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B T Nguyen

Publications and source records attributed to B T Nguyen.

At least 37 records · Page 2Linked to original sources
PubMed1989

Should intestinal continuity be restored after massive intestinal resection?

We reviewed our experience with 32 patients who underwent massive intestinal resection to determine when intestinal continuity should be maintained. An enterostomy was created in 21 patients (66 percent) at the initial resection because of questionable bowel viability and an unstable condition or the need for colonic anastomosis. Intestinal continuity was restored in only 20 percent of these patients. In 11 patients (34 percent), intestinal continuity was maintained at the time of resection. Only four of these patients (36 percent) had a satisfactory long-term outcome. Overall, intestinal continuity was maintained in 10 of the 22 patients (45 percent) followed over the long-term. Three quarters of patients with intestinal remnants shorter than 3 feet had an enterostomy. We believe intestinal continuity should be restored at the time of massive resection only in carefully selected patients when bowel viability is ensured, remnant length is greater than 3 feet, and a colonic anastomosis is not required. Maintaining intestinal continuity eliminates the inconvenience of the stoma but may cause dietary restriction and perianal discomfort.

Adolescent↗
PubMed1986

Compartmentation of guanine nucleotide precursors for DNA synthesis.

We have studied the kinetics of guanine incorporation into DNA in mouse T-lymphoma (S-49) mutant cells [PNPase (purine-nucleoside phosphorylase)- and HGPRTase (hypoxanthine: guanine phosphoribosyltransferase)-deficient] that are incapable of converting dGuo (deoxyguanosine) to Gua (guanine) ribonucleotides. Of the two possible pathways for an exogenous guanine source to reach DNA, firstly: dGuo----dGMP----dGDP----dGTP and secondly: Gua----GMP----GDP----dGDP----dGTP only the second pathway was found to be functional in providing guanine for DNA replication, although deoxyguanosine readily produced toxic cellular dGTP levels via the first pathway. The functional guanine-nucleotide-precursor pools for DNA are rather small; further, the depletion of the small GMP pool, but not that of GDP, GTP and dGTP, correlated well with the inhibition of DNA synthesis by mycophenolic acid, an IMP dehydrogenase inhibitor. These results support the hypothesis that guanine-nucleotide incorporation into DNA is highly compartmentalized and that a small functional guanine-nucleotide pool, e.g., the GMP pool, may serve a crucial role in limiting the availability of DNA precursor substrate.

Animals↗
PubMed1985

Comparative effects of cotrimoxazole (trimethoprim-sulphamethoxazole) and spiramycin in pregnant mice infected with Toxoplasma gondii (Beverley strain).

The effects of cotrimoxazole (CTX) and spiramycin (Spir) in mice infected in midpregnancy with the Beverley (Bev) strain of Toxoplasma gondii were compared. Therapeutic effectiveness was determined according to the following parameters: rate of successful delivery, litter size, offspring weight and survival. When compared with the uninfected untreated control group, CTX showed a more beneficial therapeutic effect than Spir, with a statistically significant increase in the rate of both successful delivery and offspring survival. Results based on antitoxoplasma antibody determinations in the offspring indicated a better in utero control of congenital infection by CTX than by Spir.

Animals↗
PubMed1985

Biochemical differences among four inosinate dehydrogenase inhibitors, mycophenolic acid, ribavirin, tiazofurin, and selenazofurin, studied in mouse lymphoma cell culture.

The mechanism of the cellular toxicity of four inosinate dehydrogenase (IMP-DH) inhibitors with different antitumor and antiviral pharmacological profiles was investigated in mouse lymphoma (S-49) cell culture. Drug effects on cell growth, nucleotide pools, and DNA and RNA synthesis were measured in the presence and absence of guanine salvage supplies. Both guanine and guanosine were capable of bypassing the IMP-DH block, while they also demonstrated some growth-inhibitory effects when added alone in high concentrations. All four drugs reduced cellular guanosine triphosphate levels and caused secondary changes of the uridine, cytidine, and adenosine triphosphate pools that were similar among the four drugs. However, several drug effects in addition to IMP-DH inhibition were observed except with mycophenolic acid which may represent a pure IMP-DH inhibitor. Both tiazofurin and selenazofurin interfered with the uptake and/or metabolism of uridine and thymidine tracers; however, this effect appeared not to contribute to their cellular toxicity in vitro. Moreover, selenazofurin and tiazofurin impaired the utilization of exogenous guanine salvage supplies for DNA and RNA synthesis, and guanine was particularly ineffective in reversing the toxic effects of tiazofurin on cell growth. This finding is important in view of the available guanine salvage supplies in vivo. Since tiazofurin, selenazofurin, and their known metabolites failed to inhibit hypoxanthine-guanine-phosphoribosyl transferase, guanosine monophosphate kinase, and guanosine diphosphate kinase in cell extracts or permeabilized cells, these drugs may interfere with salvage transport across cellular membranes. The toxic effects of mycophenolic acid and ribavirin were similarly reversed by salvage supplies of up to 200 microM guanine, which suggests that ribavirin primarily acts as an IMP-DH inhibitor under these conditions. This result could explain the rather low antitumor efficacy of both mycophenolic acid and ribavirin in vivo. However, increasing the guanine salvage supply in the medium above 200 microM further reversed the toxic effects of mycophenolic acid to maximum rescue, while it increased the toxicity of ribavirin (300 microM). This finding suggests the presence of a toxic mechanism of ribavirin at higher concentrations that is dependent upon the presence of guanine supplies sufficient to fully overcome the IMP-DH inhibition. This study documents that each antimetabolite displays a unique spectrum of activities with multiple toxic targets.

Adenosine Triphosphate↗
PubMed1984

Interaction among the distinct effects of adenine and guanine depletion in mouse lymphoma cells.

Toxic guanine depletion was shown previously to result in a dramatic reduction of DNA synthesis, while toxic adenine depletion failed to affect DNA synthesis (M. B. Cohen and W. Sadée, Cancer Res., 43: 1587-1591, 1983). In this study, relative DNA synthesis rates were measured in mouse lymphoma S49 cells over 24 hr after drug exposure and were compared to cell growth curves. DNA synthesis inhibition by mycophenolic acid (guanine starvation) was achieved at lower drug concentrations than was the inhibition of cell growth. This result further supports the hypothesis (reference above) that guanine starvation specifically affects cells in S phase while it allows cells with full DNA complement to divide. In contrast, L-alanosine (adenine starvation) failed to affect DNA synthesis for at least 24 hr at a concentration that inhibits cell growth by 80%. The dramatically different effects of guanine and adenine starvation on DNA synthesis can thus be used to assess the magnitude of each when blocking early de novo purine biosynthesis by 6-methyl-mercaptopurine ribonucleoside (6- MMPR ). The results suggest that, although 6- MMPR effects primarily resemble those of guanine depletion, adenine starvation measurably contributes to the overall toxicity of 6- MMPR . Drug combination experiments with L-alanosine, mycophenolic acid, and 6- MMPR suggest that the basic mechanisms underlying the toxic effects of guanine and adenine starvation act synergistically.

Adenine↗
PubMed1983

Guanine ribonucleotide depletion in mammalian cells. A target of purine antimetabolites.

In a previous report we demonstrated in mouse lymphoma (S-49) cells that DNA synthesis inhibition resulting from guanine starvation is associated with GTP rather than dGTP depletion. Since several effective anticancer drugs act via guanine depletion, it is important to test whether critical GTP depletion is unique to S-49 cells or also occurs in other cell lines. Mycophenolic acid-induced guanine starvation caused a drastic DNA synthesis inhibition in the human lymphoblastic T leukemia (CEM) and the mouse B leukemia (L1210) cell lines, which was again associated with GTP depletion rather than dGTP depletion. These results suggest that GTP depletion represents a common target of purine antimetabolites in mammalian cells.

Animals↗
PubMed1983

Comparative effects of cotrimoxazole (trimethoprim-sulphamethoxazole), pyrimethamine-sulphadiazine and spiramycin during avirulent infection with Toxoplasma gondii (Beverley strain) in mice.

The antitoxoplasm effects of cotrimoxazole (Ctx), spiramycin (Spir) and pyrimethamine-sulphadiazine (Pmm-Sdz) were compared during both proliferative and chronic phases of infection of mice with the Beverley (Bev) strain of Toxoplasma gondii of low virulence. The therapeutic efficacy of the drugs was determined according to the following criteria: (i) specific antibody response; (ii) acquired resistance to lethal challenge with the virulent RH strain of Toxoplasma; and (iii) persistence of parasites in tissues (brain, liver, spleen) of treated mice. The results indicated that Ctx, like Pmm-Sdz, had a greater effect than Spir upon toxoplasma organisms during the proliferative phase of infection. In contrast, none of the three drugs tested was active against tissue cysts in chronically infected mice.

Animals↗
PubMed1982

Ultrastructural localization of neurofilament proteins in aluminum-induced neurofibrillary tangles and rat cerebellum by immunoperoxidase labeling.

The localization of neurofilament proteins was investigated at the light and electron microscopic levels by the peroxidase-antiperoxidase procedure in the motor neurons of rabbit spinal cord accumulating bundles of filaments (neurofibrillary tangles) consequent to the intrathecal injection of aluminum and in rat cerebellum. As indicated by immunoaffinity chromatography the antisera used in this study reacted with 72,000- and 150,000-dalton polypeptides of the mammalian neurofilament "triplet". In the motor neurons of rabbit spinal cord neurofibrillary tangles were prominently stained. Regions of cytoplasm surrounded by the tangles were negative. In the cerebellar cortex the reaction product was confined to structures containing large amounts of neurofilaments, particularly the terminal branches of basket axons surrounding Purkinje cells. The absence of staining in the outer molecular layer containing processes with other types of filaments, that is, Bergmann glia (gliofilaments) and thin parallel fibers (microtubules), served as control for the specificity of the reaction. In both spinal cord and cerebellum the reaction product appeared as elongated strands. In spinal cord, filaments cut in cross-section had the appearance of peripherally stained circular structures approximately 250 A in diameter.

Aluminum↗
PubMed1982

Glial fibrillary acidic (GFA) protein in Schwann cells: fact or artifact?

Antisera to the glial fibrillary acidic (GFA) protein stained a subpopulation of Schwann cells in cryostat sections of rat sciatic nerve by indirect immunofluorescence and by the peroxidase-antiperoxidase (PAP) procedure. The staining pattern was entirely different from that obtained with vimentin antisera, which uniformly decorated endoneurial tubes. Electron microscopic examination of sciatic nerve provided a possible explanation for the relatively small number of Schwann cells decorated by GFA antisera: 10 nm filaments were mainly confined to Schwann cell processes surrounding nonmyelinated axons. A marked increase in GFA-positive Schwann cells and in Schwann cells containing filaments by electron microscopy was observed in sciatic nerves undergoing Wallerian degeneration. Conversely, immunochemical procedures failed to demonstrate the presence of antigen reacting with GFA antisera in extracts of sciatic nerve, both normal and degenerated. These include absorption experiments, double immunodiffusion, immunoaffinity chromatography, and immunoradiometric assay. Two explanations may be considered for these findings: i) Schwann cell intermediate filaments and GFA protein share common antigenic determinants, the immunohistological methods being more sensitive to detect cross-reactivity as compared to immunochemical procedures on tissue extracts; and ii) the binding of anti-GFA to Schwann cell 10 nm filaments is not due to immunological cross-reactivity.

Animals↗
PubMed1981

The fate of axonal debris in Wallerian degeneration of rat optic and sciatic nerves. Electron microscopy and immunofluorescence studies with neurofilament antisera.

Immunofluorescence demonstrated that axonal debris reacting with neurofilament antisera persist up to 4 months in rat optic nerves undergoing Wallerian degeneration. Antisera used in this study allowed the isolation of the 72,000- and 150,000-dalton neurofilament polypeptides from rat spinal cord by immunoaffinity chromatography. After 2 weeks of degeneration, proteins co-migrating with these neurofilament polypeptides were no longer identifiable in rat optic nerves, which suggests that immunofluorescent structures persisting in the nerves after this period contained neurofilament degradation products of different molecular weight. Additional evidence as to the persistence of axonal debris in degenerated optic nerves was obtained by electron microscopy. Two distinct types of axonal degeneration were observed in rat optic nerves by this method, floccular swelling and increased electron density of the axoplasm. In both types of degeneration, axoplasmic filaments and tubules were not identifiable. Although floccular material disappeared after 2 weeks of degeneration, so that only empty myelin sheaths remained, electron-dense axons persisted longer and were probably phagocytosed together with their myelin sheaths. In sciatic nerves, cross-reaction with neurofilament antisera had almost completely disappeared 10 days after transection. The same was true for nerves which had been tightly ligated to prevent axonal growth and to squeezed nerves which showed vigorous regeneration. A few scattered, brightly immunofluorescent fragments which persisted in nerves up to 2 weeks after transection were exception to these findings.

Animals↗
PubMed1979

[Modes of entry of Toxoplasma gondii trophozoites into normal mouse peritoneal macrophage and HeLa cell monolayers. A phase-contrast microcinematographic study (author's transl)].

The mode of entry of living trophozoites of Toxoplasma gondii (RH strain) into normal mouse peritoneal macrophage and HeLa cell monolayers was studied by phase-contrast microcinematography. The results have shown that Toxoplasma can enter into macrophages either by phagocytosis (Figs. 1 and 2) and/or by active penetration (Fig. 3). Only the latter process was observed with normally non-phagocytic HeLa cells (Fig. 4). During this process the parasites actively moved towards the host-cells by flexion and penetrated them always through their sharpest end. Active penetration was a rapid phenomenon (about 20 s at 37 degrees C) and was accompanied by a series of morphological changes, i.e., elongation of the anterior end, contraction and swelling of the parasite body. Contrasting with phagocytosis, toxoplasmas which had penetrated into the cell were not immediately isolated from the host-cytoplasm by a microscopically discernable vacuole. The nature of the process of penetration (pressure and/or perforation of the plasma membrane) is discussed.

Animals↗
PubMed1979

Comparative biological and antitoxoplasmic effects of particulate and water-soluble polysaccharides, in vitro.

Mouse peritoneal macrophages, but not HeLa cells, presented many characteristics of activated cells following treatment in culture with LTN or PSK. Indeed, they demonstrated increase in size, spread, endocytic and antiparasitic activities. These data lead favorably to consider that among the five polysaccharides tested under the present experimental model LTN and PSK are the most potent activators of resident mouse peritoneal macrophages in vitro. The mechanism of macrophage activation by LTN and PSK should be different from that of Di Luzio glucans and SPG since activated macrophages can be induced by the latter two compounds in experimental animals but not in vitro in cell cultures.

Animals↗