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Biomedical subjects

J Nguyen

Publications and source records attributed to J Nguyen.

At least 37 records · Page 2Linked to original sources
PubMed1999

Growth inhibition of a human ovarian tumor by a novel paclitaxel derivative in SCID mice.

We report here the toxicity and therapeutic effects of 2'-alpha-bromohexadecanoyl paclitaxel (BrC16HT), a prodrug form of paclitaxel, in mice. Paclitaxel is the active ingredient of Taxol. The maximum tolerated dose, at a one dose per day for 5-day schedule, was 37.5 mg/kg for BrC16HT compared to 12.5 for Taxol administered IP, and was 12.5-25 mg/kg for either agent administered IV. Dose-dependent therapeutic effects were found for BrC16HT against a human ovarian tumor (OVCAR-3) grown in SCID mice. IP treatments with BrC16HT against early or established IP-implanted OVCAR-3 tumor increased mean survival times more than treatment with Taxol. Long-term survivors were found only in groups treated with BrC16HT. Intravenously administered BrC16HT was more effective than Taxol against SC OVCAR-3 tumor. Early treatment (25 mg/kg x 5) completely inhibited tumor growth through 120 days after tumor implantation. Pharmacokinetic studies suggest that BrC16HT is slowly hydrolyzed to paclitaxel and circulates longer than paclitaxel from Taxol. Thus, BrC16HT may provide sustained levels of paclitaxel, which may contribute to the increased efficacy of BrC16HT compared to Taxol.

Animals↗
PubMed1998

MAGE Xp-2: a member of the MAGE gene family isolated from an expression library using systemic lupus erythematosus sera.

Two regions of the genome contain members of the MAGE gene family; Xq27-qter and Xp21.3. We isolated a transcript, MAGE Xp-2, by screening a cDNA library from the human epithelial carcinoma cell line, HEp-2, using autoantibodies from patients with systemic lupus erythematosus (SLE). The open reading frame (ORF) of MAGE Xp-2 is entirely contained in exon 4, a signature feature of the MAGE gene family. While MAGE Xp-2 shares genomic homology with MAGE Xp-1, the predicted proteins are quite divergent. Specific primers were designed to reliably distinguish between MAGE Xp-1 and MAGE Xp-2 expression. MAGE Xp-2 is expressed in testis, but not in other normal tissues. It is also expressed strongly in two of seven melanoma cell lines and one of four breast carcinomas. MAGE gene expression may be important not only for tumor recognition and cancer therapy, but, because it is the apparent target of autoantibodies in SLE sera, it may also play a role in autoimmune diseases.

Amino Acid Sequence↗
PubMed1998

Pyogenic bacterial pneumonia in human immunodeficiency virus-infected inpatients: a clinical, radiological, microbiological, and epidemiological study.

We prospectively studied features of pyogenic bacterial pneumonia in 263 consecutive human immunodeficiency virus-infected inpatients over a 6-month study period. Risk factors for bacterial pneumonia were examined by a case-control study that included 33 cases who presented with at least one episode of bacterial pneumonia and 80 controls without bacterial pneumonia. The estimated cumulative incidence of bacterial pneumonia per year was 12.5 cases per 100 inpatients (95% confidence interval [CI], 8.8-17.2). The 38 episodes of bacterial pneumonia that occurred in the 33 inpatients were mainly unilateral, but 32 episodes were patchy lobar or diffuse infiltrates. Microbiological etiologies were obtained in 33 of the 38 episodes of bacterial pneumonia. Thirty-seven pathogens were identified, including Streptococcus pneumoniae (16, of which 12 had a decreased susceptibility to penicillin), Haemophilus influenzae (6), and Pseudomonas aeruginosa (6). The risk factors for bacterial pneumonia that were identified after logistic regression included prior sinusitis within 1 month before admission (odds ratio [OR], 3.2; 95% CI, 1.1-9.1) and prior bacterial infection of the lower respiratory tract within 6 months before admission (OR, 3.1; 95% CI, 1.1-8.3).

AIDS-Related Opportunistic Infections↗
PubMed1997

Variations of teicoplanin concentrations in neutropenic patients.

The aim of this study was to measure the trough plasma concentrations of teicoplanin in neutropenic patients with a view to optimizing the loading dose. Teicoplanin trough plasma concentrations were followed in 11 neutropenic patients after repeated administration of a 6 mg/kg i.v. bolus. The first three injections were given at 12-h intervals, and the rest every 24 h. Trough plasma concentrations at 48 h varied from 5.6 to 13.1 mg/I. The mean trough plasma concentration-time curve indicated a trend towards accumulation. In conclusion, the loading dose of teicoplanin should be tailored to individual neutropenic patients.

Adolescent↗
PubMed1997

Amylase and chitinase genes in Streptomyces lividans are regulated by reg1, a pleiotropic regulatory gene.

A regulatory gene, reg1, was identified in Streptomyces lividans. It encodes a 345-amino-acid protein (Reg1) which contains a helix-turn-helix DNA-binding motif in the N-terminal region. Reg1 exhibits similarity with the LacI/GalR family members over the entire sequence. It displays 95% identity with MalR (the repressor of malE in S. coelicolor), 65% identity with ORF-Sl (a putative regulatory gene of alpha-amylase of S. limosus), and 31% identity with CcpA (the carbon catabolite repressor in Bacillus subtilis). In S. lividans, the chromosomal disruption of reg1 affected the expression of several genes. The production of alpha-amylases of S. lividans and that of the alpha-amylase of S. limosus in S. lividans were enhanced in the reg1 mutant strains and relieved of carbon catabolite repression. As a result, the transcription level of the alpha-amylase of S. limosus was noticeably increased in the reg1 mutant strain. Moreover, the induction of chitinase production in S. lividans was relieved of carbon catabolite repression by glucose in the reg1 mutant strain, while the induction by chitin was lost. Therefore, reg1 can be regarded as a pleiotropic regulatory gene in S. lividans.

Amino Acid Sequence↗
PubMed1997

Effects of postoperative peritoneal lavage on pharmacokinetics of gentamicin in horses after celiotomy.

OBJECTIVE: To evaluate the effect of peritoneal lavage on pharmacokinetics of gentamicin sulfate in healthy horses after experimental celiotomy. ANIMALS: 13 clinically normal horses. PROCEDURE: Horses were randomly assigned to control or experimental groups. All horses received gentamicin (6.6 mg/kg of body weight, IV, q 24 h) before surgery, underwent experimental abdominal surgery, and had abdominal drains placed percutaneously. Horses of the experimental group received postoperative peritoneal lavage; horses of the control group did not receive peritoneal lavage. The day after surgery, 24 hours after the preoperative dose of gentamicin, a second dose of gentamicin was administered. Three and 15 hours after this second dose of gentamicin, horses of the experimental group received peritoneal lavage. Venous blood was obtained, for determination of concentration of gentamicin, immediately before and at specified intervals during the 24-hour period after the second dose of gentamicin. RESULTS: There were no differences in any of the pharmacokinetic values of gentamicin between horses of the control and experimental groups. CONCLUSIONS: Peritoneal lavage had no effect on pharmacokinetics of gentamicin in healthy horses after abdominal surgery, in which localized nonseptic peritonitis was induced. CLINICAL RELEVANCE: Peritoneal lavage in horses with localized nonseptic peritonitis or for the prevention of intra-abdominal adhesions should not necessitate alteration of the dosage of gentamicin to maintain predictable serum concentrations.

Abdomen↗
PubMed1995

Prion protein peptides induce alpha-helix to beta-sheet conformational transitions.

The structures of synthetic peptides corresponding to regions of putative secondary structure in the cellular prion protein PrPC were studied as models for the conformational transition that features in the formation of the pathogenic isoform, PrPSc. Transgenetic studies argue that these PrP isoforms interact during the formation of PrPSc, which involves the unfolding of one or more helices of PrPC followed by refolding into beta-sheets. PrP residues 109-122 (H1), which were predicted to be alpha-helical, form beta-sheets in aqueous buffers, while the longer peptide 104-122 (104H1) and also peptide 129-141 (H2) have coil or alpha-helical structures in solution. Both 104H1 and H2 were converted into beta-sheets upon interaction with H1, as monitored by Fourier transform infrared (FTIR) and circular dichroism (CD) spectroscopy. The conversion was sequence-specific since mouse (Mo) H1, which differs from Syrian hamster (SHa) at two residues, was inefficient at converting SHa104H1 into the beta-sheet form. In buffers containing 10% acetonitrile, 104H1 was converted into the beta-sheet form by addition of as little as 1% H1. In addition, A beta 11-25 and A beta 25-35 peptides with similar physical properties to H1 were incapable of converting H2 into the beta-sheet form. How well these studies approximate the structural transitions in PrP that underlie the replication of prions remains to be established.

Amino Acid Sequence↗
PubMed1995

Induction and subcellular localization of two major stress proteins in response to copper in the fathead minnow Pimephales promelas.

In the present study we characterize the stress response induced by copper in the fathead minnow, Pimephales promelas. The fathead minnow epithelial cell line ATCC CCL 42 was used to examine the induced synthesis and subcellular localization of the two major stress proteins, stress 70 and cpn60. Western blot analysis demonstrated increased stress70 in cells exposed to 400 and 500 microM Cu. Two-dimensional analysis revealed three isoforms of stress70, one of 70 kDa and two of 72 kDa, at the highest Cu concentration. Chaperonin60 abundance did not change over the same range of Cu concentrations. Indirect immunofluorescence microscopy revealed that stress70 localized in the cytoplasm, particularly in the paranuclear region. Chaperonin60 was localized in mitochondria. Further, when we examined the stress response elicited by Cu in fathead minnow larvae in vivo, we found that Cu induced the stress response at nominal Cu concentrations that were more than an order of magnitude lower that in the cell culture. This disparity between the concentration of Cu, which induced the stress response in cells in culture and in vivo, may be the result of differences in Cu complexation that alter its availability, uptake and toxicity.

Animals↗
PubMed1995

Treatment of the upper limb in Charcot-Marie-Tooth disease.

Even though Charcot-Marie-Tooth (CMT) disease is seen frequently, relatively little has been written about the successful treatment of upper limb involvement using tendon transfers. It appears that there are several types of CMT disease and there is extreme variability in the clinical symptoms. The results of treatment were assessed by looking at four specific areas of hand function: decreased conduction velocity of the nerves, lack of opposition, weak pinch, and clawing of the fingers. A plan has been developed for tendon transfers that has worked well in clinical practice.

Adolescent↗
PubMed1995

Cloning and molecular characterization of two genes encoding adhesion proteins involved in Trichomonas vaginalis cytoadherence.

Cytoadherence to the vaginal epithelium is a critical step in infection by the eukaryotic flagellate Trichomonas vaginalis. Four trichomonad surface proteins (AP65, AP51, AP33 and AP23) mediate cytoadherence. The cDNA encoding the AP65 adhesin was isolated from a phagemid cDNA expression library by screening with antiserum and monoclonal antibody (mAb) raised against the purified trichomonad AP65 protein. Two clones, F11.2 and F11.5, coded for immuno-crossreactive recombinant proteins that possessed functional properties equal to the T. vaginalis AP65 adhesin. Analysis of full-length sequences corresponding to the F11.2 and F11.5 cDNAs revealed that both contained 1701-base open reading frames (ORFs) that encoded proteins of 63 281 daltons and 83 087 daltons, respectively. Comparison of the full-length sequences showed 87% identity at the nucleotide level and 91% identity at the protein level. Restriction-enzyme mapping and Southern analysis reaffirmed the distinctness of the F11.2 and F11.5 cDNAs, indicating that two different AP65 genes (now called ap65-1 and ap65-2) are present in the T. vaginalis genome in at least two copies each. Northern analysis detected high levels of transcript of approximately 1.8 kb for both ap65-1 and ap65-2 genes in trichomonads grown only in high-iron medium, confirming the transcriptional regulation of adhesin synthesis by iron. Homology searches revealed significant similarity (38% amino acid identity and 54% nucleotide identity) to malic enzymes. However, purified malic enzyme and mAb to AP65 crossreactive with malic enzyme neither inhibited cytoadherence of T. vaginalis to host cells nor prevented binding of the trichomonad AP65 to HeLa cells in a ligand assay.

Amino Acid Sequence↗
PubMed1995

Tone-dependent responses of histamine in feline pulmonary vascular bed.

Under conditions of controlled pulmonary blood flow and constant left atrial pressure, histamine produced tone-dependent responses in the pulmonary vascular (PV) bed of intact-chest, spontaneously breathing cats. At low, baseline PV tone, histamine produced dose-dependent increases in mean lobar arterial pressure that were antagonized by the selective histamine H1-receptor antagonist, diphenhydramine. The cyclooxygenase inhibitor, meclofenamate, and the thromboxane A2 (TxA2) receptor antagonist, SQ-29548, had no effect on these vasoconstrictor responses of histamine. After an increase in PV tone with an intralobar arterial infusion of a TxA2 mimic, U-46619, histamine produced vasodilator responses at low doses, biphasic vasodilator/vasoconstrictor responses at midrange doses, and vasoconstrictor responses at high doses. Diphenhydramine antagonized vasoconstrictor responses and the vasodilator responses of low to midrange doses and enhanced vasodilator responses of high doses of histamine at elevated PV tone. Selective H2-receptor antagonists, ranitidine and meclofenamate, and selective H3-receptor antagonist, thioperamide, did not antagonize vasodilator responses of histamine. H1- and H2-receptor antagonism was more effective in reducing the vasodilator responses of histamine at elevated PV tone than H1-receptor antagonism alone. These data support that histamine produces vasoconstrictor responses at low baseline and elevated PV tone by acting on H1 receptors that do not induce the release of vasoconstrictor prostanoids. At elevated PV tone, histamine produces vasodilation by acting on H1 receptors that are not coupled to the release of vasodilator prostaglandins and also, in part, by acting on H2 receptors.

Animals↗
PubMed1995

Characterization of cDNAs encoding adhesin proteins involved in trichomonas vaginalis cytoadherence.

Trichomonas vaginalis cytoadherence is mediated by four adhesins (AP65, AP51, AP33 and AP23). Adhesin gene expression was previously shown to be up-regulated by iron. Therefore, a cDNA library was constructed from mRNA of T. vaginalis grown in a high-iron medium. Ten cDNA clones (three for AP65, one for AP51, and six for AP33) were recognized with polyclonal antiserum or monoclonal antibody raised against these adhesins. No cross-hybridization among cDNAs of the three adhesins was observed in Southern analysis, confirming restriction mapping analysis of representative cDNAs. Southern analysis probed with representative cDNAs of the adhesins indicated multiple copies for each of the three adhesin genes. Northern analysis showed transcripts of 1.8 kilobases (kb), 1.4 kb, and 0.9 kb for AP65, AP51 and AP33, respectively. Consistent with adhesin expression, mRNAs for these adhesins were detected only when parasites were grown in high-iron conditions. Specific antibodies eluted from E. coli expressing recombinant proteins reacted only with the respective parasite adhesins. Recombinant proteins bind to fixed HeLa cells and competed with radiolabeled trichomonad adhesins for binding. Although proteinase activity is required for cytoadherence, recombinant proteins show no detectable proteinase activity. These data show that recombinant proteins from these clones exhibited characteristics of the trichomonad adhesins.

Animals↗