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Biomedical subjects

M L Nguyen

Publications and source records attributed to M L Nguyen.

30 records · Page 2Linked to original sources

Photosensitization and tissue distribution studies of the picket fence porphyrin, 3,1-TPro, a candidate for photodynamic therapy.

From a structurally distinct set of o-substituted tetraphenylporphyrins, the picket fence porphyrin (PFP), 3,1-meso-tetrakis(o-propionamidophenyl)porphyrin (3,1-TPro) has been selected as a potential candidate for use in the photodynamic therapy (PDT) of cancer. In this report, the time-dependent tissue distribution of 14C-labeled 3,1-TPro is described along with the results of various treatment regimens. The tissue distribution of radiolabeled 3,1-TPro is comparable to that of other porphyrin photosensitizers with the advantage of being most effective at 4 h and being cleared rapidly from most tissues. The results of the various treatment regimen experiments, as well as other studies, indicate that the 3,1-TPro mechanism of action is similar to that of other photosensitizers, but may include some minor differences. The conclusion is that 3,1-TPro and other PFP offer a class of effective photosensitizers that may be exploited for their structural versatility, straightforward synthesis leading to a compound of high purity and known structure, and stability (both in terms of shelf-life and in vivo metabolism) as potential candidates for PDT.

Animals↗

Anti-idiotype monoclonal antibody elicits broadly neutralizing anti-gp120 antibodies in monkeys.

Murine monoclonal antibodies (mAbs) were raised against human, polyclonal, anti-gp120 antibodies (Ab1) and were selected for binding to broadly neutralizing anti-gp120 antibodies in sera positive for human immunodeficiency virus (HIV). One anti-idiotype mAb (Ab2), 3C9, was found to be specific for human anti-gp120 antibodies directed against an epitope around the conserved CD4 attachment site of gp120. The 3C9 reactive human anti-gp120 antibodies (3C9+ Ab) neutralized MN, IIIB, RF, and four primary isolates of HIV type 1 (HIV-1). Cynomolgus monkeys were immunized with 3C9 in adjuvant to test whether this anti-idiotype mAb could induce neutralizing anti-gp120 antibodies. The results show that purified anti-anti-idiotype antibodies (Ab3) from 3C9 immune sera bind to an epitope around the CD4 attachment site of gp120SF and gp120IIIB. Furthermore, purified gp120-specific Ab3 neutralize MN, IIIB, and RF isolates. These results demonstrate that primates immunized with an anti-idiotype mAb produce broadly neutralizing anti-HIV-1 antibodies. Since this anti-idiotype mAb was selected by identifying a clonotypic marker, its biological activity can be explained as the results of clonotypic B-cell stimulation.

Animals↗

Hemorrhagic cystitis with herpes simplex virus type 2 in the bladder mucosa.

A 67-year-old woman who had underlying rheumatoid arthritis and diabetes mellitus had an 8-year history of recurrent hemorrhagic cystitis. During her most recent episode of cystitis, a specimen of urine yielded herpes simplex virus type 2 in culture. A biopsy of the bladder mucosa revealed intranuclear inclusions in multinucleated and mononuclear giant cells that were positive for herpes simplex virus type 2 by immunoperoxidase staining. She had no evidence of infection with herpes simplex virus outside her bladder.

Aged↗

Design, development, and interpretation of HIV neutralization assays.

In developing therapeutic reagents for the control of HIV infection, it is necessary to screen candidate products in vitro for their ability to reduce or neutralize viral infection. Although the current literature describes numerous neutralization assays, no universally accepted standards have been adopted. In this article, we briefly review the available neutralization assays and describe in detail the methods we have selected in our laboratory for the screening and characterization of reagents with potential anti-HIV properties. After evaluating many different technical protocols and experimental procedures, we have found the syncytium inhibition and syncytial focus assays to be particularly useful and have found p24 gag antigen production to be an excellent objective measure of HIV infection under a variety of conditions. These assays proved reproducible and sensitive and are suitable for use in the majority of laboratories.

Animals↗

Viral pneumonitis.

Viral pneumonitis can affect all age groups and normal as well as compromised hosts. This article discusses salient features of pneumonitis caused by respiratory syncytial virus, adenoviruses, varicella-zoster virus, herpes simplex virus, influenza A and B viruses, and cytomegalovirus. The clinical picture, diagnosis, treatment and prevention for each agent are discussed.

Adenoviridae Infections↗

Legionella infection.

As specialized laboratory tests became more widely available, Legionella species were found to be common causes of nosocomial and community-acquired pneumonia. Patients with chronic lung disease and organ transplants are at greatest risk. Clinical manifestations are non-specific, although fever greater than 39 degrees C and diarrhea are common. Erythromycin remains the antibiotic of choice, although many alternative agents are available. Once cases are discovered, a search for the organism in water distribution systems and respiratory equipment can be fruitful. Disinfection of water distribution systems by superheating and flushing or by hyperchlorination is feasible.

Erythromycin↗

Pantothenate kinase activity in livers of genetically diabetic mice (db/db) and hormonally treated cultured rat hepatocytes.

Preparations from livers of fed and fasted genetically diabetic and nondiabetic mice (C57BL/KsJ db/db, db/+, or +/+) were used to determine whether changes in pantothenate kinase activity and/or properties corresponded to hormonally directed changes in liver total CoA content. Livers of fasted, nondiabetic mice had ratios of pantothenate kinase (PAK) to lactate dehydrogenase (LDH) activity 1.6 times values for fed nondiabetic controls, and they had a total CoA content per milligram of DNA that was 1.8 times control values. Livers of fed genetically diabetic mice had values for PAK/LDH and total CoA per milligram of DNA that were 1.5 and 2.8 times, respectively, those of nondiabetic controls. Liver PAK from genetically diabetic mice was inhibited by acetyl-CoA to the same extent as enzyme from nondiabetic mice and by CoASH to nearly the same extent. Rat hepatocytes in primary culture incubated with dibutyryl cAMP + theophylline + dexamethasone had PAK/LDH levels 1.5 times those of cells not treated with hormonal effectors, and PAK was inhibited to the same extent by acetyl-CoA and nearly the same extent by CoASH. The data show an increase in extractable hepatic PAK activity under conditions in which the total CoA content is elevated, and they suggest that glucocorticoids and cAMP levels contribute to the increased PAK activity.

Acetyl Coenzyme A↗

Nitrate removal in riparian wetlands: interactions between surface flow and soils.

Riparian wetlands containing springs are thought to be ineffective at removing nitrate because contact times between the upwelled ground water and the underlying microbially active soils are short. Tracer experiments using lithium bromide (LiBr) and nitrate (NO3-N) injected at the surface were used to quantify residence times and NO3-N removal in a riparian swale characteristic of New Zealand hill-country pasture. An experimental enclosure was used with collecting trays at the downstream end to measure flow and concentration, shallow wells to measure subsurface concentrations, and an array of logging conductivity probes to monitor tracer continuously. The majority of added tracer reached the outlet more slowly than could be explained by surface flow, but more quickly than could be explained by Darcy seepage flow. There was evidence from the wells of tracer diffusing vertically to a depth of at least 5 cm into the surface soil layer, which was permanently saturated and highly porous. During dry weather 24 +/- 9% of added NO3-N was removed over a distance of 1.5 m largely by denitrification. The net uptake length coefficient for this wetland (K = 0.08 +/- 0.03 m(-1)) is slightly higher than the range (K = 0.01-0.07 m(-1)) measured in a small stream channel infested with macrophytes. Nitrate removal is expected to decrease with increasing flow. Seepage flow is estimated to have removed only 7 +/- 4% of the added NO3-N and we hypothesize that vertical diffusion substantially increases NO3-N removal in this type of wetland. Riparian wetlands with springs and surface flows should not be dismissed as having low NO3-N removal potential without checking whether there is significant vertical mixing.

Bromides↗

Therapeutic approaches in patients with candidemia. Evaluation in a multicenter, prospective, observational study.

OBJECTIVES: To evaluate the morbidity and mortality of Candida fungemia and to assess the efficacy of low- vs high-dose amphotericin B and fluconazole vs amphotericin B in patients with candidemia. METHODS: Multicenter, prospective, observational study of 427 consecutive patients with candidemia. RESULTS: The mortality rate for patients with candidemia was 34%. The mortality rate for patients with catheter-related candidemia in whom the catheters were retained was significantly higher than that of patients in whom the catheters were removed (41% vs 21%, P < .001). We found no overall difference in mortality in patients treated with low-dose (total amphotericin B dose of < or = 500 mg) (13%) vs high-dose amphotericin B (total amphotericin B dose of > 500 mg) (15%), but the group treated with a low dose had fewer side effects (40%) than those treated with a high dose (55%) (P = .03). Fluconazole was as efficacious as amphotericin B in the therapy of candidemia, even when stratified by risk factors for mortality. Fewer side effects were seen with fluconazole (12%) compared with amphotericin B (44%) (P < .001). CONCLUSIONS: In selected patients with candidemia, low-dose amphotericin B was as efficacious as high-dose amphotericin B. Based on other studies and ours, fluconazole seems to be an alternative therapeutic option to amphotericin B in selected patients.

Aged↗