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E Kahana

Publications and source records attributed to E Kahana.

At least 19 recordsLinked to original sources
PubMed2005

Fast collapse but slow formation of secondary structure elements in the refolding transition of E. coli adenylate kinase.

The various models proposed for protein folding transition differ in their order of appearance of the basic steps during this process. In this study, steady state and time-resolved dynamic non-radiative excitation energy transfer (FRET and trFRET) combined with site specific labeling experiments were applied in order to characterize the initial transient ensemble of Escherichia coli adenylate kinase (AK) molecules upon shifting conditions from those favoring denaturation to refolding and from folding to denaturing. Three sets of labeled AK mutants were prepared, which were designed to probe the equilibrium and transient distributions of intramolecular segmental end-to-end distances. A 176 residue section (residues 28-203), which spans most of the 214 residue molecule, and two short secondary structure chain segments including an alpha-helix (residues 169-188) and a predominantly beta-strand region (residues 188-203), were labeled. Upon fast change of conditions from denaturing to folding, the end-to-end distance of the 176 residue chain section showed an immediate collapse to a mean value of 26 A. Under the same conditions, the two short secondary structure elements did not respond to this shift within the first ten milliseconds, and retained the characteristics of a fully unfolded state. Within the first 10 ms after changes of the solvent from folding to denaturing, only minor changes were observed at the local environments of residues 203 and 169. The response of these same local environments to the shift of conditions from denaturing to folding occurred within the dead time of the mixing device. Thus, the response of the CORE domain of AK to fast transfer from folding to unfolding conditions is slow at all three conformational levels that were probed, and for at least a few milliseconds the ensemble of folded molecules is maintained under unfolding conditions. A different order of the changes was observed upon initiation of refolding. The AK molecules undergo fast collapse to an ensemble of compact structures where the local environment of surface probes seems to be native-like but the two labeled secondary structure elements remain unfolded.

Adenylate Kinase↗
PubMed2002

The natively helical chain segment 169-188 of Escherichia coli adenylate kinase is formed in the latest phase of the refolding transition.

The refolding transition of Escherichia coli adenylate kinase (AK) was investigated by monitoring the refolding kinetics of a selected 20 residue helical segment in the CORE domain of the protein. Residues 169 and 188 were labeled by 1-acetamido-methyl-pyrene, and by bimane, respectively. The experiment combines double-jump stopped-flow fast mixing initiation of refolding and time-resolved Förster energy transfer spectroscopy for monitoring the conformational transitions (double-kinetics experiment). Two kinetic phases were found in the denaturant-induced unfolding of AK. In the first phase, the fluorescence quantum yields of both probes decreased. The distribution of the distances between them transformed from the native state's narrow distribution with the mean distance corresponding to the distance in the crystal structure, to a distribution compatible with an unordered structure. In the second, slow step of denaturation, neither the fluorescence parameters of the probes nor the distance distribution between them changed. This step appeared to be a transformation of the fast-folding species formed in the first phase, to the slow-folding species. Refolding of the fast-folding species of the denatured state of AK was also a two-phase process. During the first fast phase, within less than 5ms, the fluorescence emission of both probes increased, but the distance distribution between the labeled sites was unchanged. Only during the second slow refolding step did the intramolecular distance distribution change from the characteristic of the denatured state to the narrow distribution of the native state. This experiment shows that for the case of the CORE domain of AK, the large helical segment of residues 169-188 was not formed in the first compaction step of refolding. The helical conformation of this segment is established only in the second, much slower, refolding phase, simultaneously with the completion of the native structure.

Adenylate Kinase↗
PubMed2001

Successful aging among people with HIV/AIDS.

With advances made in the treatment of people with HIV/AIDS, there is an increasing number of persons who are reaching old age. This is a heterogeneous group. Yet, all of these diverse patients share in common the challenge of aging successfully despite their condition. There is little room in most gerontological conceptualizations for consideration of success for older persons unfortunate enough to live with chronic and particularly life-threatening illnesses in late life. Ideals of successful aging certainly leave little room for older adults with HIV/AIDS, a highly stigmatized, life-threatening, and disabling condition. In this article, we briefly review a new model of successful aging that we have developed, and show how it can be meaningfully applied to expectations of successful aging even among disabled and chronically ill populations of older adults such as persons with HIV/AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed2001

History and mobility exam index to identify community-dwelling elderly persons at risk of falling.

BACKGROUND: Falls are common in community-dwelling elderly persons and are a frequent source of morbidity. Simple indices to prospectively stratify people into categories at different fall-risk would be useful to health care practitioners. Our goal was to develop a fall-risk index that discriminated between people at high and low risk of falling. METHODS: We evaluated the risk of falling over a one-year period in 557 elderly persons (mean age 81.6) living in a retirement community. On the baseline interview, we asked subjects if they had fallen in the previous year and evaluated risk factors in six additional conceptual categories. On the follow-up interview one year later, we again asked subjects if they had fallen in the prior year. We evaluated risk factors in the different conceptual categories and used logistic regression to determine the independent predictors of falling over a one-year period. We used these independent predictors to create a fall-risk index. We compared the ability of a prior falls history with other risk factors and with the combination of a falls history and other risk factors to discriminate fallers from nonfallers. RESULTS: A fall in the previous year (OR = 2.42, 95% CI = 1.49-3.93), a symptom of either balance difficulty or dizziness (OR = 1.83, 95% CI = 1.16-2.89), or an abnormal mobility exam (OR = 2.64, 95% CI = 1.64-4.26) were independent predictors of falling over the subsequent year. These three risk factors together (c statistic =.71) discriminated fallers from nonfallers better than previous history of falls alone (c statistic =.61) or the symptomatic and exam risk factors alone (c statistic =.68). When combined into a risk index, the three independent risk factors stratify people into groups whose risk for falling over the subsequent year ranges from 10% to 51%. CONCLUSION: A history of falling over the prior year, a risk factor that can be obtained from a clinical history (balance difficulty or dizziness), and a risk factor that can be obtained from a physical exam (mobility difficulty) stratify people into groups at low and high risk of falling over the subsequent year. This risk index may provide a simple method of assessing fall risk in community-dwelling elderly persons. However, it requires validation in other subjects before it can be recommended for widespread use.

Accidental Falls↗
PubMed2000

Epidemiologic studies of multiple sclerosis: a review.

There is evidence for genetic factors in multiple sclerosis (MS). The evidence come from epidemiologic studies, racial predilection, risk in family members (sibs, half sibs, adoptees) and twins studies. MS is not a Mendelian inherited disease; only the susceptibility to the disease is inherited, the risk of MS being also related to an environmental factor. Many candidate genes were screened, and there are four research groups trying to study the whole genome. MS seem to be an oligo- or multigenic disorder with an apparently similar phenotype for the different genes involved.

Genetic Predisposition to Disease↗
PubMed2000

Outcome of infants with unilateral Sturge-Weber syndrome and early onset seizures.

Patients with Sturge-Weber syndrome often present with seizures during the first year of life. Currently, only patients with clinically significant seizures who do not respond to medical treatment are candidates for early epileptic surgery. However, a delay of surgical treatment may result in cognitive deterioration. We studied the correlation between parameters and outcome of seizures to re-examine the criteria for early epilepsy surgery. We performed a retrospective chart review combined with telephone interviews of parents of all Israeli infants with unilateral Sturge-Weber syndrome and early onset seizures, and we examined whether age of seizure onset and seizure intensity were correlated with cognitive level and the degree of hemiparesis at follow-up. We recruited a total of 15 patients with unilateral Sturge-Weber syndrome and early onset seizures, five of whom underwent epilepsy surgery. The mean follow-up period of all the patients was 15 years: six patients had normal intelligence, four had borderline cognitive level, three had mild mental retardation and two had moderate mental retardation. Eight of the ten non-operated patients still experience seizures at follow-up. Cognitive delay was significantly correlated with seizure intensity in the early period, but not with the age of seizures onset, the degree of hemiparesis, or the presence of ongoing seizures. We conclude that high seizure intensity in young patients with Sturge-Weber syndrome is a prognostic marker for mental deterioration.

Age of Onset↗
PubMed2000

Muscular dystrophy due to dysferlin deficiency in Libyan Jews. Clinical and genetic features.

The cluster in Jews of Libyan origin of limb-girdle muscular dystrophy type 2B due to a dysferlin 1624delG mutation is described. The carrier frequency of this mutation is calculated to be approximately 10% in this population, in which the disease prevalence is at least 1 per 1300 adults. Twenty-nine patients from 12 families were all homozygous for the same mutation. However, clinical features were heterogeneous even within the same family: in half of the patients onset was in the distal muscles of the legs, which is similar to Miyoshi myopathy, while in others onset was in the proximal musculature, which is similar to other forms of limb-girdle dystrophies. Age at onset varied from 12 to 28 years (mean 20.3 +/- 5.5 years). One patient was presymptomatic at age 28 years. Progression was slow regardless of age of onset, patients remaining ambulatory until at least 33 years. Five patients described subacute, painful enlarged calves as an early, unusual feature. The variable features in this ethnic cluster contribute to the definition of the clinical spectrum of dysferlinopathies in general. The cause of the observed heterogeneity remains unclear.

Adult↗
PubMed2000

Creutzfeldt-Jakob disease profile in patients homozygous for the PRNP E200K mutation.

We identified 70 Creutzfeldt-Jakob disease patients with the previously described E200K mutation in the prion protein gene. The purpose of this study was to define the clinical features of E200K homozygous patients (n = 5), compared with heterozygotes. We found a statistically significant younger age at disease onset for the homozygous patients, although the average age at onset in this group was still in midlife. Disease features were not statistically different in the two groups. Possible explanations are discussed.

Adult↗
PubMed1999

Preliminary evidence for anticipation in genetic E200K Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease (CJD) linked to the E200K mutation of the prion protein (PrP) gene presents within a wide range of phenotypic heterogeneity, including the age at disease onset. We report an earlier disease onset for mutation carriers of the offspring generation when compared with that of their parents, suggesting the possibility of anticipation. A still unidentified environmental or genetic element may affect the age at onset in mutation carriers of different generations.

Age Factors↗
PubMed1999

Depressive symptoms and 3-year mortality in older hospitalized medical patients.

BACKGROUND: Depressive symptoms are common in hospitalized older persons. However, their relation to long-term mortality is unclear because few studies have rigorously considered potential confounders of the relation between depression and mortality, such as comorbid illness, functional impairment, and cognitive impairment. OBJECTIVE: To measure the association between depressive symptoms and long-term mortality in hospitalized older persons. DESIGN: Prospective cohort study. SETTING: General medical service of a teaching hospital. PATIENTS: 573 patients 70 years of age or older. MEASUREMENTS: Depressive symptoms (Geriatric Depression Scale score), severity of acute illness (Acute Physiology and Chronic Health Evaluation II score), burden of comorbid illness (Charlson comorbidity index score), physical function (a nurse assessed dependence in six activities of daily living), and cognitive function (modified Mini-Mental State Examination) were measured at hospital admission. Mortality over the 3 years after admission was determined from the National Death Index. Mortality rates among patients with six or more depressive symptoms were compared with those among patients with five or fewer symptoms. RESULTS: The mean age of the patients was 80 years; 68% of patients were women. Patients with six or more depressive symptoms had greater comorbid illness, functional impairment, and cognitive impairment at admission than patients with fewer depressive symptoms. Three-year mortality was higher in patients with six or more depressive symptoms (56% compared with 40%; hazard ratio, 1.56 [95% CI, 1.22 to 2.00]; P < 0.001). After adjustment for age, acute illness severity, comorbid illness, functional impairment, and cognitive impairment at the time of admission, patients with six or more depressive symptoms continued to have a higher mortality rate during the 3 years after admission (hazard ratio, 1.34 [CI, 1.03 to 1.73]). Although depressive symptoms contributed less to the mortality rate than did the total burden of comorbid medical illnesses, the excess mortality rate associated with depressive symptoms was greater than that conferred by one additional comorbid medical condition. CONCLUSIONS: Depressive symptoms are associated with long-term mortality in older patients hospitalized with medical illnesses. This association is not fully explained by greater levels of comorbid illness, functional impairment, and cognitive impairment in patients with more depressive symptoms.

Activities of Daily Living↗
PubMed1999

Evidence for the genetic role of human leukocyte antigens in low frequency DRB1*1501 multiple sclerosis patients in Israel.

A strong association exists between multiple sclerosis (MS) and the DRB1*1501 haplotype, in most populations. Linkage of Multiple Sclerosis (MS) with the MHC or HLA region on chromosome 6p21 has previously been observed in DRB1*1501 positive MS families. A group of 13 Israeli multiplex MS families with a very low frequency of DRB1*1501 haplotype were examined in this study. Association and a linkage test were performed in order to identify a non-DRB1*1501 effect of HLA on susceptibility for MS. MS multiplex families and healthy controls were molecularly typed for six highly polymorphic markers located within the MHC region: DRB1, DQA1 and DQB1, BAT-2, MIB and D6S248. Data analyses included: (a) an association study comparing the patient group with both healthy relative, and healthy control groups (b) a transmission test for linkage disequilibrium (TDT) of the MS-associated alleles in the multiplex families, and (c) multipoint non-parametric linkage (NPL) and parametric LOD score analyses using the GENEHUNTER program. The DRB1*1303 allele was significantly more frequent among the MS patients. There was a trend towards transmission disequilibrium of DRB1*1303, but was not statistically significant. Allele sharing and LOD score analyses revealed no evidence for linkage. The high frequency of DRB1*1303 observed in our family patients provides evidence to support the association with this allele that previously described in sporadic non-Ashkenazi MS patients. Thus, DRB1*1303 may serve as genetic risk factor for MS. Our study exemplifies the genetic heterogeneity in MS as there is a genetic effect of HLA on MS susceptibility in our low frequency DRB1*1501 patients.

Alleles↗
PubMed1999

Altruistic moral judgment among older adults.

This study investigated altruistic moral judgment among the elderly, and examined its relationships to demographic and personality variables, self-reported helping, and subjective social integration (the perception that one is integrated into one's social milieu). The moral judgment interview included three stories, each of which contained a moral dilemma. Participants solved each dilemma and gave reasons for their solutions. The moral dilemmas and scoring system emphasized the positive, prosocial aspects of morality, rather than a prohibition-oriented approach. The categories used most often were, in descending order of frequency 1) pragmatic needs-of-others oriented reasons, 2) empathy-based reasons, 3) reasons based on internalized and/or abstract moral principles, and 4) hedonistic reasons. Of the higher levels of moral judgment, only reasoning based on abstract internalized principles had significant positive relationships with self-reported helping, the personality correlates of helping, and with subjective social integration into one's social milieu.

Aged↗
PubMed1998

A statistical method for quantitative evaluation of the progression of chronic diseases: the mean score graph (MSG).

We present a quantitative method of evaluation of the clinical course of chronic disease with long-term progressive deterioration. The method takes into account information on all patients, whatever their duration of follow-up. We present the 'mean score graph' as a descriptive device which is an extension of a survival graph. The description of progression of idiopathic torsion dystonia, comparing progression in males and females, is used as an example of the application. A test for group comparison is described.

Age of Onset↗
PubMed1998

Improving functional outcomes in older patients: lessons from an acute care for elders unit.

BACKGROUND: Hospitalization often marks the beginning, and may be partially responsible for, a downward trajectory characterized by declining function, worsening quality of life, placement in a long term care facility, and death. At the University Hospitals of Cleveland, an Acute Care for Elders (ACE) unit that reengineered the process of caring for older patients (> or = 70 years of age) to improve functional outcomes was established in September 1990. DESCRIPTION OF INTERVENTION: The general principles of ACE included an approach to care guided by the biopsychosocial model and recognition of the importance of fitting the hospital environment to the patient's needs. The design of the intervention was consistent with principles of comprehensive geriatric assessment and continuous quality improvement. Care, which focused on maintaining function, was directed by an interdisciplinary team that considered the patient's needs both at home and in the hospital. The major components of the ACE Unit intervention included patient-centered nursing care (daily assessment of functional needs by nursing, nursing-based protocols to improve outcomes, daily rounds by a multidisciplinary team), a prepared environment, planning for discharge, and medical care review. RESULTS: In a randomized trial comparing ACE with usual care, patients receiving ACE had improved functional outcomes at discharge. The costs to the hospital for ACE unit care were less than for usual care. The functional status of ACE and usual care patients was similar 90 days after discharge. FUTURE DIRECTIONS: The ACE unit intervention is being expanded to preserve the improvements observed during the hospitalization in the outpatient setting. In addition, needs other than function which are critical to patients' long-term quality of life are being considered.

Activities of Daily Living↗
PubMed1998

Nursing practice models: implications for information system design.

Nursing practice models (NPMs) describe the structural and contextual features of nursing practice environments. They offer direction in the design of information systems. Eleven factors describing NPMs emerged from a modified Delphi process: continuity of care, participation in management, collaboration, leadership, learning environment, nurse's role, staffing, communication, specialization, orientation of temporary staff, and group commitment. These factors provide nurse administrators with specific features of the clinical practice environment that IS applications should support.

Health Facility Environment↗
PubMed1998

Environmental risk factors for subacute sclerosing panencephalitis (SSPE).

In Israel, SSPE has been shown to be much more frequent among Sephardic Jews and Arabs than among Ashkenazic Jews. In the present study, we tried to explore environmental factors that may be of etiological importance and explain these differences in prevalence. The study is a case-control one, which includes 95 patients and 2 groups of controls, with 95 people in each. The general population controls were group-matched to the case group by sex, age, and ethnic origin. The family controls consisted of the sibling closest in age to each patient. A statistically significant positive correlation was found between risk of SSPE and early measles infection, large family, overcrowding in the home, older age of the mother, higher birth order, fewer years of schooling of the parents, fewer cultural activities, and rural place of birth. All these factors are interpreted as contributing to a higher risk of early measles infections, which thus may well be the main risk factor for SSPE.

Adolescent↗
PubMed1997

Physical properties of dystrophin rod domain.

We have prepared two fragments of the human dystrophin rod domain, each containing eight spectrin-like repeating units, by expression in Escherichia coli. The first corresponds to the central portion of the rod, the other to three repeats from the N-terminal end, fused to five repeats from the C-terminal end. The latter makes up the entire mutant rod, found in a patient with mild (Becker-type) muscular dystrophy. Both fragments were found to possess an ordered, stable structure, and had the form of short rod-like particles in the electron microscope. Molecular weight determinations by sedimentation equilibrium revealed that both polypeptides were monomeric in solution, suggesting that the dystrophin rod domain is incapable of forming an antiparallel homodimer. This supports the inference from sequence analyses [Winder et al., 1995: FEBS Lett. 369:27-33, 1996: Biochem. Soc. Trans. 24:2805] that the dystrophin rod domain lacks the arrangement of sites required for lateral self-association, and that dystrophin, unlike the other known proteins of the spectrin superfamily, may thus exist as a monomer.

Circular Dichroism↗