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D T Nguyen

Publications and source records attributed to D T Nguyen.

At least 73 records · Page 4Linked to original sources
PubMed1990

Role of tumor necrosis factor-alpha in lipopolysaccharide-induced pathologic alterations.

Tumor necrosis factor-alpha (TNF) has been implicated strongly as a principal mediator in the pathogenesis of septic shock. The authors investigated the in vivo production of TNF in CBA/J and CD-1 mice that had been primed by an intraperitoneal injection of complete Freund's adjuvant followed 2 weeks later by an intraperitoneal injection of lipopolysaccharide (LPS). TNF bioactivity peaked in both the ascites and plasma one hour after challenge, and TNF mRNA expression in the ascites cells peaked 30 minutes after LPS. After the induction of bioactivity, an interstitial pulmonary neutrophilic infiltrate occurred that was quantitated both morphometrically and by a myeloperoxidase (MPO) assay. Peripheral blood neutrophilia and lymphopenia developed after the LPS injection (PMNs: control, 46 +/- 2%; LPS, 65 +/- 3%; Lymphs control, 53 +/- 2%; LPS, 37 +/- 3%). Treatment with dexamethasone (Dex) completely inhibited the pulmonary neutrophilic infiltrate as measured by the (MPO) assay. Because Dex will inhibit the production of several cytokines, anti-TNF antiserum was given to mice at the same time as the LPS challenge to assess specifically the role of TNF in inducing these changes. This antiserum partially blocked the pulmonary neutrophil infiltrate, and completely blocked the peripheral blood changes at one hour after LPS. These data demonstrate that TNF plays an important role in the early pathophysiologic alterations that occur after systemic exposure to LPS.

Animals↗
PubMed1989

Two-dimensional NMR and photo-CIDNP studies of the insulin monomer: assignment of aromatic resonances with application to protein folding, structure, and dynamics.

The aromatic 1H NMR resonances of the insulin monomer are assigned at 500 MHz by comparative studies of chemically modified and genetically altered variants, including a mutant insulin (PheB25----Leu) associated with diabetes mellitus. The two histidines, three phenylalanines, and four tyrosines are observed to be in distinct local environments; their assignment provides sensitive markers for studies of tertiary structure, protein dynamics, and protein folding. The environments of the tyrosine residues have also been investigated by photochemically induced dynamic nuclear polarization (photo-CIDNP) and analyzed in relation to packing constraints in the crystal structures of insulin. Dimerization involving specific B-chain interactions is observed with increasing protein concentration and is shown to depend on temperature, pH, and solvent composition. In the monomer large variations are observed in the line widths of amide resonances, suggesting intermediate exchange among conformational substates; such substates may relate to conformational changes observed in different crystal states and proposed to occur in the hormone-receptor complex. Additional evidence for multiple conformations in solution is provided by comparative studies of an insulin analogue containing a peptide bond between residues B29 and A1 (mini-proinsulin). This analogue forms dimers and higher-order oligomers under conditions in which native insulin is monomeric, suggesting that the B29-A1 peptide bond stabilizes a conformational substate favorable for dimerization. Such stabilization is not observed in corresponding studies of native proinsulin, in which a 35-residue connecting peptide joins residues B30 and A1; this extended tether is presumably too flexible to constrain the conformation of the B-chain. The differences between proinsulin and mini-proinsulin suggest a structural mechanism for the observation that the fully reduced B29-A1 analogue folds more efficiently than proinsulin to form the correct pattern of disulfide bonds. These results are discussed in relation to molecular mechanics calculations of insulin based on the available crystal structures.

Circular Dichroism↗
PubMed1989

Cyclosporine A inhibits TNF production without decreasing TNF mRNA levels.

The role of cytokines in health and disease has received increasing attention and numerous investigations have explored the regulation of cytokine gene expression. Tumor necrosis factor-alpha (TNF) has received particular attention because of its central role in septic shock and more recent work has shown its participation in transplant immunology. We explored the mechanism of cyclosporine A (CsA) modulation of complete Freunds adjuvant macrophage (CFA-MO) TNF gene expression. From 0.001 to 1 microgram/ml, CsA dose-dependently inhibited lipopolysaccharide (LPS) induced secreted bioactivity; at doses above 10 micrograms/ml CSA was directly toxic to CFA-MO. However, there was no suppression of TNF mRNA levels, and CsA also did not inhibit the accumulation of cell-associated TNF. Thus, CsA modulates TNF gene expression in a previously undescribed manner.

Animals↗
PubMed1989

Adjuvant activity of respirable iron ore dust.

The influence of the respirable fraction of an iron ore dust on immunity has been studied. The iron ore dust enhanced the specific immune responses to both sheep erythrocytes and a bacterial lipopolysaccharide. The IgG class of antibody was enhanced significantly and its pattern of enhancement suggested that the iron ore dust was functioning as an adjuvant. In studies to test this possibility further, the pattern of antibody development over both the primary and the secondary immune response to sheep erythrocytes closely matched that of Freund's incomplete adjuvant and low levels of silica. The splenocytes, from animals that had received iron ore dust for various lengths of time, exhibited enhanced polyclonal mitogenic activity for phytohaemagglutinin, in vitro. These properties were seen when the dust had been inhaled or injected into the pleural cavity and persisted for over 1 year following the injection or inhalation of the dust. Attempts to show the induction of interleukin-1 by the macrophages from mice implanted intraperitoneally with the iron ore dust were unsuccessful.

Adjuvants, Immunologic↗
PubMed1987

Stimulation of prostaglandin E2 and thromboxane B2 production by human monocytes in response to interleukin-2.

Interleukin 2 (IL-2) is a potent lymphokine involved in the regulation of immune responses and is classically regarded as a stimulus for the activation and growth of T-cells. Recent reports have demonstrated the IL-2 dependent activation of human peripheral blood lymphocytes into lymphokine activated killer cells capable of lysing tumor cells both in vitro and in vivo. In this study we report data which clearly show IL-2 may also act to down-regulate the immune response by inducing the synthesis of arachidonic acid metabolites with known immunosuppressive actions. Stimulation of peripheral human blood monocytes with IL-2 caused an increased production of prostaglandin E2 (PGE2) and thromboxane (TXB2) in a dose-dependent manner. Kinetic analysis showed no increase above controls after 6 hours and maximal levels by 10 hours; elevated levels were maintained after 45 hours of incubation. After 20 hours of stimulation with 2000 U/ml IL-2, the level of PGE2 and TXB2 were greater than three-fold above controls, 0.7 and 19 ng/10(6) cells, respectively. The stimulation was relatively specific in that neither prostacyclin nor leukotrienes were produced in response to IL-2. These data demonstrate that IL-2 acts on human monocytes to induce the secretion of PGE2 and TXB2.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Effects of chronic daily exposure to tobacco smoke on the high leukemic AKR strain of mice.

Daily exposure of the high leukemic AKR strain of mice to low levels of fresh tobacco smoke (TS) produces significantly different mortality profiles associated with both the sex of the animals and the age at which TS exposure commences. Females tend to be susceptible and die sooner than males, where a significant proportion of animals survives longer than age-matched controls. This prolongation of life appears to be due to a failure of the leukemic state to be mobilized in the TS-exposed males. Exposure of both the females and the males to the TS does not induce significant detectable immunological reactivity against the leukemic cells for several parameters tested, possibly due to a significant enhancement of suppressor activity in the serum of the chronically exposed animals over and above that which also occurs in age-matched control animals.

Age Factors↗
PubMed1984

Microprocessor-based speech processing system.

Durational measurements of frication, aspiration, prevoicing, and voice onset are often difficult to perform from the spectrogram, and the resolution is limited to about 5 ms. In many instances, a higher resolution can be obtained from a study of waveforms than from a study of spectrum. We present a microprocessor-based speech acquisition and processing system which uses waveform analysis techniques to extract measurements from the acoustic signal. The system is low cost and portable; it operates in "real time" and employs noninvasive data-capturing techniques. The usefulness of the system is demonstrated in the VOT measurement of CV clusters and in the measurement of fundamental frequency.

Computers↗
PubMedDate not supplied

Multiparameter interpretative reporting in diagnostic laboratory hematology.

Accurate diagnosis and classification of hematologic malignancies (acute leukemias and chronic lymphoproliferative disorders) requires a multiparameter approach including peripheral blood analysis, bone marrow examination, and immunophenotyping. We have designed knowledge-based computer systems for interpretation of the hemogram and peripheral blood smears, analysis of flow cytometric immunophenotyping panels, and morphologic assessment of bone marrow specimens. The 3 modules share a relational database which includes pertinent clinical history in addition to the laboratory results. The bone marrow module automatically writes a complete interpretative report with a final diagnosis by searching all of the databases for appropriate clinical, peripheral blood, and immunophenotyping information. The ability of the 3 modules to interact, and the quality of the interpretative reports were tested on 100 consecutive patients with leukemia. The final diagnosis made by the bone marrow system agreed with the hospital diagnosis in 94 cases and the authors' interpretation in 99 of 100 cases.

Artificial Intelligence↗
PubMedDate not supplied

Multiparameter case studies using knowledge-based systems in hematology.

Knowledge-based systems in diagnostic medicine are often used for teaching medical decision making. We have extended the educational value of our suite of hematology decision support systems (peripheral blood analysis, flow cytometry immunophenotyping and DNA analysis, and bone marrow morphology) by creating case studies in a hypertext format. The case studies use the knowledge-based system screens as a background. Digitized images of blood and bone marrow smears from the teaching cases can be accessed on-line. The case studies, which are designed primarily for technologists and physicians, emphasize the proper multiparameter approach to hematopathology diagnosis.

Decision Support Techniques↗
PubMedDate not supplied

Anesthetic management of the patient scheduled for head and neck cancer surgery.

For the patient scheduled for head and neck cancer surgery, careful assessment of the airway demonstrates the most appropriate course of action for securing the airway before surgery begins. Often the patient may be anesthetized safely before intubation of the trachea. The patient may require an awake examination of the airway under sedation and topical analgesia or an awake fiberoptic intubation before the induction of general anesthesia. To secure the airway in some patients, a tracheostomy may be needed. After the operation, extubation of the trachea requires careful attention and may be even more of a challenge than the original intubation. Current principles and techniques for the anesthetic management of the patient undergoing head and neck cancer surgery are reviewed. Emphasis is placed on avoiding the airway problems associated with this kind of surgery.

Anesthesia↗
PubMedDate not supplied

Correlates of drug use and abuse among Indochinese refugees: mental health implications.

The results of this study suggest that problems with alcohol and other drugs, including tobacco, will become an increasingly important issue for the Indochinese refugee community. Although the problem is relatively small in comparison to the magnitude of the problem among other disadvantaged populations, the refugees still view this issue as troublesome for their community, especially for the younger generation. A significant number of refugees use alcohol and other drugs, including tobacco, as coping mechanisms to deal with their problems, and find their own behavior troublesome. This warrants further study in order to find the conditions under which substance abuse can be decreased and prevented. The present study suggests that adjustment and mental health problems, with the lack of social and institutional support, may be one of the major reasons refugees turn to psychoactive substances to alleviate their stresses and to forget their problems. Substance abuse among refugees creates enormous health risks for a population that is already at greater risk than the general American population. Preventive measures should be implemented at this critical moment in time so that this small problem will not grow into a larger one.

Adaptation, Psychological↗
PubMedDate not supplied

Are normative expert systems appropriate for diagnostic pathology?

Conceptual models for diagnostic reasoning proposed in the medical literature are presented to stimulate discussion about the issue of the appropriateness of probabilistic knowledge-based systems for medical diagnosis. Evidence is presented to corroborate the authors' view that diagnosis is a problem-solving task, rather than a decision-making task. In the authors' opinion, probabilistic reasoning is better suited to situations dealing with choices for clinical intervention, rather than to those dealing with determining the correct diagnosis. A critique is given of a diagnostic Bayesian expert system for lymph node pathology. In empirical studies, diagnostic Bayesian systems have been shown to typically list the correct diagnosis as the program's first choice 60% to 70% of the time. One reason for this undistinguished level of diagnostic performance is that Bayesian systems are not designed to represent and use knowledge the same way that an expert does.

Bayes Theorem↗