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Biomedical subjects

T D Nguyen

Publications and source records attributed to T D Nguyen.

At least 109 records · Page 6Linked to original sources

Measurement of bioreduction rates of cells with distinct responses to ionizing radiation and cisplatin.

A low frequency electron paramagnetic resonance (EPR) spectrometer has been used to measure the bioreduction rate of an exogenously added nitroxide free radical species. Measurements have been made in a well controlled, in vitro system using an X-ray and cisplatin sensitive Chinese hamster ovary (CHO) cell line, xrs-5, and partial revertants which display wild-type levels of sensitivity to X-rays but retain xrs-5 levels of cisplatin sensitivity. The xrs-5 cells reduce this radical species at a rate which is approx. 50% that of the wild-type CHO cell line, K1. The partial revertants maintain this defect in bioreduction despite their decrease in radiosensitivity. However, the bioreduction rate observed in these cells correlates with their sensitivity to the chemotherapeutic drug cisplatin. Low frequency EPR allows measurements and imaging of living tissue and may be of value as a predictive assay of human tumor response to chemotherapy.

Animals↗

Stimulation of secretion by the T84 colonic epithelial cell line with dietary flavonols.

Flavonols are dietary compounds widely distributed in plants and characterized by a 2-phenyl-benzo(alpha)pyrane nucleus possessing hydroxyl and ketone groups at positions 3 and 4, respectively. Kaempferol, quercetin, and myricetin are flavonols that are further mono-, di-, or trihydroxylated on the phenyl ring, respectively. To test whether these ingested flavonols might exert a direct secretory effect on intestinal epithelial cells, monolayers of the T84 colonocyte cell line were mounted in Ussing chambers and examined for ion transport response. Twenty minutes after addition of 100 microM quercetin to either the serosal or mucosal side, the short-circuit current change was maximal at 16.6 microA/cm2. Kaempferol was less potent than quercetin, while myricetin and glycosylated quercetin (rutin) did not induce secretion. The secretion induced by quercetin did not seem to be mediated by the reactive oxygen species generated by quercetin through auto-oxidation and/or redox cycling (superoxide, hydrogen peroxide, and the hydroxyl radical) because it was neither enhanced by iron, nor inhibited by desferroxamine B or catalase (alone or in combination with superoxide dismutase). Like vasoactive intestinal peptide, quercetin induced a secretory response that was inhibited by barium chloride and bumetanide, and which exhibited synergism with carbachol. Quercetin also stimulated a modest increase in intracellular cAMP levels and the phosphorylation of endogenous protein substrates for cAMP-dependent protein kinase. Thus, quercetin is a potent stimulus of colonocyte secretion that resembles secretagogues which act via a cAMP-mediated signaling pathway.

Carbachol↗

Cross-sectional transmission electron microscopy of X-ray multilayer thin film structures.

A simple method for preparing cross-sectional transmission electron microscopy specimens and discussions of possible artifacts from specimen preparation and observation of x-ray multilayer thin film structures are presented. The specimen preparation method employs mechanical grinding and polishing to approximately 20 microns, followed by ion milling, without dimpling. Artifacts such as preferential ion milling and crystallization under the electron beam, as well as effects of Fresnel fringes at interfaces, are important factors in interpretation of the images. Care in identifying them is required to avoid erroneous results in studies of morphology and microstructures within the layers and at their interfaces. Example high-resolution TEM results of cross-sectional W/C, Ru/C, and Mo/Si multilayers are presented.

Artifacts↗

The effects of diet on the maximal activities of glutaminase, citrate synthase, hexokinase, 6-phosphofructokinase and lactate dehydrogenase in the skin of haired and hairless mice of various ages.

1. The maximal activities of hexokinase (HK), 6-phosphofructokinase (PFK), lactate dehydrogenase (LDH), citrate synthase (CS) and glutaminase (GLU) which provide a quantitative indices of flux through several important pathways have been measured in the skin of haired Balb/c and hairless Balb/c (nu/nu) mice under normal and dietary stress. 2. The skin of old haired mice exhibited higher PFK and LDH activities with lower HK, CS and GLU activities. All activities of enzymes associated with energy metabolism in the skin of old hairless mice were higher than those in the skin of haired mice. 3. HK, LDH, CS and GLU activities were maintained at normal levels in the skin of haired mice when these mice were fed diets deficient in energy or protein components (HPLE, LPNE). These enzymes however were severely suppressed when mice were fed a diet deficient in both energy and protein components (LPLE). Recovery of activities of these enzymes to the control level was observed when mice were refed with the normal diet for a week.

Aging↗

Localized adenocarcinoma of the lung: a retrospective study of 186 non-metastatic patients from the French Federation of Cancer Institutes--the Radiotherapy Cooperative Group.

From January 1980 to December 1984, 186 patients with non-metastatic primary adenocarcinoma of the lung were treated in 10 different French Cancer Institutes. All patients have a minimal 5-year follow-up. There were 19 Stage I, 58 Stage II, and 109 Stage III. Survival was correlated with treatment modality. Survival rates for patients treated with surgery (36 pts), surgery and radiotherapy (65 pts), or radiotherapy with or without chemotherapy (80 pts) were 44.7%, 28.5%, and 6%, respectively. In the group of patients who were operated on, local control rate was improved by adjunctive radiotherapy delivering more than 50 Gy in 5 weeks. The cumulative risk of developing distant metastasis was 37% at the end of the first year following diagnosis and 68% at 5 years. Stage of the disease, nodal involvement, and location of the primary were the main factors of prognosis.

Adenocarcinoma↗

Ethnic populations in public mental health: services choice and level of use.

BACKGROUND: Barriers to access and use of mental health care by Asians, Blacks, and Hispanic Americans have been a source of concern for many years. Limitations in our knowledge base persist regarding patterns of use in public sector programs of certain services. Using a sample of almost 27,000 persons, this study examined access and level of use by ethnic minority groups of emergency services, inpatient care, individual outpatient visit, and case management. METHODS: Data from the management information systems of San Francisco and Santa Clara counties were analyzed for fiscal year 1987/1988. Multivariate models were evaluated at two stages, reflecting whether or not a service had been used, and if used, the level of use. RESULTS: Asians and Hispanics used less emergency and inpatient but more outpatient care than did Whites; Blacks used more emergency and less outpatient care. CONCLUSIONS: Ethnicity continues to play a role in understanding the utilization of mental health services. Regarding emergency and inpatient care, Asian and Hispanic patterns of use appear relatively favorable, whereas the patterns of Blacks continue to be problematic.

Black or African American↗

Neuropeptide Y. Differential binding to rat intestinal laterobasal membranes.

Neuropeptide Y (NPY), a neurotransmitter contained within intrinsic nerves of the small intestine, inhibits secretion when added to the serosal side of intestinal mucosa mounted in Ussing chambers. Using NPY radiolabeled with IODO-GEN, lactoperoxidase, or the Bolton-Hunter reagent, we have localized high affinity NPY receptors to the serosal laterobasal membranes of the rat intestinal epithelial cell, isolated according to a recently described protocol that minimizes contamination with endoplasmic reticulum, Golgi, and brush-border membranes. In addition, certain species of radiolabeled NPY, including those labeled with IODO-GEN at the tyrosine residue 36, also demonstrated an ability to bind to brush-border membranes. These receptors were specific for NPY since the homologous peptides, pancreatic polypeptide and peptide YY, were less efficient than NPY in inhibiting the membrane binding of radiolabeled NPY. By cross-linking NPY to its receptor with either disuccinimidyl suberate or dithiobis(succinimidyl propionate) and analyzing the resulting complexes on sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by radioautography, we identified two NPY receptor species with molecular sizes of 52-59 kDa and 37-39 kDa. The 37-39-kDa species further possesses a disulfide bond which may attach it to a separate approximately 5-kDa subunit, as evidenced by retarded migration in the absence of the reducing agent dithiothreitol. The intestinal NPY receptor is slightly smaller than the rat brain receptor previously characterized using similar techniques. The localization of NPY receptors on laterobasal membranes is consistent with previous anatomic and physiologic findings, and their identification by cross-linking techniques will constitute the basis for detailed characterization.

Animals↗

Nonrandom induction of pyrimidine-pyrimidone (6-4) photoproducts in ultraviolet-irradiated human chromatin.

Radioimmunoassays that detect pyrimidine-pyrimidone (6-4) photoproducts and cyclobutane dimers were used to determine the relative induction of these photoproducts in nucleosomal (core) and internucleosomal (linker) DNA in human cell chromatin irradiated with UV light. Cyclobutane dimers were formed in equal amounts/nucleotide in core and linker DNA, whereas (6-4) photoproducts occurred with 6-fold greater frequency/nucleotide in linker DNA.

Cell Line↗

Relation between responses to induction chemotherapy and subsequent radiotherapy in advanced or multicentric squamous cell carcinomas of the head and neck.

Between 1984 and 1986, 85 consecutive patients with Stage III-IV or multi-centric squamous cell carcinoma of the head and neck were given three courses of chemotherapy followed by curative external radiotherapy. Induction chemotherapy consisted of either DDP (100 mg/m2, d 1) + 5 FU (1 g/m2/d, d 1-5, continuous infusion) or DDP (100 mg/m2, d4) + Etoposide (60 mg/m2/d, d 1-5, intravenously). Radiotherapy was delivered 70 Gy over 7 weeks in gross tumor and palpable nodes and 50 Gy over 5 weeks in clinically negative nodal areas. Complete response (CR) rates of both the chemotherapies were 39% for the primary and 20% for the nodes whereas partial response (PR) rates were 22% and 40%, respectively. Six months after completion of radiotherapy, 70% of the primaries and 63% of the nodes achieved complete response. The analysis of responses to chemotherapy on one hand and to subsequent radiotherapy on the other shows that the response to chemotherapy can be regarded as predictive for subsequent radiotherapy (p less than 0.001) except in T1-T2 tumors. In these early stages radiotherapy can be efficacious despite a previous failure of chemotherapy (p less than 0.01).

Adult↗

The production of reactive oxygen species by dietary flavonols.

Flavonols are a group of naturally occurring compounds which are widely distributed in nature where they are found glycosylated primarily in vegetables and fruits. A number of studies have found both anti- and prooxidant effects for many of these compounds. The most widely studied because of their ubiquitous nature have been quercetin, a B-dihydroxylated and myricetin, a B-trihydroxylated flavonol. Some of their prooxidant properties have been attributed to the fact that they can undergo autooxidation when dissolved in aqueous buffer. Studying a number of factors affecting autooxidation, we found the rate of autooxidation for both quercetin and myricetin to be highly pH dependent with no autooxidation detected for quercetin at physiologic pH. Both the addition of iron for the two flavonols and the addition of iron followed by SOD for quercetin at physiologic pH. Both the addistantially. Neither kaempferol, a monohydroxylated flavonol nor rutin, a glycosylated quercetin showed any ability to autooxidize. The results with rutin differ from what we expected based on the B-ring structural similarity to quercetin. The autooxidation of quercetin and myricetin was further studied by electron spin resonance spectroscopy (ESR). Whereas quercetin produced a characteristic DMPO-OH radical, it was not detected below a pH of 9. However, the addition of iron allowed the signal to be detected at a pH as low as 8.0. On the other hand, myricetin autooxidation yielded a semiquinone signal which upon the addition of iron, converted to a DMPO-OH signal detected at a pH of 7.5. In a microsome-NADPH system, quercetin produced an increase in oxygen utilization and with ESR, an ethanol-derived radical signal which could be completely suppressed by catalase indicating the dependence of the signal on hydrogen peroxide. These studies demonstrate that the extracellular production of active oxygen species by dietary flavonols is not likely to occur in vivo but the potential for intracellular redox cycling may have toxicologic significance.

Animals↗

Comparison of the neuropeptide Y receptor in the rat brain and intestine.

Neuropeptide Y (NPY) is widely distributed in the central and peripheral nervous systems where it serves neuromodulator and neurotransmitter functions. NPY is contained within intrinsic nerves of the small intestine and can be demonstrated to inhibit intestinal secretion when added to the serosal side of intestine mucosa mounted in Ussing chambers. When injected centrally it has potent effects on food intake, blood pressure, sexual activity and circadian rhythms. Using NPY radiolabeled with iodogen, lactoperoxidase, or the Bolton-Hunter reagent, we have localized high-affinity NPY receptors on brain membranes and on the serosal laterobasal membranes of the rat intestinal epithelial cell. We have demonstrated that enzymatic degradation may limit the ability to demonstrate NPY binding to brush border membranes. In other experiments NPY was cross-linked to its receptors in brain and intestine using disuccinimido suberate and the resulting complexes analyzed on SDS polyacrylamide gel electrophoresis followed by radioautography. We identified two main NPY receptor species in the intestine with molecular sizes of 52-59 kDa and 37-39 kDa. The 37-39 kDa species may possess a disulfide bond which gives the receptor a fixed conformation, or it may be composed of two subunits (37-39 kDa and approximately 5 kDa subunits). This conclusion is based on the different migration of the smaller band in the presence of the reducing agent, dithiothreitol. The intestinal NPY receptor exhibits differences from the rat brain receptor previously characterized by us using similar techniques. The brain receptor has a molecular weight of approximately 58 kDa with a smaller species of about 35 kDa which shows no differences in migration after exposure to dithiothreitol. The localization of NPY receptors on laterobasal membranes and brain membranes is consistent with previous anatomic and physiologic findings. The different characteristics of each receptor type provides physical evidence of receptor heterogeneity. However, it is possible that the greater enzymatic degradation observed in intestinal membranes might explain the differences in receptor sizes in the two organs.

Animals↗

The toxicity of flavonoids to guinea pig enterocytes.

Flavonoids, a group of compounds found primarily in vegetables and fruits, are generally believed to be beneficial to biological systems. Isolated guinea pig enterocytes were exposed to three of these compounds (kaempferol, quercetin, and myricetin) in concentrations of 50-450 microM. Toxicity was examined using trypan blue exclusion and lactic dehydrogenase (LDH) leakage. All three flavonoids produced cellular damage at 450 microM: compared with a control incubation, cellular viability was 12-60% lower and LDH leakage 28-41% greater after a 3-hr incubation. In addition, as assessed by trypan blue exclusion, quercetin and myricetin, both of which produce superoxide on autoxidation, appeared to be more toxic than kaempferol. These results suggest that dietary flavonoids may have the potential for producing intestinal injury.

Animals↗

Epidermal growth factor receptor of the intestinal enterocyte. Localization to laterobasal but not brush border membrane.

Interaction of epidermal growth factor (EGF) with its specific receptor (EGFR) was explored in the intact rat small intestine and in highly purified isolated enterocyte membrane preparations. Despite the fact that the EGF ligand is known to be present at physiological concentrations within the intestinal cavity, no significant binding of the ligand to the brush border surface was observed. Instead, binding of EGF to the EGFR was confined to other membrane populations, and correlation of ligand interaction with the laterobasal membranes (LBM) was nearly perfect (p less than 0.001) across a special equilibrium gradient enriched in brush border and LBM but devoid of intracellular membranes. Specific binding to another minor population of intracellular membranes that migrated to a position less dense than typical endoplasmic reticulum-Golgi vesicles on equilibrium gradients was also observed. Immunocytochemical exposure of intestine to EGFR antibody confirmed the localization of the EGFR to LBM and intracellular membranes. As estimated from the intensity of the staining, there may be immunologically active but nonbinding receptor species in the intracellular membrane compartment. Thus, despite the secretion of EGF into the intestinal lumen, the growth and maturational effects of EGF probably result from a specific interaction between EGF and EGFR solely at the laterobasal surface of the enterocyte. The functional role of the intracellular membrane species of EGFR, which remains to be established, may involve a source of inactive receptor that can be rapidly recruited and transferred to the LBM surface under changing environmental conditions.

Animals↗

Neoadjuvant chemotherapy and irradiation in multiple synchronous squamous cell carcinoma of the upper aero digestive tract.

Twenty-four patients with multiple, synchronous carcinoma of the head and neck, lung or esophagus, were treated with induction chemotherapy followed by irradiation to involved areas. Chemotherapy regimen consisted of cisplatinum either alone, or in combination with 5-FU or etoposide. Subsequently, external radiotherapy, 60-65 Gy and 70-75 Gy to the mediastinum and the head and neck areas, respectively, was carried out. Following chemotherapy, three patients (12.5%) had a complete clinical remission in both cervical and mediastinal sites. That rate was significantly increased by radiotherapy (66%). Tolerance was fair or mild even though half of the patients needed a rest break during irradiation. Follow-up ranges from 24 to 38 months. The median survival is 12 months and the actuarial survival rates are 45% and 5% at 12 and 24 months, respectively. It is suggested that induction chemotherapy will not drastically improve the overall prognosis of multiple squamous cell carcinoma of the upper aero digestive tract and that external irradiation remains a major part of treatment which should not be reduced in treated volumes, or in total dose delivered.

Adult↗

Cross-linking of neuropeptide Y to its receptor on rat brain membranes.

The receptor for neuropeptide Y (NPY) was identified on rat brain membranes after covalent labeling with 125I-NPY using the homobifunctional cross-linkers disuccinimido suberate and disuccinimido dithiobis(propionate) and the heterobifunctional photoactive cross-linker succinimido 4-azidobenzoate. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography revealed the presence of two bands at Mr 62,000 and 39,000. Both species showed the same high affinity for 125I-NPY. Exposure to reducing agents did not change the migration of these bands. When the NPY receptor complex was solubilized from the membranes with 1% Triton X-100 and analyzed by gel filtration chromatography, it eluted from a Fractogel TSK 55F column as a peak at approximately 65 kDa. This peak was asymmetric with a shoulder of radioactivity that probably reflects the smaller receptor species. These data indicate that the NPY receptor on rat brain membranes is a monomeric 58-kDa unit (62 kDa minus the mass of the cross-linked NPY) without covalently or noncovalently linked subunits. The smaller 39-kDa species may be an immature form of the 62-kDa species, a second distinct receptor, or a degradation product of the 62-kDa band.

Animals↗

Single brain metastasis of non-small cell lung carcinoma. Study of survival among 54 patients.

We studied 54 patients treated for non-small cell lung carcinoma with single brain metastasis presenting between 1980 and 1985. Better survival was obtained in cases of patients presenting a fair neurological condition who were treated by surgery. Histological condition and date of onet of metastasis had no significant influence on survival. Combined treatment of both primary lung tumour and brain metastasis was a favourable prognosis element, and surgical resection of both locations led to the best results in terms of duration and quality of survival.

Brain Neoplasms↗

Squamous cell carcinoma of the upper aero-digestive tract in women.

Between 1970 and 1985, 95 women presenting carcinomas of the oral cavity, pharynx or larynx, were treated at the Institut Jean-Godinot. Classification of these patients according to age shows a bimodal curve and the existence of two different populations. The main difference between groups appears to be the existence or not of tobacco intoxication. According to this criteria, the two groups of patients are statistically different in mean age (nonusers 16 years older than users, p less than 0.01) and in the site of the primary, with an excess of carcinomas of the oral cavity in the nonusers group (p less than 0.01). In contrast, no difference was found in the locoregional extension of the tumor (TNM), in the modalities and result of treatment or in the evolution and survival of patients.

Adult↗