Detection of a conformational change in maltose binding protein by (129)Xe NMR spectroscopy.
Explore the source record for details and available documents.
ATP-Binding Cassette Transporters↗
Biomedical subjects
S M Rubin
Publications and source records attributed to S M Rubin.
Functionalized xenon as a biosensor.
The detection of biological molecules and their interactions is a significant component of modern biomedical research. In current biosensor technologies, simultaneous detection is limited to a small number of analytes by the spectral overlap of their signals. We have developed an NMR-based xenon biosensor that capitalizes on the enhanced signal-to-noise, spectral simplicity, and chemical-shift sensitivity of laser-polarized xenon to detect specific biomolecules at the level of tens of nanomoles. We present results using xenon "functionalized" by a biotin-modified supramolecular cage to detect biotin-avidin binding. This biosensor methodology can be extended to a multiplexing assay for multiple analytes.
Avidin↗
Characterization of the effects of nonspecific xenon-protein interactions on (129)Xe chemical shifts in aqueous solution: further development of xenon as a biomolecular probe.
The sensitivity of (129)Xe chemical shifts to weak nonspecific xenon-protein interactions has suggested the use of xenon to probe biomolecular structure and interactions. The realization of this potential necessitates a further understanding of how different macromolecular properties influence the (129)Xe chemical shift in aqueous solution. Toward this goal, we have acquired (129)Xe NMR spectra of xenon dissolved in amino acid, peptide, and protein solutions under both native and denaturing conditions. In general, these cosolutes induce (129)Xe chemical shifts that are downfield relative to the shift in water, as they deshield the xenon nucleus through weak, diffusion-mediated interactions. Correlations between the extent of deshielding and molecular properties including chemical identity, structure, and charge are reported. Xenon deshielding was found to depend linearly on protein size under denaturing solution conditions; the denaturant itself has a characteristic effect on the (129)Xe chemical shift that likely results from a change in the xenon solvation shell structure. In native protein solutions, contributions to the overall (129)Xe chemical shift arise from the presence of weak xenon binding either in cavities or at the protein surface. Potential applications of xenon as a probe of biological systems including the detection of conformational changes and the possible quantification of buried surface area at protein-protein interfaces are discussed.
Amino Acids↗
Evidence of nonspecific surface interactions between laser-polarized xenon and myoglobin in solution.
The high sensitivity of the magnetic resonance properties of xenon to its local chemical environment and the large (129)Xe NMR signals attainable through optical pumping have motivated the use of xenon as a probe of macromolecular structure and dynamics. In the present work, we report evidence for nonspecific interactions between xenon and the exterior of myoglobin in aqueous solution, in addition to a previously reported internal binding interaction. (129)Xe chemical shift measurements in denatured myoglobin solutions and under native conditions with varying xenon concentrations confirm the presence of nonspecific interactions. Titration data are modeled quantitatively with treatment of the nonspecific interactions as weak binding sites. Using laser-polarized xenon to measure (129)Xe spin-lattice relaxation times (T(1)), we observed a shorter T(1) in the presence of 1 mM denatured apomyoglobin in 6 M deuterated urea (T(1) = 59 +/- 1 s) compared with that in 6 M deuterated urea alone (T(1) = 291 +/- 2 s), suggesting that nonspecific xenon-protein interactions can enhance (129)Xe relaxation. An even shorter T(1) was measured in 1 mM apomyoglobin in D(2)O (T(1) = 15 +/- 0.3 s), compared with that in D(2)O alone (T(1) = 506 +/- 5 s). This difference in relaxation efficiency likely results from couplings between laser-polarized xenon and protons in the binding cavity of apomyoglobin that may permit the transfer of polarization between these nuclei via the nuclear Overhauser effect.
Animals↗
Efficacy of screening mammography. A meta-analysis.
OBJECTIVE: To determine the efficacy of screening mammography by age, number of mammographic views per screen, screening interval, and duration of follow-up. DESIGN: Literature review and meta-analysis. DATA IDENTIFICATION AND ANALYSIS: Literature search of English-language studies reported from January 1966 to October 31, 1993, using MEDLINE, manual literature review, and consultation with experts. A total of 13 studies were selected, and their results were combined using meta-analytic techniques based on the assumption of fixed effects. MAIN RESULTS: The overall summary relative risk (RR) estimate for breast cancer mortality for women aged 50 to 74 years undergoing screening mammography compared with those who did not was 0.74 (95% confidence interval [CI], 0.66 to 0.83). The magnitude of the benefit in this age group was similar regardless of number of mammographic views per screen, screening interval, or duration of follow-up. In contrast, none of the summary RR estimates for women aged 40 to 49 years was significantly less than 1.0, irrespective of screening intervention or duration of follow-up. The overall summary RR estimate in women aged 40 to 49 years was 0.93 (95% CI, 0.76 to 1.13); the summary RR estimate for those studies that used two-view mammography was 0.87 (95% CI, 0.68 to 1.12) compared with 1.02 (95% CI, 0.73 to 1.44) for those studies that used one-view mammography, and for those studies with 7 to 9 years of follow-up, the summary RR estimate was 1.02 (95% CI, 0.82 to 1.27) compared with 0.83 (95% CI, 0.65 to 1.06) for those studies with 10 to 12 years of follow-up. CONCLUSION: Screening mammography significantly reduces breast cancer mortality in women aged 50 to 74 years after 7 to 9 years of follow-up, regardless of screening interval or number of mammographic views per screen. There is no reduction in breast cancer mortality in women aged 40 to 49 years after 7 to 9 years of follow-up. Screening mammography may be effective in reducing breast cancer mortality in women aged 40 to 49 years after 10 to 12 years of follow-up, but the same benefit could probably be achieved by beginning screening at menopause or 50 years of age.
Adult↗
Increasing the completion of the durable power of attorney for health care. A randomized, controlled trial.
OBJECTIVE: Wider use of written advance directives may prevent many ethical dilemmas about life-sustaining interventions for patients who have lost decision-making capacity. We investigated whether a simple educational intervention increased patient completion of the durable power of attorney for health care. DESIGN: A randomized, controlled trial. SETTING: A health maintenance organization. SUBJECTS: All patients aged 65 years and older and discharged from a hospital between January 1991 and May 1991 (n = 1101) were randomized to either an intervention group or a control group. INTERVENTION: An educational pamphlet on the durable power of attorney for health care and a durable power of attorney for health care form were mailed to all patients in the intervention group. The control group received conventional care only. MAIN OUTCOME MEASURE: Completion of the durable power of attorney for health care form. RESULTS: There were no significant baseline differences between the intervention group and the control group. Following our intervention, 18.5% of the subjects in the experimental group completed a durable power of attorney for health care form, compared with 0.4% of the control group (P < .0001). CONCLUSIONS: A simple educational intervention significantly increased the completion of the durable power of attorney for health care. Our findings should stimulate further efforts to empower patients to make informed decisions about their health care.
Advance Directives↗
The postmenopausal estrogen/breast cancer controversy.
Explore the source record for details and available documents.
Breast Neoplasms↗
Hormone therapy to prevent disease and prolong life in postmenopausal women.
PURPOSE: To critically review the risks and benefits of hormone therapy for asymptomatic postmenopausal women who are considering long-term hormone therapy to prevent disease or to prolong life. DATA SOURCES: Review of the English-language literature since 1970 on the effect of estrogen therapy and estrogen plus progestin therapy on endometrial cancer, breast cancer, coronary heart disease, osteoporosis, and stroke. We used standard meta-analytic statistical methods to pool estimates from studies to determine summary relative risks for these diseases in hormone users and modified lifetable methods to estimate changes in lifetime probability and life expectancy due to use of hormone regimens. RESULTS: There is evidence that estrogen therapy decreases risk for coronary heart disease and for hip fracture, but long-term estrogen therapy increases risk for endometrial cancer and may be associated with a small increase in risk for breast cancer. The increase in endometrial cancer risk can probably be avoided by adding a progestin to the estrogen regimen for women who have a uterus, but the effects of combination hormones on risk for other diseases has not been adequately studied. We present estimates for changes in lifetime probabilities of disease and life expectancy due to hormone therapy in women who have had a hysterectomy; with coronary heart disease; and at increased risk for coronary heart disease, hip fracture, and breast cancer. CONCLUSIONS: Hormone therapy should probably be recommended for women who have had a hysterectomy and for those with coronary heart disease or at high risk for coronary heart disease. For other women, the best course of action is unclear.
Breast Neoplasms↗
Results of bone densitometry affect women's decisions about taking measures to prevent fractures.
OBJECTIVE: To describe how the results of bone densitometry affect women's decisions about measures to prevent fractures and to determine whether labeling women as having below-normal bone density has adverse effects. DESIGN: Mail survey of a random sample of women. SETTING: Four community hospitals in the San Francisco Bay area. PATIENTS: A total of 261 women (response rate, 81.3%) who had undergone bone densitometry. MEASUREMENTS: Bone densitometry and self-report of changes in attitude and behaviors. RESULTS: Fifty-three percent of the women reported that their first bone density measurements were below normal, and 44% said that they were diagnosed as having osteoporosis on the basis of their test results. Women who reported that their bone density measurements were below normal were much more likely than women with normal results to begin some type of measure to prevent fractures (94% compared with 56%; P less than 0.01), to start hormone therapy (38% compared with 8%; P less than 0.01), and to take precautions to avoid falling (50% compared with 9%; P less than 0.01). Women reporting low bone density, however, also became more fearful of falling (38% compared with 2%; P less than 0.01) and limited their activities to avoid falling (24% compared with 2%; P less than 0.01). CONCLUSIONS: The results of bone densitometry substantially influence women's decisions about beginning estrogen replacement therapy and other preventive measures for osteoporotic fractures. The potential effects of labeling a woman as having below-normal bone density need to be considered before densitometry is widely used for unselective screening of women.
Absorptiometry, Photon↗
Mortality following unilateral twin interstitial ectopic pregnancy. A case report.
Twin ectopic pregnancy is an uncommon event, usually occurring as simultaneous intrauterine and tubal gestations. Interstitial implantation of an ectopic pregnancy is also a rare event, associated with a high mortality rate. Twin interstitial pregnancy has been previously reported only three times in the English literature. We report a recent case of unilateral twin interstitial ectopic pregnancy that resulted in maternal death and review the literature with regard to both ectopic pregnancy and factors associated with mortality from interstitial implantation.
Female↗
Management of the pregnant patient with a cerebral venous angioma: a report of two cases.
Though there is a large body of knowledge regarding the management of pregnant women with arterial lesions in the central nervous system, little information is available on venous malformations. We report our experience with two pregnant patients with cerebral venous angiomas. These lesions are usually asymptomatic and only rarely cause seizures or subarachnoid hemorrhage. Based on our experience and literature review, we suggest that patients with venous angiomas without a history of hemorrhage can safely undergo labor and vaginal delivery.
Adult↗
High blood cholesterol in elderly men and the excess risk for coronary heart disease.
OBJECTIVE: To determine whether high blood cholesterol is an important risk factor for mortality from coronary heart disease in elderly men. DESIGN: Cohort study with a mean follow-up of 10.1 years. SETTING: A health maintenance organization. PATIENTS: The cohort included 2746 white men 60 to 79 years of age who had no self-reported history of coronary heart disease. MEASUREMENT AND MAIN RESULTS: A total of 260 deaths occurred during 27,842 person-years of follow-up. The relative risk for mortality from coronary heart disease in men 60 to 79 years of age in the highest serum cholesterol quartile was 1.5 (95% CI, 1.2 to 2.0) compared with those in the three lower quartiles combined. The relative risk did not change greatly with age, ranging from 1.4 in men 60 to 64 years of age to 1.7 in men 75 to 79 years of age. However, because mortality from coronary heart disease increased with age, the excess risk for such mortality attributable to elevated serum cholesterol levels increased fivefold over these 20 years, from 2.2 deaths per 1000 person-years to 11.3 deaths per 1000 person-years. CONCLUSIONS: Our results support those of other observational studies in elderly men. If treatment of high blood cholesterol is as effective in reducing cholesterol-related risk for coronary heart disease after 65 years of age as it is in middle-aged men, it might actually produce greater reductions in mortality due to coronary heart disease. A clinical trial is needed to confirm this extrapolation.
Age Factors↗
The future of hip fractures in the United States. Numbers, costs, and potential effects of postmenopausal estrogen.
Because of the increasing number of elderly people in the United States, the total number of hip fractures in persons 50 years and older will rise from 238,000 to 512,000 by the year 2040, with a concomitant increase in avoidable deaths, disability, and medical costs. The total annual cost of hip fractures (in 1984 dollars) will increase from approximately 7.2 billion dollars currently to 16 billion dollars in the year 2040. Universal use of estrogen therapy by postmenopausal white women may slow but not prevent this rise in hip fractures. New, effective, and widely applicable strategies to prevent hip fractures are urgently needed.
Aged↗
The cost-effectiveness of counseling smokers to quit.
Cigarette smoking is the most important preventable cause of death in the United States. Surveys of patients, however, suggest that many physicians do not routinely counsel smokers to quit. Because physicians may not consider counseling against smoking to be as worthwhile as other medical practices, we examined its cost-effectiveness. We based our estimates of the effectiveness of physician counseling on published reports of randomized trials and our estimates of its cost on average charges for physician office visits. Our results indicate that the cost-effectiveness of brief advice during routine office visits ranges from $705 to $988 per year of life saved for men and from $1204 to $2058 for women. Follow-up visits about smoking appear to be similarly cost-effective. Physician counseling against smoking, therefore, is at least as cost-effective as several other preventive medical practices and should be a routine part of health care for patients who smoke.
Adult↗
Lifetime risks of hip, Colles', or vertebral fracture and coronary heart disease among white postmenopausal women.
Lifetime risk is a useful way to estimate and compare the risk of various conditions. Hip fractures, Colles' fractures, and coronary heart disease, and breast and endometrial cancers are important conditions in postmenopausal women that might be influenced by the use of hormone replacement therapy. We used population-based data to estimate a woman's lifetime risk of suffering a hip, Colles', or vertebral fracture and her risk of dying of coronary heart disease. A 50-year-old white woman has a 16% risk of suffering a hip fracture, a 15% risk of suffering a Colles' fracture, and a 32% risk of suffering a vertebral fracture during her remaining lifetime. These risks exceed her risk of developing breast or endometrial cancer. She has a 31% risk of dying of coronary heart disease, which is about 10 times greater than her risk of dying of hip fractures or breast cancer. These lifetime risks provide a useful description of the comparative risks of conditions that might be influenced by postmenopausal hormone therapy.
Aged↗
The examination of physicians' awareness of dementing disorders.
Despite a significant increase in the amount of research being conducted on the etiology, diagnosis, and treatment of Alzheimer's disease and other dementing disorders, there has been little assessment of the utilization of this new wealth of information by the primary care physician. It was hypothesized that there would be a wide variation in physicians' knowledge of dementing disorders and the procedures used to diagnose these disorders. To quantitate the present status of primary care physicians' knowledge of dementing disorders and to investigate possible relationships between this knowledge and different physician and practice characteristics, 50 general internists and family practitioners from Winnebago County, Illinois, were interviewed regarding their recall of causes of dementia, procedures used in diagnosing these diseases, treatment recommendations, and comfort in making a differential diagnosis. Results revealed a wide variation in both physicians' familiarity with the causes of dementia as well as the procedures used in making the diagnosis. Although a majority (80%) of the physicians reported some degree of confidence in making a differential diagnosis of dementing disorders, a significant trend was found between physician age and comfort in making the diagnosis, with age being directly correlated with comfort. This was in spite of a significant negative association between physician age and immediate recall of causes of dementia. These data imply that younger physicians are entering the work force with at least better immediate recall of information on dementing disorders, but they have had little opportunity to become comfortable with that knowledge due to a generally smaller geriatric population in their practice.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Fluorometric prediction of successful amputation level in the ischemic limb.
The present study was undertaken to compare fluorometric documentation of fluorescein dye delivery with the standard means of determining the level at which an amputation should be performed in the dysvascular extremity. Thirty-nine patients underwent lower-extremity amputation at the level determined by the surgeon based upon physical examination, angiography, segmental pressure indices, and/or pulse volume recordings. In addition, fiberoptic fluorometry was performed preoperatively. After intravenous administration of sodium fluorescein (4-8 mg/kg), fluorometric readings were obtained by placing the fluorometer's light guide on 126 reading sites. Fluorometric findings were evaluated retrospectively, and therefore did not influence the surgeon's decision. Of the 39 amputations performed overall, only 26 healed. The accuracy of the standard criteria was lowest for the 20 below-ankle amputations, where only 12 cases healed. Alternatively, fluorometric indices separated healing from nonhealing sites in 36 of the 39 cases and in 18 of the 20 below-ankle amputations. Overall, healing sites averaged 94 percent of the fluorescence of the healthy reference area, while nonhealing sites averaged only 29 percent. We conclude that fluorometry should prove to be a valuable adjunct in the assessment of the dysvascular extremity. It uses a low dose of dye, is easy to perform, and is readily repeatable.
Amputation, Surgical↗
Hb J-Singa (alpha-78 Asn leads to Asp), a newly discovered hemoglobin variant with the same amino acid substitution as one of the two present in Hb J-Singapore (alpha-78 Asn leads to, alpha-79 Ala leads to Gly).
A new fast-moving alpha-chain Hb variant with an Asn leads to Asp substitution at position alpha-78 was found in a French-Acadian family living in Eastern Canada. The identical substitution was reported in Hb J-Singapore, which also had an additional Ala leads to Gly substitution at position alpha-79. The new variant, which did not result in any clinical symptoms, was named accordingly, Hb J-Singa.
Adult↗