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Biomedical subjects

D M Moore

Publications and source records attributed to D M Moore.

At least 19 recordsLinked to original sources
PubMed1996

Transendothelial insulin transport is not saturable in vivo. No evidence for a receptor-mediated process.

In vitro, insulin transport across endothelial cells has been reported to be saturable, suggesting that the transport process is receptor mediated. In the present study, the transport of insulin across capillary endothelial cells was investigated in vivo. Euglycemic glucose clamps were performed in anesthetized dogs (n = 16) in which insulin was infused to achieve concentrations in the physiological range (1.0 mU/kg per min + 5 mU/kg priming bolus; n = 8) or pharmacologic range (18 mU/kg per min + 325 mU/kg priming bolus; n = 8). Insulin concentrations were measured in plasma and hindlimb lymph derived from interstitial fluid (ISF) surrounding muscle. Basal plasma insulin concentrations were twice the basal ISF insulin concentrations and were not different between the physiologic and pharmacologic infusion groups (plasma/ISF ratio 2.05 +/- 0.22 vs 2.05 +/- 0.23; p = 0.0003). The plasma/ISF gradient was, however, significantly reduced at steady-state pharmacologic insulin concentrations (1.37 +/- 0.25 vs 1.98 +/- 0.21; P = 0.0003). The reduced gradient is opposite to that expected if transendothelial insulin transport were saturable. Insulin transport into muscle ISF tended to increase with pharmacologic compared with physiologic changes in insulin concentration (41% increase; 1.37 +/- 0.18 10(-2) to 1.93 +/- 0.24 10(-2) min-1; P = 0.088), while at the same time insulin clearance out of the muscle ISF compartment was unaltered (2.53 +/- 0.26 10(-2) vs 2.34 +/- 0.28 10(-2) min-1; P = 0.62). Thus, the reduced plasma/ISF gradient at pharmacologic insulin was due to enhanced transendothelial insulin transport rather than changes in ISF insulin clearance. We conclude that insulin transport is not saturable in vivo and thus not receptor mediated. The increase in transport efficiency with saturating insulin is likely due to an increase in diffusionary capacity resulting from capillary dilation or recruitment.

Animals↗
PubMed1996

Vaccinia virus A17L open reading frame encodes an essential component of nascent viral membranes that is required to initiate morphogenesis.

We generated an antiserum to the predicted C-terminal peptide of the A17L open reading frame (ORF), which encodes a 23-kDa polypeptide with hydrophobic regions characteristic of membrane proteins. Immuno-electron microscopy of infected cells indicated that the A17L protein is intimately associated with the earliest characteristic viral membranes, even those formed in the presence of the drug rifampin. To study the role of the A17L protein in morphogenesis, we constructed recombinant vaccinia viruses in which the endogenous A17L ORF was deleted and a copy of the ORF under the control of the bacteriophage T7 RNA polymerase and the Escherichia coli lac repressor was inserted into an alternative site in the vaccinia virus genome. Growth of these recombinant viruses was entirely dependent on the induction of A17L expression by isopropyl-beta-D-thiogalactopyranoside. Electron microscopic examination of cells infected in the absence of inducer revealed the accumulation of large, well-demarcated electron-dense aggregates but no characteristic membrane-associated viral structures. Viral late protein synthesis occurred under these conditions, although the maturational proteolytic processing of structural proteins was inhibited. We conclude that the product of the A17L gene is an essential component of the immature viral membrane and has an early function in viral morphogenesis.

Animals↗
PubMed1995

A proposed architecture for ambulatory systems development.

We have developed an architecture and application framework known as the Ambulatory Services Architecture (ASA) for computerized management of patient records for ambulatory care. Our primary design goals included the development of an architecture that will be readily adaptable to advances in technology needed to enhance computerized patient record systems (e.g., multimedia, human-computer interfaces such as voice-to-text, and a fully distributed objects, etc.) and a data model and database implementation capable of providing the flexibility and extensibility needed to support a broad spectrum of specialty medical practices. This report describes the data model, access control, and the client/server components of the Ambulatory Services Architecture.

Ambulatory Care Information Systems↗
PubMed1995

Collaborative social and medical service application.

Baylor College of Medicine has five Teen Health Clinics (THC) dispersed throughout Harris county. The population served by the clinics includes inner-city adolescent boys and girls 19 years of age and under. Patients receive services such as family planning, sexually transmitted disease screening and treatment, perinatal care, counseling, and support services. Adolescents may receive services at any one of the clinics at no cost to the adolescent or their dependents. Given the geographical distribution of the clinics and the reliance on paper-based records, client services cannot be provided efficiently or expeditiously. According to the statistics developed by Clinic staff, ineffective coordination of service needs and client schedules undermine the follow-up needed for effective care. For example, a counselor will often need to balance a school schedule, clinic visits, well baby follow-up, and the Best Friends Program for a new mother. In addition, the lack of ready access to patient information impairs the ability of clinical and social service staff to provide continuity of care. In fact, some cases of client dropout are attributable to these difficulties. We have developed the Collaborative Social and Medical Service Application (CSMSA) to facilitate the provision of social and medical services to this population. The CSMSA is a domain-specific application based on a robust infrastructure known as the Ambulatory Services Architecture (ASA). This system is designed to support integrated social and ambulatory care. The ASA is a Baylor developed application framework and architecture for the computerization of the patient medical record in the ambulatory care setting. The working environment for the CSMSA user is an integrated desktop which provides an operating environment for both third-party applications and the CSMSA, as well as a fundamental set of services. The integrated desktop services include a mechanism for object organization or grouping, a facility for the management of desktop objects including disposal and storage, and an embedded search utility to assist in the location of desktop objects as well as other application objects. The access control mechanism will provide the security for the desktop environment by requiring the user to log into and out of the environment. This security mechanism will also enable/disable CSMSA tools based on the user's role at the clinic. The CSMSA is designed to provide work process, functionality and data access appropriate to the responsibilities of the user, e.g., a THC clerk may have permission to view a patient's orders but does not have the facility to create an order. Patient context is defined through a patient browser containing the master patient index or a user defined patient list. Patient encounters are managed using forms based on the process for each encounter type (e.g., initial visit). Forms are used for data entry and for queries. Data entry forms are only committed to the patient database (i.e., making the patient data available to other users who have permission to access the data) when the user approves the data. The CSMSA provides a means to suspend an entry into a chart by saving incomplete or non-committed data entry forms as part of the desktop state which is restored when the user logs into the system. CSMSA was designed to provide a robust, expandable application capable of accommodating the changes in health care and social services delivery while encompassing evolving software standards and new technology. This goal was achieved using object-oriented methodologies and technologies, combined with an object-oriented database management system as the foundation of our server to facilitate the evolution of our data model.

Adolescent↗
PubMed1994

Dynamics of glucose production and uptake are more closely related to insulin in hindlimb lymph than in thoracic duct lymph.

We previously reported a striking similarity between the dynamics of both glucose turnover and thoracic duct lymph insulin during euglycemic clamps (J Clin Invest 84:1620, 1989), which suggested that transendothelial insulin transport (TET) is rate-limiting for insulin action in vivo. Thoracic duct lymph, however, is primarily derived from insulin-insensitive tissues, which raises questions as to the physiological significance of this relationship. The relationship between glucose turnover and TET was thus examined in insulin-sensitive tissues by the simultaneous measurement of insulin in plasma, thoracic duct lymph, and hindlimb lymph during euglycemic clamps in normal anesthetized dogs (n = 8). Clamps consisted of two 3-h phases: a 0.6 mU.min-1.kg-1 insulin infusion (activation phase) followed by termination of the insulin infusion (deactivation phase). Lymph insulin was less than plasma insulin during both phases (P < 0.01) with steady-state hindlimb (120 +/- 12 pM) and thoracic duct lymph insulin (138 +/- 12 pM) 38 and 45%, respectively, lower than steady-state plasma insulin (222 +/- 24 pM) at the end of the activation phase (P < 0.05). Also, the rate of increase of lymph insulin was slower than plasma insulin during hormone infusion; half-time to steady-state was 8.8 +/- 2.0 min for plasma insulin, but longer for thoracic (25.8 +/- 3.5) and hindlimb lymph insulin (40.7 +/- 5.7 min). A very close relationship was observed during activation between the rate of increase of glucose uptake (Rd) and the increase in hindlimb lymph insulin (r2 = 0.92); this relationship was weaker for thoracic lymph (r2 = 0.74) and much weaker between glucose uptake and plasma insulin (r2 = 0.35). These data support the concept that interstitial insulin (represented by hindlimb lymph) is the signal that determines glucose uptake by insulin-sensitive tissues and that the rate of increase of glucose uptake is determined by transendothelial insulin transport into insulin-sensitive tissue. Also, during activation, hindlimb lymph insulin was a very strong predictor of the rate of suppression of hepatic glucose output (HGO) (r2 = 0.96), and the correlation with HGO was stronger than that for thoracic lymph (r2 = 0.85). The evidence that the rate of increase of Rd and the rate of suppression of HGO during insulin infusion are very strongly predicted by the time course of insulin in hindlimb lymph is consistent with the single-gateway hypothesis: the insulin transport rate across endothelium in insulin-sensitive tissue (skeletal muscle) determines the rate of glucose utilization and the suppression of hepatic glucose output.(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of Variance↗
PubMed1994

Effect of cognitive style on test type (visual or verbal) and color coding.

66 field-independent undergraduates achieved significantly higher scores than 43 field-dependent students on drawing, terminology, and comprehension. Color coding was an inconclusive instructional variable, but unexpectedly, subjects who received the verbal tests scored significantly better than those who received the visual test format.

Adult↗
PubMed1994

Retinoic acid and interferon in human cancer: mechanistic and clinical studies.

Various combinations of retinoids, metabolic and synthetic derivatives of vitamin A, and interferons (IFNs) have demonstrated synergistic antiproliferative, differentiating, and antiangiogenic activity in some human hematologic and solid-tumor systems. This synergistic antitumor activity may be due to enhanced gene expression. In several cell systems, the actions of IFNs are enhanced by differentiation of cells with retinoic acid (RA). Combined RA-IFN effects have been correlated with the induction of higher levels of IFN-stimulated genes than the levels induced by either agent alone. Natural and synthetic retinoids have been found to augment the antiproliferative activity of IFNs in several squamous cell carcinoma (SCC) and breast tumor cell lines. Results of recent clinical trials indicate substantial activity of 13-cis-RA (13cRA) combined with IFN against advanced SCC of the skin and cervix, and possibly against other solid tumors. Two phase II trials have confirmed activity against locally advanced SCC of the cervix. Successful integration of this regimen with radiotherapy appears to be the most probable means of optimizing clinical outcome. Further studies are needed to determine the mechanistic details of the RA-IFN interaction.

2',5'-Oligoadenylate Synthetase↗
PubMed1994

The development of a client application for the collaborative social and medical services system.

This paper describes the design and implementation of a client application for the Baylor College of Medicine Teen Health Clinics. The application is the front end to the Collaborative Social and Medical Services System (CSMSS) under development by Baylor's Medical Informatics and Computing Research Program [8]. The application provides distributed access to an underlying object oriented database system. A process driven and patient centered design will provide staff members with a complete set of services, including forms for data entry and viewing, query, and access management to facilitate efficient and effective delivery of services. Role-specific interfaces will be supplied for clerks, nurses, nurse practitioners, physicians, and social workers. The client application is being designed using object oriented methodologies and technologies with the C++ programming language, and will operate within a Microsoft Windows operating environment utilizing Object Linking and Embedding for application interoperability.

Adolescent↗
PubMed1994

Collaborative Social and Medical Service System.

This paper describes the Collaborative Social and Medical Services System, a robust information infrastructure for integrated social and medical care. The Collaborative Social and Medical Services System design and architecture address the primary goals of creating a readily extensible social and ambulatory care system. Our initial step toward reaching this goal is the delivery of an application supporting the operations of the Baylor Teen Health Clinics. This paper discusses our prototype experiences, system architecture, components, and the standards we are addressing.

Adolescent↗
PubMed1993

Phenotypic and functional characterization of mouse attenuated and virulent variants of foot-and-mouth disease virus type O1 Campos.

A series of genetically related variants arising from a parental wild-type isolate of O1 Campos and its tissue culture adapted variant were differentiated by various cell culture markers (temperature sensitivity, plaque size, viral yield) and lethality in mice. These isolates were additionally characterized functionally and biochemically by examining poly(C) length, RNA synthesis, protein synthesis, and cell receptor binding. In primary bovine kidney cells, the virulent isolates had greater levels of protein synthesis, whereas in baby hamster kidney cells, the attenuated variant outproduced the wild-type parent. The tissue culture adapted variant had substantially greater ability to attach to cells than the parental wild type. The parental wild-type and the tissue culture-adapted variant were similarly neutralized by various sera against whole virus, but the parental wild type was less effectively neutralized by sera prepared from either full or truncated (variable region) bacterially expressed VP1 polypeptides. The capsid region of the genomes of both these variants was sequenced and a nucleotide substitution resulting in a change in amino acid 56 in VP3 was found. The nucleotide sequence change for the remaining two variants was that of the parental wild-type virus.

Animals↗
PubMed1993

Imidazole based non-peptide angiotensin II receptor antagonists. Investigation of the effect of the orientation of the imidazole ring on biological activity.

Non-peptide angiotensin II receptor antagonists related to losartan (DuP 753, CAS 114798-26-4) were prepared and evaluated for antagonist activity in the rat isolated uterus assay. The synthetic strategy concentrated on changes in the orientation of the imidazole ring relative to the substituents, which were maintained in a similar pattern to that found in losartan. The results indicate that biological activity of such antagonists shows little dependence on the orientation of the imidazole ring, but that the spacing of the substituents of primary importance.

Acrylates↗
PubMed1993

Cross-reactive idiotopes among anti-foot and mouth disease virus neutralizing antibodies.

Foot and mouth disease virus (FMDV) viral protein 1 is the only one of the four viral proteins (VP) that induces neutralizing antibodies as an isolated protein. A 32 amino acid (AA) residue (32dimer) of FMDV subtype A12 Lp ab VP1 (AA 137-168) was immunogenic against the A12 subtype. Three antibody populations each recognizing different epitopes on 32dimer were isolated by affinity chromatography (AFC) from the serum of a steer which had been immunized with the 32dimer. The 32dimer contains an AA sequence that is recognized by a protective paratope carried on a murine monoclonal antibody (mAb) (7SF-3.H3.1). Polyclonal anti-7SF-3 idiotype antibodies specifically inhibited the binding activity of one of these anti-32dimer antibody populations suggesting the existence of cross-reactive paratopic-related idiotopes between mAb 7SF-3 and antibodies elicited by the 32dimer. These anti-idiotypic antibodies were used in AFC to purify antibodies from the anti-32dimer serum. The purified antibody population has characteristics that resemble those of the mAb 7SF-3, i.e. its reactivity with FMDV A subtypes in ELISA, radioimmunoassay (RIA), mouse neutralization and its lack of reactivity with a mAb 7SF-3 neutralizing escape virus variant. Furthermore, these antibodies were specifically inhibited by either anti-mAb 7SF-3 idiotypic antibodies or peptides containing the mAb 7SF-3 epitope. Using the same experimental approach, mAb 7SF-3 idiotope-bearing antibodies were shown to be present in serum from bovine and swine convalescent from FMDV A12 Lp ab infection. Thus, the highly immunogenic area between residues 137 and 168 of FMDV VP1 elicited a cross-reactive neutralizing idiotope response conserved amongst several animal species.

Animals↗
PubMed1992

Technical note: mineral deposits on Dacron bags during ruminal incubation.

Extensive DM contamination was found on Dacron bags that were incubated for prolonged periods of time in the rumen of steers fed alfalfa hay. The ash content of the contaminant was high, and most of it was acid-soluble X-ray analysis indicated the presence of hydroxylapatite and synthetic calcium magnesium phosphate or whitlockite. The contaminant appeared as a smooth coating on the Dacron fiber, suggesting that contamination was a gradual process rather than the result of entrapment of dislodged crystals from plant material. Contamination seemed to occur exponentially within the range of observations (0 to 42 d). Contamination also occurred in steers fed orchardgrass, although to a lesser extent than in steers fed alfalfa hay. The DM contamination was less than .04 g per bag (average bag weight was 1.2 g) during the first 10 d of incubation. However, correction for contamination might be required for studies involving longterm incubation or mineral digestion.

Animal Feed↗