Biomedical subjects

J Kaye

Publications and source records attributed to J Kaye.

At least 55 records · Page 3Linked to original sources

PubMed1998

High cerebrospinal fluid tau and low amyloid beta42 levels in the clinical diagnosis of Alzheimer disease and relation to apolipoprotein E genotype.

OBJECTIVE: To evaluate cerebrospinal fluid (CSF) levels of amyloid beta protein ending at amino acid 42 (Abeta42) and tau as markers for Alzheimer disease (AD) and to determine whether clinical variables influence these levels. DESIGN: Cohort study. SETTING: Six academic research centers with expertise in dementia. SUBJECTS: Eighty-two patients with probable AD, including 24 with very mild dementia (Mini-Mental State Examination score >23/30) (AD group); 60 cognitively normal elderly control subjects (NC group); and 74 subjects with neurological disorders, including dementia (ND group). MAIN OUTCOME MEASURES: Levels of Abeta42 and tau were compared among AD, NC, and ND groups. Relationships of age, sex, Mini-Mental State Examination score, and apolipoprotein E (Apo E) genotype with these levels were examined using multiple linear regression. Classification tree models were developed to optimize distinguishing AD from NC groups. RESULTS: Levels of Abeta42 were significantly lower, and levels of tau were significantly higher, in the AD group than in the NC or ND group. In the AD group, Abeta42 level was inversely associated with Apo E epsilon4 allele dose and weakly related to Mini-Mental State Examination score; tau level was associated with male sex and 1 Apo E epsilon4 allele. Classification tree analysis, comparing the AD and NC subjects, was 90% sensitive and 80% specific. With specificity set at greater than 90%, the tree was 77% sensitive for AD. This tree classified 26 of 74 members of the ND group as having AD. They had diagnoses difficult to distinguish from AD clinically and a high Apo E epsilon4 allele frequency. Markers in CSF were used to correctly classify 12 of 13 patients who later underwent autopsy, including 1 with AD not diagnosed clinically. CONCLUSIONS: Levels of CSF Abeta42 decrease and levels of CSF tau increase in AD. Apolipoprotein E epsilon4 had a dose-dependent relationship with CSF levels of Abeta42, but not tau. Other covariates influenced CSF markers minimally. Combined analysis of CSF Abeta42 and tau levels discriminated patients with AD, including patients with mild dementia, from the NC group, supporting use of these proteins to identify AD and to distinguish early AD from aging. In subjects in the ND group with an AD CSF profile, autopsy follow-up will be required to decide whether CSF results are false positive, or whether AD is a primary or concomitant cause of dementia.

Adult↗

PubMed1998

Vasoactive intestinal peptide enhancement of antigen-induced differentiation of a cultured line of mouse thymocytes.

The prominence of vasoactive intestinal peptide (VIP) in rodent thymic neurons suggested that this potent mediator of T cell functions may alter developmental responses of thymocytes to T cell receptor (TCR) -dependent stimulation. CD4+8+ DPK cells derived from a thymic lymphoma of a TCR transgenic mouse respond to pigeon cytochrome C (PCC) antigen in association with distinct I-E MHC II haplotypes on antigen-presenting cells (APCs) by differentiating into CD4+8- T cells. The specific recognition of VIP by two types of homologous G-protein-coupled receptors (VIPR1 and VIPR2) on DPK cells was attributable predominantly to VIPR1 before and to VIPR2 after exposure to APCs and PCC, as assessed by quantification of the respective mRNAs. PCC-evoked differentiation of DPK cells was enhanced significantly by 1 to 100 nM VIP after 3 to 4 days. The effects of VIP analogs with VIPR type selectivity implied that VIP enhancement of differentiation of DPK cells was mediated principally by VIPR2. Differential reduction in the expression of each type of VIPR by transfection of DPK cells with plasmids encoding the respective antisense mRNAs confirmed the central role of VIPR2 in VIP-enhanced conversion to CD4+8- T cells. The suppression of DPK cell differentiation by inhibitors of adenylyl cyclase and protein kinase A suggested a transductional role for VIP-elicited increases in [cAMP]i. That the changes in frequency of CD4+8+ and CD4+8- DPK cells reflected principally differentiation was supported by the lack of consistent differences between the two subsets in the effects of VIP and VIPR2 agonist on cell number, viability, apoptosis, and proliferation. VIP may be one endogenous mediator that explains the unique thymic microenvironment for topographically specific development of T cells.

Animals↗

PubMed1998

Motor slowing precedes cognitive impairment in the oldest old.

Eighty-five healthy elderly subjects were prospectively evaluated for 3 years to determine motor differences between those who remain cognitively intact and those who developed cognitive impairment during prospective follow-up. The 18 subjects who developed cognitive impairment had slower finger tapping and took longer to walk 30 feet before or at the time of cognitive impairment. Coordination was more impaired and steps, but not balance, deteriorated more rapidly, independent of other variables.

Aged↗

PubMed1998

How should data be analyzed and reported in a risk-contracting environment?

Integrated delivery systems (IDSs) that enter into risk contracts with payers need sophisticated data analysis and reporting capabilities to ensure proper payment and to manage utilization. An IDS can develop these capabilities by following a six-step process: It should develop an IDS data management structure, obtain all requisite data, review and refine the data, consolidate the data, create a relational database, and develop a reporting structure. The reporting structure should consist of a set of standard reports and the ability to generate additional targeted reports that facilitate analysis of specific aspects of utilization and financial performance.

Capitation Fee↗

PubMed1997

A role for Ras signaling in coreceptor regulation during differentiation of a double-positive thymocyte cell line.

Evidence suggests that the Ras/mitogen-activated protein kinase signaling pathway is required for positive selection of thymocytes. We have asked whether Ras activation is also sufficient to mediate changes in gene expression that are associated with positive selection. To accomplish this, we expressed a constitutively active form of Ras in the immature CD4+ 8+ DPK thymocyte cell line. DPK cells that express active Ras have reduced levels of CD8alpha and CD8beta at the level of cell surface protein and mRNA. These data provide evidence of a direct link between Ras signaling pathways and coreceptor regulation during positive selection. They also suggest that a sustained or potent Ras signal may play a critical role in directing thymocytes into the CD4 lineage. DPK cells that express active Ras, however, were not fully differentiated, indicating that Ras signaling provides only a partial signal for double-positive thymocyte differentiation.

Animals↗

PubMed1997

Induction of the early growth response (Egr) family of transcription factors during thymic selection.

There is little known about the regulation of gene expression during TCR-mediated differentiation of immature CD4+8+ (double positive) thymocytes into mature T cells. Using the DPK CD4+8+ thymocyte precursor cell line, we demonstrate that the early growth response-1 gene (Erg-1), encoding a zinc finger transcription factor, is rapidly upregulated after TCR stimulation. We also report that Egr-1 is expressed by a subset of normal double positive thymocytes in the thymic cortex, as well by a majority of medullary single positive thymocytes. Expression of Egr-1 is dramatically reduced in the thymus of major histocompatibility complex knockout mice, but can be induced by anti-CD3 antibody stimulation of isolated thymocytes from these animals. These and other data suggest that high level expression of Egr-1 in the thymus is a consequence of selection. A similar pattern of expression is found for family members Egr-2 and Egr-3. Using the DPK cell line, we also demonstrate that expression of Egr-1, 2, and 3 is dependent upon ras activation, as is the initiation of differentiation to a single positive cell. In contrast, the calcineurin inhibitor cyclosporin A, which inhibits DPK cell differentiation as well as positive selection, inhibits expression of Egr-2 and Egr-3, but not Egr-1. The identification of the Egr family in this context represents the first report of a link between the two known signaling pathways involved in positive selection and downstream transcriptional regulators.

Animals↗

PubMed1997

Balance in the healthy elderly: posturography and clinical assessment.

OBJECTIVES: To measure balance changes in the healthy elderly using quantitative dynamic posturography. To relate these changes to clinical measures of balance and gait. DESIGN: Elderly subjects screened for health criteria in a longitudinal study were examined using standardized cognitive, neurological, and performance-based tests. Quantitative posturography (Equitest, Neurocom International, Clackamas, Ore) was performed to determine the subject's response to sensory (Sensory Organization Test) and motor perturbations (Motor Coordination Test). SUBJECTS: Thirty-three healthy, old old subjects (> or =80 years; mean+/-SD age, 88+/-5 years) were compared with 15 subjects younger than 80 years (mean+/-SD age, 72+/-3 years). All were free of centrally active medications. RESULTS: The old old had worse quantitative equilibrium scores compared with subjects younger that 80 years when proprioceptive input was inaccurate and visual input was either preserved or completely absent. Old old subjects showed diminished adaptation to repeated platform rotations and fell more frequently during posturography. Quantitative balance measures correlated with age and functional measures of balance (Tinetti Balance Scale score, timed 1 leg standing). CONCLUSIONS: Progressive, functionally evident, age-related quantitative balance changes occur independent of typical geriatric pathological changes. These data should facilitate clinical decisions by allowing the distinction to be made between age-related and pathological changes.

Aged↗

PubMed1997

Modulation of the age at onset of Parkinson's disease by apolipoprotein E genotypes.

Parkinson's disease (PD) patients often develop dementia, and Alzheimer's disease (AD) patients frequently develop parkinsonian signs. The apolipoprotein E epsilon4 allele is associated with increased risk and earlier onset of AD. We studied 137 unrelated white PD patients. Those with epsilon4 had the earliest onset (52.7 +/- 9.8 years), epsilon3/epsilon3 patients had an intermediate onset (56.1 +/- 11.1 years), and those with epsilon2 had the latest onset (59.1 +/- 13.4 years). The age at onset distribution for epsilon4/epsilon- was significantly earlier than for epsilon3/epsilon3 and epsilon2/epsilon3. These preliminary results suggest that apolipoprotein E genotypes modulate the age at onset of PD.

Age of Onset↗

PubMed1997

Predominance of the autoimmune response to myelin oligodendrocyte glycoprotein (MOG) in multiple sclerosis: reactivity to the extracellular domain of MOG is directed against three main regions.

Our previous analysis of the T cell reactivity to myelin antigens in a group of 24 patients with multiple sclerosis (MS) and 16 control individuals revealed that the autoimmune response to myelin oligodendrocyte glycoprotein (MOG) predominates in MS over that to myelin basic protein (MBP), proteolipid protein or myelin-associated glycoprotein, suggesting a prevalent role for the autoimmune response to MOG in the pathogenesis of MS. Using a recombinant human MOG (rhMOG) preparation corresponding to the extracellular immunoglobulin-like domain of the MOG molecule, we have now analyzed another group of 52 MS patients and 49 control individuals for reactivity of their peripheral blood lymphocytes (PBL) to rhMOG and to MBP concomitantly. Of the 52 MS patients tested 24 responded to MOG and 10 out of 49 responded to MBP, whereas only 5 MOG-reactive and 4 MBP-reactive control individuals were detected out of the 49 tested. These results are therefore highly confirmatory of the predominant reactivity to MOG in MS. The analysis of the primary proliferative response to 11 synthetic overlapping peptides (phMOG) spanning the extracellular domain of human MOG by PBL from 9 MS patients and 15 control individuals (9 healthy controls and 6 patients with neurological diseases other than MS) further supports a prevalent role for the autoimmune response to MOG in MS, as only 1 of the 15 controls tested showed reactivity to any of the phMOG, whilst 5 out of the 9 patients studied reacted to at least 1 of the phMOG. PBL from 10 MS patients, and from 4 controls, were selected in vitro with each of the phMOG. Of the 10 patients studied 7 reacted to at least 1 phMOG upon secondary stimulation and the reactivity was mostly directed to epitopes localized within three main regions (amino acids 1-22, 34-56 and 64-96), as was observed for the primary response of PBL. The predominant response to MOG of PBL from MS patients as demonstrated in two separate studies using native MOG and rhMOG as antigens, and the high incidence of reactivity of these PBL compared to the lack of response to phMOG by control PBL, emphasize the relevance of MOG in MS pathogenesis and support a primary role for the autoimmune T cell response to MOG in disease development.

Adult↗

PubMed1997

Talking while walking: the effect of a dual task in aging and Alzheimer's disease.

We determined the effects of distraction on gait in healthy elderly subjects and Alzheimer's disease (AD) patients. The effects of simultaneous performance of a verbal fluency task (effect of reciting male or female names) on the time and number of steps taken to walk 30 feet were compared using a repeated-measures design with between-group comparison between community-dwelling healthy old old (oOld; n = 20; mean age +/- SD, 86 +/- 4.4), healthy young old (yOld; n = 23; mean age +/- SD, 72 +/- 3.6), and probable AD subjects without parkinsonism (n = 15; mean age +/- SD, 74 +/- 13). AD patients slowed more than the yOld (p = 0.005) and the oOld (p = 0.002). The yOld and oOld did not differ from each other (p = 0.68). Mean (+/-SD) differences in time were as follows: yOld, -2.2 +/- 1.9; oOld, -1.6 +/- 2.0; AD, -7.1 +/- 9.2 seconds. The change in steps did not differ between groups. Walking speed of AD patients slowed more than that of elderly subjects during the dual task. This may contribute to the risk of falls in AD.

Aged↗

PubMed1997

Evidence for association of HLA-A2 allele with onset age of Alzheimer's disease.

Our earlier studies had suggested a possible association between the HLA-A2 allele and Alzheimer's disease (AD). In the present study we tested the hypothesis that A2 is associated with earlier AD onset. We performed two independent studies: a collaborative study with 111 patients and a confirmatory study with 96 patients. We found similar patterns of reduced age at onset as a function of A2 in both data sets. Overall, A2 was associated with a significant 3-year shift to earlier onset. The effects of A2 and epsilon 4 on age at onset appeared additive. Our results suggest A2, or a closely linked gene, modulates onset age of AD. Association with A2 would suggest an immune/inflammatory response mechanism for AD.

Age of Onset↗

PubMed1997

A prospective study of cognitive health in the elderly (Oregon Brain Aging Study): effects of family history and apolipoprotein E genotype.

The oldest old are the fastest-growing segment of our population and have the highest prevalence of dementia. Little is known about the genetics of cognitive health in the very old. The aim of this study was to determine whether the genetic risk factors for Alzheimer disease (AD)--namely, apolipoprotein E (APOE) epsilon4 allele and a family history of dementia-continue to be important factors in the cognitive health of the very old. Case-control studies suggest that the effect of genetic factors diminishes at age >75 years. The present prospective study provided evidence to the contrary. We studied 114 Caucasian subjects who were physically healthy and cognitively intact at age 75 years and who were followed, for an average of 4 years, with neurological, psychometric, and neuroimaging examinations. Excellent health at entry did not protect against cognitive decline. Incidence of cognitive decline rose sharply with age. epsilon4 and a family history of dementia (independent of epsilon4) were associated with an earlier age at onset of dementia. Subjects who had epsilon4 or a family history of dementia had a ninefold-higher age-specific risk for dementia than did those who had neither epsilon4 nor a family history of dementia. These observations suggest that the rate of cognitive decline increases with age and that APOE and other familial/genetic factors influence the onset age throughout life.

Age of Onset↗

PubMed1997

Comparison of 3 quantitative measures of hand radiographs in patients with rheumatoid arthritis: Steinbrocker stage, Kaye modified Sharp score, and Larsen score.

OBJECTIVE: To compare 3 quantitative hand radiograph scores, Steinbrocker stage, Larsen score, and Sharp score modified by Kaye, to one another and to other measures of clinical status in a cross sectional analysis of hand radiographs of 173 patients with rheumatoid arthritis (RA). METHODS: Radiographs were scored and compared to other measures of clinical status according to correlation and cross tabulation analyses. RESULTS: In these cross sectional studies, radiographic scores according to all 3 methods were correlated at high levels (r(s) > 0.5) with one another and duration of disease, as well as with scores for physical joint deformity and limited motion; at lower levels (0.3 < r(s) < 0.5) with physical joint swelling scores, functional status, and age; and at low levels of marginal or no clinical importance (r(s) < 0.3) with physical joint tenderness scores, laboratory data, and pain scores. CONCLUSION: The 3 scoring methods give similar quantitative information concerning hand radiographs of patients with RA. The Larsen and modified Sharp scores are preferred measures, as the detailed information facilitates comparison of different patients and monitoring of individual patients over time.

Activities of Daily Living↗

PubMed1996

A phase I trial of recombinant human interleukin-11 (neumega rhIL-11 growth factor) in women with breast cancer receiving chemotherapy.

We performed a phase I trial of recombinant human interleukin-11 (rhIL-11) in women with breast cancer. Cohorts of three to five women were accrued to five dosage levels of rhIL-11 (10, 25, 50, 75, and 100 micrograms/kg/d). rhIL-11 alone was administered by a daily subcutaneous injection for 14 days during a 28-day prechemotherapy "cycle 0." Patients (pts) subsequently received up to four 28-day cycles of cyclophosphamide (1,500 mg/m2) and doxorubicin (60 mg/m2) chemotherapy followed by rhIL-11 at their assigned dose (days 3 through 14). Sixteen pts (13 stage IV, 3 stage IIIB) were accrued to this study. Median age was 53 years and median Eastern Cooperative Oncology Group Performance Status was 0. A grade 3 neurologic event was seen in 1 pt at 100 micrograms/kg. Because of the degree of grade 2 constitutional symptoms (myalgias/arthralgias and fatigue) at 75 micrograms/kg, dose escalation was stopped and 75 micrograms/kg was the maximally tolerated dose. No other grade 3 or 4 adverse events related to rhIL-11 were seen. The administration of rhIL-11 was not associated with fever. Reversible grade 2 fatigue and myalgias/arthralgias were seen in all pts at 75 micrograms/kg. Weight gain of 3% to 5% associated with edema was seen at doses > 10 micrograms/kg but a capillary leak syndrome was not seen. rhIL-11 alone was associated with a mean 76%, 93%, 108%, and 185% increase in platelet counts at doses of 10, 25, 50, and 75 micrograms/kg, respectively. No significant changes in leukocytes were seen. A mean 19% decrease in hematocrit was observed. Acute-phase proteins increased with treatment at all doses. Compared with patients at the 10 micrograms/kg dose, patients receiving doses > or = 25 micrograms/kg experienced less thrombocytopenia in the first two cycles of chemotherapy. We conclude that rhIL-11 has thrombopoietic activity at all doses studied, is well tolerated at doses of 10, 25, and 50 micrograms/kg, and at doses > or = 25 micrograms/kg has the potential to reduce chemotherapy-induced thrombocytopenia in this model.

Adult↗

PubMed1996

Sexual harassment and hostile environments in the perioperative area.

Nursing has dealt with sexual harassment since the era of Florence Nightingale. Despite legislation and increased media attention, perioperative nurses continue to experience frustration, embarrassment, and psychological and economic repercussions because of sexual harassment. Prevention of sexual harassment must encompass individuals, employers, and the health care profession as a whole. Individuals can take steps to stop sexual harassment by reporting the incidents and confronting the harassers. Employers have a legal responsibility to maintain work environments that discourage sexual harassment. Policies and procedures strictly prohibiting sexual harassment should be well publicized and supported strongly by management. Sexual harassment prevention programs should include medical staff members, because studies indicate most harassers are physicians. Awareness and prevention are the first steps to establishing and maintaining healthy workplaces that are free of sexual harassment.

Female↗

PubMed1996

Increased risk of familial late-onset Alzheimer's disease in women.

The role of gender in the pathogenesis of Alzheimer's disease (AD) is an important issue that remains controversial. We compared men and women in late-onset familial AD kindreds for the risk of developing AD by studying 26 well-characterized familial AD kindreds from the Oregon Alzheimer Disease Center and, for confirmation, an additional 32 kindreds from the National Cell Repository (NCR) at the Indiana University Alzheimer Disease Center. Comparing women to men, the age-adjusted odds ratio estimates were 3.2 (p = 0.0002) for the Oregon data and 2.3 (p = 0.004) for the NCR data. These results suggest that gender is an independent risk factor for familial late-onset AD and may play a role in the pathogenesis of this disease.

Age of Onset↗

PubMed1996

Linking anatomy and physiology in modeling respiratory mechanics.

We present an integrated 3D virtual environment for the quantitative modeling of the anatomy and the physiology of the pulmonary system. Our approach formally integrates 3D deformable object modeling with conventional models of respiratory mechanics. We demonstrate quantitatively, aspects of the behavior of the respiratory system qualitatively known to clinicians, such as normal quiet breathing and an open sucking chest wound. Our methodology is general and can be used to model both the anatomy and the physiology at many levels of detail. Another important aspect of our approach is that based on our previously developed computer vision techniques we can make such a simulation patient specific. The usefulness of such a system is manifold. Medical education, surgical planning, disease diagnosis are some of the many areas such a system can be applied.

Computer Simulation↗

PubMed1995

Incomplete T cell receptor V beta allelic exclusion and dual V beta-expressing cells.

Recent studies have documented incomplete TCR V alpha-chain allelic exclusion and dual V alpha-bearing T cells. Herein, we show that V beta allelic exclusion is also incomplete, since a significant proportion of peripheral T cells express dual V beta in both TCR transgenic and normal mice. Studies in TCR transgenic mice indicated that although a small proportion of T cells escaped allelic exclusion in the thymus, dual V beta-expressing cells expanded dramatically in the periphery with age, and such expanded cells had an activated phenotype. Although not as pronounced, age-related increases in dual V beta-bearing cells were also observed in normal mice. These findings may have important implications for TCR selection and specificity, age-related repertoire changes, and autoimmune disease pathogenesis.

Alleles↗