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Biomedical subjects

D E Miller

Publications and source records attributed to D E Miller.

At least 37 records · Page 2Linked to original sources
PubMed1996

FISH localization of the soluble thymidine kinase gene (TK1) to human 17q25, a region of chromosomal loss in sporadic breast tumors.

Soluble thymidine kinase (TK1) is an important 17q marker in somatic cell genetics. Its activity is increased in many malignancies, including breast cancer. Through somatic cell hybrid and fluorescence in situ hybridization studies, we mapped TK1 to 17q25.2-->25.3, in region demonstrating loss of heterozygosity in primary breast tumors. It lies near D17S836 and is proximal to the avian erythroblastic leukemia viral oncogene homolog 2-like gene (ERBA2L).

Animals↗
PubMed1996

Molecular cloning of a novel receptor (CMKLR1) with homology to the chemotactic factor receptors.

We report the cloning of a novel human gene, CMKLR1, which encodes a protein that has notable sequence and structural homology to the seven transmembrane G-protein linked chemokine receptors. This gene has 55% nucleotide sequence homology to the IL-8 type 1 receptor and 53% to the N-formyl peptide related receptor 1 genes. The mRNA of this receptors is expressed in a broad array of tissues associated with hematopoietic and immune function including, spleen, thymus, appendix, lymph node, bone marrow, and fetal liver. Using fluorescence in situ hybridization the gene encoding CMLKR1 (chemokine-like receptor 1) was localized to human chromosome 12q24.1.

Amino Acid Sequence↗
PubMed1995

Chromosomal localization of the ankyrinG gene (ANK3/Ank3) to human 10q21 and mouse 10.

The ankyrin3 gene encodes a novel form of ankyrin, AnkyrinG, expressed in multiple tissues but characteristically present at the axonal initial segment and nodes of Ranvier of neurons in the central and peripheral nervous systems. We have localized ANK3 to human Chromosome 10q21 by fluorescence in situ hybridization. The position of the murine homologue was determined by intersubspecific backcross analysis, mapping Ank3 to mouse Chromosome 10, between microsatellite marker D10Mit31 and the Bcr gene. This interval is known to comprise a region syntenic to human 10q. The localization of ANK3 is a preliminary step in identifying neurological disorders potentially associated with the gene.

Animals↗
PubMed1995

The effect on diagnostic quality of using dual isotope imaging for 81Krm ventilation and 99Tcm-MAA perfusion lung scanning.

It is the practice in some centres to use dual isotope imaging to reduce imaging times in lung ventilation and perfusion studies with 81Krm gas and 99Tcm-macroaggregated albumin (99Tcm-MAA) by simultaneous acquisition of the two images. The resulting loss of image caused by cross-talk between the two energy windows was investigated using two phantoms, one with cold 99Tcm lesions of varying size and contrast, and the other a uniform field of 81Krm. It was found that, under scatter conditions typical of a patient study, the use of dual isotope acquisition and a krypton generator of 470 MBq or greater resulted in a perceptible loss of image quality with lesions up to 4 cm in diameter being missed. On an older camera system, without modern energy and linearity correction facilities, a lower generator activity of only 120 MBq was sufficient to cause image degradation even under very low scatter conditions. Seventy-five patient studies were performed using both single and dual isotope imaging with generator activities ranging from 80 to 282 MBq. At these low generator activities, the studies did not demonstrate any differences between the images that would result in a different diagnosis. We conclude that the use of dual isotope V/Q scanning reduces the diagnostic value of the perfusion image if the activity of the 81Krm generator is too high, although at generator activities of 300 MBq or less no loss of image quality will occur on modern camera systems.

Humans↗
PubMed1995

Physiological relevance of T-tube model parameters with emphasis on arterial compliances.

The T-tube model of systemic arterial circulation was examined with respect to the physiological relevance of model parameters. root aortic pressure [Pao(t)] and flow [Qao(t)] and descending aortic flow [Qb(t)] were measured in anesthetized, open-chest dogs under control conditions, during inflation of a balloon positioned in the left external iliac artery (n = 5), and during infusion of vasoactive drugs nitroprusside (NTP, n = 4) and phenylephrine (PHL, n = 5). With Pao(t) as the input, the model accurately predicted both Qao(t) and Qb(t) under all conditions (r2 > 0.96). The balloon inflation data established the ability of the model to discriminate between proximal and distal arterial mechanical properties. Furthermore, proximal properties (i.e., tube characteristic impedances and transit times) were independent of distal properties such as terminal compliances and resistances (or equivalently, wave reflections). The effects of NTP and PHL were pharmacologically consistent and served to further validate this model. NTP primarily affected distal (load) properties, whereas PHL altered both load and tube parameters. Physiological interpretation of model parameters, particularly compliance, is also discussed. The ability of the model to correctly discriminate between proximal and distal arterial properties is relevant because these properties may affect cardiovascular function differently.

Animals↗
PubMed1994

Sustained expression of TGF-beta 1 underlies development of progressive kidney fibrosis.

We found that TGF-beta 1 expression and increased matrix production is transient and self-limited in nephritic glomeruli from rats with acute, reversible glomerulonephritis induced by a single injection of an antibody reactive with glomerular mesangial cells. In contrast, in rats given a second antibody injection, one week later, the glomerular expression of TGF-beta 1 mRNA and TGF-beta 1 protein remained elevated through 18 weeks and was associated with a large infiltration of mononuclear cells, with staining features of fibroblastic/myofibroblastic cells, strongly expressing TGF-beta 1 in the tubulointerstitium of the kidney. By 18 weeks kidneys from animals receiving two antibody injections showed glomerulosclerosis and tubulointerstitial fibrosis with striking deposition of collagens type I and III, whereas kidney tissue from animals given one antibody injection was indistinguishable from normal control. The histological changes were accompanied by persistent proteinuria and elevated levels of blood urea nitrogen. Extracellular matrix markers of TGF-beta 1 activity, a special isoform of fibronectin, tenascin, biglycan and plasminogen activator inhibitor-1, were significantly elevated in kidneys undergoing fibrosis. These data suggest that sustained TGF-beta 1 expression contributes to the development of progressive kidney fibrosis.

Animals↗
PubMed1994

Angiotensin II stimulates extracellular matrix protein synthesis through induction of transforming growth factor-beta expression in rat glomerular mesangial cells.

Angiotensin II (Ang II) has been implicated in the development of progressive glomerulosclerosis, but the precise mechanism of this effect remains unclear. In an experimental model, we have shown previously that TGF-beta plays a key role in glomerulosclerosis by stimulating extracellular matrix protein synthesis, increasing matrix protein receptors, and altering protease/protease-inhibitor balance, thereby inhibiting matrix degradation. We hypothesized that Ang II contributes to glomerulosclerosis through induction of TGF-beta. Ang II treatment of rat mesangial cells in culture increased TGF-beta and matrix components biglycan, fibronectin, and collagen type I at both the mRNA and protein levels in a time- and dose-dependent manner. Saralasin, a competitive inhibitor of Ang II, prevented the stimulation. Ang II also promoted conversion of latent TGF-beta to the biologically active form. Coincubation of mesangial cells with Ang II and neutralizing antibody to TGF-beta blocked the Ang II-induced increases in matrix protein expression. Continuous in vivo administration of Ang II to normal rats for 7 d resulted in 70% increases in glomerular mRNA for both TGF-beta and collagen type I. These results indicate that Ang II induces mesangial cell synthesis of matrix proteins and show that these effects are mediated by Ang II induction of TGF-beta expression. This mechanism may well contribute to glomerulosclerosis in vivo.

Angiotensin II↗
PubMed1992

Outcome of pregnancy during imprisonment.

The scant available information on pregnancies in women in prison suggests that the outcome is poor. We studied a cohort of 69 incarcerated pregnant women cared for over a one-year period. They were compared with 69 controls who were matched for age, parity, race and date on which they entered prenatal care. Thirty-six percent of the prisoners acknowledged using illicit drugs, primarily cocaine, during their pregnancies as compared to 3% of the controls. Sixty-eight percent of the incarcerated women smoked cigarettes as compared with 20% of the controls. In spite of those facts, there was a tendency toward better pregnancy outcomes among the prisoners. They were less likely to deliver prematurely (10% vs. 22%) and significantly less likely to experience premature rupture of the membranes (2.8% vs. 2.6%, P less than .001).

Adult↗
PubMed1989

Activation-dependent redistribution of the adhesion plaque protein, talin, in intact human platelets.

Talin is a high molecular weight protein localized at adhesion plaques in fibroblasts. It binds vinculin and integrin and appears to participate in generating a transmembrane connection between the extracellular matrix and the cytoskeleton. We have recently shown that talin is an abundant protein in platelets, cells highly specialized for regulated adhesion. Although talin constitutes greater than 3% of the total protein in intact human platelets, its location within the cells had not been defined. In the work reported here, we have investigated the distribution of talin in resting and activated human platelets by immunofluorescence and immunoelectron microscopy. We have found that talin undergoes an activation-dependent change in its subcellular location. In resting platelets, which are nonadhesive, talin is uniformly distributed throughout the cytoplasm. In contrast, in thrombin- and glass-activated, substratum-adherent platelets, talin is concentrated at the cytoplasmic face of the plasma membrane. This dramatic, regulated redistribution of talin raises the possibility that talin plays a role in the controlled development of platelet adhesion.

Blood Platelets↗
PubMed1986

Superoxide dismutase and catalase: a possible role in established pancreatitis.

The mechanism of cerulein-induced acute pancreatitis may involve the production of free radicals in excess of the capacity of endogenous intracellular scavengers. These radicals destroy the cellular membranes, releasing digestive enzymes and cellular proteins into the interstitium. Thereafter, a cascade of events, including polymorphonuclear infiltration and complement activation, leads to pancreatic destruction. The present study demonstrates that superoxide dismutase and catalase reduce the ultrastructural and biochemical injury associated with cerulein-induced acute pancreatitis in rats. Pretreatment with superoxide dismutase and catalase 30 minutes before injury did not appear to be protective, presumably because the half-life of intravenous superoxide dismutase is only 6 minutes. This and similar studies suggest a potential clinical role for free radical scavengers in acute established pancreatitis.

Acute Disease↗
PubMed1986

Limited joint mobility (LJM) of the hand in patients with diabetes mellitus: relation to chronic complications.

Limited joint mobility (LJM) of the hand was studied by visual examination in 361 diabetic outpatients aged 11 to 83 years, and 45 non-diabetic controls, without evidence of arthritis. LJM was evident in 58% of diabetic subjects and 4% of controls (p less than 0.001). LJM was noted in 131 (55%) of the 238 patients with insulin-dependent diabetes mellitus (IDDM) as opposed to 31 of the 41 patients (76%) with non-insulin-dependent diabetes mellitus (NIDDM). LJM occurred in 60 of the 82 diabetic subjects (73%) receiving insulin therapy who developed diabetes after the age of 35 years. LJM was significantly related to duration of diabetes in the patients with IDDM less than 40 years of age but was not associated with duration in the patients with NIDDM. A significant association of LJM and neuropathy was noted in patients less than 40 years of age with less than 20 years of diabetes. A significant association of LJM and retinopathy was also noted in those less than 40 years of age with less than 30 years of diabetes. There was no association of LJM and nephropathy regardless of age or duration of diabetes.

Adolescent↗
PubMed1985

An economic comparison of Tubex injection systems with traditional ampuls and vials.

A time and motion study was performed at the Hospital of the University of Pennsylvania to measure and compare the direct and indirect costs of the original Tubex and Tubex Fast-Trak injection systems with comparable costs associated with single dose ampuls, vials, and multi-dose vials. Data collection involved observation of 170 injections prepared by 29 nurses on two oncology units over a 7-week period. The time and nondrug supply costs of the Tubex Fast-Trak were lower than those of all other injection systems observed, including the original Tubex. Although the drug acquisition component was higher for the Tubex systems than for conventional injection methods, an analysis of the total cost of the use of Tubex Fast-Trak demonstrated that on an annual basis, the system is nearly equal in cost to the use of single ampuls and vials. Important advantages of the prefilled cartridge system should be considered in addition to labor, supply, and drug costs when selecting cost-effective injection systems. Systems like Tubex offer advantages that may lower total cost of care, such as reduction in wastage, pilferage, contamination, dosage error, and improved cost allocation accuracy. When polled about their opinion, the majority of nurses who participated in the study indicated that Tubex Fast-Trek was their first choice over other injection methods observed.

Costs and Cost Analysis↗
PubMed1984

Improving pharmacy and therapeutics committee operations.

A panel discussion of various aspects of the operations of pharmacy and therapeutics (P & T) committees is presented. Pharmacy and therapeutics committee operations in various types and sizes of hospitals are described. Ways of stimulating physicians' interest in P & T committee activities, difficult problems faced, scope of issues dealt with by P & T committees, functions of P & T subcommittees, the value of drug information from pharmaceutical representatives, and the influence of research funds from the pharmaceutical industry on committee decisions are discussed. Panel members also present their views on therapeutic alternates, FDA-nonapproved use of drugs, and counter-detailing. Finally, suggestions for improving P & T drug evaluations, cost-containment issues, and the authority of P & T committees are discussed. A well-prepared agenda, good educational material, active members, and strong leadership are important for successful P & T committee operations.

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