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Biomedical subjects

J G Miller

Publications and source records attributed to J G Miller.

At least 37 records · Page 2Linked to original sources
PubMed1999

Investigation of female survival benefit in metastatic melanoma.

Epidemiological studies show female survival benefit in advanced metastatic melanoma. In investigating a possible mechanism for this female survival benefit, we have previously reported that the female steroid 17beta-oestradiol significantly reduces invasion of a human melanoma cell line (A375-SM cells) and ocular melanoma cells through fibronectin. Neither cell type was found to possess oestrogen receptor-alpha. The aim of the current study was to obtain further information on the extent to which progression of cutaneous melanoma might be sex steroid sensitive by (a) examining the relationship between circulating sex steroids, sex hormone binding globulin and disease progression; (b) examining the relationship between sex steroid structure and the ability of steroids to reduce invasion of a melanoma cell line in vitro; and (c) examining the effects of sex steroids on proliferation of these cells in vitro. We report a significant reduction in circulating oestrone with disease progression in male but not female patients. Examining steroids for their ability to inhibit invasion of A375-SM cells through fibronectin in vitro, oestrogenic compounds (17beta-oestradiol and oestrone) were found to inhibit invasion; in this respect, oestrone was approximately 50 times more potent than 17beta-oestradiol; steroids lacking the benzene ring structure did not inhibit invasion, indeed dehydroepiandrosterone (DHEA) which acts as a precursor to androgenic steroids significantly enhanced invasion. Proliferation of A375-SM cells was unaffected by 17beta-oestradiol, oestrone or dihydrotestosterone when cells were cultured on plastic; in contrast, all three steroids induced modest proliferation of cells when grown on fibronectin with dihydrotestosterone the most mitogenic of the three steroids. These data are consistent with sex steroids playing a role in melanoma progression.

Adolescent↗
PubMed1999

Interlaboratory comparison of ultrasonic backscatter, attenuation, and speed measurements.

In a study involving 10 different sites, independent results of measurements of ultrasonic properties on equivalent tissue-mimicking samples are reported and compared. The properties measured were propagation speed, attenuation coefficients, and backscatter coefficients. Reasonably good agreement exists for attenuation coefficients, but less satisfactory results were found for propagation speeds. As anticipated, agreement was not impressive in the case of backscatter coefficients. Results for four sites agreed rather well in both absolute values and frequency dependence, and results from other sites were lower by as much as an order of magnitude. The study is valuable for laboratories doing quantitative studies.

1-Propanol↗
PubMed1998

Effects of myocardial fiber orientation in echocardiography: quantitative measurements and computer simulation of the regional dependence of backscattered ultrasound in the parasternal short-axis view.

We measured the regional disparity in backscattered ultrasound by means of obtaining integrated backscatter images of 10 healthy subjects and placing a region of interest in 18 distinct positions. A computer model simulating the short-axis view was implemented on the basis of previously measured values for the anisotropic ultrasonic properties of myocardium. Measurements showed that the integrated backscatter value was greatest for the anterior septum and decreased by 15.9 +/- 3.5 dB for the lateral wall and 17.7 +/- 3.5 dB for the inferior septum. The value in the posterior wall was 8.1 +/- 3.8 dB below the value for the anterior septum. The regional variation of backscatter predicted with the simulation correlated well with the clinical measurements. These results suggested that analyses based on measurements of backscatter may require compensation for the inherent anisotropic properties of myocardium.

Adult↗
PubMed1998

Broadband measurements of phase velocity in Albunex suspensions.

The phase velocities in suspensions of Albunex, an ultrasound contrast agent, are determined using the technique of broadband phase spectroscopy. In these suspensions, phase velocities were measured as a function of Albunex concentration in Isoton II (buffered saline). The dispersion over the measurement bandwidth (1-15 MHz) grew with increasing Albunex concentration, exhibiting a 221-m/s change (17% increase) in phase velocity between 1.0 and 3.8 MHz at the highest concentration reported (32 microL Albunex/8 mL Isoton). The dispersion behavior of the Albunex suspensions is described using a model of encapsulated gas bubbles. The influence of the dispersion in Albunex on broadband pulses is discussed, as well as the potential impact this dispersion may have on the formation of ultrasonic images of the heart.

Albumins↗
PubMed1998

In vitro characterization of a novel, tissue-targeted ultrasonic contrast system with acoustic microscopy.

Targeted ultrasonic contrast systems are designed to enhance the reflectivity of selected tissues in vivo [Lanza et al., Circulation 94, 3334 (1996)]. In particular, these agents hold promise for the minimally invasive diagnosis and treatment of a wide array of pathologies, most notably tumors, thromboses, and inflamed tissues. In the present study, acoustic microscopy was used to assess the efficacy of a novel, perfluorocarbon based contrast agent to enhance the inherent acoustic reflectivity of biological and synthetic substrates. Data from these experiments were used to postulate a simple model describing the observed enhancements. Frequency averaged reflectivity (30-55 MHz) was shown to increase 7.0 +/- 1.1 dB for nitrocellulose membranes with targeted contrast. Enhancements of 36.0 +/- 2.3 dB and 8.5 +/- 0.9 dB for plasma and whole blood clots, respectively, were measured between 20 and 35 MHz. A proposed acoustic transmission line model predicted the targeted contrast system would increase the acoustic reflectivity of the nitrocellulose membrane, whole blood clot, and fibrin plasma clot by 2.6, 8.0, and 31.8 dB, respectively. These predictions were in reasonable agreement with the experimental results of this paper. In conclusion, acoustic microscopy provides a rapid and sensitive approach for in vitro chracterization, development, and testing of mathematical models of targeted contrast systems. Given the current demand for targeted contrast systems for medical diagnostic and therapeutic use, the use of acoustic microscopy may provide a useful tool in the development of these agents.

Acoustics↗
PubMed1998

Effects of tissue anisotropy on the spectral characteristics of ultrasonic backscatter measured with a clinical imaging system.

In this paper, we report the effects of inherent tissue anisotropy on the spectral properties of backscattered ultrasound when measured with a commercially-available imaging system. We insonified five specimens of bovine tendon immersed in a water tank and rotated in 10 degrees increments while being imaged with a Hewlett-Packard Sonos 1500 system. The backscattered RF signals corresponding to each angle of insonification were digitized and the spectral characteristics of the backscattered ultrasound were determined. The mean anisotropy, defined as the average difference between values at perpendicular and parallel insonification, for band-limited estimates of backscattered power, centroid frequency, upper-band to lower-band power ratio, and upper-band to total-band power ratio were found to be 24.6 +/- 1.1 dB, 142 +/- 27 kHz, 32 +/- 13%, and 22 +/- 5%, respectively (mean +/- SE). The magnitude of each of these backscatter spectral parameters was larger at perpendicular insonification compared with the corresponding values at parallel insonification, consistent with previous measurements of the inherent anisotropy of ultrasonic attenuation and backscatter in tissue.

Animals↗
PubMed1997

High-frequency ultrasonic detection of thrombi with a targeted contrast system.

Site-targeted acoustic contrast agents used in conjunction with high-frequency intravascular ultrasound have the potential to localize and characterize intravascular pathology. The present study quantifies the utility of a novel, site-targeted ultrasonic contrast agent with high-frequency ultrasound (30 to 50 MHz) and demonstrates the feasibility of the new agent for augmenting detection of targeted pathology with intravascular ultrasonic catheters. High-frequency acoustic microscopy was used to image avidinconjugated nitrocellulose membranes after exposure to a control or biotinylated contrast agent. Increases (p < 0.05) in backscattered power of approximately 66 dB (4-fold) were found for the biotinylated, but not the control contrast agent. Intravascular ultrasonic images (30 MHz nominal center frequency) of plasma clots after exposure to the targeted contrast agent were brighter (p < 0.05) than in controls. These results demonstrate high-frequency acoustic enhancement with a novel targeted contrast agent and may extend the potential diagnostic spectrum of intravascular ultrasound.

Avidin↗
PubMed1997

Comparison of integrated backscatter values obtained with acoustic densitometry with values derived from spectral analysis of digitized signals from a clinical imaging system.

Time-domain-based integrated backscatter values obtained with the use of acoustic densitometry (AD) were compared with values determined from a spectral-based analysis of the radio-frequency (RF) signals with a modified Hewlett-Packard Sonos 1500 imaging system. Integrated backscatter images of five specimens of bovine tendon were acquired in the AD acquisition mode, and the corresponding signals related to the backscattered RF were digitized for each angle of insonification as the specimens were rotated in 10-degree increments. The integrated backscatter images were analyzed with the AD analysis package, and the corresponding values determined from the RF power spectra were obtained from the digitized ultrasonic signals. Good agreement was found between the two methods over the entire range of measured values. The mean anisotropy in the measured integrated backscatter (mean +/- standard error) was found to be 27 +/- 2 dB for time-domain-based analysis and 25 +/- 2 dB for RF spectral-based analysis.

Acoustics↗
PubMed1997

Angiotensin II receptor blockade in Syrian hamster (T0-2) cardiomyopathy does not affect microscopic cardiac material properties: implications for mechanisms of tissue remodeling.

This study delineates the role of angiotensin II type I (AT1) receptor in the remodeling of Syrian cardiomyopathic hamsters. Twelve cardiomyopathic (T0-2) hamsters received L-158,809 treatment and libitum in their drinking water (27 micrograms/ml) and 9 cardiomyopathic and 9 normal FL-B hamsters received tap water from 1 to 4 months of age. Although pharmacologically effective with regard to complete suppression of the blood pressure response to angiotensin II infusion, L-158,809 did not diminish the progression or severity of cardiomyopathy. Heart weight/100 g body weight and left ventricular wall thickness adjusted for body weight of both L-158,809 and cardiomyopathic control hamsters did not differ and exceeded those of F1-B controls (p < 0.05). Myocardial material properties (e.g., stiffness and density) of cardiomyopathic hamsters treated with L-158,809 were not affected. Thus, the progression of fibrosis, calcification, and necrosis in T0-2 cardiomyopathic hamsters was not sensitive to AT1 receptor blockade.

Angiotensin II↗
PubMed1997

Investigation of oestrogen receptors, sex steroids and soluble adhesion molecules in the progression of malignant melanoma.

The question of whether melanoma tumours have classical oestrogen receptors (ERs) is unresolved, but epidemiological data clearly show a survival benefit for female patients with metastatic melanoma. The aims of this study were to examine to what extent the presence of ER in melanoma tumours might relate to disease progression and whether disease progression relates to patients' sex steroid status. Additionally, levels of two soluble adhesion molecules [circulating intercellular adhesion molecule-1 (sICAM-1) and circulating vascular cell adhesion molecule-1 (sVCAM-1)] were examined as independent, possibly prognostic indicators of disease progression. ER immunocytochemical assay identified only two lesions (out of 69 investigated) which had any evidence of the receptors, and staining in these lesions was very modest. No significant changes in oestrone or androstenedione levels were noted for male or female patients with disease progression. As expected, oestradiol levels reflected the menopausal status of the female patients but, for all post-menopausal female patients and male patients, there was no significant relationship to tumour stage. However, a significant decrease in sex hormone-binding globulin occurred with disease progression in male but not female patients, and sex differences in the levels of soluble adhesion molecules were also seen in advanced metastatic disease.

Adolescent↗
PubMed1997

Anisotropy of the apparent frequency dependence of backscatter in formalin fixed human myocardium.

Measurements of the frequency dependence of ultrasonic backscatter are presented for specific angles of insonification for regions of infarcted and noninfarcted human myocardium. A 5-MHz transducer was used to insonify cylindrical cores taken from 7 noninfarcted regions and 12 infarcted regions of the left ventricular free wall of 6 formalin-fixed human hearts explanted because of ischemic cardiomyopathy. The dependence of apparent (uncompensated for diffraction effects and attenuation) backscatter on frequency was approximated by a power-law dependence, magnitude of B(f)2 = afn. Under ideal conditions in a lossless medium, the effect of not compensating for the effects of diffraction and attenuation leads to the value of n to be 2.0 for Rayleigh scatterers while the frequency dependence of the fully compensated backscatter coefficient would be f4. The value of n was determined over the frequency range, 3-7 MHz. Both nonifarcted and infarcted myocardium exhibited anisotropy of the frequency dependence of backscatter, with maxima occurring at angles that were perpendicular to the predominant myofiber direction and minima when parallel to the fibers. Perpendicular insonification yielded results for n of 1.8 +/- 0.1 for noninfarcted myocardium and 1.2 +/- 0.1 for infarcted myocardium while parallel insonification yielded results of 0.4 +/- 0.1 for noninfarcted and 0.0 +/- 0.1 for infarcted myocardium. The functional form of the angle-dependent backscatter is similar for both noninfarcted and infarcted myocardium, although the frequency dependence is clearly different for both tissue states for all angles of insonification. The results of this study indicate that the anisotropy of the frequency dependence of backscatter may play a significant role in ultrasonic imaging and is an important consideration for ultrasonic tissue characterization in myocardium.

Anisotropy↗
PubMed1997

Reduction in risk behavior among adults with severe mental illness who learned to advocate for HIV prevention.

OBJECTIVES: The study evaluated the relative impact of HIV risk reduction interventions for adults with severe mental illness living in the inner city. METHODS: A total of 104 chronically mentally ill men and women were interviewed to determine sexual risk behavior over the past month and to assess HIV risk-related psychological characteristics, including their knowledge about risk behavior, their belief in their ability to change their behavior, their perceptions of peer and social norms about safer sex, their expectancies about the outcomes of these changes, and their perceived barriers to condom use. Participants were then randomly assigned to one of three conditions: a single AIDS education session, a seven-session cognitive-behavioral HIV risk reduction group intervention, or a seven-session group intervention that combined the cognitive-behavioral intervention with training to act as a risk reduction advocate to friends (advocacy training). Individuals were reinterviewed three months after completion of the intervention. RESULTS: Although all participants exhibited change at follow-up in some risk-related psychological characteristics and sexual risk behaviors, participants who received the cognitive-behavioral intervention that included the advocacy training reported greater reductions in rates of unprotected sex and had fewer sexual partners at follow-up. CONCLUSIONS: HIV prevention interventions that teach risk reduction skills and then encourage participants to advocate behavior change to others appear to strengthen participants' capacity to change their behavior to reduce HIV risk, even those from a disenfranchised group such as severely mentally ill adults.

Adult↗
PubMed1997

Gender and cutaneous melanoma.

Current evidence suggesting that a patient's sex is relevant to the progression of cutaneous melanoma is largely epidemiological. Although databases of patients with melanomas have for many years shown a survival advantage for female patients with primary melanoma, it has been difficult to evaluate contribution of other known prognostic variables such as thickness and site of the primary tumour, factors which also tend to be related to sex. In addition, there are data from a limited number of experimental studies and clinical trials which support the concept of female survival superiority in melanoma. This paper attempts to summarize the evidence for gender being an important factor in melanoma survival.

Antineoplastic Agents, Hormonal↗
PubMed1997

Targeting of ultrasound contrast material. An in vitro feasibility study.

PURPOSE: It would be beneficial to design a targetable microbubble ultrasound contrast agent that would selectively bind to the areas of interest in the body and enhance the target organ in the ultrasound examination. MATERIAL AND METHODS: We have studied the feasibility of targeting in a model system. We used avidin and biotin as a model ligand-receptor pair. Avidin was adsorbed on the surface of polystyrene, and biotin derivative was attached to microbubble shells. After removal of unincorporated biotin from the microbubbles, they were allowed to come in contact with avidin-coated or albumin-coated plastic. Unbound bubbles were washed by a stream of water. RESULTS: Binding of microbubbles to the surface occurred selectively in the areas where avidin layer was deposited. Binding of microbubbles to avidin layer was dependent on the amount of biotin incorporated in the microbubble shell. Presence of free biotin blocked targeting completely. Acoustic studies were performed using a custom-built ultrasound measurement apparatus and an ultrasound medical imaging system. Microbubble-coated areas of the plastic dish were clearly visualized with ultrasound imaging. A strong backscattered signal was obtained for microbubble surface densities as low as 3%. CONCLUSION: Microbubbles have been selectively targeted via a ligand-receptor system in vitro. Firm binding of microbubbles to avidin-coated surface has been achieved. Microbubbles deposited on the target were visualized with ultrasound imaging systems.

Animals↗