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Biomedical subjects

D L Miller

Publications and source records attributed to D L Miller.

At least 217 records · Page 12Linked to original sources
PubMed1993

Ultrasonic gas body activation in Elodea leaves and the mechanical index.

Membrane damage resulting from ultrasonic gas body activation was investigated in leaves of the aquatic plant Elodea using pulse-mode exposures from 0.745-15 MHz. The frequency response was similar to that previously observed for continuous exposures. Cell death thresholds were higher for the pulse modes; for example, at 6 MHz the threshold was 166 W/cm2 spatial-peak, pulse-average (SPPA) intensity for 1 microsecond pulses and 1 kHz pulse repetition frequency (PRF) for 60 s exposures, compared to 12 W/cm2 for 60 ms continuous exposure. Increasing the PRF for 2.5 MHz, 3 microseconds pulses from 10 Hz to 5 kHz resulted in a gradual decrease in the threshold. Increasing the pulse duration from 1 microsecond to 30 microseconds and PRF from 33 Hz to 1 kHz only weakly influenced the threshold, for the constant 60 ms total on-time. Decreasing the pulse duration for single 6 MHz pulses increased the threshold up to 1,540 W/cm2 at 30 microseconds. The gas body activity was modeled with linear theory for oscillation of the gas channel walls, and intracellular shear stress, which causes lethal damage to the plasma membranes, was modeled with theory for acoustic microstreaming. Theory and observation indicate that the minimum shear stress threshold as a function of resonance frequency has essentially the same form as the Mechanical Index (MI) in the 0.5 to 20 MHz range. Specifically, for 3 microseconds pulses with 0.2-2 kHz PRF and 60 ms total on-time, the pressure-amplitude threshold divided by the square root of the frequency was approximately constant at 0.95 MPa/MHz1/2.

Cell Death↗
PubMed1993

Cholinergic stimulation of the Na+/K+ adenosine triphosphatase as revealed by microphysiometry.

The activation of a wide range of cellular receptors has been detected previously using a novel instrument, the microphysiometer. In this study microphysiometry was used to monitor the basal and cholinergic-stimulated activity of the Na+/K+ adenosine triphosphatase (ATPase) (the Na+/K+ pump) in the human rhabdomyosarcoma cell line TE671. Manipulations of Na+/K+ ATPase activity with ouabain or removal of extracellular K+ revealed that this ion pump was responsible for 8.8 +/- 0.7% of the total cellular energy utilization by those cells as monitored by the production of acid metabolites. Activation of the pump after a period of inhibition transiently increased the acidification rate above baseline, corresponding to increases in intracellular [Na+] ([Na+]i) occurring while the pump was off. The amplitude of this transient was a function of the total [Na+]i excursion in the absence of pump activity, which in turn depended on the duration of pump inhibition and the Na+ influx rate. Manipulations of the mode of energy metabolism in these cells by changes of the carbon substrate and use of metabolic inhibitors revealed that, unlike some other cells studied, the Na+/K+ ATPase in TE671 cells does not depend on any one mode of metabolism for its adenosine triphosphate source. Stimulation of cholinergic receptors in these cells with carbachol activated the Na+/K+ ATPase via an increase in [Na+]i rather than a direct activation of the ATPase.

Biophysical Phenomena↗
PubMed1993

Rare pulmonary neoplasms.

We reviewed the clinical course and the results of various treatment modalities of 80 patients with rare pulmonary neoplasms, who constituted 0.8% of all patients with primary lung cancer treated at the Mayo Clinic from 1980 through 1990. The 50 male and 30 female patients had a median age of 60 years (range, 20 to 87). The histopathologic types of these rare pulmonary neoplasms were non-Hodgkin's lymphoma (41%), carcinosarcoma (20%), mucoepidermoid carcinoma (15%), malignant fibrous histiocytoma (5%), malignant melanoma (4%), fibrosarcoma (4%), leiomyosarcoma (4%), angiosarcoma (2%), hemangiopericytoma (2%), osteosarcoma (1%), and blastoma (1%). Follow-up was complete in all 80 patients, and the median duration of follow-up was 59 months (range, 15 to 130). Of the 80 patients, 63 (79%) underwent pulmonary resection. Of the other 17 patients, 8 underwent only bronchoscopy for diagnosis, 4 had unresectable disease at thoracotomy, 3 had metastatic disease on initial assessment, and 2 had mediastinal involvement detected on mediastinoscopy. Fifty-four patients (68%) received chemotherapy or radiation treatment (or both). The overall 5-year survival was 39%. The strongest factors that influenced survival were cell type and extent of disease at time of initial examination.

Adult↗
PubMed1993

Employment barriers and work motivation for Navajo rehabilitation clients.

The Navajo nation provides vocational rehabilitation (VR) services to Navajo clients residing on and off the Navajo reservation. To evaluate motivation among disabled Navajo workers participating in VR programs, this study investigated the sociocultural meanings of work and its importance in the self-identity of contemporary Navajo workers and clients who apply for these services. Selected sociocultural variables that focused on cultural identity and perceptions as well as attitudes towards work were included as part of an assessment designed to predict motivation for employment success. The results of this study suggest that VR counsellors who work with Native American clients should recognize sociocultural history and the cultural perceptions of work as important factors in the rehabilitation and vocational planning process.

Arizona↗
PubMed1993

Frequency dependence of cavitation activity in a rotating tube exposure system compared to the mechanical index.

Cavitation was produced by focused and unfocused ultrasonic beams in a 60-rpm rotating-tube exposure system. Hemolysis, free radical generation, and hydrogen peroxide were assayed after exposure to determine the dependence of cavitation activity on pressure-amplitude p and frequency f. For unfocused exposure, hemolysis rose rapidly from an apparent threshold pressure amplitude, to a maximum value and then declined gradually at higher amplitudes. Cavitation activity decreased with increasing ultrasonic frequency for a fixed pressure amplitude. Apparent thresholds for unfocused exposure were similar for hemolysis after 15 s and H2O2 production after 15 min. These thresholds increased roughly in proportion to increasing ultrasonic frequency. Cavitation activity was lower and thresholds were higher for focused exposures than for unfocused exposures. The approximate pf-1 = 0.20 MPa/MHz dependence of the experimental threshold of H2O2 production from 0.745 to 2.95 MHz differs from the pf-1/2 = 0.24 MPa/MHz1/2 dependence of the theoretical "mechanical index" threshold for inertial cavitation.

Animals↗
PubMed1993

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Animals↗
PubMed1993

The limited ability of inferior petrosal sinus sampling with corticotropin-releasing hormone to distinguish Cushing's disease from pseudo-Cushing states or normal physiology.

To determine whether petrosal sinus sampling is useful to distinguish patients with mild or intermittent Cushing's disease from normal subjects and individuals with pseudo-Cushing states, we performed bilateral inferior petrosal sinus sampling for ACTH before and after the administration of CRH in 7 eucortisolemic volunteers, 8 hypercortisolemic patients with pseudo-Cushing states, and 40 patients with ACTH-dependent Cushing's disease whose urinary free cortisol excretion was within the range found in patients with, pseudo-Cushing states (< 1000 nmol/day; < 360 micrograms/day). The ACTH level, the ratio of the inferior petrosal sinus ACTH to the peripheral venous ACTH concentration (the IPS:P ratio), and the greater ratio of right to left or left to right petrosal sinuses (the R:L ratio) were compared in patients with and without Cushing's disease. Maximal petrosal ACTH values were significantly elevated in patients with Cushing's disease compared to patients with pseudo-Cushing states before CRH administration (P < 0.001), but not after CRH. Maximal petrosal plasma ACTH values after the administration of CRH as high as 808 pmol/L (3670 pg/mL) and 469 pmol/L (2130 pg/mL) were found in patients with pseudo-Cushing states and in normal volunteers, respectively, whereas maximal petrosal ACTH levels as low as 10 pmol/L (46 pg/mL) were observed in patients with surgically proven Cushing's disease. Maximal and minimal IPS:P ratios were significantly greater in patients with Cushing's disease than in subjects without Cushing's disease before, but not after, CRH treatment. R:L ratios did not differ among groups either before or after CRH. All of the subjects without Cushing's disease showed large R:L gradients, consistent with the notion of one dominant petrosal sinus containing a greater percentage of pituitary effluent. The ACTH concentrations, IPS:P ratios, and R:L ratios exhibited great overlap between those with and without Cushing's disease, which resulted in a diagnostic accuracy of 81% at best for the diagnosis of Cushing's disease. We conclude that petrosal sinus sampling is of limited usefulness in distinguishing either normal individuals or patients with pseudo-Cushing states from those with mild Cushing's disease. This limited usefulness must be recognized when interpreting the results of petrosal sinus sampling in patients with mild or intermittent hypercortisolism who may have a pseudo-Cushing state. Because of these limitations, petrosal sinus sampling should be reserved for patients with clear clinical and biochemical evidence of Cushing's syndrome.

Adrenocortical Hyperfunction↗
PubMed1993

Prospective evaluation of selective venous sampling for parathyroid hormone concentration in patients undergoing reoperations for primary hyperparathyroidism.

BACKGROUND: The utility of standard radiologic imaging studies in guiding reoperative parathyroid surgery for primary hyperparathyroidism is widely known and accepted. The additional information gained by selective venous sampling in that patient population has not been well defined. We report the results of our experience with this method. METHODS: Between 1982 and 1992, 223 consecutive patients underwent reoperations for persistent or recurrent primary hyperparathyroidism after a prospectively determined series of imaging studies. Patients underwent noninvasive testing consisting of ultrasonography, computed tomography, technetium thallium scanning, and magnetic resonance imaging. Patients with negative, equivocal, or discordant results on the noninvasive studies proceeded to angiography. If angiography was negative, selective venous sampling was performed. RESULTS: Eighty-six patients (39%) with negative or equivocal noninvasive test and angiogram results underwent selective venous sampling. Seventy-six patients (88%) had a significant gradient in levels of parathyroid hormone from veins draining the left side of the neck (n = 25), the right side of the neck (n = 33), both sides of the neck (n = 7), and the thymus (n = 11). Correlation of these findings with operative findings revealed a sensitivity of 88% and a specificity of 86%. In the subgroup of patients who underwent venous sampling and had completely negative results of standard radiologic studies (35 of 86; 40%), 28 patients (80%) had venous gradients and seven patients (20%) had no gradient. Of those 28 patients in whom the venous sampling gradients were the only positive localization study, the venous samplings were helpful in 23 patients (true positive gradients), and the operative success rate was 93%. In the seven patients with no positive preoperative localizing studies including venous sampling, there were two operative failures (operative success, 71%). CONCLUSIONS: Our results show that selective venous sampling is a highly sensitive and specific method to regionally localize abnormal parathyroid glands not imaged by standard noninvasive and invasive radiologic techniques. Venous sampling is the study of choice in guiding reoperative procedures for occult abnormal parathyroid glands that are undetected despite the use of all available imaging studies.

Diagnostic Imaging↗
PubMed1993

Endocrine angiography and venous sampling.

Localization procedures are performed only after the diagnosis of endocrine disease is established. Arteriography and venous sampling may be essential to locate a small hyperfunctioning endocrine tumor or to assist in distinguishing between disease caused by a solitary tumor and disease caused by diffuse hyperplasia. These procedures require a detailed knowledge of vascular anatomy and must be performed meticulously to avoid incorrect results. Close cooperation between the radiologist and the endocrinologist is essential for optimal results. These procedures are complex and are rarely performed outside of the few centers where endocrine problems are frequently evaluated. In many cases, the patient may be best served by referral to an institution where these radiologic studies are routine.

Angiography↗
PubMed1992

Borocaptate sodium: a potential boron delivery compound for boron neutron capture therapy evaluated in dogs with spontaneous intracranial tumors.

Borocaptate sodium (Na2B12H11SH) is a boron-carrying compound under consideration for use in boron neutron capture therapy. The biodistribution of boron from borocaptate sodium administration will partly determine boron neutron capture therapy efficacy and normal tissue radiation tolerance. The biodistribution of boron was determined in 30 dogs with spontaneous intracranial tumors at 2, 6, or 12 hr after intravenous borocaptate sodium infusion. Blood and tissue boron concentrations were measured using inductively coupled plasma atomic emission spectroscopy. Mean tumor boron concentration (mean +/- standard error) was 35.9 +/- 4.6 (n = 15), 22.5 +/- 6.0 (n = 9), and 7.0 +/- 1.1 micrograms of boron per g (n = 6) at 2, 6, and 12 hr, respectively, after borocaptate sodium infusion. Peritumor boron concentrations were elevated above that of normal brain in half of the dogs. Normal brain boron concentration (mean +/- standard error) was 4.0 +/- 0.5, 2.0 +/- 0.4, and 2.0 +/- 0.3 micrograms of boron per g at 2, 6, and 12 hr after infusion, respectively. Some cranial and systemic tissues, and blood, had high boron concentration relative to tumor tissue. Geometric dose sparing should partly offset these relatively high normal tissue and blood concentrations. Borocaptate sodium biodistribution is favorable because tumor boron concentrations of recommended magnitude for boron neutron capture therapy were obtained and there was a high tumor-to-normal brain boron concentration ratio.

Animals↗
PubMed1992

PKC epsilon is involved in granulocyte-macrophage colony-stimulating factor signal transduction: evidence from microphysiometry and antisense oligonucleotide experiments.

We have used microphysiometry and antisense methodology to show that the epsilon isoenzyme of protein kinase C (PKC) is involved in the signal transduction pathway of granulocyte-macrophage colony-stimulating factor (GM-CSF) in a human bone marrow cell line, TF-1. These cells require GM-CSF or a related cytokine for proliferation. When the cells are appropriately exposed to GM-CSF, they exhibit a burst of metabolic activity that can be detected on the time scale of minutes in the microphysiometer, a biosensor-based instrument that measures the rate at which cells excrete protons. These cells express PKC alpha and -epsilon, as determined by Western blot analysis. Treatment with isoenzyme-specific antisense oligonucleotides inhibits expression appropriately, but only inhibition of PKC epsilon appreciably diminishes the burst of metabolic activity induced by GM-CSF. Consistent with the involvement of PKC epsilon, GM-CSF appears to activate phospholipase D and does not cause a detectable increase in cytosolic [Ca2+].

Alkaloids↗
PubMed1992

The identification of a domain in Escherichia coli elongation factor Tu that interacts with elongation factor Ts.

A method has been developed to search for the elongation factor Tu (EF-Tu) domain(s) that interact with elongation factor Ts (EF-Ts). This method is based on the suppression of Escherichia coli EF-Tu-dominant negative mutation K136E, a mutation that exerts its effect by sequestering EF-Ts. We have identified nine single-amino acid- substituted suppression mutations in the region 146-199 of EF-Tu. These mutations are R154C, P168L, A174V, K176E, D181G, E190K, D196G, S197F, and I199V. All suppression mutations but one (R154C) significantly affect EF-Tu's ability to interact with EF-Ts under equilibrium conditions. Moreover, with the exception of mutation A174V, the GDP affinity of EF-Tu appears to be relatively unaffected by these mutations. These results suggest that the domain of residues 154 to 199 on EF-Tu is involved in interacting with EF-Ts. These suppression mutations are also capable of suppressing dominant negative mutants N135D and N135I to various degrees. This suggests that dominant negative mutants N135D and N135I are likely to have the same molecular basis as the K136E mutation. The method we have developed in this study is versatile and can be readily adapted to map other regions of EF-Tu. A model of EF-Ts-catalyzed guanine-nucleotide exchange is discussed.

Amino Acid Sequence↗
PubMed1992

The cytosensor microphysiometer: biological applications of silicon technology.

A silicon-based device, dubbed a microphysiometer, can be used to detect and monitor the response of cells to a variety of chemical substances, especially ligands for specific plasma membrane receptors. The microphysiometer measures the rate of proton excretion from 10(4) to 10(6) cells. This article gives an overview of experiments currently being carried out with this instrument with emphasis on receptors with seven transmembrane helices and tyrosine kinase receptors. As a scientific instrument, the microphysiometer can be thought of as serving two distinct functions. In terms of detecting specific molecules, selected biological cells in this instrument serve as detectors and amplifiers. The microphysiometer can also investigate cell function and biochemistry. A major application of this instrument may prove to be screening for new receptor ligands. In this respect, the microphysiometer appears to offer significant advantages over other techniques.

Animals↗
PubMed1992

Hammerhead ribozyme cleavage of hamster prion pre-mRNA in complex cell-free model systems.

The cleavage properties of a trans-acting hammerhead ribozyme targeted 51 bases upstream of the putative splicing branch point in the hamster prion pre-mRNA intron were investigated in cell-free model systems in vitro. The specificity of cleavage was demonstrated by the inability of this ribozyme to cleave a non-homologous synthetic message encoding part of the beta amyloid peptide precursor, beta APP, and by the inability of the prion pre-mRNA to be cleaved by a ribozyme targeted to beta amyloid peptide precursor mRNA. Also, the addition of total RNA isolated from rat brain had only a minimal effect on the cleavage of the prion substrate pre-mRNA by the ribozyme. Finally neither the presence of 100 ng of nuclear or cytoplasmic proteins were found to affect the rate of cleavage in vitro.

Adenosine Triphosphate↗