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Biomedical subjects

T M Nguyen

Publications and source records attributed to T M Nguyen.

At least 109 records · Page 6Linked to original sources

Sewage coliphages studied by electron microscopy.

Sewage was enriched with 35 Escherichia coli strains, and sediments of enrichment cultures were studied in the electron microscope. They contained up to 10 varieties of morphologically different particles. T-even-type phages predominated in 14 samples. Thirteen phages were enriched, representing the families Myoviridae (seven), Styloviridae (two), Podoviridae (three), and Microviridae (one). Twelve of these corresponded to known enterobacterial phage species, namely, 121, K19, FC3-9, O1, 9266, T2, 16-19, kappa, beta 4, N4, T7, and phi X174. Cubic RNA phages and filamentous phages were not detected. Types 121 and 9266 have previously been observed only in Romania and South Africa. Identification by morphology is usually simple. Our investigative technique is qualitative and will not detect all phages present. Most enrichment strains are polyvalent, and electron microscopy is always required for phage identification. In a general way, electron microscopy seems to be the method of choice for investigation of phage geography and ecology.

Coliphages↗

Synthesis and pharmacological characterization in vitro of cyclic enkephalin analogues: effect of conformational constraints on opiate receptor selectivity.

Using a combination of solid-phase and solution methods, we synthesized a series of cyclic [Leu5]enkephalin analogues by substitution of D-alpha, omega-diamino acids in position 2 of the enkephalin sequence and cyclization of the omega-amino group to the C-terminal carboxy group of leucine. Cyclic analogues containing D-alpha, beta-diaminopropionic acid (1), D-alpha, gamma-diaminobutyric acid (2), D-ornithine (3), or D-lysine (4) in position 2 and the [D-Leu5] and [des-Leu5] analogues of 4 (5 and 6) showed, in general, high potency in the guinea pig ileum (GPI) assay and low potency in the mouse vas deferens (MVD) assay. IC50 (MVD)/IC50 (GPI) ratios ranging from 3.1 to 29.4 were obtained, indicating the preference of the cyclic analogues for mu receptors over delta receptors. With two exceptions, preferential affinity for mu receptors is reflected in the Ki ratios determined in parallel binding assays using [3H]naloxone and [3H] [D-Ala2, D-Leu5]enkephalin as mu and delta receptor selective radioligands, respectively. Comparison of the pharmacological profiles of the cyclic analogues 1-4 with those of their corresponding open-chain analogues, [D-Ala2, Leu5]enkephalinamide (1a), [D-Abu2, Leu5]enkephalinamide (2a), [D-Nva2, Leu5]enkephalinamide (3a), and [D-Nle2, Leu5]enkephalinamide (4a), revealed that the pronounced mu character of compounds 1-4 is a direct consequence of the conformational constraints introduced by cyclization. This finding is in agreement with the concept of different conformational requirements of mu- and delta-opiate receptors and raises the possibility of manipulating opiate receptor selectivity by varying the type and degree of conformational restriction.

Animals↗

Changes in plasma 1,25 and 24,25-dihydroxyvitamin D after renal transplantation in children.

The purpose of this investigation is to analyze changes in plasma 1,25-(OH)2D and 24,25-(OH)2D after successful renal transplantation in 20 children and young adults. Studies were performed on 8 subjects between the 1st and 10th month and on 12 others between the 20th and 30th to 36th month. Samples were assayed for plasma and urinary calcium, inorganic phosphate, creatinine, plasma bicarbonate, immunoreactive parathyroid hormone, 25-(OH)D, 24,25-(OH)2D, and 1,25-(OH)2D concentrations. Results showed the following: (1) All subjects had normal or high plasma levels of dihydroxyvitamin D metabolites. (2) In subjects with normal GFR's there was a significant inverse correlation between plasma 1,25-(OH)2D concentrations and tubular reabsorption of phosphorus. (3) These correlations were not found in subjects with subnormal creatinine clearances (50 to 100 ml/min/1.73 m2) even though plasma 1,25-(OH)2D concentrations in these subjects were similar to those with normal creatinine clearances. (4) In subjects with subnormal creatinine clearances, an increase in plasma 1,25-(OH)2D concentrations to very high levels was observed during the first months following renal transplantation.

24,25-Dihydroxyvitamin D 3↗

Plasma levels of vitamin D metabolites in the bovine species during the perinatal period.

Plasma vitamin D metabolites (25-OH D; 24,25-(OH)2D and 1,25-(OH)2D) were measured simultaneously in the blood plasma samples of young cows and their calves. Four of the calves were chronically catheterized in utero at least 2 weeks before the expected time of parturition. No significant hypocalcaemia occurred in the dams at calving. Plasma vitamin D metabolites showed no significant variations for 2 weeks before and 4 days after calving. But rapid changes in plasma 1,25-(OH)2D concentrations were observed in one calf during the first 48 postnatal hours. Before birth, the maternal and foetal concentrations of either 1,25-(OH)2D or 24,25-(OH)2D were positively correlated. 25-(OH) D (13 ng/ml), 24,25-(OH)2D (1 ng/ml) and 1,25-(OH)2D (76 pg/ml) were detected in one foetal plasma collected 35 days before term.

24,25-Dihydroxyvitamin D 3↗

Vitamin D3 metabolite injections to thyroparathyroidectomized pregnant rats: effects on calcium-binding proteins of maternal duodenum and of fetoplacental unit.

Fetomaternal relationships with respect to vitamin D metabolism were investigated in thyroparathyroidectomized (TPTX) pregnant rats, with or without treatment with different vitamin D3 metabolites. Calcium-binding protein (CaBP) in maternal duodenum was used as an index of 1,25-(OH)2D3 status of the mother. Pregnant rats were TPTX on day 12.5 and CaBP was measured on 21.5 days of gestation by RIA in maternal duodenal mucosa and in the fetoplacental unit (placenta, fetal membranes, and fetal intestine). In the duodenum of TPTX mothers, the CaBP concentration was reduced by 50%. This fall was associated with a decrease of 1,25-(OH)2D in maternal plasma. CaBP in maternal duodenum increased by the administration of 1,25-(OH)2D3 or 1,24,25-(OH)3D3. In contrast, 24,25-(OH)2D3 injections to TPTX mothers were ineffective. In both placenta and fetal membranes, CaBPs decreased by 20% in TPTX mothers and were normalized only in 1.25-(OH)2D3-treated TPTX mothers. In the fetal intestine, CaBP variations paralleled those of maternal duodenal CaBP. The data indicate that plasma levels of 1,25-(OH)2D in TPTX pregnant rats are partly under the control of maternal parathyroid glands, and they support that even in pregnancy, the CaBP concentration in maternal duodenum may well reflect the 1,25-(OH)2D status of the mother. The CaBP synthesis in placenta and fetal membranes are vitamin D-dependent, and their regulation differs from that of intestinal CaBP. It app]ears that 1 alpha-hydroxylase activities of the fetoplacental unit (placenta and fetal kidney) are blunted in TPTX animals and that CaBP synthesis in the fetus depends on the presence of 1 alpha-hydroxylated vitamin D3 metabolites in the mother.

24,25-Dihydroxyvitamin D 3↗

Photoaffinity labeling of the angiotensin II receptor. 1. Synthesis and biological activities of the labeling peptides.

The synthesis and biological activities of analogues of the peptide hormone angiotensin II (AT) for use in photoaffinity labeling and receptor isolation are described. In the modified sequence of AT, Sar-Arg-Val-Tyr-Val-His-Pro-Phe, the aromatic residues Tyr and Phe have been either singly or simultaneously replaced by L-4'-nitrophenylalanine, L-4'-amino-3',5'-diiodophenylalanine, L-4'-aminophenylalanine, L-4'-diazoniumphenylalanine, and L-4'-azidophenylalanine. The peptides were assembled by solid-phase synthesis and the functional groups in position 4 and/or 8 chemically modified. Radioactivity was introduced by catalytic tritiation of the iodinated peptides to form the photolabeling precursors containing L-4'-amino-3',5'-diiodophenylalanine. On rabbit aorta the AT analogues substituted in position 4 showed poor affinities (0--15%), in position 8 high relative affinities (16--118%), and in position 4 and 8 additive effects of simultaneous substitutions. It is also shown that the new Boc derivative of L-4'-amino-3',5'-diiodophenylalanine can be used in peptide synthesis without side-chain protection.

Affinity Labels↗

Photoaffinity labeling of the angiotensin II receptor; pharmacology of the labeling peptides in the dark.

The biological activities of photoaffinity labeling analogs of angiotensin II (ATII) and their precursors were measured in rabbit aorta strips in the dark. Most of the analogs behave as reversible, specific agonists, one as a competitive inhibitor. The activities are discussed in line with the current view of structural requirements. The modifications consisted of substitutions on the aromatic nuclei of Tyr4 and Phe8 in [Sar1]ATII with (4'-NO2) Phe, (4'-NH2)Phe, (4'N3)Phe, (4'-N2 +)Phe, and (4'-NH2-3', 5'-I2)Phe. It is shown that the affinity of the ATII analogs modified in position 4 depends on the electronegativity and not on space-filling properties of the aromatic residue; rising electronegativity lowers the affinity, i.e. [sar1, (4'-NO2)Phe4]ATII has no more measurable activity. Substituting the aromatic side chain in position 8 of [Sar1]ATII gives well-binding analogs with intrinsic activities from 0 to 100% and activity seems to depend only on stereochemical requirements. Agonists and partial agonists bear rather small groups like -NH2, -N3, -NO2, and -N2 +. The only antagonist [Sar1, (4'-NH2-3',5'-I2)Phe8]ATII resembles the antagonist E1Sar1, Leu8]ATII in competitivity and binding.

Angiotensin II↗

Chorioamnionitis does not affect fetal urine production in patients with premature rupture of membranes.

The objective of this study was to evaluate fetal urine production rate in patients with premature rupture of membranes in the presence or absence of chorioamnionitis and to determine its clinical usefulness. Fetal urine production was evaluated in 30 women between 24 and 39 weeks' gestational age with ruptured membranes. Fetal bladder measurements were determined every 3-5 min for 30-90 min. Chorioamnionitis was defined by both clinical criteria and histological examination of the placenta. The last determination of fetal urine production rate prior to delivery was compared in patients with and without histologic and/or clinical chorioamnionitis. Fetal urine production rate was corrected for gestational age using birth weight prior to analysis. A total of 96 assessments of fetal urine production were performed (range 1-16 per patient). Twelve subjects (40%) had no evidence of chorioamnionitis (group 1), 10 (33%) had histologic chorioamnionitis alone (group 2), and eight (27%) had both clinical and histologic chorioamnionitis (group 3). The mean (+/- SD) urine production rates in these groups were 9.43 +/- 3.15 ml/kg/hr, 10.65 +/- 3.43 ml/kg/hr, and 9.97 +/- 2.81 ml/kg/hr, respectively. The difference in fetal urine production rate between the three groups was not statistically significant. A power analysis revealed that individual group sizes were adequate to document a 50% increase in fetal urine production rate with a type II error of < 10%. There were no documented cases of fetal infection based on neonatal cultures. The presence of histologic or clinical chorioamnionitis does not significantly affect fetal urine production in patients with premature rupture of membranes. The prospective assessment of fetal urine production rate does not appear to be clinically useful as an early indicator of chorioamnionitis.

Chorioamnionitis↗

Detection of group B streptococcus: comparison of an optical immunoassay with direct plating and broth-enhanced culture methods.

The aim of this study was to compare the diagnostic accuracy of an optical immunoassay (STREP B OIA, Biostar) to direct plating and broth-enhanced culture for the detection of group B streptococcus (GBS) colonization of the lower genital tract in pregnant women. GBS cultures from the lower genital tract were obtained in a prospective fashion using a dual swab transport system from patients with risk factors for perinatal GBS infection. One swab was used to inoculate a trypticase soy agar plate with 5% sheep blood (TSA) and then placed in Lim broth. The other swab was used to perform the Strep B OIA. Growth of GBS by either direct plating or broth-enhanced culture was used as the gold standard for determining GBS colonization. Of the 524 women in the study, 90 women had positive cultures (either TSA or Lim broth). The sensitivity, specificity, positive predictive value, and negative predictive value of the Strep B OIA were 47% (42/90), 96% (416/434), 70% (42/60), 90% (416/464). The sensitivity, specificity, positive predictive value, and negative predictive value of the TSA were 61% (55/90), 100% (434/434), 100% (55/55), 93% (434/469). The sensitivity, specificity, positive predictive value, and negative predictive value of Lim broth were 97% (87/90), 100% (434/434), 100% (87/87), and 97% (434/437). The sensitivity of the Strep B OIA to detect light GBS colonization and heavy GBS colonization, as determined by the TSA, was 53% (19/36) and 90% (17/19), respectively. The Strep B OIA and direct agar plate culture appear to be of limited clinical value due to their poor sensitivities. This study also demonstrates the need to use a selective medium such as Lim broth when assessing for GBS colonization of the lower genital tract.

Adolescent↗

Comparative structure-function studies with analogs of dynorphin-(1-13) and [Leu5]enkephalin.

Analogs of dynorphin-(1-13) with modifications in the enkephalin segment were compared with correspondingly modified analogs of [Leu5]enkephalin in the guinea pig ileum (GPI) and mouse vas deferens (MVD) assay as well as in mu- and delta-receptor selective binding assays. The obtained results indicate that a) the enkephalin binding domain of the dynorphin (kappa) receptor has structural requirements which are distinct from those of the enkephalin binding site at the mu-receptor and b) the introduction of an identical conformational constraint in [Leu5]enkephalin and in the enkephalin segment of dynorphin-(1-13) produces a superpotent agonist in both cases. Fluorescence energy transfer measurements with the active [4-tryptophan]analogs of dynorphin-(1-13) and [Leu5]enkephalin and with dynorphin-(1-17) demonstrated a more extended conformation of the N-terminal tetrapeptide segment in [Trp4]dynorphin-(1-13) than in [Trp4, Leu5]enkephalin as well as the absence of an interaction between the N- and C-terminal segments of dynorphin-(1-17).

Animals↗

Subtleties of structure-agonist versus antagonist relationships of opioid peptides and peptidomimetics.

The development of novel delta opioid antagonists and delta opioid agonists structurally derived from the prototype delta antagonist TIPP (H-Tyr-Tic-Phe-Phe-OH), is reviewed. Both delta antagonists and delta agonists with extraordinary potency and unprecedented delta receptor selectivity were discovered. Some of them are already widely used as pharmacological tools and are also of interest as potential therapeutic agents for use in analgesia. The results of the performed structure-activity studies revealed that the delta antagonist versus delta agonist behavior of this class of compounds depended on very subtle structural differences in diverse locations of the molecule. These observations can be best explained with a receptor model involving a number of different inactive and active receptor conformations.

Animals↗

[Variation of the anhidrotic activities of anticholinergics with different routes of administration (author's transl)].

Anhidrotic concentrations 50 of four anticholinergics were determined in mice using an original skin palmar conductance method. Intra-peritoneal, intra-palmar and topical routes were compared. Relative anhidrotic activities according to the mode of administration of the different anticholinergics showed definite differences, e.g. hydroxyzine, which was the less active per i.p. route, was the most active per topical route. The method is likely to be a useful test for selecting the most active anticholinergic and its most efficient route of administration for the treatment of hyperhidrosis.

Administration, Topical↗