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PubMed2001

Characterization of immunoglobulin binding to isolated human erythrocyte membranes: evidence for selective, temperature-induced binding of naturally occurring autoantibodies to the cytoskeleton.

Human plasma contains naturally occurring autoantibodies to the predominant components of the erythrocyte membrane: band 3 and spectrin bands 1 and 2 of the cytoskeleton. The titer of cytoskeletal plasma autoantibodies increases in various hemolytic conditions, suggesting that opsonization of the cytoskeleton may play an important role in the clearance of hemolyzed (not senescent) erythrocytes from the circulation. In this study, we use Alexa Fluor 488 goat anti-human IgG conjugate (Molecular Probes, Eugene, OR, USA), to characterize plasma immunoglobulin binding to erythrocyte membranes from osmotically hemolyzed cells ('ghosts'). The results show that exposure of ghosts to plasma results in 4-fold more immunoglobulin binding to the cytoskeleton than is bound to the proteins contained within the lipid bilayer. Preincubation of the ghosts at 37 degrees C causes 8-fold more immunoglobulin binding to the cytoskeleton compared to bilayer proteins. This temperature-induced change resulted from selective immunoglobulin binding to the cytoskeleton, with no change in immunoglobulin binding to bilayer proteins. However, the rate of increase in cytoskeletal antigenicity at 37 degrees C did correlate with the rate of a conformational change in band 3, a transmembrane protein which serves as a major membrane attachment site for the cytoskeleton. The results of this study suggest that the cytoskeleton is the primary target in the opsonization of hemolyzed erythrocyte membranes by naturally occurring plasma autoantibodies. The conformational changes which occur in ghosts at 37 degrees C are associated with selective exposure of new immunoglobulin binding sites on the cytoskeleton, and with a change in the structure of band 3. We propose a model suggesting that opsonization of the cytoskeleton occurs prior to the decomposition of hemolyzed erythrocytes at 37 degrees C.

Autoantibodies↗

PubMed1972

Photochemical effects of sunlight.

The importance of sunlight in bringing about not only photosynthesis in plants, but also other photochemical effects, is reviewed. More effort should be devoted to photochemical storage of the sun's energy without the living plant. There is no theoretical reason to believe that such reactions are impossible. Ground rules for searching for suitable solar photochemical reactions are given, and a few attempts are described, but nothing successful has yet been found. Future possibilities are suggested. Photogalvanic cells which convert sunlight into electricity deserve further research. Eugene Rabinowitch has been an active pioneer in these fields.

Coloring Agents↗

PubMed1993

Resting myoplasmic free calcium in frog skeletal muscle fibers estimated with fluo-3.

Fluo-3 is an unusual tetracarboxylate Ca2+ indicator. For recent lots supplied by Molecular Probes Inc. (Eugene, OR), FMAX, the fluorescence intensity of the indicator in its Ca(2+)-bound form, is approximately 200 times that of FMIN, the fluorescence intensity of the indicator in its Ca(2+)-free form. (For earlier lots, impurities may account for the smaller reported values of FMAX/FMIN, 36-40). We have injected fluo-3 from a high-purity lot into intact single fibers from frog muscle and measured the indicator's absorbance and fluorescence signals at rest (A and F, respectively) and changes in absorbance and fluorescence following action potential stimulation (delta A and delta F signals substantially lagged behind that of the myoplasmic free Ca2+ transient. Our analysis of fluo-3's signals from myoplasm therefore focused on information about the level of resting myoplasmic free [Ca2+] ([Ca2+]r). From A, delta A, and in vitro estimates of fluo-3's molar extinction coefficients, the change in the fraction of fluo-3 in the Ca(2+)-bound form during activity (delta f) was estimated. From delta f, delta F, and F, the fraction of the indicator in the Ca(2+)-bound form in the resting fiber (fr) was estimated by fr = (delta f x F/delta F) + (1-FMAX/FMIN)-1. Since FMAX/FMIN is large, the contribution of the second term to the estimate of fr is small. At 16 degrees C, the mean value (mean +/- S.E.) of fr was 0.086 +/- 0.004 (N = 15). From two estimates of the apparent dissociation constant of fluo-3 for Ca2+ in the myoplasm, 1.09 and 2.57 microM, the average value of [Ca2+]r is calculated to be 0.10 and 0.24 microM, respectively. The smaller of these estimates lies near the upper end of the range of values for [Ca2+]r in frog fibers (0.02-0.12 microM) estimated by others with aequorin and Ca(2+)-selective electrodes. The larger of the estimates lies within the range of values (0.2-0.3 microM) previously estimated in this laboratory with fura red. We conclude that [Ca2+]r in frog fibers is at least 0.1 microM and possibly as large as 0.3 microM.

Action Potentials↗

PubMed1984

The life and death of Captain Charles Martell and kidney stone disease.

Hyperparathyroidism was unknown in this country until the diagnosis was first made by Eugene F. DuBois in 1926. The patient was Captain Charles Martell, a mariner who had become disabled by demineralization of the skeleton during many years. Finally, a parathyroid adenoma was removed at the seventh operation in 1932. Urinary calculi were a major part of the long illness and their complications caused death. Charles Martell contributed significantly to our knowledge of calcium metabolism in general and kidney stone disease in particular.

History, 19th Century↗

PubMed2000

Corrosion susceptibility of titanium covered by dental cements.

OBJECTIVES: The aim of this study is to determine the influence of acidic fluorinated cements (as glass ionomer (GI) cements) on the passivation of titanium, using electrochemical investigations. METHODS: We realized experimental electrodes that associate titanium and dental cements. Polarization resistance of titanium electrodes has been determined for uncovered metal and electrodes covered with three dental cements. Student's t-tests proved the reproducibility. We also compared successive voltammograms for uncovered titanium and GI covered titanium. RESULTS: Correct passivation was observed with zinc eugenate, but fluorinated GI or zinc phosphate coverage increased the corrosion susceptibility. SIGNIFICANCE: However there is no evidence of titanium depassivation when covered with cement. No clinical contraindication can be held.

Coated Materials, Biocompatible↗

PubMed2003

'Dr Steinach coming to make old young!': sex glands, vasectomy and the quest for rejuvenation in the roaring twenties.

In the 1920s, research on the endocrine glands--especially the sex glands--was widely expected to lead to revolutionary new ways of improving human life. The medical marketplace was crowded with glandular techniques to revitalize the aged. 'Monkey glands' apart, the Austrian physiologist Eugen Steinach's simple, vasectomy-like operation was perhaps the most popular of these. Steinach was one of the leading endocrine researchers of the early 20th century and the Steinach Operation was based on rigorous laboratory research. It was much more than a simple scientific error, and its history shows us how early endocrine research was shaped by broader social and cultural forces.

Aging↗

PubMed2001

The demand for consumer health information.

Using data from an evaluation of a community-wide informational intervention, we modeled the demand for medical reference books, telephone advice nurses, and computers for health information. Data were gathered from random household surveys in Boise, ID (experimental site), Billings, MT, and Eugene, OR (control sites). Conditional difference-in-differences show that the intervention increased the use of medical reference books, advice nurses, and computers for health information by approximately 15, 6, and 4%. respectively. The results also suggest that the intervention was associated with a decreased reliance on health professionals for information.

Adolescent↗

PubMed1999

Protein glycosylation in the malaria parasite.

The nature and extent of glycosylation in Plasmodium falciparum has long been controversial. It has been widely believed that O-glycosylation is the major carbohydrate modification in the intraerythrocytic stage of P. falciparum and that the parasite has no N-glycosylation capacity. Contrary to this, recent studies have demonstrated that P. falciparum has a low N-glycosylation capability, and O-glycosylation is either absent or present at an extremely low level, whereas glycosylphosphatidylinositol (GPI) anchor modification is common and is the major carbohydrate modification in parasite proteins. The GPI anchor moieties are essential for parasite survival. The parasite GPI anchors can activate signaling pathways in host cells, and thereby induce the expression of inflammatory cytokines, adhesion molecules and induced nitric oxide synthase (iNOS). This might cause erythrocyte sequestration, hypoglycemia, triglyceride lipogenesis and immune dysregulation. Thus, the parasite GPI anchor structure and biosynthetic pathways are attractive targets for antimalarial and/or antiparasite drug development, as discussed here by Channe Gowda and Eugene Davidson.

Animals↗

PubMed2002

Is nondirectiveness possible within the context of antenatal screening and testing?

Partly in order to dissociate itself from eugenics, genetic counselling values the principle of nondirectiveness as a key feature. Recent reports have upheld the importance of this approach, treating it unproblematically. However, doubts have been expressed about whether nondirective counselling is possible or indeed, desirable. Changes in organisational aspects of antenatal screening delivery in the UK have meant that genetic counselling is now being carried out by a variety of practitioners other than counsellors and specialists. These are often practitioners such as obstetricians and midwives who, in many other aspects of their work do not practise in a nondirective way. This paper explores some of the difficulties health practitioners encountered when attempting to work nondirectively. Reasons given by practitioners for not following this approach fell into categories, which in turn formed a continuum. Categories along the continuum ranged from acting directively at the request of women, through to deciding for women, either covertly or overtly, in their "best interests". It appears that for practitioners, the boundary between choice and coercion is not a clearcut one, and visualising it instead as a continuum may make it easier to see how slippage between choice and coercion can occur. The paper highlights the dilemmas which a variety of practitioners are dealing with in their daily work, in the hope of encouraging debate about these complex clinical and ethical issues.

Attitude of Health Personnel↗

PubMed2002

Too many choices? Hospital and community staff reflect on the future of prenatal screening.

Promoting informed choice is commonly recognised as the chief purpose and benefit of prenatal screening, its very presence being viewed as a key way in which the process can be distanced from eugenics. As the number of conditions and features which can potentially be screened for rises, dilemmas about how to achieve informed choice can only increase. Seventy hospital and community staff working in or attached to two English hospitals were interviewed individually on topics which included their views on genetic developments and moral beliefs and values, and how these affected their daily work. The majority then took part in small discussion groups led by an ethicist. The research identified a paradox. On the one hand, participants recognised the centrality of informed choice to prenatal screening, although they had many doubts about whether it could be achieved. On the other hand, most saw the expansion of screening, which might further compromise informed choice, as an inevitable and inexorable process over which they had little, if any, control. This was despite the fact that many of them decided, managed or implemented prenatal screening policies within their hospitals. The paper explores the factors which staff themselves identified as responsible for this perceived inevitable expansion. It then discusses more generally how the expansion of medical technologies can appear as inexorable to those involved. Finally, the paper calls for more inclusive, integrated and collaborative debate and research around the whole area of prenatal screening. This is to ensure that as far as possible, the wider consequences and implications of any proposed expansion to prenatal screening-both the promises and the potential side-effects-are debated ahead of their implementation, and also to help ensure that public policy represents and serves contemporary society.

Attitude of Health Personnel↗

PubMed1999

From what and why did genetics emerge as a medical specialism in the 1970s in the UK? A case-history of research, policy and services in the Manchester region of the NHS. National Health Service.

The history of genetics has concentrated on eugenics in the first half of the 20th century and molecular genetics in the second. There is yet little historical analysis of the emergence of genetics as a medical specialism, even for the USA. This paper explores the creation of a regional genetic service in Manchester, UK. It surveys the ways in which hereditary diseases were managed and investigated in the first two decades of the NHS (1948-68), and the marginality of geneticists in this period. It suggests that the emergence of consultant geneticists as conspicuous service specialists depended heavily on their ability to create and control laboratory and counselling services for antenatal diagnosis, especially of Down's syndrome, from the late 1960s. These services, for syndromes that were not strongly hereditary, helped extend the meaning of 'genetic' in medicine from 'hereditary' to 'related to chromosomes and genes'. The services received government support because of popular demand for diagnoses (following the Abortion Act of 1967), because 'preventive services' were seen as cost effective, and because geneticists could argue that inadequate counselling might give rise to legal difficulties. By linking laboratory services and counselling, geneticists offered an integrated service, in line with other consultant-led services (e.g. for kidneys) which linked research, laboratory services, clinical work, and education/public health functions. We suggest such services fitted the hospital-dominated political economy of medicine which underlay the NHS re-organisation of 1974; and that the salience of the new genetics owed much to this combination of high-science and public concern. Geneticists were then able to integrate molecular genetics into key regional centres, so shaping the initial phases of the 'molecular' revolution. We maintain that this local study offers useful wider insights, not only into the development of a key specialism, but also into the changing dynamics of research and policy in the NHS.

Genetics, Medical↗

PubMed2000

Life quality vs the 'quality of life': assumptions underlying prospective quality of life instruments in health care planning.

Quality of Life is a broad construct used in health planning, health economics, and medical decision-making. It is also a term that has a long currency in social and sociological literatures. This paper considers the assumptions underlying prospective QL instruments in an historical and contemporary context. It argues that as a tool in health planning and in clinical decision making life quality as a measurement has its origins in the early eugenics literature and the social policies that derived from it in first North America, the primary focus of this paper, and later in Europe. Reference to narrative and social literatures, as well as those involving coping and adaptation, are then used to critique the assumptions underlying this class of QL instruments. It concludes that to the degree now current prospective instruments reflect a purely physical perspective of "disease burden" irrespective of social conditions they create a context that works against life quality, and in some cases, the continuance of persons with physical differences.

Chronic Disease↗

PubMed2000

Iron-dependent generation of free radicals: plausible mechanisms in the progressive deterioration of the temporomandibular joint.

PURPOSE: The purposes of this study were 1) to determine whether iron concentrations detected in temporomandibular joint (TMJ) lavage fluid samples obtained from symptomatic patients are sufficient to catalyze the degradation of specific extracellular matrix (ECM) molecules in vitro, and 2) to provide evidence of oxidative stress in symptomatic TMJs by the detection of protein carbonyls in lavage fluids. PATIENTS AND METHODS: Iron concentrations in TMJ lavage samples (19 joints in 14 patients) were determined colorimetrically, and the ability of the sample to produce free radicals in the presence of hydrogen peroxide was determined with the chromogen 2,2'-azinobis (3-ethylbenzothizoline-6-sulfonic acid), diammonium salt (ABTS). The presence of oxidized proteins was measured fluorimetrically using Bodipy FL hydrazide (Molecular Probes, Eugene, OR). Degradation of fibronectin was visualized by Western blot. Relative susceptibilities of fibronectin and collagen I to free radical cleavage were measured with the Fenton reaction. RESULTS: Redox-active iron concentration in lavage samples was found to be as high as 3.66 micromol/L. A 70-kd protein band, presumed to be albumin, was found to contain higher levels of carbonyls than peripheral serum albumin, which correlated with a greater degree of oxidative damage. Fibronectin was found to be more susceptible than collagen I to free radical degradation, and fragments of the former were found in the lavage. The TMJ lavage fluid was capable of producing free radicals in the presence of peroxide. CONCLUSION: Circumstantial evidence is provided that the presence of modified and cleaved proteins isolated from lavage of symptomatic TMJs may have been subjected to oxidative stress.

Blotting, Western↗

PubMedDate not supplied

Continuity and discontinuity of the radial scaffolding in the forebrain of a lizard embryo.

We have used ventricular injections of the fluorescent carbocyanine dye DiI (Molecular Probes, Eugene, OR, USA) to demonstrate the scaffolding of the radial ventricular cells in the embryonic forebrain of lizards. The results reveal changes of density, orientation, or thickness of the radial processes between adjacent regions. On the whole, they support the idea that the hypothalamus together with the telencephalic stalk and the telencephalic hemispheres make up the anterior region of the neural tube or secondary prosencephalon, as proposed by the prosomeric model. In contrast, the thalamic eminence seems part of the diencephalon.

Animals↗

PubMed1999

Optimization of intercalation dye concentration for short tandem repeat allele genotyping using capillary electrophoresis with laser-induced fluorescence detection.

DNA analysis using capillary electrophoresis (CE) with laser-induced fluorescence (LIF) detection requires that polymerase chain reaction products either be prepared using primers with fluorescent molecules covalently bonded to them, or stained with a fluorescent intercalation dye following amplification. The intercalation technique has the advantage of allowing fluorescence detection of any double-stranded DNA (dsDNA) product regardless of the amplification primers used. The increased sensitivity of LIF detection is sometimes compromised by the intercalation dye changing the mass to charge ratio of the DNA. The purpose of this study was to evaluate the changes of migration rate, resolution and fluorescent intensity of dye-DNA complexes during electrophoretic separations, and to establish the optimal parameters for short tandem repeats alleles profiling. The alleles of three STR loci THO1, F13A01 and vWFA31 were intercalated with the monomeric dyes TOPRO-1 and YOPRO-1, and their corresponding dimers, TOTO-1 and YOYO-1 (Molecular Probes, Eugene, OR, USA). Alleles intercalated before injection onto the CE column resulted in loss of resolution and sensitivity when compared to the on-column labeling technique. The results of this experimentation were then applied to a STR typing assay using a commercially available polymer and buffer matrix. This assay included development of a unique internal standard used for migration time normalization assignment of alleles. Consequently, the 9 allele and the 9.3 microvariant of the THOI locus were separated and typed correctly with a resolution of 0.49 in less than 20 min, and the only sample preparation necessary after amplification was a dilution step.

Alleles↗

PubMedDate not supplied

Acceptance of genetic testing in a general population: age, education and gender differences.

The aim of the study was to analyze effects of age, education and gender on acceptance of genetic testing. Subjects, n = 1967 aged 15-69, were a stratified random sample of the Finnish population. One thousand, one hundred and sixty nine subjects, 530 men and 639 women, returned the questionnaire. The majority of the respondents approved of the availability of genetic testing. Young, aged 15-24, were more favourable towards testing and more willing to undergo suggested tests, but they were also more worried than others about the misuse of test results. Men aged 45-69 with only basic education were more in favour of mandatory genetic testing than other respondents. Respondents with university education were more critical towards genetic testing and expressed their worry about eugenics more often than other education groups. In conclusion, there are age, education and gender related differences in acceptance of genetic testing which need to be taken into account when considering screening programmes and informing the public.

Adolescent↗

PubMed2002

Delineating the impact of Tai Chi training on physical function among the elderly.

BACKGROUND: Through a re-analysis of a Tai Chi intervention data set, the study objective was to determine which, if any, subgroups of the study sample evidenced differential benefits from the intervention. METHOD: Re-analysis of a Tai Chi intervention study, a randomized controlled trial in Eugene and Springfield, Oregon. Physically inactive participants aged > or =65 years were randomly assigned to one of two groups: Tai Chi (n=49) and a wait-list control (n=45). The main outcome measure was self-reported physical function. RESULTS: Initial latent curve analyses indicated significant Tai Chi training effects: Participants in the Tai Chi group reported significant improvements in perceived physical function compared to those in the control group. However, there was significant interindividual variability in response to Tai Chi. The overall intervention effect was further delineated by identifying two subgroups. This delineation showed that Tai Chi participants with lower levels of physical function at baseline benefited more from the Tai Chi training program than those with higher physical function scores. Inclusion of additional measures of individual characteristics at baseline, change in movement confidence, and class attendance further explained differences in treatment responses. CONCLUSIONS: Findings from this study suggest that although an intervention may show an overall effect (or no overall effect), it may be differentially effective for subgroups of participants that differ in their pre-intervention characteristics. Examination of variability in outcome measures can provide important information for refining and tailoring appropriate interventions targeted to specific subgroups.

Activities of Daily Living↗

PubMed2002

Refractive lens exchange with the array multifocal intraocular lens.

PURPOSE: To study the safety and efficacy of refractive lens exchange as a refractive surgery modality in the presbyopic population. SETTING: Oregon Eye Institute, Eugene, Oregon, USA. METHODS: This retrospective review of patient charts included patient selection, preoperative evaluation, management of astigmatism, surgical technique, postoperative visual outcome, and complications. The study included 68 eyes comprising 32 bilateral and 4 unilateral refractive lens exchanges. RESULTS: All patients having bilateral refractive lens exchange achieved an uncorrected binocular visual acuity of 20/40 and J5 or better 1 to 3 months postoperatively. More than 90% achieved an uncorrected binocular visual acuity of 20/30 and J4 and nearly 60%, of 20/25 and J3. CONCLUSION: Refractive lens exchange was a safe and effective refractive surgery modality in presbyopic patients.

Aged↗