that were not detected by the corresponding radioiodine scans. In 16 scans, the thallium studies gave false-positive results. CONCLUSION: Iodine-131 scintigraphy for differentiated thyroid carcinoma is more sensitive and more specific than 201TI scintigraphy for detection of distant metastases and residual activity in the neck following thyroidectomy.

Adenocarcinoma, Follicular↗
PubMed1996

Molecular cloning and characterization of murine interleukin-11.

Human interleukin-11 (IL-11) has been shown to have pleiotropic action on hematopoietic, hepatic, stromal, epithelial, neural, and osteoclast cells. In the present work, the murine IL-11 cDNA has been isolated from a fetal thymic cell line, and its structure and function compared with human IL-11. The murine protein was demonstrated to have identical actions on the proliferation of a murine plasmacytoma cell line, murine primitive bone marrow progenitor cells, and megakaryocyte precursors. The murine IL-11 protein was synthesized as a soluble thioredoxin-IL-11 fusion in Escherichia coli and the expression of murine IL-11 was examined by pulse-chase radiolabeling in COS cells. The chromosomal location of the murine IL-11 gene was assigned to the proximal arm of chromosome 7.

Amino Acid Sequence↗