Search PubMed⌕ Search

Biomedical subjects

D W Miller

Publications and source records attributed to D W Miller.

At least 127 records · Page 7Linked to original sources
PubMed1994

Identification and distribution of insulin receptors on cultured bovine brain microvessel endothelial cells: possible function in insulin processing in the blood-brain barrier.

The binding of 125I-insulin to primary cultures of bovine brain microvessel endothelial cells was examined. Insulin binding was both time and temperature dependent and inhibited by excess unlabeled insulin. Furthermore, the specific binding of insulin was polarized to the apical side of the cell monolayers. Upon binding, the labeled insulin was internalized, with approximately 70% resistant to acid wash over a 90-min period. The inhibition of insulin internalization observed with cell monolayers exposed to either phenylarsine oxide or unlabeled insulin suggests a receptor-mediated endocytic process. Furthermore, the ability of chloroquine to reduce the metabolism of insulin indicates a significant portion of the peptide is processed through a lysosomal pathway. In contrast to the fluid-phase endocytosis marker, Lucifer yellow, as much as 65% of internalized insulin undergoes apical to basolateral trancytosis in brain microvessel endothelial cells. While most of the effluxed insulin was degraded, as assessed by trichloroacetic acid precipitation, the results of the present study suggest insulin receptors within the brain microvasculature may be involved in the processing and transport of blood-borne insulin.

Animals↗
PubMed1994

Relative biological effectiveness and microdosimetry of a mixed energy field of protons up to 200 MeV.

We have studied radiation effects utilizing the new 250 MeV Synchrotron at Loma Linda University Medical Center. In this paper we present the data collected for the survival of Chinese hamster lung (V79) cells, that were irradiated with a beam of mixed energy protons up to 200 MeV. The RBE for protons, when compared to 60Co gamma rays, ranged from a low of 1.2 at the high energy portion of the field to 1.3+ at the low energy portion of the field. These results are consistent with the measured lineal energy (microdosimetric) spectra.

Animals↗
PubMed1993

Characterization of vascular postsynaptic NPY receptor function and regulation and differential sensitivity of Y1 and Y2 receptor function to changes in extracellular calcium availability and prior in vitro peptide exposure.

Effects of calcium-free buffer, nifedipine, or prior cumulative neuropeptide Y (NPY) receptor agonist concentration exposure on vasoconstrictive responsiveness to the agonists were assessed in norepinephrine (NE)-conditioned isolated rat femoral artery rings. Calcium-free buffer and nifedipine partially inhibited responsiveness to initial NPY exposure; residual responsiveness to NPY re-exposure was unaffected. In contrast, these treatments markedly inhibited responsiveness to the Y2 agonist NPY13-36, the calcium channel agonist BAY K 8644 (BAY) and the partial alpha 1 adrenoceptor agonist indanidine but did not alter to the Y1 agonist [Leu31,Pro34]NPY. Responsiveness to NPY and NPY13-36 but not to BAY or indanidine was markedly reduced 120 min following conditioning regardless of prior ring exposure to the same peptide; only prior exposure reduced responsiveness to [Leu31,Pro34]NPY. Responsiveness changes to NPY at various times or after various numbers of NE and/or NPY exposures indicated that pre-exposure and time-related responsiveness reductions were discriminable and temporally unrelated to conditioning. Postsynaptic vascular Y2 receptor activation therefore accounts for the known sensitivity of NPY-induced pressor and vasoconstrictive actions to nifedipine. The 'time-dependent' loss of Y2 receptor function may also explain prior failures to observe postsynaptic arterial Y2 receptors in vitro.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1993

Effects of diethyl spermine analogues in human bladder cancer cell lines in culture.

The biochemical and antiproliferative effects of two recently developed N-alkylated analogues of naturally-occurring polyamines, N1,N14-diethylhomospermine (DEHSPM) and N1,N11-diethylnorspermine (DENSPM), were investigated in two human transitional cell carcinoma (TCC) lines, T24 and J82. Parallel studies with the ornithine decarboxylase enzyme inhibitor alpha-difluoromethylornithine (DFMO) were included for comparison. DENSPM displayed greater antiproliferative activity than DEHSPM in both TCC cell lines. Both analogues were strikingly more potent than DFMO. DEHSPM and DENSPM suppressed the activity of the major biosynthetic enzymes, ornithine decarboxylase and S-adenosylmethionine decarboxylase. However, differences in the resulting polyamine depletion suggest that the substantial antiproliferative activity of these analogues may result from mechanisms other than polyamine depletion. The greater polyamine depletion seen with DENSPM is thought to result from its striking induction of spermidine/spermine N1-acetyltransferase. DENSPM is an attractive agent for further preclinical and clinical development, possibly as a chemopreventive agent, in TCC of the bladder.

Carcinoma, Transitional Cell↗
PubMed1993

Hospital successes and failures indicate change in hospital marketing.

Marketing has become an essential management function for hospitals during the past decade. A number of changes have occurred in hospital marketing as they have progressed through the marketing adoption process. A survey of Hospital CEOs reporting hospital successes and failures in the area of marketing have recently placed emphasis on sales and advertising based upon marketing research programs thus indicating entrance into the "Integrated Tactical Marketing" phase. This study also indicates that a few hospitals have entered the "Strategic Marketing Orientation" phase while future plans reported by the CEOs provide evidence that this trend is likely to continue.

Chief Executive Officers, Hospital↗
PubMed1993

The relationship between hospital marketing orientation and CEO satisfaction with the marketing function.

Although hospitals are placing more focus on the marketing function, there is still dissatisfaction reported by CEOs with the marketing function in hospital settings. The authors investigate the relationship between the marketing orientation of a hospital and CEO satisfaction with marketing. It was found that in those hospitals that are truly marketing oriented, CEO satisfaction with marketing is very positive.

Attitude of Health Personnel↗
PubMed1993

Improving the strategic planning process at Alliant Health System.

Starting in 1986, Alliant Health System initiated a total quality management process. While strategic quality planning was not a focus initially, it became apparent that Alliant would not achieve major organizational objectives without such focus. Starting in 1989, Alliant initiated a rigorous strategic planning process. The result was alignment of the quality improvement activities in the organization, heightened management accountability, and integration of quality goals with financial incentives. This article recounts the continuing efforts to improve strategic quality planning from the point of view of the person responsible for implementing TQM at Alliant.

Hospital Administrators↗
PubMed1993

Characterization of vascular postsynaptic neuropeptide Y receptor function and regulation. 1. NPY-induced constriction in isolated rat femoral artery rings is mediated by both Y1 and Y2 receptors: evidence from benextramine protection studies.

Neuropeptide Y (NPY), a potent pressor agent and vasoconstrictor, is thought to contribute to the sympathetically mediated postsynaptic regulation of blood pressure primarily through activation of vascular Y1 rather than Y2 NPY receptors. However, data are available that conflict with this conclusion. In this article, the relative roles of postsynaptic Y1 and Y2 receptors as mediators of direct NPY-induced isolated rat femoral artery ring vasoconstriction were evaluated through use of selective Y1 and Y2 agonists, [Leu31, Pro34]NPY ([Leu, Pro]NPY) and NPY13-36 [NPY(13-36)], respectively, and the NPY receptor antagonist benextramine (BXT). NPY, [Leu, Pro]NPY and NPY(13-36) were equipotent as vasoconstrictors, and constriction induced by each peptide, but not by the calcium channel agonist BAY K 8644 (BAY), was almost completely blocked by 10 microM BXT. Each of the three peptides also induced self- and cross-desensitization and protection from BXT blockade, except that [Leu, Pro]NPY neither desensitized nor protected NPY(13-36)-associated responses. NPY also failed to protect [Leu, Pro]NPY- and NPY(13-36)-elicited constriction, and NPY(13-36) failed to provide self-protection, from BXT blockade. However, in these instances, as opposed to the [Leu, Pro]NPY-NPY(13-36) cross-protection experiments, the occurrence of protection was probably masked by the relatively large magnitude of desensitization concurrently induced by the protecting peptide. Taken together, the present findings suggest that NPY-induced rat femoral artery vasoconstriction is mediated by separate, BXT-sensitive, postsynaptic Y1 ([Leu, Pro]NPY-activated) and Y2 [NPY(13-36)-activated] receptors.

Animals↗
PubMed1992

Unilateral neostriatal kainate, but not 6-OHDA, lesions block dopamine agonist-induced ascorbate release in the neostriatum of freely moving rats.

Unilateral kainate lesions of the neostriatum and 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle were used to assess the role of neostriatal and ascending dopaminergic neurons, respectively, on dopamine-agonist induced release of neostriatal ascorbate as measured voltammetrically in freely moving rats. Electrochemically modified, carbon-fiber electrodes recorded the effects of direct (a combination of 10 mg/kg SKF-38393 and 1.0 mg/kg quinpirole) as well as indirect (2.5 mg/kg D-amphetamine or 20.0 mg/kg GBR-12909) dopamine agonists. Relative to controls, kainate, but not 6-OHDA, lesions abolished the ability of both direct and indirect dopamine agonists to induce neostriatal ascorbate release. These results suggest that unlike dopaminergic afferents, neostriatal output pathways play a critical role in the modulation of neostriatal ascorbate levels.

Animals↗
PubMed1992

The proton treatment center at Loma Linda University Medical Center: rationale for and description of its development.

Proton radiation, a continuation of radiation oncology's historic search for an optimum dose distribution, offers superior characteristics for clinical radiation therapy. A complete facility for clinical proton radiation therapy has been designed for and constructed at Loma Linda University Medical Center. To bring about this achievement, a consortium of engineers, physicists, and physicians interested in the clinical applications of protons was necessary. The accelerator, the beam transport and delivery systems, the building, and the personnel who operate the system were all brought together to fully exploit the properties of protons for patient treatments, which are now underway.

Academic Medical Centers↗
PubMed1992

Improvement of cortical morphology in infantile hydrocephalic animals after ventriculoperitoneal shunt placement.

As a sequel to our previous descriptions of the pathological changes induced by hydrocephalus in the infantile cerebral cortex, the study presented here has evaluated the effects of surgical decompression on cortical cytology and cytoarchitecture. Hydrocephalus was induced in 14 kittens by the intracisternal injection of kaolin at 4 to 11 days of age. Nine of these hydrocephalic animals received low-pressure ventriculoperitoneal shunts at 9 to 15 days after kaolin injection; these animals were monitored preoperatively and postoperatively by ultrasound and were killed at various postshunt intervals up to 30 days. Five normal or saline-injected animals served as age-matched controls. At the time of shunt placement, the ventricular index confirmed that all recipient animals had attained moderate or severe degrees of ventriculomegaly. Within 3 days after shunt placement, the size of the lateral ventricles had decreased to control levels and was accompanied by rapid and dramatic improvements in behavior and skull ossification. When the animals were killed, gross inspection revealed that about half of the animals exhibited mild to moderate ventriculomegaly, with cortical mantles 50 to 80% their normal thickness. Tissue from frontal (primary motor), parietal (association), and occipital (primary visual) cortical areas was processed for light microscopic analysis. Pyknotic or dark shrunken neurons, which are found typically in hydrocephalic brains, were observed only occasionally in the cortex of shunted animals. Gliosis and mild edema were prevalent, however, in the periventricular white matter. The laminae of the cerebral cortex could be identified in all shunted animals. In those animals with mild residual ventriculomegaly, the entire cortical mantle was somewhat compressed, as evidenced by an increased packing density of neurons. Furthermore, the somata of some neurons were disoriented. Overall, these results indicate that most of the morphological characteristics of the cerebral cortex are preserved after surgical decompression and suggest that ventriculoperitoneal shunts may prevent neuronal damage and/or promote neuronal repair.

Animals↗
PubMed1992

Battered bottom lines: the impact of eroding pharmaceutical discounts on health-care institutions.

For several years, the American Society of Hospital Pharmacists (ASHP) has voiced concern about the impact of federally mandated changes on the pharmaceutical products marketplace. Since this marketplace is relatively inelastic, manipulating one segment in the interest of cost efficiencies is likely to result in price increases in other segments. That manipulation could come through such decisions as a "one-price" policy for pharmaceuticals, mandatory rebates for certain segments of the marketplace, or the elimination of discounts. The issue of cost-effective purchasing of prescription drugs and related supplies has recently come under increased scrutiny from the U.S. Congress, the Department of Health and Human Services, the General Accounting Office, and the Federal Trade Commission. In light of these and future activities, ASHP determined that there was a need to collect credible data on the potential impact of the termination of the Robinson-Patman Act's nonprofit institutional exemption, other discounts, or both on pharmaceutical expenditures in institutional health-care settings. The authors of this paper report the results and analysis of a 1990 mail survey conducted by ASHP and Concepts in Healthcare, Inc., to collect information on pharmaceutical purchasing and discounting procedures in community hospitals and selected nonhospital settings in the United States. Survey respondents reported that they would expect substantial increases in pharmaceutical expenditures if volume and nonprofit discounts were eliminated. Nonprofit hospitals expected a 24.4% increase in pharmaceutical expenditures in the wake of discount elimination, while for-profit institutions projected an 11.9% increase. Pharmaceutical expenditures of the study hospitals averaged $1.69 million per year; respondents estimated that this sum would increase by $390,000 (23.1%) if volume and nonprofit discounts were eliminated.

Cost Control↗
PubMed1991

Biodegradation of 1-nitropyrene.

The metabolism of 14C-labeled 1-nitropyrene in microcosms containing nonsterile estuarine sediments, and in cultures of a Mycobacterium sp. previously isolated from oil-contaminated sediments was investigated. Although mineralization of 1-nitropyrene by pure cultures of the Mycobacterium sp. totaled only 12.3% after 10 days of incubation, over 80% of the ethyl acetate extractable 14C-labeled compounds consisted of 1-nitropyrene metabolites. High pressure liquid chromatographic analysis of 1-nitropyrene degradation products indicated that two major metabolites were formed. They were identified as 1-nitropyrene cis-9,10- and 4,5-dihydrodiols, based on their UV-visible, mass and NMR spectra. Time course studies in microcosms showed that 1-nitropyrene was degraded slowly under aerobic and anaerobic conditions in estuarine sediments. Less than 1% had been converted to 14CO2 after 8 weeks of aerobic incubation. The addition of 1-nitropyrene to anaerobic sediments resulted in no 14CO2 evolution; however, the nitro group of 1-nitropyrene was reduced to form 1-aminopyrene. Although the mineralization of 1-nitropyrene in sediments was slow, the Mycobacterium sp. metabolized 1-nitropyrene in pure culture. This bacterium appears promising for the bioremediation of this ubiquitous pollutant in contaminated waste.

Aerobiosis↗
PubMed1991

Formation of C8-modified deoxyguanosine and C8-modified deoxyadenosine as major DNA adducts from 2-nitropyrene metabolism mediated by rat and mouse liver microsomes and cytosols.

2-Nitropyrene, the geometric isomer of the most studied nitropolycyclic aromatic hydrocarbon (nitro-PAH), 1-nitropyrene, is an environmental contaminant detected in ambient air and a potent direct-acting mutagen. Its metabolic activation leading to the formation of DNA adducts was studied. The activated metabolite, N-hydroxy-2-aminopyrene, was prepared and reacted with calf thymus DNA. Upon enzymatic hydrolysis of the DNA, the resulting nucleosides were separated by HPLC, and the adducts were characterized by mass and proton NMR spectral analysis. Both N-(deoxyguanosin-8-yl)-2-aminopyrene and N-(deoxyadenosin-8-yl)-2-aminopyrene, in a 5:2 ratio, were identified. These adducts were then utilized as standards to identify the DNA adducts formed from reaction of [3H]2-nitropyrene with DNA mediated by liver microsomes and cytosols of mouse and rat. In all cases, both adducts were formed. The quantities of the two adducts formed in each system were: mouse liver microsomes (11.3 pmol [3H]2-nitropyrene/mg DNA), rat liver microsomes (23), mouse liver cytosol (11.4) and rat liver cytosol (5.1). Thus, these adducts were formed in highest yield from rat liver microsomes and the lowest from rat liver cytosol. The deoxyguanosine/deoxyadenosine adduct ratio was higher from rat and mouse liver microsomes (7.8:9.2) than from rat and mouse liver cytosols (2.5:3.1). Our results represent the first direct demonstration of a C8-deoxyadenosine adduct being formed as a major product from the reaction of a nitro-PAH metabolite with DNA.

Animals↗