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Biomedical subjects

S Miller

Publications and source records attributed to S Miller.

At least 55 records · Page 3Linked to original sources
PubMed2004

Lung cancer in Mayak workers.

The cohort of nuclear workers at the Mayak Production Association, located in the Russian Federation, is a unique resource for providing information on the health effects of exposure to plutonium as well as the effects of protracted external dose. Lung cancer mortality risks were evaluated in 21,790 Mayak workers, a much larger group than included in previous evaluations of lung cancer risks in this cohort. These analyses, which included 655 lung cancer deaths occurring in the period 1955-2000, were the first to evaluate both excess relative risk (ERR) and excess absolute risk (EAR) models and to give detailed attention to the modifying effects of gender, attained age and age at hire. Lung cancer risks were found to be significantly related to both internal dose to the lung from plutonium and external dose, and risks were described adequately by linear functions. For internal dose, the ERR per gray for females was about four times higher than that for males, whereas the EAR for females was less than half that for males; the ERR showed a strong decline with attained age, whereas the EAR increased with attained age until about age 65 and then decreased. Parallel analyses of lung cancer mortality risks in Mayak workers and Japanese A-bomb survivors were also conducted. Efforts currently under way to improve both internal and external dose estimates, and to develop data on smoking, should result in more accurate risk estimates in the future.

Adolescent↗
PubMed2004

[Comparison of genomes of new gigantic Pseudomonas aeruginosa phages from native populations from different regions].

To study the genome diversity of bacteriophages from geographically distant natural populations, new giant phi KZ-like Pseudomonas aeruginosa phages isolated in two different regions were compared with earlier known phages of three species (phi KZ, Lin68, EL). A broad spectrum of lytic activity was demonstrated for all phi KZ-like phages. Phages of the phi KZ species proved to be common in natural populations of various regions, while IL- and Lin68-related phages were extremely rare. Most phi KZ-related phages had unique DNA restriction patterns, but the differences between these were only minor, and the genomes did not contain nonhomologous fragments. The spectrum of capsid polypeptides proved to be conserved in each species, and was proposed as a character necessary and sufficient for express classification of phages with an accuracy of species. Phages isolated in different geographical regions showed no substantial difference. Some phages only slightly differing in DNA restriction pattern from phi KZ may be used to study the origin of phi KZ genes coding for orthologs of proteins of unrelated species (other phages, pathogenic bacteria, eukaryotes).

Blotting, Western↗
PubMed2004

Video-EEG study in an adult and a child with eyelid myoclonia with absences.

Two patients with eyelid myoclonia with absences (EMA) are described. Videotape of the eyelid myoclonia in one patient is presented. An interesting feature in one patient was the induction of clinical seizures only with daylight, and in another the presence of rare, focal, epileptiform discharges during drowsiness. Valproic acid only partially controlled eyelid myoclonia in both cases. Lamotrigine, alone or in combination with valproate, can be used as an alternative but was ineffective in our cases. [Published with video sequences].

Adult↗
PubMed2003

Myocardial infarction causes increased expression but decreased activity of the myocardial Na+-Ca2+ exchanger in the rabbit.

Na+-Ca2+ exchanger (NCX) protein levels and activity were measured in myocardium from the basal region of the left ventricle of rabbit hearts with significant left ventricular dysfunction (LVD), 8-9 weeks after an apical infarction. NCX protein abundance was higher in the tissue homogenates (121 +/- 11%) and purified membrane fractions (143 +/- 12%) in the LVD compared to the sham-operated (sham) group. NCX mRNA was also higher in the LVD group (126%). Lower NCX protein expression was observed in the membrane fractions from the epicardium compared to the endocardium in both the sham and LVD groups. Transmembrane currents were recorded in isolated cardiomyocytes by single-electrode voltage clamp; [Ca2+]i was measured using Fura-2. Rapid application of 10 mmol l-1 caffeine was used to induce Ca2+ release from the sarcoplasmic reticulum. The subsequent NCX-mediated Ca2+ efflux rate constant was lower (70% of sham) in the LVD group. NCX currents were measured in cardiomyocytes dialysed with 250 nM Ca2+ (50 mmol l-1 EGTA). A lower NCX current (75% of sham) was observed in the LVD group. Lower NCX activity was also observed in cardiomyocytes isolated from the epicardium compared to the endocardium; a transmural difference that was also seen in the LVD group. Reduced activity despite increased protein expression may result from reduced Ca2+ sensitivity of the allosteric regulation of NCX. However, measurements indicated increased Ca2+ sensitivity in the LVD group. Cardiomyocytes from LVD hearts displayed a marked reduction in the transverse tubule area (59% of sham) and the surface area/volume ratio (80% of sham). Disrupted transverse tubule structure may contribute to the decrease in NCX activity despite increased protein expression in LVD.

Algorithms↗
PubMed2003

Quality of care in institutionalized deliveries: the paradox of the Dominican Republic.

OBJECTIVES: To better understand the paradox in the Dominican Republic of a relatively high maternal mortality ratio despite nearly universal institutionalized deliveries with trained attendants, a rapid assessment using an adaptation of the strategic assessment method was conducted. METHODS: A multi-disciplinary team reviewed national statistics and hospital records, inventoried facilities, and observed peripartum client-provider interactions at 14 facilities. RESULTS: The major referral hospitals, where more than 40% of births in the country occur, were overcrowded and understaffed, with inexperienced residents overseeing care provided by medical students, interns and nurses. Uncomplicated labor and deliveries were overmedicalized, while complicated ones were not managed appropriately; emergencies were not dealt with in a timely fashion. In the peripheral hospitals physicians were seldom present and clients were either turned away or delivered by unprepared nursing staff. Providers in the busiest facilities suffered from compassion fatigue, and were demoralized and overworked. In all facilities, quality of care was lacking and the delivery and birthing process was dehumanized. CONCLUSIONS: Access and availability of institutional delivery alone is not enough to decrease MMR, it is also the quality of emergency obstetric care that saves lives.

Attitude of Health Personnel↗
PubMed2003

Bacterial production of methylglyoxal: a survival strategy or death by misadventure?

The production of MG (methylglyoxal) in bacterial cells must be maintained in balance with the capacity for detoxification and protection against this electrophile. Excessive production of MG leads to cell death. Survival of exposure to MG is best understood in the Gram-negative bacteria. The major mechanism of protection is the spontaneous reaction of MG with GSH to form hemithiolacetal, followed by detoxification by the glyoxalase system leading to the production of D-lactate. The KefB and KefC glutathione-gated K(+) efflux systems are integrated with the activity of the glyoxalase system to regulate the cytoplasmic pH in response to exposure to electrophiles. Bacteria only produce MG when an imbalance occurs in metabolism. Operation of the MG bypass enables cells to adapt, such that balance is restored to metabolism. Excessive production of MG is an adaptive ploy, which, if it fails, has fatal consequences. On this basis one might define MG-induced loss of life as "death by misadventure" rather than suicide!

Bacteria↗
PubMed2003

[Multislice TrueFISP-MR imaging for identifying stress-induced myocardial functional disturbances in coronary heart disease].

PURPOSE: This study assesses the left ventricular function using a new multislice cine sequence and determines the diagnostic accuracy of stress-induced wall motion abnormalities in patients with coronary artery disease (CAD). MATERIALS AND METHODS: 15 patients (mean age 57.7 years) with angiographically proven CAD were examined on a 1.5 T whole body system (Magnetom Sonata, Siemens, Erlangen) at rest and during dipyridamole-induced (0.56 mg/kg body weight) stress. Left ventricular function was determined using a multislice (steady-state) sequence (TR 2.3 ms, TE 1.15 ms, slice thickness 10 mm, temporal resolution 77 ms) as well as a standard single-slice true FISP 2D sequence (TR 3.2 ms, TE 1.6 ms, slice thickness 5 mm, temporal resolution 45 ms) as reference. RESULTS: Both cine sequences provide high sensitivity and excellent correlation (r = 0.95) with angiographic findings for the detection of regional wall motion abnormalities. However, the measurement of functional parameters yielded significant differences. End-systolic left ventricular volumes (ESV) were systematically overestimated in the multislice images (mean 78 ml, + 5.8 %) compared with the reference single-slice images (mean 74 ml) (p < 0.05). This resulted in underestimation of the ejection fraction with multislice images (mean 40 %, - 11.3 %) compared with single-slice images (mean 46 %) (p < 0.05). CONCLUSION: The multislice sequence results in a substantial reduction of imaging time and breath-hold periods necessary to cover the left ventricle for functional assessment. The multislice sequence yields adequate images, especially for qualitative determination of wall motion abnormalities. Due to the reduced spatial and temporal resolution of the multi-slice sequence, however, some uncertainty concerning the functional parameters has to be taken into account.

Adult↗
PubMed2002

Selenoprotein expression in endothelial cells from different human vasculature and species.

Selenium (Se) can protect endothelial cells (EC) from oxidative damage by altering the expression of selenoproteins with antioxidant function such as cytoplasmic glutathione peroxidase (cyGPX), phospholipid hydroperoxide glutathione peroxidase (PHGPX) and thioredoxin reductase (TR). If the role of Se on EC function is to be studied, it is essential that a model system be chosen which reflects selenoprotein expression in human EC derived from vessels prone to developing atheroma. We have used [75Se]-selenite labelling and selenoenzyme measurements to compare the selenoproteins expressed by cultures of EC isolated from different human vasculature with EC bovine and porcine aorta. Only small differences were observed in selenoprotein expression and activity in EC originating from human coronary artery, human umbilical vein (HUVEC), human umbilical artery and the human EC line EAhy926. The selenoprotein profile in HUVEC was consistent over eight passages and HUVEC isolated from four cords also showed little variability. In contrast, EC isolated from pig and bovine aorta showed marked differences in selenoprotein expression when compared to human cells. This study firmly establishes the suitability and consistency of using HUVEC (and possibly the human cell line EAhy926) as a model to study the effects of Se on EC function in relation to atheroma development in the coronary artery. Bovine or porcine EC appear to be an inappropriate model.

Animals↗
PubMed2002

A gender-specific HIV/STD risk reduction intervention for women in a health care setting: short- and long-term results of a randomized clinical trial.

This study assessed the short- and long-term effect of a gender-specific group intervention for women on unsafe sexual encounters and strategies for protection against HIV/STD infection. Family planning clients (N = 360) from a high HIV seroprevalence area in New York City were randomized to an eight-session, a four-session or a control condition and followed at one, six and 12 months post-intervention. Using an intention-to-treat analysis, women who were assigned to the eight-session group had about twice the odds of reporting decreased or no unprotected vaginal and anal intercourse compared to controls at one month (OR = 1.93, 95% confidence interval [CI] = 1.07, 3.48, p = 0.03) and at 12-month follow-up (OR = 1.65, 95% CI = 0.94, 2.90, p = 0.08). Relative to controls, women assigned to the eight-session condition reported during the previous month approximately three-and-a-half (p = 0.09) and five (p < 0.01) fewer unprotected sex occasions at one- and 12-month follow-up, respectively. Women in the eight-session group also reduced the number of sex occasions at both follow-ups, and had a greater odds of first time use of an alternative protective strategy (refusal, outercourse, mutual testing) at one-month follow-up. Results for the four-session group were in the expected direction but overall were inconclusive. Thus, gender-specific interventions of sufficient intensity can promote short- and long-term sexual risk reduction among women in a family planning setting.

Adolescent↗
PubMed2002

Towards a standardization of biological dosimetry by cytogenetics.

When individuals are accidentally overexposed to ionising radiations, follow-up investigations may include dose assessment by cytogenetics. Scoring of unstable chromosome aberrations (dicentrics, centric rings and acentrics) in peripheral blood lymphocytes is regarded as the most specific method to estimate the exposure dose. It has acquired, in some countries, a medico-legal recognition. Paradoxically, there is no universally adopted technique and so important variations occur in methods and these may influence the quality of results. The only published documents supplying some standardization background are International Atomic Energy Agency (IAEA) Technical Reports No 260 (1986) and 405 (2001). Even they do not address crucial areas such as the organization of service laboratories and the need for quality assurance programmes. The significant role of biological dosimetry in many countries has proved the need for a standardized technique that is compatible with national radiological protection programmes. Thus, an International Standards Organization working group for the standardization of biological dosimetry by cytogenetics was created. This group comprises 13 scientists from 11 countries plus an IAEA representative. On the basis of a group consensus, a text defining minimal constraints on all the steps of the process was proposed. A working draft was submitted to ISO in 2001 and its structure is presented here.

Animals↗
PubMed2001

Crystal structure of a heat and protease-stable part of the bacteriophage T4 short tail fibre.

Adsorption of T4 bacteriophage to the Escherichia coli host cell is mediated by six long and six short tail fibres. After at least three long tail fibres have bound, short tail fibres extend and bind irreversibly to the core region of the host cell lipopolysaccharide (LPS), serving as inextensible stays during penetration of the cell envelope by the tail tube. The short tail fibres consist of a parallel, in-register, trimer of gene product 12 (gp12). The 1.9 A crystal structure of a heat and protease-stable fragment of gp12 reveals three new folds: a central right-handed triple beta-helix, a globular C-terminal domain containing a beta-sandwich and an N-terminal beta-structure reminiscent of but different from the adenovirus triple beta-spiral. The centre of the C-terminal domain shows weak homology to gp11, a trimeric protein connecting the short fibre to the base-plate, suggesting that the trimerisation motifs of gp11 and gp12 are similar. Repeating sequence motifs suggest that the N-terminal beta-structure extends further towards the N terminus and is conserved in the long tail fibre proteins gp34 and gp37.

Amino Acid Sequence↗
PubMed2001

Limits of detection of regional differences in vasodilated flow in viable myocardium by first-pass magnetic resonance perfusion imaging.

BACKGROUND: Perfusion imaging techniques intended to identify regional limitations in coronary flow reserve in viable myocardium need to identify 2-fold differences in regional flow during coronary vasodilation consistently. This study evaluated the suitability of current first-pass magnetic resonance approaches for evaluating such differences, which are 1 to 2 orders of magnitude less than in myocardial infarction. METHODS AND RESULTS: Graded regional differences in vasodilated flow were produced in chronically instrumented dogs with either left circumflex (LCx) infusion of adenosine or partial LCx occlusion during global coronary vasodilation. First-pass myocardial signal intensity-time curves were obtained after right atrial injection of gadoteridol (0.025 mmol/kg) with an MRI inversion recovery true-FISP sequence. The area under the initial portion of the LCx curve was compared with that of a curve from a remote area of the ventricle. Relative LCx and remote flows were assessed simultaneously with microspheres. The ratio of LCx and remote MRI curve areas and the ratio of LCx and remote microsphere concentrations were highly correlated and linearly related over a 5-fold range of flow differences (y=0.96 x+/-0.07, P<0.0001, r(2)=0.87). The 95% confidence limits for individual MRI measurements were +/-35%. Regional differences of >/=2-fold were consistently apparent in unprocessed MR images. CONCLUSIONS: Clinically relevant regional reductions in vasodilated flow in viable myocardium can be detected with 95% confidence over the range of 1 to 5 times resting flow. This suggests that MRI can identify and quantify limitations in perfusion reserve that are expected to be produced by stenoses of >/=70%.

Animals↗
PubMed2001

Evidence of activity-dependent withdrawal of corticospinal projections during human development.

OBJECTIVE: To characterize the development of ipsilateral corticospinal projections from birth and compare to 1) development of contralateral projections in the same subjects and 2) ipsilateral corticospinal projections in subjects with unilateral lesions of the corticospinal system acquired perinatally or in adulthood. METHOD: Transcranial magnetic stimulation excited the motor cortex, and responses were recorded bilaterally in pectoralis major, biceps brachii, and the first dorsal interosseus muscles. Subjects studied included 9 neonates recruited at birth, studied longitudinally for 2 years; 85 healthy subjects aged from birth to adulthood; 10 subjects with hemiplegic cerebral palsy; and 8 with hemiplegia after stroke. RESULTS: In neonates, ipsilateral responses had significantly shorter onsets than contralateral responses but similar thresholds and amplitudes. Thresholds within both pathways increased in the first 3 months. Differential development was present from 3 months so that by 18 months ipsilateral responses were significantly smaller and had significantly higher thresholds and longer onset latencies than contralateral responses. A similar pattern of smaller and later ipsilateral responses was observed after transcranial magnetic stimulation of the intact cortex in subjects with stroke. In contrast, subjects with hemiplegic cerebral palsy had ipsilateral responses with onsets, thresholds and amplitudes similar to those of contralateral responses. Significant branching of contralateral corticospinal axons from the intact motor cortex was excluded by cross-correlation analysis. CONCLUSIONS: These data, together with previously published anatomic and radiologic studies, are consistent with activity-dependent corticospinal axonal withdrawal during development and maintenance of increased corticomotoneuronal projections from the intact hemisphere after unilateral perinatal lesions.

Adolescent↗
PubMed2001

Alpha-amino acid phenolic ester derivatives: novel water-soluble general anesthetic agents which allosterically modulate GABA(A) receptors.

In the search for a novel water-soluble general anesthetic agent the activity of an alpha-amino acid phenolic ester lead, identified from patent literature, was markedly improved. In addition to improving in vivo activity in mice, good in vitro activity at GABA(A) receptors was also conferred. Within the series of compounds good enantioselectivity for both in vitro and in vivo activity was found, supporting a protein-mediated mechanism of action for anesthesia involving allosteric modulation of GABA(A) receptors. alpha-Amino acid phenolic ester 19, as the hydrobromide salt Org 25435, was selected for clinical evaluation since it retained the best overall anesthetic profile coupled with improved stability and water solubility. In the clinic it proved to be an effective intravenous anesthetic in man with rapid onset of and recovery from anesthesia at doses of 3 and 4 mg/kg.

Allosteric Regulation↗
PubMed2001

Parallel solid-phase synthesis of zatebradine analogues as potential I(f) channel blockers.

The first solid-phase synthesis of zatebradine 1 and its analogues is reported. This has resulted in the preparation of compounds with increased ability to reduce the spontaneous beating of isolated guinea-pig atria in a concentration-dependent manner. One example, 8g, showed a maximum reduction of beating of 80% at 3 microM compared to a reduction of 40% at 3 microM with zatebradine 1.

Animals↗
PubMed2001

Risks for incident human papillomavirus infection and low-grade squamous intraepithelial lesion development in young females.

CONTEXT: Low-grade squamous intraepithelial lesions (LSILs) have been described as a benign cytological consequence of active human papillomavirus (HPV) replication. Several studies have reported that certain behavioral and biological risks exist for LSIL, suggesting that HPV alone is not sufficient for the development of LSIL. However, because most of these studies have been cross-sectional, it is not known whether behavioral and biological risks are simply risks for HPV infection itself. OBJECTIVE: To prospectively examine risks of incident HPV infection in HPV-negative females and of incident LSIL development in females with HPV infection. DESIGN: Prospective cohort study conducted between 1990-2000, with a median follow-up of 50 months. SETTING AND PARTICIPANTS: Females aged 13 to 21 years who attended 2 family planning clinics in the San Francisco bay area; 496 had prevalent HPV infection and 105 were HPV-negative. MAIN OUTCOME MEASURE: Incident development of HPV infection and LSIL, analyzed by various demographic, behavioral, and clinical risk factors. RESULTS: Fifty-four incident HPV infections occurred in the 105 females who were HPV-negative at study entry (median duration of follow-up for those who remained HPV-negative was 26 months). Multivariable analysis showed that risks of HPV included sexual behavior (relative hazard [RH], 10.10; 95% confidence interval [CI], 3.24-31.50 per new partner per month), history of herpes simplex virus (RH, 3.54; 95% CI, 1.37-9.10), and history of vulvar warts (RH, 2.73; 95% CI, 1.27-5.87). Current use of oral contraceptives had a significantly protective effect (RH, 0.49; 95% CI, 0.28-0.86). Among the 496 individuals who were HPV-positive at baseline or in follow-up, there were 109 incident cases of LSIL during the follow-up interval, with a median follow-up time of 60 months for those who never developed LSIL. Human papillomavirus infection was the most significant risk factor for development of LSIL. The multivariable model showed the following risks for LSIL: HPV infection for less than 1 year (RH, 7.40; 95% CI, 4.74-11.57); HPV infection for 1 to 2 years (RH, 10.27; 95% CI, 5.64-18.69); HPV infection for 2 to 3 years (RH, 6.11; 95% CI, 1.86-20.06); and daily cigarette smoking (RH, 1.67; 95% CI, 1.12-2.48). CONCLUSION: Our results indicate distinct risks for HPV and LSIL. In addition, most women with HPV infection in our study did not develop LSIL within a median follow-up period of 60 months. These findings underscore the hypothesis that certain biological risks thought to be associated with LSIL are, in fact, risks for acquisition of HPV. Cigarette smoking was a risk specific to LSIL, supporting the role of tobacco in neoplastic development.

Adolescent↗
PubMed2001

Rhenium oxo complexes of a chelating diyne ligand. Synthesis and study of the kinetics of protonation.

A series of oxo complexes, Re(O)X(diyne) (X = I, Me, Et), have been prepared from 2,7-nonadiyne and Re(O)I(3)(PPh(3))(2). Addition of B(C(6)F(5))(3) to Re(O)I(2,7-nonadiyne) (5) results in coordination of the oxo ligand to the boron. The protonation of Re(O)(X)(2-butyne)(2) and Re(O)(X)(2,7-nonadiyne)(2) with a variety of acids has been examined. With 5 and HBF(4)/Et(2)O, the ultimate product was [Re(CH(3)CN)(3)(I)(2,7-nonadiyne)](2+) (7). The conversion of 5 to 7 changes the conformation of the diyne ligand from a "chair" to a "boat" and shifts its propargylic protons considerably downfield in the (1)H NMR. The kinetics of the protonation of Re(O)I(2,7-nonadiyne) (5) by CF(3)SO(3)H in CH(3)CN have been monitored by visible spectroscopy, in a stopped-flow apparatus, and by low temperature (1)H NMR. Two second-order rate constants, presumably successive protonations, were observed in the stopped-flow, k(1) = 11.9 M(-)(1) s(-)(1) and k(2) = 3.8 M(-)(1) s(-)(1). Low temperature (1)H NMR spectroscopy indicated that the resulting solution contained a mixture of two doubly protonated intermediates X and Y, each of which slowly formed the product 7 via an acid-independent process.

Journal Article↗