Biomedical subjects

M E Miller

Publications and source records attributed to M E Miller.

At least 19 recordsLinked to original sources

PubMed2005

Benzo-[a]-pyrene increases invasion in MDA-MB-231 breast cancer cells via increased COX-II expression and prostaglandin E2 (PGE2) output.

Benzo-[a]-pyrene (B[a]P), a carcinogenic component of cigarette smoke, has been shown to increase both COX-II expression and prostaglandin output in vascular smooth muscle and oral epithelial cells. In addition, invasive breast cancer cells have been reported to over express COX-II and PGE(2). Therefore, the objective of this study was to quantify the effect of increasing B[a]P concentrations on COX-II expression, PGE(2) output, and invasion using MDA-MB-231 cells, an invasive estrogen unresponsive breast cancer cell line. B[a]P significantly increased invasion in MDA-MB-231 cells at concentrations greater than 4 x 10(-8) M. Treatment of MDA-MB-231 cells with Vomitoxin (a selective COX-II inducer) enhanced invasion whereas co-treatment with NS398 (a selective COX-II inhibitor) attenuated B[a]P-induced invasion in MDA-MB-231 cells. Immunohistochemical staining and Western blots demonstrated a significant B[a]P treatment-induced increase in both the number of COX-II immunopositive MDA-MB-231 cells and COX-II protein levels. Moreover, B[a]P-treatment induced a profound (46 fold) increase in PGE(2) production by MDA-MB-231 cells. The aryl hydrocarbon receptor (AhR) antagonists resveratrol (RES) and alpha-naphthaflavone (alpha-NF) had no effect on their own, whereas B[a]P-induced invasion was significantly inhibited by co-treatment with RES and alpha-NF. Our data demonstrate that B[a]P-induced changes in invasion are mediated through augmented COX-II expression and PGE(2) production involving an AhR regulated pathway. Moreover, these results suggest a potential role for the AhR signalling pathway in breast cancer invasion.

Benzo(a)pyrene↗

PubMed2004

Cellular basis of diabetic nephropathy: III. In vitro GLUT1 mRNA expression and risk of diabetic nephropathy in type 1 diabetic patients.

AIMS/HYPOTHESIS: Altered glucose transporter expression has been implicated in the pathogenesis of diabetic nephropathy. There is increasing evidence that genetic factors convey risk of, or protection from, diabetic nephropathy and that the behaviour of cultured skin fibroblasts from type 1 diabetic patients may reflect these genetic influences. This study aimed to compare GLUT1 mRNA expression levels in skin fibroblasts from type 1 diabetic patients with either rapid ("fast-track", n=25) or slow ("slow-track", n=25) development of diabetic nephropathy and from non-diabetic normal control subjects (controls, n=25). METHODS: Skin fibroblasts were cultured in Dulbecco's Modified Eagle's Medium with 25 mmol/l glucose for 36 h. Total RNA was isolated, and GLUT1 mRNA levels were estimated by microarray analysis and RT-PCR. RESULTS: Levels of GLUT1 mRNA expression in skin fibroblasts from "slow-track" patients were greater than those from "fast-track" patients (p=0.02), as initially detected by microarray. GLUT1 mRNA expression levels were confirmed by RT-PCR to be higher in skin fibroblasts from "slow-track" patients (4.59+/-2.04) than in those from "fast-track" patients (3.34+/-1.2, p=0.02), and were also higher than in skin fibroblasts from control subjects (3.52+/-1.66, p=0.03). There was no statistically significant difference between levels of expression in the "fast-track" patients and the control subjects. CONCLUSIONS/INTERPRETATION: This finding is consistent with the presence of cellular protection factors against diabetic nephropathy in the "slow-track" patients. These factors could be associated with the regulation of the GLUT1 pathway and may be genetically determined.

Adult↗

PubMed2004

Improving the insecticidal activity of Bacillus thuringiensis subsp. aizawai against Spodoptera exigua by chromosomal expression of a chitinase gene.

A transcriptionally fused gene comprising the P19 gene from Bacillus thuringiensis subsp. israelensis fused with a chitinase gene (chiBlA) from B. licheniformis was integrated into the B. thuringiensis subsp. aizawai BTA1 genome by homologous recombination. The resulting B. thuringiensis subsp. aizawai strain (INT1) showed growth and sporulation comparable with that of the wild-type strain. INT1 produced four chitinases of different molecular masses (i.e., 66, 55, 39, 36 kDa). Three of these (66, 55, 36 kDa) were derived from the cloned chiBlA gene, whereas the 39-kDa chitinase originated from BTA1. Using surface contamination bioassays, the 50% lethal concentration of lyophilized whole culture broth of INT1 against Spodoptera exigua neonate larvae was 12.2 microg/cm2, compared with 30.8 microg/cm2 for BTA1. Bioassays using filtered culture supernatant of INT1 (110 microg/cm2) together with trypsin-activated purified Cry1C protein of B. thuringiensis (1,280 ng/cm2) showed 75.0% mortality, compared with 56.7% mortality for Cry1C combined with BTA1 at the same concentration. Using scanning electron microscopy, clear perforations were observed in S. exigua fifth instar peritrophic membranes incubated with either crude or purified chitinase, or isolated from fifth instar S. exigua fed purified chitinase since the first instar. These results show that chitinase can increase the activity of B. thuringiensis subsp. aizawai against S. exigua. This is the first documentation of expressing a chimeric chitinase gene on the chromosome of B. thuringiensis; and chromosomal integration might be used as a potential technique for strain improvement.

Animals↗

PubMed2004

Implantable self-powered detector for on-line determination of neutron flux in patients during NCT treatment.

A novel system to determine thermal neutron flux in real time during NCT treatments was developed in the National Atomic Energy Commission of Argentina. The system is based on a special self-powered detector that can be implanted in patients owing to its small size and biocompatibility. High voltage is not required to operate this kind of detectors, which is a considerable advantage in terms of medical uses. By choosing the appropriate materials, it was possible to obtain a prototype with thermal neutron sensitivity providing for an adequate signal level in typical NCT thermal fluxes. It was also possible to minimize gamma response in order to neglect its contribution.

Argentina↗

PubMed2002

Oxytocin does not directly affect vascular tone in vessels from nonpregnant and pregnant rats.

Recent evidence suggests oxytocin (OT) may regulate vascular tone. OT and its receptor (OTR) have been identified in the rat heart and great vessels. Expression of OT and OTR is increased in some tissues during pregnancy. We hypothesized that the OT/OTR system may be a physiological regulator of vascular tone and mediate the decreased vascular resistance noted during pregnancy. Using a wire myograph system, we measured changes in vascular tone in response to OT in small mesenteric arteries, uterine arcuate arteries, and thoracic aorta from nonpregnant and pregnant rats. Additionally, we used reverse transcriptase-polymerase chain reaction (RT-PCR) to measure mRNA for OTR in these vascular tissues. Although OTR mRNA was identified by RT-PCR, OT did not elicit a vasodilatory effect in any of the vessels studied. High concentrations of OT (>10(-8) M) caused vasoconstriction that was eliminated by a specific vasopressin V(1a) receptor antagonist. Although it may have an indirect effect in regulation of peripheral resistance, we conclude that OT is unlikely to play a direct role in the physiological regulation of vascular tone.

Animals↗

PubMed2001

Group comparisons involving missing data in clinical trials: a comparison of estimates and power (size) for some simple approaches.

When using 'intent-to-treat' approaches to compare outcomes between groups in clinical trials, analysts face a decision regarding how to account for missing observations. Most model-based approaches can be summarized as a process whereby the analyst makes assumptions about the distribution of the missing data in an attempt to obtain unbiased estimates that are based on functions of the observed data. Although pointed out by Rubin as often leading to biased estimates of variances, an alternative approach that continues to appear in the applied literature is to use fixed-value imputation of means for missing observations. The purpose of this paper is to provide illustrations of how several fixed-value mean imputation schemes can be formulated in terms of general linear models that characterize the means of distributions of missing observations in terms of the means of the distributions of observed data. We show that several fixed-value imputation strategies will result in estimated intervention effects that correspond to maximum likelihood estimates obtained under analogous assumptions. If the missing data process has been correctly characterized, hypothesis tests based on variances estimated using maximum likelihood techniques asymptotically have the correct size. In contrast, hypothesis tests performed using the uncorrected variance, obtained by applying standard complete data formula to singly imputed data, can provide either conservative or anticonservative results. Surprisingly, under several non-ignorable non-response scenarios, maximum likelihood based analyses can yield equivalent hypothesis tests to those obtained when analysing only the observed data.

Aged↗

PubMed2001

A water extraction, static headspace sampling, gas chromatographic method to determine MTBE in heating oil and diesel fuel.

A method was developed to determine the fuel/water partition coefficient (KMTBE) of methyl tert-butyl ether (MTBE) and then used to determine low parts per million concentrations of MTBE in samples of heating oil and diesel fuel. A special capillary column designed for the separation of MTBE and to prevent coelution and a gas chromatograph equipped with a photoionization detector (PID) were used. MTBE was partitioned from fuel samples into water during an equilibration step. The water samples were then analyzed for MTBE using static headspace sampling followed by GC/PID. A mathematical relationship was derived that allowed a KMTBE value to be calculated by utilizing the fuel/water volume ratios and the corresponding PID signal. KMTBE values were found to range linearly from 3.8 to 10.9 over a temperature range of 5-40 degrees C. This analysis method gave a MDL of 0.7 ppm MTBE in the fuel and a relative average accuracy of +/-15% by comparison with an independent laboratory using purge and trap GC/ MS analysis. MTBE was found in home heating oil in residential tanks and in diesel fuel at service stations throughout the state of Connecticut. The levels of MTBE were found to vary significantly with time. Heating oil and diesel fuel from terminals were also found to contain MTBE. This research suggests thatthe reported widespread contamination of groundwater with MTBE may also be due to heating oil and diesel fuel releases to the environment. used extensively for the past 20 years as a gasoline additive (up to 15 wt %) to reduce automobile carbon monoxide and hydrocarbon emissions. The fact that MTBE is highly soluble in water (approximately 5 wt %) (3) and chemically inert when compared to other fuel constituents causes it to be often detected at high concentrations in groundwater in the vicinity of gasoline spills. The EPA has reported that low levels of MTBE in drinking water (above 40 microg/L) may cause unpleasant taste and odors and has designated MTBE as a possible human carcinogen (4). Past studies have concentrated on the reporting of MTBE levels in groundwater near gasoline spills. Happel et al. reported an MTBE occurrence rate of approximately 78% at locations where hydrocarbons have impacted groundwater (5). Johnson et al. estimate that 9,000 leaking underground fuel tanks have caused MTBE contamination at community water supplies in the 31 states surveyed (excluding California and Texas) (6). Robbins et al. reported finding a significant number of MTBE detections in groundwater samples taken at sites in Connecticut known to be contaminated by heating oil spills (7). Later, this same research group reported finding MTBE contamination to range from 9.7 to 906 mg/L in heating oil and from 74 to 120 mg/L in diesel fuel in samples collected from storage tanks in Connecticut (8). The method used to analyze these samples was based on fuel-water partitioning and GC analysis. This present study provides the detailed basis for that analytical method. MTBE fuel-water partition coefficients as a function of temperature, which are critical to the method, are also presented. This study also reports on variations in MTBE levels as a function of time observed at several residences and a service station. Analytical results are reported for samples taken from terminals as part of an effort to assess the sources of MTBE in heating oil and diesel fuel.

Carcinogens↗

PubMed2001

Modifiers of change in physical functioning in older adults with knee pain: the Observational Arthritis Study in Seniors (OASIS).

OBJECTIVE: To ascertain predictors of decline in physical functioning among older adults reporting knee pain. METHODS: The Observational Arthritis Study in Seniors was a longitudinal study of 480 adults over 65 years of age. Measurements of strength, sociodemographic characteristics, disease burden (including radiographic knee osteoarthritis [OA]), self-reported disability, and functional limitations were obtained on participants at baseline and at 15 and 30 months. RESULTS: Radiographic evidence of OA at baseline was moderately associated with an increased decline in both transfer (P = 0.06) and ambulatory-based performance tasks (P = 0.04) but not in self-reported disability. This effect disappeared after accounting for baseline levels of knee pain intensity and knee strength. CONCLUSION: Knee pain intensity and knee strength may mediate the relationship between radiographic evidence of knee OA and change in performance. Although it is not clear whether joint disease precedes or follows a decline in muscular strength, these results may help to identify subpopulations of older persons with knee OA who may benefit from interventions aimed at slowing the progression of disability related to transfer and ambulatory-based tasks.

Activities of Daily Living↗

PubMed2001

Human T-cell lymphotropic virus-1-associated renal disease in Jamaican children.

This report documents the clinicopathological features in two Jamaican children who presented with infective dermatitis, glomerulonephritis, renal failure and human T-cell lymphotropic virus (HTLV-1) seropositivity. Severe hypertension with hypertensive encephalopathy was the most impressive clinical feature. Histological findings from renal biopsy specimens in both cases revealed significant glomerulosclerosis with fibrosis, chronic inflammatory cell infiltrates in the interstitium, and arteriolar hypertensive changes. Membranoproliferative glomerulonephritis (MPGN) was demonstrable in case 1 and marked focal glomerulosclerosis in case 2. Case 1 developed end stage renal failure and died within 3 years of diagnosis. Case 2 remains hypertensive and in chronic renal failure. Although a causal relationship between HTLV-1 infection and renal disease cannot be proven by these two cases, it appears that renal involvement in children with HTLV-1 infection is severe, with the potential for chronic renal failure and malignant hypertension. HTLV-1 nephropathy should be suspected in children with infective dermatitis and renal disease.

Child↗

PubMed2001

Antihypertensive effect of alpha- and beta-adrenergic blockade in obese and lean hypertensive subjects.

The purpose of this study was to determine the contribution of the adrenergic system in mediating hypertension in obese and lean patients. Thirteen obese, hypertensive patients with a body mass index (BMI) > or =28 kg/m2 (obese) and nine lean patients with a BMI < or =25 kg/m2 (lean) were recruited. After a 1-week washout period, participants underwent daytime ambulatory blood pressure monitoring (ABPM). Participants were then treated with the alpha-adrenergic antagonist doxazosin, titrating to 4 mg QHS in 1 week. In the next week, the beta-adrenergic antagonist atenolol was added at an initial dose of 25 mg/day and titrated to 50 mg/day within 1 week. One month after the addition of atenolol, all patients underwent a second ABPM session. There were no differences between the obese and lean subjects in baseline systolic (SBP), diastolic (DBP), or mean arterial pressures (MAP) measured by office recording or ABPM. However, obese subjects had higher heart rates than lean subjects (87.5+/-2.4 v 76.8+/-4.9 beats/min). After 1 month of treatment with the adrenergic blockers, obese patients had a significantly lower SBP (130.0+/-2.5 v 138.9+/-2.1 mm Hg, P = .02) and MAP (99.6+/-2.3 v 107.0+/-1.5 mm Hg, P = .02) than lean patients. Obese patients also tended to have a lower DBP than lean patients (84.3+/-2.5 v 90.9+/-1.6 mm Hg, P = .057), but there was no significant difference in heart rate after 1 month of adrenergic blockade. These results indicate that blood pressure is more sensitive to adrenergic blockade in obese than in lean hypertensive patients and suggest that increased sympathetic activity may be an important factor in the maintenance of hypertension in obesity.

Adrenergic alpha-Antagonists↗

PubMed2001

Strength, balance, and the modifying effects of obesity and knee pain: results from the Observational Arthritis Study in Seniors (oasis).

OBJECTIVE: To examine the relationship between muscular strength and dynamic balance in a sample of older adults with knee pain and to determine the role that obesity and severity of knee pain play in the ability to maintain balance. DESIGN: Cross-sectional study designed to examine the association between strength and balance in a cohort of older adults with chronic knee pain. SETTING: A university health and exercise science center. PARTICIPANTS: A cohort of 480 adults age 65 and older with knee pain. MEASUREMENTS: Force platform dynamic balance measure of the center of pressure excursion during a forward and subsequent backward lean. Isokinetic strength measures of concentric and eccentric knee flexion and extension and concentric ankle plantar flexion and dorsiflexion. Body mass index (BMI) and a knee pain scale were used to measure obesity and knee pain, respectively. RESULTS: A regression model was developed to investigate the relationship between dynamic balance and muscular strength while controlling for gender, BMI, radiographic severity, knee pain, and foot length. Knee strength alone explained 18.4% of the variability in dynamic balance. The addition of knee pain, BMI, radiographic severity, gender, and foot length explained an additional 6.7%. When the knee-ankle interaction, ankle strength, and knee strength--pain interaction variables were added to the regression model, 28.9% of the variability in dynamic balance was explained. CONCLUSIONS: Strength appears to play a significant role in maintaining balance in an older, osteoarthritic population. We found that mean knee strength accounted for approximately 19% of the variability in dynamic balance. Hence, greater knee strength was associated with better dynamic balance. The best dynamic balance performances occurred in participants that had a combination of strong knees and strong ankles. However, knee osteoarthritic patients with weak knee strength could still maintain high levels of dynamic balance by having strong ankle strength. Moreover, we have shown that obesity is associated with attenuated dynamic balance performance and that poorer balance is associated with higher pain scores in the presence of weaker knees. For stronger knees, however, pain does not appear to be related to balance.

Activities of Daily Living↗

PubMed2001

Ethnic differences in asthma and associated phenotypes: collaborative study on the genetics of asthma.

BACKGROUND: In the Collaborative Study on the Genetics of Asthma, 314 families with 2584 subjects were characterized for asthma and allergy. OBJECTIVE: The purpose of this investigation was to examine clinical heterogeneity observed in asthma and allergic characteristics among 3 ethnic groups (African American, white, and Hispanic family members). METHODS: Pulmonary function parameters and asthma associated phenotypes were compared among the ethnic groups. RESULTS: In comparison with the other groups, African American sibling pairs had a significantly lower baseline FEV(1) percent of predicted (P =.0001) and a higher rate of skin test reactivity to cockroach allergen (P =.0001); Hispanic sibling pairs had significantly more skin reactivity overall (P =.001); and white sibling pairs had significantly lower total serum IgE (P <.05). In addition, there were significantly more relatives with asthma among the African American families than among the white and the Hispanic families (P =.001). CONCLUSION: Although different environmental backgrounds should be considered, these clinical differences could be due to differences in genetic susceptibility among the ethnic groups, such as those suggested by our previous genome screen.

Adolescent↗

PubMed2001

End-user exposures to synthetic vitreous fibers: II. Fabrication and installation fabrication of commercial products.

This article summarizes the results of exposure monitoring conducted during the installation and fabrication of commercial synthetic vitreous fiber (SVF) products. Included in this investigation were fiberglass duct insulation and construction applications (duct board, duct liner, and duct wrap), pipe and vessel insulation, batt insulation for prefabricated homes, and general fiberglass products. Commercial mineral wool products sampled as a part of this investigation included ceiling tiles, building safing, and loose insulation for prefabricated homes. A total of 520 valid air samples were collected as a part of this investigation and were analyzed using gravimetric, phase contrast microscopy (PCM), or scanning electron microscopy (SEM). Airborne fiber-size distributions were also determined for a subset of samples collected for SEM analysis. As a result of the task-based sampling strategy used in this study, sample times reflect exposures over the time the person was actually engaged in SVF-related work activities, and exposure results are therefore presented as task-length averages (TLAs). Thirty-five total dust samples were collected as a part of this investigation, resulting in 14 TLAs ranging from 0.3 to 7.6 mg/m3. A total of 125 PCM-based TLAs were collected, with the mean TLA time for all product and occupation categories ranging from 277 to 443 minutes. The mean PCM-based TLAs for all product/occupations were below 1.0 f/cm3, ranging from 0.04 to 0.68 f/cm3. A total of 116 SEM TLAs were determined. Average SEM-based TLA concentrations were slightly lower than the PCM-based estimates and ranged from <0.01 to 0.16 f/cm3. The geometric mean fiber diameters for commercial products and occupations sampled as a part of the investigation ranged from 0.8 microm to 1.9 microm. Geometric mean fiber length varied by a factor of approximately three, ranging from 9.5 microm to 29.5 microm.

Air Pollution, Indoor↗

PubMed2001

Self-efficacy and the progression of functional limitations and self-reported disability in older adults with knee pain.

OBJECTIVES: The prospective relationships between self-efficacy beliefs, in conjunction with measures of knee pain and knee strength, and subsequent decline in both physical performance and self-reported disability among older adults with knee pain were examined. METHODS: In this prospective epidemiological trial, 480 men and women aged 65 years and older who had knee pain on most days of the week and difficulty with daily activity were followed for 30 months. RESULTS: There was a significant interaction of baseline self-efficacy with baseline knee strength in predicting both self-reported disability and stair climb performance. Participants who had low self-efficacy and low strength at baseline had the largest 30-month decline in these outcomes. DISCUSSION: These data underscore the important role that self-efficacy beliefs play in understanding functional decline with chronic disease and aging. Self-efficacy beliefs appear to be most important to functional decline in older adults when they are challenged by muscular weakness in the lower extremities.

Activities of Daily Living↗

PubMed2001

The health risk of hypertension in south Texas: a demographic profile.

This article provides a demographic profile of the hypertensive adult in South Texas. Hypertension, a silent disease because of its lack of overt signs and symptoms, poses a major public health problem. Few prevalence studies have been completed reflecting Mexican-American populations. South Texas hypertension trends are comparable to national trends. However, the awareness of hypertension in South Texas is lower than that of the national population. The density of risk factors may be responsible for the patterns of South Texas hypertension.

Adult↗

PubMed2001

Mechanisms controlling subcellular localization of the G(1) cyclins Cln2p and Cln3p in budding yeast.

Different G(1) cyclins confer functional specificity to the cyclin-dependent kinase (Cdk) Cdc28p in budding yeast. The Cln3p G(1) cyclin is localized primarily to the nucleus, while Cln2p is localized primarily to the cytoplasm. Both binding to Cdc28p and Cdc28p-dependent phosphorylation in the C-terminal region of Cln2p are independently required for efficient nuclear depletion of Cln2p, suggesting that this process may be physiologically regulated. The accumulation of hypophosphorylated Cln2 in the nucleus is an energy-dependent process, but may not involve the RAN GTPase. Phosphorylation of Cln2p is inefficient in small newborn cells obtained by elutriation, and this lowered phosphorylation correlates with reduced Cln2p nuclear depletion in newborn cells. Thus, Cln2p may have a brief period of nuclear residence early in the cell cycle. In contrast, the nuclear localization pattern of Cln3p is not influenced by Cdk activity. Cln3p localization requires a bipartite nuclear localization signal (NLS) located at the C terminus of the protein. This sequence is required for nuclear localization of Cln3p and is sufficient to confer nuclear localization to green fluorescent protein in a RAN-dependent manner. Mislocalized Cln3p, lacking the NLS, is much less active in genetic assays specific for Cln3p, but more active in assays normally specific for Cln2p, consistent with the idea that Cln3p localization explains a significant part of Clnp functional specificity.

Amino Acid Sequence↗

PubMed2001

Cyclin specificity: how many wheels do you need on a unicycle?

Cyclin-dependent kinase (CDK) activity is essential for eukaryotic cell cycle events. Multiple cyclins activate CDKs in all eukaryotes, but it is unclear whether multiple cyclins are really required for cell cycle progression. It has been argued that cyclins may predominantly act as simple enzymatic activators of CDKs; in opposition to this idea, it has been argued that cyclins might target the activated CDK to particular substrates or inhibitors. Such targeting might occur through a combination of factors, including temporal expression, protein associations, and subcellular localization.

Animals↗

PubMed2001

Hispanic versus white, non-Hispanic physician medical practices in Colorado.

The purpose of the study was to extend the scope of earlier research on minority physicians attending to the needs of the poor and their own ethnicity by contrasting practice characteristics of Hispanic doctors in Colorado with those of their white, non-Hispanic counterparts. It was found that Hispanic physicians spent more hours per week in direct patient care, were more likely to have a primary care specialty, and were less often specialty board certified than white, non-Hispanic doctors. Hispanic generalists established practices in areas in which the percentages of the population that were (1) below poverty level, (2) Hispanic, (3) Hispanic and below poverty level, and (4) white, non-Hispanic, and below poverty level were greater than in areas in which white, non-Hispanic primary care physicians practiced. These findings argue for special provision to admit ethnic minorities to undergraduate and graduate medical education programs.

Adult↗